WorldWideScience

Sample records for beagles

  1. Penis Allotransplantation in Beagle Dog.

    Science.gov (United States)

    Zhao, Yongbin; Hu, Weilie; Zhang, Lichao; Guo, Fei; Wang, Wei; Wang, Bangqi; Zhang, Changzheng

    2016-01-01

    This is an original research of penis allotransplantation. The paper presents an experiment allogenic penis transplantation model in Beagles, with a focus on recovery of blood supply and changes in tissue architecture. Twenty adult Beagles were allocated to 10 pairs for penile transplantation. After operation, the skin and glans were observed. If adverse symptoms occurred, the transplanted penis was resected and pathologically examined. Frequency of urination, urinary stream, and patency level were recorded 7 days after transplantation. Cystourethrography was performed on Day 10. The transplanted penises were resected on Day 14 for pathological examination. The research showed that transplanted penises survived after allotransplantation, and the dogs regained urination ability. Penis autotransplantation in Beagles is feasible. This preliminary study shows a potential for application of this new procedure for penis transplantation in humans.

  2. BeagleBone media center

    CERN Document Server

    Lewin, David

    2015-01-01

    Whether you are a hobbyist or a professional, this book will get you fully equipped to resolve the most commonly occurring media-related challenges. If you want to expand your horizons beyond lighting an LED and push the limits of your board, this is just the book for you. Working knowledge of BeagleBone is assumed.

  3. UK and ESA announce Beagle 2 inquiry

    CERN Multimedia

    2004-01-01

    An investigation will be held to identify the potential reasons surrounding the inability to communicate with the British-led Beagle 2 lander once it parted from the mother ship on Christmas day (1 page).

  4. Plutonium-induced lymphadenitis in beagles

    International Nuclear Information System (INIS)

    Dagle, G.E.; Park, J.F.

    1976-01-01

    Plutonium oxide particles accumulate in the tracheobronchial lymph nodes of beagles exposed by inhalation and in the popliteal lymph nodes after subcutaneous injection in the hind paws. The sequence of histopathologic changes after phagocytosis of particles included necrosis, increased numbers of macrophages, and fibroplasia. Scar tissue eventually replaced the normal architecture of the lymph nodes and sequestered the plutonium particles from surrounding parenchyma. Electron microscopy showed that plutonium particles were aggregated in phagolysosomes of macrophages

  5. BeagleBone for secret agents

    CERN Document Server

    Datko, Josh

    2014-01-01

    If you have some experience with the BeagleBone or similar embedded systems and want to learn more about security and privacy, this book is for you. Alternatively, if you have a security and privacy background and want to learn more about embedded development, this book is for you. You should have some familiarity with Linux systems and with the C and Python programming languages.

  6. Radium rentention and dosimetry in juvenile beagles

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Jones, C.W.; Bruenger, F.W.; Atherton, D.R.; Mays, C.W.

    1983-01-01

    Retention of administered 226 Ra was substantially greater in beagles injected as 3-month-old juveniles than as 1.4-year-old adults, but the measured 222 Rn/ 226 Ra ratio in bone was significantly less in juveniles for about the first 600 days after injection. An equation that describes the total-body biological retention R in beagles injected with 226 Ra at 3 months of age at any time t (in days) after injection during the first 6.6 years is R = 0.331e/sup -0.206t/ + 0.245e/sup -0.00374t/ + 0.424e/sup -0.000114t/. The rate constant of the final term in the equation for juveniles is similar to that for young adults, suggesting that this component reflects the net turnover rate in the slowly remodeling component of adult bone. Compared to young adult beagles, animals injected as juveniles had a greater fraction of their retained 226 Ra in parts of the skeleton containing much cortical bone, such as paws, and a smaller fraction in those parts containing much trabecular bone

  7. Preliminary Investigation of Beagle Dog as Substitute for Humans in ...

    African Journals Online (AJOL)

    Purpose: To assess the suitability of beagle dog as an animal model for the evaluation of formulations in bioavailability and bioequivalence studies. Methods: A generic cetirizine 10 mg tablet formulation was compared with another reference formulation using beagle dog as animal model. A crossover oral comparative ...

  8. Skeletal lesions from inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Dagle, G.E.; Park, J.F.; Weller, R.E.; Ragan, H.A.; McClanahan, B.J.; Fisher, D.R.

    1984-10-01

    The report briefly reviews the skeletal effects observed in ongoing lifespan studies in beagle dogs at 13, 10, and 7 years, respectively, after inhalation exposure to 239 Pu oxide and nitrate or 238 Pu oxide. Plutonium nitrate was chosen to represent soluble material more readily translocated to bone and other tissues than the oxide. Bone lesions related to plutonium exposure were observed only in dogs exposed to 238 Pu oxide and 239 Pu nitrate. The skeleton accumulated approximately 2% ( 239 Pu oxide), 45% ( 238 Pu oxide) or 50% ( 239 Pu nitrate) of the final body burdens at 13, 10, and 7 years, respectively, after exposure. 11 references, 2 figures

  9. Mamary neoplasia in a closed beagle colony

    International Nuclear Information System (INIS)

    Taylor, G.N.; Shabestari, L.; Williams, J.; Mays, C.W.; Angus, W.; McFarland, S.

    1975-01-01

    The incidence rate of mammary neoplasia in a large colony of beagles and its relationship to internal skeletal and/or liver radiation, age, relatively late ovariectomy (4 years and older), endometritis, parity status, and adrenal weight was examined. Of these various factors, age was the only condition that was clearly correlated with changes in the mammary tumor incidence. The rate became significant at approximately eight years of age and increased progressively throughout the successively older age classes. Within the female dogs, the incidence of mammary cancer was higher that that of any other form of spontaneous malignancy

  10. Pathology associated with inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Dagle, G.E.; Park, J.F.; Weller, R.E.; Ragan, H.A.; Stevens, D.L.

    1986-01-01

    The pathology associated with the inhalation of plutonium was studied in beagle dogs given a single exposure to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 . The temporal-spatial relationships between plutonium deposition and the development of lesions in dogs were evaluated up to 11 years, 8 years, or 5 years, respectively, after exposures, resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Exposure of the lung to high dose levels produced a spectrum of progressively more severe morphological changes, ranging from radiation pneumonitis to fibrosis. Lung tumors occurred at exposure levels that did not result in early death from radiation pneumonitis or fibrosis. Bronchiolar-alveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and combined epidermoid and adenocarcinomas were observed. Sclerosing tracheobronchial lymphadenitis, radiation osteodystrophy, osteosarcoma, and hepatic adenomatous hyperplasia were the principal extrapulmonary lesions resulting from translocation of plutonium. 15 refs., 2 tabs

  11. Myelopoiesis in whole-body-irradiated beagles

    International Nuclear Information System (INIS)

    Stevenson, A.F.G.

    1985-01-01

    The influence of dose-rate (DR) (either 5.2 or 52 cGy/min.) on the regeneration of bone marrow (BM) myelopoietic progenitor cells was studied in beagles after exposure to whole-body-irradiation (235, 375 and 1500 cGy + autologous BM-transplantation). Myelopoietic progenitor cells were assayed as colony-forming units in agar cultures (GM-CFU), in correlation with the colony-stimulation activity (CSA) in serum. At 235 cGy, the influence of DR on the recovery of GM-CFU was insignificant. However, at 375 cGy, the recovery was critically dependent on the DR. Depletion of GM-CFU numbers elevated CSA levels above pre-irradiation values. The DR determines the regenerative ability when the dose itself is critical to survival of the least number of hematopoietic stem cells (HSC) necessary for restitution. (author)

  12. Preliminary Investigation of Beagle Dog as Substitute for Humans in ...

    African Journals Online (AJOL)

    1Department of Clinical Pharmacology and Pharmacokinetics, Ranbaxy Research ... Keywords: Cetirizine, Beagle dog, Bioavailability, Bioequivalence, Pharmacokinetics, Non- .... validated method based on the Food and Drug ... determined using high-performance liquid .... Sequence effect, if any, was tested at the 10 %.

  13. Evaluation of nanoparticle delivered cisplatin in beagles

    Science.gov (United States)

    Feldhaeusser, Brittany; Platt, Simon R.; Marrache, Sean; Kolishetti, Nagesh; Pathak, Rakesh K.; Montgomery, David J.; Reno, Lisa R.; Howerth, Elizabeth; Dhar, Shanta

    2015-08-01

    Intracranial neoplasia is a significant cause of morbidity and mortality in both human and veterinary patients, and is difficult to treat with traditional therapeutic methods. Cisplatin is a platinum (Pt)-containing chemotherapeutic agent approved by the Food and Drug Administration; however, substantial limitations exist for its application in canine brain tumor treatment due to the difficulty in crossing the blood-brain barrier (BBB), development of resistance, and toxicity. A modified Pt(iv)-prodrug of cisplatin, Platin-M, was recently shown to be deliverable to the brain via a biocompatible mitochondria-targeted lipophilic polymeric nanoparticle (NP) that carries the drug across the BBB and to the mitochondria. NP mediated controlled release of Platin-M and subsequent reduction of this prodrug to cisplatin allowed cross-links to be formed with the mitochondrial DNA, which have no nucleotide excision repair system, forcing the overactive cancer cells to undergo apoptosis. Here, we report in vitro effects of targeted Platin-M NPs (T-Platin-M-NPs) in canine glioma and glioblastoma cell lines with results indicating that this targeted NP formulation is more effective than cisplatin. In both the cell lines, T-Platin-M-NP was significantly more efficacious compared to carboplatin, another Pt-based chemotherapy, which is used in the settings of recurrent high-grade glioblastoma. Mitochondrial stress analysis indicated that T-Platin-M-NP is more effective in disrupting the mitochondrial bioenergetics in both the cell types. A 14-day distribution study in healthy adult beagles using a single intravenous injection at 0.5 mg kg-1 (with respect to Platin-M) of T-Platin-M-NPs showed high levels of Pt accumulation in the brain, with negligible amounts in the other analyzed organs. Safety studies in the beagles monitoring physical, hematological, and serum chemistry evaluations were within the normal limits on days 1, 7, and 14 after injection of either 0.5 mg kg-1 or 2 mg kg

  14. Hematologic effects of inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Ragan, H.A.; Buschbom, R.L.; Park, J.F.; Dagle, G.E.; Weller, R.E.

    1986-01-01

    Beagle dogs were exposed, by inhalation, 5 to 11 years ago, to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 , at six dose levels resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Translocation of the plutonium to extrapulmonary sites was related to the physical-chemical characteristics of the plutonium compound. The highly insoluble 239 PuO 2 was retained primarily in the lung and associated lymph nodes, whereas 239 Pu(NO 3 ) 4 was much more soluble and translocated relatively rapidly to the skeleton and other extrapulmonary tissues. The 238 PuO 2 was intermediate in solubility and translocation characteristics. The hematologic effects of plutonium inhalation were most pronounced on lymphocyte populations. Evidence suggests that these effects result from irradiation of lymphocytes via the pulmonary lymph nodes with insoluble 239 PuO 2 , and via these same lymph nodes, extrapulmonary lymph nodes, and bone marrow lymphocytes with the more soluble forms, i.e., 238 PuO 2 and 239 Pu(NO 3 ) 4 . There is no evidence suggesting that these exposures increase the risk of developing myeloid or lymphoid neoplasia. 8 refs., 4 figs., 3 tabs

  15. Atrophic thyroiditis in long-term Segment III beagles

    International Nuclear Information System (INIS)

    Stephens, L.C.; Norrdin, R.W.; Benjamin, S.A.; Brewster, R.D.; Brooks, R.K.

    1981-01-01

    Lymphocytic thyroiditis associated with progressive thyroid atrophy is described in CRHL beagles. Depressed thyroid function was present in many of these dogs, as evidenced by clinical signs of hypothyroidism, elevation of serum cholesterol levels, depressed serum triiodothyronine levels, and alteration of basophils of the antero-medial region and/or unilateral or bilateral obliteration of the thyroid glands by neoplasia. Microscopic changes in the thyroid glands included lymphocytic thyroiditis, thyroid follicular atrophy, adenomatous hyperplasia of follicula cells and C-cells, and follicular cells neoplasia. This disease occurred with no sex predisposition in dogs 2 through 11 years of age. The disease does not appear to be influenced by previous radiation exposure but may be familial. In contrast to thyroid disease in some other beagle colonies, the disease in CRHL beagles more closely resembles atrophic thyroiditis of man rather than human Hashimoto's thyroiditis

  16. External scintigraphy in measuring rate of gastric emptying in beagles

    Energy Technology Data Exchange (ETDEWEB)

    Theodorakis, M.C.

    1980-07-01

    The application of external scintigraphy and preparation of a new radiopharmaceutical agent for the investigation of the rate and pattern of gastric emptying in beagles and for the visualization of segments of the intestines have been described. 99mTc-labeled triethylenetetramine-polystyrene resin was mixed in a test meal and was administered to the animal. The gastric emptying rate of the beagle was evaluated by serially recording the gastric radioactivity by means of a scintillation camera. The experimental data indicate that the pattern of gastric emptying of beagles during the first 60 min was monoexponential and the gastric emptying half time was 1.3 h. The usefulness of external scintigraphy as a noninvasive method for determining the gastric emptying rates and for visualizing segments of GI tract in animals has been demonstrated.

  17. Early retention of 237Pu + 239Pu in mature beagles

    International Nuclear Information System (INIS)

    Lloyd, R.D.; McFarland, S.S.; Atherton, D.R.; Bruenger, F.W.; Taylor, G.N.; Mays, C.W.

    1978-01-01

    Five mature beagles, ranging in age from 57 to 84 months, were injected intravenously with about 0.05-0.1 μCi/kg of 239 Pu(IV) citrate to which tracer amounts of the photon-emitter 237 Pu had been added. Plutonium retention in liver and in non-liver tissue (mainly skeleton) was measured periodically in the living dogs for nearly 4 months after injection by a combination of total-body and partial-body counting. All excreta were collected during the first 21 days and analysed for their Pu content. One dog was sacrificed at 14 days and another at 118 days for distribution studies. About 17% (14-20%) of the injected Pu was excreted in the urine and feces in the first 3 weeks, about the same as that excreted in a corresponding time by beagles injected as young adults (14%), but substantially more than beagles injected as juveniles (11%). In contrasts to juvenile beagles injected at 3 months of age, in which early retention was about 12% in liver and 68% in the skeleton, mature beagles retained about 30% in liver and 50% in the skeleton. Retention in young adult beagles injected at 17 months of age was similar to that of mature dogs. Relative distribution of skeletal plutonium among various bones was similar in the mature animals to that seen previously in young adults, but quite different from that of juveniles. A notable exception was the humerus for which there was no significant difference (P>0.2) in the % of retained skeletal Pu represented by the humerus among the juvenile, young adult and mature dogs. (author)

  18. Beagle 2: Seeking the signatures of life on Mars

    OpenAIRE

    Gibson Jr., E. K.; Pillinger, Colin T.; Wright, Ian P.; Morse, Andy; Stewart, Jenny; Morgan, G.; Praine, Ian; Leigh, Dennis; Sims, Mark R.; Pullan, Derek

    2003-01-01

    ESA's Beagle 2 lander will land on Mars to search for signatures of present and past life. A Gas Analysis Package (GAP) with a mass spectrometer, XRF, Mossbauer, stereo cameras, microscope, environmental sensors, rock corer/grinder, and a Mole attachment are on the lander.

  19. Mars orbiter redirected in bid to find Beagle

    CERN Multimedia

    2003-01-01

    "Mission controllers in Darmstadt, Germany, have successfully redirected Europe's Mars Express orbiter into a polar orbit, putting it on course for a last-ditch attempt to contact Beagle 2, the lander that has been missing since Christmas day when it should have touched down on the red planet" (1/2 page).

  20. Focal hyalinization during experimental tooth movement in beagle dogs.

    NARCIS (Netherlands)

    Böhl, Martina von; Maltha, J.C.; Hoff, J.W. Von den; Kuijpers-Jagtman, A.M.

    2004-01-01

    The aim was to study morphological differences between the periodontal structures of beagle dogs showing different rates of tooth movement under identical experimental conditions. An orthodontic appliance was placed on the mandibular second premolar and the first molar to exert a continuous and

  1. Building networks and servers using BeagleBone

    CERN Document Server

    Pretty, Bill

    2015-01-01

    If you are a developer with BeagleBone experience and want to learn how to use it to set up a network and file server, then this book is ideal for you. To make the most of this book, you should be comfortable with the Linux operating system and know how to install software from the Internet, but you do not have to be a network guru.

  2. Subchronic feeding study of carnauba wax in beagle dogs.

    Science.gov (United States)

    Parent, R A; Cox, G E; Babish, J G; Gallo, M A; Hess, F G; Becci, P J

    1983-02-01

    Carnauba wax fed at levels of 0.1, 0.3 and 1% in the diet to beagle dogs for 28 wk did not produce evidence of toxicity or pathological effects. Body weight gain, food consumption, clinical chemical, haematological, and urine analysis data, and organ weights of animals fed carnauba wax were comparable with those of control animals. Ophthalmic, gross and histopathological examinations revealed no significant treatment-related findings.

  3. Absorption and pharmacokinetics of grapefruit flavanones in beagles

    OpenAIRE

    Mata Bilbao, María de Lourdes; Andrés Lacueva, Ma. Cristina; Roura Carvajal, Elena; Jáuregui Pallarés, Olga; Escribano Ferrer, Elvira; Torre, Celina; Lamuela Raventós, Rosa Ma.

    2007-01-01

    The present study evaluated the pharmacokinetics of three different grapefruit flavanone forms in dog plasma and demonstrated their absorption after an oral intake of a grapefruit extract; pharmacokinetic parameters of these forms were also determined. Ten healthy beagles were administered 70 mg citrus flavonoids as a grapefruit extract contained in capsules, while two additional dogs were used as controls and given an excipient. The grapefruit flavanone naringin, along with its metabolites n...

  4. Atlas of experimentally-induced neoplasia in beagle dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.; Watson, C.R.

    1996-10-01

    Beagle dogs have been utilized extensively in biomedical research. The US Department of Energy''s (DOE) Office of Health and Environmental Research (OHER) has sponsored life-span dose-effect radiation studies in beagles at various laboratories. Because results from studies in the various laboratories were to be compared, all the investigators strove to use similar nomenclature and criteria to describe biological effects. For this reason, pathologists from these laboratories met on five occasions between 1976 and 1977 to discuss nomenclature and histologic criteria for diagnoses. At these meeting, criteria were discussed for histopathologic description of lesions in bone, liver, lung, hematopoietic and lymphoid tissues, mammary gland, pituitary, testis, and thyroid. To provide further assurance of cooperation among the DOE laboratories involved, DOE organized several Task Groups in 1985, composed of staff members from the laboratories. The Task Group on Biological Effects was asked to standardize nomenclature and diagnostic criteria for pathology; this beagle pathology atlas is the result of that request. The atlas describes target organs of particular interest: lungs for radionuclides delivered by inhalation; bones for bone-seeking radionuclides; and hematopoietic and other soft tissues for external irradiation

  5. Life-span studies of inhaled plutonium in beagle dogs

    International Nuclear Information System (INIS)

    Bair, W.J.

    1990-04-01

    In 1970 a life-span study with over 300 beagle dogs was begun to gain an understanding of long-term health effects resulting from respiratory tract intakes of plutonium and to derive risk estimates that might be applied to plutonium and other transuranic elements. Groups of beagle dogs were given single exposures to 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 to obtain graded levels of initial lung burdens ranging from 1 to 1800 Bq lung. The objective of this paper is to give you a progress report on the current life-span studies of inhaled plutonium in beagle dogs at the Pacific Northwest Laboratory. I will describe the biokinetics of inhaled plutonium in dogs and the resulting health effects. I will also mention some studies directed towards understanding the mechanism leading to these effects. Finally, I will discuss the current risk estimates derived from these studies and how they might relate to plutonium exposures in humans. 5 refs., 13 figs., 4 tabs

  6. Atlas of experimentally-induced neoplasia in beagle dogs

    Energy Technology Data Exchange (ETDEWEB)

    Dagle, G.E.; Watson, C.R.

    1996-10-01

    Beagle dogs have been utilized extensively in biomedical research. The US Department of Energy`s (DOE) Office of Health and Environmental Research (OHER) has sponsored life-span dose-effect radiation studies in beagles at various laboratories. Because results from studies in the various laboratories were to be compared, all the investigators strove to use similar nomenclature and criteria to describe biological effects. For this reason, pathologists from these laboratories met on five occasions between 1976 and 1977 to discuss nomenclature and histologic criteria for diagnoses. At these meeting, criteria were discussed for histopathologic description of lesions in bone, liver, lung, hematopoietic and lymphoid tissues, mammary gland, pituitary, testis, and thyroid. To provide further assurance of cooperation among the DOE laboratories involved, DOE organized several Task Groups in 1985, composed of staff members from the laboratories. The Task Group on Biological Effects was asked to standardize nomenclature and diagnostic criteria for pathology; this beagle pathology atlas is the result of that request. The atlas describes target organs of particular interest: lungs for radionuclides delivered by inhalation; bones for bone-seeking radionuclides; and hematopoietic and other soft tissues for external irradiation.

  7. Periodontal disease in research beagle dogs--an epidemiological study.

    Science.gov (United States)

    Kortegaard, H E; Eriksen, T; Baelum, V

    2008-12-01

    To estimate the prevalence and describe the extent and severity of periodontal disease and associated periodontal parameters in beagle dogs. A full-mouth, site-specific examination was performed in 98 beagle dogs. Focus was placed on clinical attachment loss, pocket depth and bleeding on probing. The prevalence of clinical attachment loss greater than equal to 1 mm was 20 per cent in the one-year-old dogs, increasing to 84 per cent of the dogs aged more than three years. The number of sites affected with clinical attachment loss greater than equal to 1 mm showed a skewed distribution. The prevalence of clinical attachment loss greater than equal to 4 mm was only seven per cent. A probing pocket depth of 4+ mm was observed in 44 to 81 per cent of the dogs, depending on age. Also, the distribution of the number of deepened pockets/dog was skewed. The teeth most prone to clinical attachment loss greater than equal to 1 mm were the P2, the P3 and the P4 of the maxilla. The teeth most prone to pocket depth greater than equal to 4 mm were the maxillary canines. Periodontal disease in terms of clinical attachment loss greater than equal to 1 mm and pocket depth greater than equal to 4 mm is common in beagle dogs, but the major disease burden is carried by only a few dogs. The prevalence increases with increased age but is high already at the age of two years.

  8. Identification of the Beagle 2 lander on Mars

    Science.gov (United States)

    Bridges, J. C.; Clemmet, J.; Croon, M.; Sims, M. R.; Pullan, D.; Muller, J.-P.; Tao, Y.; Xiong, S.; Putri, A. R.; Parker, T.; Turner, S. M. R.; Pillinger, J. M.

    2017-10-01

    The 2003 Beagle 2 Mars lander has been identified in Isidis Planitia at 90.43° E, 11.53° N, close to the predicted target of 90.50° E, 11.53° N. Beagle 2 was an exobiology lander designed to look for isotopic and compositional signs of life on Mars, as part of the European Space Agency Mars Express (MEX) mission. The 2004 recalculation of the original landing ellipse from a 3-sigma major axis from 174 km to 57 km, and the acquisition of Mars Reconnaissance Orbiter High Resolution Imaging Science Experiment (HiRISE) imagery at 30 cm per pixel across the target region, led to the initial identification of the lander in 2014. Following this, more HiRISE images, giving a total of 15, including red and blue-green colours, were obtained over the area of interest and searched, which allowed sub-pixel imaging using super high-resolution techniques. The size (approx. 1.5 m), distinctive multilobed shape, high reflectivity relative to the local terrain, specular reflections, and location close to the centre of the planned landing ellipse led to the identification of the Beagle 2 lander. The shape of the imaged lander, although to some extent masked by the specular reflections in the various images, is consistent with deployment of the lander lid and then some or all solar panels. Failure to fully deploy the panels-which may have been caused by damage during landing-would have prohibited communication between the lander and MEX and commencement of science operations. This implies that the main part of the entry, descent and landing sequence, the ejection from MEX, atmospheric entry and parachute deployment, and landing worked as planned with perhaps only the final full panel deployment failing.

  9. Identification of the Beagle 2 lander on Mars.

    Science.gov (United States)

    Bridges, J C; Clemmet, J; Croon, M; Sims, M R; Pullan, D; Muller, J-P; Tao, Y; Xiong, S; Putri, A R; Parker, T; Turner, S M R; Pillinger, J M

    2017-10-01

    The 2003 Beagle 2 Mars lander has been identified in Isidis Planitia at 90.43° E, 11.53° N, close to the predicted target of 90.50° E, 11.53° N. Beagle 2 was an exobiology lander designed to look for isotopic and compositional signs of life on Mars, as part of the European Space Agency Mars Express (MEX) mission. The 2004 recalculation of the original landing ellipse from a 3-sigma major axis from 174 km to 57 km, and the acquisition of Mars Reconnaissance Orbiter High Resolution Imaging Science Experiment (HiRISE) imagery at 30 cm per pixel across the target region, led to the initial identification of the lander in 2014. Following this, more HiRISE images, giving a total of 15, including red and blue-green colours, were obtained over the area of interest and searched, which allowed sub-pixel imaging using super high-resolution techniques. The size (approx. 1.5 m), distinctive multilobed shape, high reflectivity relative to the local terrain, specular reflections, and location close to the centre of the planned landing ellipse led to the identification of the Beagle 2 lander. The shape of the imaged lander, although to some extent masked by the specular reflections in the various images, is consistent with deployment of the lander lid and then some or all solar panels. Failure to fully deploy the panels-which may have been caused by damage during landing-would have prohibited communication between the lander and MEX and commencement of science operations. This implies that the main part of the entry, descent and landing sequence, the ejection from MEX, atmospheric entry and parachute deployment, and landing worked as planned with perhaps only the final full panel deployment failing.

  10. Pulmonary lesions induced by inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Dagle, G.E.; Lund, J.E.; Park, J.F.

    1976-01-01

    The histopathologic features of pulmonary fibrosis and bronchiolo-alveolar carcinoma in beagles exposed to aerosols of 238 Pu or 239 Pu oxide are reviewed. A hypothesis of the pathogenesis of radiation pneumonitis induced by inhalation of plutonium oxide is presented; this hypothesis included phagocytosis of Pu particles, fibrosis responding to the necrosis, and alveolar cell hyperplasia compensating for alveolar cells killed by alpha radiation. Histopathologic features of the epithelial changes suggest a progression from hyperplasia to metaplasia and, finally, to bronchiolo-alveolar carcinoma. The possibility of concurrent radiation-induced lymphopenia contributing to the development of bronchiolo-alveolar carcinoma through a loss of immunologic surveillance is discussed

  11. Pulmonary lesions induced by inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Dagle, G.E.; Lund, J.E.; Park, J.F.

    1975-01-01

    The histopathologic features of pulmonary fibrosis and bronchiolo-alveolar carcinoma in beagles exposed to aerosols of plutonium oxide were reviewed. A hypothesis of the pathogenesis of radiation pneumonitis induced by inhalation of plutonium oxide was presented; this hypothesis included phagocytosis of plutonium particles, fibrosis responding to the necrosis, and alveolar cell hyperplasia compensating for alveolar cells killed by alpha radiation. Histopathologic features of the epithelial changes suggest a progression from hyperplasia to metaplasia and, finally, to bronchiolo-alveolar carcinoma. The possibility of concurrent radiation-induced lymphopenia contributing to the development of bronchiolo-alveolar carcinoma through a loss of immunologic surveillance was discussed

  12. Extending the BEAGLE library to a multi-FPGA platform.

    Science.gov (United States)

    Jin, Zheming; Bakos, Jason D

    2013-01-19

    Maximum Likelihood (ML)-based phylogenetic inference using Felsenstein's pruning algorithm is a standard method for estimating the evolutionary relationships amongst a set of species based on DNA sequence data, and is used in popular applications such as RAxML, PHYLIP, GARLI, BEAST, and MrBayes. The Phylogenetic Likelihood Function (PLF) and its associated scaling and normalization steps comprise the computational kernel for these tools. These computations are data intensive but contain fine grain parallelism that can be exploited by coprocessor architectures such as FPGAs and GPUs. A general purpose API called BEAGLE has recently been developed that includes optimized implementations of Felsenstein's pruning algorithm for various data parallel architectures. In this paper, we extend the BEAGLE API to a multiple Field Programmable Gate Array (FPGA)-based platform called the Convey HC-1. The core calculation of our implementation, which includes both the phylogenetic likelihood function (PLF) and the tree likelihood calculation, has an arithmetic intensity of 130 floating-point operations per 64 bytes of I/O, or 2.03 ops/byte. Its performance can thus be calculated as a function of the host platform's peak memory bandwidth and the implementation's memory efficiency, as 2.03 × peak bandwidth × memory efficiency. Our FPGA-based platform has a peak bandwidth of 76.8 GB/s and our implementation achieves a memory efficiency of approximately 50%, which gives an average throughput of 78 Gflops. This represents a ~40X speedup when compared with BEAGLE's CPU implementation on a dual Xeon 5520 and 3X speedup versus BEAGLE's GPU implementation on a Tesla T10 GPU for very large data sizes. The power consumption is 92 W, yielding a power efficiency of 1.7 Gflops per Watt. The use of data parallel architectures to achieve high performance for likelihood-based phylogenetic inference requires high memory bandwidth and a design methodology that emphasizes high memory

  13. Dental radiology: ageing changes in permanent teeth of Beagle dogs

    International Nuclear Information System (INIS)

    Morgan, J.P.; Miyabayashi, T.

    1991-01-01

    Radiographic interpretation of dental or periodontal disease is dependent in part on an understanding of ageing changes, A progressively ageing colony of healthy beagle dogs (120 to 3759 days) was studied by use of high-detail radiographs made following the death of the dog. Morphological features whose radiographic appearance was found to be especially age-dependent were: root canal size, both vertical and horizontal alveolar bone resorption, visualisation of the lamina dura dentis, and detection of hypercementosis. Understanding of these ageing changes is necessary to avoid over-diagnosis of disease

  14. Hematological effects of inhaled plutonium dioxide in beagles

    International Nuclear Information System (INIS)

    Weller, R.E.; Buschbom, R.L.; Park, J.F.

    1995-01-01

    A life-span study indicated that plutonium activity in the thoracic lymph nodes is a contributor to development of lymphopenia in beagles exposed to 239 PuO 2 . Significant lymphopenia was found in 67 (58%) beagles given a single nose-only exposure to 239 PuO 2 to result in mean initial lung depositions ranging from 0.69 to 213.3 kBq. Lymphoid atrophy and sclerosis of the thoracic lymph nodes and lymphopenia were observed in exposure-level groups with initial lung depositions ≥2.5 kBq. Those dogs with final plutonium concentrations in the thoracic lymph nodes ≥0.4 kBq/g and dose rates ≥0.01 Gy/day developed lymphopenia. Marked differences existed between chronically lymphopenic dogs and intermittently lymphopenic dogs with regard to initial lung deposition, time to lymphopenic events and absolute lymphocyte concentrations. Linear regression analysis revealed moderate correlation between reduction in lymphocyte values and initial lung deposition, in both magnitude and time of appearance after exposure. Cumulative dose and dose rate appeared to act together to produce initial effects on lymphocyte populations, while dose rate alone appeared to be responsible for the maintenance and subsequent cycles of lymphopenia seen over the life span. No primary tumors were associated with the thoracic lymph nodes in this study, although 70% of the lymphopenic dogs developed lung tumors. 28 refs., 2 figs., 7 tabs

  15. Absorption of DTPA from the respiratory tracts of Beagle dogs

    International Nuclear Information System (INIS)

    Dudley, R.E.; Muggenburg, B.A.; Cuddihy, R.G.

    1978-01-01

    Absorption of diethylenetriaminepentaacetic acid (DTPA) from the nasopharyngeal (NP), tracheobronchial (TB) and pulmonary (P) regions of Beagle dogs was determined because of the current interest in aerosolized DTPA as a method for removal of internally deposited radionuclides. Radiolabeled DTPA was instilled into the NP, TB and P regions of Beagle dogs and its subsequent translocation was followed for 48 hours. Results revealed that 16, 48 and 90% of the instilled DTPA was absorbed into the circulatory system from the NP, TB and P regions, respectively. A comparison was also made between NP absorption of aerosolized DTPA and DTPA instilled into the nasopharynx. Nasopharyngeal absorption of aerosolized DTPA, 23%, was slightly higher than that of instilled DTPA. Diethylenetriaminepentaacetic acid deposited in the respiratory tract remained in the body longer than intravenously injected DTPA. These findings indicate that substantial absorption of DTPA occurs from all regions of the respiratory tract and that DTPA need not be deposited deep within the respiratory tract to produce systemic absorption of DTPA for the removal of internally deposited radioactive isotopes

  16. Tetracycline treatment of periodontal disease in the beagle dog

    Energy Technology Data Exchange (ETDEWEB)

    Jeffcoat, M.K.; Williams, R.C.; Kaplan, M.L.; Goldhaber, P.

    1982-01-01

    Bone-seeking radiopharmaceutical uptake (BSRU) was used to examine alveolar bone metabolism in a longitudinal study of tetracycline efficacy in beagle dogs. BSRU was measured in untreated control dogs and in beagles receiving either 250 mg or 500 mg oral tetracycline-HCl daily for 16 months. The rate of bone loss was determined for radiographs taken semiannually for a 6-month pretreatment period and for a 24-month treatment period. Measurements of BSRU obtained at month 16 of treatment were correlated with rates of bone loss determined radiographically in an attempt to determine whether BSRU was indicative of the subsequent rate of bone loss. A reduced rate of alveolar bone loss was found in the 500 mg tetracycline group at month 16 of the study relative to the untreated controls which was consistent with the decreased bone-seeking radiopharmaceutical uptake observed in this group. A significantly increased BSRU (p<.0001) was found in the 250 mg tetracycline group at month 16 of study relative to the untreated and 500 mg tetracycline groups. A rapid increase in the rate of bone loss in the 250 mg tetracycline group which was not detectable prior to 16 months of treatment became evident radiographically by 24 months. Thus, increased BSRU in the 250 mg tetracycline group appeared to detect the loss of the effect of tetracycline (escape phenomenon). 13 references, 4 figures.

  17. Radon in bone as measured in neonatal, juvenile, and mature beagles and in adult St. Bernards

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Bruenger, F.W.; Mays, C.W.; Jones, C.W.

    1982-01-01

    The measured 222 Rn/ 226 Ra ratio in bone following 226 Ra injection of 5-year-old mature beagles and adult St. Bernards was similar to that predicted by an equation derived from data of beagles injected as young adults. However, Rn/Ra ratios were significantly lower in beagles injected as 3-month-old juveniles for about the first 600 days after injection, but were indistinguishable thereafter from the values predicted by the equation associated with young adult beagles. A 2-term equation was developed from the data for juveniles, the first term of which was the equation for young adults. For beagles injected as juveniles, the skeletal Rn/Ra ratio as a function of time after injection (t, in days) was Rn/Ra = 0.075 t 0 158 (1-e/sup -0.181t/) - 0.058 (e/sup -0.0061t/-e/sup -0.162t/). Beagles injected as 2-day-old neonates exhibited ratios for the first 2 weeks which were similar enough to those of juveniles that a separate equation was not derived for neonatal beagles

  18. Functional capacities of lungs and thorax in beagles after prolonged residence at 3,100 m.

    Science.gov (United States)

    Johnson, R L; Cassidy, S S; Grover, R F; Schutte, J E; Epstein, R H

    1985-12-01

    Functional capacities of the lungs and thorax in beagles taken to high altitude as adults for 33 mo or in beagles raised from puppies at high altitude were compared with functional capacities in corresponding sets of beagles kept simultaneously at sea level. Comparisons were made after reacclimatization to sea level. Lung volumes, airway pressures, esophageal pressures, CO diffusing capacities (DLCO), pulmonary blood flow, and lung tissue volume (Vt) were measured by a rebreathing technique at inspired volumes ranging from 15 to 90 ml/kg. In beagles raised from puppies we measured anatomical distribution of intrathoracic air and tissue using X-ray computed tomography at transpulmonary pressures of 20 cm H2O. Lung and thoracic distensibility, DLCO, and Vt were not different between beagles that had been kept at high altitude for 33 mo as adults and control subjects kept simultaneously at sea level. Lung distensibility, DLCO, and Vt were significantly greater in beagles raised at high altitude than control subjects raised simultaneously at sea level. Thoracic distensibility was not increased in beagles raised at high altitude; the larger lung volume was accommodated by a lower diaphragm, not a larger rib cage.

  19. The Beagle 2 Effect - public response to the UK Mars lander

    Science.gov (United States)

    Pillinger, J. M.; Pillinger, C. T.

    As a prerequisite for understanding science, the target audience must first be aware of an issue and then continue to maintain interest. We discuss the impact of the Beagle 2 mission to Mars on raising awareness amongst the general public as the first step to increasing understanding of the scientific and technological challenges and solutions such a mission addresses. The massive amount of public interest created is now being ttributed to the so-called "Beagle 2 Effect". We consider the reasons why the public, particularly, but not exclusively, in the UK took Beagle 2 to heart. Initially our strategy, as part of the PR plan for Beagle 2, was to collate media coverage for various stages and discrete campaigns in particular to use press cuttings to determine the level of recognition of Beagle 2 as a brand. At the start of the project this information was to support sponsorship bids, latterly the intrinsic value of media, and hence public, awareness was recognised by the major partners in the project. Much of the subsequent public awareness resulted from the comprehensive coverage in all branches of the media. A second opportunity to evaluate the response to the mission was presented to us as it became increasingly clear that Beagle 2 was able to engage an audience much wider than that typically interested in space, or science in general. We highlighted how far mention of Beagle 2 has spread. Additionally numerous unsolicited letters have been received from the public and these have been collated to indicate the factors which appear to have contributed to the widespread interest in Beagle 2. It is not clear whether the "Beagle 2 Effect" can, or will, be transferred to subsequent space missions.

  20. Serial ultrasonographic appearance of postpartum uterine involution in beagle dogs.

    Science.gov (United States)

    Yeager, A E; Concannon, P W

    1990-09-01

    Postpartum changes in uterine shape, architecture, echogenicity and diameter were determined during the serial examinations of five beagle bitches. During postpartum Week 1, the uterine horns were tubular structures composed of multiple layers of various echogenicity and had multiple, discrete enlargements with hypoechoic centers at placental sites. Diameters ranged from 1.1 to 3.8 cm at placental site enlargements, and 0.5 to 1.4 cm between enlargements. Uterine involution appeared to be completed by 15 wk post partum. At 15 weeks the uterine horns of each dog were uniform hypoechoic, tubular structures without enlargements and had a reduced diameter of 0.3 to 0.6 cm. These ultrasonographic findings are similar to previously reported gross and light microscopic descriptions of canine uterine involution.

  1. 241Am induced thyroid lesions in the beagle: interim observations

    International Nuclear Information System (INIS)

    Taylor, G.N.; Zizumbo, I.; Angus, W.; Jones, A.; Elliot, D.

    1976-01-01

    Injected doses of 2.88, 0.91 or 0.296 μCi 241 Am/kg in young adult beagles produced morphological changes in the thyroid gland and produce lower concentrations of thyroxin in the sera. Interstitial fibrosis without functional impairment was induced by the 0.099 μCi 241 Am/kg dose level. Clinical symptoms of hypothyroidism were not observed, even in those dogs with the most extreme thyroid lesions. The changes were characterized by a decrease in thyroid weight, interfollicular fibrosis, loss of colloid, loss of follicular epithelium, and hypertrophy and hyperplasia of the residual epithelium. Thus far, thyroid tumors have not been observed, however, a significant percentage of the animals in the lower dose levels are still living

  2. Dose-effect studies with inhaled plutonium oxide in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Buschbom, R.L.; Case, A.C.

    1976-01-01

    Beagle dogs given single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs dying due to pulmonary fibrosis-induced insufficiency during the first 3 years after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor. Three additional dogs with body burdens of 0.7 to 1.8 μCi died due to pulmonary neoplasia 4-1/2 years after exposure. None of the dogs exposed to 238 Pu have died during the first two postexposure years. After inhalation of 239 PuO 2 or 238 PuO 2 lymphocytopenia was the earliest observed effect, occuring 0.5 to 2 years after deposition of greater than or equal to 80 nCi plutonium in the lungs

  3. Effect of aging on tracheal mucociliary clearance in Beagle dogs

    International Nuclear Information System (INIS)

    Whaley, S.L.; Muggenburg, B.A.; Wolff, R.K.

    1985-01-01

    Tracheal mucous velocity measurements were made in 24 Beagle dogs, in 5 age groups, using a gamma camera to detect movement on instilled radiolabeled material. Age groups were defined as immature, young adult, middle-aged, mature, and aged dogs. Mean velocities (+/- SE) were 3.6 +/- 0.4 mm/min in the immature dogs, 9.8 +/- 0.7 mm/min in the young adults, 6.9 +/- 0.5 mm/min in the middle-aged dogs, 3.6 +/- 1.1 mm/min in the mature dogs, and 2.8 +/- 0.6 mm/min in the aged dogs. Tracheal mucous velocity was significantly faster in the young adult and middle-aged groups than in the immature, mature, and aged dog groups. 4 references, 1 figure, 1 table

  4. Toxicity of inhaled 91YCl3 in beagle dogs

    International Nuclear Information System (INIS)

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1980-01-01

    The metabolism, dosimetry and effects of inhaled 91 YCl 3 in beagle dogs are being studied. Forty-two dogs with 91 Y initial body burdens from 14 to 1300 μCi/kg body weight and 12 control dogs are being maintained for lifetime observation. Four additional dogs with a mean initial body burden of 180 μCi/kg body weight were placed in a sacrifice study. Thirty-six of the exposed dogs and 7 of the control dogs have died. Dogs with the highest activity levels died with bone marrow damage and pancytopenia. Three dogs died with nasal cavity carcinomas and three with pulmonary carcinomas and one with hepatic hemangiosarcoma that all appear related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases. Observations are continuing on 10 surviving exposed dogs and six surviving unexposed dogs

  5. Toxicity of inhaled 91YCl3 in Beagle dogs. XV

    International Nuclear Information System (INIS)

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.; Jones, R.K.; Kusewitt, D.F.; McClellan, R.O.; Pickrell, J.A.

    1981-01-01

    The metabolism, dosimetry and biological effects of inhaled 91 YCl 3 in Beagle dogs are being studied. Forty-two dogs with initial 91 Y body burdens from 14 to 1300 μCi per kilogram body weight and 12 control dogs are being maintained for lifetime observation. Four additional dogs with a mean initial body burden of 180 μCi per kilogram body weight were placed in a sacrifice study. Forty-three of the exposed dogs and 11 of the control dogs have died. Dogs with the highest initial body burdens died with bone marrow damage and pancytopenia. Three dogs died with nasal cavity carcinomas, three dogs died with pulmonary carcinomas and one dog died with hepatic hemangiosarcoma; these cancers all appeared to be related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases. Observations are continuing on three surviving exposed dogs and one surviving unexposed dog

  6. Primary joint disease in the shoulder of the beagle dog

    International Nuclear Information System (INIS)

    Morgan, J.P.; Pool, R.R.; Miyabayashi, T.; Soo, S.

    1985-01-01

    Shoulder joints of 149 beagle dogs, whose ages were over 8 years at the time of death, were examined to document primary joint disease. Clinical histories of the dogs suggested no underlying causes, i.e. no evidence of osteochondrosis, trauma or joint infection. Radiographic examinations revealed normally developing shoulders in the first years of their lives. Radiographic changes were progressive with age. Bilateral involvement was common. The changes consisted of osteophyte formation on the caudal aspect of the humeral head and glenoid. Postmortem findings included: subchondral bone sclerosis (thin-section radiographs), cartilage wearing, joint capsule thickening, and pannus formation. The authors believe that the changes occurring in the shoulder joints are those of primary joint disease. 12 references

  7. Toxicity of inhaled 91YCl3 in Beagle dogs. XVII

    International Nuclear Information System (INIS)

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1983-01-01

    The metabolism, dosimetry, and biological effects of inhaled 91 YCl 3 in Beagle dogs are being studied. Forty-two dogs with initial 91 Y body burdens from 14 to 1300 μCi/kg body weight and 12 control dogs were observed during their life spans. Four additional dogs with a mean initial body burden of 180 μCi 91 Y/kg body weight were placed in a sacrifice study. All 46 of the exposed dogs and all 12 of the control dogs have died. Dogs with the highest initial body burdens died with bone marrow damage and pancytopenia. Three dogs died with nasal cavity carcinomas, three died with pulmonary carcinomas, and one died with hepatic hemangiosarcoma. These cancers all appeared to be related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases

  8. Evaluation of a hydrophilic gingival dental sealant in beagle dogs.

    Science.gov (United States)

    Sitzman, Clarence

    2013-01-01

    A liquid solution, gingival sealant containing polymers that form a barrier film upon application was evaluated in dogs. It is a non-toxic, low viscosity, hydrophilic barrier sealant that dries in approximately 10 to 15-seconds after subgingival application. It was designed as a preventative to be applied immediately following a professional oral hygiene procedure in order to block plaque and calculus formation in the sulcus and aid in the prevention of periodontal disease in companion animals. Additionally, the polymer was designed to promote an aerobic environment in the sulcus by oxygen and water transport through engineered pores within the polymer. A 30-day split-mouth, blinded study in two groups of 15 beagle dogs was used. Plaque was significantly (p periodontal disease in dogs.

  9. Dose-effect studies with inhaled plutonium oxide in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Buschbom, R.L.; Case, A.C.

    1977-01-01

    Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor. Five additional dogs with body burdens of 0.7 to 1.8 μCi died due to pulmonary neoplasia 3 to 5 yr after exposure. None of the dogs exposed to 238 Pu have died during the first 3 postexposure yr. Lymphocytopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2 , occurring 0.5 to 2 yr after deposition of greater than or equal to 80 nCi plutonium in the lungs

  10. Radiation-induced erythroleukemia in the beagle dog

    International Nuclear Information System (INIS)

    Tolle, D.V.; Fritz, T.E.; Norris, W.P.

    1977-01-01

    Eleven cases of myeloproliferative disease occurred in a group of 24 beagle dogs placed in a 60 Co γ-ray field at about 13 months of age and irradiated at an exposure rate of 5 R/22-hour day for duration of life. Of these 11 dogs, 5 were diagnosed as having erythroleukemia. The bone marrow showed marked erythroblastic hyperplasia, with maturation arrest of the erythroid elements, and increased numbers of myeloblasts and promyelocytes. The terminal peripheral blood was characterized by marked anemia and thrombocytopenia, with circulating erythrocytic precursors and abnormal erythrocyte morphology. Splenomegaly and hepatomegaly occurred in 4 of the 5 animals. In the spleens and livers of all 5, there was extensive leukemic infiltration and proliferation. The extent of leukemic involvement in other tissues and organs varied in individual dogs

  11. Skeletal dosimetry of injected 226RA in young adult beagles

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Mays, C.W.; Atherton, D.R.

    1986-01-01

    Revised equations are presented for the skeletal dose to young adult beagles from 226 Ra injection. For 0.1 kg of skel/kg body and given 1 μCi 226 Ra/kg with 210 Pb/ 226 Ra = 0.05, the average skeletal dose in rad at 6 yr is 226 Ra = 1200, 222 Rn -> 214 Po = 1050, injected 210 Pb = 56 and 210 Pb from Rn decay in bone = 22. For a Pb/Ra ratio = 0.4, dose from injected 210 Pb is about 20% of that from 226 Ra -> 214 Po. A similar but not numerically indentical relationship obtains for ingested 226 Ra, so the dose from 210 Pb should be included in any study of 226 Ra effects. (orig.)

  12. Radium-226-induced dental disease in Beagles: a radiographic study

    International Nuclear Information System (INIS)

    Morgan, J.P.; Miyabayashi, T.; Goldman, M.; Soo, S.

    1987-01-01

    Evaluation of dental radiographs made at necropsy and during the life of the dogs clearly shows age dependent changes within the control dogs. Periodontal diseases, loss of lamina dura, root ankylosis, and loss of pulp cavity were all commonly noted. Tooth loss and dental caries were rare in the control dogs. In injected Beagles loss of lamina dura was noted earlier and was dose dependent. Tooth loss and dental carried increased with dose level and appeared earlier. Tooth loss was common by 1600-1800 days of age while dental caries were common in almost all dogs by 1600-1800 days of age in the R40 level. Dental caries was the most accurate indication of the level of 226 Ra toxicity. 18 reference, 1 table

  13. Decorporation of 241Am in beagles by DTPA

    International Nuclear Information System (INIS)

    Lloyd, R.D.; McFarland, S.S.; Taylor, G.N.; Williams, J.L.; Mays, C.W.

    1975-01-01

    Chelation treatments using daily subcutaneous injections of ZnNa 3 -DTPA were begun 2 wk after the intravenous administration of 0.3 μCi/kg 241 Am citrate to six female beagles averaging 505 days of age. Retention of americium in the liver and in non-liver tissue (mainly skeleton) was followed serially in the living dogs by a combination of total-body and partial-body counting. During the first 13 mo of DTPA therapy, the removal of 241 Am from two dogs given one DTPA injection each day of 0.027 or 0.034 mmole/kg was similar to the fraction removed from two other dogs given a similar total of 0.035 or 0.037 mmole/kg/day in five fractionated injections each day. Increasing the daily amount of DTPA to 0.36 and 5.0 mmole/kg/day in the two remaining dogs only slightly increased the removal of 241 Am. At the beginning of chelation therapy, all six dogs averaged 43 percent of the injected 241 Am in the liver and 46 percent in nonliver tissue. 241 Am retention in liver at 2 mo of therapy was about 2 percent of pretreatment liver retention, decreased to roughly 1 percent of pretreatment retention by 5 mo of DTPA administration, and was undetectable at 13 months. Nonliver retention at 2 mo was 53 percent of pretreatment retention in nonliver tissue, at 5 mo averaged about 40 percent, and had decreased to 27 percent of pretreatment values by 13 mo of chelation therapy. In contrast, for beagles of our colony not treated with DTPA, 241 Am in the liver and in nonliver tissue exhibited a biological half-time in the order of 10 yr. (U.S.)

  14. Effect of Itraconazole on the Pharmacokinetics of Diclofenac in Beagle Dogs

    OpenAIRE

    AL-JENOOBI, Fahad

    2010-01-01

    The objective of this study was to investigate the potential effect of itraconazole on the pharmacokinetics of diclofenac potassium in beagle dogs after oral coadministration. Five male beagle dogs received a single oral 50 mg dose of diclofenac potassium alone in phase I, and along with a single oral 100 mg dose of itraconazole in phase II. Blood samples obtained for 8.0 hours post dose were analysed for diclofenac concentration using a validated high performance liquid chromatography (HPLC)...

  15. Consideration of age-dependent radium retention in people on the basis of the beagle model

    International Nuclear Information System (INIS)

    Parks, N.J.; Keane, A.T.

    1982-01-01

    Skeletal calcification as a function of age has been estimated for human females on the basis of the beagle model. The interspecies scaling of radium retention characteristics has been described in terms of skeletal calcium addition rates for beagles and humans. radium retention in humans exposed to less than 200 μCi was greatest in individuals who were less than 18 years old when exposed

  16. Carcinogenesis of inhaled radio daughters with uranium ore dust in beagle dogs

    International Nuclear Information System (INIS)

    Filipy, R.E.; Dagle, G.E.; Palmer, R.F.; Stuart, B.O.

    1977-01-01

    Daily exposures of adult beagle dogs to inhaled radon daughters and to uranium ore dust for 4-1/2 to 6 yr have produced respiratory tract carcinomas, at similar cumulative working level months (WLM) of exposures to those which induced carcinomas in uranium miners. Biological data from the beagle-dog experiments can therefore be used for prediction of carcinogenic risk under changing exposure conditions in future uranium miners

  17. Radium-induced dental changes in humans and beagles: a comparative microradiographic study

    International Nuclear Information System (INIS)

    Farnham, J.E.; Morgan, J.P.; Pool, R.R.; Miyabayashi, T.

    1985-01-01

    Microradiographs made from thin sections of teeth of humans carrying skeletal deposits of 226 Ra and 228 Ra and of beagles injected with 226 Ra showed similar patterns of change with age. The patterns consisted of the presence of remodeling units of alveolar bone that extended across the gomphosis and involved the cementum and dentine. This is not described as a normal aging change in humans or beagles. 3 tables

  18. 226Ra-induced dental changes: a comparative microradiographic study of human and beagle dog

    International Nuclear Information System (INIS)

    Morgan, J.P.; Pool, R.R.; Farnham, J.E.; Miyabayashi, T.

    1984-01-01

    Comparison of microradiographs made from thin sections of teeth from human and the Beagle dog show a similar pattern of change dependent on age of exposure and duration of exposure prior to death or extraction. The pattern of change consisted of the presence of remodeling units of alveolar bone that extended across the gomphosis and involved the cementum and dentine. This pattern of change is not described as a normal aging change in either humans or the Beagle dog. 2 tables

  19. Occurrence of mammary tumors in beagls given radium-226

    International Nuclear Information System (INIS)

    Bruenger, F.W.; Lloyd, R.D.; Miller, S.C.; Taylor, G.N.; Angus, W.; Huth, D.A.

    1994-01-01

    A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with 226 Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given 226 Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon → polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. 27 refs., 5 figs., 4 tabs

  20. Life-span studies of inhaled plutonium in beagle dogs

    International Nuclear Information System (INIS)

    Bair, W.J.

    1991-01-01

    In 1970 a life-span study with over 300 beagle dogs was begun. Groups of beagle dogs were given single exposures to 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 to obtain graded levels of initial lung burdens ranging from 1 to 1800 Bq lung. After 16 years, the lungs contained about 2% of the initial lung burden of 239 PuO 2 , the thoracic lymph nodes 20%, skeleton 1% and liver 10%. After 15 years the lungs contained about 0.2% of the initial lung burden of 238 PuO 2 , thoracic lymph nodes 5%, skeleton 10%, and liver 10%. After 10 years the lungs contained about 0.29% of the initial lung burden of 239 Pu(NO 3 ) 4 , thoracic lymph nodes 0.17%, skeleton 18% and liver 13%. Chronic lymphopenia has been one of the earliest biological effects observed. Other effects associated with plutonium exposure included sclerosis of the tracheobronchial lymph nodes, focal radiation pneumonitis, adenomatous hyperplasia of the liver and dystrophic osteolytic lesions in the skeleton. In 16 years, mortality due to radiation pneumonitis and/or lung tumor increased with deposition of 24 Bq of 239 PuO 2 . In 15 years, mortality due to lung and/or bone tumors increased with deposition of 96 Bq of 238 PuO 2 . In 11 years, after exposure, mortality due to lung and/or bone tumors increased with deposition of 18 Bq of 239 Pu(NO 3 ) 4 . Lung cancers appeared to originate in the parenchymal regions of the lungs and were of several types; bronchiolar alveolar carcinoma, papillary adenocarcinomas, adenosquamous carcinoma, and epidermoid carcinoma. Metastases were primarily to the thoracic lymph nodes. Sites of osteosarcomas in the 238 PuO 2 and 239 Pu(NO 3 ) 4 dogs were in the lumbar cervical and thoracic vertebrae, humerus, pelvis, facial bones, ribs and nasal turbinates. The risk of lung cancer, based on cumulative dose to the lungs, was about 12 times higher for 239 Pu(NO 3 ) 4 than from inhaled 239 PuO 2 , and 50 times higher than for inhaled 238 PuO 2 . (J.P.N.)

  1. Multiple whole body hyperthermia treatments on normal beagles

    International Nuclear Information System (INIS)

    Geist, B.J.; Gillette, E.L.; Tucker, A.; Robertshaw, D.; Benjamin, S.A.; Macy, D.W.

    1985-01-01

    Twelve young adult male castrated beagles were randomized into either a treatment or a control group. The treatment group received 4 consecutive treatments at 1 week intertreatment intervals. A temperature and humidity controlled chamber was used to raise the core temperature to 42 0 C. Time required to raise the core temperature from 38 0 C to 42 0 C was approximately 70 minutes. Dogs were maintained at 42 0 C breathing halothane, 35% O/sub 2/ and 65 0 N/sub 2/ for 2 hours, followed by a 30 minute cool down period during which a shunt determination using 100% O/sub 2/ was done. No significant changes in temperature adjusted blood oxygen tension were noted during hyperthermia. Mean arterial blood pressure dropped an average of 15mm Hg during the 2 hour plateau. Cardiac rhythms remained stable and rates did not exceed 180 beats per minute. Central venous pressure remained stable and within normal range without treatment, 1.0 - 2.5 mm Hg. Dogs regained alertness and ambulation within 3 hours post treatment. No diarrhea was noted. The most significant acute changes appeared to be liver enzyme elevation, total protein decrement and transient changes in platelet and white blood cell counts

  2. Retention of plutonium in the beagle after gastrointestinal absorption

    International Nuclear Information System (INIS)

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

    1985-01-01

    A 0.01 M bicarbonate solution containing 130 nCi (approx. 5 kBq) of 237 Pu (90% hexavalent, 93% ultrafilterable) was administered via gelatin capsule to six adult male beagles following a 21-hr fast. The dogs were sacrificed after 5-6 weeks and the percentage of the administered plutonium retained in the liver plus skeleton and its distribution within the skeleton were determined. The mean amount retained in these tissues was (0.063 +- 0.006)% of the administered dose. The mean amounts of plutonium in the liver and the skeleton were approximately equal, and the distribution within the skeleton was similar to that observed by other workers following either intravenous injection or inhalation. The value for plutonium retention by the dog is about a factor of three less than the values the authors have reported for rodents. It is a factor of 7 greater than the product of the values for gastrointestinal absorption (f 1 ) and fractional retention (f 2 ) recommended by the ICRP for man

  3. Dose-effect studies with inhaled plutonium oxide in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Case, A.C.; Catt, D.L.

    1978-01-01

    Beagle dogs given a single exposure to 239 PuO 2 and 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor; nine additional dogs with body burdens of 0.6 to 1.8 μCi died due to pulmonary neoplasia 3 to 6 yr after exposure. Two of the dogs exposed to 238 Pu have died during the first 4 yr postexposure, due to bone and lung tumors, with body burdens at death of 10 μCi. Lymphocytopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2 , occurring 0.5 to 2 yr after deposition of equal to or greater than 80 nCi plutonium in the lungs

  4. Cutaneous papillomatous hyperplasia in cyclosporine-A treated beagles.

    Science.gov (United States)

    Seibel, W; Sundberg, J P; Lesko, L J; Sauk, J J; McCleary, L B; Hassell, T M

    1989-08-01

    All twelve Beagle dogs undergoing long-term therapy (26 weeks) with the immunosuppressive drug cyclosporine-A (30 mg/kg), developed cutaneous papillomatous hyperplasia. By week 7 all dogs developed generalized lesions distributed over the entire body. These occurred as irregular, oval, sessile, unpigmented, firm masses. The incidence and severity of the skin lesions varied among dogs and anatomic site, with no correlation to the blood level of cyclosporine. Microscopic analysis revealed that the epidermis formed short papillary folds on broad fibrovascular stalks and was hyperkeratotic and acanthotic. Mild hyperplasia of hair follicles and sebaceous glands was also evident. A mild diffuse infiltrate of lymphocytes and plasma cells was present in the papillary dermis. No histopathologic changes typical of papillomavirus infection were identified, nor were papillomavirus group-specific antigens or viral DNA detected. Other cutaneous side effects included hyperkeratosis of footpads, increased growth of hair and nails, and hyperkeratinization of the haired skin of the prepuce. All cutaneous lesions regressed spontaneously within 8 weeks following termination of cyclosporine administration. The hyperplastic lesions may have resulted from the action of cyclosporine via the T-lymphocyte system. Conversely a direct action of this drug on epithelial cells may have stimulated proliferation and keratinization.

  5. Biomedical risks of multiple lung lavages in beagle dogs

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mauderly, J.L.; Slauson, D.O.; Halliwell, W.H.

    1976-01-01

    The biomedical risk of a series of 10 lung lavages was evaluated in 10 Beagle dogs. The dogs were divided into three groups: one group of six dogs was given 10 lung lavages over a 49-day period and sacrificed at 77 days of the study; the second group contained two dogs that were controls that were not treated, but sacrificed on day 77 of the study; and the third group contained two dogs that were control dogs that were sacrificed 56 days into the study. The dogs were evaluated by cardiopulmonary function tests, clinical studies, and studies of the tissues at sacrifice. No significant changes were detected in the cardiopulmonary function tests of the dogs in the study. Clinical studies revealed a very mild, transient reaction to some of the lavage procedures. The reaction was mainly mild, scattered, moist rales heard on auscultation of the chest and a slight rise in body temperature. A mild, scattered tissue reaction was also observed on histologic examination of selected lung tissues. The observed tissue reactions did not appear to be chronic, permanent or progressive. Results of this study indicate that multiple lung lavages carry little biomedical risk and that the primary risk is that associated with general anesthesia

  6. Heart sounds analysis via esophageal stethoscope system in beagles.

    Science.gov (United States)

    Park, Sang Hi; Shin, Young Duck; Bae, Jin Ho; Kwon, Eun Jung; Lee, Tae-Soo; Shin, Ji-Yun; Kim, Yeong-Cheol; Min, Gyeong-Deuk; Kim, Myoung hwan

    2013-10-01

    Esophageal stethoscope is less invasive and easy to handling. And it gives a lot of information. The purpose of this study is to investigate the correlation of blood pressure and heart sound as measured by esophageal stethoscope. Four male beagles weighing 10 to 12 kg were selected as experimental subjects. After general anesthesia, the esophageal stethoscope was inserted. After connecting the microphone, the heart sounds were visualized and recorded through a self-developed equipment and program. The amplitudes of S1 and S2 were monitored real-time to examine changes as the blood pressure increased and decreased. The relationship between the ratios of S1 to S2 (S1/S2) and changes in blood pressure due to ephedrine was evaluated. The same experiment was performed with different concentration of isoflurane. From S1 and S2 in the inotropics experiment, a high correlation appeared with change in blood pressure in S1. The relationship between S1/S2 and change in blood pressure showed a positive correlation in each experimental subject. In the volatile anesthetics experiment, the heart sounds decreased as MAC increased. Heart sounds were analyzed successfully with the esophageal stethoscope through the self-developed program and equipment. A proportional change in heart sounds was confirmed when blood pressure was changed using inotropics or volatile anesthetics. The esophageal stethoscope can achieve the closest proximity to the heart to hear sounds in a non-invasive manner.

  7. Toxicity of inhaled 91YCl3 in Beagle dogs. XVIII

    International Nuclear Information System (INIS)

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1984-01-01

    The metabolism, dosimetry, and biological effects of inhaled 91 YCl 3 were studied in Beagle dogs. Forty-two dogs with initial 91 Y body burdens from 14 to 1300 μCi/kg (0.52-48 MBq/kg) body weight and 12 control dogs were observed during their life spans. Four additional dogs with a mean initial body burden of 180 μCi 91 Y/kg (6.7 MBq/kg) body weight were placed in a sacrifice study. All 46 of the exposed dogs and all 12 of the control dogs have died. Dogs with the highest initial body burdens died with bone marrow damage and pancytopenia. Of the dogs dying of late-occurring effects, three died with nasal cavity carcinomas, three died with pulmonary carcinomas, and one died with hepatic hemangiosarcoma. These cancers all appeared to be related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases. 1 reference, 1 figure, 3 tables

  8. Toxicity of inhaled 91YCl3 in beagle dogs. X

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Benjamin, S.A.; Boecker, B.B.; McClellan, R.O.

    1976-01-01

    Studies on the metabolism, dosimetry, and effects of inhaled 91 YCl 3 in Beagle dogs are being continued to provide information that will aid in assessing the biological consequences of nuclear accidents in which 91 Y or other radionuclides that produce a similar radiation dose pattern may be released. Forty-two dogs with 91 Y initial body burdens from 64 to 1300 μCi/kg body weight were placed in four groups with mean lung burdens of 310, 180, 75 and 40 μCi/kg body weight. These dogs and 12 control dogs are being maintained for lifetime observation. An additional group of four dogs with a mean initial 91 Y body burden of 180 μCi/kg body weight were placed in a sacrifice study. Eleven dogs within the highest activity level groups died or were euthanized at 12 to 33 days after inhalation of 91 Y with changes related to severe bone marrow damage and associated pancytopenia. Two dogs died approximately 1 yr after 91 Y inhalation with convulsive seizures that were presumed to be unrelated to the 91 Y exposure. Five 91 Y-exposed dogs died or were euthanized due to neoplasms 2000 to 3341 days after exposure. Three dogs had nasal squamous cell carcinomas, one had a bronchioloalveolar carcinoma and another, a mast cell sarcoma. One dog died of renal failure 2660 days after exposure and one control dog died of empyema. Serial observations are continuing on all surviving dogs

  9. Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Chih-Hsien Chang

    2014-01-01

    Full Text Available The pharmacokinetics of N,N-bis(2-mercapatoethly-N',N'-diethylenediamine (BMEDA, a molecule that can form a chelate with rhenium-188 (188Re to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles’ plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences. In addition, the pharmacokinetics of BMEDA was seen to be non-linear because the increase of mean AUC0–t and AUC0–∞ values tend to be greater than dose proportional while the mean Vss and CL values of BMEDA appeared to be dose dependent. The information on the pharmacokinetics of BMEDA generated from this study will serve as a basis to design appropriate pharmacology and toxicology studies for future human use.

  10. Effect of diet and tylosin on chronic diarrhea in beagles.

    Science.gov (United States)

    Westermarck, Elias; Frias, Rafael; Skrzypczak, Teresa

    2005-01-01

    Seven beagles in a colony of dogs had chronic diarrhea for at least 30 days. The dogs were subsequently treated with tylosin 20 mg/kg BW q24h PO for 10 days. During the treatment period, the feces became firmer but remained loose. When the treatment was discontinued, the diarrhea reappeared in 3 weeks. The feces remained abnormally loose in all dogs treated with metronidazole, trimethoprim-sulfadiazine, or doxycycline and prednisone. The diet was then changed for 10 days from a highly digestible moist pet food to a dry food developed for normal adult dogs. The feces again became firmer, although still loose in some dogs. The period was then extended to 3 month, but the fecal consistency continued to fluctuate from ideal to diarrhea. The dogs were treated a 2nd time with tylosin 20 mg/kg BW q24h PO for 10 days. The feces then became significantly firmer and remained so throughout a 3-month follow-up. We conclude that the combination of diet and tylosin was more effective than either agent alone in control of chronic diarrhea.

  11. Toxicity of inhaled 91YCl3 in beagle dogs. VII

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Benjamin, S.A.; Boecker, B.B.; McClellan, R.O.

    1974-01-01

    Studies on the metabolism, dosimetry, and effects of inhaled 91 YCl 3 in Beagle dogs are being continued to provide information that will aid in assessing the biological consequences of nuclear accidents in which 91 Y or other radionuclides that produce a similar radiation dose pattern may be released. Forty-two dogs with 91 Y initial body burdens from 64 to 1300 μCi/kg body weight were placed in four groups with mean lung burdens of 310, 180, 75, and 40 μCi/kg body weight. These dogs and 12 control dogs are being maintained for lifetime observation. An additional group of four dogs with a mean initial 91 Y body burden of 180 μCi/kg body weight were placed in a sacrifice study. Eleven dogs within the highest activity level groups died or were euthanized at 12 to 33 days after inhalation of 91 Y with changes related to severe bone marrow damage and associated paycytopenia. Two dogs died approximately one year after 91 Y inhalation with convulsive seizures that were presumed to be unrelated to the 91 Y exposure. Four 91 Y-exposed dogs died or were euthanized due to neoplasms 2000 to 2560 days after exposure. Two dogs had squamous cell carcinomas involving the maxillary and nasal regions, one a bronchiolo-alveolar carcinoma of the lung and another, a mast cell sarcoma. One control dog died of empyema. Serial observations are continuing on all surviving dogs. (U.S.)

  12. Development of the canine tooth in the beagle

    International Nuclear Information System (INIS)

    Amimoto, A.; Iwamoto, S.; Hachimura, H.; Miyamoto, T.; Murata, T.; Taura, Y.; Nakama, S.; Hayashi, K.

    1993-01-01

    The growth of the crown and root in the canine tooth of beagle dogs were observed macroscopically and radiographically, and changes of occlusion with age were investigated. Completion of growth in the crown of the canine tooth was observed in both mandible and maxilla, and its eruption was accompanied by development of the dental root. The permanent canine erupted on the lingual side of deciduous canine in the mandible, and on the mesial side of the deciduous canine in the maxilla. Movement of the permanent canine to normal occlusal position(buccal direction in mandibular canine, and distal direction in maxillary canine)was followed by the loss of the deciduous canine. Coexistence of the permanent and deciduous canines occurred for about 2.4 weeks in the maxilla and about 1.4 weeks in the mandible, on average. Macroscopically, the growth of the permanent canine was completed by 33 weeks of age in the mandible and about 34 weeks of age in the maxilla. The mature root of the permanent canine was recognized radiographically at about 43 weeks of age in the mandible and 47 weeks of age in the maxilla

  13. Dose-effect studies with inhaled plutonium oxide in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Case, A.C.; Catt, D.L.

    1980-01-01

    Beagle dogs given a single exposure to 239 PuO 2 and 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary-fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi; one of these dogs had a pulmonary tumor. Seventeen additional dogs, with body burdens of 0.2 to 1.8 μCi, died due to pulmonary neoplasia 3 to 8 yr after exposure. Ten of the dogs exposed to 238 Pu have died during the first 5 1/2 yr postexposure due to bone and/or lung tumors; the body burden at death ranged from 1.5 to 10 μCi. Lymphopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2 , occurring 0.5 to 2 yr after deposition of >80 nCi plutonium in the lungs

  14. Dose-effect studies with inhaled plutonium oxide in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Busch, R.H.; Case, A.C.

    1979-01-01

    Beagle dogs given a single exposure to 239 PuO 2 and 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs that dies of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi; one of these dogs had a pulmonary tumor. Eleven additional dogs with body burdens of 0.6 to 1.8 μCi died due to pulmonary neoplasia 3 to 7 yr after exposure. Four of the dogs exposed to 238 Pu have died during the first 4 1/2 yr postexposure due to bone and/or lung tumors; the body burden at death ranged from 6 to 10 μCi. Lymphopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2 , occurring 0.5 to 2 yr after deposition of greater than or equal to 80 nCi plutonium in the lungs

  15. Increased myocardial infarct size because of reduced coronary collateral blood flow in beagles

    International Nuclear Information System (INIS)

    Uemura, N.; Knight, D.R.; Shen, Y.T.; Nejima, J.; Cohen, M.V.; Thomas, J.X. Jr.; Vatner, S.F.

    1989-01-01

    Effects of permanent left circumflex coronary artery occlusion (CAO) were examined in conscious purebred beagles and mongrel dogs, instrumented with miniature left ventricular (LV) pressure gauges, wall thickness gauges in the ischemic zone, catheters in left atrium and aorta, and snares around the left circumflex coronary artery. Blood flow was measured using the radioactive microsphere technique before CAO and at 5 min, 1, 3, and 24 h after CAO. Although CAO reduced myocardial blood flow similarly in beagles and mongrels, significantly less (P less than 0.05) recovery of myocardial blood flow was observed over the following 24-h period in beagles. Infarct size, as determined by triphenyltetrazolium chloride and expressed as percentage of area at risk, was larger (P less than 0.05) in beagles (62.0 ± 5.1%) than mongrels (42.5 ± 4.2%). Thus beagles do not tolerate ischemia as well as mongrel dogs and possess fewer functional coronary collaterals resulting in larger infarcts after CAO

  16. Quantification of brown dog tick repellents, 2-hexanone and benzaldehyde, and release from tick-resistant beagles, Canis lupus familiaris

    Science.gov (United States)

    We have recently shown that repellency of the tick Rhipicephalus sanguineus sensu lato by the tick resistant dog breed Beagle is mediated by volatile organic compounds 2-hexanone and benzaldehyde present in Beagle dog odour. Ectoparasite location on animal hosts is affected by variation in odour com...

  17. Radium retention in mature beagles injected at 5 years of age

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Bruenger, F.W.; Jones, C.W.; Taylor, G.N.; Mays, C.W.

    1982-01-01

    Retention of 226 Ra was substantially lower in mature beagles injected at 5 years of age compared to corresponding values for 1 1/2-year-old young adult beagles. As with young adults, average retention in mature dogs given about 10 μCi/kg exceeded that of mature dogs given 4 μCi/kg or less. Measured 222 Rn/ 226 Ra ratios in bone were similar in mature and young adults. About 66% of the injected radium was excreted by mature dogs during the first 3 weeks, about 2/3 of the total excretion appearing in the feces. Distribution of 226 Ra within the skeleton was similar in mature and young adult beagles

  18. The early pathology and image study of percutaneous laser disc decompression in beagles

    International Nuclear Information System (INIS)

    Liao Shunming; Ding Shiyi; You Jian; Mu Wei; Hu Jun; Li Qiang

    2007-01-01

    Objective: To explore the cause, influencing factor and possible solving method of transient adverse reactions during the operation. Methods: Sixteen healthy beagles were undergone virtual PLDD. The changes of vertebral discs and the surrounding tissues were observed by high resolution CT and MRI at different periods after the operation, and the same investigation procedure was carried out after the sacrifice of beagles. Results: The beagles of the conventional vaporization group occasionally had limb tic and whining in the operations. Pieces of necrosis and edema could be found in the tissues of intervertebral foramen at the paracentetic side. The histological changes in the negative pressure suction group were less than those in the conventional group. Conclusion: The reversible damages of the surrounding tissuses were observed in the conventional group and continuing negative pressure suction during the operations can prevent the damages to the surrounding tissues, all of the changes could be clearly displayed by CT and MRI scan. (authors)

  19. Beagle puppy model of intraventricular hemorrhage: ethamsylate studies.

    Science.gov (United States)

    Ment, L R; Stewart, W B; Duncan, C C

    1984-02-01

    Intraventricular hemorrhage (IVH) remains a major problem of preterm neonates, and ethamsylate, an inhibitor of specific prostaglandin-synthetic enzymes has been demonstrated to prevent IVH in these patients. We have examined the effects of ethamsylate on newborn beagle pups who were, by randomized computerized design, assigned to four cells consisting of (a) either ethamsylate or saline pretreatment and (b) either insulted or not insulted with hemorrhagic hypovolemia/volume re-expansion. Prostaglandin levels were obtained prior to and thirty minutes following administration of the solutions and 14C iodoantipyrine autoradiography was performed for cerebral blood flow (CBF) determinations. Ethamsylate produced a significant decrease in the incidence of IVH in this model (p less than 0.05). Following drug administration, ethamsylate-pretreated pups had significant declines in thromboxane B2 and 6-keto PGF1 alpha levels, the major breakdown products of thromboxane A2 and prostacyclin. Although ethamsylate significantly lowered baseline CBF in all brain regions examined in insulted and non-insulted pups (p less than 0.05), in the drug-treated group it did not prevent the changes seen in CBF to the germinal matrix region which were detected in the saline-pretreated pups. Nor did it significantly blunt the blood pressure changes in response to the hemorrhagic hypovolemia/volume re-expansion insult found in the latter group of animals. In addition, only ethamsylate pretreated pups had marked hypotensive responses to the reperfusion phase of the insult. Although the diminution of baseline CBF may contribute to the prevention of neonatal IVH which this drug has been demonstrated to exhibit, ethamsylate may also act as a capillary stabilizing agent.

  20. Transsphenoidal hypophysectomy in beagle dogs: evaluation of a microsurgical technique

    Energy Technology Data Exchange (ETDEWEB)

    Meij, B. P. [Utrecht University, Utrecht (Netherlands); Voorhout, G.; Ingh, T.S.G.A.M. van den; Hazewinkel, H. A.W.; Verlaat, J.W. van ' t

    1997-07-15

    Objective-Assessment of a microsurgical technique for transsphenoidalhypophysectomy in dogs. Study Design-Prospective study using physicalexamination, pituitary function testing, computed tomography (CT), and histological examination at autopsy. Animals or Sample Population-Eight laboratory beagle dogs. Methods-Pituitary function was assessed before and at 10 weeks after hypophysectomy by combined administration of four releasing hormones (anterior pituitary), administration of haloperidol (pars intermedia), and infusion of hypertonic saline (posterior pituitary). Results-CT imaging enabled accurate preoperative localization of the pituitary. Appropriate positioning and surgical technique facilitated exposure of the pituitary and its extraction without hemorrhage. Postoperative recovery was generally uncomplicated. None of the eight dogs had somatotropic. gonadotropic, lactotropic, melanotropic, or posterior pituitary responses to stimulation at 10 weeks after hypophysectomy. Four dogs (ACTH nonresponders) also had no corticotropicresponse and four (ACTH responders) bad small but significant responses in the combined anterior pituitary function test. Adrenocortical atrophy was more pronounced in the ACTH nonresponders than in the responders. No residual pituitary tissue was found along the ventral hypothalamic diencephalon but nests of pituitary cells were found embedded infibrous tissue in the sella turcica. Conclusions-The surgical technique proved to be safe and effective. Microscopic nests of pituitary cells in the sella turcica may be responsible for residual corticotropic response to hypophysiotropic stimulation after hypophysectomy. Clinical Relevance-The surgical technique may be used in the treatment of dogs with pituitary-dependent hyperadrenocorticism. The corticotropic response is the most sensitive criterion in assessing completeness of hypophysectomy in dogs. (C) Copyright 1997 by The American College of Veterinary Surgeons.

  1. Transsphenoidal hypophysectomy in beagle dogs: evaluation of a microsurgical technique

    International Nuclear Information System (INIS)

    Meij, B.P.; Voorhout, G.; Ingh, T.S.G.A.M. van den; Hazewinkel, H.A.W.; Verlaat, J.W. van 't

    1997-01-01

    Objective-Assessment of a microsurgical technique for transsphenoidalhypophysectomy in dogs. Study Design-Prospective study using physicalexamination, pituitary function testing, computed tomography (CT), and histological examination at autopsy. Animals or Sample Population-Eight laboratory beagle dogs. Methods-Pituitary function was assessed before and at 10 weeks after hypophysectomy by combined administration of four releasing hormones (anterior pituitary), administration of haloperidol (pars intermedia), and infusion of hypertonic saline (posterior pituitary). Results-CT imaging enabled accurate preoperative localization of the pituitary. Appropriate positioning and surgical technique facilitated exposure of the pituitary and its extraction without hemorrhage. Postoperative recovery was generally uncomplicated. None of the eight dogs had somatotropic. gonadotropic, lactotropic, melanotropic, or posterior pituitary responses to stimulation at 10 weeks after hypophysectomy. Four dogs (ACTH nonresponders) also had no corticotropicresponse and four (ACTH responders) bad small but significant responses in the combined anterior pituitary function test. Adrenocortical atrophy was more pronounced in the ACTH nonresponders than in the responders. No residual pituitary tissue was found along the ventral hypothalamic diencephalon but nests of pituitary cells were found embedded infibrous tissue in the sella turcica. Conclusions-The surgical technique proved to be safe and effective. Microscopic nests of pituitary cells in the sella turcica may be responsible for residual corticotropic response to hypophysiotropic stimulation after hypophysectomy. Clinical Relevance-The surgical technique may be used in the treatment of dogs with pituitary-dependent hyperadrenocorticism. The corticotropic response is the most sensitive criterion in assessing completeness of hypophysectomy in dogs. (C) Copyright 1997 by The American College of Veterinary Surgeons

  2. Toxicity of inhaled 91YCl3 in beagle dogs. XI

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Rebar, A.H.; Benjamin, S.A.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1977-01-01

    Studies on the metabolism, dosimetry and effects of inhaled 91 YCl 3 in Beagle dogs are being continued to provide information that will aid in assessing the biological consequences of nuclear accidents in which 91 Y or other radionuclides that produce a similar radiation dose pattern may be released. Forty-two dogs with 91 Y initial body burdens from 64 to 1300 μCi/kg body weight were placed in four groups with mean lung burdens of 310, 180, 75 and 40 μCi/kg body weight. These dogs and 12 control dogs are being maintained for lifetime observation. An additional group of four dogs with a mean initial 91 Y body burden of 180 μCi/kg body weight were placed in a sacrifice study. Twenty-one of the exposed dogs have died and two of the control dogs have died. Eleven dogs within the highest activity level groups died or were euthanized at 12 to 33 days after inhalation of 91 Y with changes related to severe bone marrow damage and associated pancytopenia. Two dogs died approximately one year after 91 Y inhalation with convulsive seizures that were presumed to be unrelated to the 91 Y exposure. Seven 91 Y-exposed dogs died or were euthanized due to neoplasms 2000 to 3341 days after exposure. Three dogs had nasal squamous cell carcinomas, one had a bronchioloalveolar carcinoma, one, a mast cell sarcoma, one a mammary adenocarcinoma and one with a malignant lymphoma. One dog died of renal failure 2660 days after exposure, one control dog died of empyema and another control dog died with a mammary adenocarcinoma. Serial observations are continuing on all surviving dogs

  3. Absorption and pharmacokinetics of grapefruit flavanones in beagles.

    Science.gov (United States)

    Mata-Bilbao, Maria de Lourdes; Andrés-Lacueva, Cristina; Roura, Elena; Jáuregui, Olga; Escribano, Elvira; Torre, Celina; Lamuela-Raventós, Rosa Maria

    2007-07-01

    The present study evaluated the pharmacokinetics of three different grapefruit flavanone forms in dog plasma and demonstrated their absorption after an oral intake of a grapefruit extract; pharmacokinetic parameters of these forms were also determined. Ten healthy beagles were administered 70 mg citrus flavonoids as a grapefruit extract contained in capsules, while two additional dogs were used as controls and given an excipient. The grapefruit flavanone naringin, along with its metabolites naringenin and naringenin glucuronide, was detected in dog plasma. Blood samples were collected between 0 and 24 h after administration of the extract. Naringin reached its maximun plasma concentration at around 80 min, whereas naringenin and naringenin glucuronide reached their maximun plasma concentrations at around 20 and 30 min, respectively. Maximum plasma concentrations of naringin, naringenin and naringenin glucuronide (medians and ranges) were 0.24 (0.05-2.08), 0.021 (0.001-0.3) and 0.09 (0.034-0.12) micromol/l, respectively. The areas under the curves were 23.16 l (14.04-70.62) min x micromol/for nariningin, 1.78 (0.09-4.95) min x micromol/l for naringenin and 22.5 (2.74-99.23) min x micromol/l for naringenin glucuronide. The median and range values for mean residence time were 3.3 (1.5-9.3), 2.8 (0.8-11.2) and 8.0 (2.3-13.1) h for naringin, naringenin and naringenin glucuronide, respectively. The results of the present study demonstrate the absorption of grapefruit flavanones via the presence of their metabolites in plasma, thus making an important contribution to the field since the biological activities ascribed to these compounds rely on their specific forms of absorption.

  4. Toxicity of inhaled 91YCl3 in Beagle dogs. XII

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Rebar, A.H.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1978-01-01

    Studies on the metabolism, dosimetry and effects of inhaled 91 YCl 3 in Beagle dogs are being continued to provide information that will aid in assessing the biological consequences of nuclear accidents in which 91 Y or other radionuclides that produce a similar radiation dose pattern may be released. Forty-two dogs with 91 Y initial body burdens from 64 to 1300 μCi/kg body weight was placed in four groups with mean lung burdens of 310, 180, 75 and 40 μCi/kg body weight. These dogs and 12 control dogs are being maintained for lifetime observation. An additional group of four dogs with a mean initial 91 Y body burden of 180 μCi/kg body weight was placed in a sacrifice study. Twenty-six of the exposed dogs and four of the control dogs have died. Eleven dogs within the highest activity level groups died or were euthanized at 12 to 33 days after inhalation of 91 Y with changes related to severe bone marrow damage and associated pancytopenia. Two dogs died approximately one year after 91 Y inhalation with convulsive seizures that were presumed to be unrelated to the 91 Y exposure. Nine 91 Y-exposed dogs died or were euthanized due to neoplasms 2012 to 4115 days after exposure. Three dogs had nasal squamous cell carcinomas, one had a bronchioloalveolar carcinoma, one a mast cell sarcoma, one a mammary adenocarcinoma, one a malignant lymphoma, one a melanosarcoma in the mouth and one heart base tumor. Two dogs died of renal failure 2663 and 4086 days after exposure. One dog died with autoimmune hemolytic anemia 3888 days after exposure and one died with congestive heart failure 4042 days after inhalation exposure. One control dog died of empyema, another control dog died with a mammary adenocarcinoma, one died with congestive heart failure and one with malabsorption syndrome. Serial observations are continuing on all surviving dogs

  5. Toxicity of 239Pu and 226Ra in young adult beagles: risk estimate in man

    International Nuclear Information System (INIS)

    Miller, S.C.

    1985-01-01

    The overall objective of this research program is to predict the risk to humans following exposure to 239 Pu. The beagle was originally selected for this program because it is relatively long-lived and has skeletal functions and structure analogous to young adults humans, simulating that of a young adult radium dial painter or occupationally exposed person. Young adult (17 month-old) beagles from the moderately inbred colony at the University of Utah were administered one intravenous injection of 239 Pu (0.0007-2.88 μCi/kg in 238 dogs) or 226 Ra (0.007-10.4 μCi/kg in 119 dogs), and compared to appropriate age-matched control beagles. All beagles have been and are being observed clinically throughout their expected 12 to 15 year post-injection lifespan. A thorough clinical and post-mortem survey is conducted to determine causes of death or lesions at death. The clinical findings are being encoded using SNOMED terminology and entered into a computerized database. All beagles in the 226 Ra study are dead and the data are being analyzed and published. The shape of the curve for dose vs. bone tumor incidence is highly linear up to average skeletal doses of 2200 rads. In higher dose groups, the time to tumor appearance is decreased and skeletal tumors occur in almost all animals. The 226 Ra response is being compared with the 239 Pu response in beagles. This toxicity ratio will allow use of the bone tumor response in the radium dial painters to predict the toxicity of plutonium for bone tumor induction in man

  6. Real-time implementation of logo detection on open source BeagleBoard

    Science.gov (United States)

    George, M.; Kehtarnavaz, N.; Estevez, L.

    2011-03-01

    This paper presents the real-time implementation of our previously developed logo detection and tracking algorithm on the open source BeagleBoard mobile platform. This platform has an OMAP processor that incorporates an ARM Cortex processor. The algorithm combines Scale Invariant Feature Transform (SIFT) with k-means clustering, online color calibration and moment invariants to robustly detect and track logos in video. Various optimization steps that are carried out to allow the real-time execution of the algorithm on BeagleBoard are discussed. The results obtained are compared to the PC real-time implementation results.

  7. Old beagle dogs have lower faecal concentrations of some fermentation products and lower peripheral lymphocyte counts than young adult beagles.

    Science.gov (United States)

    Gomes, Márcia de Oliveira Sampaio; Beraldo, Mariana Casteleti; Putarov, Thaila Cristina; Brunetto, Márcio Antônio; Zaine, Leandro; Glória, Maria Beatriz Abreu; Carciofi, Aulus Cavalieri

    2011-10-01

    The effects of age on microbiota composition, gut fermentation end-product formation and peripheral lymphocyte numbers were compared between old and young adult Beagle dogs fed four kibble diets differing in yeast cell wall contents. The experiment had a double 4 × 4 Latin square design, one with four mature dogs (4 years old) and the other with four old dogs (10 years old), with four replicates (diets) per dog. In each period a 15 d adaptation period preceded a 5 d total collection of faeces for the digestibility trial. On day 21, fresh faecal samples were collected for the determination of bacterial enumeration, pH, biogenic amine and short-chain fatty acid. Flow cytometry was used for immunophenotypic evaluation. Dogs were fed four kibble diets with similar composition with 0, 0.15, 0.30 and 0.45 % of yeast cell wall (as-fed), respectively. Data were evaluated using general linear models of Statistical Analysis Systems statistical software (P 0.15). Faecal concentrations of butyrate, histamine, agmatine and spermine were lower (P ≤ 0.05) and faecal pH was higher (P = 0.03) in older dogs than in mature adult dogs, suggesting an alteration in bacterial metabolic activity, or in the rate of intestinal absorption of these compounds. Concentrations of T-lymphocytes, T-cytotoxic lymphocytes and B-lymphocytes were also lower (P ≤ 0.01) in older dogs than in mature adult dogs. The study confirmed alterations in peripheral lymphocytes and revealed a reduced concentration of some fermentation end products in the colon of old dogs.

  8. Effects of lifetime ingestion of 90Sr in beagle dogs

    International Nuclear Information System (INIS)

    Book, S.A.; Spangler, W.L.; Swartz, L.A.

    1982-01-01

    To investigate the effects of lifetime 90 Sr ingestion, fifteen beagle dogs were fed the equivalent of 1.3, 4.0, and 12.0 μCi 90 Sr. Exposures prior to weaning were made by maternal administration of one of the same 90 Sr levels, begining at 21 days of gestation. Median survival was 12.5 years for the 1.3 μCi/day group, 6.5 years for the 4 μCi/day group, and 5.2 years of the 12 μCi/day group, compared to unirradiated control values of 14.5 to 15 years. The normal life span of more than half of the 1.3 μCi/day group is remarkable, considering they ingested 5900 to 7500 μCi 90 Sr during their lifetimes. One of seven 1.3 μCi/day dogs died of mycloproliferative syndrome (MPS), while one of four 4 μCi/day and one of four 12 μCi/day dogs died from MPS. In addition, another 12 μCi/day dog died of osteosarcoma and two others in the same group showed skeletal changes related to 90 Sr exposure. Other deaths were as could be expected in normal canine populations. Lifetime skeletal doses, determined by periodic whole-body counting, were 1990-3750, 1880-9230, and 6360-14,680 rad for the 1.3, 4, and 12 μCi/day groups, respectively. Comparison of these values with those from the large 90 Sr toxicity study at Davis in which 90 Sr feeding ended at 18 months of age indicates similar average skeletal doses from the two types of feeding regimens. The similarity of the skeletal doses may relate to the inability of 90 Sr to be incorporated to any great extent into a mature skeleton that no longer has the high calcium turnover associated with early life. As a result, deaths from lifetime 90 Sr ingestion appeared no earlier than when 90 Sr ingestion ended in early adulthood

  9. Clotting mechanism in beagles irradiated by 4.5 Gy γ-rays

    International Nuclear Information System (INIS)

    Zhao Zhenhu; Wang Ning; Li Ming; Xing Shuang; Huang Haixiao; Ou Hongling; Xiong Guolin; Zhao Yanfang; Xie Ling; Wang Jinxiang; Miao Jingcheng; Zhu Nankang; Zhang Xueguang; Luo Qingliang; Cong Yuwen

    2010-01-01

    Objective: To explore the clotting mechanism in beagles irradiated by 4.5 Gy γ-rays after treatment with supportive care, or supportive care and combined cytokines. Methods: Sixteen beagles were divided into irradiation control group, Supportive care group and combined cytokines treatment group. Platelet aggregation test, thrombelastography (TEG) and the time measurement were analyzed in vitro. Results: In irradiation group and supportive care group, the platelet aggregation rates in beagles were decreased markedly and the k value of TEG was increased 7 d post-irradiation, while those indexes in combined cytokines treatment group changed little. At 14 d post-irradiation, each parameter of TEG in irradiated group changed obviously. The values of r, k, r + k and M were elevated significantly, clotting time and the maximum coagulation time of thrombus delayed, the Ma value was decreased markedly, and the maximum elasticity amplitude of thrombus was diminished. All parameters in combined cytokines treatment group were better than those in supportive care group. The thrombin time was prolonged obviously in irradiated group 14 d post-irradiation, while the thrombin time was the longest at 2-3 weeks post irradiation in supportive care group and combined cytokines treatment group (P>0.05). Conclusions: Cytokines could improve the platelet aggregation and the blood clotting functions of beagles suffering from acute radiation sickness. (authors)

  10. The Voyage of the Beagle: Field Work Lessons from Charles Darwin.

    Science.gov (United States)

    Smith, Louis M.

    1987-01-01

    Analyzes Charles Darwin's letters to his family during his voyage on H.M.S. Beagle. Relates the information to the development of Darwin's professional identity and the degree to which the concepts, field methods, and research methods revealed in Darwin's personal correspondence are useful to students of educational administration. (MD)

  11. Web-Beagle: a web server for the alignment of RNA secondary structures.

    Science.gov (United States)

    Mattei, Eugenio; Pietrosanto, Marco; Ferrè, Fabrizio; Helmer-Citterich, Manuela

    2015-07-01

    Web-Beagle (http://beagle.bio.uniroma2.it) is a web server for the pairwise global or local alignment of RNA secondary structures. The server exploits a new encoding for RNA secondary structure and a substitution matrix of RNA structural elements to perform RNA structural alignments. The web server allows the user to compute up to 10 000 alignments in a single run, taking as input sets of RNA sequences and structures or primary sequences alone. In the latter case, the server computes the secondary structure prediction for the RNAs on-the-fly using RNAfold (free energy minimization). The user can also compare a set of input RNAs to one of five pre-compiled RNA datasets including lncRNAs and 3' UTRs. All types of comparison produce in output the pairwise alignments along with structural similarity and statistical significance measures for each resulting alignment. A graphical color-coded representation of the alignments allows the user to easily identify structural similarities between RNAs. Web-Beagle can be used for finding structurally related regions in two or more RNAs, for the identification of homologous regions or for functional annotation. Benchmark tests show that Web-Beagle has lower computational complexity, running time and better performances than other available methods. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Differentiation of peripheral lymphocyte population in Pu-exposed beagle dogs

    International Nuclear Information System (INIS)

    Morris, J.E.

    1977-01-01

    The percentage of peripheral lymphocytes binding fluorescent-labeled anticanine antibodies was measured in plutonium-oxide-exposed and unexposed beagle dogs. With this assay system, there was a significant decrease in the percentage of lymphocytes binding the labeled antibody in exposed animals compared to control animals

  13. Principal disease or cause of death in nonsacrifice beagles receiving gamma radiation during development

    International Nuclear Information System (INIS)

    Thomassen, R.W.; Hargis, A.M.; Benjamin, S.A.

    1978-01-01

    Epilepsy, hypothyroidism, cor pulmonale, and neoplasia are the leading causes of death of Segment III beagles, accounting for 90 to 208 fatalities from 1968 through 1977. Of the four, only neoplasia appears to be related to radiation history. Fifteen of 16 dogs dying of neoplasia were irradiated. Nine of these were exposed at either 55 days post coitus (dpc) or 2 days post partum

  14. Principal disease or cause of death in nonsacrifice Segment III beagles receiving gamma radiation during development

    International Nuclear Information System (INIS)

    Bishop, L.; Kitchen, D.N.; Benjamin, S.A.; Stephens, L.C.; Hargis, A.M.; Lovering, S.L.; Lee, A.C.; Brewster, R.D.; Brooks, R.K.

    1981-01-01

    Epilepsy, hypothyroidism and neoplasia rank as the three leading causes of death in nonsacrifice Segment III beagles. Chronic renal disease is a fourth major disease entity occurring with increasing frequency in the experimental population. These four major diseases accounted for 57% of the deaths in 1979. Of the four leading causes of death, neoplasia alone can be related to the history of radiation exposure

  15. Clinical status and philosophy of clinical care of radionuclide-treated beagles

    International Nuclear Information System (INIS)

    MacMillan, K.; Holbrook, C.; White, R.; Chrisp, C.

    1975-01-01

    A manual for therapy of beagles is reviewed. The following protocol is outlined and described: antibiotic therapy, chemotherapy for neoplasms, hormone therapy, nutritional therapy, radiation therapy, steroid therapy, and miscellaneous treatments. The manual also includes sections on diagnosis and discussions of individual cases. Tables summarizing clinical cases seen during 1974 are presented

  16. Enantioselective HPLC determination of oxiracetam enantiomers and application to a pharmacokinetic study in beagle dogs.

    Science.gov (United States)

    Zhang, Qiuyang; Yang, Wei; Zhang, Qing; Yang, Yue; Li, Junxiu; Lu, Yang; Zheng, Yi; He, Jiake; Zhao, Di; Chen, Xijing

    2015-07-01

    An enantioselective high-performance liquid chromatography method was developed and validated for the determination of oxiracetam enantiomers, a cognition and memory enhancer, in beagle dog plasma. The plasma samples were prepared by methanol extraction from 200μL plasma, and then the baseline resolution was achieved on a Chiralpak ID column (250mm×4.6mm, 5μm) with mobile phase of hexane-ethanol-trifluoroacetic acid (78:22:0.1, v/v/v) at flow rate of 1.0mL/min. The column elute was monitored using ultraviolet detection at 214nm. The method was linear over concentration range 0.50-100μg/mL for both enantiomers. The relative standard deviation values for intra- and inter-day precision were 0.78-13.61 and 0.74-8.92% for (R)- and (S)-oxiracetam, respectively. The relative error values of accuracy ranged from -4.74 to 10.48% for (R)-oxiracetam and from -0.19 to 11.48% for (S)-oxiracetam. The method was successfully applied to a pharmacokinetic study of individual enantiomer and racemic oxiracetam in beagle dogs after oral administration. The disposition of the two enantiomers was not stereoselective and chiral inversion was not observed in beagle dogs. The pharmacokinetic profiles of (S)-oxiracetam were similar with racemic oxiracetam in beagle dogs. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Principal disease or cause of death in nonsacrifice Segment III beagles receiving gamma radiation during development

    International Nuclear Information System (INIS)

    Hargis, A.M.; Lovering, S.L.; Benjamin, S.A.; Thomassen, R.W.; Lee, A.C.; Brewster, R.D.; Brooks, R.K.

    1979-01-01

    Epilepsy, hypothyroidism, neoplasia, and cor pulmonale remain the leading causes of death in Segment III beagles. This past year neoplasia became the third leading cause of death with the addition of 10 animals in this category. Of the four leading causes of death, neoplasia alone can be related to history of irradiation

  18. Late effects of inhaled 238PuO2 in beagles

    International Nuclear Information System (INIS)

    Park, J.F.; Case, A.C.; Catt, D.L.; Hackett, P.L.; Lund, J.E.; Powers, G.J.; Ragan, H.A.; Watson, C.R.

    1976-01-01

    Osteosarcomas were the primary cause of death in beagle dogs 4 to 8 years after inhalation of 238 PuO 2 . The plutonium body burden at death ranged from 0.4 to 2.6 μCi with 32 to 55 percent of the plutonium in the skeleton. Pulmonary neoplasia was observed in three of the bone-tumor-bearing dogs

  19. Lung, liver and bone cancer mortality after plutonium exposure in beagle dogs and nuclear workers.

    Science.gov (United States)

    Wilson, Dulaney A; Mohr, Lawrence C; Frey, G Donald; Lackland, Daniel; Hoel, David G

    2010-01-01

    The Mayak Production Association (MPA) worker registry has shown evidence of plutonium-induced health effects. Workers were potentially exposed to plutonium nitrate [(239)Pu(NO(3))(4)] and plutonium dioxide ((239)PuO(2)). Studies of plutonium-induced health effects in animal models can complement human studies by providing more specific data than is possible in human observational studies. Lung, liver, and bone cancer mortality rate ratios in the MPA worker cohort were compared to those seen in beagle dogs, and models of the excess relative risk of lung, liver, and bone cancer mortality from the MPA worker cohort were applied to data from life-span studies of beagle dogs. The lung cancer mortality rate ratios in beagle dogs are similar to those seen in the MPA worker cohort. At cumulative doses less than 3 Gy, the liver cancer mortality rate ratios in the MPA worker cohort are statistically similar to those in beagle dogs. Bone cancer mortality only occurred in MPA workers with doses over 10 Gy. In dogs given (239)Pu, the adjusted excess relative risk of lung cancer mortality per Gy was 1.32 (95% CI 0.56-3.22). The liver cancer mortality adjusted excess relative risk per Gy was 55.3 (95% CI 23.0-133.1). The adjusted excess relative risk of bone cancer mortality per Gy(2) was 1,482 (95% CI 566.0-5686). Models of lung cancer mortality based on MPA worker data with additional covariates adequately described the beagle dog data, while the liver and bone cancer models were less successful.

  20. Age and dosage-level dependence of radium retention in beagles

    International Nuclear Information System (INIS)

    Parks, N.J.; Pool, R.R.; Williams, J.R.; Wolf, H.G.

    1978-01-01

    Radium retention was measured over the lifespan of 46 beagles exposed by eight semimonthly injections at 60 to 160, 120 to 220, or 435 to 535 days of age. Injection dosage levels ranged from 0.37 to 10 μCi of 226 Ra/kg. The fractional retention of each animal is described in terms of a modified power function, R = [(t + d)/d] - /sup b/. Young adult beagles (approximately equal to 10 kg) injected at a mean age (A) of 485 days with 226 Ra at dosage levels of 10, 3.3, 1.11, and 0.37 μCi/kg had mean values for d and b of [0.897; 0.187], [2.015; 0.206], [2.778; 0.257], and [3.894; 0.274], respectively. Juvenile beagles injected with 10 μCi/kg at A = 110 days (average weight approximately equal to 6 kg) and at A = 170 days (average weight approximately equal to 10 kg) had mean values for d and b of [137; 0.277] and [5.53; 0.086], respectively. The d values are geometric means and the units are days; b values are arithmetic means. The formula for deriving the age-dependent retention function for dogs is given. The beagle results were correlated with human data in terms of age-to-equivalent fraction of adult body calcium content and were used to construct a similar age-dependent retention function for chronically exposed people. The correlation of age-dependent retention functions for beagles and humans is used to estimate scaling factors between the two species for the fraction of injected dosage associated with bone for various ages of exposure

  1. Skeletal retention of 239Pu and 226Ra in beagles injected at ages ranging from 2 days to 5 years

    International Nuclear Information System (INIS)

    Bruenger, F.W.; Stevens, W.; Atherton, D.R.; Jee, W.S.S.; Smith, J.M.

    1982-01-01

    The age at exposure significantly affects the retention and distribution of 226 Ra and 239 Pu, both of which deposit in the skeleton, although in different patterns. Beagles aged 2 days (neonates), 90 days (juveniles), 18 months (young adults) or 5 years (old), received a single injection of one of these nuclides at a dosage level at which no significant acute effects have been observed. Nuclide concentrations in plasma and the skeleton were determined and retention equations were calculated. Initial deposition and retention of the two nuclides were age-dependent, but differences between the growing and young adult beagles were much greater than between the young adult and old beagles

  2. 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

  3. Effects of Sweet Bee Venom on cardiovascular system in the conscious telemetered Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Lim Chung-San

    2010-09-01

    Full Text Available Objectives:This study was performed to analyse the effects of Sweet Bee Venom(Sweet BV on cardiovascular system in the conscious telemetered Beagle Dogs. Methods:All experiments were conducted at Biotoxtech Company, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP. Male Beagle dogs of 13-19 months old were chosen for the pilot study and surgical implantation was performed for conscious telemetered Beagle dogs. And after confirming condition of Beagle dogs was stable, Sweet BV was administered 4 times(first: 0.0 ㎎/㎏, 2nd: 0.01 ㎎/㎏, 3rd: 0.1 ㎎/㎏, and forth: 0.5 ㎎/㎏, one time/week in thigh muscle of Beagle dogs. And blood pressure, heart rate, electrocardiography and clinical responses were measured. Equal amount of normal saline to the Sweet BV experiment groups was administered to the control group. 1. In the analysis of body weight and taking amount, Beagle dogs did not show significant changes. 2. In the clinical observation, responses of pain and edema were showed depend on dosage of Sweet BV. 3. In the analysis of blood pressure, treatment with Sweet BV did not show significant changes in the dosage of 0.01 ㎎/㎏, but in the dosage of 0.1 ㎎/㎏ and 0.5 ㎎/㎏, treatment with Sweet BV increased blood pressure significantly. 4. In the analysis of heart rate, treatment of Sweet BV did not show significant changes in all dosage and period. 5. In the analysis of electrocardiography, treatment of Sweet BV was not showed significant changes in all dosage and period. Conclusion:Above findings suggest that Sweet BV is relatively safe treatment in the cardiovascular system. But in the using of over dosage, Sweet BV may the cause of increasing blood pressure. Further studies on the subject should be conducted to yield more concrete evidences.

  4. Establishing an elite sport: the men and hounds of the National Beagle Club of America, 1890-1940

    OpenAIRE

    Garneau, Christine Elise

    2012-01-01

    This thesis argues that the National Beagle Club of America defined and regulated beagling as a way for upper class men to demonstrate their social status in a sporting context. As members of the American elite, the club’s leadership used their personal resources and social access to shape the sport for their own purposes. The club’s governing documents and regular events reinforced ideas about exclusivity, performance, and wealth. The breed standard formalized the dogs’ position as animal...

  5. Some similarities of radium and plutonium toxicity in the beagle and man

    International Nuclear Information System (INIS)

    Taylor, G.N.; Jee, W.S.S.; Mays, C.W.

    1976-01-01

    The value of many toxicity studies, involving various experimental animals, is contingent on how reliably the data can be related to man. An equation has been proposed for extrapolating the Pu syndrome from dog studies to man. It employs the extensive human radium experience and a plutonium-radium toxicity ratio in the dog. The validity of this method is contingent on similar target tissues for both Pu and Ra and approximately equal RBE's for Pu relative to Ra in both man and the dog. Thus, although the radiosensitivity might be significantly different, the endpoints within a given tissue in man and the animal model must necessarily be comparative. The degree of parallelism in the radium-induced syndromes of man and the beagle are examined in order to assess the practicability of estimating Pu risk in man through use of a Pu-Ra toxicity ratio in the beagles

  6. Mechanical and morphological evaluation of age-related changes in the Beagle spine

    International Nuclear Information System (INIS)

    Gillett, N.A.; Gerlach, R.; Cassidy, J.; Brown, S.

    1986-01-01

    Age-related changes were evaluated in the spines of Beagle dogs by biomechanical testing, radiology and pathology. Thirty age-matched healthy Beagle dogs were divided into five groups having mean ages of 2, 5, 8, 11, and 14 years. Spinal radiographs of anesthetized dogs were taken prior to euthanasia and on defleshed pines following necropsy. Cervical, thoracic, and lumbar segments were tested in compression to calculate peak stress, peak strain, and elastic modulus. Adjacent spinal segments were examined histologically. Histological evidence of the disc degeneration and changes in the mechanical properties of the intervertebral disc joint preceded radiographical evidence of spondylosis. Changes in the mechanical properties of the disc space were probably a result of the disc degeneration rather than the spondylytic lesions. 3 references, 4 figures

  7. In vitro interactions of lymphocytes and cultured cells from beagles with plutonium-induced bone tumors

    International Nuclear Information System (INIS)

    Frazier, M.E.; Lund, J.E.; Busch, R.H.

    1976-01-01

    Cell cultures have been prepared from lung and bone tumors arising in beagle dogs following exposure to inhaled plutonium. Evaluation of the cultured cells by commonly applied criteria (i.e., cell morphology, lack of contact inhibitory mechanisms, cloning efficiency, growth in soft agar, and tumor production in vivo) indicated that tumor cells were being grown in culture. Blood leukocytes and peripheral lymphocytes from beagle dogs were tested for cytotoxic effects against several cell cultures. Lymphocytes from normal dogs or dogs with unrelated tumors would not kill the bone tumor cells unless monocytes (macrophage) were present, in which case the leukocyte preparation was capable of mounting de novo cytotoxic immune reactions after 3 to 5 days in culture. In contrast, the dogs with plutonium-induced bone tumors had circulating lymphocytes that appeared to have undergone presensitization to bone-tumor-distinctive antigens in vivo. Consequently these lymphocytes interacted with cultured cells promptly after encounter in vitro

  8. The shallow-water Asellota (Crustacea: Isopoda from the Beagle Channel: Preliminary taxonomic and zoogeographical results

    Directory of Open Access Journals (Sweden)

    Brenda Lía Doti

    2005-12-01

    Full Text Available The shallow-water Asellota from the Beagle Channel were investigated, based on material collected at four localities in 2001-2002. A total of 3,124 asellotes were sorted, and three new species and 12 new records of distribution were reported. The Paramunnidae showed the highest species diversity and abundance (11 species and 1,463 specimens. The present research raises the number of species known from the Beagle Channel to 23; of these, 16 were previously reported from the Magellan Straits, representing 69% of similarity. Based on the present results and published data, the faunistic affinities for the shallow-water Asellota was 30% between the Magellan region and the Scotia Arc, and 26% between the Magellan region and the Antarctic Peninsula.

  9. How Do You Answer the Life on Mars Question? Use Multiple Small Landers Like Beagle 2

    Science.gov (United States)

    Gibson, Everett K.; Pillinger, C. T.; Wright, I. P.; Hurst, S. J.; Richter, L.; Sims, M. R.

    2012-01-01

    To address one of the most important questions in planetary science Is there life on Mars? The scientific community must turn to less costly means of exploring the surface of the Red Planet. The United Kingdom's Beagle 2 Mars lander concept was a small meter-size lander with a scientific payload constituting a large proportion of the flown mass designed to supply answers to the question about life on Mars. A possible reason why Beagle 2 did not send any data was that it was a one-off attempt to land. As Steve Squyres said at the time: "It's difficult to land on Mars - if you want to succeed you have to send two of everything".

  10. Toxicity of inhaled 239PuO2 in aged beagle dogs

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Hahn, F.F.; Guilmette, R.A.; Boecker, B.B.; McClellan, R.O.

    1980-01-01

    Studies to determine the effects of age at exposure on metabolism, dosimetry and biological effects of inhaled particles of 239 PuO 2 have been initiated in aged beagle dogs (8.0 to 10.5 years of age at exposure). Beagle dogs have been exposed to 1.5 μm AD particles of 239 PuO 2 resulting in initial lung burdens ranging from 0.03 to 0.76 μCi/kg body weight. Dogs exposed to the aerosol diluent serve as controls. There were four blocks exposed in the past year, one of males and three of female dogs. Nine dogs died during the year. Seven of these had radiation pneumonitis and two died of nonradiation induced diseases. The surviving dogs are as long as 538 days after exposure. There are three blocks of male dogs planned for exposure in the next 12 months

  11. Quantitation of uveoscleral outflow in normotensive and glaucomatous Beagles by 3H-labeled dextran

    International Nuclear Information System (INIS)

    Barrie, K.P.; Gum, G.G.; Samuelson, D.A.; Gelatt, K.N.

    1985-01-01

    In uveoscleral outflow, aqueous humor leaves the anterior chamber and passes caudally through the trabecular meshwork and the sclerociliary cleft to enter the supraciliary and suprachoroidal spaces. The fluid is then absorbed by choroidal and scleral circulations. Using 3 H-labeled dextran, uveoscleral outflow was quantitated in normotensive and glaucomatous Beagles under general anesthesia. The intrascleral plexus was isolated and 3 H-labeled dextran was injected into the anterior chamber. Intrascleral plexus contents were sampled every 5 minutes over a 30- to 60-minute period. The eyes were enucleated, sectioned, and prepared for scintillation counting. Uveoscleral outflow accounted for 15% and 3% of the total aqueous humor outflow in the normotensive dogs and in the advanced glaucomatous dogs, respectively. In the advanced glaucomatous Beagle, conventional and uveoscleral outflow pathways were reduced and contributed to the etiopathogenesis of glaucoma

  12. Meiofauna communities from the Straits of Magellan and the Beagle Channel

    Directory of Open Access Journals (Sweden)

    G. C. Chen

    1999-12-01

    Full Text Available Meiofauna from 20 stations (ranging between 8 and 550 m in the Magellan Straits and the Beagle Channel revealed 28 small sized taxa of higher categories including the temporary meiofauna. Nematoda, Copepoda Harpacticoidea and Polychaeta occurred in all samples; Turbellaria, Bivalvia, Kinorhyncha and Ostracoda were regularly present. Nematodes represented between 68% and 94% of the meiofauna at each station, followed by the copepods (2.3% to 14.5% and polychaetes (1.1% to 11.5%. Maximal total density, 9700 individuals 10 cm-2, was found in the surroundings of Picton Island, while the mean abundance per station was 3374 individuals 10 cm-2. The vertical pattern within the sediment showed that 87% of meiofauna components concentrated in the upper 0-5 cm sediment layers and 13% in the lower ( > 5cm layers. More than 95% of copepods, as well as the temporary meiofauna occurred in the top 5 cm layers. The proportion of nematodes and copepods shows opposite trends in the vertical distribution. Multivariate analysis using the total density and the 10 `true´ meiofauna taxa densities discriminates between communities in the Straits of Magellan and the Beagle Channel area. Meiofaunal density was much higher in the Beagle Channel, but the diversity was lower than that in the Straits of Magellan. The Southern Magellan meiofauna communities are compared with those found at the Antarctic Peninsula and in the Weddell Sea (high Antarctic. It is considered that hydrodynamic features (tidal currents with strong winds, geographical characteristics, together with sediment composition are the key parameters structuring the meiofauna community in the Straits of Magellan and in the Beagle Channel.

  13. Experimental induction of struvite uroliths in miniature schnauzer and beagle dogs.

    Science.gov (United States)

    Klausner, J S; Osborne, C A; O'Leary, T P; Muscoplat, C M; Griffith, D P

    1980-09-01

    Urease positive staphylococcal urinary tract infection was experimentally induced in 13 dogs. Eight dogs developed cystic and/or urethral struvite calculi in 2 to 8 weeks. No abnormalities in systemic cell mediated immunity were detected in dogs before or after the establishment of the urinary tract infection. Miniature schnauzers whose ancestors had developed stones seemed to be no more susceptible to experimental urinary tract infection and stone formation than miniature schnauzers or beagles whose ancestors did not develop stones.

  14. Early effects of inhaled 239Pu(NO3)4 aerosols in beagle dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.; Ragan, H.A.; Watson, C.R.; Stevens, D.L.; Rowe, S.E.; Madison, R.M.; Wierman, E.L.; Schirmer, R.E.

    1979-01-01

    Beagle dogs given a single inhalation exposure to 239 Pu(NO 3 ) 4 , and observed for life-span dose-effect relationship, died from radiation pneumonitis (4 of 5) at the highest dosage level, 14 to 25 mo postexposure. There were also indications in these dogs of radiation osteosis, characterized by peritrabecular fibrosis. Leukopenia, lymphopenia, neutropenia and decreased numbers of circulating monocytes and eosinophils occurred at the two highest dosage levels, as previously reported

  15. Spontaneous necrotizing sialometaplasia of the submandibular salivary gland in a Beagle dog

    OpenAIRE

    Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

    2015-01-01

    A single mass was found on the left submandibular salivary gland at necropsy of a 15-month-old male commercially bred laboratory Beagle dog from a control dose group from a repeat toxicity study. Microscopically, the mass was composed of a well-demarcated area of coagulative necrosis surrounded and separated from the normal salivary gland tissue by a thick fibrovascular capsule. Necrosis was admixed with areas of hemorrhage, fibrin, edema, fibrinoid necrosis of the vascular tunica media, and ...

  16. Experimental inoculation of beagle dogs with Ehrlichia species detected from Ixodes ovatus

    OpenAIRE

    Watanabe, Malaika; Oikawa, T; Hiraoka, Hiroko; Kaneko, N; Itamoto, Kazuhito; Mizuno, Tohru; Okuda, Masaru; Inokuma, Hisashi

    2006-01-01

    Three beagle dogs were inoculated with mice spleen/liver homogenate infected with Ehrlichia species detected from Ixodes ovatus (EIO) and one dog was used as a control. All three infected dogs did not show clinical signs of disease except for mild pyrexia throughout the 41-day study period. Splenomegaly was observed from Day 7 post-inoculation (p.i.) in two of the dogs. Hematological and biochemical abnormalities included mild thrombocytopenia, hypoproteinaemia, hypoalbuminaemia and increased...

  17. Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jie Zhao

    2015-11-01

    Full Text Available Ginkgolide B (GB, an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C18 column (1.8 μm, 2.1 × 50 mm with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM in negative ion mode, with the transitions at m/z (Q1/Q3 423.1/367.1 for GB and m/z 269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2–200 ng/mL. The intra- and inter-day precisions were <15% and the accuracies were within ±12.7%. The validated method was applied to compare the pharmacokinetic characteristics of GB in healthy beagle dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet. The Cmax values of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations.

  18. Non-neoplastic pulmonary disease from inhaled radon daughters with uranium ore dust in beagle dogs

    International Nuclear Information System (INIS)

    Filipy, R.E.; Palmer, R.F.; Stuart, B.O.

    1977-01-01

    Daily exposures of adult beagle dogs to inhaled radon daughters plus uranium ore dust, with and without concurrent cigarette smoking, for 2 to 5-1/2 yr have produced massive pulmonary fibrosis and severe emphysema. The cumulative exposure doses are similar to those associated with a 5-fold or greater increase in death rate of uranium miners due to chronic respiratory insufficiency, including pneumoconiosis, pulmonary fibrosis, and emphysema

  19. Charles Darwin's beagle voyage, fossil vertebrate succession, and "the gradual birth & death of species".

    Science.gov (United States)

    Brinkman, Paul D

    2010-01-01

    The prevailing view among historians of science holds that Charles Darwin became a convinced transmutationist only in the early spring of 1837, after his Beagle collections had been examined by expert British naturalists. With respect to the fossil vertebrate evidence, some historians believe that Darwin was incapable of seeing or understanding the transmutationist implications of his specimens without the help of Richard Owen. There is ample evidence, however, that he clearly recognized the similarities between several of the fossil vertebrates he collected and some of the extant fauna of South America before he returned to Britain. These comparisons, recorded in his correspondence, his diary and his notebooks during the voyage, were instances of a phenomenon that he later called the "law of the succession of types." Moreover, on the Beagle, he was following a geological research agenda outlined in the second volume of Charles Lyell's Principles of Geology, which implies that paleontological data alone could provide an insight into the laws which govern the appearance of new species. Since Darwin claims in On the Origin of Species that fossil vertebrate succession was one of the key lines of evidence that led him to question the fixity of species, it seems certain that he was seriously contemplating transmutation during the Beagle voyage. If so, historians of science need to reconsider both the role of Britain's expert naturalists and the importance of the fossil vertebrate evidence in the development of Darwin's ideas on transmutation.

  20. SNPs of melanocortin 4 receptor (MC4R) associated with body weight in Beagle dogs.

    Science.gov (United States)

    Zeng, Ruixia; Zhang, Yibo; Du, Peng

    2014-01-01

    Melanocortin 4 receptor (MC4R), which is associated with inherited human obesity, is involoved in food intake and body weight of mammals. To study the relationships between MC4R gene polymorphism and body weight in Beagle dogs, we detected and compared the nucleotide sequence of the whole coding region and 3'- and 5'- flanking regions of the dog MC4R gene (1214 bp). In 120 Beagle dogs, two SNPs (A420C, C895T) were identified and their relation with body weight was analyzed with RFLP-PCR method. The results showed that the SNP at A420C was significantly associated with canine body weight trait when it changed amino acid 101 of the MC4R protein from asparagine to threonine, while canine body weight variations were significant in female dogs when MC4R nonsense mutation at C895T. It suggested that the two SNPs might affect the MC4R gene's function which was relative to body weight in Beagle dogs. Therefore, MC4R was a candidate gene for selecting different size dogs with the MC4R SNPs (A420C, C895T) being potentially valuable as a genetic marker.

  1. [Pharmacokinetic study of six aconitine alkaloids in aconiti lateralis radix praeparata in beagle dogs].

    Science.gov (United States)

    Xiao, Ri-Ping; Lai, Xiao-Ping; Zhao, Yai; Yu, Liang-Wen; Zhu, Yue-Lan; Li, Geng

    2014-02-01

    To study the pharmacokinetics characteristics of six Aconitum alkaloids aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconine (BAC), benzoylmesaconine (BMA) and benzoylhypaconine (BHA) in beagle dogs. An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for simultaneous quantitation of six Aconitum alkaloids in beagle dog plasma after oral administration of Aconiti Lateralis Radix Praeparata decoction. UPLC/MS/MS system coupled with an electrospray ionization (ESI) source was performed in multiple-reaction monitoring (MRM) mode. Sample preparation was performed with solid-phase extraction(SPE) on a 3 mL HLB cartridge before the analysis. The separation was applied on a Waters C8 column (100 mm x 2.1 mm, 1.7 microm) and a gradient elution of methanol and 0.2% formic acid-water was used as mobile phase. The pharmacokinetic parameters were calculated by the results of the analysis through the DAS 2. 1 software (Drug and Statistics for Windows). The results showed that the fitting model for the six Aconitum alkaloids was the one-compartment model pharmacokinetics. The method is successfully used for the pharmacokinetic evaluation of the six Aconitum alkaloids in beagle dog plasma, it can help monitor the ADME/Tox process when taking Aconiti Lateralis Radix Praeparata by observing the pharmacokinetic process. The results provide a good reference for clinical treatment and safe application of Aconiti Lateralis Radix Praeparata.

  2. Incidence of liver tumors in beagles with body burdens of 239Pu or 241Am

    International Nuclear Information System (INIS)

    Taylor, G.N.; Mays, C.W.; Wrenn, M.E.; Shabestari, L.; Lloyd, R.D.

    1986-01-01

    Tetravalent 239 Pu or trivalent 241 Am in a citrate buffer, given via a single intravenous injection to beagles, induced very pronounced liver changes, usually at relatively long postinjection times. The lesions consisted of cell injury or cell necrosis which was followed by nodular hyperplasia and a significant incidence of primary liver tumors. The most frequent neoplasm was the bile duct adenoma, followed by the bile duct carcinoma. A lesser number of sarcomas were also induced, especially fibrosarcomas. The number of hepatic cell tumors was low. An abnormally high incidence of both hyperplastic nodules and primary liver tumors occurred at long postinjection times and at average doses extending down to ∼10 rads. The various nodular lesions and liver tumors frequently occurred as incidental findings in dogs dying from other causes, especially bone cancer. In comparison to bone neoplasia, the liver was a much less important target organ in the high-dose level groups, but in some of the low-dose groups, especially in the 241 Am groups, the risk of radiation-induced liver cancer was approximately equal to or exceeded the risk of skeletal tumors. However, in any projection of the risks observed in this animal model to man, one should be mindful that the beagle skeleton is approximately 25 times more sensitive to radiation-induced bone neoplasia than is the human skeleton (Mays et al., 1976) and that the radiosensitivity difference for the beagle and human liver is unknown. 41 refs., 8 figs., 5 tabs

  3. The biological effects of high dose total body irradiation in beagle dogs

    International Nuclear Information System (INIS)

    Luo Qingliang; Liu Xiaolan; Hao Jing; Xiong Guolin; Dong Bo; Zhao Zhenhu; Xia Zhengbiao; Qiu Liling; Mao Bingzhi

    2002-01-01

    Objective: To evaluate the biological effects of Beagle dogs irradiated by γ-rays at different doses. Methods: All Beagle dogs were divided into six groups and were subjected respectively to total-body irradiation (TBI) with a single dose of 6.5, 5.5, 5.0, 4.5, 3, 5 and 2.5 Gy γ-rays delivered by 60 Co sources at 7.224 x 10 -2 C/kg per minute. The general condition, blood cell counts and bone marrow cell CFC assays were observed. Results: Vomiting occurred at 0.5 to 2 hours after TBI in all groups. In 6.5 Gy group 3/5 dogs had blood-watery stool and 1/5 in 5.5 Gy group had watery stool. Diarrhea occurred in all other animals. Only one dog in 2.5 Gy group survived, all of others died. in order of decreasing irradiation dosage, the average survival time was 5.0, 8.0, 9.3, 9.5, 10.5 and 14.1 days, respectively. Conclusions: According to the clinical symptoms, leukocyte count and survival time of the dogs, the irradiation dose which will induce very severe hematopoietic radiation syndrome in Beagle dogs is 4.5 to 5.0 Gy

  4. Hyperhidrosis in naïve purpose-bred beagle dogs (Canis familiaris).

    Science.gov (United States)

    Carrier, Catherine A; Seeman, Jennifer L; Hoffmann, Guenther

    2011-05-01

    This case study details the unusual clinical findings in a unique paw-pad disorder that recently emerged among 2 male and 1 female naïve purpose-bred beagle dogs (Canis familiaris) newly received into our facility. During acclimation period physical examinations, the affected dogs demonstrated constantly moist, soft paw pads on all 4 feet. No information was available regarding the epidemiology and pathogenesis of this pad condition in beagle dogs. Here, we report the results of physical examination, clinical chemistry analysis, hematology, histopathology, detailed observations, and novel testing techniques performed during the acclimation period. Histopathology of several sections of affected footpads was compared with that of an age-matched dog with clinically normal paw pads. We describe the morphologic features of a distinctive cutaneous canine footpad condition and discuss the possible differential diagnoses. The histologic and clinical features were most consistent with those of hyperhidrosis; to our knowledge, this report is the first description of hyperhidrosis as a distinct condition in purpose-bred beagle dogs.

  5. Beagle puppy model of intraventricular hemorrhage: effect of indomethacin on cerebral blood flow

    International Nuclear Information System (INIS)

    Ment, L.R.; Stewart, W.B.; Duncan, C.C.; Scott, D.T.; Lambrecht, R.

    1983-01-01

    The newborn beagle puppy has been demonstrated to provide a good model for neonatal intraventricular hemorrhage (IVH). A study was designed to determine if indomethacin can prevent IVH and if indomethacin would produce changes in cerebral blood flow (CBF). Newborn beagle puppies were randomized by computer into two groups: one was pretreated with indomethacin, a known inhibitor of prostaglandin synthetase, and the other was saline. The dogs in both groups were then assigned either to undergo hemorrhagic hypotension/volume reexpansion insult or to receive no insult. Twenty percent of all pups receiving indomethacin and undergoing the insult experienced IVH, compared to 71% of the pups undergoing insult that had been pretreated with saline. Significant alterations in the blood pressure responses to the hemorrhagic hypotension/volume reexpansion insult were noted in the former group compared to the saline-pretreated pups subjected to insult. Finally, employing carbon-14 autoradiography for the determination of CBF, it was demonstrated that indomethacin decreases resting CBF of the newborn beagle pups and, in indomethacin-pretreated animals subjected to insult, prevents the increases in CBF seen in the saline-pretreated traumatized pups. 62 references, 1 figure, 3 tables

  6. Grey matter volume in healthy and epileptic beagles using voxel-based morphometry – a pilot study

    Directory of Open Access Journals (Sweden)

    Lisa Frank

    2018-02-01

    Full Text Available Abstract Background One of the most common chronic neurological disorders in dogs is idiopathic epilepsy (IE diagnosed as epilepsy without structural changes in the brain. In the current study the hypothesis should be proven that subtle grey matter changes occur in epileptic dogs. Therefore, magnetic resonance (MR images of one dog breed (Beagles were used to obtain an approximately uniform brain shape. Local differences in grey matter volume (GMV were compared between 5 healthy Beagles and 10 Beagles with spontaneously recurrent seizures (5 dogs with IE and 5 dogs with structural epilepsy (SE, using voxel-based morphometry (VBM. T1W images of all dogs were prepared using Amira 6.3.0 for brain extraction, FSL 4.1.8 for registration and SPM12 for realignment. After creation of tissue probability maps of cerebrospinal fluid, grey and white matter from control images to segment all extracted brains, GM templates for each group were constructed to normalize brain images for parametric statistical analysis, which was achieved using SPM12. Results Epileptic Beagles (IE and SE Beagles displayed statistically significant reduced GMV in olfactory bulb, cingulate gyrus, hippocampus and cortex, especially in temporal and occipital lobes. Beagles with IE showed statistically significant decreased GMV in olfactory bulb, cortex of parietal and temporal lobe, hippocampus and cingulate gyrus, Beagles with SE mild statistically significant GMV reduction in temporal lobe (p < 0.05; family- wise error correction. Conclusion These results suggest that, as reported in epileptic humans, focal reduction in GMV also occurs in epileptic dogs. Furthermore, the current study shows that VBM analysis represents an excellent method to detect GMV differences of the brain between a healthy dog group and dogs with epileptic syndrome, when MR images of one breed are used.

  7. SU-C-303-03: Dosimetric Model of the Beagle Needed for Pre-Clinical Testing of Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Shang, M; Sands, M; Bolch, W [University of Florida, Gainesville, FL (United States)

    2015-06-15

    Purpose: Large animal models, most popularly beagles, have been crucial surrogates to humans in determining radiation safety levels of radiopharmaceuticals. This study aims to develop a detailed beagle phantom to accurately approximate organ absorbed doses for therapy nuclear medicine preclinical studies. Methods: A 3D NURBS model was created subordinate to a whole body CT of an adult beagle. Bones were harvested and CT imaged to offer macroscopic skeletal detail. Samples of trabecular spongiosa were cored and imaged to offer microscopic skeletal detail for bone trabeculae and marrow volume fractions. Results: Organ masses in the model are typical of an adult beagle. Trends in volume fractions for skeletal dosimetry are fundamentally similar to those found in existing models of other canine species. Conclusion: This work warrants its use in further investigations of radiation transport calculation for electron and photon dosimetry. This model accurately represents the anatomy of a beagle, and can be directly translated into a useable geometry for a voxel-based Monte Carlo radiation transport program such as MCNP6. Work supported by a grant from the Hyundai Hope on Wheels Foundation for Pediatric Cancer Research.

  8. Surface-seeking radionuclides in the skeleton: current approach and recent developments in biokinetic modelling for humans and beagles

    International Nuclear Information System (INIS)

    Luciani, A.; Polig, E.

    2007-01-01

    In the last decade, the biokinetics of surface-seeking radionuclides in the skeleton has been the object of several studies. Investigations were carried out to determine the kinetics of plutonium and americium in the skeleton of humans and beagles. As a result of these investigations, in recent years the models presented by ICRP in Publication 67 for humans were partially revised, particularly the skeletal part. The aim of the present work is to present recent developments in the biokinetic modelling of surface-seeking radionuclides (plutonium and americium) in beagles and humans. Various assumptions and physiological interpretations of the different approaches to the biokinetic modelling of the skeleton are discussed. Current ICRP concepts and skeleton modelling of plutonium and americium in humans are compared to the latest developments in biokinetic modelling in beagles. (authors)

  9. Renal function and morphology in aged Beagle dogs before and after hydrocortisone administration.

    Directory of Open Access Journals (Sweden)

    Pascale M Y Smets

    Full Text Available Objectives of this study were to evaluate glomerular filtration rate (GFR, renal structural changes and proteinuria in aged Beagle dogs before and after hydrocortisone (HC administration. Eleven Beagle dogs ≥10 years old were treated with either hydrocortisone (HC group, n = 6 or placebo (control group, n = 5. Urinary markers, GFR and kidney biopsies were evaluated before (T0, during (T16 wks and after discontinuing HC administration (T24 wks. Results indicate that HC administration causes a significant increase in GFR. At all time points except T16 wks, proteinuria was higher in the control group than in the HC group, and there was no significant difference in urinary markers between groups. At T16 wks, proteinuria, urinary albumin-to-creatinine (c ratio, immunoglobulin G/c and retinol-binding protein/c were higher compared to baseline in the HC group. At T0, rare to mild renal lesions were detected in all HC dogs and rare to moderate changes in all control dogs. Glomerulosclerosis progressed in both groups until T24 wks. Tubular atrophy was detected in three HC dogs at T16 wks and T24 wks, but also in five control dogs throughout the study. At every time point, five HC dogs and all control dogs had rare to moderate interstitial inflammation. Rare to mild interstitial fibrosis was found in up to three HC dogs at T16 wks and T24 wks, and severe fibrosis in one HC dog at T24 wks. Up to four control dogs had rare to mild fibrosis at all time points. These findings indicate that clinically healthy, aged Beagle dogs may have considerable renal lesions and proteinuria, which could have implications for experimental or toxicological studies. Additional research is needed to elucidate glucocorticoid effects on renal structure, but functional changes such as hyperfiltration and proteinuria warrant attention to kidney function of canine patients with Cushing's syndrome or receiving exogenous glucocorticoids.

  10. Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs.

    Science.gov (United States)

    Zhao, Jie; Geng, Ting; Wang, Qi; Si, Haihong; Sun, Xiaoping; Guo, Qingming; Li, Yanjing; Huang, Wenzhe; Ding, Gang; Xiao, Wei

    2015-11-06

    Ginkgolide B (GB), an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C18 column (1.8 μm, 2.1×50 mm) with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in negative ion mode, with the transitions at m/z (Q1/Q3) 423.1/367.1 for GB and m/z 269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2-200 ng/mL. The intra- and inter-day precisions were dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet). The Cmax values of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations.

  11. Assessment of stress in laboratory beagle dogs constrained by a Pavlov sling.

    Science.gov (United States)

    Stracke, Jenny; Bert, Bettina; Fink, Heidrun; Böhner, Jörg

    2011-01-01

    The 3Rs - Replacement, Reduction and Refinement - have become increasingly important in designing animal experiments. The Pavlov sling is thought to be a non-invasive method to restrain dogs for examinations. The aim of our study was to investigate whether laboratory Beagle dogs that had been trained to tolerate restraint by a Pavlov sling are stressed by this procedure and, furthermore, to analyze their behavior during this period. Five male and five female Beagle dogs were used, each three years of age. Animals were restrained in the Pavlov sling for 30 min on six days with an interval of at least two days. The following behaviors were recorded every minute for each session: postures of body, head, and ears, as well as state of eyes, tail, legs, and mouth. Additionally, the animals were observed for the occurrence of particular stress signs, including body shaking, sweating of the paws, increased saliva production, piloerection, blinking of eyes, snout licking, yawning, and panting. As an indicator for stress, salivary cortisol levels were measured before, during, and after each session. Our results show that for most behavioral parameters, e.g., body, leg, head, tail, and ear posture, the frequency of changes between different behavior patterns, as well as cortisol concentration, were not influenced by restraint in the Pavlov sling. Therefore, the Pavlov sling does not seem to be perceived as a stressful situation by the Beagle dogs. Our study demonstrates that under certain conditions the use of the Pavlov sling in trained dogs can substitute for more ordinary methods of immobilization, e.g., the use of narcotics.

  12. BEAGLE: an application programming interface and high-performance computing library for statistical phylogenetics.

    Science.gov (United States)

    Ayres, Daniel L; Darling, Aaron; Zwickl, Derrick J; Beerli, Peter; Holder, Mark T; Lewis, Paul O; Huelsenbeck, John P; Ronquist, Fredrik; Swofford, David L; Cummings, Michael P; Rambaut, Andrew; Suchard, Marc A

    2012-01-01

    Phylogenetic inference is fundamental to our understanding of most aspects of the origin and evolution of life, and in recent years, there has been a concentration of interest in statistical approaches such as Bayesian inference and maximum likelihood estimation. Yet, for large data sets and realistic or interesting models of evolution, these approaches remain computationally demanding. High-throughput sequencing can yield data for thousands of taxa, but scaling to such problems using serial computing often necessitates the use of nonstatistical or approximate approaches. The recent emergence of graphics processing units (GPUs) provides an opportunity to leverage their excellent floating-point computational performance to accelerate statistical phylogenetic inference. A specialized library for phylogenetic calculation would allow existing software packages to make more effective use of available computer hardware, including GPUs. Adoption of a common library would also make it easier for other emerging computing architectures, such as field programmable gate arrays, to be used in the future. We present BEAGLE, an application programming interface (API) and library for high-performance statistical phylogenetic inference. The API provides a uniform interface for performing phylogenetic likelihood calculations on a variety of compute hardware platforms. The library includes a set of efficient implementations and can currently exploit hardware including GPUs using NVIDIA CUDA, central processing units (CPUs) with Streaming SIMD Extensions and related processor supplementary instruction sets, and multicore CPUs via OpenMP. To demonstrate the advantages of a common API, we have incorporated the library into several popular phylogenetic software packages. The BEAGLE library is free open source software licensed under the Lesser GPL and available from http://beagle-lib.googlecode.com. An example client program is available as public domain software.

  13. Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development

    Energy Technology Data Exchange (ETDEWEB)

    Vamathevan, Jessica J., E-mail: jessica.j.vamathevan@gsk.com [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli [BGI-Shenzen, Shenzhen (China); Kenny, Steve [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Brown, James R. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, PA (United States); Huxley-Jones, Julie [UK Platform Technology Sciences (PTS) Operations and Planning, PTS, GlaxoSmithKline, Stevenage (United Kingdom); Lyon, Jon; Haselden, John [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Min, Jiumeng [BGI-Shenzen, Shenzhen (China); Sanseau, Philippe [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom)

    2013-07-15

    Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research. - Highlights: • Genomes of the minipig and beagle dog, two species used in pharmaceutical studies. • First systematic comparative genome analysis of human and six experimental animals. • Key drug toxicology genes display unique duplication patterns across species. • Comparison of 317 drug targets show species-specific evolutionary patterns.

  14. Study of single dose toxic test of Sweet Bee Venom in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Hye-Chul, Yoon

    2010-12-01

    Full Text Available Objectives : This study was performed to analyse single dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods : All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of single dose toxicity of Sweet BV which was administered at the level of 9.0 ㎎/㎏ body weight which is 1300 times higher than the clinical application dosage as the high dosage, followed by 3.0 and 1.0 ㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group. Results : 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all the experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, brain, liver, lung, kidney, and spinal cords were removed and histologocal observation using H-E staining was conducted. In the histologocal observation of thigh muscle, cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes depend on the dose of Sweet BV. But the other organs did not showed in any abnormality. 5. The maximum dose of Sweet BV in Beagle dogs were over 9 ㎎/㎏ in this study. Conclusions : The above findings of this study suggest that Sweet BV is a relatively safe treatment medium. Further studies on the toxicity of Sweet BV should be conducted to yield more concrete evidences.

  15. Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development

    International Nuclear Information System (INIS)

    Vamathevan, Jessica J.; Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M.; Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli; Kenny, Steve; Brown, James R.; Huxley-Jones, Julie; Lyon, Jon; Haselden, John; Min, Jiumeng; Sanseau, Philippe

    2013-01-01

    Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research. - Highlights: • Genomes of the minipig and beagle dog, two species used in pharmaceutical studies. • First systematic comparative genome analysis of human and six experimental animals. • Key drug toxicology genes display unique duplication patterns across species. • Comparison of 317 drug targets show species-specific evolutionary patterns

  16. Comparison of radiological changes in humans and beagles with skeletal deposits of radium

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, J P [Univ. of California, Davis; Pool, R R; Kirsh, I E

    1983-01-01

    At the Laboratory for Energy-related Health Research at the University of California, Davis, semimonthly injections of /sup 226/Ra were given to a group of beagle dogs, and periodic skeletal radiography followed, as well as histological studies of the bones. At the Center for Human Radiobiology measurements were made of radium body content in 2259 occupationally or otherwise exposed persons. Of these, 1768 had skeletal radiography (one or more times). In humans, the radiographic changes were, in decreasing order of frequency, osteolytic cortical and cancellous bone destruction, bone sclerosis, pathological fracture, and avascular necrosis of bone. In beagles, osteolytic destruction and pathological fractures were common, avascular necrosis was not observed, but there was frequently cortical thickening and new-bone formation in cancellous bone. In both population groups, there was a high incidence of bone sarcoma. In the beagles, one high-dosage group numbering 38 dogs had 49 malignant bone tumors. Among the 2259 measured persons, there were 60 who had bone sarcoma, and 29 who had cancer of the mastoids or paranasal sinuses. No significant skeletal effects have been diagnosed radiologically in persons with systemic intakes of /sup 226/Ra or /sup 228/Ra below about 10 ..mu..Ci or with skeletal doses below about 100 rad. In humans, the lowest skeletal dose at which a bone sarcoma has been diagnosed is 890 rad, and the lowest intake associated with a bone sarcoma is 96 ..integral..Ci /sup 226/Ra or about 1.7 ..mu..Ci per kg body weight.

  17. Treatment of extremely severe acute hemopoietic radiation sickness beagles with RhG-CSF and RhIL-11

    International Nuclear Information System (INIS)

    Zhao Jianzhi; Zhang Ri; Li Ming; Xing Shuang; Luo Qingliang; Zhang Xueguang; Miao Jingcheng; Zhu Nankang

    2010-01-01

    Objective: To evaluate the effects of treatment combined recombinant human G-CSF (rhG-CSF) and recombinant human interleukin-11 (rhIL-11) on severe acute hemopoietic radiation sickness (ARS) beagles. Methods: Beagles were irradiated with 4.5 Gy 60 Co γ-ray to establish ARS models, and animals were divided into the irradiated control group and the supportive care and combined cytokines treatment cohort. After irradiation the irradiated control beagles was given no treatment, the supportive care beagles received purely symptomatic treatment including blood transfusion and anti-infection while the combined cytokines treatment beagles received rhG-CSF and rhIL-11 subcutaneously for three weeks besides symptomatic treatment.Results After irradiation, all kinds of cells' population declined sharply, but rebounded to normal basically in the combined cytokines treatment rate in the cohort. The mean blood transfusion volume of cytokines in the cohort and the period of blood transfusion all were less than those in the supportive care cohort (P<0.01). The period of administrated antibiotic of cytokines in the cohort was shorter than that in the supportive care cohort (P<0.05). In the observe period of 45 d, survival rate in the irradiated controls cohort was 0%, in the supportive care cohort was 80%, and in the combined cytokines treatment cohort was 100%(P<0.01). Conclusion: Administration of rhG-CSF and rhIL-11 early after irradiation and continued daily, in combined with supportive care in severe acute hemopoietic radiation sickness beagles can improve hematopoietic function restoration, stimulate blood cells to restore to the normal level quickly, significantly decrease the reguired volume of blood transfusion, shorten the period of anti-infection and increase survival of irradiated canines. (authors)

  18. Competitive radiation-induced carcinogenesis: an analysis of data from beagle dogs exposed to 226Ra and 90Sr

    International Nuclear Information System (INIS)

    Momeni, M.H.

    1979-01-01

    The incidence of radiation-induced primary bone sarcoma and myeloproliferative diseases was studied as a function of dose rate and time in beagles that were fed diets containing 90 SrCl 2 in equilibrium with 90 Y from midgestation to 1.5 yr of age or that were administered eight intravenous injections of 226 RaCl 2 (one injection every 2 weeks for 4 months) starting at 14 months of age. Analysis of incidence of each disease in 776 beagles showed a normal probability density function with respect to time. Median incidence time and standard deviation from the mean of distribution were calculated for primary osteosarcoma at each level of administered radioactivity. The median incidence age (T) for mortality from primary osteosarcoma increased from 4.1 yr of age, 2.6 yr after final injection of radium, for beagles injected (A 0 ) with 83.6 μCi 226 Ra, to 11.5 yr of age for beagles given A 0 = 3.14 μCi 226 Ra. A similar increase in T was observed for beagles that ingested a daily diet containing 90 Sr + 90 Y, from T = 2.8 yr of age at 36 μCi 90 Sr/day to 12.6 yr at 4 μCi 90 Sr/day. Tumor yield was calculated assuming that the causes of death from competing diseases were mutually exclusive with respect to individual diseases. Incidence and cumulative incidence for each of the diseases were calculated as a function of time and maximum dose rate. These analyses were extended to beagles administered 226 Ra by a single injection or 90 Sr by injection and inhalation. Extrapolation of the observed dose effects to lower levels of administered radioactivity (comparable to maximum permissible body burden) is discussed within the framework of a competitive mortality. (author)

  19. HPLC assay for ethiofos in plasma: Application to pharmacokinetics in the beagle dog

    International Nuclear Information System (INIS)

    Swynnerton, N.F.; Mangold, D.J.; Ludden, T.M.

    1985-01-01

    An HPLC assay for ethiofos [S-2-(3-amino-propylamino)ethyl phosphorothioate, WR 2727] in plasma is presented. Its application to the development of pharmacokinetic parameters following IV administration of the drug to beagle dogs is demonstrated and preliminary pharmacokinetics of four dosings will be presented. Following a dose of 150 mg kg -1 , the plasma concentration versus time profile was best described by a two-compartment pharmacokinetics model. Mean pharmacokinetic parameters were: terminal elimination half-life = 16.0 minutes, volume of central compartment = 129 mL kg -1 , and clearance = 11.0 mL min -1 kg -1

  20. Hypoadrenocorticism in beagles exposed to aerosols of plutonium-238 dioxide by inhalation

    International Nuclear Information System (INIS)

    Weller, R.E.; Buschbom, R.L.; Dagle, G.E.

    1996-01-01

    Hypoadrenocorticism, known as Addison's disease in humans, was diagnosed in six beagles after inhalation of at least 1.7 kBq/g lung of 238 PuO 2 . Histological examination of adrenal gland specimens obtained at necropsy revealed marked adrenal cortical atrophy in all cases. Autoadiographs showed only slight α-particle activity. Although the pathogenesis of adrenal cortical atrophy in these dogs is unclear, there is evidence to suggest an automimmune disorder linked to damage resulting from α-particle irradiation to the lymphatic system

  1. Toxicity of 239PuO2 in immature Beagle dogs. III

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Muggenburg, B.A.; Hahn, F.F.; Mauderly, J.L.; Boecker, B.B.; McClellan, R.O.

    1981-01-01

    Immature Beagle dogs have been exposed by inhalation to a monodisperse aerosol of 239 PuO 2 (1.5 μm AD) to compare the biological effects with those seen in young adult and aged dogs exposed to a similar aerosol. To date 45 dogs have been exposed to the aerosol, resulting in graded lung burdens from 0.0031 to 0.64 μCi/kg body weight. Six dogs exposed to the dilute ammonium hydroxide aerosol only serve as controls. One experimental dog has died of parvovirus enteritis. Exposures will continue during the coming year to complete the experimental design

  2. Hypodontia in the beagle after perinatal whole-body 60Co gamma irradiation

    International Nuclear Information System (INIS)

    Lee, A.C.; Angleton, G.M.; Benjamin, S.A.

    1989-01-01

    As part of a long-term study to evaluate health effects of pre- and postnatal irradiation, dental development was examined. Beagles were irradiated in utero at 8, 28, or 55 days postcoitus or postnatally at 2, 70, or 365 days postpartum. Whole-body 60 Co gamma radiation doses ranged from 0 to 3.8 Gy. There was an age-dependent dose-related increase in premolar hypodontia for animals irradiated at 55 days postcoitus or 2 days postpartum with doses of 0.83 Gy or higher and for those irradiated at 28 days postcoitus with 1.2 Gy or higher

  3. Investigations with beagles about toxicity and radioprotective effect of the chemical radioprotection substance WR 2721

    International Nuclear Information System (INIS)

    Wagner, M.; Sedlmeier, H.; Wustrow, T.; Messerschmidt, O.

    1980-01-01

    The toxicity of the chemical radioprotection substance WR 2721 (S-2-(3-aminopropylamino)ethyl-thiophosphate) was examined in 25 beagles. The study showed that the toxicity of the substance increases as the dose gets higher. Between the doses 200 and 250 mg/kg of body weight, the increase of toxicity was significantly greater than could be expected on the basis of the dose difference. Until a dose of 200 mg/kg, the authors found no side effects which would have disturbed vital functions, but higher doses led to marked symptoms of intoxication. (orig.) [de

  4. Radiation induced skeletal changes in beagle: dose rates, dose, and age effect analysis from 226Ra

    International Nuclear Information System (INIS)

    Momeni, M.H.; Williams, J.R.; Rosenblatt, L.S.

    1976-01-01

    Radiation-induced skeletal injury (E) and the rate of skeletal injury were studied as a function of time and dose in beagles administered 226 Ra Cl 2 in eight semimonthly iv injections starting at 2, 4, or 14 months of age. Skeletal changes were evaluated with a radiographic x-ray scoring system in 20 skeletal regions; each region was scored on a 0 to 6 scale. Bone changes in six regions of humeri were qualitatively analyzed for comparison with total skeletal changes. Skeletal changes were classified by endosteal or periosteal cortical sclerosis and thickening, fractures, osteolytic lesions, and trabecular coarsening

  5. Local cerebral glucose utilization in the beagle puppy model of intraventricular hemorrhage

    International Nuclear Information System (INIS)

    Ment, L.R.; Stewart, W.B.; Duncan, C.C.

    1982-01-01

    Local cerebral glucose utilization has been measured by means of carbon-14( 14 C)-autoradiography with 2-deoxyglucose in the newborn beagle puppy model of intraventricular hemorrhage. Our studies demonstrate gray matter/white matter differentiation of uptake of 14 C-2-deoxyglucose in the control pups, as would be expected from adult animal studies. However, there is a marked homogeneity of 14 C-2-deoxyglucose uptake in all brain regions in the puppies with intraventricular hemorrhage, possibly indicating a loss of the known coupling between cerebral blood flow and metabolism in this neuropathological condition

  6. Thyroid neoplasia in beagles receiving whole-body irradiation during development

    International Nuclear Information System (INIS)

    Stephens, L.C.; Norrdin, R.W.; Hargis, A.M.; Benjamin, S.A.

    1979-01-01

    Twenty malignant and 17 benign thyroid neoplasms have been diagnosed in 37 Segment III beagles. Nine males and 8 females had follicular adenomas, and 7 males and 13 females had thyroid carcinomas. The dogs ranged in age from 5.16 to 10.66 years. Twenty-nine of the 37 dogs (78.4 percent) were hypothyroid. Twenty-six (70.3 percent) dogs were irradiated. Of the 26 irradiated dogs 15 had malignant tumors. Fourteen (37.8 percent) of the 37 dogs had the same sire

  7. Deposition of inhaled LMFBR-fuel-sodium aerosols in beagle dogs

    International Nuclear Information System (INIS)

    Hackett, P.L.; Mahlum, D.D.; Briant, J.K.; Catt, D.L.; Peters, L.R.; Clary, A.J.

    1980-01-01

    Initial alveolar deposition of LMFBR-fuel aerosols in beagle dogs amounted to 30% of the inhaled activity, but only 5% of the total inhaled activity was deposited in dogs exposed to sodium-fuel aerosols. Aerosol deposition in the gastrointestinal tract amounted to 4% of the initial body burden of fuel-aerosol exposed dogs and 24% of the burden of animals receiving sodium-fuel aerosols. Preliminary analytical data for the dog exposures appear to agree with rodent data for deposition and distribution patterns of aerosols of similar sodium: fuel ratios

  8. Repeated inhalation exposure of Beagle dogs to aerosols of 239PuO2. XII

    International Nuclear Information System (INIS)

    Diel, J.H.; Hahn, F.F.; Muggenburg, B.A.

    1988-01-01

    Beagle dogs were exposed once or semi-annually for 10 yr by inhalation to aerosols of 239 PuO 2 to study the relative doses and effects of these two types of exposures. All exposures have been completed. Dogs exposed at high levels died predominantly of radiation pneumonitis and pulmonary fibrosis. Dogs exposed at lower levels, either once or repeatedly, are dying of a variety of causes including lung cancer. Dogs have survived up to 11 yr after their first exposure. Preliminary results suggest that single and repeated exposures cause similar health effects for equal accumulated radiation doses. (author)

  9. Toxicity of 90Sr inhaled in a relatively insoluble form by Beagle dogs. XVII

    International Nuclear Information System (INIS)

    Snipes, M.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1988-01-01

    This study was initiated to determine health effects resulting from inhalation of 90 Sr in relatively insoluble form. Beagle dogs were briefly exposed by inhalation to produce lung burdens of 90 Sr that ranged from 0.12 to 96 μCi (4.4-3500 kBq)/kg body weight. Exposures to the higher concentrations of 90 Sr caused radiation pneumonitis and pulmonary fibrosis, typically resulting in death 90 Sr-exposed dogs were euthanized during the past year. One remaining exposed dog and one control dog are both 14 yr old and are being maintained for lifetime observation. (author)

  10. Beagle: an appropriate experimental animal for extrapolating the organ distribution pattern of Th in humans

    International Nuclear Information System (INIS)

    Singh, N.P.; Zimmerman, C.J.; Taylor, G.N.; Wrenn, M.E.

    1988-01-01

    The concentrations and the organ distribution patterns of 228Th, 230Th and 232Th in two 9-y-old dogs of our beagle colony were determined. The dogs were exposed only to background environmental levels of Th isotopes through ingestion (food and water) and inhalation as are humans. The organ distribution patterns of the isotopes in the beagles were compared to the organ distribution patterns in humans to determine if it is appropriate to extrapolate the beagle organ burden data to humans. Among soft tissues, only the lungs, lymph nodes, kidney and liver, and skeleton contained measurable amounts of Th isotopes. The organ distribution pattern of Th isotopes in humans and dog are similar, the majority of Th being in the skeleton of both species. The average skeletal concentrations of 228Th in dogs were 30 to 40 times higher than the average skeletal concentrations of the parent 232Th, whereas the concentration of 228Th in human skeleton was only four to five times higher than 232Th. This suggests that dogs have a higher intake of 228Ra through food than humans. There is a similar trend in the accumulations of 232Th, 230Th and 228Th in the lungs of dog and humans. The percentages of 232Th, 230Th and 228Th in human lungs are 26, 9.7 and 4.8, respectively, compared to 4.2, 2.6 and 0.48, respectively, in dog lungs. The larger percentages of Th isotopes in human lungs may be due simply to the longer life span of humans. If the burdens of Th isotopes in human lungs are normalized to an exposure time of 9.2 y (mean age of dogs at the time of sacrifice), the percent burden of 232Th, 230Th and 228Th in human lungs are estimated to be 3.6, 1.3 and 0.66, respectively. These results suggest that the beagle may be an appropriate experimental animal for extrapolating the organ distribution pattern of Th in humans

  11. The two faces of Robert Fitzroy, Captain of HMS Beagle and governor of New Zealand.

    Science.gov (United States)

    Paul, Diane B; Stenhouse, John; Spencer, Hamish G

    2013-09-01

    Robert FitzRoy, Captain of HMS Beagle and second governor of New Zealand, has two contradictory reputations among modern academics. Evolutionary biologists and Darwin scholars generally view FitzRoy as a supporter of slavery, famously quarrelling with the abolitionist Darwin over that topic during a Brazilian stopover early in the voyage of HMS Beagle. He is also regarded as a political and religious reactionary, taking a biblically creationist position at the infamous 1860 Oxford meeting of the British Association for the Advancement of Science. New Zealand historians, however, view his record as governor much more positively. They emphasize that FitzRoy was wildly unpopular with the British settlers because of his enlightened insistence that the native Maori should be treated fairly. We outline the history of these seemingly inconsistent views and examine the evidence for each. We conclude by suggesting that a more nuanced account of FitzRoy's career would surely be more thought-provoking as well as respectful of the facts.

  12. Relative effectiveness of 239Pu and some other internal emitters for bone cancer induction in beagles

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Miller, S.C.; Taylor, G.N.; Bruenger, F.W.; Jee, W.S.S.; Angus, W.

    1994-01-01

    The toxicity ratio (relative effectiveness per gray of average skeletal dose) has been estimated for bone cancer induction in beagles injected as young adults with a number of bone-seeking internal emitters. These experiments yielded calculated toxicity ratios (± SD) relative to 226 Ra = 1.0 of 239 Pu = 16 ± 5 (single exposure to monomeric Pu) and 32 ± 10 (continuous exposure from an extraskeletal deposit in the body), 224 Ra = 16 ± 5 (chronic exposure) and approximately 6 ± 2 (single exposure), 228 Th = 8.5 ± 2.3, 241 Am = 6 ± 0.8, 228 Ra = 2.0 ± 0.5, 249 Cf = 6 ± 3, 252 Cf = 4 ±2, 90 Sr = 1.0 ± 0.5 (for high doses) and 0.05 ± 0.03 (for low doses) and 0.01 ± 0.01 (for extremely low doses). Because no skeletal malignancies were observed among beagles given only 253 Es, the toxicity ratio is undefined. 43 refs., 2 tabs

  13. Comparative toxicity of strontium-90 and radium-226 in beagle dogs

    International Nuclear Information System (INIS)

    Raabe, O.G.; Culbertson, M.R.; White, R.G.; Spangler, W.L.; Cain, G.R.; Parks, N.J.; Samuels, S.J.

    1990-01-01

    The authors are completing a 30-year study of the biologic effects of 90 Sr and 226 Ra in the beagle in order to predict the possible long-term hazards to people from chronic exposure to low levels of irradiation. Animals received either radionuclide by several means of administration: (a) continual ingestion of 90 Sr, (b) a single intravenous injection of 90 Sr, or (c) a series of eight intravenous injections of 226 Ra. Although administration of 90 Sr and 226 Ra ended at 540 days of age, the animals continued to receive chronic, low-level radiation doses from these bone-seeking radionuclides throughout life. This project is the largest single cohort study in beagles of internally deposited radionuclides. It is unique in use of the ingestion route for 90 Sr and in exposures that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with 90 Sr. The last of the dogs died in 1986 at age 18.5, but the authors are continuing to investigate the significance of these long-term exposures given at low dose rates with regard to cancer production, physiologic well-being, and shortening of life through the detailed records that were kept and by study of preserved materials. All the data have been successfully accumulated and entered into a main-frame computer data base management system. Current work is exclusively directed at preparing research papers summarizing the results and the associated biostatistical and survival analyses

  14. Comparative toxicity of strontium-90 and radium-226 in beagle dogs

    International Nuclear Information System (INIS)

    Raabe, O.G.; Culbertson, M.R.; White, R.G.; Spangler, W.L.; Cain, G.R.; Parks, N.J.; Samuels, S.J.

    1991-01-01

    The authors are completing a 30-year study of the biological effects of 90 Sr and 226 Ra in the beagle in order to predict the possible long-term hazards to people from chronic exposure to low levels of irradiation. Animals received either radionuclide by several means of administration: (a) continual ingestion of 90 Sr, (b) a single intravenous injection of 90 Sr, or (c) a series of eight intravenous injections of 226 Ra. Although administration of 90 Sr and 226 Ra ended at 540 days of age, the animals continued to receive chronic, low-level radiation doses from these bone-seeking radionuclides throughout life. This project is the largest single cohort study in beagles of internally deposited radionuclides. It is unique in use of the ingestion route for 90 Sr and in exposures that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with 90 Sr. The last of the dogs died in 1986 at age 18.5 years, but the authors are continuing to investigate the significance of these long-term exposures given at low dose rates with regard to cancer production, physiologic well-being, and shortening of life through the detailed records that were kept and by study of preserved materials. All the data have been successfully accumulated and entered into a main-frame computer data base management system. Current work is exclusively directed at preparing research papers summarizing the results and the associated biostatistical and survival analyses

  15. Consideration of age-dependent radium retention in people on the basis of the beagle model

    International Nuclear Information System (INIS)

    Parks, N.J.; Keane, A.T.

    1981-01-01

    This paper examines in humans the proposition emanating from studies in beagles that long-term retention of radium varies in proportion to the calcium addition rate at the time of intake. Because data on the calcium addition rate in younger humans were fragmentary, human calcium-addition rates were scaled from those in beagles, the relative calcium accretion rates in the two species at equivalent stages of skeletal growth providing the scaling factor. The variation of radium retention with age was determined by fitting a modified power function to data on the retention of radium from about 30 to 15,000 days following a series of therapeutic injections of 226 Ra in humans ranging in age from 18 to 63 yr. The fractional retention R at t days following a single injection of 226 Ra was described by R = (1 + t/d) - 0 44 . The age-dependent time constant d in the retention function was found to be proportional to the calcium addition rate at the time of injection in subjects receiving 226 Ra

  16. Age-related changes in the testes and prostate of the Beagle dog

    International Nuclear Information System (INIS)

    Lowseth, L.A.; Gerlach, R.F.; Gillett, N.A.; Muggenburg, B.A.

    1988-01-01

    Age-related changes in the histologic morphology of the Beagle dog prostate and testes must be separated from those changes that may result from the testing of experimental compounds. The prostate and testes of healthy age-matched Beagle dogs 3 to 14 yr of age were obtained. Serum to evaluate testosterone levels was also obtained from each dog at the time of euthanasia. Tissue sections from the prostate and testes were examined by light microscopy for both qualitative and quantitative morphologic assessment. A statistically significant increase in prostatic weight with increased age was noted. Significant morphometric findings in the prostate included a decrease in the relative percent of epithelial cells and an increase in the relative lumen size of glandular acini with increased age. The absolute volume of prostate interstitial tissue and inflammation showed a statistically significant increase with age. Stereological analysis of the testes showed a decrease in the relative percent epithelium with increasing age. No distinct age-related trend could be detected in serum testosterone levels. Serum testosterone levels did not correlate with the morphologic age-related changes observed in the testes or prostate. (author)

  17. Soft tissue organ masses of Beagles as a function of age

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Gillett, N.A.; Gerlach, R.F.

    1988-01-01

    Beagle dogs have been used for the past 30 yr for radio toxicological studies in several Department of Energy laboratories. Since the animals are maintained for their life span, it is important to recognize the potential importance of age-related changes in organ masses, particularly as they relate to dosimetry. To determine the extent and magnitude of soft-tissue organ mass changes relative to age and gender of Beagle dogs, groups of three male and three female dogs at ages 2.7, 6.0, 8.8, 11.7, and 14.0 yr were sacrificed. The resulting organ mass data were analyzed by linear regression both in terms of gross mass and mass normalized to whole-body mass. The results indicated that very little change in masses could be detected in this population over the age range studied, which includes the median life span of dogs In this colony. The rate of change of masses was shown to have an insignificant effect on the calculation of radiation dose, even over long time periods. (author)

  18. Pathologic changes in the hearts of beagles irradiated with fractionated fast neutrons or photons

    International Nuclear Information System (INIS)

    Zook, B.C.; Bradley, E.W.; Casarett, G.W.; Rogers, C.C.

    1981-01-01

    Thirty-nine adult male purebred beagles received either fast-neutron or photon irradiation to the right thorax to determine the effects on pulmonary tissue. The right atrium, a small portion of the right ventricle, and the right anterior abdomen were included in the field. Twenty-four dogs (six/group) received fast neutrons with a mean energy of 15 MeV to doses of 1000, 1500, 2250, or 3375 rad in four fractions per week for 6 weeks. Fifteen dogs received 3000, 4500, or 6750 rad of photons (five/group) in an identical fractionation pattern. Fourteen dogs died or were euthanatized in extremis between 47 and 708 days after radiation because of radiation damage to digestive organs. Six other dogs died of anesthetic accidents between 196 and 1144 days after radiation; these deaths were probably related to hepatic dysfunction. Two neutron-irradiated dogs developed cardiac neoplasms after 396 and 1624 days. One dog died of a myocardial infarct and one died of an unrelated infection. The major atrial lesions were hemorrhage and necrosis of myocardial cells in dogs that died 47-109 days postirradiation. Myocardial and endocardial fibrosis were most extensive in dogs that died 84 or more days following irradiation. All beagles had degenerative and occlusive vascular changes associated with atrial lesions. The relative biological effectiveness of fast neutrons for pathologic injury of the heart was estimated to be between 4 and 5

  19. Lymphocytopenia induced in beagle dogs by inhalation of 239PuO2

    International Nuclear Information System (INIS)

    Ragan, H.A.; Park, J.F.; Olson, R.J.; Buschbom, R.L.

    1976-01-01

    To determine the life-span dose-effect relationships of inhaled plutonium, we gave 124 beagle dogs a single exposure of 239 PuO 2 2 to 3 years ago at six different levels, i.e., 4, 20, 80, 300, 1100, or 5800 nCi mean initial alveolar depositions. Another group (20 dogs) served as controls. All dogs were about 18 months old. At the four highest exposure levels, a chronic lymphocytopenia developed which correlated with the initial alveolar plutonium burden in regard to magnitude of depression and time of development after exposure. The nadir occurred near 10 months after exposure in dogs receiving 5800, 1100, and 300 nCi, with corresponding lymphocyte levels 40, 55, and 75 percent, respectively, of those observed in control dogs. In the 80-nCi level the nadir occurred about 2 years after exposure at approximately 80 percent of control values. At the two lowest doses, i.e., 4 and 20 nCi, no effect on lymphocyte concentrations was noted 3 years after exposure. The persistent lymphocytopenia related to plutonium inhalation may be of significance in the subsequent development of pulmonary neoplasms previously observed in beagles at this laboratory 8 to 11 years after initial lung depositions of 200 to 1000 nCi of 239 Pu

  20. Lifetime effects of long-term exposures to strontium-90 and radium-226 in beagle dogs

    International Nuclear Information System (INIS)

    Book, S.A.; Rosenblatt, L.S.; Goldman, M.

    1986-01-01

    Graded doses of injected 226 Ra or ingested 90 Sr were given to 804 beagles in early life. The median survival times of the various irradiated groups at higher exposures were lower than the control value of 14.7 years. The 226 Ra group with the highest total skeletal dose had a median survival of 4.5 years. For 90 Sr the highest group had a median survival of 2.2 years. Normal life spans were evident in treatment groups with average skeletal doses of 226 Ra or of 2600 rads from 90 Sr. The life-shortening effects of 226 Ra and 90 Sr are related to the tumors produced from the radionuclide exposure. The significant causes of death among the 226 Ra-treated beagles were primary bone cancers, mostly osteosarcomas. Among dogs exposed to 90 Sr, significant numbers of deaths were from primary bone cancer, myeloproliferative disease, and squamous-cell carcinoma of the gingiva. In general, more of these effects were produced in the groups receiving higher doses and dose rates; at lower doses the effects, when present, appeared later than they did at higher doses. 9 refs., 6 figs., 4 tabs

  1. Evaluation of pharmacokinetics underlies the collaborated usage of lamivudine and oxymatrine in beagle dogs

    Directory of Open Access Journals (Sweden)

    Zhenbao Li

    2016-10-01

    Full Text Available Combinational therapy of lamivudine and oxymatrine has been employed in the battle against hepatitis B virus in clinical setting. However, the pharmacokinetic behavior of the drug or active metabolism in intravenous/oral co-administration regime is poorly investigated. Herein, we evaluated the pharmacokinetic characteristic through a tailor-designed 3 way crossover-Latin square experiment in adult male beagle dogs. Six dogs were randomly treated by intravenous administration of lamivudine (2.5 mg/kg, oxymatrine (15 mg/kg and combinational dosage, named as intravenous regime. Meanwhile the other six dogs were orally administrated with lamivudine (2.5 mg/kg, oxymatrine (15 mg/kg and combinational dosage, named as oral regime. The pharmacokinetic feature in simultaneous oral treatment appeared to have no significant difference when compared with individual administration, even including matrine, the active metabolite of oxymatrine. In intravenous regime, the main pharmacokinetic parameters of simultaneous administration were nearly consistent with intravenous regime remedy. The collaborated application of lamivudine and oxymatrine contributed to non-distinctive pharmacokinetic fluctuations of beagle dogs in intravenous/oral regime, compared with individual employment, which established a vital base for the clinical co-administration against hepatitis B. Furthermore, the present study demonstrated that the determination of pharmacokinetics between combinational and individual therapy might assist in the development of drug compatibility in clinical therapy.

  2. Radiation injury of the developing immune system in the beagle dog

    International Nuclear Information System (INIS)

    Miller, G.K.

    1982-01-01

    Fetal lymphoid organs of the beagle dog were studied to determine if the developing immune system displays an age-dependent sensitivity to ionizing radiation. Pregnant beagle dams received abdominal 60 Co gamma exposures to 200R or were sham irradiated at one of three ages in gestation; 35, 40, or 45 days postcoitus. The mean calculated dose to each fetus was 1.5 Gy. Half the fetuses in each litter were harvested by hysterotomy at five days and half at ten days postirradiation (PI). The volumes of the thymus lobules and lobular cortices were significantly reduced at five and ten days PI as compared to age matched controls. Radiation damage in the developing immune system was expressed in the lymphocyte populations of fetal lymphoid organs and in thymus epithelium. Damage was qualitatively and quantitatively more severe following irradiation earlier in gestation, confirming that the developing immune system displays an age-dependent sensitivity. Prenatal radiation injury to the developing lymphoid system could compromise postnatal immunologic function and could alter immunoregulation

  3. The removal of inhaled 239Pu from beagle dogs by bronchopulmonary lavage and chelation therapy

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Slauson, D.O.; Miglio, J.J.; Ruoff, L.; Mersch, S.; McClellan, R.O.

    1976-01-01

    The efficacy of bronchopulmonary lavage and chelatan therapy for removing 239 Pu from beagle dogs after inhalation of 239 Pu aerosols having different solubilities has been investigated. The four aerosols used were nebulized from a solution of 239 PuCl 4 and heat treated at temperatures of 325, 600, 900 and 1150 0 C. Groups of six beagle dogs were exposed to each of the aerosols. Subsequently, three dogs in each group were treated by lavage and intravenous injections of DTPA. The remaining three dogs in each group served as untreated controls. It was found that bronchopulmonary lavage treatment was effective in removing nearly half of the 239 Pu activity from the lung regardless of the aerosol production temperature. This early removal of 239 Pu activity resulted in a significant reduction in daily dose rate and therefore cumulative α dose to lung. The effectiveness of DTPA treatment depended on aerosol production temperature, and was effective in reducing accumulation of 239 Pu in liver and skeleton of the dogs that inhaled aerosols produced at 325 0 and 600 0 C by enhancing urinary excretion of 239 Pu. (U.K.)

  4. Mesozooplankton assemblages in two bays in the Beagle Channel (Argentina during January, 2001

    Directory of Open Access Journals (Sweden)

    Melisa Daiana Fernández-Severini

    2005-12-01

    Full Text Available This paper describes the composition and abundance of mesozooplankton of Bahía Ushuaia and Bahía Golondrina. These small bays are located in the northern Beagle Channel. Sampling was carried out from January 20 to 23, 2001 and samples were collected from the upper layer at nine stations. This study is the first research on mesozooplankton in this part of the Beagle Channel. Due to their dominance in the mesozooplankton community, we compared our Copepoda data with those reported by other authors from Antarctic coastal environments. By applying cluster analysis, we found two station groups in both bays: one in slightly polluted zones and the other in undisturbed external zones. Four assemblages in Bahía Ushuaia and two in Bahía Golondrina were determined by using non-metric multidimensional scaling (MDS and cluster analysis. Mesozooplanktonic assemblages showed a certain resemblance in zones with and without anthropogenic influence. Most of the copepod species in our samples are typical of the sub-Antarctic region. Oithona similis (=O. helgolandica sensu Ramírez, 1966, Oncaea curvata, and Ctenocalanus citer show either similar or higher abundances at Antarctic coastal sites, including the upper layer in oceanic areas, in comparison with sub-Antarctic coastal localities. This suggests that, in agreement with other findings, the Polar Front is probably not a major geographic boundary for the distribution of these species.

  5. Microanalysis of oligosaccharide HS203 in beagle dog plasma by postcolumn fluorescence derivatization method.

    Science.gov (United States)

    Sun, Shumeng; Zhao, Xia; Li, Guangsheng; Yu, Guangli; Xing, Xiaoxu; Zeng, Yangyang; Wu, Jian; Wang, Jianing

    2012-06-20

    A rapid and sensitive postcolumn fluorescence derivatization method was developed for microanalysis of antidiabetic oligosaccharide HS203 in beagle dog plasma. After plasma protein was removed by a simple and fast ultrafiltration method, chromatographic separation was performed on an Asahipak GS-320 HQ column with a mobile phase of 50 mmol/L phosphate buffer (pH 6.7) and acetonitrile (83/17, v/v). The column effluent was monitored by fluorescence detection at 249 nm (excitation) and 435 nm (emission) using guanidine hydrochloride as a postcolumn derivatizing reagent. A satisfactory resolution of the analyte was achieved and the limit of detection was found to be 4 ng (more sensitive than silver staining of HS203 in polyacrylamide gel electrophoresis). The method described above was successfully applied to a pharmacokinetic study of HS203 and to monitor blood glucose level simultaneously in beagle dog. It is also possible to be applied for microanalysis of other oligosaccharides in biological samples. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Radiographic evaluation of obesity-caused oppression of the thoracic cavity in beagles

    International Nuclear Information System (INIS)

    Morooka, T.; Niiyama, M.; Kougo, A.; Soya, M.; Nunome, K.

    2004-01-01

    Thoracic radiographs of fifteen beagles with mild-to-moderate obesity revealed that oppression of the thoracic cavity increased with increasing degree of obesity. Oppression of the thoracic cavity was evaluated based on the length, depth, width and area of the thoracic cavity. To obtain thoracic radiographs at the terminal inspiration and expiration phases, thoracic fluororadiographs were recorded with a digital video camera. Bodyweight and the depth of the back fat layer at the seventh lumbar vertebra (DB, measured by ultrasonography) were used as indicators of the degree of obesity. The length of the thoracic cavity tended to become shorter and the depth and width of the thoracic cavity tended to increase as bodyweight increased and as DB increased. On the other hand, the area of the thoracic cavity was not clearly related to bodyweight or DB. These results suggest that oppression of the thoracic cavity due to the cranial shift of the diaphragm is compensated for by increases in the depth and width of the thoracic cavity in beagles with mild-to-moderate obesity

  7. Occurrence of bone cancer among young adult Beagles given 239Pu

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Taylor, G.N.; Bruenger, F.W.; Angus, W.; Miller, S.C.

    1991-01-01

    Two hundred thirty-five young adult Beagles of both sexes were each given a single intravenous injection of 239 Pu-citrate at graded dose-levels averaging about 0.026 to 106 kBq/kg when they were about 1 1/2 years of age and were maintained for lifespan observation. An additional 133 young adult Beagles of both sexes were entered into the experiment as control animals. All of these animals have now died or have been removed from the colony, and the occurrence of skeletal malignancies has been determined from histological examination. There were a total of 85 radiographically apparent malignant bone tumors in 77 dogs given 239 Pu, and there was one control animal that developed a skeletal malignancy. Most of these were osteosarcomas, but there were seven chondrosarcomas of bone, one liposarcoma of bone, and in addition, there was one plasma cell myeloma and one ameloblastoma (admantinoma). Only those dogs that survived to at least the minimum latent period for death with radiation-induced bone sarcoma are included in the tabulation. There appeared to be a linear relationship between the percent of dogs with bone tumor and the average skeletal dose up to a dose of about 1 Gy. All dose-levels with skeletal doses of about 2 Gy and greater exhibited close to 100% occurrence

  8. Soft tissue organ masses of Beagles as a function of age

    Energy Technology Data Exchange (ETDEWEB)

    Guilmette, R A; Gillett, N A; Gerlach, R F

    1988-12-01

    Beagle dogs have been used for the past 30 yr for radio toxicological studies in several Department of Energy laboratories. Since the animals are maintained for their life span, it is important to recognize the potential importance of age-related changes in organ masses, particularly as they relate to dosimetry. To determine the extent and magnitude of soft-tissue organ mass changes relative to age and gender of Beagle dogs, groups of three male and three female dogs at ages 2.7, 6.0, 8.8, 11.7, and 14.0 yr were sacrificed. The resulting organ mass data were analyzed by linear regression both in terms of gross mass and mass normalized to whole-body mass. The results indicated that very little change in masses could be detected in this population over the age range studied, which includes the median life span of dogs In this colony. The rate of change of masses was shown to have an insignificant effect on the calculation of radiation dose, even over long time periods. (author)

  9. Comparison of axillary and rectal temperatures for healthy Beagles in a temperature- and humidity-controlled environment.

    Science.gov (United States)

    Mathis, Justin C; Campbell, Vicki L

    2015-07-01

    To compare axillary and rectal temperature measurements obtained with a digital thermometer for Beagles in a temperature- and humidity-controlled environment. 26 healthy Beagles (17 sexually intact males and 9 sexually intact females). Dogs were maintained in a temperature- and humidity-controlled environment for 56 days before rectal and axillary temperatures were measured. Axillary and rectal temperatures were obtained in triplicate for each dog by use of a single commercially available manufacturer-calibrated digital thermometer. Mean rectal and axillary temperatures of Beagles maintained in a temperature- and humidity-controlled environment were significantly different, with a median ± SD difference of 1.4° ± 0.15°C (range, 0.7° to 2.1°C). Mean rectal and axillary temperatures were 38.7°C (range, 37.6° to 39.5°C) and 37.2°C (range, 36.6° to 38.3°C), respectively. Results of this study indicated that the historical reference of a 0.55°C gradient between rectal and axillary temperatures that has been clinically used for veterinary patients was inaccurate for healthy Beagles in a temperature- and humidity-controlled environment. Rectal and axillary temperatures can be measured in veterinary patients. Reliable interpretation of axillary temperatures may accommodate patient comfort and reduce patient anxiety when serial measurement of temperatures is necessary. Further clinical studies will be needed.

  10. Comparison of freely-moving telemetry Chinese Miniature Experiment Pigs (CMEPs) to beagle dogs in cardiovascular safety pharmacology studies.

    Science.gov (United States)

    Yuan, Haitao; Zhao, Jing; Guo, Jiabin; Wu, Ruiqin; He, Li; Cui, Yaxiong; Feng, Min; Zhang, Tingfen; Hou, Mingyue; Guo, Qian; Zhang, Lijun; Jia, Li; Huang, Chang; Ye, Lin; Peng, Shuangqing

    2014-01-01

    Telemetry beagle dogs are the most frequently used species in cardiovascular telemetry assessments. However, beagle dogs may not be always suitable for all of the tests. Recently minipigs have received increased attention for these studies. Differences between the two species regarding the response of their cardiovascular systems to environmental stimuli are unclear. This study investigates how the telemetry minipig compares to beagle dog as a test subject and also refines the experimental protocols necessary to obtain accurate data. Beagle dogs and Chinese Miniature Experiment Pigs (CMEPs) were implanted with telemetry transmitters and the influences of gavage, feeding and the circadian cycle on various cardiovascular parameters were investigated. ECG signal quality from CMEPs was superior to that of the beagle dogs. Poor ECG signal quality, elevated HR, BP and locomotor activity associated with gavage and feeding were observed in both species. ECG signal quality, BP and locomotor activity recovered more quickly in the CMEPs than in the beagle dogs. Residual elevation of HR found in CMEPs lasted approximately 4h post-feeding, which has a profound influence on the circadian cycle. A diurnal rhythm in CMEP with a significant increase of body temperature during the dark period and a clear circadian rhythm of locomotor activity in both species were observed. The present data demonstrated that gavage, feeding and circadian cycle were having an enormous influence on BP, HR and locomotor activity in both species. If drug-induced effects are expected rapidly after oral administration and feeding, CMEP seems to be a favorable choice. Also, due to the effects of feeding on HR, CMEPs should fast at least 5h before the start of recording or should not be fed during the study where the Tmax of a given compound might occur very late. It also should be taken into consideration when the test article has a potential effect on body temperature by using CMEPs. In summary, the

  11. Deposition of 239Pu in the skeleton and soft tissues of beagles: effect of age at time of injection

    International Nuclear Information System (INIS)

    Stevens, W.; Atherton, D.R.; Bates, D.; Bruenger, F.W.

    1976-01-01

    Previous reports from the laboratory have clearly defined the whole body deposition of 239 Pu in beagles injected as young adults (18 mo.). However, deposition has not been evaluated as a function of skeletal maturity at the time of injection. Juvenile beagles 3 months of age were injected with 0.1 μCi 239 Pu/kg in 0.08 M citrate buffer, pH 3.5. Six of these beagles have been sacrificed at short times after injection for distribution data. Another group receiving 3.0 μCi 239 Pu/kg was allowed to live until osteosarcoma developed and they were autopsied (1228 days average). Finally an aged beagle (81 mo.) was injected with 0.1 μCi/kg plutonium (P 2.0) and sacrificed 2 weeks later. Selected soft tissues, 1/2 of the symmetrical skeleton, and a known fraction of the asymmetrical skeleton were collected and analyzed for Pu content. Independent of the age at injection, a total of approximately 80 percent of the Pu was initially deposited in liver plus skeleton, however the age of the animal at time of injection altered the relative proportion in liver and skeleton in a reciprocal manner. The percent of the injected Pu found in the liver at 14 days P.I. increased with the increase in age at time of injection (13.2 percent at 3 months, 30.9 percent at 18 months and 36.9 percent at 81 months). The lower the age at injection, the larger was the fraction of 239 Pu deposited in the skeleton. The amounts ranged from an average of 69 percent in animals injected at 3 months to 49 percent in dogs injected at 18 months and 40 percent in the dog injected at 81 months of age. The difference in skeletal deposition reflects the different rates of bone growth and remodeling in juveniles, young adults and aged beagles

  12. Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration.

    Science.gov (United States)

    Feng, Ru; Zhao, Zhen-Xiong; Ma, Shu-Rong; Guo, Fang; Wang, Yan; Jiang, Jian-Dong

    2018-01-01

    Berberine (BBR) is considered a multi-target drug that has significant advantages. In contrast to its significant pharmacological effects in clinic, the plasma level of BBR is very low. Our previous work revealed that dihydroberberine (dhBBR) could be an absorbable form of BBR in the intestine, and butyrate is an active metabolite that is generated by gut bacteria in rats. In this study, for the first time we describe gut microbiota-regulated pharmacokinetics in beagle dogs after oral administration of BBR by single (50 mg/kg) or multiple doses (50 mg/kg/d) for 7 days. GC-MS, GC, LC-MS/MS, and LC/MS n -IT-TOF were used to detect dhBBR, butyrate and BBR as well as its Phase I and II metabolites, respectively. The results showed that dhBBR was not detected in dog plasma but was excreted in small amounts in the feces of dogs examined on days 3 and 7. Butyrate was generated by gut bacteria and increased by 1.3- and 1.2-fold in plasma or feces, respectively, after 7 days of BBR treatment compared to the levels before treatment. Changes of intestinal bacterial composition were analyzed by 16S rRNA genes analysis. The results presented that dogs treated with BBR for 7 days increased both the abundance of the butyrate- and the nitroreductases- producing bacteria. We also identified chemical structures of the Phase I and II metabolites and analyzed their contents in beagle dogs. Eleven metabolites were detected in plasma and feces after BBR oral administration (50 mg/kg) to dogs, including 8 metabolites of Phase I and III metabolites of Phase II. The pharmacokinetic profile indicated that the concentration of BBR in plasma was low, with a C max value of 36.88 ± 23.45 ng/mL. The relative content of glucuronic acid conjugates (M11) was higher than those of other metabolites (M1, M2, M12, and M14) in plasma. BBR was detected in feces, with high excreted amounts on day 3 (2625.04 ± 1726.94 μg/g) and day 7 (2793.43 ± 488.10 μg/g). In summary, this is the first study to

  13. [Plasma ibuprofen enantiomers and their pharmacokinetics in Beagle dogs determined by HPLC].

    Science.gov (United States)

    Wang, Hong-yan; Kong, Ai-ying; Yang, Bo; Yan, Liang-ping; Di, Xin

    2015-12-01

    A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76

  14. Study of four week repeated dose toxic test of Sweet Bee Venom in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jae-Seuk Park

    2010-12-01

    Full Text Available Objectives: This study was performed to analyse four week repeated dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of four week repeated dose toxicity of Sweet BV which was administered at the level of 0.56㎎/㎏ body weight which is eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups were appealed pain sense in the treating time compared to the control group, and hyperemia and movement disorder were observed around the area of administration in all experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. In the urine analysis, CBC and biochemistry didn't show any significant changes in the experiment groups compared with control group. 5. For weight measurement of organs, experiment groups didn't show any significant changes compared with control group. 6. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, cerebrum, liver, lung, kidney, and spinal cords were removed and conducted histologocal observation with H-E staining. In the histologocal observation of thigh muscle, cell infiltration, inflammatory, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes were depend on the dose of Sweet BV. But another organs were not detected in any abnormalities. 7

  15. Effects of whole-body, ionizing radiation on the semen in beagle dogs

    International Nuclear Information System (INIS)

    Day, P.A.

    1988-01-01

    Six beagle dogs were exposed to a total dose of 183 R of gamma radiation at a dose rate of 1 R/day, while three other dogs were exposed to a single dose of 100 R. Weekly semen analysis was performed on all irradiated dogs plus four nonirradiated dogs. Semen volume, sperm concentration, total sperm count, sperm motility and sperm head morphometry were examined. Dogs exposed to chronic radiation showed a severe decline in sperm numbers, detected after seven weeks of exposure. Sperm concentration and total sperm count were the first parameters affected and were the only parameters consistently affected. The dogs exposed to 100 R as a single dose, did not show a significant decline in sperm numbers. During a 36 week recovery period, the chronically irradiated dogs did show a slight increase in sperm numbers, but they never approached pre-exposure levels

  16. Expression of Kirsten murine sarcoma virus sequences in Beagle dog tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kerkof, P R; Kelly, G

    1988-12-01

    Labeled cDNA synthesized from RNA extracted from {sup 238}PuO{sub 2}-, {sup 239}PuO{sub 2}-, and {sup 90}Sr-induced lung tumors in Beagle dogs, from nontumor tissue from {sup 239}PuO{sub 2}-exposed dogs, and from unexposed dog lung and liver tissue produces strong hybridization signals with a plasmid (pKSma) that contains Kirsten murine sarcoma virus (KMSV) sequences. At least 90 percent of the KMSV sequences are expressed in these dog tissues, including sequences corresponding to p21 K-ras, qp70 envelope glycoprotein, and at least one other proviral sequence. The expression of Kirsten ras and other sarcoma virus sequences may have important implications for the interpretation of carcinogenesis studies in these dogs. (author)

  17. Immunohistochemical detection of epidermal growth factor receptor in radiation-induced lung tumors in Beagle dogs

    Energy Technology Data Exchange (ETDEWEB)

    Gillett, N A; Haley, P J; Hahn, F F

    1988-12-01

    Increased levels of epidermal growth factor receptor have been reported in a variety of tumors, including pulmonary squamous cell carcinomas in man. The purpose of this study was to determine if increased levels of epidermal growth factor (EGFR) were present in lung tumors from Beagle dogs that had been exposed to {sup 239}PuO{sub 2}- Using immunohistochemical techniques, sections from 17 lung tumors were examined for the presence of EGFR. Seven of the tumors were strongly positive for EGFR; the remainder of the tumors and the normal lung sections were negative. The positive immunostaining could not be correlated with the histologic phenotype of the tumors. Work is in progress to determine the level of EGFR in preneoplastic, proliferative epithelial foci in the Iung. (author)

  18. Biological effects of cesium-137 injected in beagle dogs of different ages

    Energy Technology Data Exchange (ETDEWEB)

    Nikula, K.J.; Muggenburg, B.A.; Griffith, W.C. [and others

    1995-12-01

    The toxicity of cesium-137 ({sup 137}Cs) in the Beagle dog was investigated at the Argonne National Laboratory (ANL) as part of a program to evaluate the biological effects of internally deposited radionuclides. The toxicity and health effects of {sup 137}Cs are important to understand because {sup 137}Cs is produced in large amounts in light-water nuclear reactors. Large quantities of cesium radioisotopes have entered the human food chain as a result of atmospheric nuclear weapons test, and additional cesium radioisotopes were released during the Chernobyl accident. Although the final analyses are not complete, three findings are significant: older dogs dies significantly earlier than juvenile and young adult dogs; greater occurrence of sarcomas in the cesium-137 injected dogs; the major nonneoplastic effect in dogs surviving beyond 52 d appears to be testicular atrophy.

  19. Lifetime tumor risk coefficients for beagle dogs that inhaled cerium-144 chloride

    Energy Technology Data Exchange (ETDEWEB)

    Boecker, B.B.; Hahn, F.F.; Griffith, W.C. [and others

    1995-12-01

    Reported here is one of the life-span radionuclide toxicology studies being conducted at ITRI in Beagle dogs. These studies are examining the life-span health risks of inhaled {Beta}-, {gamma}- and {alpha}-emitting radionuclides to expand available knowledge on these risks especially for the many cases for which human data are not available. The outcomes of these studies are providing important information on dosimetry and dose-response relationships for these inhaled radionuclides and the relative importance of a broad range of dose- and effect-modifying factors. A number of these studies are currently coming to completion. Much of the ITRI effort is being directed to final reviews of the dosimetric, clinical, and pathologic results and writing summary manuscripts. Radiation doses and effects in tissues adjacent to bone, specifically those of epithelial or marrow origin, should be considered when determining risks from internally deposited, bone-seeking radionuclides such as {sup 144}Ce.

  20. Lifetime tumor risk coefficients for beagle dogs that inhaled cerium-144 chloride

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Griffith, W.C.

    1995-01-01

    Reported here is one of the life-span radionuclide toxicology studies being conducted at ITRI in Beagle dogs. These studies are examining the life-span health risks of inhaled Β-, γ- and α-emitting radionuclides to expand available knowledge on these risks especially for the many cases for which human data are not available. The outcomes of these studies are providing important information on dosimetry and dose-response relationships for these inhaled radionuclides and the relative importance of a broad range of dose- and effect-modifying factors. A number of these studies are currently coming to completion. Much of the ITRI effort is being directed to final reviews of the dosimetric, clinical, and pathologic results and writing summary manuscripts. Radiation doses and effects in tissues adjacent to bone, specifically those of epithelial or marrow origin, should be considered when determining risks from internally deposited, bone-seeking radionuclides such as 144 Ce

  1. Comparison of radiological changes in humans exposed to radium and in beagle dogs injected with radium

    International Nuclear Information System (INIS)

    Morgan, J.P.; Kirsh, J.E.; Pool, R.R.

    1982-01-01

    Data from MIT and New Jersey studies were combined with data from the Center for Human Radiobiology, Argonne National Laboratory, to create a material of 2259 persons occupationaly exposed to radium. The population studied consisted of radium-dial painters, radium chemists, and persons who had received radium in past years in attempts to treat various medical conditions. Within a colony of beagle dogs at the LEHR, UCD, which received eight semi-monthly injections of 226 Ra were 28 dogs that received a dosage of 80 to 130 times maximum permissible skeletal burden for man (0.1 μCi 226 Ra). The intravenous injections of 226 Ra began at 435 days of age

  2. Biological effects of inhaled 144CeCl3 in beagle dogs

    International Nuclear Information System (INIS)

    Hahn, F.F.; Boecker, B.B.; Griffith, W.C.; Muggenburg, B.A.

    1997-01-01

    Data on biological effects in humans exposed briefly to high levels of external X or gamma irradiation provide the foundation of protection guidelines for low linear energy transfer (LET) radiation. Unfortunately, the extrapolation of the risk of these biological effects to humans exposed to internally deposited radionuclides is complicated by the protracted exposure and differences in local doses to organs and tissues that result from internal irradiation. Therefore, data from humans exposed to external radiation may not provide all of the information necessary to understand the long-term health effects of internally deposited, beta-particle-emitting radionuclides. Because of these uncertainties, it is important to determine the spatial and temporal distribution of radionuclides such as radiocerium in the body and the relationship of their distribution to biological effects that result from acute inhalation exposure. The radiation effects of inhaled cerium 144 were studied in beagles

  3. Long-term accumulation and microdistribution of uranium in the bone and marrow of beagle dog.

    Science.gov (United States)

    Arruda-Neto, J D T; Manso Guevara, M V; Nogueira, G P; Taricano, I D; Saiki, M; Zamboni, C B; Bonamin, L V; Camargo, S P; Cestari, A C; Deppman, A; Garcia, F; Gouveia, A N; Guzman, F; Helene, O A M; Jorge, S A C; Likhachev, V P; Martins, M N; Mesa, J; Rodriguez, O; Vanin, V R

    2004-08-01

    The accumulation and microdistribution of uranium in the bone and marrow of Beagle dogs were determined by both neutron activation and neutron-fission analysis. The experiment started immediately after the weaning period, lasting till maturity. Two animal groups were fed daily with uranyl nitrate at concentrations of 20 and 100 microg g(-1) food. Of the two measuring techniques, uranium accumulated along the marrow as much as in the bone, contrary to the results obtained with single, acute doses. The role played by this finding for the evaluation of radiobiological long-term risks is discussed. It was demonstrated, by means of a biokinetical approach, that the long-term accumulation of uranium in bone and marrow could be described by a piling up of single dose daily incorporation.

  4. Toxicity of injected 137CsCl in Beagle dogs. XVIII

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1984-01-01

    Studies of the metabolism, dosimetry, and effects of intravenously administered 137 CsCl in the Beagle dog are being conducted to aid in assessing the biological consequences of exposure to 137 Cs that might occur in the event of certain nuclear accidents. Effects of the chronic, relatively uniform whole-body exposures produced by 137 CsCl are being compared with other diverse radiation dose patterns resulting from inhalation of radioactive aerosols. The fifty-four dogs that were injected with 137 CsCl have died, as have eleven control dogs; three control dogs died during the past year. Observations are continuing on the surviving control dog. 2 references, 2 figures, 1 table

  5. Spontaneous necrotizing sialometaplasia of the submandibular salivary gland in a Beagle dog.

    Science.gov (United States)

    Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

    2015-07-01

    A single mass was found on the left submandibular salivary gland at necropsy of a 15-month-old male commercially bred laboratory Beagle dog from a control dose group from a repeat toxicity study. Microscopically, the mass was composed of a well-demarcated area of coagulative necrosis surrounded and separated from the normal salivary gland tissue by a thick fibrovascular capsule. Necrosis was admixed with areas of hemorrhage, fibrin, edema, fibrinoid necrosis of the vascular tunica media, and thrombosis of small and large vessels. Within the necrotic tissue, there was marked ductal hyperplasia, and squamous metaplasia of duct and acinar epithelium. The mass was diagnosed as necrotizing sialometaplasia of the submandibular gland. Hyperplastic ductal elements and squamous metaplasia can be mistaken microscopically with squamous cell carcinoma. Therefore, pathologists should be aware of this lesion as to avoid errors in the diagnosis of this benign pathologic condition.

  6. Single inhalation exposure to 90SrCl2 in the Beagle dog: early hematological effects

    International Nuclear Information System (INIS)

    Gillett, N.; Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.; Rebar, A.H.; McClellan, R.O.

    1985-01-01

    Young adult Beagle dogs were exposed once to aerosols containing 90 SrCl 2 to obtain initial body burdens ranging from 2.5 to 250 uCi 90 Sr/kg body weight and subsequently observed throughout their life span. All of the dogs are now dead. The primary cause of death over the entire length of the study was radiation-induced osteosarcomas. However, six dogs died at less than 30 days after exposure as a result of a radiation-induced bone marrow aplasia. Review of hematological parameters of all dogs showed a similar, consistent, and often dramatic pancytopenia in those animals having a long-term retained burden of greater than 10 uCi 90 Sr/kg. The hematologic changes were similar to those seen in people exposed to high doses of whole body external radiation. 4 references, 1 figure, 1 table

  7. Toxicity of 239PuO2 inhaled by aged Beagle dogs. X

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Hahn, F.F.; Gillett, N.A.; Guilmette, R.A.; Boecker, B.B.; McClellan, R.O.

    1988-01-01

    The influence of age at exposure on the metabolism, dosimetry, and biological effects of inhaled 239 PuO 2 particles is being studied in aged Beagle dogs (8.0-10.5 yr of age at exposure). Forty-eight dogs inhaled 239 PuO 2 particles with an activity median aerodynamic diameter of 1.5 mm to achieve graded levels of initial pulmonary burdens (IPB) ranging from 0.02-0.66 μCi 239 Pu/kg body weight (0.75-24 kBq/kg). Twelve other dogs were exposed to the aerosol diluent only. All forty-eight exposed dogs have died, including two in the past year. The twelve control dogs have also died, including one in the past year. Radiation pneumonitis and pulmonary fibrosis have been the primary causes of death in these aged dogs exposed to 239 PuO 2 . (author)

  8. Further characterization of serum alkaline phosphatase from male and female beagle dogs.

    Science.gov (United States)

    Amacher, D E; Higgins, C V; Schomaker, S J; Clay, R J

    1989-01-01

    Alkaline phosphatase (AP) from the sera of both male and female beagle dogs was partially purified and then analyzed for the presence of AP isoenzymes having intestinal or osseous characteristics as detected by bromotetramisole inhibition or wheat germ lectin agarose electrophoresis, respectively. The sera from both sexes were similar in regard to the presence of AP isoenzymes with intestinal (16 vs. 20%) or osseous (19 vs. 23%) characteristics, but serum AP from the male had a greater sialic acid content and only the male serum contained a detectable constitutive acidic (pI = 3.4) AP isoenzyme. This was similar to a serum AP isoenzyme previously found elevated in the sera of dogs afflicted with hyperadrenocorticalism or of dogs treated with certain corticosteroids.

  9. Toxicity of inhaled 239PuO2 in immature beagle dogs

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Muggenburg, B.A.; Hahn, F.F.; Mauderly, J.L.; Boecker, B.B.; McClellan, R.O.

    1980-01-01

    Immature beagle dogs have been exposed by inhalation to a 1.5 μm aerodynamic diameter monodisperse aerosol of 239 PuO 2 to compare the biological effects with those seen in young adult and aged dogs exposed to a similar aerosol. To date, 18 dogs have been exposed to the aerosol, resulting in graded initial lung burdens ranging from 0.003 to 0.38 μCi/kg body weight. Two dogs have been exposed to the aerosol diluent and serve as controls. Two of the 18 exposed animals were sacrificed 8 days after exposure to provide information on initial deposition and distribution. All other exposed animals are alive 400 days after exposure. No dogs were exposed during the past year because of an outbreak of canine parvovirus enteritis which caused death in 8 to 10 week-old dogs

  10. Malignancy as a cause of death in nonsacrifice Segment III beagles receiving gamma radiation during development

    International Nuclear Information System (INIS)

    Benjamin, S.A.; Hargis, A.M.; Lovering, S.L.; Thomassen, R.W.; Angleton, G.M.; Lee, A.C.; Brewster, R.D.; Brooks, R.K.

    1979-01-01

    As of December 31, 1978, 31 Segment III beagles had died or been euthanatized because of a malignant neoplasm. Twenty-five of the 31 had been irradiated. Fifteen of the 25 irradiated dogs were exposed at either 55 days postcoitus (dpc) or 2 days postpartum (dpp) to 20 or 100R. Of these 15, 4 dogs irradiated at either 55 dpc or 2 dpp died with malignancies prior to 2 years of age, an unusual occurrence in the dog. Eight irradiated and no control dogs developed malignant lymphoma. Four of the dogs with lymphoma were irradiated at 55 dpc. These findings suggest a relatively high sensitivity for radiation carcinogenesis in dogs exposed in the perinatal period

  11. Toxicity of 90Y in a relatively insoluble form inhaled by Beagle dogs. XIV

    International Nuclear Information System (INIS)

    Hahn, F.F.; Hobbs, C.H.; Kusewitt, D.F.; McClellan, R.O.; Mauderly, J.L.; Pickrell, J.A.

    1982-01-01

    The metabolism, dosimetry and biological effects of inhaled 90 Y in fused aluminosilicate particles in Beagle dogs are being studied. Eighty-nine dogs with initial lung burdens ranging from 80 to 5200 μCi 90 Y/kg body weight and 12 control dogs are being maintained for life span observations. The lung burdens achieved, short physical half-life and relative insolubility of the 90 Y in this vector resulted in a relatively high, rapidly decreasing radiation dose rate to the lung. To date, 69 exposed dogs have died; 38 from radiation pneumonitis, seven with pulmonary neoplasms and 24 from other causes. Four control dogs have died. Twenty-nine surviving exposed and eight control dogs are being studied for their life spans

  12. Toxicity of inhaled 144CeCl3 in beagle dogs

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.; McClellan, R.O.; Pickrell, J.A.

    1980-01-01

    The metabolism, dosimetry and effects of inhaled 144 CeCl 3 in beagle dogs are being studied to assess the biological consequences of inhaling 144 Ce. Studies have shown that the 144 Ce deposited in the lung as 144 CeCl 3 is translocated at a moderately rapid rate to liver and skeleton and that significant radiation doses are accumulated by all three organs. Fifty-five dogs that inhaled 144 CeCl 3 and 17 control dogs are being observed for their life span. The 144 Ce-exposed dogs had long-term retained burdens that ranged from 2.6 to 360 μCi 144 Ce/kg body weight. Fifty-three of the dogs exposed to 144 CeCl 3 have died and twelve control dogs have died. Serial observations are continuing on the two surviving exposed dogs and five control dogs

  13. Toxicity of 90Sr inhaled in a relatively insoluble form by Beagle dogs. XIV

    International Nuclear Information System (INIS)

    Snipes, M.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1983-01-01

    Beagle dogs were exposed by inhalation to 90 Sr in a relatively insoluble form to study long-term health effects. Lung burdens ranged from 0.12 to 96 μCi of 90 Sr/kg body weight. High levels of exposure resulted in radiation pneumonitis and pulmonary fibrosis; lower level exposures caused long-term effects, including cancer of the lung, heart, and tracheobronchial lymph modes. Most of these tumors were hemangiosarcomas. Two control dogs and two 90 Sr-exposed dogs died or were euthanized during the past year. One exposed dog died with hemangiosarcoma of the spleen; the other exposed dog died with pulmonary thrombosis. One control dog died of pulmonary carcinoma, and the other control dog died of a carcinoma of the bladder. The remaining 19 exposed and 11 control dogs are being maintained for lifetime observation

  14. Pharmacokinetic evaluation of Shenfu Injection in beagle dogs after intravenous drip administration

    Directory of Open Access Journals (Sweden)

    Yuqiao Zhang

    2016-10-01

    Full Text Available Shenfu Injection (SFI is a well-defined Chinese herbal formulation that is obtained from red ginseng and processed aconite root. The main active constituents in SFI are ginsenosides and aconitum alkaloids. In this work, ginsenosides (ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rc and aconitum alkaloids (benzoylmesaconine and fuziline were used as the index components to explore the pharmacokinetic behavior of SFI. A selective and sensitive HPLC–MS/MS method was developed for the quantification of ginsenosides and aconitum alkaloids in dog plasma and was used to characterize the pharmacokinetics of the five index components after intravenous drip of three different dosages of SFI in beagle dogs. The pharmacokinetic properties of the index components were linear over the dose range of 2–8 mL/kg.

  15. Clearance patterns for 111In-oxide particles deposited in specific airways of beagle dogs

    International Nuclear Information System (INIS)

    Snipes, M.B.; Muggenburg, B.A.; Griffith, W.C.; Guilmette, R.A.

    1994-01-01

    The International Commission on Radiological Protection (ICRP) has incorporated long-term retention of radioactive particles in conducting airways into its newly approved respiratory tract dosimetry model. This model is purported to provide a better basis for assessing risk associated with human inhalation exposures to radioactive particles. However, applying the new model requires an understanding of particle retention patterns in conducting airways of the lung. Studies are being conducted at ITRI to quantify long-term retention patterns for particles deposited at specific sites in conducting airways of Beagle dogs. The dog was selected as a model because long-term retention and clearance patterns for particles deposited in the lungs of dogs and humans are similar

  16. Case report: study of a beagle with a malignant ectopic thyroid tumor

    International Nuclear Information System (INIS)

    Brewster, R.D.; Miller, C.W.; Stephens, L.C.; Jaenke, R.S.

    1981-01-01

    A Segment III beagle was noted clinically to have cervical edema and muffled heart sounds. Radiographically, masses were found at the base of the heart and throughout the lung field. An electrocardiogram revealed right bundle branch blockage. An echocardiogram demonstrated thickening of the left ventricle and conduction disturbances in the heart which could not be visualized by conventional diagnostic techniques. At necropsy, a neoplasm was found at the base of the heart that had extended into the pulmonary artery, right atria-auricle, interatrial septum, dorsal interventricular septum, and between the pericardium and epicardium over the surface of the right and left ventricles. The location of the tumor masses accounted for the clinical signs and the abnormalities in the electrocardiogram and echocardiogram. Light and electron microscopic examination of the neoplasm at the base of the heart and metastatic neoplasms in the lungs, kidney, and pancreas established a diagnosis of malignant ectopic thyroid tumor

  17. Pyovagina and stump pyometra in a neutered XX sex-reversed Beagle: a case report

    International Nuclear Information System (INIS)

    Williams, J.; Partington, B.P.; Smith, B.; Hedlund, C.S.; Law, J.M.

    1997-01-01

    An 18-month-old, neutered male beagle presented with acute abdominal signs and a suppurative infection of the urogenital tract. Chromosomal sex was female (78, XX), gonadal sex was male (testicles), and phenotypic sex was ambiguous, with evidence of both male and female duct systems. The internal and external genitalia consisted of epididymides, an underdeveloped uterus with an immature spermatic cord, communication between the uterus or cranial vagina and the membranous urethra, a urethrographically male urethra, a hypoplastic os penis, and a hypoplastic penis with hypospadia. Based on these findings and the familial history of a similarly affected litter mate, the dog was diagnosed as having the XX male syndrome with pyovagina and uterine stump pyometra. Radiographic and ultrasonographic investigations are described, and abnormalities of chromosomal sex, gonadal sex, and phenotypic sex are discussed

  18. Late biological effects of 137CsCl injected in beagle dogs

    International Nuclear Information System (INIS)

    Nikula, K.J.; Muggenburg, B.A.; Griffith, W.C.; Hahn, F.F.; Boecker, B.B.

    1994-01-01

    The toxicity of intravenously administered 137 CsCl in the Beagle dog was investigated as part of the ITRI program to evaluate the biological effects of internally deposited fission product radionuclides. The toxicity and health effects of 137 Cs are important to understand because 137 Cs is produced in large amounts in light-water nuclear reactors. Also, large quantities of cesium radioisotopes have entered the human food chain as a result of atmospheric nuclear weapons tests and additonal cesium radioisotopes were released during the Chernobyl accident. The intravenous route of exposure was chosen because it was known that after intravenous injection, inhalation, or ingestion, internally deposited 137 CsCl is rapidly adsorbed and distributed throughout the body, exposing the whole body to beta and gamma radiation, and because of the reduced radiation protection problems associated with high-level exposure via injection compared to these other routes

  19. Toxicity of injected 137CsCl in Beagle dogs. XVI

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.; Redman, H.C.

    1983-01-01

    Studies of the metabolism, dosimetry, and effects of intravenously administered 137 CsCl in the Beagle dog are being conducted to aid in assessing the biologic consequences of exposure to 137 Cs that might occur in the event of certain nuclear accidents. Effects of the chronic, relatively uniform whole-body exposures produced by 137 Cs are being compared with other diverse radiation dose patterns resulting from inhalation of radioactive aerosols. Fifty-four of the dogs that were injected with 237 CsCl have died, as have eight control dogs; four exposed and two control dogs died during the past year. Serial observations are continuing on the surviving four control dogs

  20. Expression of Kirsten murine sarcoma virus sequences in Beagle dog tissues

    International Nuclear Information System (INIS)

    Kerkof, P.R.; Kelly, G.

    1988-01-01

    Labeled cDNA synthesized from RNA extracted from 238 PuO 2 -, 239 PuO 2 -, and 90 Sr-induced lung tumors in Beagle dogs, from nontumor tissue from 239 PuO 2 -exposed dogs, and from unexposed dog lung and liver tissue produces strong hybridization signals with a plasmid (pKSma) that contains Kirsten murine sarcoma virus (KMSV) sequences. At least 90 percent of the KMSV sequences are expressed in these dog tissues, including sequences corresponding to p21 K-ras, qp70 envelope glycoprotein, and at least one other proviral sequence. The expression of Kirsten ras and other sarcoma virus sequences may have important implications for the interpretation of carcinogenesis studies in these dogs. (author)

  1. Omental leiomyosarcoma with unusual giant cells in a Beagle dog - Short communication.

    Science.gov (United States)

    Sasaki, Jun; Toyoshima, Megumi; Okamura, Yasuhiko; Goryo, Masanobu

    2016-06-01

    A 10-year-old castrated male Beagle dog was presented with a 2-month history of intermittent vomiting and abdominal pain. The dog was referred to the Veterinary Teaching Hospital at Iwate University for further evaluation, and a splenic tumour was suspected on the basis of ultrasonography and computed tomography. Surgery identified a large, solid, light-pink mass on the greater omentum with blood-coloured ascites in the abdominal cavity, and resection was performed. Microscopically, the mass comprised spindle-shaped tumour cells and scattered osteoclast-like giant cells. Most spindle-shaped cells were positive for vimentin, desmin, and smooth muscle actin (α-SMA), whereas osteoclast-like giant cells were positive only for vimentin. On the basis of histopathological and immunohistochemical findings, a diagnosis of leiomyosarcoma was made. To the best of our knowledge, this represents the first report of leiomyosarcoma associated with osteoclast-like giant cells developing from the greater omentum in a dog.

  2. Summary of dosimetry, pathology, and dose response for bone sarcomas in beagles injected with 226Ra

    International Nuclear Information System (INIS)

    Wrenn, M.E.; Taylor, G.N.; Stevens, W.

    1985-01-01

    One hundred and sixty dogs given single intravenous injections of 226 Ra citrate at age 17 +/- 2 months (116) or a non-radioactive solution (44 controls) were part of a 30 year long experiment to determine the relative radiotoxicity of injected 226 Ra and 239 Pu. The authors report a preliminary summary of the results of the 226 Ra study. Skeletal development of the beagles used in this study is analogous to a young adult human, simulating that of a young adult radium dial painter or occupationally exposed person. Injected dosage of 226 Ra, average skeletal dose, and number of dogs and dogs developing bone sarcomas in each group are presented. The lowest nominal injected activity was 0.007 μCi/kg. Each of the 8 dosage levels contained about 12 dogs, except for 23 dogs at 0.06 μCi/kg and 25 dogs at 0.02 μCi/kg

  3. Biological effects of cesium-137 injected in beagle dogs of different ages

    International Nuclear Information System (INIS)

    Nikula, K.J.; Muggenburg, B.A.; Griffith, W.C.

    1995-01-01

    The toxicity of cesium-137 ( 137 Cs) in the Beagle dog was investigated at the Argonne National Laboratory (ANL) as part of a program to evaluate the biological effects of internally deposited radionuclides. The toxicity and health effects of 137 Cs are important to understand because 137 Cs is produced in large amounts in light-water nuclear reactors. Large quantities of cesium radioisotopes have entered the human food chain as a result of atmospheric nuclear weapons test, and additional cesium radioisotopes were released during the Chernobyl accident. Although the final analyses are not complete, three findings are significant: older dogs dies significantly earlier than juvenile and young adult dogs; greater occurrence of sarcomas in the cesium-137 injected dogs; the major nonneoplastic effect in dogs surviving beyond 52 d appears to be testicular atrophy

  4. Hematological responses after inhaling 238PuO2: An extrapolation from beagle dogs to humans

    International Nuclear Information System (INIS)

    Scott, B.R.; Muggenburg, B.A.; Welsh, C.A.; Angerstein, D.A.

    1994-01-01

    The alpha emitter plutonium-238 ( 238 Pu), which is produced in uranium-fueled, light-water reactors, is used as a thermoelectric power source for space applications. Inhalation of a mixed oxide form of Pu is the most likely mode of exposure of workers and the general public. Occupational exposures to 238 PuO 2 have occurred in association with the fabrication of radioisotope thermoelectric generators. Organs and tissue at risk for deterministic and stochastic effects of 238 Pu-alpha irradiation include the lung, liver, skeleton, and lymphatic tissue. Little has been reported about the effects of inhaled 238 PuO 2 on peripheral blood cell counts in humans. The purpose of this study was to investigate hematological responses after a single inhalation exposure of Beagle dogs to alpha-emitting 238 PuO 2 particles and to extrapolate results to humans

  5. Toxicity of 144Ce inhaled in a relatively insoluble form by immature Beagle dogs. XVII

    International Nuclear Information System (INIS)

    Boeker, B.B.; Muggenburg, B.A.; Hahn, F.F.; Mauderly, J.L.; McClellan, R.O.

    1988-01-01

    Immature Beagle dogs (3-mo old) received a single, brief inhalation exposure to 144 Ce in fused aluminosilicate particles as part of a series of studies designed to study the effects of age on dose response relationships for inhaled radionuclides. Forty-nine dogs inhaled graded levels of 144 Ce that resulted in initial lung burdens ranging from 0.004-140 μCi/kg 0.15-5200 kBq/kg) body weight. Five control dogs inhaled nonradioactive fused aluminosilicate particles. Forty-one of the 144 Ce-exposed dogs have died: 11 with lung tumors 4 with tumors of the tracheobronchial lymph nodes, with a nasal cavity tumor, and 9 with non neoplastic diseases of the respiratory tract. Observations are continuing on the 8 144 Ce-exposed dogs that are surviving at this time. (author)

  6. Toxicity of {sup 144}Ce inhaled in a relatively insoluble form by immature Beagle dogs. XVII

    Energy Technology Data Exchange (ETDEWEB)

    Boeker, B B; Muggenburg, B A; Hahn, F F; Mauderly, J L; McClellan, R O

    1988-12-01

    Immature Beagle dogs (3-mo old) received a single, brief inhalation exposure to {sup 144}Ce in fused aluminosilicate particles as part of a series of studies designed to study the effects of age on dose response relationships for inhaled radionuclides. Forty-nine dogs inhaled graded levels of {sup 144}Ce that resulted in initial lung burdens ranging from 0.004-140 {mu}Ci/kg 0.15-5200 kBq/kg) body weight. Five control dogs inhaled nonradioactive fused aluminosilicate particles. Forty-one of the {sup 144}Ce-exposed dogs have died: 11 with lung tumors 4 with tumors of the tracheobronchial lymph nodes, with a nasal cavity tumor, and 9 with non neoplastic diseases of the respiratory tract. Observations are continuing on the 8 {sup 144}Ce-exposed dogs that are surviving at this time. (author)

  7. Osteoporotic-like effects of cadmium on bone mineral density and content in aged ovariectomized beagles

    International Nuclear Information System (INIS)

    Sacco-Gibson, N.; Abrams, J.; Chaudhry, S.; Hurst, D.; Peterson, D.; Bhattacharyya, M.

    1992-01-01

    Our purpose was to evaluate the effects of ovariectomy in conjunction with cadmium (Cd) exposure on bone. Aged female beagles with 45 Ca-labeled skeletons ovariectomized and exposed to Cd. Successive vertebral scans by dual photon absorptiometry monitored changes in bone mineral density (BMD) in each dog with time. Results showed that ovariectomy or Cd exposure alone caused significant decreases in BMD; ovariectomy with Cd exposure caused the greatest decrease. Ovariectomy alone did not decrease BMD in the distal end or mid-shaft of the tibia while BMD of the distal tibia decreased significantly due to Cd exposure alone. Combination treatment resulted in significant decreases in BMD of both tibial regions. At necropsy, tibiae, humeri, lumbar vertebrae and ribs were obtained for biochemical analysis. No group-to-group differences in bone weights (wet, dry, ash), in ash/dry ratios, or in long bone and vertebral Ca/dry or Ca/ash ratios were observed. Significantly higher total 45 Ca content and 45 Ca/dry and 45 Ca/ash ratios were observed in long bones and vertebrae of OV- and OV+ groups. In contrast, intact ribs showed significantly decreased Ca/dry and Ca/ash ratios compared to the SO-group. Quartered ribs demonstrated regional responses to specific treatment; decreases in total Ca content were greatest in the mid-rib region (-36 to -46%). Results suggest that in the aged female beagle, bone mineral loss associated with estrogen depletion is not only related to bone type (trabecular versus cortical) but also to bone Ca pools. Our results also suggest that a regional heterogeneity of bone plays a role in responsiveness to ovariectomy and Cd exposure. These aspects suggest that Cd is an exogenous factor affecting bone mineral loss independently of estrogen depletion. However, estrogen depletion primes bone for responsiveness to Cd-induced bone mineral loss

  8. Relationship of dose rate and total dose to responses of continuously irradiated beagles

    International Nuclear Information System (INIS)

    Fritz, T.E.; Norris, W.P.; Tolle, D.V.; Seed, T.M.; Poole, C.M.; Lombard, L.S.; Doyle, D.E.

    1978-01-01

    Young-adult beagles were exposed continuously (22 hours/day) to 60 Co γ rays in a specially constructed facility. The exposure rates were either 5, 10, 17, or 35 R/day, and the exposures were terminated at either 600, 1400, 2000, or 4000 R. A total of 354 dogs were irradiated; 221 are still alive as long-term survivors, some after more than 2000 days. The data on survival of these dogs, coupled with data from similar preliminary experiments, allow an estimate of the LD 50 for γ-ray exposures given at a number of exposure rates. They also allow comparison of the relative importance of dose rate and total dose, and the interaction of these two variables, in the early and late effects after protracted irradiation. The LD 50 for the beagle increases from 258 rad delivered at 15 R/minute to approximately 3000 rad at 10 R/day. Over this entire range, the LD 50 is dependent upon hematopoietic damage. At 5 R/day and less, no meaningful LD 50 can be determined; there is nearly normal continued hematopoietic function, survival is prolonged, and the dogs manifest varied individual responses in other organ systems. Although the experiment is not complete, interim data allow several important conclusions. Terminated exposures, while not as effective as radiation continued until death, can produce myelogenous leukemia at the same exposure rate, 10 R/day. More importantly, at the same total accumulated dose, lower exposure rates are more damaging than higher rates on the basis of the rate and degree of hematological recovery that occurs after termination of irradiation. Thus, the rate of hematologic depression, the nadir of the depression, and the rate of recovery are dependent upon exposure rate; the latter is inversely related and the former two are directly related to exposure rate

  9. Radiation-Induced Neoplasms in Beagles after Administrations of {sup 90}Sr and {sup 226}Ra

    Energy Technology Data Exchange (ETDEWEB)

    Goldman, M.; Dungworth, D. L.; Bulgin, M. S.; Rosenblatt, L. S.; Richards, W. P.C.; Bustad, L. K. [Radiobiology Laboratory and Department of Veterinary Pathology, University of California, Davis, CA (United States)

    1969-11-15

    The comparative carcinogenic efficiency of two bone-seeking radionuclides is under study in a colony of several hundred beagles. The toxicity of internally deposited alpha emitters ({sup 226}Ra and its daughters) and of beta irradiation ({sup 90}Sr) at comparable dosage rates indicates marked differences in site of appearance and mode of action in litters studied up to 7 years of age. Radiation carcinogenesis in beagles exposed to {sup 90}Sr daily from midgestation to adulthood (1.5 yr) is at present confined to dogs fed 4 {mu}Ci {sup 90}Sr/d or higher. The 20 cases constitute a spectrum of myeloproliferative disorders characterized by terminal anaemias, and ranging from myeloid metaplasia to granulocytic leukaemia. Continuous high-level {sup 90}Sr irradiation to bone and marrow from early life onward causes a thickened hypocellular bone ('pachyostosis'), some instances of myelofibrosis, and persistent mild leukopenia on which the final spectrum of terminal disoideis is superimposed. In contrast, up to 100 {mu}Cl {sup 226}Ra given intravenously (8 equally spaced injections at 14 to 18 months of age) to young adults is not a potent marrow cell carcinogen. The higher LET, shorter-range alpha particles are efficient in inducing bone cancers (14 cases) and skeletal lesions similar to those documented in watch-dial luminizers exposed to {sup 226}Ra in the early 1900's. The incidence of haematopoietic and skeletal neoplasms observed is dose-rate related, and the morphologic characteristics have several analogues in human cancer. The use of identically treated litters rather than individuals affords additional opportunity to study possible familial factors in the distribution of the neoplasms. Pathogenic evaluation at this juncture strongly indicates that continued bone and marrow irradiation in early life is more likely to induce haematopoietic neoplasms than is skeletal irradiation starting in young adulthood, which induces osseous neoplasms. (author)

  10. An artificial pancreas provided a novel model of blood glucose level variability in beagles.

    Science.gov (United States)

    Munekage, Masaya; Yatabe, Tomoaki; Kitagawa, Hiroyuki; Takezaki, Yuka; Tamura, Takahiko; Namikawa, Tsutomu; Hanazaki, Kazuhiro

    2015-12-01

    Although the effects on prognosis of blood glucose level variability have gained increasing attention, it is unclear whether blood glucose level variability itself or the manifestation of pathological conditions that worsen prognosis. Then, previous reports have not been published on variability models of perioperative blood glucose levels. The aim of this study is to establish a novel variability model of blood glucose concentration using an artificial pancreas. We maintained six healthy, male beagles. After anesthesia induction, a 20-G venous catheter was inserted in the right femoral vein and an artificial pancreas (STG-22, Nikkiso Co. Ltd., Tokyo, Japan) was connected for continuous blood glucose monitoring and glucose management. After achieving muscle relaxation, total pancreatectomy was performed. After 1 h of stabilization, automatic blood glucose control was initiated using the artificial pancreas. Blood glucose level varied for 8 h, alternating between the target blood glucose values of 170 and 70 mg/dL. Eight hours later, the experiment was concluded. Total pancreatectomy was performed for 62 ± 13 min. Blood glucose swings were achieved 9.8 ± 2.3 times. The average blood glucose level was 128.1 ± 5.1 mg/dL with an SD of 44.6 ± 3.9 mg/dL. The potassium levels after stabilization and at the end of the experiment were 3.5 ± 0.3 and 3.1 ± 0.5 mmol/L, respectively. In conclusion, the results of the present study demonstrated that an artificial pancreas contributed to the establishment of a novel variability model of blood glucose levels in beagles.

  11. Experimental study on brain injury in Beagle dogs caused by adjacent cabin explosion in warship

    Directory of Open Access Journals (Sweden)

    Yan-teng LI

    2017-04-01

    Full Text Available Objective  Through the establishment of adjacent cabin blast injury model of Beagle dog, to investigate the pathophysiological changes in the experimental animals in this scenario, then speculate on the mechanisms of injury. Methods  Several adjacent cabins were built in the same size with the real warship. Seven Beagle dogs were subjected to injuries from the explosion, from whom one was selected randomly to implant intracranial pressure transducers before blast, the others were tested on the pathophysiological changes after blast. The dogs were mounted on the platform of a cabinet in the adjacent cabin, subjected to injury from 650g bare TNT explosive blast. The transducers recorded the value of space and intracranial shock wave pressure. Following blast treatment, the serum levels of IL -6, IL -8, neuron specific enolase (NSE, brain and chest CT and pathological changes of the brain tissue were observed. Results  Serum levels of IL-6, IL-8 and NSE were elevated to varying degrees after blast. All of them increased significantly at different time points after blast (P<0.05. Brain and chest CT examinations did not show any significant positive results. Pathological results showed that there was a little necrosis in the brain, some neurons had karyopycnosis, karyolysis or disappearance of the nucleoli, and the cell boundaries were blurred. The blast wave was blocked greatly by the scalp and skull (about 90%, but could still penetrate them and cause brain injuries. Conclusions  Explosion in the adjacent cabin causes mainly mild traumatic brain injuries. Blast wave can be blocked by the scalp and skull greatly. DOI: 10.11855/j.issn.0577-7402.2017.03.11

  12. Toxicity of inhaled 90Sr in fused aluminosilicate particles in beagle dogs. VIII

    International Nuclear Information System (INIS)

    Snipes, M.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1977-01-01

    Studies on the metabolism, dosimetry and biological effects of 90 Sr inhaled in a relatively insoluble form by Beagle dogs have continued during the past year to define the biological consequences of inhaling this important radionuclide in a form which has a long retention time in the lung. One hundred and six dogs were exposed to a polydisperse aerosol of fused aluminosilicate particles labeled with 90 Sr. Initial lung burdens ranged from 0.21 to 94 μCi 90 Sr per kilogram of body weight (μCi/kg). Eighteen control dogs were exposed to an aerosol of stable strontium in fused aluminosilicate particles. These 124 dogs were assigned to the longevity study. An additional 26 dogs were exposed similarly to achieve lung burdens of approximately 1.5 to 12 μCi/kg and assigned for sacrifice at intervals after exposure to define metabolism and dosimetry of this aerosol in Beagle dogs. Of the longevity dogs, 33 dogs having initial lung burdens of 16 to 94 μCi 90 Sr/kg and cumulative doses to lung of 40,000 to 96,000 rads have died from radiation pneumonitis and/or pulmonary fibrosis from 159 to 2373 days after exposure. Thirty-one dogs with initial lung burdens of 3.7 to 36 μCi 90 Sr/kg and cumulative doses to lung of 13,000 to 68,000 rads have died from hemangiosarcomas in the lung or heart between 644 and 2565 days after exposure. In addition, one dog developed a bronchioloalveolar carcinoma, another developed epidermoid carcinoma of the lung, another died of pneumonia while recovering from anesthesia, one dog died at 1821 days after exposure with a hemangiosarcoma of the spleen and two dogs developed squamous cell carcinomas in the nasal cavity. The remaining exposed dogs and controls of the longevity study are surviving at 1022 to 2803 days after exposure

  13. Osteoporotic-like effects of cadmium on bone mineral density and content in aged ovariectomized beagles

    Energy Technology Data Exchange (ETDEWEB)

    Sacco-Gibson, N.; Abrams, J.; Chaudhry, S.; Hurst, D.; Peterson, D.; Bhattacharyya, M.

    1992-12-31

    Our purpose was to evaluate the effects of ovariectomy in conjunction with cadmium (Cd) exposure on bone. Aged female beagles with {sup 45}Ca-labeled skeletons ovariectomized and exposed to Cd. Successive vertebral scans by dual photon absorptiometry monitored changes in bone mineral density (BMD) in each dog with time. Results showed that ovariectomy or Cd exposure alone caused significant decreases in BMD; ovariectomy with Cd exposure caused the greatest decrease. Ovariectomy alone did not decrease BMD in the distal end or mid-shaft of the tibia while BMD of the distal tibia decreased significantly due to Cd exposure alone. Combination treatment resulted in significant decreases in BMD of both tibial regions. At necropsy, tibiae, humeri, lumbar vertebrae and ribs were obtained for biochemical analysis. No group-to-group differences in bone weights (wet, dry, ash), in ash/dry ratios, or in long bone and vertebral Ca/dry or Ca/ash ratios were observed. Significantly higher total {sup 45}Ca content and {sup 45}Ca/dry and {sup 45}Ca/ash ratios were observed in long bones and vertebrae of OV- and OV+ groups. In contrast, intact ribs showed significantly decreased Ca/dry and Ca/ash ratios compared to the SO-group. Quartered ribs demonstrated regional responses to specific treatment; decreases in total Ca content were greatest in the mid-rib region ({minus}36 to {minus}46%). Results suggest that in the aged female beagle, bone mineral loss associated with estrogen depletion is not only related to bone type (trabecular versus cortical) but also to bone Ca pools. Our results also suggest that a regional heterogeneity of bone plays a role in responsiveness to ovariectomy and Cd exposure. These aspects suggest that Cd is an exogenous factor affecting bone mineral loss independently of estrogen depletion. However, estrogen depletion primes bone for responsiveness to Cd-induced bone mineral loss.

  14. Retention and distribution of 241AmIII in neonatal beagles

    International Nuclear Information System (INIS)

    Stevens, W.; Atherton, D.R.; Bates, D.; Lloyd, R.D.; Buster, D.S.; Bruenger, F.W.

    1977-01-01

    The distribution of Am in newborn beagles was studied during the first week after birth. Seven litter mates (4 males, 3 females) weighing 250-280 g were injected intravenously with 3.0 μCi 241 AmIII/kg, in citrate buffer, at 1 day of age and sacrificed 1, 3 and 5 days later. At sacrifice, livers, spleens, kidneys, other selected soft tissues and skeletons were analyzed for Am content. Cumulative excretion during the time observed was 6.7% of the injected dose, 5.5% of which occurred during the first day. Skeletal retention ranged from 76% of the injected dose at 1 day to 84% by 5 days. The skeletons of dogs given the same dose of Am at 18 months of age contained 29% of the injected Am at 1 week. The relative distribution of Am within the skeleton was dependent on the state of development of its individual bones and differed considerably from that of the young adult. In neonates, the Am content of the bones of the skull was 3 times that seen in dogs injected as young adults. Initial liver deposition of Am in neonates was only 7%, in contrast to approximately 50% in young adult beagles. The subcellular distribution of Am in liver also differed in the two age groups. In neonates, a greater fraction of the nuclide was associated with soluble proteins of the cytosol, and the increase in the Am content of mitochondria and lysosomes proceeded at a much slower rate than was observed in mature animals. (author)

  15. Relationship of dose rate and total dose to responses of continuously irradiated beagles

    International Nuclear Information System (INIS)

    Fritz, T.E.; Norris, W.P.; Tolle, D.V.; Seed, T.M.; Poole, C.M.; Lombard, L.S.; Doyle, D.E.

    1978-01-01

    Young-adult beagles were exposed continuously (22 hours/day) to 60 Co gamma rays in a specially constructed facility. The exposure rates were 5, 19, 17 or 35 R/day, and the exposures were terminated at 600, 1400, 2000 or 4000 R. A total of 354 dogs were irradiated; 221 are still alive as long-term survivors, some after more than 2000 days. The data on survival of these dogs, coupled with data from similar preliminary experiments, allow an estimate of the LD 50 for gamma-ray exposures given at a number of exposure rates. They also allow comparison of the relativeimportance of dose rate and total dose, and the interaction of these two variables, in the early and late effects after protracted irradiation. The LD 50 for the beagle increases from 344 R (258 rads) delivered at 15 R/minute to approximately 4000 R (approximately 3000 rads) at 10 R/day. Over this entire range, the LD 50 is dependent upon haematopoietic damage. At 5 R/day and less, no definitive LD 50 can be determined; there is nearly normal continued haematopoietic function, survival is prolonged, and the dogs manifest varied individual responses in the organ systems. Although the experiment is not complete, interim data allow serveral important conclusions. Terminated exposures, while not as effective as irradiation continued until death, can produce myelogenous leukaemia at the same exposure rate, 10 R/day. More importantly, at the same total accumulated dose, lower exposure rates appear more damaging than higher rates on the basis of the rate and degree of haematological recovery that occurs after termination of irradiation. Thus, the rate of haematologic depression, the nadir of the depression and the rate of recovery are dependent upon exposure rate; the latter is inversely related and the first two are directly related to exposure rate. ( author)

  16. Comparative toxicity of strontium-90 and radium-226 in beagle dogs

    International Nuclear Information System (INIS)

    Raabe, O.G.; Culbertson, M.R.; White, R.G.; Spangler, W.L.; Cain, G.R.; Parks, N.J.; Samuels, S.J.

    1991-01-01

    We are completing a 30-year study of the biological effects of 90 Sr and 226 Ra in the beagle in order to predict the possible long-term hazards to people from chronic exposure to low levels of irradiation. Animals received either radionuclide by several means of administration: (a) continual ingestion of 90 Sr, (b) a single intravenous injection of 90 Sr, or (c) a series of eight intravenous injections of 226 Ra. Although administration of 90 Sr and 226 Ra ended at 540 days of age, the animals continued to receive chronic, low-level radiation doses from these bone-seeking radionuclides throughout life. This project is the largest single cohort study in beagles of internally deposited radionuclides. It is unique in use of the ingestion route for 90 Sr and in exposure that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with 90 Sr. The last of the dogs died in 1986 at age 18.5 years, but we are continuing to investigate the significance of these long-term exposures given at low dose rates with regard to cancer production, physiologic well-being, and shortening of life through the detailed records that were kept and by study of preserved materials. All the data have been successfully accumulated and entered into a main-frame computer data base management system. Current work is exclusively directed at preparing research papers summarizing the results and the associated biostatistical and survival analyses. 15 refs., 1 fig., 4 tabs

  17. Effects of a tetracycline blended polylactic and polyglycolic acid membrane on the healing of one-wall intrabony defects in beagle dogs

    International Nuclear Information System (INIS)

    Kim, Il-Young; Jung, Ui-Won; Kim, Chang-Sung; Lee, Yong-Keun; Cho, Kyoo-Sung; Chai, Jung-Kiu; Kim, Chong-Kwan; Choi, Seong-Ho

    2007-01-01

    The purpose of this study was to evaluate the regenerative effects of a tetracycline blended polylactic and polyglycolic acid (TC-PLGA) and non-blended polylactic and polyglycolic acid (PLGA) barrier membrane on one-wall intrabony defects in beagle dogs. It can be concluded that when used for guided tissue regeneration TC-PLGA membranes show a beneficial effect on one-wall intrabony defects in beagle dogs

  18. Ranges of diurnal variation and the pattern of body temperature, blood pressure and heart rate in laboratory beagle dogs.

    Science.gov (United States)

    Miyazaki, Hiroyasu; Yoshida, Mutsumi; Samura, Keiji; Matsumoto, Hiroyoshi; Ikemoto, Fumihiko; Tagawa, Masahiro

    2002-01-01

    Ranges in diurnal variation and the patterns of body temperature (T), blood pressure (BP), heart rate (HR) and locomotor activity (LA) in 61 laboratory beagle dogs were analyzed using a telemetry system. Body temperature, BP, HR and LA increased remarkably at feeding time. Locomotor activity increased sporadically during the other periods. Body temperature was maintained at the higher value after feeding but had decreased by 0.2 C by early the next morning. Blood pressure fell to a lower value after feeding but had increased by 2.8% by early the next morning. Heart rate decreased progressively after feeding and was 14.5% lower the next morning. This study determined that in laboratory beagles the ranges of diurnal variation and patterns of T, BP and HR are significantly different from those reported in humans and rodents, and that over 24 hr these physiological changes were associated with their sporadic wake-sleep cycles of the dogs.

  19. Studies on separation and pharmacokinetics of m-nisoldipine enantiomers in beagle dog plasma by LC/MS/MS.

    Science.gov (United States)

    Li, Min; Yuan, Lin; Li, Xiuqing; Zhi, Xuran; Sheng, Ning; Zhang, Lantong

    2013-11-01

    A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed and validated for the separation and determination of m-nisoldipine enantiomers in beagle dog plasma. Samples were pretreated by a single-step protein precipitation with acetonitrile. After m-nisoldipine racemic administration to beagle dogs, samples of m-nisoldipine enantiomers in beagle dog plasma were separated and determined on a ULTRON ES-OVM column (150 × 4.6 mm, 5 μm) at 20°C with a mobile phase consisted of methanol-acetonitrile-ammonium acetate (pH 7.0; 2mM) (15:15:70, v/v/v) at a flow rate of 0.8 mL/min. Chromatograms were monitored at 237 nm, and the API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM) scan mode using ElectroSpray ionization (ESI) source. The good linearity (rs=0.9958 and rr=0.9983) were found in the range 0.25-20 ng/mL. The lower limit of quantification (LLOQ) obtained was 0.25 ng/mL (n=6). All the validation data, such as accuracy, precision, intra-day and inter-day repeatability, were within the required limits. The method was successfully applied to separation and pharmacokinetics of m-nisoldipine enantiomers in beagle dog plasma. The result of statistics analysis shows that there are no significant differences between R-(-)-m-nisoldipine and S-(+)-m-nisoldipine (p>0.05). The study provides necessary evidences for the research and new drug development of m-nisoldipine enantiomers. Copyright © 2013. Published by Elsevier B.V.

  20. [Impact of different degree pulpitis on cell proliferation and osteoblastic differentiation of dental pulp stem cell in Beagle immature premolars].

    Science.gov (United States)

    Ling, L; Zhao, Y M; Ge, L H

    2016-10-18

    To compare the proliferation and osteoblastic differentiation of dental pulp stem cell (DPSC) isolated from normal and inflamed pulps of different degrees in Beagle immature premolars, and provide evidence for the use of inflammatory DPSC (IDPSC). This study evaluated 14 Beagle's young premolars (21 roots). In the experiment group, irreversible pulpitis was induced by pulp exposure and the inflamed pulps were extracted 2 weeks and 6 weeks after the pulp chamber opening.For the control group, normal pulps were extracted immediately after the exposure. HE staining and real-time PCR were performed to confirm the inflammation. The cells were isolated from the inflamed and normal pulps (IDPSC and DPSC). Cell proliferation and osteoblastic differentiation potentials of the two cells were compared. Inflammation cells infiltration was observed in the inflamed pulps by HE staining. The expression of inflammatory factor was much higher in the 6 week inflamed pulp. IDPSC had higher potential of cell proliferation and osteoblastic differentiation potentials. Furthermore, the osteoblastic differentiation potentials of IDPSC from 2 week inflamed pulp were higher than those from 6 week inflamed pulp. The potential of cell proliferation and osteoblastic differentiation of DPSC was enhanced at early stage of irreversible pulpitis, and reduced at late stage in Beagle immature premolars.

  1. Use of linear model analysis techniques in the evaluation of radiation effects on the life span of the beagle

    International Nuclear Information System (INIS)

    Angleton, G.M.; Lee, A.C.; Benjamin, S.A.

    1986-01-01

    The dependency of the beagle-dog life span on level of and age at exposure to 60 Co gamma radiation was analyzed by several techniques; one of these methods was linear model analysis. Beagles of both sexes were given single, bilateral exposures at 8, 28, or 55 days postcoitus (dpc) or at 2, 70, or 365 days postpartum (dpp). Dogs exposed at 8, 28, or 55 dpc or at 2 dpp received 0, 20, or 100 R, whereas those exposed at 70 or 365 dpp received 0 or 100 R. Beagles were designated initially either as sacrifice or as life-span animals. All deaths of life-span study animals were classified as spontaneous, hence for this group the mean age of death was a quantitative response that can be analyzed by linear model analysis techniques. Such analyses for each age group were performed, taking into account differences due to sex, linear and quadratic dependency on dose, and interaction between sex and dose. At this time most of the animals have reached 11 years of age. No significant effects of radiation on mean life span have been detected. 6 refs., 3 figs., 3 tabs

  2. Cumulative damage effect of 32P-colloidal chromic phosphate interstitial delivery on beagles

    International Nuclear Information System (INIS)

    Nie Qi; Liu Lu; Liu Zhiyong; Huang Peilin; Lan Xinghao; Gao Hailin; Wu Qinghua; Sun Jin; Huang Ying

    2010-01-01

    Objective: To explore the possibility and safety of 3 '2P-colloidal chromic phosphate interstitial injection.Methods: Ten Beagle dogs were randomly divided into 5 groups (n = 2) according to different doses (185 and 370 MBq), different sites (gluteus maximus and liver) and cold colloid as a control group. At different time-points after surgery, the weights of dogs were measured, and the blood and blood biochemical inspections were examined. ECT imaging was performed and histomorphology was observed dynamically. The radioactive counts of body surface for 90 days, blood for 12 weeks and urine and feces for 30 days were measured continuously. Measured data were expressed by mean ± standard error ((x-bar) ± s) and SPSS 13.0 software was used for statistical analysis. Results: ECT imaging demonstrated that the whole liver imaging was obtained although the radioactive distribution was uneven in liver groups, and the radioactivity concentrated continuously in the area of injection, but no liver imaging in muscle groups. Dogs in group 4 lost weight progressively and reduced by 2.7 kg till 45 d after operation. While the mean weight increments in the other groups were 3.0, 1.6, 0.8 and 3.1 kg in order. In group 4, PLT and RBC reduced obviously. Dogs died at 23 or 45 d.AST and ALT were elevated sharply before death. In the other groups, blood and blood biochemistry inspection showed there were no significant statistical differences. The highest radioactive counts after operation were obtained from the injection spot, while the urinary bladder and the spleen were followed. The peak of blood cpm in liver groups presented at 5 min.Peak values were 0.5 x 10 7 /min and 1.0 x 10 7 /min, respectively. The blood cpm in the muscle groups was always maintained at 3 x l0 5 /min. Histology study showed the hyperemia dropsy changes in muscle groups and 185 MBq liver group in 4 weeks, while after 8 weeks the organizational structure restored normally. There were partial liver cells

  3. Toxicity of inhaled 90Sr fused clay particles in beagle dogs. V

    International Nuclear Information System (INIS)

    Snipes, M.B.; Boecker, B.B.; Hahn, F.F.; Hobbs, C.H.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1974-01-01

    Studies on the metabolism, dosimetry, and biological effects of 90 Sr in fused clay particles in Beagle dogs have continued with a view toward defining the biological consequences of inhaling this important radionuclide in a relatively insoluble form. Seventy-two dogs were exposed to a polydisperse aerosol (AMAD 1.4 to 2.8 μm and sigma/sub g/ 1.4 to 2.7) of fused montmorillonite clay particles labeled with 90 Sr to achieve graded initial lung burdens (ILB) of 3.7 to 94 μCi/kg body weight; 12 control dogs were exposed to an aerosol of stable strontium in fused clay particles. These 84 dogs were assigned to the 90 Sr fused clay longevity study. An additional 26 dogs were exposed similarly (AMAD 1.9 to 2.5 μm and sigma/sub g/ 1.6 to 2.0) and assigned for sacrifice (Series II) at intervals after exposure to define metabolism and dosimetry of this aerosol in Beagle dogs. Of the 72 longevity dogs, 32 dogs having ILBs of 29 to 94 μCi/kg and cumulative doses to lung to death of 40,000 to 96,000 rads have died from radiation pneumonitis and/or pulmonary fibrosis from 159 to 477 days post-exposure. Fourteen dogs with ILBs of 15 to 36 μCi/kg and cumulative doses to lung to death of 34,000 to 68,000 rads have died from primary pulmonary hemangiosarcomas between 644 and 1214 days post-exposure. In addition, one dog developed a bronchiolo-alveolar carcinoma, another epidermoid carcinoma of the lung and a third, a squamous cell carcinoma in the nasal cavity. The remaining 26 exposed dogs and 12 controls of the longevity study are surviving at 1070 to 1707 days post-exposure. Dogs in the sacrifice series have been sacrificed to 1536 days post-exposure. (U.S.)

  4. Bone sarcoma induction by {sup 224}Ra in Beagles: An interim report

    Energy Technology Data Exchange (ETDEWEB)

    Mays, C W [Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD (United States); Taylor, G N; Lloyd, R D; Bruenger, F W; Angus, W [Radiobiology Division, University of Utah School of Medicine, Salt Lake City, UT (United States)

    1988-12-01

    During 1963-1968, 20 young adult Beagle dogs were given a single intravenous injection of {sup 224}Ra that was unintentionally contaminated with {sup 210}Pb and {sup 228}Th. All of these dogs have died, eight with bone sarcomas. In addition, 128 Beagle dogs were given purified {sup 224}Ra in one, ten or fifty weekly injections during 1977-1979. The acute lethal dosage (LD{sub 50}) for a single injection was about 400 kBq {sup 224}Ra/kg (11 {mu}Ci {sup 224}Ra/kg). As of September 14, 1987, at the highest skeletal dose of 3 Gy from purified {sup 224}Ra, bone sarcomas occurred in 5 of 6 dogs at an average {+-} SD of 2069 {+-} 302 days after the start of injections (no survivors), in 4 of 6 dogs at 2485 {+-} 1,110 days after the start of 10 injections (healthy survivor) and in 1 of 8 dogs at 3066 days after a single injection (3 healthy survivors). At 3 Gy the toxicity of {sup 224}Ra relative to {sup 239}Pu, based on the ratio of skeletal doses at equal tumor appearance times, was 1.0 for 50 injections of {sup 224}Ra, 0.7 for 10 injections, and 0.4 for one injection. In contrast, the effectiveness per Gy of a {sup 224}Ra-equivalent dose from a single injection of {sup 224}Ra contaminated with {sup 228}Th and {sup 210}Pb was equal to that from {sup 239}Pu, assuming that the {sup 224}Ra-equivalent dose equaled the {sup 224}Ra dose plus the {sup 228}Th dose pus 0.1 of the {sup 210}Pb dose. A possible explanation is that protracted irradiation from the 1.91-yr half-life {sup 228}Th and the 22.3-yr half-life {sup 210}Pb may have 'activated' residual damage from the short-lived, 3.62 day half-life {sup 224}Ra, possibly by stimulating the division of damaged stem cells to replace the bone cells killed by the protracted alpha particle irradiation. An important spin off from the study is experimental support for the assumption that the bone sarcoma effectiveness for {sup 210}Pb is similar to that from long-lived, 1600 yr half-life {sup 226}Ra. (author)

  5. Bone sarcoma induction by 224Ra in Beagles: An interim report

    International Nuclear Information System (INIS)

    Mays, C.W.; Taylor, G.N.; Lloyd, R.D.; Bruenger, F.W.; Angus, W.

    1988-01-01

    During 1963-1968, 20 young adult Beagle dogs were given a single intravenous injection of 224 Ra that was unintentionally contaminated with 210 Pb and 228 Th. All of these dogs have died, eight with bone sarcomas. In addition, 128 Beagle dogs were given purified 224 Ra in one, ten or fifty weekly injections during 1977-1979. The acute lethal dosage (LD 50 ) for a single injection was about 400 kBq 224 Ra/kg (11 μCi 224 Ra/kg). As of September 14, 1987, at the highest skeletal dose of 3 Gy from purified 224 Ra, bone sarcomas occurred in 5 of 6 dogs at an average ± SD of 2069 ± 302 days after the start of injections (no survivors), in 4 of 6 dogs at 2485 ± 1,110 days after the start of 10 injections (healthy survivor) and in 1 of 8 dogs at 3066 days after a single injection (3 healthy survivors). At 3 Gy the toxicity of 224 Ra relative to 239 Pu, based on the ratio of skeletal doses at equal tumor appearance times, was 1.0 for 50 injections of 224 Ra, 0.7 for 10 injections, and 0.4 for one injection. In contrast, the effectiveness per Gy of a 224 Ra-equivalent dose from a single injection of 224 Ra contaminated with 228 Th and 210 Pb was equal to that from 239 Pu, assuming that the 224 Ra-equivalent dose equaled the 224 Ra dose plus the 228 Th dose pus 0.1 of the 210 Pb dose. A possible explanation is that protracted irradiation from the 1.91-yr half-life 228 Th and the 22.3-yr half-life 210 Pb may have 'activated' residual damage from the short-lived, 3.62 day half-life 224 Ra, possibly by stimulating the division of damaged stem cells to replace the bone cells killed by the protracted alpha particle irradiation. An important spin off from the study is experimental support for the assumption that the bone sarcoma effectiveness for 210 Pb is similar to that from long-lived, 1600 yr half-life 226 Ra. (author)

  6. Is the beagle dog an appropriate experimental animal for extrapolating data to humans on organ distribution patterns of U, Th, and Pu

    International Nuclear Information System (INIS)

    Singh, N.P.; Wrenn, M.E.

    1989-01-01

    Concentrations and organ distribution patterns of alpha-emitting isotopes of U (238U and 234U), Th (232Th, 230Th, and 228Th), and Pu (239,240Pu) were determined for beagle dogs of our colony. The dogs were exposed to environmental levels of U and Th isotopes through ingestion (food and water) and inhalation to stimulate environmental exposures of the general human population. The organ distribution patterns of these radionuclides in beagles are compared to patterns in humans to determine if it is appropriate to extrapolate organ content data from beagles to humans. The results indicated that approximately 80% of the U and Th accumulated in bone in both species. The organ content percentages of these radionuclides in soft tissues such as liver, kidney, etc. of both species were comparable. The human lung contained higher percentages of U and Th than the beagle lung, perhaps because the longer life span of humans resulted in a longer exposure time. If the U and Th content of dog lung is normalized to an exposure time of 58 y and 63 y, median ages of the U and Th study populations, respectively, the lung content for both species is comparable. The organ content of 239,240Pu in humans and beagles differed slightly. In the beagle, the liver contained more than 60%, and the skeleton contained less than 40% of the Pu body content. In humans, the liver contained approximately 37%, and the skeleton contained approximately 58% of the body content. This difference may have been due to differences in the mode of intake of Pu in each species or to differences in the chemical form of Pu. In general, the results suggest that the beagle may be an appropriate experimental animal from which to extrapolate data to humans with reference to the percentage of U, Th, and Pu found in the organs

  7. Physical Properties of the MER and Beagle II Landing Sites on Mars

    Science.gov (United States)

    Jakosky, B. M.; Pelkey, S. M.; Mellon, M. T.; Putzig, N.; Martinez-Alonso, S.; Murphy, N.; Hynek, B.

    2003-12-01

    The ESA Beagle II and the NASA Mars Exploration Rover spacecraft are scheduled to land on the martian surface in December 2003 and January 2004, respectively. Mission operations and success depends on the physical properties of the surfaces on which they land. Surface structural characteristics such as the abundances of loose, unconsolidated fine material, of fine material that has been cemented into a duricrust, and of rocks affect the ability to safely land and to successfully sample and traverse the surface. Also, physical properties affect surface and atmospheric temperatures, which affect lander and rover functionality. We are in the process of analyzing surface temperature information for these sites, derived from MGS TES and Odyssey THEMIS daytime and nighttime measurements. Our approach is to: (i) remap thermal inertia using TES data at ~3-km resolution, to obtain the most complete coverage possible; (ii) interpret physical properties from TES coverage in conjunction with other remote-sensing data sets; (iii) map infrared brightness using daytime and nighttime THEMIS data at 100-m resolution, and do qualitative analysis of physical properties and processes; and (iv) derive thermal inertia from THEMIS nighttime data in conjunction with daytime albedo measurements derived from TES, THEMIS, and MOC observations. In addition, we will use measured temperatures and derived thermal inertia to predict surface temperatures for the periods of the missions.

  8. Thermophysical properties of the MER and Beagle II landing site regions on Mars

    Science.gov (United States)

    Jakosky, Bruce M.; Hynek, Brian M.; Pelkey, Shannon M.; Mellon, Michael T.; Martínez-Alonso, Sara; Putzig, Nathaniel E.; Murphy, Nate; Christensen, Philip R.

    2006-08-01

    We analyzed remote-sensing observations of the Isidis Basin, Gusev Crater, and Meridiani Planum landing sites for Beagle II, MER-A Spirit, and MER-B Opportunity spacecraft, respectively. We emphasized the thermophysical properties using daytime and nighttime radiance measurements from the Mars Global Surveyor (MGS) Thermal Emission Spectrometer and Mars Odyssey Thermal Emission Imaging System (THEMIS) and thermal inertias derived from nighttime data sets. THEMIS visible images, MGS Mars Orbiter Camera (MOC) narrow-angle images, and MGS Mars Orbiter Laser Altimeter (MOLA) data are incorporated as well. Additionally, the remote-sensing data were compared with ground-truth at the MER sites. The Isidis Basin surface layer has been shaped by aeolian processes and erosion by slope winds coming off of the southern highlands and funneling through notches between massifs. In the Gusev region, surface materials of contrasting thermophysical properties have been interpreted as rocks or bedrock, duricrust, and dust deposits; these are consistent with a complex geological history dominated by volcanic and aeolian processes. At Meridiani Planum the many layers having different thermophysical and erosional properties suggest periodic deposition of differing sedimentological facies possibly related to clast size, grain orientation and packing, or mineralogy.

  9. Osteosarcomas among beagles exposed to 239Plutonium. Technical report No. 34

    International Nuclear Information System (INIS)

    Whittemore, A.S.; McMillan, A.

    1980-03-01

    A Weibull distribution was fit to the osteosarcoma death times of beagles given single intravenous injections of 239 Pu. For injected doses in the range 0 to 1 μCi/kg the osteosarcoma incidence rate h(t) at t days after injection can be fit by a quadratic function of the injected dose. The best fitting linear function was rejected by the data (p < 0.001). A different formula for h(t), derived from amultistage theory for osteosarcoma induction, was also fit to these data. For this purpose microdosimetry calculations were used to estimate the dose to the cells at risk in the endosteal layer (endosteal dose). According to the best fit, h(t) is a quadratic function of endosteal dose at low doses. A linear dose-response relationship was agan rejected. The absence of a linear component at low doses might be explained by the fact that 108 of the 185 animals injected at the lowest doses (< 0.02 μCi/kg) were still alive at the time these data were collected

  10. Small intestinal emptying time in normal Beagle dogs: a contrast radiographic study

    International Nuclear Information System (INIS)

    Miyabayashi, T.; Morgan, J.P.; Atilola, M.A.O.; Muhumuza, L.

    1986-01-01

    Gastric emptying time and small intestinal transit time in dogs are frequently discussed. However, it is often of interest to the radiologist to know what normal small intestinal emptying times should be. A total of 15 upper gastrointestinal studies was performed on five internal parasite-free, normal, standard Beagle dogs with three studies on each dog, 6 days apart. The ages and weights of the dogs ranged from 2–8 years and from 12.4–13.7 kg, respectively. Following 24-hour fasting, a dose of 10 ml/kg bw of 60% wt/vol barium sulfate suspension was administered through a stomach tube. Then, sequential radiographs were made at 30-minute intervals until the entire contrast medium column was in the colon and cecum. The mean, standard deviation, and range of gastric emptying time, small intestinal transit time, and small intestinal emptying time were 76 ± 16.7 (30–120), 73 ± 16.4 (30–120), and 214 ± 25.1 (180–300) minutes, respectively. This study offers the possibility that small intestinal emptying time may be used to further evaluate patients with suspected small intestinal partial obstruction, pseudo-obstruction, ischemia, or lymphangiectasia

  11. Regional effects of ovariectomy and cadmium on bone mineral in ribs from aged female beagles

    International Nuclear Information System (INIS)

    Hurst, D.R.

    1991-01-01

    The purpose of this study was to evaluate effects of estrogen depletion and cadmium (Cd) on bone calcium and to determine if these effects were localized in specific regions of ribs. Fourteen female beagles with 45 Ca labeled skeletons were divided into four groups: sham controls (SO-); ovariectomized (OV-); shams exposed to Cd (SO+); ovariecomized exposed to Cd (OV+). Total Cd exposure period was 7 months, including 1 month by capsules and 6 months by drinking H 2 O. Ribs were taken at necropsy from 12 of the 14 dogs, and each rib was quartered. Wet, dry, and ash weights, as well as total Ca and 45 Ca content, were determined for each quarter. Analysis of ribs from control animals demonstrated that a given rib is heterogeneous in composition. One end appears to be less mineralized and more metabolically active than other regions. The OV- and OV+ mid-rib regions had significantly lower dry and ash weights than SO-. Total Ca contents of these same regions were also decreased in the OV- and OV+. The only significant change in Ca/dry and Ca/ash was observed when comparing OV+ to SO-. Analysis of treatment suggests that there are regional effects following ovariectomy increased the loss of bone mineral occurring as a result of ovariectomy. 30 refs., 1 fig

  12. Current status of life-span studies with inhaled plutonium in beagles at Pacific Northwest Laboratory

    International Nuclear Information System (INIS)

    Park, J.F.; Dagle, G.E.; Ragan, H.A.; Weller, R.E.; Stevens, D.L.

    1986-01-01

    Beagles that inhaled 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 , in dose-level groups of 20 dogs, with initial lung burdens of ∼2, 15, 70, 300, 1100, or 5500 nCi, are now 11, 9, or 5 years postexposure. Lung tumors, bone tumors, and radiation pneumonitis, the plutonium-exposure-related causes of death observed to date, have occurred in the two, three, and four highest dose-level groups exposed to 238 PuO 2 , 239 Pu(NO 3 ) 4 , and 239 PuO 2 , respectively. No plutonium-exposure-related deaths have thus far been observed in dose-level groups exposed to less than ∼40 times the current maximum permissible lung dose for a plutonium worker. Plutonium-exposure-related effects not directly related to the cause of death include chronic lymphopenia, chronic neutropenia, sclerosis of the tracheobronchial lymph nodes, focal radiation pneumonitis, adenomatous hyperplasia in the liver, and dystrophic osteolytic lesions in the skeleton. No plutonium-exposure-related effects have thus far been observed in dose-level groups that received less than ∼15 times the current maximum permissible lung dose for a plutonium worker. 10 refs., 5 figs., 4 tabs

  13. Metabolism and dosimetry of 106Ru inhaled as 106RuO4 by beagle dogs

    International Nuclear Information System (INIS)

    Snipes, M.B.

    1981-01-01

    This report provides metabolism and dosimetry data for inhaled ruthenium developed from studies in Beagle dogs that were exposed by inhalation to 106 RuO 4 . Twenty-six dogs were exposed nose-only to 106 RuO 4 and sacrificed at times from 2 hr to 512 days after inhalation exposure. Ninety-nine percent of the initial body burden was retained with an effective half-time of 1.2 days, 0.7% with a half-time of 14 days and 0.3% with a half-time of 170 days. Initial deposition was primarily in the nasopharyngeal and tracheobronchial regions. Results for deposition and retention of 106 Ru inhaled as 106 RuO 4 in dogs were similar to what has been observed for humans. The data for dogs were used to develop a model to predict potential radiation exposure patterns for humans after inhalation exposure to 106 RuO 4 . The model indicates that for humans the nasopharyngeal region, lower large intestine, and tracheobronchial epithelium would receive approx. 36, 13 and 10 times, respectively, the dose to 500 days after inhalation exposure to 106 RuO 4 that the lung would receive. The nasopharyngeal region should be considered the critical region for inhalation exposures to 106 RuO 4 . (author)

  14. Toxicity of 144Ce inhaled in a relatively insoluble form by immature Beagle dogs. XIII

    International Nuclear Information System (INIS)

    Boecker, B.B.; Muggenburg, B.A.; Hahn, F.F.; Mauderly, J.L.; McClellan, R.O.

    1984-01-01

    Immature Beagle dogs (3 months old) were exposed once by inhalation to an aerosol of 144 Ce incorporated in fused aluminosilicate particles. The influence of this age on the dose-response relationships is being compared to that of 13-month-old and 8 to 10.5-year-old dogs. This study involves 49 dogs that received graded initial lung burdens from 0.004 to 140 μCi 144 Ce/kg (0.15 to 5200 kBq/kg) body weight and five control dogs. To date, 23 of the 144 Ce-exposed dogs and three of the controls have died. Dogs with the highest initial lung burdens of 144 Ce died during the first 4 months with radiation pneumonitis, pulmonary fibrosis, and congestive heart failure. Pulmonary hemangiosarcoma was the primary finding in dogs that died at 1.5 to 2 years after exposure. Deaths beyond that time have been due primarily to extrapulmonary hemangiosarcomas. Observations are continuing on the surviving 26 144 Ce-exposed and two control dogs at 8.0 to 12.2 years after exposure. 2 figures, 1 table

  15. Toxicity of 144Ce inhaled in a relatively insoluble form by immature Beagle dogs. XII

    International Nuclear Information System (INIS)

    Boecker, B.B.; Muggenburg, B.A.; Hahn, F.F.; Mauderly, J.L.; McClellan, R.O.

    1983-01-01

    Immature Beagle dogs (3 months old) were exposed once by inhalation to an aerosol of 144 Ce incorporated in fused aluminosilicate particles. The influence of this age on the dose-response relationships is being compared to that of 13-mo-old and 8 to 10.5-yr-old dogs. This study involves 49 dogs that received graded initial lung burdens from 0.004 to 140 μCi 144 Ce/kg body weight and five control dogs. To date, 19 of the 144 Ce-exposed dogs and one of the controls have died. Dogs with the highest initial lung burdens of 144 Ce died during the first 4 months with radiation pneumonitis, pulmonary fibrosis, and congestive heart failure. Pulmonary hemangiosarcoma was the primary finding in dogs that died at 1.5 to 2 years after exposure. Deaths beyond that time have been due primarily to extrapulmonary hemangiosarcomas. Observations are continued on the surviving 30 144 Ce-exposed and four control dogs at 7.0 to 11.2 years after exposure

  16. Holocene sea-level changes along the Strait of Magellan and Beagle Channel, southernmost South America

    Science.gov (United States)

    Porter, Stephen C.; Stuiver, Minze; Heusser, Calvin J.

    1984-07-01

    Radiocarbon-dated marine sediments from five coastal sites along the Strait of Magellan and Beagle Channel in southernmost Chile permit construction of a curve of relative sea-level fluctuations during the Holocene. Morphologic and stratigraphic data point to coastal submergence during the early Holocene as the sea rose to a maximum level at least 3.5 m higher than present about 5000 yr ago. Progressive emergence then followed during the late Holocene. Data from widely separated localities define a smooth curve, the form of which is explainable in terms of isostatic and hydroisostatic deformation of the crust resulting from changing ice and water loads. Apparently anomalous data from one site located more than 100 km behind the outer limit of the last glaciation may reflect isostatic response to deglaciation. The sea-level curve resembles one derived by Clark and Bloom (1979, In "Proceedings of the 1978 International Symposium on Coastal Evolution in the Quaternary, Sao Paulo, Brasil," pp. 41-60. Sao Paulo) using a spherical Earth model, both in amplitude and in the timing of the maximum submergence.

  17. The effect of perinatal 60Co gamma radiation on brain weight in beagles

    International Nuclear Information System (INIS)

    Hamilton, B.F.; Benjamin, S.A.; Angleton, G.M.; Lee, A.C.

    1989-01-01

    Beagle dogs were given single, whole-body 60 Co gamma-radiation exposures at one of three prenatal (8, 28, or 55 days postcoitus) or three postnatal (2, 70, or 365 days postpartum) ages to evaluate the relative radiosensitivity of various stages of brain development. A total of 387 dogs received mean doses ranging from 0.16 to 3.83 Gy, and 120 dogs were sham-irradiated. Groups of dogs were sacrificed at preselected times from 70 days to 11 years of age. Brain weight decreased significantly with increasing dose in dogs irradiated at 28 or 55 days postcoitus or at 2 days postpartum. Irradiations at 28 days postcoitus were dramatically more effective in causing a reduction in brain weight than those at 55 days postcoitus or 2 days postpartum. Among dogs given 1.0 Gy or more and followed for up to 4 years, there was a radiation effect evident at all three sensitive exposure ages. Among dogs given lower doses and followed for up to 11 years, there was a significant decrease in brain weight in dogs given 0.80-0.88 Gy at 28 days postcoitus. All decreases in brain weight were present after normalization for radiation-induced reductions in skeletal (body) size. No specific morphologic changes were noted in the brains which showed the radiation-related reductions in size

  18. Early healing of the alveolar process after tooth extraction: an experimental study in the beagle dog.

    Science.gov (United States)

    Discepoli, Nicola; Vignoletti, Fabio; Laino, Luigi; de Sanctis, Massimo; Muñoz, Fernando; Sanz, Mariano

    2013-06-01

    To describe the early healing events in the alveolar socket during the first 8 weeks of spontaneous healing after tooth extraction. 16 adult beagle dogs were selected and five healing periods were analysed (4 h, 1 week, 2 weeks, 4 weeks, 8 weeks). Mandibular premolars were extracted and each socket corresponding to the mesial root was left to heal undisturbed. In each healing period, three animals were euthanatized, each providing four study sites. Healing was assessed by descriptive histology and by histometric analysis using as landmarks: the vertical distance between buccal and lingual crest (B'L') and the width of buccal and lingual walls at three different levels. Differences between means for each variable for each healing period were compared (ANOVA; p healing period to a final value of 0.18 (0.08) mm. The lingual width (Lw) remains almost unchanged while the buccal width (Bw) at 1 (Bw1) and 2 (Bw2) mm was reduced in about 40% of its initial value. Minor vertical bone reduction in both the buccal and lingual socket walls were observed. A marked horizontal reduction of the buccal bone wall was observed mostly in its coronal aspect. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Toxicity of inhaled 90SrCl2 in Beagle dogs. XIII

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1979-01-01

    The metabolism, dosimetry and biological effects of inhaled 90 SrCl 2 in the Beagle dog are being studied to provide a basis for assessing the consequences of inhaling 90 Sr such as might be released in certain nuclear accidents. Seventy-two dogs were exposed to aerosols containing 90 Sr resulting in initial body burdens ranging from 2.5 to 250 μCi 90 Sr/kg body weight. To date, 60 90 Sr-exposed dogs have died or have been euthanized, six during the first 31 days after inhalation of 90 Sr with bone marrow aplasia and 54 between 585 and 5109 days after inhalation of 90 Sr. The latter group includes 32 dogs with bone-related neoplasms, two with upper respiratory tract carcinomas and five dogs with various diseases of the lower respiratory tract and heart. The other 15 dogs and diseases in organs that received little or no radiation dose, such as the gastrointestinal tract, urinary tract and the central nervous system. The skeletons of the dogs dying with bone-related neoplasms received initial radiation dose rates of 3.2 to 55 rads/day and cumulative doses to death of 2800 to 22 000 rads. Fourteen control dogs have died or been euthanized, two during the last year with mammary carcinoma and intestinal lymphosarcoma. Serial observations are continuing on the six surviving 90 Sr dogs and six controls

  20. Toxicokinetics of beryllium following inhalation of beryllium oxide by Beagle dogs. III

    International Nuclear Information System (INIS)

    Finch, G.L.; Haley, P.J.; Hoover, M.D.; Mewhinney, J.A.; Bice, D.E.; Eidson, A.F.

    1988-01-01

    Young adult Beagle dogs inhaled radiolabeled beryllium oxide aerosols ( 7 BeO) prepared at either 500 deg. or 1000 deg. C to achieve one of two initial lung burdens (ILBs) of BeO. After exposure, animals were monitored by whole body counting for 7 Be, and excreta, clinical, and radiographic data were collected. One group of dogs was assigned for serial sacrifice for quantitation of beryllium clearance from lung, translocation to other organs, and histopathologic analysis of lung and lymph nodes. A second group of dogs was subjected to periodic bronchopulmonary lavage for analysis of lymphocyte responsiveness to beryllium. These latter dogs were subsequently re-exposed to the high ILB level of BeO prepared t 500 deg. C. ILBs following the second exposure were higher than that after the first exposure (74 vs. 42 μg BeO/kg, respectively). Except for one dog that exhibited enhanced beryllium retention after the second exposure, patterns of whole body clearance were similar to those observed after the initial exposures to the 500 deg. C-BeO. Analysis of lymphocyte responsiveness to beryllium in the second group of dogs is continuing. (author)

  1. Effects of x-irradiation of young female beagles on life span and tumor incidence

    International Nuclear Information System (INIS)

    Rosenblatt, L.S.; Book, S.A.; Goldman, M.

    1986-01-01

    Causes of death and the occurrence of neoplasia in female beagle dogs were evaluated retrospectively for 57 unexposed and 296 exposed dogs given single or fractionated whole-body x-irradiation exposures of 100 or 300 R. Some dogs subsequently were bred, and all were observed for the duration of their lives. The pathology for these dogs was derived from clinical records, gross-necropsy reports, tissue slides, and Formalin-fixed tissues. The results of this study indicated dose-related shortening of life span was clearly evident; causes of death due to either neoplasia (50%) or nonneoplastic disease (50%), with few exceptions, were similar in control and irradiated dogs; the incidences of neoplasms were not significantly greater for irradiated dogs than for controls, but the latency period decreased as dose increased; protraction increased survival in dogs given 300 R but not 100 R, which is attributable solely to amelioration of incidence rates of nonmammary neoplasia; and the cumulative rates of death due to mammary tumors were the same in dogs exposed to 100 R and 300 R. 14 refs., 6 figs., 2 tabs

  2. Prevention of radiation pneumonitis from inhaled 144Ce by lung lavage in beagle dogs

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mauderly, J.L.; Boecker, B.B.; Hahn, F.F.; McClellan, R.O.

    1975-01-01

    This study was performed to evaluate bronchopulmonary lavage and chelation therapy as a treatment method to prevent the development of radiation pneumonitis after inhalation of a radioactive aerosol. Twelve beagle dogs were exposed to an aerosol of cerium-144 in fused clay particles resulting in initial lung burdens from 47 to 64 μCi of 144 Ce per kg of body weight. Eight of the dogs were treated with a series of 10 bronchopulmonary lavages and 10 intravenous injections of calcium diethylenetriamine pentaacetate acid during the first 56 days after exposure to remove the deposited 144 Ce; the remaining 4 exposed dogs received no treatment. An additional 4 dogs were exposed to stable cerium and were given the course of treatment as an additional control group. Three of the 4 untreated dogs and 2 of the 8 treated dogs died 171 to 246 days after exposure with radiation pneumonitis or pulmonary fibrosis, or both. All but one of the remaining dogs were alive and apparently in good clinical health 550 days after exposure; the one dog had radiographic indications of pulmonary fibrosis by 365 days after exposure. The relative distribution of 144 Ce in the lungs and other major organs was similar in the treated and untreated dogs that died

  3. Occurrence and distribution of bone tumors in beagle dogs exposed to 90Sr

    International Nuclear Information System (INIS)

    Nilsson, A.; Book, S.A.; California Univ., Davis

    1987-01-01

    Radiation-induced bone tumors in beagle dogs exposed to 90 Sr have been evaluated in terms of their incidence, time of appearance, occurrence as multiple tumors, anatomic distribution, and the influence of sex on their development. Among dogs fed 90 Sr during skeletal development, the incidence of bone tumors was dose independent. Tumors thus appeared in 10 of 19 dogs receiving average skeletal doses of 130 Gy, 15 of 60 receiving 97 Gy, 5 of 61 receiving 61 Gy, 2 of 65 receiving 26 Gy, and 1 of 40 receiving 1.3 Gy. No tumors appeared among 66 dogs who received 8 Gy, 78 who received 0.3 Gy, and 80 non-irradiated controls, all of which have been observed for life. Among dogs given a single inravenous injection of 90 Sr in early adulthood, tumor production was somewhat higher than among 90 Sr-fed dogs at the same radiation dose: bone tumors were present in 6 of 25 dogs who received 62 Gy and 1 of 20 dogs who received 7.5 Gy. Bone tumors appeared sooner and were more often multiple in animals receiving the higher doses. Long bones were the sites of most of the tumors appearing after the highest dose level. Bones of the head, particularly the mandible, were the predominant site of tumors in the next highest dose level group. (orig.)

  4. Biological effects of repeated inhalation exposure of beagle dogs to relatively insoluble aerosols of 144Ce

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; McClellan, R.O.; Mauderly, J.L.; Pickrell, J.A.

    1980-01-01

    Beagle dogs were exposed repeatedly to a relatively insoluble form of 144 Ce (in fused aluminosilicate particles) to study the deposition, retention, and long-term biological effects for comparison with data from dogs that were exposed only once to a similar aerosol. Four groups of nine dogs each were exposed once every 8 weeks for 2 years (13 exposures) to achieve specified exposure goals. These goals were: to increase the lung burden by 2.5 μCi 144 Ce/kg body weight with each exposure; to reestablish lung burdens of 9 or 4.5 μCi 144 Ce/kg body weight and to expose controls to fused aluminosilicate particles containing nonradioactive cerium. To date, 19 exposed dogs and 2 control dogs have died or were euthanized. The most prevalent findings to date have been pulmonary carcinomas (7 dogs) and hemangiosarcomas in the tracheobronchial lymph nodes (3 dogs). Observations are continuing on the surviving 8 144 Ce-exposed and 7 control dogs who are now at approximately 2500 days (6.8 years) after the first exposure

  5. Toxicity of 144Ce inhaled in a relatively insoluble form by aged Beagle dogs. XII

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1983-01-01

    The toxicity of relatively insoluble 144 Ce inhaled by 8- to 10.5-year-old Beagle dogs is being investigated to determine possible age-related differences in long-term biological responses. Forty-two dogs were exposed to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 2.2 to 75 μCi 144 Ce/kg body weight, and 12 control dogs were exposed to non-radioactive fused aluminosilicate particles. All 144 Ce-exposed and control dogs have died or were euthanized between 197 and 2726 days after the inhalation exposure. Prominent findings in the 144 Ce-exposed dogs were radiation pneumonitis in 19 of the 23 dogs that died during the first 943 days after exposure, and neoplastic disease in 13 of the 20 dogs that died beyond 904 days after exposure. Pulmonary tumors were found in five of these dogs. In contrast to the study with young adult dogs, in which pulmonary hemangiosarcomas were one of the prominent findings, all of these tumors were carcinomas

  6. Biokinetics aand dosimetry of inhaled 238PuO2 in the beagle dog: An update

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Griffith, W.C.; Diel, J.H.

    1994-01-01

    The temporal and spatial distributions of 238 Pu have been measured during the course of a dose-response study of the biological effects of inhaled 238 PuO 2 in Beagle dogs. These measurements were done on the dose-response study animals, as well as a separate group of dogs exposed to similar aerosols and killed serially out to 4 y after exposure. The data from this latter group provided the basis for the development of a biokinetic/dosimetric model for 238 PuO 2 in dogs. Since the publication of this model, several important findings have been made that affected the dosimetric evaluations. The first involved the discovery of significant quantities of natural uranium (U) in the feces samples. The U was measured with the plutonium (Pu), which inflated the values for purported Pu in feces. The second finding involved the addition of Pu biokinetics data from the dose-response dogs, which increased the period of observation from 4 y to 15 y; these later data were not consistent with the earlier model predictions. The purpose of this investigation was (1) to remove the analytical bias in the 238 Pu radiochemical data due to the U and (2) to modify the original model of Mewhinney and Diel, taking into account all data from both studies

  7. Toxicity of 144Ce inhaled in a relatively insoluble form by aged Beagle dogs. X

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1981-01-01

    The toxicity of relatively insoluble 144 Ce inhaled by 8- to 10.5-year old Beagle dogs is being investigated to provide possible age-related differences in long-term biological responses. Forty-two dogs were exposed, nose-only, to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 2.2 to 75 μCi 144 Ce/kg body weight, and 12 control dogs were exposed to nonradioactive fused aluminosilicate particles. To date, 39 144 Ce-exposed dogs and 10 control dogs have died or were euthanized between 197 and 2375 days after the inhalation exposure. Prominent findings in the 144 Ce-exposed dogs were radiation pneumonitis in 19 of the 23 dogs that died during the first 943 days after exposure and neoplastic disease in nine of the 16 dogs that died beyond 943 days after exposure. Pulmonary tumors were found in four of these dogs. Observations are continuing on the three surviving 144 Ce-exposed and two control dogs

  8. Toxicity of inhaled 239PuO2 in immature Beagle dogs. VII

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Muggenburg, B.A.; Hahn, F.F.; Mauderly, J.L.; Boecker, B.B.; McClellan, R.O.

    1985-01-01

    Immature Beagle dogs have been exposed by inhalation to a monodisperse aerosol of 239 PuO 2 (1.5 μm AMAD) to compare the biological effects with those observed in dogs exposed to a similar aerosol as young or aged adults. The study includes 96 dogs exposed to 239 PuO 2 and 12 controls. The lung burdens of the plutonium-exposed dogs ranged from 0.00030 to 0.80 μCi/kg body weight (0.011-30 kBq/kg). No dogs died during this year. Seven dogs were diagnosed as having developing lung disease, mainly fibrosis, and one had a developing lung tumor. With 20 dogs having estimated cumulative radiation doses in excess of 1000 rad (10 Gy), the biological response of the dogs exposed as juveniles appears to be less than that seen in mature dogs. However, major uncertainties still exist in the current estimations of radiation dose, particularly regarding the local distribution of alpha radiation dose. 1 reference, 4 figures, 1 table

  9. Toxicity of 144Ce inhaled in a relatively insoluble form by aged Beagle dogs. XIII

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1984-01-01

    Toxicity of relatively insoluble 144 Ce inhaled by 8 to 10.5 year-old Beagle dogs is being investigated to determine possible age-related differences in long-term biological responses. Forty-two dogs were exposed to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 2.2 to 75 μCi 144 Ce/kg (81-2800 kBq/kg) body weight, and 12 control dogs were exposed to non-radioactive fused aluminosilicate particles. All 144 Ce-exposed and control dogs have died or were euthanized between 197 and 2726 days after the inhalation exposure. Prominent findings in the 144 Ce-exposed dogs were radiation pneumonitis in 19 of the 23 dogs that died during the first 943 days after exposure, and neoplastic disease in 13 of the 20 dogs that died beyond 904 days after exposure. Pulmonary tumors were found in five of these dogs. In contrast to the study with young adult dogs, in which pulmonary hemangiosarcomas were one of the prominent findings, all of these tumors were carcinomas. 1 figure, 1 table

  10. Long-term following-up of viability of spleen autotransplants in the Beagle canine model.

    Science.gov (United States)

    Sajtos, Erika; Balint, Anita; Brath, Endre; Nemeth, Norbert; Peto, Katalin; Kovacs, Judit; Galuska, Laszlo; Varga, Jozsef; Fodor, Zoltan; Furka, Istvan; Miko, Iren

    2012-02-01

    To examine the possible late complications of splenectomy or spleen autotransplantation in large laboratory animal model, in which we need non-invasive or minimal-invasive methods for long-term monitoring of the experimental animals. Experimental groups of beagle dogs were: non-operated control, sham-operated control, splenectomy, spleen autotransplantation with 5 or 10 spleen-chips taken into the greater omentum (Furka's technique). Prior to operations, on the 1(st) postoperative week, monthly till the 6(th) as well as in the 9(th) and 12(th) month, hemorheological examinations were performed. In postoperative 12(th) month colloid scintigraphy and diagnostic laparoscopy were carried out. At the end of the investigation comparative morphological examinations were performed, too. From the 4(th)-5(th) postoperative month filtration function of spleen-autotransplants showed particular restoration compared to splenectomy group. However, the functional results did not reach the values of the control or sham-operated groups. Sham-operated control's scintigraphy nicely showed activity in the spleen. In spleen autotransplantation-groups scintigraphy indicated well the activity of spleen-chips. During diagnostic laparoscopy spleen-chips with their blood supply were found. Histologically, the structure of spleen-autotransplants was similar to normal splenic tissue. The autotransplants are regenerated, their functions have been partly restored, and thus spleen autotransplantation may prevent the possible complications of splenectomy. These parameters and the presented investigative protocol are suitable for long-term following-up of viability of the spleen-autotransplants.

  11. Prussian Blue decorporation of 137Cs in beagles of different ages

    International Nuclear Information System (INIS)

    Melo, D.R.; Lundgren, D.L.; Muggenburg, B.A.; Guilmette, R.A.

    1996-01-01

    A 6-wk study was conducted using immature (4.7 mo), young adult (2.4 y), and aged (13.5 y) male beagles to determine the modifying effect of age on the effectiveness of Prussian Blue decorporation therapy for the removal of injected 137 Cs. Whole-body clearance rates for injected 137 Cs decreased with increasing age in the dogs. Treatment with Prussian Blue changed the ratio of fecal to urinary 137 Cs excretion from 0.8 in untreated dogs to 2.2 in treated animals. The 137 Cs concentrations in tissues of untreated and Prussian Blue-treated dogs at the end of the 6-wk study were similar, with the greatest concentrations in the skeletal muscle tissue, spleen, and kidneys. There was a lower concentration of 137 Cs in the livers of the treated dogs. The reductions in the average total whole-body doses resulting from Prussian Blue treatment during the course of this study were 51% in the immature, 31% in the young adult, and 38% in the aged dogs. Because of the differences in the intake of Prussian Blue by the dogs in the different groups relative to their body weight, it is unclear as to the relative effectiveness of Prussian Blue in dogs of different ages. 33 refs., 1 fig., 5 tabs

  12. Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs

    Directory of Open Access Journals (Sweden)

    Nívia Carolina Nogueira-Paiva

    2014-02-01

    Full Text Available Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78 T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model.

  13. Upper gastrointestinal examinations: a radiographic study of clinically normal Beagle puppies

    International Nuclear Information System (INIS)

    Miyabayashi, T.; Morgan, J.P.

    1991-01-01

    A total of 24 upper gastrointestinal examinations were performed on four weanling beagle puppies over six weeks, using liquid barium (10 ml/kg body weight of 60 per cent w/v barium sulphate suspension] and barium food (8 g/kg of crushed kibble dog food and 7 ml/kg body weight of 60 per cent w/v barium sulphate suspension) as contrast media. The radiographic appearance was similar to that noted in adult dogs except for the consistent location of the pylorus on or near the midline. Duodenal pseudoulcers were seen more often with liquid barium and the caecal shadows were identified more often with the longer examination time with barium food. The stomach of the puppies appeared to have discriminatory emptying function; that is, semi-solid food was emptied from the stomach at a slower rate (210 to 450 minutes) than liquid (60 to 90 minutes). Solid meals emptied faster in puppies than in adult dogs. Dosages of 13 to 15 mg/kg body weight for the liquid barium examination and 14 g of ground kibble and 16 ml of barium sulphate suspension per m2 of body surface area for the barium food examination are suggested as more appropriate for contrast studies in puppies

  14. Carcinogenic effects of radon daughters, uranium ore dust and cigarette smoke in beagle dogs

    International Nuclear Information System (INIS)

    Cross, F.T.; Palmer, R.F.; Filipy, R.E.; Dagle, G.E.; Stuart, B.O.

    1982-01-01

    The development of pulmonary lesions in beagle dogs was studied following chronic inhalation exposures to radon (at 105 +- 20 nCi/l), radon daughters (at 605 +- 169 WL), uranium ore dust (at 12.9 +- 6.7 mg/m 3 ) and cigarette smoke. Chronic exposures to mixtures of these agents caused significant lifespan shortening compared with controls. Survival times of controls and smoke-exposed dogs were equivalent during the 4 to 5-yr mean survival time of the dogs exposed to radon-daughter and ore-dust mixtures (with or without added cigarette smoke). Animals with tumors of the respiratory tract generally has cumulative radon-daughter exposures exceeding 13,000 WLM; their survival time was longer than that of nontumor-bearing animals. Exposure to cigarette smoke had a mitigating effect on radon daughter-induced tumors. Exposures to smoke from 10 cigarettes/d, 7 d/wk produced no significant respiratory tract lesions. Exposure to 20 cigarettes/d, 7 d/wk resulted in pulmonary emphysema, fibrosis and chronic bronchitis and bronchiolitis. Emphysema and fibrosis were much more prevalent and severe in the dogs exposed to mixtures including radon daughters and uranium/ore dust. These dogs also had adenomatous lesions which progressed to squamous metaplasia of alveolar epithelium, epidermoid carcinoma and bronchioloalveolar carcinoma. Pathologic changes in the airways of these dogs were most prominent in the nasal mucosa, and included a few squamous carcinomas in the nasal cavity. (author)

  15. Deposition of 0.1 μm chain aggregate aerosols in beagle dogs

    International Nuclear Information System (INIS)

    Wolff, R.K.; Kanapilly, G.M.; DeNee, P.B.; McClellan, R.O.

    1981-01-01

    Deposition and retention of ultrafine chain aggregate particles were studied in 20 beagle dogs. Aggregated particles of insoluble 67 Ga 2 O 3 in the 0.1 μm size range were generated by heat treatment of 67 Ga tetramethylheptanedione. Size characterization was done using electron microscopy, diffusion battery and electrical aerosol analyzer measurements. The average equivalent diffusion diameter of the aerosol was 0.07 μm and the volume median diameter (electrical mobility measurement) was 0.10 μm with a geometric standard deviation of 1.6. Primary particles from which the aggregates were formed were 0.01 to 0.02 μm in diameter. Whole-body counting and gamma camera imaging were used to measure deposition. Total deposition in the whole body was 33 +- 16 % (mean +-S.D.) of the inhaled particles; 82 +- 13 % of this material was deposited in the lung. Retention studies showed that 77 +- 3 % of the material deposited in the lung was in the pulmonary region. Thus, 21 % of the inhaled particles were deposited beyond ciliated airways in alveolar areas. (author)

  16. Effects of Untreated Periodontitis on Osseointegration of Dental Implants in a Beagle Dog Model.

    Science.gov (United States)

    Lee, Daehyun; Sohn, Byungjin; Kim, Kyoung Hwa; Kim, Sungtae; Koo, Ki-Tae; Kim, Tae-Il; Seol, Yang-Jo; Lee, Yong-Moo; Rhyu, In-Chul; Ku, Young

    2016-10-01

    There have been previous studies on the relationship between periodontitis and peri-implantitis, but limited information is available on how periodontitis affects osseointegration and wound healing of newly placed dental implants adjacent to natural teeth. The objective of the present experiment is to evaluate healing around dental implants adjacent to teeth with untreated experimental periodontitis. The study included six male beagle dogs. Scaling and plaque control procedures were performed on three dogs (control group). In the other three dogs (experimental group), retraction cords and ligature wires were placed subgingivally around all premolars and the first molars. Induced experimental periodontitis was confirmed after 3 months. Each control or experimental group was divided into two subgroups depending on the timing of implant placement (immediate/delayed). Twelve dental implants (two implants for each dog) were placed immediately, and the other 12 dental implants (two implants for each dog) were placed 2 months after extraction. The animals were sacrificed 2 months after implant placement. Histologic and histometric analyses were performed. Four implants (three from the immediate placement group and one from the delayed placement group) failed in the experimental group. There were significant differences in the percentage of bone-to-implant contact and marginal bone volume density between the control and experimental groups. Both parameters were significantly lower in the experimental group than in the control group (P implants is associated with a higher failure rate compared with delayed placement. Untreated experimental periodontitis was correlated with compromised osseointegration in the implants with delayed placement.

  17. Lifetime radiation risks from low-dose rate radionuclides in beagles

    International Nuclear Information System (INIS)

    Goldman, M.; Rosenblatt, L.S.

    1985-01-01

    One of the largest, long-term (25-yr) animal studies on the effects of low-dose internal irradiation is almost completed. Some 335 beagles were given continuous exposure to graded 90 Sr [low linear energy transfer (LET)] in their diets (D-dogs) through adulthood. A second group (R-dogs) was given fractionated doses of 225 Ra (high LET) as young adults. A third group of 44 was given a single injection of 90 Sr as adults (S-dogs) to compare single to continuous dosages. All dogs were followed through their lifetimes. Only one of the 848 dogs is still alive. The animals were whole-body counted over their entire life span and were examined frequently for assessment of medical status. There were no acute radiation lethalities. Analyses of the large data base from these dogs have begun and preliminary indications are that 90 Sr, which was tested over a 1500-fold skeletal dose rate range, does not cause significant life shortening at average accumulation skeletal doses of ∼2500 rads (25 Gy) and that a curvilinear dose response curve for life shortening was seen at higher accumulation doses. The data will be discussed in terms of modern epidemiological concepts and quantifications will be related to certain parameters of human risk from acute or chronic radiation exposures

  18. Toxicity of 144Ce inhaled in a relatively insoluble form by aged beagle dogs

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1980-01-01

    The toxicity of relatively insoluble 144 Ce inhaled by 8- to 10.5-year-old beagle dogs is being investigated to provide information on possible age-related differences in the resulting long-term biological responses. Forty-two dogs were exposed, nose-only, to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 2.2 to 75 μCi 144 Ce/kg body weight, and 12 control dogs were exposed to nonradioactive fused aluminosilicate particles. To date, 38 144 Ce-exposed dogs and 10 control dogs have died or were euthanized between 197 and 2375 days after inhalation of the 144 Ce. Prominent findings in the 144 Ce-exposed dogs were radiation pneumonitis in 19 dogs that died during the first 943 days post-exposure and neoplastic disease in seven of the 15 dogs. However, only one of these tumors killed the dog. No hemangiosarcomas have been observed in this study, although they were a prominent finding in immature or young adult dogs exposed to 144 Ce. Observations are continuing on the four surviving 144 Ce-exposed and two control dogs

  19. Toxicity of 144Ce inhaled in a relatively insoluble form by beagle dogs

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1980-01-01

    The metabolism, dosimetry and effects of 144 Ce inhaled in fused aluminosilicate particles are being investigated in the beagle dog to assess the long-term biological consequences of release of relatively insoluble aerosol forms of 144 Ce that could occur in nuclear accidents. The effects resulting from the relatively protracted radiation dose patterns to the lung from this form of 144 Ce are being compared with effects of other radiation dose patterns to the lung. One hundred eleven dogs were exposed to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 0.0024 to 210 μCi/kg body weight and 15 control dogs were exposed to nonradioactive fused aluminosilicate particles. To date, 65 144 Ce-exposed and 2 control dogs have died or were euthanized at 143 to 4578 days after inhalation of 144 Ce. Prominent findings in the 144 Ce-exposed dogs were radiation pneumonitis in 17 dogs that died at early times and neoplastic disease in 39 of the 48 dogs that died 750 days or later. Observations are continuing on the 46 144 Ce-exposed and 13 control dogs remaining alive at this time, at least 3337 days after exposure

  20. Toxicity of 90Sr inhaled in relatively insoluble form by Beagle dogs. XV

    International Nuclear Information System (INIS)

    Snipes, M.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1984-01-01

    Beagle dogs were exposed by inhalation to 90 Sr in a relatively insoluble form to study long-term health effects. Lung burdens ranged from 0.12 to 96 μCi (4.4 to 3550 kBq) of 90 Sr/kg body weight. High levels of exposure resulted in radiation pneumonitis and pulmonary fibrosis; lower level exposures caused long-term effects, including cancer of the lung, heart, and tracheobronchial lymph nodes. Most of these tumors were hemangiosarcomas. Two control dogs and four 90 Sr-exposed dogs died or were euthanized during the past year. One exposed dog died with hemangiosarcoma of the heart and pulmonary adenoma, another exposed dog died with angiosarcoma of tracheobronchial lymph nodes, another exposed dog died with hemangiosarcoma of the heart, and the fourth exposed dog died with hemangiosarcoma of tracheobronchial lymph nodes. One control dog died with adenocarcinoma of the prostate, and the other control dog died with adenocarcinoma of the pancreas. The remaining 15 exposed and 9 control dogs are being maintained for lifetime observation. 2 figures, 1 table

  1. Nasal metabolism of benzo[a]pyrene and dihydrosafrole in Beagle dogs and nonhuman primates

    International Nuclear Information System (INIS)

    Fischer, J.P.; Whaley, S.L.; Dahl, A.R.

    1986-01-01

    The purpose of this study was to determine the extent of nasal metabolism of 3 H-dihydrosafrole and 14 C-benzo[a]pyrene ( 14 C-BaP) by Beagle dogs and cynomolgus monkeys in two regions of the nasal cavity, the ethmoid (olfactory), and maxillary (respiratory) turbinates. Clearance of these two compounds from the nose was studied by collection of nasopharyngeal mucus, blood, urine, and feces during nasal instillation and up to 48 h afterwards. Analysis of the nasopharyngeal mucus showed that either turbinate region in both species metabolized 14 C-Bap to dihydrodiols, quinones, phenols, and tetrols. 3 H-Dihydrosafrole instilled in either turbinate region was extensively metabolized to 2-methyoxy-4-propylphenol. Other major metabolites were 2-methoxy-4-[2-propenyl]-phenol, and 3,4-methylenedioxy-1-(1-hydroxypropyl)benzene. The present study demonstrated a relatively noninvasive technique for studying regional nasal metabolic capabilities in xenobiotic in vivo. The results show that nasal cavities of dogs and monkeys are capable of metabolizing BaP into biologically significant compounds after instillation at both ethmoid and maxillary turbinates. 6 references, 4 tables

  2. 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

  3. Toxicokinetics of beryllium following inhalation of beryllium oxide by Beagle dogs. III

    Energy Technology Data Exchange (ETDEWEB)

    Finch, G L; Haley, P J; Hoover, M D; Mewhinney, J A; Bice, D E; Eidson, A F

    1988-12-01

    Young adult Beagle dogs inhaled radiolabeled beryllium oxide aerosols ({sup 7}BeO) prepared at either 500 deg. or 1000 deg. C to achieve one of two initial lung burdens (ILBs) of BeO. After exposure, animals were monitored by whole body counting for {sup 7}Be, and excreta, clinical, and radiographic data were collected. One group of dogs was assigned for serial sacrifice for quantitation of beryllium clearance from lung, translocation to other organs, and histopathologic analysis of lung and lymph nodes. A second group of dogs was subjected to periodic bronchopulmonary lavage for analysis of lymphocyte responsiveness to beryllium. These latter dogs were subsequently re-exposed to the high ILB level of BeO prepared t 500 deg. C. ILBs following the second exposure were higher than that after the first exposure (74 vs. 42 {mu}g BeO/kg, respectively). Except for one dog that exhibited enhanced beryllium retention after the second exposure, patterns of whole body clearance were similar to those observed after the initial exposures to the 500 deg. C-BeO. Analysis of lymphocyte responsiveness to beryllium in the second group of dogs is continuing. (author)

  4. Ovariectomy-induced changes in aged beagles: Histomorphometry and mineral content of the rib

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, A.K.; Bhattacharyya, M.H.; Hurst, D. [Argonne National Lab., IL (United States). Center for Mechanistic Biology and Biotechnology; Miller, S. [Univ. of Utah, Salt Lake City, UT (United States). Radiobiology Div.; Sacco-Gibson, N. [Proctor and Gamble Pharmaceuticals, Cincinnati, OH (United States)

    1997-08-01

    The effects of ovariectomy on the aged beagle skeleton were studied by histomorphometric analysis of the cortical bone in sequential rib biopsies. Biopsies were taken from each ovariectomized (OV) or sham-operated (SO) dog at the time of surgery and at 1, 4, and 8.5 months after surgery. Tetracycline, calcein, and xylenol orange, respectively, were administered by a fluorochrome labeling procedure (2d-10d-2d) just prior to each postoperative biopsy to provide markers of bone formation. Analysis of sequential biopsies provided a means to follow the response to ovariectomy over time and compare each animal against its own baseline. Examination of sequential biopsies indicated that cortical porosity increased by the fourth month after ovariectomy and remained high at 8.5 months. Ovariectomy did not influence histomorphometric indices at one month after surgery, but substantial differences were observed at later times. Ovariectomy stimulated a transient increase in bone formation and was increased six-fold over that of SO dogs at four months. Ribs were also analyzed for mineral content at necropsy. The rib was heterogeneous along its length for calcium content and concentration. In the midrib where biopsies for histomorphometric analysis were taken, ovariectomy induced a decrease in mass and mineral content; total calcium was decreased by approximately 31%. These data demonstrate that the rib cortical bone is a responsive site for the effects of ovariectomy in female dogs.

  5. Bone sarcoma induction by radium 224 in beagles: an interim report

    International Nuclear Information System (INIS)

    Mays, C.W.; Taylor, G.N.; Lloyd, R.D.; Bruenger, F.W.; Angus, W.

    1989-01-01

    Twenty beagles were given an injection of Ra 224 contaminated with 210 Pb and 228 Th. All have died, 8 with bone sarcoma. In a new study, 128 dogs were given purified Ra 224 in 1, 10 or 50 weekly injections from 1977-1979 (LD 50 for single injection ∼ 400 kBq 224 Ra/kg). As of 14 September 1987, at the highest skeletal dose of 3 Gy from 224 Ra, bone sarcomas had occurred in 5 of 6 dogs at an average of ± SD of 2069±302 days after the start of 50 injections (0 survivors), in 4 of 6 dogs at 2485±1110 days after the start of 10 injections (1 survivor), and in 1 of 8 dogs at 3066 days after a single injection (3 survivors). At 3 Gy, the toxicity of 224 Ra relative to 239 Pu, was 1.0 for 50 injections of 224 Ra, 0.7 for 10, and 0.4 for 1. The effectiveness per Gy of 224 Ra-equivalent dose from 1 injection of 224 Ra contaminated with 228 Th and 210 Pb was equal to that of 239 Pu. (UK)

  6. Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs.

    Science.gov (United States)

    Pan, Liping; Qian, Yafang; Cheng, Minlu; Gu, Pan; He, Yanna; Xu, Xiaowen; Ding, Li

    2015-01-01

    This paper describes the development and validation of a liquid chromatography-mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test), as an instant-release tablet (IR-reference) and as the market leader sustained-release capsule (Rythmol, SR-reference) in male beagle dogs (n=8). In Study A comparing SR-test with IR-reference in a crossover design T max and t 1/2 of propafenone for SR-test were significantly higher than those for IR-reference while C max and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed C max and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively) were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively) although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

  7. Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs

    Directory of Open Access Journals (Sweden)

    Liping Pan

    2015-01-01

    Full Text Available This paper describes the development and validation of a liquid chromatography–mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test, as an instant-release tablet (IR-reference and as the market leader sustained-release capsule (Rythmol, SR-reference in male beagle dogs (n=8. In Study A comparing SR-test with IR-reference in a crossover design Tmax and t1/2 of propafenone for SR-test were significantly higher than those for IR-reference while Cmax and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed Cmax and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

  8. Histological Evaluation of Nano-Micro Titanium Implant Surface Treatment in Beagle Humerus.

    Science.gov (United States)

    Yun, Kwidug; Kang, Seongsoo; Oh, Gyejeong; Lim, Hyunpil; Lee, Kwangmin; Yang, Hongso; Vang, Mongsook; Park, Sangwon

    2016-02-01

    The objective of this study was to investigate the effects of nano-micro titanium implant surface using histology in beagle dogs. A total of 48 screw-shaped implants (Megagen, Daegu, Korea) which dimensions were 4 mm in diameter and 8.5 mm in length, were used. The implants were classified into 4 groups (n = 12): machined surface (M group), RBM (Resorbable Blasting Media) surface (R group), nano surface which is nanotube formation on the machined surface (MA group) and nano-micro surface which is nanotube formation on the RBM surface (RA group). Anodic oxidation was performed at a constant voltage of 20 V for 10 min using a DC power supply (Fine Power F-3005; SG EMD, Anyang, Korea). The bone blocks were investigated using histology. There was no inflammation around implants, and new bone formation was shown along with the nano-micro titanium implant surfaces. The amount of bone formation was increased depending on time comparing 4 weeks and 12 weeks. At 12 weeks, lamellar bone was more formed along with the nano-micro titanium implant surfaces than 4 weeks. It indicated that nano-micro surface showed good result in terms of osseointegration.

  9. Toxicity of 239PuO2 in immature Beagle dogs. VIII

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.; McClellan, R.O.

    1986-01-01

    Immature Beagle dogs have been exposed by inhalation to a monodisperse aerosol of 239 PuO 2 (1.5 μm AMAD) to compare the biological effects with those observed in dogs exposed to a similar aerosol as young or aged adults. The study includes 96 dogs exposed to 239 PuO 2 and 12 controls. The lung burdens of the plutonium-exposed dogs ranged from 0.00030 to 0.80 μCi/kg body weight (0.011-30 kBq/kg). A total of 82 experimental and 11 control dogs are still alive. Seven dogs died this year. Of these, six died of radiation-induced lung disease; the other of a nonradiation cause. As is the case for dogs exposed as young adult animals, the primary causes of death have been lung carcinomas and radiation pneumonitis and fibrosis. However, it is premature to compare the dose-response relationships for the two age groups. 4 figures

  10. Nonparametric statistical techniques used in dose estimation for beagles exposed to inhaled plutonium nitrate

    International Nuclear Information System (INIS)

    Stevens, D.L.; Dagle, G.E.

    1986-01-01

    Retention and translocation of inhaled radionuclides are often estimated from the sacrifice of multiple animals at different time points. The data for each time point can be averaged and a smooth curve fitted to the mean values, or a smooth curve may be fitted to the entire data set. However, an analysis based on means may not be the most appropriate if there is substantial variation in the initial amount of the radionuclide inhaled or if the data are subject to outliers. A method has been developed that takes account of these problems. The body burden is viewed as a compartmental system, with the compartments identified with body organs. A median polish is applied to the multiple logistic transform of the compartmental fractions (compartment burden/total burden) at each time point. A smooth function is fitted to the results of the median polish. This technique was applied to data from beagles exposed to an aerosol of 239 Pu(NO 3 ) 4 . Models of retention and translocation for lungs, skeleton, liver, kidneys, and tracheobronchial lymph nodes were developed and used to estimate dose. 4 refs., 3 figs., 4 tabs

  11. Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs.

    Science.gov (United States)

    Eapen, Alex K; de Cock, Peter; Crincoli, Christine M; Means, Charlotte; Wismer, Tina; Pappas, Christopher

    2017-07-01

    Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Life expectancy for the University of Utah beagle colony and selection of a control group

    International Nuclear Information System (INIS)

    Atherton, D.R.; Stevens, W.; Bruenger, F.W.; Woodbury, L.; Stover, B.J.; Smith, J.M.; Wrenn, M.E.

    1986-01-01

    In the internal-emitters toxicity program at the University of Utah Radiobiology Laboratory, each experimental group carries its own specific control cohort, which is the same size as most of the individual experimental cohorts. Variations in average lifetime are observed among individual control cohorts. This may be due to external causes, genetic variances such as the occurrence of epileptic syndromes, or changes such as those that result from improved medical core or husbandry. The Stover-Eyring method was used to eliminate from control and experimental cohorts those dogs with specific diseases such as epilepsy - dogs that were at risk for too short a time for a later pathological response to occur. By the use of conventional statistical techniques, it ws shown to be reasonable to pool individual control cohorts into a much larger selected cohort that provided greater precision in the estimate of control survival and thus a more sensitive basis for the estimation of the relative life shortening in the experimental groups. The analysis suggested that control groups could be combined, and a control population of 114 beagles was proposed. Their average lifespan was 4926 +- 849 days, and the time when half the animals had died was 5000 days. 3 refs., 2 figs., 5 tabs

  13. 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.

  14. Selection of the landing site in Isidis Planitia of Mars probe Beagle 2

    Science.gov (United States)

    Bridges, J. C.; Seabrook, A. M.; Rothery, D. A.; Kim, J. R.; Pillinger, C. T.; Sims, M. R.; Golombek, M. P.; Duxbury, T.; Head, J. W.; Haldemann, A. F. C.; Mitchell, K. L.; Muller, J.-P.; Lewis, S. R.; Moncrieff, C.; Wright, I. P.; Grady, M. M.; Morley, J. G.

    2003-01-01

    This paper describes selection and characterization of the landing site for the Mars 2004 Beagle 2 mission. The site is within Isidis Planitia between 10°-12°N, 266°-274°W, centered at 11.6°N, 269.5°W. This is at low elevation (-3600 to -3900 m MOLA), is flat (MOLA RMS slope = 0.57°), radar data suggest a smoother surface at decimeter to meter scales than the Pathfinder site and it has a moderate rock abundance (2-17%, mean 11%). In addition to this, Isidis shows evidence for concentration and remobilization of volatiles. In particular, the basin contains conical landforms. We favor models involving the formation of tuff cones during magma-ice interaction. Structures identified as dykes in MOC images may be remnants of magma conduits. The pattern of bulk thermal inertia in Isidis (higher values of 500 Jm-2s-0.5K-1 around the SW-S-E margin decreasing toward the center and north) suggests that an influx of sediment spread from the Noachian areas around the southern half of the basin over the basin floor. The coarse, higher thermal inertia material was deposited closest to the sediment source. The variable state of erosion of the tuff cones suggests that they formed intermittently over a long period of time during Amazonian and possibly Hesperian epochs. Geologically recent resurfacing of Isidis has also occurred by aeolian processes, and this is shown by a deficit in impact craters duricrust.

  15. Raw beef bones as chewing items to reduce dental calculus in Beagle dogs.

    Science.gov (United States)

    Marx, F R; Machado, G S; Pezzali, J G; Marcolla, C S; Kessler, A M; Ahlstrøm, Ø; Trevizan, L

    2016-01-01

    Evaluate the effect of raw bovine cortical bone (CB) (medullary bone cross-sectioned) and marrow or epiphyseal 'spongy' bone (SB) as chew items to reduce dental calculus in adult dogs. Eight 3-year-old Beagle dogs were observed in two study periods. In the first study, the dogs each received a piece of bovine femur CB (122 ± 17 g) daily and in the second study, a piece of bovine femur SB (235 ± 27 g). The first study lasted 12 days and the second 20 days. Dental calculus was evaluated using image integration software. At the start of the studies, dental calculus covered 42.0% and 38.6% of the dental arcade areas, respectively. In study one, the chewing reduced the established dental calculus area to 27.1% (35.5% reduction) after 3 days and after 12 days the dental calculus covering was reduced to 12.3% (70.6% reduction). In study two, the dental calculus covered 16.8% (56.5% reduction) after 3 days, 7.1% (81.6% reduction) after 12 days and 4.7% (87.8% reduction) after 20 days. The CB remained largely intact after 24 h, but SB was reduced to smaller pieces and in some cases totally consumed after 24 h. No complications such as tooth fractures, pieces of bone stuck between teeth or intestinal obstructions were observed during the studies. Chewing raw bovine bones was an effective method of removing dental calculus in dogs. The SB bones removed dental calculus more efficiently in the short term. © 2016 Australian Veterinary Association.

  16. Distribution of skeletal malignancies in beagles injected with 239Pu citrate

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Taylor, G.N.; Angus, W.

    1994-01-01

    The distribution of skeletal malignancies among our beagles injected with 239 Pu as young adults roughly seems to follow the distribution of skeletal mass and skeletal 239 Pu. These findings are similar to those we reported previously for a group of dogs given 226 Ra. Although there were differences in tumor distribution between the animals given 239 Ra and those given 239 Pu, most of them were not statistically significant; however, the radium dogs seemed to show a greater sensitivity to bone tumor origin in the tibia, while there may have been a tendency among the plutonium dogs toward increased relative sensitivity in the scapula, lumbar vertebrae, sacrum, and ribs. In contrast, the most common site for the formation of naturally-occurring bone malignancy in the dog is the distal radius. Perhaps there were too few tumors and too few dogs to establish statistical significance. A correlation between tumor location and at least two anatomical-physiological factors in the skeleton indicated that these two factors (site-specific bone turnover rate and percent of red marrow at the site, which is correlated with vascularity) may influence the appearance of malignancies both individually and in combination. Except for the femur, there appeared to be no difference between the relative distribution of skeletal malignancies of low-level (30 Bq-2 Bq kg -1 injected) and high-level (3-122 kBq kg -1 ) dogs. Distribution of bone tumors between the axial and appendicular skeleton was 50% vs. 50% for 239 Pu (42 and 42), but it was 39% axial vs. 61% appendicular (22 and 35, respectively) for dogs given 226 Ra. This difference was not significant (p > 0.2). 15 refs., 4 tabs

  17. Pharmacokinetics, bioavailability and PK/PD relationship of cefquinome for Escherichia coli in Beagle dogs.

    Science.gov (United States)

    Zhou, Y F; Zhao, D H; Yu, Y; Yang, X; Shi, W; Peng, Y B; Liu, Y H

    2015-12-01

    The pharmacokinetics and bioavailability of cefquinome in Beagle dogs were determined by intravenous (IV), intramuscular (IM) or subcutaneous (SC) injection at a single dose of 2 mg/kg body weight (BW). The minimum inhibitory concentrations (MIC) of cefquinome against 217 Escherichia coli isolated from dogs were also investigated. After IV injection, the plasma concentration-time curve of cefquinome was analyzed using a two-compartmental model, and the mean values of t1/2α (h), t1/2β (h), Vss (L/kg), ClB (L/kg/h) and AUC (μg·h/mL) were 0.12, 0.98, 0.30, 0.24 and 8.51, respectively. After IM and SC administration, the PK data were best described by a one-compartmental model with first-order absorption. The mean values of t1/2Kel , t1/2Ka , tmax (h), Cmax (μg/mL) and AUC (μg·h/mL) were corresponding 0.85, 0.14, 0.43, 4.83 and 8.24 for IM administration, 0.99, 0.29, 0.72, 3.88 and 9.13 for SC injection. The duration of time that drug levels exceed the MIC (%T > MIC) were calculated using the determined MIC90 (0.125 μg/mL) and the PK data obtained in this study. The results indicated that the dosage regimen of cefquinome at 2 mg/kg BW with 12-h intervals could achieve %T > MIC above 50% that generally produced a satisfactory bactericidal effect against E. coli isolated from dogs in this study. © 2015 John Wiley & Sons Ltd.

  18. Removal of inhaled industrial mixed oxide aerosols from Beagle dogs by lung lavage and chelation therapy

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Eidson, A.F.; Guilmette, R.A.

    1978-01-01

    An experiment was conducted in 15 adult Beagle dogs to evaluate lung lavage and chelation therapy for the removal of inhaled particles of mixed actinide oxides. The dogs were divided into three groups of five dogs each. Each group was exposed to an aerosol from a different industrial process. Group 1 was exposed to mixed oxide material which had been calcined at 750 0 C collected from a ball milling process. Group 2 was exposed to mixed oxide material from a centerless grinding operation which had been previously heat treated to 1750 0 C. The third group was exposed to 239 PuO 2 not containing uranium from a V-blending procedure which had been heat treated at 850 0 C. After exposure, three dogs in each group were given ten lung lavages and 18 intravenous injections of calcium trisodium diethylenetriaminepentaacetate (DTPA). All dogs were sacrificed 64 days after inhalation exposure. The tissues were radioanalyzed for plutonium and americium. Fluorimetric analyses for uranium in the tissues are in progress. The urine, feces and lavage fluid are also being analyzed for plutonium, americium and uranium. The distribution of plutonium and americium expressed as percentages of the sacrifice body burden was similar in the tissues of the treated and unteated dogs. The lungs contained most of the radionuclides with a small amount in the liver, skeleton and tracheobronchial lymph nodes. The percentage of the sacrifice body burden of americium and plutonium that was present in the lung was less in the treated dogs and was higher in the TBLN's and skeleton than in the untreated dogs. The ratio of Pu/Am was higher in the lungs than in the original material obtained from the industrial sites suggesting a shorter retention time for americium than plutonium to 64 days in the dog

  19. Estimation of initial lung deposition of inhaled 238PuO2 in beagles

    International Nuclear Information System (INIS)

    Stevens, D.L.; Park, J.F.

    1986-01-01

    Studies to determine the life-span dose-effect relationship of inhaled 238 PuO 2 in dogs require an estimate of initial lung deposition (ILD) to calculate the radiation dose to several organs. Ideally, this estimate of ILD is obtained by a summation of plutonium body burden at death plus all the plutonium excreted during the life of the dog. However, the high costs of excreta collection and of plutonium analyses for all excreta from each dog made it necessary to approximate the ILD by other less expensive methods. These methods could introduce error into the estimate of ILD and, consequently, into the radiation dose calculation. The objective of this work was to evaluate the potential error for several methods of estimating ILD. Thirteen beagle dogs were given a single 5- to 30-min exposure to 238 PuO 2 aerosols, resulting in estimated ILD of 0.85 to 11.7 μCi of plutonium-238. Plutonium analyses of the tissues at death and of all excreta from these dogs were used for this evaluation. The estimate of ILD, obtained by summation of the plutonium body burden at death plus all the plutonium excreted, was compared to the estimated ILD obtained by the plutonium whole-body retention function for each dog, using all excreta data; the mean plutonium whole-body retention function for each dog, using all excreta data; the plutonium whole-body retention function for each dog, using partial excreta data; and a mean plutonium whole-body retention function for all dogs, using partial excreta data. 4 refs., 3 figs., 4 tabs

  20. Toxicity of inhaled 90SrCl2 in beagle dogs. XI

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Rebar, A.H.; Benjamin, S.A.; Boecker, B.B.; Jones, R. K.; McClellan, R.O.; Pickrell, J.A.

    1977-01-01

    Studies on the metabolism, dosimetry, and effects of inhaled 90 SrCl 2 in the Beagle dog are continuing in an effort to provide a basis for assessing the consequences of inhaling 90 Sr such as might be released in certain nuclear accidents. Seventy-two dogs were exposed to aerosols containing 90 Sr resulting in initial body burdens ranging from 2.5 to 250 μCi 90 Sr/kg body weight. Forty-eight of these dogs are being maintained for lifetime observation. Twenty-five unexposed dogs serve as controls. The long-term retained burden (LTRB) in these dogs ranged from 1 to 120 μCi 90 Sr/kg. Twenty-four dogs with a mean LTRB of 38 μCi 90 Sr/kg have been assigned to a sacrifice study. Two of these dogs and one control dog were sacrificed at five days, one month and one year after inhalation of 90 Sr. To date, 51 90 Sr-exposed dogs have died or have been euthanized, six during the first 31 days after inhalation of 90 Sr with bone marrow aplasia and 45 between 585 and 4236 days after inhalation of 90 Sr. The latter group includes 12 dogs with bone-related hemangiosarcomas, 16 with osteosarcomas, three with fibrosarcomas, three with osteochondrosarcomas, one with osteochondrofibrosarcoma, two with leukemia, one with a baso-squamous carcinoma of the skull, one with a squamous cell carcinoma of the maxilla, one with a squamous cell carcinoma of the frontal sinus, one with a hemangiosarcoma of the heart, one with a myxosarcoma of the skull, one with transitional cell carcinoma, one with bronchioalveolar carcinoma, one with an epileptic seizure, one with pneumonia, one with cerebellar hemorrhage and three with a malabsorption syndrome

  1. Toxicity of injected 137CsCl in beagle dogs. X

    International Nuclear Information System (INIS)

    Rebar, A.H.; Hanika-Rebar, C.; Benjamin, S.A.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1977-01-01

    Studies on the metabolism, dosimetry and effects of intravenously administered 137 CsCl in the Beagle dog are being conducted to aid in assessing the biologic consequences of exposure to 137 Cs such as occurs in the event of certain nuclear accidents. Effects of the chronic, relatively uniform whole-body exposure produced by 137 Cs are being compared with other diverse radiation dose patterns resulting from inhalation of radioactive aerosols. Sixty-six dogs were entered into the study: six with a mean initial 137 Cs body burden of 3780 μCi/kg and five groups of 12 dogs each with mean initial 137 Cs body burdens of 2820, 1940, 1420, 970 and 0 μCi/kg. Eighteen of the dogs injected with 137 CsCl have died: 11 from 19 to 81 days after injection and cumulative whole-body doses of 860 to 1400 rads died with severe bone marrow damage and resultant pancytopenia; two at 2471 days and at 2707 days after injection and cumulative doses of 690 and 1800 rads with a neurofibrosarcoma of the liver and a mast cell tumor of the skin; five from 693 to 3162 days after injection and cumulative doses of 840 to 2000 rads with shock, aspiration pneumonia, severe arthritis, renal amyloidosis and congestive heart failure. Three control dogs died; one at 647 days with auto-immune hemolytic anemia, one at 2442 days with renal amyloidosis and one at 3088 days with disseminated complex mammary adenocarcinoma. Serial observations are continuing on the 36 137 CsCl dogs and nine control dogs. The 137 CsCl dogs now alive have cumulative whole-body doses of 550 to 2200 rads from 2777 to 3031 days after injection

  2. Late effects of protracted whole-body irradiation of beagles by cobalt-60 gamma rays

    International Nuclear Information System (INIS)

    Fritz, T.E.; Seed, T.M.; Tolle, D.V.; Lombard, L.S.

    1986-01-01

    So that a stronger basis for extrapolation of low-level radiation effects to man can be provided, existing data from small laboratory animals are being supplemented by studies in a longer lived animal, the dog. Beagle dogs are exposed to continuous cobalt-60 irradiation either throughout life or until predetermined total doses are accumulated. The radiation-specific excess-mortality rate and associated causes of death will be related to both dose rate and total dose. The ongoing studies also emphasize the pathogenesis of myelogenous leukemia. At dose rates of 3.75 to 26.25 rads/day, given continuously, responses were consistent, highly dose-rate dependent, and limited primarily to the hematopoietic system. At rates as low as 0.3 rad/day, the hematopoietic system is still the limiting factor for survival, but below 3.75 rads/day present evidence suggests that the responses are independent of dose rate. Longitudinal studies of peripheral blood and bone marrow detected four preclinical phases of myelogenous leukemia. These phases were characterized by standard hematologic end points, ultrastructural features, in vitro cloning assays, and the acute radiation sensitivity of stem cells. Results suggest that an induced error-prone repair mechanism is the basis for the onset of radiation-induced myelogenous leukemia. Interim data from dogs given terminated exposures suggest that the types of tumors and times to death are different from controls but the numbers of tumors are not yet greater than in controls. 26 refs., 12 figs., 5 tabs

  3. Microdistribution and local dosimetry of 226Ra in trabecular bone of the beagle

    International Nuclear Information System (INIS)

    Polig, E.; Jee, W.S.; Dell, R.B.; Johnson, F.

    1988-01-01

    Sections of lumbar vertebral bodies of young adult beagle dogs have been analyzed autoradiographically to characterize and quantify the local distribution of 226Ra by means of a scanning microscope photometer. The animals received a single injection of 355 kBq/kg body weight and were serially sacrificed at 5 to 1381 days postinjection. Hotspot concentrations decreased from about 51 kBq/g bone at 5 days to 20 kBq/g at 1381 days postinjection. The diffuse concentration changed from 8.3 to 1.9 kBq/g. The mean 226Ra concentration in the trabecular areas scanned was initially higher and at the end of the observation period lower than the average calculated for the whole lumbar vertebral column. Density and area of, and fraction of bone activity in, hotspots virtually remained constant. With time hotspots tended to become translocated into bone volume. Mean dose rates to lining cells from both hotspots and diffuse labels decreased from about 210 mGy/d at early postinjection times to 105 mGy/d. This corresponds to 2.5 to 1.1 times the average skeletal dose rate. A discussion of the level of irradiation in terms of hit frequencies shows that osteoblasts in the initial phase of hotspot formation receive about 60 hits to their nucleus for the duration of bone formation. After about 6 months, however, the 226Ra concentration in new bone and the corresponding hit frequency appears to be low enough that interference with bone formation is unlikely. Morphometric measurements showed that abnormal bone accretion and thickening of trabeculae occurred. This was interpreted as an imbalance between bone formation and resorption. Both formation and resorption seem to be substantially lowered compared to control animals

  4. Skeletal muscle tissue transcriptome differences in lean and obese female beagle dogs.

    Science.gov (United States)

    Grant, R W; Vester Boler, B M; Ridge, T K; Graves, T K; Swanson, K S

    2013-08-01

    Skeletal muscle is a large and insulin-sensitive tissue that is an important contributor to metabolic homeostasis and energy expenditure. Many metabolic processes are altered with obesity, but the contribution of muscle tissue in this regard is unclear. A limited number of studies have compared skeletal muscle gene expression of lean and obese dogs. Using microarray technology, our objective was to identify genes and functional classes differentially expressed in skeletal muscle of obese (14.6 kg; 8.2 body condition score; 44.5% body fat) vs. lean (8.6 kg; 4.1 body condition score; 22.9% body fat) female beagle adult dogs. Alterations in 77 transcripts was observed in genes pertaining to the functional classes of signaling, transport, protein catabolism and proteolysis, protein modification, development, transcription and apoptosis, cell cycle and differentiation. Genes differentially expressed in obese vs. lean dog skeletal muscle indicate oxidative stress and altered skeletal muscle cell differentiation. Many genes traditionally associated with lipid, protein and carbohydrate metabolism were not altered in obese vs. lean dogs, but genes pertaining to endocannabinoid metabolism, insulin signaling, type II diabetes mellitus and carnitine transport were differentially expressed. The relatively small response of skeletal muscle could indicate that changes are occurring at a post-transcriptional level, that other tissues (e.g., adipose tissue) were buffering skeletal muscle from metabolic dysfunction or that obesity-induced changes in skeletal muscle require a longer period of time and that the length of our study was not sufficient to detect them. Although only a limited number of differentially expressed genes were detected, these results highlight genes and functional classes that may be important in determining the etiology of obesity-induced derangement of skeletal muscle function. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation

  5. Use of the carbon dioxide laser in guided tissue regeneration wound healing in the beagle dog

    Science.gov (United States)

    Rossmann, Jeffrey A.; Parlar, Ates; Abdel-Ghaffar, Khaled A.; El-Khouli, Amr M.; Israel, Michael

    1996-04-01

    The concept of guided tissue regeneration (GTR) allowing cells from the periodontal ligament and alveolar bone to repopulate the treated root surface has shown the ability to obtain periodontal new attachment. Healing studies have also shown that conventional GTR therapy still does not exclude all the epithelium. This epithelial proliferation apically interferes with the establishment of the new connective tissue attachment to the root surface. The objective of this research study was to examine whether controlled de-epithelialization with the carbon dioxide laser during the healing phase after periodontal surgery, would retard the apical migration of the epithelium and thereby enhance the results obtained through guided tissue regeneration. Eight beagle dogs were used, the experimental side received de-epithelialization with the CO2 laser in conjunction with flap reflection and surgically created buccal osseous defects. Selected defects on each side were treated with ePTFE periodontal membranes. The laser de-epithelialization was repeated every 10 days until removal of the membranes. The control side received the same surgical treatment without laser application. This experimental design allowed histologic study of the new attachment obtained in defects treated with flap debridement with or without laser de-epithelialization and with or without ePTFE membranes. A statistical analysis was performed on the histometric data from 48 teeth in the 8 dogs after 4 months of healing. The results showed significant amounts of new attachment obtained from all four treatment modalities with no statistically significant differences for any one treatment. However, the trend towards enhanced regeneration with the combined treatment of laser and membrane vs. membrane alone or debridement alone was evident. The histologic analysis revealed a significant amount of newly formed `fat cementum' seen only on the laser treated teeth. This feature was the most remarkable finding of the

  6. Neoplasia in beagles that received whole-body irradiation during prenatal or postnatal development

    International Nuclear Information System (INIS)

    Benjamin, S.A.; Angleton, G.M.; Lee, A.C.; Saunders, W.J.; Miller, G.K.; Jaenke, R.S.; Brewster, R.D.; Long, R.I.

    1986-01-01

    Sensitivity to radiation carcinogenesis is being studied in 1680 beagle dogs that received whole-body 60 Co gamma radiation exposures during development. Eight treatment groups of 120 dogs each received 0.16 or 0.83 Gy at one of three prenatal (8, 28, or 55 days postcoitus) ages or at one postnatal (2 days postpartum) age. One treatment group of 120 dogs received 0.83 Gy as juveniles at 70 days postpartum, and one treatment group of 240 young adult dogs received 0.83 Gy at 365 days postpartum. Three-hundred-sixty control dogs were sham irradiated. Of the 1680 dogs, 1058 are dead. Approximately 25% of these deaths were related to malignant neoplasia. The age-related incidence of neoplasia is being evaluated. While the incidence of all neoplasms is being studied, particular emphasis is being placed on types of cancer with known susceptibility to induction by radiation such as those of breast, thyroid, and hematopoietic tissues. Neoplasms are classed as (1) incidental, i.e., those found at necropsy in dogs that died of an unrelated cause; (2) mortality independent, i.e., those seen in live dogs and removed surgically, or (3) fatal, i.e., those directly or indirectly responsible for death. Analyses of incidental tumors are done by a prevalence method, whereas analyses of mortality-independent and fatal tumors use an onset-rate or death-rate method. The results of these methods are then combined to give a composite age-related incidence of specific neoplasms. Analyses also are done on disease subgroups to attempt to delineate the effect of intercurrent disease on tumor incidence. The results of such analyses support the concept that age at exposure is an important factor in radiation carcinogenesis. 28 refs., 7 tabs

  7. Toxicity of inhaled 90Y in fused clay particles in beagle dogs. VI

    International Nuclear Information System (INIS)

    Hobbs, C.H.; Chiffelle, T.L.; Hahn, F.F.; Jones, R.K.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1974-01-01

    Studies on the metabolism, dosimetry, and effects of inhaled 90 Y in fused clay in the Beagle dog are being continued to assess the consequences of inhalation of an energetic beta emitter that has a short effective half-life in the lung. A radiation dose pattern study in which 12 dogs were sacrificed in pairs at 0, 2, 4, 6, 8, and 12 days post-inhalation exposure has been completed. A longevity study in which 89 dogs have been exposed to 90 Y fused clay with initial lung burdens ranging from 80 to 5200 μCi/kg body weight and 12 control dogs were exposed to stable yttrium in fused clay is in progress. The 90 Y was retained in lung with a half-life similar to its physical half-life (64 hours) and with only small quantities translocated to tracheobronchial lymph nodes, skeleton, and liver. The infinite radiation doses to lung, tracheobronchial lymph nodes, skeleton, and liver for an initial lung burden of 100 μCi 90 Y/kg of body weight were estimated to be 1600, 170, 0.54, and 0.38 rads, respectively. Thirty-eight of 39 dogs with doses to lung from 9300 to 70,000 rads have died at 7.5 to 903 days post-exposure. The one surviving dog in this dose range has radiographic evidence of pulmonary fibrosis at 1316 days post-exposure. All the dogs that died had radiation pneumonitis. The dog that died at 903 days post-exposure with a dose to lung of 11,000 rads also had 2 small pulmonary adenomas. Fifty exposed dogs with doses to lung of 1300 to 7900 rads are surviving with no significant abnormalities at 1278 to 1834 days post-exposure and will be studied for the remainder of their lifespan. (U.S.)

  8. Toxicity of 144Ce inhaled in a relatively insoluble form by Beagle dogs. XI

    International Nuclear Information System (INIS)

    Hahn, F.F.; Hanika-Rebar, C.; Boecker, B.B.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1978-01-01

    The metabolism, dosimetry and effects of 144 Ce inhaled in fused aluminosilicate particles are being investigated in the Beagle dog to assess the biological consequences of release of 144 Ce in a relatively insoluble form such as might occur in certain types of nuclear accidents. The toxicity of inhaled 144 Ce is also of general interest since it is representative of intermediate-lived beta-emitting radionuclides. Two major studies with young adult dogs (12 to 14 months of age at exposure) are involved: (1) a metabolism and dosimetry study in which 24 dogs were serially sacrificed over an extended period of time, and (2) a longevity study with two series of dogs. Series I contains 15 dogs exposed to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 11 to 210 μCi/kg body weight and three control dogs exposed to nonradioactive fused aluminosilicate particles. Series II contains 96 dogs exposed to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 0.0024 to 66 μCi/kg body weight and 12 control dogs exposed to nonradioactive, fused aluminosilicate particles. To date, 51 dogs have died or were euthanized at 143 to 3280 days after inhalation of 144 Ce. The prominent findings were radiation pneumonitis in 17 dogs that died or were euthanized at 750 days or later. The cumulative radiation dose to the lung at time of death has ranged from 550 to 140,000 rads. Serial observations are continuing on the 60 survivors and 15 controls

  9. Toxicity of 144Ce inhaled in a relatively insoluble form by immature Beagle dogs. VIII

    International Nuclear Information System (INIS)

    Boecker, B.B.; Merickel, B.S.; Hahn, F.F.; Mauderly, J.L.; McClellan, R.O.

    1979-01-01

    The influence of age at exposure on the resulting patterns of deposition, retention, dosimetry and biological effects from a single inhalation exposure to a relatively insoluble form of a beta-emitting radionuclide with a relatively long physical half-life is being investigated. Immature Beagle dogs (3 months of age) have been exposed once, by inhalation, to an aerosol of 144 Ce incorporated in fused aluminosilicate particles. Eighteen of these dogs were serially sacrificed to study the patterns of deposition, retention and dosimetry and the remaining 49 dogs received graded initial lung burdens that ranged from 0.004 to 140 μCi 144 Ce/kg body weight and are being observed over their life span for study of the resulting long-term biological effects. Five control dogs are also included in this study. To date, 13 of the 144 Ce-exposed dogs in the longevity study and none of the controls have died. Dogs with the highest initial lung burdens of 144 Ce died first (during the first 4 months) with radiation pneumonitis, pulmonary fibrosis and congestive heart failure. Pulmonary hemangiosarcoma was the primary finding in dogs that died at 1.5 to 2 years after exposure. Deaths beyond that time have primarily involved extrapulmonary hemangiosarcomas. One dog, 627B, with an initial lung burden of 24 μCi 144 Ce/kg body weight died during the past year at 2341 days after exposure with a widely disseminated hemangiosarcoma showing heavy involvement of the liver and skin. Observations are continuing on the surviving 36 144 Ce-exposed and five control dogs

  10. Toxicity of 144Ce fused clay particles inhaled by immature beagle dogs. III

    International Nuclear Information System (INIS)

    Boecker, B.B.; McClellan, R.O.; Hahn, F.F.; Hobbs, C.H.; Mauderly, J.L.

    1974-01-01

    The metabolism, dosimetry, and biological effects of 144 Ce fused clay particles inhaled by immature Beagle dogs (approximately 3 months of age at exposure) are being investigated for comparison with studies of dogs exposed at 12 to 14 months of age and 8 to 10.5 years of age. These studies will assess possible age-related differences in the biological behavior and effects of inhaled radionuclides, differences that may be of significance in predicting the response of accidentally-exposed human populations that include individuals of different ages. Eighteen immature dogs have been entered into a radiation dose pattern study to be serially sacrificed at different intervals after inhalation exposure. During the first 2 months post-exposure, lung clearance and uptake by the tracheobronchial lymph nodes appeared to be greater in the immature dogs than in young adult dogs. Also, skeletal uptake was greater than hepatic uptake in the immature dogs. Three blocks of longevity animals, 10 per block, with graded initial lung burdens ranging from 0.004 to 120 μCi 144 Ce/kg body weight and 1 control, are currently on experiment. Three dogs with initial lung burdens of 73 to 120 μCi 144 Ce/kg body weight died at 66 to 121 days after exposure with pulmonary injury and congestive heart failure. Another dog with an initial lung burden of 70 μCi 144 Ce/kg body weight died at 511 days after exposure with pulmonary injury. Serial observations are continuing on the surviving 26 144 Ce-exposed and 3 control dogs. (U.S.)

  11. Primary degenerative joint disease of the shoulder in a colony of Beagles

    International Nuclear Information System (INIS)

    Morgan, J.P.; Pool, R.R.; Miyabayashi, T.

    1987-01-01

    Shoulder joints of 149 Beagles over 8 years old at the time of death (mean age, 13.8 years +/- 3.21), were examined radiographically throughout their life-times for the frequency of degenerative joint disease (DJD). Clinical histories revealed no underlying cause for DJD. The shoulder joints of a subgroup of 18 dogs were examined at necropsy, and thin sections of the joints were evaluated radiographically and histologically. Serial clinical radiographic studies indicated that normal shoulder joint development during the first year of life was followed by the appearance of subchondral bone sclerosis and bony remodeling of normal joint contour, and by the formation of periarticular osteophytes and enthesiophytes. All changes were progressive with age and typical for DJD in dogs. Bilateral involvement was common. Evaluation of specimens obtained at necropsy revealed: articular cartilage change with roughening of the surface layer, degeneration and death of superficial chondrocytes, exposure of deeper layers of chondrocytes that had proliferated with fissuring of the damaged cartilage, total cartilage loss with polishing of the exposed subchondral bone, mixed patterns of subchondral bone sclerosis and osteoporosis, change in contour of the articular surfaces, and formation of periarticular osteophytes and enthesiophytes. Joint capsule thickening, synovitis, pannus formation, and synovial chondroma formation were observed. Because of the available clinical information, in addition to the typical changes of DJD, it was thought that the changes were primary. Instability appeared to play a role in the pathogenesis of the joint disease described; however, it was not clear whether the instability caused abnormal forces on healthy cartilage or whether the primary cartilage wear caused the instability

  12. Toxicity of 91Y inhaled in a relatively insoluble form by Beagle dogs. IX

    International Nuclear Information System (INIS)

    Hobbs, C.H.; Hahn, F.F.; McClellan, R.O.; Mauderly, J.L.; Muggenburg, B.A.; Pickrell, J.A.

    1978-01-01

    Studies of the radiation hazards due to inhalation of 91 Y in fused aluminosilicate particles have been undertaken in Beagle dogs to assess the biological consequences of inhaling a relatively insoluble, energetic beta emitter with an intermediate effective half-life in the lung. A radiation-dose pattern study in which 30 dogs were serially sacrificed from 0 to 320 days after inhalation exposure to 91 Y in fused aluminosilicate particles has been completed. A longevity study is in progress in which 96 dogs were exposed to achieve initial lung burdens ranging from 11 to 300 μCi 91 Y in fused aluminosilicate particles/kg body weight and 12 dogs were exposed to stable yttrium in fused aluminosilicate particles. To date, 56 dogs have died in the longevity study between 113 and 2841 days after exposure. Forty of these dogs, with cumulative radiation doses to lung between 8,300 and 60,000 rads, died with clinicopathologic findings of radiation pneumonitis and/or pulmonary fibrosis at 113 to 1011 days after exposure. Fifteen dogs that died between 1115 and 2841 days after exposure with cumulative doses to lung ranging from 16,000 to 25,000 rads had pulmonary carcinomas. One dog that died at 1847 days after exposure with a cumulative dose to lung of 9,700 rads had a hemangiosarcoma of the spleen. Forty exposed dogs with doses to lung of 2,400 to 18,000 rads and 12 control dogs remain alive from 2563 to 3116 days after inhalation exposure and will continue to be studied throughout the remainder of their life span to determine the relationship between radiation dose, dose rate and biologic effects

  13. Radiation-induced quantitative alterations in prenatal thymic development in the beagle dog

    International Nuclear Information System (INIS)

    Miller, G.K.; Benjamin, S.A.

    1985-01-01

    Quantitative morphology of the canine fetal thymus was studied to evaluate the age-dependent radiosensitivity of the developing immune system. Pregnant beagle dams received abdominal 60 Co gamma exposures (200 R) or were sham irradiated at one of three ages in gestation, 30, 40, or 45 days. The mean calculated dose to each fetus was 1.5 Gray. One-half of the fetuses in each litter were harvested by hysterotomy at 5 days and one-half at 10 days post-irradiation (PI). The volumes of the thymic lobules and lobular cortices were significantly reduced at 5 and 10 days PI when compared with age-matched controls. Thymic cortical volumes in irradiated fetuses were reduced between 13 and 29% from control volumes by 5 days PI and 8 and 13% by 10 day PI. Thymic medullary volumes in irradiated fetuses were reduced 18 to 23% by 5 days PI and 27 to 54% by 10 days PI. The reductions in medullary volumes in fetuses irradiated at 35, 40, and 45 days of gestation and evaluated at 10 days PI were 54, 38, and 27%, respectively. Although injury to both thymic cortices and medullas was greater following exposures earlier in gestation, damage to medullas was relatively more severe than in cortices following exposure at any one age. The degree of reduction of medullary volume reflects thymic epithelial injury and is surprising since thymic epithelium is considered to be radioresistant in the adult. Such injury may have serious consequences postnatally as normal differentiation of T cell subpopulations is dependent upon the integrity of the thymic microenvironment. Damage to the thymic microenvironment could result in defects in immunologic regulation and in immune deficiencies

  14. Lovelace ITRI studies on the toxicity of inhaled radionuclides in beagle dogs

    International Nuclear Information System (INIS)

    McClellan, R.O.; Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.

    1986-01-01

    This paper reviews 19 studies conducted by the Lovelace ITRI on the toxicity of inhaled radionuclides in beagle dogs. These studies provide information to estimate potential health effects in accidentally exposed people. Specific radionuclides ( 90 Sr, 90 Y, 91 Y, 137 Cs, 144 Ce, 238 Pu, and 239 Pu), chemical forms, and particle sizes were selected for study because they are abundant in nuclear operations and deliver a wide range of radiation dose patterns. Depending upon the aerosol, one or more of the following organs or tissues received the significant irradiation: lung, nasal cavity, lung-associated lymph nodes, whole body, liver, or skeleton, with the radiation dose delivered over durations of time ranging from a few days to several years. In eight studies monodisperse particles of either 238 PuO 2 or 239 PuO 2 were used to evaluate the influence of particle number and total dose on lung cancer induction. Most studies involved single, brief exposures of young adult dogs, but two studies used immature dogs, two used aged dogs, and two studies involved repeated brief exposures. For each aerosol two types of studies were conducted. One was used to evaluate the time course of retention of radioactivity in various tissues of the body for calculating radiation doses. The second was used to determine health effects in animals exposed to achieve different initial lung burdens and observed for the remainder of their life spans. Initial lung burdens were selected to produce early morbidity and mortality at the highest levels and an excess of late-occurring diseases such as cancer at the lowest levels. The latter dogs have had an excess incidence of cancer, especially of the lung, lung-associated lymph nodes, nasal cavity, skeleton, and liver. Relationships between radiation doses to various tissues and effects have been evaluated for individual studies

  15. 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

  16. Biological effects of repeated exposure of beagle dogs to relatively insoluble aerosols of 144Ce. IV

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Hanika-Rebar, C.; McClellan, R.O.; Mauderly, J.L.; Pickrell, J.A.

    1977-01-01

    This experiment is being conducted to study the behavior and long-term biological effects in Beagle dogs of 144 Ce inhaled in fused aluminosilicate particles in repeated inhalation exposures for comparison with similar data from dogs that were exposed only once to a similar aerosol. Four groups of nine dogs each were exposed once every eight weeks for two years (13 exposures) to achieve specified exposure goals. The 144 Ce-exposed dogs received increasing or relatively constant beta radiation dose rates in contrast to the steadily decreasing dose rate seen after a single inhalation exposure. Exposures in the first and second groups were planned to yield a cumulative absorbed dose to lung of approximately equal to 35,000 rads and those in the third group approximately equal to 17,000 rads within two years after the first exposure. Singly exposed dogs that had died with pulmonary tumors when this experiment was initiated had cumulative doses to death of 29,000 to 61,000 rads. All 13 exposures have been completed. One dog in the 4.5-μCi 144 Ce/kg body weight group died at 771 days after first exposure with emaciation, adrenal cortical degeneration and bone marrow aplasia. One control dog died accidentally during anesthesia. During the past year, two additional dogs have died. One dog in the repeated 2.5-μCi 144 Ce/kg body weight group died at 1256 days after the first exposure with radiation pneumonitis and pulmonary fibrosis and a control dog died at 1052 days with autoimmune hemolytic anemia. The remaining 32 dogs appear to be in good physical condition except for a persistent lymphopenia at approximately equal to 4 years after the first exposure. They are being maintained for life span observations

  17. Irradiation-induced erythroleukemia and myelogenous leukemia in the beagle dog: hematology and ultrastructure

    International Nuclear Information System (INIS)

    Seed, T.M.; Tolle, D.V.; Fritz, T.E.; Devine, R.L.; Poole, C.M.; Norris, W.P.

    1977-01-01

    A high incidence of leukemia in adult beagle dogs was induced by continuous whole-body exposure to low doses of 60 Co gamma irradiation. At 5, 10, and 17 R per 22-hr exposure day, 20 animals of 53 died of either myelogenous leukemia (15 of 20) or erythroleukemia (5 of 20); the latter occurred only at 5 R/day. Consistent preclinical changes occurred in the peripheral blood, including a partial recovery from an initial severe leukopenia, a prolonged accommodation-to-irradiation phase, and marked oscillations in platelet values in the preleukemic period. In the terminal condition the dogs were severely anemic, thrombocytopenic, and commonly leukopenic. Peripheral blood buffy-coat preparations contained circulating ''blast'' cells and juvenile forms. Abnormal erythrocyte and platelet morphology was consistently present. The bone marrow was altered most severely; other organs showed variable degrees of leukemic infiltration and proliferation and loss of normal tissue architecture. The marrow was hyperplastic with little or no fat remaining. Differential marrow cell counts showed increased numbers of immature cell forms. Myeloid:erythroid (M:E) ratios ranged from 2.6:1 to 61.5:1 in the granulocytic leukemias, and 0.2:1 to 1:1 in the erythroleukemias. Juvenile leukemic cells (both circulating and tissue forms) displayed a number of distinctive cytologic features, including asynchronous patterns of nuclear-cytoplasmic maturation, increased incidence of nuclear clefts, coalescence of cytoplasmic granules, and bizarre arrangements of endoplasmic reticulum. These experimentally induced canine leukemias have many hematologic and cytologic features in common with both spontaneous and radiation-induced leukemias of man. Thus, they may provide a useful model for the study of human leukemia

  18. Carcinogenesis and Inflammatory Effects of Plutonium-Nitrate Retention in an Exposed Nuclear Worker and Beagle Dogs

    International Nuclear Information System (INIS)

    Nielsen, Christopher E.; Wang, Xihai; Robinson, Robert J.; Brooks, Antone L.; Lovaglio, Jamie A.; Patton, Kristin M.; McComish, Stacey; Tolmachev, Sergei Y.; Morgan, William F.

    2014-01-01

    The genetic and inflammatory response pathways elicited following plutonium exposure in archival lung tissue of an occupationally exposed human and experimentally exposed beagle dogs were investigated. These pathways include: tissue injury, apoptosis and gene expression modifications related to carcinogenesis and inflammation. In order to determine which pathways are involved, multiple lung samples from a plutonium exposed worker (Case 0269), a human control (Case 0385), and plutonium exposed beagle dogs were examined using histological staining and immunohistochemistry. Examinations were performed to identify target tissues at risk of radiation-induced fibrosis, inflammation, and carcinogenesis. Case 0269 showed interstitial fibrosis in peripheral and subpleural regions of the lung, but no pulmonary tumors. In contrast, the dogs with similar and higher doses showed pulmonary tumors primarily in brochiolo-alveolar, peripheral and subpleural alveolar regions. The TUNEL assay showed slight elevation of apoptosis in tracheal mucosa, tumor cells, and nuclear debris was present in the inflammatory regions of alveoli and lymph nodes of both the human and the dogs. The expression of apoptosis and a number of chemokine/cytokine genes was slightly but not significantly elevated in protein or gene levels compared to that of the control samples. In the beagles, mucous production was increased in the airway epithelial goblet cells and glands of trachea, and a number of chemokine/cytokine genes showed positive immunoreactivity. This analysis of archival tissue from an accidentally exposed worker and in a large animal model provides valuable information on the effects of long-term retention of plutonium in the respiratory tract and the histological evaluation study may impact mechanistic studies of radiation carcinogenesis

  19. Microdistribution of radium 226 in the beagle skeleton and the resulting radiation dose to the target cells

    International Nuclear Information System (INIS)

    Polig, E.; Jee, W.S.S.

    1989-01-01

    The microdistribution of radium 226 in bone sections of beagle dogs, receiving a single injection of 355 or 37 kBq/kg body weight, was analysed by means of a photometric scanning technique. The animals were sacrificed at 5-3000 days post-injection. Time dependence of the concentration of radium 226 was measured in lumbar vertebra and proximal ulnar bones. Hotspot/diffuse ratios, fraction of activity in hotspots and local radiation dose rates to lining cells and hit frequencies to cell nuclei were also determined. Intense irradiation in the high level animals led to abnormal bone formation not observed at the lower level. (author)

  20. A Novel HA/β-TCP-Collagen Composite Enhanced New Bone Formation for Dental Extraction Socket Preservation in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Ko-Ning Ho

    2016-03-01

    Full Text Available Past studies in humans have demonstrated horizontal and vertical bone loss after six months following tooth extraction. Many biomaterials have been developed to preserve bone volume after tooth extraction. Type I collagen serves as an excellent delivery system for growth factors and promotes angiogenesis. Calcium phosphate ceramics have also been investigated because their mineral chemistry resembles human bone. The aim of this study was to compare the performance of a novel bioresorbable purified fibrillar collagen and hydroxyapatite/β-tricalcium phosphate (HA/β-TCP ceramic composite versus collagen alone and a bovine xenograft-collagen composite in beagles. Collagen plugs, bovine graft-collagen composite and HA/β-TCP-collagen composite were implanted into the left and right first, second and third mandibular premolars, and the fourth molar was left empty for natural healing. In total, 20 male beagle dogs were used, and quantitative and histological analyses of the extraction ridge was done. The smallest width reduction was 19.09% ± 8.81% with the HA/β-TCP-collagen composite at Week 8, accompanied by new bone formation at Weeks 4 and 8. The HA/β-TCP-collagen composite performed well, as a new osteoconductive and biomimetic composite biomaterial, for socket bone preservation after tooth extraction.

  1. Serum thromboxane B2 (TXB2 Determination is Influenced by Sample Incubation Temperature in Healthy Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Aleš Jerin

    2009-01-01

    Full Text Available The measurement of serum thromboxane B2 (TXB2 production by platelets is a specific test for assessment of platelet cyclooxygenase (COX-1 activity following administration of non-steroidal anti-inflammatory drugs (NSAIDs. The aim of this study was to investigate the influence of sample incubation at 37 °C for one hour on serum TXB2 concentration in comparison with incubation at room temperature. A total of 54 blood samples for serum TXB2 measurements were collected from six healthy beagle dogs into two separate serum tubes. While one group of tubes was incubated in a 37 °C water bath, the second group of tubes was left to coagulate at room temperature, both for one hour. Serum TXB2 concentrations were measured by ELISA. The mean concentration (± SD of serum TXB2 in the group of samples that were incubated at 37 °C was significantly (P 2 concentration in healthy beagle dogs and demonstrate that validated methods for assessment of COX-1 activity by measurement of serum TXB2 should be used in order to make results more reliable and comparable between different studies. The results of this study might be of great help in planning NSAID studies in dogs by providing the information that TXB2 generation by platelets is influenced profoundly by incubation temperature.

  2. Multistage cancer models of bone cancer induction in beagles and mice by radium and plutonium, compared to humans

    Energy Technology Data Exchange (ETDEWEB)

    Bijwaard, H.; Brugmans, M. [RIVM-National Inst. for Public Health and the Environment, Lab. for Radiation Research, MA Bilthoven (Netherlands)

    2005-07-01

    Two-mutation carcinogenesis models of mice injected with Pu-239 and Ra-226 have been derived as an extension of previous modellings of beagle dogs injected with Pu-239 and Ra-226 and dial painters that ingested radium. In all cases the data could be fitted adequately using no more than five free model parameters. Apart from three parameters for the background, these include two dose-related parameters: a linear mutation coefficient that is equal in both mutational steps and a usually non-zero cell-killing coefficient in the second mutational step. After a simple scaling the animal models compare reasonably well with each other and with the model for the radium dial painters. From the toxicity ratio of beagle models for Pu-239 and Ra-226, together with the human model for Ra-226, an approximate model for the exposure of humans to Pu-239 has been constructed. Relative risk calculations with this approximate model are in good agreement with epidemiological findings for the plutonium-exposed Mayak workers. This promising result may indicate new possibilities for estimating risks for humans from animal experiments. (orig.)

  3. Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs

    Directory of Open Access Journals (Sweden)

    Wang CL

    2015-05-01

    Full Text Available Chunling Wang,1 Xiaobo Cheng,2 Yuqing Su,1 Ying Pei,3 Yanzhi Song,1 Jiao Jiao,1 Zhenjun Huang,1 Yanfei Ma,1 Yinming Dong,1 Ying Yao,1 Jingjing Fan,1 Han Ta,1 Xinrong Liu,1 Hui Xu,1 Yihui Deng1 1College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Deli Wei Biological Technology Co, Ltd, Beijing, People’s Republic of China; 3Shenyang Women’s and Children’s Hospital, Shenyang, People’s Republic of China Abstract: The cross-administration of nanocarriers modified by poly(ethylene glycol (PEG, named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers. In this study, we investigated the ABC phenomenon induced by the intravenous cross-administration of various PEGylated nanocarriers, including PEGylated liposomes (PL, PEG micelles (PM, PEGylated solid lipid nanoparticles (PSLN, and PEGylated emulsions (PE, in beagle dogs. The results indicated that the magnitude of the immune response elicited by the cross-administration was in the following order (from the strongest to the weakest: PL, PE, PSLN, PM. It is specifically PEG in the brush structure that elicits a significant immune response, in both the induction phase and the effectuation phase. Furthermore, the present study suggests that there is a considerable difference between the effect of repeated injections and

  4. Toxicity of injected 137CsCl in the beagle dog. VII

    International Nuclear Information System (INIS)

    Lustgarten, C.S.; Hobbs, C.H.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.; Redman, H.C.

    1974-01-01

    Studies on the metabolism, dosimetry, and effects of intravenously administered 137 CsCl in the Beagle dog are being conducted to aid in assessing the biologic consequences of exposure to 137 Cs such as might occur in the event of certain nuclear accidents. Effects of the chronic, relatively uniform whole-body exposure produced by 137 Cs are being compared with other diverse radiation dose patterns resulting from inhalation of radioactive aerosols. Sixty-six dogs were entered into the study; 6 with a mean initial 137 Cs body burden of 3780 μCi/kg, and 5 groups of 12 dogs each with mean initial 137 Cs body burdens of 2820, 1940, 1420, 970, and 0 μCi/kg. All six of the highest level dogs died 19 to 33 days post-injection with cumulative whole-body doses of 950 to 1400 rads. Three dogs in the 2820 μCi/kg level died at 24 to 27 days post-injection with cumulative whole-body doses of 860 to 910 rads. One dog in the 2820 μCi/kg level and one dog in the 1940 μCi/kg level died at 77 and 81 days after injection with cumulative whole-body doses of 1300 to 1400 rads. These early deaths were attributed to severe bone marrow damage which was reflected in an early dose related pancytopenia. A dog injected with 1900 μCi/ 137 Cs/kg died 693 days post-injection with necropsy findings attributed to shock. A dog injected with 2800 μCi/kg died 1594 days post-injection with aspiration pneumonia and a dog with 2900 μCi/kg was euthanized 1704 days post-injection with severe arthritis. A control dog died 647 days after initiation of the study with clinicopathological manifestations of auto-immune hemolytic anemia. Forty 137 Cs dogs and 11 controls are surviving at 2047 to 2301 days after being placed on experiment. The surviving 137 Cs dogs had initial body burdens that ranged from 880 to 3000 μCi/kg and received cumulative whole-body doses of 550 to 2200 rads. Serial observations are continuing on all survivors. (U.S.)

  5. Toxicity of 144Ce inhaled in a relatively insoluble form by immature Beagle dogs. VII

    International Nuclear Information System (INIS)

    Hanika-Rebar, C.; Hahn, F.F.; Boecker, B.B.; Mauderly, J.L.; McClellan, R.O.

    1978-01-01

    Immature Beagle dogs (approx. = 3 months of age at exposure) have been exposed by inhalation to a relatively insoluble form of 144 Ce (in fused aluminosilicate particles) to compare the resulting patterns of metabolism, dosimetry and biological effects with those seen in dogs exposed at 12 and 14 months of age and at 8 to 10.5 years of age. Five blocks of longevity animals, each consisting of 10 exposed dogs and one control, are currently being studied. The initial lung burdens of the 144 Ce-exposed dogs range from 0.004 to 140 μCi 144 Ce/kg body weight. Three dogs with initial lung burdens of 73 to 120 μCi 144 Ce/kg body weight died at 66 to 121 days after exposure with pulmonary injury and congestive heart failure. One dog with an initial lung burden of 140 μCi 144 Ce/kg body weight died at 91 days after exposure with severe radiation pneumonitis and minimal pulmonary fibrosis and another dog whose initial lung burden was 70 μCi 144 Ce/kg body weight died at 511 days after exposure with pulmonary injury that was mainly fibrotic in nature. Four dogs with initial lung burdens of 52 to 79 μCi/kg body weight had primary pulmonary hemangiosarcomas and died between 618 and 738 days, with cumulative average absorbed beta doses to lung of 23,000 to 31,000 rads. Two of these dogs, 1027S and 1024D, died within the past year. One dog with an initial lung burden of 28 μCi/kg body weight was euthanized at 1227 days after exposure with an hemangiosarcoma of the mediastinum. Within the past year, Dog 627S, with an initial lung burden of 48 μCi/kg body weight, died 1732 days after exposure with hemangiosarcoma primary in the liver or spleen. A dog with an initial lung burden of 12 μCi/kg body weight died from epilepsy at 1520 days after exposure. Serial observations are continuing on the surviving 37 exposed and five control dogs

  6. Characterisation of tramadol, morphine and tapentadol in an acute pain model in Beagle dogs.

    Science.gov (United States)

    Kögel, Babette; Terlinden, Rolf; Schneider, Johannes

    2014-05-01

    To evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive pain, the tail-flick model in dogs. Prospective part-randomized pre-clinical research trial. Fifteen male Beagle dogs (HsdCpb:DOBE), aged 12-15 months. On different occasions separated by at least 1 week, dogs received intravenous (IV) administrations of tramadol (6.81, 10.0 mg kg(-1) ), tapentadol (2.15, 4.64, 6.81 mg kg(-1) ) or morphine (0.464, 0.681, 1.0 mg kg(-1) ) with subsequent measurement of tail withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1). Tapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg(-1) and 0.71 mg kg(-1) , respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociceptive effect of tramadol in this experimental pain model in dogs. Different breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting. This contrasts to many clinical situations described in the literature, where tramadol appears to provide useful analgesia in dogs for post-operative pain relief and in more chronically pain states. © 2014 Association of Veterinary

  7. Toxicity of 90Sr inhaled in a relatively insoluble form by Beagle dogs. IX

    International Nuclear Information System (INIS)

    Snipes, M.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1978-01-01

    Studies on the biological effects of 90 Sr inhaled in a relatively insoluble form by Beagle dogs are being conducted to define the biological consequences of inhaling this radionuclide in a form which has a long retention time in the lung. One hundred and six dogs were exposed to a polydisperse aerosol (AMAD 1.4 to 2.8 μm and sigma/sub g/ 1.4 to 2.7) of fused aluminosilicate particles labeled with 90 Sr. Initial lung burdens ranged from 0.21 to 94 μCi 90 Sr per kilogram of body weight (μCi/kg). Eighteen control dogs were exposed to an aerosol of stable strontium in fused aluminosilicate particles. To date, 34 dogs having initial lung burdens of 8.9 to 94 μCi 90 Sr/kg and cumulative doses to lung of 33,000 to 96,000 rads have died from radiation pneumonitis and/or pulmonary fibrosis between 159 and 2596 days after exposure. Twenty-nine dogs with initial lung burdens of 3.7 to 36 μCi 90 Sr/kg and cumulative doses to lung of 13,000 to 68,000 rads have died from hemangiosarcomas in the lung, heart or mediastinum between 644 and 2565 days after exposure. In addition, one dog developed a bronchioloalveolar carcinoma, another developed epidermoid carcinoma of the lung, another died of pneumonia while recovering from anesthesia, one dog died at 1821 days after exposure with an hemangiosarcoma of the spleen and two dogs developed squamous cell carcinomas in the nasal cavity. During the past year one dog was euthanized 2753 days after exposure (34,000 rads lung dose) as a result of an hemangiosarcoma which developed in a rib and spread widely. Another dog died 2830 days after exposure (35,000 rads lung dose) with a squamous cell carcinoma in the lung. An additional dog was euthanized 2636 days after exposure (12,000 rads lung dose) with widespread hemangiosarcoma of unknown origin. The remaining 36 exposed dogs and 18 controls are surviving at 1387 to 3168 days after exposure

  8. Toxicity of inhaled 144Ce fused clay particles in beagle dogs. VII

    International Nuclear Information System (INIS)

    Hahn, F.F.; Boecker, B.B.; Hobbs, C.H.; Jones, R.K.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1974-01-01

    The metabolism, dosimetry, and effects of inhaled 144 Ce in fused clay particles are being investigated in the Beagle dog to aid in assessing the biological consequences of release of 144 Ce in a relatively insoluble form such as might occur in certain types of nuclear accidents. The toxicity of inhaled 144 Ce fused clay is also of general interest since it is representative of intermediate-lived beta-emitting radionuclides. Two major studies with young adult dogs (12 to 14 months of age at exposure) are involved: (1) a metabolism and dosimetry study in which 24 dogs were serially sacrificed over an extended period of time, and (2) a longevity study with 2 series of dogs; Series I with 15 dogs exposed to aerosols of 144 Ce in fused clay particles to yield initial lung burdens of 11 to 210 μCi/kg body weight and 3 control dogs exposed to nonradioactive fused clay particles and Series II with 96 dogs exposed to aerosols of 144 Ce in fused clay particles to yield initial lung burdens of 0.0024 to 66 μCi/kg body weight and 12 control dogs exposed to nonradioactive fused clay particles. Twenty-eight dogs died or were euthanized at 143 to 2396 days after inhalation of 144 Ce. The prominent findings were radiation pneumonitis in 17 dogs that died or were euthanized at early time periods and neoplastic disease in 10 of the 11 dogs that died or were euthanized at 750 days or later; 5 with hemangiosarcoma of the lung, 1 with both a hemangiosarcoma and a fibrosarcoma of the lung, 1 with both a bronchiolo-alveolar carcinoma and a hemangiosarcoma of lung, 1 with a hemangiosarcoma of lung, bronchiolo-alveolar carcinoma, and a bronchiogenic adenocarcinoma, and 1 each with a hemangiosarcoma of the mediastinum and of the spleen. The cumulative radiation dose to the lung at time of death has ranged from 22,000 to 140,000 rads. Serial observations are continuing on the 83 survivors and 15 controls. (U.S.)

  9. [Characteristics of sublingual vein and expressions of vascular endothelial growth factor and hypoxia-inducible factor 1alpha proteins in sublingual tissues of Beagle dogs with portal hypertension].

    Science.gov (United States)

    Li, Bai-yu; Wang, Li-na; Yue, Xiao-qiang; Li, Bai

    2009-05-01

    To observe sublingual vein characteristics and the expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha) proteins in sublingual tissues of Beagle dogs with cirrhotic portal hypertension. Twelve Beagle dogs were randomly divided into normal control group and cirrhotic portal hypertension group. There were 6 dogs in each group. A canine model of cirrhosis portal hypertension was established by injecting dimethylnitrosamine (DMN) into portal vein once a week for 7 weeks. The characteristics of sublingual vein were observed. Portal venous pressure was measured by using bioelectric recording techniques. The expressions of VEGF and HIF-1alpha proteins in sublingual vein were detected by immunohistochemical method. The shape and color of sublingual vein in beagle dogs in the cirrhotic portal hypertension group changed obviously as compared with the normal control group. Immunohistochemical results showed that there were almost no expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the normal control group; however, the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the cirrhotic portal hypertension group significantly increased. Changes of portal pressure may lead to the formation of the abnormal sublingual vein by increasing the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in Beagle dogs with portal hypertension.

  10. [Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration of Ajuga decumbens extract in beagle dog].

    Science.gov (United States)

    Wen, Bin-Yu; Li, Jian-Rong

    2013-06-01

    8-O-acetylharpagide and harpagide are two kinds of effective component of Ajuga decumbens extract. A sensitive LC-MS/MS method has been established for pharmacokinetics of 8-O-acetylharpagide and harpagide in beagle dog after oral administration of from A. decumbens extract. Female beagle dogs received orally 12.9, 25.7 mg x kg(-1) p. o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartment analysis. The mobile phase consisted of 0.1% formic acid in water (A) and acetonitrile (B), which was run at a flow rate of 0.3 mL x min(-1). Chromatographic separation was achieved on an Agilent ZORBAX XDB-C18 column (2.1 mm x 50 mm, 3.5 microm) using a gradient elution of 5% B at 0-2 min, 95% B at 2. 1-5 min and 5% B at 5. 1-10 min. All analytes, including the IS, were monitored under positive ionization conditions and quantified in MRM mode with transitions of m/z 429.2-369.2 for 8-O-acetylharpagide, m/z 387.2-207.2 for harpagide, and m/z 149.2-103.1 for IS. High purity nitrogen was employed as both the nebulizing and drying gas. Other parameters of the mass spectrometer were optimized as follows: drying gas flow 10.0 L x min(-1); drying gas temperature 300 degrees C; capillary voltage 4 000 V. Results showed that 8-O-acetylharpagide and harpagide showed a dose-dependence profile. T(max) of 8-O-acetylharpagide is 1.7 h, and T(max) of harpagide is 1.57 h, which was higher than T(max) of 8-O-acetylharpagide and harpagide after oral administration of from A. decumbens extract in rats. The different pharmacokinetic parameters may be due to the species differences of rat and beagle dog.

  11. [Pharmacokinetics of (-)-clausenamide and its major metabolite 6-hydroxyl-clausenamide in beagle dogs by HPLC/MS].

    Science.gov (United States)

    Song, Min; Qian, Wen; Hang, Tai-Jun; Zhang, Zheng-Xing

    2005-10-01

    To establish a sensitive and accurate method to study the pharmacokinetics of (-)-clausenamide [(-)-clau] and its major metabolite 6-hydroxyl-clausenamide (6-OH-clau) in the plasma of the Beagle dog. (-)-Clau was orally administered to six Beagle dogs at the dose of 30 mg x kg(-1), venous blood from front leg was sampled and plasma was separated for analysis. After extraction with ethyl acetate, the plasma samples were analyzed by HPLC/MS and the mobile phase was a mixture of methanol-water-acetic acid (60: 40: 0. 8) at the flow rate of 1.0 mL x min(-1). The API-ES positive ion SIM detection was carried out for the detection of both (-)-clau ([M + H] (+), m/z 298 ) and 6-OH-clau ([M + H - H2 O](+), m/z 296) with glipzide (glip) ([M + H](+), m/z 446) as internal standard. The pharmacokinetic parameters were calculated by 3P97 software. There was good linear relationship ( r > 0. 999) between the SIM responses and the concentrations for (-)-clau and 6-OH-clau at the range from 1.0 to 200 ng x mL(-1) and 0.2 to 40.0 ng x mL(-1), respectively. The absolute recovery was greater than 85%. The plasma concentration-time curves of (-)-clau and 6-OH-clau were both best fitted to a two-compartment model. The C(max) of (-)-clau and 6-OH-clau were (21 +/- 10) ng x mL(-1) and (3.9 +/- 2.2) ng x mL(-1), T(max) were (0.8 +/- 0.5) h and (1.3 +/- 0.5) h, T 1/2 alpha were (0.9 +/- 0.6) hand (1.4 +/- 0.6) h, T 1/2 beta were (19 +/- 23) hand (13 +/- 12) h, AUC(0-24 h) were (69 +/- 14) h x ng x mL(-1) and (12 +/- 7) h x ng x mL(-1) respectively. The established HPLC/MS method was sensitive and specific for the determination of (-)-clau. It was shown that the absorption and first phase elimination of (-)-clau were very quick in Beagle dogs, but the terminal elimination was very slow. The plasma concentration profile of its major metabolite 6-OH-clau was similar to (-)-clau and the AUC was relatively small in comparison with (-)-clau.

  12. "My appointment received the sanction of the Admiralty": why Charles Darwin really was the naturalist on HMS Beagle.

    Science.gov (United States)

    van Wyhe, John

    2013-09-01

    For decades historians of science and science writers in general have maintained that Charles Darwin was not the 'naturalist' or 'official naturalist' during the 1831-1836 surveying voyage of HMS Beagle but instead Captain Robert FitzRoy's 'companion', 'gentleman companion' or 'dining companion'. That is, Darwin was primarily the captain's social companion and only secondarily and unofficially naturalist. Instead, it is usually maintained, the ship's surgeon Robert McCormick was the official naturalist because this was the default or official practice at the time. Although these views have been repeated in countless accounts of Darwin's life, this essay aims to show that they are incorrect. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Reproductive ability of female dogs (beagles) surviving a single, midlethal, whole-body x-ray exposure

    International Nuclear Information System (INIS)

    Andersen, A.C.; Rosenblatt, L.S.

    1976-01-01

    The ability of 82 irradiated and sham-treated female beagles to whelp and wean pups was tested over a major portion of their reproductive life span. The dogs were exposed to 290 or 300 R of x rays (250 kVp) either as young pups, prior to puberty, or at puberty. Although all of the irradiated dogs were fertile and produced approximately the same number of litters as controls, litters of the pup irradiated and prepubertal irradiated dams surviving throughout the study were smaller than those of controls by 17 and 9 percent, respectively. Pup survival was also reduced relative to controls; the number of pups weaned was 38 percent lower in the pup irradiated group and 18 percent lower in the prepubertal irradiated group, as compared with controls. The overall reproductive ability of dogs irradiated at puberty was similar to that of sham-treated controls

  14. Effect of biphasic calcium phosphate nanocomposite on healing of surgically created alveolar bone defects in beagle dogs

    Science.gov (United States)

    Wang, Lanlei; Guan, Aizhong; Shi, Han; Chen, Yangxi; Liao, Yunmao

    2009-09-01

    The aim of the present study was to investigate the effect of porous biphasic calcium phosphate nanocomposite (nanoBCP) scaffolds bioceramic. Alveolar bone defects were surgically created bilaterally at the buccal aspects of the upper second premolar in fourteen beagle dogs. After root conditioning with ethylenediaminetetraacetate (EDTA), nanoBCP was randomly filled in the defects and nothing was put into the contralaterals as controls. Dogs were killed at the 12th weeks. Histological observations were processed through a light microscopy. The results revealed that a great amount of functional periodontal fissures formed in the defects in the nanoBCP groups while minimal bone took shape in the controls. In this study, nanoBCP has proved to work well as a biocompatible and osteoconductive scaffold material to promote periodontal regeneration effectively.

  15. The effects of age at time of exposure on the distribution and toxicity of radium 226 in the beagle dog

    International Nuclear Information System (INIS)

    Bruenger, F.W.; Lloyd, R.D.; Egger, M.J.

    1989-01-01

    The influence of age at time of injection of radium 226 on its skeletal deposition, retention and distribution, the pattern of bone tumour formation and the post-injection survival has been studied in beagles. Dogs received a single intravenous injection of radium 226 at an age of 3 months (juveniles), 17-19 months (young adults) or 60 months (mature), respectively. In spite of large differences in distribution and retention of the nuclide, the influence of age on bone tumour induction was moderate and the post-injection survivals were not significantly different, although a larger skeletal dose combined with a longer survival indicated a trend to a lower overall toxicity in the juvenile age group. (author)

  16. Tissue characteristics of high- and low-incidence plutonium-induced osteogenic sarcoma sites in life-span beagles

    International Nuclear Information System (INIS)

    Miller, S.C.; Jee, W.S.S.; Smith, J.M.; Wronski, T.J.

    1986-01-01

    On the basis of information gathered from the 239 Pu life-span study in beagles at the University of Utah, the tissue features were found to be characteristic of high-incidence bone-tumor sites compared to low-incidence sites included more hematopoietic tissues in the bone marrow; greater trabecular bone mass; greater bone remodeling rates; greater mineral apposition rates; greater density and activity of bone surface cells; greater density of putative bone-cell precursors; greater initial uptake of plutonium on bone surfaces; and greater marrow vascular volumes and a venous sinusoidal bed. Although most of these studies are not yet complete, the information being collected should contribute to our understanding of the mechanisms of radiation-induced osteogenic sarcomas. This should aid in predicting the types and characteristics of osseous tissues where radiation-induced osteogenic sarcomas may arise in humans. 25 refs., 4 figs., 3 tabs

  17. Hematological responses after inhaling {sup 238}PuO{sub 2}: An extrapolation from beagle dogs to humans

    Energy Technology Data Exchange (ETDEWEB)

    Scott, B.R.; Muggenburg, B.A.; Welsh, C.A.; Angerstein, D.A.

    1994-11-01

    The alpha emitter plutonium-238 ({sup 238}Pu), which is produced in uranium-fueled, light-water reactors, is used as a thermoelectric power source for space applications. Inhalation of a mixed oxide form of Pu is the most likely mode of exposure of workers and the general public. Occupational exposures to {sup 238}PuO{sub 2} have occurred in association with the fabrication of radioisotope thermoelectric generators. Organs and tissue at risk for deterministic and stochastic effects of {sup 238}Pu-alpha irradiation include the lung, liver, skeleton, and lymphatic tissue. Little has been reported about the effects of inhaled {sup 238}PuO{sub 2} on peripheral blood cell counts in humans. The purpose of this study was to investigate hematological responses after a single inhalation exposure of Beagle dogs to alpha-emitting {sup 238}PuO{sub 2} particles and to extrapolate results to humans.

  18. Theoretical consideration of metabolic and histomorphometric data for alkaline earth and actinide distribution dynamics in the beagle skeleton

    International Nuclear Information System (INIS)

    Parks, N.J.

    1989-01-01

    The beagle has been used for thirty years as a putative model for human skeletal dynamics in terms of metabolic behaviour and response to in situ radiation insults. The partitioned clearance model (PCM) is a bone by bone description of radionuclide redistribution in the beagle skeleton after the end of exposure to 226 Ra by eight semi-monthly injections at 435-535 days or by continuous ingestion of 90 Sr from in utero to 540 days. The PCM describes both the clearance of radium after deposition on surfaces following injection and the clearance of 90 Sr after uniform deposition in the skeleton as a function of Ca mass. The PCM relates the metabolically determined time-zero deposition fraction (% A) per skeletal component to the calcium fraction (%Ca) per component. The ratio of these two fractions is defined as an estimator of relative 'surface',S, in PCM for the alkaline earths (ae). A comparison is made of 'surface' as defined, in PCM, by activity fraction per mass fraction in a given skeletal component for bone seeking alkaline earths (S ae ), to similarly defined 'surface' (S act ) for injected plutonium citrate. For inhaled soluble plutonium nitrate that translocates to bone, the S act values are very similar to the S ae values for injected radium. The physiochemical determinants of Pu deposition in bone after inhalation appear to be similar to those for alkaline earths. Histomorphometric data from actual bone surfaces marked in vivo with fluorescent labels given to a juvenile dog and then 13 years later give direct evidence that actinides not removed metabolically may never be removed by remodelling processes. (author)

  19. Application of collagen hydrogel/sponge scaffold facilitates periodontal wound healing in class II furcation defects in beagle dogs.

    Science.gov (United States)

    Kosen, Y; Miyaji, H; Kato, A; Sugaya, T; Kawanami, M

    2012-10-01

    A three-dimensional scaffold may play an important role in periodontal tissue engineering. We prepared bio-safe collagen hydrogel, which exhibits properties similar to those of native extracellular matrix. The aim of this study was to examine the effect of implantation of collagen hydrogel/sponge scaffold on periodontal wound healing in class II furcation defects in dogs. The collagen hydrogel/sponge scaffold was prepared by injecting collagen hydrogel, cross-linked to the ascorbate-copper ion system, into a collagen sponge. Class II furcation defects (of 5 mm depth and 3 mm width) were surgically created in beagle dogs. The exposed root surface was planed and demineralized with EDTA. In the experimental group, the defect was filled with collagen hydrogel/sponge scaffold. In the control group, no implantation was performed. Histometric parameters were evaluated 2 and 4 wk after surgery. At 2 wk, the collagen hydrogel/sponge scaffold displayed high biocompatibility and biodegradability with numerous cells infiltrating the scaffold. In the experimental group, reconstruction of alveolar bone and cementum was frequently observed 4 wk after surgery. Periodontal ligament tissue was also re-established between alveolar bone and cementum. Volumes of new bone, new cementum and new periodontal ligament were significantly greater in the experimental group than in the control group. In addition, epithelial down-growth was suppressed by application of collagen hydrogel. The collagen hydrogel/sponge scaffold possessed high tissue compatibility and degradability. Implantation of the scaffold facilitated periodontal wound healing in class II furcation defects in beagle dogs. © 2012 John Wiley & Sons A/S.

  20. Determination of antazoline hydrochloride in Beagle dog plasma by HPLC-UV and its application to pharmacokinetics.

    Science.gov (United States)

    Li, Xiaotian; Chu, Yanle; Ke, Yu; Wang, Linxi; Yu, Tong; Hao, Lianqi

    2013-06-15

    In order to evaluate the pharmacokinetics characteristic of antazoline hydrochloride in Beagle dogs, a sensitive and specific HPLC method was developed and validated using phenacetin as the internal standard (IS). The analyte and the IS were extracted from dog plasma by ethyl acetate under the basic condition. The analyte was separated by a C18 column and detected with a variable wavelength UV-detector. The mobile phase consisted of methanol-5mmolL(-1) tetrabutyl ammonium bromide (45:55, v/v) containing 0.5% glacial acetic acid in a flow rate of 1.0mLmin(-1). Standard calibration graph for antazoline was linear over a curve range of 20-1600ngmL(-1) (R>0.99) and the lower limit of quantification was 20ngmL(-1) using a plasma sample of 500μL. The intra- and inter-day precision values were less than 14.3% relative standard deviation (RSD). The intra-day assay accuracy was in the range of 98.1-100.6% and the inter-day assay accuracy in the range of 99.2-101.1%. The extraction recoveries were on the average of 88.4% for antazoline and 76.8% for IS. Plasma samples were stable at least for 1 month at -20°C. This method was successfully applied to pharmacokinetics study of antazoline after intravenous administration to Beagle dogs. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Peri-implant and Paracrestal Inflammatory Biomarkers at Failing Versus Surviving Implant Sites in a Beagle Dog Study.

    Science.gov (United States)

    Montero, Javier; Aragón, Fernando; Blanco, Leticia A; Guadilla, Yasmina; García-Cenador, Begona; López-Valverde, Antonio

    This study sought to quantify three biochemical mediators of inflammation (tumor necrosis factor alpha [TNF-α], superoxide anion [SOA], and myeloperoxidase [MPO]) by analyzing crestal (peri-implants) and paracrestal gingival biopsy samples obtained from an experimental study on beagle dogs treated with implants inserted immediately into fresh sockets with circumferential defects. In 10 beagle dogs, 4 roughened titanium implants (3.8 mm wide × 8 mm high) were placed in the distal sockets of the third and fourth premolars, where a circumferential defect (5 mm wide and 5 mm deep) had been previously created by trephination. After varying follow-up periods, ranging from 80 to 190 days, the dogs were explored clinically to assess implant survival, peri-implant pocket depth, and implant stability. The levels of three biochemical mediators of inflammation (MPO, TNF-α, and SOA) were investigated using the crestal and paracrestal gingival biopsy samples with ELISA tests. It was found that 37.5% of the implants were either absent or mobile. Higher levels of the inflammatory mediators were found in the crestal samples than in the paracrestal samples. The final implant stability values were significantly correlated with the final probing depth (r = -0.83, P < .01), but neither of the clinical measures were significantly correlated with any biochemical marker. The risk of implant failure was significantly proportional to the level of MPO (odds ratio: 1.1) and TNF-α (odds ratio: 1.1) in both the crestal and paracrestal regions. All the inflammatory mediators studied were higher in the crestal areas than in the paracrestal regions, but only the values of MPO and TNF-α were significant predictors of implant failure.

  2. Anatomical and ultrasonographic study of the femoral nerve within the iliopsoas muscle in beagle dogs and cats.

    Science.gov (United States)

    Mogicato, Giovanni; Layssol-Lamour, Catherine; Mahler, Stephan; Charrouin, Maxime; Boyer, Guillaume; Verwaerde, Patrick; Jourdan, Géraldine

    2015-07-01

    An ultrasound (US)-guided ventral suprainguinal approach to block the femoral nerve (FN) within the iliopsoas muscle (IPM) has recently been described in dogs. The goal of the present study was to provide the operator with additional information to locate the FN within the IPM in dogs and cats using US. The study was carried out in three phases: a dissection of the FN (phase 1); an in vivo US-assisted nerve study (phase 2), and an anatomical cross-sectional study (phase 3). Nine healthy adult beagle dogs and nine healthy adult cats. Dissections were performed to investigate the anatomical characteristics of the FN and its related structures in one dog and one cat. Ultrasound scans of the left and right FN were performed in eight dogs and eight cats. The FN diameter and the distance between the FN and the external iliac artery (EIA) in US images and in anatomical cryosections were measured. The median FN diameter did not differ significantly between cats and dogs (1.1 mm versus 1.0 mm) or between the two techniques (US versus anatomical cross-sectional study) (1.1 mm versus 1.1 mm in dogs; 1.0 mm versus 1.1 mm in cats). The US and anatomical measurements of the median distances between the FN and EIA differed significantly between dogs and cats (8.2 mm versus 5.8 mm by US; 5.7 mm versus 4.8 mm in the anatomical study). The distance between the EIA and FN is reproducible in beagle dogs and cats and can be used in locating the FN within the IPM. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  3. Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles

    Directory of Open Access Journals (Sweden)

    Jie Lai

    2009-12-01

    Full Text Available Jie Lai1,2, Yi Lu1, Zongning Yin2, Fuqiang Hu3, Wei Wu11School of Pharmacy, Fudan University, Shanghai, China, 2West China School of Pharmacy, Sichuan University, Chengdu, China, 3School of Pharmacy, Zhejiang University, Hangzhou, ChinaAbstract: Efforts to improve the oral bioavailability of cyclosporine A (CyA remains a challenge in the field of drug delivery. In this study, glyceryl monooleate (GMO/poloxamer 407 cubic nanoparticles were evaluated as potential vehicles to improve the oral bioavailability of CyA. Cubic nanoparticles were prepared via the fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by sonication and homogenization. The cubic inner structure formed was verified using Cryo-TEM. The mean diameters of the nanoparticles were about 180 nm, and the entrapment efficiency of these particles for CyA was over 85%. The in vitro release of CyA from these nanoparticles was less than 5% at 12 h. The results of a pharmacokinetic study in beagle dogs showed improved absorption of CyA from cubic nanoparticles as compared to microemulsion-based Neoral®; higher Cmax (1371.18 ± 37.34 vs 969.68 ± 176.3 ng mL-1, higher AUC0–t (7757.21 ± 1093.64 vs 4739.52 ± 806.30 ng h mL-1 and AUC0–∞ (9004.77 ± 1090.38 vs 5462.31 ± 930.76 ng h mL-1. The relative oral bioavailability of CyA cubic nanoparticles calculated on the basis of AUC0–∞ was about 178% as compared to Neoral®. The enhanced bioavailability of CyA is likely due to facilitated absorption by cubic nanoparticles rather than improved release.Keywords: nanoparticles, cubosomes, cyclosporine A, glyceryl monooleate, oral drug delivery, bioavailability, beagle dogs

  4. Cobalt-60 oxide aerosols: methods of production and short-term retention and distribution kinetics in the beagle dog

    International Nuclear Information System (INIS)

    Barnes, J.E.; Kanapilly, G.M.; Newton, G.J.

    1976-01-01

    Cobalt-60 has been used extensively in nuclear applications and has been considered for use in nuclear auxiliary power devices. The most common chemical form used is the oxide. This study of the retention and distribution of two differnt exoides of cobalt when administered by inhalation was conducted to assess the potential inhalation hazard associated with its use. Cobaltosic oxide (Co 3 O 4 ) was formed by passing a cobalt nitrate aerosol through a heating column at 850 0 C before delivery to the dog. Cobaltous oxide (CoO) was formed by raising the heating column temperature to 1400 0 C. Three beagle dogs were exposed to 60 Co 3 O 4 and sacrificed singly at 8, 64 and 128 days. Three beagle dogs were exposed to 60 CoO and sacrificed at 8, 16 and 64 days after exposure. Whole-body retention patterns showed that 60 CoO left the body with a shorter effective half-life than 60 Co 3 O 4 . The concentration of 60 Co detected in the blood was at least an order of magnitude higher in the dogs exposed to 60 CoO than in the dogs exposed to 60 Co 3 O 4 . Cobalt-60 translocated from the lung accumulated predominantly in the kidney, liver, skeleton and cartilagenous structures such as the trachea. Higher concentrations were reached earlier in the dogs exposed to 60 CoO. After early fecal excretion of material deposited in the upper respiratory tract, excretion was greatest via the urine. The higher solubility of the 60 CoO formed at 1400 0 C relative to 60 Co 3 O 4 formed at 850 0 C is noteworthy considering that generally aerosols formed at higher temperatures are more insoluble than aerosols formed at lower temperatures. (author)

  5. Re-induction of obese body weight occurs more rapidly and at lower caloric intake in beagles.

    Science.gov (United States)

    Nagaoka, D; Mitsuhashi, Y; Angell, R; Bigley, K E; Bauer, J E

    2010-06-01

    For the purpose of investigating the mechanism of obesity-induction/re-induction including weight-cycling in beagles, a study was conducted using commercially available dog food combined with human food to mimic at home-snacking and diet-supplementation behaviours. Adult female beagles, which had free access to water and exercise, were used (n = 9). All dogs were initially offered two times their daily calculated number of calories using a dry extruded diet plus blend of canola and soybean oils and allowed to eat ad libitum. After 3 weeks, Pecan shortbread cookies were added to the diet mixture. Obesity was induced during a 19-week period with 1875-2250 kcal/day consumed, on average, during this period. The dogs were then subjected to a weight-loss regimen while consuming 490-730 kcal/day. After weight loss, a similar degree of obesity was re-induced for 17 weeks even though dogs consumed only 1125-1250 kcal/day. Body weight, body condition scores, kcal consumption and food efficiency were recorded. Results indicated that less time and fewer kcal were required to re-induce the same degree of obesity compared with the initial obesity induction. Human snack foods appeared to stimulate appetite and thus contribute to the obese state. Food efficiency was also increased during the obesity-reinduction period compared with the induction period. This information may help pet owners better understand the need to limit table scraps and human-type food snacks in dogs prone to obesity as well as weight maintenance after weight loss.

  6. 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 ...

  7. 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.

  8. A Novel Self-Expandable, Radioactive Airway Stent Loaded with 125I Seeds: A Feasibility and Safety Study in Healthy Beagle Dog.

    Science.gov (United States)

    Wang, Yong; Guo, Jin-He; Zhu, Guang-Yu; Zhu, Hai-Dong; Chen, Li; Lu, Jian; Wang, Chao; Teng, Gao-Jun

    2017-07-01

    Airway stent placement is an effective treatment for the immediate palliation of malignant airway obstruction. However, restenosis caused by tumor ingrowth and/or overgrowth after stenting is common. The purpose of this study was to investigate the feasibility and safety of a novel self-expandable stent loaded with 125 I seeds in healthy beagle dog. Under fluoroscopic guidance, forty-eight self-expandable airway stents loaded with 125 I seeds were perorally placed in the main trachea of 48 healthy beagle dogs, who were randomly divided into four groups (Group A: 0.3 mCi; Group B: 0.6 mCi; Group C: 0.9 mCi; Control group: 0 mCi). The estimated radiation dose was calculated using the isotropic point source approximation. Radiological follow-up examinations and histopathological examinations of stented tracheal segments and their adjacent organs and tissues were performed at 2, 4, 8, and 16 weeks following the stenting. All stents were successfully deployed in the targeted tracheal segment in the beagle dogs without procedure-related complications. Tracheal stenosis became severe gradually in all the four groups, which was not associated with the radioactivity of 125 I seeds (p > 0.05). The tracheal injury scores increased along with the higher dose of radioactive seeds which reached peak at 8 weeks and then turned back slightly at 16 weeks. The adjacent tissue did not show pathohistological changes under microscope, while mild and reversible ultrastructure changes were showed under electronic microscope. This study demonstrates that it is feasible and safe to insert this novel self-expandable airway stent loaded with 125 I seeds in healthy beagle dog.

  9. Bovine Colostral Antibody Against Verotoxin 2 Derived from Escherichia coli O157:H7: Resistance to Proteases and Effects in Beagle Dogs

    Science.gov (United States)

    Kuribayashi, Takashi; Seita, Tetsuro; Matsumoto, Mariko; Furuhata, Katsunori; Tagata, Kazutoshi; Yamamoto, Shizuo

    2009-01-01

    A bovine colostral antibody against verotoxin (VT) 2 of Escherichia coli O157:H7 was administered orally to beagle dogs. The antibody remained in the dogs’ small intestine for at least 2 h, whereas little serum antibody remained 1.5 h after administration. Furthermore, the antibody activity of secretory IgA did not change until 2 h after administration; however, the activity of IgG and IgM antibodies decreased by approximately 60% and 40% at 2 h after administration, respectively. Seven beagle dogs inoculated with Escherichia coli O157:H7 producing VT2 were administered bovine colostral antibody or bovine colostral whey without antibody. With administration of bovine colostral whey without antibody, the amount of VT2 in feces decreased gradually after administration and increased again at 5 d after inoculation, whereas bovine colostral antibody significantly reduced the amount of VT2 in feces on the day after administration. In addition, 9 beagle dogs were given bovine colostral antibody, bovine plasma antibody, or saline. The amount of VT2 in feces again decreased significantly more rapidly after administration of bovine colostral antibody than after administration of bovine plasma antibody or saline. PMID:19389308

  10. Microdistribution and Long-Term Retention of 239Pu (NO3)4 in the Respiratory Tracts of an Acutely Exposed Plutonium Worker and Experimental Beagle Dogs

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Christopher E.; Wilson, Dulaney A.; Brooks, Antone L.; McCord, Stacey; Dagle, Gerald E.; James, Anthony C.; Tolmachev, Sergei Y.; Thrall, Brian D.; Morgan, William F.

    2012-11-01

    The long-term retention of inhaled soluble forms of plutonium raises concerns as to the potential health effects in persons working in nuclear energy or the nuclear weapons program. The distributions of long-term retained inhaled plutonium-nitrate [239Pu (NO3)4] deposited in the lungs of an accidentally exposed nuclear worker (Human Case 0269) and in the lungs of experimentally exposed beagle dogs with varying initial lung depositions were determined via autoradiographs of selected histological lung, lymph node, trachea, and nasal turbinate tissue sections. These studies showed that both the human and dogs had a non-uniform distribution of plutonium throughout the lung tissue. Fibrotic scar tissue effectively encapsulated a portion of the plutonium and prevented its clearance from the body or translocation to other tissues and diminished dose to organ parenchyma. Alpha radiation activity from deposited plutonium in Human Case 0269 was observed primarily along the sub-pleural regions while no alpha activity was seen in the tracheobronchial lymph nodes of this individual. However, relatively high activity levels in the tracheobronchial lymph nodes of the beagles indicated the lymphatic system was effective in clearing deposited plutonium from the lung tissues. In both the human case and beagle dogs, the appearance of retained plutonium within the respiratory tract was inconsistent with current biokinetic models of clearance for soluble forms of plutonium. Bound plutonium can have a marked effect on the dose to the lungs and subsequent radiation exposure has the potential increase in cancer risk.

  11. High-Throughput Determination of Sodium Danshensu in Beagle Dogs by the LCMS/MS Method, Employing Liquid-Liquid Extraction Based on 96-Well Format Plates.

    Science.gov (United States)

    Jiang, Jingjing; Zhao, Xin; Li, Xiuxiu; Wu, Shengyuan; Yu, Shidan; Lou, Yuefen; Fan, Guorong

    2017-04-25

    Sodium Danshensu (sodium d-(+)-β-(3,4-dihydroxyphenyl) lactate), one of the water-soluble ingredients in Salvia miltiorrhiza , exhibits potent relaxation of the coronary artery and anticoagulation effection. A high-throughput, rapid, and sensitive method combining liquid chromatography with electrospray ionization tandem mass spectrometry to determine the sodium danshensu in beagle dog plasma was developed and validated, using gallic acid as an internal standard (IS). Acidified plasma samples were extracted using 96-well liquid-liquid extraction, and were eluted on a CNW Athena C18 column (3 μm, 2.1 × 100 mm) by using a gradient mobile phase system of methanol and water (containing 0.2% formic acid). The mass spectrometric detection was achieved using negative ion electrospray ionization mode and monitoring the precursor→production combinations of m / z 197→135 for sodium danshensu and 169→125 for IS, in multiple reaction monitoring modes. Good linearity was achieved, and the linear range was 10-1000 ng/mL (R² > 0.996) with a quantification limit of 10 ng/mL for sodium danshensu in beagle dog plasma. The intra- and inter-day precision (RSD) ranged from 2.1% to 9.0%. The accuracy (RE) was between -8.6% and 5.7% at all quality control levels. The validated method was successfully applied to the pharmacokinetics study of sodium danshensu in beagle dog plasma after intravenous injection and oral administration of sodium danshensu.

  12. Development of tissue-engineered self-expandable aortic stent grafts (Bio stent grafts) using in-body tissue architecture technology in beagles.

    Science.gov (United States)

    Kawajiri, Hidetake; Mizuno, Takeshi; Moriwaki, Takeshi; Ishibashi-Ueda, Hatsue; Yamanami, Masashi; Kanda, Keiichi; Yaku, Hitoshi; Nakayama, Yasuhide

    2015-02-01

    In this study, we aimed to describe the development of tissue-engineered self-expandable aortic stent grafts (Bio stent graft) using in-body tissue architecture technology in beagles and to determine its mechanical and histological properties. The preparation mold was assembled by insertion of an acryl rod (outer diameter, 8.6 mm; length, 40 mm) into a self-expanding nitinol stent (internal diameter, 9.0 mm; length, 35 mm). The molds (n = 6) were embedded into the subcutaneous pouches of three beagles for 4 weeks. After harvesting and removing each rod, the excessive fragile tissue connected around the molds was trimmed, and thus tubular autologous connective tissues with the stent were obtained for use as Bio stent grafts (outer diameter, approximately 9.3 mm in all molds). The stent strut was completely surrounded by the dense collagenous membrane (thickness, ∼150 µm). The Bio stent graft luminal surface was extremely flat and smooth. The graft wall of the Bio stent graft possessed an elastic modulus that was almost two times higher than that of the native beagle abdominal aorta. This Bio stent graft is expected to exhibit excellent biocompatibility after being implanted in the aorta, which may reduce the risk of type 1 endoleaks or migration. © 2014 Wiley Periodicals, Inc.

  13. Therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles

    International Nuclear Information System (INIS)

    Zhao Jianzhi; Li Ming; Xing Shuang; Hu Zhiqing; Xiong Guolin; Xie Ling; Ou Hongling; Huang Haixiao; Zhao Zhenhu; Wang Ning; Wang Jinxiang; Miao Jingcheng; Zhu Nankang; Zhang Xueguang; Cong Yuwen; Zhang Ri; Luo Qingliang

    2010-01-01

    Objective: To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy 60 Co γ-rays irradiation in beagles, and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness (ARS). Methods: 16 beagles were given 4.5 Gy 60 Co γ-rays total body irradiation, and then randomly assigned into irradiation control group, supportive care group and cytokines group. In addition to supportive care, recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human interleukin-11 (rhIL-11) and recombinant human interleukin-2 (rhIL-2) were administered subcutaneouly to dogs in cytokines group. Peripheral blood hemogram was examined once every two days. Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation. Conventional histopathological sections sternum were prepared to observe the histomorphology changes. Results: After irradiation, the population of all kinds of cells in peripheral blood declined sharply. WBC nadir was elevated (1.04 x 10 9 /L, but 0.28 x 10 9 /L and 0.68 x 10 9 /L for the irradiation control group and the supportive care group separately), the duration of thrombocytopenia was shortened (24 days, but 33 days for the supportive care group) and red blood cell counts were maintained in the range of normal values after cytokines treatment in combination. The colony forming efficiency of haemopoietic stem cells (HSCs) in bone marrow and peripheral blood decreased obviously 1 d post irradiation, but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment. Hematopoietic cells disappeared in bone marrow of animals in irradiation control group, but hematopoietic functions were recovered after cytokines were administrated. Conclusions: RhG-CSF, rhIL-11 and rhIL-2 used in combination could elevate WBC nadir, accelerate the

  14. Survival, dosimetry, and skeletal malignancy experience in the beagle 226Ra life-span study at the University of Utah

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Miller, S.C.; Taylor, G.N.; Bruenger, F.W.; Angus, W.; Jee, W.S.S.

    1988-01-01

    The initial phase of the experiment with 226 Ra exposure of young adult Beagle dogs at the University of Utah is now complete; all of the dogs are dead. This report summarizes the experimental design, skeletal dosimetry, survival and bone malignancy experience for these animals. Skeletal doses resulting from the injection of 226 Ra and from its radioactive daughters ranged from 0 Gy among the control dogs to a maximum of about 183 Gy (18,326 rad) for one dog that died 1380 days after injection, and averaged nearly 146 Gy (14,553 rad) among all 10 of the animals at the highest injection level. Mean survival among groups injected with up to 12.5 kBq/kg was similar to that of the controls, but the 39.6, 119- nd 383-kBq/kg groups exhibited respective average survivals that were only 0.516, 0.368 and 0.243 as long. This decreased survival was mainly a result of the occurrence of bone malignancies at the higher dose levels. Whereas the bone cancer incidence was 8% at 0.651 kBq/kg, 8.7% at 2.31 kBq/kg and 14.3% at 6.13 kBq/kg, it was 41.7%, 91.7%, 92.3% and 90% at 12.5, 39.6, 119 and 383 kBq/kg, respectively. (author)

  15. Bone modelling at fresh extraction sockets: immediate implant placement versus spontaneous healing: an experimental study in the beagle dog.

    Science.gov (United States)

    Vignoletti, Fabio; Discepoli, Nicola; Müller, Anna; de Sanctis, Massimo; Muñoz, Fernando; Sanz, Mariano

    2012-01-01

    The purpose of this investigation is to describe histologically the undisturbed healing of fresh extraction sockets when compared to immediate implant placement. In eight beagle dogs, after extraction of the 3P3 and 4P4, implants were inserted into the distal sockets of the premolars, while the mesial sockets were left to heal spontaneously. Each animal provided four socket sites (control) and four implant sites (test). After 6 weeks, animals were sacrificed and tissue blocks were dissected, prepared for ground sectioning. The relative vertical buccal bone resorption in relation to the lingual bone was similar in both test and control groups. At immediate implant sites, however, the absolute buccal bone loss observed was 2.32 (SD 0.36) mm, what may indicate that while an apical shift of both the buccal and lingual bone crest occurred at the implant sites, this may not happen in naturally healing sockets. The results from this investigation showed that after tooth extraction the buccal socket wall underwent bone resorption at both test and control sites. This resorption appeared to be more pronounced at the implant sites, although the limitations of the histological evaluation method utilized preclude a definite conclusion. © 2011 John Wiley & Sons A/S.

  16. RBC-/Cr-51/ half-life and albumin turnover in growing Beagle dogs during chronic radial acceleration

    Science.gov (United States)

    Beckman, D. A.; Evans, J. W.; Oyama, J.

    1979-01-01

    The effects of chronic centrifugation on growing Beagle dogs exposed to -2 or -2.6 Gx on albumin and RBC turnover rates, albumin concentration and space, and total blood volume were determined and compared with caged and run control of animals. Albumin-(I-125) and autologous RBC-(Cr-51) preparations were injected into all dogs at day 82 of the centrifugation periods, and the disappearance curves were determined by successive bleedings of the animals over the next 35 d, during which the centrifugation was continued. There were no differences in albumin turnover rates or space. Two populations of RBCs were found in both centrifugated groups, one with a normal half-life of 27 + or - 1 S.E.M. d, and one with a significantly (p less than 0.01) shorter half-life of 15 + or - 2 S.E.M. d. An absolute polycythemia was also observed in both centrifuged groups. The results suggest that chronic centrifugation acts through some as-yet unknown mechanism to affect RBC population kinetics.

  17. 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.

  18. Radiologic study of the healing process of the extracted socket of beagle dogs using cone beam CT

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Bong Won; Lee, Won; Lee, Byung Do [Department of Oral and Maxillofacial Radiology, School of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Kim, De Sok [Department of Electrical Engineering, Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2009-03-15

    To longitudinally observe the healing process of extracted socket and the alterations of the residual ridge in healthy adult dogs using cone beam CT (CBCT). The mandibular premolars of two beagle dogs were removed and the extraction sites were covered with the gingival tissue. CBCTs (3D X-ray CT scanner, Alphard vega, Asahi Co.) were taken at baseline and at 1 week interval for 12 weeks. Radiographic density of extracted wounds was measured on normalized images with a custom-made image analysis program. The amount of alveolar crestal resorption after the teeth extraction was measured with a reformatted three-dimensional image using CBCT. Bony healing pattern of extracted wound of each group was also longitudinally observed and analyzed. Dimensional changes occurred during the first 6 weeks following the extraction of dogs' mandibular premolars. The reduction of the height of residual ridge was more pronounced at the buccal than at the lingual aspect of the extraction socket. Radiographic density of extracted wounds increased by week 4, but the change in density stabilized after week 6. New bone formation was observed at the floor and the peripheral side of extracted socket from week 1. The entrance of extracted socket was sealed by a hard-tissue bridge at week 5. The healing process of extracted wound involved a series of events including new bone formation and residual ridge resorption.

  19. Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in beagle dogs: a placebo-controlled study.

    Science.gov (United States)

    Landsberg, G M; Beck, A; Lopez, A; Deniaud, M; Araujo, J A; Milgram, N W

    2015-09-12

    The objective of the study was to assess the effects of a dog-appeasing pheromone (DAP) collar in reducing sound-induced fear and anxiety in a laboratory model of thunderstorm simulation. Twenty-four beagle dogs naïve to the current test were divided into two treatment groups (DAP and placebo) balanced on their fear score in response to a thunderstorm recording. Each group was then exposed to two additional thunderstorm simulation tests on consecutive days. Dogs were video-assessed by a trained observer on a 6-point scale for active, passive and global fear and anxiety (combined). Both global and active fear and anxiety scores were significantly improved during and following thunder compared with placebo on both test days. DAP significantly decreased global fear and anxiety across 'during' and 'post' thunder times when compared with baseline. There was no significant improvement in the placebo group from baseline on the test days. In addition, the DAP group showed significantly greater use of the hide box at any time with increased exposure compared with the placebo group. The DAP collar reduced the scores of fear and anxiety, and increased hide use in response to a thunder recording, possibly by counteracting noise-related increased reactivity. British Veterinary Association.

  20. Safety and biodistribution of a double-deleted oncolytic vaccinia virus encoding CD40 ligand in laboratory Beagles

    Directory of Open Access Journals (Sweden)

    Karoliina Autio

    2014-01-01

    Full Text Available We evaluated adverse events, biodistribution and shedding of oncolytic vaccinia virus encoding CD40 ligand in two Beagles, in preparation for a phase 1 trial in canine cancer patients. Dog 1 received one dose of vaccinia virus and was euthanized 24 hours afterwards, while dog 2 received virus four times once weekly and was euthanized 7 days after that. Dogs were monitored for adverse events and underwent a detailed postmortem examination. Blood, saliva, urine, feces, and organs were collected for virus detection. Dog 1 had mild fever and lethargy while dog 2 experienced a possible seizure 5.5 hours after first virus administration. Viral DNA declined quickly in the blood after virus administration in both dogs but was still detectable 1 week later by quantitative polymerase chain reaction. Only samples taken directly after virus infusion contained infectious virus. Small amounts of viral DNA, but no infectious virus, were detected in a few saliva and urine samples. Necropsies did not reveal any relevant pathological changes and virus DNA was detected mainly in the spleen. The dogs in the study did not have cancer, and thus adverse events could be more common and viral load higher in dogs with tumors which allow viral amplification.

  1. Life-span radiation effects studies in prenatally and postnatally exposed beagle dogs at Colorado State University

    International Nuclear Information System (INIS)

    Benjamin, S.A.; Lee, A.C.; Angleton, G.M.; Jaenke, R.S.; Saunders, W.J.; Miller, G.K.; Brewster, R.D.

    1986-01-01

    The lifetime hazards associated with exposure to ionizing radiation during development are studied in 1680 beagle dogs given whole-body exposures to 60 Co gamma radiation. Eight groups of 120 dogs each received 20-R or 100-R exposures at 8, 28, or 55 days postcoitus (dpc) or at 2 days postpartum (dpp). In addition, exposures of 100 R were given to 120 dogs at 70 dpp and to 240 dogs at 365 dpp. An additional 360 dogs were sham exposed. Smaller groups of dogs were used to identify organs and tissues of particular sensitivity to radiation injury during development and to evaluate mechanisms of radiation injury. The research is concerned primarily with evaluating the role of age at exposure as a factor influencing response to radiation injury. As of December 31, 1982, of the 1680 dogs, 1058 were dead. Survivors ranged from 9.9 to 15 years of age. Through 10 years of age, no differences in survival were evident in any exposure groups. A variety of clinical, pathophysiologic, and pathologic responses have been studied. Irradiation during development has been found to be associated with abnormalities of skeletal, dental, and central nervous system development. Irradiation during ocular development has induced dysplastic and atrophic retinal lesions. Perinatal irradiation of the kidney has resulted in dysplasia, and, in animals receiving higher doses, significant chronic renal disease. The thymus gland, particularly thymic epithelium, has been found to be highly radiosensitive during fetal development

  2. Effect on Bone Architecture of Marginal Grooves in Dental Implants Under Occlusal Loaded Conditions in Beagle Dogs.

    Science.gov (United States)

    Kato, Hatsumi; Kuroshima, Shinichiro; Inaba, Nao; Uto, Yusuke; Sawase, Takashi

    2018-02-01

    The aim of this study was to clarify whether marginal grooves on dental implants affect osseointegration, bone structure, and the alignment of collagen fibers to determine bone quality under loaded conditions. Anodized Ti-6Al-4V alloy dental implants, with and without marginal grooves (test and control implants, respectively), were used (3.7 × 8.0 mm). Fourth premolars and first molars of 6 beagle mandibles were extracted. Two control and test implants were placed in randomly selected healed sites at 12 weeks after tooth extraction. Screw-retained single crowns for first molars were fabricated. Euthanasia was performed at 8 weeks after the application of occlusal forces. Implant marginal bone level, bone to implant contact (BIC), bone structure around dental implants, and the alignment of collagen fibers determining bone quality were analyzed. The marginal bone level in test implants was significantly higher than that in control implants. Occlusal forces significantly increased BIC in test implants ( P = .007), whereas BIC did not change in control implants, irrespective of occlusal forces ( P = .303). Moreover, occlusal forces significantly increased BIC in test implants compared with control implants ( P = .032). Additionally, occlusal forces preferentially aligned collagen fibers in test implants, but not control implants. Hence, marginal grooves on dental implants have positive effects on increased osseointegration and adapted bone quality based on the preferential alignment of collagen fibers around dental implants under loaded conditions.

  3. Removal of inhaled 241Am oxide of various particle sizes from beagle dogs by lung lavage and chelation treatment

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Mo, T.; Felicetti, S.A.

    1976-01-01

    The removal of 241 Am oxide aerosols of various particle sizes from the lung was studied in 24 Beagle dogs. There were four groups of dogs with six dogs per group and each group inhaled an aerosol of 241 Am oxide of a different particle size or particle size distribution. The four aerosols had sizes of: 0.75 μm AD, sigma/sub g/ 1.1; 1.5 μm AD, sigma/sub g/ 1.1; 3.0 μm AD, sigma/sub g/ 1.1; or 1.5 μm AMAD and sigma/sub g/ of 1.6. Three of the dogs in each group were treated with 10 lung lavages, the first lavage performed 2 days after exposure and the last lavage on day 49 after exposure. Each of these treated dogs was also given 100 mg diethylenetriaminepentaacetic acid (DTPA) intravenously daily for 4 days after 241 Am exposure and twice per week thereafter to the end of the study. Daily excreta collections were made on each of the dogs until sacrifice at 64 days after exposure. The sacrifice body burden (SBB) was much lower for all of the treated dogs compared to the untreated dogs. The 241 Am activity found in the recovered lavage fluid was two to four times greater than the sacrifice body burden. These results suggest that the treatment procedures were effective in reducing the lung and body burden of 241 Am

  4. Trypanosoma cruzi: blood parasitism kinetics and their correlation with heart parasitism intensity during long-term infection of Beagle dogs

    Directory of Open Access Journals (Sweden)

    Vanja M Veloso

    2008-09-01

    Full Text Available The goals of the present study were to evaluate the kinetics of blood parasitism by examination of fresh blood, blood culture (BC and PCR assays and their correlation with heart parasitism during two years of infection in Beagle dogs inoculated with the Be-78, Y and ABC Trypanosoma cruzi strains. Our results showed that the parasite or its kDNA is easily detected during the acute phase in all infected animals. On the other hand, a reduced number of positive tests were verified during the chronic phase of the infection. The frequency of positive tests was correlated with T. cruzi strain. The percentage of positive BC and blood PCR performed in samples from animals inoculated with Be-78 and ABC strains were similar and significantly larger in relation to animals infected with the Y strain.Comparison of the positivity of PCR tests performed using blood and heart tissue samples obtained two years after infection showed two different patterns associated with the inoculated T. cruzi strain: (1 high PCR positivity for both blood and tissue was observed in animals infected with Be-78 or ABC strains; (2 lower and higher PCR positivity for the blood and tissue, respectively, was detected in animals infected with Y strains. These data suggest that the sensitivity of BC and blood PCR was T. cruzi strain dependent and, in contrast, the heart tissue PCR revealed higher sensitivity regardless of the parasite stock.

  5. Spontaneous cell-mediated cytolysis by peripheral blood cells obtained from whole-body chronically irradiated beagle dogs

    International Nuclear Information System (INIS)

    Dyck, J.A.; Shifrine, M.; Klein, A.K.; Rosenblatt, L.S.; Kawakami, T.

    1986-01-01

    The level of natural killer (NK) activity of continuously gamma-irradiated (whole body) beagle dogs and their nonirradiated controls was studied. For analytical purposes, irradiated dogs were segregated into groups according to their clinical status: clinically normal, hypocellular, or with acute non-lymphocytic leukemia. Since unirradiated control animals exhibited a wide range of NK responses, the data from each irradiated animal were compared to its own age-matched or litter-matched unirradiated control. Of the eight clinically normal irradiated dogs (median = 146% activity of control) only one animal had a NK activity lower than that of its control. The hypocellular group (n = 5, median = 21.8% of control) and the leukemic group (n = 4, median = 52.5% of control) each contained one responder with higher activity than its control. The difference between the percentage of control of the clinically normal and clinically abnormal dogs was found to be significant (P less than 0.05). There is a negative correlation between the NK results obtained and the total accumulated dose of radiation at the time of sampling (correlation coefficient = -0.739, P less than 0.01), suggesting a radiation effect upon natural killer activity, which is evidence by enhancement at lower doses and depression at higher doses of irradiation

  6. Radiologic study of the healing process of the extracted socket of beagle dogs using cone beam CT

    International Nuclear Information System (INIS)

    Cho, Bong Won; Lee, Won; Lee, Byung Do; Kim, De Sok

    2009-01-01

    To longitudinally observe the healing process of extracted socket and the alterations of the residual ridge in healthy adult dogs using cone beam CT (CBCT). The mandibular premolars of two beagle dogs were removed and the extraction sites were covered with the gingival tissue. CBCTs (3D X-ray CT scanner, Alphard vega, Asahi Co.) were taken at baseline and at 1 week interval for 12 weeks. Radiographic density of extracted wounds was measured on normalized images with a custom-made image analysis program. The amount of alveolar crestal resorption after the teeth extraction was measured with a reformatted three-dimensional image using CBCT. Bony healing pattern of extracted wound of each group was also longitudinally observed and analyzed. Dimensional changes occurred during the first 6 weeks following the extraction of dogs' mandibular premolars. The reduction of the height of residual ridge was more pronounced at the buccal than at the lingual aspect of the extraction socket. Radiographic density of extracted wounds increased by week 4, but the change in density stabilized after week 6. New bone formation was observed at the floor and the peripheral side of extracted socket from week 1. The entrance of extracted socket was sealed by a hard-tissue bridge at week 5. The healing process of extracted wound involved a series of events including new bone formation and residual ridge resorption.

  7. Feeding habits of the false southern king crab Paralomis granulosa (Lithodidae in the Beagle Channel, Tierra del Fuego, Argentina

    Directory of Open Access Journals (Sweden)

    Laura Inés Comoglio

    1999-12-01

    Full Text Available Stomach contents of 282 false southern king crabs (Paralomis granulosa, between 10 to 90 mm CL from the Beagle Channel (Golondrina Bay and Roca Mora, Argentina, were examined by the frequency of occurrence method of analysis and by a food index. Roca Mora is an area where juveniles ( 60 mm CL are common; in this last area sexual segregation was also observed. The principal food groups for crabs of Golondrina Bay were algae, molluscs, crustaceans, bryozoans and foraminiferans; for crabs from Roca Mora the natural diet consisted of three major food groups: hydrozoans, echinoderms and foraminiferans. The relative frequency of different prey groups varied in relation to the size, season and sex. There were no significant differences in the quantity of food consumed by sexes in both areas. Generally small crabs ( 50 mm CL. Juveniles consumed a greater amount of food during winter and spring. In summer (moulting period, juveniles had the highest vacuity index. Adults consumed minor amounts of food during autumn, before the spawning-moulting-mating period when the vacuity index was higher (spring.

  8. 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.

  9. [Histochemical and histological investigations on the vagina of the beagle she-dog during various functional conditions (author's transl)].

    Science.gov (United States)

    Wrobel, K H; El Etreby, M F; Günzel, P

    1975-01-01

    Histotopochemistry and histology of vaginal epithelium in female beagles were studied during oestrus, metoestrus-dioestrus, post partum period and at days 20, 30, 40, 50, 60 of pregnancy. During oestrus the epithelium is uniform throughout the whole vagina: it presents itself as a high, uncornified, stratified squamous epithelium with some glycogen and lipid droplets but devoid of leucocytes. The intercellular gaps of the stratum intermedium give strong reactions for ATPase and alkaline phosphatase. The activities of oxidoreductases studied decrease continuously from basal to apical. During gravidity, post partum period and metoestrus-dioestrus distinct morphological and histochemical differences can be stated between the cranial and caudal vaginal portions. Caudal vaginal epithelium outside oestrus remains of stratified squamous type. It exhibits strong mucification during pregnancy. The PAS-positive mucous substances prefer a position in the enlarged intercellular gaps of stratum intermedium and superficiale. During pregnancy the epithelium is relatively rich in acid and completely devoid of alkaline phosphatases. Outside oestrus the epithelium of the cranial vaginal region is a relatively flat, stratified columnar one and contains leucocytes with regularity. Also the cranial vaginal portion undergoes mucification during pregnancy with a maximum about day 33. The mucous material is situated intracellularly and not within the intercellular gaps. Further, larger intraepithelial mucus cysts are observed. Alkaline phosphatase is found during gravidity in the basal region and an adluminal border of the epithelium. The reactions for oxidoreductases are strongest in the columnar cell layer which shows more functional adaptations than the remainder of the epithelium. Histochemical tests for beta-D-glucuronidase and leucine aminopeptidase give negative results in the whole vagina during all different functional stages studied.

  10. Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles

    Directory of Open Access Journals (Sweden)

    I.R.M. Padua

    2016-06-01

    Full Text Available ABSTRACT The aim of this study was to evaluate changes in intraocular pressure (IOP, pupil size (PS, blood pressure (BP, heart rate (HR, and ECG variables (Pms wave PmV, PR interval, QRS complex, RMV wave and QT intervals over time during the instillation of 0.5% timolol, 0.5% levobunolol and 0.5% apraclonidine in clinically normal dogs. Ten adult beagles were used. Baseline values were measured at 8a.m., 2p.m. and 8p.m., for three consecutive days. A waiting period of 10 days between the administrations of each drug was established. For 15 consecutive days, the drug being tested was instilled in one eye of each dog twice a day (7a.m. and 7p.m.. The parameters were evaluated at the aforementioned times on days 3, 6, 9, 12 and 15. Data were statistically compared using the Bonferroni test and one-way repeated measures analysis of variance (P<0.05. The Pearson test was used to evaluate any correlation between QT interval, HR and BP. The tested drugs did not find a decrease in IOP. A significant decreased in PS was observed in almost all dogs following levobunolol administration, relative to the control eye. A significant decrease in HR was observed on day 3 following levobunolol treatment, while apraclonidine induced an increase on day 15. Blood pressure was reduced in all measurement time points following apraclonidine treatment. A negative correlation between QT interval and HR was only observed in dogs treated with timolol. In conclusion, levobunolol was the only drug that induced significant alterations in PS. Apraclonidine was the only drug that induced systemic hypotension. Timolol was the only drug to that induced a negative correlation between QT and HR.

  11. Effect of age on the efficacy of Zn-diethylenetriaminepentaacetic acid therapy for removal of Am and Pu from beagles

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Mays, C.W.; Jones, C.W.; Lloyd, C.R.; Taylor, G.N.; Wrenn, M.E.

    1985-01-01

    Decorporation of intravenously injected monomeric 241 Am and /sup 237+239/Pu by the administration of 30 μmole Zn-diethylenetriaminepentaacetic acid (DTPA)/kg each day beginning 2 weeks after radionuclide injection was compared in beagles entered into the experiment when 3 months (juveniles), 1.9 years (young adults), or 10 years (mature adults) old and studied for about 5 months. DTPA therapy was most effective in the juvenile dogs and least effective in the mature adults. Retention of 241 Am in the liver decreased from a pretreatment value for adults of about 50% of the injected activity to about 10% in the mature adults and less than 1% in the young adults at 140 days of treatment, while the liver retention of juveniles decreased from pretreatment values of about 16% to undetectable levels by 28 days of treatment. Plutonium retention in the liver decreased from adult pretreatment levels of about 30% to near 10% in the mature adults and 6% in the young adults at 140 days of treatment, while juvenile liver retention decreased from pretreatment values near 15% to undetectable levels by 56 days of treatment. Nonliver Am retention (mainly skeleton) decreased in mature adults from pretreatment values of about 45% of the injected activity to near 25%, in young adults from 35 to 20%, and in juveniles from roughly 70 to 9% by 140 days of DTPA administration. Nonliver Pu retention decreased from pretreatment values of about 50% for mature and young adults to about 30% by 140 days and from 75 to 16% in juveniles over the same period

  12. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiaobing [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China); Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Li, Bo, E-mail: libo@nifdc.org.cn [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China)

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species. - Highlights: • Urinary NGAL, clusterin and NAG levels were significantly elevated in canine AKI. • NGAL and clusterin gene expression were increased following treatment with gentamicin. • NGAL and clusterin have high specificity and sensitivity for detection of AKI.

  13. The Osteogenesis Effect and Underlying Mechanisms of Local Delivery of gAPN in Extraction Sockets of Beagle Dogs

    Science.gov (United States)

    Hu, Hongcheng; Pu, Yinfei; Lu, Songhe; Zhang, Kuo; Guo, Yuan; Lu, Hui; Li, Deli; Li, Xuefen; Li, Zichen; Wu, Yuwei; Tang, Zhihui

    2015-01-01

    A plastic and biodegradable bone substitute consists of poly (l-lactic-co-glycolic) acid and 30 wt % β-tricalcium phosphate has been previously fabricated, but its osteogenic capability required further improvement. We investigated the use of globular adiponectin (gAPN) as an anabolic agent for tissue-engineered bone using this scaffold. A qualitative analysis of the bone regeneration process was carried out using μCT and histological analysis 12 weeks after implantation. CBCT (Cone Beam Computed Tomography) superimposition was used to characterise the effect of the different treatments on bone formation. In this study, we also explored adiponectin’s (APN) influence on primary cultured human jaw bone marrow mesenchymal stem cells gene expressions involved in the osteogenesis. We found that composite scaffolds loaded with gAPN or bone morphogenetic protein 2 (BMP2) exhibited significantly increased bone formation and mineralisation following 12 weeks in the extraction sockets of beagle dogs, as well as enhanced expression of osteogenic markers. In vitro investigation revealed that APN also promoted osteoblast differentiation of primary cultured human jaw bone marrow mesenchymal stem cells (h-JBMMSCs), accompanied by increased activity of alkaline phosphatase, greater mineralisation, and production of the osteoblast-differentiated genes osteocalcin, bone sialoprotein and collagen type I, which was reversed by APPL1 siRNA. Therefore, the composite scaffold loaded with APN exhibited superior activity for guided bone regeneration compared with blank control or Bio-Oss® (a commercially available product). The composite scaffold with APN has significant potential for clinical applications in bone tissue engineering. PMID:26492241

  14. The Osteogenesis Effect and Underlying Mechanisms of Local Delivery of gAPN in Extraction Sockets of Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Hongcheng Hu

    2015-10-01

    Full Text Available A plastic and biodegradable bone substitute consists of poly (l-lactic-co-glycolic acid and 30 wt % β-tricalcium phosphate has been previously fabricated, but its osteogenic capability required further improvement. We investigated the use of globular adiponectin (gAPN as an anabolic agent for tissue-engineered bone using this scaffold. A qualitative analysis of the bone regeneration process was carried out using μCT and histological analysis 12 weeks after implantation. CBCT (Cone Beam Computed Tomography superimposition was used to characterise the effect of the different treatments on bone formation. In this study, we also explored adiponectin’s (APN influence on primary cultured human jaw bone marrow mesenchymal stem cells gene expressions involved in the osteogenesis. We found that composite scaffolds loaded with gAPN or bone morphogenetic protein 2 (BMP2 exhibited significantly increased bone formation and mineralisation following 12 weeks in the extraction sockets of beagle dogs, as well as enhanced expression of osteogenic markers. In vitro investigation revealed that APN also promoted osteoblast differentiation of primary cultured human jaw bone marrow mesenchymal stem cells (h-JBMMSCs, accompanied by increased activity of alkaline phosphatase, greater mineralisation, and production of the osteoblast-differentiated genes osteocalcin, bone sialoprotein and collagen type I, which was reversed by APPL1 siRNA. Therefore, the composite scaffold loaded with APN exhibited superior activity for guided bone regeneration compared with blank control or Bio-Oss® (a commercially available product. The composite scaffold with APN has significant potential for clinical applications in bone tissue engineering.

  15. Neoplastic and other pathologic effects of fractionated fast neutrons or photons on the thorax and anterior abdomen of beagles

    International Nuclear Information System (INIS)

    Zook, B.C.; Bradley, E.W.; Casarett, G.W.; Rogers, C.C.

    1986-01-01

    Thirty-nine adult male beagle dogs received either fast-neutron or photon irradiation to the right hemithorax and right rostral abdomen. Twenty-four dogs (six per group) received fast neutrons (15 MeV) to total doses of 1000, 1500, 2250, or 3375 cGy in four fractions per week for six weeks. Fifteen dogs received 3000, 4500, or 6750 cGy of photons in an identical fractionation pattern. One photon-irradiated dog and 13 neutron-irradiated dogs died or were euthanatized because of hepatic and gastrointestinal disturbances 47 to 708 days after irradiation; 20 dogs died of other causes. These 34 dogs were necropsied and have been studied microscopically; the remaining five dogs are still alive seven years after irradiation. Neutron-induced lesions included hemorrhage, necrosis, fibrosis, and atrophy of the heart, liver, pancreas, pylorus, duodenum, and kidney. All lesions were associated with degenerative and occlusive vascular changes including coronary arteriosclerosis. The relative biological effectiveness (RBE) of fast neutrons, assessed by clinical signs and by gross and microscopic pathology, is between 3 and 4.5 for pancreas, ∼4.5 for heart, pylorus, duodenum, and kidney, and greater than 6.75 for liver. Ten malignancies and two benign tumors developed in the irradiated field of six of 12 neutron-exposed dogs that survived over one year after irradiation. Two malignancies and one benign tumor arose in three of 12 photon-exposed dogs surviving over one year postirradiation. Only one neoplasm developed in the same field in 11 nonirradiated controls or in 62 dogs irradiated at sites other than the thorax or abdomen. The neutron RBE for neoplasia is approximately 6.75. 85 refs., 8 figs., 3 tabs

  16. Long-term Observation of Regenerated Periodontium Induced by FGF-2 in the Beagle Dog 2-Wall Periodontal Defect Model.

    Directory of Open Access Journals (Sweden)

    Jun Anzai

    Full Text Available The long-term stability and qualitative characteristics of periodontium regenerated by FGF-2 treatment were compared with normal physiological healing tissue controls in a Beagle dog 2-wall periodontal defect model 13 months after treatment by assessing tissue histology and three-dimensional microstructure using micro-computed tomography (μCT. After FGF-2 (0.3% or vehicle treatment at the defect sites, serial changes in the bone mineral content (BMC were observed using periodic X-ray imaging. Tissues were harvested at 13 months, evaluated histomorphometrically, and the cortical bone volume and trabecular bone structure of the newly formed bone were analyzed using μCT. FGF-2 significantly increased the BMC of the defect area at 2 months compared with that of the control group, and this difference was unchanged through 13 months. The cortical bone volume was significantly increased by FGF-2, but there was no difference between the groups in trabecular bone structure. Bone maturation was occurring in both groups because of the lower cortical volume and denser trabecular bone than what is found in intact bone. FGF-2 also increased the area of newly formed bone as assessed histomorphometrically, but the ratios of trabecular bone in the defect area were similar between the control and FGF-2 groups. These results suggest that FGF-2 stimulates neogenesis of alveolar bone that is of similar quality to that of the control group. The lengths of the regenerated periodontal ligament and cementum, measured as the distance from the defect bottom to the apical end of the gingival epithelium, and height and area of the newly formed bone in the FGF-2 group were larger than those in the control group. The present study demonstrated that, within the limitation of artificial periodontal defect model, the periodontal tissue regenerated by FGF-2 was maintained for 13 months after treatment and was qualitatively equivalent to that generated through the physiological

  17. The comparison of bolus tracking and test bolus techniques for computed tomography thoracic angiography in healthy beagles

    Directory of Open Access Journals (Sweden)

    Nicolette Cassel

    2013-05-01

    Full Text Available Computed tomography thoracic angiography studies were performed on five adult beagles using the bolus tracking (BT technique and the test bolus (TB technique, which were performed at least two weeks apart. For the BT technique, 2 mL/kg of 300 mgI/mL iodinated contrast agent was injected intravenously. Scans were initiated when the contrast in the aorta reached 150 Hounsfield units (HU. For the TB technique, the dogs received a test dose of 15% of 2 mL/kg of 300 mgI/mL iodinated contrast agent, followed by a series of low dose sequential scans. The full dose of the contrast agent was then administered and the scans were conducted at optimal times as identified from time attenuation curves. Mean attenuation in HU was measured in the aorta (Ao and right caudal pulmonary artery (rCPA. Additional observations included the study duration, milliAmpere (mA, computed tomography dose index volume (CTDI[vol] and dose length product (DLP. The attenuation in the Ao (BT = 660 52 HU ± 138 49 HU, TB = 469 82 HU ± 199 52 HU, p = 0.13 and in the rCPA (BT = 606 34 HU ± 143 37 HU, TB = 413 72 HU ± 174.99 HU, p = 0.28 did not differ significantly between the two techniques. The BT technique was conducted in a significantly shorter time period than the TB technique (p = 0.03. The mean mA for the BT technique was significantly lower than the TB technique (p = 0.03, as was the mean CTDI(vol (p = 0.001. The mean DLP did not differ significantly between the two techniques (p = 0.17. No preference was given to either technique when evaluating the Ao or rCPA but the BT technique was shown to be shorter in duration and resulted in less DLP than the TB technique.

  18. Bronchopulmonary lavage and DTPA treatment for the removal of inhaled 239Pu of varied solubility in beagle dogs. II

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Miglio, J.J.; Slauson, D.O.; McClellan, R.O.

    1974-01-01

    The efficacy of bronchopulmonary lavage and chelation therapy was determined for removing 239 Pu from Beagle dogs after inhalation of 239 Pu aerosols of differing in vivo solubility. The four aerosols used were nebulized from a solution of 239 PuCl 4 and heat treated at temperatures of 325, 600, 900, and 1150 0 C, respectively. Six dogs were exposed to each of the four aerosols and three dogs in each group were treated subsequently by lavage and intravenous diethylenetriaminepentaacetic acid (DTPA); three dogs served as untreated controls. Tissue accumulation of 239 Pu in the untreated control dogs at sacrifice 56 days post-exposure, expressed as a percentage of the initial lung burden (ILB), was 6 percent in liver and 9 percent in skeleton for the 325 0 C aerosol group, 1 percent in liver and 2 percent in the skeleton for the 600 0 C group, and less than 0.6 percent in these tissues for the 900 0 and 1150 0 C aerosol groups. Tissue accumulation was 1.0 percent or less of the ILB for all organs in the treated groups of dogs. The urinary excretion of 239 Pu was increased in the treated dogs compared to the control dogs that inhaled the 325 0 C and 600 0 C aerosols and was low in all dogs exposed to the 900 0 and 1150 0 C treated aerosol particles. Ten bronchopulmonary lavage procedures removed a mean of 44 percent of the ILB of 239 Pu from the lungs. The aerosol temperature and resulting differences in solubility of the particles did not influence the efficacy of the lavage procedure. An in vitro solubility test predicted the relative in vivo solubility of the four aerosols. These results are discussed in relation to the choice of therapy and its timing. (U.S.)

  19. Effects of cilostazol and k-134 on reconstructive surgery using prosthetic grafts in the abdominal aorta of beagle dogs.

    Science.gov (United States)

    Inoue, Yoshinori; Sugano, Norihide; Jibiki, Masatoshi; Kudo, Toshifumi; Iwai, Takehisa

    2008-01-01

    Problems associated with prosthetic graft replacement are stenosis at the anastomosis site and thrombus formation on the inner surface. Cilostazol is known to have antiplatelet activity and inhibit vascular smooth muscle cell proliferation and neointima thickening. A cilostazol derivative, (-)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido]-propoxy]-2-(1H)-quinolinone (K-134), has more potent anti-platelet activity and anti-neointimal thickening activity than cilostazol in the in-vitro platelet aggregation and in-vivo anti-hyperplastic activity assay. The aim of this study was to investigate effects of cilostazol and K-134 on thrombus formation and neointimal thickening at the site of prosthetic graft replacement. Beagle dogs underwent infrarenal abdominal aortic resection with straight Dacron graft replacement, which were allocated to the control, cilostazol, and K-134 groups. Two dogs were dead without confirming the cause of death. After 6 months, all dogs were necropsied. All prosthetic grafts were patent in each group. Ratios of red thrombus to prosthetic graft area were 0.3+/-6.4%, and 3.3+/-4.5% in the cilostazol and K-134 groups, respectively, which were significant different from that in the control group (24.4+/-16.8%). However, no clear difference was seen among the 3 groups with respect to neointimal thickness (control group, 0.70+/-0.13 mm; cilostazol group, 0.59+/-0.14 mm; K-134 group, 0.67+/-0.14 mm). Cilostazol and K-134 significantly inhibited thrombus formation on the inner surface of the prosthetic graft at 6 months after graft replacement. Neointimal thickening on the inner surface was slight even in control-group animals, and the effects of cilostazol and K-134 on such thickening were unclear.

  20. Preliminary data on chronic effects of ultraviolet radiation on the growth of some phytoplankton species of the Beagle Channel, Argentina

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    Marcelo P. Hernando

    1999-12-01

    Full Text Available Serious concerns exist that the thinning of stratospheric ozone and the resulting enhancement in the solar UVB radiation, may impair marine primary productivity. Also, UVB may alter food web dynamics and food availability for higher trophic levels in marine ecosystems inducing changes in phytoplankton species composition. The main goal of this study was to examine the responses of different species of marine phytoplankton to solar UVR. Specifically, we compared the UV sensitivity of a phytoplankton natural community isolated from the Beagle Channel (54°52´S, 68°18´W, Ushuaia, Argentina, as well as the response of two taxa which were isolated from that community (i.e., a pennate diatom, Navicula sp., and a phytoflagellate pertaining to the Class Cryptophyceae to UV radiation. Exposure to UVB or UVA radiation treatments had no significant effects (p > 0.05 on exponential growth rate in Navicula sp. However, when the phytoflagellate [Class Cryptophyceae] was exposed to UVB, the growth rate in the exponential phase was inhibited significantly (p < 0.01 compared with the PAR control. Marked changes in the relative abundance of the main taxonomic groups were observed in the community cultures: the relative abundance of phytoflagellates was significantly lower after exposure to the UVB treatment than after exposure to the PAR treatment (p < 0.05. However, the percentage of centric diatoms increased significantly (p < 0.05 when they were exposed to UVB. The growth rate at the end of the exponential phase of growth of the community was inhibited significantly (p < 0.01 when the algae were exposed to UVB and UVA.

  1. Chronic effects of maternal ethanol and low-protein intake on growth and blood measurements of beagle pups

    International Nuclear Information System (INIS)

    Switzer, B.R.; Anderson, J.J.B.; Pick, J.R.

    1986-01-01

    Pups used in this study were born to nulliparous, purebred female beagles fed either 17% control (CP) or 8.5% low protein (LP) diets and were given twice daily either 1.8 g/kg ethanol (E) or an equivalent isocaloric dose of sucrose (S) throughout pregnancy. After parturition, all mothers were fed the CP diet and no E or S. On day 1 and each week up to 4 weeks, the weight (WT), crown-rump length (LT) and head circumference (HC) of the pups were measured. These measurements were taken for a post-weaning subset at 6, 8 and 10 weeks. Blood samples were collected each week. At birth, mean WT, LT and HC were significantly lower in pups from E-mothers as compared to S-mothers with either CP or LP diets. The birth WT, LT and HC were significantly lower when mothers were fed LP as compared to the CP diet with either S or E. The prenatal effects of E and LP were significantly associated with lower pup WT, HT and hematocrit values, but not HC up to 4 weeks. At 10 weeks, the growth measurements and hematocrits were significantly lower with prenatal E exposure but not with LP. Pup red cell levels of folate were significantly lower with prenatal E during the first 4 weeks, whereas the effect of prenatal LP but not E was significant at 10 weeks. These data suggest that growth parameters and hematocrit values of pups prenatally exposed to E do not catch up to those of pups from S-mothers fed either diet

  2. Use of plasma creatine kinase pharmacokinetics to estimate the amount of excercise-induced muscle damage in Beagles.

    Science.gov (United States)

    Chanoit, G P; Lefebvre, H P; Orcel, K; Laroute, V; Toutain, P L; Braun, J P

    2001-09-01

    To assess the effects of moderate exercise on plasma creatine kinase (CK) pharmacokinetics and to estimate exercise-induced muscle damage in dogs. 6 untrained adult Beagles. The study was divided into 3 phases. In phase 1, dogs ran for 1 hour at a speed of 9 km/h, and samples were used to determine the area under the plasma CK activity versus time curve (AUC) induced by exercise. In phases 2 and 3, pharmacokinetics of CK were calculated in dogs during exercise and at rest, respectively. Values for AUC and plasma clearance (CI) were used to estimate muscle damage. At rest, values for Cl, steady-state volume of distribution (Vdss), and mean retention time (MRT) were 0.32+/-0.02 ml/kg of body weight/min, 57+/-173 ml/kg, and 3.0+/-0.57 h, respectively. During exercise, Cl decreased significantly (0.26+/-0.03 ml/kg/min), MRT increased significantly, (4.4+/-0.97 h), and Vdss remained unchanged. Peak of plasma CK activity (151+/-58.8 U/L) was observed 3 hours after completion of exercise. Estimated equivalent amount of muscle corresponding to the quantity of CK released was 41+/-29.3 mg/kg. These results revealed that exercise had a minor effect on CK disposition and that the equivalent amount of muscle damaged by moderate exercise was negligible. This study illustrates the relevance for use of the minimally invasive and quantitative pharmacokinetic approach when estimating muscle damage.

  3. The removal of inhaled 239Pu and 238Pu from beagle dogs by lung lavage and chelation treatment

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Miglio, J.J.; Slauson, D.O.; McClellan, R.O.

    1976-01-01

    Studies were conducted in beagle dogs to determine the efficiency of treatment by lung lavage and injections of chelating agents in removing inhaled plutonium of varied chemical forms and particle sizes. Polydisperse aerosols of 239 Pu were produced at different temperatures from 325 0 C to 1150 0 C to evaluate the effect of the chemical form of the particles. Aerosols of 238 Pu were produced at 1150 0 C only but were of different particle size or size distributions. Three dogs that inhaled each different plutonium aerosol were treated by lung lavages starting two days after the exposure. Subsequent lavages were performed on days 7, 10, 14, 21, 28, 35, 42, and 49 after exposure. Intravenous injections of 100 mg of diethylenetriaminepentaacetic acid (DTPA) as the calcium salt were given on days 1, 2, 3 and 4 after exposure and twice weekly thereafter to the time of sacrifice, 56 days after exposure. The 10 lung lavages removed from 18 to 49% of the initial lung burden of plutonium. The recovery of plutonium by lavage was similar irrespective of the temperature at which the aerosol was produced, however, lavage recovery decreased somewhat with increasing particle size. The efficacy of DTPA treatment increased with decreasing production temperature of the 239 Pu. Treatment with DTPA was not affected by particle size of the 0.8- and 1.9-μm monodisperse 239 Pu aerosol. The effectiveness of lung lavage decreased as the solubility of the aerosol particles increased whereas the effectiveness of the DTPA treatment increased as the solubility of the inhaled aerosol increased as shown by the lowest temperature aerosol and the aerosol-containing soluble fraction. These findings correlated qualitatively with a 2-hour in-vitro solubility test on the exposure aerosols. (author)

  4. 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.

  5. High-Throughput Determination of Sodium Danshensu in Beagle Dogs by the LCMS/MS Method, Employing Liquid-Liquid Extraction Based on 96-Well Format Plates

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    Jingjing Jiang

    2017-04-01

    Full Text Available Sodium Danshensu (sodium d-(+-β-(3,4-dihydroxyphenyl lactate, one of the water-soluble ingredients in Salvia miltiorrhiza, exhibits potent relaxation of the coronary artery and anticoagulation effection. A high-throughput, rapid, and sensitive method combining liquid chromatography with electrospray ionization tandem mass spectrometry to determine the sodium danshensu in beagle dog plasma was developed and validated, using gallic acid as an internal standard (IS. Acidified plasma samples were extracted using 96-well liquid-liquid extraction, and were eluted on a CNW Athena C18 column (3 μm, 2.1 × 100 mm by using a gradient mobile phase system of methanol and water (containing 0.2% formic acid. The mass spectrometric detection was achieved using negative ion electrospray ionization mode and monitoring the precursor→production combinations of m/z 197→135 for sodium danshensu and 169→125 for IS, in multiple reaction monitoring modes. Good linearity was achieved, and the linear range was 10–1000 ng/mL (R2 > 0.996 with a quantification limit of 10 ng/mL for sodium danshensu in beagle dog plasma. The intra- and inter-day precision (RSD ranged from 2.1% to 9.0%. The accuracy (RE was between −8.6% and 5.7% at all quality control levels. The validated method was successfully applied to the pharmacokinetics study of sodium danshensu in beagle dog plasma after intravenous injection and oral administration of sodium danshensu.

  6. Development and validation of a liquid chromatography-tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study.

    Science.gov (United States)

    Ye, Ling; Shi, Jian; Wan, Shanhe; Yang, Xiaoshan; Wang, Ying; Zhang, Jiajie; Zheng, Dayong; Liu, Zhongqiu

    2013-11-01

    Topotecan (TPT) is an important anti-cancer drug that inhibits topoisomerase I. A sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that potentially determines TPT in beagle dog plasma is needed for a bioequivalence study of TPT formulations. We developed and validated LC-MS/MS to evaluate TPT in beagle dog plasma in terms of specificity, linearity, precision, accuracy, stability, extraction recovery and matrix effect. Plasma samples were treated with an Ostro(TM) sorbent plate (a robust and effective tool) to eliminate phospholipids and proteins before analysis. TPT and camptothecin (internal standard) were separated on an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 50 mm) with 0.1% formic acid and methanol as the mobile phase at a flow rate of 0.25 mL/min. TPT was analyzed using positive ion electrospray ionization in multiple-reaction monitoring mode. The obtained lower limit of quantitation was 1 ng/mL (signal-to-noise ratio > 10). The standard calibration curve for TPT was linear (correlation coefficient > 0.99) at the concentration range of 1-400 ng/mL. The intra-day and inter-day precision, accuracy, stability, extraction recovery and matrix effect of TPT were within the acceptable limits. The validated method was successfully applied in a bioequivalence study of TPT in healthy beagle dogs. Copyright © 2013 John Wiley & Sons, Ltd.

  7. The effect of dose protraction on the incidence of lung carcinomas in beagle dogs with internally deposited β-emitting radionuclides

    International Nuclear Information System (INIS)

    Griffith, W.C.; Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Snipes, M.B.

    1992-01-01

    Studies using Beagle dogs were conducted to understand health effects when lung is the primary organ irradiated after inhaling insoluble radioactive particles containing one of four β-emitting radionuclides, 90 Y, 91 Y, 144 Ce, or 90 Sr. The low-LET β irradiation was delivered over a wide range of total doses and dose rate patterns that protracted the dose to lung from about 1 wk to several years. The tumor incidence rates for lung carcinomas were estimated using a proportional hazard rate model. These studies suggest that dose protraction only affects production of lung carcinomas at doses above 50 Gy

  8. Quantitative response of bone marrow colony-forming units (CFU-C and PFU-C) in weaning beagles exposed to acute whole-body γ irradiation

    International Nuclear Information System (INIS)

    Wilson, F.D.; Stitzel, K.A.; Klein, A.K.; Shifrine, M.; Graham, R.; Jones, M.; Bradley, E.; Rosenblatt, L.S.

    1978-01-01

    Using a methylcellulose-supported bone marrow culture system, the dose-response relationships of suspended granulocyte-monocyte colonies (CFU-C) and adherent fibroblastic colonies (PFU-C) were investigated in 2- to 3-month-old beagles exposed to acute whole-body γ irradiation. Groups of weanling beagles were exposed at a rate of 140 R/hr delivered from a 60 Co γ source achieving total exposures ranging from 0 to 586 R. Twenty-four hours following irradiation, bone marrow was collected, plated into methylcellulose, and after 1 week of incubation both colony types were quantitated. In addition, bone marrow cellularity determinations were made for a variety of bones using an 59 Fe-labeling technique. The results show a D 37 for the linear part of the slope of 70 R for CFU-C. Although within the limits of the experiment a D 37 could not be established for the fibroblastic populations, the results indicate a substantial degree of radioresistance for these elements supporting our previous studies on PFU-C, performed on mice, which suggested a D 37 of approximately 400 R for the progenitors of these fibroblastic elements

  9. On-Line Organic Solvent Field Enhanced Sample Injection in Capillary Zone Electrophoresis for Analysis of Quetiapine in Beagle Dog Plasma

    Directory of Open Access Journals (Sweden)

    Yuqing Cao

    2016-01-01

    Full Text Available A rapid and sensitive capillary zone electrophoresis (CZE method with field enhanced sample injection (FESI was developed and validated for the determination of quetiapine fumarate in beagle dog plasma, with a sample pretreatment by LLE in 96-well deep format plate. The optimum separation was carried out in an uncoated 31.2 cm × 75 μm fused-silica capillary with an applied voltage of 13 kV. The electrophoretic analysis was performed by 50 mM phosphate at pH 2.5. The detection wavelength was 210 nm. Under these optimized conditions, FESI with acetonitrile enhanced the sensitivity of quetiapine about 40–50 folds in total. The method was suitably validated with respect to stability, specificity, linearity, lower limit of quantitation, accuracy, precision and extraction recovery. Using mirtazapine as an internal standard (100 ng/mL, the response of quetiapine was linear over the range of 1–1000 ng/mL. The lower limit of quantification was 1 ng/mL. The intra- and inter-day precisions for the assay were within 4.8% and 12.7%, respectively. The method represents the first application of FESI-CZE to the analysis of quetiapine fumarate in beagle dog plasma after oral administration.

  10. Development and validation of an enantioselective SFC-MS/MS method for simultaneous separation and quantification of oxcarbazepine and its chiral metabolites in beagle dog plasma.

    Science.gov (United States)

    Yang, Zhichao; Xu, Xueyu; Sun, Lingxia; Zhao, Xue; Wang, Hao; Fawcett, John Paul; Yang, Yan; Gu, Jingkai

    2016-05-01

    A rapid and sensitive assay based on supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) has been developed and validated for the determination of oxcarbazepine (OXC) and its chiral metabolite licarbazine (Lic) in beagle dog plasma using carbamazepine as internal standard. Chiral analysis in a run time of only 3 min was performed on an ACQUITY UPC(2) ™ Trefoil™ CEL2 column (3.0 × 150 mm, 2.5 μm) at 50 °C by isocratic elution with a mobile phase of supercritical carbon dioxide (purity ≥ 99.99%) and methanol (60:40, v/v) at a flow rate of 2.3 mL/min. The assay was linear over the concentration ranges 5-1000 ng/mL for OXC and 0.5-100 ng/mL for the enantiomers of Lic with corresponding lower limits of quantitation of 5 ng/mL and 0.5 ng/mL. Intra- and inter-day precisions were in the range 0.78-14.14% with accuracies in the range -10.80% to 0.42%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of 16 mg/kg OXC as Trileptal(@) tablets to beagle dogs. Copyright © 2016. Published by Elsevier B.V.

  11. Simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a bioequivalence study.

    Science.gov (United States)

    Hu, Ziyan; Zou, Qiaogen; Tian, Jixin; Sun, Lili; Zhang, Zunjian

    2011-12-15

    A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma has been developed and validated. Following liquid-liquid extraction, the analytes were separated on a reversed-phase C(18) column (150 mm × 2.0 mm, 3 μm) using formic acid:10 mM ammonium acetate:methanol (0.2:62:38, v/v/v) as mobile phase at a flow rate of 0.2 mL/min and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode. The method was linear for all analytes over the following concentration (ng/mL) ranges: codeine 0.08-16; ephedrine 0.8-160; guaiphenesin 80-16,000; chlorpheniramine 0.2-40. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method was successfully applied to a bioequivalence study in 6 healthy beagle dogs. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Development of a UPLC-ESI-MS/MS method for the determination of larotaxel in beagle dog plasma: application to the pharmacokinetic study.

    Science.gov (United States)

    Liu, Zhenzhen; Zhang, Bo; Liu, Zhihong; Li, Song; Li, Guofei; Geng, Lulu; Zhao, Xu; Bi, Kaishun; Tang, Xing; Chen, Xiaohui

    2012-04-01

    A UPLC-ESI-MS/MS method has been developed and validated for the determination of larotaxel in beagle dog plasma. After addition of the internal standard, plasma samples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a 50×2.1 mm ACQUITY 1.7 μm C18 column (Waters, USA), with acetonitrile and 5 mM ammonium acetate as mobile phase, within a runtime of 3.0 min. The analytes were detected without interference in Multiple Reaction Monitoring mode with positive electrospray ionization. The linear range was 2.5-5,000 ng/mL. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 9.3% and 10.2%, respectively, and the accuracy (relative error, RE, %) was less than 11.5%. The validated method was successfully applied to a pharmacokinetic study of larotaxel in beagle dogs after intravenous administration of larotaxel-loaded lipid microsphere with different doses of 0.4, 0.8, and 1.6 mg/kg. The area under the concentration-time curve and the peak concentration of larotaxel seemed to increase with increasing dose proportionally, suggesting linear pharmacokinetics.

  13. Quantification of a Novel Photosensitizer of Chlorin e6-C15-Monomethyl Ester in Beagle Dog Plasma Using HPLC: Application to Pharmacokinetic Studies

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    Xiuxiu Li

    2017-04-01

    Full Text Available Chlorin e6-C15-monomethyl ester (CMME is a novel photosensitizer, which is synthetized from the degradation products of silkworm excrement. Preclinical studies on the promising photosensitizer CMME are necessary to determine its therapeutic efficacy and druglikeness. A high-performance liquid chromatography with UV detection (HPLC–UV method was established for the determination of CMME in beagle dog plasma. The sample preparation involved a protein-precipitation method with acetonitrile after the addition of tanshinone IIA as an internal standard (IS. CMME and the IS were separated on a Diamonsil C18 (2 column (100 mm × 4.6 mm, 5 μm with a isocratic system of methanol–water containing 20 mM ammonium acetate with 0.3% glacial acetic acid (85:15, v/v. The flow rate was 1.0 mL/min with UV detection using a wavelength of 400 nm. The method was sensitive enough with a lower limit of quantitation (LLOQ of 0.05 μg/mL and had a good linearity (r2 > 0.999 over the linear range of 0.05–5.00 μg/mL. The intra-day and inter-day accuracies ranged from 98.5% to 102.8% and precisions (RSD were within 6.8%. The validated method was successfully applied to the pharmacokinetic study of CMME after intravenous administration of single and multiple doses in beagle dogs.

  14. Relative radiosensitivity of bone tumor induction among beagles as a function of age at injection of 239Pu or 226Ra

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Taylor, G.N.; Jee, W.S.S.; Miller, S.C.

    1999-01-01

    A comparison was made of the response to induction of skeletal malignancy from exposure of beagles to monomeric 239 Pu or to 226 Ra as juveniles (3 mo of age), young adults (1.5 y of age), or mature adults (5 y of age). This indicated that of these age groups, animals injected as young adults are most sensitive per Gy of average skeletal dose evaluated at 1 y before death. Dogs exposed either as juveniles or as mature adults appeared to be less sensitive. Relative radiosensitivities (RRS) of juvenile and mature beagles ranged between about 0.3 and 0.7 that of dogs injected as young adults. Mean values of RRS for both radionuclides were about 0.5, but RRS values derived from dogs given monomeric 239 Pu appeared to be most reliable and were 0.27 ± 0.09 for dogs injected as juveniles and 0.41 ± 0.13 for animals exposed as mature adults

  15. Preclinical evaluation of intravenously administered 111In-and 90Y-labeled B72.3 immunoconjugate (GYK-DTPA) in beagle dogs

    International Nuclear Information System (INIS)

    Quadri, S.M.; Vriesendorp, H.M.; Yi Shao; Blum, J.E.; Leichner, P.K.; Williams, J.R.

    1993-01-01

    B72.3, a monoclonal antibody with reactivity against human adenocarcinomas was obtained from the Cytogen Corporation in the form of an immunoconjugate coupled with linker-chelator GYK-DTPA by using proprietary carbohydrate directed site specific chemistry. The immunoconjugate was radiolabeled with indium-111 or yttrium-90. A preclinical analysis was performed in 10 normal beagle dogs. The pharmacokinetics of intravenously administered indium- and yttrium-labeled immunoconjugates were compared serially in blood, bone marrow and urine samples. Compared to 90 Y less of the 111 In label ended up in urine and more was found in blood and bone marrow. Indium-labeled B72.3 GYK-DTPA had relatively higher uptake in most glandular tissues than 111 In-labeled antiferritin immunoconjugate. Bone marrow toxicity was the dose limiting side effect after intravenous infusion of 90 Y-labeled B72.3 GYK-DTPA. Toxicity was also observed in the liver but not in other organ systems. Recently other investigators obtained similar results with these immunoconjugates in human patients. A preclinical pharmacokinetic analysis of radioimmunoconjugates in beagle dogs provided useful information regarding bone marrow toxicity, liver toxicity and in vivo instability of the immunoconjugate. Data suggest that for future trials in human patients, a more stable chelated immunoconjugate for yttrium is needed to achieve less liver uptake and a better correlation with the 111 In-labeled product than the 90 Y-labeled B72.3 GYK-DTPA used in this investigation. (Author)

  16. /sup 144/Ce in tissue of beagle dogs after inhalation of CeCl/sub 3/ with special emphasis on endocrine glands and reproductive organs

    Energy Technology Data Exchange (ETDEWEB)

    Cuddihy, R G; Boecker, B B; McClellan, R O; Kanapilly, G M [Lovelace Foundation for Medical Education and Research, Albuquerque, N.Mex. (USA)

    1976-01-01

    Beagle dogs inhaled aerosols containing /sup 144/CeCl/sub 3/. Deposition of /sup 144/Ce in tissues was determined in serially sacrificed dogs to characterize radiation dose patterns at early times after exposure. Uptakes of /sup 144/Ce in endocrine glands and reproductive organs were also measured; radiation doses were calculated and those doses were compared with the doses to the major organs of deposition - lung, liver and skeleton. Integrated radiation doses in pituitary and adrenal glands, pancreas, ovaries, testes, prostate and uterus were less than 2 % of those in lung and liver, while the thyroid dose was about 30 % of the dose in liver. These findings were consistent with previously reported biological responses in beagle dogs exposed to high levels of /sup 144/CeCl/sub 3/ wherein no radiation effects related to endocrine glands or the reproductive system have been observed. Use of these results in predicting the dosimetry of /sup 144/Ce in exposed humans re-emphasized the importance of radiation damage to lung, liver, skeleton and gastrointestinal tract compared to other organ systems.

  17. Long-term following-up of viability of spleen autotransplants in the Beagle canine model Avaliação em longo prazo da viabilidade do autotransplante de baço em cães Beagle

    Directory of Open Access Journals (Sweden)

    Erika Sajtos

    2012-02-01

    Full Text Available PURPOSE: To examine the possible late complications of splenectomy or spleen autotransplantation in large laboratory animal model, in which we need non-invasive or minimal-invasive methods for long-term monitoring of the experimental animals. METHODS: Experimental groups of beagle dogs were: non-operated control, sham-operated control, splenectomy, spleen autotransplantation with 5 or 10 spleen-chips taken into the greater omentum (Furka's technique. Prior to operations, on the 1st postoperative week, monthly till the 6th as well as in the 9th and 12th month, hemorheological examinations were performed. In postoperative 12th month colloid scintigraphy and diagnostic laparoscopy were carried out. At the end of the investigation comparative morphological examinations were performed, too. RESULTS: From the 4th-5th postoperative month filtration function of spleen-autotransplants showed particular restoration compared to splenectomy group. However, the functional results did not reach the values of the control or sham-operated groups. Sham-operated control's scintigraphy nicely showed activity in the spleen. In spleen autotransplantation-groups scintigraphy indicated well the activity of spleen-chips. During diagnostic laparoscopy spleen-chips with their blood supply were found. Histologically, the structure of spleen­autotransplants was similar to normal splenic tissue. CONCLUSIONS: The autotransplants are regenerated, their functions have been partly restored, and thus spleen autotransplantation may prevent the possible complications of splenectomy. These parameters and the presented investigative protocol are suitable for long-term following-up of viability of the spleen-autotransplants.OBJETIVO: Examinar as possíveis complicações tardias da esplenectomia ou do autotransplante de baço em modelo animal de grande porte, no qual faz-se necessário o uso de métodos não invasivos ou minimamente invasivos para monitorizar os animais de

  18. Removal of inhaled 241Am oxide particles from beagle dogs by combined treatment with lung lavage and a chelating agent

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Mo, T.; Slauson, D.O.

    1978-01-01

    This experiment was performed to evaluate combined therapy of lung lavage and chelation treatments to remove inhaled particles of 241 Am oxide. Twenty-four Beagle dogs were divided into four groups of 6 dogs each. Each group was exposed to an aerosol of different-sized particles of 241 Am oxide: monodisperse particles with AD of 0.75, 1.5 or 3.0 μm; polydisperse particles with AMAD = 1.5 μm. Three dogs in each group were treated with 5 lung lavages of the right lung (day 2, 7, 14, 28 and 42), and 5 lavages of the left lung (days 2, 10, 21, 35, and 49). In addition, each of the treated dogs was given 22 μmoles of trisodium calcium diethylenetriaminepentaacetate (Na 3 Ca DTPA) by intravenous injection 18 times from day 1 to 52 after exposure. The remaining 3 dogs in each group were untreated control dogs. All of the dogs were sacrificed 64 days after exposure and tissues, excreta, and lavage fluids were analyzed for 241 Am activity. Tissue distribution of 241 Am activity at sacrifice varied with aerosol particle size. Less 241 Am activity was found in the lungs of the dogs exposed to 0.75 and 1.5 μm AD aerosols groups than in those exposed to 3.0 μm particles. Lung lavage removed from 24 to 58% of the initial lung burden (ILB). Particle size did not affect the usefulness of lung lavage but it did influence the effectiveness of Na 3 Ca DTPA treatment. Na 3 Ca DTPA enhanced urinary excretion of 241 Am; dogs exposed to 0.75 μm particles excreted 31% of the ILB, and those exposed to 3.0 μm particles excreted only 10%. This experiment showed the effectiveness of combined treatment with lung lavage and chelation therapy for the removal of 241 Am oxide in the first 64 days after exposure. (author)

  19. Dietary fish oil alters the lysophospholipid metabolomic profile and decreases urinary 11-dehydro thromboxane B₂ concentration in healthy Beagles.

    Science.gov (United States)

    Hall, Jean A; Brockman, Jeffrey A; Jewell, Dennis E

    2011-12-15

    Increased concentrations of dietary fish oil and antioxidants have been shown previously to change circulating concentrations of individual fatty acids (FAs) and vitamin E. The purpose of this study was to further investigate the effects of vitamins E and C, in combination with dietary fish oil, on selected blood and urinary biomarkers. Fifty adult Beagle dogs (mean age 5.3 years, range 1.4-14.2 years) were randomized into five dietary treatment groups for 90 days. All foods were complete and balanced and met the nutrient profiles of AAFCO for adult dogs. For 60 days before study initiation, dogs consumed a pretrial food that contained 74 IU/kg vitaminE and 0mg/kg vitaminC. The five experimental foods were confirmed by analytical methods to contain ≥ 640 IU/kg vitaminE and 130 mg/kg vitaminC (as fed). Experimental foods ranged from low levels of EPA and DHA (pretrial food and lowest experimental food had 0.01% EPA and no detectable DHA) to the highest experimental food with 0.25% EPA and 0.17% DHA. Serum was analyzed for FAs, vitamin E, and cholesterol concentrations; urine was analyzed for 11-dehydro thromboxane B(2) (TXB(2)). Serum was also used for metabolomic analysis. FA intake ranged from 0.02 g/day EPA and 0.02 g/day DHA to 0.58 g/day EPA and 0.39 g/day DHA. Increasing dietary concentrations of EPA and DHA resulted in increased serum concentrations of EPA and DHA in a dose-dependent fashion. Greater dietary vitamin E intake resulted in increased serum vitamin E concentrations (Pvitamin E concentrations (Pvitamin E concentration is enhanced primarily by feeding vitamin E and secondarily by serum cholesterol concentration. When feeding diets enriched with fish oil, the major negative predictor of urinary 11-dehydro TXB(2) concentration is serum EPA concentration. Plasma lysophospholipids can be dynamically regulated by dietary fish oil supplementation. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Simultaneous quantification of MTC-220 and its metabolites in beagle dog plasma by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Liu, Xin; Zhao, Manman; Mi, Jiaqi; Liu, Zhihao; Hu, Jinping; Sheng, Li; Wang, Baolian; Li, Dan; Yang, Shuang; Li, Yan

    2014-10-01

    A sensitive LC-ESI-MS/MS method for simultaneous determination of MTC-220 and its metabolites (paclitaxel and MDA-linker) in dog plasma has been developed and validated. After addition of docetaxel (internal standard), plasma samples containing MTC-220, paclitaxel and MDA-linker were prepared based on a simple protein precipitation by adding two volumes of acetonitrile. The separation was performed on a ZorbaxSB-C18 column (3.5μm, 2.1mm×100mm) at a flow rate of 0.2ml/min, using acetonitrile/water containing 0.1% formic acid (v/v) as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by selected reaction monitoring (SRM). The MS/MS ion transit ions monitored were 1444.4→623.8 for MTC-220, 876.4→307.9 for paclitaxel, 631.2→531.2 for MDA-linker and 830.2→549.1 for the internal standard. Linear detection responses were obtained for MTC-220, paclitaxel and MDA-linker ranging from 10 to 5000, 5 to 2500 and 5 to 500ng/ml, respectively. The lower limits of quantitation (LLOQs) for MTC-220, paclitaxel and MDA-linker were 10, 5 and 5ng/ml, respectively. The intra-day and inter-day precisions (RSD, %) of the three analytes do not exceed 10.9% except for LLOQs (≤17.50), and the accuracy (RE, %) were within ±17.5% for LLOQs and ±12.6% for the others. The average recoveries of three compounds were greater than 85.0%. The analytes were proved to be stable during all sample storage, preparation and analytic procedures. The validated method was successfully applied to pharmacokinetic studies of MTC-220 and its metabolites in beagle dogs after intravenous infusion of MTC-220 at 2.5mg/kg. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Pharmacokinetics and metabolism of cyadox and its main metabolites in beagle dogs following oral, intramuscular and intravenous administration

    Directory of Open Access Journals (Sweden)

    Adeel Sattar

    2016-08-01

    Full Text Available Cyadox (Cyx is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO, intramuscular (IM and intravenous (IV routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females were administered Cyx through PO (40 mg kg-1 b.w., IM (10 mg kg-1 b.w. and IV (10 mg kg-1 b.w. routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1, cyadox-1-monoxide (Cy2, N-(quinoxaline-2-methyl-cyanide acetyl hydrazine (Cy4 and quinoxaline-2-carboxylic acid (Cy6 in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC of Cyx after PO, IM and IV administration were 1.22 h×µg mL-1, 6.3 h×µg mL-1, and 6.66 h×µg mL-1, while mean resident times (MRT were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology.

  2. Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ: electrocardiographic, echocardiographic, and morphologic studies

    Directory of Open Access Journals (Sweden)

    Machida Noboru

    2006-12-01

    Full Text Available Abstract Background Cardiac mortality in Duchenne muscular dystrophy (DMD has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. The cardiac involvement is characterized by distinctive electrocardiographic abnormalities or dilated cardiomyopathy, but the pathogenesis has remained obscure. In research on DMD, Golden retriever-based muscular dystrophy (GRMD has attracted much attention as an animal model because it resembles DMD, but GRMD is very difficult to maintain because of their severe phenotypes. We therefore established a line of dogs with Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ and examined the cardiac involvement. Methods The cardiac phenotypes of eight CXMDJ and four normal male dogs 2 to 21 months of age were evaluated using electrocardiography, echocardiography, and histopathological examinations. Results Increases in the heart rate and decreases in PQ interval compared to a normal littermate were detected in two littermate CXMDJ dogs at 15 months of age or older. Distinct deep Q-waves and increase in Q/R ratios in leads II, III, and aVF were detected by 6–7 months of age in all CXMDJ dogs. In the echocardiogram, one of eight of CXMDJ dogs showed a hyperechoic lesion in the left ventricular posterior wall at 5 months of age, but the rest had not by 6–7 months of age. The left ventricular function in the echocardiogram indicated no abnormality in all CXMDJ dogs by 6–7 months of age. Histopathology revealed myocardial fibrosis, especially in the left ventricular posterobasal wall, in three of eight CXMDJ dogs by 21 months of age. Conclusion Cardiac involvement in CXMDJ dogs is milder and has slower progression than that described in GRMD dogs. The distinct deep Q-waves have been ascribed to myocardial fibrosis in the posterobasal region of the left ventricle, but our data showed that they precede the lesion on echocardiogram and

  3. Comparison of three continuous positive airway pressure (CPAP) interfaces in healthy Beagle dogs during medetomidine-propofol constant rate infusions.

    Science.gov (United States)

    Meira, Carolina; Joerger, Fabiola B; Kutter, Annette P N; Waldmann, Andreas; Ringer, Simone K; Böehm, Stephan H; Iff, Samuel; Mosing, Martina

    2018-03-01

    To compare the efficacy of three continuous positive airway pressure (CPAP) interfaces in dogs on gas exchange, lung volumes, amount of leak during CPAP and rebreathing in case of equipment failure or disconnection. Randomized, prospective, crossover, experimental trial. Ten purpose-bred Beagle dogs. Dogs were in dorsal recumbency during medetomidine-propofol constant rate infusions, breathing room air. Three interfaces were tested in each dog in a consecutive random order: custom-made mask (M), conical face mask (FM) and helmet (H). End-expiratory lung impedance (EELI) measured by electrical impedance tomography was assessed with no interface (baseline), with the interface only (No-CPAP for 3 minutes) and at 15 minutes of 7 cmH 2 O CPAP (CPAP-delivery). PaO 2 was assessed at No-CPAP and CPAP-delivery, partial pressure of inspired carbon dioxide (PICO 2 ; rebreathing assessment) at No-CPAP and the interface leak (ΔP leak ) at CPAP-delivery. Mixed-effects linear regression models were used for statistical analysis (pCPAP-delivery, all interfaces increased EELI by 7% (pCPAP, less rebreathing occurred with M (0.5 kPa, 4 mmHg) than with FM (1.8 kPa, 14 mmHg) and with H (1.4 kPa, 11 mmHg), but also lower PaO 2 was measured with M (9.3 kPa, 70 mmHg) than with H (11.9 kPa, 90 mmHg) and FM (10.8 kPa, 81 mmHg). All three interfaces can be used to provide adequate CPAP in dogs. The leak during CPAP-delivery and the risk of rebreathing and hypoxaemia, when CPAP is not maintained, can be significant. Therefore, animals should always be supervised during administration of CPAP with any of the three interfaces. The performance of the custom-made M was not superior to the other interfaces. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  4. Development of novel sibutramine base-loaded solid dispersion with gelatin and HPMC: physicochemical characterization and pharmacokinetics in beagle dogs.

    Science.gov (United States)

    Lim, Hyun-Tae; Balakrishnan, Prabagar; Oh, Dong Hoon; Joe, Kwan Hyung; Kim, Young Ran; Hwang, Doo Hyung; Lee, Yong-Bok; Yong, Chul Soon; Choi, Han-Gon

    2010-09-15

    To develop a novel sibutramine base-loaded solid dispersion with enhanced solubility and bioavailability, various solid dispersions were prepared using a spray drying technique with hydrophilic polymers such as gelatin, HPMC and citric acid. Their solubility, thermal characteristics and crystallinity were investigated. The dissolution and pharmacokinetics of the sibutramine base-loaded solid dispersion were then compared with a sibutramine hydrochloride monohydrate-loaded commercial product (Reductil). The solid dispersions prepared with gelatin gave higher drug solubility than those prepared without gelatin, irrespective of the amount of polymer. The sibutramine base-loaded solid dispersions containing hydrophilic polymer and citric acid showed higher drug solubility compared to sibutramine base and sibutramine hydrochloride monohydrate. Among the formulations tested, the solid dispersion composed of sibutramine base/gelatin/HPMC/citric acid at the weight ratio of 1/0.8/0.2/0.5 gave the highest solubility of 5.03+/-0.24 mg/ml. Our DSC and powder X-ray diffraction results showed that the drug was present in an altered amorphous form in this solid dispersion. The difference factor (f(1)) values between solid dispersion and commercial product were 2.82, 6.65 and 6.31 at pH 1.2, 4.0 and 6.8, respectively. Furthermore, they had the similarity factor (f(2)) value of 65.68, 53.43 and 58.97 at pH 1.2, 4.0 and 6.8, respectively. Our results suggested that the solid dispersion and commercial product produced a similar correlation of dissolution profiles at all pH ranges. The AUC, C(max) and T(max) of the parent drug and metabolite I and II from the solid dispersion were not significantly different from those of the commercial product, suggesting that the solid dispersion might be bioequivalent to the commercial product in beagle dogs. Thus, the sibutramine base-loaded solid dispersion prepared with gelatin, HPMC and citric acid is a promising candidate for improving the

  5. The Effect of Hierarchical Micro/Nanotextured Titanium Implants on Osseointegration Immediately After Tooth Extraction in Beagle Dogs.

    Science.gov (United States)

    Fu, Qian; Bellare, Anuj; Cui, Yajun; Cheng, Bingkun; Xu, Shanshan; Kong, Liang

    2017-06-01

    Owing to simplify the operation and shorten the overall duration of treatment, immediate implantation earned much satisfactory from patients and dentists. The results of immediate implantation determined by osseointegration, we fabricated a micro/nanotextured titanium implants to improve osseointegration immediately after tooth extraction. The aim of this study was to investigate the effect of hierarchical micro/nanotextured titanium implant on osseointegration immediately after tooth extraction. The micro/nanotextured titanium implants were fabricated by etching with 0.5 wt% hydrofluoric (HF) acid followed by anodization in HF electrolytes. Implants with a machined surface as well as implants a microtextured surface prepared by 0.5 wt% HF etching served as control groups. The machined, microtextured, and micro/nanotextured implants were inserted into fresh sockets immediately after tooth extraction in beagle dogs. Twelve weeks after implantation, the animals were sacrificed for micro-CT scanning, histological analysis and biomechanical test. The micro-CT imaging revealed that the bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th) in the micro/nanotextured group was significantly higher than that in the machined group and microtextured group, and the trabecular separation (Tb.Sp) in the micro/nanotextured group was significantly lower than that in the other groups. For the histological analysis, the bone-to-implant contact in the machined, micro and micro/nanotextured groups were 47.13 ± 6.2%, 54.29 ± 4.18%, and 63.38 ± 7.63%, respectively, and the differences significant. The maximum pull-out force in the machined, micro, and micro/nanotextured groups were 216.58 ± 38.71 N, 259.42 ± 28.93 N, and 284.73 ± 47.09 N, respectively. The results indicated that implants with a hierarchical micro/nanotextured can promote osseointegration immediately after tooth extraction. © 2016 Wiley Periodicals, Inc.

  6. Detection of myocardial metabolic abnormalities by 18F-FDG PET/CT and corresponding pathological changes in beagles with local heart irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Rul [Nursing College of Shanxi Medical University, Taiyuan (China); Song, Jianbo; Wu, Zhi Fang; Liu, Jian Zhang; Hao, Xin Zhong; Li, Sijin [Dept. of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan (China); Guo, Min [Dept. of Cardiology, First Hospital of Shanxi Medical University, Taiyuan (China); Li, Jianguo [Dept. of Radiological and Environmental Medicine, China Institute for Radiation Protection, Taiyuan (China)

    2015-08-15

    To determine the efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of radiation-induced myocardial damage in beagles by comparing two pre-scan preparation protocols as well as to determine the correlation between abnormal myocardial FDG uptake and pathological findings. The anterior myocardium of 12 beagles received radiotherapy locally with a single X-ray dose of 20 Gy. 18F-FDG cardiac PET/CT was performed at baseline and 3 months after radiation. Twelve beagles underwent two protocols before PET/CT: 12 hours of fasting (12H-F), 12H-F followed by a high-fat diet (F-HFD). Regions of interest were drawn on the irradiation and the non-irradiation fields to obtain their maximal standardized uptake values (SUVmax). Then the ratio of the SUV of the irradiation to the non-irradiation fields (INR) was computed. Histopathological changes were identified by light and electron microscopy. Using the 12H-F protocol, the average INRs were 1.18 ± 0.10 and 1.41 ± 0.18 before and after irradiation, respectively (p = 0.021). Using the F-HFD protocol, the average INRs were 0.99 ± 0.15 and 2.54 ± 0.43, respectively (p < 0.001). High FDG uptake in irradiation field was detected in 33.3% (4/12) of 12H-F protocol and 83.3% (10/12) of F-HFD protocol in visual analysis, respectively (p = 0.031). The pathology of the irradiated myocardium showed obvious perivascular fibrosis and changes in mitochondrial vacuoles. High FDG uptake in an irradiated field may be related with radiation-induced myocardial damage resulting from microvascular damage and mitochondrial injury. An F-HFD preparation protocol used before obtaining PET/CT can improve the sensitivity of the detection of cardiotoxicity associated with radiotherapy.

  7. Standardisation of tracer and type of meal in the evaluation of gastric emptying and colon transit rates in normal Beagle dogs

    International Nuclear Information System (INIS)

    Dormehl, I.C.; Jordaan, J.H.; Jacobs, D.J.; Plessis, M. du; Pilloy, W.

    1984-01-01

    The transit of 111 In-labelled polymer beads of different particle sizes in the stomach and colon of five healthy Beagle dogs was monitored after intake of different kinds of meal by a gamma camera and data processor system. The various meals studied were a solid balanced type of dog food mixed with molk, pure milk, and finally a metal of raw meat. The polymer beads carried triethylenetetramine type functions which efficiently chelated 111 In +3 from an aqueous solution of InCl 3 . These labelled beads were well mixed into the food before being offered to the dogs. Gastric emptying curves from which half-times of emptying (Tsub(1/2)) could be obtained are presented and statistically compared. Good quality images with quantification of the colon transit rate also became possible. It appeared that standardisation of the tracer and of the metal is compulsory for relevant and reproducible results. (orig.)

  8. Standardisation of tracer and type of meal in the evaluation of gastric emptying and colon transit rates in normal Beagle dogs

    Energy Technology Data Exchange (ETDEWEB)

    Dormehl, I.C.; Jordaan, J.H.; Jacobs, D.J.; Plessis, M. du; Pilloy, W.

    1984-01-01

    The transit of /sup 111/In-labelled polymer beads of different particle sizes in the stomach and colon of five healthy Beagle dogs was monitored after intake of different kinds of meal by a gamma camera and data processor system. The various meals studied were a solid balanced type of dog food mixed with molk, pure milk, and finally a meal of raw meat. The polymer beads carried triethylenetetramine type functions which efficiently chelated /sup 111/In/sup +3/ from an aqueous solution of InCl/sub 3/. These labelled beads were well mixed into the food before being offered to the dogs. Gastric emptying curves from which half-times of emptying (Tsub(1/2)) could be obtained are presented and statistically compared. Good quality images with quantification of the colon transit rate also became possible. It appeared that standardisation of the tracer and of the metal is compulsory for relevant and reproducible results.

  9. Effects of concomitant use of fibroblast growth factor (FGF)-2 with beta-tricalcium phosphate (β-TCP) on the beagle dog 1-wall periodontal defect model

    International Nuclear Information System (INIS)

    Anzai, Jun; Kitamura, Masahiro; Nozaki, Takenori; Nagayasu, Toshie; Terashima, Akio; Asano, Taiji; Murakami, Shinya

    2010-01-01

    Research highlights: → Concomitant use of FGF-2 and β-TCP (an osteo-conductive scaffold) significantly promotes periodontal regeneration in the severe periodontitis model (1-wall defect model) of beagle dog. → FGF-2 enhanced new bone formation via β-TCP at the defects. → In particular, FGF-2 dramatically regenerated new periodontal ligament and cementum formations at the defects, that is one of the most important healing outcomes during the process of periodontal regeneration. → Epithelial downgrowth (undesirable wound healing) was decreased by administration of FGF-2. → This manuscript indicates for the first time that concomitant use of FGF-2 and β-TCP is efficacious in regenerating periodontal tissue following severe destruction of the tissue by progression of periodontitis. -- Abstract: The effects of concomitant use of fibroblast growth factor-2 (FGF-2) and beta-tricalcium phosphate (β-TCP) on periodontal regeneration were investigated in the beagle dog 1-wall periodontal defect model. One-wall periodontal defects were created in the mesial portion of both sides of the mandibular first molars, and 0.3% FGF-2 plus β-TCP or β-TCP alone was administered. Radiographic evaluation was performed at 0, 3, and 6 weeks. At 6 weeks, the periodontium with the defect site was removed and histologically analyzed. Radiographic findings showed that co-administration of FGF-2 significantly increased bone mineral contents of the defect sites compared with β-TCP alone. Histologic analysis revealed that the length of the regenerated periodontal ligament, the cementum, distance to the junctional epithelium, new bone height, and area of newly formed bone were significantly increased in the FGF-2 group. No abnormal inflammatory response or ankylosis was observed in either group. These findings indicate the efficacy of concomitant use of FGF-2 and β-TCP as an osteoconductive material for periodontal regeneration following severe destruction by progressive

  10. Comparative toxicity of strontium-90 and radium-226 in beagle dogs. Report of first year, December 16, 1989--December 15, 1990

    Energy Technology Data Exchange (ETDEWEB)

    Raabe, O.G.; Culbertson, M.R.; White, R.G.; Spangler, W.L.; Cain, G.R.; Parks, N.J.; Samuels, S.J.

    1990-12-31

    The authors are completing a 30-year study of the biologic effects of {sup 90}Sr and {sup 226}Ra in the beagle in order to predict the possible long-term hazards to people from chronic exposure to low levels of irradiation. Animals received either radionuclide by several means of administration: (a) continual ingestion of {sup 90}Sr, (b) a single intravenous injection of {sup 90}Sr, or (c) a series of eight intravenous injections of {sup 226}Ra. Although administration of {sup 90}Sr and {sup 226}Ra ended at 540 days of age, the animals continued to receive chronic, low-level radiation doses from these bone-seeking radionuclides throughout life. This project is the largest single cohort study in beagles of internally deposited radionuclides. It is unique in use of the ingestion route for {sup 90}Sr and in exposures that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with {sup 90}Sr. The last of the dogs died in 1986 at age 18.5, but the authors are continuing to investigate the significance of these long-term exposures given at low dose rates with regard to cancer production, physiologic well-being, and shortening of life through the detailed records that were kept and by study of preserved materials. All the data have been successfully accumulated and entered into a main-frame computer data base management system. Current work is exclusively directed at preparing research papers summarizing the results and the associated biostatistical and survival analyses.

  11. Comparative toxicity of strontium-90 and radium-226 in beagle dogs. Progress report of second year, December 16, 1990--December 15, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Raabe, O.G.; Culbertson, M.R.; White, R.G.; Spangler, W.L.; Cain, G.R.; Parks, N.J.; Samuels, S.J.

    1991-12-01

    We are completing a 30-year study of the biological effects of {sup 90}Sr and {sup 226}Ra in the beagle in order to predict the possible long-term hazards to people from chronic exposure to low levels of irradiation. Animals received either radionuclide by several means of administration: (a) continual ingestion of {sup 90}Sr, (b) a single intravenous injection of {sup 90}Sr, or (c) a series of eight intravenous injections of {sup 226}Ra. Although administration of {sup 90}Sr and {sup 226}Ra ended at 540 days of age, the animals continued to receive chronic, low-level radiation doses from these bone-seeking radionuclides throughout life. This project is the largest single cohort study in beagles of internally deposited radionuclides. It is unique in use of the ingestion route for {sup 90}Sr and in exposure that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with {sup 90}Sr. The last of the dogs died in 1986 at age 18.5 years, but we are continuing to investigate the significance of these long-term exposures given at low dose rates with regard to cancer production, physiologic well-being, and shortening of life through the detailed records that were kept and by study of preserved materials. All the data have been successfully accumulated and entered into a main-frame computer data base management system. Current work is exclusively directed at preparing research papers summarizing the results and the associated biostatistical and survival analyses. 15 refs., 1 fig., 4 tabs.

  12. Comparative toxicity of strontium-90 and radium-226 in beagle dogs. Report of second year, December 16, 1990--December 15, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Raabe, O.G.; Culbertson, M.R.; White, R.G.; Spangler, W.L.; Cain, G.R.; Parks, N.J.; Samuels, S.J.

    1991-12-31

    The authors are completing a 30-year study of the biological effects of {sup 90}Sr and {sup 226}Ra in the beagle in order to predict the possible long-term hazards to people from chronic exposure to low levels of irradiation. Animals received either radionuclide by several means of administration: (a) continual ingestion of {sup 90}Sr, (b) a single intravenous injection of {sup 90}Sr, or (c) a series of eight intravenous injections of {sup 226}Ra. Although administration of {sup 90}Sr and {sup 226}Ra ended at 540 days of age, the animals continued to receive chronic, low-level radiation doses from these bone-seeking radionuclides throughout life. This project is the largest single cohort study in beagles of internally deposited radionuclides. It is unique in use of the ingestion route for {sup 90}Sr and in exposures that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with {sup 90}Sr. The last of the dogs died in 1986 at age 18.5 years, but the authors are continuing to investigate the significance of these long-term exposures given at low dose rates with regard to cancer production, physiologic well-being, and shortening of life through the detailed records that were kept and by study of preserved materials. All the data have been successfully accumulated and entered into a main-frame computer data base management system. Current work is exclusively directed at preparing research papers summarizing the results and the associated biostatistical and survival analyses.

  13. Evaluation of 3D printed PCL/PLGA/β-TCP versus collagen membranes for guided bone regeneration in a beagle implant model.

    Science.gov (United States)

    Won, J-Y; Park, C-Y; Bae, J-H; Ahn, G; Kim, C; Lim, D-H; Cho, D-W; Yun, W-S; Shim, J-H; Huh, J-B

    2016-10-07

    Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PCL/PLGA/β-TCP) membranes with the widely used collagen membranes for guided bone regeneration (GBR) in beagle implant models. For mechanical property comparison in dry and wet conditions and cytocompatibility determination, we analyzed the rate and pattern of cell proliferation of seeded fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning electron microscopy. Osteogenic differentiation was verified using alizarin red S staining. At 8 weeks following implantation in vivo using beagle dogs, computed tomography and histological analyses were performed after sacrifice. Cell proliferation rates in vitro indicated that early cell attachment was higher in collagen than in PCL/PLGA/β-TCP membranes; however, the difference subsided by day 7. Similar outcomes were found for osteogenic differentiation, with approximately 2.5 times greater staining in collagen than PCL/PLGA/β-TCP, but without significant difference by day 14. In vivo, bone regeneration in the defect area, represented by new bone formation and bone-to-implant contact, paralleled those associated with collagen membranes. However, tensile testing revealed that whereas the PCL/PLGA/β-TCP membrane mechanical properties were conserved in both wet and dry states, the tensile property of collagen was reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo that PCL/PLGA/β-TCP membranes have similar levels of biocompatibility and bone regeneration as collagen membranes. In particular, considering that GBR is always applied to a wet environment (e.g. blood, saliva), we demonstrated that PCL/PLGA/β-TCP membranes maintained their form more reliably than collagen membranes in a wet setting, confirming their appropriateness as a GBR membrane.

  14. A tricalcium phosphate/polyether ether ketone anchor bionic fixation device for anterior cruciate ligament reconstruction: Safety and efficacy in a beagle model.

    Science.gov (United States)

    Mao, Genwen; Qin, Zili; Li, Zheng; Li, Xiang; Qiu, Yusheng; Bian, Weiguo

    2018-05-02

    The goal of this study was to develop a bionic fixation device based on the use of a tricalcium phosphate/polyether ether ketone anchor and harvesting of the ulnar carpal flexor muscle tendon for application as a ligament graft in a beagle anterior cruciate ligament (ACL) reconstruction model, with the goal of accelerating the ligament graft-to-bone tunnel healing and providing a robust stability through exploration of this new kind of autologous ligament graft. The safety and efficacy of this fixation device were explored 3 and 6 months after surgery in a beagle ACL reconstruction model using biomechanical tests and comprehensive histological observation. The data were compared using a two-tailed Student's t test and a paired t test. A p value <0.05 was defined as statistically significant. All the models were successfully established. This fixation device possessed the excellent mechanical properties for ACL reconstruction. A comprehensive histological observation revealed that a cartilage layer was visible in the transition zone between the tendon and bone interface at both 3 and 6 months postoperation. The trabecular of the new bone was observed six months after surgery and was found to be similar to a direct connection. This fixation technique provided not only a robust primary mechanical fixation but also a bionic fixation for long-term knee joint stability by accelerating the healing of the tendon to the bone tunnel, showing a high potential for use in clinical practice. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

  15. Development of a rapid and sensitive UPLC-MS/MS assay for the determination of TM-2 in beagle dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Lin, Hongli; Zhao, Yunli; Men, Lei; Yang, Mingjing; Liu, Hui; Shao, Yanjie; Wang, Pei; Tang, Xing; Yu, Zhiguo

    2015-01-01

    A simple and sensitive method based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of TM-2, which was a novel semi-synthetic taxane derivative in beagle dog plasma. Cabazitaxel was chosen as internal standard. Following extraction by methyl tert-butyl ether, the chromatographic separation was achieved on a Thermo Syncronis C18 column (50 × 2.1 mm, 1.7 µm) by gradient elution within a runtime of 3.5 min. The mobile phase consisted of (A) acetonitrile and (B) 2 mmol/L ammonium acetate in water. The detection was accomplished using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 812.39 → 551.35 for TM-2 and 836.36 → 555.26 for IS, respectively. The method was linear for TM-2 (r = 0.9924) ranging from 2.5 to 1000 ng/mL. The intra-day and inter-day precisions (relative standard deviation) were within 8.0 and 17.6%, respectively, and the accuracy (relative error) was less than 2.3%. The extraction recovery ranged from 83.1 to 97.1%. The reliable method was successfully applied to a pharmacokinetic study of TM-2 in beagle dogs after intravenous drip with different doses of 0.6, 1.2, and 2.4 mg/kg, respectively. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Development of a supercritical fluid chromatography-tandem mass spectrometry method for the determination of lacidipine in beagle dog plasma and its application to a bioavailability study.

    Science.gov (United States)

    Geng, Yajie; Zhao, Longshan; Zhao, Juanhang; Guo, Bei; Ma, Panqin; Li, Yuanyuan; Zhang, Tianhong

    2014-01-15

    A simple, novel, rapid and sensitive supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method was developed and validated for the determination of lacidipine in beagle dog plasma with nimodipine as internal standard. The method involved a simple liquid-liquid extraction method with tert-butyl methyl ether. The analytes were analyzed on an Acquity UPC(2) with a HSS C18 SB column (3mm×100mm, 1.8μm) set at 50°C. The mobile phase was carbon dioxide (≥99.99%) and methanol (92:8, v/v) at a flow rate of 2ml/min, the compensation solvent was methanol with 2% formic acid at a flow rate of 0.2ml/min and a total analysis time of 1.5min for each sample. The multiple reaction-monitoring mode was used for quantification of ion transitions at m/z 473.32→354.10 and 419.00→343.10 for lacidipine and internal standard, respectively. The linearity range of proposed method was 0.10-100ng/ml) (r(2)≥0.9990). The intra- and inter-day precision values were less than 15% and accuracy was from -0.83% to 3.27% at all quality control levels. The proposed method was successfully applied to a pharmacokinetic study of lacidipine in beagle dogs. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Effects of concomitant use of fibroblast growth factor (FGF)-2 with beta-tricalcium phosphate ({beta}-TCP) on the beagle dog 1-wall periodontal defect model

    Energy Technology Data Exchange (ETDEWEB)

    Anzai, Jun, E-mail: anzai_jun@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Kitamura, Masahiro, E-mail: kitamura@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nozaki, Takenori, E-mail: tnozaki@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nagayasu, Toshie, E-mail: nagayasu_toshie@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Terashima, Akio, E-mail: terashima_akio@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Asano, Taiji, E-mail: asano_taiji@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Murakami, Shinya, E-mail: ipshinya@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2010-12-17

    Research highlights: {yields} Concomitant use of FGF-2 and {beta}-TCP (an osteo-conductive scaffold) significantly promotes periodontal regeneration in the severe periodontitis model (1-wall defect model) of beagle dog. {yields} FGF-2 enhanced new bone formation via {beta}-TCP at the defects. {yields} In particular, FGF-2 dramatically regenerated new periodontal ligament and cementum formations at the defects, that is one of the most important healing outcomes during the process of periodontal regeneration. {yields} Epithelial downgrowth (undesirable wound healing) was decreased by administration of FGF-2. {yields} This manuscript indicates for the first time that concomitant use of FGF-2 and {beta}-TCP is efficacious in regenerating periodontal tissue following severe destruction of the tissue by progression of periodontitis. -- Abstract: The effects of concomitant use of fibroblast growth factor-2 (FGF-2) and beta-tricalcium phosphate ({beta}-TCP) on periodontal regeneration were investigated in the beagle dog 1-wall periodontal defect model. One-wall periodontal defects were created in the mesial portion of both sides of the mandibular first molars, and 0.3% FGF-2 plus {beta}-TCP or {beta}-TCP alone was administered. Radiographic evaluation was performed at 0, 3, and 6 weeks. At 6 weeks, the periodontium with the defect site was removed and histologically analyzed. Radiographic findings showed that co-administration of FGF-2 significantly increased bone mineral contents of the defect sites compared with {beta}-TCP alone. Histologic analysis revealed that the length of the regenerated periodontal ligament, the cementum, distance to the junctional epithelium, new bone height, and area of newly formed bone were significantly increased in the FGF-2 group. No abnormal inflammatory response or ankylosis was observed in either group. These findings indicate the efficacy of concomitant use of FGF-2 and {beta}-TCP as an osteoconductive material for periodontal

  18. Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs.

    Science.gov (United States)

    Marsella, Rosanna; Ahrens, Kim; Sanford, Rachel

    2018-02-01

    IL-31 is a cytokine that is believed to play an important role in atopic dermatitis (AD). IL-31 levels positively correlate with disease severity in children with AD. Currently, there is no study that has investigated such a correlation in atopic dogs. The purpose of this study was to evaluate the correlation between IL-31 serum levels and severity of dermatitis. It was hypothesized that a positive correlation exists between severity of AD and circulating levels of IL-31. Sixteen atopic beagles experimentally sensitized to house dust mites. Atopic beagles were exposed to dust mites epicutaneously twice weekly for four weeks. Severity of dermatitis was scored by the Canine Atopic Dermatitis and Extent Severity Index, 3 rd iteration (CADESI-03) on days 0 and 28. Blood samples were taken on days 0 and 28 to measure serum IL-31 using a commercially available ELISA. Correlation between CADESI-03 scores and serum IL-31 levels was not detected on day 0 (Pearson, r = -0.2609, P = 0.3291). After flare-up of dermatitis was induced with allergen exposure, a significant positive correlation was detected between serum IL-31 and CADESI-03 on Day 28 (r = 0.6738, P = 0.004). Positive correlation was detected in active disease between severity of dermatitis and circulating levels of IL-31. Additional studies are needed to investigate this correlation in other breeds of dogs and to test whether circulating levels of IL-31 may predict clinical response to biological agents aimed at IL-31. © 2017 ESVD and ACVD.

  19. Influence of dietary long-chain n-3 fatty acids from menhaden fish oil on plasma concentrations of alpha-tocopherol in geriatric beagles.

    Science.gov (United States)

    Hall, Jean A; Tooley, Katie A; Gradin, Joseph L; Jewell, Dennis E; Wander, Rosemary C

    2002-01-01

    To determine effects of dietary n-3 fatty acids from Menhaden fish oil on plasma alpha-tocopherol concentrations in Beagles. 32 female Beagles. For 82 days, dogs were fed diets that contained 1 of 2 ratios of n-6:n-3 fatty acids (40:1 [low n-3] and 1.4:1 [high n-3]) and 1 of 3 concentrations of all-rac-alpha-tocopheryl acetate (low, 17 mg/kg of diet; medium, 101 mg/kg; and high, 447 mg/kg) in a 2 X 3 factorial study. Diets high in n-3 fatty acids significantly increased total content of n-3 fatty acids in plasma (17.0 g/100 g of fatty acids), compared with low n-3 diets (2.02 g/100 g of fatty acids). Mean +/- SEM plasma concentration of cholesterol was significantly lower in dogs consuming high n-3 diets (4.59 +/- 0.48 mmol/L), compared with dogs consuming low n-3 diets (5.71 +/- 0.48 mmol/L). A significant interaction existed between the ratio for n-6 and n-3 fatty acids and amount of alpha-tocopheryl acetate in the diet (plasma alpha-tocopherol concentration expressed on a molar basis), because the plasma concentration of alpha-toco-pherol was higher in dogs consuming low n-3 diets, compared with those consuming high n-3 diets, at the 2 higher amounts of dietary alpha-tocopheryl acetate. Plasma alpha-tocopherol concentration expressed relative to total lipid content did not reveal effects of dietary n-3 fatty acids on concentration of alpha-tocopherol. Plasma alpha-tocopherol concentration is not dependent on dietary ratio of n-6 and n-3 fatty acids when alpha-tocopherol concentration is expressed relative to the total lipid content of plasma.

  20. 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.

  1. GMP-grade α-TEA lysine salt: a 28-Day oral toxicity and toxicokinetic study with a 28-Day recovery period in Beagle dogs

    International Nuclear Information System (INIS)

    Guerrouahen, Bella S.; Hahn, Tobias; Alderman, Zefora; Curti, Brendan; Urba, Walter; Akporiaye, Emmanuel T.

    2016-01-01

    Alpha-tocopheryloxyacetic acid (α-TEA) is a semi-synthetic derivative of naturally occurring vitamin E (alpha-tocopherol) that can be delivered via an oral route. Preclinical in vitro and in vivo data demonstrated that α-TEA is a potent anti-tumor agent with a safe toxicity profile in mice. We report a comprehensive study to evaluate the toxokinetics of good manufacturing practice (GMP)-grade α-TEA in dogs after daily oral administration for 28 days, followed by a 28-day recovery period. Male and female beagle dogs received capsules of α-TEA Lysine Salt at doses of 100, 300, 1500 mg/kg/day. α-TEA plasma levels were determined by high-performance liquid chromatography (HPLC) with mass spectrometric detection. During the treatment, animals were observe for clinical signs, food consumption, body weight, and subjected to ophthalmoscopic, and electrocardiographic assessments. At the end of the dosing period, blood was taken and toxicokinetic analyses and histopathology assessments were performed when animals were necropsied. Our findings showed that there was no α-TEA-related mortality or moribundity. At the highest dose, increases in white blood cells and fibrinogen levels were observed. These levels returned to normal at the end of the recovery period. Histopathological evaluation of major organs revealed no significant lesions related to α-TEA-treatment. We demonstrate that for designing clinical trials in patients, the highest non-severely toxic dose (HNSTD) of α-TEA is 1500 mg/kg/day in Beagle dogs and this data informed the design of dose-escalation studies of α-TEA in patients with advanced cancer

  2. Comparison of the osteogenesis and fusion rates between activin A/BMP-2 chimera (AB204) and rhBMP-2 in a beagle's posterolateral lumbar spine model.

    Science.gov (United States)

    Zheng, Guang Bin; Yoon, Byung-Hak; Lee, Jae Hyup

    2017-10-01

    Activin A/BMP-2 chimera (AB204) could promote bone healing more effectively than recombinant bone morphogenetic protein 2 (rhBMP-2) with much lower dose in a rodent model, but there is no report about the effectiveness of AB204 in a large animal model. The purpose of this study was to compare the osteogenesis and fusion rate between AB204 and rhBMP-2 using biphasic calcium phosphate (BCP) as a carrier in a beagle's posterolateral lumbar fusion model. This is a randomized control animal study. Seventeen male beagle dogs were included. Bilateral posterolateral fusion was performed at the L1-L2 and L4-L5 levels. Biphasic calcium phosphate (2 cc), rhBMP-2 (50 µg)+BCP (2 cc), or AB204 (50 µg)+BCP (2 cc) were implanted into the intertransverse space randomly. X-ray was performed at 4 and 8 weeks. After 8 weeks, the animals were sacrificed, and new bone formation and fusion rate were evaluated by manual palpation, computed tomography (CT), and undecalcified histology. The AB204 group showed significantly higher fusion rate (90%) than the rhBMP-2 group (15%) or the Osteon group (6.3%) by manual palpation. On x-ray and CT assessment, fusion rate and the volume of newly formed bone were also significantly higher in AB204 group than other groups. In contrast, more osteolysis was found in rhBMP-2 group (40%) than in AB204 group (10%) on CT study. In histologic results, new bone formation was sufficient between transverse processes in AB204 group, and obvious trabeculation and bone remodeling were observed. But in rhBMP-2 group, new bone formation was less than AB204 group and osteolysis was observed between the intertransverse spaces. A low dose of AB204 with BCP as a carrier significantly promotes the fusion rate in a large animal model when compared with the rhBMP-2. These findings demonstrate that AB204 could be an alternative to rhBMP-2 to improve fusion rate. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Impact of four different recumbencies on the distribution of ventilation in conscious or anaesthetized spontaneously breathing beagle dogs: An electrical impedance tomography study.

    Directory of Open Access Journals (Sweden)

    Tamas D Ambrisko

    Full Text Available The aim was to examine the effects of recumbency and anaesthesia on distribution of ventilation in beagle dogs using Electrical Impedance Tomography (EIT. Nine healthy beagle dogs, aging 3.7±1.7 (mean±SD years and weighing 16.3±1.6 kg, received a series of treatments in a fixed order on a single occasion. Conscious dogs were positioned in right lateral recumbency (RLR and equipped with 32 EIT electrodes around the thorax. Following five minutes of equilibration, two minutes of EIT recordings were made in each recumbency in the following order: RLR, dorsal (DR, left (LLR and sternal (SR. The dogs were then positioned in RLR, premedicated (medetomidine 0.01, midazolam 0.1, butorphanol 0.1 mg kg-1 iv and pre-oxygenated. Fifteen minutes later anaesthesia was induced with 1 mg kg-1 propofol iv and maintained with propofol infusion (0.1-0.2 mg kg-1 minute-1 iv. After induction, the animals were intubated and allowed to breathe spontaneously (FIO2 = 1. Recordings of EIT were performed again in four recumbencies similarly to conscious state. Centre of ventilation (COV and global inhomogeneity (GI index were calculated from the functional EIT images. Repeated-measures ANOVA and Bonferroni tests were used for statistical analysis (p < 0.05. None of the variables changed in the conscious state. During anaesthesia left-to-right COV increased from 46.8±2.8% in DR to 49.8±2.9% in SR indicating a right shift, and ventral-to-dorsal COV increased from 49.8±1.7% in DR to 51.8±1.1% in LLR indicating a dorsal shift in distribution of ventilation. Recumbency affected distribution of ventilation in anaesthetized but not in conscious dogs. This can be related to loss of respiratory muscle tone (e.g. diaphragm and changes in thoracic shape. Changing position of thoraco-abdominal organs under the EIT belt should be considered as alternative explanation of these findings.

  4. The influence of age at time of exposure to 239Pu or 226Ra on retention, distribution, survival and tumor induction in Beagles

    International Nuclear Information System (INIS)

    Bruenger, F.W.; Miller, S.C.; Lloyd, R.D.

    1991-01-01

    The influence of age at injection of 226 Ra or 239 Pu on skeletal deposition and local distribution, the pattern of bone tumor formation and post-injection survival were studied in parallel short-term mechanistic and lifetime toxicity experiments. Beagles received a single intravenous injection of 226 Ra or 239 Pu at age 3 months (juveniles), 17-19 months (young adults) or 60 months (mature). Data from short-term mechanistic-dosimetric studies and from one dosage level (41 kBq 226 Ra/kg or 11 kBq 239 Pu/kg body mass) of each of the toxicity experiments were compared. Skeletal growth and turnover produced differential initial deposition and distribution patterns typical for each age group. The highest bone tumor incidence was seen in the young adult groups. Differences were observed in bone tumor location between dogs in the same age group given radium or plutonium and among age groups injected with either radionuclide, and some of these could be explained by differences in local dose distributions (e.g., trabecular vs. cortical bone). Cox regression indicated no significant differences in post-injection survivals (uncorrected for the different pre-injection periods) of Ra-injected groups, but there was a statistically significant difference among the Pu-injected groups. Neutron-induced autoradiography showed that differences in the effects of Pu in the three age groups were due primarily to the age- and time-dependent local distribution of the nuclide

  5. Changes of electrocardiogram and hemodynamics in response to dipyridamole: In vivo comparative analyses using anesthetized beagle dogs and microminipigs.

    Science.gov (United States)

    Ando, Kentaro; Takahara, Akira; Nakamura, Yuji; Wada, Takeshi; Chiba, Koki; Goto, Ai; Lubna, Nur Jaharat; Hagiwara-Nagasawa, Mihoko; Izumi-Nakaseko, Hiroko; Hoshiai, Kiyotaka; Akie, Yasuki; Naito, Atsuhiko T; Sugiyama, Atsushi

    2018-02-01

    Microminipigs are expected as a novel animal model for cardiovascular pharmacological experiments. Since inherent vulnerability of coronary circulation of microminipigs has not been characterized, we performed dipyridamole-stress test to both microminipigs and beagle dogs, and compared the results. Dipyridamole in doses of 0.056 and 0.56 mg/kg were intravenously infused over 10 min (n = 4 for each animal). Dipyridamole decreased the systolic/diastolic blood pressures and double product in dogs as well as in microminipigs; but it did not significantly alter the heart rate or the global balance between the myocardial oxygen demand and supply in either animal. While organic coronary arterial stenosis was not detected in either animal, dogs have well-developed epicardial intracoronary networks unlike microminipigs. Like in humans, dipyridamole did not affect the ST segment of microminipigs, whereas it substantially depressed that in dogs. The results indicate the onset of subendocardial ischemia by dipyridamole in dogs may be partly associated with their well-developed native coronary collateral channels. Microminipigs would be more useful to evaluate the drugs which may affect the coronary circulation in the pre-clinical study than dogs. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  6. Collaborative Radiological Health Laboratory annual report 1986: health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog

    International Nuclear Information System (INIS)

    1987-08-01

    The Collaborative Radiological Health Laboratory was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining in a carefully controlled animal experiment the life-time hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. This is a long-term (lifespan) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages-at-irradiation selected for comparison reflect the primary concern with medical exposures during the development period. The basis experiment under this contract contains 1,680 beagles that will be maintained and evaluated for most of their natural lives. Commitment of animals began in December 1967 and was completed in October 1972. The annual report summarizes the current status of the study for the reporting period of November 21, 1985 through November 20, 1986

  7. Collaborative Radiological Health Laboratory annual report 1987: health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog. Annual report

    International Nuclear Information System (INIS)

    1988-09-01

    The Collaborative Radiological Health Laboratory (CRHL) was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining in a carefully controlled animal experiment the lifetime hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. It is a long-term (life span) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages-at-irradiation selected for comparison reflect the primary concern with medical exposures during the developmental period. The basic experiment under the contract contains 1,680 beagles that will be maintained and evaluated for most of their natural lives. The annual report summarizes the current status of the study for the reporting period of November 21, 1986 through November 20, 1987

  8. 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.

  9. Incidence of bone cancer in beagles after inhalation of 90SrCl2 or 238PuO2: Implications for estimation of risk to humans

    International Nuclear Information System (INIS)

    Mewhinney, J.A.; Griffith, W.C.; Hahn, F.F.; Snipes, M.B.; Boecker, B.B.; McClellan, R.O.

    1986-01-01

    Among the life-span studies conducted with beagle dogs, bone cancer has been in two studies the predominant effect at death. These studies involved dogs that inhaled 90 SrCl 2 , which is very soluble in body fluids; and dogs that inhaled 238 PuO 2 , which is initially insoluble but eventually becomes fragmented and more soluble. Both radionuclides were deposited in the skeleton after dissolution in the lung and absorption into the bloodstream. All dogs in the 90 Sr study are dead, and all living dogs in the 238 Pu study are at least 7 years postexposure. Results from these two studies were compared to determine the relative biological effectiveness (RBE) of chronic beta and alpha radiation delivered from these two radionuclides. These data also were used to estimate the risk of bone cancer in man by using comparisons with data from the 90 Sr-, 239 Pu-, and 226 Ra-injected dogs at the University of Utah and data on humans who ingested 226 Ra or were injected with 224 Ra. Such comparisons provided a link between studies in laboratory animals and the available human data. In this way risks of bone cancer in humans from inhaled plutonium or strontium were estimated, even though currently no human cases of bone cancer are known to have resulted from the inhalation of either of these radionuclides. 15 refs., 7 figs., 7 tabs

  10. Collaborative Radiological Health Laboratory annual report, 1988: Health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog

    International Nuclear Information System (INIS)

    1989-09-01

    The Collaborative Radiological Health Laboratory was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining, in a carefully controlled animal experiment, the life-time hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. This is a long-term (life span) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages-at-irradiation selected for comparison reflect the primary concern with medical exposures during the developmental period. The basic experiment under the contract contains 1,680 beagles that will be maintained and evaluated for most of their natural lives. Commitment of animals began in December 1967 and was completed in February 1973. The annual report summarizes the current status of the study for the reporting period of November 21, 1987 through November 20, 1988

  11. Collaborative Radiological Health Laboratory annual report 1985: health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog

    International Nuclear Information System (INIS)

    1986-07-01

    The Collaborative Radiological Health Laboratory was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining in a carefully controlled animal experiment the life-time hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. This is a long-term (lifespan) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages-at-irradiation selected for comparison reflect the primary concern with medical exposures during the development period. The basic experiment under the contract contains 1,680 beagles that will be maintained and evaluated for most of their natural lives. Commitment of animals began in December 1967 and was completed in October 1972. The annual report summarizes the current status of the study for the reporting period of November 21, 1984 through November 20, 1985

  12. Risk estimates for lung tumours from inhaled 239PuO2, 238PuO2, and 239Pu(NO3)4 in beagle dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.; Park, J.F.; Gilbert, E.S.; Weller, R.E.

    1989-01-01

    Lung cancer risks are being studied in beagle dogs given single exposures to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 . A major objective of these studies is to examine the risk of lung cancer relative to the specific activity of the radionuclide, rate of dose accumulation due to differences in solubilities of the radionuclides, and the presence of competing risk from extrapulmonary lesions. Dose-response relationships were studied for the three groups of dogs, with analyses specifically designed to evaluate differences in response. Based on estimated cumulative dose to the lung, risks were found to differ significantly among the radionuclides; they were highest for 239 Pu(NO 3 ) 4 and lowest for 238 PuO 2 . A model in which the risk was assumed to be a pure quadratic function of dose fitted the data much better than a pure linear model. Currently, all three groups of dogs can be compared only to 10 years after exposure. However, it is apparent that the average cumulative dose to the lung may not be an adequate predictor of lung cancer risk for different isotopic and physicochemical forms of plutonium. (author)

  13. Translocation dynamics of Pu(NO3)4 and PuO2 from puncture wounds to lymph nodes and major organs of beagles

    International Nuclear Information System (INIS)

    Bistline, R.W.; Lebel, J.L.; Dagle, G.E.

    1976-01-01

    The translocation dynamics of plutonium and americium from simulated puncture wounds in the paws of beagle dogs following contamination with Pu(NO 3 ) 4 and high-fired PuO 2 was studied. Fractions of initial implant transported to the first major lymph node and to major body organs were measured with in vivo counting equipment and by radiochemical analysis of tissue material collected at necropsy. Samples were obtained from serial necropsies ranging from 2 weeks to 1 year after implant. The difference in lymph node and organ-accumulation dynamics between the two chemical forms and the effects of diethylenetriaminepentaacetate (DTPA) chelation treatment are presented. Active mechanisms to transport plutonium to and from the lymph system appear to exist. Equations for buildup in the lymph nodes and organs are included. The data suggest a buildup in the lymph node to a maximum, followed by a long negative slope, and a possible dose-rate effect from Pu(NO 3 ) 4 in lymph nodes

  14. Biological alterations resulting from chronic lung irradiation. II. Connective tissue alterations following inhalation of 144Ce fused clay aerosol in beagle dogs

    International Nuclear Information System (INIS)

    Pickrell, J.A.; Harris, D.V.; Pfleger, R.C.; Benjamin, S.A.; Belasich, J.J.; Jones, R.K.; McClellan, R.O.

    1975-01-01

    Beagle dogs were exposed by inhalation to an aerosol of 144 Ce clay to quantitate the relationship between pulmonary radiation dose and induced fibrosis. Collagen, elastin, glucosamine, and the ratios of elastin/collagen, hydroxyproline/hydroxylysine, and hydroxyproline/proline were determined to indicate changes in connective tissue constituents. Total lung collagen was partitioned into native collagen, soluble collagen, and ultrafilterable hydroxyproline peptides. Increased total lung collagen correlated best with increasing cumulative radiation dose and increasing time after inhalation exposure. The increase in total lung collagen was not seen until more than 4 mo after exposure and a cumulative dose of about 40,000 rad. Soluble collagen and low molecular weight hydroxyproline peptide quantities both increased at 2 mo after exposure and cumulative doses of 20,000 to 27,000 rad. A variable elastin response apparently was not related to either increasing time or increasing radiation dose after exposure. These results indicate that collagen accumulation is an important factor in pulmonary fibrosis. Although collagen synthesis and breakdown were both activated at a relatively early time after inhalation, a significant increase in native collagen (scarring) occurred only when the metabolic balance was altered by protracted time or irradiation after exposure. The interrelationships observed in this study provide insight into the mechanism of fibrosis induced by chronic pulmonary injury. (U.S.)

  15. Alteration by lung lavage of the biological effects from inhalation of a relatively insoluble form of 144Ce by beagle dogs

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.; Mauderly, J.L.; McClellan, R.O.

    1977-01-01

    The efficacy of lung lavage to remove a relatively insoluble form of 144 Ce from the lung as a means to prevent or alter serious biological effects was evaluated in 21 Beagle dogs. The dogs were divided into five groups. Eight dogs (Group 1) were treated with a series of ten lung lavages between day 2 and day 56 after exposure to 144 Ce. Three dogs (Group 2) were treated with 20 lung lavages from day 2 to day 82 after exposure to 144 Ce. The third group consisted of four dogs and was exposed to 144 Ce but was not treated. Four dogs (Group 4) were given ten lung lavages as in Group 1 but were not exposed to 144 Ce. Two dogs (Group 5) were given 20 lung lavages like the Group 2 dogs but were not exposed to 144 Ce. All but one of the exposed untreated dogs died between 209 to 240 days after inhalation exposure with radiation pneumonitis. The remaining dog died 1072 days after inhalation exposure with a pulmonary carcinoma. All of the treated dogs (Groups 1 and 2) have died except for one dog. Two dogs died with radiation pneumonitis at 170 and 296 days after 144 Ce exposure. The remaining dogs died from 815 to 1773 days after exposure with malignant tumors. The unexposed treated dogs are all alive. Lung lavage appeared to prolong life in the treated dogs and most dogs died with neoplasia rather than with any acute or chronic inflammatory disease

  16. In Vivo Evaluation of 3D-Printed Polycaprolactone Scaffold Implantation Combined with β-TCP Powder for Alveolar Bone Augmentation in a Beagle Defect Model

    Directory of Open Access Journals (Sweden)

    Su A. Park

    2018-02-01

    Full Text Available Insufficient bone volume is one of the major challenges encountered by dentists after dental implant placement. This study aimed to evaluate the efficacy of a customized three-dimensional polycaprolactone (3D PCL scaffold implant fabricated with a 3D bio-printing system to facilitate rapid alveolar bone regeneration. Saddle-type bone defects were surgically created on the healed site after extracting premolars from the mandibles of four beagle dogs. The defects were radiologically examined using computed tomography for designing a customized 3D PCL scaffold block to fit the defect site. After fabricating 3D PCL scaffolds using rapid prototyping, the scaffolds were implanted into the alveolar bone defects along with β-tricalcium phosphate powder. In vivo analysis showed that the PCL blocks maintained the physical space and bone conductivity around the defects. In addition, no inflammatory infiltrates were observed around the scaffolds. However, new bone formation occurred adjacent to the scaffolds, rather than directly in contact with them. More new bone was observed around PCL blocks with 400/1200 lattices than around blocks with 400/400 lattices, but the difference was not significant. These results indicated the potential of 3D-printed porous PCL scaffolds to promote alveolar bone regeneration for defect healing in dentistry.

  17. Development and validation of an LC-MS/MS method for the determination of mesalazine in beagle dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Qin, Juan; Di, Xin; Wang, Xin; Liu, Youping

    2015-02-01

    A simple, specific and sensitive LC-MS/MS method was developed and validated for the determination of mesalazine in beagle dog plasma. The plasma samples were prepared by protein precipitation, then the separation of the analyte was achieved on a Waters Spherisorb C6 column (150 × 4.6 mm, 5 µm) with a mobile phase consisting of 0.2% formic acid in water-methanol (20:80, v/v). The flow rate was set at 1.0 mL/min with a split ratio of 3:2. Mass spectrometric detection was achieved by a triple-quadrupole mass spectrometer equipped with an electrospray source interface in positive ionization mode. Quantitation was performed using selected reaction monitoring of precursor-product ion transitions at m/z 154 → m/z 108 for mesalazine and m/z 285 → m/z 193 for diazepam (internal standard). The linear calibration curve of mesalazine was obtained over the concentration range 50-30,000 ng/mL. The matrix effect of mesalazine was within ±9.8%. The intra- and inter-day precisions were dogs after rectal administration of mesalazine suppository. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Age validation and growth of yolked larvae of Patagonotothen tessellata (Richardson, 1845 (Pisces: Nototheniidae from the rocky littoral of the Beagle Channel, Argentina

    Directory of Open Access Journals (Sweden)

    Gustavo Alfredo Rae

    1999-12-01

    Full Text Available Age and growth estimation of Patagonotothen tessellata larvae over the endogenous period was estimated by examining their otolith microstructure and the associated increment deposition rate. Analyzed specimens were incubated from egg-masses collected in Lapataia Bay, Beagle Channel, Argentina. Validation was performed by monitoring reared larvae of known ages. Actual age and increment count were regressed suggesting a daily deposition of one ring in the otolith, which began at hatching time and continued until larvae reached sixteen days old (time of massive mortality. Mean lengths at each age were estimated using Richards´ growth function; their constant (m attained a value close to zero indicating that the data fitted to the von Bertalanffy model. Absolute growth rate was 0.55 mm*d-1of total length at hatching, dropped near zero on the fifth day after hatching and afterwards, there was no growth. Yolk absorption rate (expressed as a ratio between minor axis/major axis of the vitelline-sac showed a similar variation as that observed in absolute growth rate during the endogenous period. The total yolk absorption took five days in the unfed larvae group and seven days in the fed larvae group. The rapid absorption of the yolk and the observed growth pattern suggest that Patagonotothen tessellata larvae have a short endogenous period, reaching the state of first food uptake five days after hatching.

  19. Age-related effects on the disposition and dosimetry of inhaled 239Pu or 144Ce in immature or aged beagle dogs

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Boecker, B.B.; Muggenburg, B.A.; Hahn, F.F.; McClellan, R.O.

    1987-01-01

    Immature (90 days of age), young adult (18 months of age), and aged (8-10.5 years of age) male and female beagle dogs received a single brief pernasal inhalation exposure to an aerosol of 144 Ce in an insoluble fused aluminosilicate matrix or 239 PuO 2 . These isotopes were selected to represent low- and high-LET emitters, respectively. No age-related differences in the retention of Pu in the lungs of dogs have been observed, nor have there been any detectable differences in the uptake and retention of Pu in the tracheobronchial lymph nodes. Age-related effects have been seen in the uptake of Pu in the skeleton, with the amount of Pu being greatest in the skeleton of immature dogs. For the dogs exposed to the 144 Ce aerosol, there was a statistically significant difference in the retention of 144 Ce in the lungs of immature dogs compared to young adults. Increased uptake of 144 Ce in the immature dog skeleton was also noted. 14 refs.; 4 figs

  20. Beagle I and II Voyages: Charles Darwin's rocks and the quest for Mars rock; the Open University's virtual microscope has both

    Science.gov (United States)

    Schwenzer, S. P.; Tindle, A. G.; Anand, M.; Gibson, E. K.; Pearson, V. K.; Pemberton, D.; Pillinger, C.; Smith, C. L.; Whalley, P.; Kelley, S. P.

    2011-12-01

    Exploration is in itself a fascinating subject, and a strong draw to engaging the public in understanding science. Nearly two hundred years ago Charles Darwin took part in an exploration of the Earth, and more recently we have begun to explore the solar system and in particular the surface of Mars. The engagement is made easier if an element of exploration is involved in the public engagement, using modern internet and even mobile technologies. The Open University combines all those aspects in a series of virtual microscopes for Earth science that are freely available on the web, installed in museums, or built into its teaching material. The basis of the virtual microscope is a mosaic of several hundred microscopic images of each thin section taken in plane polarised light, between crossed polars and in reflected light, which are then assembled into three high resolution images. Rotation movies for selected points in the thin section illustrate changing optical properties such as birefringence. The user is able to pan and zoom around to explore the section, studying the mineralogy and rock texture, and view the rotation movies linked to points in the section to see the changing birefringence colours. We have created several collections of terrestrial rocks, mainly for teaching purposes, and outreach directly linked to exploration: Charles Darwin returned from the Voyage of the Beagle with a large variety of rock samples, and although thin sections were not being made at that time, they were created from his rocks in the late 19th century. The historic material is part of the "Darwin the Geologist" exhibition at the Sedgwick Museum in Cambridge. Our Darwin virtual microscope includes hand specimen illustrations and thin sections together with documentation and an interactive map allow internet users and museum visitors alike to have a close look at Darwin's rocks and study the petrology of them. Charles Darwin explored distant horizons on Earth in the 19th century

  1. The influence of age at time of exposure to 226Ra or 239Pu on distribution, retention, postinjection survival, and tumor induction in beagle dogs

    International Nuclear Information System (INIS)

    Bruenger, F.W.; Lloyd, R.D.; Miller, S.C.

    1991-01-01

    The influence of age at injection of 226Ra or 239Pu on skeletal deposition and local distribution, the pattern of bone tumor formation, and postinjection survival was assessed in parallel short-term studies of mechanisms and lifetime toxicity. Beagles received a single intravenous injection of 226Ra or 239Pu at 3 months (juveniles), 17-19 months (young adults) or 60 months (mature). Data from short-term studies of mechanisms and dosimetry and from one dosage level of each of the toxicity experiments were compared. Skeletal growth and turnover produced differential initial deposition and distribution patterns typical for each age group. At 1 week after injection, skeletal retention of 226Ra or 239Pu was 68 and 68%, respectively, in the juveniles, 32 and 46% in the young adults, and 31 and 43% in the mature dogs. Comparing individual bones in the juveniles, gradients in the concentration of 239Pu were small since all bones were actively growing, but substantial gradients, corresponding to centers of ossification, were present within individual bones. In other age groups, local concentration gradients were less pronounced, but much larger differences were present among the various bones. In the toxicity study all animals injected with either 41 kBq 226Ra/kg or 11 kBq 239Pu/kg have died. The cumulative average skeletal doses to the presumed time of start of tumor growth (1 year before death) were 25 and 4 Gy, respectively, for the juveniles, 22 and 5 Gy for the young adults, and 15 and 4 Gy for the mature dogs. The highest bone tumor incidence was seen in the young adult groups. Differences were observed in location of bone tumors between dogs in the same age group given radium or plutonium and among age groups injected with either radionuclide, some of which could be explained by differences in local dose distributions

  2. Studies on the role of routes of allergen exposure in high IgE-producing beagle dogs sensitized to house dust mites.

    Science.gov (United States)

    Marsella, R; Nicklin, C; Lopez, J

    2006-10-01

    The current study aimed to investigate the role played by oral, epicutaneous, and inhalation routes of exposure to house dust mites (HDM). The colony of high IgE-producing beagle dogs has been shown to develop pruritic dermatitis compatible with atopic dermatitis following environmental exposure (EE) to HDM. In crossover experiments, the response to EE was compared to two modified challenges, oral exposure (OE) and snood and muzzle exposure (SME). For OE, HDM were fed daily for 3 days. For SME, ingestion of allergen was prevented but there was inhalation and epicutaneous exposure to all body regions except to one ear. In all experiments, dogs were challenged for three consecutive days, and evaluated before, 6 h after exposure and daily thereafter, for 5 days. After a wash-out period, groups were crossed-over so that each dog was randomly challenged to all three protocols. Clinical scores were analysed using least squares analysis of variance. All dogs developed pruritic dermatitis regardless of the protocol. With OE, lesions developed in the same body regions as with EE although scores were lower. This difference became more evident after the first 3 days when OE scores decreased and EE scores continued to increase. The scores of covered and uncovered ears did not differ with SME. Scores for the remainder of the body were significantly lower than for EE. The development of lesions on covered ears supports the importance of inhalation or a systemic reaction to epicutaneous exposure in other areas. It is concluded that all routes are important and have additive effects, that route of exposure does not determine the distribution of lesions and that continuous epicutaneous exposure probably plays the most important role.

  3. Impaired absorption of marked oligopeptide Glycine-I Tyrosine-Glycine after successful autologous-allotopic ileal mucosa transplantation in beagles.

    Science.gov (United States)

    Beiler, H A; Steinorth, J; Witt, A; Mier, W; Mohammed, A; Waag, K L; Zachariou, Z

    2004-10-01

    After establishing a method for ileal mucosa transplantation in an animal model, the authors investigated the absorptive capacity for oligopeptides of the transplanted mucosa. In 14 beagle dogs the authors transplanted ileal mucosa in a vascularized demucosed segment of the transverse colon. The colonic wall-ileal mucosa complex then was integrated in the ileal continuity. Six animals were lost owing to operative complications. Absorptive capacity for oligopeptides was measured in the remaining 8 animals with the iodine 131 (131I)-marked tripeptide glycine-tyrosine-glycine before and 4 weeks after transplantation. The results were compared and analyzed with the Student's t test for matched pairs. Blood concentrations of the marked tripeptide with P value less than .05 were considered as a significant reduction in the absorptive capacity of the transplanted ileal mucosa. After fixation with glutaraldehyd graft, uptake of the colonic wall-ileal mucosa complex was evaluated histologically in 8 animals. In all 8 animals, a 100% graft uptake was verified in all sections. Fifteen minutes after application of 15 MBc Glycine-131I-Tyrosine-Glycine there was no significant difference in the absorption between normal and transplanted ileal mucosa. After 30 minutes, the absorption of the transplanted ileal mucosa showed a tendency (P < .1) for an impaired uptake of the marked tripeptide. However, 60 minutes after application the difference in the absorptive capacity of the transplanted ileal mucosa was significant (P < .05). Autologous allotopic ileal mucosa transplantation is feasible; however, an impaired absorption of oligopeptides of the transplanted mucosa 4 weeks after transplantation could be observed.

  4. Single blinded, randomized, placebo-controlled study on the effects of ciclosporin on cutaneous barrier function and immunological response in atopic beagles.

    Science.gov (United States)

    White, Amelia G; Santoro, Domenico; Ahrens, Kim; Marsella, Rosanna

    2018-03-01

    Ciclosporin (CsA) is a common treatment for canine atopic dermatitis (cAD). cAD is a very common skin disease with a multifactorial pathogenesis due to complex interactions between the host and the environment. The purpose of this study was to describe the physical and immunological effects of CsA in cAD using a canine model of AD. Fourteen beagles were enrolled; seven received CsA orally every 24 h for 28 days, and seven received placebo. All dogs were exposed to relevant allergens, house dust mite solution, one day prior to treatment and once weekly thereafter for 28 consecutive days. Canine atopic dermatitis extent and severity index-03 (CADESI-03) and skin biopsies were performed on day 0, 14, and 28. Quantitative RT-PCR was used to determine levels of cutaneous cytokines and barrier function markers. Indirect immunofluorescence was used to determine protein expression and distribution of nuclear messengers, barrier function and inflammatory [thymic stromal lymphopoietin (TSLP)] markers. The data were tested for normality and then the upaired two samples Student's t-test and the repeated measurements ANOVA, followed by the Dunnett's Multiple Comparison Test as post-hoc analysis, were performed. A P value of immunologic milieu or barrier markers despite evident improvement of physical signs in the treatment group. Although this study confirmed the usefulness of CsA for the treatment of cAD, a clear involvement of CsA on some of the currently known immunological alterations present in cAD was not determined. However, it is important to note that there was no measurable exacerbation of skin barrier dysfunction secondary to CsA administration in this model. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Rapid and Sensitive LC-MS/MS Method for the Determination of Metoprolol in Beagle Dog Plasma with a Simple Protein Precipitation Treatment and Its Pharmacokinetic Applications

    Directory of Open Access Journals (Sweden)

    Aihua Hong

    2012-03-01

    Full Text Available : A rapid LC-MS/MS method with good accuracy and sensitivity was developed and validated for the pharmacokinetics study of metoprolol (MP in beagle dogs. The plasma samples were simply precipitated by methanol and then analyzed by LC-MS/MS. An Ultimate XB-C18 column (150 × 2.1 mm ID, 5 μm was used for separation, with methanol-water containing 0.2% formic acid (65:35, v/v as the mobile phase at a flow rate of 0.2 mL/min. Monitoring ions of MP and internal standard (hydroxypioglitazone were m/z 268.1/115.6 and m/z 373.1/150.2, respectively. The linear range was 3.03–416.35 ng/mL with an average correlation coefficient of 0.9996, and the limit of quantification was 3.03 ng/mL. The intra- and inter-day precision was less than 15%. At low, middle and high concentrations, the recovery, the matrix effect and the accuracy was in the range of 76.06%–95.25%, 93.67%–104.19% and 95.20%–99.96% respectively. The method was applied for the pharmacokinetics study of MP tartrate tablets (50 mg. The AUC0-t, Tmax and Cmax were respectively 919.88 ± 195.67 μg/L·h, 0.96 ± 0.33 h, 349.12 ± 78.04 ng/mL.

  6. The effect of changes in core body temperature on the QT interval in beagle dogs: a previously ignored phenomenon, with a method for correction.

    Science.gov (United States)

    van der Linde, H J; Van Deuren, B; Teisman, A; Towart, R; Gallacher, D J

    2008-08-01

    Body core temperature (Tc) changes affect the QT interval, but correction for this has not been systematically investigated. It may be important to correct QT intervals for drug-induced changes in Tc. Anaesthetized beagle dogs were artificially cooled (34.2 degrees C) or warmed (42.1 degrees C). The relationship between corrected QT intervals (QTcV; QT interval corrected according to the Van de Water formula) and Tc was analysed. This relationship was also examined in conscious dogs where Tc was increased by exercise. When QTcV intervals were plotted against changes in Tc, linear correlations were observed in all individual dogs. The slopes did not significantly differ between cooling (-14.85+/-2.08) or heating (-13.12+/-3.46) protocols. We propose a correction formula to compensate for the influence of Tc changes and standardize the QTcV duration to 37.5 degrees C: QTcVcT (QTcV corrected for changes in core temperature)=QTcV-14 (37.5 - Tc). Furthermore, cooled dogs were re-warmed (from 34.2 to 40.0 degrees C) and marked QTcV shortening (-29%) was induced. After Tc correction, using the above formula, this decrease was abolished. In these re-warmed dogs, we observed significant increases in T-wave amplitude and in serum [K(+)] levels. No arrhythmias or increase in pro-arrhythmic biomarkers were observed. In exercising dogs, the above formula completely compensated QTcV for the temperature increase. This study shows the importance of correcting QTcV intervals for changes in Tc, to avoid misleading interpretations of apparent QTcV interval changes. We recommend that all ICH S7A, conscious animal safety studies should routinely measure core body temperature and correct QTcV appropriately, if body temperature and heart rate changes are observed.

  7. Assessing adverse effects of intra-articular botulinum toxin A in healthy Beagle dogs: A placebo-controlled, blinded, randomized trial.

    Science.gov (United States)

    Heikkilä, Helka M; Jokinen, Tarja S; Syrjä, Pernilla; Junnila, Jouni; Hielm-Björkman, Anna; Laitinen-Vapaavuori, Outi

    2018-01-01

    To investigate the clinical, cytological, and histopathological adverse effects of intra-articularly injected botulinum toxin A in dogs and to study whether the toxin spreads from the joint after the injection. A longitudinal, placebo-controlled, randomized clinical trial was conducted with six healthy laboratory Beagle dogs. Stifle joints were randomized to receive either 30 IU of onabotulinum toxin A or placebo in a 1:1 ratio. Adverse effects and spread of the toxin were examined by evaluating dynamic and static weight-bearing of the injected limbs, by assessing painless range of motion and pain on palpation of joints, and by performing synovial fluid analysis, neurological examination, and electrophysiological recordings at different examination time-points in a 12-week period after the injections. The dogs were then euthanized and autopsy and histopathological examination of joint structures and adjacent muscles and nerves were performed. Intra-articular botulinum toxin A did not cause local weakness or injection site pain. Instead, static weight-bearing and painless range of motion of stifle joints decreased in the placebo limbs. No clinically significant abnormalities associated with intra-articular botulinum toxin A were detected in the neurological examinations. Electrophysiological recordings showed low compound muscle action potentials in two dogs in the botulinum toxin A-injected limb. No significant changes were detected in the synovial fluid. Autopsy and histopathological examination of the joint and adjacent muscles and nerves did not reveal histopathological adverse effects of the toxin. Intra-articular botulinum toxin A does not produce significant clinical, cytological, or histopathological adverse effects in healthy dogs. Based on the electrophysiological recordings, the toxin may spread from the joint, but its clinical impact seems to be low.

  8. Evaluation of Temporal Changes in Urine-based Metabolomic and Kidney Injury Markers to Detect Compound Induced Acute Kidney Tubular Toxicity in Beagle Dogs.

    Science.gov (United States)

    Wagoner, M P; Yang, Y; McDuffie, J E; Klapczynski, M; Buck, W; Cheatham, L; Eisinger, D; Sace, F; Lynch, K M; Sonee, M; Ma, J-Y; Chen, Y; Marshall, K; Damour, M; Stephen, L; Dragan, Y P; Fikes, J; Snook, S; Kinter, L B

    2017-01-01

    Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute Drug Induced Kidney Injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metabolites in urine from male and female beagle dogs. Gentamicin- induced kidney lesions in male dogs were characterized by moderate to severe tubular epithelial cell degeneration/necrosis, epithelial cell regeneration and dilation; and a unique urinebased metabolomic fingerprint. These metabolite changes included time and treatment-dependent increases in lactate, taurine, glucose, lactate, alanine, and citrate as well as 9 other known metabolites. As early as 3 days post dose, gentamicin induced increases in urinary albumin, clusterin, neutrophil gelatinase associated protein (NGAL) and total protein concentrations. Urinary albumin, clusterin, and NGAL showed earlier and more robust elevations than traditional kidney safety biomarkers, blood urea nitrogen and serum creatinine. Elevations in urinary kidney injury molecule 1 (KIM-1) were less reliable for detection of gentamicin nephrotoxicity in dogs based on values generated utilizing multiple first-generation, canine-specific KIM-1 immunoassays. The metabolic fingerprint was further evaluated in male and female dogs that received Compound A which induced slightly reversible renal tubular alterations characterized as degeneration/necrosis and concurrent significant increases in urinary taurine amongst other markers. These data support further investigations to demonstrate the value of urinary metabolites, albumin, clusterin, NGAL and taurine as promising markers to enable early detection of DIKI in dogs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. 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.

  10. Simultaneous determination of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside, senkyunolide I in Beagle dogs plasma by UPLC-MS/MS and its application to a pharmacokinetic study after Oral Administration of Shaofu Zhuyu Decoction.

    Science.gov (United States)

    Huang, Xiaochen; Su, Shulan; Cui, Wenxia; Liu, Pei; Duan, Jin-ao; Guo, Jianming; Li, Zhenhao; Shang, Erxin; Qian, Dawei; Huang, Zhijun

    2014-07-01

    In this present study, a sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside and senkyunolide I in Beagle dog plasma after oral administration of the Shao-Fu-Zhu-Yu Decoction. Chloramphenicol and clarithromycin were used as internal standards. Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100mm×2.1mm, 1.7μm) at a flow-rate of 0.4mL/min, using 0.1% formic acid-acetonitrile as mobile phase. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. After validation, this method was successfully applied to a pharmacokinetic study. The results showed that the apparent plasma clearance of paeoniflorin, albiflorin, typhaneoside and senkyunolide I were significantly higher than others. Double peak was observed in plasma concentration curves of tetrahydropalmatine, the ferulic acid had a good absorption in Beagle dog plasma, and senkyunolide I was detected in plasma from the first blood sampling time (15min) and rapidly reached Tmax. The compound of typhaneoside has a low bioavailability according to the results. Copyright © 2014. Published by Elsevier B.V.

  11. A comparison of the natural survival of beagle dogs injected intravenously with low levels of 239Pu, 226Ra, 228Ra, 228Th, or 90Sr

    International Nuclear Information System (INIS)

    Bruenger, F.W.; Miller, S.C.; Lloyd, R.D.

    1991-01-01

    The natural survival, relative to properly chosen controls, of 26 beagle dogs injected once intravenously with an average of 0.58 +/- 0.04 kBq 239 Pu/kg, 23 dogs injected with 2.31 +/- 0.43 kBq 226 Ra/kg, 13 dogs injected with 1.84 +/- 0.26 kBq 228 Ra/kg, 12 dogs injected with 0.56 +/- 0.030 kBq 228 Th/kg, and 12 dogs injected with 21.13 +/- 1.74 kBq 90 Sr/kg was evaluated statistically. The amounts of these radionuclides are related directly to the estimated maximum permissible body burdens for humans suggested in ICRP II (1959). They constitute a level of exposure that initially was assumed to cause no deleterious effects in dogs. This study had two objectives: (1) identification of homogeneous control groups against which to evaluate the survival of the irradiated groups and (2) comparison of the survival characteristics and estimation of mortality or hazard rate ratios for control dogs vs dogs injected with the baseline dosages given above. It was shown, by goodness-of-fit plots, that the Cox proportional hazards model was an appropriate method of analysis. Therefore, covariates that possibly could influence survival were tested for significance. Only the effects of grand mal seizure, which is caused in epileptic dogs by an external stimulus and can be fatal if untreated, were significant (P less than 0.0001). Consequently, in the final model, death from grand mal seizure was considered as accidental. After censoring the dogs dying from grand mal seizure, it was established that the data for the control groups from previous and contemporary experiments could be pooled. The change in hazard rates relative to controls resulting from exposure to the baseline radionuclide level was modest, 1.6 times for 239 Pu (P = 0.033), 1.0(4) for 226 Ra (P = 0.86), 1.9 for 228 Ra (P = 0.035), 2.5 for 228 Th (P less than 0.001), and 0.52 for 90 Sr (P = 0.041)

  12. Complete Biological Evaluation of Therapeutical Radiopharmaceuticals in Rodents, Laboratory Beagles and Veterinary Patients - Preclinical Distribution-, Kinetic-, Excretion-, Internal Dosimetry-, Radiotoxicological-, Radiation Safety- and Efficacy Data

    International Nuclear Information System (INIS)

    Balogh, L.; Domokos, M.; Polyak, A.; Thuroczy, J.; Janoki, G.

    2009-01-01

    The research and development of various novel therapeutical radiopharmaceuticals is a huge demand in many laboratories world-wide. Beside of multiple bone metastases pain-palliation and radiosynovectomy agents a number of specific radiopharmaceutical applicants mainly for oncological applications are in the pipeline. Numerous in vitro methods are available in the first line to test the radiolabelling efficiency, the possible radioactive and non-labelled impurities, the stability of the label at different conditions and mediums, and some specific characteristics of radiopharmaceutical applicants eg.: receptor binding assays, antigen-antibody assays. But, still before human clinical trials there are several questions to be solved in regards of toxicology, radiotoxicology, radiation safety and maybe most importantly the efficacy tasks. All these issues cannot be answered without animal tests. Several decades back animal tests in radiopharmacy meant only standard bioassays in a large number of healthy rodents. Later on pathological models eg.: human tumor xenografts in immunodeficient animals came-out and through them radiopharmaceutical tumor-uptake by the targets were available to evaluate in vivo as well. Xenografts are still popular and widely used models in the field but instead of wide-scaled bioassays nowadays repeated scintiscans or hybrid images (SPECT/CT, PET/CT) are more and more often used to answer kinetic-, excretion-, tumor uptake, internal dosimetry (Minimum Effective Dose, Maximum Tolerable Dose, critical organ doses, tumor doses) questions. Greater animals like laboratory Beagles are more closely in size, clinical and metabolic parameters to the human objects so playing a more perfect role of human medical doctor and especially veterinary patients. Easy to understand that many of the spontaneously occurring companion animal diseases are a good model of human pathological diseases. The need of a better diagnosis and treatment of that animals meets with

  13. Temporal kinetics and concentration-response relationships for induction of CYP1A, CYP2B, and CYP3A in primary cultures of beagle dog hepatocytes.

    Science.gov (United States)

    Graham, Richard A; Tyler, Lindsey O; Krol, Wojciech L; Silver, Ivin S; Webster, Lindsey O; Clark, Philip; Chen, Liangfu; Banks, Troy; LeCluyse, Edward L

    2006-01-01

    Compared to other species, little information is available on the xenobiotic-induced regulation of cytochrome P450 enzymes in the beagle dog. Dogs are widely used in the pharmaceutical industry for many study types, including those that will impact decisions on compound progression. The purpose of this study was (1) to determine the temporal kinetics of drug-induced changes in canine CYP1A, CYP2B, and CYP3A mRNA and enzymatic activity, and (2) to characterize concentration-response relationships for CYP1A2, CYP2B11, and CYP3A12 using primary cultures of canine hepatocytes treated with beta-naphthoflavone (BNF), phenobarbital (PB), and rifampin (RIF), respectively. CYP1A1 and CYP1A2 mRNA exhibited maximal expression (12,700-fold and 206-fold, respectively) after 36 h of treatment with BNF. PB treatment, but not RIF treatment, caused maximal induction of CYP2B11 mRNA (149-fold) after 48 h of treatment. CYP3A12 and CYP3A26 mRNA levels were increased maximally after 72 h of treatment with PB and RIF (CYP3A12, 35-fold and 18-fold, and CYP3A26, 72-fold and 22-fold with PB and RIF treatment, respectively). Concentration-response relationships for BNF induced 7-ethoxyresorufin O-dealkylation (EROD) (EC(50) = 7.8 +/- 4.2 microM), PB induced 7-benzyloxyresorufin O-dealkylation (BROD) (EC(50) = 123 +/- 30 microM), and PB and RIF induced testosterone 6beta-hydroxylation (EC(50) = 132 +/- 28 microM and 0.98 +/- 0.16 microM) resembled the relationship for human CYP induction compared to that of rodent. Interestingly, RIF had no effect on CYP2B11 expression, which represents a species difference overlooked in previous investigations. Overall, the induction of dog CYP1A, CYP2B, and CYP3A exhibits characteristics that are intermediate to those of rodent and human. (c) 2006 Wiley Periodicals, Inc.

  14. Higher neonatal growth rate and body condition score at 7 months are predictive factors of obesity in adult female Beagle dogs.

    Science.gov (United States)

    Leclerc, Lucie; Thorin, Chantal; Flanagan, John; Biourge, Vincent; Serisier, Samuel; Nguyen, Patrick

    2017-04-13

    The risks during early growth on becoming overweight in adulthood are widely studied in humans. However, early-life predictive factors for canine adult overweight and obesity have not yet been studied. To identify factors that may help explain the development of overweight and obesity at adulthood in dogs, a longitudinal study of 2 years was conducted in 24 female Beagle dogs of the same age, sexual status, and raised under identical environmental conditions. By means of a hierarchical classification on principal components with the following quantitative values: fat-free mass (FFM), percentage fat mass and pelvic circumference at 2 years of age, three groups of dogs were established and were nominally named: ideal weight (IW, n = 9), slightly overweight (OW1, n = 6) and overweight (OW2, n = 9). With the aim of identifying predictive factors of development of obesity at adulthood parental characteristics, growth pattern, energy balance and plasma factors were analysed by logistic regression analysis. At 24 months, the group compositions were in line with the body condition scores (BCS 1-9) values of the IW (5 or 6/9), the OW1 (6/9) and the OW2 (7 or 8/9) groups. Logistic regression analysis permitted the identification of neonatal growth rate during the first 2 weeks of life (GR 2W ) and BCS at 7 months as predictors for the development of obesity at adulthood. Seventy percent of dogs with either GR 2W >125% or with BCS > 6/9 at 7 months belonged to the OW2 group. Results from energy intake and expenditure, corrected for FFM, showed that there was a greater positive energy imbalance between 7 and 10 months for the OW2, compared to the IW group. This study expands the understanding of previously reported risk factors for being overweight or obese in dogs, establishing that (i) 15 out of 24 of the studied dogs became overweight and (ii) GR 2W and BCS at 7 months of age could be used as predictive factors as overweight adult dogs in the OW2

  15. Cinnarizine food-effects in beagle dogs can be avoided by administration in a Self Nano Emulsifying Drug Delivery System (SNEDDS).

    Science.gov (United States)

    Christiansen, Martin Lau; Holm, Rene; Kristensen, Jakob; Kreilgaard, Mads; Jacobsen, Jette; Abrahamsson, Bertil; Müllertz, Anette

    2014-06-16

    To elucidate if a SNEDDS approach can eliminate the food-effect on cinnarizine absorption and to, investigate if a nutritional drink, Fresubin energy, could mimic food effect in dogs for the poorly soluble compound cinnarizine. A conventional tablet, a SNEDDS capsule or a SNEDDS tablet, containing cinnarizine, were dosed to beagles dogs in fed or fasted state (n=5), with a one week wash-out period between dosing. Dogs were pre-treated with pentagastrin. Fed state was induced by a nutritional drink (Fresubin Energy®). The food-effect was evaluated by comparing Tmax, Cmax and Bioavailability (F) for the different formulations. Food effect was observed on all three parameters for the conventional tablet; Tmax was delayed 2.5times and bioavailability increased in fed state (from 20.9±5.7 to 53.8±30.1). Apart from an extended Tmax (2.5 and 3.3 times longer in fed state compared to fasted state for the SNEDDS tablets and SNEDDS capsules respectively), food effect on absorption for the SNEDDS capsules and SNEDDS tablets was not observed. The SNEDDS capsules had a higher bioavailability in both fed and fasted state compared to SNEDDS tablets (Ffasted=58.1±16.7, vs. 32.7±11.5), (Ffed=79.3±14.7 vs. 43.7±6.7) There were no significant differences in bioavailability between the conventional tablet in fed state and the SNEDDS capsules. Food effect was observed when dosing cinnarizine with ingestion of the nutritional drink Fresubin Energy. Food effect on cinnarizine could be significantly reduced by dosing either as a SNEEDS capsule or a SNEDDS tablet, however, the SNEDDS tablet resulted in an overall lower absorption than the SNEDDS capsules in both fed and fasted state. The delay in fed state absorption could not be changed by dosing with SNEDDS formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Determination of the Tissue Distribution and Excretion by Accelerator Mass Spectrometry of the Nonadecapeptide 14C-Moli1901 in Beagle dogs after Intratracheal Instillation

    Energy Technology Data Exchange (ETDEWEB)

    Rickert, D E; Dingley, K H; Ubick, E; Dix, K J; Molina, L

    2004-07-02

    Administration of {sup 14}C-Moli1901 (duramycin, 2622U90), a 19 amino acid polycyclic peptide by intratracheal instillation (approximately 100 {micro}g) into the left cranial lobe of the lung of beagle dogs resulted in retention of 64% of the dose in the left cranial lobe for up to 28 days. In this study, we used accelerator mass spectrometry (AMS) to quantify Moli901 following administration of only 0.045 {micro}Ci of {sup 14}C-Moli901 per dog. Limits of quantitation of AMS were 0.03 (urine) to 0.3 (feces) ng equiv. Moli1901/g. Whole blood and plasma concentrations of {sup 14}C were <5ng/ml at all times after the dose. Concentrations of {sup 14}C in whole blood and plasma declined over the first day after the dose and rose thereafter, with the rise in plasma concentrations lagging behind those in whole blood. During the first 3 days after the dose, plasma accounted for the majority of {sup 14}C in whole blood, but after that time, plasma accounted for only 25-30% of the {sup 14}C in whole blood. Tissue (left and right caudal lung lobe, liver, kidney, spleen, brain) and bile concentrations were low, always less than 0.25% the concentrations found in the left cranial lung lobe. Approximately 13% of the dose was eliminated in urine and feces in 28 days, with fecal elimination accounting for about 10% of the dose. The data presented here are consistent with that obtained in other species. Moli1901 is slowly absorbed and excreted from the lung, and it does not accumulate in other tissues. Moli1901 is currently in the clinic and has proven to be safe in single dose studies in human volunteers and cystic fibrosis patients by the inhalation route. No information on the disposition of the compound in humans is available. This study in dogs demonstrates the feasibility of obtaining that information using {sup 14}C-Moli1901 and AMS.

  17. Even at the uttermost ends of the Earth: how seabirds telecouple the Beagle Channel with regional and global processes that affect environmental conservation and social-ecological sustainability

    Directory of Open Access Journals (Sweden)

    Andrea N. Raya Rey

    2017-12-01

    Full Text Available Human-wildlife dynamics exhibit novel characteristics in the Anthropocene, given the unprecedented degree of globalization that has increased the linkages between habitats and people across space and time. This is largely caused by transnational mobility and migration, international labor, resource markets, and trade. Understanding the relationship between humans and wildlife, and their associated telecoupling processes, helps to promote better management practices and governance for reconciling socioeconomic and conservation interests. Even remote places on the globe exhibit these features. For example, in southern Patagonia's coastal and marine ecosystems, seabirds are not only very abundant and charismatic members of the wildlife community, nowadays, their colonies are a main tourism attraction of global significance, and in the past they were used for consumptive and scientific purposes that also linked the "uttermost ends of the Earth" with distant places. Thus, in this study, we review human-seabird interactions in the iconic Beagle Channel (BC in the Argentine portion of the Tierra del Fuego Archipelago. We adapted and employed the coupled human and natural systems (CHANS approach and telecoupling framework to integrate disparate social and biological information and obtain a more holistic understanding of current human-seabird dynamics and trends in the BC. Although our assessment includes the temporal scale of human-seabird relationships, we centered the CHANS and telecoupling analysis on the modern seabird-tourism interaction, focused on the channel's Argentine sector, in which tourism is most intensively developed. Our synthesis of the BC's telecoupled CHANS allowed us to recognize the strong historical local-to-global interactions between both human and natural subsystems and the sharp increase in distance telecoupling during the 20th century. Despite this globalizing trend in seabirds connecting the BC's local ecosystems to distant

  18. Toxicity of inhaled 238PuO2 in Beagle dogs: A. Monodisperse 1.5 μm AMAD particles. B. Monodisperse 3.0 μm particles. XV

    International Nuclear Information System (INIS)

    Mewhinney, J.A.; Gillett, N.A.; Muggenburg, B.A.; Hahn, F.F.; Diel, J.H.; Mauderly, J.L.; Boecker, B.B.; McClellan, R.O.

    1988-01-01

    Beagle dogs inhaled one of two sizes of monodisperse aerosols of 238 PuO 2 that resulted in graded levels of 238 Pu in the lung. All dogs are being studied for their life span. One hundred and thirty-seven dogs that had initial lung burdens ranging from 0.01 to 1.5 μCi 238 Pu/kg body weight (0.37 to 56 kBq/kg) have died, 8 with radiation pneumonitis and pulmonary fibrosis, 8 with lung tumors, 88 with bone tumors, 10 with liver tumors, and 25 of miscellaneous causes. Eighteen control dogs have died. Observations are being continued on 8 exposed and 6 control dogs alive at 4577-5274 days after exposure. (author)

  19. The detection and evaluation of drug-induced changes in the gastrointestinal motility of beagle dogs using a 111In-labelled resin mixed into a standard meal as tracer

    International Nuclear Information System (INIS)

    Dormehl, I.C.; Du Plessis, M.; Pilloy, W.; Meyer, B.J.; Maree, M.

    1985-01-01

    An investigation was performed to establish the usefulness of 111 In-labelled polymer beads mixed into a standard meal as a tracer of gatrointestinal (GI)-motility changes due to the influence of various drugs. The labelled polymer beads were well mixed into the food, which was then fed to healthy beagle dogs undergoing drug therapy. GI motility was monitored using a gamma camera and data processor. The results were compared to those obtained from corresponding placebo studies on the same dogs. A significant acceleration of gastric emptying and colon transit was noted under the influence of a gastric and intestinal prokinetic coded R 51619. No influence on GI motility could, however, be detected after the administration of a calcium-blocking agent to the dogs. (orig.)

  20. Toxicity of inhaled {sup 238}PuO{sub 2} in Beagle dogs: A. Monodisperse 1.5 {mu}m AMAD particles. B. Monodisperse 3.0 {mu}m particles. XV

    Energy Technology Data Exchange (ETDEWEB)

    Mewhinney, J A; Gillett, N A; Muggenburg, B A; Hahn, F F; Diel, J H; Mauderly, J L; Boecker, B B; McClellan, R O

    1988-12-01

    Beagle dogs inhaled one of two sizes of monodisperse aerosols of {sup 238}PuO{sub 2} that resulted in graded levels of {sup 238}Pu in the lung. All dogs are being studied for their life span. One hundred and thirty-seven dogs that had initial lung burdens ranging from 0.01 to 1.5 {mu}Ci {sup 238}Pu/kg body weight (0.37 to 56 kBq/kg) have died, 8 with radiation pneumonitis and pulmonary fibrosis, 8 with lung tumors, 88 with bone tumors, 10 with liver tumors, and 25 of miscellaneous causes. Eighteen control dogs have died. Observations are being continued on 8 exposed and 6 control dogs alive at 4577-5274 days after exposure. (author)

  1. Detection and evaluation of drug-induced changes in the gastrointestinal motility of beagle dogs using a /sup 111/In-labelled resin mixed into a standard meal as tracer

    Energy Technology Data Exchange (ETDEWEB)

    Dormehl, I.C.; Du Plessis, M.; Pilloy, W.; Meyer, B.J.; Maree, M.

    1985-03-01

    An investigation was performed to establish the usefulness of /sup 111/In-labelled polymer beads mixed into a standard meal as a tracer of gatrointestinal (GI)-motility changes due to the influence of various drugs. The labelled polymer beads were well mixed into the food, which was then fed to healthy beagle dogs undergoing drug therapy. GI motility was monitored using a gamma camera and data processor. The results were compared to those obtained from corresponding placebo studies on the same dogs. A significant acceleration of gastric emptying and colon transit was noted under the influence of a gastric and intestinal prokinetic coded R 51619. No influence on GI motility could, however, be detected after the administration of a calcium-blocking agent to the dogs.

  2. Studies on mechanism of treatment of granulocyte colony-stimulating factor, recombinant human interleukin-11 and recombinant human interleukin-2 on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles

    International Nuclear Information System (INIS)

    Li Ming; Ou Hongling; Xing Shuang; Huang Haixiao; Xiong Guolin; Xie Ling; Zhao Yanfang; Zhao Zhenhu; Wang Ning; Wang Jinxiang; Miao Jingcheng; Zhu Nankang; Luo Qingliang; Cong Yuwen; Zhang Xueguang

    2010-01-01

    Objective: To investigate the mechanism of treatment of granulocyte colony-stimulating factor (rhG-CSF), recombinant human interleukin-11 (rhIL-11) and recombinant human interleukin-2 (rhIL-2) on hematopoietic injuries induced by 4.5 Gy 60 Co γ-ray irradiation in beagles, and to provide experimental evidence for the clinical treatment of extremely severe myeloid acute radiation sickness (ARS). Methods: Sixteen beagle dogs were given 4.5 Gy 60 Co γ-ray total body irradiation (TBI), then randomly assigned into irradiation control group, supportive care group or cytokines + supportive care (abbreviated as cytokines) group. In addition to supportive care, rhG-CSF, rhIL-11 and rhIL-2 were administered subcutaneously to treat dogs in cytokines group. The percentage of CD34 + cells, cell cycle and apoptosis of nucleated cells in peripheral blood were examined by Flow cytometry. Results: After 4.5 Gy 60 Co γ-ray irradiation, the CD34 + cells in peripheral blood declined obviously (61.3% and 52.1% of baseline for irradiation control and supportive care group separately). The cell proportion of nucleated cells in G 0 /G 1 phase was increased notably notably (99.27% and 99.49% respectively). The rate of apoptosis (26.93% and 21.29% separately) and necrosis (3.27% and 4.14%, respectively) of nucleated cells were elevated significantly when compared with values before irradiation (P 0 /G 1 phase blockage of nucleated cells became more serious (99.71%). The rate of apoptosis (5.66%) and necrosis (1.60%) of nucleated cells were significantly lower than that of irradiation control and supportive care groups 1 d after exposure. Conclusions: Cytokines maybe mobilize CD34 + cells in bone marrow to peripheral blood, indce cell block at G 0 /G 1 phase and reduce apoptosis, and eventually cure hematopoietic injuries induced by irradiation. (authors)

  3. Development and validation of a rapid HPLC method for the determination of cefdinir in beagle dog plasma integrated with an automatic on-line solid-phase extraction following protein precipitation in the 96-well plate format.

    Science.gov (United States)

    Li, Ji; Wang, Li; Chen, Zhao; Xie, Rui; Li, You; Hang, Taijun; Fan, Guorong

    2012-05-01

    The high-performance liquid chromatography (HPLC) coupled with on-line solid phase extraction (SPE) and ultraviolet (UV) detection was developed for determining cefdinir in beagle dog plasma. After simple pretreatment for plasma with 6% perchloric acid, a volume of 100 μL upper layer of the plasma sample was injected into the self-made on-line SPE column. The analytes were retained on the trap column (Lichrospher C(18), 4.6 mm × 37 mm, 25 μm), and the biological matrix was washed out with the solvent (20mM KH(2)PO(4) adjusted pH 3.0) at flow rate of 2 mL/min. By rotation of the switching valve, the target analytes could be eluted from trap column to analytical column in the back-flush mode by the mobile phase (methanol-acetonitrile-20mM KH(2)PO(4) adjusted pH 3.0, 11.25:6.75:82, v/v/v) at flow rate of 1.5 mL/min, and then separated on the analytical column (Ultimate XB-C(18), 4.6 mm × 50 mm, 5 μm). The complete cycle of the on-line SPE preconcentration, purification and HPLC separation of the analytes was 4 min. The UV detection was performed at 286 nm. The calibration curves showed excellent linear relationship (R(2)=0.9995) over the concentration range of 0.05-50 μg/mL. The optimized method showed good performance in terms of specificity, linearity, detection and quantification limits, precision and accuracy. This method was successfully applied to quantify cefdinir in beagle dog plasma to support the pre-clinical pharmacokinetic trial. Copyright © 2012. Published by Elsevier B.V.

  4. Development and validation of a rapid and high-sensitivity liquid chromatography-tandem mass spectrometry assay for the determination of neostigmine in small-volume beagle dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Cao, Di; Li, Wenxue; Zhao, Xin; Ye, Xiaolan; Sun, Fanlu; Li, Jinying; Song, Fenyun; Fan, Guorong

    2014-03-01

    A simple, rapid and high sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of neostigmine in small-volume beagle dog plasma was developed to assess the plasma pharmacokinetics of neostigmine. After protein precipitation in a Sirocco 96-well filtration plate, the filtrate was directly injected into the LC-MS/MS system. The analytes were separated on a Hanbon Hedera CN column (100 × 4.6 mm, 5 µm) with a mobile phase composed of methanol-water (60:40, v/v) and the water containing 0.01% formic acid at a flow rate of 0.6mL/min, with a split ratio of 1:1 flowing 300 μL into the mass spectrometer. The run time was 3 min. Detection was accomplished by electrospray ionization source in multiple reactions monitoring mode with the precursor-to-product ion transitions m/z 223.0 → 72.0 and 306.0 → 140.0 for neostigmine and anisodamine (internal standard), respectively. The method was sensitive with a lower limit of quantitation of 0.1 ng/mL, and good linearity in the range 0.1-100ng/mL for neostigmine (r ≥ 0.998). All the validation data, such as accuracy, intra-run and inter-run precision, were within the required limits. The method was successfully applied to pharmacokinetic study of neostigmine methylsulfate injection in beagle dogs. Copyright © 2013 John Wiley & Sons, Ltd.

  5. Simultaneous determination of triamcinolone acetonide palmitate and triamcinolone acetonide in beagle dog plasma by UPLC-MS/MS and its application to a long-term pharmacokinetic study of triamcinolone acetonide palmitate lipid emulsion injection.

    Science.gov (United States)

    Liu, Hui; Yang, Mingjing; Wu, Panpan; Guan, Jiao; Men, Lei; Lin, Hongli; Tang, Xing; Zhao, Yunli; Yu, Zhiguo

    2015-02-01

    In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid-liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C18 column (50 mm × 2.1mm, 1.7 μm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5→397.3, 435.3→415.3 and 393.3→355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1-1,000 ng/ml for TAP and 0.5-500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of -8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7-104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Simultaneous determination of notoginsenoside R₁, ginsenoside Rg₁, ginsenoside Re and 20(S) protopanaxatriol in beagle dog plasma by ultra high performance liquid mass spectrometry after oral administration of a Panax notoginseng saponin preparation.

    Science.gov (United States)

    Wu, Huichao; Liu, Huimin; Bai, Jie; Lu, Yang; Du, Shouying

    2015-01-01

    20(S) protopanaxatriol is the main metabolite of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re in Panax notoginseng and has significant activities. A ultra high performance liquid mass spectrometry method has been developed and validated for the simultaneous determination of notoginsenoside R₁ (R1), ginsenoside Rg₁ (Rg₁), ginsenoside Re (Re) and 20(S) protopanaxatriol (PPT) in beagle dog plasma after oral administration of a Panax notoginseng saponin preparation. After the addition of the internal standard (digoxin), plasma samples were subjected to liquid-liquid extraction with acetone and methanol and separated on a 100 × 2.1 mm ACQUITY 1.7 μm C₁₈ column (Waters, USA), with acetonitrile and water as the mobile phase, within a runtime of 7.0 min. The analytes were detected without interference in Selected Reaction Monitoring mode with a change in the electrospray ionization from positive to negative. The detection limits were 0.01 to 0.04 mg/L and the calibration curves of the peak areas for the four ingredients were linear over four orders of magnitude with a correlation coefficient greater than 0.9957. The intra-day and inter-day precision values (relative standard deviation, RSD, %) were within 10.25% and 13.51%, respectively, and the accuracy (relative error, RE, %) was less than 7.81%. The validated method was successfully applied to a comparative pharmacokinetic study of four saponins in beagle dogs after oral administration of a Panax Notoginseng Saponins preparation. The pharmacokinetic parameters were calculated with DAS 3.20. The Tmax and Cmax values indicate a dose-dose relationship between the saponins (R1, Rg1, and Re) and their sapogenin (PPT). Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Hematological effects: comparative studies on the radiation survival characteristics in vivo and in vitro of bone marrow-derived clonogenic populations (CFU-C and PFU-C) and some observations on bone marrow cellularity in beagles

    International Nuclear Information System (INIS)

    Wilson, F.D.; O'Grady, L.; Momeni, M.; Wheeling, J.A.; Klein, K.; Graham, R.; Jow, N.; Di Bartola, S.

    1975-01-01

    Data accumulated for the hematological effects program are reviewed. Particular emphasis is given to the effects of acute and chronic irradiation on hematopoietic progenitor populations (CFU-C, colony-forming units in culture) and ''candidate'' mesenchymal progenitors (PFU-C, plaque-forming units in culture) using methylcellulose bone marrow culture systems and both in vivo and in vitro radiation exposure protocols. Preliminary results of studies on the temporal effects of acute x-irradiation on the capacity of PFU-C to generate colony stimulating activity (CSA) are also presented. The results of such experiments are providing the basis upon which future RBE studies on a variety of nuclides will be structured. Data (including age related changes) is also presented on in vivo bone marrow cellularity determinations, as well as for marrow stem cell quantitative studies using nondestructive techniques for normal Beagles. In these studies, two techniques for correction of variable effects of hemodilution are compared. Such studies are also providing baseline data for the 60 Co hematological effects program

  8. Risk estimates for lung tumors from inhaled 239PuO2, 238PuO2, and /sup 239Pu/(NO3)4 in beagle dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.; Park, J.F.; Gilbert, E.S.; Weller, R.E.

    1988-06-01

    Lung-cancer risks are being studied in beagle dogs given single exposures to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 . A major objective of these studies is to examine the risk of lung cancer relative to the specific activity of the radionuclide, rate of dose accumulation due to differences in solubilities of the radionuclides, and the presence of competing risk from extrapulmonary lesions. Dose-response relationships were studied for the three groups of dogs, with analyses specifically designed to evaluate differences in response. Based on estimated cumulative dose to the lung, risks were found to differ significantly among the radionuclides; they were highest for 239 Pu(NO 3 ) 4 and lowest for 238 PuO 2 . A model in which the risk was assumed to be a pure quadratic function of dose fit the data much better than a pure linear model. Currently, all three groups of dogs can be compared only to 10 years after exposure. However, it is apparent that the average cumulative dose to the lung may not be an adequate predictor of lung-cancer risk for different isotopic and physicochemical forms of plutonium. 13 refs., 2 tabs

  9. Life-span effects of ionizing radiation in the beagle dog: A summary account of four decades of research funded by the US Department of Energy and its predecessor agencies

    International Nuclear Information System (INIS)

    Thompson, R.C.

    1989-01-01

    Nearly 40 years ago, the US Atomic Energy Commission made a far- reaching commitment to the support of life-span radiation-effects studies in a relatively long-lived animal, the beagle dog. Something in the range of 200 million dollars has already been spent on a group of closely related experiments, many of which are only now coming to fruition. Responsible fiscal management of these studies, directed toward securing an optimum return from past investments, and toward creative planning of future directions, requires a comprehensive view of this total effort. This report is designed to provide that comprehensive view. This is primarily intended as a research management document. Evaluation and interpretation are tasks for those directly involved in conducting these experiments. The limited objective of the present document is to describe what has been done, to give some of the background for why it was done, to describe results already realized and applications that have been made of these results -- all in a manner designed to display the total effort rather than piecemeal details. While proposing no specific answers to the questions ''Where do we go from here?''it is hoped that the document will provide a basis for approaching that question in an informed manner. The maintenance of a continuity of scientific understanding and direction in these experiments, which often continue beyond the initiating investigators' working life, is no small part of the problem involved in conducting these experiments

  10. Life-span effects of ionizing radiation in the beagle dog: A summary account of four decades of research funded by the US Department of Energy and its predecessor agencies

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, R.C.

    1989-01-01

    Nearly 40 years ago, the US Atomic Energy Commission made a far- reaching commitment to the support of life-span radiation-effects studies in a relatively long-lived animal, the beagle dog. Something in the range of 200 million dollars has already been spent on a group of closely related experiments, many of which are only now coming to fruition. Responsible fiscal management of these studies, directed toward securing an optimum return from past investments, and toward creative planning of future directions, requires a comprehensive view of this total effort. This report is designed to provide that comprehensive view. This is primarily intended as a research management document. Evaluation and interpretation are tasks for those directly involved in conducting these experiments. The limited objective of the present document is to describe what has been done, to give some of the background for why it was done, to describe results already realized and applications that have been made of these results -- all in a manner designed to display the total effort rather than piecemeal details. While proposing no specific answers to the questions ''Where do we go from here.''it is hoped that the document will provide a basis for approaching that question in an informed manner. The maintenance of a continuity of scientific understanding and direction in these experiments, which often continue beyond the initiating investigators' working life, is no small part of the problem involved in conducting these experiments.

  11. An Optimized and Sensitive Pharmacokinetic Quantitative Method of Investigating Gastrodin, Parishin, and Parishin B, C and E in Beagle Dog Plasma using LC-MS/MS after Intragastric Administration of Tall Gastrodia Capsules

    Directory of Open Access Journals (Sweden)

    Junqiu Liu

    2017-11-01

    Full Text Available Gastrodia elata Blume, called Tianma in China, has been widely used to treat headaches, convulsions and epilepsy for thousands of years. In the present study, a series of optimizations were employed to develop a rapid, sensitive, and reliable high-performance liquid chromatography-triple quadrupole mass spectrometry method, which was then used for the simultaneous determination of gastrodin, parishin, parishin B, parishin C and parishin E in beagle dog plasma after intragastric administration of tall Gastrodia capsules (Tianma brand. The chromatographic separation was achieved on a C18 column with gradient elution by using a mixture of 0.4% formic acid aqueous solution and acetonitrile as the mobile phase at a flow rate of 0.15 mL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring (MRM via electrospray ionization (ESI source in negative ionization mode. Samples were pre-treated by a single-step protein precipitation with methanol, and bergenin was used as internal standard (IS. Under the optimized conditions, the lower limit of quantification (LLOQ was 0.10 ng/mL for gastrodin, 0.40 ng/mL for parishin B, 0.02 ng/mL for parishin E and 0.20 ng/mL for parishin and parishin C, all of which previously were the highest levels of sensitivity. The methods were optimized for selectivity, calibration curves, accuracy and precision. Extraction recoveries, matrix effects and stability were within acceptable ranges. Pharmacokinetic parameters of the tested substances were also quantitatively determined. Finally, a possible metabolic pathway was induced based on correlations obtained from quantitative and qualitative data analysis in vivo.

  12. Periodontal Wound Healing by Transplantation of Jaw Bone Marrow-Derived Mesenchymal Stem Cells in Chitosan/Anorganic Bovine Bone Carrier Into One-Wall Infrabony Defects in Beagles.

    Science.gov (United States)

    Zang, Shengqi; Jin, Lei; Kang, Shuai; Hu, Xin; Wang, Meng; Wang, Jinjin; Chen, Bo; Peng, Bo; Wang, Qintao

    2016-08-01

    This study aims to evaluate the performance of chitosan/anorganic bovine bone (C/ABB) scaffold seeded with human jaw bone marrow-derived mesenchymal stem cells (hJBMMSCs) in supporting the healing/repair of 1-wall critical-size periodontal defects. Physical properties of the C/ABB scaffold were compared with those of the chitosan scaffold. hJBMMSCs were obtained from healthy human alveolar bone during the extraction of third molar impacted teeth. One-wall (7 × 4 mm) infrabony defects were surgically created at the bilateral mandibular third premolars and first molars in six beagles. The defects were randomly assigned to six groups and implanted with different scaffolds: 1) chitosan (C) scaffold; 2) C scaffold with hJBMMSCs (C + cell); 3) C/ABB scaffold (C/ABB); 4) C/ABB scaffold with hJBMMSCs (C/ABB + cell); 5) ABB scaffold (ABB); and 6) open flap debridement (control). The animals were euthanized 8 weeks after surgery for histologic analysis. The C/ABB scaffold had a porous structure and increased compressive strength. Both C/ABB and C/ABB + cell exhibited the newly formed cellular mixed-fiber cementum, woven/lamellar bone, and periodontal ligament. Cementum formation was significantly greater in group C/ABB + cell than in group C/ABB (2.64 ± 0.50 mm versus 0.91 ± 0.55 mm, P <0.05). For new bone (NB) height, group C/ABB + cell and C/ABB showed mean ± SD values of 2.83 ± 0.29 mm and 2.65 ± 0.52 mm and for NB area 8.89 ± 1.65 mm and 8.73 ± 1.94 mm(2), respectively. For NB (height and area), there was no significant difference between the two groups. The combination of hJBMMSCs and C/ABB scaffolds could promote periodontal repair. Future studies are expected to further optimize the combination and lead to an ideal periodontal regeneration.

  13. Toxicity of inhaled 238PuO2 in beagle dogs. A. Monodisperse 1.5 μm 238PuO2. B. Monodisperse 3.0 μm 238PuO2 particles. III

    International Nuclear Information System (INIS)

    Lustgarten, C.S.; Mewhinney, J.A.; Hobbs, C.H.; Halliwell, W.H.; Jones, R.K.; Mauderly, J.L.; McClellan, R.O.; Mo, T.; Pickrell, J.A.

    1976-01-01

    To obtain essential information on the importance of the homogeneity or non-homogeneity of the radiation dose to lung (the hot particle question), Beagle dogs have been exposed to monodisperse aerosols (sigma/sub g/ 238 PuO 2 of either 1.5 μm or 3.0 μm aerodynamic diameter (AD). By using monodisperse particles of these two sizes, the average dose to lung is held constant for a given initial lung burden, but the local alpha dose around the two sizes of particles varies by a factor of about ten. All exposures have been completed with 72 days exposed to each of the two particle sizes of 238 PuO 2 (total of 144 dogs) resulting in graded initial lung burdens which range from .005 to 2.2 μCi/kg of body weight. Twenty-four dogs exposed to the diluent aerosol are serving as controls. The animals will be studied over their total life span. Two exposed dogs have died from pulmonary injury: Dog 710C (with an initial lung burden of 2.0 μCi/kg) died at 631 days after inhalation of 3.0 μm AD aerosol. The cause of death was radiation pneumonitis and pulmonary fibrosis, Dog 746B (with an initial lung burden of 1.3 μCi/kg) died at 791 days after inhalation of 1.5 μm AD aerosol. Death was attributed to intrapulmonic hemorrhage resulting from a degenerative vasculitis. One control dog (721A) was euthanized at 820 days after exposure due to a meningitis and encephalomalacia that caused a severe central nervous system disorder that made the dog difficult to handle.A leukopenia in exposed dogs to date has occurred earlier and to a greater degree in dogs exposed to 3.0 μm AD particles than in dogs that recevied 1.5 μm AD particles. One hundred forty-two exposed and 23 control dogs are surviving at 175 to 1024 days after exposure

  14. Subcellular distribution of curium in beagle liver

    International Nuclear Information System (INIS)

    Bruenger, F.W.; Grube, B.J.; Atherton, D.R.; Taylor, G.N.; Stevens, W.

    1976-01-01

    The subcellular distribution of curium ( 243 244 Cm) was studied in canine liver from 2 hr to 47 days after injection of 3 μCi 243 244 Cm/kg of body weight. The pattern of distribution for Cm was similar to other trivalent actinide elements studied previously (Am, Cf). Initially (2 hr), most of the nuclide was found in the cytosol and at least 90 percent was protein bound. About 70 percent of the Cm was bound to ferritin, approximately 5 percent was associated with a protein of MW approximately 200,000, and approximately 25 percent was found in the low-molecular-weight region (approximately 5000). The decrease in the Cm content of cytosol, nuclei, and microsomes coincided with an increase in the amount associated with mitochondria and lysosomes. The concentration of the Cm in the mitochondrial fraction was higher than it was in the lysosomal fraction at each time studied. In the mitochondrial fraction approximately 30 percent of the Cm was bound to membranous or granular material, and 70 percent was found in the soluble fraction. The Cm concentration initially associated with cell nuclei was high but had diminished to 20 percent of the 2 hr concentration by 20 days post injection (PI). The subcellular distribution of Cm in the liver of a dog which had received the same dose and was terminated because of severe liver damage was studied at 384 days PI. The liver weighed 130 g and contained approximately 30 percent of the injected Cm. In contrast, a normal liver weighs 280 g and at 2 hr PI contains approximately 40 percent of the injected dose. The subcellular distribution of Cm in this severely damaged liver differed from the pattern observed at earlier times after injection. The relative concentration of Cm in the cytosol was doubled; it was higher in the nuclei-debris fraction; and it was lower in the mitochondrial and lysosomal fractions when compared to earlier times

  15. Lymphocyte mobilization by dextran sulfate in beagles

    International Nuclear Information System (INIS)

    Ragan, H.A.; Debban, K.H.

    1978-01-01

    Dogs manifesting 239 Pu-induced lymphopenia responded to the lymphocyte-mobilizing agent, dextran sulfate, to a degree similar to that observed in control dogs. No life-threatening increase in prothrombin times or hemorrhagic tendencies were observed

  16. Toxicity of inhaled 239PuO2 in Beagle dogs. A. Monodisperse 0.75 μm AD particles. B. Monodisperse 1.5 μm AD particles. C. Monodisperse 3.0 μm AD particles. II

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Guilmette, R.A.; Hahn, F.F.; McClellan, R.O.; Mauderly, J.L.; Mewhinney, J.A.; Pickrell, J.A.; Boecker, B.B.

    1978-01-01

    Studies on the metabolism, dosimetry and biological effects of inhaled particles of 239 PuO 2 have been initiated in Beagle dogs. To obtain information on the relative importance of homogeneity of radiation doses to the lung, dogs have been exposed to particles of monodisperse aerosols (sigma/sub g/ 239 PuO 2 ; 40 dogs to the 0.75 μm AD particles, 72 dogs to the 1.5 μm AD particles and 60 dogs to the 3.0 μm AD particles. The exposures have resulted in graded ILB's, which range from 0.0002 to 2.6 μCi/kg body weight. Twenty-nine dogs were exposed to the aerosol diluent and serve as controls. Five dogs have died 336 to 561 days after exposure in the 1.5 μm AD study. Four dogs have died 116 to 589 days after exposure in the 3.0 μm AD study. These dogs had radiation pneumonitis and pulmonary fibrosis at death. The remaining dogs have survived up to 634 days after exposure. It is anticipated that the other dogs planned for these studies will be exposed over the next 12 months

  17. Toxicity of inhaled 239PuO2 in Beagle dogs. A. Monodisperse 0.75 μm AMAD particles. B. Monodisperse 1.5 μm AMAD particles. C. Monodisperse 3.0 μm AMAD particles. V

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Guilmette, R.A.; Hahn, F.F.; Boecker, B.B.; McClellan, R.O.; Mauderly, J.L.; Pickrell, J.A.

    1982-01-01

    Studies on the metabolism, dosimetry and biological effects of inhaled particles of 239 PuO 2 in Beagle dogs are in progress. To obtain information on the relative importance of homogeneity versus nonhomogeneity of radiation doses to the lung, dogs have been exposed to monodisperse aerosols of 239 PuO 2 of 0.75, 1.5 or 3.0 μm activity median aerodynamic diameter (AMAD). The exposures have resulted in graded initial lung burdens ranging from 0.0002 to 2.6 μCi 239 Pu per kilogram body weight. Other dogs were exposed to the aerosol diluent to serve as controls. Ten dogs have died in the study with 0.75 μm AMAD particles, 40 dogs have died in the study with 1.5 μm AMAD particles and 35 dogs have died in the study with 3.0 μm AMAD particles of 239 PuO 2 . Dogs have died with radiation pneumonitis and pulmonary fibrosis and carcinomas of the lung. The remaining dogs have survived up to 2100 days after inhalation exposure and are being observed for the remainder of their life span

  18. Toxicity of inhaled 239PuO2 in Beagle dogs: A. Monodisperse 0.75-μm AMAD particles. B. Monodisperse 1.5-μm AMAD particles. C. Monodisperse 3.0--μm AMAD particles. XI

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Guilmette, R.A.; Hahn, F.F.; Boecker, B.B.; McClellan, R.O.

    1988-01-01

    Beagle dogs were exposed to monodisperse aerosols of 239 PuO 2 of 0.75, 1.5, or 30 μm activity median aerodynamic diameter (AMAD) to obtain information on the relative importance of homogeneity of alpha irradiation doses to the lung in producing biological effects. The dogs' initial pulmonary burdens (IPB) ranged from 0.0002-2.0 μCi (0.0074 to 74 kBq) 239 Pu/kg of body mass. Thirty-six dogs were exposed to the aerosol diluent as controls. Forty-two of 48 dogs exposed to 0.75 μm AMAD particles have died; 67 of 96 have died in the study involving 1.5 μm AMAD particles; and 62 of 72 have died in the study involving the 3.0 μm AMAD particles. Seven of 36 control dogs have died. Most dogs exposed to 239 Pu that have failed to survive have died with radiation pneumonitis and fibrosis and/or lung cancer. Surviving dogs have lived up to 4300 days after exposure. The data obtained to date indicate that the degree of uniformity of dose to the lung does not significantly modify the risk of lung cancer. (author)

  19. Perinatal radiation-induced renal damage in the beagle

    International Nuclear Information System (INIS)

    Jaenke, R.S.; Angleton, G.M.

    1990-01-01

    The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated

  20. Biological effects of inhaled cigarette smoke in beagle dogs

    International Nuclear Information System (INIS)

    Stuart, B.O.; Palmer, R.F.; Filipy, R.E.; Dagle, G.E.

    1978-01-01

    A group of twenty dogs has received up to 7 yr of daily cigarette smoking (10 cigarettes per day, 5 days per week), using realistic methods of oral inhalation and nose-plus-mouth exhalation. Three dogs that received 20 cigarettes per day over 9 mo developed respiratory tract lesions, including pleural thickening, alveolar septal fibrosis, vesicular emphysema, and chronic bronchitis, more rapidly than dogs receiving 10 cigarettes per day

  1. Effects on inhaled uranium mine air contaminants in beagle dogs

    International Nuclear Information System (INIS)

    Filipy, R.E.; Stuart, B.O.; Palmer, R.F.; Ragan, H.A.; Hackett, P.L.

    1974-01-01

    The high incidence of lung cancer among uranium miners of the Colorado plateau is a matter of national concern in a period of increasing demand for uranium ore. These miners are exposed to a variety of inhalation hazards, including radon daughters, uranium ore dust, and cigarette smoking, that may cause or contribute to respiratory tract pathology. Over 98 percent of the miners developing lung cancer have had histories of cigarette smoking. In order to determine the combined or separate roles of radon daughters and cigarette smoking in the development of lung cancer and other respiratory tract pathology, groups of 20 dogs each received daily life span exposures to 4 hours of 600 working levels of radon daughters with ore dust, and/or cigarette smoking over 16 hours per day, 7 days per week, or both; control dogs received sham smoking. After 4 years of exposure, respiratory tract pathology included macrophage accumulation, septal fibrosis, epithelial hyperplasia, endothelial proliferation, vesicular and bullous emphysema, and extensive epithelial changes involving squamous metaplasia with atypical nuclei. These effects were primarily related to exposure to radon daughters and uranium ore dust, with and without cigarette smoke

  2. Characterization of a monodispersed aerosol exposure system for beagle dogs

    International Nuclear Information System (INIS)

    Cannon, W.C.; Herring, J.P.; Craig, D.K.

    1978-01-01

    A monodispersed aerosol exposure system for dogs is described and data are presented on aerosol depositions in the exposure system which could affect the aerosol presented to the animals by reducing the concentration and changing the particle size distribution

  3. Rapid BeagleBoard prototyping with MATLAB and Simulink

    CERN Document Server

    Qin, Fei

    2013-01-01

    This book is a fast-paced guide with practical, hands-on recipes which will show you how to prototype Beagleboard-based audio/video applications using Matlab/Simlink and Sourcery Codebench on a Windows host.Beagleboard Embedded Projects is great for students and academic researchers who have practical ideas and who want to build a proof-of-concept system on an embedded hardware platform quickly and efficiently. It is also useful for product design engineers who want to ratify their applications and reduce the time-to-market. It is assumed that you are familiar with Matlab/Simulink and have som

  4. Radiation-induced liver lesions in beagle dogs

    International Nuclear Information System (INIS)

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.

    1994-01-01

    The risk for liver disease from internally deposited beta-emitting radionuclides is unknown because there are no human populations exposed to hepatotropic beta-emitting radionuclides available for study. In this report, we discuss the hepatic lesion in dogs exposed to a beta-emitting radionuclide, 144 CeCl 3 , and held for their life spans

  5. 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.)

  6. Dose-effect studies with inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    Data are presented for all dogs employed in current life-span dose effect studies with inhaled 239 PuO 2 , and 239 Pu nitrate. Information is presented on the estimated initial alveolar deposition, based on external thorax counts and on estimated lung weights at time of exposure. Information is also provided on the current interpretation of the most prominent clinical-pathological features associated with the death of animals

  7. Ontogeny of the granulocyte/macrophage progenitor cell (GM-CFC) pools in the beagle.

    Science.gov (United States)

    Nothdurft, W; Braasch, E; Calvo, W; Prümmer, O; Carbonell, F; Grilli, G; Fliedner, T M

    1984-04-01

    The pattern of development of the granulocyte/macrophage progenitor cell (GM-CFC) pools in the course of canine ontogeny was studied by means of the agar culture technique. Colony formation was stimulated by colony stimulating activity (CSA) in serum from lethally irradiated dogs in combination with erythrocyte-depleted peripheral blood leukocytes from normal adult dogs. The colonies thus obtained in cultures from the different organs were in general large (estimated maximum 50 000 cells) and consisted predominantly of mononucleated macrophages, suggesting that, in these studies, a progenitor cell with high proliferative potential (HPP-CFC) has been monitored. In the yolk sac, a transitory GM-CFC pool became established between day 23 and day 48 of gestation, reaching maximum numbers of approximately 41 X 10(3) per organ on days 36/37. At the same time the GM-CFC concentration in blood collected from the heart also reached a maximum of about 31 X 10(3)/ml, indicating its carrier function for the migration of GM-CFC. In the liver a quasi-exponential increase in the GM-CFC numbers took place between days 36/37 and days 57 to 59 when a total of about 15.2 X 10(6) was found but thereafter and up to day 4 post partum the GM-CFC numbers decreased by almost two orders of magnitude. A continuous increase in the GM-CFC numbers was found in the spleen between day 42 of gestation and day 4 post partum when a maximum of 5.1 X 10(6) to 8.7 X 10(6) was reached. In contrast to the GM-CFC numbers in the liver, the splenic GM-CFC dropped only by 50% of peak values when the dogs reached adulthood. The bone marrow always had the highest incidence of GM-CFC, the concentration per 10(6) cells being 18.7 X 10(3)/10(6) cells on days 45/46, the earliest time point at which cultures could be set up. The absolute GM-CFC numbers in the two femora increased continuously between days 45/46 and day 4 post partum in parallel with the growth of the bones. In the thymus a relatively small population of GM-CFC developed between days 42 and 48 of gestation that was kept quite constant at average numbers between 13 X 10(3) and 30 X 10(3) up to day 4 post partum.

  8. Evaluation of the Inhalation Toxicology Research Institute beagle dog closed breeding colony: a progress report

    International Nuclear Information System (INIS)

    Lustgarten, C.S.; Hobbs, C.H.; Muggenburg, B.A.; Benjamin, S.A.; Slauson, D.O.; Hahn, F.F.

    1974-01-01

    Since early 1968, a closed breeding colony has been in operation at the Inhalation Toxicology Research Institute to produce experimental dogs for inhalation toxicology studies and to replace colony breeding stock for producing dogs with a stable gene pool. From March 1, 1968 through July 15, 1974, 123 bitches were bred 613 times, resulting in 540 litters and 2809 puppies: a conception rate for this period of 88.9 percent. An average of 3.74 pups survived to one year of age. (U.S.)

  9. Effects of hyperbaric oxygen treatment on healing of maxillary distraction osteogenesis in beagle dogs

    International Nuclear Information System (INIS)

    Kudoh, Atsuo

    2008-01-01

    Distraction osteogenesis has been widely used even in the craniofacial region. A long fixation time during the consolidation period, however, is a major clinical disadvantage. Hyperbaric oxygen (HBO) has been used to improve healing in ischemic wounds. We have recently started applying hyperbaric oxygen to cleft palate patients after maxillary distraction, but there is little basic evidence. We hypothesized that hyperbaric oxygen would enhance the healing of distraction osteogenesis in the cleft palate model in dogs. A bony segment including a canine was transported proximally into an artificial bone defect in the left palate. Three dogs were treated with hyperbaric oxygen for 20 days just after the distraction and three other dogs underwent only the distraction process (control group). Blood flow of the canine pulp in the bone segment was monitored using a laser Doppler flowmeter throughout the experiment. All the dogs were sacrificed on day 100, and radiological analysis using peripheral quantitative CT and histomorphometric evaluations were performed. Blood flow in the HBO-treated group recovered to the original level about 30 days faster than in the control group (p<0.05). Cortical bone mineral density was significantly higher at the distraction site in the HBO-treated group than in the control group (p<0.05). The histomorphometric analysis revealed that the newly formed bone area was also larger in the HBO-treated group than in the control group (p<0.05). These results suggest that hyperbaric oxygen treatment could be useful for early removal of the distraction device in distraction osteogenesis. (author)

  10. [Effects of hyperbaric oxygen treatment on healing of maxillary distraction osteogenesis in beagle dogs].

    Science.gov (United States)

    Kudoh, Atsuo

    2008-03-01

    Distraction osteogenesis has been widely used even in the craniofacial region. A long fixation time during the consolidation period, however, is a major clinical disadvantage. Hyperbaric oxygen (HBO) has been used to improve healing in ischemic wounds. We have recently started applying hyperbaric oxygen to cleft palate patients after maxillary distraction, but there is little basic evidence. We hypothesized that hyperbaric oxygen would enhance the healing of distraction osteogenesis in the cleft palate model in dogs. A bony segment including a canine was transported proximally into an artificial bone defect in the left palate. Three dogs were treated with hyperbaric oxygen for 20 days just after the distraction and three other dogs underwent only the distraction process (control group). Blood flow of the canine pulp in the bone segment was monitored using a laser Doppler flowmeter throughout the experiment. All the dogs were sacrificed on day 100, and radiological analysis using peripheral quantitative CT and histomorphometric evaluations were performed. Blood flow in the HBO-treated group recovered to the original level about 30 days faster than in the control group (p<0.05). Cortical bone mineral density was significantly higher at the distraction site in the HBO-treated group than in the control group (p<0.05). The histomorphometric analysis revealed that the newly formed bone area was also larger in the HBO-treated group than in the control group (p<0.05). These results suggest that hyperbaric oxygen treatment could be useful for early removal of the distraction device in distraction osteogenesis.

  11. Toxicological study of the hepatotherapeutic herbal formula, Chunggan extract, in beagle dogs

    Institute of Scientific and Technical Information of China (English)

    Woo-Jin Choi; Hwa-Seung Yoo; Yeon-Weol Lee; Chang-Gue Son; Jang-Woo Shin; Jin-Young Son; Dong-Seok Seo; Hark-Soo Park; Seung-Hyun Han; Ha-Jung Sung; Jung-Hyo Cho; Chong-Kwan Cho

    2006-01-01

    AIM: To evaluate the pharmaceutical safety of a Chinese herbal formula, Chunggan extract (CGX), traditionally prescribed as a hepatotherapeutic drug via systemic acute and subacute toxicological study.METHODS: Twenty male dogs and 20 female dogs were fed doses 50 times and 4 times greater than the clinically-recommended drug dosages in an acute and a subacute toxicological study, respectively. Adverse effects were examined by comparing the differences between normal and drug-administered groups using clinical signs, necropsies, histopathologic findings, haematology,urinalysis, and biochemical analysis.RESULTS: In the acute study no change in the body weight, diarrhoea, apetite, mortality rate and histopathology of major organs was observed in male or female dogs with a single administration of CGX at 5 g/kg. No drug-induced abnormalities at analysis of histopathology,haematology, urinalysis, and biochemistry were found with any dose of this drug.CONCLUSION: CGX is supposed to be very safe when used in a clinical application with a wide therapeutic index.

  12. Comparative pathogenesis of radium-induced intracortical bone lesions in humans and beagles

    International Nuclear Information System (INIS)

    Pool, R.R.; Morgan, J.P.; Parks, N.J.; Farnham, J.E.; Littman, M.S.

    1982-01-01

    An interlaboratory research team from our Laboratory and the Center for Human Radiobiology at Argonne National Laboratory has performed an initial comparison of intracortical lesions in the long bones of dog and man following chronic radium deposition in the skeleton. The sequential radiographic appearance and morphology of radiation osteodystrophy is discussed. The role of osteodystrohy in the evaluation of bone tumors in the dog is examined

  13. Boron biodistribution in Beagles after intravenous infusion of 4-dihydroxyborylphenylalanine-fructose complex

    International Nuclear Information System (INIS)

    Kulvik, M.E.; Vaehaetalo, J.K.; Benczik, J.; Snellman, M.; Laakso, J.; Hermans, R.; Jaerviluoma, E.; Rasilainen, M.; Faerkkilae, M.; Kallio, M.E.

    2004-01-01

    Boron biodistribution after intravenous infusion of 4-dihydroxyborylphenylalanine-fructose (BPA-F) complex was investigated in six dogs. Blood samples were evaluated during and following doses of 205 and 250 mg/kgbw BPA in a 30 min infusion, and 500 mg/kgbw in a 1 h infusion. Samples from whole blood, urine, brain and other organs were analysed for boron content after varying times following the onset of infusion. The whole blood boron concentrations declined from 27 to 8.4 ppm over the period of 39-165 min after the onset of infusion and the levels increased from 1.9 to 12 ppm in the grey matter of the brain over the same period. The boron concentrations in whole blood decreased steadily, whereas the boron values in brain tissue rose steadily with time. It was concluded that whole blood boron concentrations do not seem to reflect accurately the boron concentration in brain tissue at respective time points

  14. PULMONARY IMMUNITY TO RAGWEED IN A BEAGLE DOG MODEL OF ALLERGIC ASTHMA. (R826442)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  15. Disposition of 238Pu(NO3)4 following inhalation by beagle dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.; Cannon, W.C.; Schirmer, R.E.; Stevens, D.L. Jr.

    1979-01-01

    Twelve dogs were given a single inhalation exposure to 238 Pu(NO 3 ) 4 to study deposition and translocation up to 1 yr. Preliminary data suggest a greater and more rapid translocation of 238 Pu(NO 3 ) 4 to bone and liver than was observed for 239 Pu(NO 3 ) 4

  16. Dose-response relationships for bone tumors in beagles exposed to 226Ra and 90Sr

    International Nuclear Information System (INIS)

    Raabe, O.G.; Parks, N.J.; Book, S.A.

    1981-01-01

    385 dogs were exposed to 90 Sr in food from mid-gestation to 540 days of age. 243 young adult dogs were given eight fortnightly injections of 226 Ra. Comparison was made with available mouse and human 226 Ra bone tumor data. The major findings were: a) the occurrence of bone tumor related deaths was much less for 90 Sr than for 226 Ra exposed dogs. b) RBE for bone tumors from 90 Sr-Y varied as a function of average dose rate to bone. c) people require 10 times as long as mice and 3.6 times as long as dogs to develop 226 Ra-induced bone tumors at a given skeletal dose rate. d) based on the results, a practical threshold for bone cancer from 226 Ra was estimated to exist at cumulative doses of about 50-110 rad for dogs, mice and people. (author)

  17. Toxicity of 144Ce inhaled in a relatively insoluble form by aged Beagle dogs. VII

    International Nuclear Information System (INIS)

    Hahn, F.F.; Hanika-Rebar, C.; Boecker, B.B.; McClellan, R.O.; Pickrell, J.A.

    1978-01-01

    The toxicity of 144 Ce inhaled in fused aluminosilicate particles by 8- 10.5-year-old dogs is being investigated to provide information on age-related differences in the response of older members of the human population to accidental inhalation of radioactive aerosols. These data on aged dogs will be compared to the results of similar studies of dogs exposed at approximately 3 months or 12 to 14 months of age. Six blocks of five female dogs each have been divided into four exposure levels with mean initial lung burdens of 7.2, 14, 28, and 57 μCi 144 Ce/kg body weight. Six blocks of four male dogs each have been divided into three exposure levels with mean initial lung burdens of 7.2, 14, and 28 μCi 144 Ce/kg body weight. Controls in each block were exposed to fused aluminosilicate particles containing stable cerium. Nineteen dogs with initial lung burdens ranging from 14 to 75 μCi 144 Ce/kg body weight and cumulative doses to lung of from 20,000 to 74,000 rads have died or were euthanized 197 to 1849 days after exposure with clinicopathologic findings of radiation pneumonitis and pulmonary fibrosis. Eight control dogs have died. Pulmonary retention of the inhaled 144 Ce was similar to that observed previously in dogs exposed at 18 to 22 months of age in a radiation dose pattern study. Serial observations are continuing on the nine surviving 144 Ce-exposed and four control dogs

  18. Toxicity of 144Ce inhaled in a relatively insoluble form by aged beagle dogs. VI

    International Nuclear Information System (INIS)

    Hahn, F.F.; Hanika-Rebar, C.; Boecker, B.B.; Hobbs, C.H.; McClellan, R.O.; Pickrell, J.A.

    1977-01-01

    The toxicity of 144 Ce inhaled in fused aluminosilicate particles by 8 to 10.5-year-old dogs is being investigated to provide information on age-related differences in the response of older members of the human population to accidental inhalation of radioactive aerosols. These data on aged dogs will be compared to the results of similar studies of dogs exposed at approximately 3 months or 12 to 14 months of age. Six blocks of five female dogs each have been divided into four exposure levels with mean initial lung burdens of 7.2, 14, 28 and 57 μCi 144 Ce/kg body weight. Six blocks of four male dogs each have been divided into three exposure levels with mean initial lung burdens of 7.2, 14 and 28 μCi 144 Ce/kg body weight. Controls in each block were exposed to fused aluminosilicate particles containing stable cerium. Eighteen dogs with initial lung burdens ranging from 14 to 75 μCi 144 Ce/kg body weight and cumulative doses to lung of from 22,000 to 74,000 rads have died or were euthanized 197 to 1207 days after exposure with clinicopathologic findings of radiation pneumonitis and pulmonary fibrosis

  19. Summary of dosimetry, pathology, and dose response for bone sarcomas in beagles injected with radium-226

    International Nuclear Information System (INIS)

    Wrenn, M.E.; Taylor, G.N.; Stevens, W.

    1986-01-01

    In the completed 226 Ra portion of a 30-year-long experiment to determine the relative radiotoxicity of injected 226 Ra and 239 Pu, 42 of 116 animals injected with 226 Ra developed 63 bone sarcomas; none were observed in 44 controls. Average alpha plus beta dose to the skeleton to death was calculated on the basis of mathematical functions developed from sequential measurements of radium and radon retention in each dog. Bone sarcomas were identified radiographically or clinically, with subsequent histopathological confirmation and classification. Most primary bone tumors were classified as osteosarcomas if osteoid arose from a malignant stroma. The dose-response curve over the six lowest injected dose levels fits well to a linear, no-threshold, least squares fit, through a control incidence of 0.8%, and with a slope of 0.042% incidence per rad. 19 refs., 5 figs., 2 tabs

  20. Toxicity of 144Ce inhaled in a relatively insoluble form by aged Beagle dogs. VIII

    International Nuclear Information System (INIS)

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

    1979-01-01

    The toxicity of relatively insoluble 144 Ce inhaled by 8- to 10.5-year-old dogs is being investigated to provide information on age-related differences in the response of dogs to lung burdens of this fission product. These data on aged dogs will be compared to the results of similar studies of dogs exposed at approximately 3 months or 12 to 14 months of age. Forty-two dogs were exposed, nose only, to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 2.2 to 75 μCi/kg body weight and 12 control dogs were exposed to nonradioactive fused aluminosilicate particles. To date, 37 dogs have died or were euthanized 197 to 2375 days after inhalation of 144 Ce. The prominent findings were radiation pneumonitis in 19 dogs that died at early times with cumulative doses to lung of 20 000 to 74 000 rads and neoplastic disease in six of 14 dogs that died 943 days after exposure or later. Pulmonary tumors were found in four of these dogs. However, only one of these tumors killed the dog. No hemangiosarcomas have been observed in this study. This result is in contrast to the results with immature or young adult dogs exposed to 144 Ce. The difference may be a dose-related phenomenon since dogs which developed hemangiosarconomas had greater initial lung burdens of 144 Ce. Aged dogs with similar burdens died at earlier times with radiation pneumonitis. Observations are continuing on the five surviving 144 Ce-exposed and four control dogs

  1. Biological effects in beagle dogs of inhaled radon daughters, uranium ore dust, and cigarette smoke

    International Nuclear Information System (INIS)

    Palmer, R.F.; Filipy, R.E.; Stuart, B.O.; Hackett, P.; Ragan, H.A.; McDonald, K.E.

    1975-01-01

    After 5 years of daily inhalation exposures to 600 WL radon daughters plus uranium ore dust and/or cigarette smoking, observed pulmonary lesions include macrophage proliferation, septal fibrosis, epithelial hyperplasia, emphysema, endothelial proliferation, and bronchiolar-alveolar epithelial changes involving multiple foci of squamous metaplasia with atypia. Epithelial neoplasms were found in the respiratory tracts of three dogs. (U.S.)

  2. Affecting mortality of whole-body gamma-irradiated Beagle dogs

    International Nuclear Information System (INIS)

    Dostal, M.; Kuna, P.; Neruda, O.; Petyrek, P.; Simsa, J.; Vavrova, J.; Skopec, F.

    1982-01-01

    The efficacy is compared of radioprotection and the complex treatment of acute radiation syndrome in laboratory dogs. One group of dogs was administered an injection of radioprotectives, the other was a control group. The treated group was administered vitamins and antibiotics in injections after the irradiation. It was found that complex treatment between days 1 and 28 after irradiation is relatively effective. In the treated dogs radioprotection does not significantly influence survival or even reduces survival. (M.D.)

  3. Oleic acid-associated bronchiolitis obliterans-organizing pneumonia in beagle dogs.

    Science.gov (United States)

    Li, X; Botts, S; Morton, D; Knickerbocker, M J; Adler, R

    2006-03-01

    Accidental intra-airway exposure of dogs with pure oleic acid produced bronchiolitis obliterans and bronchopneumonia. Pulmonary changes included multifocal to coalescing necrosis of bronchioles and adjacent alveoli, hemorrhage, inflammation, and exudation of fibrin. Hyperplasia of bronchiolar and alveolar epithelial cells and proliferation of loose fibrovascular connective tissue formed polyps or plugs of variable size and shape. Polyps in the airways primarily consisted of fibroblasts with loose or myxoid stroma and were variably covered with attenuated epithelial cells. Some polyps had prominent vasculature, mixed inflammatory cell infiltration, and/or necrosis. Polyps or plugs variably effaced bronchioles and adjacent alveoli. The changes closely resembled human bronchiolitis obliterans-organizing pneumonia (BOOP). Controlled intra-airway delivery of oleic acid in dogs may be a potential animal model of obstructive pulmonary diseases such as BOOP or bronchiolitis obliterans.

  4. Administration of cyclosporine by inhalation: A feasibility study in Beagle dogs

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Hoover, M.D.; Haley, P.J.; Snipes, M.B.; Wolff, R.K.; Yeh, H.C.; Griffith, B.P.; Burckart, J.; Mauderly, J.L.

    1988-01-01

    Oral cyclosporine inhibits the primary,but-not the secondary immune responses in the lung. These findings suggest that the local administration of cyclosporine by inhalation could be a useful tool for increasing our understanding of lung immunity. Five dogs were each treated with inhaled, oral and intravenous cyclosporine, aerosol vehicle (ethyl alcohol), and no treatment, over a 5-wk period. One treatment per week was given to each dog. A radiolabel, 99m Tc was included in the cyclosporine aerosol to allow visualization of lung distribution of the aerosol. Blood plasma concentrations of cyclosporine were approximately the same at 4 h and were essentially cleared by 24 h for all routes of administration. Aerosol distribution in the lung appeared uniform, based on 99m Tc scintigrams. In a second study, two dogs inhaled cyclosporine once a day for five days, two dogs inhaled the aerosol vehicle, and one dog was not treated. No evidence of acute lung injury, based on cell counts, total protein, alkaline phosphatase, or lactic dehydrogenase levels in the bronchoalveolar lavage fluid, was found at 24 h after one or five administrations of cyclosporine. These data indicate that cyclosporine administered by aerosol either once or five times was distributed throughout the lung and was absorbed into the blood without producing an acute inflammatory reaction in the lung. Our results suggest that cyclosporine may be safely given by inhalation for studies of local immune responses in the lung. (author)

  5. Increased Serum and Urinary Oxytocin Concentrations after Nasal Administration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Andrea Temesi

    2017-09-01

    Full Text Available In recent years more and more studies have revealed the effect of extraneous oxytocin on the social behavior of dogs. The distribution of administered oxytocin in different physiologically relevant compartments is important because this knowledge forms the basis for the timing of behavior tests after the administration. Most behavioral studies rely on the non-invasive intranasal application of oxytocin. The aim of this study was to determine the time course of intranasal administered oxytocin secretion into blood and urine and also establish a connection between intranasal received oxytocin and urinary cortisol in dogs. In our experiment, four dogs received three puffs, 12 IU intranasal oxytocin treatment, two dogs received three puffs intranasal placebo treatment. Blood and urine samples were collected immediately prior to the administration then regularly during 4 h. After nasal oxytocin application, the serum oxytocin concentration increased, reached a maximum 15 min after the treatment and then rapidly returned to baseline levels 45 min later. The peak urinary oxytocin concentration occurred between 45 and 60 min after administration and returned to baseline levels slowly. We found considerable differences among individuals in the secretion of oxytocin in both the serum and the urinary oxytocin concentration measurements. Our results confirm that intranasally administered oxytocin passes into the blood stream. The time course of intranasally administered oxytocin secretion is similar to the time course of intravenously administered oxytocin secretion, and the peak values are also similar in both the serum and the urinary oxytocin concentration measurements, although there are large individual differences.

  6. Progressive glomerulosclerosis and renal failure following perinatal gamma radiation in the beagle

    International Nuclear Information System (INIS)

    Jaenke, R.S.; Phemister, R.D.; Norrdin, R.W.

    1980-01-01

    The renal effects of whole body irradiation in the perinatal period were studied in the dog. Ninety-three dogs received a single sublethal exposure in the range of 270 to 435 R in either late gestation (55 days postcoitus) or early postnatal life (2 days postpartum) and were sacrificed at 70 days, 2, or 4 years of age. Early renal lesions in 70-day-old irradiated dogs were characterized by arrested glomerular maturation and degeneration resulting in reduced functional renal mass. Mature glomeruli exhibited mesangial proliferation. At 2 and 4 years of age, surviving irradiated dogs exhibited sever renal disease associated with progressive glomerular damage which was characterized by mesangial proliferation and compression of capillary lumina, epithelial degeneration and focal capsular adhesions, and ultimately obliterative glomerulosclerosis. Twenty-one of the 93 irradiated dogs died in renal failure before 4 years of age with advanced glomerulosclerosis. The phatogenesis of this progressive renal lesion may be related to the interaction of three specific factors. These include (1) the effect of direct radiation damage to mature kidney components; (2) the loss of outer cortical nephrons resulting in increased work load of the surviving nephrons; and (3) the effect of compensatory hypertrophy related to the loss of renal parenchyma as the rapid growth rates associated with kidney maturation

  7. In vitro cell-mediated immunity studies of plutonium-exposed beagle dogs

    International Nuclear Information System (INIS)

    Morris, J.E.; Graham, T.; Park, J.F.

    1980-01-01

    Mitogen-induced activation was measured in spleen and mesenteric lymph node cell preparations from dogs exposed to a single inhalation exposure of plutonium oxide ( 238 Pu or 239 Pu). Reduced stimulation indices of splenic lymphocytes from exposed animals suggest that a reduction in lymphocyte function has occurred in this tissue. No apparent reduction in mitogen stimulation indices was observed in mesenteric lymph node cultures

  8. Rasberry Pi and BeagleBones: Evaluating a cost-effective GPS ...

    African Journals Online (AJOL)

    ... main purpose of this requirement is to ensure that all employees are aware and can take all the necessary precautions against un-planned breakthroughs, falls of ground and subsidence. In the case where mines are mining through abandoned workings in order to remove remnant pillars and previously unmined reserves ...

  9. The Beagle Channel Dispute between Argentina and Chile: An Historical Analysis

    Science.gov (United States)

    1985-11-22

    and the desire for a more independent foreign policy contributed significantly to the overwhelming electoral victories of the 7 Peronists in 1973...mencionada gentincts qua naveguen slmultsnoamente derecho do pt o ajc~oaJsrga *ARTICULO 381 ats sellata en to Canta NI III ad junta. a n Is ruta desenta...Tecad. biqeqollc e eoceure a Iu&%sLttSes normaas d l derecho intenomu-od aqu s saf"I&s-vd de Magallanies ysealos no. Durant@ eI Paso dacleos bisques a

  10. The induction of micronuclei in X-irradiated Beagle dog lymphocytes

    International Nuclear Information System (INIS)

    Rithidech, K.; Lozano, D.; Brooks, A.L.

    1988-01-01

    We developed a simple, sensitive, and reproducible method using the micronucleus assay in dog blood lymphocytes for detecting genotoxic effects of ionizing radiation. Micronuclei (MM) are expressed in cells that have undergone 1 cell division. Thus, it was important to determine the optimum culture condition and sampling time to obtain a maximum number of such cells. To identify cells that have divided, cytochalasin B was added to block cytokinesis. Cells were harvested at 72, 76, or 94 h after incubation with different concentrations of phytohaemagglutinin (PHA) 15 or 16. After optimizing the culture time and PHA concentration, the system was calibrated by evaluating the dose response for the induction of MN by X rays. Blood samples were drawn, X-irradiated (0.0, 0.5, 1.0, 2.0, or 4.0 Gy), grown in optimum culture medium, harvested at 94 h after incubation, and the frequency of MN analyzed in binucleated cells. The dose-response relationship was fit by a quadratic model; micronuclei/binucleated cell = 0.017 + 0.046D + 0.0093D 2 , where D = dose. The MN assay in dog blood lymphocytes provides a sensitive and reliable technique for measuring genotoxic damage in a large animal model. The MN assay will be very useful for evaluating genotoxic effects of hazardous agents after both chronic and acute exposures and for estimating radiation dose. (author)

  11. Effect of radiation on gestation periods in dams of Segment III beagles

    International Nuclear Information System (INIS)

    Angleton, G.M.; Lee, A.C.

    1981-01-01

    The lengths of the gestation periods for bitches whose offspring were potentially assignable to Segment III of the Long-Term Study were not affected by radiation exposure (P = .998). Other factors were found to significantly correlate with the duration of the gestation periods, including the length of the first gestation period (P < .001), size of first litter (P = .175), the average environmental temperature during pregnancy (P = .055) and the size of the second litter

  12. Mammary gland cancer in a colony of beagle dogs: Inheritance, and p53 ampersand erbB-2 expression

    International Nuclear Information System (INIS)

    Kelly, G.; Griffith, W.C.; Muggenburg, Tierney, L.A.; Lechner, J.F.; Hahn, F.F.

    1994-01-01

    One American woman in nine will be diagnosed with breast cancer in her lifetime. This somber statistic translates into 182,000 new diagnoses and 46,000 deaths per year. Efforts to decrease breast cancer mortality have focused on early detection and improved treatment. Such efforts would be facilitated by the identification of individuals predisposed to the disease. A family history of the disease can increase a woman's risk for developing breast cancer by two- to six-fold. Inheritance of this disease is consistent with at least one susceptibility locus on chromosome 17 (17q12-21) with incomplete penetrance. However, other mechanisms of inherited susceptibility also contribute to the high incidence of the disease. The purpose of the present study was to characterize familial pattern of mammary cancer development in the dog colony. In addition, the expression of the p53 tumor supressor gene and c-erbB2 (p185 erbB2 ) oncogene proteins, which are frequently altered in human breast cancer, were examined in dogs susceptible and resistant to mammary cancer

  13. Distribution patterns of inhaled polydisperse 147Pm fused clay particles in the beagle dog thorax with and without lavage therapy

    International Nuclear Information System (INIS)

    Snipes, M.B.; Runkle, G.E.; Muggenburg, B.A.; Hulbert, A.J.

    1974-01-01

    An experiment was designed to examine dispersion and retention patterns for polydisperse aerosols of fused montmorillonite clay particles labeled with 147 Pm. Fourteen dogs were exposed and scheduled for serial sacrifice at 0, 8, 64, and 365 days post-exposure. Experimental procedures included producing a series of slices through the thorax at approximately 1 cm intervals and obtaining a series of autoradiograms and 35 mm color transparencies for each set of thorax slices to define (1) the average doses to lung, lung lobes, and other tissues of interest, (2) the number of hot spots of activity per unit volume in the lung, and (3) a size distribution for these hot spots. Comparable data will be analyzed for 4 additional dogs subjected to lavage therapy to remove a portion of the burden from either the left or right lung using 1 or 5 treatments. Totals of 31 to 71 percent of the initial left or right lung burden were removed by the lavage therapy but only preliminary observations are completed on the autoradiography data. (U.S.)

  14. Incidence of urinary bladder tumors in the control Beagle dog population at the Inhalation Toxicology Research Institute

    International Nuclear Information System (INIS)

    King, R.R.; Kusewitt, D.F.; Hahn, F.F.; Muggenburg, B.A.

    1982-01-01

    The report reviews the incidence and types of urinary bladder tumors in 94 dogs that have died in a population of 250 control dogs (median life span 14.0 years). Six bladder tumors, two papillomas and four transitional cell carcinomas, were found. The cumulative incidence for bladder tumors was 10.5 percent at 16 to 19 years of age; this was a 20 percent age-specific incidence

  15. ULTRASONOGRAPHIC ELASTOGRAPHY OF THE LIVER, SPLEEN, KIDNEYS, AND PROSTATE IN CLINICALLY NOR-MAL BEAGLE DOGS [corrected].

    Science.gov (United States)

    Jeon, Sunghoon; Lee, Gahyun; Lee, Sang-Kwon; Kim, Hyunwoo; Yu, Dohyeon; Choi, Jihye

    2015-01-01

    Standard ultrasonography is often insensitive for distinguishing normal vs. diseased states for canine abdominal organs. Ultrasonographic elastography is a new technique that is becoming increasingly available and may help to improve sensitivity. This study evaluated the feasibility, repeatability, and reproducibility of strain elastography of the liver, spleen, kidneys, and prostate in healthy dogs and described the elasticity of each organ using strain values and strain ratios. The reproducibility of strain elastography was excellent, and intraobserver repeatability was moderate to excellent. The strain value of each organ was not significantly different among dogs (liver = 143.38 ± 7.41, spleen = 141.04 ± 9.03, left renal cortex = 141.26 ± 7.50, right renal cortex = 145.80 ± 7.79, and prostate = 135.46 ± 5.80), except for the renal medulla (left = 51.19 ± 4.54 and right = 51.93 ± 5.09) (P spleen, renal cortex, and prostate were similar with no significant difference (liver = 10.20 ± 1.47, spleen = 8.40 ± 1.53, left renal cortex = 9.62 ± 1.56, right renal cortex = 8.29 ± 1.63, and prostate = 8.20 ± 1.21), except for the renal medulla (left = 3.48 ± 0.68 and right = 2.95 ± 0.63) (P spleen, kidneys, and prostate. This study provides basic information for strain values and strain ratios for the liver, spleen, kidneys, and prostate in clinically normal dogs. © 2015 American College of Veterinary Radiology.

  16. 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.

  17. Population structure and maturity stages of Fritillaria borealis (Appendicularia, Tunicata: seasonal cycle in Ushuaia Bay (Beagle Channel

    Directory of Open Access Journals (Sweden)

    María Laura Presta

    2015-09-01

    Full Text Available AbstractFritillaria borealis is a cosmopolitan species, very frequent in sub-antarctic and antarctic waters. The objective of this paper was to analyze its size structure and maturity stages at two sites in Ushuaia Bay: a coastal site exposed to anthropogenic pressure (E1 and a reference site (E2 located in the external zone of the bay. Zooplankton was collected during the 2012 seasonal cycle. The sampling method involved the use of a 67 µm-mesh net. Appendicularians were classified in four maturity stages: I undifferentiated gonads, II testis and ovary differentiated, III expanded testis, IV discharged testis, expanded ovary. Our results showed that the highest densities of F. borealisoccurred in spring and summer at both sites; coinciding with high values of chlorophyll-a. The percentage of juveniles (I and II exhibited a spatial and temporal pattern similar to that observed for chlorophyll-a values. During spring-summer, juveniles and mature specimens (III and IV showed a greater gonadal development than those individuals found in autumn-winter. In conclusion, the mismatching in the population structure and the pattern of densities of F. borealis between coastal and external zones would suggest the existence of two sub-populations susceptible to the influence of the anthropogenic impact in the bay.

  18. UPLC–MS/MS for the determination of azilsartan in beagle dog plasma and its application in a pharmacokinetics study

    Directory of Open Access Journals (Sweden)

    Cheng Gong

    2015-06-01

    Full Text Available The purpose of the study is to develop an ultra performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS to determinate the concentration of azilsartan in the dog plasma. After precipitated by methanol, the plasma sample containing azilsartan and diazepam (internal standard, IS was determined by UPLC–MS/MS. The mobile phase consisted of acetonitrile-water was pumped at a flow rate of 0.3 ml/min in gradient elution. Kinetex 2.6 μ XB-C18 column (50 × 2.1 mm, 100 Å; Phenomenex, USA were used for LC separations. The column temperature was 30 °C and the injection volume was 5 μl. The electrospray ionization (ESI and multiple reaction monitoring (MRM were applied at the transitions of m/z 457 → 279 (azilsartan and m/z 285 → 193 (diazepam, respectively. The developed method was identified a good linearity over a concentration range of 2.5–5000 ng/ml. The lower limit of quantitation (LLOQ was 2.5 ng/ml. The intra-day and inter-day precision (relative standard deviation, RSD% were less than 10% and accuracy (relative error, RE % was less than 5% at three quality control levels. The extraction recovery of azilsartan at three quality control levels were 82.41 ± 0.68%, 98.66 ± 11.00%, 102.43 ± 0.82%. And the recovery for IS (100 ng/ml was 91.75 ± 0.54%. A validated UPLC–MS/MS method was firstly developed for the quantification of azilsartan in dog plasma and it was applied to the pharmacokinetics study.

  19. Safety studies on intravenous administration of oncolytic recombinant vesicular stomatitis virus in purpose-bred beagle dogs.

    Science.gov (United States)

    LeBlanc, Amy K; Naik, Shruthi; Galyon, Gina D; Jenks, Nathan; Steele, Mike; Peng, Kah-Whye; Federspiel, Mark J; Donnell, Robert; Russell, Stephen J

    2013-12-01

    VSV-IFNβ-NIS is a novel recombinant oncolytic vesicular stomatitis virus (VSV) with documented efficacy and safety in preclinical murine models of cancer. To facilitate clinical translation of this promising oncolytic therapy in patients with disseminated cancer, we are utilizing a comparative oncology approach to gather data describing the safety and efficacy of systemic VSV-IFNβ-NIS administration in dogs with naturally occurring cancer. In support of th