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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. Penis Allotransplantation in Beagle Dog

    Directory of Open Access Journals (Sweden)

    Yongbin Zhao

    2016-01-01

    Full Text Available 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.

  3. Mars Express releases Beagle 2

    Science.gov (United States)

    2003-12-01

    At 9:31 CET, the crucial sequence started to separate the Beagle 2 lander from Mars Express. As data from Mars Express confirm, the pyrotechnic device was fired to slowly release a loaded spring, which gently pushed Beagle 2 away from the mother spacecraft. An image from the onboard visual monitoring camera (VMC) showing the lander drifting away is expected to be available later today. Since the Beagle 2 lander has no propulsion system of its own, it had to be put on the correct course for its descent before it was released. For this reason, on 16 December the trajectory of the whole Mars Express spacecraft had to be adjusted to ensure that Beagle 2 would be on course to enter the atmosphere of Mars. This manoeuvre, called "retargeting'' was critical: if the entry angle is too steep, the lander could overheat and burn up in the atmosphere; if the angle is too shallow, the lander might skim like a pebble on the surface of a lake and miss its target. This fine targeting and today's release were crucial manoeuvres for which ESA's Ground Control Team at ESOC (European Space Operations Centre) had trained over the past several months. The next major milestone for Mars Express will be the manoeuvre to enter into orbit around Mars. This will happen at 3:52 CET on Christmas morning, when Beagle 2 is expected to land on the surface of Mars. "Good teamwork by everybody - ESA, industry and the Beagle 2 team - has got one more critical step accomplished. Mars, here comes Europe!" said David Southwood, ESA Director of Science.

  4. The Legacy of Beagle 2

    Science.gov (United States)

    Pillinger, Judith; Bridges, John; Sims, Mark; Clemmet, Jim; Wright, Ian

    2015-04-01

    The Beagle 2 lander spun off from the ESA Mars Express spacecraft on 19 December 2003 and headed off towards Isidis Planitia on Mars. The scheduled landing of the 60 kg lander was 6 days later on Christmas morning, 25 December. It is universally known that no signal was received from the lander and its fate remained unknown. What is not questioned is the impact that the mission, and not least its charismatic leaders headed by the late Professor Colin Pillinger, had on the general public of the UK, Europe and worldwide. More than a decade after Beagle 2 was last seen, we review the legacy of the mission on the public perception of the value of space exploration, economically, commercially and cultural, and look forward to an expanding programme. The spin off from Beagle 2 science and technology into terrestrial applications will be addressed as will the ongoing career destinations of many of the original team; both supporting the significance that the mission had on determining the future pathway of space science and exploration in Europe and beyond. The ongoing search for evidence that Beagle 2 did in fact land as planned on Mars will be addressed and images from Mars orbiting spacecraft assessed.

  5. 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.

  6. Lunar Beagle and Lunar Astrobiology

    Science.gov (United States)

    Gibson, Everett K.; Pillinger, Colin T.; Waugh, Lester J.

    2010-12-01

    The study of the elements and molecules of astrobiological interest on the Moon can be made with the Gas Analysis Package (GAP) and associated instruments developed for the Beagle 2 Mars Express Payload. The permanently shadowed polar regions of the Moon may offer a unique location for the "cold-trapping" of the light elements (i.e. H, C, N, O, etc.) and their simple compounds. Studies of the returned lunar samples have shown that lunar materials have undergone irradiation with the solar wind and adsorb volatiles from possible cometary and micrometeoroid impacts. The Beagle 2's analytical instrument package including the sample processing facility and the GAP mass spectrometer can provide vital isotopic information that can distinguish whether the lunar volatiles are indigenous to the moon, solar wind derived, cometary in origin or from meteoroids impacting on the Moon. As future Lunar Landers are being considered, the suite of instruments developed for the Mars Beagle 2 lander can be consider as the baseline for any lunar volatile or resource instrument package.

  7. UK and ESA announce Beagle 2 inquiry

    CERN Document Server

    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).

  8. Beagle-2 landing site atlas

    Science.gov (United States)

    Michael, G.; Chicarro, A.; Rodionova, J.; Shevchenko, V.; Ilukhina, J.; Kozlova, K.

    2003-04-01

    The Beagle-2 lander of the Mars Express mission will come to rest on the surface of Isidis Planitia in late December 2003 to carry out a range of geochemistry and exobiology experi-ments. We are compiling an atlas of the presently available data products pertinent to the landing site at 11.6N 90.75E, which is intended for distribution both as a printed and an electronic resource. The atlas will include Viking and MOC-WA image mosaics, and a catalogue of high-resolution im-ages from MOC and THEMIS with location maps. There will be various MOLA topography-based products: colour-scaled, contoured, and shaded maps, slope, and detrended relief. Simulated camera panoramas from various potential landing locations may assist in determining the spacecraft’s position. Other maps, both raw, and in composites with image mosa-ics, will cover TES thermal inertia and spectroscopy, and Odyssey gamma and neutron spectroscopy. Maps at the scale of the Isidis context will additionally cover geology, tem-perature cycles, and atmospheric circulation. Sample are shown below.

  9. Beagle 2: Mission to Mars - Current Status

    Science.gov (United States)

    Gibson, E. K., Jr.; Pillinger, C. T.; Wright, I. P.; Morgan, G. H.; Yau, D.; Stewart, J. L. C.; Leese, M. R.; Praine, I. J.; Sheridan, S.

    2004-01-01

    Beagle 2 is a 72 kg probe (with a 32 kg lander) developed in the United Kingdom for inclusion on the European Space Agency's 2003 Mars Express. Beagle 2 was launched on June 2, 2003 with Mars Express on a Soyuz-Fregat rocket from the Baikonur Cosmodrome in Kazakhstan. Beagle 2 landed on Mars on December 25th, 2003 in Isidis Planitia (approx. 10.7 N and 268.6 W), a large sedimentary basin that overlies the boundary between ancient highlands and northern plains. Isidis Planitia, the third largest impact basin on Mars, which is possibly filled with sediment deposited at the bottom of long-standing lakes or seas, offers an ideal environment for preserving traces of life. The team is awaiting signals from the Beagle 2 lander at the time when this abstract was written. Current status of the mission will be reported. Beagle 2 was developed to search for organic material and other volatiles on and below the surface of Mars in addition to the study of the inorganic chemistry and mineralogy. Several fundamental properties can be used to determine the existence of an active or past biology on any planet, Earth or Mars. Beagle 2's targets for investigation included: (a) The presence of water, or the existence of minerals deposited from water to show that water was present, even if only transiently; (b) The detection of carbonaceous debris, the remains of organisms that might have lived in water or were washed to a final resting place by the action of water; (c) The structure of organic matter, to demonstrate that it might have been synthesized for a biological purpose; (d) The recognition of isotopic fractionation between carbonaceous phases (organic vs inorganic carbon phases), a condition which on Earth suggests that life emerged nearly 4 billion years ago.

  10. 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.

  11. Beagle 2: Seeking the Signatures of Life on Mars

    Science.gov (United States)

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

    2003-01-01

    Beagle 2 is a 60 kg probe (with a 30 kg lander) developed in the United Kingdom for inclusion on the European Space Agency s 2003 Mars Express. Beagle 2 will deliver to the Martian surface a payload which consists of a high percentage of science instruments to landed spacecraft mass. Beagle 2 will be launched in June 2003 with Mars Express on a Soyuz-Fregat rocket from the Baikonur Cosmodrome in Kazakhstan. Beagle 2 will land on Mars in December 2003 in Isidis Planitia (approx. 11.5 deg.N and 275 deg.W), a large sedimentary basin that overlies the boundary between ancient highlands and northern plains. Isidis Planitia, the third largest basin on Mars, which is possibly filled with sediment deposited at the bottom of long-standing lakes or seas, offers an ideal environment for preserving traces of life. Beagle 2 is completed and undergoing integration with the Mars Express orbiter prior to launch.

  12. Modelling and interpreting spectral energy distributions of galaxies with BEAGLE

    Science.gov (United States)

    Chevallard, Jacopo; Charlot, Stéphane

    2016-10-01

    We present a new-generation tool to model and interpret spectral energy distributions (SEDs) of galaxies, which incorporates in a consistent way the production of radiation and its transfer through the interstellar and intergalactic media. This flexible tool, named BEAGLE (for BayEsian Analysis of GaLaxy sEds), allows one to build mock galaxy catalogues as well as to interpret any combination of photometric and spectroscopic galaxy observations in terms of physical parameters. The current version of the tool includes versatile modelling of the emission from stars and photoionized gas, attenuation by dust and accounting for different instrumental effects, such as spectroscopic flux calibration and line spread function. We show a first application of the BEAGLE tool to the interpretation of broad-band SEDs of a published sample of ˜ 10^4 galaxies at redshifts 0.1 ≲ z ≲ 8. We find that the constraints derived on photometric redshifts using this multipurpose tool are comparable to those obtained using public, dedicated photometric-redshift codes and quantify this result in a rigorous statistical way. We also show how the post-processing of BEAGLE output data with the PYTHON extension PYP-BEAGLE allows the characterization of systematic deviations between models and observations, in particular through posterior predictive checks. The modular design of the BEAGLE tool allows easy extensions to incorporate, for example, the absorption by neutral galactic and circumgalactic gas, and the emission from an active galactic nucleus, dust and shock-ionized gas. Information about public releases of the BEAGLE tool will be maintained on http://www.jacopochevallard.org/beagle.

  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. Incidencia de agenesia dental en perros Beagle. Resultados preliminares(Dental agenesis incidence in Beagle dogs. Preliminary results)

    OpenAIRE

    Rodríguez Sosa; Cabrera García, A; Domínguez López, HA; Soca Pérez, M; Purón Guzméli, CA; Macías Hernández, I; Gil Díaz, F; Aliaga Aleaga, Y; Guerrero Contreras, M; Acosta Berbes, A

    2011-01-01

    ResumenEn el presente trabajo se examinaron 49 perros Beagle procedentes del CENPALAB que fueron mantenidos bajo el mismo régimen de convivencia, alimentación y manejo en el Bioterio de la Facultad de Medicina “Victoria de Girón” tributarios todos a estudios de implantes dentales.AbstractForty-nine Beagle dogs coming from CENPALAB were maintained under the same coexistence, feeding and handling regime in the Bioterio of Medicine High School “Victoria de Girón” tributary to studies of dental i...

  15. Incidencia de agenesia dental en perros Beagle. Resultados preliminares(Dental agenesis incidence in Beagle dogs. Preliminary results

    Directory of Open Access Journals (Sweden)

    Rodríguez Sosa

    2011-11-01

    Full Text Available ResumenEn el presente trabajo se examinaron 49 perros Beagle procedentes del CENPALAB que fueron mantenidos bajo el mismo régimen de convivencia, alimentación y manejo en el Bioterio de la Facultad de Medicina “Victoria de Girón” tributarios todos a estudios de implantes dentales.AbstractForty-nine Beagle dogs coming from CENPALAB were maintained under the same coexistence, feeding and handling regime in the Bioterio of Medicine High School “Victoria de Girón” tributary to studies of dental implant all them.

  16. Introducing Students to Darwin via the Voyage of HMS "Beagle"

    Science.gov (United States)

    Swab, Janice C.

    2010-01-01

    I use the diary that Darwin wrote during the voyage of HMS Beagle and recent images of a few of the places he visited to illustrate some comparisons between Darwin's world and ours. For today's students, increasingly committed to environmental issues, this may be an especially promising way to introduce Darwin.

  17. 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).

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

    NARCIS (Netherlands)

    Böhl, M. 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 cons

  19. 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.

  20. Identification and in vitro derivation of spermatogonia in beagle testis.

    Directory of Open Access Journals (Sweden)

    Kyung Hoon Lee

    Full Text Available BACKGROUND: In vitro culture of spermatogonial stem cells (SSCs is important for exploration of SSCs self-renewal, differentiation, and manipulation. There are several reports on rodent SSC cultures; however, data on SSC cultures in domestic animals are limited. To provide basic scientific information on canine SSC cultures, we report canine testes development, and the development of spermatogonia-derived colonies (SDCs for in vitro cultures. METHODOLOGY/PRINCIPAL FINDINGS: Testes from 2-, 3-, and 12-month-old beagles were used for histology, immunohistochemistry, in vitro culture, immunocytochemistry, and PCR. Protein gene product 9.5 (PGP9.5-positive spermatogonia, both single and paired, were found to be abundant in the testes of 2-month-old beagles. stempro-34 and Dulbecco's modified Eagle medium with 5% fetal bovine serum provided as useful substrates for culture of SDCs, and fibroblast growth factor (FGF played a key role in colony formation. Colonies were positive for alkaline phosphatase and anti-PGP9.5 staining. The early spermatogonia and stem cell markers such as octamer binding protein 4 (Oct4, Nanog homeobox (Nanog, promyelocytic leukemia zinc finger (PLZF, PGP9.5, and GDNF family receptor alpha-1 (GFRα-1 were expressed in the colonies at higher levels than in the testis tissue. CONCLUSIONS: Testes of the 2-month-old beagles had abundant single and paired spermatogonia, which can be used for derivation of SDCs, and FGF was important for colony formation.

  1. 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.

  2. How do you Answer the Life on Mars Question? Use Multiple Small Landers like Beagle 2

    Science.gov (United States)

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

    2012-06-01

    Beagle 2 lander is a flight qualified scientific payload and it offers a unique suite of instruments which can offer answers to the life on Mars question. Using multiple Beagle 2 landers on Mars offers a low-cost and outstanding scientific option.

  3. Occurrence of mitral valve insufficiency in clinically healthy Beagle dogs.

    Science.gov (United States)

    Vörös, Károly; Szilvási, Viktória; Manczur, Ferenc; Máthé, Ákos; Reiczigel, Jenő; Nolte, Ingo; Hungerbühler, Stephan

    2015-12-01

    Chronic degenerative valve disease (CDVD) is the most common cardiac disease in dogs, usually resulting in mitral valve insufficiency (MVI). The goal of this study was to investigate the occurrence of MVI in clinically healthy Beagle populations. A total of 79 adult healthy Beagles (41 females and 38 males; age: 5.6 ± 2.7 years, range 1.4 to 11.7 years) were examined. The diagnosis of MVI was based on the detection of a systolic murmur heard above the mitral valve, and was confirmed by colour flow Doppler (CFD) echocardiography. Systolic mitral valve murmurs were detected in 20/79 dogs (25.3%), of them 11 males and 9 females with no statistically significant gender difference (P = 0.6059). The strength of the murmur on the semi-quantitative 0/6 scale yielded intensity grade 1/6 in 10 dogs, grade 2/6 in 4 dogs, and grade 3/6 in 6 dogs. Mild to moderate MVI was detected by CFD in all these 20 dogs with systolic murmurs. Of them, 17 dogs had mild and 3 demonstrated moderate MVI, showing 10-30% and 30-50% regurgitant jets compared to the size of the left atrium, respectively. The age of dogs with MVI was 7.1 ± 2.3 years, which was significantly different from that of dogs without MVI (5.1 ± 2.7 years, P = 0.0029). No significant differences in body weight (P = 0.1724) were found between dogs with MVI (13.8 ± 2.8 kg) and those without MVI (12.8 ± 3.0 kg). Mitral valve disease causing MVI is relatively common in Beagle dogs, just like in other small breed dogs reported in the literature.

  4. Pharmacokinetics and bioavailability study of neoline in Beagle dogs.

    Science.gov (United States)

    Gong, Xiao-hong; Zhao, Meng-jie; Yuan, An; Li, Yan; Xiong, Liang; Peng, Cheng; Li, Yun-xia

    2015-07-01

    This paper is aim to investigate the pharmacokinetics and absolute bioavailability of neoline in Beagle dogs, and provide a theoretical basis for further study. Ethyl acetate was used for liquid-liquid extracting after 10% ammonia alkalizing. The method of UPLC-Q-TOF-MS was established for the determination of neoline plasma concentrations. Beagle dogs were orally or intravenously administered with neoline for pharmacokinetic and absolute bioavailability study. Good linear relationship of neoline was found over the range of 0.1-4 mg x L(-1) (R2 = 0.9982) and 2-100 microg x L(-1) (R2 = 0.9945). Intra-and inter-day precision, expressed as the relativestandard (RSD) were less than 5.0%. Accuracy, expressed as the relative error (RE) was within 90.0%-115%. The recovery of neoline in dog plasma was more than 80%. After 6 mg x kg(-1) for ig and 1 mg x kg(-1) for iv administration of neoline, the main pharmacokinetic parameters were analyzed with Winnonlin software. t(1/2) were (313.88 +/- 63.18), (236.33 +/- 229.84) min, and AUC(0-infinity) were (58,027.40 +/- 14,132.69), (473,578.02 +/- 82,333.08) min x microg x L(-1) for ig and iv administration respectively. The absolute bioavail ability was (73.15 +/- 10.29) %. The method of UPLC-Q-TOF-MS described in the report was sensitive, reliable and specific, and suitable for pharmacokinetic study of neoline in Beagle dog. The high absolute bioavailability of neoline in dog suggested good absorption of neline which was worth of further investigation.

  5. Beagle Rupes and Rembrandt scarp: a comparison on Mercury surface

    Science.gov (United States)

    Ferrari, S.; Massironi, M.; Rothery, D. A.; Cremonese, G.

    2011-10-01

    Areas of crustal convergence and shortening on Earth, Mars and Venus are often characterized by structural domains where thrust faults are associated with strike-slip systems [1]. In the case of Mercury most structures maintain a wide elongated frontal scarp and only few of them show kinematic indicators of lateral slip. The comparison between two Mercurian linked fault systems like Beagle Rupes [2] [3] and Rembrandt scarp [4] could aid understanding of whether diverse hermean strike-slip structures are influenced by geological context such as surface heterogeneity and crustal layering or have different deformational history.

  6. Pharmacokinetics and bioavailability of R-phencynonate in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    LI Jing-lai; CUI Meng-cun; WANG Xiao-ying; QIAO Jian-zhong; ZHANG Zhen-qing; RUAN Jin-xiu; ZhONG Bo-hua; LIU Ke-liang

    2008-01-01

    Objective To evaluate the pharmacokinetics (PK) properties and bioavailability of R-pbencynonate (L-8021) in Beagle dogs. Methods Fifteen healthy Beagle dogs were randomly divided into three groups, each group was orally given single dose of 0.1 mg·kg-1, 0.4 mg·kg-1 and 1.2 mg·kg-1 R-pbencynonate respectively. After one week cleaning, the middle dose group was injected 0.4 mg·kg-1 dose. Blood samples (about 2 mL) were collected in heparinized tubes before dosing and at 0. 033, 0. 083, 0.25, 0.5, 0.75, 1,2, 4, 6, 8, 12 h after administration, and were then immediately centrifuged at 2000 g for 15 min. The pharmacokineties (PK) properties and bioavailability of the drugs was evaluated using the liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method. Results After p. o. administration of 0.1, 0.4 and 1.2 mg·kg-1 R-phencynonate, tmax ranged within 0.65-1.2 h;t1/2 ranged within 2.84-3.36 h; CLz/F ranged within 5.00-9.32 L·h-1·kg-1; Cmax ranged within 1.87-70.34 ng·mL-1; AUC(0.t) ranged within 9.80-250.12 μg·L-1. h; After i. v. administration of 0.4 mg·kg-1, t1/2 was 2.52 h; AUG(0-t) was 238.11 μg·L-1·h. Conclnsions L-8021 was dose-dependent within the range of 0.1-1.2 mg·kg-1 in Beagle dogs and the blood drug concentration-time curves were all best fitted to first order absorption two-compartment open model after via po administration of three different dosages. Following oral administration to Beagle dogs, the absolute bioavailability of L-8021 was 17.82 %, which was very low and resulted from poor absorption.

  7. Modelling and interpreting spectral energy distributions of galaxies with BEAGLE

    CERN Document Server

    Chevallard, Jacopo

    2016-01-01

    We present a new-generation tool to model and interpret spectral energy distributions (SEDs) of galaxies, which incorporates in a consistent way the production of radiation and its transfer through the interstellar and intergalactic media. This flexible tool, named BEAGLE (for BayEsian Analysis of GaLaxy sEds), allows one to build mock galaxy catalogues as well as to interpret in terms of physical parameters any combination of photometric and spectroscopic galaxy observations. The current version of the tool includes the versatile modeling of the emission from stars and photoionized gas, attenuation by dust and the accounting for different instrumental effects. We show a first application of the BEAGLE tool to the interpretation of broadband SEDs of a published sample of ${\\sim}10^4$ galaxies at redshifts $0.1 \\lesssim z\\lesssim8$. We find that the constraints derived on photometric redshifts using this multi-purpose tool are comparable to those obtained using public, dedicated photometric-redshift codes and ...

  8. Beagle 2: The Next Exobiology Mission to Mars

    Science.gov (United States)

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

    2001-01-01

    Beagle 2 is a 60 kg probe (with a 30 kg lander) developed in the United Kingdom for inclusion on the European Space Agency's 2003 Mars Express. Beagle 2 will deliver to the Martian surface a payload which consists of a high percentage of science instruments to landed spacecraft mass. Beagle 2 will be launched in June, 2003 with Mars Express on a Soyuz-Fregat rocket from the Baikonur Cosmodrome in Kazakhstan. Beagle 2 will land on Mars on December 26, 2003 in the Isidis Planitia basin (approximately 10 degrees N and 275 degrees W), a large sedimentary basin that overlies the boundary between ancient highlands and northern plains. Isidis Planitia, the third largest basin on Mars, which is possibly filled with sediment deposited at the bottom of long-standing lakes or seas, offers an ideal environment for preserving traces of life. Beagle 2 was developed to search for organic material and other volatiles on and below the surface of Mars in addition to the study of the inorganic chemistry and mineralogy. Beagle 2 will utilize a mechanical mole and grinder to obtain samples from below the surface, under rocks and inside rocks. A pair of stereo cameras will image the landing site along with a microscope for examination of surface and rock samples. Analyses will include both rock and soil samples at various wavelengths, X-ray spectrometer and Mossbauer spectrometer as well as a search for organics and other light element species (e.g. carbonates and water) and measurement of their isotopic compositions. Beagle 2 has as its focus the goal of establishing whether evidence for life existed in the past on Mars at the Isidis Planitia site or at least establishing if the conditions were ever suitable. Carbonates and organic components were first recognized as existing on Mars when they were found in the Martian meteorite Nakhla. Romanek et al showed the carbonates in ALH84001 were formed at low temperatures. McKay et al noted possible evidence of early life on Mars within the

  9. A new Wind Sensor for the Beagle 2 Mars Lander

    Science.gov (United States)

    Wilson, C. F.; Calcutt, S. B.; Jones, T. V.

    2001-12-01

    A hot-film anemometer has been developed for Beagle2, a British Mars lander to be launched in 2003. The sensor will measure wind speed (up to 30 m/s) and horizontal component of wind direction. The position of the wind sensor position at the end of Beagle2's motorised arm allows several new possibilities for wind measurement on Mars that were unavailable in previous missions. The height of the wind sensor can be adjusted to any height between ~20 cm and ~110 cm above the lander body, or can be moved laterally at a given height to study the effects of lander interference. Alternatively, the wind sensor may be positioned with its axis horizontal, thus allowing measurements of vertical wind speed. The wind sensor was calibrated in a new wind tunnel facility, in which Martian surface wind conditions are simulated. Wind speeds of 0.5 - 60 m/s can be created in a CO2 or air atmosphere at pressures of 5 - 10 mbar and temperatures of 200 - 300 K. The facility can also be used in its current configuration to simulate stratospheric winds on Earth. >http://www.atm.ox.ac.uk/user/wilson/matacf.html

  10. 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.

  11. 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.

  12. [Pharmacodynamics and pharmacokinetics of batroxobin in Beagle dog].

    Science.gov (United States)

    Zheng, Zi-Hua; Zhu, Xiao-Xia; Gan, Hui; Gu, Ruo-Lan; Wu, Zhuo-Na; Meng, Zhi-Yun; Dou, Gui-Fang

    2013-08-01

    Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.

  13. Lunar Beagle: An Experimental Package for Measuring Polar Ice and Volatiles Beneath the Lunar Surface

    Science.gov (United States)

    Gibson, E. K.; Pillinger, C. T.; McKay, D. S.; Wright, I. P.; Sims, M. R.; Richter, L.; Waugh, L.; Lunar Beagle Consortium

    2008-07-01

    Lunar Beagle payload has the capabilities of determining the presence of polar ice and volatiles in the permanently shadowed regions of the moon. The instrument suite can provide critical information to assist "living off the land".

  14. Observaciones conductuales en el viaje de Darwin abordo del Beagle

    Directory of Open Access Journals (Sweden)

    Segura Alejandro

    2007-01-01

    Full Text Available Si bien la obra de Darwin ha sido analizada en detalle por historiadores de la ciencia, el papel de la conducta en el desarrollo de la teoría de la evolución no ha sido suficientemente abordado en este tipo de estudios. En este estudio se extraen, describen y analizan las observaciones de comportamiento realizadas por Darwin en El viaje del Beagle. Se presenta el contexto del viajey se describe la ruta, objetivos y características del mismo. Se lleva a cabo una clasificación de los diferentes tipos de observación y los diferentes tipos de comportamiento de múltiplesespecies presentadas por Darwin

  15. Electron imaging of calcium oxalate crystals in beagle dogs’ urine

    Directory of Open Access Journals (Sweden)

    Walaa I. Mohamaden

    2014-06-01

    Full Text Available Calcium oxalate crystalluria appears to be a common problem in most of small animal clinics. This current study aimed at inducing a condition of oxalate crystalluria in beagles and record the primary changes in canine blood and urine on response to oxalates injection. 15 dogs were divided into two groups; those in the treatment group were injected intravenously with 0.5 M potassium oxalate and the dogs of control group were injected with physiological saline for five successive days. Urine test revealed a significant decrease in urinary creatinine and urinary urea nitrogen levels. The ultrastructural examination of urine sediment showed typical and atypical phases of calcium oxalate crystals and the X-ray defractionation of these crystals showed high content of calcium in addition to other minerals. Therefore potassium oxalate injection may provide an example of calcium oxalate crystalluria which may answer some question around the pathogenesis of this problem in dogs.

  16. Photometric Observations of Main-belt Asteroids 656 Beagle and 2649 Oongaq

    Science.gov (United States)

    Sonka, Adrian Bruno; Popescu, Marcel; Nedelcu, Dan Alin

    2016-01-01

    We present photometric observations for two main-belt asteroids, 656 Beagle and 2649 Oongaq, carried out at Astronomical Institute of Romanian Academy between 2014 September and 2015 March. For 656 Beagle, we found a synodic rotation period of 7.034 ± 0.003 h and for 2649 Oongaq a synodic rotation period of 7.789 ± 0.006 h. Both are in good agreement with recent results.

  17. Facies del subfondo del canal Beagle, Tierra del Fuego Sub-bottom facies of the Beagle Channel, Tierra del Fuego

    Directory of Open Access Journals (Sweden)

    Gustavo Bujalesky

    2004-03-01

    Full Text Available El canal Beagle conecta los océanos Pacífico y Atlántico en el extremo meridional de Sudamérica y se ubica en el ambiente subantártico. Conforma una cuenca de unos 300 m de profundidad máxima y está separada del océano Atlántico por un umbral de 30 m de profundidad. El canal es un valle tectónico que fue completamente cubierto por el hielo glacial durante la última glaciación. Posteriormente, el canal fue ocupado por un lago glacial desde los 12.000 a los 8.000 años A.P., cuando fue invadido por el mar que alcanzó un nivel máximo entre los 6.000 y 5.000 años A.P. Con el objetivo de analizar las facies sedimentarias superficiales y del subfondo del canal se realizó un relevamiento geofísico con sonar de barrido lateral y un perfilador de 3,5 kHz. Sobre un basamento constituido por rocas metamórficas del Mesozoico, se identificaron depósitos de till y secuencias granodecrecientes que representan distintos estadios del retroceso glaciar, evidenciando hacia la sección superior facies lacustres y por encima depósitos de la transgresión marina del Holoceno. Además, se han identificado paleocauces y secuencias fluviales cubiertas por sedimentos marinos transgresivos.The Beagle Channel connects the Pacific and Atlantic oceans in the southernmost part of South America, and has a subantarctic environment. It is a deep basin (300 m depth separated from the Atlantic Ocean by a shallow sill (30 m depth. The Beagle Channel is a tectonic valley that was completely covered by ice during the Last Glaciation. Later, it was occupied by a glacial lake from 12,000 to 8,000 years B.P. and then flooded by the sea, reaching a maximum sea level between 6,000 and 5,000 years B.P. A geophysical survey (side scan sonar and 3.5 kHz profiler was carried out in the channel to analyze the sea-bed and sub-bottom sedimentary facies. Metamorphic Mesozoic basement rocks are overlain by glacial deposits (till and fining upwards sequences. These sequences

  18. Hypertonic Saline Dextran Ameliorates Organ Damage in Beagle Hemorrhagic Shock.

    Directory of Open Access Journals (Sweden)

    Jing-xiang Zhao

    Full Text Available The goal of this study was to investigate the effect of hypertonic saline with 6% Dextran-70 (HSD resuscitation on organ damage and the resuscitation efficiency of the combination of HSD and lactated ringers (LR in a model of hemorrhage shock in dogs.Beagles were bled to hold their mean arterial pressure (MAP at 50 ± 5 mmHg for 1 h. After hemorrhage, beagles were divided into three groups (n = 7 to receive pre-hospital resuscitation for 1 h (R1: HSD (4 ml/kg, LR (40 ml/kg, and HSD+LR (a combination of 4 ml/kg HSD and 40 ml/kg LR. Next, LR was transfused into all groups as in-hospital resuscitation (R2. After two hours of observation (R3, autologous blood was transfused. Hemodynamic responses and systemic oxygenation were measured at predetermined phases. Three days after resuscitation, the animals were sacrificed and tissues including kidney, lung, liver and intestinal were obtained for pathological analysis.Although the initial resuscitation with HSD was shown to be faster than LR with regard to an ascending MAP, the HSD group showed a similar hemodynamic performance compared to the LR group throughout the experiment. Compared with the LR group, the systemic oxygenation performance in the HSD group was similar but showed a lower venous-to-arterial CO2 gradient (Pv-aCO2 at R3 (p < 0.05. Additionally, the histology score of the kidneys, lungs and liver were significantly lower in the HSD group than in the LR group (p < 0.05. The HSD+LR group showed a superior hemodynamic response but higher extravascular lung water (EVLW and lower arterial oxygen tension (PaO2 than the other groups (p < 0.05. The HSD+LR group showed a marginally improved systemic oxygenation performance and lower histology score than other groups.Resuscitation after hemorrhagic shock with a bolus of HSD showed a similar hemodynamic response compared with LR at ten times the volume of HSD, but HSD showed superior efficacy in organ protection. Our findings suggest that

  19. Beagle 2 and NASA's Mars 2003 Orbiter: A Unique Exobiology Opportunity with an Orbiter

    Science.gov (United States)

    Gibson, Everett K., Jr.; Pillinger, Colin T.; Thatcher, John; Westall, Frances

    2000-01-01

    With the exploration strategy for Mars undergoing reexamination, the opportunity exists for the incorporation of the 60 kg Beagle 2 lander, developed in the United Kingdom for inclusion on ESA's 2003 Mars Express mission, with NASA's Mars 2003 orbiter derived from the Mars Global Orbiter. The combination of Beagle 2 with a Mars orbiter would result in a unique mission which could obtain information on Mars' life, climate and resources both from orbit as well as on the surface of the planet. Beagle 2 has been developed in the LJK for ESA as a low-cost opportunity to study the exobiology of Mars and the spacecraft is in its final stages of manufacture. Only limited modifications to the Beagle 2 package would be required for inclusion on NASA's Mars 2003 orbiter. With the ESA Mars Express mission launch in 2003 and a potential NASA Mars orbiter in 2003, both Beagle 2 landers on Mars would offer a low-cost, decreased risk and increased science return opportunity for the exploration of Mars at two distinct geologically interesting sites.

  20. 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.

  1. [Endoscopic and histopathological studies of experimental esophageal cancer in beagles].

    Science.gov (United States)

    Takeshita, K; Sunagawa, M; Nakajima, A; Ochi, K; Habu, H; Hoshi, K

    1985-02-01

    In order to obtain a reliable experimental model simulating human esophageal cancer, endoscopic and histopathological studies were undertaken in the esophageal cancer produced in the beagle dog. Thirty-seven dogs had been given a solution of N-Ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at a concentration of 150 micrograms/ml for 3-9 months. Follow-up studies included serial endoscopy and biopsy, and almost all animals were eventually sacrificed for histological examination. The results were as follows: Squamous cell carcinoma was observed in 5 out of 22 female dogs, while none in male dogs at all. For the induction of squamous cell carcinoma in the esophagus, administration in the condition of 150 micrograms/ml (75mg/day) for 6-9 months was most suitable. Almost all of esophageal lesions were protruding and well-differentiated squamous cell carcinoma with invasion of the submucosa. The stages of hyperplasia, dysplasia and squamous cell carcinoma in the esophagus were chronologically followed. Carcinoma had been observed in the stomach about 4 months prior to the appearance of esophageal carcinoma. This experimental model was proved to be useful for studies on histogenesis of human esophageal cancer both light and electron microscopically.

  2. 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...

  3. Electroretinography recordings using a light emitting diode active corneal electrode in healthy beagle dogs.

    Science.gov (United States)

    Itoh, Yoshiki; Maehara, Seiya; Itoh, Norihiko; Yamashita, Kazuto; Izumisawa, Yasuharu

    2013-01-01

    Electroretinography (ERG) is a well-established diagnostic procedure for objectively evaluating retinal function. In this study, ERG in beagle dogs, which are a popular experimental animal, was performed to determine the normal range of ERG variables and assess differences between the left and right eyes. ERG findings including rod, combined rod-cone, single-flash cone, and 30-Hz flicker responses were recorded with an LED-electrode in 43 sedated beagle dogs. The subjects were divided into young (beagle dogs differed by age due to age-related retinal changes. Thus, we propose that normal ERG ranges should be determined according to age in each clinic and laboratory using its own equipment because each institution usually has different systems or protocols for ERG testing.

  4. Heavy metal concentrations in litteral sediments from the Beagle Channel, Tierra del Fuego, Argentina.

    Science.gov (United States)

    Amin, O; Ferrer, L; Marcovecchio, J

    1996-07-01

    For the first time the concentration of trace metals (Fe, Pb, Cu, Zn, Cd and total Hg) of sediments from the coastal zone of the Beagle Channel (Tierra del Fuego, in Southern Argentina) were measured. Atomic absorption spectrophotometry was utilized in order to determine the metal contents. The level of metals as observed in the sediments was recognized as the natural background, even though the use of normalization of lead, copper, and zinc to iron allowed the identification of the main sources of metal pollution for this environment. In order to develop future environmental monitoring programmes for the area of Ushuaia city and the Beagle Channel, the present results need to be considered.

  5. Influence of parity and litter size on gestation length in beagle dogs.

    Science.gov (United States)

    Seki, Makoto; Watanabe, Norio; Ishii, Kenyo; Kinoshita, Yoh-ichi; Aihara, Takehiro; Takeiri, Shuji; Otoi, Takeshige

    2010-01-01

    This study was conducted to investigate the effects of parity and litter size on gestation length in beagle bitches. The mean duration of the initial elevation (>2 ng/mL) in progesterone concentrations after the onset of proestrus was shorter (P gestation length in the nulliparous bitches was noted to be similar to that in the multiparous bitches (64.3 d versus 64.2 d). No significant correlation between gestation length and litter size was observed in any of the bitches. Our results indicate that the gestation length in beagle bitches is not affected by parity or litter size.

  6. Birth of Beagle dogs by somatic cell nuclear transfer.

    Science.gov (United States)

    Hossein, Mohammad Shamim; Jeong, Yeon Woo; Park, Sun Woo; Kim, Joung Joo; Lee, Eugine; Ko, Kyeong Hee; Hyuk, Park; Hoon, Song Seung; Kim, Yeun Wook; Hyun, Sang Hwan; Shin, Taeyoung; Hwang, Woo Suk

    2009-09-01

    The present study was undertaken to evaluate two enucleation methods for somatic cell nuclear transfer (SCNT), and to standardize the optimum number of embryos for transfer to each recipient for canines. Oocytes retrieved from outbreed dogs were reconstructed with adult somatic cells from a male Beagle dog. A total of 134 or 267 oocytes were enucleated either by aspiration or squeezing method, fused with two DC pulses of 1.75 kV/cm for 15 micros electrical stimulation, chemically activated after 1h of fusion using 10 microM calcium ionophore for 4 min and cultured 4h in 1.9 mM 6-dimethylaminopurine. Finally, 103 or 214 embryos for aspiration or squeezing method were transferred to 6 or 11 naturally synchronized recipients, respectively. A total of 53, 317 and 342 embryos were transferred to 7, 17 and 12 recipients for the group of 4-10, 11-25 and 26-40 embryos, respectively. There was no difference between fusion rate (76.87% vs. 80.15%), full term pregnancy rate (16.66% vs. 27.27%) and percent of live puppies born (0.97% vs. 1.87%) for aspiration and squeezing method (P>0.05). Production efficiency of cloned dogs was significantly affected by the number of embryos transferred to each recipient. No pregnancy was established for the group of 4-10 embryos (n=7) and 26-40 embryos (n=12) while pregnancy was detected in 23.53% recipients received a group of 11-25 embryos (n=17). Among them, five (1.76%) live puppies were born (P<0.05). These data show an increase in the overall efficiency of SCNT in canine species.

  7. Facies del subfondo del canal Beagle, Tierra del Fuego

    Directory of Open Access Journals (Sweden)

    Gustavo Bujalesky

    2004-03-01

    Full Text Available El canal Beagle conecta los océanos Pacífico y Atlántico en el extremo meridional de Sudamérica y se ubica en el ambiente subantártico. Conforma una cuenca de unos 300 m de profundidad máxima y está separada del océano Atlántico por un umbral de 30 m de profundidad. El canal es un valle tectónico que fue completamente cubierto por el hielo glacial durante la última glaciación. Posteriormente, el canal fue ocupado por un lago glacial desde los 12.000 a los 8.000 años A.P., cuando fue invadido por el mar que alcanzó un nivel máximo entre los 6.000 y 5.000 años A.P. Con el objetivo de analizar las facies sedimentarias superficiales y del subfondo del canal se realizó un relevamiento geofísico con sonar de barrido lateral y un perfilador de 3,5 kHz. Sobre un basamento constituido por rocas metamórficas del Mesozoico, se identificaron depósitos de till y secuencias granodecrecientes que representan distintos estadios del retroceso glaciar, evidenciando hacia la sección superior facies lacustres y por encima depósitos de la transgresión marina del Holoceno. Además, se han identificado paleocauces y secuencias fluviales cubiertas por sedimentos marinos transgresivos.

  8. 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)

  9. 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.

  10. 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.

  11. Elimination Half-Lives of Acute Phase Proteins in Rats and Beagle Dogs During Acute Inflammation.

    Science.gov (United States)

    Kuribayashi, Takashi; Seita, Tetsuro; Momotani, Eiichi; Yamazaki, Shunsuke; Hagimori, Kohei; Yamamoto, Shizuo

    2015-08-01

    The half-lives of typical acute phase proteins in rats and beagle dogs during acute inflammation were investigated. Acute inflammation was induced by injection of turpentine oil in rats and administration of indomethacin in beagle dogs. Serum concentrations of α2-macroglobulin (α2M) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay and α1-acid glycoprotein (AAG) was measured by single radial immunodiffusion. Half-life was calculated as 0.693/elimination rate constant (K). The mean half-lives in the terminal elimination phase of α2M and AAG were 68.1 and 164.8 h, respectively. The half-life of AAG was significantly longer than that of α2M. Mean half-lives in the terminal elimination phase of CRP and AAG were 161.9 and 304.4 h, respectively. The half-life of AAG was significantly longer than that of CRP in beagle dogs. No significant differences in the half-life of AAG were observed between rats and beagle dogs. Furthermore, serum concentrations in the terminal elimination phase could be simulated with the K data acquired in this study.

  12. Assessment of thirteen-week subchronic oral toxicity of cyadox in Beagle dogs.

    Science.gov (United States)

    Wang, Xu; Zhou, Wen; Ihsan, Awais; Chen, Dongmei; Cheng, Guyue; Hao, Haihong; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2015-11-01

    Cyadox (2-formylquinoxaline-N(1),N(4)-dioxide cyanocetylhydrazone) is a new antimicrobial agent and growth-promoter to be used in food-producing animals. Although its toxicity has been clearly documented in rodents, no study is available in non-rodent animals. Therefore, we studied the subchronic effects of cyadox in Beagle dogs to provide additional information with which to establish safety criteria for human exposure. For this purpose, 36 Beagle dogs, 18 males and 18 females, were divided into four groups and fed diets containing 0, 100, 450 and 2500 mg/kg of cyadox, respectively, for 13 weeks. It was found that there were no significant changes among the examined parameters, except for an increase in the level of serum potassium (K(+)) in 2500 mg/kg cyadox group in males at week 13 of the study. However, the K(+) level returned to normal during the recovery period. In conclusion, cyadox showed slight effects in Beagle dogs in the subchronic oral toxicity study. The no-observed-adverse-effect level of cyadox was considered to be 450 mg/kg diet, which equates to approximately 15.3-15.4 mg/kg b.w./day. The study provided subchronic effects of cyadox in Beagle dogs, suggesting that cyadox might present mild toxicity in non-rodents.

  13. Neosporosis in Beagle dogs clinical signs, diagnosis, treatment, isolation and genetic characterization of Neospora caninum.

    Science.gov (United States)

    Clinical neosporosis was diagnosed in a litter of five pups born to a Beagle bitch from Virginia, USA. Four of the pups developed limb weakness starting at 4 weeks of age. The dogs were suspected to have neosporosis based on clinical signs and empirically treated with Clindamycin (75 mg, oral, twice...

  14. Beagle Rupes -- Evidence for a Basal Decollement of Regional Extent in Mercury's Lithosphere

    Science.gov (United States)

    Rothery, D. A.; Massironi, M.

    2009-03-01

    Beagle Rupes is a thrust bounded by transpressive lateral ramps. To remain in the elastic lithosphere, the dip of the fault must become shallower at depth. This is evidence for thin-skinned tectonics, with out-of-sequence thrusts, on Mercury.

  15. Polyactive as a bone-filler in a beagle dog model

    NARCIS (Netherlands)

    Meijer, G.J.; Dooren, van A.; Gallard, M.L.; Dalmeijer, R.; Putter, de C.; Koole, R.; Blitterswijk, van C.A.

    1996-01-01

    Calcification is a crucial step in the bone-bonding mechanism of PEO/PBT hydrogel copolymers (Polyactive®), a new generation of bone-fillers. A beagle dog study was conducted to determine whether the preoperative presence of a calcium phosphate layer (precalcification) on a PEO/PBT 80/20 copolymer w

  16. Meteorites, Mars and Beagle 2--from novel analysis in the laboratory to pioneering experiments in space.

    Science.gov (United States)

    Wright, I P

    2003-11-01

    On 25 December 2003, the British-built Beagle 2 probe will land on the surface of Mars to carry out one of the most potentially important pieces of analytical science ever conceived: to search for evidence of extra terrestrial life. Dr Ian Wright of the Open University talks us through the difficulties of performing measurements in such a harsh environment.

  17. Absorption and pharmacokinetics of green tea catechins 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 M

    2008-09-01

    The present study evaluates for the first time in dogs, the kinetics of green tea catechins and their metabolic forms in plasma and urine. Ten beagles were administered 173 mg (12.35 mg/kg body weight) of catechins as a green tea extract, in capsules. Blood samples were collected during 24 h after intake and urine samples were collected during the following periods of time: 0-2, 2-6, 6-8 and 8-24 h. Two catechins with a galloyl moiety and three conjugated metabolites were detected in plasma. Most of the detected forms in plasma reached their maximum plasma concentration (Cmax) at around 1 h. Median Cmax for ( - )-epigallocatechin-3-gallate (EGCG), ( - )-epicatechin-3-gallate (ECG), ( - )-epigallocatechin glucuronide (EGC-glucuronide), ( - )-epicatechin glucuronide (EC-glucuronide), ( - )-epicatechin sulphate (EC-sulphate) were 0.3 (range 0.1-1.9), 0.1 (range 0-0.4), 0.8 (range 0.2-3.9), 0.2 (range 0.1-1.7) and 1 (range 0.3-3.4) micromol/l, respectively. The areas under the plasma concentration v. time curves (AUC0 --> 24) were 427 (range 102-1185) micromol/l x min for EGC-glucuronide, 112 (range 53-919) micromol/l x min for EC-sulphate, 71 (range 26-306) micromol/l x min for EGCG, 40 (range 12-258) micromol/l x min for EC-glucuronide and 14 (range 0.1-124) micromol/l x min for ECG. The values of mean residence time (MRT0 --> 24) were 5 (range 2-16), 2 (range 1-11), 10 (range 2-13), 3 (range 2-16) and 2.4 (range 1-18) h for EGCG, ECG, EGC-glucuronide, EC-glucuronide and EC-sulphate, respectively. In urine, catechins were present as conjugated forms, suggesting bile excretion of EGCG and ECG. Green tea catechins are absorbed following an oral administration and EGC-glucuronide is the metabolic form that remains in the organism for a longer period of time, suggesting that this compound could suffer an enterohepatic cycle.

  18. 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.

  19. Recloned dogs derived from adipose stem cells of a transgenic cloned beagle.

    Science.gov (United States)

    Oh, Hyun Ju; Park, Jung Eun; Kim, Min Jung; Hong, So Gun; Ra, Jeong Chan; Jo, Jung Youn; Kang, Sung Keun; Jang, Goo; Lee, Byeong Chun

    2011-04-15

    A number of studies have postulated that efficiency in mammalian cloning is inversely correlated with donor cell differentiation status and may be increased by using undifferentiated cells as nuclear donors. Here, we attempted the recloning of dogs by nuclear transfer of canine adipose tissue-derived mesenchymal stem cells (cAd-MSCs) from a transgenic cloned beagle to determine if cAd-MSCs can be a suitable donor cell type. In order to isolate cAd-MSCs, adipose tissues were collected from a transgenic cloned beagle produced by somatic cell nuclear transfer (SCNT) of canine fetal fibroblasts modified genetically with a red fluorescent protein (RFP) gene. The cAd-MSCs expressed the RFP gene and cell-surface marker characteristics of MSCs including CD29, CD44 and thy1.1. Furthermore, cAd-MSCs underwent osteogenic, adipogenic, myogenic, neurogenic and chondrogenic differentiation when exposed to specific differentiation-inducing conditions. In order to investigate the developmental potential of cAd-MSCs, we carried out SCNT. Fused-couplets (82/109, 75.2%) were chemically activated and transferred into the uterine tube of five naturally estrus-synchronized surrogates. One of them (20%) maintained pregnancy and subsequently gave birth to two healthy cloned pups. The present study demonstrated for the first time the successful production of cloned beagles by nuclear transfer of cAd-MSCs. Another important outcome of the present study is the successful recloning of RFP-expressing transgenic cloned beagle pups by nuclear transfer of cells derived from a transgenic cloned beagle. In conclusion, the present study demonstrates that adipose stem cells can be a good nuclear donor source for dog cloning.

  20. 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.

  1. Spontaneous lesions in endocrine glands of experimental Wistar rats and beagle dogs.

    Science.gov (United States)

    Nataraju, G J; Ranvir, Ramchandra K; Kothule, Viren R; Kadam, Shekhar B; Ravichandra, B V; Bhatnagar, Upendra; Jain, Mukul R

    2016-01-01

    A retrospective analysis was undertaken at Zydus Research Centre to understand the incidences of spontaneous lesions in endocrine glands of Wistar rats and beagle dogs. The data from a total of 841 Wistar rats (418 males and 423 females) and 144 beagle dogs (72 males and 72 females) was used from placebo/vehicle treated control group of different non-clinical toxicity studies. The lesions in various endocrine glands were classified according to the species and age of the animals at termination of study. Among the endocrine glands, the highest numbers (types) of spontaneous lesions were observed in adrenal glands followed in descending order by pituitary, thyroid, endocrine pancreas and parathyroid glands in Wistar rats. In beagle dogs, highest numbers (types) of spontaneous lesions were seen in adrenals followed by thyroid, endocrine pancreas, pituitary and parathyroid gland. In adrenal glands of Wistar rats, the incidences of cortical cell vacuolation, hemorrhages and hemangiectasis/peliosis were increased with age. Incidence of peliosis at ∼110 weeks of age was higher in female rats. Among the proliferative lesions in rats, higher incidences of cortical cell hyperplasia was observed followed by medullary hyperplasia, complex pheochromocytoma, cortical cell adenoma and cortical adenocarcinoma. In beagle dogs, the incidences of hemangiectasis and cortical cell vacuolation in adrenal glands were higher in 18-21 months aged dogs in both the sexes as compared to 10-12 months of age. In pituitary gland, the incidences of cystic changes were higher in older rats and dogs and the incidences were more in beagles as compared to rats. In thyroid glands, C-cell (parafollicular cells) hyperplasia/complex was observed more frequently in both the species. Few incidences of cystic changes were observed in parathyroid of 18-21 months aged beagle dogs. In endocrine pancreas, few incidences of islet-cell vacuolation, atrophy and hyperplasia were observed in both the species. The

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

    Science.gov (United States)

    de Oliveira Filho, Jaires Gomes; Sarria, André Lucio Franceschini; Ferreira, Lorena Lopes; Caulfield, John C; Powers, Stephen J; Pickett, John A; de León, Adalberto A Pérez; Birkett, Michael A; Borges, Lígia Miranda Ferreira

    2016-06-01

    We have recently shown that repellency of the tick Rhipicephalus sanguineus sensu lato by the tick resistant dog breed, the beagle, is mediated by volatile organic compounds (VOCs) 2-hexanone and benzaldehyde present in beagle odour. Ectoparasite location of animal hosts is affected by variation in these odour components and their ratios. The aim of this study was to quantify the release rate, and the ratio, of 2-hexanone and benzaldehyde from beagles. The odour of three beagles was collected, for four days, over one week (day 0, day 1, day 4 and day 7). The compounds were identified using coupled high-resolution gas chromatography-mass spectrometry (GC-MS), and authentic standards of compounds were used to generate external calibration curves for quantification. Both compounds were found in all dogs on all days. The amount of benzaldehyde was always higher than that of 2-hexanone and so their ratio varied from unity, on average (over time) being 3.128±0.365, 1.902±0.390, 1.670±0.671ngmL(-1) for beagle 1, 2 and 3, respectively. There was no significant (pbenzaldehyde in beagle odour samples covering a 7-day period. This knowledge enables development of repellents to protect dogs from R. sanguineus s. l. infestation.

  3. The Scientific Management for High Quality Beagle Dogs Research Resources%高质量Beagle犬研究资源的科学管理

    Institute of Scientific and Technical Information of China (English)

    陈伟平; 刘运忠; 罗甜义

    2003-01-01

    Guangdong Beagle Resource Research and Development Center (abbreviated as GBRDC ) was Founded by Guangzhou Pharmaceutical Industry Research Institute in 1983, it is named as GBRDC by Guangdong Province Sci. &Tech. Commission. It is then first Beagle Dag Research Resources according to Laboratory Animal Science standard to maintain the Beagle Dogs research resource in China. Currently, it is playing a leading role in Beagle Dog research resource in China. During the 20 past years, GBRDC' s Management, Technology, Research are all focused on the regula-tory testing and animal welfare.

  4. Spectroscopic investigation of asteroids belonging to the Themis and Beagle families

    Science.gov (United States)

    Fornasier, S.; Perna, D.; Barucci, M. A.; Merlin, F.; Dotto, E.

    2012-09-01

    24 Themis is the largest body of the Themis family. Within this big family a cluster of very young asteroids (age Beagle sub-family, has been identified. Recently water ice and organics were detected on 24 Themis indicating that the Themis family may be an important reservoir of ice. Moreover, the main belt comets 133P, 238P, and 176P may be related with the Themis family because of orbital proximities and spectral properties analogies. The aim of this work is to spectroscopically investigate some asteroids belonging to the Themis family and to the young Beagle sub-family in order to look for absorption bands related to water ice, hydrated silicates and organics.

  5. The Themis-Beagle families: clues into space weathering processes on primitive asteroids

    Science.gov (United States)

    Fornasier, S.; Perna, D.; Lantz, C.; Barucci, M. A.

    2015-10-01

    The Themis family is a natural laboratory to study the asteroids-comets continuum and space weathering effects. Recently water ice and organics were detected on 24 Themis indicating that the Themis family may be an important reservoir of ice. Moreover, some main belt comets may be related with the Themis family because of orbital proximities and spectral properties analogies. Within the old Themis family members, a young sub-family, Beagle, formed less than 10 Myr ago, has been identified. Thus the Themis family is very important to shed light on the asteroid-comet continuum, to constrain the abundances of water ices in the outer part of the main belt, and to probe space weathering effects on old Themis and young Beagle families' members.

  6. 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.

  7. Neutron metrology in the HFR. Neutron and gamma metrology in two beagles and one cylindrical phantom

    Energy Technology Data Exchange (ETDEWEB)

    Voorbraak, W.P.; Freudenreich, W.E.; Stecher-Rasmussen, F.; Verhagen, H.W.

    1991-10-01

    Neutron fluence rate and gamma dose data are presented for the first series of experiments at the filtered HFR beam HB11 at full reactor power. Measurements were performed on two beagle dogs and one cylindrical phantom. The main results for thermal and epithermal fluence rates, physical neutron dose and gamma dose are presented in the tables 1 and 2. (author). 10 refs.; 9 figs.; 8 tabs.

  8. Serum alkaline phosphatase isoenzymes in laboratory beagle dogs detected by polyacrylamide-gel disk electrophoresis.

    Science.gov (United States)

    Hatayama, Kazuhisa; Nishihara, Yoshito; Kimura, Sayaka; Goto, Ken; Nakamura, Daichi; Wakita, Atsushi; Urasoko, Yoshinaka

    2011-10-01

    Serum alkaline phosphatase (ALP) activity is frequently measured in toxicity studies. Itoh et al. (2002) reported that a commercially available polyacrylamide-gel (PAG) disk electrophoresis kit used in humans (AlkPhor System, Jokoh Co., Ltd., Tokyo, Japan) for identifying serum ALP isoenzymes was useful for veterinary clinicopathological diagnosis in mongrel dogs. In the present study, based on the report of Itoh et al. (2002), we tried to expand the application range of this kit to laboratory beagle dogs which are commonly used in toxicity studies. In order to identify the origin of each ALP isoenzyme, tissue ALP extracts from the liver, bone and small intestine and serum samples were treated with neuraminidase, anti-small intestinal ALP antibody, ALP inhibitor levamisole and/or wheat germ agglutinin (WGA). The main serum ALP isoenzymes in 5-month-old intact beagle dogs were bone-derived (bone and atypical ALP: corresponding to human variant bone ALP) and they tended to decrease with age. However, liver-derived ALP isoenzyme greatly increased in the serum of cholestasis model dogs. The cholestasis model dogs also had a large molecular ALP detected in the resolving gel. This ALP could be originated from intestinal ALP or corticosteroid-induced ALP (CALP), because the activity remained even after levamisole inhibition. CALP was observed in intact laboratory beagle dogs with individual differences. These results suggest that the present method is a useful tool for detecting serum ALP isoenzymes in laboratory beagle dogs and concomitant levamisole inhibition with another gel is applicable for the evaluation of organ toxicity.

  9. 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 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.

  10. The Beagle Rupes area - evidence for a basal decollement of regional extent in Mercury's lithosphere

    Science.gov (United States)

    Rothery, David; Massironi, Matteo

    2010-05-01

    The Beagle Rupes lobate scarp was particularly clearly imaged during the outbound leg of MESSENGER's first flyby, thanks to its location at low latitude and proximity to the terminator. Previous interpretations of mercurian lobate scarps regard them as surface expressions of thrusts whose fault planes dip uniformly and die out at depth, and that lack lateral ramps or any extensive detachment horizon. However, we interpret Beagle Rupes as a component of a linked fault system, consisting of a frontal scarp terminated by transpressive lateral ramps. The terrain bounded by these features is the hanging-wall block of a thrust sheet and must be underlain by a basal decollement (a detachment horizon) constituting the fault zone at depth. Displacement at the Beagle Rupes frontal scarp is no more than about 3 km. However, the decollement must extend a minimum of 150 km eastwards from the frontal scarp, and at least 400 km if displacement is transferred to features interpreted as out-of sequence thrusts and offset lateral ramps that appear to continue the linked fault system to the east. The depth of the basal decollement could be controlled by crustal stratigraphy or by rheological change within, or at the base of, the lithosphere. One such candidate horizon could be the brittle-ductile transition in quartz-bearing lower crust as predicted by some models of Mercury's early differentiation history (Brown and Elkins-Tanton, 2009). Further analysis of the terrain north and south of Beagle Rupes reveals ridges (10s of km wide and 100s of km long) that we interpret as pop-up structures probably associated with blind thrusts and very likely providing additional evidence of a decollement of regional extent. Brown, S. M., Elkins-Tanton, L. T., 2009, Compositions of Mercury's earliest crust from magma ocean models. Earth Planet. Sci. Lett. 286, 446-455.

  11. 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.

  12. Baseline trace metals in gastropod mollusks from the Beagle Channel, Tierra del Fuego (Patagonia, Argentina).

    Science.gov (United States)

    Conti, Marcelo Enrique; Stripeikis, Jorge; Finoia, Maria Grazia; Tudino, Mabel Beatriz

    2012-05-01

    With the aim to evaluate the mollusk Nacella (P)magellanica as biomonitor of elemental pollution in seawater of the Beagle Channel, more than one hundred individuals of the gastropod were sampled, separated in viscera and muscle, and then examined with respect to the accumulation of Cd, Cr, Cu, Ni, Pb and Zn. Collection was performed in seven strategic locations along 170 km of the coastal area of the Beagle Channel (Tierra del Fuego, Argentina) in two campaigns during 2005 and 2007. Samples of surrounding seawater in the different sites were obtained and tested for the same metals as well. The accumulation capacity of Nacella (P)magellanica and thus its aptitude as biomonitor, was evaluated through the calculus of the preconcentration factors of the metals assayed. A discussion involving the comparison with other mollusks previously tested will be given. Several statistical approaches able to analyze data with environmental purposes were applied. Non parametric univariate tests such as Kruskal-Wallis and Mann-Whitney were carried out to assess the changes of the metal concentrations with time (2005 and 2007) in each location. Multivariate methods (linear discriminant analysis on PCA factors) were also applied to obtain a more reliable site classification. Johnson's probabilistic method was carried out for comparison between different geographical areas. The possibility of employing these results as heavy metals' background levels of seawater from the Beagle Channel will be debated.

  13. Pharmacokinetic comparisons of S-oxiracetam and R-oxiracetam in beagle dogs.

    Science.gov (United States)

    Wang, Wusan; Ji, Hui; Li, Tingting; Jia, Yuanwei; Xie, Haitang

    2016-06-01

    A pharmacokinetic comparison and conformational stability study of S-oxiracetam (S-ORT) and R-oxiracetam (R-ORT) in beagle dogs was used to investigate the possible mechanism of different effects of two oxiracetam enantiomers through a random crossover design. After drug administration to beagle dogs, blood samples were collected at different time points for pharmacokinetic analysis using the UPLC-ESI-MS/MS method. Parts of plasma samples were used for conformation transformation studies using a normal phase high performance liquid chromatographic (NP HPLC) method. The study showed that oxiracetam enantiomers maintained their original conformation when administered orally to beagle dogs. Concentrations of S-ORT were significantly higher than R-ORT 1.5 and 2 h after administration; the AUC0-∞ of S-ORT after oral administration tended to be higher than that of R-ORT, which showed that the different effects between S-ORT and R-ORT may be partly associated with their distinctive absorption at least.

  14. Development of the Endocrine Pancreas in the Beagle Dog: From Fetal to Adult Life.

    Science.gov (United States)

    Bricout-Neveu, Emilie; Pechberty, Severine; Reynaud, Karine; Maenhoudt, Cindy; José Lecomte, Marie; Ravassard, Philippe; Czernichow, Paul

    2017-03-14

    Our objectives were to describe, in Beagle dogs, the ontogenesis of beta (insulin-producing) and alpha (glucagon-producing) cells from fetal to early postnatal life and adulthood. In addition, to have some insight into interspecies comparison, Beagle dog pancreases were compared to pancreases from a Labrador and Chow Chow. At midgestation, the epithelium was dense, beta cells scarce, and alpha cells numerous and concentrated in the center of the pancreatic bud. From 36 to 45 days post conception (pc), beta cell numbers increased and the epithelium expanded and branched out. At 55 days pc, large beta cell aggregates were seen. At weaning, the islets were similar to those in adults, with limited alpha cells intermingled with numerous beta cells. Quantification of the Alpha to Beta cells ratio has shown a gradual increase of beta cells proportion throughout development. Similar findings were obtained in the 2 other breeds. In conclusion, in the fetal Beagle dog beta cells emerge from the pancreatic bud at midgestation, but the endocrine structure is mature only in early postnatal life. The ontogenesis of the endocrine pancreas demonstrated in dogs resembles that reported in rats and mice. In contrast, human beta cells appear earlier, at the beginning of the second trimester of gestation. Our study provides a detailed morphological description of pancreatic development in dogs but supplies no information on alpha- or beta-cell function during fetal life. The morphological data reported here provide a foundation for building physiological studies. This article is protected by copyright. All rights reserved.

  15. Pharmacokinetic comparisons of S-oxiracetam and R-oxiracetam in beagle dogs

    Directory of Open Access Journals (Sweden)

    Wang Wusan

    2016-06-01

    Full Text Available A pharmacokinetic comparison and conformational stability study of S-oxiracetam (S-ORT and R-oxiracetam (R-ORT in beagle dogs was used to investigate the possible mechanism of different effects of two oxiracetam enantiomers through a random crossover design. After drug administration to beagle dogs, blood samples were collected at different time points for pharmacokinetic analysis using the UPLC-ESI-MS/MS method. Parts of plasma samples were used for conformation transformation studies using a normal phase high performance liquid chromatographic (NP HPLC method. The study showed that oxiracetam enantiomers maintained their original conformation when administered orally to beagle dogs. Concentrations of S-ORT were significantly higher than R-ORT 1.5 and 2 h after administration; the AUC0-∞ of S-ORT after oral administration tended to be higher than that of R-ORT, which showed that the different effects between S-ORT and R-ORT may be partly associated with their distinctive absorption at least.

  16. 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.

  17. Pharmacokinetics study of extended release formulations of buspirone hydrochloride in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    CUI Meng-cun; LI Jing-lai; CHEN Yan; WANG Xiao-ying; QIAO Jian-zhong; ZHANG Zhen-qing; RUAN Jin-xiu

    2008-01-01

    Objective To evaluate the pharmacokinetics (PK) properties of extended release formulations of buspirone hydrochloride in Beagle dogs. Methods A randomized, two period, two treatment, two sequence crossover bioequivalenee study was designed; six healthy Beagle dogs were randomly divided into two groups, each group was orally given buspirone tablets or buspirone extended capsule containing 15 mg buspirone hydrochloride. Blood samples (about 1 mL) were collected in heparinized tubes before dosing and at 0.33, 0.67, 1,2, 3, 4, 6, 8, 10, 12, 18, 24 h after administration, and were then immediately centrifuged at 3000 rpm for 15 min. The pharmacokinetics (PK) properties of the drugs were evaluated using the liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method. Results The mean tmax was 4.7, 0.8 h and Cmax values was 1.8, 6.9 μg·L-1, respectively for the sustained-release test (capsule) and reference formulation (tablet). When compared to the tablets, the residence time of the sustained capsules was dramatically prolonged and Cmax Was reduced (P<0.01). The initial release speed was slow and stable. The bioavailability was similar to the common tablets. Conclusions The sustained capsule had showed good pharmacokinetics property of sustained-release in the Beagle dogs.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lowseth, L.A.; Gerlach, R.F.; Gillett, N.A.; Muggenburg, B.A. (Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States))

    1990-01-01

    Age-related changes in the histologic morphology of the Beagle dog prostate have been used as a model for similar changes that occur in human beings. Previous studies of the aging changes in Beagle dogs have been limited to animals less than 10 years of age. In this study, the prostate, testes, and serum testosterone levels were evaluated in healthy Beagle dogs that were grouped by age to provide five groups of dogs that ranged from 3 to 14 years of age. Tissue sections from the prostate and testes were examined qualitatively and quantitatively by light microscopy. All animals 6 years of age and older had histologic characteristics of complex benign prostatic hyperplasia. A mean statistically significant increase in prostatic weight with increased age was noted. Morphometric analysis of the prostatic tissue suggested that similar to the change observed in human males, the increase in size was primarily due to an increase in the absolute volume of interstitial tissues. The epithelial component did not contribute to the increase noted, with the exception that the percentage of glandular lumen did increase with age, indicating progressive cystic dilatation of the glands. Stereologic analysis of the testes showed a decrease in the relative percentage of germ cells with increasing age. No distinct age-related trend was detected in serum testosterone concentrations. These findings indicate that the progression of benign prostatic hyperplasia occurs throughout the entire life span of the dog; an association with changes in the testes was not identified.

  19. Spectral variability on primitive asteroids of the Themis and Beagle families: space weathering effects or parent body heterogeneity?

    CERN Document Server

    Fornasier, S; Perna, D; Campins, H; Barucci, M A; Nesvorny, D

    2016-01-01

    Themis is an old and statistically robust asteroid family populating the outer main belt, and resulting from a catastrophic collision that took place 2.5$\\pm$1.0 Gyr ago. Within the old Themis family a young sub-family, Beagle, formed less than 10 Myr ago, has been identified. We present the results of a spectroscopic survey in the visible and near infrared range of 22 Themis and 8 Beagle families members. The Themis members investigated exhibit a wide range of spectral behaviors, while the younger Beagle family members look spectrally bluer with a smaller spectral slope variability. The best meteorite spectral analogues found for both Themis and Beagle families members are carbonaceous chondrites having experienced different degrees of aqueous alteration, prevalently CM2 but also CV3 and CI, and some of them are chondrite samples being unusual or heated. We extended the spectral analysis including the data available in the literature on Themis and Beagle families members, and we looked for correlations betwe...

  20. 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.

  1. 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.

  2. 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.

  3. Localization of Helicobacter spp. in the fundic mucosa of laboratory Beagle dogs: an ultrastructural study

    Directory of Open Access Journals (Sweden)

    Lanzoni Anna

    2011-03-01

    Full Text Available Abstract In dogs Helicobacter spp. are found in all gastric regions usually localized in the surface mucus, gastric glands and parietal cells. The aim of this study was to detail the distribution of Helicobacter spp. in the fundic mucosa of asymptomatic Beagle dogs and their intracellular localization within parietal cells, in order to evaluate species-specific pathogenetic effects on gastric cells. The presence of Helicobacter spp. was investigated by immunohistochemistry, TEM, and PCR in the fundic mucosa of six Beagle dogs. Helicobacter spp. were found in all dogs examined, and H. bizzozeronii and H. felis were identified by PCR and confirmed by TEM. In the lumen of the fundic glands, co-localization was common. H. bizzozeronii was present in larger numbers than H. felis in both intraluminal and intraparietal localization. The amounts of H. bizzozeronii were similar in superficial and basal portions of the glands. H. felis was predominantly localized in the superficial portions of gastric glands but almost absent from the base. Within parietal cells, most Helicobacter organisms were intracanalicular, but intact and degenerate Helicobacter organisms were also visualized free in the cytoplasm or in secondary lysosomes. No specific degenerative lesions were found in infected parietal cells. Helicobacter organisms were also observed within macrophages in the lamina propria. In conclusion, there is a differential distribution of H. bizzozeronii and H. felis in the fundic mucosa of Beagle dogs, and their intracellular localization in parietal cells and macrophages suggests novel pathogenic scenarios for the development of immune response and maintenance of chronic gastritis in dogs.

  4. 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.

  5. Basic data on the hematology, serum biochemistry, urology, and organ weights of beagle dogs.

    Science.gov (United States)

    Choi, So-Young; Hwang, Jae-Sik; Kim, Ill-Hwa; Hwang, Dae-Yeon; Kang, Hyun-Gu

    2011-12-01

    This study was conducted to provide basic data on physiological and hematological characteristics, and organ weights of beagle dogs. A total of 237 beagle dogs were used to determine differences in physiological and hematological parameters, and organ weights depending on sex and age. The respiratory rate of both sexes tended to increase as they grew older and the female heart rate was slightly higher than that of males. Male and female body weights increased rapidly to 33 weeks old followed by a gradual increase to 41-weeks-old. The relative weight of the brain was negatively correlated with body weight, whereas the weight of reproductive organs was positively correlated with body weight. The platelet count of female dogs was slightly higher than that of males. The red blood cell, hemoglobin, and hematocrit of both sexes increased non-significantly with age. In the leukocyte differential count, the neutrophils, and eosinophils of both sexes tended to increase as they grew older, whereas basophils, lymphocytes, and monocytes decreased. In the serum biochemical profiles, alkaline phosphatase was slightly higher in males than females, while the total cholesterol of female dogs at 9-months-old was higher than that of males at the same age. Other biochemical components, including alanine aminotransferase, blood urea nitrogen, creatinine, triglyceride, and total protein increased non-significantly with age in both sexes. To conclude, we observe no significant physiological or hematological differences with sex or age, although decreasing and increasing trends were detected with some parameters. These data provide valuable reference indices of the normal physiological and hematological characteristics of beagle dogs, which should prove useful in toxicological and pharmacological studies.

  6. 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.

  7. Lymphocytic adrenal medullitis and lymphocytic thyroiditis in a laboratory beagle dog.

    Science.gov (United States)

    Doi, Takuya; Tomonari, Yuki; Kawasako, Kazufumi; Yamada, Naoaki; Tsuchitani, Minoru

    2017-02-04

    Lymphocytic adrenal medullitis characterized by inflammation and atrophy in the medulla of the bilateral adrenal glands was observed in an 18-month-old male laboratory beagle dog. It might be that the present lymphocytic adrenal medullitis is an autoimmune-mediated disease as the histological characteristics are consistent with an autoimmune pathogenesis. However, the actual cause remains unclear as the existence of serum autoantibodies against the adrenal medulla could not be confirmed. Although this dog also contracted lymphocytic thyroiditis along with serum thyroglobulin autoantibodies, indicating that the thyroiditis occurred with an autoimmune basis; the relation between the adrenal medullitis and thyroiditis is unknown.

  8. Flora bucal en perros de la raza Beagle con enfermedad periodontal inducida

    OpenAIRE

    Cabrera García, Alexei; Guerra Barroso Mabel; Soto Cantero Luis; Soca Pérez, Maylin; Rodríguez Sosa, Víctor Manuel; Dominguez López, Heberto Arides; Purón Guzmeli, Carlos Alberto; Macías Hernández, Ileana; Aliaga Aleaga, Yilenis; Acosta Berbes, Anais; Guerrero Contreras, Miladys; Gil Díaz, Felipe Alejandro

    2012-01-01

    ResumenLa enfermedad periodontal afecta a los perros durante toda su vida y se debe a la acumulación de placa dental bacteriana en las coronas dentales a lo largo de la encía, lo que conlleva a una reacción inflamatoria de la misma, conocida como gingivitis. Con el fin determinar la flora bucal en perros con enfermedad periodontal inducida se estudiaron 10 canes de la raza Beagle que previamente fueron sometidos a una intervención quirúrgica para inducir la enfermedad.SummaryPeriodontal disea...

  9. Beagle Rupes - Evidence for a basal decollement of regional extent in Mercury’s lithosphere

    Science.gov (United States)

    Rothery, D. A.; Massironi, M.

    2010-09-01

    Thanks to its location at low latitude and close to the terminator in the outbound view of Mercury obtained during MESSENGER's first fly-by, the Beagle Rupes lobate scarp on Mercury has been particularly clearly imaged. This enables us to interpret it as a component of a linked fault system, consisting of a frontal scarp terminated by transpressive lateral ramps. The terrain bounded by these surface manifestations of faulting is the hanging-wall block of a thrust sheet and must be underlain by a basal decollement (a detachment horizon) constituting the fault zone at depth. The decollement must extend a minimum of 150 km eastwards from the frontal scarp, and at least 400 km if displacement is transferred to features interpreted as out-of-sequence thrusts and offset lateral ramps that appear to continue the linked fault system to the east. The depth of the basal decollement could be controlled by crustal stratigraphy or by rheological change within, or at the base of, the lithosphere. Previous interpretations of mercurian lobate scarps regard their thrusts as uniformly dipping and dying out at depth, lacking lateral ramps and any extensive detachment horizon. Anticipated improvements in image resolution and lighting geometry should make it possible to document what percentage of lobate scarps share the Beagle Rupes style of tectonics.

  10. Framing Space: UK Newspaper Reporting of the Beagle 2 and Cassini-Huygens Space Missions

    Science.gov (United States)

    Jergovic, B.; Miller, S.

    2008-05-01

    Relatively little scholarly work has been done on looking at the portrayal of astronomy and space science in the media. This short article examines the UK press coverage of two space missions: the Beagle 2 mission to Mars and the Cassini-Huygens mission to Saturn and its moon Titan. In both cases, the leading scientists exerted a strong influence on what journalists reported, to the extent that some journalists appeared to be almost "embedded" in the mission. For the most part the coverage is positive in tone and the loss of the Beagle 2 spacecraft does not reflect badly on the (later) Cassini-Huygens coverage. Most journalists only covered the actual mission events and, in the case of Huygens, did not follow up to cover the peer-reviewed scientific articles that appeared later. Off-the-cuff comments made by scientists at the time of the missions were widely reported. There appears to be an appreciation by journalists and (by inference) their readership that this was science in the making, and that allowances should be made if these comments later turned out to be inaccurate.

  11. Mucoactive effects of naringin in lipopolysaccharide-induced acute lung injury mice and beagle dogs.

    Science.gov (United States)

    Chen, Yan; Wu, Hao; Nie, Yi-chu; Li, Pei-bo; Shen, Jian-gang; Su, Wei-wei

    2014-07-01

    Our previous study has demonstrated that naringin attenuates EGF-induced MUC5AC hypersecretion in A549 cells by suppressing the cooperative activities of MAPKs/AP-1 and IKKs/IκB/NF-κB signaling pathways. However, the volume of airway mucus is determined by two factors including the number of mucous cells and capacity of mucus secretion. The aim of the present study is to explore the mucoactive effects of naringin in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and beagle dogs. The results demonstrated that naringin of 12.4 mg/kg treatment significantly decreased LPS-induced enhancement of sputum volume and pulmonary inflammation, remarkably increased the subglottic sputum volume and solids content in sputum of lower trachea, while partially, but not fully, significantly increased the elasticity and viscosity of sputum in lower trachea of beagle dogs. Moreover, the MUC5AC content in BALF and goblet-cells in large airways of LPS-induced ALI mice were significantly attenuated by dexamethasone (5 mg/kg), ambroxol (25 mg/kg), and naringin (15, 60 mg/kg). However, the goblet-cells hyperplasia in small airways induced by LPS was only significantly inhibited by dexamethasone and naringin (60 mg/kg). In conclusion, naringin exhibits mucoactive effects through multiple targets which including reduction of goblet cells hyperplasia and mucus hypersecretion, as well as promotion of sputum excretion.

  12. Evaluation of Immunosuppressive Activity of Demethylzeylasteral in a Beagle Dog Kidney Transplantation Model.

    Science.gov (United States)

    An, Huimin; Zhu, Yu; Xu, Wenping; Liu, Yujun; Zhang, Jianping; Lin, Zongming

    2015-12-01

    Several monomers isolated from Tripterygium wilfordii Hook f. (Celastraceae) have attracted worldwide interest. In this study, we established a simple and reliable kidney transplantation model in beagle dog to evaluate the immunosuppressive activity of demethylzeylasteral (T-96), an immunosuppressive monomer isolated from the root xylem of T. wilfordii. Recipient and donor male beagle dogs were obtained from two different breeders to ensure MHC mismatching. All dogs were randomly divided into six groups following kidney transplantation, and different doses of T-96 or cyclosporine A (CsA) were administered to each group during 14 days of observation. The results showed that T-96 alone at a dosage of 10 or 20 mg/kg/day prolonged graft survival up to 10.83 ± 1.47 or 11.17 ± 1.47 days. A combination of T-96 and CsA significantly prolonged the survival time to 13.33 ± 1.75 days. The results demonstrated that T-96 can inhibit acute rejection in kidney transplantation, and the inhibitory effect of T-96 was enhanced when combined with CsA, which suggests the possible use in organ transplantation to prevent immune rejection.

  13. Energy density of sub-Antarctic fishes from the Beagle Channel.

    Science.gov (United States)

    Fernández, D A; Lattuca, M E; Boy, C C; Pérez, A F; Ceballos, S G; Vanella, F A; Morriconi, E R; Malanga, G F; Aureliano, D R; Rimbau, S; Calvo, J

    2009-03-01

    The energy density (ED) of nine species of sub-Antarctic fishes was estimated by calorimetry. The fish, seven notothenioids, one atherinopsid and one galaxiid, represents some of the more abundant species in the ichthyofauna of the Beagle Channel. Principal-components analysis (PCA) of the ED of the different organs/tissues indicated that PC(1) and PC(2) accounted for 87% of the variability. Separation along PC(1) corresponded to differences in muscle and liver energy densities whereas separation along PC(2) corresponded to differences in the ED of the gonads. Differences between species were significant except for P. sima. Inclusion of the gonadosomatic index (GSI) as an explanatory variable enabled us to establish the existence of energy transfer from muscle and liver to the gonads in ripe P. tessellata females. Total ED values varied between 4.21 and 6.26 kJ g(-1), the pelagic Odontesthes sp. being the species with the highest ED. A significant relationship between ED and muscle dry weight (DW(M)) was found for all the species except P. tessellata. These data are the first direct estimates of ED of fishes from the Beagle Channel.

  14. 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.

  15. Effect of low intensity pulsed ultrasound on repairing the periodontal bone of Beagle canines

    Institute of Scientific and Technical Information of China (English)

    Xiao-Qi Gu; Yong-Mei Li; Jing Guo; Li-Hua Zhang; Dong Li; Xiao-Dong Gai

    2014-01-01

    Objective: To investigate the repairing effect of low intensity pulsed ultrasound (LIPUS) on the Beagle canines periodontal bone defect. Methods: A total of 12 Beagle dogs with periodontal bone defect model were randomly divided into control group, LIPUS group, guided tissue regeneration (GTR) group and LIPUS+GTR group, with three in each. After completion of the models, no other proceeding was performed in control group; LIPUS group adopt direct exposure to radiation line LIPUS processing 1 week after modeling; GTR group adopted treatment with GTR, following the CTR standard operation reference; LIPUS+GTR group was treated with LIPUS joint GTR. Temperature change before treatment and histopathological change of periodontal tissue after repair was observed. Results: There was no significant difference in temperature changes of periodontal tissue between groups (P>0.05). The amount and maturity of LIPUS+GTR group were superior to other groups; new cementum, dental periodontal bones of GTR group were superior to the control group but less than LIPUS group; new collagen and maturity of the control group is not high relatively. Conclusions: LIPUS can accelerate the calcium salt deposition and new bone maturation, thus it can serve as promoting periodontal tissue repair, and shortening the periodontal tissue repair time.

  16. Pharmacokinetics study of calf thymus DNA in rats and beagle dogs with (3)H-labeling and tracing method.

    Science.gov (United States)

    Yang, Shuoye; Talbi, Amer; Wang, Xin; Song, Hanlin; Chen, Xijing

    2014-01-01

    This study developed a radioisotope detection and tracing method to investigate the pharmacokinetic properties of calf thymus DNA (ctDNA) in rats and beagle dogs. The radioactivity labeling result was detected through gel electrophoresis analysis, and pharmacokinetic analytical methods for (3)H-ctDNA in rat and beagle dog plasma were developed, respectively. Full method validation indicated that the established radioisotope method was sensitive, specific, rapid and reliable, and the results were all in accordance with the analysis requirement in biological samples. After intravenous administration of the planned doses of (3)H-ctDNA to the rats and beagle dogs, plasma concentrations from the various dose groups declined rapidly. In addition, the radioactive concentration of (3)H-ctDNA in the plasma from single and multiple dosings decreased in a similar trend. Through comparative analysis of the pharmacokinetic parameters, we inferred that the elimination of ctDNA accorded with the linear pharmacokinetic characteristic. The results demonstrated that ctDNA was rapidly eliminated in rat and beagle dog plasma and would not accumulate, indicating the safe use of ctDNA as an immunoadsorptive material without bringing out potential risk.

  17. Synthesis of a highly water-soluble acacetin prodrug for treating experimental atrial fibrillation in beagle dogs.

    Science.gov (United States)

    Liu, Hui; Wang, Ya-Jing; Yang, Lei; Zhou, Mei; Jin, Man-Wen; Xiao, Guo-Sheng; Wang, Yan; Sun, Hai-Ying; Li, Gui-Rong

    2016-05-10

    We previously reported that duodenal administration of the natural flavone acacetin can effectively prevent the induction of experimental atrial fibrillation (AF) in canines; however, it may not be used intravenously to terminate AF due to its poor water-solubility. The present study was to design a water-soluble prodrug of acacetin and investigate its anti-AF effect in beagle dogs. Acacetin prodrug was synthesized by a three-step procedure. Aqueous solubility, bioconversion and anti-AF efficacy of acacetin prodrug were determined with different methodologies. Our results demonstrated that the synthesized phosphate sodium salt of acacetin prodrug had a remarkable increase of aqueous solubility in H2O and clinically acceptable solution (5% glucose or 0.9% NaCl). The acacetin prodrug was effectively converted into acacetin in ex vivo rat plasma and liver microsome, and in vivo beagle dogs. Intravenous infusion of acacetin prodrug (3, 6 and 12 mg/kg) terminated experimental AF without increasing ECG QTc interval in beagle dogs. The intravenous LD50 of acacetin prodrug was 721 mg/kg in mice. Our preclinical study indicates that the synthesized acacetin prodrug is highly water-soluble and safe; it effectively terminates experimental AF in beagle dogs and therefore may be a promising drug candidate for clinical trial to treat patients with acute AF.

  18. A frameshift mutation in the cubilin gene (CUBN) in Beagles with Imerslund-Gräsbeck syndrome (selective cobalamin malabsorption).

    Science.gov (United States)

    Drögemüller, Michaela; Jagannathan, Vidhya; Howard, Judith; Bruggmann, Rémy; Drögemüller, Cord; Ruetten, Maja; Leeb, Tosso; Kook, Peter H

    2014-02-01

    Mammals are unable to synthesize cobalamin or vitamin B12 and rely on the uptake of dietary cobalamin. The cubam receptor expressed on the intestinal endothelium is required for the uptake of cobalamin from the gut. Cubam is composed of two protein subunits, amnionless and cubilin, which are encoded by the AMN and CUBN genes respectively. Loss-of-function mutations in either the AMN or the CUBN gene lead to hereditary selective cobalamin malabsorption or Imerslund-Gräsbeck syndrome (IGS). We investigated Beagles with IGS and resequenced the whole genome of one affected Beagle at 15× coverage. The analysis of the AMN and CUBN candidate genes revealed a homozygous deletion of a single cytosine in exon 8 of the CUBN gene (c.786delC). This deletion leads to a frameshift and early premature stop codon (p.Asp262Glufs*47) and is, thus, predicted to represent a complete loss-of-function allele. We tested three IGS-affected and 89 control Beagles and found perfect association between the IGS phenotype and the CUBN:c.786delC variant. Given the known role of cubilin in cobalamin transport, which has been firmly established in humans and dogs, our data strongly suggest that the CUBN:c.786delC variant is causing IGS in the investigated Beagles.

  19. Spectral variability on primitive asteroids of the Themis and Beagle families: Space weathering effects or parent body heterogeneity?

    Science.gov (United States)

    Fornasier, S.; Lantz, C.; Perna, D.; Campins, H.; Barucci, M. A.; Nesvorny, D.

    2016-05-01

    Themis is an old and statistically robust asteroid family populating the outer main belt, and resulting from a catastrophic collision that took place 2.5 ± 1.0 Gyr ago. Within the old Themis family a young sub-family, Beagle, formed less than 10 Myr ago, has been identified. We present the results of a spectroscopic survey in the visible and near infrared range of 22 Themis and 8 Beagle families members. The Themis members investigated exhibit a wide range of spectral behaviors, including asteroids with blue/neutral and moderately red spectra, while the younger Beagle family members look spectrally bluer than the Themis ones and they have a much smaller spectral slope variability. Four Themis members, including (24) Themis, have absorption bands centered at 0.68-0.73 μm indicating the presence of aqueously altered minerals. The best meteorite spectral analogues found for both Themis and Beagle families members are carbonaceous chondrites having experienced different degrees of aqueous alteration, prevalently CM2 but also CV3 and CI, and some of them are chondrite samples being unusual or heated. The presence of aqueous altered materials on the asteroids surfaces and the meteorite matches indicate that the parent body of the Themis family experienced mild thermal metamorphism in the past. We extended the spectral analysis including the data available in the literature on Themis and Beagle families members, and we looked for correlations between spectral behavior and physical parameters using the albedo and size values derived from the WISE data. The analysis of this larger sample confirms the spectral diversity within the Themis family and that Beagle members tend to be bluer and to have an higher albedo. The differences between the two families may be partially explained by space weathering processes, which act on these primitive surfaces in a similar way than on S-type asteroids, i.e. producing reddening and darkening. However we see several Themis members

  20. Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2012-06-01

    Full Text Available Yongxue Zhao, Long Wang, Mina Yan, Yanling Ma, Guangxi Zang, Zhennan She, Yihui DengCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of ChinaAbstract: Surface modification of nanocarriers with amphiphilic polymer polyethylene glycol (PEG, known as PEGylation, is regarded as a major breakthrough in the application of nanocarriers. However, PEGylated nanocarriers (including liposomes and polymeric nanoparticles induce what is referred to as the “accelerated blood clearance (ABC phenomenon” upon repeated injection and consequently they lose their sustained circulation characteristics. Despite this, the present authors are not aware of any reports of accelerated clearance due to repeated injection for PEGylated solid lipid nanoparticles (SLNs, another promising nanocarrier. This study investigated the pharmacokinetics of PEGylated SLNs upon repeated administration in mice; moreover, the impact of circulation time on the induction of the ABC phenomenon was studied in beagles for the first time. The ABC index, selected as the ratio of the area under the concentration-time curve from time 0 to the last measured concentration of a second injection to that of the first injection, was used to evaluate the extent of this phenomenon. Results showed that the PEGylated SLNs exhibited accelerated clearance from systemic circulation upon repeated injection, both in mice and in beagles, and the ratio for the different time intervals, which showed that the ABC index exhibited significant difference within 30 minutes following the second injection, was good enough to evaluate the magnitude of ABC. This ABC index indicated that the 10 mol% PEG SLNs with a suitable prolonged circulation time induced the most marked ABC phenomenon in this research. This study demonstrated that, like PEGylated nanocarriers such as liposomes and polymeric nanoparticles, PEGylated SLNs induced the ABC phenomenon upon repeated injection

  1. [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

  2. 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

  3. Beagle 2 the Moon: An Experimental Package to Measure Polar Ice and Volatiles in Permanently Shadowed Areas or Beneath the Lunar Surface

    Science.gov (United States)

    Gibson, E. K.; McKay, D. S.; Pillinger, C. T.; Wright, I. P.; Sims, M. R.; Richter, L.

    2008-03-01

    The Gas Analysis Package and associated instruments from Beagle 2 is the ideal payload to measure the abundances and isotopic compositions of ice and volatiles found in the polar regions of the Moon. The hardware has already been flight qualified.

  4. 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.

  5. 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.

  6. Seasonal and pollution-induced variations in biomarkers of transplanted mussels within the Beagle Channel.

    Science.gov (United States)

    Giarratano, Erica; Gil, Mónica N; Malanga, Gabriela

    2011-06-01

    The occurrence of biomarker variations linked to environmental factors makes it difficult to distinguish the effect of pollution. In an attempt to evaluate spatial and seasonal effects of environmental parameters on biomarker responses, mussels Mytilus edulis chilensis coming from an aquaculture farm were transplanted to several points within Ushuaia Bay (Beagle Channel) for 6 weeks in summer and winter. Activities of superoxide dismutase, catalase, glutathione-S-transferase and levels of lipid peroxidation were measured in gills and digestive gland. Cu, Zn, Fe, Cd and Pb concentrations were also assessed. Results indicated a significant effect of seasons on biological responses as well as in metal bioaccumulation showing the influence of natural factors such as dissolved oxygen, temperature and food availability. The interdependence of those environmental factors is important for the homeostasis of thermoconformers, especially regarding their oxidative metabolism and should also be taken into consideration to distinguish natural from pollution-induced variations.

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

    Science.gov (United States)

    Zhang, Yuqiao; Tian, Dali; Huang, Yuyou; Li, Ling; Mao, Juan; Tian, Juan; Ding, Jinsong

    2016-11-01

    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.

  8. Mechanical characteristics of the pulmonary artery in beagle dogs with hepatopulmonary syndrome and portopulmonary hypertension.

    Science.gov (United States)

    Yan, Guozhen; He, Junfeng; Yu, Yueli; Liu, Yang; Yuan, Yanfen; Guo, Zhiyong

    2016-01-01

    The continuous changes in pulmonary hemodynamic properties in hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) have not been fully characterized in large animal models of HPS and PoPH. Beagle dog models of HPS and PoPH were induced by chronic common bile duct ligation and Sephadex microspheres, respectively. The model was validated by catheter examination and pathological analyses, and the hemodynamic characteristics of the models were observed. The results revealed that the cross-sectional area of the blood vessel was significantly increased in HPS models, but it was significantly decreased in the PoPH models. Furthermore, the resistance of pulmonary circulation was elevated in models of HPS, but it was decreased in models of PoPH. The present findings renew the traditional view that pulmonary hypertension is due to the enhanced peripheral resistance.

  9. 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.

  10. A case of spontaneous myocardial necrosis and cerebral ischemic lesions in a laboratory beagle dog.

    Science.gov (United States)

    Matsushita, Kohei; Kohara, Yukari; Ito, Yuko; Yoshikawa, Tsuyoshi; Sato, Makoto; Kitaura, Keisuke; Matsumoto, Satoshi

    2015-10-01

    A beagle dog treated with saline as a control animal in a preclinical study was euthanized due to sudden systemic deterioration. On histopathological examination, contraction band necrosis of myocardial cells was observed widely in the left ventricular wall, including the papillary muscle and apex, and observed slightly in the ventricular septum and left atrium. In the brain, necrosis was observed in neurons and glia of the cerebral cortex, hippocampal pyramidal cells, glial cells of the rostral commissure and Purkinje cells of the cerebellar vermis. It is highly probable that the marked systemic deterioration was caused by cardiac dysfunction due to the spontaneous contraction band necrosis of the myocardial cells, although the pathogenesis of the myocardial lesions remains unclear. Given the distribution of neuronal necrosis in the brain, it is likely that these lesions resulted from the ischemia responsible for acute cardiac failure.

  11. Pharmacokinetics of a florfenicol-tylosin combination after intravenous and intramuscular administration to beagle dogs.

    Science.gov (United States)

    Kim, Eun-Young; Gebru, Elias; Lee, Joong-Su; Kim, Jong-Choon; Park, Seung-Chun

    2011-04-01

    A pharmacokinetic study of a commercial florfenicol-tylosin (2:1) combination product was conducted in six beagle dogs after intravenous (IV) and intramuscular (IM) administration at doses of 10 mg/kg (florfenicol) and 5 mg/kg (tylosin). Serum drug concentrations were determined by a validated high performance liquid chromatography (HPLC) using UV detection. A rapid and nearly complete absorption of both drugs with a mean IM bioavailability of 103.9% (florfenicol) and 92.6% (tylosin), prolonged elimination half-life, and high tissue penetration with steady state volume of distribution of 2.63 l/kg (florfenicol) and 1.98 l/kg (tylosin) were observed. Additional studies, including pharmacodynamic and toxicological evaluation are required before recommendations can be made regarding the clinical application of the product in dogs.

  12. Flora bucal en perros de la raza Beagle con enfermedad periodontal inducida

    Directory of Open Access Journals (Sweden)

    Cabrera García, Alexei

    2012-01-01

    Full Text Available ResumenLa enfermedad periodontal afecta a los perros durante toda su vida y se debe a la acumulación de placa dental bacteriana en las coronas dentales a lo largo de la encía, lo que conlleva a una reacción inflamatoria de la misma, conocida como gingivitis. Con el fin determinar la flora bucal en perros con enfermedad periodontal inducida se estudiaron 10 canes de la raza Beagle que previamente fueron sometidos a una intervención quirúrgica para inducir la enfermedad.SummaryPeriodontal diseases affect the dogs all its life and this is due to the accumulation of bacterial dental plaque along the gums as results this provokes a well known inflammatory reaction defined as gingivitis. The purpose of this paper was to determine the bucal flora in dogs with periodontal disease induced.

  13. Urethral tissue regeneration using collagen scaffold modified with collagen binding VEGF in a beagle model.

    Science.gov (United States)

    Jia, Weisheng; Tang, He; Wu, Jianjian; Hou, Xianglin; Chen, Bing; Chen, Wei; Zhao, Yannan; Shi, Chunying; Zhou, Feng; Yu, Wei; Huang, Shengquan; Ye, Gang; Dai, Jianwu

    2015-11-01

    Extensive urethral defects have a serious impact on quality of life, and treatment is challenging. A shortage of material for reconstruction is a key limitation. Improving the properties of biomaterials and making them suitable for urethral reconstruction will be helpful. Previously, we constructed a fusion protein, collagen-binding VEGF (CBD-VEGF), which can bind to collagen scaffold, stimulate cell proliferation, and promote angiogenesis and tissue regeneration. We proposed that CBD-VEGF could improve the performance of collagen in reconstruction of extensive urethral defects. Our results showed that collagen scaffolds modified with CBD-VEGF could promote urethral tissue regeneration and improve the function of the neo-urethra in a beagle extensive urethral defect model. Thus, modifying biomaterials with bioactive factors provides an alternative strategy for the production of suitable biomaterials for urethral reconstruction.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Il-Young [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Jung, Ui-Won [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Kim, Chang-Sung [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Lee, Yong-Keun [Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-750 (Korea, Republic of); Cho, Kyoo-Sung [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Chai, Jung-Kiu [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Kim, Chong-Kwan [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Choi, Seong-Ho [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of)

    2007-09-15

    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.

  16. Diversity of antibody responses to Borrelia burgdorferi in experimentally infected beagle dogs.

    Science.gov (United States)

    Baum, Elisabeth; Grosenbaugh, Deborah A; Barbour, Alan G

    2014-06-01

    Lyme borreliosis (LB) is a common infection of domestic dogs in areas where there is enzootic transmission of the agent Borrelia burgdorferi. While immunoassays based on individual subunits have mostly supplanted the use of whole-cell preparations for canine serology, only a limited number of informative antigens have been identified. To more broadly characterize the antibody responses to B. burgdorferi infection and to assess the diversity of those responses in individual dogs, we examined sera from 32 adult colony-bred beagle dogs that had been experimentally infected with B. burgdorferi through tick bites and compared those sera in a protein microarray with sera from uninfected dogs in their antibody reactivities to various recombinant chromosome- and plasmid-encoded B. burgdorferi proteins, including 24 serotype-defining OspC proteins of North America. The profiles of immunogenic proteins for the dogs were largely similar to those for humans and natural-reservoir rodents; these proteins included the decorin-binding protein DbpB, BBA36, BBA57, BBA64, the fibronectin-binding protein BBK32, VlsE, FlaB and other flagellar structural proteins, Erp proteins, Bdr proteins, and all of the OspC proteins. In addition, the canine sera bound to the presumptive lipoproteins BBB14 and BB0844, which infrequently elicited antibodies in humans or rodents. Although the beagle, like most other domestic dog breeds, has a small effective population size and features extensive linkage disequilibrium, the group of animals studied here demonstrated diversity in antibody responses in measures of antibody levels and specificities for conserved proteins, such as DbpB, and polymorphic proteins, such as OspC.

  17. Study on Plasma Concentration and Bioavailability of Wogonin in Beagle's Dogs

    Institute of Scientific and Technical Information of China (English)

    LI Jian-chun; CHEN Fei-hu; DONG Hai-jun; GAO Shu

    2011-01-01

    Objective To develop an LC-MS/MS method for determining the concentration of wogonin in dog plasma and investigate the pharmacokinetics and bioavailability by different administrations of wogonin in Beagle's dogs. Methods LC-MS/MS was employed in determining the concentration of wogonin with the selected ion monitoring model after liquid-liquid extraction with ethyl acetate of dog plasma samples. The lower limit of quantification was 0.105 μg/L. Target ions were at m/z 285.0→270.0 for wogonin and 373.3→305.3 for finasteride. In a randomized, self-control, and cross-over study, six male Beagle's dogs were treated with different administration methods in three test periods. Pharmacokinetic parameters were calculated with DAS software (Ver. 2.0). Results The calibration curve was linear in the range of 0.105-107.36 μg/L for wogonin in dog plasma samples. The main pharmacokinetic parameters of ig administration (native drug of 15 mg/kg and solution preparation of 5 mg/kg) and iv route were as follows: Cmax (2.5 ± 1.1), (7.9 ± 3.3), and (6838.7 ± 1322.1) μg/L, tmax (0.7 ± 0.3) and (0.3 ± 0.2) h for the both former, AUC0-1 (7.1 ± 2.0), (21.0 ± 3.2), and (629.7 ±111.8) μg·h/L. The absolute bioavailability of native and solution of wogonin were (0.59 ± 0.35)% and (3.65 ± 2.00)%, respectively. Conclusion The validated method is convenient, sensitive, and specific, and the improvement of wogonin solubility could remarkably increase the absolute bioavailability.

  18. Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    Yue YUAN; Xiao-yan CHEN; San-ming LI; Xiu-yan WEI; Hui-min YAO; Da-fang ZHONG

    2009-01-01

    Aim:The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs.Methods:The experiment was a two-period,crossover design using 6 Beagle dogs.Meloxicam tablets were administered orally at a dose of 0.31 mg/kg,and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg.Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS).The pharmacokinetic parameters were calculated using the Topfit 2.0 program.Results:The pharmacokinetic results showed that AUCo-t (23.9±8.26 μg·h-mL-1) in plasma after oral administration was significantly higher than after transdermal delivery (1.00±0.43 μg·h-mL-1).In contrast,the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery.The synovial fluid concentration in the treated leg was much higher than that in the untreated leg,whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration.Conclusion:The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue.This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point.Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.

  19. 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.

  20. 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.

  1. Reconstruction of beagle hemi-mandibular defects with allogenic mandibular scaffolds and autologous mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    ChangKui Liu

    Full Text Available Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs can increase the integration of massive allografts (hemi-mandible in a large animal model.Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at 4 (n = 4, 12 (n = 4, 24 (n = 4 or 48 weeks (n = 3 postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD of transplants were used to evaluate defect reconstruction outcomes.Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05, and all micro-architectural parameters were significantly different between groups (p<0.05. Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed.Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a combination of MSCs and osteoinductive growth

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

    Energy Technology Data Exchange (ETDEWEB)

    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 /sup 60/Co ..gamma.. 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/sub 50/ for ..gamma..-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/sub 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/sub 50/ is dependent upon hematopoietic damage. At 5 R/day and less, no meaningful LD/sub 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.

  3. The Themis-Beagle families: Investigation of space-weathering processes on primitive surfaces

    Science.gov (United States)

    Fornasier, S.; Perna, D.; Lantz, C.; Barucci, M.

    2014-07-01

    features associated to hydrated silicates, and, recently, water-ice and organics features have been detected on the surface of (24) Themis (Campins et al. 2010, Rivkin & Emery 2010). Hydrated silicates are produced by the aqueous-alteration process, which require low temperature (Beagle, formed less than 10 Myr ago, has been identified. This sub-family has 65 members up to 2 km of diameter (Nesvorny et al. 2008). So, the Themis family is very important to shed light on the asteroid-comet continuum, to constrain the abundances of water ices in the outer part of the main belt, and to probe space-weathering effects on old Themis and young Beagle families' members. To investigate all these aspects, we carried out a spectroscopic survey in the visible and near-infrared range at the 3.6-m Italian telescope TNG (La Palma, Spain) during 6 nights in February and December 2012. We got new spectra of 8 Beagle and 22 Themis members using the DOLORES (with the LR-R and LR-B grisms) and the NICS (with the Amici prism) instruments. To look for possible coma around the targets, we also performed deep imaging in the R filter. Data are currently under analysis, and the results will be presented at the ACM meeting. None of the investigated spectra show water-ice absorption features at 1.5 and 2 microns, while few Themis members have visible absorption bands associated with hydrated silicates. The best meteoritic analogues to both Themis and Beagle members are the carbonaceous chondrites, especially CM2. The spectra of Beagle and Themis asteroids show significant differences: 'old' Themis members exhibit a wide range of spectra, including asteroids with blue/neutral and moderately red spectra (relative to the Sun), while the young Beagle members investigated are bluer and brighter than the Themis ones. These preliminary results seem to indicate that the SW effects on primitive asteroids are similar to those observed on silicate asteroids, that is, they produce reddening of the spectra and

  4. Effects of competitive and noncompetitive 5α-reductase inhibitors on serum and intra-prostatic androgens in beagle dogs

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xiao-feng; YANG Yong; WANG Wei; QIU Zhi; ZHANG Peng; WANG Biao

    2013-01-01

    Background 5α-Reductase inhibitors (5α-RI) act by inhibiting the conversion of testosterone to dihydrotestosterone (DHT),thereby preventing DHT induced benign prostatic hyperplasia.The existing 5α-RIs can be classified into two types:competitive and noncompetitive.Currently,limited evidence is available concerning the effect differences between the two types of 5α-RI on androgens.The purpose of this study was to assess the effects of competitive and noncompetitive 5α-RIs on serum and intra-prostatic androgens in beagle dogs.Methods Twenty beagles with spontaneous benign prostatic hyperplasia were randomly allocated into two groups:epristeride group (n=10) in which beagles were treated with epristeride at 1 mg/kg once a day for 3 months,and finasteride group (n=10) in which beagles were treated with finasteride at 1 mg/kg once a day for 3 months.The levels of intra-prostatic testosterone and DHT were measured before treatment and on day one after three months medication.Serum levels of testosterone and DHT were measured at the same time points.Changes in androgen levels before and after treatment were analyzed,and comparisons were made within each treatment group and between treatment groups.Results After 3-month treatment,serum and intra-prostatic DHT levels all decreased significantly in both the epristeride and finasteride groups.The change of DHT in serum was significantly higher in the finasteride group (-14% and-43% in epristeride and finasteride groups respectively,with P<0.001); however there was no significant difference in the changes of intra-prostatic DHT between the two groups (-47% and-51% in epristeride and finasteride groups,respectively,P=0.304).The decreases in DHT levels were accompanied by reciprocal increases in serum and intra-prostatic testosterone levels.Changes of testosterone were significantly higher in finasteride group both in serum (20% and 42%in epristeride and finasteride groups,respectively,P<0.001) and in

  5. Histological response of soda-lime glass-ceramic bactericidal rods implanted in the jaws of beagle dogs.

    Science.gov (United States)

    Moya, José S; Martínez, Arturo; López-Píriz, Roberto; Guitián, Francisco; Díaz, Luis A; Esteban-Tejeda, Leticia; Cabal, Belén; Sket, Federico; Fernández-García, Elisa; Tomsia, Antoni P; Torrecillas, Ramón

    2016-08-12

    Bacterial and fungal infections remain a major clinical challenge. Implant infections very often require complicated revision procedures that are troublesome to patients and costly to the healthcare system. Innovative approaches to tackle infections are urgently needed. We investigated the histological response of novel free P2O5 glass-ceramic rods implanted in the jaws of beagle dogs. Due to the particular percolated morphology of this glass-ceramic, the dissolution of the rods in the animal body environment and the immature bone formation during the fourth months of implantation maintained the integrity of the glass-ceramic rod. No clinical signs of inflammation took place in any of the beagle dogs during the four months of implantation. This new glass-ceramic biomaterial with inherent bactericidal and fungicidal properties can be considered as an appealing candidate for bone tissue engineering.

  6. 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.

  7. The fossil mammals collected byCharles Darwin in South America during his travels on board the HMS Beagle

    OpenAIRE

    2009-01-01

    Duringthe first two years of his voyage aboard HMS Beagle, Charles Darwin collected aconsiderable number of fossil mammals from various localities in Argentina andUruguay. Among these remains are those of large mammals that Darwin informallyassigned to Megatherium and Mastodon, the only large taxa thenknown for South America, and of small and mediumsized mammals that Darwinrecognized as representing at least two rodents and a horse. The study ofDarwin's collection was entrusted to Richard Owe...

  8. Effect of meloxicam and meloxicam with misoprostol on serum prostaglandins and gastrointestinal permeability in healthy beagle dogs

    OpenAIRE

    Roškar Tina; Nemec Svete Alenka; Jerin A.; Butinar J.; Kobal Silvestra

    2011-01-01

    The aim of the present study was to investigate the effect of meloxicam and meloxicam with misoprostol on prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) serum concentration, as well as on gastrointestinal permeability. NSAIDs, such as meloxicam, have gastrointestinal side effects, which are due to prostaglandins depletion and topical damage. Seven adult beagle dogs were included in the study. Three different 20 days long treatments were carried out (pl...

  9. Implantation study of a tissue-engineered self-expanding aortic stent graft (bio stent graft) in a beagle model.

    Science.gov (United States)

    Kawajiri, Hidetake; Mizuno, Takeshi; Moriwaki, Takeshi; Iwai, Ryosuke; Ishibashi-Ueda, Hatsue; Yamanami, Masashi; Kanda, Keiichi; Yaku, Hitoshi; Nakayama, Yasuhide

    2015-03-01

    The use of stent grafts for endovascular aortic repair has become an important treatment option for aortic aneurysms requiring surgery. This treatment has achieved excellent outcomes; however, problems like type 1 endoleaks and stent graft migration remain. Bio stent grafts (BSGs), which are self-expanding stents covered with connective tissue, were previously developed using "in-body tissue architecture" technology. We assessed their early adaptation to the aorta after transcatheter implantation in a beagle model. BSGs were prepared by subcutaneous embedding of acryl rods mounted with self-expanding nitinol stents in three beagles for 4 weeks (n = 3/dog). The BSGs were implanted as allografts into infrarenal abdominal aortas via the femoral artery of three other beagles. After 1 month of implantation, aortography revealed no stenosis or aneurysmal changes. The luminal surface of the BSGs was completely covered with neointimal tissue, including endothelialization, without any thrombus formation. The cover tissue could fuse the luminal surface of the native aorta with tight conjunctions even at both ends of the stents, resulting in complete impregnation of the strut into the reconstructed vascular wall, which is expected to prevent endoleaks and migration in clinical applications.

  10. Artificial periodontal defects and frequency of tooth brushing in beagle dogs (II). Clinical findings after a period of healing.

    Science.gov (United States)

    Corba, N H; Jansen, J; Pilot, T

    1986-03-01

    This investigation was designed to determine the influence of different frequencies of tooth brushing on artificial periodontal defects in the beagle dog after a period of healing. In 12 beagle dogs, periodontal defects were created using elastic bands placed in the sulci below the gingival margin after having cut the dento-gingival fibres to the level of the alveolar bone crest. This active phase of creating defects lasted for 6 weeks. After removal of the elastic bands, the created defects were left undisturbed during the remainder of the pre-experimental period (12 weeks). 6 premolars in the lower jaw were used (2P2, 3P3, 4P4). After the pre-experimental period, the 12 dogs were distributed into 3 groups of 4 dogs each. Each group was brushed with a certain frequency, i.e., 7 times, 3 times or once a week. Registrations of plaque index, gingival index and probing depth using a constant force probe were carried out on approximal surfaces. The experiment lasted for 24 weeks. A brushing effect was calculated for each dog to include information on all within-dog and between-dog variations. It was shown in relation to artificially-induced periodontal defects in beagle dogs that after a period of healing, brushing 7 times a week is superior to brushing 3 times a week in establishing and maintaining gingival health.

  11. Artificial periodontal defects and frequency of tooth brushing in beagle dogs (I). Clinical findings after creation of the defects.

    Science.gov (United States)

    Corba, N H; Jansen, J; Fidler, V

    1986-02-01

    This investigation was designed to determine the influence of different frequencies of tooth brushing on artificial periodontal defects in the beagle dog shortly after creation. In 12 beagle dogs, periodontal defects were created using elastic bands placed in the sulci below the gingival margin after having cut the dento-gingival fibres to the level of the alveolar bone. This active phase of creating defects lasted for 6 weeks. 6 premolars in the lower jaw were used (2P2, 3P3, 4P4). After removal of the elastic bands, the 12 dogs were distributed into 3 groups of 4 dogs each. Each group was brushed with a certain frequency, i.e., 7 times, 3 times or once a week. Plaque index, gingival index and probing depth, using a constant force probe, were assessed interproximally. The experiment lasted for 24 weeks. For hypothesis testing, a brushing effect was calculated for each dog. Furthermore, an analysis was performed based on the absolute scores at week 24. From the statistical analysis, it was concluded that in artificially-induced periodontal defects in beagle dogs immediately after creation, brushing 7 times a week is superior to brushing 3 times a week to establish and maintain gingival health.

  12. Geomorphological evolution of a paraglacial coastal system: Moat Sector, Beagle Channel, Tierra de Fuego, Argentina

    Science.gov (United States)

    Blanco-Chao, R.; Pérez-Alberti, A.; Martínez-Cortizas, A.; Valcárcel-Díaz, M.; Costa-Casais, M.

    2009-04-01

    The morphodynamics of paraglacial coastal systems is controlled by a number of factors, including rock basement structure, sediment disposal, changes in the relative sea-level and wave regime. Of great importance is the thickness and the particle size composition of the glacial deposits because they are not only the main source of material, but also a major element in the coast plan form and in the processes of sediment redistribution. The Moat sector in the Beagle Channel (Tierra del Fuego, Argentina), is a shallow embayment opened in a previously glaciated landscape, in which the Beagle glacier left several drumlins and moraines. After deglaciation the rising sea-level led to the erosion of the till sediments at least until 2550 yr BP, exposing the rock substrate in which up to three narrow shore platforms were modelled. The erosion of the till produced cliffs up to 18 m high, capped with Holocene sediments. After 2550 yr BP a fall in the relative sea-level enhanced wave dissipation on the rocky areas and forced the diffraction of the incoming waves. The limits of the sedimentary cell were then set and a shadow zone developed in the east section of the beach, where the cliff became stabilized meanwhile erosion persisted on the west section. The coarser till of the west cliff was then the main source of sediments, and the retreat of the cliff left a boulder pavement that created a secondary limit of the cell. The clasts were redistributed by a dominant west to east transport that still dominates today. The 14C dates obtained in the sedimentary deposit developed on top of the cliff suggest that, when the bluff retreat stopped at the east end, a phase of stabilization began and the talus was covered by a layer of organic-rich sediments. Later, an environmental change to drier conditions, occurred after 1310-1180 cal. yr BP, led to the desiccation and degradation of the organic-sediments of the talus, which started to be eroded exposing the till again

  13. Transcriptome comparison in the pituitary-adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure.

    Science.gov (United States)

    Luo, Wei; Fang, Meixia; Xu, Haiping; Xing, Huijie; Nie, Qinghua

    2015-10-01

    Chronic stress can induce a series of maladjustments, and the response to stress is partly regulated by the hypothalamus-pituitary-adrenal axis. The aim of this study was to investigate the genetic mechanisms of this axis regulating stress responsiveness. The pituitary and adrenal cortex of Beagle and Chinese Field Dog (CFD) from a stress exposure group [including Beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), Beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)] and a control group [including Beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), Beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)], selected to perform RNA-seq transcriptome comparisons, showed that 40, 346, 376, 69, 70, 38, 57 and 71 differentially expressed genes were detected in BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1, BP2 vs. CFDP2, BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2 respectively. NPB was a gene common to BAC1 vs. BAC2 and CFDAC1 vs. CFDAC2, indicating it was a potential gene affecting response to chronic stress, regardless of the extent of chronic stress induced. PLP1 was a gene common to BP1 vs. CFDP1 and BP2 vs. CFDP2, suggesting its important roles in affecting the stress-tolerance difference between the two breeds, regardless of whether there was stress exposure or not. Pathway analysis found 12, 4, 11 and 1 enriched pathway in the comparisons of BP1 vs. CFDP1, BP2 vs. CFDP2, CFDP1 vs. CFDP2 and BAC1 vs. BAC2 respectively. Glutamatergic synapse, neuroactive ligand-receptor interaction, retrograde endocannabinoid signaling, GABAergic synapse, calcium signaling pathway and dopaminergic synapse were the most significantly enriched pathways in both CFDP1 vs. CFDP2 and BP1 vs. CFDP1. GO, KEGG pathway and gene network analysis demonstrated that GRIA3, GRIN2A, GRIN2B and NPY were important in regulating the stress response in CFD. Nevertheless, ADORA1, CAMK2A, GRM1, GRM7 and NR4A1 might be critical genes contributing to the stress

  14. Design and Implementation of a Controller for a BeagleBone Quadcopter

    Science.gov (United States)

    Olejnik, Peter

    Unmanned aerial vehicles are quickly becoming a significant and permanent feature in today's world of aviation. Amongst the various types of UAVs, a popular type is the quadcopter. Also referred to as a quadrotor, this rotor craft's defining feature is that it has four propellers. While its use is common in the hobbyist community, this aircraft's use within industry is blooming. Presented are the efforts to design and implement a controller for a BeagleBone based quadcopter. As part of this effort, characteristics of the quadcopter were experimentally determined. These characteristics consist of physical properties of the quadcopter, such as the moments of inertia, the motor performance characteristics, and variance within its sensors. A model was then created and implemented within a MATLAB environment to simulate the flight of the quadcopter. With a simulated environment created, a controller was designed to control the flight of the quadcopter and a Kalman Filter was implemented to filter a sensor input. These designs were then verified in the simulated environment.

  15. 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.

  16. Invivo absorption behaviour of theophylline from starch-methyl methacrylate matrix tablets in beagle dogs.

    Science.gov (United States)

    Fernández-Campos, F; Ferrero, C; Colom, H; Jiménez-Castellanos, M R

    2015-01-30

    This study evaluates in vivo the drug absorption profiles from potato starch-methyl methacrylate matrices(*) using theophylline as a model drug. Healthy beagle dogs under fasting conditions were used for in vivo studies and plasma samples were analyzed by a fluorescence polarization immunoassay analysis (FPIA method). Non-compartmental and compartmental (population approach) analysis was performed to determine the pharmacokinetic parameters. The principle of superposition was applied to predict multiple dose plasma concentrations from experimental single dose data. An in vitro-in vivo correlation (IVIVC) was also assessed. The sustained absorption kinetics of theophylline from these formulations was demonstrated by comparison with two commercially available oral sustained-release theophylline products (Theo-Dur(®) and Theolair(®)). A one-compartment model with first order kinetics without lag-time best describes the absorption/disposition of theophylline from the formulations. Results revealed a theophylline absorption rate in the order FD-HSMMA≥Theo-Dur(®)≥OD-CSMMA>Theolair(®)≥FD-CSMMA. On the basis of simulated plasma theophylline levels, a twice daily dosage (every 12h) with the FD-CSMMA tablets should be recommended. A Level C IVIVC was found between the in vitrot50% and the in vivo AUC/D, although further optimization of the in vitro dissolution test would be needed to adequately correlate with in vivo data.

  17. 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.

  18. Seasonal phytoplankton dynamics in extreme southern South America (Beagle Channel, Argentina)

    Science.gov (United States)

    Almandoz, Gastón O.; Hernando, Marcelo P.; Ferreyra, Gustavo A.; Schloss, Irene R.; Ferrario, Martha E.

    2011-08-01

    The phytoplankton biomass and composition dynamics in relation with environmental factors were explored during an annual cycle (July 2006-2007) for the first time in the Beagle Channel. Samples were examined by light and scanning electron microscopy and carbon biomass was estimated using measured cell biovolumes. The annual cycle was characterized by a sharp contrast between low density and biomass during the autumn-winter period and a significant increase during spring and summer. The maximum biomass peak was observed during early spring (141 μg C l - 1 and 8.7 μg Chl a l - 1 ) and was associated with a bloom of the diatom genus Chaetoceros. In spite of a strong nutrient depletion that lead to the subsequent bloom decline, a second peak of biomass was observed after 2 weeks, mainly represented by the diatoms T. mendiolana and T. anguste-lineata. Towards the end of spring and during summer diatom density decreased and assemblages were enriched by unidentified tiny phytoflagellates and dinoflagellates. A total of 138 taxa were identified during the study period. From these, 10 are known as potentially toxic species: Alexandrium catenella, A. ostenfeldii, A. tamarense, Dinophysis acuminata, D. rotundata, Prorocentrum cordatum, Pseudo-nitzschia australis, P. calliantha, P. fraudulenta and P. cf. seriata. Their presence is noteworthy since the area sustains a growing aquiculture production.

  19. Sub-chronic safety evaluation of the ethanol extract of Aralia elata leaves in Beagle dogs.

    Science.gov (United States)

    Li, Fengjin; He, Xiaoli; Niu, Wenying; Feng, Yuenan; Bian, Jingqi; Kuang, Haixue; Xiao, Hongbin

    2016-08-01

    Aralia elata Seem. (A. elata) is a traditional Chinese medicine to treat some diseases. This investigation aims to evaluate the pharmaceutical safety of the ethanol extract of A. elata leaves, namely ethanol leaves extract (ELE), in Beagle dogs. In sub-chronic oral toxicity study, dogs were treated with the ELE at doses of 50, 100 and 200 mg/kg for 12 weeks and followed by 4 weeks recovery period. During experimental period, clinical signs, mortality, body temperature, food consumption and body weight were recorded. Analysis of electrocardiogram, urinalysis, ophthalmoscopy, hematology, serum biochemistry, organ weights and histopathology were performed. The results showed that both food consumption and body weight significantly decreased in high-dose group. Treatment-related side effects and mortality were observed in high-dose female dogs. Some parameters showed significant alterations in electrocardiogram, urinalysis, serum biochemistry and relative organ weights. These alterations were not related to dose or consistent across gender, which were ascribed to incidental and biological variability. The findings in this study indicated that the no-observed adverse effect level (NOAEL) of the ELE was 100 mg/kg in dogs and provided a vital reference for selecting a safe application dosage for human consumption.

  20. 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.

  1. 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.

  2. Biodegradable effect of PLGA membrane in alveolar bone regeneration on beagle dog.

    Science.gov (United States)

    Hua, Nan; Ti, Vivian Lao; Xu, Yuanzhi

    2014-11-01

    Guided bone regeneration (GBR) is a principle adopted from guided tissue regeneration (GTR). Wherein, GBR is used for the healing of peri-implant bony dehiscences, for the immediate placement of implants into extraction sockets and for the augmentation of atrophic alveolar ridges. This procedure is done by the placement of a resorbable or non-resorbable membrane that will exclude undesirable types of tissue growth between the extraction socket and the soft tissue to allow only bone cells to regenerate in the surgically treated lesion. Here, we investigated the biodegradable effect of polylactic-co-glycolic acid (PLGA) membrane in the alveolar bone on Beagle dogs. Results show that both collagen and PLGA membrane had been fully resorbed, biodegraded, at four weeks post-operative reentry into the alveolar bone. Histological results under light microscopy revealed formation of new bone trabeculae in the extraction sites on both collagen and PLGA membrane. In conclusion, PLGA membrane could be a potential biomaterials for use on GBR and GTR. Nevertheless, further studies will be necessary to elucidate the efficiency and cost effectiveness of PLGA as GBR membrane in clinical.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hurst, D.R. (Miami Univ., Oxford, OH (USA). Dept. of Zoology)

    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 {sup 45}Ca labeled skeletons were divided into four groups: sham controls (SO{minus}); ovariectomized (OV{minus}); 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{sub 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 {sup 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{minus} and OV+ mid-rib regions had significantly lower dry and ash weights than SO{minus}. Total Ca contents of these same regions were also decreased in the OV{minus} and OV+. The only significant change in Ca/dry and Ca/ash was observed when comparing OV+ to SO{minus}. 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.

  4. [Histopathology of meibomian gland abnormalities in experimental PenCB intoxicated beagle treated with squalane].

    Science.gov (United States)

    Kohno, T; Ohnishi, Y

    1989-05-01

    In order to examine the effect of squalane to excrete PCB from the intoxicated animals, histopathological studies of Meibomian gland abnormalities were carried out in experimental PenCB (3,4,5,3',4'-pentachlorobiphenyl) intoxicated beagles treated with squalane. All experimental animals except a control group showed characteristic changes of Meibomian glands: dilation of the duct and squamous metaplasia of the alveolar cells. According to the degree of these findings, five stages were divided in the processes of Medibomian gland changes. The PenCB intoxicated dogs initially showed mild pathological changes of the glands and later moderate to severe degrees of findings. In the PenCB intoxicated animals treated with squalane, severe degree of Meibomian gland findings were found in the early stage and mild to moderate abnormalities in the late stage. The concentration of PenCB in blood varied in each animal, and the animals with advanced Medibomian gland abnormalities tended to have high level of PenCB concentration in blood. In conclusion, the effect of squalane to excrete PCB from the intoxicated animals were not determined in this study.

  5. Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs

    Institute of Scientific and Technical Information of China (English)

    Jin Sun; Jie-Ming Shi; Tian-Hong Zhang; Kun Gao; Jing-Jing Mao; Bing Li; Ying-Hua Sun; Zhong-Gui He

    2005-01-01

    AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo formulation was achieved by mixing slow- and rapid-of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs68.7%. From release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67±0.52 h vs9.83±0.98 h and the Cmax being 1 334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn preparations were statistically bioequivalent. Furthermore,percentage absorption in vivo and the cumulative percentage release in vitro.CONCLUSION: The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Christopher E. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Wang, Xihai [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Robinson, Robert J. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Brooks, Antone L. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Lovaglio, Jamie A. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Patton, Kristin M. [Battelle Toxicology Northwest, Richland, WA (United States); McComish, Stacey [United States Transuranium and Uranium Registries, Washington State University, College of Pharmacy, Richland, WA (United States); Tolmachev, Sergei Y. [United States Transuranium and Uranium Registries, Washington State University, College of Pharmacy, Richland, WA (United States); Morgan, William F. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

    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.

  7. A comparison of the pharmacokinetics of three different preparations of total flavones of Hippophae rhamnoides in beagle dogs after oral administration.

    Science.gov (United States)

    Duan, Jingze; Dang, Yang; Meng, Houjun; Wang, Huizhen; Ma, Ping; Li, Guowen; Wu, Tao; Xie, Yan

    2016-06-01

    Pharmacokinetic properties of isorhamnetin, quercetin, and kaempferol in three different total flavones of Hippophae rhamnoides (TFH) preparations were compared after oral administration to beagle dogs by a UPLC-MS method. The pharmacokinetic results showed that C max of isorhamnetin and quercetin in TFH solid dispersion (TFH-SD) and TFH self-emulsifying (TFH-SE) preparations was significantly enhanced than that in TFH preparations (p beagle dogs can be significantly increased in TFH-SD and TFH-SE preparations compared to TFH preparations, which was helpful to explore the new forms for oral administration TFH and explain their in vivo processes.

  8. "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.

  9. Improvement in cardiac function after sarcoplasmic reticulum Ca2+-ATPase gene transfer in a beagle heart failure model

    Institute of Scientific and Technical Information of China (English)

    MI Ya-fei; LI Xiao-ying; TANG Li-jiang; LU Xiao-chun; FU Zhi-qing; YE Wei-hua

    2009-01-01

    Background Heart failure (HF) is a major cause of morbidity and mortality worldwide, but current treatment modalities cannot reverse the underlying pathological state of the heart. Gene-based therapies are emerging as promising therapeutic modalities in HF patients. Our previous studies have shown that recombinant adeno-associated viral (rAAV) gene transfer of Sarco-endoplasmic reticulum calcium ATPase (SERCA2a) can be effective in treating rats with chronic heart failure (CHF). The aim of this study was to examine the effects of SERCA2a gene transfer in a large HF animal model.Methods HF was induced in beagles by rapid right ventricular pacing (230 beats/min) for 30 days. A reduced rate ventricular pacing (180 beats/min) was continued for another 30 days. The beagles were assigned to four groups: (a) control group (n=4); (b) HF group (n=4); (c) enhanced green fluorescent protein group (n=4); and (d) SERCA2.a group (n=4). rAAVl-EGFP (lx1012 μg) and rAAVl-SERCA2a (lx1012 μg) were delivered intramyocardially. SERCA2.a expression was assessed by Western blotting and immunohistochemistry.Results Following 30 days of SERCA2a gene transfer in HF beagles its protein expression was significantly higher than in the HF group than in the control group (P <0.05). Heart function improved along with the increase in SERCA2a expression. Left ventricular systolic function significantly improved, including the ejection fraction, left ventricular systolic pressure, maximal rate of rise of left ventricular pressure (+dp/dtmax), and the maximal rate of decline of left ventricular pressure (-dp/dtmax) (P <0.05). Left ventricular end-diastole pressure significantly decreased (P <0.05). The expression of SERCA2a in the myocardial tissue was higher in the SERCA2a group than in the HF group (P<0.05). Conclusions Intramyocardial injection of rAAVl-SERCA2a can improve the cardiac function in beagles induced with HE We expect further studies on SERCA2a's long-term safety, efficacy, dosage

  10. Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in beagle dogs: a placebo-controlled study

    OpenAIRE

    2015-01-01

    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 train...

  11. 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

  12. Characterization and Bioavailability of Wogonin by Different Administration Routes in Beagles.

    Science.gov (United States)

    Zhu, Na; Li, Jian-Chun; Zhu, Jin-Xiu; Wang, Xiu; Zhang, Jin

    2016-10-16

    BACKGROUND With the gradually accumulating research on pharmacological activity of wogonin, the in vitro analysis research on wogonin has become more and more popular, but there are very few reports about in vivo detection, and there are no solid dispersions (SDs) of Wogonin. The aim of this study was to explore the formation of solid dispersions (SDs) of wogonin. The reasons for the low bioavailability were studied through different routes of administration. MATERIAL AND METHODS SDs was formulated using the solvent evaporation method via polyvinylpyrrolidone K30 (PVP). The characterization of the drug and its carrier was detected by X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The serum concentrations of Wogonin were detected using the LC-MS/MS method. Six beagles were fed 3 different formulations of wogonin in 3 cycles. RESULTS The SDs of wogonin had a higher solubility than the physical mixtures. Based on XRD and DSC, wogonin was transformed from a crystalline morphology to an amorphous structure. The main pharmacokinetic parameters of i.g. administration (crude material and SD) and i.v. route were as follows: Cmax (2.5±1.1), (7.9±3.3), and (6838.7±1322.1) μg/L, tmax (0.7±0.3) and (0.3±0.2) h for the former, AUC0-t (7.1±2.0), (21.0±3.2) and (629.7±111.8) μg·h/L. The absolute bioavailability of native wogonin and wogonin arginine solution were (0.59±0.35)% and (3.65± 2.60)%. Further research showed that the low bioavailability of wogonin might be associated with low solubility and rapid combination with glucuronic acid in vivo. CONCLUSIONS The significantly increased solubility of SDs and the further preparation of arginine solution could significantly increase the bioavailability of wogonin.

  13. Guided bone regeneration for immediate non-submerged implant placement using bioabsorbable materials in Beagle dogs.

    Science.gov (United States)

    Brunel, G; Benqué, E; Elharar, F; Sansac, C; Duffort, J F; Barthet, P; Baysse, E; Miller, N

    1998-10-01

    The aim of the present study was to evaluate the combined application of different bioabsorbable materials for healing of residual peri-implant defects after placement of non-submerged implants into fresh extraction sockets. Second and third mandibular premolars were extracted from 10 Beagle dogs, the coronal part of the distal sockets were surgically enlarged and this was followed by immediate placement of specially designed hollow-screw non-submerged dental implants. For each animal, the coronal peri-implant defects were further treated with one of the 4 following procedures: 1) no treatment, control site; 2) grafting with porous hydroxyapatite (HA); 3) collagen membrane tightly secured around the implant and over the defect and 4) grafting with HA covered with a collagen membrane. After 16 weeks of healing, specimens were removed from the mandibule and prepared for a histomorphometric evaluation. The bone-to-implant contact length (BIC) was measured and compared amongst the different treatment modalities. In the defect area, the irregular bone regeneration was similar between all the treatment procedures (P > 0.10). In the sites covered with a collagen membrane alone, the total BIC (47%) was greater than in control sites (28.7%, P < 0.05) or sites grafted with HA (22.2%, P < 0.02). Total BIC in sites treated with the HA-membrane combination (43%) was only significantly different from sites treated with HA (P < 0.05). It is concluded that the use of bioabsorbable materials results in a limited increase of osseointegration when used in conjunction with immediate placement of non-submerged implants, although the principle of the one stage surgical approach can be maintained.

  14. Increased type 1 chemokine expression in experimental Chagas disease correlates with cardiac pathology in beagle dogs.

    Science.gov (United States)

    Guedes, Paulo M M; Veloso, Vanja M; Talvani, André; Diniz, Livia F; Caldas, Ivo S; Do-Valle-Matta, Maria A; Santiago-Silva, Juliana; Chiari, Egler; Galvão, Lucia M C; Silva, João S; Bahia, Maria T

    2010-11-15

    Chemokines and chemokine receptors interaction have presented important role in leukocyte migration to specific immune reaction sites. Recently, it has been reported that chemokine receptors CXC (CXCR3) and CC (CCR5) were preferentially expressed on Th1 cells while CCR3 and CCR4 were preferentially expressed on Th2 cells. This study evaluated the mRNA expression of type 1 and type 2 chemokine and chemokine receptors in the cardiac tissue of Beagle dogs infected with distinct genetic groups of Trypanosoma cruzi (Y, Berenice-78 and ABC strains) during acute and chronic phases. To analyze the correlation between chemokine and chemokine receptors expression and the development of heart pathology, the chronic infected animals were divided into groups, according to the parasite strain and based on the degree of heart damage: cardiac and indeterminate form of Chagas disease. Our results indicated that cardiac type1/2 chemokines and their receptors were partially dependent on the genetic diversity of parasites as well as the polarization of clinical forms. Also, dogs presenting cardiac form showed lower heart tissue mRNA expression of CCL24 (type 2) and higher expression of CCL5, CCL4 and CXCR3 (type 1) when compared with those with indeterminate form of disease. Together, these data reinforce a close-relation between T. cruzi genetic population and the host specific type 1 immune response and, for the first time, we show the distribution of type 1/2 chemokines associated with the development of cardiac pathology using dogs, a well similar model to study human Chagas disease.

  15. 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.

  16. S-carboxymethyl-L-cysteine and it (R/S)-S-oxides in beagle dog plasma and hepatic cytosol.

    Science.gov (United States)

    Panagopoulos, Panayotis; Mitchell, Stephen C; Steventon, Glyn B

    2015-01-01

    1. Incubation of beagle hepatic cytosol, under conditions promoting phenylalanine hydroxylase activity, led to the formation of the sulfoxide derivatives of S-carboxymethyl-L-cysteine, N-acetyl-S-carboxymethyl-L-cysteine, S-methyl-L-cysteine and N-acetyl-S-methyl-L-cysteine. Thiodiglycolic acid was not a substrate. Enzyme kinetic parameters (Km, Vmax) were derived indicating S-carboxymethyl-L-cysteine had the greatest clearance; no enantioselective preference was observed for this S-oxygenation reaction. 2. Following oral administration of S-carboxymethyl-L-cysteine to beagle dogs, the parent substance and its sulfoxide were the only compounds identified in the plasma. Pharmacokinetic data have been obtained indicating that the small amount of sulfoxide formed persisted within the body for longer than the parent material, but that the majority of the ingested dose remained in the administered sulfide form. 3. The sulfide moiety within the muco-regulatory drug, S-carboxymethyl-L-cysteine, is thought to be vital as it acts as a free radical scavenger, resulting in the inactive sulfoxide. Additional extensive enyzme-mediated sulfoxidation would decrease the amount of active sulfide available. In the dog this appears to not be an issue, signalling possible exploitation for therapeutic benefit in treating airway disease.

  17. Effect of a botanical composition, UP446, on respiratory, cardiovascular and central nervous systems in beagle dogs and rats.

    Science.gov (United States)

    Yimam, Mesfin; Lee, Young Chul; Jia, Qi

    2016-06-01

    Extensive safety evaluation of UP446, a botanical composition comprised of standardized extracts from roots of Scutellaria baicalensis and heartwoods of Acacia catechu, has been reported previously. Here we carried out additional studies to assess the effect of UP446 on respiratory, cardiovascular and central nervous (CNS) systems. A Functional observational battery (FOB) and whole body plethysmography system in rats and implanted telemetry in dogs were utilized to evaluate the potential CNS, respiratory and cardiovascular toxicity, respectively. UP446 was administered orally at dose levels of 800, 2000 and 5000 mg/kg to SpragueDawley rats and at 4 ascending dose levels (0, 250, 500 and 1000 mg/kg) to beagle dogs. No abnormal effects were observed on the cage side, open field, hand held, and sensori-motor observations suggestive of toxicity in respiratory, cardiovascular and central nervous (CNS) systems. Rectal temperatures were comparable for each treatment groups. Similarly, respiratory rate, tidal volume and minute volume were unaffected by any of the treatment groups. No UP446 related changes were observed on blood pressure, heart rate and electrocardiogram in beagle dogs at dose levels of 250, 500 and 1000 mg/kg. Some minor incidental, non-dose correlated changes were observed in the FOB assessment. These data suggest that UP446 has minimal or no pharmaco-toxicological effect on the respiratory, cardiovascular and central nervous systems.

  18. Spontaneous Pathology and Routine Clinical Pathology Parameters in Aging Beagle Dogs: A Comparison With Adolescent and Young Adults.

    Science.gov (United States)

    Barnes, J; Cotton, P; Robinson, S; Jacobsen, M

    2016-03-01

    AstraZeneca ran a bespoke study to generate age-matched clinical pathology and histopathology data from a cohort of Beagle dogs aged between 25 and 37 months to support the use of these older animals in routine preclinical toxicology studies. As the upper age range of Beagle dogs routinely used in toxicology studies does not normally exceed 24 months, there is an absence of appropriate age-matched historical control data. The generation of such data was crucial to understand whether age-related differences in spontaneous findings might confound the interpretation of toxicology study data. While the majority of the histopathology findings in all the older dogs occurred at a similar prevalence as those expected in young adult dogs (<24 months), a number of differences were observed in the thymus (involution), bone marrow (increased adiposity), testes (degenerative changes), and lung (fibrosis, pigment and alveolar hyperplasia) that could be misinterpreted as a test article effect. Minor differences in some clinical pathology values (hemoglobin, alkaline phosphatase, absolute reticulocytes) were of a small magnitude and considered unlikely to affect the interpretation of study data.

  19. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin after intravenous and intramuscular administration in beagle dogs.

    Science.gov (United States)

    Yohannes, Sileshi; Awji, Elias Gebru; Lee, Seung-Jin; Park, Seung-Chun

    2015-03-01

    1.The aim of the present study was to determine the PKs of marbofloxacin in beagle dogs after intravenous (i.v.) and intramuscular (i.m.) administration, the ex vivo and in vitro PK/PD indices of marbofloxacin against clinical isolates of Staphylococcus pseudintermedius, and the ex vivo AUC/MIC ratios associated with different levels of antibacterial activity. 2.After i.v. of marbofloxacin (2 mg/kg), the mean ± SEM values of AUC, t1/2β, Vss, and CL were 8.47 ± 3.51 h µg/mL, 8.08 ± 6.25 h, 2.32 ± 1.00 L/kg and 0.23 ± 0.06 L/kg/h and corresponding values after intramuscular injection were 11.37 ± 3.07 h µg/mL, 7.51 ± 3.70, 1.80 ± 0.90 L/kg and 0.17 ± 0.04 L/kg/h. After i.m. administration, a Cmax of 1.76 ± 0.09 µg/mL was achieved at Tmax of 0.47 ± 0.08 h. The ex-vivo AUC/MIC ratios required to produce bacteriostasis, bactericidal action and elimination of S. pseudintermedius were 65.03, 97.02 and 136.84 h. 3.The in vivo AUC/MIC ratios obtained after i.v. and i.m. administration of 2 mg/kg marbofloxacin (67.76 ± 1.23 and 91.18 ± 2.61) were below the ex vivo AUC/MIC ratios required for bactericidal activity and bacterial elimination (97.02 ± 9.24 2 mg/kg and 136.21 ± 7.58), suggesting that the recommended daily dosage (2 mg/kg) may not suffice to kill and eradicate S. pseudintermedius strains encountered in clinical area.

  20. Characterization and Bioavailability of Wogonin by Different Administration Routes in Beagles

    Science.gov (United States)

    Zhu, Na; Li, Jian-chun; Zhu, Jin-xiu; Wang, Xiu; Zhang, Jin

    2016-01-01

    Background With the gradually accumulating research on pharmacological activity of wogonin, the in vitro analysis research on wogonin has become more and more popular, but there are very few reports about in vivo detection, and there are no solid dispersions (SDs) of Wogonin. The aim of this study was to explore the formation of solid dispersions (SDs) of wogonin. The reasons for the low bioavailability were studied through different routes of administration. Material/Methods SDs was formulated using the solvent evaporation method via polyvinylpyrrolidone K30 (PVP). The characterization of the drug and its carrier was detected by X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The serum concentrations of Wogonin were detected using the LC-MS/MS method. Six beagles were fed 3 different formulations of wogonin in 3 cycles. Results The SDs of wogonin had a higher solubility than the physical mixtures. Based on XRD and DSC, wogonin was transformed from a crystalline morphology to an amorphous structure. The main pharmacokinetic parameters of i.g. administration (crude material and SD) and i.v. route were as follows: Cmax (2.5±1.1), (7.9±3.3), and (6838.7±1322.1) μg/L, tmax (0.7±0.3) and (0.3±0.2) h for the former, AUC0-t (7.1±2.0), (21.0±3.2) and (629.7±111.8) μg·h/L. The absolute bioavailability of native wogonin and wogonin arginine solution were (0.59±0.35)% and (3.65±2.60)%. Further research showed that the low bioavailability of wogonin might be associated with low solubility and rapid combination with glucuronic acid in vivo. Conclusions The significantly increased solubility of SDs and the further preparation of arginine solution could significantly increase the bioavailability of wogonin. PMID:27744456

  1. 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

  2. Comparison of Different Periodontal Healing of Critical Size Noncontained and Contained Intrabony Defects in Beagles

    Science.gov (United States)

    Zang, Sheng-Qi; Kang, Shuai; Hu, Xin; Wang, Meng; Wang, Xin-Wen; Zhou, Tao; Wang, Qin-Tao

    2017-01-01

    Background: Regenerative techniques help promote the formation of new attachment and bone filling in periodontal defects. However, the dimensions of intraosseous defects are a key determinant of periodontal regeneration outcomes. In this study, we evaluated the efficacy of use of anorganic bovine bone (ABB) graft in combination with collagen membrane (CM), to facilitate healing of noncontained (1-wall) and contained (3-wall) critical size periodontal defects. Methods: The study began on March 2013, and was completed on May 2014. One-wall (7 mm × 4 mm) and 3-wall (5 mm × 4 mm) intrabony periodontal defects were surgically created bilaterally in the mandibular third premolars and first molars in eight beagles. The defects were treated with ABB in combination with CM (ABB + CM group) or open flap debridement (OFD group). The animals were euthanized at 8-week postsurgery for histological analysis. Two independent Student's t-tests (1-wall [ABB + CM] vs. 1-wall [OFD] and 3-wall [ABB + CM] vs. 3-wall [OFD]) were used to assess between-group differences. Results: The mean new bone height in both 1- and 3-wall intrabony defects in the ABB + CM group was significantly greater than that in the OFD group (1-wall: 4.99 ± 0.70 mm vs. 3.01 ± 0.37 mm, P < 0.05; 3-wall: 3.11 ± 0.59 mm vs. 2.08 ± 0.24 mm, P < 0.05). The mean new cementum in 1-wall intrabony defects in the ABB + CM group was significantly greater than that in their counterparts in the OFD group (5.08 ± 0.68 mm vs. 1.16 ± 0.38 mm; P < 0.05). Likewise, only the 1-wall intrabony defect model showed a significant difference with respect to junctional epithelium between ABB + CM and OFD groups (0.67 ± 0.23 mm vs. 1.12 ± 0.28 mm, P < 0.05). Conclusions: One-wall intrabony defects treated with ABB and CM did not show less periodontal regeneration than that in 3-wall intrabony defect. The noncontained 1-wall intrabony defect might be a more discriminative defect model for further research into periodontal

  3. Algunas consideraciones sobre la deshidratación en perros beagle antes de su uso en investigaciones biomédicas - Some considerations on the dehydration in beagle dogs before their use in biomedical research

    Directory of Open Access Journals (Sweden)

    Arencibia Arrebola, Daniel Francisco

    2009-11-01

    Full Text Available ResumenEl agua y los electrolitos son elementos vitales para la vida, debenmantenerse en constante equilibrio en el interior del organismo, dentro de límites de variación muy estrechos. Para ello los mamíferos poseen mecanismos que compensan las agresiones del medio, que tienden a romper este equilibrio. Estos reciben el nombre de mecanismos reguladores (el riñón, la hormona antidiurética y la aldosterona. Las alteraciones patológicas del equilibrio hidrosalino o lo que es igual, el equilibrio del agua y del sodio, se conocen como contracciones y expansiones del volumen del espacio extracelular. Una de las causas fundamentales de disminución de peso, la aparición de animales con anemia y desfavorable estado físico en los perrosde la raza beagle lo constituyen los cuadros de diarreas, vómitos einapetencia por otras enfermedades sobre todo en la etapa de cuarentena o durante nuestras investigaciones biomédicas las cuales impiden que se utilicen animales aptos y sanos para dicho fin. En el presente trabajo tenemos como objetivo realizar una guía práctica sobre como clasificar, diagnosticar y tratar la deshidratación en perros beagle, para de esta forma llegar al final delos estudios con la mayor calidad y cantidad de animales requeridos,asegurando la rapidez con la cual contrarrestar los efectos desfavorables que ocasiona la deshidratación. Para un buen diagnóstico, pronóstico y tratamiento es fundamental saber el tipo de deshidratación, cantidad de líquido perdido, estado de salud integral del animal y fluidos con los que contamos.SummaryThe water and electrolytes are vital elements for the life; they should be stay in constant balance inside the organism, among limits of very narrow variation. For it the mammals possess mechanisms that compensate the aggressions of the environment that spread to break this balance. These receive the name of mechanisms regulators (the kidney, antidiuretic hormone and the aldosterone. The

  4. 基于Linux嵌入式平台BeagleBone Black的EtherCAT主站设计%EtherCAT Master Based on Linux Embedded Platform BeagleBone Black

    Institute of Scientific and Technical Information of China (English)

    高恩博; 颜钢锋

    2016-01-01

    EtherCAT是一种开放的实时以太网通讯协议,提出了一套完整的EtherCAT主站设计方案,旨在进一步提高工业控制实时性。其中,选用基于AM3358处理器的BeagleBone Black作为Linux嵌入式开发平台,并且在该平台上运行集成Xenomai实时补丁的Linux操作系统,然后在操作系统上构建IgH EtherCAT Master for Linux开源框架,最后基于这套开源框架进行应用层程序的设计,完成整套主站设计。实验结果表明,同步误差控制在ns级的水准,报文的传输时间在μs级,可以满足工业控制系统对实时性的要求。%For the purpose of improve the real-time performance of industrial control,a complete EtherCAT master design is presented in this paper. Firstly,choose the BeagleBone Black based on AM3358 as the Linux embedded platform and im-plement the embedded real-time Linux system with Xenomai on the platform.Then,build the IgH EtherCAT Master for Linux open-source framework on the system.Lastly,this paper designs the application program with the framework and complete the whole EtherCAT master.

  5. 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.

  6. 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.

  7. The effects of repeated intravenous iohexol administration on renal function in healthy beagles – a preliminary report

    Directory of Open Access Journals (Sweden)

    Kirberger Robert M

    2012-08-01

    Full Text Available Abstract Background Contrast induced nephrotoxicity (CIN is a well described syndrome in humans undergoing contrast medium examinations. To date CIN has received minimal attention in the veterinary literature despite increasing use of contrast medium examinations in computed tomographic studies. Methods This prospective study evaluated the effect of 1290 mg/kg iohexol given intravenously to 5 normal beagle dogs in a divided dose at an interval of 6–8 weeks. Renal function was evaluated by means of scintigraphically determined glomerular filtration rate (GFR and a variety of laboratory assays. Results Only GFR showed a significant decrease (17% after the second injection but not to a clinically or pathologically significant level. Conclusions No clinically significant effect of repeated contrast medium administration was determined in this limited study. However in dogs with reduced renal function the risk of CIN is likely to increase dramatically post contrast administration.

  8. Pyridoxine neuropathy: correlation of functional tests and neuropathology in beagle dogs treated with large doses of vitamin B6.

    Science.gov (United States)

    Schaeppi, U; Krinke, G

    1982-10-01

    Neurologic examination, electrophysiologic testing and microscopic post-mortem examination was used to study the neuropathy induced in the beagle dog by administration of excessive amounts of vitamin B6. Two female dogs received repeated daily oral doses of 3 g. The treatment was ceased when the dogs developed severe general morbidity, including uncoordinated gait and abnormal neurologic symptoms. The symptoms were most severe during and early after cessation of treatment, and in general they regressed during the subsequent 2 months of treatment-free observation. Sensory central and peripheral maximum nerve conduction velocity started to decrease after a considerable delay; the decrease progressed until late after termination of treatment and failed to fully regress. Morphologic lesions were confined to large, first order sensory neurons. The neurologic examination thus revealed the early changes, while electrodiagnostics and microscopic neuropathology were indicators of more advanced stages of toxic neuropathy and disclosed selective lesions in individuals whose gait appeared to be unremarkable.

  9. Placebo-controlled double-blind clomipramine trial for the treatment of anxiety or fear in beagles during ground transport.

    Science.gov (United States)

    Frank, Diane; Gauthier, Audrey; Bergeron, Renée

    2006-11-01

    The purpose of this explorative study was, first, to document changes in physiological parameters and behavior observed in dogs following ground transport and, second, to measure the effects on the above variables of a short-term administration of clomipramine, anecdotally already prescribed in private veterinary practice to reduce fear, anxiety, or both. Twenty-four beagles were randomly allocated to either clomipramine (2 mg/kg, q12h for 7 d) or placebo treatment, and then transported 3 times in a truck for 1 hour. Physiological parameters (cortisol, neutrophil:lymphocyte (N:L) ratio, heart rate) and behavior were recorded and analyzed. Clomipramine significantly reduced plasma cortisol (P anxiety, or both during transport. More research is needed to confirm the efficacy of this treatment and the appropriate dosage.

  10. 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

  11. Development of self-nanoemulsifying drug delivery system for oral bioavailability enhancement of valsartan in beagle dogs.

    Science.gov (United States)

    Li, Zhenbao; Zhang, Wenjuan; Gao, Yan; Xiang, Rongwu; Liu, Yan; Hu, Mingming; Zhou, Mei; Liu, Xiaohong; Wang, Yongjun; He, Zhonggui; Sun, Yinghua; Sun, Jin

    2017-02-01

    Valsartan, an angiotensin II receptor antagonist, is widely used to treat high blood pressure in the clinical setting. However, its poor water solubility results in the low oral bioavailability. The aim of this study was to improve dissolution rate and oral bioavailability by developing a self-nanoemulsifying drug delivery system. Saturation solubility of valsartan in various oils, surfactants, and cosurfactants was investigated, and the optimized formulation was determined by central composite design-response surface methodology. The shape of resultant VAL-SNEDDS was spherical with an average diameter of about 27 nm. And the drug loading efficiency is approximately 14 wt%. Differential scanning calorimetry and XRD studies disclosed the molecular or amorphous state of valsartan in VAL-SNEDDS. The dissolution study indicated that the self-nanoemulsifying drug delivery systems (SNEDDS) exhibited significantly enhanced dissolution compared with market capsules (Diovan®) in various media. Furthermore, the stability of formulation revealed that valsartan SNEDDS was stable under low temperature and accelerated test condition. Furthermore, the pharmacokinetics demonstrated that C max and AUC(0-∞) of SNEDDS capsules were about three- and twofold higher than Diovan® in beagle dogs, respectively. Meanwhile, the safety evaluation implied that VAL-SNEDDS was innocuous to beagle dogs during 15 days of continuous administration. Our results suggested that VAL-SNEDDS was a potential and safe delivery system with enhanced dissolution rate and oral bioavailability, as well as offered a strategy for the engineering of poorly water-soluble drugs in the clinical setting.

  12. Proliferation capacity of T-lymphocytes is affected transiently after a long-term weight gain in Beagle dogs.

    Science.gov (United States)

    Van de Velde, H; Janssens, G P J; Rochus, K; Duchateau, L; Scharek-Tedin, L; Zentek, J; Nguyen, P; Cox, E; Buyse, J; Biourge, V; Hesta, M

    2013-04-15

    Across species obesity is associated with several disorders but in companion animals little information is available on the impact of chronic obesity on immune competence. The aim of the present study was to investigate whether weight gain and stable obese bodyweight affects the immune cell response. Obesity was induced in eight adult healthy beagle dogs (weight gain group; WGG) by a weight gain period (WGP) of 47 weeks, which was immediately followed by a period (stable period: SP) of stable obesity of 26 weeks. Eight adult healthy beagle dogs were included as a control group (CG) and remained at their ideal bodyweight throughout the entire study. Body composition was measured at five intervening time-points. Concentration of serum leptin and inflammatory cytokines, functionality of lymphocytes and phagocytic activity of neutrophils and monocytes were evaluated at ten intervening time-points. Serum leptin concentration was rising during the WGP in the WGG but went to lower concentrations during the SP. At the end of long-term weight gain, a decreased mitogen-induced proliferation of T-lymphocytes was noted but this alteration seemed to be transient after stabilization of bodyweight. This finding may imply an altered immune response for dogs with different energy balances. However, no systemic low grade inflammation or alteration in other immune cell functions was observed. Consequently it is suggested that the change in energy balance during the onset of obesity (becoming obese versus being obese), evokes an additional obesity-related disorder in dogs, i.e. impaired T-lymphocyte immune function.

  13. Regenerative effect of hOPG gene-modified autologous PDLs in combination with cell transplantation on periodontal defection in beagle dogs.

    Science.gov (United States)

    Jiang, Su; Tang, Kunqi; Chen, Bin; Yan, Fuhua

    2016-12-01

    This study evaluated the ability of human osteoprotegerin gene-modified autologous periodontal ligament cells (PDLCs) in combination with cell transplantation to promote periodontal regeneration in beagle dogs. Adenovirus Ad5-hOPG-EGFP-transfected PDLCs and BME-10X collagen membranes were fabricated and used for periodontal repair. Buccal periodontal defects (mesiodistal width × depth: 5 × 5 mm) were created on the second, third, and fourth mandibular premolars in six normal beagle dogs, and the defects were histologically and histomorphometrically assessed for periodontal regeneration in the following four groups: (1) hOPG-PDLCs + BME-10X, (2) mock-PDLCs + BME-10X, (3) PDLCs + BME-10X, and (4) BME-10X. The radiographic and histological results suggested that hOPG-PDLCs significantly promoted periodontal defect repair. This study demonstrates the potential of hOPG-modified PDLCs for periodontal tissue regeneration.

  14. A longitudinal study assessing lens thickness changes in the eye of the growing beagle using ultrasound scanning: relevance to age of dogs in regulatory toxicology studies.

    Science.gov (United States)

    Maynard, Juliana; Sykes, Angela; Powell, Helen; Healing, Guy; Scott, Marietta; Holmes, Andrew; Ricketts, Sally-Ann; Stewart, Jane; Davis, Stewart

    2014-12-01

    The lens is formed in utero with new secondary lens fibres added as outer layers throughout life in a growth pattern characteristic of the species. This study examined the time course of beagle lens growth to better understand the optimal starting age of dogs for safety studies to support adult versus paediatric indications, and to assess the feasibility of non-invasively monitoring lens growth with high frequency ultrasound. Ultrasound scanning was performed in six female beagle dogs using the Vevo770. All dogs were imaged in B-mode using local anaesthetic but without sedation. Imaging was carried out every 2 weeks from 8 to 22 weeks of age and then monthly until 62 weeks of age. The dogs tolerated the procedure well. The lens was visible in all dogs and measuring the lens thickness with high frequency ultrasound demonstrated good analytical reproducibility [Root Mean Square (RMS) = 3.13%]. No differences between the left and right eye existed and lens thickness correlated with body weight. The highest weekly growth rate was before 12 weeks of age. A statistically significant difference between monthly thickness was detected until 42 weeks of age at which point growth reached a plateau. During the experiment, lenses grew by 29.7% reaching an average thickness of 6.4 mm ± 0.03. By 10 months of age (the typical age used for routine toxicological evaluation), beagles have reached a plateau in lens growth that is analogous to human adults. Where lens is a target organ of concern it is suggested that beagles under 6 months old may be a better model for determining paediatric safety.

  15. Development and Validation of an UPLC-Q-TOF-MS Method for Quantification of Fuziline in Beagle Dog After Intragastric and Intravenous Administration.

    Science.gov (United States)

    Gong, Xiao-hong; Li, Yan; Li, Yun-xia; Yuan, An; Zhao, Meng-jie; Zhang, Ruo-qi; Zeng, Dai-wen; Peng, Cheng

    2016-03-01

    A specific and sensitive UPLC-Q-TOF-MS method operated in the positive ion mode was developed and validated for the quantification of Fuziline in Beagle dog plasma. Fuziline and Neoline internal standard were separated on an Acquity UPLC BEH C18 column with the total running time of 4 min using gradient elution at the flow rate of 0.25 mL/min. The calibration curves for Fuziline showed good linearity in the concentrations ranging from 2 to 400 ng/mL with correlation coefficients (r) greater than 0.9971. The lower limit of quantification was 0.8 ng/mL. Intra- and interbatch relative standard deviations ranged from 2.11 to 3.11% and 3.12 to 3.81%, respectively. Fuziline was stable under different sample storage and processing conditions. The developed method was successfully applied to the comparative pharmacokinetic study of Fuziline in Beagle dog after intravenous and oral administration. Low absolute bioavailability of Fuziline (1.45 ± 0.76%) suggested a significant metabolism transformation extent in Beagle dog.

  16. Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs.

    Science.gov (United States)

    Guan, Su; Hu, Chun-Yun; He, Meng-Ying; Yang, Ying-Ying; Tang, Yu-Xin; Chen, Jie-di; Huang, Li-Jie; Tan, Wen

    2015-12-01

    This study was to compare pharmacokinetics and bile transformation of R-enantiomer bambuterol with its racemate. Pharmacokinetics of R-enantiomer was investigated after single-dose intravenous and three doses of oral administration to rats and beagle dogs. To compare the pharmacokinetics with racemic bambuterol, the same oral doses of racemic bambuterol were also administrated; the blood and bile samples were collected by cannulation. A validated LC-MS/MS method was used to assess the level of bambuterol in plasma and bile. After single intravenous administration, no significant differences were observed between the two drugs in pharmacokinetic data. After oral dosing of R-bambuterol, the AUCs of R-enantiomer presented linear correlation. After same oral dosing of R-enantiomer and its racemate, all the pharmacokinetic parameters were equivalent. However, the clearance and apparent distribution had different results due to species and administration route difference. The bile transformation of these two compounds was similar and implicated that liver transformation accounted for the major metabolism of them. The bioavailability of R-enantiomer and racemate were comparative and relatively high in beagle dogs. Thus, R-enantiomer had a comparative pharmacokinetic profile and bile transformation with racemic bambuterol in rats and beagle dogs. These findings provided references for further clinical study.

  17. Hydroacoustical evidence of the expansion of pelagic swarms of Munida gregaria (Decapoda, Munididae) in the Beagle Channel and the Argentine Patagonian Shelf, and its relationship with habitat features

    Science.gov (United States)

    Diez, Mariano J.; Cabreira, Ariel G.; Madirolas, Adrián; Lovrich, Gustavo A.

    2016-08-01

    Squat lobsters are highly diversified and widespread decapods, of which only three species form pelagic swarms. Here we infer the expansion of Munida gregaria populations in the Beagle Channel and the Argentine Patagonian Shelf by means of acoustic surveys of pelagic swarms. We also describe the habitat characteristics in which these swarms occur. Acoustic data was collected during three multidisciplinary scientific cruises on board of the R/V Puerto Deseado during 2009, 2012 and 2014. Despite differences in the environmental conditions between the two surveyed areas, between 2009 and 2014 pelagic swarms increased their occurrence and abundance both in the Beagle Channel and on the Argentine Patagonian Shelf. Towards the end of the studied period, pelagic swarms of M. gregaria occurred in new locations, supporting the notion of a population expansion. Within the Beagle Channel swarm expansions were more marked than on the Patagonian Shelf. We here postulate that M. gregaria expansions occur in association with productive areas of the Argentine continental shelf, such as frontal zones, favoured by the squat lobster phenotypic plasticity that permit to exploit resources in both the neritic and benthic environments. At a regional scale on the Patagonian Shelf, three main groups of pelagic swarms of M. gregaria were clearly associated to respective frontal zones. The information presented here is necessary to understand fluctuations in both distribution and abundance patterns of a key species on the Argentine continental shelf. These fluctuations could be direct or indirect indicators of changes in the ecosystem.

  18. 26-week repeated oral dose toxicity study of UP446, a combination of defined extracts of Scutellaria baicalensis and Acacia catechu, in beagle dogs.

    Science.gov (United States)

    Yimam, Mesfin; Lee, Young Chul; Jia, Qi

    2016-07-01

    The needs for relatively safe botanical alternatives to relieve symptoms associated to arthritis have continued to grow in parallel with the ageing population. UP446, a standardized bioflavonoid composition from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, has been used as over the counter joint care dietary supplements and a prescription medical food. Significant safety data have been documented in rodents and human for this composition. Here we evaluated the potential adverse effects of orally administered UP446 in beagle dogs following a 26-week repeated oral dose toxicity study. UP446 at doses of 250, 500 and 1000 mg/kg/day were administered orally to beagle dogs for 26 weeks. A 4-week recovery group from the high dose (1000 mg/kg) and vehicle treated groups were included. No morbidity or mortality was observed for the duration of the study. No significant differences between groups in body weights, food consumption, ophthalmological examinations, electrocardiograms, urinalysis, hematology, clinical chemistry, organ weights, gross pathology and histopathology were documented. Emesis, loose feces and diarrhea were noted in both genders at the 1000 mg/kg treatment groups. These clinical signs were considered to be reversible as they were not evident in the recovery period. In conclusion, the no-observed-adverse-effect-level (NOAEL) of UP446 was considered to be 500 mg/kg/day both in male and female beagle dogs.

  19. 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.

  20. 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.

  1. The chiral bioconversion and preclinical pharmacokinetic analysis of (R)-(+)-rabeprazole in beagle dogs by HPLC and HPLC-MS/MS.

    Science.gov (United States)

    Gao, Yan-hui; Xu, Jia-xing; Su, Zhong-xue; Song, Li; Lou, Hong-xiang

    2013-11-01

    In order to accurately investigate the preclinical pharmacokinetics of (R)-(+)-rabeprazole sodium injection, a reliable high-performance liquid chromatography (HPLC) method was developed using a Chiral-AGP column to prove that there is no chiral bioconversion of (R)-(+)-rabeprazole to (S)-(-)-rabeprazole in beagle dogs after single intravenous administration of (R)-(+)-rabeprazole sodium injection. An HPLC-tandem mass spectrometry (HPLC-MS/MS) method for analysis of (R)-(+)-rabeprazole was developed and validated, and used to acquire the pharmacokinetic parameters in beagle dogs. (R)-(+)-Rabeprazole and internal standard omeprazole were extracted from plasma samples by protein precipitation and separated on a C18 column using methanol-5 mm ammonium acetate as mobile phase. Detection was performed using a turbo-spray ionization source and mass spectrometric positive multi-reaction monitoring mode. The linear relationship was achieved in the range from 2.5 to 5000 ng/mL. The method also afforded satisfactory results in terms of sensitivity, specificity, precision, accuracy and recovery as well as the stability of the analyte under various conditions, and was successfully applied to a preclinical pharmacokinetic study in beagle dogs after single intravenous administrations of (R)-(+)-rabeprazole sodium injection at 0.33, 2 and 6 mg/kg.

  2. 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.

  3. Liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry for Simultaneous Determination of Metformin and Glimepiride in Beagle Dog Plasma and Bioequivalence Study

    Institute of Scientific and Technical Information of China (English)

    BAI Jing; SHI Xiao-wei; DU Ying-feng; XIANG Bai; WANG Shuai; CAO De-ying

    2012-01-01

    A sensitive and selective liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS/MS) was used for the simultaneous determination of metformin and glimepiride in beagle dog plasma with glipizide as internal standard(IS).After simplified protein precipitation with methanol,both the analytes and IS were chromatographed on a Zorbax CN column via gradient elution with methanol(containing 5 mmol/L ammonium acetate) and 5 mmol/L aqueous ammonium acetate as the mobile phase.Detection was performed by multiple reaction monitoring(MRM) scanning via ESI source operated in positive ionization mode.Specificity,linearity,accuracy,precision,recovery,matrix effect and stability were validated for metformin and glimepiride in beagle dog plasma.The calibration curves were linear in a concentration range of 10--10000 ng/mL for metformin and 4--4000 ng/mL for glimepiride with both correlation coefficients higher than 0.99.The recoveries obtained for the analytes and IS were all between 82.7% and 101.2%.The method exhibited excellent performance in terms of selectivity,robustness,short analytical time and simplicity of sample preparation.Finally,the proposed method was applied to a bioequivalence study of self-made bilayer tablet and commercial formulation containing 500 mg of metformin and 1 mg of glimepiride in beagle dogs.

  4. Microdistribution and long-term retention of 239Pu (NO3)4 in the respiratory tracts of an acutely exposed plutonium worker and experimental beagle dogs.

    Science.gov (United States)

    Nielsen, Christopher E; Wilson, Dulaney A; Brooks, Antone L; McCord, Stacey L; 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 [(239)Pu (NO(3))(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 histologic lung, lymph node, trachea, and nasal turbinate tissue sections. These studies showed that both the human and dogs had a nonuniform 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 subpleural 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 to increase cancer risk.

  5. 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

    2009-04-01

    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.

  6. Comparison of miRNA expression profiles in pituitary-adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure.

    Science.gov (United States)

    Luo, Wei; Fang, Meixia; Xu, Haiping; Xing, Huijie; Fu, Jiangnan; Nie, Qinghua

    2016-01-01

    MicoRNAs (miRNAs), usually as gene regulators, participate in various biological processes, including stress responses. The hypothalamus-pituitary-adrenal axis (HPA axis) is an important pathway in regulating stress response. Although the mechanism that HPA axis regulates stress response has been basically revealed, the knowledge that miRNAs regulate stress response within HPA axis, still remains poor. The object of this study was to investigate the miRNAs in the pituitary and adrenal cortex that regulate chronic stress response with high-throughput sequencing. The pituitary and adrenal cortex of beagles and Chinese Field dogs (CFD) from a stress exposure group (including beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)) and a control group (including beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)), were selected for miRNA-seq comparisons. Comparisons, that were made in pituitary (including BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1 and BP2 vs. CFDP2) and adrenal cortex (including BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2), showed that a total of 39 and 18 common differentially expressed miRNAs (DE-miRNAs) (Total read counts > 1,000, Fold change > 2 & p-value 2 & p-value < 0.05) from those target genes in pituitary and adrenal cortex were obtained separately, in combination with our previous corresponding transcriptome study. Meanwhile, in line with that miRNAs usually negatively regulated their target genes and the dual luciferase reporter assay, we finally identified cfa-miR-205 might play an important role by upregulating MMD in pituitary and hippocampus, thus enhancing the immune response, under chronic stress exposure. Our results shed light on the miRNA expression profiles in the pituitary and adrenal cortex with and without chronic stress exposure, and provide a new insight into miR-205 with its

  7. 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.

  8. 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.

  9. Dietary Mannoheptulose Increases Fasting Serum Glucagon Like Peptide-1 and Post-Prandial Serum Ghrelin Concentrations in Adult Beagle Dogs.

    Science.gov (United States)

    McKnight, Leslie L; Eyre, Ryan; Gooding, Margaret A; Davenport, Gary M; Shoveller, Anna Kate

    2015-06-16

    There is a growing interest in the use of nutraceuticals for weight management in companion animals. The purpose of this study was to determine the effects of mannoheptulose (MH), a sugar in avocados that inhibits glycolysis, on energy metabolism in adult Beagle dogs. The study was a double-blind, randomized controlled trial where dogs were allocated to a control (CON, n = 10, 10.1 ± 0.4 kg) or MH containing diet (168 mg/kg, n = 10, 10.3 ± 0.4 kg). Blood was collected after an overnight fast and 1 h post-feeding (week 12) to determine serum satiety related hormones and biochemistry. Resting and post-prandial energy expenditure and respiratory quotient were determined by indirect calorimetry (weeks 4 and 8). Physical activity was measured using an accelerometer (weeks 3, 7, 11). Body composition was assessed using dual X-ray absorptiometry (week 12). MH significantly (p < 0.05) increased fasting serum glucagon-like peptide-1 and post-prandial serum ghrelin. MH tended (p < 0.1) to increase fasting serum gastric inhibitory peptide and decrease physical activity. Together, these findings suggest that dietary MH has the ability to promote satiation and lowers daily energy expenditure.

  10. 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.

  11. 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.

  12. Pharmacokinetics of honokiol after intravenous guttae in beagle dogs assessed using ultra-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Liang, Yi; Cui, Gang; Wang, Xiaoxue; Zhang, Wei; An, Quan; Lin, Zongtao; Wang, Hong; Chen, Shizhong

    2014-10-01

    A simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of honokiol in beagle dog plasma after intravenous guttae. With addition of the internal standard magnolol, plasma samples were precipitated with methanol and separated on a Shim-pack XR-ODS II (2.0 × 100 mm, 2.2 µm) with isocratic elution of methanol and water (80:20) solution at a flow rate of 0.2 mL/min. A good separation of honokiol was achieved within 3.5 min. Quantification was performed on a Waters Quattro Premier XE triple quadrupole mass spectrometer with electrospray ionization inlet in the negative multiple reaction monitoring mode. Good linearity was obtained over the concentration range of 5.12-15580 ng/mL (r(2) > 0.998). Intra- and inter-day precisions were <13.10%, and accuracy ranged from 89.21 to 99.92%. The lower limit of quantification for honokiol was 5.12 ng/mL, and honokiol was stable under various conditions (three freeze-thaw cycles, short-term temperature, post-preparative and long-term temperature conditions.). This validated method was successfully applied to the pharmacokinetic study of honokiol in dogs by intravenous guttae.

  13. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs.

    Science.gov (United States)

    Zhou, Xiaobing; Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng; Li, Bo

    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.

  14. Moult cycle and growth of the crab Halicarcinus planatus (Brachyura, Hymenosomatidae) in the Beagle Channel, southern tip of South America

    Science.gov (United States)

    Diez, Mariano J.; Lovrich, Gustavo A.

    2013-09-01

    The crab Halicarcinus planatus is the only hymenosomatid crab that inhabits the southern tip of South America and is the only decapod species that reproduces twice a year in the Beagle Channel. In this article, we study the moult cycle in the field (moult frequency, analysis of size frequency distribution) and linked it with growth studied in the laboratory (absolute and per cent growth increment, Hiatt function). Hiatt functions were similar for males and females. Moult frequency was seasonal: in early austral spring and in austral summer. In females, the pubertal moult is the terminal moult, whereas males continue moulting after attaining the size of morphometric maturity. Moult increment was highly variable. The relationship between absolute moult increment and crab size was described by a quadratic function. Per cent growth increment decreased with size, and relationships were different for each sex: linear for females and quadratic for males. Seven and eight modal groups explained the size frequency distributions for females and males from the field, respectively, and revealed the existence of two cohorts of recruits per year. Further modal analysis was mainly hampered by the high variability of size increment that could make any moulting individual fall in its own or one of two following modal groups. The antagonism between growth and reproduction was evident in small males. We hypothesize that the terminal pubertal moult is an advantageous feature that allows females to maximize their investment in reproduction after their terminal moult, which allows this species to have two spawnings per year.

  15. Effectiveness of two regeneration materials in autogenous tooth transplantation in larger sockets:an experimental study in beagle dogs

    Institute of Scientific and Technical Information of China (English)

    Samjhana Kashaju; Yarning Chen; Ting Chen

    2008-01-01

    Objective:To evaluate the effectiveness of regenerous tissue and bone substitute in autogenous tooth transplantation in the larger recipient socket. Methods:In 3 Beagle dogs, 18 incisors were transplanted to the recipient sockets, 2 mm wider mesio-distally. The regenerous tissue group, the bone substitute group and the control group contained 7, 7 and 4 teeth respectively. No additional material was used in control group. Clinical and radiographic examinations were done every month and were sacrificed 3 months later. Subsequently, decalcified sections were prepared for routine histological evaluation. Ordinal scores for root surface resorption were analyzed using the Kruskal-Wallis test. Results:All donor teeth survived. A statistically significant difference was found among.all three treatment groups(P=0.0001). The proliferating tissue in space positively affected the periodontal healing without any resorption. Inflammatory resorption of the root surface and formation of new bone were observed in the bone substitute group. Surface resorptions of the roots were found in the control group. Conclusion:Proliferating tissues enhance the regeneration of periodontal tissues in larger recipient sockets and prevent root resorption. Sinbone HT is beneficial for the stabilization of the transplanted teeth in larger sockets.

  16. Safety and biodistribution of a double-deleted oncolytic vaccinia virus encoding CD40 ligand in laboratory Beagles.

    Science.gov (United States)

    Autio, Karoliina; Knuuttila, Anna; Kipar, Anja; Pesonen, Sari; Guse, Kilian; Parviainen, Suvi; Rajamäki, Minna; Laitinen-Vapaavuori, Outi; Vähä-Koskela, Markus; Kanerva, Anna; Hemminki, Akseli

    2014-01-01

    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.

  17. The fossil mammals collected byCharles Darwin in South America during his travels on board the HMS Beagle

    Directory of Open Access Journals (Sweden)

    Juan Carlos Fernicola

    2009-04-01

    Full Text Available Duringthe first two years of his voyage aboard HMS Beagle, Charles Darwin collected aconsiderable number of fossil mammals from various localities in Argentina andUruguay. Among these remains are those of large mammals that Darwin informallyassigned to Megatherium and Mastodon, the only large taxa thenknown for South America, and of small and mediumsized mammals that Darwinrecognized as representing at least two rodents and a horse. The study ofDarwin's collection was entrusted to Richard Owen, who described eleven taxabetween 1837 and 1845, including the six following ones: Toxodon platensis,Macrauchenia patachonica, Equus curvidens, Scelidotherium leptocephalum,Mylodon darwini and Glossotherium sp. This contribution provides asynthesis of Darwin's preliminary assignments and evaluates the reasons thatled him to recognize only megatheres and mastodonts for the large fossilremains. Also, it discusses the current taxonomic status of the taxa describedor erected by Owen between 1837 and 1845 and the influence that Owen'staxonomic and phylogenetic conclusions had on the development of Darwin's ideason evolution.

  18. Preparation and pharmacokinetics in beagle dogs of once-a-day tetramethylpyrazine phosphate sustained-release pellets.

    Science.gov (United States)

    Yanyu, Xiao; Qineng, Ping; Zhigui, Su; Hongying, Li; Jiangxiu, Niu

    2012-03-01

    In this study, once-a-day tetramethylpyrazine phosphate (TMPP) sustained-release pellets were successfully prepared. The pellets cores were carried out in extrusion-spheronization machine and then coated in fluidized-bed. To optimize cumulative release profile, two different coating systems with the same the TMPP pellets cores were employed. The first coating system consisted of surlease, containing HPMC E5 (0.1% w/w), i.e., P1. The second coating system only consisted of surlease, i.e., P2. The two kinds of coating systems were both given coating levels in terms of weight gain of 10%. The resulted once-a-day TMPP sustained-release pellets (OTSP), the mixture of P1 and P2 with the weight proportion of 1:1, were filled in a capsule (150 mg TMPP/capsule). The relative bioavailability of OTSP was studied in six beagle dogs after oral administration using a commercial TMPP tablets as a reference. The C(max) and T(max) for OTSP and TMPP tablets were 213.06 ng/mL, 2.50 h and 3402.13 ng/mL, 0.33 h, respectively and the relative bioavailability of P3 was 97.18% compared with TMPP tablets. Based on the results, it was indicated that TMPP sustained-release pellets and TMPP conventional tablets were bioequivalent.

  19. Development of novel prasugrel base microsphere-loaded tablet with enhanced stability: Physicochemical characterization and in vivo evaluation in beagle dogs.

    Science.gov (United States)

    Kim, Kyeong Soo; Kim, Jin Cheul; Jin, Sung Giu; Kim, Dong Wuk; Kim, Dong Shik; Yong, Chul Soon; Kim, Jong Oh; Youn, Yu Seok; Oh, Kyung Taek; Woo, Jong Soo; Choi, Han-Gon

    2016-10-01

    The objective of this study was to develop a novel prasugrel base microsphere-loaded tablet (PBMST) with enhanced stability as a bioequivalent to the commercial prasugrel hydrochloride-loaded tablet. Numerous prasugrel base-loaded microspheres were prepared with hydroxypropylmethyl cellulose (HPMC), colloidal silica and various acidifying agents using a spray-drying process, and the physicochemical properties, solubility and stability were investigated. The PBMSTs were prepared and their dissolution, pharmacokinetics in beagle dogs and stability were evaluated compared to commercial prasugrel hydrochloride-loaded tablets. Among the acidifying agents tested, phosphoric acid provided the greatest increase in drug solubility, by as much as 110-fold. The prasugrel base-loaded microspheres composed of prasugrel base, HPMC, colloidal silica and phosphoric acid at a weight ratio of 10/10/5/2.5 provided an amorphous drug and reduced particle size of about 11.3μm. Moreover, it exhibited excellent solubility and improved stability compared to prasugrel base and hydrochloride. Moreover, PBMST drug dissolution was improved in comparison to the prasugrel base-loaded tablet (PBT), with similar dissolution to the commercial prasugrel hydrochloride-loaded tablet at pH 1.2 and 4.0. PBMST provided significantly higher plasma concentrations of AUC and Cmax in beagle dogs compared to PBT. In particular, the AUC of PBMST was approximately four times greater than PBT, leading to improved oral bioavailability. There were no significant differences observed for all pharmacokinetic parameters between PBMST and the commercial prasugrel hydrochloride-loaded tablet, suggesting their bioequivalence in beagle dogs. Furthermore, the prepared PBMSTs were stable for at least six months. Therefore, this novel prasugrel base microsphere-loaded tablet could be a potential alternative for enhancing the stability and bioavailability of prasugrel.

  20. The Beagle 2 entry descent and landing system (EDLS) software - development and re-use of software for the Red Planet

    Science.gov (United States)

    Symonds, Martin

    2002-07-01

    This paper provides a brief introduction to the Beagle 2 Mars probe and the associated mission, followed by a description of Logica's software responsibility on this programme. The approach taken during software development and implementation of the missioncritical entry, descent and landing system software is then described. This has focussed on maximising re-use of expertise from similar programmes such as Huygens and Rosetta. At the same time effort was devoted to ensure that re-use was enabled within the programme as well as opening up the possibility for re-use on subsequent missions. Finally, the lessons learned are highlighted and a number of conclusions are drawn.

  1. Ultrastructural study of the adenohypophysis pars tuberalis of the Beagle%比格犬脑垂体结节部细胞的电镜观察

    Institute of Scientific and Technical Information of China (English)

    李玉谷; 张媛; 程树军; 孔小明; 黄韧; 王平利

    2004-01-01

    透射电镜观察表明,比格犬(Beagle)脑垂体结节部实质中含有2类细胞,即含分泌颗粒的细胞和不含分泌颗粒的细胞.前者根据分泌颗粒的大小至少可以分为3种,其分泌颗粒直径分别约为310~605、155~388和124~202 nm.

  2. Carcinogenesis From Inhaled (PuO2)-Pu-239 in Beagles: Evidence for Radiation Homeostasis at Low Doses?

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, Darrell R.; Weller, Richard E.

    2010-09-01

    From the early 1970s to the late 1980s, Pacific Northwest National Laboratory conducted life-span studies in beagle dogs on the biological effects of inhaled plutonium (239PuO2, 238PuO2, and 239Pu[NO3]4) to help predict risks associated with accidental intakes in workers. Years later, the purpose of the present follow-up study is to reassess the dose-response relationship for lung cancer induction in the 239PuO2 dogs compared to controls, with particular focus on the dose-response at low lung doses. A 239PuO2 aerosol (2.3 μm AMAD, 1.9 μm GSD) was administered to six groups of 20 young (18-month old) beagle dogs (10 males and 10 females) by inhalation at six different activity levels, as previously described in Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial pulmonary lung depositions were 130 ± 48 Bq (3.5 ± 1.3 nCi), corresponding to 1 Bq g-1 lung tissue (0.029 ± 0.001 nCi g-1. Groups 2 through 6 received initial lung depositions (mean values) of 760, 2724, 10345, 37900, and 200000 Bq (22, 79, 300, 1100, and 5800 nCi) 239PuO2, respectively. For each dog, the absorbed dose to lungs was calculated from the initial lung burden and the final lung burden at time of death and lung mass, assuming a single, long-term retention function. Insoluble plutonium oxide exhibited long retention times in the lungs. Increased dose-dependent mortality due to lung cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, epidermoid carcinoma) and radiation pneumonitis (highest exposures group) was observed in dogs exposed to 239PuO2. Calculated lung doses ranged from a few cGy in early-sacrificed dogs to 7764 cGy in dogs that experienced early deaths from radiation pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function of lung tumor incidence. Lung tumor incidence in controls and zero-dose exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs with the lowest lung doses (8 to 22 cGy, mean 14.4 ± 7.6 c

  3. Non-clinical safety and pharmacokinetic evaluations of propylene glycol aerosol in Sprague-Dawley rats and Beagle dogs.

    Science.gov (United States)

    Werley, Michael S; McDonald, Paddy; Lilly, Patrick; Kirkpatrick, Daniel; Wallery, Jeffrey; Byron, Peter; Venitz, Jürgen

    2011-09-05

    Aerosolized propylene glycol (PG) was generated as log-normally distributed particulate clouds in different concentrations using a novel capillary aerosol generator (CAG) and evaluated in a battery of non-clinical studies intended to assess its potential inhalation and systemic toxicity in 2 species before ICH-compliant "first-time-in-man" studies. Exposures were nose-only in rats, and via face mask with oropharyngeal tube in dogs. The CAG-generated PG aerosol had a mass median aerodynamic diameter (MMAD) of 2.29μm, with a 1.56 geometric standard deviation (GSD) in the rat studies, and a MMAD of 1.34μm (1.45 GSD) in the dog studies, consistent with expected particle size exposures in man. International Congress on Harmonization (ICH) Guidelines were followed, which recommend preliminary non-clinical safety studies using the vehicle and device (CAG-PG) prior to the first human exposure including safety pharmacology, pharmacokinetic (PK) studies, single dose toxicity studies, and repeated dose toxicity studies in two species. In the rat, the only biologically relevant findings included clinical signs of ocular and nasal irritation indicated by minor bleeding around the eyes and nose, and minimal laryngeal squamous metaplasia. This finding is commonly observed in inhalation studies in the rat, and likely related to the unique sensitivity of the tissue, as well as the circuitous airflow pathway through the larynx which increases particle deposition. In the female Beagle dog, treatment-related decreases in hemoglobin, red blood cells and hematocrit were observed in the two highest exposure groups, equivalent to approximately 18 and 60mg/kg/day. In male dogs from the high dose group, similar small decreases, albeit, non-statistically significant decreases were observed in these hematological markers as well. PK studies in rats and dogs showed that the absorption of PG following pulmonary inhalation exposure occurs rapidly, and equilibrium between lung tissue and plasma

  4. Cross equator transport of 137Cs from North Pacific Ocean to South Pacific Ocean ( BEAGLE2003 cruises)

    Science.gov (United States)

    Aoyama, M.; Fukasawa, M.; Hirose, K.; Hamajima, Y.; Kawano, T.; Povinec, P. P.; Sanchez-Cabeza, J. A.

    2011-04-01

    The anthropogenic radionuclides such as 137Cs, 90Sr, 99Tc, 129I and some transuranics are important tracers of transport and biogeochemical processes in the ocean. 137Cs, with a half-life of 30 years, a major fission product present in a dissolved form in seawater, is a good tracer of oceanic circulation at a time scale of several decades. At WOCE P6 line along 30°S during the BEAGLE cruise in 2003, surface seawater (around 80 L) was collected a few meters below the ocean surface by a pumping system. Water column samples (from 5 to 20 L) were collected using a Rosette multisampling system and Niskin bottles. 137Cs was separated from seawater samples using ammonium phosphomolybdate (AMP) and analysed for 137Cs in low-level HPGe gamma-ray spectrometers. Results allowed to draw a detailed picture of the distribution of 137Cs in the South Pacific Ocean along P6 line. A 137Cs depth section was depicted from about 160 samples. 137Cs concentrations in the subsurface layers ranged from 0.07 ± 0.04 Bq m -3 to 1.85 ± 0.145 Bq m -3, high in the Tasman Sea and very low in the eastern region where upwelling occurs. Water column inventories of 137Cs from surface to 1000 dbar depth ranged from 270 ± 104 to 1048 ± 127 Bq m -2. It was concluded that the source of higher 137Cs concentration and inventories in the Tasman Sea was 137Cs deposited in the mid latitude of the North Pacific Ocean and transported across the equator during four decades.

  5. 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

    2015-10-20

    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 OPEN ACCESS Int. J. Mol. Sci. 2015, 16 24947 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.

  6. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

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    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.

  7. 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

    2013-02-01

    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.

  8. Periodontal regeneration in experimentally-induced alveolar bone dehiscence by an improved porous biphasic calcium phosphate ceramic in beagle dogs.

    Science.gov (United States)

    Shi, Han; Ma, Jia; Zhao, Ning; Chen, Yangxi; Liao, Yunmao

    2008-12-01

    Regeneration of lost periodontium is the focus of periodontal therapy. To achieve the effective regeneration, a number of bone graft substitute materials have been developed. This study aimed to investigate the histological response in alveolar bone dehiscences which were filled with an improved biphasic calcium phosphate (BCP) ceramic with more reasonable pore diameter, pore wall thickness and porosity. Twenty-four alveolar bone dehiscences were made surgically in twelve beagle dogs by reflecting mucoperiosteal flaps on the buccal aspect of bilateral lower second premolars and removing alveolar bone. The left dehiscences were treated with BCP ceramic and the contralaterals were cured with the open flap debridement (OFD) as controls. Three dogs were used at week 4, 12, and 24 respectively. Histological observations were processed through three-dimensional micro-computed tomographic imaging, fluorescence and light microscopy. The histological study indicated that the biphasic ceramic was biocompatible, and regeneration was achieved more effectively through the BCP treatment. There were also arrest of epithelial migration apically and formation of new bone and cementum, as well as proliferation of fibrous connective tissues that became attached to the newly formed cementum at week 24, while there was no significant periodontal regeneration in the OFD group only with epithelial tissue migrating into the dehiscence regions. Clinically speaking, though the surgical location formed a limitation to the application of the improved BCP on the periodontal regeneration, the actual result was positive. It proved that the BCP had biocompatibility and was able to act as a stable scaffold to induce periodontal regeneration effectively.

  9. Long-term Observation of Regenerated Periodontium Induced by FGF-2 in the Beagle Dog 2-Wall Periodontal Defect Model.

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    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

  10. Action Mechanism of Fibroblast Growth Factor-2 (FGF-2 in the Promotion of Periodontal Regeneration in Beagle Dogs.

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    Toshie Nagayasu-Tanaka

    Full Text Available Fibroblast growth factor-2 (FGF-2 enhances the formation of new alveolar bone, cementum, and periodontal ligament (PDL in periodontal defect models. However, the mechanism through which FGF-2 acts in periodontal regeneration in vivo has not been fully clarified yet. To reveal the action mechanism, the formation of regenerated tissue and gene expression at the early phase were analyzed in a beagle dog 3-wall periodontal defect model. FGF-2 (0.3% or the vehicle (hydroxypropyl cellulose only were topically applied to the defect in FGF-2 and control groups, respectively. Then, the amount of regenerated tissues and the number of proliferating cells at 3, 7, 14, and 28 days and the number of blood vessels at 7 days were quantitated histologically. Additionally, the expression of osteogenic genes in the regenerated tissue was evaluated by real-time PCR at 7 and 14 days. Compared with the control, cell proliferation around the existing bone and PDL, connective tissue formation on the root surface, and new bone formation in the defect at 7 days were significantly promoted by FGF-2. Additionally, the number of blood vessels at 7 days was increased by FGF-2 treatment. At 28 days, new cementum and PDL were extended by FGF-2. Moreover, FGF-2 increased the expression of bone morphogenetic protein 2 (BMP-2 and osteoblast differentiation markers (osterix, alkaline phosphatase, and osteocalcin in the regenerated tissue. We revealed the facilitatory mechanisms of FGF-2 in periodontal regeneration in vivo. First, the proliferation of fibroblastic cells derived from bone marrow and PDL was accelerated and enhanced by FGF-2. Second, angiogenesis was enhanced by FGF-2 treatment. Finally, osteoblastic differentiation and bone formation, at least in part due to BMP-2 production, were rapidly induced by FGF-2. Therefore, these multifaceted effects of FGF-2 promote new tissue formation at the early regeneration phase, leading to enhanced formation of new bone, cementum

  11. 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.

  12. Action Mechanism of Fibroblast Growth Factor-2 (FGF-2) in the Promotion of Periodontal Regeneration in Beagle Dogs.

    Science.gov (United States)

    Nagayasu-Tanaka, Toshie; Anzai, Jun; Takaki, Shu; Shiraishi, Noriko; Terashima, Akio; Asano, Taiji; Nozaki, Takenori; Kitamura, Masahiro; Murakami, Shinya

    2015-01-01

    Fibroblast growth factor-2 (FGF-2) enhances the formation of new alveolar bone, cementum, and periodontal ligament (PDL) in periodontal defect models. However, the mechanism through which FGF-2 acts in periodontal regeneration in vivo has not been fully clarified yet. To reveal the action mechanism, the formation of regenerated tissue and gene expression at the early phase were analyzed in a beagle dog 3-wall periodontal defect model. FGF-2 (0.3%) or the vehicle (hydroxypropyl cellulose) only were topically applied to the defect in FGF-2 and control groups, respectively. Then, the amount of regenerated tissues and the number of proliferating cells at 3, 7, 14, and 28 days and the number of blood vessels at 7 days were quantitated histologically. Additionally, the expression of osteogenic genes in the regenerated tissue was evaluated by real-time PCR at 7 and 14 days. Compared with the control, cell proliferation around the existing bone and PDL, connective tissue formation on the root surface, and new bone formation in the defect at 7 days were significantly promoted by FGF-2. Additionally, the number of blood vessels at 7 days was increased by FGF-2 treatment. At 28 days, new cementum and PDL were extended by FGF-2. Moreover, FGF-2 increased the expression of bone morphogenetic protein 2 (BMP-2) and osteoblast differentiation markers (osterix, alkaline phosphatase, and osteocalcin) in the regenerated tissue. We revealed the facilitatory mechanisms of FGF-2 in periodontal regeneration in vivo. First, the proliferation of fibroblastic cells derived from bone marrow and PDL was accelerated and enhanced by FGF-2. Second, angiogenesis was enhanced by FGF-2 treatment. Finally, osteoblastic differentiation and bone formation, at least in part due to BMP-2 production, were rapidly induced by FGF-2. Therefore, these multifaceted effects of FGF-2 promote new tissue formation at the early regeneration phase, leading to enhanced formation of new bone, cementum, and PDL.

  13. Long-term Observation of Regenerated Periodontium Induced by FGF-2 in the Beagle Dog 2-Wall Periodontal Defect Model.

    Science.gov (United States)

    Anzai, Jun; Nagayasu-Tanaka, Toshie; Terashima, Akio; Asano, Taiji; Yamada, Satoru; Nozaki, Takenori; Kitamura, Masahiro; Murakami, Shinya

    2016-01-01

    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 healing process.

  14. [Comparison of the action of Cordemcura on selected cardiovascular parameters following intraduodenal and intravenous application in beagles].

    Science.gov (United States)

    Hübler, D; Mudhaffar, A A; Schilling, G; Elze, M; Chemnitius, K H

    1986-03-01

    The novel cardiotonic Cordemcura was tested for its cardiovascular effects after intraduodenal application to anaesthetized dogs. For this purpose, beagles received Cordemcura intraduodenally as a Tylose suspension, with 4 bolus injections (10(-5), 3 X 10(-5), 6 X 10(-5), and 10(-4) mol/kg) given at 30-min intervals. The test parameters used to analyze the onset of action and its course include: heart frequency (HFR), maximum rate of pressure rise (dp/dtmax) and decline (dp/dtmin) in the left ventricle, cardiac output (CO), stroke volume (SV), total peripheral resistance (TPR) and peripheral arterial blood pressure, systolic (Ps) and diastolic (Pd), and dose-effect curves determined for the individual test parameters. There was a dose-dependent increase of dp/dtmax up to a maximum of 130%, which 3 h afterwards was still about 60% above the initial value. The heart frequency, too, rose dose-dependently by a maximum of 80%, though not being significantly different from the initial value any longer 3 h after the last bolus injection. The Ps was slightly, but significantly decreased with the higher dose levels used. The influence on dp/dtmin and Pd was insignificant. A significant rise was found in the cardiac output, whereas the peripheral resistance showed a slight decline. After 3 h, a significant rise was still seen in the contractility (dp/dtmax), whereas the other parameters were no longer significantly different from the initial values. Moreover, selected dose levels of Cordemcura were tested after i. v. application, and a comparison was made of their effect on heart frequency, peripheral blood pressure, and inotropism. The importance of the findings was discussed.

  15. Comparative experimental re-evaluation of the two implanting methods of silicone gel testicular prostheses in beagle dogs

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    Chen Peng

    2011-04-01

    Full Text Available Abstract Background Testicular prosthesis has been applied clinically for decades, and implantation of testis prosthesis under the tunica albuginea has been considered to be the standard method in the most of the reports. However, postoperative scrotal appearance, the mobilization and the palpitation of the prosthesis are not always satisfactory to all the patients. Modifications in surgical techniques might be necessary to bring improvements to the clinical outcomes in testicular prosthesis implantation. Findings In a group of 9 beagle dogs in this study, an orchiectomy succeeded with a testicular prosthesis implantation under the tunica vaginalis, and a complete mechanical denudation of the testicular parenchyma succeeded with an implantation under the tunica albuginea were performed, respectively. Histopathological evaluations of the scrotal tissues and the implants, which were made at the end of the follow-up, showed that all the tested animals lived uneventful lives during the follow-up period, and no rejections or infections were found. Prostheses implanted under the tunica vaginalis showed a more satisfying mobilization and palpation than those implanted under the tunica albuginea. Chronic inflammation in the para-prosthesis tissues with vascular proliferation and fibrinogenesis were more common in the "under tunica albuginea" group than that in the "under tunica vaginalis" group, although differences in fibrinogenesis between the two groups were found to be statistically insignificant. Conclusions In this comparative study, we have re-evaluated the two most popular implantation methods of testicular prosthesis, the "under the tunica albuginea" and the "under the tunica vaginalis" pathways, in animal models. We found that the testicular prosthesis were all well tolerated, but the prosthesis implanted under the tunica vaginalis showed a more satisfying result concerning appearance, palpability, and histopathological findings than that of

  16. Development and validation of an UPLC-Q/TOF-MS assay for the quantitation of neopanaxadiol in beagle dog plasma: Application to a pharmacokinetic study.

    Science.gov (United States)

    Geng, Cong; Wang, Chun-Hong; Hu, Hong; Gao, Xiao-Ping; Gong, Ai-Hua; Lin, Ying-Wei; Fan, Xiu-Shuang; Li, Heng; Yin, Jian-Yuan

    2016-10-27

    Neopanaxadiol (NPD), the main panaxadiol constituent of Panax ginseng C. A. Meyer (Araliaceae), has been regarded as the active component for the treatment of Alzheimer's disease. However, few references are available about pharmacokinetic evaluation for NPD. Accordingly, a rapid and sensitive method for quantitative analysis of NPD in beagle dog plasma based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry was developed and validated. Analytes were extracted from plasma by liquid-liquid extraction and chromatographic separation was achieved on an Agilent Zorbax Stable Bond C18 column. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions both at m/z 461.4 → 425.4 for NPD and internal standard of panaxadiol. All validation parameters, such as lower limit of quantitation, linearity, specificity, precision, accuracy, extraction recovery, matrix effect and stability, were within acceptable ranges and the method was appropriate for multitude sample determination. After oral intake, NPD was slowly absorbed and eliminated from circulatory blood system and corresponding plasma exposure was low. Application of this quantitative method will yield the first pharmacokinetic profile after oral administration of NPD to beagle dog. The information obtained here will be useful to understand the pharmacological effects of NPD.

  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 beagle dogs after rectal administration of mesalazine suppository.

  18. 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.

  19. On-Line Organic Solvent Field Enhanced Sample Injection in Capillary Zone Electrophoresis for Analysis of Quetiapine in Beagle Dog Plasma.

    Science.gov (United States)

    Cao, Yuqing; Wen, Jun; Zhou, Tingting; Fan, Guorong

    2016-01-21

    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.

  20. Analysis and pharmacokinetic study of polyphyllin H in beagle dog plasma after oral administration of Rhizoma Paridis extracts by LC-MS/MS.

    Science.gov (United States)

    Yin, Xingbin; Lin, Longfei; Shen, Mingrui; Zhai, Yujing; Cao, Sali; Fu, Jing; Li, Xuechun; Yang, Chunjing; Xia, Zhenwen; Zhao, Yang; Li, Shangxin; Bai, Ying; Xue, Dan; Ni, Jian

    2014-12-01

    A highly sensitive, rapid assay method has been developed and validated for the analysis of polyphyllin H in beagle dog plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves extraction of polyphyllin H and ginsenoside Re (IS) from beagle dog plasma. Chromatographic separation was carried out on an Agilent Zorbax XDB-C18 (100 × 2.1 mm, 1.8μm) column by isocratic elution with acetonitrile and water (50:50, v/v) at a flow rate of 0.25 mL/min with a total run time of 2.5 min. The MS/MS ion transitions monitored were m/z 869.60 → 869.60 for polyphyllin H and m/z 969.60 → 969.60 for IS. [corrected] Linear responses were obtained for polyphyllin H ranging from 1 to 50 ng/mL. The intra-and inter-day precisions (RSDs) <1.77 and 3.39% and the extraction recovery ranged from 91.89 to 93.33% with RSD <2.68%. Stability studies showed that polyphyllin H was stable in the preparation and analytical process. The results indicated that the validated method was successfully used to determine the concentration-time profiles of polyphyllin H.

  1. The Association of Inbreeding With Lung Fibrosis Incidence in Beagle Dogs That Inhaled 238PuO2 or 239PuO2.

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Dulaney A.; Brigantic, Andrea M.; Morgan, William F.

    2011-09-12

    Studies of health effects in animals after exposure to internally deposited radionuclides were intended to supplement observational studies in humans. Both nuclear workers and Beagle dogs have exhibited plutonium associated lung fibrosis; however, the dogs smaller gene pool may limit the applicability of findings to humans. Data on Beagles that inhaled either plutonium-238 dioxide (238PuO2) or plutonium-239 dioxide (239PuO2) were analyzed. Wright's Coefficient of Inbreeding was used to measure genetic or familial susceptibility and was assessed as an explanatory variable when modeling the association between lung fibrosis incidence and plutonium exposure. Lung fibrosis was diagnosed in approximately 80% of the exposed dogs compared with 23.7% of the control dogs. The maximum degree of inbreeding was 9.4%. Regardless of isotope, the addition of inbreeding significantly improved the model in female dogs but not in males. In female dogs an increased inbreeding coefficient predicted decreased hazard of a lung fibrosis diagnosis. Lung fibrosis was common in these dogs with inbreeding affecting models of lung fibrosis incidence in females but not in males. The apparent protective effect in females predicted by these models of lung fibrosis incidence is likely to be minimal given the small degree of inbreeding in these groups.

  2. 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.

  3. UPLC-MS/MS determination of ephedrine, methylephedrine, amygdalin and glycyrrhizic acid in Beagle plasma and its application to a pharmacokinetic study after oral administration of Ma Huang Tang.

    Science.gov (United States)

    Yan, Tianhua; Fu, Qiang; Wang, Jing; Ma, Shiping

    2015-02-01

    An ultra performance liquid chromatography-mass spectrometric (UPLC-MS) method was developed to investigate the pharmacokinetic properties of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid after oral gavage of Ma Huang Tang (MHT) in Beagles. Beagle plasma samples were pretreated using liquid-liquid extraction, and chromatographic separation was performed on a C18 column using a linear gradient of water-formic acid mixture (0.1%). The pharmacokinetic parameters of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid from MHT in Beagles were quantitatively determined by UPLC with tandem mass detector. The qualitative detection of the four compounds was accomplished by selected ion monitoring in negative/positive ion modes electrospray ionization-mass spectrometry (ESI-MS). Detection was based on multiple reaction monitoring with the precursor-to-product ion transitions m/z 166.096-116.983 (ephedrine), m/z 179.034-146.087 (methylephedrine), m/z 456.351-323.074 (amygdalin), and m/z 821.606-351.062 (glycyrrhizic acid). The selectivity, sensitivity, linearity, accuracy, precision, extraction recovery, ion suppression, and stability were within the acceptable ranges. The method described was successfully applied to reveal the pharmacokinetic properties of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid after oral gavage of MHT in Beagles.

  4. DNA Fingerprinting and RAPD for Genetic Monitoring of Laboratory Beagle%DNA指纹图及RAPD技术在比格犬群体遗传检测中的应用

    Institute of Scientific and Technical Information of China (English)

    战大伟; 陈振文; 李瑞生; 欧阳兆和

    2003-01-01

    With small somatotype, gentle temperament, balanced hematological and blood biochemical index, Beagle was ideal for laboratory use. Since 1980, beagle has been introducted into our country. They were successfully bred and multiplied in Guangdong , Shanghai and Beijing . But the control of heredity, balance of gene frequency, gene diversity and gene differentiation and protection of idioplasm has not been well studied. Falk & Holsinger( 1991 )point out: we can not protect what were unknowed. For operative preventing the inbreeding diminution , gene segregation and differentiation,the DFP and randomly amplified polymorphic (RAPD) technique were applied to assess the genetic variation and colony heredity structural analysis among the population of three internal beagle centers and Marshell beagle in America. The experimental exponent of the heredity analysis in different colony were from Guangdong, Shanghai, Beijing and Marshell (Amereca), and they were not relative. The experimental exponent of the different generation were from Beijing colony,and they were direct maternal side in different generation, but each individual were no relative in the same generation.

  5. 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.

  6. Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration.

    Science.gov (United States)

    Sattar, Adeel; Xie, Shuyu; Huang, Lingli; Iqbal, Zahid; Qu, Wei; Shabbir, Muhammad A; Pan, Yuanhu; Hussain, Hafiz I; Chen, Dongmei; Tao, Yanfei; Liu, Zhenli; Iqbal, Mujahid; Yuan, Zonghui

    2016-01-01

    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.

  7. Simultaneous determination of harmine, harmaline and their metabolites harmol and harmalol in beagle dog plasma by UPLC-ESI-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Zhang, Lei; Teng, Liang; Gong, Can; Liu, Wei; Cheng, Xuemei; Gu, Shenghua; Deng, Zhongping; Wang, Zhengtao; Wang, Changhong

    2013-11-01

    Harmine (HAR) and harmaline (HAL) were metabolized by demethylation to form harmol (HOL) and harmalol (HAM) both in vivo and in vitro. It has been demonstrated tremendous value of HAR, HAL and their metabolites in the therapy of Alzheimer's disease. A rapid, selective and sensitive UPLC-ESI-MS/MS method was firstly developed and validated for the simultaneous determination of HAR, HAL, HOL, and HAM in beagle dog plasma with 9-aminoacridine as the internal standard (IS). After protein precipitation with acetonitrile, the analytes were separated within 4.5 min on an ACQUITY UPLC BEH C18 column with a gradient elution system composed of 0.1% formic acid and acetonitrile at a flow rate of 0.4 ml/min. Detection was performed using multiple reactions monitoring mode under a positive ionization condition. The calibration curves of four analytes showed good linearity (r(2)>0.9959) within the tested concentration ranges. The low limit of quantification for HAR, HAL, HOL, and HAM were all 1.00 ng/ml. The mean accuracy of the analytes was within the range of 94.56-112.23%, the R.S.D. values of intra-day and the inter-day precision were less than 6.26% and 7.51%, respectively. Matrix effects and extraction recoveries of the analytes from the beagle dog plasma were within the range of 94.48-105.77% and 89.07-101.44%, respectively. The validated method was successfully applied to a pharmacokinetic study of HAR, HAL, HOL, and HAM in beagle dogs after intravenous administration of HAR and HAL both of 1.0mg/kg. The main pharmacokinetic parameters of Cmax, Vd, CL, AUC and MRT, except Ke and t1/2 values, showed significant difference between the two parent drug HAR and HAL, respectively (p<0.05-0.001). Because of the different metabolic rate of HAR and HAL in vivo, the two metabolites, HOL and HAM, exhibited unique pharmacokinetic properties.

  8. 实验Beagle犬贾第鞭毛虫感染情况调查%Prevalence of Experimental Beagles with Giardia Infections

    Institute of Scientific and Technical Information of China (English)

    毕甜甜; 张晋; 文润来; 韩杰; 富强; 王小珂; 卢胜明

    2011-01-01

    In order to provide high quality of experimental Beagles to institutes of scientific research in both China and foreign countries, the presence of Giardia infections is periodically detected by our monitor lab. This study was carried out a survey for the presence of Giardia infections in Beagles using a Synbiotics OVASSAY Plus kit. Nine hundred and ten dogs were examined for Giardia infections in four age groups. The result also shows that: Slightly more female dogs ( 14. 76% ) than male (7.86%) dogs were affected; there was no significant difference between the two groups. The overall positive rates of Giardia infections were 11.98%, there is no significant difference between different gender, and X2 analysis revealed a significantly higher prevalence in the < 2-month-old group than in the other groups. Through periodical detection, Giardia infection situations can acquire, immediately diagnose and control can carry out, which further ensure the high quality of experimental Beagles that our company provided.%为了掌握Beagle犬贾第鞭毛虫的感染情况,本实验室在2009年3月~2010年2月共抽样检测了910只实验Beagle犬,其中109只检测到了贾第鞭毛虫包囊,贾第鞭毛虫感染的总阳性率为11.98%.结果 还表明,不同月份间差异极显著,不同性别间差异不显著,幼犬感染率大于成犬,不同年龄组间差异极显著.通过检测可掌握犬群中贾第鞭毛虫的感染情况,对及时诊断、发现并控制疾病的传播有积极的指导意义.

  9. 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.

  10. Protocolo combinado de PEV y ERG en perros beagle para evaluar la integridad funcional de las vías visuales

    Directory of Open Access Journals (Sweden)

    D Torres-Soriano

    2014-01-01

    Full Text Available Los potenciales evocados visuales (PEV y la electrorretinografía (ERG son dos métodos de análisis objetivo y cuantitativo de la funcionalidad de las vías visuales, que se realizan de forma independiente en la clínica oftalmológica para la evaluación de la retina o de las vías visuales centrales, respectivamente. El presente trabajo propone un protocolo clínico combinado de ambas técnicas en una única sesión, además de una base de datos normales para la raza beagle. Se emplearon 12 beagles para diseñar un protocolo de 90 minutos de duración que incluía el uso de midriáticos, protocolo anestésico y colocación apropiada de electrodos de registro. La técnica de estimulación luminosa seleccionada fueron flashes de luz blanca emitidos de modo monocular. Diversos parámetros de estimulación, registro, amplificación y filtrado fueron calibrados. La secuencia de estimulación fue: PEV, ERG escotópico y ERG fotópico. Las 2 primeras técnicas se realizaron en oscuridad con previa adaptación ocular de 20 minutos, mientras que la última se realizó con luminosidad ambiente y previa adaptación a la luz de 10 minutos. La gráfica de PEV mostró 4 picos (P1, N1, P2, N2, mientras que el ERG mostró las típicas ondas (a y b sin presencia de onda-c. Este procedimiento permite recoger los registros de ambas pruebas electrodiagnósticas de la manera más simple y menos estresante para el paciente canino, y propone una base de datos normales actualizada para el beagle.

  11. Urinary recovery of orally administered chromium 51-labeled EDTA, lactulose, rhamnose, d-xylose, 3-O-methyl-d-glucose, and sucrose in healthy adult male Beagles.

    Science.gov (United States)

    Frias, Rafael; Steiner, Jörg M; Williams, David A; Sankari, Satu; Westermarck, Elias

    2012-05-01

    Objective-To provide values for gastrointestinal permeability and absorptive function tests (GIPFTs) with chromium 51 ((51)Cr)-labeled EDTA, lactulose, rhamnose, d-xylose, 3-O-methyl-d-glucose, and sucrose in Beagles and to evaluate potential correlations between markers. Animals-19 healthy adult male Beagles. Procedures-A test solution containing 3.7 MBq of (51)Cr-labeled EDTA, 2 g of lactulose, 2 g of rhamnose, 2 g of d-xylose, 1 g of 3-O-methyl-d-glucose, and 8 g of sucrose was administered intragastrically to each dog. Urinary recovery of each probe was determined 6 hours after administration. Results-Mean ± SD (range) percentage urinary recovery was 6.3 ± 1.6% (4.3% to 9.7%) for (51)Cr-labeled EDTA, 3.3 ± 1.1% (1.7% to 5.3%) for lactulose, 25.5 ± 5.0% (16.7% to 36.9%) for rhamnose, and 58.8% ± 11.0% (40.1% to 87.8%) for 3-O-methyl-d-glucose. Mean (range) recovery ratio was 0.25 ± 0.06 (0.17 to 0.37) for (51)Cr-labeled EDTA to rhamnose, 0.13 ± 0.04 (0.08 to 0.23) for lactulose to rhamnose, and 0.73 ± 0.09 (0.60 to 0.90) for d-xylose to 3-O-methyl-d-glucose. Median (range) percentage urinary recovery was 40.3% (31.6% to 62.7%) for d-xylose and 0% (0% to 0.8%) for sucrose. Conclusions and Clinical Relevance-Reference values in healthy adult male Beagles for 6 of the most commonly used GIPFT markers were determined. The correlation between results for (51)Cr-labeled EDTA and lactulose was not as prominent as that reported for humans and cats; thus, investigators should be cautious in the use and interpretation of GIPFTs performed with sugar probes in dogs with suspected intestinal dysbiosis.

  12. Heavy metal concentrations and biomarkers of oxidative stress in native mussels (Mytilus edulis chilensis) from Beagle Channel coast (Tierra del Fuego, Argentina).

    Science.gov (United States)

    Duarte, Claudia A; Giarratano, Erica; Amin, Oscar A; Comoglio, Laura I

    2011-08-01

    The aim of this study was to evaluate the usefulness of oxidative stress biomarkers of pollution in native mussels Mytilus edulis chilensis from the Beagle Channel. Spatial and seasonal variations of catalase, glutathione-S-transferase and lipid peroxidation in gills and digestive gland were analyzed in relation to environmental parameters, heavy metals in sediment and in tissue. Four sites with anthropogenic impact and a control site were selected and monitored during the four seasons of 2007. We found significant differences among sites in concentrations of dissolved nutrients and heavy metals in sediments, with the highest values recorded at sites with anthropogenic pressure. Different patterns were observed between concentrations of metals in tissues and in sediments suggesting differences in bioavailability. There were also significant differences in biomarker responses among sites, despite the strong seasonal variability. Our results showed relatively moderate levels of pollution in the study area as a result of urban influences.

  13. Beagle to the Moon: An Experiment Package to Measure Polar Ice and Volatiles in Permanently Shadowed Areas or Beneath the Lunar Surface

    Science.gov (United States)

    Gibson, E. K.; McKay, D. S.; Pillinger, C. T.; Wright, I. P.; Sims, M. R.; Richter, L.

    2007-01-01

    Near the beginning of the next decade we will see the launch of scientific payloads to the lunar surface to begin laying the foundations for the return to the moon in the Vision for Space Exploration. Shortly thereafter, astronauts will return to the lunar surface and have the ability to place scientific packages on the surface that will provide information about lunar resources and compositions of materials in permanently shadowed regions of the moon (1). One of the important questions which must be answered early in the program is whether there are lunar resources which would facilitate "living off the land" and not require the transport of resources and consumables from Earth (2). The Beagle science package is the ideal payload (3) to use on the lunar surface for determining the nature of hydrogen, water and lunar volatiles found in the polar regions which could support the Vision for Space Exploration

  14. Histopathology of Spontaneous Lesions in Beagles Used for Toxicity Studies%比格犬自发疾病的病理组织学研究

    Institute of Scientific and Technical Information of China (English)

    朱奎成; 刘娜; 王纯耀; 金树兴

    2011-01-01

    A histopathological study was carried out on spontaneous lesions in 40 beagle dogs employed in toxicity studies.Lesions detected included acidophilic crystalline intraocular inclusion in the liver and kidney, atrophy and cyst formation in the thymus, siderofibrotic nodules in the spleen, and parafollicular cell hyperplasia in the thyroid.In addition, fatty and vacuolar degeneration, and nodular hyperplasia in the adrenal gland also be found%为了解比格犬组织器官的自发疾病,为药物的安全性评价提供背景资料,采用病理组织学方法对8~12月龄的36只比格犬主要脏器进行了观察,发现,肝脏、心脏、脾脏、肺脏、肾脏等组织器官均有不同程度的自发病变.

  15. Preparation of codeine-resinate and chlorpheniramine-resinate sustained-release suspension and its pharmacokinetic evaluation in beagle dogs.

    Science.gov (United States)

    Zeng, Huan-Xiang; Cheng, Gang; Pan, Wei-San; Zhong, Guo-Ping; Huang, Min

    2007-06-01

    the release rate of both drugs. But the release of codeine from its resinate beads was much more rapid than chlorpheniramine released from its resinate beads in the same ionic strength release medium. The drug release specification of the CCSS, where release mediums were 0.05 M KCl solution for codeine and 0.5 M KCl solution for chlorpheniramine, was established to be in conformance with in vivo performance. Relative bioavailability and pharmacokinetics evaluation of the CCSS, using commercial immediate-release tablets as the reference preparation, were performed following a randomized two-way crossover design in beagle dogs. The drug concentrations in plasma were measured by a validated LC-MS/MS method to determine the pharmacokinetic parameters of CCSS. This LC-MS/MS method demonstrated high accuracy and precision for bioanalysis, and was proved quick and reliable for the pharmacokinetic studies. The results showed that the CCSS had the longer value of Tmax and the lower value of Cmax, which meant an obviously sustained release effect, and its relative bioavailability of codeine and chlorpheniramine were (103.6 +/- 14.6)% and (98.1 +/- 10.3)%, respectively, compared with the reference preparation. These findings indicated that a novel liquid sustained release suspension made by using IERs as carriers and subsequent fluidized bed coating might provide a constant plasma level of the active pharmaceutical ingredient being highly beneficial for various therapeutic reasons.

  16. Development and application of a LC-MS/MS assay for the simultaneous quantification of edaravone and taurine in beagle plasma.

    Science.gov (United States)

    Yu, Yan-yan; Zheng, Xiao-xiao; Bian, Ting-ting; Li, Yin-jie; Wu, Xiao-wen; Yang, Dong-zhi; Jiang, Shui-shi; Tang, Dao-quan

    2013-12-01

    An LC-MS/MS method was developed and validated for the simultaneous quantification of edaravone and taurine in beagle plasma. The plasma sample was deproteinized using acetonitrile containing formic acid. Chromatographic separations were achieved on an Agilent Zorbax SB-Aq (100 × 2.1 mm, 3.5 μm) column, with a gradient of water (containing 0.03% formic acid) and methanol as the mobile phase at a flow rate of 0.3 mL/min. The analyte detection was carried out in multiple reaction monitoring mode and the optimized precursor-to-product transitions of m/z [M+H](+) 175.1 → 133.0 (edaravone), m/z [M+H](+) 189.1 → 147.0 (3-methyl-1-p-tolyl-5-pyrazolone, internal standard, IS), m/z [M-H](-) 124.1→80.0 (taurine), and m/z [M-H](-) 172.0 → 80.0 (sulfanilic acid, IS) were employed to quantify edaravone, taurine, and their corresponding ISs, respectively. The LOD and the lower LOQ were 0.01 and 0.05 μg/mL for edaravone and 0.66 and 2 μg/mL for taurine, respectively. The calibration curves of these two analytes demonstrated good linearity (r > 0.99). All the validation data including the specificity, precision, recovery, and stability conformed to the acceptable requirements. This validated method has successfully been applied in the pharmacokinetic study of edaravone and taurine mixture in beagle dogs.

  17. 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.

  18. Bioequivalence and Population Pharmacokinetic Modeling of Two Forms of Antibiotic, Cefuroxime Lysine and Cefuroxime Sodium, after Intravenous Infusion in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Longshan Zhao

    2012-01-01

    Full Text Available To investigate the bioequivalence and the population pharmacokinetics of cefuroxime lysine and cefuroxime sodium in healthy beagle dogs. A randomized 2-period crossover design in 18 healthy beagle dogs after receiving 20, 40, and 80 mg/kg of cefuroxime lysine or cefuroxime sodium was conducted. A 3-compartment open model was used as the basic model for the population pharmacokinetic study. Both of the antibiotics exhibited dose-proportional pharmacokinetics over the dose range of 20–80 mg/kg. The mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium was 1.05 (range, 0.71 to 1.42, with a significant difference between males and females. The estimates of population pharmacokinetic of CL, V1, Q2, V2, Q3, V3 were 3.74 mL/h, 1.70 mL, 29.5 mL/min, 3.58 mL, 0.31 mL/min, and 158 mL for cefuroxime lysine and 4.10 mL/h, 1.00 mL, 38.5 mL/min, 4.19 mL, 0.06 mL/min, and 13.6 mL for cefuroxime sodium, respectively. The inter-individual variability was determined to be less than 29.1%. A linear pharmacokinetic was revealed for cefuroxime lysine and cefuroxime sodium in dogs after intravenous infusion, and the bioequivalence of these forms of the antibiotic was observed with the significant gender-related differences in mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Reconstrucción de la vegetación posglacial y su relación con el ascenso relativo del nivel del mar en el extremo este del canal Beagle, Tierra del Fuego, Argentina

    OpenAIRE

    Borromei, Ana María; Ponce, Juan Federico; Coronato, Andrea; Candel,María Soledad; Olivera,Daniela; Okuda,Masaaki

    2014-01-01

    A partir del análisis polínico de una turbera de Donatia-Astelia ubicada en Punta Moat (Moat-2; 54°58' 50"S, 66°44'10"W; 40 m s.n.m.), este del canal Beagle, y de modelos digitales de terreno vinculados a la curva de ascenso del mar posglacial, se reconstruye la evolución de la línea de costa y la vegetación desde el Último Máximo Glacial (UMG, ca. 25 ka cal AP) hasta el Holoceno medio (5.000 años cal AP). La evolución de las comunidades vegetales en el extremo este del canal Beagle coincide ...

  5. Paleoambientes litorales durante el inicio de la trasgresión marina holocena en bahía Lapataia, canal Beagle, parque nacional Tierra del Fuego Littoral paleoenvironments during the beginning of the Holocene marine transgression in Lapataia Bay, Beagle Channel, National Park of Tierra del Fuego

    Directory of Open Access Journals (Sweden)

    Jorge Rabassa

    2009-12-01

    Full Text Available Los sitios Aserradero Lapataia 1 y 2 presentan depósitos limo-arcillosos portadores de valvas de moluscos: Mulinia edulis, Mytilus chilensis, Aulacomya atra y Yoldia sp. Además predominan los quistes de dinoflagelados, revestimientos de foraminíferos bentónicos y huevos de copépodos. Valvas de Mulinia edulis fueron datadas radiocarbónicamente en 8.094 ± 43 (AA74047 y 8.167 ± 43 (AA74048 a A.P. En Arroyo Baliza depósitos limo-arcillosos son portadores de Venus antiqua, Aulacomya atra, Mytilus chilensis, entre otros. La microflora está dominada por dinoquistes protoperidinioideos, acritarcos y restos de copépodos. Se sugiere ambientes marino-marginales, con baja a moderada salinidad, y altas concentraciones de nutrientes en las aguas superficiales. La datación radiocarbónica sobre Venus antiqua en Arroyo Baliza indica 2.844 ± 34 a A.P. (AA74046. Aserradero Lapataia confirma las edades más antiguas conocidas para la fase estuárica de la transgresión holocena en el canal Beagle. Arroyo Baliza aporta nueva evidencia de la fase regresiva en este canal durante el Holoceno tardío.The Aserradero Lapataia 1 and 2 sites present clayey silty sediments including mollusk shell; Mulinia edulis, Mytilus chilensis, Aulacomya atra and Yoldia sp. Besides, dinoflagelate cysts, covers of benthonic foraminifera and copepod eggs are dominant. The microflora is represented by sporomorphs and fresh to salty water microplancton. Radiocarbon dates on Mulinia edulis shells yielded ages of 8094 ± 43 (AA74047 and 8167 ± 43 (AA74048 yr B.P. At Arroyo Baliza, clayey silts were found including Venus antiqua, Aulacomya atra, Mytilus chilensis, among others, accompanied by acritarchs and remnants of copepods. This association suggests marginal marine environments, with low to moderate salinity, and high nutrient concentration in the surface waters. Radiocarbon dating on Venus antiqua shells yielded 2844 ± 34 yr B.P. (AA74046. Marine deposits of the Aserradero

  6. Effect of electroacupuncture on abducens nerve injury in Beagle dog%电针刺激对Beagle犬展神经损伤修复的研究

    Institute of Scientific and Technical Information of China (English)

    张毅; 陈霞; 周凌云; 王旭东; 虞昊

    2015-01-01

    Objective To establish Beagle dogs’model of abducens nerves injury and to observe the clinical therapeu⁃tic effect of electroacupuncture treatment. Methods Twenty-four Beagle dogs were randomly divided into simple crush group (control group) and crush with electrical stimulation group (experimental group). Cisternal segment of the abducens nerve was given a crush injury, then electrodes were implanted to stimulate the abducens nerve and lateral rectus muscle. Distance between the center of the pupil to medial margin of extraocular adjoin was measured from 1 to 12 weeks after opera⁃tions. Results All procedures used in the study were well tolerated by Beagle dogs. Electrode implantation to stimulate the lateral rectus muscle and the abducens nerve behind of cavemous sinus was successful. There was no statistical significance of the distance between the two groups from 1 to 2 weeks after operations, and the distance was shorter in experimental group than that in control group from 4 to 12 weeks after operations (P<0.01). Conclusion The animal models established to study electroacupuncture treatment of the injured abducens nerves was successful. Electroacupuncture can promote the re⁃covery of the injured abducens nerves obviously.%目的:建立展神经损伤电针刺激的动物模型,研究电针刺激对展神经损伤修复的疗效。方法24只Bea⁃gle犬随机均分为单纯损伤组(对照组)及损伤后电针刺激组(实验组)。行展神经脑池段压榨损伤,展神经刺激电极及外直肌记录电极植入。于术后1~12周,测量2组瞳孔中心至外眦内侧缘距离。结果所有Beagle犬均能耐受手术,颅内刺激电极和外直肌记录电极成功植入;术后1~2周,2组Beagle犬瞳孔中心至外眦内侧缘距离比较差异无统计学意义,术后4~12周,实验组Beagle犬瞳孔中心至外眦内侧缘距离小于对照组(P<0.01)。结论成功建立应用于展神经损伤电针

  7. In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs

    Directory of Open Access Journals (Sweden)

    Kim JS

    2016-06-01

    Full Text Available Jeong Soo Kim,1 Kwang Ho Cha,1 Seung Yeob Kang,1 Donghan Won,1 Sun Woo Jang,1 Miwon Son,1 Moon Ho Son,1 Ho Jung Choi,2 Young Won Lee,2 Myung Joo Kang3 1Dong-A Pharmaceutical Co. Ltd., Giheung-gu, Yongin, Gyeonggi, 2College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungnam National University, Daejeon, 3College of Pharmacy, Dankook University, Dongnam-gu, Cheonan, Chungnam, South Korea Objective: DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR tablets of DA-9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR tablets of DA-9601.Method: In vitro buoyancy behavior (floating lag time and duration and release profile of eupatilin were assessed in acidic medium. The in vivo intragastric behaviors of the barium sulfate-loaded IR and GR tablets were evaluated in beagle dogs by radiographic studies. Local gastroprotective effect was compared in an experimentally induced gastric lesion in beagle dogs after oral administration of IR (three times per day or GR (twice daily tablets for 15 days.Results: Upon contact with gastric juice, a low-density floating tablet (apparent density of 0.93 g/cm3 was buoyant on the medium and was upheld for 14 hours, providing sustained drug release profile, whereas the IR tablet disintegrated within 10 minutes, showing complete drug release within 2 hours. In vivo radiographic studies showed that the GR tablet was retained for >4 hours in the stomach. Both DA-9601 formulations remarkably alleviated gastric mucosal injury compared to placebo group, when observed by gastric endoscopy.Conclusion: Twice-daily GR tablets exhibited a prolonged gastric residence

  8. Pharmacokinetic study of calenduloside E and its active metabolite oleanolic acid in beagle dog using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Shi, Meiyun; Yang, Yan; Sun, Yantong; Cheng, Longmei; Zhao, Sen; Xu, Huibo; Fawcett, J Paul; Sun, Xiaobo; Gu, Jingkai

    2014-03-01

    Aralia mandshrica is a well-known traditional Chinese medicine from Northeast China commonly used to treat digestive, circulatory and immune system disorders. Calenduloside E is one of its bioactive components currently under evaluation as a pure drug. In this study, a highly sensitive and rapid method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous quantitation of calenduloside E and its active metabolite oleanolic acid in beagle dog plasma has been developed and validated. Samples containing the ammonium salt of simvastatin acid as internal standard (IS) were purified by solid phase extraction and separated on a SUPELCO Ascentis-C18 column (50mm×4.6mm i.d., 5μm) using gradient elution with 0.35% formic acid and acetonitrile. Analytes and IS were detected in a cycle time of 5min after ionization in the negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 631.4→455.4 and m/z 435.4→319.0 for calenduloside E and IS respectively and by single ion monitoring of the ion at m/z 455.4 for oleanolic acid. The method was linear over the concentration range 0.4-100ng/mL for both analytes using 0.5mL plasma. Inter- and intra-day precisions were both beagle dogs were given oral doses of calenduloside E (1.05, 2.10 and 4.20mg/kg) and an intravenous injection of 2.10mg/kg. The absolute bioavailability of calenduloside E was only 0.58%. Area under the plasma concentration time curve (AUC(0-t)) for the oral doses of calenduloside E was approximately dose proportional while other PK parameters (t1/2, Tmax and MRT) showed no significant differences among the three doses (P>0.05). The PK data provide a useful platform on which to base future clinical studies of calenduloside E.

  9. Antidiabetic and hypolipidemic effects of a novel dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, E3030, in db/db mice and beagle dogs.

    Science.gov (United States)

    Kasai, Shunji; Inoue, Takashi; Yoshitomi, Hideki; Hihara, Taro; Matsuura, Fumiyoshi; Harada, Hitoshi; Shinoda, Masanobu; Tanaka, Isao

    2008-09-01

    We investigated the antidiabetic effects of E3030, which is a potent dual activator of peroxisome proliferator-activated receptor (PPAR) alpha and PPARgamma, in an animal model of diabetes, C57BL/KsJ-db/db mice (db/db mice), and the lipidemic effects of E3030 in beagle dogs, whose PPARalpha and PPARgamma transactivation responses to E3030 were similar to those of humans. E3030 activated human PPARalpha, mouse PPARalpha, dog PPARalpha, human PPARgamma, mouse PPARgamma, and dog PPARgamma with EC(50) values of 65, 920, 87, 34, 73, and 34 nM, respectively, in the chimeric GAL4-PPAR receptor transactivation reporter assay. In db/db mice orally administered E3030 decreased blood glucose, triglyceride (TG), non-esterified fatty acids (NEFA), and insulin levels and increased blood adiponectin levels during a 14-day experimental period. Significant effects on blood glucose and adiponectin levels were observed at a dose of 3 mg/kg or greater. Furthermore, significant effects on blood TG, NEFA, and insulin levels were observed at doses of 1 mg/kg or more. An oral glucose tolerance test (OGTT) performed on Day 15 showed that E3030 at 3 mg/kg improved glucose tolerance in this model. Fourteen days of oral treatment with E3030 at a dose of 0.03 mg/kg or greater showed remarkable TG- and non high-density lipoprotein (non-HDL) cholesterol-lowering effects in beagle dogs. These results were similar to those observed for the PPARalpha agonist fenofibrate. E3030 also reduced apo C-III levels on Days 7 and 14, and elevated lipoprotein lipase (LPL) levels on Day 15. These results indicate that the TG- and non-HDL cholesterol-lowering actions of E3030 involve combined effects on reduction of apo C-III and elevation of LPL, resulting in increased lipolysis. The experimental results in animals suggest that E3030 has potential for use in the treatment of various aspects of metabolic dysfunction in type 2 diabetes, including dyslipidemia, hyperglycemia, hyperinsulinemia, and impaired

  10. In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

    Science.gov (United States)

    Ghimire, Manish; McInnes, Fiona J; Watson, David G; Mullen, Alexander B; Stevens, Howard N E

    2007-09-01

    The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.

  11. 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.

  12. The effects of oral administration of Yunnan Baiyao on blood coagulation in beagle dogs as measured by kaolin-activated thromboelastography and buccal mucosal bleeding times.

    Science.gov (United States)

    Frederick, Jami; Boysen, Søren; Wagg, Catherine; Chalhoub, Serge

    2017-01-01

    We examined the effects of oral administration of Yunnan Baiyao (YB) on hemostasis by measuring buccal mucosal bleeding times (BMBTs) and doing citrated kaolin-activated whole-blood thromboelastography (TEG). In a randomized controlled crossover trial 8 beagle dogs were given either placebo or 1000 mg of YB orally every 12 h for 5 consecutive treatments. Blood was drawn 24 h before treatment and 2 and 24 h after the last treatment, and the BMBT was measured in each sample in duplicate. The TEG analysis was done in duplicate 60 ± 5 min after sample collection. There were no adverse effects of treatment and no significant differences between the control and treatment BMBTs or TEG parameters at any time point. Significant differences were found between baseline and 24 h after the last treatment within the treatment group for the TEG parameters LY30 and LY60 and within the control group for the TEG parameters MA, G, LY30, and LY60. Thus, at the dose and frequency of administration in this study YB did not appear to have any clinically significant effects on the measured coagulation parameters. The differences within the treatment group were likely due to analytic error since similar differences were seen in the control group. Further studies with a larger sample, as well as more direct measures of platelet function, are needed.

  13. Quantification of 3-n-butylphthalide in beagle plasma samples by supercritical fluid chromatography with triple quadruple mass spectrometry and its application to an oral bioavailability study.

    Science.gov (United States)

    Li, Yun; Zhao, Longshan; Li, Xiaoting; Guo, Bei; Zhao, Juanhang; Wang, Xianglin; Zhang, Tianhong

    2015-02-01

    A high-throughput, rapid, sensitive, environmentally friendly, and economical supercritical fluid chromatography with triple quadruple mass spectrometry method was established and validated for the first time to determine a cerebral stroke treatment drug named 3-n-butylphthalide in dog plasma. Plasma samples were prepared by protein precipitation with methanol and the analytes were eluted on an ACQUITY UPC(2TM) HSS-C(18) SB column (3 × 100 mm, 1.8 μm) maintained at 50°C. The mobile phase comprised supercritical carbon dioxide/methanol (90:10, v/v) at a flow rate of 1.5 mL/min, the compensation solvent was methanol at a flow rate of 0.2 mL/min and the total run time was 1.5 min per sample. The detection was carried out on a tandem mass spectrometer with an electrospray ionization source. Calibration curves were linear over the concentration range of 1.02-1021.00 ng/mL (r(2) ≥ 0.993) with the lower limit of quantification of 1.02 ng/mL. The intra- and inter-day precision values were below 15% and the accuracy was from 97.90 to 103.70% at all quality control levels. The method was suitable for a pharmacokinetic study of 3-n-butylphthalide in beagle dogs.

  14. Simultaneous determination of leucine, isoleucine and valine in Beagle dog plasma by HPLC-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Wang, Ting; Xie, Huiru; Chen, Xu; Jiang, Xuehua; Wang, Ling

    2015-10-10

    Leucine (Leu), isoleucine (Ile) and valine (Val) are three branched-chain amino acids (BCAAs), which have been widely used as dietary supplements for professional athletes and patients with liver failure or catabolic diseases. To date, no pharmacokinetic studies of BCAAs in vivo useful for the assessment of clinical effect following daily intake has been reported. Thus in this study, an HPLC-MS/MS method for simultaneous determination of Leu, Ile and Val in Beagle dog plasma using homoarginine as the internal standard was developed and validated in terms of specificity, linearity, precision, accuracy, and stability. This assay method was then applied to a pharmacokinetic study of BCAAs in dogs following oral administration of 0.25 g/kg and 0.50 g/kg BCAAs. The HPLC-MS/MS method was found to be sensitive and reproducible for quantification of BCAAs in dog plasma and successfully applied to the pharmacokinetic study. All these BCAAs were well absorbed with a substantial increase in the plasma concentration after a baseline modification. No statistical significance was identified in different gender group and no drug accumulation was observed following multiple doses.

  15. The effects of hydroxyapatite/calcium phosphate glass scaffold and its surface modification with bovine serum albumin on 1-wall intrabony defects of beagle dogs: a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Um, Yoo-Jung; Jung, Ui-Won; Chae, Gyung-Joon; Kim, Chang-Sung; Cho, Kyoo-Sung; Kim, Chong-Kwan; Choi, Seong-Ho [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752 l (Korea, Republic of); Lee, Yong-Keun [Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-750 (Korea, Republic of)], E-mail: shchoi726@yuhs.ac

    2008-12-15

    The purpose of this study was to evaluate the effects of biphasic hydroxyapatite/calcium phosphate glass (HA/CPG) scaffold and its surface modification with bovine serum albumin (BSA) on periodontal regeneration. 1-wall intrabony defects were surgically created on five beagle dogs. HA/CPG scaffolds, with a hydroxyapatite (HA)/calcium phosphate glass (CPG) ratio of 95:5 by weight (%) and surface modification done by 2% bovine serum albumin, were used. The control group received surgical flap operation, and the experimental groups were filled with HA/CPG scaffolds and HA/CPG(BSA) scaffolds. The animals were sacrificed eight weeks after surgery. Histological findings revealed better space maintenance in the experimental groups than the control group, and showed new bone formation intermittently in between the residual material particles. The newly formed bone was mostly woven bone and the residual particles were undergoing resorption. Cementum regeneration was observed with limited root resorption in all the groups. Histometric analysis also revealed greater mean values in new bone formation, cementum regeneration and bone area than the control group in both experimental groups. However, similar findings were presented between HA/CPG and HA/CPG(BSA). The result of the present study revealed the newly fabricated HA/CPG scaffold to have a potential use as a bone substitute material.

  16. Spontaneous and Dosing Route-related Lung Lesions in Beagle Dogs from Oral Gavage and Inhalation Toxicity Studies: Differentiation from Compound-induced Lesions.

    Science.gov (United States)

    Mukaratirwa, Sydney; Garcia, Begonya; Isobe, Kaori; Petterino, Claudio; Bradley, Alys

    2016-10-01

    This study was conducted to characterize lung microscopic lesions in control beagle dogs from inhalation and oral gavage toxicity studies, to determine differences associated with the route of administration, and to discuss distinguishing features from compound-induced lung lesions. Samples from 138 control dogs from oral gavage studies and 124 control dogs from inhalation (vehicle control) studies were evaluated microscopically. There was no significant sex-related difference in the incidence of all lesions. Perivascular mononuclear cell infiltration, centriacinar mixed cell infiltration, bronchopneumonia, subpleural septal fibrosis, and alveolar macrophage accumulation were the most common lesions. Aspiration pneumonia was more common in dogs from gavage studies, suggesting reflux after gavage dosing or accidental administration of test formulation as possible causes. Centriacinar mixed cell infiltration was more common in dogs from inhalation studies, suggesting mild irritation by the vehicles used. Vascular lesions, which included pulmonary arteriopathy and smooth muscle mineralization, were observed in a few animals. Some of the spontaneous lesions are similar to lesions induced by test compounds. Compared to spontaneous lesions, compound-induced lesions tend to be multifocal or diffuse, follow a pattern of distribution (e.g., centriacinar, perivascular, and interstitial), show a dose response in the incidence and severity, and may show cell-specific toxicity.

  17. Diffusion tensor imaging of white and grey matter within the spinal cord of normal Beagle dogs: Sub-regional differences of the various diffusion parameters.

    Science.gov (United States)

    Yoon, Hakyoung; Park, Noh-Won; Ha, Yun-Mi; Kim, Jaehwan; Moon, Won-Jin; Eom, Kidong

    2016-09-01

    Diffusion tensor imaging (DTI) is an advanced diffusion weighted imaging technique that can identify early stage lesions and Wallerian degeneration within the spinal cord; these changes are difficult to recognise on conventional magnetic resonance imaging (MRI). The only DTI parameters previously investigated in dogs are fractional anisotropy and mean diffusivity (MD). The aim of this study was to evaluate multiple DTI parameters in sub-regional areas of the spinal cord in normal Beagles. All imaging data were obtained from the lumbar spinal cord (L1-L3) of ten normal dogs using a 3 Tesla MRI scanner. Transverse multi-shot echo planar imaging sequences (b values = 0 and 800 s/mm(2); 12 directions) were used for DTI. Regions of interest were selected from sub-regions of the white and grey matter, and from the whole spinal cord, in the transverse plane in all DTI maps. The DTI parameters in spinal cord sub-regions in the transverse plane were significantly different amongst the white matter, grey matter and whole spinal cord (P matter sub-regions (P grey matter may be useful for regional evaluation of the dog spinal cord.

  18. Capromorelin increases food consumption, body weight, growth hormone, and sustained insulin-like growth factor 1 concentrations when administered to healthy adult Beagle dogs.

    Science.gov (United States)

    Zollers, B; Rhodes, L; Smith, R G

    2017-04-01

    This study's objective was to determine the effects in dogs of oral capromorelin, a ghrelin agonist, at different doses for 7 days on food consumption, body weight and serum concentrations of growth hormone (GH), insulin-like growth factor 1 (IGF-1), and cortisol. Adult Beagles (n = 6) were dosed with placebo BID, capromorelin at 3.0 mg/kg SID, 4.5 mg/kg SID, or 3.0 mg/kg BID. Food consumption, body weight, serum capromorelin, GH, IGF-1, and cortisol were measured at intervals on days 1, 4, 7, and 9. Capromorelin increased food consumption and body weight compared to placebo and caused increased serum GH, which returned to the baseline by 8 h postdose. The magnitude of the GH increase was less on days 4 and 7 compared to Day 1. IGF-1 concentrations increased on Day 1 in capromorelin-treated dogs and this increase was sustained through Day 7. Serum cortisol increased postdosing and returned to the baseline concentrations by 8 h. The magnitude of the increase was less on days 4 and 7 compared to Day 1. A dose of 3 mg/kg was chosen for further study in dogs based on this dose causing increased food consumption and sustained IGF-1 serum concentrations that may increase lean muscle mass when administered over extended periods.

  19. 比格犬下颌骨微种植体的置入部位和方法%Mandibular interradicular place of beagles for microscrew implantation

    Institute of Scientific and Technical Information of China (English)

    刘雯; 胡赟; 邓锋; 宋锦璘; 郑雷蕾; 赵志河; 唐甜; 王智强

    2011-01-01

    背景:比格犬下颌骨解剖结构复杂,微种植体置入位置不恰当会造成微种植体周骨量不足和微种植体松脱.目的:观察比格犬下颌骨相应解剖结构及微种植体的置入部位和方法.方法:取成年雄性比格犬尸体下颌骨,测量下颌第二双尖牙牙尖至下颌第一磨牙远中颊尖的长度;下颌第二、三、四双尖牙和第一磨牙根分叉度及牙根分叉处距离下颌神经管的垂直高度;于牙槽嵴下4,6 mm 处用游标卡尺测量下颌第二、三、四双尖牙和第一磨牙颊舌向牙槽嵴厚度和近远中根的水平距离.结果与结论:下颌第二双尖牙牙尖至下颌第一磨牙远中颊尖的长度平均为52.70 mm;距离下颌神经管的垂直高度最远的是第一磨牙,最近的是第四双尖牙,根分叉度最大的是第一磨牙,最小的是第四双尖牙.下颌第二、三、四双尖牙和第一磨牙的颊舌向骨质厚度随着距离牙槽嵴顶深度的增加而增加.在距离牙槽嵴顶4,6 mm 的深度,下颌第二、三、四双尖牙和第一磨牙近远中根的水平距离均大于5 mm,且随着距离牙槽嵴深度的增加而增加.说明比格犬下颌第二双尖牙至第一磨牙牙槽骨段骨质结构均匀.在距离牙槽嵴顶4~6 mm 深度,单颗牙自身近远中牙根之间足以提供微种植体置入所需骨量.%BACKGROUND: The structure of Beagle's mandible is complex, and improper place for microscrew implantation would lead to deficiency of bone mass surrounding the microscrew and microscrew loosening. OBJECTIVE: To study the anatomic structure of Beagle's mandible and find out the place suitable for placing the orthodontic microscrew. METHODS: Five male Beagles corpses were collected. The distance between P2 and M1, the distance between tooth root crotch and inferior maxillary nerve, the degree of tooth root crotch, the mesiodistal width between the roots of teeth and the buccolingual sickness from 4 mm and 6 mm beneath the top of

  20. Paleoambientes litorales durante el inicio de la trasgresión marina holocena en bahía Lapataia, canal Beagle, parque nacional Tierra del Fuego

    Directory of Open Access Journals (Sweden)

    Jorge Rabassa

    2009-12-01

    Full Text Available Los sitios Aserradero Lapataia 1 y 2 presentan depósitos limo-arcillosos portadores de valvas de moluscos: Mulinia edulis, Mytilus chilensis, Aulacomya atra y Yoldia sp. Además predominan los quistes de dinoflagelados, revestimientos de foraminíferos bentónicos y huevos de copépodos. Valvas de Mulinia edulis fueron datadas radiocarbónicamente en 8.094 ± 43 (AA74047 y 8.167 ± 43 (AA74048 a A.P. En Arroyo Baliza depósitos limo-arcillosos son portadores de Venus antiqua, Aulacomya atra, Mytilus chilensis, entre otros. La microflora está dominada por dinoquistes protoperidinioideos, acritarcos y restos de copépodos. Se sugiere ambientes marino-marginales, con baja a moderada salinidad, y altas concentraciones de nutrientes en las aguas superficiales. La datación radiocarbónica sobre Venus antiqua en Arroyo Baliza indica 2.844 ± 34 a A.P. (AA74046. Aserradero Lapataia confirma las edades más antiguas conocidas para la fase estuárica de la transgresión holocena en el canal Beagle. Arroyo Baliza aporta nueva evidencia de la fase regresiva en este canal durante el Holoceno tardío.

  1. Development of an ultra fast liquid chromatography-tandem mass spectrometry method for simultaneous determination of cefazedone and etimicin in beagle dog plasma: Application to the pharmacokinetic study of the combination of cefazedone and etimicin injections.

    Science.gov (United States)

    Cui, Yan; Ma, Ning; Li, Xiaoyan; Lv, Chunxiao; Li, Mingjie; Li, Minghua; Song, Liangwei; Liu, Mingxia; Li, Qing; Bi, Kaishun

    2014-10-23

    A new, sensitive and efficient ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed and validated for simultaneous quantification of cefazedone and etimicin in beagle dog plasma. After addition of the internal standard (IS) metronidazole, plasma samples were treated by protein precipitation procedure, and then separated on a Venusil MP C18 column (100mm×2.1mm, 3.0μm) (Venusil, China) using gradient elution with the mobile phase consisting of 0.01% heptafluorobutyric acid (HFBA) in acetonitrile and 0.01% HFBA in water at a flow rate of 0.4mLmin(-1). The detection of the analytes was performed on 4000Q UFLC-MS/MS system with turbo ion spray source in the positive ion and multiple reaction-monitoring (MRM) mode. The linear range was 1.0-200μgmL(-1) for cefazedone and 0.5-100μgmL(-1) for etimicin, with lower limits of quantification of 1.0 and 0.5μgmL(-1), respectively. Intra-day and inter-day precisions were within 7.2% and 4.3%, respectively for both analytes, and the accuracy (relative error, RE, %) was less than 10.7% and 12.7%, respectively. The mean absolute extraction recoveries of analytes and IS from beagle dog plasma were all more than 73.22%. The validated method was successfully applied to the pharmacokinetic study of cefazedone and etimicin in beagle dog after intravenous administration of cefazedone injection combined with etimicin injection and the two single injections alone, respectively. The results indicated there were not obvious differences between the pharmacokinetic behaviors between the combined group and either of the single groups.

  2. Study on the Treating Hemorrhagic Shock of Beagle Dogs with Canine Plasma from Other Individuals%异体犬血浆治疗失血性休克Beagle犬的实验研究

    Institute of Scientific and Technical Information of China (English)

    李学勇; 渠凯; 付少才; 刘欣; 张博; 魏永俊; 李巧伶; 朱海波

    2012-01-01

    Objective To explore the effect of treating hemorrhagic shock Beagle dogs with canine plasma from other individuals, which will lay the foundation for clinical application. Method Bloodletting by femoral artery to establish hemorrhagic shock models of Beagle dogs. Then, observing the effect on treating hemorrhagic shock of Beagle dogs by transfusing canine plasma from other individuals. Result Transfused canine plasma from other individuals by vein, the mean artery pressure, the content of serum protein, blood glucose, concentration and part-pressure of carbon dioxide, anionic gap, BEECF and lots of ions, had improved obviously. Comparing canine plasma from other individuals with physiological saline, the statistical data had significant difference (P≤0. 05) or extreme significant difference ( P ≤1 0. 01). However, lots of metabolic products such as ALP, TBIL, had no significant difference ( P > 0. 05 ) . Conclusion The canine plasma from other individuals had significant effect on treating hemorrhagic shock of Beagle dogs, and it could be used to clinical practices.%目的 观察异体犬血浆对失血性休克Beagle犬的治疗作用,为临床应用奠定基础.方法 通过股动脉放血建立Beagle犬失血性休克模型,静脉输入受试异体犬血浆观察其治疗实验性休克的作用.结果 静脉输入受试异体犬血浆后,Beagle犬的平均动脉压、血清蛋白含量、血糖含量、二氧化碳浓度及其分压、阴离子间隙、细胞外液碱剩余、多种离子等多项指标均显著改善,与输入生理盐水相比,统计学有显著性差异(P≤0.05)或极显著差异(P≤0.01),而碱性磷酸酶、总胆红素等多种代谢产物含量未见显著差异(P>0.05).结论 受试异体犬血浆对失血性休克Beagle犬的治疗效果明显,具有临床应用价值.

  3. 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

  4. Pharmacokinetics and Pharmacodynamics of Subcutaneous Single Doses of Pegylated Human G-CSF Mutant (PEG30-rhG-CSF) in Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    Yongming Cai; Zhengmin Chen; Ling Jiang; Ming Li; Changxiao Liu

    2008-01-01

    OBJECTIVE To compare the pharmacokinetics and pharmacodynamics of PEG30-rhG-CSF administered to beagle dogs at three different dosages with PEG20-rhG-CSF administered at one dosage,and to provide an experimental basis for clinical trials.METHODS Beagle dogs received single,subcutaneous doses of PEG30-rhG-CSF at 100,200 and 400 μg/kg or PEG20-rhG-CSF at 200 μg/kg.PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzyme-linked immunosorbent assay (ELISA).WBC,ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation.Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis software.RESULTS The pharmacokinetic parameters of PEG30-rhG-CSF calculated from the serum concentration data determined by ELISA were as follows:the mean elimination half-life (t1/2ke) was 40.6 h (33.5~45.4 h);the mean time to reach peak concentration (Tmax) was 19.2 h (11.7~24.0 h);the drug clearance from the serum (CL) was decreased with increasing doses:the peak concentration (Cmax) and the area under the serum concentration-time curve (AUC) were increased with increasing doses.For PEG20-rhG-CSF,the half-life was shorter (12 h) and Tmax was achieved much earlier (10 h) relative to PEG30-rhG-CSF.The AUC of PEG30-rhG-CSF was much greater than that of PEG20-rhG-CSF,and the relative bioavailability with a subcutaneous injection was 158.7%.Administration of single doses of PEG30-rhG-CSF resulted in substantial increases in the absolute neutrophil count (ANC).The time to reach ANCmax (ANCTmax) was 72 h.The maximum observed absolute neutrophil counts (ANCmax) and the area over the baseline effect curve (AOBEC) was increased with increasing doses.The effect-elimination half-life (t1/2E) ranged from 60 h to 80 h after subcutaneous administration.The PLT count was slightly elevated 8-12 h after s.c.injection,and declined after 24 h.CONCLUSION The mean elimination half-life of PEG30-rh

  5. Pharmacokinetics of salvianolic acid B in beagle dogs%丹酚酸B药动学动物实验研究

    Institute of Scientific and Technical Information of China (English)

    王亚辉; 胡斌; 那丽; 丁国臣

    2012-01-01

    Objective To study the pharmacokinetics of salvianolic acid B in beagle dogs using LC - MS/MS method. Methods Salvianolic acid B in beagle dogs'vein and plasma samples were collected at different time points after administration. After a liquid -liquid extraction process with ethyl - acetate, salvianolic acid B and indapamide were separated on Symmetry C18. The mobile phase was a mixture of acetonitrile and water (containing 0. 3% formic acid). Detection was performed on a triple - quadrupole tandem mass spectrometer by selecting the reaction monitoring (SRM) mode via electricity spray ionization ( ESI). Quantification was performed using the transitions of m/z 717.2→m/z 519. 2 for salvianlic acid B and m/z 364. 0→rn/z 189. 0 for indapamide respectively. Results The nominal retention time for salvianolic acid B and indapamide was 1.03 and 1.24 min, respectively. Linear calibration curves were obtained o-ver the concentration range of 10. 24 ~ 1. 200 X 104 ng/ml for salvianolic acid B. The lower limit of quantification (LLOQ) of salvianolic acid B of was 10. 24 ng/ml. The intra - and inter - day accuracy of assay was less than 15% and the accuracy( RE) was - 2. 8% ~ 1. 9% at all the three QC levels. Conclusions This method has proved to be of high specifcity,sensitivity and has been successfully used for evaluation of pharmacokinetics of salvianolic acid B. The half life is short and metabolization shows a first - order linear pharmacokinetic.%目的 采用液相色谱-串联质谱法进行丹酚酸B药动学动物实验研究.方法 比格犬静脉滴注丹酚酸B后不同时间经前腿静脉采血.血浆样品经液-液萃取后,以乙腈-水(含0.5%甲酸):70-30(V/V)作为流动相,采用Symmetry C18(2.0 mm×50 mm,3 μm)柱分离,通过ESI源电离在负离子方式下进行检测,以选择反应监测(SRM)方式.用于定量分析的离子分别为 m/z 717.2→m/z 519.2(丹酚酸B)和 m/z 364.0→m/z 189.0(吲达帕胺,内标).结果 在该测定条件下

  6. 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.

  7. Enhancing in vivo Bioavailability in Beagle Dogs of GLM-7 as a Novel Anti-Leukemia Drug through a Self-Emulsifying Drug Delivery System for Oral Delivery.

    Science.gov (United States)

    Wang, Yuli; Yu, Ning; Guo, Rui; Yang, Meiyan; Shan, Li; Huang, Wei; Gong, Wei; Shao, Shuai; Chen, Xiaoping; Gao, Chunsheng

    2016-01-01

    GLM-7 is a novel anti-leukemia drug in the pre-clinical study. The previous study shows that GLM-7 is a poorly water-soluble drug with low oral bioavailability. In this study, we employed the self-emulsifying drug delivery system (SEDDS) to improve the oral bioavailability of GLM-7. The GLM-7 SEDDS formulation was prepared using MCT as oil, ovolecithin as surfactant and Transcutol as co-surfactant, and the formulation parameters were optimized by the response surface methodology. The optimized GLM-7 SEDDS formulation showed a stable liquid state, and can automatically emulsify to form the isotropic emulsion once exposure to the water phase. The generated emulsion showed the spherical shape, and had an average size of about 399 nm and a zeta potential of about -42 mV. Compared to the GLM-7 dissolution less than 1.4% from pure GLM-7 powder (reference), the GLM-7 SEDDS formulation could remarkably enhance the in vitro dissolution to 83% in the medium of 0.1N HCL. The in vivo oral bioavailability of GLM-7 SEDDS formulation was investigated in beagle dogs. The results demonstrated that the GLM-7 SEDDS formulation significantly enhanced the plasma concentrations of GLM-7, and the Cmax reached to 878 ng/ml and was 9.2 folds as high as the Cmax 95.85 ng/ml of reference. Moreover, the area under the curve (AUC) of GLM-7 SEDDS formulation was 13.6 times higher than that of reference, which suggested that the SEDDS formulation remarkably increased the oral bioavailability of GLM-7.

  8. Impact of Tetrahydropalmatine on the Pharmacokinetics of Probe Drugs for CYP1A2, 2D6 and 3A Isoenzymes in Beagle Dogs.

    Science.gov (United States)

    Zhao, Yong; Liang, Aihua; Zhang, Yushi; Li, Chunying; Yi, Yan; Nilsen, Odd Georg

    2016-06-01

    Tetrahydropalmatine (Tet) exhibit multiple pharmacological activities and is used frequently by clinical practitioners. In this study, we evaluate the in vivo effects of single and repeated oral Tet administrations on CYP1A2, 2D6 and 3A activities in six beagle dogs in a randomized, controlled, open-label, crossover study. A cocktail approach, with dosages of the probe drugs caffeine (3.0 mg/kg), metoprolol (2.33 mg/kg) and midazolam (0.45 mg/kg), was used to measure cytochrome P450 (CYP) metabolic activities. The cocktail was administered orally as a single dose (12 mg/kg) 1 day prior to and 4 days after repeated oral Tet administrations (12 mg/kg three times daily). The probe drugs and their metabolites in plasma were quantified simultaneously by a validated HPLC technique, and non-compartmental parameters were used to evaluate metabolic variables for assessment of CYP inhibition or induction. Tet had no or minor impact on the pharmacokinetics and metabolism of the probe drugs caffeine and metoprolol, CYP1A2 and CYP2D6 substrates, respectively. However, Tet increased AUC0-24 h and decreased AUCratio(0-24 h) (1-hydroxymidazolam/midazolam ratio) for midazolam statistically significant, both in single or multiple dosing of Tet, with up to 39 or 57% increase for AUC0-24 h and 29% or 22 decrease for AUCratio(0-24 h), respectively, in line with previous in vitro findings for its CYP3A4 inhibition. The extensive use of Tet and herbal medicines containing Tet makes Tet a candidate for further evaluation of CYP3A-mediated herb-drug interactions. Copyright © 2016 John Wiley & Sons, Ltd.

  9. An ADAMTSL2 founder mutation causes Musladin-Lueke Syndrome, a heritable disorder of beagle dogs, featuring stiff skin and joint contractures.

    Directory of Open Access Journals (Sweden)

    Hannah L Bader

    Full Text Available BACKGROUND: Musladin-Lueke Syndrome (MLS is a hereditary disorder affecting Beagle dogs that manifests with extensive fibrosis of the skin and joints. In this respect, it resembles human stiff skin syndrome and the Tight skin mouse, each of which is caused by gene defects affecting fibrillin-1, a major component of tissue microfibrils. The objective of this work was to determine the genetic basis of MLS and the molecular consequence of the identified mutation. METHODOLOGY AND PRINCIPAL FINDINGS: We mapped the locus for MLS by genome-wide association to a 3.05 Mb haplotype on canine chromosome 9 (CFA9 (50.11-54.26; p(raw T; p.R221C perfectly associated with MLS (p-value=10(-12. Murine ADAMTSL2 containing the p.R221C mutation formed anomalous disulfide-bonded dimers when transiently expressed in COS-1, HEK293F and CHO cells, and was present in the medium of these cells at lower levels than wild-type ADAMTSL2 expressed in parallel. CONCLUSIONS/SIGNIFICANCE: The genetic basis of MLS is a founder mutation in ADAMTSL2, previously shown to interact with latent TGF-β binding protein, which binds fibrillin-1. The molecular effect of the founder mutation on ADAMTSL2 is formation of disulfide-bonded dimers. Although caused by a distinct mutation, and having a milder phenotype than human GD, MLS nevertheless offers a new animal model for study of GD, and for prospective insights on mechanisms and pathways of skin fibrosis and joint contractures.

  10. Plasma Pharmacokinetics and Routes of Excretion of [14C]-Labeled Arruva, a High-Potency Sweetener, Following Oral Administration to Beagle Dogs.

    Science.gov (United States)

    Casterton, Phillip L; Crincoli, Christine M; Brathwaite, Witty A; Rihner, Marisa O; Nikiforov, Andrey I; Thomas, Jennifer A

    2014-05-01

    [(14)C]-Labeled arruva [sodium/potassium (2R,4R)-2-amino-4-carboxy-4-hydroxy-5-(3-indolyl) pentanoate] was administered as a single gavage dose (10 mg/kg bw) to male and female Beagle dogs and 1 bile duct-cannulated male. The mean peak arruva plasma concentration equivalent of 1.2 µg/g occurred at first sampling time point of 1 hour postdosing. The mean area under the concentration versus time curve from 0 hour postdosing to the last time point was approximately 20 µg·h/g and the mean terminal plasma elimination half-life ranged from 15 hours in females to 21 hours in males. Over 168 hours postdosing, 35% to 50% of the administered arruva was eliminated in the urine with 44% to 53% eliminated in feces; 1.3% of the administered dose was recovered in bile. Arruva and its derivatives were identified using tandem mass spectrometry, and the relative percentage of each substance was quantified via radio high-performance liquid chromatography. Over a 168-hour collection period, combined urine and feces extract data from the 6 noncannulated dogs showed that approximately 91% of the dose was excreted as unchanged parent arruva (41% in urine and 50% in feces). In the cannulated male, 95.3% was excreted as unchanged parent arruva; 50.2% in urine, 43.9% in feces, and 1.3% in bile. Lactone and lactam derivatives of arruva and 1 unidentified substance were detected in urine only during the first 24 hours postdosing with the greatest amounts detected during the first 6 hours of collection; up to 1% of lactone or lactam derivatives were detected in bile samples. Plasma pharmacokinetics data indicated rapid absorption of arruva with the majority of radioactivity located in the feces collected in the first 48 hours.

  11. The effect of right ventricular apical pacing on ERK1/2 phosphorylation in Beagle myocardium%右心室心尖部起搏对 Beagle 犬心室肌ERK1/2磷酸化水平的影响

    Institute of Scientific and Technical Information of China (English)

    程俊华; 洪俊; 郑程; 陈学思; 陈星星; 赵景琳; 李进; 林加锋

    2014-01-01

    目的:探讨右心室心尖部起搏对Beagle犬心室肌电重构及细胞外信号调节激酶(ERK)1/2磷酸化水平的影响。方法成年雄性Beagle犬12只,年龄3~4年,体重20~24kg,随机分为对照组(n=6)和起搏组(n=6),均植入DDD起搏器后程控至关闭状态,起搏组术后1周时开启起搏器并使心室起搏最大化。于术前及术后1周、4周关闭起搏器后行心电图及超声心动描记术检查,术后4周时处死动物,观察心肌病理结果,采用免疫印迹法检测犬右心室心肌总ERK1/2及其磷酸化水平的变化。结果两组心室肌病理及超声心动描记术、心率、QRS时间、总ERK1/2的表达差异均无统计学意义(均P>0.05);与对照组相比,术后4周时起搏组Tp- e间期、Q- T间期均增大,p- ERK增多(均P<0.05)。结论右心室心尖部起搏可以导致心肌复极延长及促进心肌ERK1/2的磷酸化。%Objective To investigate the effects of right ventricular apical pacing on electrical remodeling and ERK1/2 phosphorylation in beagle myocardium. Methods 12 male beagles, 3- 4 years old, underwent DDD pacemaker implanta-tion and were randomly divided into two groups (n=6). The pacemakers were turned on and programmed to ensure ventric-ular pacing 1 week after implantation in pacing group and turned off al the time in control group. The ECG and UCG were recorded before, 1 and 4 weeks after procedure with the pacemaker turned off. The beagles were sacrificed 4 weeks after procedure and phosphorylated ERK1 / 2 of right ventricular myocardium was determined by Western blotting. Results There was no statistical difference in the expression of ERK1 / 2, heart rate, QRS duration, BNP, ventricular myocardial pathology and parameters of UCG between the two groups. Tpeak- Tend interval and QT duration were prolonged and the expression of phosphorylated ERK1/2 increased in pacing group compared with control group(P<0.05) 4 weeks after pro

  12. Acute toxicological study of Shenzhi Jiannao Capsule on Beagle Dogs%参知健脑胶囊对Beagle犬的急性毒理研究

    Institute of Scientific and Technical Information of China (English)

    马大勇; 韩振蕴; 范吉平

    2012-01-01

    Objective: To observe the acute toxicity reaction of Beagle dogs after poured Shenzhi Jiannao Capsule into their stomachs to provide reference for toxicity study of dosing repeatedly before clinical research and safe use of drugs in clinical research. Methods: Six Beagle dogs were randomly divided into three groups, including QDTMTL, QDTMTM and QDTMTH with one male and one female in every group. The drug administration was oral gavage. The dosages of original design were designed as 1 000, 2 000 and 5 000 mg/kg, but due to vomitting of QDTMTM and QDTMTH after oral gavage, the actual dosage of QDTMTM was both approximately 2 OOOmg/kg, and the actual dosage of QDTMTH were approximately 2 209 and 3 092 mg/kg. There was a 14-day clinical observation after dose, and among that period, the animals' weight, temperature, ECG, blood cell count, blood coagulation, blood biochemistry, eye examination were observed. Afer clinical observation, all the dogs were euthanized, and observed for the gross anatomy. Results: In the period of test, there wasn't animal death or articulo mortis; there wasn't abnormal clinical reaction found in QDTMTL, but transient vomiting and loose stools after oral gavage were observed in QDTMTM and QDTMTH. However, there wasn't abnormal clinical reaction from morrow to end of the experiment. There wasn't any regularly change of drug-related in the results of all the animals 'weight, temperature, ECG, blood cell count, blood coagulation, blood biochemistry, eye examination. There was no change abnormal in the gross anatomy of animals'tissue and viscera. Conclusion: In this experiment condition, the safe dose of single gavage of Shenzhi Jiannao Capsule for Beagle dogs is 1 000 mg/kg, and MTD is greater than 3 000 mg/kg.%目的:观察Beagle犬灌胃给予参知健脑胶囊后,所出现的急性毒性反应情况,为临床前反复给药的毒性研究和临床安全用药提供参考.方法:试验用Beagle犬6只,随机分为3组,分别

  13. 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.

  14. Clinical Investigation of Beagle's Ehrlichiosis Experimentally Produced with E.platys and E.canis%比格犬人工感染埃立克体病的临床研究

    Institute of Scientific and Technical Information of China (English)

    马玉海; 潘华; 佟世德; 孙洋; 胡永辉; 宋阳

    2001-01-01

    为了表述比格犬感染埃立克体(Ehrlichia)后的临床表现,用已确证为E.platys和E.canis混合感染的犬血对5条比格犬进行了人工感染,并对临床和血液学变化进行了观察。埃立克体病的潜伏期为6~29天,其后的临床表现为急性发热、眼结膜苍白、厌食、精神沉郁、体重严重减轻、腹泻带血、多处有淤血斑点出现、6~45天内全部死亡。血液学变化显示血红蛋白和白细胞明显减少(P<0.001,P<0.05)。由此可见,比格犬对2种埃立克体(E.canis和E.platys)混合感染的敏感性很高,严重的临床表现与美国学者普遍认为的亚临床状态相左,这可能是中国Gzh981株(E.platys)和Gzh982株(E.canis)与国外株在毒力上的差异所致。%To elucidate the clinical aspect of Beagle's,five Beagles were inoculated with blood samples that had been proved to be positive for E.plays and E.canis.The inoculated Beagles had a latency of about 5 to 29 days,and the followed clinical appearances were characterized by acute fever,anorexia,pale mucous membranes,depression,weakness,serious weight loss,and diarrhea with blood stools.Ecchymoses and petechiae of blood commonly occurred at mulitiple sites.The death occurred as early as the sixth day and all died within 45 days,WBC counts and hemoglobin values significantly decreased(p<0.001,p<0.05).It can be seen from the results that Beagles are more susceptible to the coinfection of E.platys and E.canis,and display the acute febrile clinical presentations which are different from what American researchers considered that the Beagle's ehrlichiosis was of subclinical.The acute forms of infections in this study might also attributed to the virulence differences between Chinese strain Gzh981(E.platy),Gzh982, and foreign strains.

  15. An experimental approach for archeological soil micromorphology: building a model for site taphonomy in coastal shell middens of the Beagle Channel (Argentina)

    Science.gov (United States)

    Balbo, Andrea; Suarez Villagran, Ximena; Madella, Marco; Vila, Asumpcio; Estevez, Jordi

    2010-05-01

    There are still many archaeological contexts where soil micromorphology has been little applied. Examples of such are anthropic shell deposits, common in coastal settings worldwide. These archaeological sites have complex stratigraphies composed mainly of shell from diverse species of local mollusks and gastropods. They have the peculiarity of being highly porous sediments with a coarse fraction that is dominated by gravel-sized bioclastic remains (shell, fish bones) and a fine fraction composed of organic material (charcoal, organic matter). The use of soil micromorphology in shell deposits was started by the Spanish-Argentinean research team working in Tierra del Fuego (Argentina) since 1986. This project focused on excavation of hunter-gatherer sites from the contact period. One of the main objectives was to develop a detailed excavation method for shell middens that maximized the amount of recorded data during archaeological excavation. In this perspective, microstratigraphy was conceived as a fundamental complement for the study of site formation processes, as it would provide with high definition data for identification of shell accumulation episodes, trampling on site, abandonment periods, taphonomic alterations etc. A reference collection of known environmental and anthropic control features, such as hearths, trampling areas, wood ashes from local species, among others, was built to help in the microscopic characterization of archaeological samples. In this work, we analyze this experimental collection and compare it with samples from the Tunel VII archaeological site, located in the northern coast of the Beagle Channel and dated from the 18th-19th centuries. The set of modern samples included: trampling area from an animal pathway; beach deposit; forest litter; soil under the forest; hearths lit in diverse contexts (on the prairie, the beach and from the archaeologist camp site); and experimental burnt valves of Mytilus edulis, the main malacological

  16. 比格犬脑垂体远侧部细胞的电镜观察%Ultrastructural Study of the Adenohypophysis Pars Distalis of the Beagle Dog

    Institute of Scientific and Technical Information of China (English)

    李玉谷; 张媛; 孔小明; 程树军; 黄韧

    2003-01-01

    透射电镜观察表明,比格犬(Beagle)脑垂体远侧部实质中含有6种细胞,即生长激素细胞、催乳激素细胞、促甲状腺激素细胞、促性腺激素细胞、促肾上腺皮质激素细胞和滤泡一星形细胞,它们各有其超微结构特征.生长激素细胞呈圆形;胞核为圆形;分泌颗粒很多,圆形,直径约233~465 nm.催乳激素细胞多呈不规则形;胞核为不规则形;分泌颗粒很多,圆形,直径约310~620 nm.促甲状腺激素细胞呈圆形或卵圆形;胞核为圆形或卵圆形;分泌颗粒较少,直径约78~232 nm.促肾上腺皮质激素细胞呈圆形或卵圆形;胞核为圆形或卵圆形;分泌颗粒较多,圆形,直径约155~310 nm,分布于细胞周边.促性腺激素细胞呈圆形或椭圆形;胞核为圆形或椭圆形;分泌颗粒较少,呈圆形、卵圆形、杵状或不规则形,长径约155~434 nm.滤泡一星形细胞呈星形或不规则形,有突起伸入相邻细胞之间;胞核为圆形或卵圆形;胞质内无分泌颗粒.

  17. 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.

  18. Feeding healthy beagles medium-chain triglycerides, fish oil, and carnitine offsets age-related changes in serum fatty acids and carnitine metabolites.

    Directory of Open Access Journals (Sweden)

    Jean A Hall

    Full Text Available The purpose of this study was to determine if feeding dogs medium-chain triglycerides (MCT, fish oil, and L-carnitine enriched foods offsets age-associated changes in serum fatty acids (FA and carnitine metabolites. Forty-one healthy Beagles, mean age 9.9 years (range 3.1 to 14.8, were fed control or one of two treatment foods for 6 months. All foods were complete and balanced and met the nutrient requirements for adult dogs, and had similar concentrations of moisture, protein, and fat (approx. 7.4%, 14.0%, and 18.1%, respectively. The treatment diets both contained added L-carnitine (300 mg/kg and 0.6% (treatment food 1 or 1.5% (treatment food 2 added fish oil. Treatment food 2 also had increased MCT from coconut oil, added corn oil, and reduced animal fat. Composition of serum FA was determined by gas chromatography of FA methyl esters. Metabolomic profiles of serum samples were determined from extracted supernatants that were split and run on GC/MS and LC/MS/MS platforms, for identification and relative quantification of small metabolites. Body composition was determined by dual energy x-ray absorptiometry. Among dog groups, there was no change in total-lean-body weight, or in serum total protein and serum albumin concentrations, based on time or dietary treatment. Serum concentrations of carnitine metabolites were decreased in geriatric (>7 years vs. mature adult (≤ 7 years dogs, and supplementation with L-carnitine attenuated the effects of aging. The ratio of PUFA to SFA was significantly greater in mature dogs at baseline (P ≤ 0.05. Serum concentrations of eicosapentaenoic and docosahexaenoic FA increased in a dose-dependent manner. Dogs consuming treatment food 2 also had increased serum concentrations of lauric and myristic FA, and decreased concentrations of SFA, MUFA, and arachidonate (all P ≤ 0.05 and their PUFA to SFA ratio increased. In summary, dietary MCT, fish oil, and L-carnitine counterbalanced the effects of aging on

  19. Pharmacokinetics of gliclazide osmotic pump tablets in Beagle dogs%格列齐特渗透泵片在Beagle犬体内的药动学

    Institute of Scientific and Technical Information of China (English)

    高国义; 刘志东; 解江纯

    2009-01-01

    目的 建立格列齐特血药浓度的高效液相色谱测定方法,研究Beagle犬单、多剂量口服格列齐特渗透泵片的药动学.方法 用HPLC法测定6只健康Beagle犬单剂量和多剂量口服格列齐特缓释片和渗透泵片的血药浓度,以DAS 2.0软件计算药动学参数.结果 格列齐特的药一时曲线符合单室模型.单剂量给药后,缓释片和渗透泵片的t1/2分别为(6.0±s 1.6)h和(7.4±2.3)h,tmax分别为(8.0±2.5)h和(6.2±2.9)h,pmax分别为(8.1±3.2)mg·L-1和(6.6±1.6)mg·L-1,AUC0-∞分别为(146±8)mg·h·L-1和(144±17)mg·h·L-1,渗透泵片的相对生物利用度为(99±15)%.多剂量给药后,缓释片和渗透泵片的t1/2分别为(8.0±2.5)h和(9±3)h,tmax分别为(4.2±0.4)h和(5.3±0.5)h,pmax分别为(14.4±1.8)mg·L-1和(12.5±1.7)mg·L-1,pmax分别为(4.1±1.5)mg·L-1和(5.8±1.5)mg·L-1,pav分别为(10.2±1.1)mg·L-1和(11.0±1.2)mg·L-1,AUC0-∞分别为(263±29)mg·h·L-1和(270±31)mg·h·L-1,DF分别为(103±21)%和(61±26)%.渗透泵片的相对生物利用度为(103±9)%.结论 本方法准确、灵敏,格列齐特在犬体内的药动学符合单室模型,2种片剂生物等效.%AIM To establish a method of HPLC for studying the pharmacokinetics of gliclazide osmotic pump tablets after a single and multiple oral administrations in Beagle dogs. METHODS To determine the plasma concentrations of sustained-release tablets and osmotic pump tablets after a single and multiple oral administration in Beagle dogs by HPLC. The pharmacokinetic parameters were calculated with DAS 2.0 software.RESULTS The drug concentration-time curves fitted to a one-compartment model. The pharmacokinetic parameters for the single oral administration of the sustained-release tablets and osmotic pump tablets were t1/2 (6.0 ± s 1.6) h and (7.4 ± 2.3) h, tmax(8.0 ± 2.5) h and (6.2 ± 2.9) h, pmax,(8.1 ± 3.2) mg·L-1 and (6.6 ± 1.6) mg·L-1, AUC(0-∞) (146 ± 8) mg·h·L-1 and (144 ±17) mg·h·L-1, respectively. The

  20. 不同繁育饲养设施对Beagle犬生产性能的影响%Comparison of the Performance of Beagle Dogs Bred in Two Kinds of Breeding Houses

    Institute of Scientific and Technical Information of China (English)

    康纪平; 李秋波; 冯晓科; 廖婷彬; 杨杰

    2011-01-01

    目的 探索不同繁育饲养设施对Beagle犬主要生产性能的影响.方法 使用两种不同Beagle犬繁育饲养设施(设施Ⅰ、设施Ⅱ)对母犬产仔状况、仔犬初生重、60 d离乳犬只存活率、60 d离乳犬只体重、1~6月龄犬只体重月增长等生产性能进行了比较研究.结果 两种设施比较母犬产仔状况,仔犬初生重无差异(P>0.05);设施Ⅱ比设施Ⅰ的60 d离乳犬只存活率高18.4%,差异极显著(P0.05).结论 设施Ⅱ优于设施Ⅰ.%Objective To analyze the performance of Beagle dogs bred in two kinds of breeding houses. Methods Performance of Beagle dogs bred in different breeding houses ( house Ⅰ and house Ⅱ ) such as litter situation, birth weight, survival rate and body weight of weaning dogs 60-days old, and weight gain per month was compared.Results The birth weights of Beagle dogs bred in house Ⅰ and house Ⅱ were statistically not significant different( P >0.05), while the survival rate of weaning dogs 60 days old bred in house Ⅱ was 18.4% higher than that in house Ⅰ (P < 0. 01 ) and the weight of weaning dogs 60-day old bred in house Ⅱ was 0. 62 ± 0. 13 kg higher than that in house Ⅰ (P <0.01 ), as well as weight gain per month of the dogs bred in house Ⅱ was 0. 29 ±0. 14 kg higher than that in house Ⅰ (P = 0. 08 > 0. 05). Conclusion The House Ⅱ is better than house Ⅰ .

  1. 犬乳牙牙髓干细胞体外培养及生物学性能研究%Biological characteristics of stem cells from deciduous tooth pulp of Beagle dog

    Institute of Scientific and Technical Information of China (English)

    刘飞; 刘阳; 戴姗姗; 马宁虎; 张林; 郭青玉

    2016-01-01

    Objective:To culture and characterize the deciduous tooth pulp stem cells(DTPSCs)of Beagle dog.Methods:DTPSCs were cultured using enzyme tissue block method from Beagle dog aged 6 weeks.The cells were purified by cloning culture,identified by immunohistochemistry and flowcytometry.The biological characteristics were studied by CCK-8 assay,osteogenetic induction,li-pogenic induction and dentinogenic induction assays.Results:Beagle stem cells from deciduous tooth pulp were obtained,the cell colony formation rate was 32%.The cells were STRO-1 and CD146 positive,CD14,CD45 and CD86 negative.After multiple induc-tion culture the cells were positive for alizarin red staining,oil red staining,ALP expression and DSSPP expression.Conclusion:The deciduous tooth pulp stem cells of Beagle dog have multilineage differentiation abilities.%目的:体外分离培养比格犬乳牙牙髓干细胞(DTPSCs),研究其生物学特性。方法:用酶解组织块法培养6周龄比格犬 DTPSCs,克隆法纯化,检测细胞克隆形成能力及增殖曲线;免疫组化鉴定细胞来源,流式细胞术鉴定细胞表面标记物;进行细胞多向诱导分化能力检测。结果:获得了成集落状生长的犬乳牙牙髓细胞,其克隆形成率为32%;免疫组化确定细胞为间充质而非造血来源;流式细胞术鉴定 STRO-1、CD146阳性表达,而 CD14、CD45及 CD86阴性表达;细胞成骨、成脂诱导后分别对茜素红、油红 O 染色阳性,成牙本质诱导后细胞碱性磷酸酶、牙本质涎磷蛋白染色阳性,且细胞内碱性磷酸酶活性显著增高。结论:比格犬乳牙牙髓中存在具有间充质干细胞表型、自我更新及多向分化能力的干细胞。

  2. Establishment of normal reference ranges for clinical pathology indexes of Beagle dogs in GLP system%GLP体系下比格犬临床病理学指标正常参考值的建立

    Institute of Scientific and Technical Information of China (English)

    贾栗; 王以美; 张利军; 李利忠; 彭双清

    2016-01-01

    目的 建立实验室操作规范(GLP)体系下比格(Beagle)犬临床病理学指标的正常参考值范围. 方法检测117只比格犬的16项血清生化指标、17项血液学指标及3项凝血指标,计算并比较各项平均值及正常参考值范围. 结果 血清生化指标仅有碱性磷酸酶(alkaline phosphatase, ALP)一项雌雄性别差异显著(P<0.01),且雄性高于雌性;血液学指标中红细胞(red blood cell, RBC)、血红蛋白(hemoglobin, HGB)、红细胞压积(hematocrit, HCT)3项雌雄性别差异显著(P<0.01),均为雄性低于雌性;凝血指标无雌雄性别差异. 结论 比格犬仅有个别临床病理指标存在雌雄性别差异,因此在毒性实验中,可考虑将雌雄动物检测结果合并进行统计分析. 该研究建立了GLP体系下比格犬的临床病理学指标正常参考值,为毒理学研究提供了参考数据.%Objective To establish the normal reference ranges of clinical pathology for Beagle dogs in the Good Laboratory Practice ( GLP ) system.Method Sixteen biochemical indexes , seventeen hematological indexs and three coagulation function indexes of 117 Beagle dogs were detected , and the mean value of each index and the normal reference ranges were calculated and compared .Results Only alkaline phosphatase ( ALP ) from the biochemical items was significantly different between males and females (P<0.01),which was higher among males than among females .Three in-dexes of hematology were significantly different between males and females (P<0.01),with red blood cell(RBC), hemo-globin(HGB)and hematocrit(HCT)lower among males than among females.The coagulation function items were not signif-icantly different between the two sexes .Conclusion Some indexes of clinical pathology were significantly different between males and females , which should be considered during statistic analysis on toxicity .Our study has established the normal reference range of clinical pathology for Beagle dogs in the GLP system

  3. 比格犬严重多发伤动物模型的研制%Establishment of an animal model of severe multiple trauma in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    李庆新; 郑军; 张世范; 孟辉; 杨俊峰; 高炜; 刘传兰

    2012-01-01

    目的:研制严重多发伤动物模型,探讨动物模型的稳定性及其救生效应.方法:选健康比格犬31只,随机分组,制备严重多发伤、出血性休克模型和严重多发伤、胸腹联合伤、上呼吸道梗阻窒息模型,探讨模型指标在不同分组间的敏感度及特异度.结果:2种动物模型成型率均可满足不同实验要求,用本装置行自体输血+液体复苏,动物全部存活,单一液体复苏半数死亡;窒息组总病死率为23.1%,窒息≤6 min动物全部存活,≥9 min成活率为60%.结论:严重多发伤、上气道梗阻窒息模型、出血性休克模型符合现场临床实际,有较高的成型率和稳定性,基本涵盖了重危伤情多个层面,半数致死率和预期概率接近,为研究现场救护技术、救护装备、评价救护效能提供了依据.%Objective;To establish an animal model of severe multiple trauma, and to explore its stability and rescuing effect. Methods; Thirty - one healthy Beagle dogs were randomly divided into two groups. One was the group of severe multiple trauma, haemorrhegic shock model and another was the group of severe multiple trauma, thoraco - abdominal combined trauma, upper respiratory tract obstruction asphyxia model. Sensibility and specificity between the two groups were compared. Results; Shaping rates of two groups could meet with all the requirement of different experiments. All the animals survived when autologous blood transfusion plus fluid resuscitation were taken by our patented equipment. Half of the animals survived when single fluid resuscitation was applied. The general mortality of asphyxia was 23. 1 % . All the animals with asphyxia for less than 6 min survived and the survival rate of animals with asphyxia for more than 9 min was 60%. Conclusion; Severe multiple trauma, upper respiratory tract obstruction asphyxia and haemorrhegic shock model is fit for on - site clinical reality with a higher shaping rate and stability. It

  4. Pharmacokinetics and metabolism studies on the glucagon-like peptide-1 (GLP-1)-derived metabolite GLP-1(9-36)amide in male Beagle dogs.

    Science.gov (United States)

    Eng, Heather; Sharma, Raman; McDonald, Thomas S; Landis, Margaret S; Stevens, Benjamin D; Kalgutkar, Amit S

    2014-09-01

    Glucagon-like peptide-1 (GLP-1)(7-36)amide is a 30-amino acid peptide hormone that is secreted from intestinal enteroendocrine L-cells in response to nutrients. GLP-1(7-36)amide possesses potent insulinotropic actions in the augmentation of glucose-dependent insulin secretion. GLP-1(7-36)amide is rapidly metabolized by dipeptidyl peptidase-IV to yield GLP-1(9-36)amide as the principal metabolite. Contrary to the earlier notion that peptide cleavage products of native GLP-1(7-36)amide [including GLP-1(9-36)amide] are pharmacologically inactive, recent studies have demonstrated cardioprotective and insulinomimetic effects with GLP-1(9-36)amide in mice, dogs and humans. In the present work, in vitro metabolism and pharmacokinetic properties of GLP-1(9-36)amide have been characterized in dogs, since this preclinical species has been used as an animal model to demonstrate the in vivo vasodilatory and cardioprotective effects of GLP-1(9-36)amide. A liquid chromatography tandem mass spectrometry assay was developed for the quantitation of the intact peptide in hepatocyte incubations as opposed to a previously reported enzyme-linked immunosorbent assay. Although GLP-1(9-36)amide was resistant to proteolytic cleavage in dog plasma and bovine serum albumin (t1/2>240 min), the peptide was rapidly metabolized in dog hepatocytes with a t1/2 of 110 min. Metabolite identification studies in dog hepatocytes revealed a variety of N-terminus cleavage products, most of which, have also been observed in human and mouse hepatocytes. Proteolysis at the C-terminus was not observed in GLP-1(9-36)amide. Following the administration of a single intravenous bolus dose (20 µg/kg) to male Beagle dogs, GLP-1(9-36)amide exhibited a mean plasma clearance of 15 ml/min/kg and a low steady state distribution volume of 0.05 l/kg, which translated into a short elimination half life of 0.05 h. Following subcutaneous administration of GLP-1(9-36)amide at 50 µg/kg, systemic exposure of

  5. The study of enamel matrix proteins on periodontal healing after autotransplantation of incisors in Beagle dogs%釉基质蛋白促进自体移植牙牙周愈合的实验研究

    Institute of Scientific and Technical Information of China (English)

    郑朝; 李洪发; 赵艳红; 林姝慧

    2012-01-01

    目的:研究釉基质蛋白对比格犬恒切牙自体移植后牙周愈合的影响.方法:选取3只比格犬的24颗切牙拔出后在生理盐水纱布中保存30min,然后将对照组12颗切牙直接植入同颌对侧同名牙牙槽窝中,实验组12颗切牙牙根涂釉基质蛋白后也植入对侧牙槽窝中.8周后通过组织学观察牙根的纵切片.结果:两组表面性吸收和炎症性吸收无统计学差异,但实验组牙根替代性骨吸收明显减少.结论:釉基质蛋白可减少牙根的替代性吸收,促进自体移植牙的牙周愈合.%Objective: To evaluate the effect of enamel matrix proteins (EMPs) on periodontal healing after autotransplantation of permanent incisors in Beagle dogs. Methods: A total of 24 incisors of 3 Beagle dogs were selected for autotransplantation after 30 min covered with wet saline gauge; 12 incisors of the control group were implanted in the opposite corresponding positions of the same jaw; 12 incisors of the experimental group were coated with EMPs and then implanted in the same positions. After 8 weeks, the longitudinal section of the incisor roots was observed with histological evaluation. Results: there was no significant difference between the control group and experimental group in surface absorption and inflammatory absorption, but there was significant decrease in replacement resorption. Conclusion: Enamel matrix protein can decrease the replacement resorption, and promote periodontal healing of autotransplanted teeth.

  6. 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.

  7. 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.

  8. A LC-MS/MS Assay for the Quantification of O-Desmethylvenlafaxine in Beagle Plasma and Applications to Preclinical Pharmacokinetic Studies on Desvenlafaxine Fumarate Administered to Beagles%定量比格犬血浆中去甲文拉法辛LC-MS/MS方法的建立及比格犬血浆中富马酸去甲文拉法辛药代动力学研究

    Institute of Scientific and Technical Information of China (English)

    时红娇; 程远国; 孟庆芳; 陈知航; 刘运龙; 单成启; 许先兴; 车津晶; 谭莉; 侯禹男

    2011-01-01

    目的:建立一种快速灵敏的液质联用方法定量比格犬血浆中去甲文拉法辛,并进行比格犬体内富马酸去甲文拉法辛药代动力学研究,同时与琥珀酸去甲文拉法辛比格犬体内药代参数进行对比.方法:样品处理采用叔丁基甲醚进行液液萃取,液相分离采用Agilent Eclipse Plus C18色谱柱(2.1 mm×100 mm,3.5μm),以乙腈-乙酸铵缓冲液(1 mmol/L)(体积比80:20)进行等度洗脱.采用单次给药和多次给药试验进行比格犬体内药代动力学研究.结果:此方法具有良好的线性、精密度、准确度,定量下限(0.5 ng/mL)高于文献报道.液液萃取的样品提取方法简便,液质联用分析时间相对较短(3 min).结论:此方法可成功地应用于比格犬血浆中去甲文拉法辛定量分析.比格犬体内富马酸去甲文拉法辛的药代参数(单次给药和多次绐药试验)与对照品琥珀酸去甲文拉法辛没有明显的统计学差异.%Objective: To establish a highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/ MS) method for the quantification of O-desmethylvenlafaxine(ODV) in beagle dog plasma and applied to a phar-macokinetic study of desvenlafaxine fumarate (DVF) in beagles, while made a phaimacokinetics comparation with desvenlafaxine succinate(DVS). Methods: Sample pretreatment includes liquid-liquid extraction by adding tert-butyl methyl ether to the plasma sample containing the internal standard. HPLC separations were performed on an Agilent Eclipse Plus C18 column (2.1 mm x 100 mm, 3.3 (xm I.d.). Samples were eluted using a mobile phase composed of acetonitrile and 1 mmol/L ammonium acetate in water (80:20 V/V). Single-time studies and multi-time studies were applicated to pharmacokinetic study. Results: The method has high linearity, precision and accuracy, and a sufficiently low detection limit (0.5 ng/mL) which was lower than the limit of previous reports. The liquid-liquid extraction process was simple and the

  9. Bupivacaine 0,25% versus ropivacaine 0,25% in brachial plexus block in dogs of beagle breedBupivacaína 0,25% versus ropivacaína 0,25% no bloqueio do plexo braquial em cães da raça beagle

    Directory of Open Access Journals (Sweden)

    Thiago Ignácio Wakoff

    2013-06-01

    Full Text Available The brachial plexus block (BPB is a regional anesthesia technique which enables the attainment of surgical procedures distal scapulohumeral articulation. This study aimed to compare the efficacy of ropivacaine and bupivacaine 0.25% without vasoconstrictor in BPB guided by electrical stimulation in dogs. Thirteen male and female beagle dogs underwent a BPB using bupivacaine and ropivacaine 0.25% (4mg/kg, both alone and in different times. The anesthesic block was performed in the right forelimb and as control group the block proceeded in the left forelimb using a solution of sodium chloride 0.9% in volume corresponding to the drug in the contralateral limb. The block was performed after the localization of the radial nerve with the aid of eletrical stimulation, which was infiltrated half the volume of anesthetic calculated and subsequently the remaining solution was administered on the median nerve. We evaluated sensitive and motor latencies and sensitive and motor block total time by clamping technique. In the present study, a technique for electrical stimulation was effective in 100% of animals. Bupivacaine had lower motor latency period, however, the sensitive latency between the two groups showed no statistically significant differences. In the block total time, bupivacaine obtained time significantly higher. Clinical signs characteristic of Horner’s syndrome were present in 15% of animals treated with bupivacaine. Furthermore, two animals presented signs of cardiotoxicity in bupivacaine group. The use of bupivacaine (4mg/kg without vasoconstrictor in dogs brachial plexus block provided longer analgesia and motor blockade, however, ropivacaine at the same dose and concentration was found to be free of deleterious effects associated of cardiovascular instability, hemodynamic and respiratory. O bloqueio do plexo braquial (BPB é uma técnica de anestesia regional que possibilita a realização de procedimentos cirúrgicos distais a articula

  10. 比格犬胸部多发伤出血性休克模型建立%A Model of Traumatic Hemorrhagic Shock with Multiple Thoracic Injuries in Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    孟辉; 郑军; 李庆新; 洪波; 张世范; 李乃斌; 高明; 杨俊峰; 王海芳

    2012-01-01

    目的 建立一种胸部多发伤失血性休克大动物模型,满足一线与后续救护实验研究需要.方法 普通级比格犬18只随机分为微创血气胸、失血休克组(A组,n=6),多根多段肋骨骨折、创伤性血胸、张力性气胸、失血性休克组(B组,n=12),后者又分为自体血回输组(B1组,n=6)、非自体血回输组(B2组,n=6).A、B2组常规液体复苏,B1组在液体复苏的基础上用自制救护装置自体输血复苏.观察动物的存活率、生理指标、血常规、凝血、动脉血气各项参数.结果 A、B1组动物全部成活(6/6,12/18),B2组半数死亡(3/6).与A组相比,伤后B1组RBC、HGB、HCT、PaO2、氧合指数有显著性差异(P<0.05),明显优于B2组;伤后4~8h,B2组RBC、HGB、HCT、PaO2、氧合指数降低较为明显,与B1组相比有显著性差异(P<0.05).结论 本法制作的胸部多发伤失血性休克模型成功率高,可重复性强.%Objective To establish a model of traumatic hemorrhagic shock with multiple thoracic injuries in Beagle dogs for the experimental study of the rescuing effect of the first - line and follow - up comprehensive rescue devices. Methods Eighteen beagle dogs of common grade were randomly divided into two groups, which included mini - traumatic shock and hemopneumothorax group( group A, n = 6) , multiple fractured ribs and traumatic hemothorax and tension pneumothorax and hemorrhagic shock group(group B, n = 12) ,and then the latter was dirided into with autologous blood transfusion group (group B1 ,n =6) and without autologous blood transfusion group (group B2 ,n = 6) . Routine liquid resuscitation were applied in group A and B2 , and autotransfusion of self - made serial first - aid life supporting devices in group B1. Animal survival rate, physiological index, and parameters of routine blood test,blood gas and coagulation were observed. Results The survival rate in group A and B1 was 100% but it was 50% in group B2. Compared with the control

  11. Correlation between hepatic CT perfusion imaging and portal vein pressure in normal Beagles%肝脏CT灌注成像与门静脉压力相关性的动物实验研究

    Institute of Scientific and Technical Information of China (English)

    林元为; 陈伟建; 张启瑜; 梁盼; 杨博洋

    2011-01-01

    目的:探讨正常比格犬门静脉压力与肝脏CT血流灌注参数的相关性.方法:采用螺旋CT对24只犬行肝脏灌注成像扫描,去卷积法计算肝脏血流灌注参数,包括血流量(blood flow,BF)、血容量(blood volume,BV)、平均通过时间(mean transit time,MTT)、肝动脉分数(hepatic arterial fraction,HAF)、肝动脉灌注量(hepatic arterial perfusion,HAP)、门静脉灌注量(portal venous perfusion,PVP).扫描后3 d内开腹,采用玻璃水柱法测定门静脉压力.利用直线回归与相关分析门静脉压力与肝脏CT血流灌注参数的相关性.结果:(1)正常比格犬实测门静脉压力值为(13.57±1.15)cmH2O.(2)正常比格犬门静脉压力与BF、PVP呈负相关,与HAF呈正相关,其中以PVP相关性最显著(r=-0.764,P<0.05),两者关系的直线回归方程为Y=16.507-0.037X.结论:肝脏CT灌注成像为无创、有效监测门静脉压力提供了一种新途径.%Objective To evaluate the correlation between the parameters of spiral CT perfusion imaging and portal vein pressure in normal Beagles. Methods Twenty-four normal beagles were selected to receive hepatic spiral CT perfusion imaging. The parameters of hepatic perfusion , including blood flow (BF) , blood volume (BV) ,mean transit time ( MTT) , hepatic arterial fraction ( HAF) , hepatic arterial perfusion ( HAP) , and portal venous perfusion (PVP) , were calculated hy the method of deconvolution. The portal vein pressure was measured by glass column method in laparotomy surgery three days after CT imaging. Results Portal vein pressure of the beagles were ( 13.57 ± 1.15) cmH2O. Portal vein pressure was negatively correlated with the BF and PVP , but was positively correlated with HAF. PVP was the most significant parameter that correlated with portal vein pressure (r = -0.764,P<0.05) , and their linear regression equation was Y = 16.507-0.037X. Conclusion CT perfusion imaging is a new non-invasive and eff'ective method for assessing portal vein

  12. 附子不同炮制品灌胃Beagle犬的急性毒性研究%Acute Toxicity Study on Intragastric Administration of Different ProcessedRadix Aconiti Lateralis PraeparataProducts to Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    宋玉琴; 张雪; 董艳红; 代良萍; 彭成; 谢晓芳

    2015-01-01

    This article was aimed to study the acute toxicities on intragastric administration of differentRadix Aconiti Lateralis Praeparataprocessed products to Beagle dogs. A total of 16 healthy and qualified Beagle dogs were randomly divided into the blank group,Pao-Fu-Pian(PFP) group,Pao-Tian-Xiong(PTX) group andHei-Shun-Pian(HSP) group according to the body weight. The intragastric administration of 4 g crude herb per kg was given. Before medication, 1 h, 24 h, and 3, 7, 14 days after medication, the body weight, food consumption, rectal temperature, electrocardiogram, blood routine and blood biochemistry were measured. The results showed that after medication, all dogs in three experimental groups were depressed. And there were significant differences in the electrolytes of blood. Among them, the HSP group was the most obvious one. The red blood cells, blood sugar and triglycerides of dogs in the PFP group had significant difference. The lymphocytes and blood sugar had significant difference of dogs in the PTX group. However, after the medication of HSP, the lymphocytes of the dogs were decreased significantly. It was concluded that the toxicity of three processed products followed the order of HSP > PFP > PTX.%目的:探讨附子不同炮制品灌胃Beagle犬的急性毒性。方法:取健康、合格Beagle犬16只,按体质量随机分为空白组、刨附片组、炮天雄组和黑顺片组。以4 g生药/kg灌胃给药,实验前及给药后1 h、24 h和第3、7、14天测定体质量、耗食量、肛温、心电图及血常规、血生化。结果:3个实验组Beagle犬在给药后均精神萎靡,血液电解质有显著性差异,其中黑顺片组最明显;刨附片组犬的红细胞、血糖和甘油三酯有显著性差异;炮天雄组犬的淋巴细胞和血糖有显著性差异,而黑顺片给药后犬的淋巴细胞显著降低。结论:3个炮制品毒性大小依次为黑顺片>刨附片>炮天雄。

  13. Establishment of Chronic Renal Failure Model in Beagle Dogs by Integrative Operation%综合手术方法制作犬慢性肾功能衰竭模型

    Institute of Scientific and Technical Information of China (English)

    林若勤; 傅晓晴; 杨朝阳; 朱龙; 李慧勇

    2011-01-01

    Objective To study the surgical method for establishing chronic renal failure model at azotaemic stage in beagle dogs. Methods The integrative operation was preformed by electric cautery of renal cortex and renal artery ligation in left kidney. Right kidney was removed one week later. Blood urea nitrogen and creatinine were detected 3 days after surgery and every week after surgery. Results The urea nitrogen was 7.21±0.72 mmol/L and the creatinine was 82.40±9.42 μmol/L before surgery, 30 days after surgery was 11.22±5.69 mmol/L and 125.55±68.50 umol/L respectively. Both of their P- value were less than 0.05. Conclusions Ideal chronic renal failure model at azotaemic stage in beagle dogs can be obtained by the combination of electric cautery of left renal cortex and left renal artery ligation.%目的 研究慢性肾功能衰竭氮质血症期中医脾肾虚型比格犬模型的手术造模方法.方法 采用左肾皮质电灼法与肾动脉狭窄结扎法相结合,1周后切除右肾.术后3d及每周检测血尿素氮、肌酐.结果 造模前尿素氮为7.21±0.72 mmol/L,肌酐为82.40±9.42 μtmol/L,造模术后30 d尿素氮为11.22±5.69 mmol/L,肌酐为125.55±68.50 μmol/L(P值均<0.05).临床表现为脾肾虚证候.结论 采用左肾皮质电灼法与肾动脉狭窄结扎法相结合,可以造成理想的慢性肾功能衰竭氮质血症期脾肾虚型比格犬模型.

  14. 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.

  15. 氨氯地平与比索洛尔在Beagle犬体内的药动学相互作用研究%Pharmacokinetics interaction study between amlodipine and bisoprolol in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    常会超; 陈山乔; 关晓多; 钱忠直; 范国荣; 毕开顺

    2013-01-01

    Objective To investigate whether there is pharmacokinetic interaction between amlodipine and bi-soprolol when administered jointly into Beagle dogs. Methods Six healthy adult beagle dogs were evenly divided into 3 groups according to a self-controlled randomized 2-way crossover design. The 3 groups were o-rally given amlodipine powder,bisoprolol powder or compound powder of amlodipine and bisoprolol,respectively. The concentrations of amlodipine and bisoprolol in Beagle dog plasma were determined respectively at specified time points by HPLC-UV and HPLC-FLD method;the pharmacokinetic parameters were calculated subsequently. Results ρmax and AUC0-∞ were(110. 2 ± 6. 3) μg·L-1 and (1 984 ± 594) μg· h· L-1 when administered amlodipine alone and those were( 102.0 ±23.5) μg·L-1 and(2 016 ±394) μg·h·L-1 when combined amlodipine with bisoprolol, respectively. pmav and AUC0-∞, were (35.77 ±8. 17) μg·L-1 and (230. 2 ± 93. 9) μg·h·L-1 when administered bisoprolol alone and those were(31.74 ±7. 57) μg·L-1 and (224. 8 ± 106. 1) μg· h· L-1 when combined bisoprolol with amlodipine,respectively. There were no significant differences in ρmax and AUC0- ∞ of the two drugs when they were used alone or jointly. Conclusions There is no obvious pharmacokinetic interaction between amlodipine and bisoprolol when they are administered jointly into Beagle dogs.%目的 探讨氨氯地平与比索洛尔联合用药时有无显著的药动学相互作用.方法 采用自身对照、随机交叉试验方法,将Beagle犬分成3组,每组2条,分别按试验周期服用氨氯地平对照药物、比索洛尔对照药物以及氨氯地平与比索洛尔复方药物.采用HPLC-UV和HPLC-FLD分别测定不同时间点氨氯地平与比索洛尔的血药质量浓度,计算药动学参数.结果 氨氯地平单用时ρmax为(110.2±6.3)μg·L-1,AUCo-∞为(1 984±594) μg·h·L-1;联合用药时ρmax为(102.0±23.5) μg·L-1,AUC0.∞为(2 016±394)μg·h·L-1.

  16. Frontal and Profile Photographs, the “Truth” and the Memory. From the Beagle Etchings (1839 and the Anthropological Photography (by the End of the 19th Century to the Current Identification Photos

    Directory of Open Access Journals (Sweden)

    Marta Penhos

    2013-07-01

    Full Text Available The article proposes an analysis of front and profile typologies from the 19th century to these days. From a reflection on the photographic image and its relationship with truth and memory, a three stages review is outlined taking into account the official report of the so called Beagle journey and the etchings that illustrate it (1826-1836, the photographs taken to the Patagonian indigenous groups who were defeated after the military campaigns started in 1879 in Argentina as well as some cases of artists and human rights activists who appropriated the typology in the last 30 years. In the etchings and photographs, a tension between the romanticism conception and a positivistic point of view is evidenced. On the one hand, the indian transformation through a civilizatory education contrasted, on the other hand, with the objectivation of the indigenous bodies entrusted to scientific inquiry. On their behalf, the contemporary cases pose a shift in the interpretation of the representation in the construction of a historical memory: the posthumous nature of photography getting along with another dimension linked to its capacity of giving a renewed existence to the dead and ensuring a transcendence that defies forgetfulness.

  17. Establishment of a Beagle dog model of obesity and type 2 diabetes%实验性Beagle犬肥胖症并2型糖尿病模型的建立

    Institute of Scientific and Technical Information of China (English)

    付唆林; 朱惠明; 郑丽

    2011-01-01

    目的:为肥胖症和2型糖尿病的手术和内镜介入治疗研究建立一种大型动物实验模型.方法:选用10只健康♂成年Beagle犬,随机分成两组,对照组5只全程(16 wk)给予标准饲料喂养,模型组5只全程给予高脂高热量饲料喂养,并于第8周给予小剂量链脲佐菌素(STZ)静脉注射.定时检测动物体质量、体长、空腹血糖、静脉葡萄糖实验(IVGTT)、血脂等与肥胖症及2型糖尿病相关临床指标.结果:在第8周,模型组平均体质量是16.9 kg±0.8 kg,较对照组体质量(14.8 kg±1.03 kg)有显著升高(P<0.01),Lee指数与对照组比较也有显著差异(P<0.05);模型组血清胰岛素、C-肽较对照组明显上升(P<0.01).STZ注射后1wk,模型组空腹血糖明显高于对照组(P<0.05),IVGTT-2h血糖比注射前增高(143 mg/dL±7.4 mg/dL vs 127 mg/dL±4.2 mg/dL,P<0.05),血清胰岛素、C-肽分泌比注射前明显下降(P<0.01).STZ注射后8 wk,模型组空腹血糖显著高于对照组(P<0.01),IVGTT-2 h血糖较注射前显著增高(323 mg/dL±12.1 mg/dL vs 127mg/dL±4.2 mg/dL,P<0.01).本实验模型组Beagle犬成模率为100%,实验期间Beagle犬未见死亡.结论:联合高脂高热量喂养和小剂量STZ注射可在Beagle犬上成功建立肥胖症并2型糖尿病动物模型,此模型接近人类2型糖尿病的发病过程和代谢特征,可用于肥胖症和2型糖尿病的手术和内镜介入治疗的研究.%AIM: To establish a big animal model of obesity and type 2 diabetes for further investigation of surgical or endoscopic interventional therapy of this disease.METHODS: Ten healthy adult male Beagle dogs were randomly and equally divided into two groups: control group and model group. The control group was feed a standard diet during the whole experiment (16 wk), while the model group was feed a high-fat hypercaloric diet. At week 8, the model group was intravenously injected with small dose of streptozotocin (STZ). The body mass, length

  18. Ověření možností komunikačních periferií jednodeskového systému BeagleBoard.

    OpenAIRE

    Hladík, René

    2012-01-01

    Obsah bakalářská práce zahrnuje druhy a možnosti komunikace, jenž nabízí rozhraní jednodeskového počítače. Ověření rozsahu komunikace při použití v mobilní robotice a následné shrnutí pro daný systém. Cílem této práce bylo poskytnout uživatelům konfiguraci jednotlivých periferií při následném využití systému BeagleBoard xM Rev C. Úvodní část práce je zaměřena na definici a shrnutí jednodeskových počítačových systémů. Přehled hlavních rozdílů mezi jednodeskovými systémy. Dále konkurence a char...

  19. Pharmacokinetics of melatonin sustained release tablets and common tablets in Beagle dogs%美乐托宁缓释片与普通片在Beagle犬体内药代动力学及检测方法

    Institute of Scientific and Technical Information of China (English)

    杨大龙; 狄斌; 林荣锦; 尤淋君

    2011-01-01

    Objective: To compare the in vivo pharmacokinetic parameters of melatonin sustained release tablets and common tablets in Beagle dogs. Methods: Three-way crossover design was used. Six Beagle dogs orally took 6 mg melatonin sustained release tablets, melatonin common tablets, or foreign sustained release tablets. Then, plasma concentration was determined by a LC-MS-MS method and calculated. Results: Pharmacokinetic parameters of the 3 preparations were as follows; Cmax (8. 929 ± 5. 220) , (29. 653 ± 14. 503 ) and (8. 196 ± 4.723) ng·mL-1; Tmax, (1. 140 ±0.608), (0.250 ±0.051) and (1.083 ±0.492) h; t1/2, (1.723 ±1.080), (0.946 ±0.548) and (1.105 ±0.308) h; MRT, (1. 834 ±0.651), (0.784 ±0.637) and (1. 617 ±0.296) h; AUC0-12, (13.832 ±6.967), (12.272 ±5.623) and (14. 190 ±7.003) ng·mL-1·h; AUC0_∞ , (13.873 ± 6.941), (12.308 ±5.556) and (14. 216 ±7. 004) ng·mL-1·h. Conclusion: Compared with the common tablets , the sustained release tablets show slower absorption, longer peak time, lower peak concentration, and longer duration. The 3 formulations are bioequivalent.%目的:比较美乐托宁缓释片与普通片在Beagle犬体内的药动学参数.方法:6条Beagle犬三交叉单剂量口服美乐托宁缓释片、普通片和国外缓释片6 mg后,采用LC-MS-MS法测定血浆药物浓度,计算各制剂的药动学参数.结果:上述3种制剂在Beagle犬血浆中的Cmax分别为(8.929±5.220),(29.653±14.503)和(8.196±4.723 )ng· mL-1,Tmax分别为(1.140±0.608),(0.250±0.051)和(1.083±0.492)h,t1/2分别为(1.723±1.080),(0.946±0.548)和(1.105±0.308)h,MRT分别为(1.834±0.651),(0.784±0.637)和(1.617±0.296)h,AUC0-12分别为(13.832±6.967),(12.272±5.623)和(14.190±7.003) ng·mL-1·h,AUC0~∞分别为(13.873±6.941),(12.308±5,556)和(14.216±7.004) ng.mL -·h.结论:与普通片比较,缓释片吸收较慢,药物达峰时间更长,峰浓度更低,维持时间更长.3种制剂具有生物等效性.

  20. Effect of Low-intensity Pulsed Ultrasound on Periodontitis in Beagle Dogs%低强度脉冲超声波对Beagle犬牙周炎组织修复效应的初步研究

    Institute of Scientific and Technical Information of China (English)

    董妮; 宋锦璘; 冯格; 刘珉懿; 邓锋

    2012-01-01

    目的 探讨低强度脉冲超声波(LIPUS)对Beagle犬牙周炎组织的初步修复效应.方法 采用牙槽骨缺损联合弹性结方法制备慢性牙周炎的Beagle犬动物模型,在相同常规治疗基础上选用LIPUS不同强度(50mW/cm2、100 mW/cm2)脉冲波和50 mW/cm2连续波治疗(频率1.5 MHz、调制信号波宽200 μs、重复率1 kHz),共治疗8周(1次/d,20 min/次),并进行牙周临床指标检测与组织学切片检查.结果 LIPUS治疗8周后,治疗组牙龈组织肿胀减轻,菌斑指数(PLI)、牙龈指数(GI)、牙周探针深度(PD)均较对照组低(P<0.05),未发现明显的牙龈退缩、附着丧失和根分叉病变等;组织学切片检查发现LIPUS治疗组牙龈组织黏膜上皮增生不明显,有丰富的胶原纤维生成,牙槽骨组织中骨吸收陷窝减少,成骨细胞较活跃地排列在新骨周围.结论 LIPUS具有潜在的牙周炎组织修复效应,应进一步考虑LIPUS在引导组织再生术(GTR)治疗中的辅助修复效应.%Objective To investigate the effect of low intensity pulsed ultrasound (LIPUS) on periodontitis in Beagle dogs. Methods The animal model of chronic periodontitis was established with elastic ligature-induced alveolar bone defect in Beagle dogs. LIPUS with different intensity (50 mW/cm2, 100 mW/cm2) pulse wave and 50 mW/cm2 continuous wave, 1. 5 MHz of frequency, 200 μs of pulse width modulated signal, and 1 kHz of repetition rate were applied to the dogs for 8 weeks (once a day and 20 minutes every time). The periodontal clinical examinations and histological biopsy were performed. Results With increased exposure to LIPUS, gum tissue swelling of the dogs was reduced. The plaque index (PL1), gingival index ( GI), pocket depth (PD) of the treatment groups were lower than the control groups (P<0. 05). No significant gingival recession, attachment loss or furcation was found. The histological examination revealed that there was no obvious gingival hyperplasia in epithelial

  1. Establishment and identification of the animal model with bacterial inflammation in the lower urinary tract of the Beagle dogs%Beagle犬细菌性下尿路炎动物模型的建立

    Institute of Scientific and Technical Information of China (English)

    何玮; 李路; 余虓; 兰儒竹; 王少刚; 李家贵; 刘继红; 叶章群

    2012-01-01

    目的 建立一种简单、稳定、符合临床模式的细菌性下尿路炎Beagle犬动物模型.方法 选用24个月成年Beagle犬6条,随机分为模型组(3条)和对照组(3条),每次模型组采用标准致病菌大肠杆菌(ATCC25922)2.5 ml,对照组采用相同体积的灭菌生理盐水膀胱灌注.模型成功后进行细菌培养鉴定、药敏实验和病理学观察.结果 与对照组比较,模型组的细菌培养差异有统计学意义(P<0.05),细菌鉴定为同型大肠杆菌,对氨苄西林的耐药率最高,对美罗培南最敏感.病理切片中组织形成改变明显,镜下可见大量炎性细胞浸润.结论 大肠杆菌能导致Beagle犬下尿路炎,并与人类的下尿路炎具有相似性,多次膀胱灌注是建立动物模型简洁、有效的试验方法,并证实细菌的耐药性是导致下尿路感染的主要病因之一.%Objective To establish a clinical animal model of bacterial inflammation in the lower urinary tract and to provide a research platform for the physical treatment of lower urinary tract inflammation.Methods Six 24-month-old adult Beagle dogs were randomly divided into model group (n =3) and control group (n =3).By bladder irrigation,the dogs were given the standard pathogenic E.coli (ATCC25922) 2.5 mL in the model group and the same dose of saline in the control group every time.Bacteria were cultured and identified cation,subjected to susceptibility testing and observed pathologically after the model was constructed.Results Compared with the control group,the bacterial culture in the model group was positive and the bacteria identified was the same type of E.coli,the resistance rate of E.coli to ampicillin was the highest and they to meropenem was the most sensitive.HE dyeing show that the changes of tissues were significantly and a great number of inflammatory cells infiltrated under microscope.Conclusion E.coli can cause inflammation in Beagle dogs' lower urinary tract,and the clinical and tissue

  2. 体位改变对Beagle犬心脏自主神经控制的影响%Effect of Postural Changes on Autonomic Nervous Control of Heart in Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    潘永明; 陈亮; 何欢; 徐孝平; 陈民利

    2012-01-01

    Objective The aim of this study was to observe the effect of postural changes on autonomic nervous control of heart in Beagle dogs. Methods Electrocardiogram (ECG) was recorded in static posture (lying, standing, sitting and hanging) and moving posture (walking) from conscious and unrestrained female Beagle dogs using a non-invasive telemetry system, and the autonomic nervous function was investigated by power spectral analysis of heart rate variability (HRV). Results In static postures, the RR interval, SDNN, RMSSD, pNNabs (50) , total power (TP) , very low frequency ( VLF) power and normalized high frequency ( HF) power were significantly higher than those in moving posture (P < 0. 05 , P < 0. 01) , while the heart rate, normalized LF and the LF to HF ratio were significantly lowered (P < 0.05, P < 0. 01). Conclusions The parasympathetic nervous activity is dominant in static state of different postures, while sympathetic nervous activity is dominant in moving state. Postural changes can influence the heart rate and inevitably affect the cardiac autonomic nervous control. It depends on the intensity of the vagus nerve activity, and leads to the disturbance of LF/HF balance.%目的 观察体位改变对Beagle犬心脏自主神经控制的影响.方法 利用大动物无创生理遥测技术,监测清醒活动状态下雌性Beagle犬在静态姿势(lying、standing、sitting、hanging)和运动(walking)姿势下的心电图(ECG),并用HRV功率谱分析其自主神经功能.结果 在静态姿势下,Beagle犬RR间期(RRI)、RR间期的标准差SDNN(SDNN)、相邻RR间期差值平方和的均方根RMSSD(RMSSD)、相邻R-R间期差值>50 ms的窦性个数占心搏总数的百分比pNNabs (50)( pNNabs (50))、TP总功率(TP)、VLF极低频功率(VLF)、标准化高频功率(HFnorm)均明显高于运动状态(P <0.05,P<0.01),而心率(HR)、标准化低频功率(LFnorm)和低频功率/高频功率(LF/HF)平衡指数则明显低于运动状态(P<0.05,P<0.01).

  3. Study on bioequivalence of two kinds of Levodopa tablets in Beagle%2种左旋多巴片剂在Beagle犬体内的生物等效性研究

    Institute of Scientific and Technical Information of China (English)

    陈雪珊; 滕亮; 贺鑫韬; 马桂芝

    2016-01-01

    Objective To study the pharmacokinetic properties of two kinds of levodopa tablets in Beagle. Methods The method of HPLC was established to determine Levodopa in beagle dog plasma.Using two-period randomized crossover design with Madopar as reference preparation,the main pharmacokinetic pa-rameters were calculated by the software 3P97 using the dates in vivo after given a single oral dose of Madopar and Levodopa microcapsules floating tablets. The bioequivalence between Levodopa microcapsules floating tablets and reference preparation was preliminarily evaluated.Results The method of HPLC was established to determine Levodopa in beagle dog plasma which complies with methodology requirements.The main pharmacokinetic parameters were as following respectively:tmax were (0.73±0.12)h and (1.47±0.20)h,Cmax were (5.04±0.92)μg/mL and (2.54±0.68)μg/mL,MRT were (1.96±0.21)h and (3.41±0.32)h,AUC0-∞ were (11.33±0.97)μg·h-1·mL-1 and (10.38±1.52)μg·h-1·mL-1, respectively.According to the guideline of pharmaceutical preparations of human bioavailability and bio-equivalence test,the 90% confidence intervals for the geometric mean ratio of AUC0-∞ and Cmax values for the test and reference preparation were 83.00%~99.90%,52.10%~64.40%,respectively.According to the results of rank sum test,the tmax were different between the test and reference preparation.Conclu-sion The extent of absorption of Levodopa between the test and reference preparation was bioequivalent. Compared with the reference preparation,the Levodopa microcapsules floating tablets had a good sus-tained-release property.%目的:考察单剂量给药后左旋多巴微囊漂浮片和美多芭片在 Beagle犬体内的生物等效性。方法建立可用于测定beagle犬血浆中左旋多巴含量的高效液相色谱法,以美多芭片为参比制剂,采用双周期交叉试验设计进行试验,采用3P97药物动力学软件求算单剂量给药后药动学参数,对其生物等效性进

  4. Effects of Mannitol and Glycerol Injection on Experimental Beagle Dog Intracranial Hypertension%甘露醇甘油注射液对Beagle犬实验性颅内高压的影响

    Institute of Scientific and Technical Information of China (English)

    蒋飞荣; 马丽; 曾贵荣; 邓青; 邓友田; 姜德建

    2016-01-01

    Obj ective]To study the influence of the mannitol and glycerin inj ection (containing 1 5% mannitol and 1 5% glycerin) on intracranial hypertension of experimental beagle dogs.[Methods]48 health qualified beagle dogs were randomly divided according to the sex and body weight into eight groups (6 in each ):the normal control group (0.9% sodium chloride injection 4 ml/kg);the model group (40 )were injected with autologous blood clots to establish model of intracranial hypertension,intracerebroventricular cannula was connected with baroreceptor to monitor intracranial pressure,including the model control group (0.9% sodium chloride injection 4 mL/kg),the group of mannitol and glycerin inj ection 2 mL/kg,the group of mannitol and glycerin inj ection 4 mL/kg,the group of mannitol and glycerin injection 8 mL/kg,the group of compound mannitol injection 4 mL/kg ,the group of 20% mannitol 4 mL/kg and the group of 1 0% glycerol and sodium chloride inj ection 4 mL/kg.The effect of mannitol and glycerin inj ection on intracranial pres-sure was observed.[Results]Intravenous drip of mannitol and glycerin inj ection (2 mL,4 mL,8 mL/kg)can significantly reduce the Beagle canine intracranial pressure which was induced by cerebral hematoma,and there was a dose dependent relationship therewith;The effect of reducing intracranial pressure of 4 mL/kg mannitol and glycerin injection was equivalent to that of the same dose of 20%mannitol and compound mannitol inj ection,and the action time was longer.There was no significant difference between the effects of mannitol and glycerin injection on renal function and electrolyte compared with the control group (P>0.05).[Conclusion]The manni-tol and glycerin injection could significantly reduce the intracranial pressure,and are equivalent to the same efficiency of 20%mannitol and compound mannitol inj ection with a long duration of reducing intracranial pressure without obvious renal impairment and electrolyte disorder.%【目的】探讨甘

  5. 比格犬雌激素受体β的原核表达、纯化及鉴定%Prokaryotic Expression, Purification and Identification of Estrogen Receptor in Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    许琴; 赵彦斌; 任秀梅; 孙兆增; 叶华虎; 刘一; 李微; 白杰英; 曾林

    2013-01-01

    Objective To obtain the estrogen receptor β (ERβ) and its splicing isoforms for elucidating its functional roles in the reproductive manipulation of Beagle dogs,the prokaryotic expressed canine pMAL-p5x/ERβ480 was established and optimized.Methods The cDNA specifically encoding ERβ was amplified from the total RNA of the Beagle dog hypothalamus,sequenced and blasted against other ERβ cDNA sequences in the GeneBank.The amplified cDNA fragment was then cloned into a prokaryotic expression vector,pMAL-p5x,to produce recombinant plasmid pMAL-p5x/ERβ480.The constructed recombinant plasmid was transformed into E.coli DH 5α and E.coli BL21(DE3).The MBP-ERβ fusion protein was induced after the addition of IPTG into the growth media.The expressed product was purified by Amylom Resin affinity chromatography,and identified by SDS-PAGE.Results Sequence analysis indicated that the coding region of the cDNA fragment was about a length of 480 bp.The fusion protein was expressed comparatively well under the following conditions:in 0.2% glucose,100 μg/ml Ampcillin,0.1mmol/L IPTG at 37℃ for 5h or in 0.2% glucose,50 μg/mL Ampcillin,0.2 mmol/L IPTG at 37℃ for 3h.The SDS-PAGE results showed that the molecular weight of recombinant ERβ was of about 60 000,just as expected.Conclusion The pMAL-p5x/ERβ prokaryotic recombinant plasmid was developed successfully,and the beagle dogs MBP-ERβ fusion protein was obtained and biochemical characterized to some extent.It was anticipated that the fusion protein would be useful for the production of the dog species-specific ER(a) polyclonal antibody and for the further functional analysis.%目的 研究比格犬雌激素受体β(Estrogen receptor β,ERβ)及其剪接异构体在生殖调控中的功能,构建比格犬ERβ的pMAL-p5x/ERβ 480 DE3 E.coli重组菌株,并进行纯化和鉴定.方法 Trizol法提取发情期比格犬下丘脑总RNA,RT-PCR获得cDNA,以NCBI网站公布的比格犬ERβ基因CDS序列设计特异性引

  6. Pharmacokinetics of bergenin inclusion complex osmotic pump tablets in Beagle dogs%岩白菜素包合物渗透泵片的Beagle犬体内药动学研究

    Institute of Scientific and Technical Information of China (English)

    吴敏; 谢佳; 曾建; 刘洪; 李德银

    2013-01-01

    Objective: To investigate the pharmacokinetics of bergenin inclusion complex osmotic pump tablets in beagle dogs, and its in vitro-in vivo correlation and rationality of formulation design. Methods: The in vitro release was tested according to Pharmacopoeia of the People's Republic of China, Method 1 of Appendices XC. The HPLC-DAD methods were developed and validated for bergenin assay in plasma samples using bergenin conventional tablets as reference preparation, and the in vivo pharmacokinetics was studied by Loo-Riegelman method. Results: The linear regressive equation was established between the absorption percentage in vivo and the accumulated release percentage in vitro of bergenin as F = 0. 88R + 4. 262 (γ = 0. 923 0 , P < 0. 01). Conclusion: There is a significant correlation between the in vivo absorption and the in vitro release of bergenin inclusion complex osmotic pump tablets, and it can effectively promote drug absorption in vivo compared with the conventional tablets.%目的:研究岩白菜素包合物渗透泵片在Beagle犬体内的药动学,对体外释放和体内吸收的相关性做出评价,确认其处方设计的合理性.方法:按照《中华人民共和国药典》附录中转篮法测定体外释放度,以岩白菜素普通片为对照,采用HPLC-DAD测定犬血浆中岩白菜素浓度.采用Loo-Riegelman法计算药物体内吸收百分率.结果:体外释放度数据(R)与相应各时间点的体内药物吸收百分率(F)回归方程为:F=0.88R +4.262(r =0.923 0,P<0.01).结论:岩白菜素包合物渗透泵片体内吸收和体外释放相关性良好,与普通片相比可有效促进药物的体内吸收.

  7. 锥形束CT对Beagle犬减阻-牵张快速牙移动的评价%Evaluation of rapid teeth movement through reducing resistance and distraction in Beagle dogs with cone-beam computed tomography

    Institute of Scientific and Technical Information of China (English)

    陈曦; 李宁; 刘建林; 彭早霞; 黄亚莉; 徐然; 刘会婷; 杨乐乐

    2013-01-01

    Objective To evaluate the effect of rapid teeth movement through reducing resistance and distraction using cone-beam computed tomography (CBCT). Methods The left or right side of the mandible of 10 beagles (5 males and 5 females) was randomly selected as the control side (for the conventional distraction with a force of about 85 g) and the other side as the experimental side (subjected to reducing resistance and distraction). CBCT images were taken at 5, 10, and 15 days and also after retaining for 10 and 90 days after distraction for 15 days. The distance of teeth transportation, degree of inclination, alveolar bone density of the compressive area and root resorption were evaluated based on the CBCT images and Ez3D2009 visualization software. Results No significant difference was found between CBCT-based measurement and direct measurement of teeth transportation distance within the mouths (P>0.05). Teeth inclination on the experimental side was slightly greater than that on the control side (P0.05);(2)实验侧移动牙发生倾斜程度略大于对照侧(P<0.05);(3)实验侧移动牙牙根未发生广泛吸收,其压力侧牙槽骨密度伴随牙齿移动呈逐渐增高趋势,且新生骨密度、影像学特征与对照侧牙槽骨无显著差异。结论CBCT三维成像技术能够弥补二维影像重叠、变形等不足,尤其在减阻牵张过程中牙齿倾斜度、牙槽骨密度测量方面更具优势,具有无创性及可重复性。

  8. 左乙拉西坦缓释片的制备与体内外相关性研究%Preparation and in vitro-in vivo correlation in Beagle dogs of levetiracetam sustained-release tablets

    Institute of Scientific and Technical Information of China (English)

    伍衢; 王悦; 王永禄; 李学明; 毛利娟

    2011-01-01

    Objective: To prepare levetiracetam sustained release tablets, and investigate in vitro-in vivo correlation in Beagle dogs. Methods: Mixed HPMC and EC matrix was used to prepare levetiracetam sustained release tablets. The in vitro release characteristics and in vivo pharmacokinetics in dogs of the tablets were investigated. Results: Higuchi model was optimal for the description of drug release profile. The mean elimination half-lives (t1/2 ) after administration of conventional tablets, reference sustained release tablets and our sustained release tablets were (2.09±0.45), (5.35±0.76) and (7.44±1.48) h, respectively. The peak levels were (1.184± 0. 38) , (3. 87 ± 0. 37 ) and (4. 07 ± 0. 56) hj AUCs were calculated to be ( 175. 40 ± 15. 47 ) , (240. 93 ± 19.73) and (251.47 ± 13. 22) μg·h·Ml-1, respectively. Conclusion: The levetiracetam sustained release tablets exhibit the sustained release characteristics in vitro, and show a good correction in vitro release and in vivo absorption.%目的:研制左乙拉西坦缓释片并考察其体外释放及犬体内药动学.方法:以羟丙甲基纤维素,乙基纤维素为混合骨架材料制备日服一次的缓释片,测定其体外释放度和Beagle犬口服单剂量缓释片后血浆中药物的浓度,推算药动学参数.结果:自制缓释片体外释放符合Higuchi模型.左乙拉西坦普通片,上市缓释片和自制缓释片的有关药动学参数如下:t1/2分别为(2.09±0.45),(5.35±0.76),(7.44±1.48)h,T( peak)分别为(1.184±0.38),(3.87±0.37),(4.07±0.56)h,AUC分别为为(175.40±15.47),(240.93±19.73),(251.47±13.22) μg·h·mL-1.结论:自制缓释片具体良好的缓释特性.体外释放和体内吸收有良好的相关性.

  9. 低强度脉冲超声波对Beagle犬Ⅱ度根分叉病变的辅助效应%Secondary repair effects of low-intensity pulsed ultrasound on class Ⅱ furcation involvement in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    何平; 高翔; 宋锦?; 邓锋; 赵纯亮; 王智彪; 李娜

    2011-01-01

    背景:低强度脉冲超声波主要用于促进骨折愈合及提高新生骨组织密度,尚未见其对Ⅱ度根分叉病变组织学修复效应的报道.目的:观察低强度脉冲超声波对Ⅱ度根分叉病变的组织学修复效应.方法:5只Beagle犬各取2颗下颌第4前磨牙颊侧作为实验区,建立Ⅱ度根分叉病变模型,分别分为超声组和对照组并在颊侧缺损龈方根面制备切迹作为参照点,高糖饲养8周.超声组行根面平整术,术后1周行低强度脉冲超声波(90 mW/cm2,1.5 MHz,200 μs,1 kHz)处理20 min/d,对照组行根面平整术和假处理.6周后取实验区域组织制备脱钙切片,苏木精-伊红染色、Masson染色行根分叉区域组织测量分析.结果与结论:超声组根分叉区新生牙槽骨沿根面生长,根分叉区可见牙龈上皮;对照组根分叉区以结缔组织生长为主,可见大量牙龈上皮和少量新生骨组织.超声组新生牙槽骨胶原呈"红-蓝"相间,以红染为主;对照组呈现蓝染,即超声组的新生牙槽骨胶原较对照组成熟.超声组牙槽骨、牙骨质、牙周膜新生量均大于对照组(P < 0.05).提示90 mW/cm2低强度脉冲超声波可促进根分叉病变新生牙槽骨胶原成熟和改建.%BACKGROUND: There were many reports on low-intensity pulsed ultrasound (LIPUS) to promote fracture healing and increase bone density, there were not literature involved in tissue repair effects of LIPUS on class Ⅱ furcation involvement.OBJECTIVE: To investigate the tissue repair effects of LIPUS treatment on class Ⅱ furcation involvement.METHOD: Beagle dogs' class Ⅱ furcation involvement models were established at buccal region of the dogs' fourth premolar of bilateral mandibular and randomly divided into ultrasonic treatment group (UT group) and control group (C group) and set notch at the gingival side of buccal root surface as the reference point. Then, Beagle dogs were fed with high glucose for 8 weeks.Scaling and planning of

  10. 胆碱非诺贝酸缓释胶囊在犬体内的药动学研究%Study on the pharmacokinetics of Trilipix in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    冯利; 孙文霞; 毛旭东; 程强

    2013-01-01

    目的 采用HPLC法测定Beagle犬血浆中非诺贝酸的浓度,初步研究胆碱非诺贝酸缓释胶囊在犬体内的药动学特征.方法 用乙腈直接沉淀血浆蛋白,以萘丁美酮为内标.采用Hypersil BDS C18色谱柱(200 mm×4.6 mm,5μm),流动相为乙腈-0.2%磷酸(50∶50),检测波长为286 nm.6只Beagle犬单次口服胆碱非诺贝酸缓释胶囊135 mg,于后肢静脉取血,采用HPLC测定非诺贝酸的血药浓度,并用DAS2.0程序计算药动学参数.结果 非诺贝酸的血药浓度0.20 ~ 40.00 μg· mL-1与峰面积比的线性关系良好(r=0.999);相对回收率为88.22% ~ 98.94%,绝对回收率为57.73%~58.65%;批内RSD<6.76%,批间RSD<5.05%.非诺贝酸在犬体内的药动学过程符合开放二房室模型,平均主要药动学参数t1/2α、t1/2B、V1/F、CL/F和AUC(0-t)分别为1.57h、13.25 h、8.28 L、1.12 L·h-1和127.34 μg·h·mL-1.结论 所用方法简便、灵敏、准确,适合于胆碱非诺贝酸缓释胶囊的药动学研究.非诺贝酸缓释胶囊在Beagle犬体内吸收和消除较慢,具有缓释特征.%OBJECTIVE To establish a method to determine the fenofibric acid in Beagle dog' s plasma by HPLC,and to study the pharmacokinetics of Trilipix in Beagle dogs. METHODS The plasma samples were pretreated by acetonitrile. Nabumetone was used as internal standard. A Hypersil BDS C18 column(200 mm ×4.6 mm,5 μm)with UV detection at 286 nm was used. The mobile phase was composed of 0. 2% phosphoric acid - acetonitrile (50 : 50). The flow rate was 1. 0 mL · min -1. six dogs were orally administered with a single dose of 1 Trilipix capsule ( 135 mg). The main pharmacokinetic parameters were calculated by DAS2. 0 software. RESULTS The range of linearity was 0. 20-40. 00 μg·mL-1 (r = 0. 999). The average recovery rates were 86. 22% - 98. 94% . And the average extraction recovery rates were 57. 72% -58. 63% . Both the intra - day and inter - day RSD were less than 7. 0% . After oral

  11. Pharmacokinetic Study of Timosaponin B-H in Beagle Dogs%知母皂苷B-Ⅱ在比格犬体内的药代动力学研究

    Institute of Scientific and Technical Information of China (English)

    蔡飞; 朱宏辉; 孙亮; 高守红; 王维泓; 陈万生

    2013-01-01

    Objective To develop a LC-MS/MS method for the determination of timosaponin B-II and to apply for its pharmacokinetic study. Methods The analytes were separated on an ODS column(150 mm×2.1 mm, 5 μm) with the mobile phase of acetonitrile-0.05 % formic acid (35 : 65) and detected by electrospray ionization mass spectrom-etry in the negative multiple reaction monitoring(MRM) mode. Six beagle dogs were randomized into two groups by crossover design. The animals were given intravenous administration of 2 mg·kg-1 or oral use of 30 mg·kg-1 of timosaponin B-II, respectively. The concentration of timosaponin B-II was determined after collection of the dog plasma, and then the main pharmacokinetic parameters were calculated. Results The parameters in intravenous vs oral administration were as follows: Cmax being(21507±7307) ng·mL-1 vs (313+149) ng·mL-1, AUC0-t being(19177±5692) ng·h·mL-1 vs (1879±738) ng·h·mL-1, AUC0-∞ being(l9770±5879) ng·h·mL-1 vs (2153±695) ng·h·mL-1, tv2 being (7.81±2.61) h vs (6.01±5.28) h, MRT0-t being(2.89±0.39) h vs (6.27±1.80) h, and MRT0-∞ being(3.88±0.39) h vs (8.59±3.18) h. Conclusion The method has been successfully applied to determine the concentration of timosaponin B-II and assess the pharmacokinetics in beagle dogs, with the absolute bioavailability being(0.72±0.29) % after oral adminstration.%目的 建立比格犬血浆中知母皂苷B-Ⅱ的LC-MS/MS测定方法,并应用于知母皂苷B-Ⅱ的药代动力学研究.方法 液相色谱分离采用ODS柱(150 mm×2.1 mm,5μm),以乙腈-0.05%甲酸溶液(35∶65)为流动相,质谱检测采用ESI离子源,MRM负离子模式.将6只比格犬随机分成2组,单剂量交叉静注或口服知母皂苷B-Ⅱ,剂量分别为2,30 mg·kg-1,定时采集血样,测定比格犬体内的血药浓度,并计算药代动力学参数.结果 比格犬静注和口服知母皂苷B-Ⅱ后的主要药代动力学参数如下:Cmax分别为(21507±7307)、(313±149)ng·mL-1

  12. 济泰片对人肝及Beagle犬肝中美沙酮代谢活性的影响%Effect of Jitai tablets on metabolic activity of methadone in human and Beagle dog livers

    Institute of Scientific and Technical Information of China (English)

    老东辉; 严东明; 马璟

    2012-01-01

    OBJECTIVE To evaluate metabolic inhibition potential of Jitai tablet (JTP) on methadone in human liver and induction potential in Beagle dog liver for predicting drug-drug interactions while coadministrating. METHODS JTP 1.5- 150 mg·L-1, positive inhibitors of CYP3A4 ketoconazole and positive inhibitor of CYP2D6 quinidine were added into human liver microsome ( HLM ) incubation system with methadone for coincubation. Formation rate of EDDP ( a metabolite of methadone) indicated metabolic activity on methadone for inhibition evaluation. After Beagle dogs were administered by JTP 0, 0. 1875, 0. 625 and 1. 875 g'kg-1 for 36 weeks, dog liver microsome (DLM) was prepared. Methadone was added in DLM incubation system. EDDP formation rate and metabolic ability in JTP groups were determined for induction evaluation of JTP on methadone. RESULTS Significant inhibitory effect on methadone demethylation was found in ketoconazole, quinidine, and ketoconazole + quinidine groups, but there was no inhibitory effect in JTP group. The metabolic rate, metabolic ability and metabolic ability per body mass of methadone demethylation in JTP 1.875 g · kg-1 group were greater than those in normal control group, and were 0.86 ± 0.17 vs (0.49 ±0.10)cps·min-1·mg-1 protein, 228 ±62 vs (115 ±13)cps·min-1·mg-1 protein, 10.6 ±0. 8 vs (24.4+5.6) cps·min-1·mg-1 protein·g-1, respectively (P <0. 05 ) . CONCLUSION JTP has no inhibitory effect on methadone metabolism in human liver. JTP shows certain inductive effect on methadone metabolism in DLM.%目的 评价济泰片对人肝中美沙酮代谢活性潜在的抑制作用及对Beagle犬肝中美沙酮代谢活性潜在的诱导作用.方法 在人肝微粒体中加入济泰片1.5 ~150 mg·L-1,CYP3A4抑制剂酮康唑及CYP2D6抑制剂奎尼丁,再加入美沙酮进行共孵育30 min.用美沙酮的代谢产物2-亚乙基-1,5-二甲基-3,3-二苯基吡咯烷(EDDP)的生成速率反映美沙酮的代谢活性,评价济泰片对美沙

  13. Pharmacokinetics of piroxicam-β-cyclodextrin inclusion complexes in Beagle dogs%吡罗昔康环糊精包合物在Beagle犬体内的药物动力学研究

    Institute of Scientific and Technical Information of China (English)

    张建明; 吴江; 方晓玲

    2012-01-01

    目的 研究吡罗昔康环糊精包合物Beagle犬体内药物动力学.方法 6只Beagle犬采用随机、双周期交叉给药,单剂量灌胃给予吡罗昔康受试制剂或参比制剂,用HPLC法测定吡罗昔康血浆浓度,用统计矩原理进行血药浓度-时间数据分析.结果 吡罗昔康包合物的达峰时间tmax快于普通片剂,分别为(0.89 ±0.09)、(3.92±0.49)h,两者有显著差异(P<0.01),两者的半衰期t1/2分别为(31.30±4.38)、(29.38±1.83)h,曲线下面积(AUC0~1)分别为(242.92±30.04)、(230.55±8.06)μg(h·ml),最高血药浓度(Cmax)分别为(7.82±0.44)、(7.49±0.36)μg/ml,清除率(Cl)分别为(80.92±10.65)、(85.27±2.95)ml/h,表观分部容积(Vd)分别为(3.36±0.51)、(3.22±0.19)L,均无明显差异(P>0.05),吡罗昔康包合物相对于市售片剂的相对生物利用度为106.74%.结论 建立的HPLC分析方法准确可靠.两种剂型的生物利用度相似,将吡罗昔康制成包合物后能大大加快药物在体内的吸收速度,使其更快发挥药效.%Objective To study the pharmacokinetics of piroxicam-|3-cyclodextrin inclusion complexes in Beagle dogs. Methods An open randomized two-period crossover self-control trial was conducted in 6 Beagle dogs. Piroxicam in the plasma was assayed by HPLC after a single oral dose of 20 mg piroxicam in test complexes (capsules) and reference tablets. The serum concentration-time data were analyzed by non-compartment-al model. Results The tmaxof the capsules and the tablets were 0. 89 ±0.09 and 3.92 ±0.49 h, respectively, with the former significantly shorter than the latter. The t1/2 were 31.30 ±4.38 and 29.38 ± 1.83 h, respectively. The AUC were 242.92 ±30.04 and 230.55 ±8.06 g/(h ? ml). The Cmaxwere 7.82 ±0.44 and 7.49 ±0.36 g/ml. The Cl were 80.92 ± 10.65 and 85.27 ±2.95 ml/h. The Vd were 3.36 ±0.51 and 3.22 ±0.19 L, respectively. These above indexes had no significant difference between 2 groups. The relative bioavailability of

  14. 改性钠基蒙脱石对盐酸雷尼替丁胶囊犬药代动力学的影响%Effects of modified Na-montmorillonite on pharmacokinetics of ranitidine hydrochloride in beagle dogs

    Institute of Scientific and Technical Information of China (English)

    方颖颖; 陈爱瑛; 叶小弟; 程敏; 缪云萍; 董文彬; 郑高利

    2012-01-01

    Objective To determination of ranitidine hydrochloride ( RH) in blood plasma to observe the changes of pharmacokinetic of rani-tidine hydrochloride caused by the adsorption of modified Na - montmoril-lonite (NM) in vivo. Methods Totally 16 beagle dogs were randomly divided into 8 groups with 2 in each group: the control group of RH; RH/NM group; three groups treated with Na - montmorillonite before RH respectively with the time interval of 0. 5, 1 and 2 h; the other three groups treated with Na - montmorillonite after RH respectively with the time interval of 0. 5,1 and 2 h. A 3 - period intercross trial was carried out. The blank plasma samples of all the dogs were collected at first, then the plasma samples of the control group, all the groups were collect-ed at the time points of 0,0. 5,1. 0,1. 5 ,2. 0,3. 0,4. 0,5. 0,6. 0,8. 0, 10. 0,12. 0 h after treating with RH. The ranitidine in plasma were deter-mined by the HPLC method. The pharmacokinetic parameters were pro-cessed by DAS 2. 1. 1. Results The main pharmacokinetic parameters of RH were calculated by the statistical moment method; Cmax was (3.615±1.321) μg·mL-1, AUC0-t was (8. 733 ±1. 883) μg·mL-1 ·h, AUC0-∞, was (9.381 ±2.347) μg·mL-1·h, MRT0-t was (2. 901 ±0. 152) h, t1/2z was (3. 824 ±3. 126) h, Tmax was (0. 917 ±0. 376) h. The relative bioavailability of RH/ NM, NM/0.5hRH, NM/1hRH, NM/2hRH, RH/0.5hNM, RH/1hNM and RH/2hNM were 29.1%, 52.0%, 73. 1% , 86. 4% , 57. 0% , 64. 8% and 86. 9%. Conclusion Modified Na - montmorillonite has an obvious inhibi-tion effects on the adsorption of RH in Beagle dogs. It suggests the dosing interval should be less than 1 hour which a-voids the adsorption of RH from overinhibiting by NM as well as improves the relative bioavailability in vivo.%目的 HPLC法观察改性钠基蒙脱石(NM)对盐酸雷尼替丁(RH)胶囊犬药代动力学的影响.方法 随机分成8组(每组2只):RH对照组、RH/NM组、NM后3个不同时间(0.5,1.0,2.0h) RH组、NM前3

  15. Preliminary research of Er:YAG laser used for pulpotomy of Beagle dogs%Er:YAG 激光用于比格犬牙髓切断术

    Institute of Scientific and Technical Information of China (English)

    郭怡丹; 张笋

    2016-01-01

    目的:通过比格犬动物试验,观察铒钇铝石榴石(erbium:yttrium aluminium garnet,Er:YAG)激光去除比格犬冠髓后剩余牙髓的变化及牙本质桥形成情况,探索 Er:YAG 激光照射与牙髓反应及牙本桥形成的关系。方法:选取2只12月龄雄性比格犬前磨牙为试验牙,共24颗,分别应用200 mJ/20 Hz Er:YAG 激光、100 mJ/20 Hz Er:YAG 激光及传统机械方法去除冠髓,三氧化矿物凝聚体(mineral trioxide aggregate,MTA)盖髓后充填。通过临床检查试验牙的动度和牙龈情况评价临床效果,拍摄试验牙平行投照 X 线根尖片评价影像学效果。试验术后1 d、2周、4周、8周拔牙,苏木精-伊红染色(Hematoxylin-Eosin staining,HE)下观察根髓情况及牙本质桥形成情况。结果:牙髓切断术后1 d、2周、4周、8周后机械去髓组和激光去髓组试验牙均无松动,牙龈无红肿瘘管等异常;X 线片发现机械去髓组和激光去髓组试验牙均未见牙周膜增宽、根尖周低密度影、牙根内外吸收等影像学异常表现;HE 染色组织学切片检查发现术后1 d、2周、4周、8周机械去髓组和激光去髓组试验牙根髓均未见明显炎症反应,2周时可见激光去髓组牙本质桥完全覆盖牙髓断面,而机械切髓组未见完整牙本质桥。结论:100 mJ/20 Hz 和200 mJ/20 Hz Er:YAG 激光去髓对剩余根髓未见影响。%Objective:To investigate the effects of erbium:yttrium aluminium garnet (Er:YAG)laser irradiation on pulp and formation of dentin bridge.The beagle dogs'coronal pulp is amputated by Er:YAG laser.Methods:In the study,24 premolar teeth of two one-year-old Beagle dogs were used.They were divided into 3 groups:bur group,200 mJ laser group,100 mJ laser group.The coronal pulp were removed by traditional bur or 200 mJ/20 Hz or 100 mJ/20 Hz Er:YAG laser.Then,they were dressed with mineral trioxide aggregate (MTA)and sealed with

  16. 胶体~(32) P-磷酸铬间质给药对犬累积损伤效应的研究%Cumulative damage effect of ~(32) P-colloidal chromic phosphate interstitial delivery on beagles

    Institute of Scientific and Technical Information of China (English)

    聂琦; 刘璐; 刘志勇; 黄培林; 兰兴昊; 高海林; 吴清华; 孙晋; 黄鹰

    2010-01-01

    其致死剂量.肌肉给药463.98-772.93 MBq/m~2是安全剂量范围.~(32)P-CP间质给药是适用于治疗凡穿刺所能到达的乏血供及中等血供实体瘤的安全手段.%Objective To explore the possibility and safety of ~(32)P-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) ±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 × 10~7/min and 1.0 × 10~7/min,respectively.The blood cpm in the muscle groups was always maintained at 3 × l0~5/min.Histology study showed the hyperemia dropsy changes in muscle groups and 185 MBq liver

  17. 单硝酸异山梨酯盐酸伊伐布雷定复方对Beagle犬的长期毒性研究%Experimental Study on the Long-term Toxicity of Isosorbide Mononitrate and Ivabradine Hydrochloride Compound in Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    胡晓乐; 李会恩; 李斌; 王恩力; 冯中; 赵涛

    2015-01-01

    目的:观察Beagle犬连续30天口服单硝酸异山梨酯盐酸伊伐布雷定复方(ISMN-I)所产生的毒性反应,为临床剂量的拟定提供依据。方法Beagle犬32只,雌雄各半,分为4组:空白对照组,复方低、中、高(30、75、180 mg·kg-1)剂量组,每组8只动物。每日给药1次,连续给药30天,停药观察14天。实验期间,每日进行一般状态观察,每周测定1次体质量及摄食量,于给药前、给药末期及停药恢复期末,各组动物分别进行眼科、体温、尿液、血压、心电图(Ⅱ导联)、血液学指标、血液生化学检测,给药期及恢复期结束剖检并进行病理组织学检查。结果ISMN-I复方高剂量组、中剂量组给药末期可使舒张压(DBP)出现降低,且高剂量组、中剂量组均可导致Beagle犬在给药期间出现呕吐、振颤、抽搐、无力等反应,低剂量组个别犬偶尔出现一次性的呕吐反应。结论本试验条件下,单硝酸异山梨酯盐酸伊伐布雷定复方对Beagle犬无不良反应剂量(NOAEL)为30 mg·kg-1。%Objective To observe the toxicity of isosorbide mononitrate and ivabradine hydrochloride compound (ISMN-I) in beagle dogs, and to provide safety evidences for clinical experiment. Methods 32 healthy beagle dogs, half male and half female, were randomly disvided into control, low-, mid-, and high-dose (30, 75, and 180 mg·kg-1) groups, 8 dogs in each group. The beagle dogs were administered for 30 days, and observed for 14 days after the last administration. During the experiment, the general conditions of animals were observed daily. Body weight and food consumption were weighed weekly. The related indexes including ophthalmology, body temperature, urinary routine, blood pressure, electrocardiogram, hematological and blood biochemical indexes were detected at different time points such as before administration, the end of administration and the end of recovery period

  18. 犬牙囊干细胞膜片的构建及生物学特性的研究%Construction of Dental Follicle Stem Cell Sheet and its Biological Characteristics in Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    黄闯; 宋镜明; 宋扬; 刘佳; 王丽颖; 金作林

    2012-01-01

    Objective: To study the construction of dental follicle stem cell sheet and its biological characteristics in Beagle dogs. Methods: After identification.DFSCs were sub-cultured to construct DFSCs sheet. Cell sheet was investaged by inverted microscope, HE staining and scanning electron microscope (SEM). DFSCs sheets were induced by adipogenesis inducing medium and osteogenic medium for 14 days separately. Oil red staining and Alizarin red staining was applied to examine adipogenic induction and osteogenic induction. Results: DFSCs showed typical spindle shape.. Colony-forming assay results showed about 5.1% DFSCs colony formation. DFSCs were positive for CD29 and CD44, but negative for CD34. MTT manifested the growth and proliferation was good. Cell cycle testing showed: G1=87.1%,G2=5.54%. DFSCs sheets were constructed successfully and its growth in multilayer. It found that DFSCs expanded adequately and extracellular matrix(ECM) was clear and numerous in scanning electron micrescopy.Oil red staining and alizarin red staining both demonstrated positive reactions in DFSCs sheet after induction. Conclusion: It suggested that DFSCs cell sheet may be constructed and has a strong bone-forming ability.%目的:利用犬牙囊干细胞(Dental Follicle Stem Cells,DFSCs)构建细胞膜片并研究其生物学特性.方法:取4至6月龄犬尖牙牙胚,分离培养DFSCs,鉴定.用含抗坏血酸的培养基诱导2周构建细胞膜片,并通过倒置显微镜、HE染色、茜素红染色、油红染色、扫描电镜(SEM)对膜片进行形态学检测,检测成骨、成脂能力.结果:DFSCs于体外被成功分离、纯化、培养,细胞克隆形成率约为5.1%.流式鉴定为CD29+CD44+CD34-,增殖能力及克隆形成能力较强,并能成功构建成细胞膜片.光镜和电镜显示膜片细胞排列紧密,细胞基质分泌多,油红O染色后可见细胞内有大量脂滴形成.(B)茜素红染色后可见大量清晰的钙结节形成.结论:成功构建犬DFSCs膜

  19. 去髓年轻恒牙牙髓组织再生的动物实验%Experimental study on pulp revitalization of Beagle dog′s immature permanent teeth after pulpectomy

    Institute of Scientific and Technical Information of China (English)

    杨剑珍; 欧阳勇; 廖志清

    2011-01-01

    Objective To observe the process of pulp revitalization of immature permanent teeth after pulpectomy. Methods Thirty-two single-rooted teeth with open apices from 4 Beagle dogs aged 4 months were included in the study. The pulpal tissues of 8 front teeth with single root of each dog were removed, and a blood clot was produced to the level of the cementoenamel junction followed by a double seal of mineral trioxide aggregate and composite resin. At day 7, 14, 21 and 28, respectively after operation, the dog was sacrificed, and then longitudinal paraffin sections were made for histologic investigation. ResultsAfter 7 days, about one thirth of the pulp chamber had an ingrowth of new tissue. After 14, 21, 28 days, there were more and more new tissue in the chamber. This new tissue consisted of well-organized and well-vascularized connective tissue. Hard tissue was too observed in the root canal. In some cases, the newly generated hard tissue even deposited against the canal dentinal walls. Conclusions The pulp of immature permanent teeth can revitalize after removal of the original pulp tissue under suitable conditions.%目的 观察年轻恒牙去髓后牙髓组织的再生状态,研究牙髓组织的再生过程,为进一步探讨牙髓组织的再生机制提供依据.方法 选取4只Beagle犬,每只犬8颗单根管上下颌切牙作为实验牙,拔除上下颌切牙牙髓并使血块充满髓腔,严密封闭开髓孔,分别于术后第7、14、21、28天处死动物,对牙齿及颌骨标本进行组织学观察.对照牙为2颗下颌切牙,未作任何处理.结果 实验第7、14、21、28天实验牙根管内均富含细胞、血管分化良好的新生组织长入,并随观察时间的延长而增多,28 d时新生组织基本长满髓腔.根尖部及根中部可见硬组织沉积,部分牙齿的根管内壁有钙化组织沉积,管壁增厚.对照牙根管内为正常牙髓组织.结论 在保持根管无菌并严密封闭开髓孔的情况下,Beagle犬年轻

  20. Release of azithromycin extended release for oral suspension and evaluation of in vitro-in vivo correlation in beagle dogs%阿奇霉素缓释干混悬剂释放度测定及Beagle犬体内外相关性评价

    Institute of Scientific and Technical Information of China (English)

    阚淑玲; 谢卫锋; 周永强

    2012-01-01

    目的 进行阿奇霉素缓释干混悬剂体外释放度的测定及比格犬体内外相关性评价.方法 按2010版中国药典释放度测定法测定阿奇霉素缓释干混悬剂体外释放度,用液相色谱-串联质谱(LC/MS/MS)法测定阿奇霉素在比格犬体内的血药浓度,并用WinNonlin Professional v5.2进行数据处理.结果 以体内吸收分数(fa)对体外累积释放度(F)进行线性回归,得方程fa=1.1553F-52.931(r=0.9475).结论 体内吸收分数与体外累积释放度具有良好的相关性,阿奇霉素缓释干混悬剂所采用的释放度测定方法合理,可以较好反映体内吸收情况.%Objective To study the release of azithromycin extended release for oral suspension and to evaluate the correlation between in vitro and in vivo in Beagle dogs. Methods Release test method in azithromycin extended release for oral suspension adopted by ChP was used for determination of release in vitro. The concentrations of azithromycin in Beagle plasma were determined by LC/MS/MS. Results The linear equation based on the accumulation( F ) and absorption percentage( fa )was fa = 1. 1553F -52. 931 and the correlation coefficient was 0. 9475. Conclusion To a certain extent,the vitro release test in ChP could reflect the vivo absorption.

  1. Tissue engineered allograft total disc transplantation using exogenous nucleus pulposus cells: an experimental study in a beagle model%犬同种异体椎间盘复合髓核细胞移植初探

    Institute of Scientific and Technical Information of China (English)

    辛洪奎; 张超; 王德利; 吴剑宏; 王超峰; 何勍; 阮狄克

    2012-01-01

    功能的潜力,有望保证同种异体椎间盘移植的远期疗效.%Objectives: To investigate in vivo rehepitation of the transplanted tissue engineered allograft total disc and to explore the biological effect of nucleus pulposus(NP) cells or hTERT gene transfected NP cells on allograft total disc transplantation. Methods: Eighteen canine lumbar intervertebral discs were obtained from 5 canines and cryopreserved in liquid nitrogen. Canine nucleus pulposus cells were isolated and transduced with rAAV-hTERT. The cells were injected into the discs to construct a "tissue-engineered" allograft disc(group A). NP cells and DMEM/F12 were used for positive control(group B) and blank control(group C) respectively. 18 beagle dogs received the 3 groups of allograft IVD composites implantation respectively. Radiographic examination was performed at 4, 8 and 12 weeks after implantation. At 12 weeks after operation, all dogs were sacrificed and the lumbar spines were harvested for the biomechanical test and histological analysis, ectogenic NP cell tracing and hTERT mRNA analysis. Results: Bony fusion between intervertebral disc allograft and adjacent host intervertebral body was observed in all animals. The disc height and T2 signal intensity preservation'in "group A and B were better than group C. MRI showed typical degenerative changes in group C. In group A, the normalized grayscale of the transplanted disc in MRI image was significant higher than that of the controls at 12 weeks. Biomechanical test showed a poor stability preservation in group C compared with group A and B. PKH-26 positive cells were identified within the allograft discs in group A at 12 weeks, which provided matrix for cell survival. Histological analysis showed the NP cell morphology, cell number and distribution of the allograft discs were better preserved in group A and B than group C at 12 weeks of follow -up. Conclusions: NP cells or hTERT loaded NP cells intervention can effectively resist the

  2. Pharmacokinetic Study on Hyperoside in Beagle's Dogs

    Institute of Scientific and Technical Information of China (English)

    AI Guo; HUANG Zheng-ming; LIU Chang-xiao

    2012-01-01

    Objective To develop and validate a simple,rapid,sensitive,and reproducible HPLC method for determination of hyperoside in plasma of dogs and for the subsequent pharmacokinetic (PK) study.Methods An accurate and reproducible HPLC-UV method was developed and validated for the determination of hyperoside in plasma of dogs,using kaempferol as internal standard.The plasma samples of dogs following ig administration of hyperoside were analyzed for the detection of quercetin after enzymatic hydrolysis treatment with combined β-glucuronidase and sulphatase.The analytes were separated on a Diamonsil C18 column (250 mm × 4.6 mm,5 μm).The mobile phase consisted of methanol-buffer solution (0.1mol/L NH4Ac + 0.3 mmol/L EDTA-Na2)-acetic acid (60:40:1) and was delivered at a flow rate of 1mL/min.The UV detector was set at 370 nm and the column temperature was maintained at 35 ℃.The sample injection volume was 20 μL.Data were collected and analyzed using the ANASTAR software.PK parameters were calculated with DAS software (2.0).Results Linear relationships were validated over the range of 0.01-1μg/mL for hyperoside (r =0.9997).The intra-and inter-day precision values for all samples were within 10.0%,and the accuracies of intra-and inter-day assays were within the range of 92.4%-102.4%.The validated method was successfully used to determine the hyperoside concentration in plasma of dogs for up to 12 h,after a single ig administration (25 mg/kg).The mean PK parameters for male and female dogs were as follows:Cmax (0.18 ± 0.05) and (0.16 ± 0.05) μg/mL,AUC0-∞ (0.79 ± 0.34) and (0.86 ± 0.27) μg/(mL·h),t1/2(ka) (0.89 ± 0.41) and (0.88 ± 0.28) h,respectively.Statistical analysis on the PK of hyperoside in male and female groups showed that sex had no significant impact on the PK of hyperoside (P > 0.05).Conclusion The method is able and sufficient to be used in drug PK studies of hyperoside.

  3. 心率变异性评估运输应激对Beagle犬自主神经功能的影响%Assessment of the effect of transportation stress on autonomic nervous function in beagle dogs based on heart rate variability (HRV) analysis

    Institute of Scientific and Technical Information of China (English)

    潘永明; 何欢; 陈亮; 徐孝平; 杨玉伟; 朱科燕; 陈民利

    2011-01-01

    目的 基于心率变异性(heart rate variability,HRV)分析评估运输应激对Beagle犬自主神经功能的影响,并界定其恢复期.方法 16只Beagle犬随机分成两组(每组8只),即对照组和运输应激组,利用大动物无创生理信号遥测技术,分别监测清醒自由活动状态下对照组和运输应激组应激4 h后、恢复1、2、3周时,Beagle犬的心电图(ECG)的改变情况,并用HRV分析评估其自主神经功能情况.结果 ①Beagle犬HRV参数具有明显的昼夜节律变化(P<0.01),与对照组比,运输应激后Beagle犬的HRV时域分析参数中RR间期、SDNN、RMSSD、TI、pNN50、STV和LTV参数均出现明显的降低 (P<0.05,P<0.01),且恢复3周后时域分析参数恢复至正常水平; ②与对照组比,运输应激后Beagle犬频域分析参数中HR、LFnorm、LF/HF比值均显著升高(P<0.01),而LnTP、LnVLF、HFnorm均出现明显的降低(P<0.01),且恢复3周后频域分析参数恢复正常水平;③运输应激后,Beagle犬HR与HRV参数具有显著的相关性(P<0.01).结论 运输应激可引起Beagle犬交感神经活动增强,使得交感神经/副交感神经活动平衡发生紊乱,导致HRV降低,其可能是引起Beagle犬自主神经功能紊乱的主要原因之一.Beagle犬运输应激后,最好进行2周以上或3周的恢复期.%Objective To assess the effect of transportation stress on autonomic nervous function in beagle dogs based on heart rate variability (HRV) analysis, and define its recovery.Methods Sixteen beagle dogs were randomly divided into two groups (n= 8 in each): the control group and transportation stress group.Using a non-invasive telemetry system in conscious and unrestrained beagle dogs, electrocardiograms (ECG) were recorded in both groups after a 4 h transportation stress and after a recovery of 1, 2 and 3 weeks.HRV analysis was used to assess the autonomic nervous function.Results (1) There was an obvious circadian rhythm in beagle dogs (P <0.01 ).Compared with

  4. 皮卡佐剂狂犬病治疗性疫苗对暴露后实验动物和人体免疫记忆的效果%The effects treated with PICKCa rabies vaccine to mice and beagle dogs infected rabies wild viruses and volunteers immunized with PICKCa rabies vaccine

    Institute of Scientific and Technical Information of China (English)

    林海祥; 徐葛林; 吴杰; 张守峰; 扈荣良; 李烈涛; 刘芳; 张师瑞; 张译

    2016-01-01

    Objective To test the immune therapeutic effects of PICKCa adjuvant rabies vaccine for the post-exposure mice and beagle dogs and immune memory effect for human.Methods For the mice and beagle dogs first to infect with rabies wild virus and then immunize with PICKCa rabies vaccine.For volunteers, first to immunize with PICKCa rabies vaccine after 2.5 years to take peripheral blood mononuclear cell and then to check cells secreted interferon-gwith flow cytometry. Results In 3 independent assays of post-explosure immunization of mice and beagle dogs PICKCa rabies vaccine were much better then commercial adjuvant-free rabies vaccines, the protective rate from 20%-30%to 70%-100%Also, in the assay of cells secreted IFN-γby peripheral blood mononuclear cells from volunteers immunized by PICKCa rabies vaccine the IFN-γcell levels were much higher than control.Conclusions Compared with commercial adjuvant-free rabies vaccines the PICKCa rabies vaccine had significant immune therapeutic effects in the mice and dogs.Also PICKCa rabies vaccine had good immune memory effect in human.%目的:检测皮卡佐剂狂犬病疫苗对暴露后实验动物免疫治疗作用和对人的免疫记忆效果。方法模仿人体暴露后免疫,对小白鼠和Beagle犬进行了先感染狂犬病毒野毒株病毒再用不同狂犬病灭活疫苗免疫,观察保护效果;对犬咬伤志愿者用皮卡佐剂狂犬病疫苗免疫2.5年后分离外周血单个核细胞,用流式细胞仪检测干扰素免疫记忆细胞数量。结果在法国巴斯德研究所、武汉生物制品研究所、军事医学科学院军事兽医研究所三次独立实验结果均显示在没有联合应用抗狂犬病免疫球蛋白的情况下,国内外市售人用狂犬病疫苗保护率为0%~30%,皮卡佐剂狂犬病疫苗保护率为70%~100%,统计学分析有极其显著的差异。暴露后志愿者用皮卡佐剂狂犬病疫苗免疫,2.5年后外周血单个核细胞仍能

  5. 新型盐酸二甲双胍控释片的研制及在Beagle犬体内的药代动力学研究%Preparation of novel metformin hydrochloride osmotic pump controlled release tablets and study on pharmacokinetics in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    殷健; 冯岩; 卢骏; 刘志东; 师健鑫

    2012-01-01

    Objective;To prepare novel large-dose metformin hydrochloride osmotic pump controlled release tablets, and to investigate the pharmacokinetics of the marketed metformin hydrochloride tablets and the self-made ones in Beagle dogs and the in vitro-in vivo correlation. Methods; Polyethylene oxide (PEO) was used as suspension agent and SDS was applied as surfactant. The similarity factor f2 was used to evaluate the release behavior between the self-made formulation and marketed tablets. In the cross-over study of single-dose and multiple-dose , the in vivo pharmacokinetics of the self-made formulation and the marketed tablets were studied in Beagle dogs. Results; Compared to marketed metformin hydrochloride tablets, the f2 value was 75.0. The relative bioavailabilities of the self-made formulation after single-dose and multiple-dose administration were (101.31 ± 15.81 )% and (99. 46 ± 12.55)% , respectively. Conclusion; Compared with the marketed tablets, self-made metformin hydrochloride osmotic pump controlled release tablets have similar pharmacokinetic profile and bioavailability.%目的:制备新型大剂量盐酸二甲双胍渗透泵控释片,以市售控释片为对照,对服用渗透泵片的Beagle犬进行体内药代动力学研究,并对体外释放和体内吸收的相关性做出评价.方法:选用聚环氧乙烷(PEO)和十二烷基硫酸钠(SDS)等为主要辅料,制备盐酸二甲双胍单层渗透泵片;用f2相似因子法考察剂型的体外释放行为,并与市售控释片释放度进行比较;采用单剂量和多剂量交叉试验进行Beagle犬体内药代动力学研究.结果:与市售控释片进行比较,相似因子f2 =75.0.单剂量和多剂量犬体内试验相对生物利用度分别为(101.31±15.81)%和(99.46±12.55)%.结论:自制盐酸二甲双胍渗透泵片具有与市售片相似的缓释效果,主要药代动力学参数无显著差异,两个制剂的生物利用度接近.

  6. The anti-aging study of human umbilical cord mesenchymal stem cells combined with lycopene treatment in the aging beagles%人脐带间充质干细胞联合番茄红素延缓比格犬的自然衰老

    Institute of Scientific and Technical Information of China (English)

    王琳琳; 崔晓兰; 时瀚; 成雪; 刘佳; 申义; 李倩倩; 王意忠

    2014-01-01

    BACKGROUND:Previous tudies have shown that the anti-aging effects of stem cel s with lycopene are more significant, and can also significantly improve the aging body immune function. OBJECTIVE:To investigate the anti-aging effects of human umbilical cord mesenchymal stem cel s combined with lycopene on the aging beagles. METHODS:Sixteen aging beagles (6-7 years old) were randomly divided into two groups:aging control group and aging treatment group;young beagles (3-4 years old) were chosen as young control group. In the aging treatment group, human umbilical cord mesenchymal stem cel s combined with lycopene was given;while in the other two group, an equal amount of DMEM/F12 cel culture medium and sunflower oil was given. Each dog's general conditions were observed regularly during the whole progress. The changes of superoxide dismutase, malondialdehyde, glutathione peroxidase in the serum were detected at regular time of the whole process, and the structure changes of each organ were observed at 24 weeks of treatment. RESULTS AND CONCLUSION:(1) Before treatment, the levels of superoxide dismutase and glutathione peroxidase in the aging control and treatment groups were lower than those in the young control group (P0.05). (2) For the aging treatment group at 24 weeks of treatment:the beagle fur became clearer and smoother, motility was strengthened, appetite became better;and the activity of superoxide dismutase in serum at 8 to 24 weeks of treatment increased significantly compared with before treatment (P  目的:观察人脐带间充质干细胞联合番茄红素对自然衰老比格犬的抗衰老作用。  方法:选用自然衰老的健康比格犬(6至7岁龄)16只,随机分为衰老对照组和衰老治疗组,以健康青年犬(3至4岁龄)作为青年对照组。衰老治疗组给予人脐带间充质干细胞和番茄红素联合治疗,其余两组给予等量的DMEM/F12细胞培养液和等量葵花籽油。治疗过程中定期观察

  7. Preparation and in vitro-in vivo Correlation in Beagle Dogs of Hawthorn Leaves Flavonoids Sustained-release Tablets%山楂叶总黄酮缓释片的制备及Beagle犬体内外相关性研究

    Institute of Scientific and Technical Information of China (English)

    黄平; 何春柏; 赵子明; 唐翠

    2009-01-01

    以山楂叶总黄酮为模型药物,羟丙甲纤维素(HPMC)、乙基纤维素(EC)及丙烯酸树脂(Eudragit L100)为混合骨架材料制备日服两次的缓释片,以牡荆素为指标成分,考察Beagle犬单剂量Lj服缓释片后的药代动力学特征.结果表明,本品缓释特征较好,体外释放较符合WeibuU模型,本品体外释放度与Beagle犬体内药物吸收分数之间相关系数为0.98.%Twice a day sustained-release tablets were developed for the Hawthorn leaves flavonoids, using hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC) and Eudragit L100 as combined matrix materials. Pharmacokinetics of the tablets were investigated in Beagle dogs with vitexin as marker compound. Results showed that the prepared tablets possessed a good sustained-release characteristic. Weibull model was the optimal model for the description of drug release profile. The correlation coefficient between the fraction of absorption in vivo and the release rate in vitro was 0.98.

  8. Simultaneous determination of protocatechuic acid, isoorientin and scutellarin in Beagle dog plasma by UPLC-MS/MS%UPLC-MS/MS同时测定Beagle犬血浆中原儿茶酸、异荭草素和野黄芩苷

    Institute of Scientific and Technical Information of China (English)

    黄勇; 何峰; 郑林; 张治蓉; 陈慧; 李勇军; 王爱民; 兰燕宇; 王永林

    2011-01-01

    目的 建立Beagle犬血浆中同时测定原儿茶酸、异荭草素和野黄芩苷的超高效液相色谱-串联质谱分析方法.方法 Beagle犬单次股静脉注射88 mg·kg-1的注射用复方荭草(冻干粉针),分时取血处理.色谱采用Waters BEH C18反相柱,流动相为乙腈-水(含0.1%甲酸)梯度洗脱,质谱采用多反应离子监测(MRM)方式进行检测,用于定量分析的离子对分别为原儿茶酸m/z109.0→m/z152.8、异荭草素m/z449.2→m/z299.1、野黄芩苷m/z463.1→m/z287.1.结果 原儿茶酸、异荭草素和野黄芩苷的线性范围分别为0.002~0.569、0.022~5.450和0.024~5.860 mg·L-1,方法 的准确度,日内、日间精密度和稳定性均符合要求.结论 该方法快速、灵敏、专属性强,可用于原儿茶酸、异荭草素和野黄芩苷的药代动力学研究.%Aim To develop an UPLC-MS method for simultaneous determination of protocatechuic acid,isoorientin and scutellarin in Beagle dog plasma. Methods Blood samples from Beagle dogs were collected at scheduled time points after intravenous injection of 88 mg· kg-1 Compound Hongcao injection. The analysis column was a Waters BEH C18 column, the mobile phase consisted of acetonitrile and water( 0. 1% formic acid included ), and the detection was carried out in the multiple reaction monitoring (MRM) mode. The ion pairs for quantitation were m/z109.0→m/z152.8 for protocatechuic acid, m/z449.2 → m/z299. 1 for isoorientin and m/z463.1 →m/z287.1 for scutellarin,respectively. Results The linear range of protocatechuic acid, isoorientin and scutellarin was 0. 002 ~0.569, 0.022 ~5.450, and 0.024 ~5.860 mg·L-1, respectively. The accuracy, intra- and inter-day precisions, and the stability of the analytes met the requirements. Conclusion The above mentioned method is sensitive, specific, and suitable for pharmacokinetic studies of protocatechuic acid, isoorientin and scutellarin.

  9. Identification of Biological Characteristics of Mesenchymal Stem Cell-like Cells from Laryngeal Mucos in Beagle%比格犬会厌黏膜来源干细胞的分离培养与生物学特性鉴定

    Institute of Scientific and Technical Information of China (English)

    梁媛媛; 韩鹏; 杨润琴; 刘阳; 邓志宏

    2013-01-01

    目的:探讨建立喉部黏膜间充质干细胞的分离培养方法,并对其生物学特性进行鉴定,为进一步研究其在喉部瘢痕中形成的作用及喉部组织工程提供参考.方法:以比格犬喉部会厌背侧(舌面)黏膜为研究对象,采用消化培养的方法分离具有间充质干细胞样细胞.选取第3代细胞对其进行生物学特性鉴定,首先利用MTT法检测其增殖活性及克隆形成情况,然后通过流式细胞术检测细胞表面分子标记物CD29及CD34的表达情况,最后应用第3代细胞对其进行成脂肪细胞和成骨细胞分化培养,观察其分化能力.结果:分离培养细胞形态较为一致,绝大多数呈梭形,排列不规则.MTT增殖活性实验及克隆形成试验结果显示,所分离的细胞具有良好的增殖活性和克隆形成率;流式细胞术结果显示,该细胞表达CD29间充质干细胞细胞表面标记物,低表达造血干细胞细胞表面标记物CD34;同时,该细胞诱导分化成脂肪细胞和成骨细胞实验表明,其具有多向分化潜能.结论:从比格犬会厌背侧黏膜分离的细胞具有间充质干细胞样特性,为进一步研究喉部瘢痕形成机制及喉部组织工程提供了技术基础.%Objective:To establish the methods of isolation and cultivation of mesenchymal cells from laryngeal mucosa of beagle and investigate the biological characteristics of the isolated cells.Methods:Laryngeal mucosa were harvested by enzyme digestion.And the third passage of cells were collected to determine the clone formation ability and growth kinetics.And flow cytometry method was used to detect the expression of CD29 and CD34.Then the third passage of isolated cells was treated with adipogenic nutrient media and osteogenic nutrient media respectively.Results:After being subcultured,the sizes of isolated cells were similar,and the majority of them were spindle-shaped with disorderly arrangement.The flow cytometry results showed that the

  10. Preparation of Isosorbide Mononitrate Controlled Release Tablets and Evaluation of Their Bioavailability in Beagle Dogs%单硝酸异山梨酯控释片的制备及在Beagle犬体内生物利用度研究

    Institute of Scientific and Technical Information of China (English)

    李欣; 姜庆伟; 杜丽娜

    2011-01-01

    目的 制备单硝酸异山梨酯控释片,考察其在Beagle犬体内的药动学及相对生物利用度.方法 采用单室渗透泵技术制备控释片,采用两制剂、双周期交叉试验设计,气相色谱-电子捕获法对犬体内血药浓度进行分析;DAS 2.0软件计算药动学参数.结果 受试犬服用自制控释片和市售缓释片(参比制剂)后药时曲线相似,主要药动学参数分别为:t1/2(5.083±1.524)和(4.866±1.361)h,Cmax(0.617±0.213)和(0.753±0.228)μg/ml,Tmax(2.250±0.880)和(2.722±0.935)h,AUC0-t)(5.086±0.832)和(4.997±0.916)μg·h/ml,AUC(0-∞)(5.254±0.754)和(5.258±1.032)μg·h/ml,相对生物利用度为(101.0±17.7)%.结论 单硝酸异山梨酯控释片与市售缓释片主要药动学参数无显著性差异,两制剂具有生物等效性.%Objective To prepare isosorbide mononitrate controlled release tablets and study their pharmacokinetics and relative bioavailability in Beagle dogs. Methods Isosorbide mononitrate controlled release tablets were prepared by monolithic osmotic pump technique. These tablets and isosorbide mononitrate sustained release tablets (reference formulation) were given orally to Beagle dogs by a two-crossover design. Drug concentrations in plasma were determined by gas chromatography-electron capture detector and the pharmacokinetic parameters of isosorbide mononitrate were analyzed by DAS 2.0. Results The main pharmacokinetic parameters of the self-made controlled release tablets and reference formulation were as follows: t 1/2 was ( 5. 083 ± 1. 524 ) and (4.866 ± 1.361 )h, Cmaxwas(0.617 ±0.213)and(0.753 ±0.228)μg/ml, Tmaxwas(2.250 ±0.880) and (2.722 ±0.935) h;AUC(0-t) was (5. 086 ± 0. 832 ) and ( 4. 997 ± 0. 916 ) μg · h/ml, AUC(0-∞ ) was ( 5. 254 ± 0. 754 ) and ( 5. 258 ±1. 032 )μg ·h/ml. The relative bioavailability was ( 101.0 ± 17.7 ) %. Conclusion Compared with the sustained release tablets, isosorbide mononitrate controlled release tablets have a

  11. A potential biological therapy with interleukin-10 and transforming growth factor-β for intervertebral disc degeneration in an in vitro beagle model%IL-10和TGF-β介导的生物学治疗犬椎间盘退变的体外实验研究

    Institute of Scientific and Technical Information of China (English)

    李威; 唐勇; 刘天懿; 贾治伟; 白雪东; 阮狄克

    2015-01-01

    Objective To explore the biological function and mechanism of underlying suppression of the release of inflammatory cytokines from degenerative disc cells and to evaluate the effectiveness of interleukin ( IL )-10 and transforming growth factor ( TGF )-β in suppressing the release of inflammatory cytokines from degenerative disc cells. Methods Six 1-year-old male beagle dogs were used. A beagle model of intervertebral disc degeneration ( IDD ) was established using an anular stab. The intervertebral discs were incised when the dogs were sacriifced 6 weeks later, and nucleus pulposus ( NP ) cells were isolated and cultured in vitro. The cultured degenerative NP cells were divided into 4 groups, including untreated degenerative NP cells, degenerative NP cells treated with 20 ng/ml IL-10, degenerative NP cells treated with 20 ng/ml TGF-βand degenerative NP cells treated with 20 ng/ml IL-10 and 20 ng / ml TGF-β. An enzyme-linked immunosorbent assay ( ELISA ) and real-time polymerase chain reaction ( PCR ) were performed to determine the effects of IL-10 and TGF-βon the protein and gene expressions of inflammatory cytokines. Results Higher expressions of inflammatory cytokines were observed in untreated degenerative NP cells. IL-10 and TGF-βblocked the cascade of inflammatory cytokines produced by degenerative disc cells and limited the development of inlfammatory responses. Conclusions The expressions of IL-1βand tumor necrosis factor ( TNF )-αin degenerative disc cells can be signiifcantly and stably suppressed by IL-10 and TGF-β. Thus, IL-10 and TGF-βmay be suitable biological therapeutic agents for IDD.%目的:探索利用细胞因子抑制退变椎间盘细胞释放炎症因子的生物学机制及作用,评价IL-10和TGF-β抑制退变椎间盘细胞释放炎症因子的有效性。方法建立6条1岁龄比格犬针刺退变模型,6周后处死动物取出退变椎间盘髓核组织,体外分离培养,将培养的退变髓核细胞分为4

  12. Study on in vitro release and bioequivalence in Beagle dogs of ambroxol hydrochloride push-pull osmotic pump controlled-release tablets%盐酸氨溴索双层渗透泵控释片体外释放及Beagle犬生物等效性

    Institute of Scientific and Technical Information of China (English)

    马银玲; 赵锋; 金晓利; 王静; 曹德英

    2011-01-01

    目的:研究自制片的体外释药行为及体内生物等效性.方法:采用相似因子(f2)为评价指标,考察自制片的体外释放行为;采用单剂量交叉试验考察Beagle犬口服自制片与参比制剂的生物等效性及体内外相关性.结果:自制片体外释放零级特征明显(r=0.992 1)且释药完全(90%).犬体内两制剂生物等效,相对生物利用度(100.0±12.6)%,自制片体内外相关性良好(r=0.98).结论:盐酸氨溴索双层渗透泵控释片具有很好的开发前景.%OBJECTIVE In vitro release and bioequivalence of self-made tablets were evaluated. METHODS Using similar factor (f2) as evaluate index, in vitro release of self-made tablets were evaluated. In vivo study, ultilizing Beagle dogs orally single-dose crossing administrated, the bioequivalence between the self-made controlled-release tablets and marketed sustained capsules and the correlation coefficient between the fraction of absorption in vivo and the release rate in vitro were investigated. RESULTS Self-made tablets possessed character of zero-order release (r = 0.992 1) and drug release completely(90%) in vitro release. The relative bioavailability was (100. 0 ± 12. 6) %. The correlation coefficient between the fraction of absorption in vivo and the release rate in vitro was 0. 98. CONCLUSION Ambroxol hydrochloride push-pull osmotic pump controlled-releasetablets have much developing potential.

  13. 成年比格犬骨髓间充质干细胞体外定向成骨诱导实验研究%An in vitro experimental study on the induction of bone marrow mesenchymal stem cells of adult beagle dogs into osteoblasts

    Institute of Scientific and Technical Information of China (English)

    许蕾; 李家锋; 唐巍; 韩建国; 孙晋虎

    2015-01-01

    Objective To cultivate the bone marrow mesenchmyal stem cells ( BMSCs) of adult beagle dogs in vitro and observe their morphology.These cells were then induced into osteoblasts, facilitating the development of bone tissue engineering in the future.Methods The BMSCs were first collected from adult beagle dogs and then cultivated in vitro using the semi-marrow adherence method.The second generation of BMSCs were divided into the following two groups:an experimental group with addition of fetal bovine serum ( FBS) as well as equivalent amounts of Inducer 1 ( dexametha-sone,β-glycerol phosphate disodium salt pentahydrate, and L-ascorbic acid) and Inducer 2 ( BMP-2) , and a con-trol group cultured in media containing FBS alone.Then, on Days 3, 7, 14, and 21 of induction, both groups were de-termined for alkaline phosphatase ( ALP) activity, followed by alizarin red staining and ALP staining three weeks later. The differentiation of induced osteoblasts was identified by Von-Kossa staining.Results On Days 3, 7, 14, and 21 of induction, the activity of ALP in the experimental group became weakened, despite after initial enhancement.In con-trast, no significant changes were found in the control group.After three weeks of induction, positive results were shown for alizarin red staining, ALP staining and Von-Kossa staining in the experimental group, in comparison with negative staining in the control group.These findings were consistent with the characteristics of osteoblasts, indicating the forma-tion of osteoblasts in the experimental group.Conclusion The BMSCs of adult beagle dogs can directionally differentiate into osteoblasts in the presence of an inducing agent.%目的:通过将成年比格犬骨髓间充质干细胞(BMSCs)建立体外培养体系,观察及掌握细胞生长形态,运用诱导剂体外定向诱导分化为成骨细胞,为后期建立骨组织工程提供种子细胞。方法提取成年比格犬的BMSCs,运用半骨髓直接贴壁法进

  14. 低强度脉冲超声波联合引导组织再生术促进牙周骨开窗缺损修复的动物实验%Low intensity pulsed ultrasound combined with guided tissue regeneration for promoting the repair of defect at canines periodontal fenestration in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    郑鸿; 卢礼; 宋锦璘; 高翔; 邓锋; 王智彪

    2011-01-01

    Objective To evaluate the effects of low intensity pulsed ultrasound(LIPUS)combined with guided tissue regeneration(GTR) for the repair of the periodontal fenestration defect at the canines in Beagle dogs. Methods Four Beagle dogs were used for establishing the periodontal fenestration defect. Sixteen canines of four Beagle dogs were simple randomly assigned into experimental group 1[LIPUS(60 mW/cm2,20 min/d)irradiation + GTR + the periodontal fenestration defect], experimental group 2[LIPUS(60 mW/cm2,20 min/d)irradiation + the periodontal fenestration defect], experimental group 3(GTR+ the periodontal fenestration defect) and control group(the periodontal fenestration defect). Experiments conducted 28 d. The temperature of the gingive′s surface of each group was tested every 14 days(analyzed by Wilcoxon rank sum test with SPSS 13.0). The demineralized bone tissue slices of the periodontal fenestration were obtained for histologic staining after 4 weeks treatment. Results Clinically all the treatment groups healed well. The change of gingive′s surface temperature[M(Q)] before and after LIPUS irradiating were:0.225(0.463)℃(experimental group 1),0.265(0.133)℃ (experimental group 2),0.090(0.115)℃(experimental group 3);-0.175(0.370)℃(control group). The P value of experimental group 1 and 2 with pre-and post-treatment each time were both 0.027. Histology of the demineralized bone tissue revealed that in experimental group 1, the bone defect was filled with fresh bone-like tissues, proliferatively active osteoblasts and newly formed cementum-like tissues along the defect surface. In experimental group 3, there were more new cementum-and bone-like tissues than in experimental group 2 and control group. In experimental group 2,the new bone collagen was more mature than in experimental group 3 and control group. In control group,there was less growth of new cementum along the notch, and the new bone collagen was immature. Conclusions LIPUS combined with GTR may

  15. Changes in the behavior and physiological data of the beagles during the test of the floating escape device%漂浮救生装置上浮试验期间犬行为及部分生理指标的变化

    Institute of Scientific and Technical Information of China (English)

    张玲; 冯旭; 张凯; 蒋定文; 张建国; 沈先荣; 王海军; 何颖; 杨翊方; 储智勇; 余浩

    2012-01-01

    目的 观察漂浮救生装置上浮试验期间犬的行为及部分生理指标变化,评价该装置对动物的安全性.方法 采用数字表法,将6条比格犬随机分为2组,实验组和对照组各3条.将实验组置于漂浮救生装置内,在该装置上浮试验期间,通过高清数码摄像,采用Observer系统分析2组犬的行为,采用G3多参数监护仪连续监测记录2组犬的心率、心电图、血压、体温及呼吸频率.结果 漂浮救生装置上浮试验期间,实验组犬的平均血压、呼吸频率、平均体温漂浮前期分别为(108±14) mm Hg、(55±31)次/min、(37.9±0.1)℃,与对照犬(98±15)mm Hg、(4l±20)次/min、(37.5±0.4)℃比较差异有统计学意义(P<0.05),较对照组犬要高,与实验组犬的环境变化有关;实验组犬情绪比较安定,不同阶段之间实验组犬行为存在差异但未发现挣扎、狂躁等行为.结论 漂浮救生装置动物上浮试验结果表明,装置的释放、浮起和海面拖带过程对动物是安全的,实验期间未观察到该漂浮救生装置对犬有不可逆损伤.%Objective To observe changes in the behavior and physiological data of the beagles during the test of the floating escape device and also to evaluate the safety of the floating escape device.Methods Six male beagles were randomly divided into the experimental group and the control group,each consisting of 3 animals.The animals in the experimental group were put in the floating escape device.The high-definition digital video camera and the observer system were used to analyze the animal behavior.Heart rate,electrocardiogram (ECG),blood pressure,body temperature and respiration of the animals were continuously monitored by using the G3 multi-parameter monitoring system,during the process of the floating test.Results During the floating test,respiratory frequency,blood pressure,heart rate and temperature of the beagles in the experimental group fluctuated within normal range

  16. Reconstruction of Anterior Cruciate Ligament of Beagle Dogs by Autologous Tendon with Platelet﹣rich Plasma%自体肌腱加富血小板血浆重建比格犬前交叉韧带的实验研究

    Institute of Scientific and Technical Information of China (English)

    马震胜; 张磊; 鄂钢; 马骏驰; 孙欣; 马超; 刘志奎; 刘子洪

    2016-01-01

    Objective To research early histological and biomechanical outcome of reconstruction anterior cruciate liga-ment of beagle dogs by autologous tendon adding platelet-rich plasma. Methods We selected 36 healthy adult male beagle dogs and divided them into model group and research group. The same side tendons of the flexor digitorum longus(8 cm in length)were harvested in all dogs and folded in half to create a 4-cm-long double-stranded graft in two groups,but we added platelet-rich plasma when reconstruction of autologous tendon in research group. At the four,eight and twelve-week,6 beagle dogs drawing randomly from two groups were sacrificed and 12 knee joints were obtained including the femoral components and the anterior cruciate ligament. Eight of them were to study the biomechanics and the rest were for histological examination. At last,statistical analysis was carried out on the experimental data. Results Four-weeks after opertiaon,histological findings showed that there were the formation of fibrovascular in the tendon-bone interface in model group and there were more intensive fibrovascular and arranged in order associated with type Ⅱcollagen deposition of chondriod cells from bone growth to the tendon in the tendon-bone interface in research group. Eight-week after operation,there were formation of the new bone around ten-dons and the thickening of the bone tunnel wall. However,during this period,the collagen fibers machine were not sufficient and tendon continuity of bone could only occasionally be seen in model group. In research group,the collagen fibers grow to maturity and the continuity of the tendon bone and the small amounts of vertical arrangement of Sharpey-like fibers in the tendon bone interface center visible could be seen. At the twelve-week,the small amounts of vertical arrangement of Sharpey-like fibers could be seen in model group. In research group,the tendon bone healing process to enter a period of chronic inflammato-ry reaction and the

  17. 国产与进口重组人胰岛素注射液Beagle犬皮下注射的生物等效性研究%Bioequivalence of domestic and imported recombinant human insulin injections after sc administration in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    申文晋; 宋紫辉; 范明源; 项宗尚; 蔡永明; 张宗鹏

    2014-01-01

    目的:以美国礼来公司重组人胰岛素注射液(优泌林R,Humulin R)为对照品,评价国产重组人胰岛素注射液(Insulin R)的相对生物利用度和生物等效性。方法采用自身随机交叉给药方案,12只健康Beagle犬分别sc同剂量Insulin R和Humulin R,按设计采集6 h内动态血标本。采用罗氏血糖仪与检测血药浓度同步测定动物血糖水平;放射免疫分析(RIA)法检测血药浓度;试验数据采用DAS 3.0药动学程序拟合计算参数,并进行生物等效性分析。结果 Beagle犬自身交叉sc Insulin R和Humulin R 0.5 U/kg后的血浆最低葡萄糖浓度(Cmin)分别为(1.6±0.4)、(1.6±0.2)mmol/L;达到最低浓度所需时间(tmin)分别为(1.0±0.5)、(1.1±0.6)h。Insulin R和Humulin R的主要药动学参数均值分别为:达峰时间(tmax)为(0.43±0.21)、(0.42±0.09)h;峰浓度(Cmax)为(203.2±63.3)、(193.5±63.1)μU/mL;药时曲线下面积(AUC0-6 h)为(281.2±47.5)、(266.6±62.5)μU/(mL·h);受试药Insulin R相对于对照药Humulin R的相对生物利用度为(109.4±25.5)%。结论两种重组人胰岛素注射剂在健康Beagle犬体内具有生物等效性。%Objective To assess the pharmacokinetic and bioequivalence of two formulations of recombinant human insulin injection, using locally manufactured Insulin R as test and Humulin R (Eli Lilly and Company) as reference. Methods Twelve Beagle dogs were assigned into two groups in which the dogs were sc given Insulin R and Humulin R at the dose of 0.5 U/kg according to a randomized two-phase crossover. The plasma concentration of Insulin R and Humulin R at 6 h intervals was determined using radioimmunoassay (RIA) method with the time course of changes in blood glucose level monitored. The pharmacokinetic parameters were calculated by DAS 3.0 software. Results Beagle dogs were treated with Insulin R and Humulin R following single

  18. LC-MS/MS simultaneous determination and pharmacokinetics of trimebutine and it's metabolite in Beagle plasma%LC-MS/MS同时测定曲美布汀和活性代谢物在Beagle犬体内的血药浓度及其药代动力学研究

    Institute of Scientific and Technical Information of China (English)

    杨振东; 张琪; 马博; 胡莹莹; 郑雅雅; 王永禄

    2012-01-01

    Objective:To develop an LC -MS/MS method for the simultaneous determination of trimebutine(TM) and N-monodemethyltrimebutine(N - TM) concentration in dog plasma to study the pharmacokinetics of TM maleate in healthy Beagles. Method;The analytes were extracted from plasma samples by liquid -liquid extraction and sibutramine was selected to be the internal standard. Detection was carried out on a triple quadrupole tandem mass spectrometer in multiple reactions monitoring ( MRM) mode using positive electrospray ionization (ESI). The ion combination of m/z 388.2-w/z 343. 2,m/z 374. 2-m/z 195. 2,m/z 280. 3-wn/z 125. 1 was used to qualify TM,N - TM and the internal standard,respectively. After a single oral dose of 300 mg TM ,the concentrations of TM and N - TM were detected and the pharmacokinetic parameters were calculated by DAS 2.0. Result: The calibration curve was in good linearity over the range of 1 -500 ng · mL-1 (r =0. 9959) for TM and 0. 2 - 100 ng · mL-1 (r =0.9951) for N - TM. The intra - day and inter -day precisions (RSD) were lower than 10% and the extraction recovery was higher than 85% for both determined compounds. The main pharmacokinetic parameters of Cma,Tmax and Tl/2 were (192 ±32.1 )ng · mL-1, (0.667 ±0. 258)h, (10. 8 ±4. 27)h for trimebutine(47. 1 ±22. 6)ng · mL-1 ,(1.08 ±0. 492)h,7. 06 ±2. 53 h for N -TM,respectively. Conclusion; The method is shown to be simple, accurate, sensitive and specific for the simultaneous determination of TM and N - TM in Beagles plasma and can be used for the pharmacokinetic study.%目的:建立灵敏稳定的HPLC-MS/MS方法,用于测定Beagle犬血浆中的曲美布汀(TM)及N-去甲基曲美布汀(NTM)含量,并研究曲美布汀片剂在健康Beagle犬体内的药代动力学.方法:样品处理采用液液萃取方法,选择西布曲明(IS)为内标.进行HPLC-MS/MS分析,采用ESI源,MRM离子检测模式,TM、N-TM和IS的检测离子对分别为m/z 388.2→343.2,m/z 374.2→195.2,m/z 280.3→125.1.

  19. Pharmacokinetics and tissue distribution of FGFC1,a novel marine fibrinolytic compound in Beagle dogs%比格犬体内FGFC1药物代谢动力学特征及组织分布的研究

    Institute of Scientific and Technical Information of China (English)

    王格; 吴文惠; 王小雨; 张朝燕; 包斌

    2015-01-01

    Aim To detect the concentration of the no-vel marine fibrinolytic compound FGFC1 ( fungi fi-brinolytic compound 1 ) on Beagle dogs ’ plasma and tissue by high performance liquid chromatography ( HPLC) , and also to investigate the pharmacokinetics and tissue distribution in Beagle dogs with intravenous injection, and to evaluate the FGFC1 into medicinal. Methods Chromatographic column: HP-C18 ( 4. 6 mm × 250 mm,5 μm); the column temperature was 40℃;the mobile phase was acetonitrile -0. 1% triflu-oroacetic acid gradient elute, the flow rate of 1 mL· min-1; the ultraviolet detection wavelength was 265 nm. The dog plasma samples were collected at different intervals after intravenous injection of three different doses (7. 5, 5. 0, 2. 5 mg·kg-1 ) of FGFC1, and the concentration of FGFC1 in plasma and tissue was deter-mined by HPLC method for estimating pharmacokinetic parameters and tissue distribution. Results The pa-rameters of 7. 5, 5. 0, 2. 5 mg·kg-1 were as follows:its elimination half-life ( T1/2β) was ( 49. 035 ± 2. 171 ) , ( 48. 422 ± 2. 113 ) and ( 48. 811 ± 2. 372 ) min, respectively;the peak concentration was (56. 48 ± 6. 23 ) , ( 48. 63 ± 5. 53 ) , ( 13. 64 ± 2. 76 ) mg · L-1 , respectively;clearance rate ( CL ) was ( 0. 0062 ± 0. 0004 ) , ( 0. 0071 ± 0. 0008 ) and ( 0. 0092 ± 0. 0006) L·min-1 ·kg-1 , respectively; mean reten-tion time ( MRT ) was ( 28. 17 ± 1. 16 ) , ( 26. 23 ± 0. 35) and (28. 66 ± 0. 84) min, respectively. Tissue distribution revealed that FGFC1 could quickly distrib-uted into the heart, liver, spleen, lung, kidney, intes-tine, stomach, brain, intestine, testicle, urine and fe-ces. Interestingly, the highest drug (FGFC1) concen-tration level was detected in the liver. Conclusions The above study shows a good pharmacokinetic profile as well as a good tissue distribution, indicating a drug-gable nature of the structure. Therefore, we consider that FGFC1 is promising for further study.%

  20. Effect of Low-Intensity Pulsed Ultrasound Combined with Guided Bone Regeneration on Canine Periodontal Fenestration Defect in Beagle Dogs%低强度脉冲超声波联合引导骨再生术对Beagle犬牙周骨开窗缺损修复效应的研究

    Institute of Scientific and Technical Information of China (English)

    高翔; 宋锦璘; 邓锋; 赵纯亮; 王智彪

    2012-01-01

    The aim of this work is to investigate the effect of combined application of low-intensity pulsed ultrasound (LIPUS) and guided bone regeneration (GBR) on canine periodontal fenestration defect in Beagle dogs. In the experiments, five Beagle dogs were used for establishing 5 mm ×5 mm periodontal fenestration defect. Four canines in each dog were randomly divided into LIPUS (90 mW/cm , 20 min/d) group, LIPUS (90 mW/cm , 20 min/d) + GBR group, GBR group and Control group. Each group had 5 teeth. In order to compare the tissue repair among the groups, the specimens of periodontal fenestration were obtained for histological analysis (HE and Masson staining) , Micro-CT test and histometric analysis (the measurement of new bone area, NBA and its percentage in initial defect area, NBA% ) after 4 weeks. Micro-CT test results showed that the area of new alveolar bone from large to small was LIPUS + GBR group, GBR group, LIPUS group, and Control group. Histological analysis showed that the Masson staining of new bone in LIPUS and LIPUS + GBR group was mainly red while GBR and control group was mainly blue.. It suggested the new bone collagen in LIPUS group and LIPUS + GBR group was more mature than in GBR group and control group. Histometric analysis showed that NBA and NBA% were 0. 39 mm and 7. 74% in respectively LIPUS group; 0. 52 mm2 and 10. 30% respectively in LIPUS + GBR group; 0. 41 mm2 and 7. 44% respectively in GBR group; 0. 24 mm and 4. 64% respectively in Control group. Differences between groups were significant (P <0. 05). It suggested the amount of new alveolar bone from large to small was LIPUS + GBR group, GBR group, LIPUS group, and Control group. LIPUS combined with guided bone regeneration (GBR) can promote early repair of periodontal fenestration defect.%本研究探讨了低强度脉冲超声波(LIPUS)联合引导骨再生术(GBR),对Beagle犬牙周骨开窗缺损的修复效应.构建5只Beagle犬尖牙颊侧根中1/3处5 mm×5 mm矩形牙周骨开

  1. Experimental study on the potential role of BME-10X collagen/hydroxyapatite bone graft in periodontal tissue regeneration of beagle%BME-10X型胶原/羟磷灰石人工骨引导 比格犬牙周组织再生的实验研究

    Institute of Scientific and Technical Information of China (English)

    陈斌; 吴文蕾; 张其清; 黄晓峰; 陈湘华

    2011-01-01

    Objective To evaluate the potential role of BME-10X collagen/hydroxyapatite (HA) bone graft in perio-dontal tissue regeneration. Methods Four 18 months old male beagles in the experiment were treated with non-surgical periodontal therapy. At the sites of mandibular 3rd and 4th premolars at the time of dogs were treated with non-surgical periodontal therapy one week later, the teeth with the same name in (he same jaw were selected to the experimental groupCT group) or the control group(C group) at random. The defects in T group were filled with BME-10X collagen/HA bone graft while the defects in C group were filled with nothing. The dogs were sacrificed in twelve weeks and analyzed by histopathology. Results The defects in T group got more tissue regeneration compared with the defects in C group. The height of new boneCNB) was G.01±0.14) mm in T group versus (1.32±O.ll) nun in C group(P0.05). The new tissue guided by the bone graft was the same as the normal tissue in histopathology analysis. Conclusion The results of the study suggest that BME-10X collagen/HA bone graft is a good bone graft for periodontal tissue regeneration.%目的 评估BME-10X型胶原/羟磷灰石人工骨引导比格犬牙周组织再生的能力.方法 选取18月龄雄性比格犬4只,进行牙周基础治疗.基础治疗结束1周后,选取下颌第3、4前磨牙,同颌对侧同名牙随机纳入实验组或者对照组,制造牙周缺损,实验组植入BME-10X型胶原/羟磷灰石人工骨,对照组不植入任何材料.术后12周处死动物,进行组织病理学分析.结果 与对照组相比,实验组获得了较多的组织再生,实验组和对照组新生牙槽骨的高度分别为(3.01 ±0.14)、(1.32±0.11) mm,二者间差异有统计学意义(P<0.05).实验组和对照组新生牙周膜组织的高度分别为(3.12±0.19)、(1.35±0.12) mm,二者间差异有统计学意义(P<0.05).实验组和对照组新生牙骨质的高度分别为(3.30±0.15)、(2.70±0.12) mm,二

  2. 即刻种植后采用GBR术和植入PRF对骨结合影响的实验研究%A comparative evaluation of immediate dental implant with guided bone regeneration versus PRF:an experimental study in the beagle dog

    Institute of Scientific and Technical Information of China (English)

    肖慧娟; 柳忠豪; 杨云东; 许胜

    2014-01-01

    目的:比较研究即刻种植后用GBR术和植入PRF对种植体周骨缺损区的成骨能力。方法:以成年Bea-gle犬为实验动物,拔除犬双侧下颌P2、 P3、 P4牙,即刻植入种植体,所植入的种植体距近中根拔牙窝的近中壁有3~4mm的骨缺损间隙,采用半口自身对照,一侧行即刻种植+GBR (A组),一侧即刻种植+PRF (B组),术后三个月处死动物,取下带有种植体的下颌骨标本,进行组织学观察。对两组种植体周围的骨结合率和新骨生成率运用统计软件SPSS13.0进行统计学分析。结果: A组、 B组骨缺损处3个月时均被新骨充填,两组种植体周围的骨结合率和新骨生成率差异无统计学意义。结论:限于本研究中,即刻种植术中采用GBR和植入PRF对骨缺损区的引导骨再生效果相同。%Objective:The aim of the study was to compare the bone formation of the bone defect area around immediate dental implant combined with GBR and with PRF. Methods: This study was carried out on six beagle dogs. Six implants were placed in 2P2, 3P3 and 4P4 regions in each dog immediately after tooth extraction. The width of the bone defect between the mesial wall of the mesial root socket and the implant was 3~4 mm. The bone defect area was disposed with GBR (A group) and was filled with PRF (B group). After 3 months of healing, the dogs were sacrificed and prepared for histological analysis of bone to implant contact and new bone formation. Results:The bone defect area around the implant was filled with new bone in both group A and B. No statistically significant difference of the percentage of new bone formation and bone-to-implant contact ration (BIC) were observed among two groups. Conclusion: Limited in this study, the bone formation ability of the bone defect area around immediate dental implant combined with GBR and with PRF was basically the same.

  3. Keynote Address: Science Since the Medicean Stars and the Beagle

    Science.gov (United States)

    Partridge, B.; Hillenbrand, L. A.; Grinspoon, D.

    2010-08-01

    In 2009, the world celebrates both the International Year of Astronomy (IYA), commemorating the 400th anniversary of Galileo's first observations of the heavens with his telescope, and the 200th anniversary of the birth of Charles Darwin and the 150th anniversary of the publication of his Origin of Species, a key impetus for the 2009 Year of Science. In this keynote address, the three presenters (distinguished scientists themselves) will reflect on how these recent centuries of astronomical and scientific discovery have changed our perspectives about the universe, the natural world, and ourselves—and underpin our education and public outreach efforts to help ensure continued scientific advance in the future.

  4. 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

  5. Progestogen-related gross and microscopic changes in female Beagles.

    Science.gov (United States)

    Nelson, L W; Kelly, W A

    1976-01-01

    Long-term studies of megestrol acetate and chlormadinone acetate in 100 female dogs are in progress. Doses of zero, one, 10 and 25 times the expected human dose of megestrol acetate and 25 times the expected human dose of chlormadinone acetate (on a milligram per kilogram body weight basis) are being given daily. During the first 4 years, eight dogs from each of the five groups were killed. The principal gross findings included enlarged uteri with mucoid material in the lumina, mammary development in dogs given middle and high doses of megestrol acetate and chlormadinone acetate, and thickened gallbladder walls in dogs given high doses of each. Histologic evaluation showed inhibition of ovulation for progestogen-treated dogs and suppression of ovarian follicular development with the high doses. Cystic endometrial hyperplasia was slight in the low-dose dogs and moderate to severe in most of the high-dose dogs; a few also had ulcerative endometritis and pyometra. The mammary glands of dogs given the middle and high doses produced lobules, acini, and secretion exceeding natural metestrus. Slight to marked cystic mucinous hyperplasia occurred in the gallbladders of most dogs given the high doses. Tow high-dose megestrol dogs had clinical signs and microscopic pancreatic, renal, and ocular changes indicative of diabetes mellitus.

  6. 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%细胞因子治疗4.5 Gyγ射线照射比格犬造血损伤的机制初探

    Institute of Scientific and Technical Information of China (English)

    李明; 王金香; 缪竞诚; 朱南康; 罗庆良; 从玉文; 张学光; 欧红玲; 邢爽; 黄海潇; 熊国林; 谢玲; 赵燕芳; 赵振虎; 王宁

    2010-01-01

    目的 探讨多种细胞因子配伍应用治疗4.5 Gyγ射线照射比格犬造血系统损伤的作用及可能机制.方法 16只比格犬均给予4.5 Gy60Coγ射线全身照射,随机分为照射对照、综合对症和细胞因子3组.细胞因子组在综合对症支持治疗的基础上应用rhG-CSF、rhIL-11和rhIL-2联合治疗,采用流式细胞术检测外周血中CD34+细胞含量、有核细胞周期及凋亡比例.结果 4.5 Gyγ射线照射犬外周血中CD34+细胞含量在照射后1 d明显下降(照射对照组和综合对症组分别为照前值的61.3%和52.1%),G0/G1期有核细胞比例增加(分别为99.27%和99.49%),且凋亡率(分别为26.93%和21.29%)和坏死率(分别为3.27%和4.14%)明显升高(与照前值比较,P<0.05);而经过细胞因子治疗后,外周血中CD34+细胞含量在照射后1 d即明显升高(为照前值的135.6%),G0/G1期有核细胞比例(99.71%)进一步增加,其凋亡率(5.66%)和坏死率(1.60%)明显低于照射对照和综合对症组.结论 本研究的细胞因子组合可能通过动员骨髓中CD34+细胞到外周血,使细胞周期阻滞在G0/G1期,减少细胞凋亡,从而促进极重度骨髓型急性放射病犬造血功能的恢复.%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 Gy60 Coγ-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 Gy60 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,rhlL-11 and rhIL-2 were administered subcutaneously to treat dogs in cytokines group.The percentage of CD34+cells,cell cycle and

  7. 雌二醇在人、比格犬和大鼠的肝微粒体中体外代谢比较研究%In vivo comparison of estradiol metabolism in liver microsomes of human, Beagle dog and rat

    Institute of Scientific and Technical Information of China (English)

    宋玉乔; 廖杰; 刘华伟; 艾常虹; 张峰

    2012-01-01

    The inter-species differences of estradiol metabolism were investigated in human, Beagle dog and rat liver microsomes by comparing enzyme kinetics of parent drug and the formation of its major metabolites. The incubation systems of estradiol with liver microsomes of the three species were optimized in terms of estradiol concentration, microsomal protein content and incubation time. The concentrations of estradiol and its metabolites were measured by LC-MS/MS method. The t1/2 Clint,CLh, Km and Vmax of estradiol incubated with male human liver microsomes were 40.02 ± 8.32 min, 41.39 ± 6.57 mL·min-1·kg-1, 13.81 ± 12.36 mL·min-1·kg-1, 26.8 ± 6.99 umol·L-1 and 0.75 ± 0.92 μmol·L-1·min-1, respectively. The corresponding parameters of female human were 44.71 ± 10.21 min, 29.85 ± 8.97 mL·min-1·kg-1, 0.01 ± 0.68 mLmin-1·kg-1, 44.2 ± 7.73 μmol·L-1 and 1.27 ± 4.41 μmol·L-1·min-1, that of male dog were 21 ± 7.33 min, 165.53 ± 29.33 mL·min-1·kg-1, 26.01 ± 8.39 mL·min-1·kg-1, 19.5 ± 7.34 μmol·L-1 and 1.6 ± 0.65 μmol·L-1·min-1, that of female dog were 25.5 ± 5.32 min, 135.11 ± 42.34 mL·min-1·kg-1, 0.24 ± 3.18 mL·min-1·kg-1, 8.33 ± 6.32 μmol·L-1 and 0.51 ± 2.15 umol·L-1·min-1, that of male rat were 5.11 ± 3.84 min, 485.63 ± 36.52 mL·min-1·kg-1, 49.57 ± 15.29 mL·min-1·kg-1u, 62 ± 13.74 umol·L-1 and 19.16 ± 9.67 μmolL·min-1, and that of female rat were 7.0 ± 3.69 min, 354.82 ± 33.33 mL·min-1·kg-1, 8.04 ± 3.23 mL·min-1·kg-1, 35.38 ± 7.65 umol·L-1 and 8.39 ± 4.91 μmol·L-1·min-1, respectively. There were nine metabolites detected from all the three species, but the relative amounts of the metabolites generated were different in three species. The results indicted that the major phase I metabolic pathway of estradiol was similar in the liver microsomes from all the three species. However, the inter-species differences were found in the view of relative amounts of the metabolites as well as the metabolic

  8. Study on Bioequivalence of Levodopa Micro-capsule Floating Tablets in Beagle Dogs after Multi-dose Ad-ministration%复方左旋多巴微囊漂浮片多剂量给药后在Beagle犬体内的生物等效性研究Δ

    Institute of Scientific and Technical Information of China (English)

    陈雪珊; 滕亮; 贺鑫韬; 马桂芝

    2016-01-01

    目的:研究左旋多巴微囊漂浮片多剂量给药后在Beagle犬体内的生物等效性。方法:取犬6只,平均分为左旋多巴微囊漂浮片组和复方左旋多巴制剂组(多巴丝肼片,参比制剂),每次ig 200 mg(以左旋多巴计),每8 h给药1次,连续给药4 d,进行双周期交叉实验。以高效液相色谱法测定犬体内左旋多巴的血药浓度,计算药动学参数,评价生物等效性和左旋多巴稳态时的血药浓度波动情况。结果:左旋多巴微囊漂浮片和参比制剂在犬体内的cmax分别为(4.23±0.75)、(8.47±1.18)µg/ml,AUC0-∞分别为(12.18±1.16)、(13.81±2.12)μg·h/ml,tmax分别为(1.83±0.26)、(0.67±0.13)h;微囊漂浮片AUC0-∞与参比制剂AUC0-∞的几何均值比的90%置信区间为80.61%~97.90%,cmax几何均值比的90%置信区间为42.75%~57.63%;二者的tmax差异有统计学意义。二者血药浓度的波动度分别为(283.914±43.217)%、(506.489±78.965)%,波动系数分别为(177.463±7.873)%、(187.405±1.650)%,微囊漂浮片的波动度明显小于参比制剂。结论:左旋多巴微囊漂浮片具有良好的缓释特性;多剂量给药后与参比制剂吸收程度生物等效,且血药浓度的波动程度较小。%OBJECTIVE:To study the bioequivalence of Levodopa micro-capsule floating tablets in Beagle dogs after multi-dose administration. METHODS:6 dogs were collected and divided into Levodopa micro-capsule floating tablets group and Com-pound levodopa preparation group (Benserazide tablet,reference preparation). They were given levodopa 200 mg intragastrically, every 8 h,for consecutive 4 day. In two-period crossover test,HPLC method was established to determine the concentration of le-vodopa in dog. The pharmacokinetic parameter,bioequivalence and plasma concentration fluctuation of steady state were calculated. RESULTS:The main pharmacokinetic

  9. 绿色荧光蛋白基因转染示踪比格犬体内骨髓间充质干细胞分化%Green fluorescent protein genes transdution and tracer the differentiation of bone mesenchymal stem cells in beagles

    Institute of Scientific and Technical Information of China (English)

    张海峰; 杜子婧; 赵丹阳; 韩修国; 韩冬

    2016-01-01

    Objective To observe differentiation and transformation of bone mesenchymal stem cells (BMSCs)labeled with green fluorescent protein (GFP)technology in bone tissue engineering.Methods Adenoviral delivery of GFP genes (Ad-GFP)transfected to canine BMSCs.The morphology of BMSCs,alkaline phosphatase (ALP)and alizarin red staining were observed with the help of invert light microscope,and the expression of GFP was scrutinized by using fluorescence microscope.Once succeeding,the centrifuged BMSCs were collected and mixed with beta-tricalcium phosphate (β-TCP),then they were transplanted under tibial periosteum.The beagles using the above way to construct tissue engineering bone were marked group A,which only withβ-TCP transplated into tibial periosteum were marked group B, and which withβ-TCP subcutaneously placed were marked group C.In the postoperative 2 weeks,histology and immunohistochemistry results were studied and the expression of GFP was observed by laser scanning confocal microscope.Results After induced differentiation in vitro, observing BMSCs found that ALP staining and alizarin red mineralization nodules staining were positive.Histology observation revealed that compared with group B,abundant bone formed and neovascularized significantly in group A,and bone formation did not exist in group C. Immunohistochemistry staining showed that type Ⅰ collagen and platelet endothelial cell adhesion molecule-1 (CD31)were positive in group A, type Ⅰ collagen and CD31 were positive partly in group B rather than group C.The expression of typeⅠcollagen and CD31 were analyzed in group A and group B by the way of semi-quantitative immunohistochemical staining.The value of type Ⅰ collagen and CD31 had significant differences between group A and group B.The expression of GFP was observed by laser scanning confocal microscope in group A not in group B nor group C.Conclusion BMSCs is the important factor to accelerate the generation of tissue engineering bone instead

  10. Vector flow mapping for assessing Beagle dogs′ left ventricular vortex in selective bi-polar single site cardiac pacing%超声血流向量成像评价健康比格犬心脏不同位点起搏左心室血流涡旋

    Institute of Scientific and Technical Information of China (English)

    丁戈琦; 尹立雪; 王志刚; 陆景; 李文华; 张红梅

    2015-01-01

    Objective To investigate the changes of left ventricular(LV) vortex strength(VS) and distribution during selective cardiac pacing in a phases of cardiac cycle using vector flow mapping techniques ,and associate with LV mechanical performance ,so as to provide basic experimental database for optimizing the sites of the artificial cardiac pacing in clinic conditions .Methods Eight heathy open‐chest Beagle dog models were employed for selective right ventricular apical (RVAP ) ,left ventricular apical (LVAP) and lateral wall pacing (LVLP) .The standard two‐dimensional apical three views with color Doppler flow and dynamic two‐dimensional images were acquired consecutively in three cardiac cycles for further off‐line analysis ,conventional parameters were measured at same time .Results Compared with baseline ,LVSV ,LVEF ,LVCO and dp/dtmax were both reduced ,and the parameters obtained leftside cardiac pacing were lower than that of right ventricular pacing ( P < 0 0.5) ,there′s no significant difference in E/Vp .The vortex pattern ,distribution and vorticity at six typical phases induced by selective cardiac pacing were totally different from those at baseline with sinus rhythm ,and leftside pacing were worsen than RVAP ,the LVAP were most obvious .On multivariable regression analysis ,the VS during ES (VSES ) at baseline was independently related to late‐diastolic VS and longitudinal strain (R2 = 0 6.3 ,P < 0 0.01 and P=0 0.03 ,respectively) .Conclusions The selective cardiac pacing could induce intracardiac vortex changes and differ from that at baseline ,and the persistence of vortex from late diastole into ES is a haemodynamic measure of coupling between diastole and systole .%目的:应用超声血流向量成像(VFM)技术评价健康比格犬心脏不同位点起搏心动周期内左室流场涡旋分布、强度变化及心肌力学参数,探讨起搏状态下心腔内涡旋变化特征,为临床优化人工心脏起搏位点提供流体

  11. Progressive glomerulosclerosis and renal failure following perinatal gamma radiation in the beagle

    Energy Technology Data Exchange (ETDEWEB)

    Jaenke, R.S.; Phemister, R.D.; Norrdin, R.W.

    1980-06-01

    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.

  12. A Two-Mutation Model of Carcinogenesis: Application to Ra-226 Induced Osteosarcoma Prevalence in Beagles

    NARCIS (Netherlands)

    Venema LB; Leenhouts HP; LSO

    1994-01-01

    Dit rapport is een aanvulling op het RIVM-rapport (nr. 749251001) van Leenhouts en Chadwick en is bedoeld als achtergrond-document voor het twee-mutatie-carcinogenese model en voor zijn implementatie. Het twee-mutatie-carcinogenese model is gebaseerd op een gemodificeerd twee-stappen model van

  13. Oxidative stress in limpets exposed to different environmental conditions in the Beagle Channel

    Energy Technology Data Exchange (ETDEWEB)

    Malanga, Gabriela; Estevez, Maria Susana; Calvo, Jorge; Puntarulo, Susana

    2004-09-20

    The aim of this work was to study the oxidative profile of digestive glands of two limpets species (Nacella (Patinigera) magellanica and Nacella (Patinigera) deaurata) exposed to different environmental conditions. The intertidal population of N. (P.) magellanica is subjected to a wide variety of stresses not experienced by N. (P.) deaurata. Although a typical electron paramagnetic resonance (EPR) spectrum of ascorbyl radical in digestive gland from both limpets was observed, neither ascorbyl radical content nor the ascorbyl radical content/ascorbate content ratio was significantly different, suggesting that the difference in the environmental conditions did not appear to be responsible for developing alterations in the oxidative status of both organisms at the hydrophilic level (e.g. cytosol). Lipid peroxidation in the digestive glands was estimated, both as the content of thiobarbituric acid reactive substances (TBARS) and as the content of lipid radicals assessed by EPR, in both organisms. TBARS and lipid radical content were 34.8 and 36.5%, respectively, lower in N. (P.) magellanica as compared to N. (P.) deaurata. On the other hand, total iron content and the rate of generation of superoxide anion were 47.9 and 51.4%, respectively, lower in N. (P.) magellanica as compared to N. (P.) deaurata. The activity of catalase and superoxide dismutase (SOD) was 35.3 and 128.6% higher in N. (P.) magellanica as compared to N. (P.) deaurata, respectively. No significant differences were determined between the digestive glands of both molluscs regarding the content of total thiols. {alpha}-Tocopherol and {beta}-carotene content were significantly lower in N. (P.) magellanica as compared to N. (P.) deaurata. A distinctive EPR signal for the adduct Fe-MGD-NO (g = 2.03 and a{sub N} = 12.5 G) was detected in the homogenates of digestive glands of both limpets. A significant difference in the content of the Fe-MGD-NO adduct in digestive glands from N. (P.) magellanica and N. (P.) deaurata (491 {+-} 137 and 839 {+-} 63 pmol/g FW, respectively) was observed. Taken as a whole, the data presented here indicated that coping with environmental stressing conditions requires a complex adjustment of the physiological metabolic pathways to ensure survival by minimizing intracellular damage. It is likely that N. (P.) magellanica has a particular evolutionary adaptation to extreme environmental conditions by keeping iron content low and antioxidant activities high.

  14. Campus Renewal in the 1980's: The New Voyage of the Beagle.

    Science.gov (United States)

    Hewitt, Clinton N.

    1982-01-01

    An approach to campus planning and renewal during declining enrollment is described. The process uses computer programing to integrate seven factors: building suitability to program, schedule, existing commitments, cost, effect on general use spaces, campus planning compatibility, and disturbance of current assignments of units not in the study.…

  15. 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...

  16. Incomplete restoration of immobilization induced softening of young beagle knee articular cartilage after 50-week remobilization.

    Science.gov (United States)

    Haapala, J; Arokoski, J; Pirttimäki, J; Lyyra, T; Jurvelin, J; Tammi, M; Helminen, H J; Kiviranta, I

    2000-01-01

    The aim of this study was to characterize the biomechanical and structural changes in canine knee cartilage after an initial 11-week immobilization and subsequent remobilization period of 50 weeks. Cartilage from the immobilized and remobilized knee was compared with the tissue from age-matched control animals. Compressive stiffness, in the form of instant shear modulus (ISM) and equilibrium shear modulus (ESM) of articular cartilage, was investigated using an in situ indentation creep technique. The local variations in cartilage of glycosaminoglycan (GAG) concentration were measured with a microspectrophotometer after safranin O staining of histological sections. Using a computer-based quantitative polarized light microscopy method, collagen-related optical retardation, gamma, of cartilage zones were performed to investigate the collagen network of cartilage. Macroscopically, cartilage surfaces of the knee joint remained intact both after immobilization and remobilization periods. Immobilization caused significant softening of the lateral femoral and tibial cartilages, as expressed by ESM (up to 30%, p test points. The changes of ESM were positively correlated with the alterations in GAG content of the superficial and deep zones after immobilization and remobilization. This confirms the key role of protoglycans in the regulation of the equilibrium stiffness of articular cartilage. As a conclusion, immobilization of the joint of a young individual may cause long-term, if not permanent, alterations of cartilage biomechanical properties. This may predispose joint to degenerative changes later in life.

  17. The beagle dog MicroRNA tissue atlas: identifying translatable biomarkers of organ toxicity

    OpenAIRE

    2016-01-01

    Background MicroRNAs (miRNA) are varied in length, under 25 nucleotides, single-stranded noncoding RNA that regulate post-transcriptional gene expression via translational repression or mRNA degradation. Elevated levels of miRNAs can be detected in systemic circulation after tissue injury, suggesting that miRNAs are released following cellular damage. Because of their remarkable stability, ease of detection in biofluids, and tissue specific expression patterns, miRNAs have the potential to be...

  18. 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.

  19. Chronic effects of the novel glucocorticosteroid RPR 106541 administered to beagle dogs by inhalation.

    Science.gov (United States)

    Miller, G K; Valerio, M G; Pino, M V; Larson, J L; Viau, A; Hamelin, N; Labbé, R; Banks, C M

    2000-01-01

    The preclinical safety of RPR 106541, a novel 17-thiosteroid, was evaluated in young adult and mature dogs by inhalation exposure for 26 weeks and 52 weeks, respectively. A dry powder formulation of RPR 106541 in lactose was administered to young adult dogs (approximately 6 months of age at initiation) at doses of 0 (air and placebo controls), 10, 100, or 1,000 microg/kg/d for 26 weeks. A solution-based aerosol formulation was administered to mature dogs (approximately 10 months at initiation) from a pressurized metered dose inhaler at 0 (air and placebo controls), 10, 50, and 150 microg/kg/d for 52 weeks. Clinical evidence of glucocorticosteroid-induced immunosuppression was observed by weeks 20-26 following relatively high dose exposures (100 microg/kg/d and 1,000 microg/kg/d) in young dogs receiving the dry powder formulation for 26 weeks. Classic glucocorticosteroid effects were observed, including adrenocortical atrophy, reduced bone mass with retention of epiphyseal growth plates in long bones, prominence of stromal adipose tissue in bone marrow, and atrophy of lymphoid tissues. Inhalation administration of RPR 106541 to sexually mature dogs facilitated more definitive characterization of endocrine affects of RPR 106541 as compared with administration in younger, sexually immature animals. Significant effects in female reproductive organs included absence of corpora lutea in association with atresia of vesicular follicles within the ovaries, endometrial hyperplasia, and lobular development of mammary tissue. Discordant development of mammary tissue, accumulation of secretory material within hyperplastic endometrial glands, and hypertrophy of uterine lining epithelium in absence of ovulation were consistent with a secondary progestin effect by a potent glucocorticosteroid.

  20. Phenotypic analysis and effects of sequential administration of activated canine lymphocytes on healthy beagles.

    Science.gov (United States)

    Hoshino, Yuki; Takagi, Satoshi; Osaki, Tomohiro; Okumura, Masahiro; Fujinaga, Toru

    2008-06-01

    We attempted to accumulate the basic data for evaluation of activated lymphocyte therapy for small animal medicine. The peripheral blood mononuclear cells (PBMCs) collected from healthy dogs were activated using anti-CD3 antibody and human recombinant (hr) interleukin (IL)-2 and reactivated using hr interferon (IFN)-alpha and hr IL-2. The property of obtained cells was compared with PBMCs. The number of cells was shown to have increased approximately>50 -fold by cultivation. The proportion of CD8+ cells was significantly increased, the cytotoxicity of the cultured cells was revealed to have been reinforced. Additionally, CD56 mRNA levels tended to have increased. The cells obtained by this method were confirmed to be activated lymphocytes. Furthermore, we investigated the effects of sequential administration of the obtained cells to healthy dogs. By sequential administration of the activated lymphocytes, the cell proliferative activity, proportion of CD4+ cells and CD8+ cells, and serum IFN-gamma concentration were shown to have increased, and no severe adverse effects were observed. Consequently, activated lymphocytes could be induced using anti-CD3 antibody and IL-2 in healthy dogs, and sequential administration of activated lymphocytes reinforced the recipient's immunity.

  1. The Beagle Channel Dispute between Argentina and Chile: An Historical Analysis

    Science.gov (United States)

    1985-11-22

    Superba, are crustaceans with a maximum length of 6 cm. They are found in swarms in the upper 200 meters of water and are a high source of protein...Sudan 160 I0 .1,* Rhodc-ia 92 6Nigeria 91 6 North Africa I 158 8 Libya 694 60 Algeria 223 19 Morocco 213 18 Tunisia 29 3 South America I 069 8 Brazil...Italy 16. Algeria 882 2.2 USSR 17. Taiwan 737 1.9 USA 18. Kuwait 664 1.7 USSR 19. Argentina 642 1.6 FR Germany 20. Brazil 641 1.6 United Kingdom 21

  2. Part II: bioavailability in beagle dogs of nimodipine solid dispersions prepared by hot-melt extrusion.

    Science.gov (United States)

    Zheng, Xin; Yang, Rui; Zhang, Yu; Wang, Zhijun; Tang, Xing; Zheng, Liangyuan

    2007-07-01

    The aim of the present work was to investigate the in vitro dissolution properties and oral bioavailability of three solid dispersions of nimodipine. The solid dispersions were compared with pure nimodipine, their physical mixtures, and the marketed drug product Nimotop. Nimodipine solid dispersions were prepared by a hot-melt extrusion process with hydroxypropyl methylcellulose (HPMC, Methocel E5), polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA, Plasdone S630), and ethyl acrylate, methyl methacrylate polymer (Eudragit EPO). Previous studies of XRPD and DSC data showed that the crystallinity was not observed in hot-melt extrudates, two T(g)s were observed in the 30% and 50% NMD-HPMC samples, indicating phase separation. The weakening and shift of the N-H stretching vibration of the secondary amine groups of nimodipine as determined by FT-IR proved hydrogen bonding between the drug and polymers in the solid dispersion. The dissolution profiles of the three dispersion systems showed that the release was improved compared with the unmanipulated drug. Drug plasma concentrations were determined by HPLC, and pharmacokinetic parameters were calculated after orally administering each preparation containing 60 mg of nimodipine. The mean bioavailability of nimodipine was comparable after administration of the Eudragit EPO solid dispersion and Nimotop, but the HPMC and PVP/VA dispersions exhibited much lower bioavailability. However, the AUC(0-12 hr) values of all three solid dispersions were significantly higher than physical mixtures with the same carriers and nimodipine powder.

  3. Comparison of Different Periodontal Healing of Critical Size Noncontained and Contained Intrabony Defects in Beagles

    Directory of Open Access Journals (Sweden)

    Sheng-Qi Zang

    2017-01-01

    Conclusions: One-wall intrabony defects treated with ABB and CM did not show less periodontal regeneration than that in 3-wall intrabony defect. The noncontained 1-wall intrabony defect might be a more discriminative defect model for further research into periodontal regeneration.

  4. Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration.

    Science.gov (United States)

    Kenward, Hannah; Pelligand, Ludovic; Elliott, Jonathan

    2014-08-01

    Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies.

  5. 13N-ammonia PET/CT detection of myocardial perfusion abnormalities in Beagle dogs after local heart irradiation.

    Science.gov (United States)

    Song, Jianbo; Yan, Rui; Wu, Zhifang; Li, Jianguo; Yan, Min; Hao, Xinzhong; Liu, Jianzhong; Li, Sijin

    2016-12-01

    To determine the potential value of (13)N-ammonia positron emission tomography (PET)/computed tomography (CT) myocardial perfusion imaging (MPI) for detection of myocardial perfusion changes at early stage induced by radiation damage.

  6. 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.

  7. Fourteen-Day Subacute Intravenous Toxicity Study of Hypertonic Saline/ Dextran 70 and its Constituents in Beagle Dogs

    Science.gov (United States)

    1989-11-01

    NCj00 ()- OL - N Ln r rn~~ -(> 00) N:) uf 0) c c ni CNt oj5 r-~n& f (rin 1) ( (Y 0 (Y) ~DC) 1 D -4C \\𔃻 D (~N (, D0 -4 rn1 C𔃻N Lflr r q n nlf >1 x D4...increased amounts of eosinophilic fibers ( collagen ) , and by an increase in pale amphophilic background material (matrix).4 --Endocarditis, Valvular: One

  8. Cicatrización de implantes inmediatos con carga inmediata y sin carga. Estudio experimental en perro Beagle

    OpenAIRE

    Mareque Bueno, Santiago

    2015-01-01

    Los implantes inmediatos muestran una alta tasa de éxito en numerosos estudios (Chen y cols. 2004). Así mismo, la carga inmediata de implantes oseointegrados muestra tasas de éxito parecidas a los implantes cargados de forma diferida, siempre y cuando se cumplant una serie de requisitos (Del Fabbro y col. 2006). Existen estudios clínicos que han evaluado la supervivencia y el éxito del uso combinado de ambas técnicas de forma simultánea (Crespi y cols. 2010). Sin embargo, ex...

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

    OpenAIRE

    Ko-Ning Ho; Eisner Salamanca; Kuo-Chi Chang; Tsai-Chin Shih; Yu-Chi Chang; Haw-Ming Huang; Nai-Chia Teng; Che-Tong Lin; Sheng-Wei Feng; Wei-Jen Chang

    2016-01-01

    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 pur...

  10. Studies on Beagle Dogs and C3H Mice Experimentally Infected with Ehrlichia canis%犬埃立克体动物感染实验

    Institute of Scientific and Technical Information of China (English)

    马玉海; 潘华; 佟世德; 陈香蕊; 孙洋; 张雪颍; 莫卓寿

    2001-01-01

    为探讨比格犬和C3H小鼠对犬埃立克体的敏感性,建立犬埃立克体病实验模型,用我国埃立克体病病犬血白细胞分别接种比格犬和C3H小鼠.接毒后比格犬和C3H小鼠均为PCR阳性,比格犬与最易感的德国牧羊犬自然感染埃立克体病的临床表现和病理学变化基本一致.结果表明比格犬和C3H小鼠对犬埃立克体均有较高敏感性.

  11. Comparison of bone cancer risks in beagle dogs for inhaled plutonium-238 dioxide, inhaled strontium-90 chloride, and injected strontium-90

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-01

    There is a continuing need to understand dose-response relationships for ionizing radiation in order to protect the health of the public and nuclear workers from undue exposures. However, relatively few human populations have been exposed to doses of radiation high enough to cause observable, long-term health effects from which to derive dose-response relationships. This is particularly true for internally deposited radionuclides, although much effort has been devoted to epidemiological studies of the few types of exposures available, including lung cancers in uranium miners form the inhalation of the radioactive decay products of Ra, liver cancers in patients injected with Thorotrast X-ray contrast medium containing Th, bone cancers in radium dial painters who ingested Ra, and bone cancers in patients who received therapeutic doses of Ra. These four types of exposures to internally deposited radionuclides provide a basis for understanding the health effects of many other radionuclides for which a potential for exposure exists. However, potential exposures to internally deposited radionuclides may differ in many modifying factors, such as route of exposure, population differences, and physical, chemical, and elemental forms of radionuclides. The only means available to study many of these modifying factors has been in laboratory animals, and to then extrapolate the results to humans. Three conclusions can be drawn from this example.

  12. PK/PD Modelling of the QT Interval: a Step Towards Defining the Translational Relationship Between In Vitro, Awake Beagle Dogs, and Humans.

    Science.gov (United States)

    Marostica, Eleonora; Van Ammel, Karel; Teisman, Ard; Gallacher, David; Van Bocxlaer, Jan; De Ridder, Filip; Boussery, Koen; Vermeulen, An

    2016-07-01

    Inhibiting the human ether-a-go-go-related gene (hERG)-encoded potassium ion channel is positively correlated with QT-interval prolongation in vivo, which is considered a risk factor for the occurrence of Torsades de Pointes (TdP). A pharmacokinetic/pharmacodynamic model was developed for four compounds that reached the clinic, to relate drug-induced QT-interval change in awake dogs and humans and to derive a translational scaling factor a 1. Overall, dogs were more sensitive than humans to QT-interval change, an a 1 of 1.5 was found, and a 10% current inhibition in vitro produced a higher percent QT-interval change in dogs as compared to humans. The QT-interval changes in dogs were predictive for humans. In vitro and in vivo information could reliably describe the effects in humans. Robust translational knowledge is likely to reduce the need for expensive thorough QT studies; therefore, expanding this work to more compounds is recommended.

  13. Comparative Analysis of Hemorheology Indexes Between Beagle Dog and Human%比格犬和人血液流变学指标的比较分析

    Institute of Scientific and Technical Information of China (English)

    袁进; 陈丽; 吴清洪; 张嘉宁; 顾为望

    2009-01-01

    目的 探讨比格犬的血液流变学特性,并和人的血液流变性进行比较.方法 采集成年比格犬和人的血液样品,分别检测其全血黏度(高、中、低切变率)、血浆黏度、红细胞比容、血沉及血浆纤维蛋白原等5项血液流变学指标.结果 (1)雄性比格犬的WBV值(150s-1、1s-1)均显著低于雌性(P<0.05,P<0.05);(2)人类中,男性的WBV值(1s-1)和HCT值显著高于女性(P<0.05,P<0.01),而男性的ESR值则显著低于女性(P<0.01);(3)比格犬的血液流变学指标中WBV(1s-1)、ESR均显著低于人类(P<0.05),而PV、HCT和Fi则显著高于人类(P<0.01).结论 比格犬的血液流变学指标与人类相比相差较远.

  14. Pharmacokinetics of N, N-diacetylcystine in Beagle dogs%N,N-双乙酰胱氨酸在毕格犬体内的药动学

    Institute of Scientific and Technical Information of China (English)

    廖建民; 吴小云; 张奉国; 沈子龙; 张瑾

    2007-01-01

    目的 研究毕格犬静脉注射不同剂量N,N-双乙酰胱氨酸(DiNAC)后的药动学.方法 毕格犬12只随机分成3组,分别静脉注射DiNAC 25,12.5,6.25 mg/kg,在设定的时间点采血,反相高效液相色谱法测定血浆中的DiNAC浓度,DAS程序计算其药动学参数.结果 毕格犬静脉给予DiNAC后,其血药浓度-时间曲线符合二室模型一级动力学过程.AUC0→∞分别为3 849.7±157.7,1 683.0±60.5,757.1±344.2 mg/(L·min),与给药剂量成良好的线性关系(r=0.999 3);Gmax分别为91.99±15.13,53.37±3.88,23.20±7.07 mg/L,与给药剂量呈线性关系(r=0.993);而t1/2α为1.1~1.9 min,t1/2β为34.2~47.3 min,分布容积(Vd)为0.38~0.49 L/kg,显示非剂量依赖性特征.结论 DiNAC在毕格犬体内的药动学过程为二室模型一级动力学过程,具有分布快,消除迅速的特点.

  15. INHALATION OF ULTRAFINE PARTICLES HAS NO EFFECT ON IMMUNE RESPONSE AND AIRWAY REACTIVITY 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...

  16. Comparative Efficacies of a 3D-Printed PCL/PLGA/β-TCP Membrane and a Titanium Membrane for Guided Bone Regeneration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jin-Hyung Shim

    2015-10-01

    Full Text Available This study was conducted to evaluate the effects of a 3D-printed resorbable polycaprolactone/poly(lactic-co-glycolic acid/β-tricalcium phosphate (PCL/PLGA/β-TCP membrane on bone regeneration and osseointegration in areas surrounding implants and to compare results with those of a non-resorbable titanium mesh membrane. After preparation of PCL/PLGA/β-TCP membranes using extrusion-based 3D printing technology; mechanical tensile testing and in vitro cell proliferation testing were performed. Implant surgery and guided bone regeneration were performed randomly in three groups (a no membrane group, a titanium membrane group, and a PCL/PLGA/β-TCP membrane group (n = 8 per group. Histological and histometric analyses were conducted to evaluate effects on bone regeneration and osseointegration. Using the results of mechanical testing; a PCL/PLGA/β-TCP ratio of 2:6:2 was selected. The new bone areas (% in buccal defects around implants were highest in the PCL/PLGA/β-TCP group and significantly higher than in the control group (p < 0.05. Bone-to-implant contact ratios (% were also significantly higher in the PCL/PLGA/β-TCP and titanium groups than in the control group (p < 0.05. When the guided bone regeneration procedure was performed using the PCL/PLGA/β-TCP membrane; new bone formation around the implant and osseointegration were not inferior to those of the non-resorbable pre-formed titanium mesh membrane.

  17. Determination of Oleanolic Acid in Plasma of Beagle by HPLC-MS%Beagle犬血浆中齐墩果酸浓度的测定

    Institute of Scientific and Technical Information of China (English)

    唐芳; 郭歆; 李焕德

    2007-01-01

    目的 建立测定Beagle犬血浆中齐墩果酸的HPLC-MS测定法,以进行齐墩果酸滴丸的生物利用度和药动学研究.方法 采用HPLC-MS,以Hypersil GOLD(2.1 mm×150 mm,5 μm)色谱柱,流动相为20 mmoL·L-1醋酸铵-乙腈(24∶76),流速0.3 mL·min-1,检测波长为210 nm.结果 Beagle犬血浆内源性物质不干扰样品的测定,血浆中齐墩果酸浓度在3.88~240.00 μg·L-1内线性关系良好(r=0.999 3);最低检测浓度为3.88 μg·L-1;方法平均回收率大于85%;平均提取回收率大于80%;日内和日间RSD均小于10%.结论 所建立的测定方法准确可靠,符合生物样品分析要求.

  18. RP-HPLC测定血浆中间硝苯地平的浓度%Determination of M-nifedipine in Beagle Dogs by RP-HPLC

    Institute of Scientific and Technical Information of China (English)

    杨志福; 周四元; 杨铁宏; 梅其炳

    2006-01-01

    目的建立高效液相色谱法测定Beagle犬血浆中间硝苯地平(m-nifedipine,m-Nif)的浓度,并研究其代谢动力学规律.方法采用正交设计优选色谱和提取条件,血浆样品中m-Nif经碱化、萃取后,用反相高效液相色谱法(RP-HPLC)进行分析测定.色谱分析柱为C18柱(250mm×4.6mm,5μm);流动相为甲醇-10mmol·L-1磷酸盐缓冲液pH5(83∶17);流速为1.0ml/min;检测波长为350nm;内标为MN9201(二氢吡啶类).结果线性范围为10~500ng·ml-1,最低检测浓度为10ng·ml-1,低、中、高3种不同浓度的方法回收率分别为110.84%、105.60%、104.23%;提取回收率分别为92.75%、104.46%、105.12%,日内RSD分别为9.70%、3.05%和1.75%;日间RSD分别为14.53%、7.21%和5.44%.结论本方法稳定、简便、准确,可用于Beagle犬血浆中m-Nif的浓度测定及药代动力学研究.

  19. HPLC法测定Beagle犬血浆中芹菜素的浓度%HPLC in determination of apigenin in plasma of Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    朱亮; 李盈

    2008-01-01

    芹菜素(apigenin)属于黄酮类化合物,广泛存在于水果、蔬菜、豆类、茶叶中。一,其中芹菜含量最高。车前子、络石藤、藿香等药用植物中均含有大量芹菜素口一。研究发现,其有抗癌、抗病毒、抗菌、抗过敏,抗血管脆性和血小板聚集及抗糖尿病并发症等多种生理活性与药理作用,对人类的肿瘤、衰老、心血管病等退行性疾病的治疗和预防有重要意义。

  20. Pharmacokinetics of m-nifedipine in Beagle dogs%间硝苯地平在Beagle犬体内的药代动力学

    Institute of Scientific and Technical Information of China (English)

    杨志福; 周四元; 杨铁虹; 梅其炳

    2004-01-01

    目的用反相高效液相色谱法研究间硝苯地平(m-nifedipine,m-Nif)在Beagle犬体内的药代动力学特征.方法正交设计优化色谱分离条件,Beagle犬分别iv给予m-Nif 0.288 mg·kg-1和ig m-Nif 1.152,3.456,10.370mg·kg-1.用反相高效液相色谱法分析血浆中原型药物浓度,血浆药物浓度-时间数据用3P97药代动力学软件分析.结果Beagle犬iv m-Nif,其体内过程符合二室模型,T1/2β为116.8 min;ig给予m-Nif后在Beagle犬体内的代谢符合一室模型,其中低剂量(1.152 mg·kg-1)组Cmax为20μg·L-1,T1/2(Ke)为147 min;中剂量(3.456 mg·kg-1)组Cmax为36μg·L-1,T1/2(Ke)为122 min;高剂量(10.37 mg·kg-1)组Cmax为69μg·L-1,T1/2(Ke)为144 min.结论Beagle犬ig和iv m-Nif后,血浆中药物消除迅速,口服绝对生物利用度较低.

  1. Allotransplantation of the lung without immunosuppression after transplantation. II. Combined autotransplantation of bone marrow and allotransplantation of lung. [Gamma radiation, beagles

    Energy Technology Data Exchange (ETDEWEB)

    Blumenstock, D.A.; Cannon, F.D.; Franck, W.A.; Hales, C.A.; Kazemi, H.; Ferrebee, J.W.

    1977-09-01

    A series of seven animals underwent allotransplantation of a lung from a donor matched for the recognition of serologically defined (SD) antigens by the use of alloantisera followed by autotransplantation of bone marrow without further immunosuppression. In two animals, the lung was transplanted into the recipient immediately before the administration of total-body irradiation and in five, the lung was transplanted after completion of total-body irradiation. In the first group, one animal is living at 46 months with good function of the transplant. The other was killed at 6 months with chronic rejection. In the second group, three of five animals are alive 46 to 47 months after transplantation. Two others died early, one of cardiac tamponade and the other of diffuse hemorrhage before engraftment of marrow could be accomplished. Significant function of the transplant was demonstrated in all long-term survivors. Four control animals, subjected to marrow harvest and reimplantation of the left lung followed by total-body irradiation and marrow reinfusion, were studied to determine the possible deleterious effects of the total-body irradiation and marrow transplant procedure. Pulmonary function studies showed some reduction in ventilation and perfusion to the upper lobe areas, which was probably related to technical factors but did demonstrate no severe adverse effects to the procedures. Autologous bone marrow reconstitution after total-body irradiation combined withallotransplantation of the lung has allowed long-term survival and function of lung transplants without the necessity for administration of immunosuppressive drugs after the transplantation procedure.

  2. Estudio comparativo del contacto hueso-implante y el área ósea periimplantaria en implantes inmediatos con y sin carga inmediata en el perro beagle

    OpenAIRE

    Villaverde Ramírez, Gabriel

    2012-01-01

    Introducción: Aunque en la actualidad ya disponemos de suficiente literatura clínica que avala la utilización de la carga inmediata como un protocolo estándar bajo determinadas circunstancias clínicas y radiográficas, en realidad, muy poco sabemos sobre los mecanismos biológicos íntimos que intervienen en la cicatrización ósea periimplantaria en tales condiciones. Y, sobre todo, cómo estos mecanismos biológicos de unión entre hueso-implante podrían no alterarse con la realizaci...

  3. Determination of the Chronic Mammalian Toxicological Effects of TNT. Twenty-Six Week Subchronic Oral Toxicity Study of Trinitrotoluene (TNT) in the Beagle Dog.

    Science.gov (United States)

    1983-06-01

    gums. In addition, high dose dogs showed reduced food Intake with associated loss of body weight. Slight reductions In body weight gains were apparent...sensitive than males In the Increase of liver weights. Enlargement of the liver and microscopic evidence of cirrhosis were also seen, but were...urinalysis showed an Increase in levels of urinary protein and billrubin in TNT fed dogs, however histologic changes In the kidneys were not In evidence

  4. SD大鼠及beagle犬肾组织形态参数研究%Studies on Renal Histological Parameters in SD Rats and Beagles

    Institute of Scientific and Technical Information of China (English)

    徐勤; 沈逸萍; 苏俊芳; 罗振亮; 许安丽

    2006-01-01

    [目的]了解SD大鼠及beagle犬肾组织学参数,为肾毒理病理诊断提供组织学判断依据.[方法]以40只成年SD大鼠及20只成年beagle犬为研究对象,雌雄各半,大鼠在12周龄处死,beagle犬在12月龄时处死.以体积分数为10%中性福尔马林固定肾脏,石蜡包埋,5μm切片,苏木素-伊红(HE)染色.以Spot Advanced图像分析软件测量犬和大鼠皮质及近髓肾单位、肾小球长径、短径及平均直径,同时比较种属间及不同性别动物之间的区别.[结果]beagle犬皮质肾单位肾小球长径大约为96μm,短径大约为76μm;近髓肾单位肾小球长径约为120μm,短径约为94μm,雌雄犬无显著性差异,但近髓肾单位长径、短径均大于皮质肾单位长径及短径.SD大鼠皮质肾单位肾小球长径约为87μm,短径约为64μm,近髓肾单位肾小球长径约为88μm,短径约为64μm,雌雄大鼠间无显著性差异,皮质及近髓肾单位肾小球长、短径亦无显著性差异.beagle犬组的皮质和近髓肾单位的长、短径均大于SD大鼠组(P<0.05或P<0.01).[结论]beagle犬近髓肾单位大于皮质肾单位,而SD大鼠近髓肾单位及皮质肾单位大小无显著性差异;beagle犬肾小球较SD大鼠肾小球稍大,性别对beagle犬及SD大鼠肾小球大小无影响.

  5. Correction: Zhao, J., et al. Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs. Molecules 2015, 20, 20031-20041.

    Science.gov (United States)

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

    2016-06-09

    The authors wish to correct the funding projects number of "Natural Science Foundation of Jiangsu Province" in the Acknowledgments section of this paper [1]: The correct funding projects number should be "No. BK20130403", not "No. BK2013403".[...].

  6. Cinnarizine food-effects in beagle dogs can be avoided by administration in a Self Nano Emulsifying Drug Delivery System (SNEDDS)

    DEFF Research Database (Denmark)

    Christiansen, Martin Lau; Holm, Rene; Kristensen, Jakob;

    2014-01-01

    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....

  7. Cloning and Sequence Analysis of Signaling Lymphocyte Activation Molecule Gene in Beagle Dog%比格犬SLAM基因的克隆与序列分析

    Institute of Scientific and Technical Information of China (English)

    苏建青; 褚秀玲; 江成; 马秀亮; 张吉清

    2011-01-01

    对比格犬的犬瘟热病毒细胞受体——信号淋巴细胞激活因子(SLAM)基因进行克隆及测序分析,并与其他物种的SLAM受体进行比较,以期发现其关键结构部分.用RT-PCR从Con A刺激后的犬外周血淋巴细胞中扩增SLAM基因,将目的片段连接到PMD18-T载体上,转化感受态细胞,筛选阳性克隆,测序.结果显示,克隆的比格犬SLAM基因序列全长1 029 bp,编码342 aa.与人、牛、狐、羊和海豹等SLAM序列同源性约74.6%~98.4%.SLAM基因序列的系统进化树分析显示,犬、狐狸和海豹的关系较近.理化分析显示SLAM属于具有信号肽的Ⅰ型跨膜糖蛋白,信号肽位于N段1 aa~26 aa,跨膜区位于239aa~263 aa,膜外区存在5个潜在的糖基化位点,膜内区包括3个保守的酪氨酸基序.SLAM基因部分区域的高度保守性,为犬瘟热病毒的宿主范围扩大奠定了基础.

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

    Science.gov (United States)

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

    2014-06-01

    NP260 was designed as a first-in-class selective antagonist of α4-subtype GABAA receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog>human>rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity.

  9. Using Buildroot for building Embedded Linux Systems

    OpenAIRE

    Ruiz González, Mariano

    2013-01-01

    This document describes the basic steps to developed and embedded Linux-based system using the BeagleBoard. The document has been specifically written to use a BeagleBoard development system based on the OMAP `processor.

  10. Marsikulguri hukutas meetrine eksimus / Arko Olesk

    Index Scriptorium Estoniae

    Olesk, Arko, 1981-

    2005-01-01

    Briti teadlased usuvad, et on leidnud kahe aasta eest kaduma läinud marsikulguri Beagle 2. Euroopa Kosmoseagentuuri teadlased lootsid, et Beagle 2 maandub tasasele pinnasele. Paraku põrkas Marsile elu otsima pidanud Beagle 2 teadlaste väitel vastu kraatri äärt, aparaadid said kahjustada ning ühendus Maaga kadus

  11. 纳米红色元素硒在Beagle犬的药代动力学分析%Pharmacokinetic study of the nano red elemental selenium in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    王学文; 郑青山; 张劲松; 桂常青; 胡剑北; 孙瑞元

    2004-01-01

    目的:观察纳米红色元素硒(Nse)在Beagle犬的药代动力学特点.方法:催化荧光法测定用药前基线值和用药后不同时间血硒浓度,分别用血硒实测值和上升值计算药动学参数.结果:Nse代谢符合一室模型,吸收较快,药峰值为155 mg·L-1(实测值)和135.4 mg·L-1(上升值),达峰时间约为2 h,但消除较慢,清除率极低,t1/2长达34.6 h(实测值)和20h(上升值).结论:长时间、大剂量服用Nse可能导致药物蓄积;体内具有基线值时,计算药动学参数宜用变化值,不宜用实测值.

  12. 西藏小型猪、小猎犬与人血液流变学指标的比较研究%Comparative studies of hemorheological parameters in Tibet mini-pigs, Beagle dogs and human

    Institute of Scientific and Technical Information of China (English)

    袁进; 吴清洪; 陈丽; 张嘉宁; 顾为望

    2009-01-01

    目的 探讨西藏小型猪、比格犬与人血液流变学指标的相互关系.方法 采集成年西藏小型猪、比格犬和人的血液样品,用全自动血液粘度计分别测定其全血粘度(WBV,高、中、低切变率)、血浆粘度、红细胞压积、血沉及血浆纤维蛋白原5项血液流变学指标.结果 (1)雄性西藏小型猪的WBV值(150、30、5、1s~(-1))和血浆纤维蛋白原含量均显著低于雌性(P0.05).结论 与比格犬相比,西藏小型猪的血液流变学指标更接近于人.

  13. Effects of dose and duration of continuous GnRH-agonist treatment on induction of estrus in beagle dogs: competing and concurrent up-regulation and down-regulation of LH release.

    Science.gov (United States)

    Concannon, P W; Temple, M; Montanez, A; Newton, L

    2006-10-01

    Dose-response estrus-induction trials were conducted during anestrus in 93 treated and 6 control bitches, a continuous administration of the GnRH-agonist lutrelin with a potency 150 x GnRH, and at six different doses from 0.2 to 4.8 microg/kg/d for 7-14 days in 15 groups of six to eight dogs each in defined stages of natural or pharmacologically determined anestrus. Agonist treatment induced clinically and cytologically normal proestrus (in 89% of cases) within 4.8 +/- 0.2 x days, and resulted in behavioral estrus (71%), spontaneous late-proestrus LH (and FSH) surges, ovulation (59%) and pregnancy (44%) in a dose dependent manner. Outcomes of ovulation and pregnancy in most cases required that the dose be sufficiently large enough to routinely stimulate a large initial increase in LH and FSH (i.e., > or = 0.6 microg/kg/d), and of sufficient duration (i.e., > 7 days) to ensure that supra-basal gonadotropin levels persistedntil no longer needed for spontaneous continuation of an induced proestrus. Success additionally required that the GnRH dose be modest enough (i.e., induction results, including pregnancy rates of 100% in six bitches treated in natural-anestrus bitches, six bitches in which anestrus had been advanced by a luteolytic prostaglandin treatment and in six bitches in which anestrus had been extended by progesterone implants administered for 3 months. Although lutrelin is not commercially available, these results provide guidelines for the development of estrus-inducing protocols with other GnRH-agonists of known biopotencies.

  14. Pharmacokinetics of Tramadol, Venlafaxine hydrochloride, Sulpiride and Rotundine after simultaneous administration in Beagles%4种药物联用在Beagle犬体内的药物动力学

    Institute of Scientific and Technical Information of China (English)

    李颐; 粱茂植; 王莉

    2006-01-01

    目的测定舒必利、曲马多、颅通定和盐酸文拉法新联合给药后,Beagle犬体内的药物动力学的参数变化,揭示4种药物在Beagle犬体内的药物动力学特征.方法 24只Beagle犬单次ig不同剂量的舒必利、曲马多、颅通定和盐酸文拉法新的均匀混合粉末,HPLC-Fluor法测定血浆中各成分的浓度,观察剂量增加对4种药物在体内的影响.结果曲马多高剂量组的t 1/2较中、低剂量组延长,使C max和AUC 0-∞显著增高;随着文拉法新剂量的增加,t 1/2延长,C max和AUC 0-∞显著增高;颅通定高剂量组与中、低剂量组比较,C max和AUC 0-∞的差异均有统计学意义;舒必利亦呈相似的统计学结果.结论 Beagle犬体内4种药物的药-时曲线变化均呈一室开放模型,梯度剂量给药后的药-时曲线显示剂量依赖关系,呈一级动力学过程;4种药物间存在药物的相互作用,影响各自在Beagle犬体内的药物动力学过程,尤其显著延长曲马多、万拉法新和舒必利的t 1/2.

  15. Determination of mesalazine and its major metabolite in Beagle dog plasma by LC-MS/MS%LC-MS/MS法测定Beagle犬血浆中的美沙拉嗪及其代谢物的浓度

    Institute of Scientific and Technical Information of China (English)

    田玉林; 邸欣; 王鑫; 覃娟; 刘有平

    2013-01-01

    目的 建立柱前衍生化LC-MS/MS法测定Beagle犬血浆中美沙拉嗪(5-ASA)及其主要代谢物N-乙酰-5-氨基水杨酸(N-Ac-5-ASA)的浓度,并将此方法用于美沙拉嗪肠溶片在Beagle犬体内的药物动力学研究.方法 血浆样品经丙酸酐衍生后,以乙酸乙酯进行液液萃取.色谱分离采用Thermo ODS-2 HYPERSIL(150 mm ×4.6 mm,5 μm)色谱柱,流动相为体积分数为0.2%的甲酸水溶液-甲醇(体积比为60∶40),流速为1.0 mL· rnin-1(柱后分流比为5∶3).质谱检测采用选择反应监测(SRM)模式,在电喷雾电离(ESI)源负离子化方式下,监测反应分别为m/z 208→107(美沙拉嗪衍生物),m/z 194→107(N-乙酰-5-氨基水杨酸),和m/z192→148(内标物对氨基苯甲酸衍生物).测定6只Beagle犬分别单次给予美沙拉嗪肠溶片500 mg后不同时刻血浆中美沙拉嗪及代谢物N-乙酰-5-氨基水杨酸的浓度,采用DAS 2.1.1软件以非房室模型计算药物动力学参数.结果 血浆中美沙拉嗪和N-乙酰-5-氨基水杨酸的线性范围分别为0.05 ~50.00 mg·L-1和0.01~1.00 mg·L-1,定量下限分别为0.05 mg·L-和0.01 mg·L-1;低、中、高3个质量浓度质控样品的日内,日间精密度均小于14.6%,准确度分别为95.8%~96.4%和93.3%~98.4%,提取回收率均在70.2%~ 80.8%之间.美沙拉嗪的主要药物动力学参数:t1/2为(3.9±1.3)h,tmax为(3.7±0.5)h,ρmax为(27.8±6.3) mg·L-1,AUC0-t为(144.4±39.4) mg·h·L-1,AUC0-∞为(150.8±33.3)mg·h·L-1.结论 本法适用于血浆中美沙拉嗪及N-乙酰-5-氨基水杨酸的浓度测定.

  16. 盐酸坦洛新缓释胶囊在犬体内的药动学%Pharmacokinetic study of tamsulosin hydrochloride sustained-release capsules in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    张晓梅; 朱梅; 孙天慧; 王明新; 刘津爱; 赵怀清

    2011-01-01

    目的 建立犬血浆中坦洛新浓度的测定方法,并应用于盐酸坦洛新缓释胶囊中坦洛新犬体内的药动学研究.方法 液相色谱-串联质谱法(LC-MS/MS)测定犬血浆中的坦洛新浓度.坦洛新血浆样品经乙酸乙酯萃取,Agilent ZORBAX SB-C18柱(150 mm×2.1 mm,5 μm)分离,阿立哌唑为内标,流动相A为体积分数为0.1%的甲酸水溶液,B为乙腈,线性梯度洗脱,电喷雾电离源(ESI),以多反应离子监测(multiple reaction monitoring,MRM)方式进行正离子检测,用于分析的定量离子分别为n/z409→m/z228(坦洛新),m/z 447.5→m/z 284.8(内标:阿立哌唑).结果 犬血浆中坦洛新的线性为0.1~20.0 μg·L-1,定量下限为0.1μg·L-1,日内和日间精密度(RSD)均小于13.59%,准确度(relative error,RE)为-2.54%~4.27%.结论 本方法适用于盐酸坦洛新缓释胶囊在犬体内的药动学研究.%Objective To develop a method for the determination of tamsulosin in dog plasma and apply the method to evaluate the pharmacokinetics of tamsulosin in dog. Methods The plasma containing tamsulosin was extracted by liquid-liquid extraction and then the analyte and internal standard aripiprazole were separated on an Agilent ZORBAX SB-C18 column( 150 mm ×2.1 mm,5 μm) with a mobile phase of A-0.1 % (φ) formic acid solution,B-acetonitrile in a manner of linear gradient elution at a flow rate of 0. 3 mL·min-1, Detection was performed on a triple quadrupole tandem mass spectrum by multiple reaction monitoring (MRM) mode using the electrospray ionization technique in positive mode. Quantitation analysis was performed using multiple reaction monitoring (MRM) of the transitions of m/z409→m/z228 for tamsulosin,m/ z 447.5→m/z 284. 8 for aripiprazole, respectively, with a scan time of 200 ms per transition. Results The method was linear over the concentration range of 0.1 -20.0μg·L-1. The lower limit of quantification (LLOQ) was 0.1 μg·L-1 in dog plasma with acceptable precision and accuracy. The intra-and inter-day precision was less than 13.59% determined from quality control(QC)samples at concentrations of 0.2,2.0 and 16.0 μg·L-1,and the accuracy was between-2. 54% and 4.27%. Conclusions The method can be utilized for pharmacokinetic study of tamsolusin in dog plasma, which provide the advantage of sensitivity,specificity and simplicity.

  17. Torque de desinserción y propiedades fisico-químicas de implantes dentales grabados con ácidos fluorhídrico y nítrico: estudio experimental en perros Beagle

    OpenAIRE

    Martínez González, José María; García Sabán, Francisco; Ferrándiz Bernal, Javier; Gonzalo Lafuente, Juan Carlos; Cano Sánchez, Jorge

    2006-01-01

    Objetivo: Estudiar la composición, características superficiales y respuesta al torque de desinserción de una superficie implantaria tratada inicialmente con ácido fluorhídrico y posterior pasivado con ácidos fluorhídrico y nítrico. Diseño del estudio: En una primera fase, se seleccionaron 12 implantes en los que se estudiaron las características fisico-químicas mediante mediciones de energía dispersa de rayos X (EDS), microscopio electrónico de barrido y análisis de XPS (espectrometría de...

  18. Preparation and Bioavailability of Fenofibrate Nanosuspension in Beagle Dogs%非诺贝特纳米悬液的制备及在Beagle犬体内的生物利用度

    Institute of Scientific and Technical Information of China (English)

    翁腾飞; 戚建平; 卢懿; 尹宗宁; 吴伟

    2014-01-01

    采用沉淀法结合高压均质法制备非诺贝特纳米混悬液,利用单因素试验所得优化处方为:选择羟丙甲纤维素E3120 mg和十二烷基硫酸钠30 mg的组合为稳定剂,无水乙醇1 ml为有机溶剂,最高均质压力1 000 bar.所得制品粒径为(439.1±30) nm,多分散指数(PDI)为(0.226±0.015),ζ电位为(-28.3±0.8) mV.以市售胶囊(Lipanthyl)为参比制剂,考察纳米混悬液的体外溶出与Beagle犬的口服生物利用度.结果表明,制品在2和5 min时溶出度为76%和98%,溶出明显快于参比制剂(5和60 min时溶出度为8%和83%).Beagle犬口服非诺贝特纳米混悬液后,tmax显著缩短,Cmax和AUC0→t分别是Lipanthyl的8倍和6倍,相对生物利用度为598%.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-01

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

  20. Anti-Metastasis Effect of "Wei Chang An Decoction" on Postoperative Gastric Cancer in Beagle Dogs%中药胃肠安对比格犬胃癌术后转移的抑制作用

    Institute of Scientific and Technical Information of China (English)

    韩颖盈; 沈克平; 杨金坤

    2008-01-01

    目的:观察中药胃肠安对比格犬胃癌术后转移的防治作用.方法:以乙基硝基亚硝基胍(ENNG)致比格犬胃癌后手术切除建立胃癌术后模型,术后3周随机分为中药组、化疗组和模型组.中药组连续喂服胃肠安煎剂,化疗组每4周予1疗程FAM方案化疗,模型组不予任何药物干预.观察各组生存期、生存质量及复发转移率等.结果:中药组术后生存期、生存质量明显优于模型组和化疗组(P<0.05);对于各组生存2个月以上的复发转移率统计显示,中药组生存2个月以上者与模型组存在显著性差异(P<0.05),而化疗组与模型组之间无显著性差异.结论:中药胃肠安对胃癌术后比格犬的复发转移有一定的防治作用.

  1. Chronopharmacokinetics of compound ranitidine dispersible tablet in Beagle dogs%复方雷尼替丁分散片在Beagle犬体内的时辰药物动力学

    Institute of Scientific and Technical Information of China (English)

    石少栋; 邸欣; 王鑫; 刘有平

    2015-01-01

    目的 对Beagle犬早、晚服用复方雷尼替丁分散片后,探讨其血药浓度及药物动力学参数的时辰变化规律,为制定给药方案提供参考.方法 采用RP-HPLC法,测定6只Beagle犬于早、晚分别给予复方雷尼替丁分散片后不同时间的血药浓度,将计算得到的药物动力学参数进行统计分析.结果 雷尼替丁血药浓度在Beagle犬体内存在明显的节律性,早上给药组的药时曲线下面积(AUC)和达峰浓度(ρmax)均高于晚上给药组(P<0.05),其他药物动力学参数没有显著性差异(P>0.05).结论 雷尼替丁在Beagle犬体内血药浓度随着昼夜更替呈现节律性变化.

  2. Beagle狗口服盐酸脂壬仲胺180天的安全性评价%Toxicity of aliphatic nonyl secondary amine hydrochloride administed orally for 180 days in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    王爱平; 孙辉业; 刘宝兴; 廖明阳; 沈伽弟; 孙永立; 袁本利; 余寿忠; 瞿文生; 王和枚; 郑德琪; 李培忠

    2003-01-01

    目的: 评价Beagle狗口服盐酸脂壬仲胺(aliphatic nonyl secondary amine hydrochloride, ANSA)6 mon产生的毒性作用, 提供毒性反应的靶器官及其损害的可逆性,确定无毒反应剂量.方法:本试验设ANSA 8.0、2.0和 0.5 mg*kg-1 3个剂量组,分别相当于人临床拟用剂量的56、14和 3.5 倍;相当于狗有效治疗剂量的64、16和4倍.另设空白对照组.每组Beagle犬6只,雌雄各半.每周给药 6 d,每天口服1次,连续 180 d.结果:8.0 mg*kg-1组动物先后于给药后出现眼球向外眼角上方斜视,结膜下部充血,瞬膜呈半闭合状态,瞳孔对光反射迟纯,精神不振,严重者出现肌肉颤抖.这些症状约在药后 40 min 开始出现,持续约 8 h,第2天完全恢复正常.2.0 mg*kg-1组约2/6动物出现同样症状,但症状较轻.0.5 mg*kg-1组和对照组动物未见异常,病理组织学检查未见Beagle狗给予供试品后造成的直接脏器损伤.各组13项血液学和17项血液生化学指标均在正常范围之内.结论:在本次试验条件下,盐酸脂壬仲胺的无毒反应剂量为 0.5 mg*kg-1.

  3. Metabolites identification of nicergoline in beagle dog blood by the study of CID fragmentation pathways using HPLC/TOF-MS%HPLC/TOF-MS联用鉴定尼麦角林比格犬体内代谢物研究

    Institute of Scientific and Technical Information of China (English)

    刘炜; 王建华

    2009-01-01

    目的:尼麦角林是麦角菌中主要活性成分麦角碱的衍生物,在体内的实验中表现了显著的阻断α受体和扩张血管的活性.本文首次采用高效液相色谱串联飞行时间质谱法,对尼麦角林比格犬体内的主要代谢产物进行了研究.方法:高效液相色谱串联飞行时间质谱法,安捷伦TC-C18反相色谱柱(150 mm ×4.6 mm,5μm,USA).流动相为二元系统梯度洗脱:A:水,含1 mL/L甲酸;B:乙腈,含1 mL/L甲酸.结果:共鉴定了3个代谢产物,其中10α-甲氧基.6-二甲基-8β-羟甲基尼麦角林(MDL)是丰要的代谢产物.同时详细地研究了尼麦角林及其代谢产物的多级质谱裂解决规律,提出了菲杂环的逐级裂解规律.结论:方法准确,可为血药浓度监测提供精密的分析方法.

  4. Bioequivalence Study of Zhengqing Fengtongning Enteric-coated Tablets in Beagle Dogs%正清风痛宁肠溶片在Beagle犬体内的生物等效性研究

    Institute of Scientific and Technical Information of China (English)

    王柯静; 颜雨

    2010-01-01

    目的:研究正清风痛宁肠溶片在Beagle犬体内的生物等效性.方法:12只Beagle犬随机交叉单剂量灌胃100 mg湖南正清风痛宁肠溶片(受试制剂)或西安正清风痛宁肠溶片(参比制剂),采用高效液相色谱法测定青藤碱的血药浓度,用3p97软件拟合药动学参数,并计算生物利用度.结果:2种药物在犬体内药-时曲线符合一室模型,t_(1/2)(Ke)分别为(84.77±19.33)和(87.63±18.26)min,C_(max)分别为(0.18±0.049)和(0.13±0.018)μg·mL~(-1),t_(max)分别为(79.27±15.62)和(69.66±16.41)min,AUC_(0~t)分别为(38.51±13.23)和(35.43±9.84)μg·h~(-1)·mL~(-1);相对生物利用度为(108.71±8.97)%.结论:经方差分析和双单侧t检验,2种正清风痛宁肠溶片具有生物等效性(P>0.05).

  5. Microstructure Studies on Platelet-rich Fibrin Repairing Bone Defects in the Beagle Dog%富血小板纤维蛋白修复犬股骨髁骨缺损的微观结构研究

    Institute of Scientific and Technical Information of China (English)

    肖琼; 董露; 杨琴秋; 孙勇; 陈红亮; 赵峰; 芦帅

    2016-01-01

    目的:通过建立beagle犬股骨髁的骨缺损模型,观察富血小板纤维蛋白(platelet-rich fibrin,PRF)诱导骨再生过程中新生骨的微观结构,评价PRF修复骨缺损的特点和优势,为PRF在诱导骨再生及颌骨重建的临床应用提供新的实验依据.方法:在实验犬股骨髁制备骨缺损,按Choukroun方法制备PRF膜,将PRF膜、Bio-Oss骨替代材料及自体骨骨松质随机填入3处骨缺损.12周、24周处死动物并取材,采用微焦点计算机断层摄影系统(microfocus computerizedtomography system,Micro-CT)检测分析新生骨的几何信息和结构信息.结果:PRF新生诱导骨骨小梁结构呈板状,厚度较厚,连续性和成熟度良好,数量稍少,接近自体骨组的成骨情况,优于Bio-Oss组;观察期内均数随时间延长,有向天然骨组衍变的趋势;PRF诱导成骨表现为向心性的特点.结论:PRF可诱导新生骨形成,成骨效果接近生理状态,表现为向心性成骨方式,具有良好的应用前景.

  6. Comparison of Prognosis of Beagle Dogs Endodontic Microsurgery between Cone Beam CT and Periapical Radiography%锥形束CT与根尖片对beagle犬显微根尖手术的预后评估

    Institute of Scientific and Technical Information of China (English)

    高静; 申静; 张海峰; 靳淑凤

    2016-01-01

    目的:采用根尖片和锥形束CT(cone beam computed tomography,CBCT)对beagle犬实验性根尖周炎显微根尖手术的预后进行评估.方法:将3条beagle犬18颗前磨牙髓腔暴露于口腔环境中8周,拍摄根尖片及CBCT显示36个牙根均形成实验性根尖周炎.根管治疗后行显微根尖外科手术,术后即刻、6月分别拍摄根尖片和CBCT,根据根尖片和CBCT的根尖透射影像面积,比较二者在识别根尖骨质缺损的差别.结果:显微根尖手术后即刻CBCT矢状面、冠状面根尖透射影像面积均大于根尖片,差别具有统计学意义(P=0.000,P=0.026);CBCT矢状面、冠状面比较两组间差别无统计学意义(P=0.070).显微根尖手术后6月复查CBCT矢状面、冠状面根尖透射影像面积均大于根尖片,差别具有统计学意义(P=0.000,P=0.012);CBCT矢状面根尖透射影像面积大于冠状面,两组间差别有统计学意义(P=0.001).结论:CBCT在根尖周骨质缺损的识别优于根尖片,CBCT在根尖手术骨缺损预后评估中是一项有效的评价手段.

  7. Estudio sobre diferentes protocolos de irrigación y medicación intraconducto para la revascularización pulpar en dientes inmaduros y necróticos de perros beagle

    OpenAIRE

    Rodríguez Benítez, María Soledad

    2015-01-01

    La Endodoncia una de las técnicas más utilizadas en el día a día de la clínica dental, que consiste en la remoción del tejido pulpar inflamado y/o necrótico, la instrumentación mecánica, desinfección química del sistema de conductos radiculares, y su posterior obturación y sellado. La eliminación del tejido pulpar conlleva, pérdida de la sensibilidad pulpar, anulación de la capacidad de producir dentina y detención del desarrollo radicular. Por ello, se deben realizar todos los esfuerzo...

  8. LC-MS/MS Simultaneous Determination of Naringin and Neohesperidin in Beagle Dog Plasma%LC-MS/MS法同时测定Beagle犬血浆中柚皮苷和新橙皮苷的含量

    Institute of Scientific and Technical Information of China (English)

    刘莹莹; 陈海芳; 李明; 张瑜; 袁金斌; 杨武亮

    2011-01-01

    目的:建立同时测定Beagle犬血浆中柚皮苷和新橙皮苷的LC-MS/MS分析方法.方法:以芦丁为内标,血浆样品经乙腈沉淀蛋白处理,采用Diamonsil C18(150 mm ×4.6mm,5μm)色谱柱,以乙腈-0.1%甲酸水(25∶75)为流动相,流速为0.4 ml/min,柱温20℃;采用ESI(+)离子源,MRM扫描检测离子对为柚皮苷m/z 581→273、新橙皮苷m/z 611→303、芦丁(内标)m/z611→303.结果:血浆中柚皮苷在0.025~2.5 μg/ml、新橙皮苷在0.015~1.5 μg/ml浓度范围内线性关系良好,二者的方法回收率均近100%,分析方法的日内日间精密度RSD值均小于10%,内源性物质不干扰样品测定.结论:本方法简便、准确、灵敏度高、专属性好,适用于Beagle犬血浆中柚皮苷和新橙皮苷测定及其体内药代动力学的研究.

  9. 盐酸伊伐布雷定对单硝酸异山梨酯在比格犬体内的药动学影响%Effect of Ivabradine on isosorbide-5-mononitrate pharmacokinetics in Beagle's dogs

    Institute of Scientific and Technical Information of China (English)

    商庆节

    2015-01-01

    目的 研究盐酸伊伐布雷定对单硝酸异山梨酯在比格犬体内的药动学影响.方法 采用HPLC法测定单硝酸异山梨酯单独给药或联合盐酸伊伐布雷定给药后不同时间比格犬体内的血药浓度,采用非房室模型计算单硝酸异山梨酯药动学参数.结果 单硝酸异山梨酯单独给药及与盐酸伊伐布雷定联合使用后,在比格犬体内单硝酸异山梨酯的主要药动学参数差异无统计学意义(P<0.05).单硝酸异山梨酯联合盐酸伊伐布雷定给药相对单硝酸异山梨酯单独给药的生物利用度为100%.结论 盐酸伊伐布雷定与单硝酸异山梨酯联合用药后对单硝酸异山梨酯在比格犬体内的药动学过程无影响.

  10. Beagle犬1个月经口给予盐酸伊伐布雷定毒代动力学研究%Toxicokinetics of Ivabradine Hydrochloride in Beagles Dogs During One Month Oral Administration

    Institute of Scientific and Technical Information of China (English)

    胡海勋; 姚景春; 王现珍; 吕圆圆; 姜晓飞; 商庆节

    2014-01-01

    目的 研究盐酸伊伐布雷定在1个月经口给药长期毒性实验过程中,药物在Beagle犬体内的毒代动力学特征,及其在体内的蓄积情况.方法 在进行盐酸伊伐布雷定对Beagle犬1个月经口给药长期毒性实验过程中,分别于给药第一天和最后一天在不同的时间点采血,并用HPLC测定血浆中药物浓度.结果 高、中和低剂量组Beagle犬初次给药后的平均AUC0-t值分别为22 9、9.53和2.45 mg· h·L-1;平均AUC 0-∞值分别为26.3、9.66和2.58mg· h·L-1;平均ρmax值分别为9.19、4.72和1.91 mg·L-1;平均t1/2值分别为2.15、0.811和0.721 h.高、中和低剂量组Beagle犬末次给药后的平均AU0-t值分别为30.8、11.3和3.02mg· h·L-1;平均AUC0-∞值分别为44.7、11.6和3.45 mg··L-1;平均ρmax值分别为6.80、4.11和1.91 mg·L-1;平均t1/2值分别为4.16、1.04和1.06h.结论盐酸伊伐布雷定在Beagle犬体内毒代动力学呈现线性动力学的特征,并且无明显的药物蓄积现象,无性别差异.

  11. INTRAOPERATIVE IRRADIATION OF THE CANINE PANCREAS - SHORT-TERM EFFECTS

    NARCIS (Netherlands)

    HEIJMANS, HJ; MEHTA, DM; KLEIBEUKER, JH; SLUITER, WJ; OLDHOFF, J; HOEKSTRA, HJ

    1993-01-01

    Intraoperative electron beam radiotherapy (IORT) is clinically used as a potential adjunctive treatment to surgery of locally advanced pancreatic and gastric cancer. The tolerance of the pancreas to IORT was studied in 15 adult beagles, divided in 3 groups of 5 beagles in which 25, 30 or 35 Gy IORT

  12. GETDB: 113500 [GETDB

    Lifescience Database Archive (English)

    Full Text Available GRC Genome Viewer: 113500 CG13130 CG31875 bib HMS-Beagle{}333 4687 A FlyBase Insertion: P{GawB}NP4687 NP lin...Link to DGRC Genome Viewer: 113500 Related Genes CG13130 CG31875 bib HMS-Beagle{}333 Original Number 4687 Ch

  13. GETDB: 113150 [GETDB

    Lifescience Database Archive (English)

    Full Text Available 113150 Link to Original w[*]; P{GawB}NP3190 27D3 Link to DGRC Genome Viewer: 113150 CG13776 HMS-Beagle...elated Genes CG13776 HMS-Beagle{}318 Original Number 3190 Chr. 2 Comments FlyBase Insertion: P{GawB}NP3190 N

  14. GETDB: 105061 [GETDB

    Lifescience Database Archive (English)

    Full Text Available ink to DGRC Genome Viewer: 105061 CG31258 CG7994 HMS-Beagle{}1266 5940 2 NP line. Received from the National...A3 Map Viewer Link to DGRC Genome Viewer: 105061 Related Genes CG31258 CG7994 HMS-Beagle

  15. GETDB: 103917 [GETDB

    Lifescience Database Archive (English)

    Full Text Available ink to DGRC Genome Viewer: 103917 CG31816 CG5953 HMS-Beagle{}390 1178 2 FlyBase Insertion: P{GawB}NP1178 NP ...on Site 36A3 Map Viewer Link to DGRC Genome Viewer: 103917 Related Genes CG31816 CG5953 HMS-Beagle{}390 Orig

  16. GETDB: 104875 [GETDB

    Lifescience Database Archive (English)

    Full Text Available ink to DGRC Genome Viewer: 104875 CG13130 CG31875 bib HMS-Beagle{}333 5149 2 FlyBase Insertion: P{GawB}NP514...Genome Viewer: 104875 Related Genes CG13130 CG31875 bib HMS-Beagle{}333 Original Number 5149 Chr. 2 Comments

  17. GETDB: 112921 [GETDB

    Lifescience Database Archive (English)

    Full Text Available 112921 Link to Original w[*]; P{GawB}NP2432 / CyO 27D3 Link to DGRC Genome Viewer: 112921 CG13776 HMS-Beagle... DGRC Genome Viewer: 112921 Related Genes CG13776 HMS-Beagle{}318 Original Number 2432 Chr. 2 Comments FlyBa

  18. GETDB: 104899 [GETDB

    Lifescience Database Archive (English)

    Full Text Available ink to DGRC Genome Viewer: 104899 CG31816 CG5953 HMS-Beagle{}390 5209 2 FlyBase Insertion: P{GawB}NP5209 NP ...lacZ.UW14}UW14 Insertion Site 36A3 Map Viewer Link to DGRC Genome Viewer: 104899 Related Genes CG31816 CG5953 HMS-Beagle

  19. GETDB: 113146 [GETDB

    Lifescience Database Archive (English)

    Full Text Available 113146 Link to Original w[*]; P{GawB}NP3185 27D3 Link to DGRC Genome Viewer: 113146 CG13776 HMS-Beagle... Link to DGRC Genome Viewer: 113146 Related Genes CG13776 HMS-Beagle{}318 Original Number 3185 Chr. 2 Commen

  20. GETDB: 112362 [GETDB

    Lifescience Database Archive (English)

    Full Text Available Viewer: 112362 CG13130 CG31875 bib HMS-Beagle{}333 844 2 FlyBase Insertion: P{GawB}NP0844 NP line. Received ...er: 112362 Related Genes CG13130 CG31875 bib HMS-Beagle{}333 Original Number 844 Chr. 2 Comments FlyBase Ins

  1. GETDB: 113424 [GETDB

    Lifescience Database Archive (English)

    Full Text Available o DGRC Genome Viewer: 113424 CG13130 CG31875 bib HMS-Beagle{}333 4281 2 FlyBase Insertion: P{GawB}NP4281 NP ...enome Viewer: 113424 Related Genes CG13130 CG31875 bib HMS-Beagle{}333 Original N

  2. GETDB: 112221 [GETDB

    Lifescience Database Archive (English)

    Full Text Available 112221 CG13130 CG31875 bib HMS-Beagle{}333 564 2 FlyBase Insertion: P{GawB}NP0564 NP line. Received from the...nes CG13130 CG31875 bib HMS-Beagle{}333 Original Number 564 Chr. 2 Comments FlyBase Insertion: P{GawB}NP0564

  3. GETDB: 113623 [GETDB

    Lifescience Database Archive (English)

    Full Text Available o DGRC Genome Viewer: 113623 CG31816 CG5953 HMS-Beagle{}390 5187 2 FlyBase Insertion: P{GawB}NP5187 NP line....ertion Site 36A3 Map Viewer Link to DGRC Genome Viewer: 113623 Related Genes CG31816 CG5953 HMS-Beagle{}390

  4. GETDB: 104925 [GETDB

    Lifescience Database Archive (English)

    Full Text Available ink to DGRC Genome Viewer: 104925 bun HMS-Beagle{}347 5263 2 FlyBase Insertion: P{GawB}NP5263 NP line. Recei...AS-lacZ.UW14}UW14 Insertion Site 33E9 Map Viewer Link to DGRC Genome Viewer: 104925 Related Genes bun HMS-Beagle

  5. Dicty_cDB: Contig-U15636-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available one: CAS01_020_O16, 3'end. 44 0.11 2 ( BV286792 ) S232P6569RB8.T0 Beagle Canis familiaris STS genom... 40 0....D-2021A8 from 7, complet... 50 0.11 4 ( BV291216 ) S232P6154FH6.T0 Beagle Canis familiaris STS genom... 44 0

  6. GETDB: 113496 [GETDB

    Lifescience Database Archive (English)

    Full Text Available k to DGRC Genome Viewer: 113496 CG31258 CG40249 CG40250 CG7994 HMS-Beagle{}1266 4677 A FlyBase Insertion: P{...C Genome Viewer: 113496 Related Genes CG31258 CG40249 CG40250 CG7994 HMS-Beagle{}

  7. GETDB: 112984 [GETDB

    Lifescience Database Archive (English)

    Full Text Available 112984 Link to Original w[*]; P{GawB}NP2627 / CyO 33E9 Link to DGRC Genome Viewer: 112984 bun HMS-Beagle...E9 Map Viewer Link to DGRC Genome Viewer: 112984 Related Genes bun HMS-Beagle{}347 Original Number 2627 Chr.

  8. GETDB: 104066 [GETDB

    Lifescience Database Archive (English)

    Full Text Available enome Viewer: 104066 HMS-Beagle{}1214 mdg3{}1215 2035 3 FlyBase Insertion: P{GawB}NP2035 NP line. Received f...o DGRC Genome Viewer: 104066 Related Genes HMS-Beagle{}1214 mdg3{}1215 Original N

  9. Operate A Chemical Surety Program And Studies Supporting The Medical Chemical Defense Research Program

    Science.gov (United States)

    2010-05-01

    Administrations Following Intravenous Poisoning with Potassium Cyanide in Adult Male Beagle Dogs...Administrations Following Intravenous Poisoning with Potassium Cyanide in Adult Male Beagle Dogs Task Leader: Dr. Frances Reid / Dr. Brian Roche...agents, synthesis , pharmacokinetics, efficacy testing, seizure control, bioscavengers, toxicology testing and test kit evaluations. In addition, TO

  10. Space Weathering Trends Among Carbonaceous Asteroids

    CERN Document Server

    Kaluna, Heather M; Meech, Karen J

    2015-01-01

    We present visible spectroscopic and albedo data of the 2.3 Gyr old Themis family and the 15 km) and small (< 15 km) Themis members suggest these phyllosilicate feature and albedo trends result from regolith variations as a function of diameter. Observations of the Beagle asteroids show a small, but notable fraction of members with phyllosilicate features. The presence of phyllosilicates and the dynamical association of the main-belt comet 133P/Elst-Pizarro with the Beagle family imply the Beagle parent body was a heterogenous mixture of ice and aqueously altered minerals.

  11. Oceanographic profile temperature measurements collected using bottle from the A.T. CAMERON, GADUS ATLANTICA, RYURIK, BLAGONAMERENNI, PREDPRIYATIE, and other platforms in the Antarctic, Equatorial Pacific, and other locations from 1772 to 1866 (NODC Accession 0000571)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Temperature profile data were collected using bottle casts from the BEAGLE in the North / South Pacific Ocean, Indian Ocean, Southern Oceans, and Red Sea. Data were...

  12. Getting started with electronic projects

    CERN Document Server

    Pretty, Bill

    2015-01-01

    This book is aimed at hobbyists with basic knowledge of electronics circuits. Whether you are a novice electronics project builder, a ham radio enthusiast, or a BeagleBone tinkerer, you will love this book.

  13. Pacific Northwest Laboratory annual report for 1980 to the DOE Assistant Secretary for Environment. Part 1. Biomedical sciences. [Lead abstract

    Energy Technology Data Exchange (ETDEWEB)

    Drucker, H.

    1981-02-01

    Separate abstracts were prepared for 31 sections in this progress report. The appendix which deals with dose-effect studies with inhaled plutonium in beagles is not represented by a separate abstract. (KRM)

  14. Argentina: Nationality, Demography and Security

    Science.gov (United States)

    1993-04-22

    The Western Border It extends along the Andes ridge from the North of Argentina’s Catamarca Province to the intersection of the Beagle Channel with the...And the Chilean workers are not powerless. For example, during the Chilean-Argentine clash over the Beagle Channel (1980), coal production almost...and others. "Probiemas Argentinosy sus Soluciones", Ed. Pleamar, Buenos Aires, 1976. 3. Levene, H. " Historia Argentina", Ed. Pleamar, Buenos Aires

  15. hPDGF-B基因转染对Beagle犬牙龈成纤维细胞生物学活性的影响%Biological Effects of Human Platelet-Derived Growth Factor-B Gene Transfection on Gingival Fibroblasts of Beagle Dog

    Institute of Scientific and Technical Information of China (English)

    钟泉; 闫福华; 李艳芬; 陈超

    2013-01-01

    Objective To evaluate the biological effects of human platelet-derived growth factor-B gene transfection on gingival fibroblasts . Methods The plasmid(EX-A0380-M03) carried human plate-let-derived growth factor-B(hPDGF-B) gene was transfected into gingival fibroblasts by LipofectamineTM 2000 . Morphological changes of transfected cells were recorded by optical and fluorescent microscope . Then ,MTT and flow cytometry were used to estimate the proliferation and apoptosis of gene-modified cells . The expression of collagen I and XII ,as well as theα-SMA(α-Smooth Muscle Actin) was detected by Real-time Quantitative PCR . Results Compared to the normal cells ,partial transfected cells presen-ted startlike ,polygonal ,and neuron-like . Cells proliferation was enhanced after gene interference ,but apoptosis did not appeared . At transcription level ,the expression of Collagen I was up-regulated ,while Collagen XII and α-SMA were down-regulated . Conclusion The enhanced proliferation of gingival fibro-blasts were due to paracrine and autocrine modes of fusion protein PDGF-BB-eGFP synthetized by gene modified cells . Transfeced cells did not present reverse differentiation ,and the extracellular matrix re-modeling ability of those cells were down . The synthesis of Collagen I of hPDGF-B gene modified cells ascended no tably .%目的:检测hPDGF-B基因转染对Beagle犬牙龈成纤维细胞生物学活性的影响。方法使用脂质体LipofectamineTM 2000将携带hPDGF-B基因的质粒EX-A0380-M03转染至Beagle犬牙龈成纤维细胞,观察转染后细胞的形态以及增殖的变化;流式细胞仪检测转染细胞的周期以及凋亡情况;Real-time PCR法检测转染后细胞表达Collagen I、Collagen XII、α-SM A的变化。结果转染后的牙龈成纤维细胞形态多样,但增殖显著;转染组S期细胞比率增高,转染细胞未出现凋亡;转染后细胞上调Collagen I基因的表达,下调Collagen XII和α-SM A的表达。结论 hPDGF-B基因转染牙龈成纤维细胞后,产生PDGF-BB-eGFP融合蛋白,融合蛋白可能通过自分泌和旁分泌的方式作用于牙龈成纤维细胞,从而促进细胞增殖。hPDGF-B基因转染牙龈成纤维细胞后,细胞并不能出现逆向分化,细胞对外周基质的改建能力下降,但细胞合成胶原的能力显著增强。

  16. 星点设计-效应面法优化盐酸氨溴索漂浮渗透泵给药系统及犬体内药动学%Optimization of a floating osmotic pump system of ambroxol hydrochloride using central composite design-response surface methodology and its pharmacokinetics in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    赵锋; 马银玲; 金晓利; 王静; 曹德英

    2011-01-01

    This paper reported that a new type of floating osmotic pump of ambroxol hydrocbloride was designed. Third method apparatus (Chinese Pharmacopeia 2010, appendix XD) was employed to simultaneously evaluate the release and floating behavior in vitro. The system was optimized using central composite design-response surface methodology. Similar factor (f2) between the release profile of self-made formulation and the target release profile was chosen as dependent factor. The amount of glucose (A, mg), pore former (B, %) and weight of coating (C, %) were employed as independent factors. Optimized formulation was: A (100.99 mg), B (1.70%), C (4.21%). The value of f2 (89.14) was higher than that of market capsules (69.02) and self-made tablets (72.15). It was showed that self-made capsules possessed character of zero-order release (r = 0.994 4) and drug release completely (>90%). It was showed in result of in vivo study that tmax and Cmax of self-made capsules were significantly lower than that of market capsules and self-made tablets. The correlation coefficient between the fraction of absorption in vivo and the release rate in vitro was 0.985 1, and relative bioequivalence of self-made capsules was 110.77%. Accordingly, self-made capsules displayed obviously characteristics of controlled release both in vivo and in vitro.%本文设计了具有漂浮特性的盐酸氨溴索渗透泵胶囊.采用中国药典(2010版)附录XD释放度测定法第三法装置同时评价制剂的体外释放和漂浮性能.以葡萄糖用量、致孔剂用量和包衣增重为自变量,自制处方释放曲线与目标释放曲线相比而得的相似因子(f2)为应变量,采用星点设计-效应面法优化系统.优化处方:葡萄糖100.99 mg,致孔剂用量11.70%,包衣增重4.21%.f2为89.14,高于市售胶囊(69.02)和自制片(72.15).优化后零级释药明显(r=0.994 4),释药完全(>90%).Beagle犬体内实验证明,自制胶囊Cmax、tmax低于市售胶囊、自制片,体内外相关性好(r=0.985 1),且生物利用度高(110.77%),说明自制胶囊有明显的控释特征.

  17. Effects of Micronization and Solid Dispersion Technologies on Oral Bioavailability of Piroxicam in Beagle Dogs%微粉化和固体分散体技术对吡罗昔康在Beagle犬体内口服生物利用度的影响

    Institute of Scientific and Technical Information of China (English)

    李模勇; 杨澄; 彭强

    2015-01-01

    为增加吡罗昔康(1)的溶出速度,采用气流粉碎法对1原药进行微粉化处理,或采用溶剂法以共聚维酮S630为载体制备固体分散体.将所得的微粉化药物和固体分散体分别制成片剂,并以市售1片为参比制剂,采用Beagle犬为模型进行药动学研究.结果表明,微粉化处理对1在Beagle犬体内的药动学行为无显著影响,但制备固体分散体能有效提高1的口服生物利用度.与参比制剂相比,采用微粉化1制备的片剂口服相对生物利用度为103.6%;当固体分散体片剂中1与共聚维酮S630质量比为1∶3和1∶5时,口服相对生物利用度为128.9%和138.9%.

  18. 口服紫锥菊对清醒比格犬心率、心电、血压和呼吸的影响%Effects of Oral Echinacea purpurea on Heart Rate,ECG,Blood Pressure and Respiration of Awake Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    庞云露; 钟英杰; 付海宁; 钟雁; 蒋贻海

    2014-01-01

    本试验研究了口服紫锥菊对清醒比格犬心率、心电、血压和呼吸的影响.结果显示,口服0.125~1.25 g/kg紫锥菊对清醒比格犬心率有明显降低作用,对心电图P波、T波、R波、Q-T间期、QRS间期、P-R间期及血压、呼吸均无显著影响(P>0.05).表明紫锥菊对犬的呼吸系统和心血管系统均无明显影响,在药效剂量应用时安全可靠.

  19. 经犬肝动/静脉输入反义c-myc重组腺病毒的安全性研究%The Safety of Adenovirus-Mediated Antisense c-myc Infused into Hepatic Artery or Portal Vein in Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    余昌中; 林晨; 张海增; 查圆圆; 梁萧; 付明; 张雪艳; 吴旻

    2004-01-01

    目的:经Beagle犬肝脏血管注射重组腺病毒介导反义c-myc基因(Ad-ASmyc)载体,观测其体内分布及毒副作用,以评价Ad-ASmyc治疗肝癌的临床前期安全性.方法:选择4只体重8~10kg健康Beagle犬,全麻后开腹,经肝动脉或门静脉注射Ad-ASmyc,注射Ad-ASmyc前及注射后第3,7,14,21天取肝组织及抽取静脉血化验,PCR检测Ad-ASmyc在各器官组织中的分布,常规切片观察各器官病理变化,ELISA方法检测血中抗腺病毒抗体的产生.结果:经Beagle犬肝脏血管注射后,Ad-ASmyc可持续转导正常肝细胞达3周,实验犬一般情况好,血、肝、肾功能无明显异常,在肝脏、脾脏、肾脏、胃、心脏、皮肤中可检测到重组腺病毒的分布,镜下可见Ad-ASmyc剂量依赖性的肝组织轻微的炎症反应,注射后7d血中有抗腺病毒载体的抗体产生,14d达高峰,21d开始下降.结论:经Beagle犬肝动脉或门静脉途径注射Ad-ASmyc均可转导至肝细胞,Ad-ASmyc对实验犬的毒副作用较轻.

  20. 牙龈成纤维细胞-玉米醇溶蛋白-中药双黄补复合体对犬牙周组织再生的实验性研究%Gingival fibroblast-Zein-Shuanghuangbu complex promotes periodontal regeneration in beagle dogs:An experimental study

    Institute of Scientific and Technical Information of China (English)

    刘健; 翟文静; 吴景景; 张晓静; 许彦枝

    2013-01-01

    目的 牙周炎是最常见的口腔疾病之一,可导致牙周支持组织的破坏,最终造成牙齿丧失.组织工程技术在牙周组织修复再生中的应用为牙周炎的治疗开辟了新途径.研究旨在探讨牙龈成纤维细胞(gingival fibroblast,GF)-玉米醇溶蛋白(Zein)-中药双黄补复合体促进犬牙周组织修复再生的作用.方法 以2只Beagle犬双侧上颌5445、下颌743347共20个牙位作为实验部位,将其配对分为4组,每组5个牙位分别制备骨缺损模型.实验Ⅰ组:翻瓣术+Zein支架植入;实验Ⅱ组:翻瓣术+GF-Zein支架植入;实验Ⅲ组:翻瓣术+ GF-Zein-中药双黄补复合体植入;对照组:单纯翻瓣术.于术后3个月进行组织学观察、测量及锥形束CT(cone-beam computed tomography,CBCT)检查.结果 实验Ⅰ、Ⅱ、Ⅲ组术后3个月新生牙槽骨高度均高于对照组(P0.05).结论 中药双黄补可促进犬牙周骨缺损的修复,有利于牙周组织的再生.

  1. 布洛芬缓释微丸胶囊在Beagle犬体内的药动学及体内外相关性研究%Pharmacokinetics and in vitro-in vivo Correlation of Ibuprofen Sustained-release Pellet-filled Capsules in Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    唐靖; 张海龙; 梁丰; 周彦彬; 丁劲松

    2013-01-01

    以芬必得为参比制剂,考察自制布洛芬缓释微丸胶囊在Beagle犬体内的药动学.结果表明,自制布洛芬缓释微丸胶囊与芬必得的主要药动学参数如下:t1/2为(4.14±1.12)和(3.84±0.77)h,Cmax为(81.30±24.52)和(88.81±16.87) μg/ml,AUC0→t为(420.79±96.17)和(410.10±85.06) μg·h·ml-1.自制布洛芬缓释微丸胶囊具有较好的体内缓释特性,相对生物利用度为(104.70±27.86)%.其体内吸收与体外释放具有相关性.

  2. 恒河猴、比格犬、树鼩、兔、大鼠及小鼠消化管的比较组织学%Comparison histologic study on digestive tract of rhesus monkey, beagle dog, japanese rabbit, tree shrew, SD rat and KM mouse

    Institute of Scientific and Technical Information of China (English)

    徐文漭; 李霞; 李涛; 王媛媛; 戴芳; 和占龙; 王丽; 蔡琳; 黎贵芸

    2013-01-01

    目的 对恒河猴、比格犬、树鼩、日本大耳白兔、SD大鼠及昆明小鼠(KM小鼠)的消化管进行比较组织学研究,为实验动物病理学检测标准及以它们为基础的科学研究提供理论依据.方法 选取按照现行实验动物质量国家检测标准检测合格的恒河猴30只、比格犬16只、树鼩20只、日本大耳白兔18只、SD大鼠20只及KM小鼠20只,经麻醉后处死并剖检.选取消化管组织经10%中性福尔马林固定,常规石蜡切片,行HE、免疫组化及特殊染色,光镜观察,比较它们在组织学结构方面的异同.结果 所有动物直肠的组织学结构基本一致,下列部位组织学存在差异:(1)舌肌的排列方式及舌腺的组成类型,舌乳头发达程度及其内味蕾的多少;(2)食管黏膜表面上皮形态、有无食管腺及其组成类型、肌层的排列方式;(3)胃的大体结构,有无贲门腺、胃底腺及幽门腺等组织学结构,胃底表面上皮细胞形态及AB染色情况;(4)十二指肠、空肠及回肠黏膜下层的组织学结构;(5)结肠黏膜层组织学结构及部分实验动物的特有结构;(6)炎症是消化管普遍存在的自发性病变.结论 (1)通过对上述实验动物消化管的剖检及组织学观察,获得宝贵的组织学资料;通过比较分析,揭示了不同物种组织学特点和进化规律,丰富了比较组织学的研究资料.(2)消化管是与外界相通的开放性管道,易受外界影响而产生自发性病变.

  3. 犬血浆中柚皮苷和新橙皮苷的LC-MS/MS法测定及其药动学%Determination of Naringin and Neohesperidin in Beagle Dog Plasma by LC-MS/MS and Its Pharmacokinetics

    Institute of Scientific and Technical Information of China (English)

    徐智儒; 肖峰; 蒋春红; 秦燕; 杨小玲

    2016-01-01

    建立了液相色谱-串联质谱法测定Beagle犬血浆中的柚皮苷(1)、新橙皮苷(2)及其苷元柚皮素(3)和橙皮素(4),并考察枳实总黄酮苷提取物给药后1、2在犬体内的药动学情况.采用C18色谱柱,以甲醇为流动相,采用ESI源负离子模式、多反应监测进行定量分析.Beagle犬灌胃(17、50、150 mg/kg)及静脉(5 mg/kg)给予枳实总黄酮苷提取物.灌胃给药后1和2的药动学参数分别如下:t1n (5.32±2.13)、(5.23±3.20)、(5.98±3.49)和(3.82±1.98)、(3.58±1.02)、(5.06±4.04)h,cm.(107±35)、(310±136)、(501±269)和(101±34)、(297± 118)、(481±240) ng/ml,AUC0→t (391±161)、(605±229)、(964±333)和(277±43)、(684±377)、(927±224) ng·ml-1·h.生物利用度分别为(3.51±1.44)%、(1.84±0.70)%、(0.98±0.34)%和(2.27±0.35)%、(1.91±0.96)%、(0.8±0.21)%.静脉给药后1和2的药动学参数如下:t1/2(5.48±4.17)和(3.68±1.91)h,AUC0→t(3 590652)和(3 281±594) ng·ml-1·h.

  4. The Effect of Isosorbide-5-Mononitrate on Ivabradine Hydrochloride Pharmacokinetics in Beagles%5-单硝酸异山梨酯对盐酸伊伐布雷定在比格犬体内的药动学影响

    Institute of Scientific and Technical Information of China (English)

    王现珍; 姚景春; 胡海勋; 罗涟荣; 吕圆圆; 王洪臣; 商庆节

    2014-01-01

    目的 研究5-单硝酸异山梨酯对盐酸伊伐布雷定在比格犬体内的药动学影响.方法 采用高效液相色谱法测定盐酸伊伐布雷定单独给药和联合5-单硝酸异山梨酯给药后不同时间比格犬体内盐酸伊伐布雷定的血药浓度,采用非房室模型计算盐酸伊伐布雷定药动学参数.结果 盐酸伊伐布雷定单独给药与联合5-单硝酸异山梨酯给药,主要药动学参数分别为tmax(0.38±0.13)和(0.48±0.20)h,ρmax(2.27±0.70)和(1.96±0.45) mg· L-1,AUC0-l(2.60±0.67)和(3.39±1.66)mg· h· L-1,t1/2(0.831±0.244)和(0.691±0.246)h.联合5-单硝酸异山梨酯给药后,盐酸伊伐布雷定的生物利用度为单独给药的133%.结论 5-单硝酸异山梨酯与盐酸伊伐布雷定联合使用可提高盐酸伊伐布雷定的生物利用度.

  5. Are you ready for Mars? - Main media events surrounding the arrival of ESA's Mars Express at Mars

    Science.gov (United States)

    2003-11-01

    Launched on 2 June 2003 from Baikonur (Kazakhstan) on board a Russian Soyuz launcher operated by Starsem, the European probe -built for ESA by a European team of industrial companies led by Astrium - carries seven scientific instruments that will perform a series of remote-sensing experiments designed to shed new light on the Martian atmosphere, the planet’s structure and its geology. In particular, the British-made Beagle 2 lander, named after the ship on which Charles Darwin explored uncharted areas of the Earth in 1830, will contribute to the search for traces of life on Mars through exobiology experiments and geochemistry research. On Christmas Eve the Mars Express orbiter will be steered on a course taking it into an elliptical orbit, where it will safely circle the planet for a minimum of almost 2 Earth years. The Beagle 2 lander - which will have been released from the mother craft a few days earlier (on 19 December) - instead will stay on a collision course with the planet. It too should also be safe, being designed for atmospheric entry and geared for a final soft landing due to a sophisticated system of parachutes and airbags. On arrival, the Mars Express mission control team will report on the outcome of the spacecraft's delicate orbital insertion manoeuvre. It will take some time for Mars Express to manouvre into position to pick communications from Beagle 2. Hence, initially, other means will be used to check that Beagle 2 has landed: first signals from the Beagle 2 landing are expected to be available throughout Christmas Day, either through pick-up and relay of Beagle 2 radio signals by NASA’s Mars Odyssey, or by direct pick-up by the Jodrell Bank radio telescope in the UK. Mars Express will then pass over Beagle 2 in early January 2004, relaying data and images back to Earth. The first images from the cameras of Beagle 2 and Mars Express are expected to be available between the end of the year and the beginning of January 2004. The key dates

  6. Effect of testicular irradiation on established BPH in the dog: evidence of a non-steroidal testicular factor for BPH maintenance

    Energy Technology Data Exchange (ETDEWEB)

    Grayhack, J.T.; Lee, C.; Brand, W.

    1985-12-01

    Irradiation of the testes of four to 13-year-old male beagles with benign prostatic hyperplasia (BPH) was undertaken to attempt to evaluate the possibility that the testes secrete a non-androgenic accessory sex gland-stimulating substance that may have a critical role in the development of BPH. Thirteen non-irradiated and shoulder irradiated control and 16 beagles subjected to 1500 to 2200 rads single dose testis irradiation had pre-irradiation, interval post-irradiation and terminal caliper measurements of prostatic length, width and depth, prostatic and testicular biopsies, and determination of serum testosterone and estradiol levels. Four beagles survived in a group observed for 109 weeks post testis irradiation, 12 in a group observed for 51 and 10 in a group observed for 59 weeks. The wet weight of the prostate was determined at sacrifice. Ratios of the final/initial length and width and final actual/initial calculated weight of the prostate were significantly decreased in testis-irradiated as compared to control beagles. Histologic evaluation also demonstrated a significant difference in degree of prostatic stimulation in control and testis-irradiated groups. The serum testosterone and estradiol levels were not significantly different in the testis-irradiated and control beagles.

  7. Characteristics of sublingual vein and expressions of vascular endothelial growth factor and hypoxia-inducible factor la proteins in sublingual tissues of Beagle dogs with portal hypertension%肝硬化门静脉高压模型犬舌下络脉形态和舌下组织血管内皮生长因子及低氧诱导因子1α的表达

    Institute of Scientific and Technical Information of China (English)

    李白羽; 王丽娜; 岳小强; 李柏

    2009-01-01

    目的:观察肝硬化门静脉高压犬舌下络脉变化及舌下组织血管内皮生长因子(vascular endothelial growth factor,VEGF)和低氧诱导因子1α(hypoxia-inducible factor 1α,HIF-1α)的表达情况.方法:将12只Beagle犬随机分为正常组和模型组.用二甲基亚硝胺(dimethylnitrosamine,DMN)诱导肝硬化门静脉高压,观察Beagle犬舌下络脉形态、颜色;生物电记录系统测定其门静脉压力;免疫组织化学EnVision法检测犬舌下组织VEGF及HIF-1α蛋白的表达.结果:模型组Beagle犬舌下血管形态学和颜色较正常组有明显改变.免疫组织化学结果显示,正常对照组犬舌下血管VEGF、HIF-1α几乎无表达;模型组犬舌下组织VEGF、HIF-1α蛋白表达显著增高,差异有统计学意义(P<0.01).结论:门静脉压力变化可能是肝硬化门静脉高压模型犬异常舌下络脉形成的一个重要因素,舌下血管VEGF和HIF-1α蛋白表达增加可能参与了这一过程.

  8. Reproduction of superior sagittal sinus animal model by bypass transplantation of biomaterial graft

    Directory of Open Access Journals (Sweden)

    Qing-yong LUO

    2011-03-01

    Full Text Available Objective To establish the beagles model of superior sagittal sinus bypass graft,and explore the feasibility of reconstruction of superior sagittal sinus with biomaterials using this model.Methods Eight adult male beagles(weight: 12.5-22.0kg were involved in the present study.The superior sagittal sinus was exposed and blocked via bone window,and then anastomosed side-to-end to the biomaterial graft under the dedicated microscope of neurosurgery surgery,expectant treatment such as anti-inflammatory was given for the animals.The digital subtraction venography(DSV and color Doppler flow imaging(CDFI of superior sagittal sinus were performed in 1,2,4 and 8 weeks after the operation.Eight weeks after the operation,all the animals were sacrificed and the material graft was examined histologically.Results The DSV and CDFI of superior sagittal sinus showed that the stomas of 2 beagles were with slight stenosis and high flow velocity,of 1 beagle with small leakage and low flow velocity,while of other 5 beagles were normal.The histological examination showed endothelial cells were growing on the graft and superior sagittal sinus,and crawling toward the lumen of graft 8 weeks after the operation.Conclusion The beagles model of superior sagittal sinus bypass graft was established successfully.The short-term effect of the model was satisfactory,while further work should be performed to determine the long-term effects.

  9. Short communication: imputing genotypes using PedImpute fast algorithm combining pedigree and population information.

    Science.gov (United States)

    Nicolazzi, E L; Biffani, S; Jansen, G

    2013-04-01

    Routine genomic evaluations frequently include a preliminary imputation step, requiring high accuracy and reduced computing time. A new algorithm, PedImpute (http://dekoppel.eu/pedimpute/), was developed and compared with findhap (http://aipl.arsusda.gov/software/findhap/) and BEAGLE (http://faculty.washington.edu/browning/beagle/beagle.html), using 19,904 Holstein genotypes from a 4-country international collaboration (United States, Canada, UK, and Italy). Different scenarios were evaluated on a sample subset that included only single nucleotide polymorphism from the Bovine low-density (LD) Illumina BeadChip (Illumina Inc., San Diego, CA). Comparative criteria were computing time, percentage of missing alleles, percentage of wrongly imputed alleles, and the allelic squared correlation. Imputation accuracy on ungenotyped animals was also analyzed. The algorithm PedImpute was slightly more accurate and faster than findhap and BEAGLE when sire, dam, and maternal grandsire were genotyped at high density. On the other hand, BEAGLE performed better than both PedImpute and findhap for animals with at least one close relative not genotyped or genotyped at low density. However, computing time and resources using BEAGLE were incompatible with routine genomic evaluations in Italy. Error rate and allelic squared correlation attained by PedImpute ranged from 0.2 to 1.1% and from 96.6 to 99.3%, respectively. When complete genomic information on sire, dam, and maternal grandsire are available, as expected to be the case in the close future in (at least) dairy cattle, and considering accuracies obtained and computation time required, PedImpute represents a valuable choice in routine evaluations among the algorithms tested.

  10. Experimental reconstruction of cervical esophageal defect with artificial esophagus made of polyurethane in a dog model.

    Science.gov (United States)

    Jiang, H; Cui, Y; Ma, K; Gong, M; Chang, D; Wang, T

    2016-01-01

    The defect of esophagus after surgical excision in patients is usually replaced by autologous stomach, jejunum, or colon. The operation brings severe trauma and complications. Using artificial esophagus to replace the defect in situ can reduce the operative trauma, simplify the operative procedures, and decrease the influence to digestive function. A variety of experiments have been designed for developing a practical artificial esophagus. Nevertheless, a safe and reliable artificial esophagus is not yet available. The objective is to evaluate the possibility of the artificial esophagus made of non-degradable polyurethane materials being used in reconstruction of the segmental defect of cervical esophagus in beagles, observe the regeneration of esophageal tissue, and gather experience for future study. The cervical esophageal defects in 13 beagles were designed to 2-cm long and were constructed by the artificial esophagus made of non-degradable polyurethane materials. Nutrition supports were given after the operation. The operative mortality, anastomotic leakage, migration of artificial esophagus, and dysphagia were followed up. The regeneration of the esophageal tissues was evaluated by histopathology and immunohistochemical labeled streptavidin-biotin method. The surgical procedures were successfully completed in all beagles, and 12-month follow-ups were done. Only one beagle died of severe infection, and all others survived until being killed. The anastomotic leakage occurred in nine beagles, most of them (8/9) were cured after supportive therapy. The migration of artificial esophagus occurred in all 12 surviving beagles, and one artificial esophagus stayed in situ after migration. All 12 surviving beagles showed dysphagia with taking only fluid or soft food. No beagle died of malnutrition. The neo-esophagus was composed of granulation tissue, and the inner surface was covered by epithelium in 2-3 months completely. But the inner surface of neo-esophagus with

  11. The Case for Spacecrime: The Rise of Crime and Piracy in the Space Domain

    Science.gov (United States)

    2013-06-01

    resulted in generally outdated hardware with limited capabilities.21 More recent hardware platforms such as Arduino, BeagleBone, Raspberry Pi and others...www.citizensinspace.org; Arduino platform, http://www.arduino.cc; Beaglebone platform, http://www.beagleboard.org; Raspberry Pi platform, http

  12. MATHWORKS宣布对AKDUINO等平台硬件实现SIMULINK内置支持

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    MathWorks近日宣布,Simulink模型现在可以直接在Arduino、BeagleBoard和LEGO MINDSTORMS NXT平台上运行。这些通用的低成本设备在学术界中广泛使用在机器人、机电一体化、音频信号处理、

  13. The short and long term effects of intraoperative electron beam radiotherapy (IORT) on thoracic organs after pneumonectomy an experimental study in the canine model

    NARCIS (Netherlands)

    de Boer, Willem; Mehta, DM; Timens, W; Hoekstra, HJ

    1999-01-01

    Purpose: The tolerance of mediastinal structures and thoracic organs to intraoperative radiotherapy (IORT) was investigated in the canine model. Methods and Materials: Twenty-two adult beagles divided into three groups were subjected to a left pneumonectomy and IORT (10 MeV electrons) at doses of 20

  14. Marine anthropogenic radiotracers in the Southern Hemisphere: New sampling and analytical strategies

    DEFF Research Database (Denmark)

    Levy, I.; Povinec, P.P.; Aoyama, M.;

    2011-01-01

    The Japan Agency for Marine Earth Science and Technology conducted in 2003–2004 the Blue Earth Global Expedition (BEAGLE2003) around the Southern Hemisphere Oceans, which was a rare opportunity to collect many seawater samples for anthropogenic radionuclide studies. We describe here sampling and ...

  15. A Blur track on Mars: how do you top that?

    CERN Multimedia

    Cooke, Rachel

    2003-01-01

    "On the eve of the landing of the Beagle 2 space probe on Mars, one of its instigators, Blur bassist Alex James, talks exclusively about his new-found passion for space 'Talking with scientists makes me feel giddy with excitement. Life on Mars, I mean, come on! How dead do you have to be not to find that interesting?' (1 page).

  16. Mars Express met l'Europe en orbite autour de la Planete rouge

    CERN Document Server

    2003-01-01

    "Apres une nuit sans sommeil, le Centre europeen d'operations spatiales (ESOC) de Darmstadt, en Allemagne, a annonce la nouvelle, jeudi 25decembre au matin: la sonde Mars Express a bien ete "capturee" par la gravite de la Planete rouge, tandis que le petit atterrisseur Beagle-2 tentait de se poser dans la plaine d'Isidis Planitia" (1 page).

  17. Dicty_cDB: Contig-U10957-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 90747 ) S232P6152RH9.T0 Beagle Canis familiaris STS genom... 34 5.7 3 ( BD460593 ) Diagnosis of Diseases Ass...enomic clone ZM... 38 4.5 2 ( BV379572 ) S245P629FC1.T0 SpanishGrayWolf Canis lupus STS ge... 34 4.8 3 ( BV2

  18. Bone regeneration of hydroxyapatite/alumina bilayered scaffold with 3 mm passage-like medullary canal in canine tibia model.

    Science.gov (United States)

    Kim, Jong Min; Son, Jun Sik; Kang, Seong Soo; Kim, Gonhyung; Choi, Seok Hwa

    2015-01-01

    The aim of this study was to evaluate the bone regeneration of hydroxyapatite (HA)/alumina bilayered scaffold with a 3 mm passage-like medullary canal in a beagle tibia model. A porous HA/alumina scaffold was fabricated using a polymeric template-coating technique. HA/alumina scaffold dimensions were 10 mm in outer diameter, 20 mm in length, and with either a 3 mm passage or no passage. A 20 mm segmental defect was induced using an oscillating saw through the diaphysis of the beagle tibia. The defects of six beagles were filled with HA/alumina bilayered scaffolds with a 3 mm passage or without. The segmental defect was fixated using one bone plate and six screws. Bone regeneration within the HA/alumina scaffolds was observed at eight weeks after implantation. The evaluation of bone regeneration within the scaffolds after implantation in a beagle tibia was performed using radiography, computerized tomography (CT), micro-CT, and fluorescence microscopy. New bone successfully formed in the tibia defects treated with 3 mm passage HA/alumina scaffolds compared to without-passage HA/alumina scaffolds. It was concluded that the HA/alumina bilayered scaffold with 3 mm passage-like medullary canal was instrumental in inducing host-scaffold engraftment of the defect as well as distributing the newly formed bone throughout the scaffold at 8 weeks after implantation.

  19. The Nature of War Theory

    Science.gov (United States)

    2011-03-10

    mind, this paper explores and advances a new idea for how to apply Charles Darwin ‟s Theory of Natural Selection to better understand the biological... Charles Darwin had embarked on the HMS Beagle for a five-year scientific voyage that would last from 1831 to 1836. Darwin would later publish two

  20. Charles Darwin: His Life, Journeys and Discoveries. A Teacher's Guide.

    Science.gov (United States)

    Overy, Caroline

    This handbook aims to: (1) introduce teachers and pupils to Charles Darwin, his life and work at Down House, his voyage on the Beagle, and his evolutionary theory; (2) set his ideas within the wider context of the 19th century; (3) link the subject areas to the British National Curriculum, particularly in history, science, and English at various…

  1. Brown dog tick, Rhipicephalus sanguineus sensu lato, infestation ofsusceptible dog hosts is reduced by slow release of semiochemicalsfrom a less susceptible host

    Science.gov (United States)

    Domestic dog breeds are hosts for the tick Rhipicephalus sanguineus sensu lato, but infestation levels vary among breeds. Beagles are less susceptible to tick infestations than English cocker spaniels due to enhanced production of 2-hexanone and benzaldehyde that act as tick repellents. We report th...

  2. Intraosseous Versus Intravenous Infusion of Hydroxocobalamin for the Treatment Of Acute Severe Cyanide Toxicity in a Swine Model

    Science.gov (United States)

    2014-11-01

    20. Borron SW, Stonerook M, Reid F. Efficacy of hy- droxocobalamin for the treatment of acute cyanide poisoning in adult beagle dogs . Clin Toxicol... Cardiology , the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Institute of Criti- cal Care Medicine, the Safar Center

  3. Hydroxocobalamin and Epinephrine Both Improve Survival in a Swine Model of Cyanide-Induced Cardiac Arrest

    Science.gov (United States)

    2012-10-01

    the American College of Cardiology , the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Institute of Critical Care...Borron SW, Stonerook M, Reid F. Efficacy of hydroxocobalamin for the treatment of acute cyanide poisoning in adult beagle dogs . Clin Toxicol (Phila

  4. University scientists test Mars probe equipment

    CERN Multimedia

    2002-01-01

    Scientists at Leicester University have spent four years researching and designing the Flight Model Position Adjustable Workbench (PAW) at the university. It will be attached to the Beagle 2 probe before being sent to the Red Planet in the spring (1/2 page).

  5. Antibodies reacting to carbonic anhydrase isozymes (I and II) and albumin in sera from dogs.

    Science.gov (United States)

    Nishita, Toshiho; Miyazaki, Rui; Miyazaki, Takae; Ochiai, Hideharu; Orito, Kensuke

    2016-06-01

    IgGs to carbonic anhydrase isozymes (CA-I and CA-II) and albumin were identified in dog serum. IgG titers were determined in the sera of asymptomatic dogs, and in dogs with atopic dermatitis, diarrhea and/or vomiting, diabetes and/or pancreatitis, kidney disease, hepatic disease, and thyroid gland disease, using ELISA. Low titres of IgG-reactive CA-I, CA-II, BSA, and CSA were found in the sera of healthy beagles. Compared with healthy beagles, there was a significant difference in the titers of antibodies against CA-I in asymptomatic dogs, dogs with diabetes and/or pancreatitis, or thyroid gland disease, or hepatic disease. Compared with healthy beagles, there was a significant difference in the antibody titer of anti-CA-II IgG in asymptomatic dogs and in those with hepatic disease. There was a significant difference in the antibody titer of anti-BSA IgG between healthy beagles and dogs with hepatic disease.

  6. ANGSD

    DEFF Research Database (Denmark)

    Korneliussen, Thorfinn Sand; Albrechtsen, Anders; Nielsen, Rasmus

    2014-01-01

    is available at http://www.popgen.dk/angsd. The program is tested and validated on GNU/Linux systems. The program facilitates multiple input formats including BAM and imputed beagle genotype probability files. The program allow the user to choose between combinations of existing methods and can perform...

  7. Subchronic (13-week) oral toxicity study of α-cyclodextrin in dogs

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    2004-01-01

    The oral toxicity of α-cyclodextrin (α-CD) was examined in a 13-week feeding study in which groups of Beagle dogs received α-CD in the diet at concentrations of 0 (control), 5, 10, or 20% (4dogs/sex/group). No treatment-related changes were noted in behavior or appearance of the dogs and no mortalit

  8. Avian Influenza (H5N1) Susceptibility and Receptors in Dogs

    OpenAIRE

    Maas,; Tacken, M.G.J.; Ruuls-van Stalle, E.M.F.; G. Koch; Rooij, De; Stockhofe-Zurwieden, N.

    2007-01-01

    Inoculation of influenza (H5N1) into beagles resulted in virus excretion and rapid seroconversion with no disease. Binding studies that used labeled influenza (H5N1) showed virus attachment to higher and lower respiratory tract tissues. Thus, dogs that are subclinically infected with influenza (H5N1) may contribute to virus spread.

  9. Bone Regeneration of Hydroxyapatite/Alumina Bilayered Scaffold with 3 mm Passage-Like Medullary Canal in Canine Tibia Model

    Directory of Open Access Journals (Sweden)

    Jong Min Kim

    2015-01-01

    Full Text Available The aim of this study was to evaluate the bone regeneration of hydroxyapatite (HA/alumina bilayered scaffold with a 3 mm passage-like medullary canal in a beagle tibia model. A porous HA/alumina scaffold was fabricated using a polymeric template-coating technique. HA/alumina scaffold dimensions were 10 mm in outer diameter, 20 mm in length, and with either a 3 mm passage or no passage. A 20 mm segmental defect was induced using an oscillating saw through the diaphysis of the beagle tibia. The defects of six beagles were filled with HA/alumina bilayered scaffolds with a 3 mm passage or without. The segmental defect was fixated using one bone plate and six screws. Bone regeneration within the HA/alumina scaffolds was observed at eight weeks after implantation. The evaluation of bone regeneration within the scaffolds after implantation in a beagle tibia was performed using radiography, computerized tomography (CT, micro-CT, and fluorescence microscopy. New bone successfully formed in the tibia defects treated with 3 mm passage HA/alumina scaffolds compared to without-passage HA/alumina scaffolds. It was concluded that the HA/alumina bilayered scaffold with 3 mm passage-like medullary canal was instrumental in inducing host-scaffold engraftment of the defect as well as distributing the newly formed bone throughout the scaffold at 8 weeks after implantation.

  10. Android for the Beaglebone Black

    CERN Document Server

    Henderson, Andrew

    2015-01-01

    If you are an Android app developer who wants to experiment with the hardware capabilities of the BeagleBone Black platform, then this book is ideal for you. You are expected to have basic knowledge of developing Android apps but no prior hardware experience is required.

  11. Pacific Northwest Laboratory annual report for 1976 to the ERDA Assistant Administrator for Environment and Safety. Part 1. Biomedical Sciences

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, R.C.

    1977-05-01

    Separate abstracts were prepared for individual sections of this publication. In addition to research reports the publication also contains organization charts, author index, and appendixes showing data on selected parameters relative to life-span dose-effect studies with inhaled /sup 239/PuO/sub 2/, /sup 238/PuO/sub 2/, and /sup 239/Pu in beagles. (HLW)

  12. Bone reactions at implants subjected to experimental peri-implantitis and static load. A study in the dog

    DEFF Research Database (Denmark)

    Gotfredsen, K; Berglundh, T; Lindhe, J

    2002-01-01

    AIM: The aim of the present experiment was to study peri-implant tissue reactions to lateral static load at implants subjected to experimental mucositis or peri-implantitis. MATERIAL AND METHODS: 5 beagle dogs were used. The mandibular premolars were extracted. After 12 weeks, 3 implants were ins...

  13. The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate.

    NARCIS (Netherlands)

    Song, G.; Habibovic, P.; Bao, C.; Hu, J.; Blitterswijk, van C.A.; Yuan, H.; Chen, W.; Xu, H.H.K.

    2013-01-01

    Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagl

  14. Effect of short-term scrotal hyperthermia on spermatological parameters, testicular blood flow and gonadal tissue in dogs

    NARCIS (Netherlands)

    Henning, H; Masal, C; Herr, A; Wolf, K; Urhausen, C; Beineke, A; Beyerbach, M; Kramer, S; Günzel-Apel, A-R

    2014-01-01

    The objective was to assess the effect of a short-term scrotal hyperthermia in dogs on quantitative and qualitative ejaculate parameters, testicular blood flow and testicular and epididymal histology. After a control period, the scrotum of seven normospermic adult beagle dogs was insulated with a se

  15. Subchronic (13-week) oral toxicity study of y-cyclodextrin in dogs

    NARCIS (Netherlands)

    Til, H.P.; Bär, A.

    1998-01-01

    The oral toxicity of γ-cyclodextrin (γ- CD) was examined in a 13-week feeding study in which four groups of four male and four female Beagle dogs received γ-CD in the diet at concentrations of 0 (control), 5, 10, or 20%. No treatment-related changes were noted in behavior or appearance of the dogs a

  16. Phasing of many thousands of genotyped samples.

    Science.gov (United States)

    Williams, Amy L; Patterson, Nick; Glessner, Joseph; Hakonarson, Hakon; Reich, David

    2012-08-10

    Haplotypes are an important resource for a large number of applications in human genetics, but computationally inferred haplotypes are subject to switch errors that decrease their utility. The accuracy of computationally inferred haplotypes increases with sample size, and although ever larger genotypic data sets are being generated, the fact that existing methods require substantial computational resources limits their applicability to data sets containing tens or hundreds of thousands of samples. Here, we present HAPI-UR (haplotype inference for unrelated samples), an algorithm that is designed to handle unrelated and/or trio and duo family data, that has accuracy comparable to or greater than existing methods, and that is computationally efficient and can be applied to 100,000 samples or more. We use HAPI-UR to phase a data set with 58,207 samples and show that it achieves practical runtime and that switch errors decrease with sample size even with the use of samples from multiple ethnicities. Using a data set with 16,353 samples, we compare HAPI-UR to Beagle, MaCH, IMPUTE2, and SHAPEIT and show that HAPI-UR runs 18× faster than all methods and has a lower switch-error rate than do other methods except for Beagle; with the use of consensus phasing, running HAPI-UR three times gives a slightly lower switch-error rate than Beagle does and is more than six times faster. We demonstrate results similar to those from Beagle on another data set with a higher marker density. Lastly, we show that HAPI-UR has better runtime scaling properties than does Beagle so that for larger data sets, HAPI-UR will be practical and will have an even larger runtime advantage. HAPI-UR is available online (see Web Resources).

  17. Radiation exposure and risk estimates for inhaled airborne radioactive pollutants including hot particles. Annual report 1 July 1976--30 June 1977

    Energy Technology Data Exchange (ETDEWEB)

    Mewhinney, J.A.

    1978-03-01

    Contents: Mixed-oxide fuel fabrication; Generation of aerosols of mixed uranium-plutonium oxides from dry powders for animal inhalation exposures; Analytical radiochemical determination of U, Pu and Am in biological samples; Physical chemical characterization of mixed uranium-plutonium oxide nuclear fuel as samples during animal inhalation exposure; Pilot studies of deposition and retention of industrial mixed-oxide aerosols in the laboratory rat; Extended radiation dose pattern studies of aerosols of mixed uranium-plutonium oxides treated at 750C inhaled by Fishcer-344 rats, beagle dogs and cynomolgus monkeys; Extended radiation dose pattern studies of aerosols of plutonium dioxide, treated at 850C and inhaled by Fischer-344 rats, beagle dogs and cynomolgus monkeys.

  18. Oral absorption and bioavailability of fenbendazole in the dog and the effect of concurrent ingestion of food.

    Science.gov (United States)

    McKellar, Q A; Galbraith, E A; Baxter, P

    1993-06-01

    Fenbendazole was administered orally without food to six beagle dogs at 2.5, 5.0, 10, 20, 40 and 80 mg/kg of body weight. Increasing the dose rate did not significantly increase the amount of fenbendazole absorbed. In a separate study fenbendazole was administered to the same six beagle dogs at a dose rate of 20 mg/kg of bodyweight in food with high, medium and low fat content. The food provided 1.52, 0.70 or 0.34 g of fat per kg of body weight. Administration of fenbendazole in food with different fat contents did not affect its relative bioavailability. Administration of fenbendazole at a dose rate of 20 mg/kg in food, irrespective of fat content, did however significantly increase its bioavailability when compared to administration of the same dose as a bolus on an empty stomach.

  19. Charles Robert Darwin and Argentina's National Academy of Sciences

    Directory of Open Access Journals (Sweden)

    Pedro José Depetris

    2009-04-01

    Full Text Available Over 175 years ago Charles Robert Darwin arrived in Argentina to find a bare and boundless plain, the brave centaur called "gaucho", Quaternary fossils everywhere, and a society strikingly strange and aggressive to the British eyes of the young traveller. Although the voyage aboard HMS Beagle was the indispensable way towards increasing his stature as a biologist, Lyell's work awakened an inquisitive geological mind which allowed him to wonder at the splendour of the Andes. Forty-two years after having concluded his voyage on the Beagle, the National Academy of Sciences of Argentina appointed him as an Honorary Member. This must be interpreted as an early gesture of recognition -in the context of those times- to the magnificence of his scientific work.

  20. Brachytherapy for the prevention of neointimal hyperplasia in the canine inferior vena cava after stent placement

    Energy Technology Data Exchange (ETDEWEB)

    Isota, Masayuki; Kaminou, Toshio; Sakai, Yukimasa; Nakamura, Kenji; Yamada, Ryusaku [Osaka City Univ. (Japan). Medical School

    2002-06-01

    The aim of this study was to evaluate the efficacy of brachytherapy for preventing neointimal hyperplasia in the inferior vena cava (IVC) after stent placement. Sixteen beagles underwent Z-stent placement in the IVC and the aorta. For 8 of 16 beagles, irradiation (15 Gy) was delivered endoluminally to the stented segments of each vessel immediately after stent placement using the {sup 192}Ir. All animals were sacrificed after 6 weeks for morphometric and histopathologic examination. Morphometrically, neointimal thickness in the IVC of the radiation group was significantly decreased compared with the control group as well as that in the aorta (p<0.05). Histopathologic findings showed the neointima in the IVC of the control group contained markedly organization of thrombus and neovascularization though that in the IVC of the radiation group consisted mainly of smooth muscle cells without organization of thrombus and neovascularization. From these data intravenous irradiation may prevent clinical restenosis after stent placement. (author)

  1. Thrombin-activatable fibrinolysis inhibitor activity in healthy and diseased dogs

    DEFF Research Database (Denmark)

    Jessen, Lisbeth Rem; Wiinberg, Bo; Kjelgaard-Hansen, Mads

    2010-01-01

    Background: In people, increased thrombin-activatable fibrinolysis inhibitor (TAFI) antigen has been associated with increased risk of thrombosis, and decreased TAFI may contribute to bleeding diathesis. TAFI activity in dogs has been described in experimental models, but not in dogs...... with spontaneous disease. Objective: The aim of this study was to compare TAFI activity in healthy dogs with TAFI activity in dogs with spontaneous disease. Methods: Plasma samples from 20 clinically healthy Beagles and from 35 dogs with various diseases were analyzed using a commercial chromogenic assay...... that measured TAFI activity relative to activity in standardized pooled human plasma. Results: Median TAFI activity for the 20 Beagles was 46.1% (range 32.2-70.8%) compared with 62.6% (29.1-250%) for the 35 diseased dogs, and 14/35 (40%) had TAFI activities >the upper limit for controls. The highest individual...

  2. Transport and scavenging of Pu in surface waters of the Southern Hemisphere Oceans

    DEFF Research Database (Denmark)

    Gastaud, J.; Povinec, P.P.; Aoyama, M.

    2011-01-01

    The distribution of 239Pu in Atlantic and Indian Ocean waters about four decades after their main injection from atmospheric nuclear weapons tests is discussed. Recent data obtained in the framework of the SHOTS (Southern Hemisphere Ocean Tracer Studies) projects are evaluated and compared...... with previous investigations. Seawater samples were collected during the round the globe BEAGLE2003 (Blue Ocean Global Expedition) along the 30°S transect in the Atlantic and the 20°S transect in the Indian Ocean. The results indicate transport of surface waters labelled with 239Pu from the western North...... Pacific via the Indonesian Seas to the South Indian Ocean and then to the South Atlantic Ocean. Along the whole BEAGLE2003 sampling route, the Atlantic Ocean has the lowest 239Pu content due to its particle scavenging on the long way from the western North Pacific. On the other hand, concentrations...

  3. Screening for periodontal disease in research dogs - a methodology study

    DEFF Research Database (Denmark)

    Kortegaard, Hanne E; Eriksen, Thomas; Bælum, Vibeke

    2014-01-01

    BackgroundIt has been shown that the prevalence of both clinical attachment loss (CAL) >1 mm and pocket probing depth (PPD) >4 mm is relatively high even in younger dogs, but also that only a minority of the dogs have such clinical signs of periodontal disease (PD) in more than a few teeth. Hence...... is the central variable in assessing PD extent and severity while PPD is the central variable used in treatment planning which make these two variables obvious in a screening protocol with the dual aim of disease identification and treatment planning. The main purpose of the present study in 98 laboratory Beagle.......2% of all teeth positive for CAL ¿1mm. The results presented here only pertain to the present study population.ConclusionsThis screening protocol is suitable for examination of larger groups of laboratory Beagle dogs for PD and our findings indicate that diseased dogs are identified with a high degree...

  4. Mammary tumors and serum hormones in the bitch treated with medroxyprogesterone acetate or progesterone for four years

    Energy Technology Data Exchange (ETDEWEB)

    Frank, D.W.; Kirton, K.T.; Murchison, T.E.; Quinlan, W.J.; Coleman, M.E.; Gilbertson, T.J.; Feenstra, E.S.; Kimball, F.A.

    1978-01-01

    After four years of a long term contraceptive steroid safety study, the incidence and the histologic type of mammary dysplasia produced is similar in beagles treated with medroxyprogesterone acetate (medroxyprogesterone) or progesterone. Serum insulin, thyroid stimulating hormone (TSH), triiodothyronine, growth hormone, prolactin, 17..beta..-estradiol, progesterone, and cortisol were determined by radioimmunoassay on samples collected after 45 months of treatment. Serum growth hormone and insulin concentrations were elevated in a dose related manner in both treatment groups. Triiodothyronine, cortisol, and estradiol-17..beta.. (medroxyprogesterone only) were lowered. TSH and prolactin concentrations were not changed. Pituitary--gonadal hormone interaction in the pathogenesis of mammary neoplasia of the dog is discussed. Prolonged treatment of the beagle with massive doses of progesterone or medroxyprogesterone results in a dose related incidence of mammary modules.

  5. Statistical methods for longitudinal data with agricultural applications

    DEFF Research Database (Denmark)

    Anantharama Ankinakatte, Smitha

    The PhD study focuses on modeling two kings of longitudinal data arising in agricultural applications: continuous time series data and discrete longitudinal data. Firstly, two statistical methods, neural networks and generalized additive models, are applied to predict masistis using multivariate...... algorithm. This was found to compare favourably with the algorithm implemented in the well-known Beagle software. Finally, an R package to apply APFA models developed as part of the PhD project is described...

  6. Neutron metrology in the HFR

    Energy Technology Data Exchange (ETDEWEB)

    Voorbraak, W.P.; Freudenreich, W.E.; Stecher-Rasmussen, F.; Verhagen, H.W.

    1991-10-01

    Neutron fluence rate and gamma dose data are presented for the first series of experiments at the filtered HFR beam HB11 at full reactor power. Measurements were performed on two beagle dogs and one cylindrical phantom. The main results for thermal and epithermal fluence rates, physical neutron dose and gamma dose are presented in the tables 1 and 2. (author). 10 refs.; 9 figs.; 8 tabs.

  7. A boost for Europe's space industry%蓬勃发展的欧洲航天业

    Institute of Scientific and Technical Information of China (English)

    王其

    2003-01-01

    It's a race between the old and the new eontinent: For the first time. Eurnpean space agencies compete with NASA to be the first explorer under the surface of Mars. The European space probe “beagle 2” was successfully launched with the shuttle “Mars Express” in June. It could land ou the red planet already by christmas-and unveil unexplored secrets.

  8. Solar Structures Program

    Science.gov (United States)

    2015-03-27

    them in connection with a variety of different CubeSat form factors with differing motherboard combinations. Progress has been made on these goals...team at COSMIAC recently created a spacecraft command and data handling unit that is based on the popular Beagle Bone Black motherboard . This... motherboard operates on a state-of-the-art Texas Instrument’s processor. The control system was written in the object oriented programming language

  9. Geology of the area of Bahía Blanca, Darwin's view and the presentknowledge: a story of 10 million years Geología del área de Bahía Blanca, los comentarios de Darwin y elconocimiento actual: una historia de 10millones de años

    OpenAIRE

    Quattrocchio,Mirta E; Cecilia M. Deschamps; Carlos A. Zavala; Silvia C. Grill; Ana M. Borrome

    2009-01-01

    Theaim of this paper is to give an updated outlook of the scenery described byCharles Darwin when he visited Bahía Blanca and surrounding areas, following the itinerary during hisvoyage on board HMS Beagle. Such an outlook is a state of the art of thecurrent understanding of the Late Miocene-Holocene history in the southwestern Pampas (Argentina). Multidisciplinaryresults were integrated in a chronosequence chart synthesizing the suggestedspace-time correlation of the recognized events. Some ...

  10. Charles Darwin and the 1835 earthquake at Concepcion, Chile

    Science.gov (United States)

    Spall, H.

    1981-01-01

    On a stormy night in October 1836, H.M.S Beagle hove to and dropped anchor at Falmouth, a remote harbor in southwest England. Charles Darwin, the ship's naturalist, came ashore to take the mail coach to Shrewsbury. This was inauspicious end to an epic 5-year voyage around the coast of South America, the results of which were to have a tumultuous impact on scientific thought that has lasted to this day. 

  11. Acute Electrocardiographic ST Segment Elevation May Predict Hypotension in a Swine Model of Severe Cyanide Toxicity

    Science.gov (United States)

    2012-04-21

    were also detected before hypotension. Keywords Cyanide . Cardiology . Toxicology . Electrocardiography . Hypotension . STelevation Background Cyanide... Cardiology , the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Institute of Critical Care Medicine, the Safar Center for...Reid F (2006) Efficacy of hydroxoco balamin for the treatment of acute cyanide poisoning in adult beagle dogs . Clin Toxicol (Phila) 44(Suppl 1):5 15 290 J. Med. Toxicol. (2012) 8:285 290

  12. Hydroxocobalamin Versus Sodium Thiosulfate for the Treatment of Acute Cyanide Toxicity in a Swine (Sus scrofa) Model

    Science.gov (United States)

    2012-06-01

    treatment of acute cyanide poisoning in adult beagle dogs . Clin Toxicol (Phila). 2006;44(suppl 1):5-15. 15. Posner MA, Tobey RE, McElroy H...cobalamine and acute cyanide poisoning in dogs . Life Sci. 1965;4:1785-1789. 18. Borron SW, Baud FJ, Barriot P, et al. Prospective study of hydroxocobalamin... Cardiology , the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Institute of Critical Care Medicine, the Safar Center for

  13. A Physiologically Based Pharmacokinetic (PB/PK) Model for Multiple Exposure Routes of Soman in Multiple Species

    Science.gov (United States)

    2006-01-01

    per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing...Although the beagle is extensively used susceptible to the neurotoxicity induced by ivermectin , a in the safety assessment studies of new drug candidates...tissueainto CYP isozyme polymorphism in dogs. Recently, a single ivermectin not to be extruded from the brain tissue into nucleotide polymorphism

  14. HEALING OF PERI-IMPLANT TISSUES AFTER FLAPLESS AND FLAPPED IMPLANT INSTALLATION

    OpenAIRE

    Bayounis, Abeer; Alzoman, Hamad; Jansen, John; Babay, Nadir

    2011-01-01

    Abstract Aim: The aim of this study was to investigate the consequences of different flapless procedures for the installation of dental implants on peri-implant bone response Materials and methods: After bilateral extraction of the mandibular second and third premolars and a three-month healing period, 30 SLActive ? implants were installed for three months in 10 Beagle dogs according to three different surgical approaches, i.e.: (1) flapped (F), (2) tissue punch flapless (P), an...

  15. The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds

    OpenAIRE

    Kim, Ju-Won; Lee, Jong-Hwan; Lyoo, Young S.; JUNG, Dong-In; Park, Hee-Myung

    2013-01-01

    Background Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow