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Sample records for aged beagle dogs

  1. Adrafinil disrupts performance on a delayed nonmatching-to-position task in aged beagle dogs.

    PubMed

    Siwak, Christina T; Tapp, P Dwight; Milgram, Norton W

    2003-08-01

    Previous studies in humans and dogs have reported beneficial effects of adrafinil on specific cognitive functions. The effects in dogs are limited to a single study examining discrimination learning. We wanted to further explore the cognitive effects of adrafinil in dogs. The purpose of the present study was to determine the effect of oral administration of adrafinil on visuospatial function in dogs. Eighteen aged beagle dogs were tested on a delayed nonmatching-to-position (DNMP) task 2 h following one of three possible treatments; 20 mg/kg of adrafinil, 10 mg/kg of adrafinil or a placebo control. All dogs were tested under each treatment for eight test sessions. A 2-day washout period was given between treatments and the order of treatments was varied. Treatment with 20 mg/kg of adrafinil produced a significant impairment in working memory as indicated by an increase in the number of errors over the 8-day test period. The disturbance of memory functions from adrafinil could be a result of increased noradrenergic transmission in the prefrontal cortex.

  2. Oral administration of adrafinil improves discrimination learning in aged beagle dogs.

    PubMed

    Milgram, N W; Siwak, C T; Gruet, P; Atkinson, P; Woehrlé, F; Callahan, H

    2000-06-01

    Aged beagle dogs were trained on either a size or intensity discrimination task 2 h following treatment with either 20 mg/kg of adrafinil or a placebo control. Training continued until the dogs reached a predetermined criterion level of performance, or failed to acquire the task after 40 sessions. The treatments and tasks were then reversed, with both the test order and treatment order counterbalanced. Thus, half of the animals were first tested on the intensity discrimination, and half of these were first tested under adrafinil. Treatment with adrafinil produced significant improvement in learning, as indicated by a decrease in both errors and trials to criterion. An effect of adrafinil on motivation may partially account for these findings; however, adrafinil did not significantly affect response latency. Adrafinil is believed to serve as an alpha-1 adrenoceptor agonist. The improved learning may also result from enhancement of vigilance due to facilitation of noradrenergic transmission in the central nervous system.

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

    SciTech Connect

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

    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.

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

    PubMed

    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.

  5. Comparison of expression of inflammatory cytokines in the spinal cord between young adult and aged beagle dogs.

    PubMed

    Lee, Dae Hwan; Ahn, Ji Hyeon; Park, Joon Ha; Yan, Bing Chun; Cho, Jeong-Hwi; Kim, In Hye; Lee, Jae-Chul; Jang, Sang-Hun; Lee, Myoung Hyo; Hwang, In Koo; Moon, Seung Myung; Lee, Bonghee; Cho, Jun Hwi; Shin, Hyung-Cheul; Kim, Jin Sang; Won, Moo-Ho

    2013-07-01

    Aging is an inevitable process that occurs in the whole body system accompanying with many functional and morphological changes. Inflammation is known as one of age-related factors, and inflammatory changes could enhance mortality risk. In this study, we compared immunoreactivities of inflammatory cytokines, such as interleukin (IL)-2 (a pro-inflammatory cytokine), its receptor (IL-2R), IL-4 (an anti-inflammatory cytokine), and its receptor (IL-4R) in the cervical and lumbar spinal cord of young adult (2-3 years old) and aged (10-12 years old) beagle dogs using immunohistochemistry and western blotting. IL-2 and IL-2R-immunoreactive nerve cells were found throughout the gray matter of the cervical and lumbar spinal cord of young adult and aged dogs. In the spinal cord neurons of the aged dog, immunoreactivity and protein levels were apparently increased compared with those in the young adult dog. Change patterns of IL-4- and IL-4R-immunoreactive cells and their protein levels were also similar to those in IL-2 and IL-2R; however, IL-4 and IL-4R immunoreactivity in the periphery of the neuronal cytoplasm in the aged dog was much stronger than that in the young adult dog. These results indicate that the increase of inflammatory cytokines and their receptors in the aged spinal cord might be related to maintaining a balance of inflammatory reaction in the spinal cord during normal aging.

  6. Penis Allotransplantation in Beagle Dog.

    PubMed

    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.

  7. Penis Allotransplantation in Beagle Dog

    PubMed Central

    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. PMID:26977412

  8. 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.

    PubMed

    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.

  9. Cholinesterase inhibitors improve both memory and complex learning in aged beagle dogs.

    PubMed

    Araujo, Joseph A; Greig, Nigel H; Ingram, Donald K; Sandin, Johan; de Rivera, Christina; Milgram, Norton W

    2011-01-01

    Similar to patients with Alzheimer's disease (AD), dogs exhibit age-dependent cognitive decline, amyloid-β (Aβ) pathology, and evidence of cholinergic hypofunction. The present study sought to further investigate the role of cholinergic hypofunction in the canine model by examining the effect of the cholinesterase inhibitors phenserine and donepezil on performance of two tasks, a delayed non-matching-to-position task (DNMP) designed to assess working memory, and an oddity discrimination learning task designed to assess complex learning, in aged dogs. Phenserine (0.5 mg/kg; PO) significantly improved performance on the DNMP at the longest delay compared to wash-out and partially attenuated scopolamine-induced deficits (15 μg/kg; SC). Phenserine also improved learning on a difficult version of an oddity discrimination task compared to placebo, but had no effect on an easier version. We also examined the effects of three doses of donepezil (0.75, 1.5, and 6 mg/kg; PO) on performance of the DNMP. Similar to the results with phenserine, 1.5 mg/kg of donepezil improved performance at the longest delay compared to baseline and wash-out, indicative of memory enhancement. These results further extend the findings of cholinergic hypofunction in aged dogs and provide pharmacological validation of the canine model with a cholinesterase inhibitor approved for use in AD. Collectively, these studies support utilizing the aged dog in future screening of therapeutics for AD, as well as for investigating the links among cholinergic function, Aβ pathology, and cognitive decline.

  10. Renal dysplasia in Beagle dogs: four cases.

    PubMed

    Bruder, Marc C; Shoieb, Ahmed M; Shirai, Norimitsu; Boucher, Germaine G; Brodie, Thomas A

    2010-12-01

    Anomalies of renal development comprise abnormalities in the amount of renal tissue (agenesis and hypoplasia); anomalies of renal position, form, and orientation; and renal dysplasia. There are previous reports of canine renal dysplasia in different breeds but none in the Beagle breed. This is the first report of renal dysplasia in this breed of dog. Morphologic descriptions of the range of microscopic features observed in four cases of renal dysplasia from preclinical studies in laboratory Beagle dogs are presented (including persistent primitive mesenchyme, persistence of metanephric ducts, asynchronous differentiation of nephrons, and atypical tubular epithelium), along with a basis for the classification of the lesion.

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

    PubMed

    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.

  12. Effects of Age on Measures of Complex Working Memory Span in the Beagle Dog (Canis familiaris) Using Two Versions of a Spatial List Learning Paradigm

    PubMed Central

    Tapp, P. Dwight; Siwak, Christina T.; Estrada, Jimena; Holowachuk, Daniel; Milgram, Norton W.

    2003-01-01

    The present study used two versions of a spatial list learning (SLL) paradigm to examine the effects of increased cognitive load on visuospatial working memory processes in young and old beagle dogs. In the first experiment, young, and a select group of old dogs were first presented with one item, then two, and then three, and were rewarded for responding to the novel position. The dogs were able to learn the task at short delays, but compared with young dogs, old dogs performed worse at delays of 10 sec, and could not reach longer delays. Analysis of errors indicated that memory was best for end items in the spatial list and that within sessions, the number of errors in later trials was greater than the number of errors in earlier trials. A second version of the task, a modified SLL (mSLL) was developed to control for the use of non-mnemonic strategies on the SLL task. In this version, the first two items were presented individually. Acquisition and maximal memory performance were better in the young relative to the old dogs. Similar to the original SLL design, memory for early list items was worse than memory for later list items in both young and old dogs. The within-session pattern of errors however, did not change from trial to trial on the mSLL. The present results suggest that multiple working memory processes are engaged during complex tests of visuospatial function and the neuroanatomical substrates controlling these processes are affected differentially by age in the beagle dog. PMID:12663753

  13. Microdosimetry of plutonium in beagle dog lung

    SciTech Connect

    Fisher, D.R.; Roesch, W.C.

    1980-08-01

    A better understanding of the microdosimetry of internally-deposited radionuclides should provide new clues to the complex relationships between organ dose distribution and early or late biological effects. Our current interest is the microdosimetry of plutonium and other alpha emitters in the lung. Since the lung is an inhomogeneous tissue, it was necessary to characterize the microscopic distributions of alveolar tissue, air space, and epithelial cell nuclei to define source-target parameters. A statistical representation of the microstructure of beagle dog lung was developed from automated image analysis of specimens from three healthy adult male dogs. The statistical distributions obtained constituted a data base from which it was possible to calculate both the energy dissipation of an alpha particle as it traversed a straight line path through pulmonary tissue, and the probability of intersecting a potentially sensitive biological site in the cell. Computer methods were modified to accomodate tissues with air space regions such as one finds in lung tissue. With the lung model description, these methods were used to determine probability density curves in specific energy for inhaled plutonium aerosols. It was assumed that the activity was randomly distributed on alveolar walls. Calculated examples are given for various activities of inhaled plutonium point sources deposited in lung tissue.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. Experimental gingivitis and frequency of tooth brushing in the beagle dog model. Clinical findings.

    PubMed

    Tromp, J A; van Rijn, L J; Jansen, J

    1986-03-01

    The aim of this experiment was to study clinical parameters when 3 different frequencies of tooth brushing were applied to sites of experimental gingivitis in beagle dogs. 12 beagle dogs, at the start of the experiment 2 years of age, were used. After a thorough cleaning, the maxillary left and right first, second and third premolars were brushed daily for a period of 8 weeks. Subsequently, for 4 weeks, all brushing was omitted in order to establish an experimental gingivitis. After this pre-experimental period, the dogs were distributed into 3 groups of 4 dogs each: one group was brushed 7 times a week, a second was brushed 3 times a week and the third group was brushed only once a week. Brushing was carried out for 24 weeks, only on the right sides of the upper jaws, the left upper jaws serving as controls. At regular intervals, plaque index, gingival index and probing depths were assessed. A brushing effect was calculated for each dog, to include information on all within-dog and between-dog variations. The present study demonstrated that only by brushing every day can clinically healthy gingivae be obtained in the beagle dog model with experimental gingivitis at baseline. The state of gingival health at baseline may be used to determined the frequency of brushing necessary to create or maintain healthy gingivae.

  16. Gingival health and frequency of tooth brushing in the beagle dog model. Clinical findings.

    PubMed

    Tromp, J A; Jansen, J; Pilot, T

    1986-02-01

    The aim of this experiment was to study clinical parameters when 3 different frequencies of plaque removal were applied to healthy gingivae in the beagle dog model. The maxillary first, second and third premolars of 12 beagle dogs, at the start of the experiment 2 years of age, were, after a thorough cleaning, submitted to daily plaque removal during a pre-experimental period of 8 weeks. At the start of the experiment, the dogs were distributed into 3 groups of 4 dogs each: one group was brushed 7 times a week, a second group was brushed 3 times a week and another group was brushed only once a week. Brushing was executed over a period of 24 weeks, on the right sides of the upper jaws. The left upper jaws served as controls. At regular intervals, the plaque index, the gingival index and probing depths were assessed. A "brushing effect" was calculated for each dog, to include information on all within-dog and between dog variations. Comparison of brushing effects revealed that in this experimental model, plaque removal with a frequency of 3 times a week was sufficient to preserve gingival health, whereas tooth brushing once a week resulted in gingival inflammation. Therefore it can be concluded that 3 times a week is the critical brushing frequency in the beagle dog model with healthy gingiva at baseline.

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

    PubMed

    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

  18. Biological effects of {sup 137}CsCl injected in beagle dogs of different dogs

    SciTech Connect

    Nikula, K.J.; Boecker, B.B.; Griffith, W.C.

    1996-11-01

    The toxicity of {sup 137}Cs in the beagle dog was investigated at the Inhalation Toxicology Research Institute (ITRI) and Argonne National Laboratory (ANL) as part of programs to evaluate the biological effects of both radionuclides in atomic bomb fallout and internally deposited fission-product radionuclides. In the ITRI study, young adult dogs were exposed once by intravenous injection to a range of {sup 137}Cs concentrations; the results have recently been published. The purpose of the present report is to summarize the ANL study and to compare the results of the two studies. At ANL, 63 dogs in three age groups (15 juveniles, 142-151 days old; 38 young adults, 388-427 days old; and 10 middle-aged dogs, 1387-2060 days old) were given {sup 137}Cs intravenously at levels (61-162f MBq/kg) near those expected to be lethal within 30 days after injection. There were 17 control dogs from the same colony. Twenty-three of the dogs injected with {sup 137}Cs, including all middle-aged dogs, died within 52 days after injection due to hematopoietic cell damage resulting in severe pancytopenia that led to fatal hemorrhage and/or septicemia. The other significant early effect was damage to the germinal epithelium of the seminiferous tubules. The design of the ANL study revealed an age- and gender-related differential radiosensitivity for early effects. The middle-aged dogs died significantly earlier due to complications of hematological dyscrasia compared to the juvenile and young adult dogs, and the middle-aged females died significantly earlier than the middle-aged males. The most significant non-neoplastic late effects in the {sup 137}Cs-injected dogs from ANL and ITRI were atrophy of the germinal epithelium of seminiferous tubules with azoospermia, and a significant dose-dependent decrease in survival. The survival of the ANL dogs was decreased more than that of the ITRI dogs at similar radiation doses from {sup 137}Cs. 19 refs., 6 figs., 4 tabs.

  19. Response and adaptation of Beagle dogs to hypergravity

    NASA Technical Reports Server (NTRS)

    Oyama, J.

    1975-01-01

    Eight male Beagle dogs, five months old, were centrifuged continuously for three months at progressively increasing loads. Heart rate and deep body temperature were monitored continuously by implant biotelemetry. Initially, centrifuged dogs showed transient decreases in heart rate and body temperature along with changes in their diurnal rhythm patterns. Compared with normal gravity controls, exposed dogs showed a slower growth rate and a reduced amount of body fat. Blood protein, total lipids, cholesterol, calcium, packed cell volume, red blood cell count, and hemoglobin were also decreased significantly. Absolute weights of the leg bones of centrifuged dogs were significantly greater than controls. Photon absorptiometry revealed significant density increases in selective regions of the femur and humerus of centrifuged dogs. In spite of the various changes noted, results from this and other studies affirm the view that dogs can tolerate and adapt to sustained loads as high as 2.5 g without serious impairment of their body structure and function.

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

    PubMed

    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.

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

    PubMed

    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 (< 1 year old), adult (1 ˜ 5 years old), and senile animals (≥ 6 years old). Normal ERG ranges were obtained. Significant differences in b-wave amplitude along with b/a ratio of the combined rod-cone response were found between the young and adult animals as well as young and senile dogs. No significant differences were observed between the left and right eyes. ERG variables in 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.

  2. Sulfur dioxide-induced chronic bronchitis in beagle dogs

    SciTech Connect

    Greene, S.A.; Wolff, R.K.; Hahn, F.F.; Henderson, R.F.; Mauderly, J.L.; Lundgren, D.L.

    1984-01-01

    This study was done to produce a model of chronic bronchitis. Twelve beagle dogs were exposed to 500 ppm sulfur dioxide (SO/sub 2/) for 2 h/d, 5d/wk for 21 wk and 4 dogs were sham-exposed to filtered ambient air for the same period. Exposure effects were evaluated by periodically examining the dogs using chest radiographs, pulmonary function, tracheal mucous clearance, and the cellular and soluble components of bronchopulmonary lavage fluids. Dogs were serially sacrificed after 13 and 21 wk of exposure and after 6 and 14 wk of recovery. Clinical signs produced in the SO/sub 2/-exposed dogs included mucoid nasal discharge, productive cough, moist rales on auscultation, tonsilitis, and conjunctivitis. Chest radiographs revealed mild peribronchiolar thickening. Histopathology, tracheal mucous clearance measurements, and lavage cytology were consistent with a diagnosis of chronic bronchitis. It is concluded that repeated exposure to 500 ppm SO/sub 2/ for 21 wk produced chronic bronchitis in the beagle dog. Complete recovery occurred within 5 wk following cessation of SO/sub 2/ exposure. 43 references, 2 figures, 2 tables.

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

    PubMed

    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.

  4. Beagle Dog Tissue Archive (previously part of National Radiobiology Archives): from the Janus Tissue Archive at Northwestern University

    DOE Data Explorer

    Watson, Charles R.

    Following the advent of the atomic age, many nations have investigated the effects of radioactive exposure in animal models. Some of these investigations involved costly and unique experiments that produced tissue and data archives which are unlikely to be reproduced. In an effort to extract the value from these collections, programs have started in Japan, Europe, and America to preserve and make public the data and tissues from these studies for further investigation. The Beagle Dog Experiments, carried out at Argonne National Laboratory from 1952 to 1991 by Thomas Fritz, William Norris, and Tom Seed and supported by grants from the Atomic Energy Commission, investigated the effects of Cobalt-60 radiation on beagle dogs. Documentation from these studies is availible in pdf form. This web portal seeks to make accessible the animal tissues and study data from the Beagle Dog Experiments using data organized by Charles Watson. Use the search form to the left to look for dog data from particular experimental conditions. Click a dog number to return the full dog record. Use the dog record to find tissues of interest and make a sample tissue request. These tissue samples and the data were known until recently as the the U.S. National Radiobiology Archives (NRA) and were maintained as the United States Transuranium and Uranium Registries (USTUR) at Washington State University. Life-span studies using beagle dogs were done at the Argonne National Laboratory, University of California at Davis, Pacific Northwest National Laboratory, Inhalation Toxicology Research Institute, and the University of Utah. The results and many microscope slides from these life-span studies, totaling some 6000 dogs, are now available to researchers. A seminal work included in the Archive is The Atlas of Experimentally-Induced Neoplasia in the Beagle Dog (Watson et al, 1997).

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

    PubMed

    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. Toxicity of inhaled plutonium dioxide in beagle dogs

    SciTech Connect

    Muggenburg, M.A.; Guilmette, R.A.; Mewhinney, J.A.

    1996-03-01

    This study was conducted to determine the biological effects of inhaled {sup 238}PuO{sub 2} over the life spans of 144 beagle dogs. The dogs inhaled one of two sizes of monodisperse aerosols of {sup 238}PuO{sub 2} to achieve graded levels of initial lung burden (ILB). The aerosols also contained {sup 169}Yb to provide a {gamma}-ray-emitting label for the {sup 238}Pu inhaled by each dog. Excreta were collected periodically over each dog`s life span to estimate plutonium excretion; at death, the tissues were analyzed radiochemically for plutonium activity. The tissue content and the amount of plutonium excreted were used to estimate the ILB. These data for each dog were used in a dosimetry model to estimate the ILB. These data for each dog were used in a dosimetry model to estimate tissue doses. The lung, skeleton and liver received the highest {alpha}-particle doses, ranging from 0.16-68 Gy for the liver. At death, all dogs were necropsied, and all organs and lesions were sampled and examined by histopathology. Findings of non-neoplastic changes included neutropenia and lymphopenia that developed in a dose-related fashion soon after inhalation exposure. These effects persisted for up to 5 years in some animals, but no other health effects could be related to the blood changes observed. Radiation pneumonitis was observed among the dogs with the highest ILBs. Deaths from radiation pneumonitis occurred from 1.5 to 5.4 years after exposure. Tumors of the lung, skeleton and liver occurred beginning at about 3 years after exposure. These findings in dogs suggest that similar dose-related biological effects could be expected in humans accidentally exposed to {sup 238}PuO{sub 2}. 89 refs., 10 figs., 11 tab.

  7. Atlas of experimentally-induced neoplasia in beagle dogs

    SciTech Connect

    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.

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

    PubMed

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

    2011-01-01

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

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

    PubMed

    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.

  10. Americium in the beagle dog: biokinetic and dosimetric model.

    PubMed

    Luciani, A; Polig, E; Lloyd, R D; Miller, S C

    2006-05-01

    A biokinetic model of the systemic distribution of americium in the beagle dog is presented. The model is based on a previous biokinetic model of plutonium. The data sets used for the development of the model were the measurements of excreted activity (urine and feces) and organ burdens (skeleton, liver, and other soft tissues) for different levels of initial injected activity. In developing the model, the compartmental structure of the skeleton of the plutonium model was adopted, and only the numerical values of parameters were adapted. The model well describes the fractions of americium in the skeleton, liver, and soft tissues and the total fraction excreted in urine and feces. The tuning of the liver clearance parameter provides a realistic description of the change in the partitioning between liver and skeleton for different injection levels. The most significant features of the biokinetics and dosimetry of americium and plutonium in beagles are compared. The total fractions of the clearance to the skeleton and the liver are roughly equal to the value for plutonium, but the partitioning of americium between these organs is reversed with respect to the partitioning of plutonium. 241Am doses to liver and skeleton are similar to 239Pu doses, owing to some counteracting factors. For the highest injection level, the liver mass is dependent on the time post injection. For the skeletal tissues, the dose to the cortical endosteum by far exceeds the dose to the trabecular endosteum and the red marrow. The model provides the basis for statistical survival analyses and risk estimates.

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

    PubMed

    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.

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

    SciTech Connect

    Miller, G.K.

    1982-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. Novel phenotype in beagle dogs characterized by skin response to compound 48/80 focusing on skin mast cell degranulation.

    PubMed

    Uchida, Mitsuhiro; Ito, Fumi; Tsuchiya, Toshiyuki; Shoji, Yoko; Kurosawa, Toru

    2015-01-01

    Beagle dogs have long been employed in toxicology studies and as skin disease models. Compared with other experimental animal species, they are known to be susceptible to skin responses, such as rashes, from exposure to various chemical compounds. Here, a unique dog phenotype was identified that showed no skin response to compound 48/80, a mast cell degranulating agent. Although the skin responses to intradermal injection of polyoxyethylene castor oil derivative (HCO-60, a nonionic detergent), histamine dihydrochloride, concanavalin A (IgE receptor-mediated stimuli), or calcium ionophore A23187 were comparable in wild-type (WT) dogs and these nonresponder (NR) dogs, only the response to compound 48/80 was entirely absent from NR dogs. The skin mast cell density and histamine content per mast cell were histologically comparable between WT and NR dogs. By checking for skin responses to compound 48/80, NR dogs were found to exist at the proportion of 17-20% among four animal breeders. From retrospective analysis of in-house breeding histories, the NR phenotype appears to conform to the Mendelian pattern of recessive inheritance. The standard skin response in WT dogs developed at 2-4 months of age. In conclusion, this unique phenotype, typified by insensitivity in the compound 48/80-induced degranulation pathway in mast cells, has been widely retained by recessive inheritance in beagle dogs among general experimental animal breeders. The knowledge concerning this phenotype could lead to better utilization of dogs in studies and aid in model development.

  15. Prussian Blue decorporation of {sup 137}Cs in beagles of different ages

    SciTech Connect

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

    1996-08-01

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

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    Zeng, Ruixia; Zhang, Yibo; Du, Peng

    2014-01-01

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

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

    SciTech Connect

    Day, P.A.

    1988-01-01

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

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

    PubMed

    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.

  3. Calcium-excess causes subclinical changes of bone growth in Beagles but not in Foxhound-crossbred dogs, as measured in X-rays.

    PubMed

    Dobenecker, B; Kasbeitzer, N; Flinspach, S; Köstlin, R; Matis, U; Kienzle, E

    2006-10-01

    Numerous investigations and reports have covered the potential negative effects of an excess of calcium (Ca) in the skeletal development of young dogs. However, it still remains unclear why not all puppies, particularly of larger breeds, develop clinical signs of skeletal disorders after an overexposure to Ca. This trial with the small Beagle breed and a larger Foxhound-crossbred dog (with an adult weight of around 35 kg) investigated the effects of Ca-excess on parameters of bone growth. The employed small breed is known for its chondrodystrophic predispositions, no such data are reported for the slender hound-type Foxhound-crossbred dogs. The Ca-supply had no influence on weight development and general health of the dogs. The measurements of bone lengths and widths in X-rays of the forearm of Beagles and Foxhound-crossbred dogs at 6 weeks of age, and again after a period of overexposure to Ca at about 27 weeks of age, revealed a growth-reducing influence only in Beagles, without influence on clinical parameters of skeletal health.

  4. Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine

    PubMed Central

    Araujo, Joseph A.; Landsberg, Gary M.; Milgram, Norton W.; Miolo, Alda

    2008-01-01

    Aged dogs demonstrate cognitive decline that is linked to brain aging. The purpose of the present study was to examine if a commercially available nutraceutical supplement that may be neuroprotective and contains phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine could improve cognitive function in aged beagles. Nine aged beagles were tested on performance on a delayed-non-matching-to-position task, which is a neuropsychological test of short-term visuospatial memory. All subjects were tested on 5 baseline sessions; then, to assess the supplement, a crossover design was used in which 1 group received the supplement and the other a control substance in the 1st phase, with treatment conditions being reversed in the 2nd phase. Performance accuracy was significantly improved in supplemented dogs compared with control dogs and the effect was long lasting. These findings suggest that the nutraceutical supplement can improve memory in aged dogs. PMID:18481547

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

    PubMed

    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 <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.

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

    PubMed Central

    2011-01-01

    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. PMID:21366900

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

    PubMed

    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.

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

    PubMed Central

    Al-Jenoobi, Fahad I.

    2010-01-01

    The objective of this study was to investigate the potential effect of itraconazole on the pharmacokinetics of diclofenac potassium in beagle dogs after oral coadministration. Five male beagle dogs received a single oral 50 mg dose of diclofenac potassium alone in phase I, and along with a single oral 100 mg dose of itraconazole in phase II. Blood samples obtained for 8.0 hours post dose were analysed for diclofenac concentration using a validated high performance liquid chromatography (HPLC) assay method. The area under plasma concentration-time curve (AUC0–∞), maximum plasma concentration (Cmax), time to reach Cmax (Tmax) and elimination half-life (t1/2), were calculated for diclofenac before and after itraconazole administration. The coadministration of itraconazole with diclofenac potassium has resulted in a significant reduction in AUC0–∞ and Cmax of diclofenac, which was about 31 and 42%; respectively. No statistically significant differences were observed for Tmax and t1/2 of diclofenac between the two phases. Therefore, it could be concluded that oral coadministration of itraconazole may have the potential to affect the absorption of diclofenac as indicated by the significant reduction in its AUC and Cmax in beagle dogs. PMID:21179359

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

    PubMed Central

    DOI, Takuya; TOMONARI, Yuki; KAWASAKO, Kazufumi; YAMADA, Naoaki; TSUCHITANI, Minoru

    2016-01-01

    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. PMID:27885217

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

    PubMed

    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.

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

    PubMed

    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.

  12. Cannabinoid receptor antagonist-induced striated muscle toxicity and ethylmalonic-adipic aciduria in beagle dogs.

    PubMed

    Tomlinson, Lindsay; Tirmenstein, Mark A; Janovitz, Evan B; Aranibar, Nelly; Ott, Karl-Heinz; Kozlosky, John C; Patrone, Laura M; Achanzar, William E; Augustine, Karen A; Brannen, Kimberly C; Carlson, Kenneth E; Charlap, Jeffrey H; Dubrow, Katherine M; Kang, Liya; Rosini, Laura T; Panzica-Kelly, Julieta M; Flint, Oliver P; Moulin, Frederic J; Megill, John R; Zhang, Haiying; Bennett, Michael J; Horvath, Joseph J

    2012-10-01

    Ibipinabant (IBI), a potent cannabinoid-1 receptor (CB1R) antagonist, previously in development for the treatment of obesity, causes skeletal and cardiac myopathy in beagle dogs. This toxicity was characterized by increases in muscle-derived enzyme activity in serum and microscopic striated muscle degeneration and accumulation of lipid droplets in myofibers. Additional changes in serum chemistry included decreases in glucose and increases in non-esterified fatty acids and cholesterol, and metabolic acidosis, consistent with disturbances in lipid and carbohydrate metabolism. No evidence of CB1R expression was detected in dog striated muscle as assessed by polymerase chain reaction, immunohistochemistry, Western blot analysis, and competitive radioligand binding. Investigative studies utilized metabonomic technology and demonstrated changes in several intermediates and metabolites of fatty acid metabolism including plasma acylcarnitines and urinary ethylmalonate, methylsuccinate, adipate, suberate, hexanoylglycine, sarcosine, dimethylglycine, isovalerylglycine, and 2-hydroxyglutarate. These results indicated that the toxic effect of IBI on striated muscle in beagle dogs is consistent with an inhibition of the mitochondrial flavin-containing enzymes including dimethyl glycine, sarcosine, isovaleryl-CoA, 2-hydroxyglutarate, and multiple acyl-CoA (short, medium, long, and very long chain) dehydrogenases. All of these enzymes converge at the level of electron transfer flavoprotein (ETF) and ETF oxidoreductase. Urinary ethylmalonate was shown to be a biomarker of IBI-induced striated muscle toxicity in dogs and could provide the ability to monitor potential IBI-induced toxic myopathy in humans. We propose that IBI-induced toxic myopathy in beagle dogs is not caused by direct antagonism of CB1R and could represent a model of ethylmalonic-adipic aciduria in humans.

  13. Stereospecific pharmacodynamics and chiral inversion of NG-nitro-arginine in the beagle dogs.

    PubMed

    Xin, Yan-Fei; Gu, Li-Qiang; Zhang, Sheng; Bai, Yun-Sheng; Zhou, Guo-Liang; You, Zhen-Qiang; Xuan, Yao-Xian

    2010-11-01

    In the present study, we analyzed the stereospecific pharmacodynamics and inversion of N(G)-nitro-arginine by an intravenous blous injection of L-N(G)-nitro-arginine (L-NNA) or D-N(G)-nitro-arginine (D-NNA) (10 mg/kg) in beagle dogs. Significant pressor responses were observed for both substances, though a similar maximum response induced by L-NNA was reached at 120 min slower as compared with D-NNA. The rise in mean arterial pressure (MAP) of D-NNA dogs was also shown to be slower than the L-NNA group. Our data showed that D-NNA had no impact on MAP within 60 min after its injection. Plasma L-NNA started to appear after 45 min posterior to the i.v. bolus injection of D-NNA. This chiral inversion is unidirectional because no D-NNA was not produced from L-NNA. The pressor response in the D-NNA-injected dogs was well parallel to the plasma L-NNA concentration. Similar disposition of N(G)-nitro-arginine enantiomers and 4% of chiral inversion ratio from D-NNA to L-NNA was found in the beagle dogs. Given that D-amino acid oxidase (DAAO) is the essential enzyme in chiral inversion of D-NNA, we further compared the enzymatic activity of the renal DAAO between dogs and rats. Our data showed that dogs had a significantly lower enzymatic activity than rats, thus supported a lower inversion ratio of D-NNA in dogs.

  14. Radiation-induced liver lesions in beagle dogs

    SciTech Connect

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.

    1994-11-01

    The risk for liver disease from internally deposited beta-emitting radionuclides is unknown because there are no human populations exposed to hepatotropic beta-emitting radionuclides available for study. In this report, we discuss the hepatic lesion in dogs exposed to a beta-emitting radionuclide, {sup 144}CeCl{sub 3}, and held for their life spans.

  15. Primary liver tumors in beagle dogs exposed by inhalation to aerosols of plutonium-238 dioxide.

    PubMed Central

    Gillett, N. A.; Muggenburg, B. A.; Mewhinney, J. A.; Hahn, F. F.; Seiler, F. A.; Boecker, B. B.; McClellan, R. O.

    1988-01-01

    Primary liver tumors developed in Beagle dogs exposed by inhalation to aerosols of 238PuO2. Initial deposition of 238PuO2 in the respiratory tract was followed by translocation of a portion of the 238Pu to the liver and skeleton, which resulted in a large dose commitment and tumor risk to all three tissues. In a population of 144 dogs exposed to 238PuO2, 112 dogs died or were killed 4000 days after 238Pu exposure, 100 dogs had osteosarcoma, and 28 dogs had lung cancers. At increasing times after exposure, however, liver lesions have become more pronounced. Ten primary liver tumors in nine animals were diagnosed in the dogs dying before 4000 days after exposure. An additional five primary liver tumors in three dogs occurred in 9 animals killed after 4000 days after exposure. The majority of these tumors have been fibrosarcomas. The liver tumors were usually not the cause of death, and rarely metastasized. The occurrence of liver tumors in this study indicates that 238Pu is an effective hepatic carcinogen. Liver carcinogenesis is assuming an increasing importance in this study at late times after inhalation exposure. These results suggest that the liver may be an important organ at risk for the development of neoplasia in humans at time periods long after inhalation of 238Pu. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:3142267

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

    PubMed

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

    1989-01-01

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

  17. Clearance patterns for {sup 111}In-oxide particles deposited in specific airways of beagle dogs

    SciTech Connect

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

    1994-11-01

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

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

    PubMed

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

    PubMed

    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.

  20. Effects of four-week feed restriction on toxicological parameters in beagle dogs

    PubMed Central

    TAKAMATSU, Kazuhiko; YAMASHITA, Hiroyuki; SATAKE, Shigeru; KAZUSA, Katsuyuki; TABATA, Hajime; NISHIKATA, Takahito

    2015-01-01

    This study was conducted to examine any changes caused by feed restriction in dogs to contribute to safety evaluation in toxicity studies. Two male 7-month-old beagle dogs/group were fed 300 (control), 150 (50% of control), or 70 g/animal of diet daily (23% of control) for 4 weeks. Effects of feed restriction, except for clinical signs, were noted depending on the feed dosage in almost all examinations. The principal outcomes were: decreased body weight and water consumption, ECG changes (decreased heart rate and prolonged QTc), and hematopoietic and lymphopoietic suppression (decreased reticulocyte ratio or white blood cell count in hematology, decreased nucleated cell count in bone marrow, decreased erythroid parameters in myelography, and hypocellularity of bone marrow and thymic atrophy in histopathology). In addition, some changes were noted in urinalysis (decreased urine volume and sodium and potassium excretion), blood chemistry (decreased ALP and inorganic phosphorus and increased creatinine), organ weights, and gastric histopathology. These results provide important reference data for distinguishing the primary effects of test compounds from secondary effects of decreased food consumption in toxicity studies in beagle dogs. PMID:25818481

  1. [Pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in Beagle dogs].

    PubMed

    Chen, He-Li; Zhang, Wen-Ping; Yang, Fu-Ying; Wang, Xin-Yu; Yang, Wen-Cheng; Dang, Hong-Wan

    2013-05-01

    The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.

  2. Carcinogenicity and chronic toxicity of copovidone (Kollidon VA 64) in Wistar rats and Beagle dogs.

    PubMed

    Mellert, W; Deckardt, K; Gembardt, C; Hildebrand, B; Schulte, S

    2004-10-01

    Kollidon VA 64 (copovidone, CAS-No. 25086-89-9) was administered in the diet to male and female Wistar rats (0, 700, 1400, and 2800 mg/kg body weight) for 24 months, and to male and female beagle dogs (0, 500, 1500, and 2500 mg/kg body weight/day) for 52 weeks. Clinical signs, body weight, food consumption, hematology, and gross and histopathological evaluations were conducted on both rats and dogs, and dogs also underwent hearing tests, ophthalmoscopic examinations, electrocardiograms, blood pressure measurement, and clinical chemistry and urinalysis evaluations. No adverse in-life observations related to treatment were observed in either species. The rats exhibited dark discoloration of the feces that was attributed to the intake and excretion of large amounts of test substance and was not considered to be an adverse effect. No treatment-related hematological changes, or gross or histopathological lesions were observed in either species that could be considered clinically relevant. Vacuolated histiocytosis in the mesenteric lymph nodes of four dogs that was not accompanied by inflammation or degenerative changes reflected histiocytic removal and degradation of the test article rather than a toxic effect. The results of these studies demonstrate the absence of any significant toxicological findings of high dietary levels copovidone in rats and dogs, resulting in no-observed-adverse-effect levels of 2800 mg/kg body weight/day in rats and 2500 mg/kg body weight/day in dogs, the highest doses tested.

  3. Cardiopulmonary function and morphologic changes in beagle dogs after multiple lung lavages

    SciTech Connect

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

    1980-03-01

    This study evaluated the long-term biomedical risks of multiple, massive saline lung lavage using dogs. Risks were assessed using clinical examinations of cardiopulmonary function, thoracic radiographs, auscultation of the chest, body temperature, and hematologic values. Thirty-six dogs given 10 lavages over a 49-day period had no gross lesions at time of necropsy 7 days after the last lavage. Six dogs, followed with clinical examinations after each of 10 lung lavages, had no detectable effects from the lavage except for elevated body temperature and bronchial breathing at 24 hr after some procedures. No gross lesions were found at sacrifice 28 days after the last lavage. The only histologic lesions found were those also found in unlavaged control dogs. Six dogs that were lavaged 10 or more times had normal pulmonary function values for 4 yr after the last lung lavage. No chronic sequelae were found in healthy beagle dogs given 10 or more lung lavages suggesting a minimal long-term risk associated with these procedures.

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

    PubMed

    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.

  5. Ovariectomy-induced changes in aged beagles : histomorphometry of rib cortical bone.

    SciTech Connect

    Wilson, A. K.; Bhattacharyya, M. H.; Miller, S.; Sacco-Gibson, N.; Center for Mechanistic Biology and Biotechnology; Univ. of Utah; Procter & Gamble Pharmaceuticals

    1998-03-01

    Bone loss associated with estrogen depletion is well documented in cancellous bone but less well characterized in cortical bone. 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 or sham-operated dog at the time of surgery and at 1, 4, and 8.5 months after surgery. Just prior to each postoperative biopsy, tetracycline, calcein, and xylenol orange, respectively, were administered by a fluorochrome labeling procedure (2d-10d-2d) to provide markers of bone formation. Analysis of sequential rib biopsies provided a means to follow the ovariectomy response over time and to compare each animal against its own baseline. Though ovariectomy did not influence histomorphometric indices at 1 month after surgery, a transient increase in cortical bone formation occurred thereafter, with a sixfold increase over that of sham-operated dogs at 4 months (P < 0.001) and a return to near control levels at 8.5 months. Cortical porosity increased by the fourth month after ovariectomy and remained high at 8.5 months. These data demonstrate for the first time that rib cortical bone is a responsive site for the effects of ovariectomy in aged female dogs.

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

    PubMed

    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

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

    PubMed

    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.

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

    PubMed

    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.

  9. Biological effects of {sup 137}CsCl injected in beagle dogs

    SciTech Connect

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

    1995-06-01

    The toxicity of intravenously administered {sup 137}CsCl in the beagle dog was investigated as part of a program to evaluate the biological effects of internally deposited fission-product radionuclides. The intravenous route of exposure was chosen for simplicity and accuracy because it was known that after intravenous injection, inhalation or ingestion, internally deposited {sup 137}CsCl is rapidly absorbed and distributed throughout the body, exposing the whole body to {beta}-particle and {gamma} radiations. Fifty-four dogs were injected intravenously with {sup 137}Cs to provide one group of six dogs with mean initial body burdens of 141 MBq {sup 137}Cs/kg body mass and four groups of 12 dogs each with mean initial body burdens of 104, 72, 52 and 36 MBq {sup 137}Cs/kg. Twelve dogs were injected with isotonic saline as study controls. Because the number of study controls dogs was small, data from an additional 49 control dogs from other studies at the Inhalation Toxicology Research Institute that were performed over a similar span of years were also used. There was a significant, dose-dependent decrease in survival of the {sup 137}Cs-injected dogs. Eleven {sup 137}Cs-injected dogs, including all six in the highest initial body burden group, died within 81 days after injection, primarily due to hematopoietic cell damage resulting in severe pancytopenia. An additional 25 dogs had transient hematological dyscrasia but survived for long times. All {sup 137}Cs-injected male dogs had marked damage to the germinal epithelium of the testicular seminiferous tubules with azoospermia in the long-term survivors. benign and malignant neoplasms occurred in a variety of organs in {sup 137}Cs-injected dogs, rather than in a single target organ. When individual organs were considered, the incidence of malignant neoplasms was increased in the liver and in the nasal cavity and paranasal sinuses of the {sup 137}Cs-injected dogs. 34 refs., 6 figs., 6 tabs.

  10. Bilateral Ovotestes in a 78, XX SRY-Negative Beagle Dog.

    PubMed

    Pérez-Gutiérrez, José F; Monteagudo, Luís V; Rodríguez-Bertos, Antonio; García-Pérez, Enrique; Sánchez-Calabuig, María J; García-Botey, Concepción; Whyte, Ana; de la Muela, Mercedes Sánchez

    2015-01-01

    This report describes a disorder of the sexual development in a beagle dog resulting in an intersex condition. A 6 mo old beagle was presented for evaluation of a protruding structure from the vulva consistent with an enlarged clitoris. Ultrasonographic examination revealed the presence of both gonadal and uterine structures. Retrograde cystourethrovaginogram showed the presence of an os clitoris and severe vaginal stenosis. Histological studies revealed the presence of bilateral ovotestes and uterus. The gonad had interstitial cells within seminiferous-like tubules lined only with Sertoli cells and abundant interstitial cells among primordial, primary, and secondary follicles. Hormone assays completed before and after gonadohysterectomy showed an elevation in the levels of progesterone and dihydrotestosterone that returned to baseline 3 mo after surgery. Testosterone levels that were within the male reference ranges before surgery decreased to basal levels postsurgically. 17-β-Estradiol levels showed little variation and values were always within the reference ranges for a male. Cytogenetic analysis showed a normal female karyotype (2n = 78, XX) and polymerase chain reaction analysis revealed the absence of the sex-determining region Y gene. In summary, the dog presented bilateral ovotestes and a 2n = 78, XX chromosomal complement lacking the sex determining region Y gene, consistent with a diagnosis of true hermaphroditism.

  11. Preparation and pharmacokinetics in beagle dogs of ganershu sustained-release pellets

    PubMed Central

    Pan, Jin-huo; Wang, Jian-chun; Jiang, Zhi-tao; Zhang, Ting; Ge, Shao-bo; Zhang, Ye-xia; Jin, Xin; Yan, Guo-jun

    2014-01-01

    Background: The active ingredients of Ganershu compound recipe, which are effective for hepatitis treatment in liver protection and transaminase reduction. However, the active ingredients of Ganershu compound recipe are poor absorption, which conduct it has a low oral bioavailability. Objective: We prepared Ganershu sustained-release pellets (GSPs) by fluidized-bed on central composite design-response surface methodology and increase its bioavailability in beagle dogs. Materials and Methods: In this study, GSPs were successfully prepared. The Drug-loaded pellets and sustained-release coated were carried out in fluidized-bed machine. GSP was optimized for fitting release, roundness, and the overall desirability by central composite design-response surface methodology. Results: To optimize cumulative release profile, the outermost ethyl cellulose coating layer and the hydroxypropyl methyl cellulose (HPMC) swelling layer were employed, which were respectively given coating levels in terms of weight gain of 22% and 6%, the concentration of HPMC is 4.5% (g/ml). The pharmacokinetics of Ganershu normal pellets (GNPs) and GSP was studied in beagle dogs after oral administration. The naringenin as an index, the area under the curve0-∞ of naringenin in GSP was 1.38 times greater than that of GNP. Meanwhile, Tmax of GSP was prolonged for about 74%. Conclusion: This study can clearly indicate that we enhanced the oral bioavailability of Ganershu by preparing the GSP, which had the sustained dissolution and improved the potential of it for clinical application. PMID:25210307

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    SciTech Connect

    Wilson, A.K.; Bhattacharyya, M.H.; Hurst, D.; Miller, S.; Sacco-Gibson, N.

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

    PubMed

    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.

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

    PubMed

    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.

  18. Effect of tecarfarin, a novel vitamin K epoxide reductase inhibitor, on coagulation in beagle dogs

    PubMed Central

    Choppin, A; Irwin, I; Lach, L; McDonald, MG; Rettie, AE; Shao, L; Becker, C; Palme, MP; Paliard, X; Bowersox, S; Dennis, DM; Druzgala, P

    2009-01-01

    Background and purpose: Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs. Experimental approach: Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT). Key results: Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K1 treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model. Conclusions and implications: Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients. PMID:19845677

  19. Excipient effects on gastrointestinal transit and drug absorption in beagle dogs.

    PubMed

    Schulze, Julia D R; Peters, Erin E; Vickers, Ann W; Staton, J Scott; Coffin, Mark D; Parsons, Gary E; Basit, Abdul W

    2005-08-26

    Previous work has shown that polyethylene glycol 400 (PEG 400) has an accelerating effect on gastrointestinal transit and a modulating influence on drug absorption in humans. The aim of this study was to assess the impact of various excipients, PEG 400, propylene glycol, d-alpha-tocopheryl-polyethylene glycol-1000 succinate (TPGS) and Labrasol on gastrointestinal transit and drug absorption in four beagle dogs using scintigraphy. Each dog received, on five separate occasions, water (control) or a dose of excipient equivalent to 1 g PEG 400, 2 g propylene glycol, 1 g TPGS or 2 g Labrasol dissolved in water and administered in the form of two capsules. The model drugs ampicillin (200mg) and antipyrine (100mg) were co-administered in the capsules. The capsule solutions were radiolabelled with technetium-99m to follow their transit using a dual-headed gamma camera, and blood samples were collected to determine drug pharmacokinetics. On a separate occasion, the drugs were dissolved in saline and given intravenously. The capsules rapidly disintegrated in the stomach liberating their liquid contents. The mean small intestinal transit times for the different treatments (control, PEG 400, propylene glycol, TPGS and Labarasol) were 183, 179, 195, 168 and 154 min, respectively. The corresponding mean absolute oral bioavailability figures were 36, 32, 39, 42 and 32% for ampicillin and 76, 74, 85, 73 and 74% for antipyrine, respectively. The transit and bioavailability data for the excipient treatments were not significantly different from the control. In summary, these excipients, at the doses administered, have limited influence on gastrointestinal transit and drug in beagle dogs.

  20. Histomorphometry and stability analysis of early loaded implants with two different surface conditions in beagle dogs

    PubMed Central

    Kim, Dong-Seok; Kim, Dae-Gon; Park, Chan-Jin

    2009-01-01

    STATEMENT OF PROBLEM Despite an improved bone reactions of Mg-incorporated implants in the animals, little yet has been carried out by the experimental investigations in functional loading conditions. PURPOSE This study investigated the clinical and histologic parameters of osseointegrated Mg-incorporated implants in early loading conditions. MATERIAL AND METHODS A total of 36 solid screw implants (diameter 3.75 mm, length 10 mm) were placed in the mandibles of 6 beagle dogs. Test groups included 18 Mg-incorporated implants. Turned titanium implants served as control. Gold crowns were inserted 4 weeks after implant placement and the dogs were immediately put on a food diet. Implants were observed for 10 weeks after loading. Radiographic assessments and stability tests were performed at the time of fixture installation, 2nd stage surgery, 4 weeks after loading, and 10 weeks after loading. Histological observations and morphometrical measurements were also performed. RESULTS Of 36 implants, 33 displayed no discernible mobility, corresponding to successful clinical function. There was no statistically significant difference between test implants and controls in marginal bone levels (P = .46) and RFA values. The mean BIC% in the Mg-implants was 54.5 ± 8.4%. The mean BIC% in the turned implant was 45.3 ± 12.2%. These differences between the Mg-implant and control implant were statistically significant (P = .005). CONCLUSIONS The anodized, Mg-incorporated implant demonstrated significantly more bone-to-implant contact (BIC) in early loading conditions. CLINICAL IMPLICATIONS The results of this study in beagle dogs suggest the possibility of achieving predictable stability of early loaded free-standing dental implants with Mg-incorporated surface. PMID:21165249

  1. Inhibition of experimental gingivitis in beagle dogs with topical salivary histatins.

    PubMed

    Paquette, D W; Waters, G S; Stefanidou, V L; Lawrence, H P; Friden, P M; O'Connor, S M; Sperati, J D; Oppenheim, F G; Hutchens, L H; Williams, R C

    1997-04-01

    Histatins, histidine-rich proteins found within parotid and submandibular secretions, are a novel class of endogenous peptides with antimicrobial properties. This masked, randomized, placebo-controlled preclinical investigation examined the effect of 3 topical histatins on the development of plaque and gingivitis in beagle dogs. 16, female, 1-year-old beagles were brought to optimal gingival health by mechanical scaling and polishing followed by rigorous daily tooth brushing. At the conclusion of this pretreatment period, dogs were randomly divided into 4 groups for the application of test formulations, and were placed on a plaque-promoting diet. Test agents included 3 synthetic salivary histatins (histatin 5, P-113 and P-113D) which were incorporated in hydroxypropyl methylcellulose gel at a concentration of 0.125%, and a placebo, or negative control, which was the gel vehicle alone. Throughout the 10-week treatment period, test formulations (2.0 ml) were applied 2 x daily to all premolar teeth using a Monojet syringe. Plaque formation and gingival inflammation were assessed using the plaque (PI) and gingival (GI) indices on days 0, 7, 14, 21, 28, 42, 56 and 70. Furthermore, bleeding to probing was recorded as a percent of sites (%BOP) and according to the modified sulcus bleeding index (mSBI). Comparisons among groups and between group pairs (active versus placebo) were made with Kruskal-Wallis tests with the average of data over the interval, days 14-42, being the primary focus of the analysis. From baseline to day 7, all groups expressed similar indices. Thereafter, overall significant differences among the groups were noted at day 42 for PI, at days 21, 28, 42 and 70 for GI, and at days 14 and 28 for %BOP (p < 0.05). In particular, beagles treated with P-113 demonstrated significantly lower PI scores at day 42 (p < 0.05), significantly lower GI scores from days 21 through 42 (p < 0.05), and significantly lower %BOP scores at days 14 and 28 (p < 0.05) compared

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

    PubMed

    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 (p<0.05, F-test) effect of time. The overall mean was 2.233±0.387ngmL(-1). These results further previous findings by documenting the presence of 2-hexanone and benzaldehyde 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. Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in beagle dogs: a placebo-controlled study.

    PubMed

    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.

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

    PubMed Central

    Landsberg, G. M.; Beck, A.; Lopez, A.; Deniaud, M.; Araujo, J. A.; Milgram, N. W.

    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 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. PMID:26311736

  5. Contrast enhanced ultrasonography of kidney in conscious and anesthetized beagle dogs

    PubMed Central

    CHOI, Soo-Young; JEONG, Woo-Chang; LEE, Young-Won; CHOI, Ho-Jung

    2015-01-01

    Contrast enhanced ultrasound (CEUS) is useful to evaluate tissue perfusion in the kidney. In veterinary medicine, sedation or anesthesia may be required in uncooperative or panting patients. The aim of this study was to evaluate and compare the normal kidney perfusion patterns in conscious and anesthetized dogs using CEUS. Eight healthy beagles were used in this study. Scanning was performed in conscious dogs using manual restraint (conscious group), or under general anesthesia using tiletamine-zolazepam and medetomidine (TZM group) or medetomidine (M group). The contrast agent (Sonovue®) was administered as an IV bolus. The peak intensity (PI), time to peak enhancement from injection (TTP0) and the time to peak enhancement from the initial rise (TTPup), upslope, downslope and area under the curve (AUC) were analyzed. Compared to the cortical values in the conscious group, TTP0 was significantly delayed in the TZM group, and upslope, TTP0 and TTPup were significantly different in the M group. The AUCs in the TZM and M groups were not different from those in the conscious group. The upslope of renal medullary perfusion was significantly decreased in the TZM and M groups. TTP0 and TTPup were also significantly delayed in these groups. The AUC of the medulla was significantly decreased in the M group. Therefore, TZM is useful as an anesthetic protocol when performing CEUS, and the obtained data may serve as reference values in the evaluation of renal perfusion using CEUS in dogs under anesthesia. PMID:26412201

  6. Deposition of Crocidolite asbestos and glass microfibers inhaled by the beagle dog

    SciTech Connect

    Griffis, L.C.; Pickrell, J.A.; Carpenter, R.L.; Wolff, R.K.; McAllen, S.J.; Yerkes, K.L.

    1983-01-01

    The respiratory tract deposition of neutron activated Crocidolite asbestos and glass microfibers was determined in two groups of four Beagle dogs. The dogs were given 60-minute, nose-only inhalation exposures to an aerosol of either asbestos or glass fibers. The radioactivity in tissues and excreta four days after exposure was used to determine the fraction of inhaled fibers deposited in the upper respiratory tract and the deep lung. The activity median aerodynamic diameter (AMAD), count median diameter (CMD) and count median length (CML) were determined from fibers sampled during exposure. Crocidolite asbestos fibers had an AMAD of 1.8 ..mu..m, a CMD of 0.25 ..mu..m and a CML < 5 ..mu..m. The fraction of inhaled mass deposited in deep lung was 13-19%, while total deposition in the respiratory tract was 54-72%. Glass microfibers had an AMAD of 2.5 ..mu..m, a CMD of 0.15 ..mu..m and a CML of 5.4 ..mu... Five to 17% of the mass of glass fiber was deposited in the deep lung; total respiratory tract deposition was 45-64%. The deposition patterns were similar for these small asbestos and glass fibers inhaled by dogs and in good agreement with previous predictions made for man. 24 references, 4 figures, 5 tables.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

    2015-01-01

    A single mass was found on the left submandibular salivary gland at necropsy of a 15-month-old male commercially bred laboratory Beagle dog from a control dose group from a repeat toxicity study. Microscopically, the mass was composed of a well-demarcated area of coagulative necrosis surrounded and separated from the normal salivary gland tissue by a thick fibrovascular capsule. Necrosis was admixed with areas of hemorrhage, fibrin, edema, fibrinoid necrosis of the vascular tunica media, and 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. PMID:26441480

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

    SciTech Connect

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

    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.

  12. Single inhalation exposure to 90SrCl2 in the beagle dog: hematological effects

    SciTech Connect

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

    1987-05-01

    The toxicity of /sup 90/Sr administered by the inhalation route was studied in young adult Beagle dogs exposed once to aerosols containing /sup 90/SrCl/sub 2/. Due to its relatively soluble chemical form, /sup 90/Sr was rapidly translocated from lung to bone where a substantial portion was retained for a long period of time. This resulted in only a brief radiation exposure of the respiratory tract and a protracted exposure of the skeleton. The long-term retained burdens ranged from 0.037 to 4.4 MBq /sup 90/Sr/kg body wt. Dogs were subsequently observed throughout their life span. Six dogs with long-term retained burdens of 1.7 to 4.1 MBq /sup 90/Sr/kg died at less than 32 days after exposure from radiation-induced bone marrow hypoplasia. Review of hematological parameters of all dogs showed a similar, consistent, and dose-related pancytopenia in those animals having a long-term retained burden of greater than 0.37 MBq /sup 90/Sr/kg. Thrombocytopenia and neutropenia persisted in all exposed dogs through 1000 days after exposure. For reference purposes, a burden of 0.37 MBq /sup 90/Sr/kg is calculated to deliver an average radiation dose to the skeleton over 30, 100, and 1000 days after intake of 1.0, 2.8, and 17 Gy, respectively. The hematologic changes were similar to those seen in people exposed to high doses of whole-body external radiation.

  13. A safety study of a novel photosensitizer, sinoporphyrin sodium, for photodynamic therapy in Beagle dogs.

    PubMed

    Lin, Ni; Li, Chao; Wang, Zhonghua; Zhang, Jingxuan; Ye, Xiangfeng; Gao, Wenjing; Wang, Aiping; Jin, Hongtao; Wei, Jinfeng

    2015-04-01

    Sinoporphyrin sodium (DVDMS) is a novel hematoporphyrin-like photosensitizer developed for photodynamic therapy (PDT), an effective therapeutic modality for tumor treatment; however, the safety of photosensitizer-based PDT is always of great concern. The purpose of the current study was to investigate the potential repeated-dose toxicity and describe the toxicokinetic process of DVDMS-based PDT in Beagle dogs. The dogs were randomly allocated to six groups, and then were administrated a DVDMS preparation intravenously at dose levels of 0, 1, 3, 9, 1 and 9 mg per kg body weight, respectively; then, the latter two groups were illuminated 24 h later with a 630 nm laser for 10 min, once every seven days for 5 weeks. During the study period, clinical signs, mortality, body weight, food consumption, body temperature, ophthalmoscopy, hematology, serum biochemistry, urinalysis, electrocardiograms, toxicokinetics, organ weights, gross anatomy and histopathology were examined. After the administration, no deaths were observed; however, the dogs that received PDT showed skin swelling and ulceration, indicating that DVDMS-PDT induced a phototoxic effect. DVDMS led to an increase in blood coagulation in dogs in the 9 mg kg(-1) group and in the two PDT groups on Day 35, whereas it induced a decrease in dogs in the 3 mg kg(-1) group and in the two PDT groups on Day 49. The toxicokinetic study showed that the systematic exposure of DVDMS in dogs occurred in a dose-dependent manner, and DVDMS did not accumulate in blood plasma. The DVDMS-based PDT group showed no obvious treatment-related pathological changes; however, slight or mild brown-and-yellow pigmentation of DVDMS (or its metabolite) was observed to deposit in the liver, spleen, local lymph nodes and marrow of dogs in the mid- and high-dose groups, as well as the high-dose PDT group. In females, the absolute and relative spleen weights increased in dogs in the 9 mg kg(-1) DVDMS groups with and without PDT during the

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

    SciTech Connect

    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.

  15. Long-Term Study of Vascularized Free-Draining Intraperitoneal Pancreatic Segmental Allografts in Beagle Dogs

    PubMed Central

    Kyriakides, George K.; Rabinovitch, Alexander; Mintz, Daniel; Olson, Les; Rapaport, Felix T.; Miller, Joshua

    1981-01-01

    The purpose of the present study was to evaluate the significance of immunogenetic factors on the survival of pancreatic allografts in beagle dogs. Donors and recipients were leukocyte antigen (DLA)-typed and mixed lymphocyte culture (MLC)-tested. Recipients were made diabetic by total pancreatectomy and immediately implanted intraperitoneally with a vascularized, free-draining (duct unligated) pancreatic segmental (FDPS) allograft. Two groups of dogs were studied. In group I consisting of donor-recipient littermates, recipients were immunosuppressed with prednisone and azathioprine (n = 16 dogs), or not immunosuppressed (n = 4). In group II, recipients were made specifically unresponsive by total body radiation, autologous marrow implantation, and kidney transplantation from DLA-MLC identical donors, 1 yr before FDPS transplantation from the corresponding original kidney donors. Survival of the FDPS grafts in group I was inversely related to pretransplant MLC reactivity, irrespective of DLA genotyped match between donor and recipient. Thus, immunosuppressed high MLC reactors (n = 8) rejected FDPS grafts between 7 and 14 d, whereas immunosuppressed low MLC reactors (n = 8) accepted grafts for 25 to 260+ days, and nonimmunosuppressed low MLC reactors (n = 4) accepted grafts for 9-55 d. Rejection (hyperglycemia) of FDPS grafts was sudden, permanent, and unpredictable despite weekly intravenous glucose tolerance tests with measurements of glucose disappearance rates and serum insulin responses. Nevertheless, serial in vitro cell-mediated lymphocytotoxicity (CML) assays revealed increases in CML before graft rejection in low MLC reactors, and decreases in both CML and MLC responses before graft rejection in high MLC reactors. FDPS graft survival was indefinite (>6 mo) in group II dogs, despite low-grade MLC reactivity (2:4 dogs) and CML responses (4:4 dogs). Biopsies of FDPS grafts at 6 mo in normoglycemic dogs showed disappearance of exocrine tissue and coalescence of

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

    PubMed Central

    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

    2016-01-01

    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. PMID:27515388

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

    PubMed

    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.

  18. Effects of palmitoylethanolamide on the cutaneous allergic inflammatory response in Ascaris hypersensitive Beagle dogs.

    PubMed

    Cerrato, Santiago; Brazis, Pilar; Della Valle, Maria Federica; Miolo, Alda; Petrosino, Stefania; Di Marzo, Vincenzo; Puigdemont, Anna

    2012-03-01

    Palmitoylethanolamide (PEA) is an endogenous lipid mediator with anti-inflammatory and anti-hyperalgesic properties. The main objective of the present study was to evaluate the effects of PEA on the cutaneous allergic inflammatory reaction induced by different immunological and non-immunological stimuli in hypersensitive dogs. Six spontaneously Ascaris hypersensitive Beagle dogs were challenged with intradermal injections of Ascaris suum extract, substance P and anti-canine IgE, before and after a single oral administration of PEA at doses of 3, 10 and 30 mg/kg. A significant reduction in wheal area induced by both antigen and anti-canine IgE challenge was observed after PEA administration. No significant differences were observed between the two higher doses studied, suggesting that the 10 mg/kg dose had exerted the maximum inhibitory effect. When blood levels of PEA were compared with the effects at different times, an evident correlation was obtained. However, the anti-inflammatory effects of PEA were more long-lasting than their plasma concentrations. The intradermal injection of substance P did not reveal any skin reaction (wheal or erythema formation) at any of the concentrations tested. In conclusion, PEA might constitute a new therapeutic strategy for the treatment of allergic inflammatory skin diseases in companion animals.

  19. Evolution of blood parameters during weight loss in experimental obese Beagle dogs.

    PubMed

    Diez, M; Michaux, C; Jeusette, I; Baldwin, P; Istasse, L; Biourge, V

    2004-04-01

    The effects of weight loss on hormonal and biochemical blood parameters were measured monthly [carnitine, creatinine, urea, free T4 (fT4), total T4 (TT4), plasma alkaline phosphatases (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), potassium and total proteins] or bimonthly [cholesterol, triglycerides, non-esterified fatty acids (NEFA), insulin-like growth factor I (IGF-I), glucose, insulin] in eight obese Beagles dogs fed either a high protein dry diet, DP (crude protein 47.5%, on dry matter basis) or a commercial high fibre diet, HF (crude protein 23.8%, crude fibre 23.3%). The dogs were allotted to two groups according to sex and body weight (BW) and they were respectively fed with the DP or the control HF diet during 12-26 weeks, until they reach their optimal BW. The plasma basal triglycerides and cholesterol concentrations were decreased by the two diets but the difference was only significant for the DP diet. The plasma mean NEFA concentration increased regularly over the period with the HF diet, without significant difference between the two diets. No effect of diet or weight loss was observed on plasma carnitine, urea, creatinine, ALP, AST, ALT, potassium, TT4, FT4, IGF-I, glucose and insulin. Weight loss induced a decrease in fT4 plasma concentration (p < 0.001). The high protein diet allowed a safe weight loss.

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

    PubMed

    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.

  1. Cystoisospora canis Nemeséri, 1959 (syn. Isospora canis), infections in dogs: clinical signs, pathogenesis, and reproducible clinical disease in beagle dogs fed oocysts.

    PubMed

    Mitchell, Sheila M; Zajac, Anne M; Charles, Sam; Duncan, Robert B; Lindsay, David S

    2007-04-01

    Canine intestinal coccidiosis is a cause of diarrhea in young dogs and dogs that are immunocompromised. Reports in the literature indicate that experimental reproduction of clinical coccidiosis with Cystoisospora canis (syn. Isospora canis) is difficult, and few studies have been done with C. canis. Experimental oral infections were attempted in 22, 6- to 8-wk-old female beagles with 5 x 10(4) (n = 2) or 1 x 10(5) (n = 20) sporulated C. canis oocysts. Diarrhea was observed in all inoculated dogs. Diarrhea began 2-3 days before oocyst excretion. Five of the 22 dogs were given an anticoccidial (sulfadimethoxine) because of their clinical signs. The mean prepatent period was 9.8 days (range, 9-11 days, n = 22 dogs), and the patent period was 8.9 days (range, 7-18 days, n = 20 dogs). Two dogs exhibiting clinical coccidiosis were examined at necropsy 10 days after infection. Developmental stages of C. canis were present in cells in the lamina propria throughout the entire small intestine in both dogs. Microscopic lesions observed in both of these dogs were villous atrophy, dilation of lacteals, and hyperplasia of lymph nodes in Peyer's patches. Results of bacterial and viral examinations of these 2 dogs were negative, indicating that intestinal coccidiosis was the cause of the diarrhea. Our study indicates that C. canis can be a primary cause of diarrhea in young dogs.

  2. The impact of weight loss on circulating cytokines in Beagle dogs.

    PubMed

    Bastien, Berenice C; Patil, Avinash; Satyaraj, Ebenezer

    2015-02-15

    Chronic low-grade inflammation in obesity is characterized by an increased production of pro-inflammatory and chemotactic cytokines that are contributing to insulin resistance and related co-morbidities. Cytokines act in networks and exhibit pleiotropic effects so we investigated the circulating levels of a wide array of cytokines (pro and anti-inflammatory, chemotactic and growth factors) in a canine model of weight loss. The dogs served as their own control in order to study the impact of weight loss independent of potential confounding factors, such as history of excess weight or gender. While low-grade inflammation had been previously investigated in obese dogs by measuring changes in adipokines, acute phase proteins and key pro-inflammatory cytokines, to the best of our knowledge this is the first study to evaluate how weight loss impacts a wide array of circulating cytokines. Eighteen overweight Beagle dogs were recruited (six spayed females and 12 neutered males), and none of them were grossly obese according to the body condition score (BCS). All the dogs reached an ideal weight by the end of the program. Parameters were assessed before (baseline), at mid-point (month 3) and at end-point (month 6). Plasma GM-CSF, IL-2, Il-4, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, IFNγ, IP-10, TNFα, monocyte chemotactic protein 1 (MCP-1), keratinocyte chemokine (KC) were measured with canine multiplex immunoassays. Fat mass was assessed by dual energy X-ray absorption (DEXA). Several cytokines decreased throughout the weight loss program (p<0.01) and were correlated with the percentage of fat measured by DEXA (p<0.05): chemotactic (MCP-1), growth factors (GM-CSF, IL-7 and IL-2), and pro-inflammatory (KC and IL-18). We could not show trends for several cytokines, possibly because their level may be lower than the assay sensitivity: anti-inflammatory (IL-4 and IL-10), and pro-inflammatory (IL-6 and TNFα). In conclusion, while our findings for several pro-inflammatory and

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

    PubMed Central

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

    2005-01-01

    AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride (SM•HCl) on its pharmacokinetics in beagle dogs. METHODS: The in vitro release behavior of two SM•HCl 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 SM•HCl pharmacokinetics was investigated and compared. RESULTS: The optimal SM•HCl sustained-release formulation was achieved by mixing slow- and rapid-release pellets (9:1, w/w). The SM•HCl release profiles 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% vs 68.7%. From a pharmacokinetic standpoint, the 24-h SM•HCl sustained-release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67×0.52 h vs 9.83×0.98 h and the Cmax being 1 334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM•HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM•HCl 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. PMID:16052686

  4. Relative radiosensitivity of bone tumor induction among beagles as a function of age at injection of {sup 239}Pu or {sup 226}Ra

    SciTech Connect

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

    1999-01-01

    A comparison was made of the response to induction of skeletal malignancy from exposure of beagles to monomeric {sup 239}Pu or to {sup 226}Ra as juveniles (3 mo of age), young adults (1.5 y of age), or mature adults (5 y of age). This indicated that of these age groups, animals injected as young adults are most sensitive per Gy of average skeletal dose evaluated at 1 y before death. Dogs exposed either as juveniles or as mature adults appeared to be less sensitive. Relative radiosensitivities (RRS) of juvenile and mature beagles ranged between about 0.3 and 0.7 that of dogs injected as young adults. Mean values of RRS for both radionuclides were about 0.5, but RRS values derived from dogs given monomeric {sup 239}Pu appeared to be most reliable and were 0.27 {+-} 0.09 for dogs injected as juveniles and 0.41 {+-} 0.13 for animals exposed as mature adults.

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

    NASA Astrophysics Data System (ADS)

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

    1996-04-01

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

  6. Enhanced oral bioavailability of the hydrophobic chemopreventive agent (SR13668) in beagle dogs.

    PubMed

    Banerjee, Aryamitra A; Shen, Hao; Hautman, Mathew; Anwer, Jaseem; Hong, Seungpyo; Kapetanovic, Izet M; Liu, Ying; Lyubimov, Alexander V

    2013-01-01

    Potency and activity of SR13668 in cancer prevention have been proven in several in vitro and in vivo cancer models. However, the compound is highly hydrophobic and its limited oral bioavailability has hindered its clinical translation. In this study, we encapsulated SR13668 into polymeric nanoparticles to increase compound aqueous solubility and therefore bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (100-200 nm) encapsulating SR13668 with narrow size distribution and high drug loading were generated by a continuous and scalable process of flash nanoprecipitation integrated with spray dry. A single gavage dose of SR13668-PLGA nanoparticles at 2.8 mg/kg was administered in eight beagle dogs. Drug levels in animal whole blood and plasma were measured over 24 hours. Enhanced bioavailability of SR13668 using nanoparticles compared with formulations of Labrasol® and neat drug in 0.5% methylcellulose is reported. This is the first attempt to study pharmacokinetics of SR13668 in large animals with orally administrated nanoparticle suspension.

  7. Enhancement of the oral bioavailability of cinnarizine in oleic acid in beagle dogs.

    PubMed

    Tokumura, T; Tsushima, Y; Tatsuishi, K; Kayano, M; Machida, Y; Nagai, T

    1987-04-01

    The present study was an attempt to develop a new dosage form of cinnarizine, which is slightly soluble in water, using lipid as a vehicle. The solubility of cinnarizine in several organic solvents was determined. It was found that cinnarizine dissolved well in oleic and linoleic acids. The bioavailability of cinnarizine from the oral administration of an oleic acid solution in a hard capsule was investigated and compared with that of a cinnarizine tablet, using beagle dogs. When cinnarizine was administered in a capsule, the bioavailability was greatly enhanced [i.e., the maximum concentration (Cmax) and AUC values were 2.9 and 4.0 times larger than those of a cinnarizine tablet, respectively]. Meanwhile, the tmax value (the time to reach Cmax) was unchanged. The absorption of cinnarizine from an oleic acid solution was considered to depend on the action of bile salts. This was supported by the results of a dissolution test using a bile salts solution as the dissolution test medium.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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 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. PMID:26579428

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

    PubMed

    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.

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

    PubMed Central

    Nogueira-Paiva, Nívia Carolina; Fonseca, Kátia da Silva; Vieira, Paula Melo de Abreu; Diniz, Lívia Figueiredo; Caldas, Ivo Santana; de Moura, Sandra Aparecida Lima; Veloso, Vanja Maria; Guedes, Paulo Marcos da Matta; Tafuri, Washington Luiz; Bahia, Maria Terezinha; Carneiro, Cláudia Martins

    2013-01-01

    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. PMID:24271001

  13. Effect of low-intensity pulsed ultrasound on orthodontically induced root resorption in beagle dogs.

    PubMed

    Al-Daghreer, Saleh; Doschak, Michael; Sloan, Alastair J; Major, Paul W; Heo, Giseon; Scurtescu, Cristian; Tsui, Ying Y; El-Bialy, Tarek

    2014-06-01

    We investigated the effect of low-intensity pulsed ultrasound (LIPUS) on orthodontically induced inflammatory root resorption in vivo. Ten beagle dogs were treated with an orthodontic appliance to move the mandibular fourth premolars bodily. The orthodontic movement was carried out for 4 wk with a continuous force of 1 N/side; using a split-mouth model, LIPUS was applied daily for 20 min. Fourth premolar and surrounding periodontal tissue were evaluated with micro-computed tomography and hematoxylin and eosin and tartrate-resistant acid phosphatase staining. We calculated the number, volume and distribution of root resorption lacunae and their percentage relative to total root volume, orthodontic tooth movement and periodontal ligament space. There was no significant difference in orthodontic tooth movement between the two sides. LIPUS significantly reduced the number of orthodontically induced inflammatory root resorption initiation areas by 71%, reduced their total volume by 68% and reduced their volume relative to the affected root total volume by 70%. LIPUS induced the formation of a precementum layer, thicker cementum and reparative cellular cementum.

  14. Neurobiology of the aging dog.

    PubMed

    Head, Elizabeth

    2011-09-01

    Aged canines naturally accumulate several types of neuropathology that may have links to cognitive decline. On a gross level, significant cortical atrophy occurs with age along with an increase in ventricular volume based on magnetic resonance imaging studies. Microscopically, there is evidence of select neuron loss and reduced neurogenesis in the hippocampus of aged dogs, an area critical for intact learning and memory. The cause of neuronal loss and dysfunction may be related to the progressive accumulation of toxic proteins, oxidative damage, cerebrovascular pathology, and changes in gene expression. For example, aged dogs naturally accumulate human-type beta-amyloid peptide, a protein critically involved with the development of Alzheimer's disease in humans. Further, oxidative damage to proteins, DNA/RNA and lipids occurs with age in dogs. Although less well explored in the aged canine brain, neuron loss, and cerebrovascular pathology observed with age are similar to human brain aging and may also be linked to cognitive decline. Interestingly, the prefrontal cortex appears to be particularly vulnerable early in the aging process in dogs and this may be reflected in dysfunction in specific cognitive domains with age.

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

    SciTech Connect

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

    2014-01-01

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

  16. Secreted phospholipase A2 inhibitor modulates fatty acid composition and reduces obesity-induced inflammation in Beagle dogs.

    PubMed

    Xu, J; Bourgeois, H; Vandermeulen, E; Vlaeminck, B; Meyer, E; Demeyere, K; Hesta, M

    2015-05-01

    Secreted phospholipase A2 inhibitor (sPLA2i) has been reported to have an anti-inflammatory function by blocking the production of inflammatory mediators. Obesity is characterized by low-grade inflammation and oxidative stress. The aim of this study was to investigate the effects of dietary supplementation of sPLA2i on inflammation, oxidative stress and serum fatty acid profile in dogs. Seven obese and seven lean Beagle dogs were used in a 28-day double blind cross-over design. Dogs were fed a control diet without supplemental sPLA2i or an sPLA2i supplemented diet. The sPLA2i diet decreased plasma fibrinogen levels and increased the protein:fibrinogen ratio in obese dogs to levels similar to those of lean dogs fed the same diet. Obese dogs had a higher plasma concentration of the lipophilic vitamin A with potential antioxidative capacity and a lower ratio of retinol binding protein 4:vitamin A compared to lean dogs, independent of the diets. A higher proportion of myristic acid (C14:0) and a lower proportion of linoleic acid (C18:2n-6) were observed in the dogs fed with the sPLA2i diet compared to dogs fed with the control diet. Furthermore, a higher ratio of n-6 to n-3, a lower proportion of n-3 polyunsaturated fatty acids and lower omega-3 index were observed in obese compared to lean dogs. The results indicate that obese dogs are characterized by a more 'proinflammatory' serum fatty acid profile and that diet inclusion of sPLA2i may reduce inflammation and alter fatty acid profile.

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

    PubMed

    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. Periodontal pocket treatment in beagle dogs using subgingival doxycycline from a biodegradable system. I. Initial clinical responses.

    PubMed

    Polson, A M; Southard, G L; Dunn, R L; Yewey, G L; Godowski, K C; Polson, A P; Fulfs, J C; Laster, L

    1996-11-01

    The present study evaluated the clinical response of periodontal pockets in beagle dogs after treatment with a biodegradable delivery system containing 10% doxycycline hyclate (ABDS-D). Eight adult, female beagle dogs had generalized, severe periodontitis with plaque and calculus-laden pockets. In each animal, 3 teeth with multiple pocket sites > or = 4 mm (mean depth = 6.0 mm) associated with attachment loss (mean = 5.4 mm) and which bled on probing (mean score = 2.5) were treated with a single application of either ABDS-D (experimental group) or the delivery system alone without the doxycycline (control group). Residual polymer was removed at day 7. Bioassay of doxycycline in gingival crevicular fluid associated with presence of ABDS-D gave mean levels of bioactivity of approximately 250 micrograms/ml. Levels of bioactive doxycycline were detected for approximately 7 days after ABDS-D removal. Periodontal maintenance consisted of thrice-weekly toothbrushing the treated sites. Clinical responses were evaluated at 2 weeks, and at bi-weekly intervals thereafter for 4 months. Analyses of the data from the control group showed that there was only slight clinical improvement. In contrast, in the experimental group, bleeding on probing and probing depths were significantly reduced from baseline at all post-treatment time points. At 1 month, mean probing depth reduction was 2.4 mm and this was maintained at 4 months (mean reduction = 2.5 mm). These probing depth reductions occurred primarily through gain of clinical attachment which was 2.0 mm at 4 months. Bleeding had been virtually eliminated (mean = 0.2). It was concluded that, for the beagle dogs with severely infected periodontal pockets in this study, treatment with subgingival doxycycline using the delivery system resulted in substantial improvement in periodontal health.

  19. Dynamics of Alloplastic Bone Grafts on an Early Stage of Corticotomy-Facilitated Orthodontic Tooth Movement in Beagle Dogs

    PubMed Central

    Choi, Hyung-Joo; Kim, Tae-Woo

    2014-01-01

    Alveolar augmented corticotomy is effective in accelerating orthodontic tooth movement, but the effect only lasts for a relatively short time. Therefore, the purpose of this study was to investigate the underlying biology of the immediate periodontal response to orthodontic tooth movement after a corticotomy with alloplastic bone grafts. The results demonstrated that measurable tooth movement began as early as 3 days after the intervention in beagle dogs. Based on the results and histological findings, augmented corticotomy-facilitated orthodontic tooth movement might enhance the condition of the periodontal tissue and the stability of the outcomes of orthodontic treatment. PMID:25276787

  20. Stability and bioequivalence studies of two marketed formulations of coenzyme Q10 in beagle dogs.

    PubMed

    Kommuru, T R; Ashraf, M; Khan, M A; Reddy, I K

    1999-07-01

    Coenzyme Q10 (CoQ10), a highly lipophilic compound present in the inner mitochondrial membrane, is essential for production of cellular energy in the form of ATP. CoQ10 is used as an antioxidant and also in the treatment of various cardiovascular disorders. The relative bioavailabilities of powder filled capsule (I) and oil-based formulation (II) of CoQ10 were compared in beagle dogs in an open, randomized, multiple dose, cross-over design. Poor and slow absorption characteristics were observed for both the formulations. The AUC, Cmax, and Tmax for formulation I and II are comparable (p < 0.05) where the values for formulation I are 22.84 +/- 6.3 micrograms ml-1 h, 0.51 +/- 0.11 microgram/ml, and 6.1 +/- 2.0 h whereas the values for formulation II are 24.32 +/- 5.6 micrograms ml-1 h, 0.55 +/- 0.16 microgram/ml, and 6.6 +/- 2.3 h, respectively. Stability of CoQ10 at various temperature and humidity conditions and its photostability were studied. Various antioxidants were evaluated to determine the type and amount of antioxidant(s) required to improve the stability of CoQ10. Large extent of degradation was observed at 45 degrees C and 55 degrees C. The effect of humidity conditions on degradation was insignificant. Among the various antioxidants studied, mixture of ascorbic acid (5%) and EDTA (0.1%) offered better protection than phenolic antioxidants such as butylated hydroxy anisole (BHA), butylated hydroxy toluene (BHT), or propyl gallate (PG). Further, increasing concentrations of phenolic antioxidants (from 0.1 to 0.3%) accelerated the degradation.

  1. Pulmonary and percutaneous absorption of 2-propoxyethyl acetate and 2-ethoxyethyl acetate in beagle dogs

    SciTech Connect

    Guest, D.; Hamilton, M.L.; Deisinger, P.J.; DiVincenzo, G.D.

    1984-08-01

    A comparison was made of the absorption and elimination rates of 2-propoxyethyl acetate (PEA) and 2-ethoxyethyl acetate (EEA) following inhalation, dermal application of IV administration. Male beagle dogs were exposed to 50 ppm PEA or EEA for 5 hr, and breath samples were collected during the exposure and a 3-hr recovery period. Both compounds were rapidly absorbed through the lungs. After 10 min of exposure, the concentrations of the parent compounds in the expired breath were 5 to 10 ppm (80-90% absorption) and reached plateau values at about 3 hr of 13 ppm for PEA (74% absorption) and 16 ppm for EEA (68% absorption). Post-exposure breath samples declined exponentially to 0.5 ppm and 2 ppm after 3 hr for PEA and EEA, respectively. Expired concentrations of PEA were slightly, but significantly (p < 0.025), lower than those of EEA at corresponding times during the exposure. After IV dosing with 1 mg/kg (ethyl-1,2-/sup 14/C)PEA, the urine contained 61% and 88% of the dose in 4 and 24 hr, respectively. (/sup 14/C)EEA was eliminated more slowly, with 20% and 61% of the dose appearing in the urine in 4 and 24 hr, respectively. Blood elimination half-lives were 1.6 hr for (/sup 14/C)PEA and 7.9 hr for (/sup 14/C)EEA. Only trace amounts of /sup 14/CO/sub 2/ (<1%) or volatile materials (<0.1%) were detected in the expired air with either compound. For studies of percutaneous absorption, (/sup 14/C)PEA or (/sup 14/C)EEA was added to undiluted compounds and applied in a glass cell to a shaved area on a dog's thorax for 30 or 60 min. Blood and expired air were collected for 8 hr and urine for 24 hr. The pattern of urinary elimination for each compound was similar to that seen after IV dosing with (/sup 14/C)PEA being excreted more rapidly than (/sup 14/C)EEA. 15 references, 4 figures, 4 tables.

  2. Effect of biphasic calcium phosphate nanocomposite on healing of surgically created alveolar bone defects in beagle dogs

    NASA Astrophysics Data System (ADS)

    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.

  3. Preclinical Safety of the Root Extract of Polygala tenuifolia Willdenow in Sprague-Dawley Rats and Beagle Dogs

    PubMed Central

    Shin, Ki Young; Won, Beom Young; Ha, Hyun Jee; Yun, Yeo Sang; Lee, Hyung Gun

    2014-01-01

    The root of Polygala tenuifolia Willdenow has been used for the treatment of insomnia, depression, and amnesia. However, the toxicological properties of the herb have been overlooked, because it has been used for a long time for various purposes. In this study, we evaluated the preclinical safety of the root extract in rats and beagle dogs. First, the acute oral toxicity was tested in both rats and dogs. In the rats, only one female of 2 g/kg died, but no treatment-related death or clinical and gross findings were observed after the administration. No toxicological changes or mortalities related to the test substance were also observed after the administration in the dogs. Although vomiting, discoloration, or hemorrhage was found in some dogs, there were no serious abnormalities. Second, the subchronic toxicity was investigated in the rats. Two animals were found dead in the female group of 1,000 mg/kg/day, but there were no abnormal findings associated with the test substance. There also were no adverse effects on the clinical signs, body weight, and hematological and biochemical findings. Therefore, our results showed that the acute or subchronic toxicity of the root extract of Polygala tenuifolia might not be toxic to rats and dogs. PMID:25431613

  4. Increased bioavailability of primaquine using poly(ethylene oxide) matrix extended-release tablets administered to beagle dogs

    PubMed Central

    Bertol, C D; Oliveira, P R; Kuminek, G; Rauber, G S; Stulzer, H K; Silva, M A S

    2011-01-01

    Primaquine (PQ) is used for the radical cure of Plasmodium vivax malaria and can cause serious side effects in some individuals. The development of an extended-release dosage with poly(ethylene oxide) as a hydrophilic polymer has been investigated to improve drug efficacy and tolerability. The aim of this study was to evaluate in vivo a new extended-release formulation of PQ (60 mg). The formulation was administered to beagle dogs and plasma PQ concentrations were compared to a conventional immediate-release formulation of PQ (60 mg). The evaluation was carried out using a validated high-performance liquid chromatography method using solid-phase extraction. Total PQ exposure in beagle dogs was 2.2 times higher (area under curve of 12 193 versus 5678 ng h/ml) and the elimination half-life of PQ was a 19-fold greater (12.95 hours versus 0.68 hours) with the extended-release tablets compared with the immediate-release tablets. These findings suggest that the extended-release formulation of PQ merits further evaluation for the treatment of P. vivax malaria and/or chemoprophylaxis. PMID:22185941

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

    PubMed

    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.

  6. Safety and tolerability of 0.1% tacrolimus solution applied to the external ear canals of atopic beagle dogs without otitis.

    PubMed

    Kelley, Laura S; Flynn-Lurie, Alison K; House, Rossi A; Simpson, Andrew C; Marsella, Rosanna

    2010-12-01

    Tacrolimus is a nonsteroidal alternative to treat noninfectious otitis externa (OE) in people. This 21-day study investigated whether twice daily application (0.2 mL/dose) of sterile olive oil based 0.1% tacrolimus suspension in ears of atopic beagle dogs without OE was associated with adverse local reactions, development of OE, change in otic cytology, vestibular dysfunction, or hearing loss detected by brainstem auditory evoked response (BAER). The study was randomized, double-blinded, and placebo-controlled. Twenty-two dogs matched for age and sex were randomized to tacrolimus or vehicle control treatment groups. Two investigators independently evaluated dogs for signs of adverse effects including OE the first 4 days of treatment, then every 3 days. A logistic regression model was fit for each investigator's clinical scores (SAS, 9.2, 2008). Time (P = 0.0032) and group (P = 0.0167) were always significant for OE. Inter-observer reliability of clinical scores was strong, measured using Kappa coefficients and proportion of agreement. All nine exclusions (7/10 control- and 2/12 tacrolimus-treated dogs) were excluded for yeast OE. Inter-observer agreement to exclude was 100%. All dogs not excluded had normal BAER assessments before treatment, weekly during treatment, and after 21 days of treatment. None showed vestibular abnormalities at these times. Tacrolimus blood concentrations (Abbott IMx Tacrolimus II) were below detection limits (3 ng/mL) at baseline and after 21 days of treatment. Results suggest otic application of olive oil based tacrolimus suspension to canine ears with intact tympanic membranes is unlikely to result in hearing loss or vestibular dysfunction but yeast OE is a possible risk.

  7. Myocyte repolarization modulates myocardial function in aging dogs.

    PubMed

    Sorrentino, Andrea; Signore, Sergio; Qanud, Khaled; Borghetti, Giulia; Meo, Marianna; Cannata, Antonio; Zhou, Yu; Wybieralska, Ewa; Luciani, Marco; Kannappan, Ramaswamy; Zhang, Eric; Matsuda, Alex; Webster, Andrew; Cimini, Maria; Kertowidjojo, Elizabeth; D'Alessandro, David A; Wunimenghe, Oriyanhan; Michler, Robert E; Royer, Christopher; Goichberg, Polina; Leri, Annarosa; Barrett, Edward G; Anversa, Piero; Hintze, Thomas H; Rota, Marcello

    2016-04-01

    Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions.

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

    PubMed

    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.

  9. Biokinetics aand dosimetry of inhaled {sup 238}PuO{sub 2} in the beagle dog: An update

    SciTech Connect

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

    1994-11-01

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

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

    PubMed

    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

  11. Comparative toxicity of strontium-90 and radium-226 in beagle dogs. Report of first year, December 16, 1989--December 15, 1990

    SciTech Connect

    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.

  12. Comparative toxicity of strontium-90 and radium-226 in beagle dogs. Report of second year, December 16, 1990--December 15, 1991

    SciTech Connect

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

    1991-12-31

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

  13. Comparative toxicity of strontium-90 and radium-226 in beagle dogs. Progress report of second year, December 16, 1990--December 15, 1991

    SciTech Connect

    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.

  14. UV Photofunctionalization Effect on Bone Graft in Critical One-Wall Defect around Implant: A Pilot Study in Beagle Dogs

    PubMed Central

    Kim, Min-Young; Lee, Jae-Hoon; Kim, Jee-Hwan; Jung, Han-Sung; Park, Young-Bum

    2016-01-01

    The purpose of this study was to compare and evaluate, through histomorphometric and radiological analysis, the effects of UV photofunctionalization on an implant placed over a critical defect area with and without a bone graft. Four female beagle dogs were first divided into control and bone graft groups. Each group was then subdivided into UV-treated and UV-untreated groups. The mandibular premolars in each dog were extracted. 12 weeks after extraction, implants were placed according to the condition of each group. Four and 12 weeks after implantation on left and right mandible, the dogs were sacrificed. The specimens were prepared for histomorphometric and micro-computed tomographic analysis. In both 4-week and 12-week groups, UV-treated implant surfaces showed better osseointegration than SA implant surfaces. Also, with implant surfaces placed over the critical defect with bone graft, UV photofunctionalization increased bone-to-implant contact (BIC) and new bone formation at the initial stage (4 weeks). Based on the results of this study, it can be suggested that UV photofunctionalization on the surface of implants placed over large critical defects with bone graft aids initial osseointegration and osteogenesis. PMID:28116296

  15. Hematological responses after inhaling {sup 238}PuO{sub 2}: An extrapolation from beagle dogs to humans

    SciTech Connect

    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.

  16. Cardiorespiratory and anesthetic effects produced by the combination of butorphanol, medetomidine and alfaxalone administered intramuscularly in Beagle dogs

    PubMed Central

    LEE, Jongsung; SUH, Sangil; CHOI, Ran; HYUN, Changbaig

    2015-01-01

    This study evaluated anesthesia quality, degree of analgesia and cardiorespiratory parameters after intramuscular (IM) injection of a combination of butorphanol (0.1 mg/kg), medetomidine (10 µg/kg) and alfaxalone (1.5 mg/kg) in ten healthy adult Beagle dogs. Rectal temperature (T), heart rate (HR), respiratory rate (fR), arterial pressure, arterial blood gases and M-mode echocardiographic left ventricular (LV) indices were measured before drug administration and every 10 min thereafter until extubation. Mean duration of anesthesia, recovery and analgesia were 89 ± 17, 6 ± 1 and 80 ± 12 min. HR, fR, partial pressure of arterial CO2 and O2, arterial pressure, and LV contractility were significantly altered during anesthesia. IM administration of the drug combination provided acceptable anesthesia, but produced substantial cardiorespiratory suppression. PMID:26256405

  17. Estimation of pharmacokinetic parameters of sodium tungstate after multiple-dose during preclinical studies in beagle dogs.

    PubMed

    Le Lamer, S; Cros, G; Serrano, J J; Piñol, C; Fernändez-Alvarez, J; Bressolle, F

    2001-12-01

    In this paper, an empirical Bayes methodology was used to determine the pharmacokinetic profile of sodium tungstate in beagle dogs after multiple oral dosing using the P-PHARM computer program. The population estimation algorithm used in P-PHARM is an EM-type procedure. Sodium tungstate was administered orally, three times a day, (i) for 11 days (21 and 42 mg/kg per day) to 18 dogs (nine males and nine females) and (ii) for 13 weeks (15, 30 and 60 mg/kg per day) to 28 dogs (14 males, 14 females). Six other dogs received the compound intravenously (25 and 50 mg/kg). Plasma concentration profiles versus time were compatible with a two-compartment model and first-order kinetics. After oral administration, F (0.61+/-0.086 vs. 0.48+/-0.093), and normalized (to a 7-mg/kg dose of sodium tungstate) AUC (54+/-8.4 vs. 41.2+/-8.5 mg/l x h), C(max) (10.6+/-0.49 vs. 8.5+/-0.57 microg/ml) and C(min) (3.04+/-0.23 vs. 2.04+/-0.22 microg/ml), were higher in male than in female dogs. However, the introduction of the gender in the final model did not contribute statistically to an improvement of the fit of the population pharmacokinetic model. In males, t(1/2) elimination averaged 3.1+/-0.56 vs. 2.6+/-0.18 h in females. The duration of treatment did not modify statistically the pharmacokinetic parameters. After repeated multiple oral administration of 15-60 mg/kg per day of sodium tungstate, tungsten plasma concentrations increased in proportion to dose. No dose-dependent changes in pharmacokinetic parameters occurred.

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

    PubMed

    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.

  19. A short-term study of the effects of SBHAN, a novel compound, on gingival inflammation in the beagle dog.

    PubMed

    Cutler, C W; Ghaffar, K A

    1997-05-01

    Unique hydroxyl ion-modulating compounds based on the amino acid glycine have been developed that possess both antimicrobial and pro-healing properties. The purpose of the present study was to determine the effects of one of these compounds, 8.5% (w/v) sodium N, N-bis-2 (hydroxylethyl) aminoacetate (SBHA) with 0.3% (w/v) NaOH (SBHAN) on ligature-induced gingival inflammation in the beagle dog. Fifteen purebred beagle dogs were subjected to a 14-day oral hygiene regimen, consisting of manual scaling and daily toothbrushing with plain pumice. Gingival inflammation was then initiated by tying ligatures around 12 study teeth per dog and by placing the dogs on water-softened dog chow. After 30 days, ligatures were removed, dogs were placed on a hard diet and randomly assigned to five treatment groups by the flip of two coins. The five treatments included: 1) distilled, pyrogen-free water; 2) 8.5% (w/v) SBHAN; 3) 4.3% (w/v) SBHAN; 4) 0.12% chlorhexidine; and 5) 8.5% SBHA (w/v) (SBHAN without added NaOH). Solutions were placed in opaque spray bottles to shield their identity from the examiner. Treatment consisted of a daily aerosol application of 2 ml of each solution in a calibrated spray bottle to the affected teeth. The following measures were taken from the dogs at baseline (after hygienic phase), 30 days after initiation of gingival inflammation (before ligature removal), and 2 weeks and 4 weeks after ligature removal: 1) plaque index (PI); 2) gingival index (GI); 3) probing depths (PD); 4) relative attachment levels (RAL); and 5) gingival crevicular fluid volume (GCF). Analysis of subgingival plaque for anaerobic and aerobic colony forming units/ml was also performed at each time point. Gingival biopsies were performed, sectioned and stained with hematoxylin and eosin to quantify the inflammatory cell infiltrate (ICI). After ligature placement, increases were observed in PI, GI, PD, RAL, GCF, aerobic and anaerobic subgingival microbial counts, and ICI. After

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

    SciTech Connect

    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.

  1. The electrocardiogram of the Beagle dog: reference values and effect of sex, genetic strain, body position and heart rate.

    PubMed

    Hanton, G; Rabemampianina, Y

    2006-04-01

    The aim of the study was to establish a database for electrocardiographic parameters of Beagle dogs used for toxicological studies and to evaluate the influence of supplier, sex, heart rate (HR) and body position for electrocardiogram (ECG) recording on ECG parameters. Peripheral ECG leads were recorded from 934 female and 946 male dogs from Marshall Farms and 27 females and 30 males from Harlan, either standing on a table or restrained in a hammock. HR, RR, PQ and QT intervals, P and QRS duration and P-wave amplitude were measured. There were no major differences between sexes for ECG parameters. The axis of the heart was shifted to the left when the animals were restrained in a hammock compared to when they were standing on a table. The PQ interval was higher (about 9%) in Harlan than in Marshall dogs. HR was negatively correlated with QT (coefficient of linear correlation: r=-0.61 to -0.74), which emphasizes the need for a formula correcting QT interval for HR when interpreting changes in QT interval. HR was also negatively correlated with PQ intervals (r=-0.26 to -0.11), whereas a positive correlation was found between HR and the amplitude of the P wave (r=0.21-0.34). The level of the respiratory sinus arrhythmia (SA) was quantified by calculating the ratio of maximum to minimum RR interval measured over a 10 s period. This ratio was negatively correlated with HR (r =-0.49 to -0.33). Therefore, at high HRs, SA was less marked than at low HRs, but it did not completely disappear. Analysis of beat-to-beat variation indicated that QT and PQ intervals and the amplitude of P wave fluctuated over time and the degree of this variability was positively correlated with the level of SA. In conclusion, we have established reference values for the duration and/or amplitude of some ECG parameters both in terms of means and variability over the recording period, and we have evaluated the influence of body position, genetic strain and HR on the ECG parameters. These data can

  2. Bovine colostral antibody against verotoxin 2 derived from Escherichia coli O157:H7: resistance to proteases and effects in beagle dogs.

    PubMed

    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.

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

    PubMed

    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 < 0.05) in bitches without (nulliparous) whelping experience than in bitches with (multiparous) whelping experience (6.9 d versus 8.0 d). When calculated as the interval between the day of initial elevation in progesterone concentrations and the day of whelping, the 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.

  4. The safety evaluation of fluvastatin, an HMG-CoA reductase inhibitor, in beagle dogs and rhesus monkeys.

    PubMed

    Hartman, H A; Myers, L A; Evans, M; Robison, R L; Engstrom, R G; Tse, F L

    1996-01-01

    Fluvastatin is a potent synthetic competitive inhibitor of beta-hydroxy-beta-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the biosynthetic pathway for hepatic cholesterol synthesis. The therapeutic indication is reduction of elevated total and low-density lipoprotein cholesterol levels. Results from four toxicity studies in beagle dogs and one study in rhesus monkeys following oral administration of fluvastatin are reported. In two 26-week dog studies, doses were 0, 1, 8, or 48 mg/kg/day (reduced to 36 mg/kg/day in Week 7) and 0, 6, 24, or 36 mg/kg/day (reduced to 30 mg/kg/day in Week 2). In a 2-year dog study, doses were 0, 1, 8, or 16 mg/kg/day. Dose levels in the 26-week monkey study were 0, 0.6, 12, and 48 mg/kg/day (raised to 84 mg/kg/day in Week 17 and to 108 mg/kg/day in Week 22). In these studies, evaluations included clinical and physical examinations, body weight and food consumption, electrocardiography, ophthalmoscopy, hematology and clinical chemistries, urinalysis, blood drug concentration, and macroscopic and microscopic examinations of observed lesions and representative tissues. In the 26- and 52-week dog studies and the monkey study, lenticular biochemistry, the HMG-CoA reductase activity of liver microsomes, and serum lipid concentrations were investigated. The fourth dog study was a single-dose toxicokinetic study in which 48 mg/kg [3H]-fluvastatin was monitored for up to 2 weeks. Sampling was limited to ocular tissues for enzyme analysis. Doses of > or = 24 mg/kg/day were lethal in dogs. At lethal doses, ataxia, convulsions, fecal blood, multifocal congestion and hemorrhage, isolated foci of malacia in the medulla oblongata, and liver necrosis were observed. Reduced weight gain, emesis, cataracts, elevated liver enzymes, reduced cholesterol, and gallbladder inflammation with mucosal hyperplasia occurred at > or = 8 mg/kg/day. In contrast to other HMG-CoA reductase inhibitors, fluvastatin did not cause significant

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

    PubMed

    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.

  6. Integration of Pharmacokinetic and Pharmacodynamic Indices of Orbifloxacin in Beagle Dogs after a Single Intravenous and Intramuscular Administration▿

    PubMed Central

    Gebru, Elias; Lee, Joong-Su; Chang, Zhi-Qiang; Hwang, Mi-Hyun; Cheng, Henrique; Park, Seung-Chun

    2009-01-01

    The pharmacokinetics (PK) and pharmacodynamics (PD) of orbifloxacin were studied in beagle dogs after intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 2.5 mg/kg body weight. An absolute bioavailability of 100.1% ± 4.76%, a terminal half-life of 4.23 ± 0.2 h and 3.95 ± 0.15 h after i.v. and i.m. administration, a steady-state volume of distribution of 1.61 ± 0.13 liters/kg, and clearance of 0.31 ± 0.03 liters/h/kg were observed. Orbifloxacin showed rapid, concentration-dependent killing against the Escherichia coli, Staphylococcus aureus, Staphylococcus intermedius, and Proteus mirabilis clinical isolates. Computations based on PK-PD analysis indicated that the recommended dose is unlikely to be clinically effective against some strains like S. intermedius. Therefore, a higher dose of orbifloxacin would be worthy of consideration for treatment of certain bacterial infections in dogs. PMID:19398644

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  10. RBC-/Cr-51/ half-life and albumin turnover in growing Beagle dogs during chronic radial acceleration

    NASA Technical Reports Server (NTRS)

    Beckman, D. A.; Evans, J. W.; Oyama, J.

    1979-01-01

    The effects of chronic centrifugation on growing Beagle dogs exposed to -2 or -2.6 Gx on albumin and RBC turnover rates, albumin concentration and space, and total blood volume were determined and compared with caged and run control of animals. Albumin-(I-125) and autologous RBC-(Cr-51) preparations were injected into all dogs at day 82 of the centrifugation periods, and the disappearance curves were determined by successive bleedings of the animals over the next 35 d, during which the centrifugation was continued. There were no differences in albumin turnover rates or space. Two populations of RBCs were found in both centrifugated groups, one with a normal half-life of 27 + or - 1 S.E.M. d, and one with a significantly (p less than 0.01) shorter half-life of 15 + or - 2 S.E.M. d. An absolute polycythemia was also observed in both centrifuged groups. The results suggest that chronic centrifugation acts through some as-yet unknown mechanism to affect RBC population kinetics.

  11. Effects of Nigella sativa, Lepidium sativum and Trigonella foenum-graecum on sildenafil disposition in beagle dogs.

    PubMed

    Al-Mohizea, Abdullah M; Ahad, Abdul; El-Maghraby, Gamal M; Al-Jenoobi, Fahad I; AlKharfy, Khalid M; Al-Suwayeh, Saleh A

    2015-06-01

    The present study was conducted to investigate the effects of some commonly used herbs namely Nigella sativa, Lepidium sativum and Trigonella foenum-graecum on the pharmacokinetics of sildenafil in beagle dogs. The study design involved four treatments in a non-balanced crossover design. Sildenafil was given one tablet 100 mg orally to each dog and blood samples were obtained. After a suitable washout period, animals were commenced on a specific herb treatment for 1 week. Blood samples were withdrawn at different time intervals and sildenafil was analyzed by HPLC method. Oral administration of Nigella sativa resulted in reduction of AUC0-∞, C max and t 1/2 as compared to the control. Treatment of Lepidium sativum resulted in a significant reduction in the C max and AUC. There were no significant differences between the rests of the pharmacokinetic parameters relative to those of the control. For Trigonella foenum-graecum, the effects were similar to those obtained in case of Lepidium sativum. It was concluded that concurrent use of investigated herbs alters the pharmacokinetics of sildenafil. Co-administration of investigated herbs should be cautious since their concomitant use might result in decrease in sildenafil bioavailability.

  12. Determination of andrograpolide sodium bisulphite in Beagle dog plasma by LC-MS/MS and its application to pharmacokinetics.

    PubMed

    Zhang, Shuang-Qing; Fan, Yu-Ming

    2012-10-15

    A sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated for the determination of andrographolide sodium bisulphite (ASB) in dog plasma using dehydroandrographolide (DAG) as an internal standard. Chromatographic separation was achieved on a Hypersil Gold C(18) column (50 mm × 2.1 mm, 1.9 μm) with gradient elution that consisted of methanol and water at a flow rate of 0.2 mL/min. Quantification was done using selected reaction monitoring (SRM) mode to monitor precursor-product ion transitions of m/z 413.2→287.2 for ASB and 331.2→303.3 for DAG at negative ionization mode. Good linearity was obtained over the range of 10-1000 ng/mL and the correlation coefficient was better than 0.99. The intra- and inter-day accuracies ranged from 97.2% to 107.8% and precisions (RSD) were within 13.9%. ASB was found stable under three freeze-thaw cycles, short-term temperature, post-preparative and long-term temperature conditions. The method was successfully applied to a pharmacokinetic study of ASB intravenously administered to Beagle dogs.

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

    PubMed

    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.

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

    PubMed

    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.

  15. 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.

    PubMed

    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.

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

    PubMed

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

    PubMed

    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.

  18. Microdistribution and Long-Term Retention of 239Pu (NO3)4 in the Respiratory Tracts of an Acutely Exposed Plutonium Worker and Experimental Beagle Dogs

    SciTech Connect

    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.

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

    PubMed

    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

  20. Effectiveness of a dental gel to reduce plaque in beagle dogs.

    PubMed

    Hennet, Philippe

    2002-03-01

    Tooth brushing is considered a superior technique for reducing plaque accumulation. Chemical agents may be used to reduce plaque accumulation on tooth surfaces since many owners may not be willing or able to brush their dog's teeth. Following a professional teeth cleaning procedure, a dental gel containing chlorhexidine was applied in 11 dogs BID for 7-days, while 11 other dogs received a control dental gel applied in the same manner. Dogs in the treatment group had significantly less plaque accumulation during the trial period compared with dogs in the control group. The dental gel applied in the study reported here decreases plaque accumulation in the short-term and may be beneficial in reducing the severity of gingivitis and associated periodontal disease if provided on a long-term basis.

  1. Effectiveness of an enzymatic rawhide dental chew to reduce plaque in beagle dogs.

    PubMed

    Hennet, P

    2001-06-01

    Tooth brushing is considered a superior technique for reducing plaque accumulation. Other methods of maintaining oral hygiene have been investigated since many owners may not be willing or able to brush their dog's teeth. Following a professional teeth cleaning procedure, 11 dogs were offered a rawhide dental chew BID for 7-days, while 11 other dogs were fed the same diet without receiving the chew device. Dogs in the treatment group had significantly less plaque formation during the trial period compared with dogs in the control group. The rawhide dental chew provided in the study reported here decreases plaque formation in the short-term and may be beneficial in the prevention of progressive periodontal disease associated with attachment loss if provided on a long-term basis.

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

    PubMed Central

    Zhang, Xiaofang; Zhang, Xiaodong; Yuan, Bojun; Ren, Lijun; Zhang, Tianbao; Lu, Guocai

    2016-01-01

    Histone deacetylase inhibitors (HDACIs), such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb) HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD) rats was identified. Dogs and rats received HZ1006 orally (0–80 and 0–120 mg/kg/day, respectively) on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006’s NOAEL (No Observed Adverse Effect Level) by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies. PMID:27916918

  3. Pharmacokinetic and pharmacodynamic interactions of aspirin with warfarin in beagle dogs.

    PubMed

    Shen, Chenlin; Huang, Xiaohui; Li, Jun; Zhang, Ping; Li, Lin; Zhang, Wei; Hu, Tingting; Pappoe, Faustina; Huang, Jihan; Tang, Haiqin

    2016-01-01

    1. Warfarin and aspirin are widely used in a wide spectrum of thromboembolic and atherothrombotic diseases. Despite the potential efficacy of warfarin-aspirin therapy, the safety and side effect of combined therapy remains unclear. 2. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and aspirin in beagles after single and multiple doses. 3. Coadministration of aspirin had no significant effects on the area under the plasma concentration time curve (AUC(0-t)) and maximum plasma concentration (Cmax) of R- and S-warfarin after a single dose of warfarin, but significantly increase the AUC(0-t) and Cmax and dramatically decrease the clearance (CL) of R- and S-warfarin after multiple dose of warfarin. Accordingly, there was a slight increase in the AUEC(0-t) and Emax of activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) after multiple dose of warfarin. 4. Coadministration of warfarin had no markedly effects on the AUC(0-t) and Cmax of aspirin and its metabolite salicylic acid after single or multiple dose of aspirin. Meanwhile, the AUEC(0-t) and Emax of inhibition of platelet aggregation (IPA) were not significantly affected by warfarin. 5. Our animal study indicated that coadministration of aspirin with warfarin can cause significant pharmacokinetic and pharmacodynamic drug-drug interactions in beagles. However, more studies are urgently needed to assess related information of warfarin-aspirin drug interactions in healthy volunteers or patients.

  4. Effects of a canine Elizabethan collar on ambulatory electrocardiogram recorded by a Holter recording system and spontaneous activities measured continuously by an accelerometer in Beagle dogs.

    PubMed

    Yamada, M; Tokuriki, M

    2000-05-01

    Ambulatory electrocardiogram (ECG) has been recorded in dogs wearing a jacket to protect a Holter recording system, but the jacket was often damaged by dogs. We compared ECG recorded by a Holter recording system and spontaneous activity measured by an accelerometer in Beagle dogs with or without an Elizabethan collar. There were few significant differences in mean values (per hr) of the heart rate and the amount of spontaneous activity between dogs with or without the Elizabethan collar. Mean values (per 23 hr) of them had no significant difference between them. We concluded that the Elizabethan collar did not have any effect on ambulatory ECG and canine movements and was effective to protect the recording apparatus.

  5. Comparison of 51chromium-labeled ethylenediamine tetra-acetic acid and iohexol as blood markers for intestinal permeability testing in Beagle dogs.

    PubMed

    Frias, Rafael; Strube, Katrin; Ternes, Waldemar; Collado, M Carmen; Spillmann, Thomas; Sankari, Satu; Westermarck, Elias

    2012-04-01

    (51)Chromium-labeled ethylenediamine tetra-acetic acid ((51)Cr-EDTA) is the gold standard probe for assessing intestinal permeability (IP) in dogs, but exposure to radioactivity is a disadvantage. Iohexol is a safe contrast medium commonly used for medical imaging purposes and has been successfully applied more recently for the assessment of IP in animal models and humans. This study aimed at comparing (51)Cr-EDTA and iohexol as IP blood markers in dogs. A test solution containing (51)Cr-EDTA and iohexol was administered intragastrically to seven healthy laboratory Beagle dogs, and percentage recoveries in serum were calculated. The strong linear association (correlation, r=0.76 and linear regression, y=0.03+5.04x) between (51)Cr-EDTA and iohexol supports the potential usefulness of iohexol as an IP blood marker in dogs.

  6. [Pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in Beagle dogs determined with LC-MS/MS].

    PubMed

    Xia, Tian; Liu, De-Ding; Shi, Li-Fu; Hu, Jin-Hong

    2011-08-01

    The study aims to elucidate the characteristics of pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in healthy Beagle dogs. Chromatographic separation was performed on a C18 column (100 mm x 3.0 mm, 3.5 microm) with methanol - 2 mmol x L(-1) ammonium formate (25 : 75) as the mobile phase. A trip-quadrupole tandem mass spectrum with the electrospray ionization (ESI) source was applied and positive ion multiple reaction monitoring mode was operated. Six Beagle dogs were randomly devided into two groups. They received oral single dose of scopolamine hydrobromide oral disintegrative microencapsule tablets 0.6 mg (test tablet) or scopolamine hydrobromide normal tablets (reference tablet). Plasma samples were collected at designed time. Plasma concentration of scopolamine hydrobromide was determined by LC-MS/MS and pharmacokinetic parameters were calculated. The pharmacokinetic parameters of test tablet vs reference tablet were as follows: C(max): (8.16 +/- 0.67) ng x mL(-1) vs (3.54 +/- 0.64) ng x mL(-1); t1/2: (2.83 +/- 0.45) h vs (3.85 +/- 0.82) h; t(max): (1.25 +/- 0.27) h vs (0.42 +/- 0.09) h; AUC(0-12h): (25.06 +/- 3.75) h x ng x mL(-1) vs (9.59 +/- 1.02) h x ng x mL(-1); AUC(0-infinity): (26.30 +/- 3.92) h x ng x mL(-1) vs (10.80 +/- 1.45) h x ng x mL(-1); MRT(0-12h): (3.38 +/- 0.34) h vs (3.86 +/- 0.26) h; MRT(0-infinity): (3.98 +/- 0.63) h vs (5.37 +/- 1.00) h. The absorption rate and AUC of test tablet is different from that of reference tablet. The bioavailability of test tablet is better than those of reference tablet.

  7. Assessment of frailty in aged dogs.

    PubMed

    Hua, Julie; Hoummady, Sara; Muller, Claude; Pouchelon, Jean-Louis; Blondot, Marc; Gilbert, Caroline; Desquilbet, Loic

    2016-12-01

    OBJECTIVE To define a frailty-related phenotype-a clinical syndrome associated with the aging process in humans-in aged dogs and to investigate its association with time to death. ANIMALS 116 aged guide dogs. PROCEDURES Dogs underwent a clinical geriatric assessment (CGA) and were followed to either time of death or the study cutoff date. A 5-component clinical definition of a frailty phenotype was derived from clinical items included in a geriatric health evaluation scoresheet completed by veterinarians during the CGA. Univariate (via Kaplan-Meier curves) and multivariate (via Cox proportional hazards models) survival analyses were used to investigate associations of the 5 CGA components with time to death. RESULTS 76 dogs died, and the median time from CGA to death was 4.4 years. Independent of age at the time of CGA, dogs that had ≥ 2 of the 5 components (n = 10) were more likely to die during the follow-up period, compared with those that had 1 or no components (adjusted hazard ratio, 3.9 [95% confidence interval, 1.4 to 10.9]). After further adjustments for subclinical or clinical diseases and routine biomarkers, the adjusted hazard ratio remained significant. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that signs of frailty appeared to be a risk factor for death in dogs. The concept of frailty in dogs requires further development. IMPACT FOR HUMAN MEDICINE The concept of frailty, as defined for humans, seems transposable to dogs. Given that they share humans' environments and develop several age-related diseases similar to those in humans, dogs may be useful for the study of environmental or age-related risk factors for frailty in humans.

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

    SciTech Connect

    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. - 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.

  9. Mini-tablet combination for sustained release of clonidine hydrochloride and hydrochlorothiazide: Preparation and pharmacokinetics in beagle dogs.

    PubMed

    Xu, Bohui; Wang, Yubin; Zhu, Hongyan

    2016-02-01

    Mini-tablets are increasingly gaining attention in solid dosage form design as multiple-unit systems combining different active compounds and providing a single or combined pattern of modified release for polypharmacy or combined treatments. A combination therapy of clonidine hydrochloride and hydrochlorothiazide achieves effective blood pressure control and reduction in adverse effects. However, the combination formulation of immediate release must be taken several times a day, which causes noticeable fluctuation of blood pressure and inconveniences to the patients. The present study was performed to develop a mini-tablet combination for sustained release of clonidine hydrochloride and hydrochlorothiazide independently, in which the two drugs and fraction doses were formulated into separate mini-tablets with different release patterns. The mini-tablets were prepared by a direct compression method followed by filling into capsules and the factors that affected drug release were addressed. Further, studies of the pharmacokinetics were performed in beagle dogs. Finally, in vivo-in vitro correlations of the sustained release systems and bioequivalence with conventional preparations were evaluated. The mini-tablet combination released the two drugs over 24h in vivo with a steady plasma concentration, a markedly lower Cmax, extended Tmax and better bioavailability. In conclusion, sustained releases of the two drugs were obtained with this mini-tablet combination, which offers a feasible formulation and promising development value for hypertensive patients who need long-term therapy.

  10. A Population Pharmacokinetic Approach to Describe Cephalexin Disposition in Adult and Aged Dogs

    PubMed Central

    Prados, Ana Paula; Kreil, Verónica; Monfrinotti, Agustina; Quaine, Pamela; Tarragona, Lisa; Hallu, Ruben

    2014-01-01

    This study was conducted in order to characterize the pharmacokinetics of orally administered cephalexin to healthy adult and aged dogs, using a population pharmacokinetic approach. Two hundred and eighty-six cephalexin plasma concentrations obtained from previous pharmacokinetic studies were used. Sex, age, pharmaceutical formulation, and breed were evaluated as covariates. A one-compartment model with an absorption lag-time (Tlag) best described the data. The final model included age (adult; aged) on apparent volume of distribution (Vd/F), apparent elimination rate (ke/F), and Tlag; sex (female; male) on ke/F, and breed (Beagle; mixed-breed) on Vd/F. Addition of the covariates to the model explained 78% of the interindividal variability (IIV) in Vd/F, 36% in ke/F, and 24% in Tlag, respectively. Formulation did not affect the variability of any of the pharmacokinetic parameters. Tlag was longer, whereas Vd/F and ke/F were lower in aged compared to adult animals; in female aged dogs ke/F was lower than in male aged dogs; however, the differences were of low magnitude. Different disposition of cephalexin may be expected in aged dogs. PMID:25431741

  11. Development and uniform evaluation of ropinirole osmotic pump tablets with REQUIP XL both in vitro and in beagle dogs.

    PubMed

    Li, Zhiping; Yu, Fanglin; Di, Zhong; Zhao, Xiqing; Zhao, Shiqing; Liu, Yan; Li, Ying; Wang, Zhiyuan; Gong, Wei; Zhang, Hui; Yang, Yang; Xie, Xiangyang; Mei, Xingguo

    2016-01-01

    REQUIP XL, prolonged release formulation of ropinirole hydrochloride (RH) in market, could release ropinirole constantly and showed satisfactory therapeutic effect and good compliance. REQUIP XL was composed of more than 10 kinds of excipients and prepared by Geomatrix technology, which was complex and laborious. The purpose of this study was to obtain a dosage form of RH with similar in vitro release profile and bioequivalence in vivo compared to REQUIP XL. Osmotic pump tablet combined with fast release phase was selected as the delivery system of RH and similar release curves were obtained in different media. The tablets were also administered to beagle dogs and the pharmacokinetic parameters were calculated using a non-compartmental model. Cmax, tmax, mean residence time (MRT), and area under the curve from 0 to 24 h (AUC0-24) were 3.97 ± 0.53 ng/mL, 3.58 ± 0.49 h, 8.29 ± 0.93 h, and 35.20 ± 8.11 ng/mL ċ h for ropinirole osmotic pump tablets (ROPT) and 4.15 ± 1.07 ng/mL, 2.92 ± 0.49 h, 7.84 ± 1.09 h, and 34.34 ± 10.06 ng/mL ċ h for REQUIP XL. The log-transformed mean Cmax and AUC0-24 of ROPT were about 92.15% and 102.49% relative to that of REQUIP XL, respectively. The 90% confidence intervals of Cmax and AUC0-24 for ROPT were 75.69-115.31% and 88.89-122.30%, respectively. So it could be concluded that ROPT was uniform with REQUIP XL both in vitro and in beagles and the release profiles of Geomatrix technology may be obtained by osmotic pump combined with fast release technology.

  12. Root resorption of primary molars without successor teeth. An experimental study in the beagle dog.

    PubMed

    Lin, Bi-Chen; Zhao, Yu-Ming; Yang, Jie; Ge, Li-Hong

    2012-04-01

    Tooth agenesis is a common craniofacial congenital malformation in humans, but little is known about the mechanisms of root resorption in this condition. The purpose of this study was to investigate the mechanisms of root resorption in primary molars without successors. An animal model without permanent tooth germs was established by surgery in beagles. The times of onset of primary molar root resorption, with and without successors, were compared. The distribution of immune cells, odontoclasts, and their activating factors were determined by histochemistry and immunohistochemistry. Root resorption of primary mandibular molars without successors began later than physiological resorption. In primary molars without permanent germs, odontoclasts and immune cells were present mainly in the apical pulp at the start of root resorption, whereas in control teeth receptor activator of nuclear factor-κB ligand (RANKL)-positive cells were found mainly in the region of the periodontal ligament. CD14(+) and CD3(+) cells were found in both the pulp and the periodontal ligament region. These results suggest that the dental pulp of primary molars, as well as immune cells, may play an important role in root resorption in primary molars without permanent tooth germs.

  13. Distribution of fibre types and fibre sizes in the tibialis cranialis muscle of beagle dogs.

    PubMed Central

    Newsholme, S J; Lexell, J; Downham, D Y

    1988-01-01

    The percentages of Type I muscle fibres were measured systematically in ATPase-stained, transverse cryostat sections of whole tibialis cranialis muscles from 8 young, adult beagles. The distance of the section from the origin of the muscle does not significantly affect the mean percentage. There are no identifiable differences in mean percentages between right and left muscles. Differences in mean percentages between individuals are significant when sexes are combined (P less than 0.01) and within sexes (males: P less than 0.01; females: P less than 0.05). Within sections, the percentage tends to be lowest at the superficial (craniolateral) border and to vary less from site to site deeper within the muscle. Fibre cross sectional areas were measured systematically in the same sections of the right muscle from 3 males and 3 females. Mean areas for each section were greater for Type II than for Type I fibres. Mean areas for each fibre-type varied moderately and non-systematically between the sample sites within sections. A needle biopsy taken from deep within this muscle should provide a more consistent and reliable estimate of fibre-type proportion in the whole muscle than a superficial specimen. Proportions are not affected by the distance of the sample site from the muscle origin, and left or right muscles are suitable for sequential samples. PMID:3253248

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

    SciTech Connect

    Hurst, D.R. . 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.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:27536243

  17. (13)N-Ammonia PET/CT Detection of Myocardial Perfusion Abnormalities in Beagle Dogs After Local Heart Irradiation.

    PubMed

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

    2017-04-01

    Our objective was to determine the potential value of (13)N-ammonia PET/CT myocardial perfusion imaging (MPI) for early detection of myocardial perfusion changes induced by radiation damage. Methods: Thirty-six Beagle dogs were randomly divided into a control group (n = 18) or an irradiation group (n = 18). The latter underwent local irradiation to the left ventricular anterior cardiac wall with a single dose of 20 Gy, whereas the former received sham irradiation. All dogs underwent (13)N-ammonia PET/CT MPI 1 wk before irradiation and at 3, 6, and 12 mo after sham or local irradiation. One week after undergoing (13)N-ammonia PET/CT MPI, the irradiation group underwent coronary angiography. Six randomly selected dogs from each group were sacrificed and used to detect pathologic cardiac injury at 3, 6, and 12 mo after irradiation. Results: Compared with the control group and baseline, the irradiation group showed significantly increased perfusion in the irradiated area of the heart at 3 mo after irradiation, perfusion reduction at 6 mo after irradiation, and a perfusion defect at 12 mo after irradiation. There was no significant difference in the left ventricular ejection fraction between the control and irradiation groups at baseline or at 3 mo after irradiation. The irradiation group showed a reduction of left ventricular ejection fraction compared with the control group at 6 mo (50.0% ± 8.1% vs. 59.3% ± 4.1%, P = 0.016) and 12 mo (47.2% ± 6.7% vs. 57.4% ± 3.3%, P = 0.002) after irradiation. No coronary stenosis was observed in the irradiation group. Regional wall motion abnormalities appeared in the irradiated area at 6 mo after irradiation, and its extent was enlarged at 12 mo after irradiation. Pathologic changes were observed; radiation-induced myocardial tissue damage and microvascular fibrosis in the irradiated area progressively increased over time. Conclusion:(13)N-ammonia PET/CT MPI can dynamically detect myocardial perfusion changes together with

  18. Beagle 2

    NASA Astrophysics Data System (ADS)

    Hall, D. S.; Pillinger, C. T.; Sims, M. R.; Pullan, D.; Whitehead, S.; Thatcher, J.; Clemmet, J.; Linguard, S.; Underwood, J.; Richter, L.

    2000-07-01

    Beagle 2 is the British-led lander of the ESA Mars Express mission. The prime objectives of Beagle 2 are to (1) search for criteria relating to past life on Mars, (2) seek trace atmospheric species indicative of extant life, (3) measure the detailed atmospheric composition to establish the geological history of the planet and to document the processes involved in seasonal climatic changes or diurnal cycling, (4) investigate the oxidative state of the Martian surface, rock interiors and beneath boulders, (5) examine the geological nature of the rocks, their chemistry, mineralogy, petrology and age, (6) characterise the geomorphology of the landing site, and (7) appraise the environmental conditions including temperature, pressure, wind speed, UV flux, etc. The entry system comprises a front shield/aeroshell, a back cover/bioshield and release mechanisms. The descent system depends on a mortar, pilot chute, main parachute and main parachute release mechanism. The Lander itself has a clam-like structure and lands cocooned within gas-filled airbags. The outer shell provides energy absorption and thermal insulation within a casing that must spread the impact loads and resists tearing. Many of the Beagle 2 science instruments are integrated with a robotic arm that transports them to deploy them in positions where they can study or obtain samples of the rocks and soil. Sub-surface samples are obtained using a Pluto (PLanetary Undersurface TOol) which has the ability to crawl across, and burrow below the planetary surface. The constraints placed on Beagle 2 by mass restrictions of the Mars Express mission has meant that many innovations are necessary to ensure delivery of a sufficient science payload mass capable of the full range of measurements necessary to achieve the mission objectives. In particular a highly integrated approach to lander sytems and science instruments has been essential. This approach and the necessary technology developments have important

  19. Study of haemostatic disorders in experimentally induced leishmaniasis in Beagle dogs.

    PubMed

    Valladares, J E; Ruiz De Gopegui, R; Riera, C; Alberola, J; Gállego, M; Espada, Y; Portús, M; Arboix, M

    1998-01-01

    Haemostatic alterations in dogs experimentally infected with Leishmania infantum were studied before and after therapy with meglumine antimonate. Haemostatic function tests including platelet count, collagen-induced platelet aggregation, prothrombin time, activated partial thromboplastin time, thrombin time, plasma fibrinogen determination, and serum fibrinogen/fibrin degradation products concentration were performed. In the course of infection and before treatment, moderate thrombocytopenia (P<0.00001), decreased collagen induced platelet aggregation (P=0.0003), prolonged thrombin time (P=0.0117) and increased fibrinogen/fibrin degradation products were observed. Statistically significant differences of plasma fibrinogen concentration, prothrombin time, and activated partial thromboplastin time were not encountered. Haemostatic parameters returned to normal values after therapy. The results indicate that Leishmania infection may impair haemostasis suggesting induction of disseminated intravascular coagulation (DIC), and that treating dogs in an early stage of infection may potentially avoid the possibility of developing an uncompensated DIC.

  20. Toxicological study of the hepatotherapeutic herbal formula, Chunggan extract, in beagle dogs

    PubMed Central

    Choi, Woo-Jin; Shin, Jang-Woo; Son, Jin-Young; Seo, Dong-Seok; Park, Hark-Soo; Han, Seung-Hyun; Sung, Ha-Jung; Cho, Jung-Hyo; Cho, Chong-Kwan; Yoo, Hwa-Seung; Lee, Yeon-Weol; Son, Chang-Gue

    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. PMID:17167840

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

    PubMed

    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.

  2. Apoptosis in the aged dog brain.

    PubMed

    Kiatipattanasakul, W; Nakamura, S; Hossain, M M; Nakayama, H; Uchino, T; Shumiya, S; Goto, N; Doi, K

    1996-09-01

    Apoptosis similar to that seen in Alzheimer's disease patients was found in the brain of aged dogs by the TUNEL method of detecting in situ DNA fragmentation. Apoptosis was observed in both neurons and glial cells, and was morphologically characterized by round and swollen cytoplasm and aggregated nuclear chromatin, although these changes were slight. Neurons and astrocytes in the gray matter and oligodendrocytes in the white matter were affected. The number of ApopTag-positive brain cells increased slightly with age, but was not correlated to the number of senile plaques. A good correlation between the number of ApopTag-positive cells and the dementia index was clearly found. The present study indicates that brain cell apoptosis could account for dementia in aged dogs and suggested that aged dogs may be useful as a simplified animal model for Alzheimer's disease in man.

  3. Bone remodeling at microscrew interface near extraction site in the beagle dog mandible-histologic and immunohistochemical analyses

    PubMed Central

    WEI, Guangxi; HU, Yun; ZHENG, Leilei; HUO, Jinfeng; TANG, Tian; DENG, Feng

    2013-01-01

    Extraction is often used as part of orthodontic therapy, and good control of anchorage is a key step after extraction. Although microscrews can be implanted close to the extraction site in order to achieve orthodontic support, the efficiency of bone remodeling at the implant-bone interface near the extraction region is dubious. Objective The purpose of this study was to investigate bone remodeling of the bone-microscrew interface near the tooth extraction site, in the absence of loading. Material and Methods Third and fourth premolars were extracted from the mandibles of beagle dogs, followed by placement of test microscrews near the extraction sites. Control microscrews were placed further away from the extraction site. All samples were collected after 1, 3, 8, or 12 weeks of healing following extraction. The bone remodeling process at the interface was evaluated using histologic and immunohistochemical analyses. Results Initially, a large number of inflammatory cells were aggregated at the interface. The expression levels of core binding factor (Cbfa1), osteocalcin (OC) and transforming growth factor beta (TGF-β) were inconspicuous in both groups, whereas tumor necrosis factor alpha (TNF-α) was strongly expressed, especially in the test groups (P<0.05). Subsequently, the expression levels of Cbfa1, OC and TGF-β were found to increase significantly, and active osteogenesis was observed. Conclusions During week 1, inflammatory reaction is a major concern at the bone-microscrew interface near the extraction site. However, with healing, the influence of extraction on the remodeling of bone surrounding the microscrews decreases, thus facilitating successful treatment. PMID:24212991

  4. Guided bone regeneration utilizing expanded polytetrafluoroethylene membranes in combination with submerged and nonsubmerged dental implants in beagle dogs.

    PubMed

    Fiorellini, J P; Engebretson, S P; Donath, K; Weber, H P

    1998-05-01

    Treatment of partial and total edentulism with submerged and nonsubmerged dental implants which follows the concept of osseointegration has become an accepted treatment modality. With compromised implant sites, practitioners have begun to combine one-stage implants with established techniques including guided bone regeneration. However, the clinical evaluation of this technique is limited. Therefore, the purpose of this study was to evaluate osseointegration and bone regeneration around nonsubmerged or submerged implants placed directly into surgically created osseous defects with or without expanded polytetrafluoroethylene (ePTFE) membranes. A total of 24 implants were placed in the mandibles of 4 beagle dogs and randomly assigned to 1 of 3 treatment groups. In group A, nonsubmerged implants were placed into osseous defects and treated with a poncho style ePTFE membrane. These membranes had a hole punched into the center and were slipped over the nonsubmerged implants. In group B, nonsubmerged implants were placed into osseous defects without an ePTFE membrane. In group C, submerged implants were placed into osseous defects and covered with an ePTFE membrane. Histometric measurements of each treatment group were made to determine percent bone gain or loss along the implant surface. Although a number of membrane removals occurred during the healing period, histological analysis indicated osseous ingrowth and osseointegration around nonsubmerged and submerged implants. An overall comparison of the treatment groups with ANOVA revealed that there were no significant differences between treatment groups, P > or = 0.05. However, when the data were stratified into sites which retained or lost the ePTFE membrane, the percent of bone regeneration was reduced in group A. Therefore, it may be recommended that nonsubmerged implants be placed with a submerged or "semi-submerged" protocol when utilized in conjunction with ePTFE membranes.

  5. Pharmacokinetics and pharmacodynamics of a new reformulated microemulsion and the long-chain triglyceride emulsion of propofol in beagle dogs

    PubMed Central

    Lee, S-H; Ghim, J-L; Song, M-H; Choi, H-G; Choi, B-M; Lee, H-M; Lee, E-K; Roh, Y-J; Noh, G-J

    2009-01-01

    Background and purpose: Microemulsion propofol was developed to eliminate lipid solvent-related adverse events of long-chain triglyceride emulsion (LCT) propofol. We compared dose proportionality, pharmacokinetic and pharmacodynamic characteristics of both formulations. Experimental approach: The study was a randomized, two-period and crossover design with 7-day wash-out period. Microemulsion and LCT propofol were administered by zero-order infusion (0.75, 1.00 and 1.25 mg·kg−1·min−1) for 20 min in 30 beagle dogs (male/female = 5/5 for each rate). Arterial samples were collected at preset intervals. The electroencephalographic approximate entropy (ApEn) was used as a measure of propofol effect. Dose proportionality, pharmacokinetic and pharmacodynamic bioequivalence were evaluated by non-compartmental analyses. Population analysis was performed using nonlinear mixed effects modelling. Key results: Both formulations showed dose proportionality at the applied dose range. The ratios of geometric means of AUClast and AUCinf between both formulations were acceptable for bioequivalence, whereas that of Cmax was not. The pharmacodynamic bioequivalence was indicated by the arithmetic means of AAC (areas above the ApEn time curves) and E0 (baseline ApEn)–Emax (maximally decreased ApEn) between both formulations. The pharmacokinetics of both formulations were best described by three compartment models. Body weight was a significant covariate for V1 of both formulations and sex for k21 of microemulsion propofol. The blood-brain equilibration rate constants (ke0, min−1) were 0.476 and 0.696 for microemulsion and LCT propofol respectively. Conclusions and implications: Microemulsion propofol was pharmacodynamically bioequivalent to LCT propofol although pharmacokinetic bioequivalence was incomplete, and demonstrated linear pharmacokinetics at the applied dose ranges. PMID:19925493

  6. The Osteogenesis Effect and Underlying Mechanisms of Local Delivery of gAPN in Extraction Sockets of Beagle Dogs.

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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

  10. Decorporation of systemically distributed americium by a novel orally administered diethylenetriaminepentaacetic acid (DTPA) formulation in beagle dogs.

    PubMed

    Wilson, James P; Cobb, Ronald R; Dungan, Nathanael W; Matthews, Laura L; Eppler, Bärbel; Aiello, Kenneth V; Curtis, Shiro; Boger, Teannetta; Guilmette, Raymond A; Weber, Waylon; Doyle-Eisele, Melanie; Talton, James D

    2015-03-01

    Novel decorporation agents are being developed to protect against radiological accidents and terrorists attacks. Radioactive americium is a significant component of nuclear fallout. Removal of large radioactive materials, such as 241Am, from exposed persons is a subject of significant interest due to the hazards they pose. The objective of this study was to evaluate the dose-related efficacy of daily doses of NanoDTPA™ Capsules for decorporating Am administered intravenously as a soluble citrate complex to male and female beagle dogs. In addition, the efficacy of the NanoDTPA™ Capsules for decorporating 241Am was directly compared to intravenously administered saline and DTPA. Animals received a single IV administration of 241Am(III)-citrate on Day 0. One day after radionuclide administration, one of four different doses of NanoDTPA™ Capsules [1, 2, or 6 capsules d(-1) (30 mg, 60 mg, or 180 mg DTPA) or 2 capsules BID], IV Zn-DTPA (5 mg kg(-1) pentetate zinc trisodium) as a positive control, or IV saline as a placebo were administered. NanoDTPA™ Capsules, IV Zn-DTPA, or IV saline was administered on study days 1-14. Animals were euthanized on day 21. A full necropsy was conducted, and liver, spleen, kidneys, lungs and trachea, tracheobronchial lymph nodes (TBLN), muscle samples (right and left quadriceps), gastrointestinal (GI) tract (stomach plus esophagus, upper and lower intestine), gonads, two femurs, lumbar vertebrae (L1-L4), and all other soft tissue remains were collected. Urinary and fecal excretion profiles were increased approximately 10-fold compared to those for untreated animals. Tissue contents were decreased compared to untreated controls. In particular, liver content was decreased by approximately eightfold compared to untreated animals. The results from this study further demonstrate that oral NanoDTPA™ Capsules are equally efficient compared to IV Zn-DTPA in decorporation of actinides.

  11. Pharmacokinetic Studies of Sustained-Release Depot of Dexamethasone in Beagle Dogs

    PubMed Central

    Desai, Ankita; Driscoll, Arthur

    2016-01-01

    Abstract Purpose: To examine the pharmacokinetic characteristics of sustained-release dexamethasone depots in two separate canine studies. Methods: Dexamethasone depots loaded with a clinically representative (0.4 mg) dose (DEXTENZA™; Ocular Therapeutix) or an elevated (0.7 mg) dose were inserted into the canaliculi of beagle eyes (n = 37 and n = 34, respectively). Tear fluid was collected for pharmacokinetic analysis of dexamethasone in both studies at predetermined time points. Explanted 0.4 mg depots were collected weekly to measure remaining drug level. Clinical observations and ophthalmic examinations were performed in both studies at each visit. Results: The 0.4 mg depots released a median 308 μg by day 15 and tapered to complete drug release by day 28. Median dexamethasone tear fluid concentrations in the 0.4 mg study group decreased from 2,805 ng/mL at day 7 to 0 ng/mL on day 28. Median dexamethasone tear fluid concentrations in the 0.7 mg study group decreased from 4,370 ng/mL at 6 h post insertion to 830 ng/mL on day 35. Mean ± standard deviation intraocular pressures in the 0.4 and 0.7 mg study groups were 20.7 ± 2.8 and 19.0 ± 4.1 mmHg at baseline, respectively, and demonstrated no meaningful change (20.5 ± 3.0 and 20.6 ± 2.9 mmHg, respectively) over the studies' durations. No ocular toxicities were attributed to the dexamethasone depot. Conclusion: Sustained-release dexamethasone produced no identifiable ocular toxicity in this animal model, and pharmacokinetics demonstrated a sustained and tapered drug release over 28 days at a 0.4 mg dose and exceeded 35 days at a 0.7 mg dose. PMID:27483129

  12. Subchronic toxicity study of tetrahydroisohumulone and hexahydroisohumulone in the beagle dog.

    PubMed

    Chappel, C I; Smith, S Y; Chagnon, M

    1998-11-01

    Hops and hop extracts are approved and widely used bittering agents in the brewing of beer. During recent years, preisomerized alpha hop acids and reduced preisomerized alpha hop acids have been introduced as effective and economical bittering agents that may be added late in the brewing process. Although hops have been used for centuries, there are few studies in the literature on the safety of this ingredient. The study herein was conducted to determine the effects associated with subchronic oral administration of the reduced preisomerized hop acids, hexahydroisohumulone and tetrahydroisohumulone, in the dog. The results show that these materials are generally well tolerated in the dog. At high dose levels they induce vomiting, and much of the material administered was excreted in the faeces. The no-observed-adverse-effect level (NOAEL) of the compounds were 50 and 100 mg/kg body weight, respectively. Consumption of these ingredients by adult humans drinking 1 litre of beer daily is less than 0.25 mg/kg body weight; their use is thus associated with wide safety margins.

  13. Pharmacokinetics of methylphenidate after oral administration of immediate and sustained-release preparations in Beagle dogs.

    PubMed

    Lavy, E; Prise, U; Soldani, G; Neri, D; Brandriss, N; Bar Chaim, A; Giorgi, M

    2011-09-01

    Methylphenidate (MPH) is a drug administered either as an immediate- or sustained-release preparation for the treatment of attention deficit hyperactivity disorder in humans. The aim of this study was to determine the pharmacokinetics of two different MPH formulations in the dog. Eight dogs were randomly assigned to two treatment groups using a two-part randomised, cross-over experimental design. Each subject received a single dose of 20 mg d,l-MPH as an immediate- (IR) or sustained-release (SR) tablet. Blood was collected at specific times, and the plasma concentrations of d,l-MPH were evaluated using high performance liquid chromatography. There were no adverse effects following the oral administration of d,l-MPH in either the IR or SR groups, apart from mild hyperkinesia which was observed in some of the IR group. The plasma concentration data of d,l-MPH were best described by a one-compartment model. There were significant differences in the maximum concentration (C(max)), time to C(max) (T(max)), area under the curve (AUC) and clearance (Cl) between the two formulations. The relative bioavailability of the SR formulation was 30.58±13.73% and, despite low drug plasma concentrations, the SR formulation resulted in uniform plasma concentrations of d,l-MPH. However, the dose rate of the SR formulation used in this study resulted in plasma concentrations that were below effective levels for clinical efficacy, so further studies are required to confirm the suitability of higher dose rates for clinical use.

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

    PubMed

    Hall, Jean A; Jewell, Dennis E

    2012-01-01

    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 circulating

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

    PubMed

    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.

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

    PubMed

    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 < 0.05). The AUCs of isorhamnetin and quercetin in TFH-SD were 5.9- and 3.1-fold higher than that of TFH, while the AUCs of isorhamnetin and quercetin in TFH-SE were 3.4- and 2.4-fold higher than that of TFH. These findings suggested that the oral bioavailability of isorhamnetin and quercetin in 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.

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

    PubMed

    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.

  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.

    PubMed

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

    PubMed

    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.

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

    PubMed

    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. 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.

    PubMed

    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 <7.9% and the accuracy (relative error) was within ±3.5%. The validated method was successfully applied to investigate the pharmacokinetics of mesalazine in healthy beagle dogs after rectal administration of mesalazine suppository.

  2. Simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a bioequivalence study.

    PubMed

    Hu, Ziyan; Zou, Qiaogen; Tian, Jixin; Sun, Lili; Zhang, Zunjian

    2011-12-15

    A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma has been developed and validated. Following liquid-liquid extraction, the analytes were separated on a reversed-phase C(18) column (150 mm × 2.0 mm, 3 μm) using formic acid:10 mM ammonium acetate:methanol (0.2:62:38, v/v/v) as mobile phase at a flow rate of 0.2 mL/min and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode. The method was linear for all analytes over the following concentration (ng/mL) ranges: codeine 0.08-16; ephedrine 0.8-160; guaiphenesin 80-16,000; chlorpheniramine 0.2-40. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method was successfully applied to a bioequivalence study in 6 healthy beagle dogs.

  3. Determination of thymopentin in beagle dog blood by liquid chromatography with tandem mass spectrometry and its application to a preclinical pharmacokinetic study.

    PubMed

    Shi, Meiyun; Yang, Yan; Zhou, Xiaotong; Cai, Lanlan; Fang, Chunxue; Wang, Can; Sun, Heping; Sun, Yantong; Gao, Yin; Gu, Jingkai; Fawcett, J Paul

    2015-05-01

    The pentapeptide thymopentin (Arg-Lys-Asp-Val-Tyr, RKDVY) corresponds to amino acids 32-36 of the 49 amino acid immunomodulatory polypeptide, thymopoietin, whose biological activity is partially reproduced. Thymopentin is widely used in the clinic and represents a promising target for drug design but bioanalytical and pharmacokinetic data are limited due to its enzymatic instability. This paper reports a rapid and sensitive method based on liquid chromatography with tandem mass spectrometry for the determination of thymopentin in beagle dog blood. To inactivate peptidases and stabilize thymopentin, acetonitrile was added to blood samples immediately after collection followed by addition of stable isotope-labeled thymopentin as internal standard and washing with dichloromethane. Chromatography was carried out on an Ascentis Express Peptide ES-C18 column using gradient elution with methanol and aqueous 0.1% formic acid at a flow rate of 0.6 mL/min. Positive electrospray ionization mass spectrometry with selected reaction monitoring achieved linearity in the range of 1.5-800 ng/mL with good accuracy/precision and minimal matrix effects. The method was successfully applied to a pharmacokinetic study in beagle dogs after intravenous administration of 0.2 mg/kg thymopentin.

  4. New clopidogrel napadisilate salt and its solid dispersion with improved stability and bioequivalence to the commercial clopidogrel bisulphate salt in beagle dogs.

    PubMed

    Kim, Yong-Il; Kim, Kyung Soo; Suh, Kwee-Hyun; Shanmugam, Srinivasan; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

    2011-08-30

    The purpose of this study was to develop a novel clopidogrel napadisilate-loaded solid dispersion with improved stability and bioequivalence to the clopidogrel bisulphate-loaded commercial product. Clopidogrel napadisilate prepared in this study appeared as a white crystalline powder unlike clopidogrel base. However, this salt did not improve the solubility of clopidogrel, even with improved stability compared to clopidogrel bisulphate. To improve the solubility of clopidogrel napadisilate, a novel clopidogrel napadisilate-loaded solid dispersion was prepared by the spray-drying technique using HPMC and colloidal silica, and the physicochemical properties, dissolution and bioavailability in beagle dogs were evaluated compared to the clopidogrel bisulphate-loaded commercial product. The solid dispersion composed of clopidogrel napadisilate, HPMC and colloidal silica at a weight ratio of 11.069/3/3.5 improved solubility by 6.5-fold compared to clopidogrel napadisilate, even if it did not improve drug solubility compared to clopidogrel bisulphate. However, unlike clopidogrel bisulphate, this formulation improved the stability of clopidogrel. Furthermore, the clopidogrel napadisilate solid dispersion-loaded tablet showed similar dissolution to the clopidogrel bisulphate-loaded commercial product and was bioequivalent to the commercial product in beagle dogs. Thus, this clopidogrel napadisilate-loaded solid dispersion could be a promising candidate for improving the stability and bioavailability of clopidogrel.

  5. Development of novel sibutramine base-loaded solid dispersion with gelatin and HPMC: physicochemical characterization and pharmacokinetics in beagle dogs.

    PubMed

    Lim, Hyun-Tae; Balakrishnan, Prabagar; Oh, Dong Hoon; Joe, Kwan Hyung; Kim, Young Ran; Hwang, Doo Hyung; Lee, Yong-Bok; Yong, Chul Soon; Choi, Han-Gon

    2010-09-15

    To develop a novel sibutramine base-loaded solid dispersion with enhanced solubility and bioavailability, various solid dispersions were prepared using a spray drying technique with hydrophilic polymers such as gelatin, HPMC and citric acid. Their solubility, thermal characteristics and crystallinity were investigated. The dissolution and pharmacokinetics of the sibutramine base-loaded solid dispersion were then compared with a sibutramine hydrochloride monohydrate-loaded commercial product (Reductil). The solid dispersions prepared with gelatin gave higher drug solubility than those prepared without gelatin, irrespective of the amount of polymer. The sibutramine base-loaded solid dispersions containing hydrophilic polymer and citric acid showed higher drug solubility compared to sibutramine base and sibutramine hydrochloride monohydrate. Among the formulations tested, the solid dispersion composed of sibutramine base/gelatin/HPMC/citric acid at the weight ratio of 1/0.8/0.2/0.5 gave the highest solubility of 5.03+/-0.24 mg/ml. Our DSC and powder X-ray diffraction results showed that the drug was present in an altered amorphous form in this solid dispersion. The difference factor (f(1)) values between solid dispersion and commercial product were 2.82, 6.65 and 6.31 at pH 1.2, 4.0 and 6.8, respectively. Furthermore, they had the similarity factor (f(2)) value of 65.68, 53.43 and 58.97 at pH 1.2, 4.0 and 6.8, respectively. Our results suggested that the solid dispersion and commercial product produced a similar correlation of dissolution profiles at all pH ranges. The AUC, C(max) and T(max) of the parent drug and metabolite I and II from the solid dispersion were not significantly different from those of the commercial product, suggesting that the solid dispersion might be bioequivalent to the commercial product in beagle dogs. Thus, the sibutramine base-loaded solid dispersion prepared with gelatin, HPMC and citric acid is a promising candidate for improving the

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

    PubMed

    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 < 0.001), that shared in at least two pituitary comparisons and at least two adrenal cortex comparisons, were detected separately. These identified DE-miRNAs were predicted for target genes, thus resulting in 3,959 and 4,010 target genes in pituitary and adrenal cortex, respectively. Further, 105 and 10 differentially expressed genes (DEGs) (Fold change > 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

  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.

    PubMed

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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 < 0.05 for all DTI parameters except MD), as well as between white matter sub-regions (P < 0.05 for most DTI parameters except radial diffusivity, MD and planar index). DTI-based sub-regional analysis of white and grey matter may be useful for regional evaluation of the dog spinal cord.

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

    PubMed

    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.

  13. Effect of age and severity of cognitive dysfunction on spontaneous activity in pet dogs - part 1: locomotor and exploratory behaviour.

    PubMed

    Rosado, B; González-Martínez, A; Pesini, P; García-Belenguer, S; Palacio, J; Villegas, A; Suárez, M-L; Santamarina, G; Sarasa, M

    2012-11-01

    Age-related cognitive dysfunction syndrome (CDS) has been reported in dogs and it is considered a natural model for Alzheimer's disease in humans. Changes in spontaneous activity (including locomotor and exploratory behaviour) and social responsiveness have been related to the age and cognitive status of kennel-reared Beagle dogs. The aim of this study was to assess the influence of age and severity of CDS on locomotor and exploratory behaviour of privately owned dogs. This is the first part of a two-part report on spontaneous activity in pet dogs. An open-field (OF) test and a curiosity test were administered at baseline and 6 months later to young (1-4 years, n=9), middle-aged (5-8 years, n=9), cognitively unimpaired aged (≥ 9 years, n=31), and cognitively impaired aged ( ≥ 9 years, n=36) animals. Classification of cognitive status was carried out using an owner-based observational questionnaire, and in the cognitively impaired group, the dogs were categorised as having either mild or severe cognitive impairment. Dogs were recorded during sessions in the testing room and the video-recordings were subsequently analysed. The severity of CDS (but not age) influenced locomotion and exploratory behaviour so that the more severe the impairment, the higher the locomotor activity and frequency of corner-directed (aimless) behaviours, and the lower the frequency of door-aimed activities. Curiosity directed toward novel stimuli exhibited an age-dependent decline although severely affected animals displayed more sniffing episodes directed towards the objects. OF activity did not change after 6 months. Testing aged pet dogs for spontaneous behaviour might help to better characterise cognitively affected individuals.

  14. 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.

    PubMed

    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.

  15. 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

    SciTech Connect

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

    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

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

    PubMed Central

    Kim, Jeong Soo; Cha, Kwang Ho; Kang, Seung Yeob; Won, Donghan; Jang, Sun Woo; Son, Miwon; Son, Moon Ho; Choi, Ho Jung; Lee, Young Won; Kang, Myung Joo

    2016-01-01

    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 time and a remarkable mucosal restoration effect in animal models. Therefore, the GR system of DA-9601 could be a substitute dosage form for the treatment of gastritis, while reducing the dosing frequency and thus improving patient compliance. PMID:27354765

  17. Evaluation of renal function in rhesus monkeys and comparison to beagle dogs following oral administration of the organic acid triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid).

    PubMed

    Timchalk, C; Finco, D R; Quast, J F

    1997-03-01

    The current study evaluated the effects of triclopyr (3,5, 6-trichloro-2-pyridinyloxyacetic acid) on renal function following oral administration in the beagle dog and rhesus monkey. Male rhesus monkeys were orally administered triclopyr by gavage at a dose of 5 mg/kg/day, 7 days/week for 28 days, after which the dosage was increased to 20 mg/kg/day for 102 consecutive days. Groups of male dogs were administered either a single oral dose of 5 mg/kg triclopyr or were fed a diet spiked with triclopyr at a dose of 5 mg/kg/day for 47 consecutive days. The following functional and clinical chemistry parameters were evaluated: exogenous phenolsulfonphthalein (PSP) excretion, inulin and para-aminohippurate (PAH) clearance (monkeys only), endogenous serum creatinine, and blood urea nitrogen (BUN) at multiple time points during the study. Creatinine, BUN, and inulin clearance were within the normal range from both species following triclopyr administration which indicates that repeated administration of triclopyr in the dog and monkey had no effect on glomerular filtration rate (GFR). In monkeys, the percentage excretion of PSP and PAH appeared to increase following triclopyr administration (20 mg/kg/day), suggesting that these weak organic acids may be competing for the same plasma protein-binding site enhancing their clearance. More importantly, these data strongly suggest that triclopyr is not competing with PSP or PAH for the active secretory site within the monkey kidney proximal tubules. In contrast, PSP clearance studies in dogs clearly demonstrated that triclopyr administration (5 mg/kg) can significantly decrease the percentage PSP excretion even following a single dose administration. The decrease in percentage PSP was reversible and inversely related to the plasma triclopyr concentration. Overall, these data clearly indicate that triclopyr effectively competes with PSP for the active secretory site within the dog kidney proximal tubules. In contrast, the monkey

  18. Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs.

    PubMed

    Pan, Yuanlong; Larson, Brian; Araujo, Joseph A; Lau, Winnie; de Rivera, Christina; Santana, Ruben; Gore, Asa; Milgram, Norton W

    2010-06-01

    The present study focused on the hypothesis that dietary supplementation with medium-chain TAG (MCT) will improve cognitive function in aged dogs by providing the brain with energy in the form of ketones. Aged Beagle dogs were subjected to a baseline battery of cognitive tests, which were used to establish cognitively equivalent control or treatment groups. The dogs in the treatment group were maintained on a diet supplemented with 5.5 % MCT. After an initial wash-in period, all the dogs were tested with a battery of cognitive test protocols, which assessed sequentially landmark discrimination learning ability, egocentric visuospatial function and attention. The groups were maintained on the diets for 8 months. The MCT-supplemented group showed significantly better performance in most of the test protocols than the control group. The group differences also varied as a function of task difficulty, with the more difficult task showing greater supplementation effects than the easier tasks. The group given the MCT supplement showed significantly elevated levels of beta-hydroxybutyrate, a ketone body. These results indicate, first, that long-term supplementation with MCT can have cognition-improving effects, and second, that MCT supplementation increases circulating levels of ketones. The results support the hypothesis that brain function of aged dogs can be improved by MCT supplementation, which provides the brain with an alternative energy source.

  19. Age, sex and reproductive status affect boldness in dogs.

    PubMed

    Starling, Melissa J; Branson, Nicholas; Thomson, Peter C; McGreevy, Paul D

    2013-09-01

    Boldness in dogs is believed to be one end of the shy-bold axis, representing a super-trait. Several personality traits fall under the influence of this super-trait. Previous studies have found that boldness is affected by breed and breed groups, influences performance in sporting dogs, and is affected in some cases by the sex of the dogs. This study investigated the effects of dog age, sex and reproductive status on boldness in dogs by way of a dog personality survey circulated amongst Australian dog owners. Age had a significant effect on boldness (F=4.476; DF=16,758; P<0.001), with boldness decreasing with age in years. Males were bolder than females (F=19.219; DF=1,758; P<0.001) and entire dogs were bolder than neutered dogs (F=4.330; DF=1,758; P<0.038). The study indicates how behaviour may change in adult dogs as they age and adds to the literature on how sex and reproductive status may affect personality in dogs.

  20. Ontogenetic allometry of the Beagle

    PubMed Central

    2013-01-01

    Background Mammalian juveniles undergo dramatic changes in body conformation during development. As one of the most common companion animals, the time line and trajectory of a dog’s development and its body’s re-proportioning is of particular scientific interest. Several ontogenetic studies have investigated the skeletal development in dogs, but none has paid heed to the scapula as a critical part of the mammalian forelimb. Its functional integration into the forelimb changed the correspondence between fore- and hindlimb segments and previous ontogenetic studies observed more similar growth patterns for functionally than serially homologous elements. In this study, the ontogenetic development of six Beagle siblings was monitored between 9 and 51 weeks of age to investigate their skeletal allometry and compare this with data from other lines, breeds and species. Results Body mass increased exponentially with time; log linear increase was observed up to the age of 15 weeks. Compared with body mass, withers and pelvic height as well as the lengths of the trunk, scapula, brachium and antebrachium, femur and crus exhibited positive allometry. Trunk circumference and pes showed negative allometry in all, pelvis and manus in most dogs. Thus, the typical mammalian intralimb re-proportioning with the proximal limb elements exhibiting positive allometry and the very distal ones showing negative allometry was observed. Relative lengths of the antebrachium, femur and crus increased, while those of the distal elements decreased. Conclusions Beagles are fully-grown regarding body height but not body mass at about one year of age. Particular attention should be paid to feeding and physical exertion during the first 15 weeks when they grow more intensively. Compared with its siblings, a puppy’s size at 9 weeks is a good indicator for its final size. Among siblings, growth duration may vary substantially and appears not to be related to the adult size. Within breeds, a longer

  1. beta-cyclodextrin derivatives, SBE4-beta-CD and HP-beta-CD, increase the oral bioavailability of cinnarizine in beagle dogs.

    PubMed

    Järvinen, T; Järvinen, K; Schwarting, N; Stella, V J

    1995-03-01

    The absolute bioavailabilities (Fabs) of cinnarizine after oral administration as two modified beta-cyclodextrin (SBE4-beta-CD or HP-beta-CD) solutions, an aqueous suspension, and two capsules in fasted beagle dogs were determined. Cinnarizine was administered orally (25.0 mg) and intravenously (12.5 mg) to four dogs. Blood samples were drawn for 24.5 h postdosing, and cinnarizine levels in plasma were determined by HPLC with spectrofluorometric detection. Cinnarizine pharmacokinetics after iv administration as a 1.25 mg/mL SBE4-beta-CD solution followed triexponential behavior (t1/2 = 12.6 +/- 0.4 h and CI = 1.4 +/- 0.17 L/h/kg). A very low bioavailability of cinnarizine with a wide interanimal variation was observed after oral administration as a suspension (Fabs = 8 +/- 4%) or capsule containing only cinnarizine (Fabs = 0.8 +/- 0.4%). Administration of cinnarizine as a CD complex either as a solution (Fabs = 55-60%) or in a capsule (Fabs = 38 +/- 12%) significantly enhanced the bioavailability. Since the solutions showed excellent bioavailability, the logical conclusion is that, once presented as a solution, cinnarizine is well absorbed and that cinnarizine rapidly dissociates from its inclusion complexes. Presumably, the elevated bioavailability from the SBE4-beta-CD containing capsule was due to rapid dissolution and release of cinnarizine.

  2. Glucose-β-CD interaction assisted ACN field-amplified sample stacking in CZE for determination of trace amlodipine in beagle dog plasma.

    PubMed

    Li, Ji; Li, You; Zhang, Wenting; Chen, Zhao; Fan, Guorong

    2013-06-01

    A simple, sensitive and low-cost method using CE coupled with glucose-β-CD interaction assisted ACN stacking technique has been developed for quantification of trace amlodipine in dog plasma. The plasma samples were extracted with methyl tert-butyl ether. The separation was performed at 25°C in a 31.2 cm × 75 μm fused-silica capillary with an applied voltage of 15 kV. The BGE was composed of 6.25 mM borate/25 mM phosphate (pH 2.5) and 5 mg/mL glucose-β-CD. The detection wavelength was 200 nm. Because CD could diminish the interaction between drugs and matrix, and derivation groups of CD play an important role in separation performance, the effects of β-CD, and its derivatives on the separation were studied at several concentrations (0, 2.5, 5.0, 10.0 mg/mL). In this study, organic solvent field-amplified sample stacking technique in combination with glucose-β-CD enhanced the sensitivity about 60-70 folds and glucose-β-CD could effectively improve the peak shape. All the validation data, such as accuracy, precision extraction recovery, and stability, were within the required limits. The calibration curve was linear for amlodipine from 1 to 200 ng/mL. The method developed was successfully applied to the pharmacokinetic studies of amlodipine besylate in beagle dogs.

  3. Pre-clinical toxicology and pathology of 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748), a novel anti-cancer agent in male Beagle dogs.

    PubMed

    Ashok, B T; Tadi, K; Banerjee, D; Konopa, J; Iatropoulos, M; Tiwari, R K

    2006-08-29

    We have developed a group of 4-substituted-1-nitroacridines with potent anti-tumor activity against prostate cancer and less toxic than parent 1-nitroacridines. The most active 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748) was selected for pre-clinical studies. The current study was undertaken to evaluate clinical and/or morphological adverse effects of C-1748 as a single intravenous dose at concentrations ranging from 0.16 to 4.6 mg/kg administered to male Beagle dogs. The maximum tolerated dose was 1.5 mg/kg. Emesis was observed in all groups lasting an average of 30 min to 12 h post-dosing. At high dose, extreme aggression was observed in one dog followed by disorientation and depression lasting for 48 h a frequent observation with chemotherapy. Reductions in platelets and white blood cells were observed which was similar to that seen with other chemotherapeutic agents. A compensatory hyperplasia of lymph nodes and a transient and limited extravasation in the intestinal mucosa were also observed. Increases in aspartate aminotransferase, alkaline phosphatase and creatine phosphokinase were transient with normal levels restored by day 9. These enzyme increases were accompanied by epithelial hypertrophy of larger bile ductules in the periportal triads of the liver. The low toxicity profile and high tumor target activity make this novel class of drug a promising chemotherapeutic agent.

  4. In vivo reference point indentation reveals positive effects of raloxifene on mechanical properties following 6 months of treatment in skeletally mature beagle dogs

    PubMed Central

    Aref, Mohammad; Gallant, Maxime A.; Organ, Jason M.; Wallace, Joseph M; Newman, Christopher L.; Burr, David B.; Brown, Drew M.; Allen, Matthew R.

    2013-01-01

    Raloxifene treatment has been shown previously to positively affect bone mechanical properties following 1 year of treatment in skeletally mature dogs. Reference point indentation (RPI) can be used for in vivo assessment of mechanical properties and has been shown to produce values that are highly correlated with properties derived from traditional mechanical testing. The goal of this study was to use RPI to determine if raloxifene-induced alterations in mechanical properties occurred after 6 months of treatment. Twelve skeletally mature female beagle dogs were treated for 6 months with oral doses of saline vehicle (VEH, 1 ml/kg/day) or a clinically relevant dose of raloxifene (RAL, 0.5 mg/kg/day). At 6 months, all animals underwent in vivo RPI (10 N force, 10 cycles) of the anterior tibial midshaft. RPI data were analyzed using a custom MATLAB program, designed to provide cycle-by-cycle data from the RPI test and validated against the manufacturer-provided software. Indentation distance increase (IDI), a parameter that is inversely related to bone toughness, was significantly lower in RAL-treated animals compared to VEH (− 16.5%), suggesting increased bone toughness. Energy absorption within the first cycle was significantly lower with RAL compared to VEH (− 21%). These data build on previous work that has documented positive effects of raloxifene on material properties by showing that these changes exist after 6 months. PMID:23871851

  5. In vivo reference point indentation reveals positive effects of raloxifene on mechanical properties following 6 months of treatment in skeletally mature beagle dogs.

    PubMed

    Aref, Mohammad; Gallant, Maxime A; Organ, Jason M; Wallace, Joseph M; Newman, Christopher L; Burr, David B; Brown, Drew M; Allen, Matthew R

    2013-10-01

    Raloxifene treatment has been shown previously to positively affect bone mechanical properties following 1 year of treatment in skeletally mature dogs. Reference point indentation (RPI) can be used for in vivo assessment of mechanical properties and has been shown to produce values that are highly correlated with properties derived from traditional mechanical testing. The goal of this study was to use RPI to determine if raloxifene-induced alterations in mechanical properties occurred after 6 months of treatment. Twelve skeletally mature female beagle dogs were treated for 6 months with oral doses of saline vehicle (VEH, 1 ml/kg/day) or a clinically relevant dose of raloxifene (RAL, 0.5 mg/kg/day). At 6 months, all animals underwent in vivo RPI (10N force, 10 cycles) of the anterior tibial midshaft. RPI data were analyzed using a custom MATLAB program, designed to provide cycle-by-cycle data from the RPI test and validated against the manufacturer-provided software. Indentation distance increase (IDI), a parameter that is inversely related to bone toughness, was significantly lower in RAL-treated animals compared to VEH (-16.5%), suggesting increased bone toughness. Energy absorption within the first cycle was significantly lower with RAL compared to VEH (-21%). These data build on previous work that has documented positive effects of raloxifene on material properties by showing that these changes exist after 6 months.

  6. Pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) in the beagle dog and rhesus monkey: perspective on the reduced capacity of dogs to excrete this organic acid relative to the rat, monkey, and human.

    PubMed

    Timchalk, C; Nolan, R J

    1997-06-01

    The pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) were measured in the beagle dog and rhesus monkey and compared with the kinetics observed in rats and humans. In addition, studies were conducted in anesthetized dogs to better understand the mechanism by which [14C]triclopyr is eliminated in this species. Triclopyr was dissolved in distilled water, and administered as a single oral dose of 0.5, 5, or 20 mg/kg to three male dogs. A single male rhesus monkey was given an intravenous dose of 30 mg [14C]triclopyr/kg body wt on two occasions separated by 10 days. Anesthetized male dogs, were implanted with venous, arterial, and urethral catheters and given increasing amounts of triclopyr to produce plasma triclopyr levels ranging from 0.3 to 27 microg eq/mL. In the monkey, triclopyr was rapidly eliminated from the plasma (t1/2 = 6.3 hr) with >95% of the urinary 14C activity excreted within 24 hr postdosing. In the dog, orally administered triclopyr was rapidly and effectively absorbed at every dose level with virtually all of it excreted in the urine by 72 hr postdosing. However, the kinetics were slightly nonlinear, and the fraction of the dose excreted in the urine decreased with increasing dose. Several nonlinear processes may collectively contribute to the modest nonlinear pharmacokinetics in the dog. Plasma protein binding of triclopyr in the dog ranged from 94 to 99%, was nonlinear, and was an important determinant in the renal clearance of triclopyr. The nonlinear plasma protein binding indicates that glomerular filtration became disproportionately more important as plasma triclopyr concentration increased. There was good evidence for a high-affinity low-capacity active-secretory process that was saturated by low plasma triclopyr concentrations. As plasma triclopyr concentrations increased, tubular reabsorption begins to exceed secretion, resulting in decreased renal clearance. The volume of distribution, normalized for body weight

  7. Preclinical toxicity evaluation of erythrocyte-encapsulated thymidine phosphorylase in BALB/c mice and beagle dogs: an enzyme-replacement therapy for mitochondrial neurogastrointestinal encephalomyopathy.

    PubMed

    Levene, Michelle; Coleman, David G; Kilpatrick, Hugh C; Fairbanks, Lynette D; Gangadharan, Babunilayam; Gasson, Charlotte; Bax, Bridget E

    2013-01-01

    Erythrocyte-encapsulated thymidine phosphorylase (EE-TP) is currently under development as an enzyme replacement therapy for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), an autosomal recessive disorder caused by a deficiency of thymidine phosphorylase. The rationale for the development of EE-TP is based on the pathologically elevated metabolites (thymidine and deoxyuridine) being able to freely diffuse across the erythrocyte membrane where the encapsulated enzyme catalyses their metabolism to the normal products. The systemic toxic potential of EE-TP was assessed when administered intermittently by iv bolus injection to BALB/c mice and Beagle dogs for 4 weeks. The studies consisted of one control group receiving sham-loaded erythrocytes twice weekly and two treated groups, one dosed once every 2 weeks and the other dosed twice per week. The administration of EE-TP to BALB/c mice resulted in thrombi/emboli in the lungs and spleen enlargement. These findings were also seen in the control group, and there was no relationship to the number of doses administered. In the dog, transient clinical signs were associated with EE-TP administration, suggestive of an immune-based reaction. Specific antithymidine phosphorylase antibodies were detected in two dogs and in a greater proportion of mice treated once every 2 weeks. Nonspecific antibodies were detected in all EE-TP-treated animals. In conclusion, these studies do not reveal serious toxicities that would preclude a clinical trial of EE-TP in patients with MNGIE, but caution should be taken for infusion-related reactions that may be related to the production of nonspecific antibodies or a cell-based immune response.

  8. Audiograms estimated from brainstem tone-evoked potentials in dogs from 10 days to 1.5 months of age.

    PubMed

    Poncelet, Luc C; Coppens, Angélique G; Deltenre, Paul F

    2002-01-01

    The objective of this study was to build audiograms from thresholds of brainstem tone-evoked potentials in dogs and to evaluate age-related change of the audiogram in puppies. Results were obtained from 9 Beagle puppies 10-47 days of age. Vertex to mastoid brainstem auditory-evoked potentials in response to 5.1-millisecond Hanning-gated sine waves with frequencies octave-spaced from 0.5 to 32 kHz were recorded. Three dogs were examined at 10, 13, 19, 25, and 45 days. Four other dogs were examined at 16 days. Data from 7 dogs between 42 and 47 days of age were pooled to obtain audiogram reference values in 1.5-month-old puppies. The best auditory threshold lowered from above 60 dB sound pressure level (SPL) to values close to 0 dB SPL between 13 and 25 days of age and then stabilized. The audible frequency range widened, including 32 kHz in all tested dogs from the 19th day. In the 7 1.5-month-old puppies, the mean auditory threshold decreased by 11 dB per octave from 0.5 to 2 kHz. The auditory threshold was lowest and held the same value from 2 to 8 kHz. The mean auditory threshold increased by 20 dB per octave from 8 to 32 kHz. Near threshold, click-evoked potentials test only a small part of the audible frequency range in dogs. Use of tone-evoked potentials may become a powerful tool in investigating dogs with possible partial hearing loss, including during the auditory system maturation period.

  9. Evaluation of a transcutaneous method to assess canine liver function by indocyanine green plasma disappearance rate in healthy adult Beagle dogs.

    PubMed

    Grobelna, A P; Honkavaara, J; Restitutti, F; Huuskonen, V; Sakka, S G; Spillmann, T

    2016-03-01

    A non-invasive, transcutaneous method using near infrared spectroscopy to assess indocyanine green plasma disappearance rate (ICG-PDR) in healthy dogs subjected to different conditions was evaluated in eight healthy purpose-bred Beagles under isoflurane-anaesthesia (Trial 1) and when they had initially recovered from anaesthesia (Trial 2). Plasma ICG concentrations (0, 5, 10, 15, 30 min after rapid ICG injection (0.5 mg/kg) into a peripheral vein were determined by high-performance liquid chromatography in parallel with transcutaneous measurements. ICG clearance (mL/min/kg) and retention rate after 15 min (R15, %) were calculated from plasma concentrations to be 3.09 ± 0.83 (mean ± SD) and 30.6 ± 8.3 in anaesthetised dogs and 3.63 ± 0.88 and 28.1 ± 7.3 in recovering dogs, respectively. ICG-PDR (%/min) and R15 (%) obtained using the transcutaneous method were 7.11 ± 3.18 and 34.6 ± 12.4 (Trial 1) and 7.79 ± 3.33 and 32.3 ± 9.2 (Trial 2). The coefficients of determination (r(2)) for ICG clearance and ICG-PDR were 0.14 (Trial 1) and 0.81 (Trial 2) and 0.47 (Trial 1) and 0.29 (Trial 2) for R15, respectively. The mean bias (lower, upper limit of agreement) for R15 were 5.6 (-12.3, 23.5) (Trial 1) and 3.9 (-12.4, 20.1) (Trial 2). The results suggest good agreement between the two methods in dogs recovering from isoflurane-anaesthesia and the transcutaneous method might be useful in real-time assessment of liver function in conscious dogs.

  10. Effect of umbilical cord mesenchymal stem cell in peri-implant bone defect after immediate implant: an experiment study in beagle dogs

    PubMed Central

    Hao, Peng-Jie; Wang, Zhi-Guo; Xu, Quan-Chen; Xu, Sheng; Li, Zhuo-Ri; Yang, Pi-Shan; Liu, Zhong-Hao

    2014-01-01

    Background: For the sake of reducing post extraction resorption, getting optimal positioning of the implant and shortening treatment time, immediate implant placement following tooth extraction has been proposed as a treatment option. However, the large bone defect peri-implant has a negative influence on the process of bone healing. In this study, umbilical cord mesenchymal stem cells (UCMSCs) were transplanted into the bone defect peri-implant in beagle dogs and the effect of UCMSCs on bone regeneration in peri-implant were assessed. Methods: The mandibular second, third and fourth premolars of 8 beagle dogs were extracted bilaterally. The defects in one side were filled with platelet-rich fibrin (PRF) and then UCMSCs were injected into the defect area, while the defects in the other side were filled with PRF only as control group. The titanium implant was placed into the distal root socket of each extracted tooth. The animals were sacrificed at week 2, 4 and 8 post operation. The bone defects adjacent to the implant which are 4 mm in height, 4 mm in the mesio-distal direction and 3.5 mm in the bucco-lingual direction were made after immediate implant. Histomorphometric analysis was performed using methylene blue-fuchsin acid staining and hematoxylin and eosin (HE) staining to evaluate bone regeneration. Results: The direct bone-to-implant contact (BIC) in the experiment after 4 and 8 weeks was 56.47 ± 1.18% and 76.23 ± 2.08%; and in the control group was40.79 ± 0.65% and 61.17 ± 2.79%, respectively. The percentage of newly formed bone after 2, 4 and 8 weeks was 17.60 ± 1.5%, 49.82 ± 4.02% and 67.16 ± 2.1% in experiment group; and in control group 14.30 ± 1.25%, 37.04 ± 2.29% and 58.83 ± 3.36%, respectively. These results represented significant differences statistically. Conclusion: Intra-bone marrow injection of UCMSCs can promote new bone formation. UCMSCs can be used to as excellent seed cells to repair the large defect peri-implant after immediate

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

    PubMed

    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 <6.96% with accuracies <6.40%. In the pharmacokinetic (PK) study, 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.

  12. Preliminary Study Characterizing the Use of Sitagliptin for Glycemic Control in Healthy Beagle Dogs with Normal Gluco-Homeostasis

    PubMed Central

    ODA, Hitomi; MORI, Akihiro; LEE, Peter; SAEKI, Kaori; ARAI, Toshiro; SAKO, Toshinori

    2014-01-01

    ABSTRACT Sitagliptin is a dipeptidyl peptidase-4 inhibitor aimed at treating Type 2 diabetes mellitus (T2DM) and T1DM, by increasing blood levels of Glucagon-like peptide 1 (GLP-1) and insulin. The objective of this preliminary study is to characterize Sitagliptin’s ability for glycemic control, in healthy dogs under an oral glucose tolerance test (OGTT) environment. Overall, Sitagliptin did not result in any significant changes to temporal glucose and insulin concentrations. However, a ~55% increase in median total GLP-1 AUC0–120min was observed, as compared to baseline control in healthy dogs (n=5), thus indicating a similar mode of action of Sitagliptin between healthy dogs and humans. Future studies to validate the use of Sitagliptin with dogs suffering from insulin independent diabetes are warranted. PMID:24931645

  13. Protective immunity against challenge with Leishmania (Leishmania) chagasi in beagle dogs vaccinated with recombinant A2 protein.

    PubMed

    Fernandes, Ana Paula; Costa, Míriam Maria Silva; Coelho, Eduardo Antônio Ferraz; Michalick, Marilene Suzan Marques; de Freitas, Eloísa; Melo, Maria Norma; Luiz Tafuri, Wagner; Resende, Daniela de Melo; Hermont, Vinícius; Abrantes, Christiane de Freitas; Gazzinelli, Ricardo Tostes

    2008-10-29

    In this study, we investigated in dogs the immunogenicity and protective immunity against Leishmania (Leishmania) chagasi infection induced by vaccination with a formulation containing the recombinant A2 protein, an amastigote specific antigen, and saponin. Vaccinated animals produced significantly increased levels of total IgG and IgG2, but not IgG1 anti-A2 antibodies, and remained negative in conventional leishmaniasis serodiagnostic methods. Significantly increased IFN-gamma and low IL-10 levels were detected in vaccinated animals before and after challenge, as compared to control animals. Importantly, while the symptoms onset appeared as early as three months after infection in most control dogs, 14 months after challenge, 5 out of 7 vaccinated dogs remained asymptomatic. Therefore, immunization with rA2 antigen was immunogenic and induced partial protection in dogs, and allowed the serological differentiation between vaccinated and infected animals, an important requirement for a canine visceral leishmaniasis (CVL) vaccine.

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

    PubMed

    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

  15. Acute toxicity of sodium formononetin-3'-sulphonate (Sul-F) in Sprague-Dawley rats and Beagle dogs.

    PubMed

    Li, Guisheng; Yang, Menglin; Hao, Xinmiao; Li, Chunmei; Gao, Yonglin; Tao, Jun

    2015-11-01

    Sodium formononetin-3'-sulphonate (Sul-F, C16H12O7SNa), a water-soluble derivate of formononetin, provided significant neuroprotective and cardioprotective effects in vitro and in vivo. The aim of this study was to evaluate acute toxicity of Sul-F after intravenous administration in rats and dogs. Animals were intravenously administered Sul-F at the maximum dosage of 2000 mg/kg and 1000 mg/kg in rats and dogs, respectively. After treatment, rats and dogs were monitored for 14 days. Body weight, clinical signs, the hematological and biochemical findings, and pathological examination were performed. The results showed that no Sul-F related clinical signs of toxicity or mortality were observed in rats. Of note, the transient vomiting was found in dogs after Sul-F administration 15-20 min. In addition, a white crystal, non-metabolic Sul-F, was found after urine volatilization in Sul-F treated animals (rats and dogs). However, neither biochemical findings nor histopathological changes due to Sul-F treatment were found in tests. In summary, the present study results provided practical guidance for selecting a safe dosage for Sul-F further studies and clinical trials in the future.

  16. Development of a colon delivery capsule and the pharmacological activity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in beagle dogs.

    PubMed

    Takaya, T; Ikeda, C; Imagawa, N; Niwa, K; Takada, K

    1995-06-01

    A peroral dosage form was examined to deliver recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the colon in beagle dogs. A new gelatin capsule with its inside surface coated with ethylcellulose was prepared for this purpose. RhG-CSF was dissolved with propylene glycol and was filled in the capsule. Several kinds of ethylcellulose-gelatin capsules with an ethylcellulose layer of thickness 46 to 221 mm were used. The capsule was filled with propylene glycol solution containing fluorescein as an absorption marker, castor oil derivative and citric acid. The hardness of the capsule was tested after the gelatin layer was dissolved using a hardness tester and was dependent on the thickness of the ethylcellulose layer of the capsule. The time, Tmax, at which plasma fluorescein level reaches its maximum following oral administration of ethylcellulose capsules was used as a parameter for the in-vivo disintegration time of the ethylcellulose capsule into the colon. Capsules of thickness 84 mm with a Tmax of 4-6 h were filled with rhG-CSF solution containing fluorescein and were administered to dogs. After administration, blood samples were collected for 96 h and the blood total leucocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The maximum BTL count appeared at 10 h then gradually decreased and returned to its normal level at 48 h. These results suggest the usefulness of ethylcellulose capsules for the delivery of rhG-CSF to the colon and the possibility of a new oral rhG-CSF dosage form has been elucidated.

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

    PubMed

    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.

  18. 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.

    PubMed

    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.

  19. 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.

    PubMed

    Um, Yoo-Jung; Jung, Ui-Won; Chae, Gyung-Joon; Kim, Chang-Sung; Lee, Yong-Keun; Cho, Kyoo-Sung; Kim, Chong-Kwan; Choi, Seong-Ho

    2008-12-01

    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.

  20. Solid dispersion tablets of breviscapine with polyvinylpyrrolidone K30 for improved dissolution and bioavailability to commercial breviscapine tablets in beagle dogs.

    PubMed

    Cong, Wenjuan; Shen, Lan; Xu, Desheng; Zhao, Lijie; Ruan, Kefeng; Feng, Yi

    2014-09-01

    Breviscapine, one of cardiovascular drugs extracted from a Chinese herb Erigeron breviscapinus, has been frequently used to treat cardiovascular diseases such as hypertension, angina pectoris, coronary heart disease and stroke. However, its poor water solubility and low bioavailability in vivo severely restrict the clinical application. To overcome these drawbacks, breviscapine solid dispersion tablets consisting of breviscapine, polyvinylpyrrolidone K30 (PVP K30), microcrystalline cellulose and crospovidone were appropriately prepared. In vitro dissolution profiles showed that breviscapine released percentage of solid dispersion tablets reached 90 %, whereas it was only 40 % for commercial breviscapine tablets. Comparative pharmacokinetic study between solid dispersion tablets and commercial products was investigated on the normal beagle dogs after oral administration. Results showed that the bioavailability of breviscapine was greatly increased by 3.45-fold for solid dispersion tablets. The greatly improved dissolution rate and bioavailability might be attributed to intermolecular hydrogen bonding reactions between PVP K30 and scutellarin. These findings suggest that our solid dispersion tablets can greatly improve the bioavailability as well as the dissolution rate of breviscapine.

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

    PubMed

    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.

  2. Role of aortic input impedance in the decreased cardiovascular response to exercise with aging in dogs.

    PubMed Central

    Yin, F C; Weisfeldt, M L; Milnor, W R

    1981-01-01

    The diminished cardiac output response to exercise with advancing age may be attributable to intrinsic inability of the old ventricle to respond appropriately and/or to an additional loading imposed upon the ventricle by the aged vascular system. The steady (resistance) and pulsatile (characteristic impedance) load components together comprise the vascular load faced by the ejecting ventricle. To study the effect of exercise on both vascular components of load, the aortic input impedance was measured in chronically instrumented young and old beagle dogs during graded treadmill exercise before and after beta blockade. Ascending aortic flow was measured by a cuff electromagnetic flow probe, and pressure was measured by a high-fidelity semiconductor transducer. At low levels of exercise the old animals demonstrated a striking 20% increase in characteristic impedance and a 28% decrease in peripheral resistance with no increase in stroke volume. This vascular loading and limitation in stroke volume persisted across the higher exercise levels. In contrast, the young group demonstrated no increase in characteristic impedence, a progressive decrease in peripheral resistance, and a progressive increase in stroke volume across the same exercise levels. These age differences in vascular response and ventricular output were abolished by beta blockade. The groups did not demonstrate a difference in heart rate response, but the young had a greater increase in external left ventricular power than the old across exercise. These data demonstrated a profound difference in the response of young and old vasculature to exercise. At low and intermediate exercise levels the pulsatile vascular load appeared to be a major factor in the limitation of stroke volume in old dogs. At high levels of exercise, the limited exercise response in the old dog may be caused in part by a diminished inotropic responsiveness as well as by the vascular loading. PMID:7251864

  3. Full-field ERGs obtained using a contact lens electrode with built-in high intensity white light-emitting diodes in beagle dogs can be applied to toxicological assessments.

    PubMed

    Sasaki, Shoji; Yamashita, Haruhiro; Yagi, Kumiko; Iwaki, Yoshinobu; Kimura, Masaaki

    2006-10-10

    We investigated full-field ERGs in beagle dogs using a contact lens electrode with built-in LED. Experiment 1 was performed to determine the appropriate conditions for stimulus intensity and background illumination. We found that full-field ERGs could be recorded under the following conditions: stimulus intensity: -2.5logcd*s/m(2) in rod responses (RRs), 1.2logcd*s/m(2) in maximal responses (MRs), oscillatory potentials (OPs), cone responses (CRs), 30-Hz flicker responses (FRs), and background illumination: more than 25cd/m(2) in CRs and FRs. Experiment 2 was performed to apply full-field ERGs in beagle dogs to the detection of retinal toxicities. A dog was given one 30mg/kg dose of sodium iodate (NaIO(3)) intravenously. ERGs were recorded before administration and 1, 3, 5, 8, 24h, 7 and 14 days after administration of NaIO(3). The RRs disappeared completely at 1h when MRs and OPs decreased. On the other hand, CRs and FRs were recorded even at 8h. All responses disappeared at 24h. These findings indicate that retinal toxicity by NaIO(3) is first expressed in rods, followed by cones. These results suggest that full-field ERGs in beagle dogs using an LED contact lens can be used to evaluate toxic effects on rods and cones separately, with the potential to prove more useful than conventional methods for toxicological assessments of developing pharmaceuticals, and can be applied to it.

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

    PubMed

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

    2013-01-01

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

  5. Determination of the Tissue Distribution and Excretion by Accelerator Mass Spectrometry of the Nonadecapeptide 14C-Moli1901 in Beagle dogs after Intratracheal Instillation

    SciTech Connect

    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.

  6. Cadmium effects on bone metabolism: accelerated resorption in ovariectomized, aged beagles.

    PubMed

    Sacco-Gibson, N; Chaudhry, S; Brock, A; Sickles, A B; Patel, B; Hegstad, R; Johnston, S; Peterson, D; Bhattacharyya, M

    1992-04-01

    The purpose of this study was to evaluate, in an animal whose skeleton is comparable to humans, the combined effects of estrogen depletion and Cd exposure on bone resorption by monitoring skeletal release of 45Ca and to determine whether Cd-induced bone resorption occurred independent of osteotropic hormone changes and renal dysfunction. Cd exposure following ovariectomy or sham surgery was for 7 months: 1 month by oral ingestion of capsules (1, 5, 15, 50 ppm) and 6 months via drinking water (15 ppm). Serum and fecal 45Ca were increased at 1 week following ovariectomy (OV) (54 +/- 9% and 122 +/- 40%, respectively), but this response was attenuated by 2 weeks. Five of seven exposed dogs had increased serum and fecal 45Ca during the 50-ppm Cd capsule period (15-40% and 15-190%, respectively). Serum 45Ca levels in OV/+Cd dogs showed a significant and consistent increase within 1 week of initiating each of three separate Cd.H2O exposure cycles. Blood Cd levels increased over time from 2 to 15 micrograms/l, coinciding with the elevated serum 45Ca concentrations. No correlation was observed between serum 45Ca increases and parathyroid hormone, 1,25-(OH)2-vitamin D, or calcitonin. No effects of ovariectomy and/or Cd were observed in total serum Ca, calciotropic hormone concentrations, serum or urinary phosphorus and creatinine, creatinine clearance, or urinary specific gravity. Urinary Cd concentrations ranged from 7 to 50 micrograms/l in exposed dogs but were not detectable in nonexposed dogs. Urinary protein concentrations showed no differences between groups. Cd increased bone resorption (skeletal 45Ca release) in ovariectomized and sham-operated dogs without renal dysfunction or calciotropic hormone interaction. Based on our results, Cd is an exogenous factor which exacerbates bone mineral loss in postmenopausal osteoporosis.

  7. 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.

    PubMed

    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.

  8. ULTRASONOGRAPHIC ELASTOGRAPHY OF THE LIVER, SPLEEN, KIDNEYS, AND PROSTATE IN CLINICALLY NOR-MAL BEAGLE DOGS [corrected].

    PubMed

    Jeon, Sunghoon; Lee, Gahyun; Lee, Sang-Kwon; Kim, Hyunwoo; Yu, Dohyeon; Choi, Jihye

    2015-01-01

    Standard ultrasonography is often insensitive for distinguishing normal vs. diseased states for canine abdominal organs. Ultrasonographic elastography is a new technique that is becoming increasingly available and may help to improve sensitivity. This study evaluated the feasibility, repeatability, and reproducibility of strain elastography of the liver, spleen, kidneys, and prostate in healthy dogs and described the elasticity of each organ using strain values and strain ratios. The reproducibility of strain elastography was excellent, and intraobserver repeatability was moderate to excellent. The strain value of each organ was not significantly different among dogs (liver = 143.38 ± 7.41, spleen = 141.04 ± 9.03, left renal cortex = 141.26 ± 7.50, right renal cortex = 145.80 ± 7.79, and prostate = 135.46 ± 5.80), except for the renal medulla (left = 51.19 ± 4.54 and right = 51.93 ± 5.09) (P < 0.05). The strain ratios for the liver, spleen, renal cortex, and prostate were similar with no significant difference (liver = 10.20 ± 1.47, spleen = 8.40 ± 1.53, left renal cortex = 9.62 ± 1.56, right renal cortex = 8.29 ± 1.63, and prostate = 8.20 ± 1.21), except for the renal medulla (left = 3.48 ± 0.68 and right = 2.95 ± 0.63) (P < 0.05). Our results indicated that strain elastography was feasible for estimating tissue stiffness in the canine liver, spleen, kidneys, and prostate. This study provides basic information for strain values and strain ratios for the liver, spleen, kidneys, and prostate in clinically normal dogs.

  9. Duration-dependent effects of clinically relevant oral alendronate doses on cortical bone toughness in beagle dogs.

    PubMed

    Burr, David B; Liu, Ziyue; Allen, Matthew R

    2015-02-01

    Bisphosphonates (BPs) have been shown to significantly reduce bone toughness in vertebrae within one year when given at clinical doses to dogs. Although BPs also reduce toughness in the cortical bone when given at high doses, their effect on cortical bone material properties when given at clinical doses is less clear. In part, this may be due to the use of small sample sizes that were powered to demonstrate differences in bone mineral density rather than the bone's material properties. Our lab has conducted several studies in which dogs were treated with alendronate at a clinically relevant dose. The goal of this study was to examine these published and unpublished data collectively to determine whether there is a significant time-dependent effect of alendronate on toughness of the cortical bone. This analysis seemed particularly relevant given the recent occurrence of atypical femoral fractures in humans. Differences in the toughness of ribs taken from dogs derived from five separate experiments were measured. The dogs were orally administered saline (CON, 1ml/kg/day) or alendronate (ALN) at a clinical dose (0.2mg/kg/day). Treatment duration ranged from 3months to 3years. Groups were compared using ANOVA, and time trends analyzed with linear regression analysis. Linear regressions of the percent difference in toughness between CON and ALN at each time point revealed a significant reduction in toughness with longer exposure to ALN. The downward trend was primarily driven by a downward trend in post-yield toughness, whereas toughness in the pre-yield region was not changed relative to CON. These data suggest that a longer duration of treatment with clinical doses of ALN results in deterioration of cortical bone toughness in a time-dependent manner. As the duration of treatment is lengthened, the cortical bone exhibits increasingly brittle behavior. This may be important in assessing the role that long-term BP treatments play in the risk of atypical fractures of the

  10. Histologic evaluation of probe penetration during clinical assessment of periodontal attachment levels. An investigation of experimentally induced periodontal lesions in beagle dogs.

    PubMed

    Jansen, J; Pilot, T; Corba, N

    1981-04-01

    The purpose of this study was to evaluate histologically the extent and characteristics of the penetration of a periodontal probe during clinical assessment of loss of periodontal attachment in three different situations: (1) experimental mild gingivitis, (2) experimental severe periodontal inflammation and (3) experimental moderate periodontal inflammation. Mild gingivitis was obtained by merely allowing plaque to accumulate on the teeth. Severe periodontal inflammation was created using copper bands for a period of 3 weeks followed by placement of cotton ligatures for another 11 weeks. Moderate periodontal inflammation group was obtained by allowing the experimental defects to recover for a period of 3 to 31 weeks. At different times gutta percha imitations of a thin periodontal probe were inserted into the pockets using a gentle but unknown force. Histologic observation in 30 specimens showed that epithelium was always present around the probe tip, in most instances forming a continuous layer of epithelial cells. Histometrical analysis showed that in mild gingivitis the probe tip failed to reach the apical termination of the junctional epithelium (mean = -0.84 mm). In severe periodontal inflammation the tip of the probe went past this point (mean = +0.50 mm), while in moderate periodontal inflammation the probe tip came closest to the apical termination of the junctional epithelium (mean = -0.05 mm). It is concluded that the epithelial lining of a pocket stays intact, even in severe periodontal inflammation where the probe tip is situated apical to the apical termination of the junctional epithelium, indicating that during clinical probing the periodontal tissues are compressed and displaced but not perforated. It is also concluded that in beagle dogs the extent of probe penetration in experimentally inflamed periodontal tissues is dependent upon the degree of inflammation.

  11. 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.

    PubMed

    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.

  12. Adhesion of stainable, calcium-rich deposits on substrata with different surface free energies. An in vivo study in beagle dogs.

    PubMed

    Uyen, H M; van Dijk, L J; Busscher, H J

    1989-08-01

    Calculus plays an important role in chronic inflammatory periodontal disease and tooth loss. Patients can suffer from calculus formation despite good oral hygiene. The strength of adhesion between calculus and the enamel surface, though not determinant for the formation of calculus itself, determines whether calculus remains on the teeth during eating and toothbrushing. In this study, the amount and the strength of adhesion of calcium-rich deposits formed in vivo on different materials are related to substrate surface free energies (sfe). In 4 beagle dogs, fenestrated crowns were made on the upper fourth premolars. Smooth facings of glass (sfe 120 mJ.m-2), polished bovine enamel (sfe 85 mJ.m-2), polymethylmethacrylate (PMMA sfe 56 mJ.m-2) and polytetafluorethylene (PTFE sfe 20 mJ.m-2) were inserted in the crowns for 1, 3, 7, 14 or 28 days. The amount of deposit was evaluated both gravimetrically and planimetrically using Alizarin Red S for staining. Adhesion of calcium-rich deposits was evaluated planimetrically by studying their removal in a brushing machine. Dry weight increased linearly with time (approximately 0.18 mg.cm-2 per day) and was slightly less on PTFE than on the other materials. After 1 to 3 days, staining already revealed a 100% coverage by calcium-rich deposits. The number of strokes required to reduce the planimetric scores by 63% was extremely small on PTFE and PMMA and related with substrate surface free energies. This study shows that a possible way to reduce calculus formation in vivo is to decrease the surface free energy of the enamel using appropriate surfactants in, e.g., toothpastes.

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

    PubMed

    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.

  14. Mammary gland cancer in a colony of beagle dogs: Inheritance, and p53 & erbB-2 expression

    SciTech Connect

    Kelly, G.; Griffith, W.C.; Muggenburg, Tierney, L.A.; Lechner, J.F.; Hahn, F.F.

    1994-11-01

    One American woman in nine will be diagnosed with breast cancer in her lifetime. This somber statistic translates into 182,000 new diagnoses and 46,000 deaths per year. Efforts to decrease breast cancer mortality have focused on early detection and improved treatment. Such efforts would be facilitated by the identification of individuals predisposed to the disease. A family history of the disease can increase a woman`s risk for developing breast cancer by two- to six-fold. Inheritance of this disease is consistent with at least one susceptibility locus on chromosome 17 (17q12-21) with incomplete penetrance. However, other mechanisms of inherited susceptibility also contribute to the high incidence of the disease. The purpose of the present study was to characterize familial pattern of mammary cancer development in the dog colony. In addition, the expression of the p53 tumor supressor gene and c-erbB2 (p185{sup erbB2}) oncogene proteins, which are frequently altered in human breast cancer, were examined in dogs susceptible and resistant to mammary cancer.

  15. Effect of umbilical cord mesenchymal stem cell in peri-implant bone defect after immediate implant: an experiment study in beagle dogs

    PubMed Central

    Hao, Peng-Jie; Wang, Zhi-Guo; Xu, Quan-Chen; Xu, Sheng; Li, Zhuo-Ri; Yang, Pi-Shan; Liu, Zhong-Hao

    2014-01-01

    Background: For the sake of reducing post extraction resorption, getting optimal positioning of the implant and shortening treatment time, immediate implant placement following tooth extraction has been proposed as a treatment option. However, the large bone defect peri-implant has a negative influence on the process of bone healing. In this study, umbilical cord mesenchymal stem cells (UCMSCs) were transplanted into the bone defect peri-implant inbeagle dogs and the effect of UCMSCs on bone regeneration in peri-implant were assessed. Methods: The mandibular second, third and fourth premolars of 8 beagle dogs were extracted bilaterally. The defects in one side were filled with platelet-rich fibrin (PRF) and then UCMSCs were injected into the defect area, while the defects in the other side were filled with PRF only as control group. The titanium implant was placed into the distal root socket of each extracted tooth. The animals were sacrificed at week 2, 4 and 8 post operative. The bone defects adjacent to the implant which are 4 mm in height, 4 mm in the mesio-distal direction and 3.5 mm in the bucco-lingual direction were made after immediate implant. Histomorphometric analysis was performed using methylene blue-fuchsin acid staining and hematoxylin and eosin (HE) staining to evaluate bone regeneration. Results: The direct bone-to-implant contact (BIC) in the experiment after 4 and 8 weeks was 56.47±1.18% and 76.23±2.08%; and in the control group was40.79±0.65% and 61.17±2.79%, respectively. The percentage of newly formed bone after 2, 4 and 8 weeks was 17.60±1.5%, 49.82±4.02% and 67.16±2.1% in experiment group; and in control group 14.30±1.25%, 37.04±2.29% and 58.83±3.36%, respectively. These results represented significant differences statistically. Conclusion: Intra-bone marrow injection of UCMSCs can promote new bone formation. UCMSCs can be used to as excellent seed cells to repair the large defect peri-implant after immediate implant. PMID

  16. Metastatic thymoma and acquired generalized myasthenia gravis in a beagle.

    PubMed

    Moffet, Adrienne C

    2007-01-01

    A 16-year-old, spayed female beagle was diagnosed with metastatic thymoma causing a probable paraneoplastic syndrome of generalized acquired myasthenia gravis. Anticholinesterase treatment was initiated; however, 5 days later the dog died.

  17. 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.

    PubMed

    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.

  18. Transition of the intestinal microbiota of dogs with age

    PubMed Central

    MASUOKA, Hiroaki; SHIMADA, Kouya; KIYOSUE-YASUDA, Tomoyo; KIYOSUE, Masaharu; OISHI, Yukie; KIMURA, Seiji; YAMADA, Akio; HIRAYAMA, Kazuhiro

    2016-01-01

    Although it is established that the composition of the human intestinal microbiota changes with age, transition of the intestinal microbiota of animals with age has not been well studied. In the present study, we collected fresh fecal samples from dogs of 5 different age groups (pre-weanling, weanling, young, aged, senile) and analyzed the compositions of their intestinal microbiota with a culture-based method. The results suggested that the composition of the canine intestinal microbiota also changes with age. Among intestinal bacteria predominant in dog intestines, lactobacilli appeared to change with age. Both the number and the prevalence of lactobacilli tended to decrease when dogs became older. Bifidobacteria, on the other hand, was not predominant in the intestine of the dogs. We also identified lactobacilli at the species level based on 16S rRNA gene sequences and found that the species composition of Lactobacillus also changed with age. It was further suggested that bacteria species beneficial to host animals may differ depending on the host species. PMID:28243548

  19. Collaborative Radiological Health Laboratory annual report 1985: health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog

    SciTech Connect

    Not Available

    1986-07-01

    The Collaborative Radiological Health Laboratory was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining in a carefully controlled animal experiment the life-time hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. This is a long-term (lifespan) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages-at-irradiation selected for comparison reflect the primary concern with medical exposures during the development period. The basic experiment under the contract contains 1,680 beagles that will be maintained and evaluated for most of their natural lives. Commitment of animals began in December 1967 and was completed in October 1972. The annual report summarizes the current status of the study for the reporting period of November 21, 1984 through November 20, 1985.

  20. Collaborative Radiological Health Laboratory annual report, 1988: Health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog

    SciTech Connect

    Not Available

    1989-09-01

    The Collaborative Radiological Health Laboratory was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining, in a carefully controlled animal experiment, the life-time hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. This is a long-term (life span) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages-at-irradiation selected for comparison reflect the primary concern with medical exposures during the developmental period. The basic experiment under the contract contains 1,680 beagles that will be maintained and evaluated for most of their natural lives. Commitment of animals began in December 1967 and was completed in February 1973. The annual report summarizes the current status of the study for the reporting period of November 21, 1987 through November 20, 1988.

  1. Collaborative Radiological Health Laboratory annual report 1987: health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog. Annual report

    SciTech Connect

    Not Available

    1988-09-01

    The Collaborative Radiological Health Laboratory (CRHL) was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining in a carefully controlled animal experiment the lifetime hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. It is a long-term (life span) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages-at-irradiation selected for comparison reflect the primary concern with medical exposures during the developmental period. The basic experiment under the contract contains 1,680 beagles that will be maintained and evaluated for most of their natural lives. The annual report summarizes the current status of the study for the reporting period of November 21, 1986 through November 20, 1987.

  2. Collaborative Radiological Health Laboratory annual report 1986: health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog

    SciTech Connect

    Not Available

    1987-08-01

    The Collaborative Radiological Health Laboratory was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining in a carefully controlled animal experiment the life-time hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. This is a long-term (lifespan) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages-at-irradiation selected for comparison reflect the primary concern with medical exposures during the development period. The basis experiment under this contract contains 1,680 beagles that will be maintained and evaluated for most of their natural lives. Commitment of animals began in December 1967 and was completed in October 1972. The annual report summarizes the current status of the study for the reporting period of November 21, 1985 through November 20, 1986.

  3. Collaborative Radiological Health Laboratory annual report 1984: health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog

    SciTech Connect

    Not Available

    1985-08-01

    The Collaborative Radiological Health Laboratory was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining in a carefully controlled animal experimentthe life-time hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. This is a long-term (lifespan) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages-at-irradiation selected for comparison reflect the primary concern with medical exposures during the developmental period. The basic experiment under this contract contains 1,680 beagles that will be maintained and evaluated for most of their natural lives. Commitment of animals began in December 1967 and was completed in October 1972. This annual report summarizes the current status of the study for the reporting period of November 21, 1983 through November 20, 1984.

  4. Age-related changes in the propensity of dogs to bite.

    PubMed

    Messam, L L McV; Kass, P H; Chomel, B B; Hart, L A

    2013-08-01

    This retrospective cohort study was aimed at describing the effects of age at acquisition, age, and duration of ownership of dogs on the risk of (1) bites during play and (2) non-play bites to humans. Data were collected on 110 dogs that had bitten during play with a person, 161 dogs that had bitten outside of play and 951 non-biting dogs from veterinary clients in Kingston (KGN), Jamaica and San Francisco (SF), USA. Modified Poisson regression was employed to model the relationships of both types of bites to each variable separately. Effects of the variables on dog bite risk (1) during and (2) outside of play with the dog, differed from each other and by type of bite. Effects varied with the dog's age and age-related associations were strongest in dogs younger than 1 year old. Ages at acquisition of dogs at highest risk for bites during play were substantially lower than those at risk for non-play bites. Ages and durations of ownership of dogs at highest risk for bites during play were also lower than those of dogs at highest risk for non-play bites. The propensity of a dog to bite changes as it ages and relationships between dog bites occurring during and outside of play and the dog's age at acquisition, current age, and duration of ownership, differ from each other.

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

    SciTech Connect

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

    1989-08-01

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

  6. 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.

    PubMed

    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.

  7. 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.

    PubMed

    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.

  8. CSU-FDA collaborative radiological health laboratory annual report, 1980: health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog

    SciTech Connect

    Benjamin, S.A.

    1982-01-01

    A long-term study of the mortality, morbidity, and physiopathology of beagles exposed to a single dose of ionizing radiation during one of six stages of either prenatal or postnatal development. The results of this study will provide insight into the lifetime risks associated with prenatal and postnatal exposure to low levels of ionizing radiation. This annual report describes the long-term study and the short-term experiments being performed to evaluate spontaneous and radiation-induced problems, as well as the computer storage and retrieval system and its uses in the study.

  9. Neoplasia in fast neutron-irradiated beagles

    SciTech Connect

    Bradley, E.W.; Zook, B.C.; Casarett, G.W.; Deye, J.A.; Adoff, L.M.; Rogers, C.C.

    1981-09-01

    One hundred fifty-one beagle dogs were irradiated with either photons or fast neutrons (15 MeV) to one of three dose-limiting normal tissues--spinal cord, lung, or brain. The radiation was given in four fractions per week for 5 weeks (spinal cord), 6 weeks (lung), or 7 weeks (brain) to total doses encompassing those given clinically for cancer management. To date, no nonirradiated dogs or photon-irradiated dogs have developed any neoplasms. Seven dogs receiving fast neutrons have developed 9 neoplasms within the irradiated field. Of the neutron-irradiated dogs at risk, the incidence of neoplasia was 15%. The latent period for radiation-induced cancers has varied from 1 to 4 1/2 years at this time in the study.

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

    SciTech Connect

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

    1994-06-01

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

  11. Short-term supplementation with acetyl-L-carnitine and lipoic acid alters plasma protein carbonyl levels but does not improve cognition in aged beagles

    PubMed Central

    Christie, Lori-Ann; Opii, Wycliffe O.; Head, Elizabeth; Araujo, Joseph A.; De Rivera, Christina; Milgram, Norton W.; Cotman, Carl W.

    2009-01-01

    Previous work has shown that a diet enriched with antioxidants and mitochondrial co-factors improves cognition in aged dogs, which was accompanied by a reduction oxidative damage in the brain. The objective of the present study was to assess the effects of supplementation with mitochondrial co-factors on cognition and plasma protein carbonyl levels in aged dogs. Specifically, we aimed to test whether the individual or combined action of lipoic acid (LA) and acetyl-L-carnitine (ALCAR) could account for the beneficial effects of the enriched diet that contained both plus antioxidants. Dogs were given LA or ALCAR, alone and then in combination and cognition was assessed using a spatial learning task and two discrimination and reversal paradigms. Dogs receiving the ALCAR supplement showed an increase in protein carbonyl levels that was associated with increased error scores on the spatial task, and which was reduced upon additional supplementation with LA. We did not observe significant positive effects on cognition. The present findings suggest that short-term supplementation with LA and ALCAR is insufficient to improve cognition in aged dogs, and that the beneficial effects of the full spectrum diet arose from either the cellular antioxidants alone or their interaction with LA and ALCAR. PMID:19735717

  12. Ultrasonographic evaluation of the adrenal glands in healthy dogs: repeatability, reproducibility, observer-dependent variability, and the effect of bodyweight, age and sex.

    PubMed

    Mogicato, G; Layssol-Lamour, C; Conchou, F; Diquelou, A; Raharison, F; Sautet, J; Concordet, D

    2011-02-05

    Adrenal length and width were determined from two-dimensional ultrasound longitudinal images. In study 1, 540 measurements of adrenal glands were attempted from five healthy beagle dogs by three different observers with different levels of expertise in ultrasonography, to determine the variability of adrenal gland measurements. Of these, 484 measurements were included in the statistical analysis, since 16 measurements of the left adrenal gland and 40 for the right could not be visualised by the observer. In study 2, a single measurement of both adrenal glands was taken from each of 146 dogs by the most trained observer from study 1, and the effects of different health status (healthy dogs v dogs with non-adrenal diseases), bodyweight, age and sex were assessed. A total of 267 measurements were included in the statistical analysis. The lowest intra- and inter-day coefficient of variation values were observed for the left adrenal gland and by the most trained observer. The health status had no statistically significant effect on adrenal gland length or width, whereas age had a significant effect only for the left adrenal gland (the greater the age, the greater the width or length) and sex had a significant effect only for the right adrenal gland (the width was larger in males and the length larger in females). The bodyweight had a significant effect for the length of both adrenal glands (the greater the bodyweight, the greater the length), but not the width. The differences between sd and coefficient of variation values for the width of the left adrenal gland were not statistically significant between the three observers, whereas they were statistically significant for the right adrenal gland.

  13. 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

    SciTech Connect

    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.

  14. Neoplasia in fast neutron-irradiated beagles

    SciTech Connect

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

    1981-09-01

    One hundred fifty-one beagle dogs were irradiated with either photons or fast neutrons (15 MeV) to one of three dose-limiting normal tissues - spinal cord, lung, or brain. The radiation was given in four fractions per week for 5 weeks (spinal cord), 6 weeks (lung), 7 weeks (brain) to total doses encompassing those given clinically for cancer management. To date, no nonirradiated dogs or photon-irradiated dogs have developed neoplasms within the irradiated field. Of the neutron-irradiated dogs at risk, the incidence of neoplasia was 15%. The latent period for radiation-induced cancers has varied from 1 to 4 1/2 years at this time in the study.

  15. Prevalence of owner-reported behaviours in dogs separated from the litter at two different ages.

    PubMed

    Pierantoni, L; Albertini, M; Pirrone, F

    2011-10-29

    The present study examined the prevalence of behaviours in dogs separated from the litter for adoption at different ages. Seventy adult dogs separated from their dam and littermates and adopted between the ages of 30 and 40 days were compared with 70 adult dogs that had been taken from the litter for adoption at two months. Owners were asked to complete a questionnaire eliciting information on whether their dog exhibited potentially problematic behaviours when in its usual environment. Binary logistic regression analysis was performed to investigate whether the age at which the dog was separated from the litter might predispose it to developing undesirable behaviours. The odds of displaying destructiveness, excessive barking, fearfulness on walks, reactivity to noises, toy possessiveness, food possessiveness and attention-seeking were significantly greater for the dogs that had been removed from the litter earlier during the socialisation period. In addition, dogs purchased from a pet shop at 30 to 40 days of age were reported to exhibit some of the listed behaviours with a significantly higher frequency than dogs purchased from a pet shop at two months. No significant differences were observed with dogs obtained from other types of sources. The dogs in the youngest age group (18 to 36 months) had a higher probability of displaying destructiveness and tail chasing. These findings indicate that, compared with dogs that remained with their social group for 60 days, dogs that had been separated from the litter earlier were more likely to exhibit potentially problematic behaviours, especially if they came from a pet shop.

  16. Prenatal and neonatal irradiation in dogs: hematologic and hematopoietic responses

    SciTech Connect

    Nold, J.B.; Miller, G.K.; Benjamin, S.A.

    1987-12-01

    Hematologic and hematopoietic responses were evaluated in beagle dogs following a single prenatal (35 days gestation) or neonatal (10 days postpartum) exposure to 1.5 Gy /sup 60/Co gamma radiation. Hematopoiesis was studied by the in vitro culture of bone marrow granulocyte-macrophage progenitors (CFU-GM). Prenatally irradiated dogs exhibited a progressive, significant reduction in CFU-GM which was accompanied by decreases in peripheral blood leukocytes up to 24 weeks of age. Dogs which were neonatally irradiated also demonstrated a significant reduction in CFU-GM which was accompanied by significant alterations in peripheral white and red blood cell parameters. This was transient, however, and these dogs showed partial recovery of CFU-GM and hematologic parameter by 24 weeks of age. The persistent CFU-GM deficit in prenatally irradiated dogs suggests a relatively greater sensitivity of fetal marrow as compared to neonatal bone marrow for long-term damage by ionizing radiation.

  17. Use of serologic tests to predict resistance to Canine distemper virus-induced disease in vaccinated dogs.

    PubMed

    Jensen, Wayne A; Totten, Janet S; Lappin, Michael R; Schultz, Ronald D

    2015-09-01

    The objective of the current study was to determine whether detection of Canine distemper virus (CDV)-specific serum antibodies correlates with resistance to challenge with virulent virus. Virus neutralization (VN) assay results were compared with resistance to viral challenge in 2 unvaccinated Beagle puppies, 9 unvaccinated Beagle dogs (4.4-7.2 years of age), and 9 vaccinated Beagle dogs (3.7-4.7 years of age). Eight of 9 (89%) unvaccinated adult dogs exhibited clinical signs after virus challenge, and 1 (13%) dog died. As compared to adult dogs, the 2 unvaccinated puppies developed more severe clinical signs and either died or were euthanized after challenge. In contrast, no clinical signs were detected after challenge of the 9 adult vaccinated dogs with post-vaccination intervals of up to 4.4 years. In vaccinated dogs, the positive and negative predictive values of VN assay results for resistance to challenge were 100% and 0%, respectively. Results indicate that dogs vaccinated with modified live CDV can be protected from challenge for ≤4.4 years postvaccination and that detection of virus-specific antibodies is predictive of whether dogs are resistant to challenge with virulent virus. Results also indicate that CDV infection in unvaccinated dogs results in age-dependent morbidity and mortality. Knowledge of age-dependent morbidity and mortality, duration of vaccine-induced immunity, and the positive and negative predictive values of detection of virus-specific serum antibodies are useful in development of rational booster vaccination intervals for the prevention of CDV-mediated disease in adult dogs.

  18. Asymptomatic heart valve dysfunction in healthy middle-aged companion dogs and its implications for cardiac aging.

    PubMed

    Urfer, Silvan R; Kaeberlein, Tammi L; Mailheau, Susan; Bergman, Philip J; Creevy, Kate E; Promislow, Daniel E L; Kaeberlein, Matt

    2017-02-01

    Heart disease is the leading cause of death in the USA, accounting for about one in every four deaths. Age is the greatest risk factor for heart disease in both people and dogs; however, heart disease is generally not considered as a major cause of morbidity or mortality in dogs. As part of the preliminary selection process for a veterinary clinical trial, 40 companion dogs with no history of cardiac pathology that were at least 6 years old and weighed at least 18 kg underwent a cardiac screening using Doppler echocardiography. Eleven dogs from this cohort were diagnosed with valvular regurgitation by echocardiography, and seven of these cases were of sufficient severity to warrant exclusion from the clinical trial. In only one case was a heart murmur detected by auscultation. Serum alkaline phosphatase levels were significantly higher in the dogs with moderate to severe valvular regurgitation compared to the rest of the cohort. These observations suggest that asymptomatic degenerative valvular disease detectable by echocardiography, but not by a standard veterinary exam including auscultation, may be present in a significant fraction of middle-aged companion dogs, indicating a previously underappreciated similarity between human and canine aging. Further, these data suggest that companion dogs may be a particularly useful animal model for understanding mechanisms of age-related degenerative valve disease and for developing and testing interventions to ameliorate cardiac disease. Future studies should address whether dogs with asymptomatic valve disease are at higher risk for subsequent morbidity or early death.

  19. Multiple morbidities in companion dogs: a novel model for investigating age-related disease

    PubMed Central

    Jin, Kelly; Hoffman, Jessica M.; Creevy, Kate E.; O’Neill, Dan G.; Promislow, Daniel E.L.

    2016-01-01

    The proportion of men and women surviving over 65 years has been steadily increasing over the last century. In their later years, many of these individuals are afflicted with multiple chronic conditions, placing increasing pressure on healthcare systems. The accumulation of multiple health problems with advanced age is well documented, yet the causes are poorly understood. Animal models have long been employed in attempts to elucidate these complex mechanisms with limited success. Recently, the domestic dog has been proposed as a promising model of human aging for several reasons. Mean lifespan shows twofold variation across dog breeds. In addition, dogs closely share the environments of their owners, and substantial veterinary resources are dedicated to comprehensive diagnosis of conditions in dogs. However, while dogs are therefore useful for studying multimorbidity, little is known about how aging influences the accumulation of multiple concurrent disease conditions across dog breeds. The current study examines how age, body weight, and breed contribute to variation in multimorbidity in over 2,000 companion dogs visiting private veterinary clinics in England. In common with humans, we find that the number of diagnoses increases significantly with age in dogs. However, we find no significant weight or breed effects on morbidity number. This surprising result reveals that while breeds may vary in their average longevity and causes of death, their age-related trajectories of morbidities differ little, suggesting that age of onset of disease may be the source of variation in lifespan across breeds. Future studies with increased sample sizes and longitudinal monitoring may help us discern more breed-specific patterns in morbidity. Overall, the large increase in multimorbidity seen with age in dogs mirrors that seen in humans and lends even more credence to the value of companion dogs as models for human morbidity and mortality. PMID:27876455

  20. Sulfadiazines prevent plaque formation and gingivitis in beagles.

    PubMed

    Howell, T H; Reddy, M S; Weber, H P; Li, K L; Alfano, M C; Vogel, R; Tanner, A C; Williams, R C

    1990-07-01

    The effect of zinc sulfadiazine (ZnSD) and silver sulfadiazine (AgSD) on developing plaque formation and gingivitis was studied in 12 beagle dogs over a 14-week period. Plaque and gingival indices were used to measure plaque formation and gingivitis. During a 2-wk baseline period each dog was brought to optimal gingival health with prophylaxis and tooth brushing. Thereafter, 4 dogs were treated twice daily with topical application of 3.0% zinc sulfadiazine; 4 dogs were treated with 2.0% silver sulfadiazine while 4 dogs treated with placebo gel served as controls over a 12-wk treatment period. At wk 2 of treatment, all three groups of dogs showed an increase in plaque build-up on their teeth from baseline. By wk 6, plaque accumulation on the teeth was significantly less in dogs treated with either ZnSD or AgSD compared to control dogs. At wk 2 of treatment, gingival inflammation was increased from baseline in all three groups. Thereafter, over the course of the 12-wk treatment period, gingival inflammation in the ZnSD and the AgSD treated dogs was significantly less than the placebo treated dogs. The data indicate that both ZnSD and AgSD inhibit developing plaque formation in beagles. This significant inhibition of plaque formation was accompanied by a significant reduction in gingival inflammation.

  1. Extended acclimatization is required to eliminate stress effects of periodic blood-sampling procedures on vasoactive hormones and blood volume in beagle dogs.

    PubMed

    Slaughter, M R; Birmingham, J M; Patel, B; Whelan, G A; Krebs-Brown, A J; Hockings, P D; Osborne, J A

    2002-10-01

    Important in all experimental animal studies is the need to control stress stimuli associated with environmental change and experimental procedures. As the stress response involves alterations in levels of vasoactive hormones, ensuing changes in cardiovascular parameters may confound experimental outcomes. Accordingly, we evaluated the duration required for dogs (n = 4) to acclimatized to frequent blood sampling that involved different procedures. On each sampling occasion during a 6-week period, dogs were removed from their pen to a laboratory area and blood was collected either by venepuncture (days 2, 15, 34, 41) for plasma renin activity (PRA), epinephrine (EPI), norepinephrine, aldosterone, insulin, and atrial natriuretic peptide, or by cannulation (dogs restrained in slings; days 1, 8, 14, 22, 30, 33, 37, 40) for determination of haematocrit (HCT) alone (days 1 to 22) or HCT with plasma volume (PV; days 30 to 40). PRA was higher on days 2 and 15 compared with days 34 and 41 and had decreased by up to 48% by the end of the study (day 41 vs day 15; mean/SEM: 1.18/0.27 vs 2.88/0.79 ng ANG I/ml/h, respectively). EPI showed a time-related decrease from days 2 to 34, during which mean values had decreased by 51% (mean/SEM: 279/29 vs 134/20.9 pg/ml for days 2 and 34, respectively), but appeared stable from then on. None of the other hormones showed any significant variability throughout the course of the study. HCT was relatively variable between days 1 to 22 but stabilized from day 30, after which all mean values were approximately 6% lower than those between days 1 and 8. We conclude that an acclimatization period of at least 4 weeks is required to eliminate stress-related effects in dogs associated with periodic blood sampling.

  2. Rural origin, age, and endoparasite fecal prevalence in dogs surrendered to the Regina Humane Society, 2013

    PubMed Central

    Schurer, Janna M.; Hamblin, Brie; Davenport, Laura; Wagner, Brent; Jenkins, Emily J.

    2014-01-01

    We report the results of fecal parasite surveillance in dogs surrendered to the Regina Humane Society, Saskatchewan, Canada, between May and November 2013. Overall, 23% of 231 dogs were infected with at least 1 intestinal parasite. Endoparasite infection was positively associated with rural origin (P = 0.002) and age (< 12 months; P < 0.001). PMID:25477549

  3. The novel formulation design of self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion I: enhancing effects on oral bioavailability of poorly water soluble compounds in rats and beagle dogs.

    PubMed

    Araya, Hiroshi; Nagao, Shunsuke; Tomita, Mikio; Hayashi, Masahiro

    2005-08-01

    We examined the design of the versatile novel self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion formulation which enhances the oral bioavailability by raising the solubility of poorly water soluble compounds. Namely, seven kinds of poorly water soluble compounds such as disopyramide, ibuprofen, ketoprofen, tolbutamide, and other new compounds, as the model compounds were used to compare the plasma concentration profile of the compound following single oral administration of each compound to rats and beagle dogs as a solution, an oily solution, a suspension (or a powder), an O/W microemulsion, and a SEDDS type O/W microemulsion. And the enhancing effect of the SEDDS type O/W microemulsion on the gastrointestinal absorption of these compounds was evaluated. In the components of the SEDDS type O/W microemulsion, medium chain fatty acid triglyceride (MCT), diglyceryl monooleate (DGMO-C), polyoxyethylene hydrogenated castor oil 40 (HCO-40), and ethanol were used as an oil, a lipophilic surfactant, a hydrophilic surfactant, and a solubilizer, at the mixture ratio of 25/5/45/25 (w/w%), respectively. Thereby, to six kinds of the model compounds except disopyramide, the solubility was from 340 to 98,000 times that in water, and the AUCs in plasma concentration of the compound were equivalent to that of solution or O/W microemulsion administration, or was increased by 1.5 to 78 times that of suspension administration. Accordingly, this novel SEDDS type O/W microemulsion is the versatile, useful formulation which enhances the oral bioavailability by raising the solubility of poorly water soluble compounds.

  4. Aging effects on discrimination learning, logical reasoning and memory in pet dogs.

    PubMed

    Wallis, Lisa J; Virányi, Zsófia; Müller, Corsin A; Serisier, Samuel; Huber, Ludwig; Range, Friederike

    2016-02-01

    In laboratory dogs, aging leads to a decline in various cognitive domains such as learning, memory and behavioural flexibility. However, much less is known about aging in pet dogs, i.e. dogs that are exposed to different home environments by their caregivers. We used tasks on a touchscreen apparatus to detect differences in various cognitive functions across pet Border Collies aged from 5 months to 13 years. Ninety-five dogs were divided into five age groups and tested in four tasks: (1) underwater photo versus drawing discrimination, (2) clip art picture discrimination, (3) inferential reasoning by exclusion and (4) a memory test with a retention interval of 6 months. The tasks were designed to test three cognitive abilities: visual discrimination learning, logical reasoning and memory. The total number of sessions to reach criterion and the number of correction trials needed in the two discrimination tasks were compared across age groups. The results showed that both measures increased linearly with age, with dogs aged over 13 years displaying slower learning and reduced flexibility in comparison to younger dogs. Inferential reasoning ability increased with age, but less than 10 % of dogs showed patterns of choice consistent with inference by exclusion. No age effect was found in the long-term memory test. In conclusion, the discrimination learning tests used are suitable to detect cognitive aging in pet dogs, which can serve as a basis for comparison to help diagnose cognition-related problems and as a tool to assist with the development of treatments to delay cognitive decline.

  5. Effects of dietary protein on glomerular mesangial area and basement membrane thickness in aged uninephrectomized dogs.

    PubMed Central

    McCarthy, R A; Steffens, W L; Brown, C A; Brown, S A; Ard, M; Finco, D R

    2001-01-01

    The primary objective of this study was to determine the effects of diets containing 18% or 34% protein on glomerular mesangial area (GMA) and basement membrane thickness (GBMT) in uninephrectomized aged dogs. A secondary objective was to determine the combined effects of aging and uninephrectomy on GMA and GBMT in dogs. Ten clinically healthy, pure-bred dogs were unilaterally nephrectomized at about 8 y of age. After 2 mo, 5 dogs were fed an 18% protein diet and 5 dogs were fed a 34% protein diet for 48 mo. At month 48, the dogs were euthanized and the remaining kidney was collected. Samples of kidney from both times of collection were used to measure GMA and GBMT using electron microscopy. The effects of diet on GMA and GBMT were analyzed (student's t-test) using necropsy/nephrectomy score ratios. The effects of time-nephrectomy were determined by comparing nephrectomy values for GMA and GBMT with necropsy values (paired t-test). Dogs fed 34% dietary protein did not have a significant increase in GMA and GBM thickness when compared to dogs fed the 18% protein diet. A significant increase in GMA and GBMT occurred with time-nephrectomy (P = 0.011 and 0.018, respectively). Although dietary protein intake was not a significant factor in causing structural changes to glomeruli in uninephrectomized aged dogs, the power to detect a difference was low. However, significant effects of aging and nephrectomy were detected despite the low power of the study. These results suggest that the increases in GMA and GBMT that occur over time are not markedly influenced by dietary protein intake. However, subtle protein effects cannot be eliminated as a possibility based on this study. Images Figure 2. Figure 3. PMID:11346257

  6. Dogs

    MedlinePlus

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  7. Collaborative Radiological Health Laboratory annual report 1983: health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog. Report for 1 January-20 November 1983

    SciTech Connect

    Benjamin, S.A.

    1985-01-01

    The Collaborative Radiological Health Laboratory was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining in a carefully controlled animal experiment the life-time hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. This is a long-term (lifespan) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages at irradiation selected for comparison reflect the primary concern with medical exposures during the developmental period. The basic experiment under this contract contains 1680 beagles that will be maintained and evaluated for most of their natural lives. Commitment of animals began in December 1967 and was completed in October 1972. This annual report summarizes the current status of the study for the reporting period of January 1 through November 20, 1983.

  8. Evaluation of the Applicability of Different Age Determination Methods for Estimating Age of the Endangered African Wild Dog (Lycaon Pictus)

    PubMed Central

    Steenkamp, Gerhard; Groom, Rosemary J.

    2016-01-01

    African wild dogs (Lycaon pictus) are endangered and their population continues to decline throughout their range. Given their conservation status, more research focused on their population dynamics, population growth and age specific mortality is needed and this requires reliable estimates of age and age of mortality. Various age determination methods from teeth and skull measurements have been applied in numerous studies and it is fundamental to test the validity of these methods and their applicability to different species. In this study we assessed the accuracy of estimating chronological age and age class of African wild dogs, from dental age measured by (i) counting cementum annuli (ii) pulp cavity/tooth width ratio, (iii) tooth wear (measured by tooth crown height) (iv) tooth wear (measured by tooth crown width/crown height ratio) (v) tooth weight and (vi) skull measurements (length, width and height). A sample of 29 African wild dog skulls, from opportunistically located carcasses was analysed. Linear and ordinal regression analysis was done to investigate the performance of each of the six age determination methods in predicting wild dog chronological age and age class. Counting cementum annuli was the most accurate method for estimating chronological age of wild dogs with a 79% predictive capacity, while pulp cavity/tooth width ratio was also a reliable method with a 68% predictive capacity. Counting cementum annuli and pulp cavity/tooth width ratio were again the most accurate methods for separating wild dogs into three age classes (6–24 months; 25–60 months and > 60 months), with a McFadden’s Pseudo-R2 of 0.705 and 0.412 respectively. The use of the cementum annuli method is recommended when estimating age of wild dogs since it is the most reliable method. However, its use is limited as it requires tooth extraction and shipping, is time consuming and expensive, and is not applicable to living individuals. Pulp cavity/tooth width ratio is a

  9. Testicular gene expression of steroidogenesis-related factors in prepubertal, postpubertal, and aging dogs.

    PubMed

    Ogawa, E; Kawate, N; Inaba, T; Tamada, H

    2017-03-01

    Developmental and aging changes in testicular factors related to steroidogenesis are unknown in dogs. Using reverse transcription quantitative real-time PCR, this study examined testicular mRNA levels of CYP11A1 (P450 cholesterol side-chain cleavage enzyme, P450scc), CYP17A1 (P450 17α-hydroxylase/C17-20 lyase, P450c17), HSD3B2 (3β-hydroxysteroid dehydrogenase, 3β-HSD), CYP19A (P450 aromatase, P450arom), STAR (steroidogenic acute regulatory protein, StAR), cyclooxygenase (COX) -1 and COX-2 in prepubertal (4-6 months of age), postpubertal (1 year of age), and aging (2-18 years of age) dogs. Testicular mRNA levels for P450scc, 3β-HSD, StAR, COX-1, and COX-2 did not change from prepubertal to postpubertal stages, whereas that for P450arom markedly and abruptly increased and that for P450c17 gradually decreased. In postpubertal and aging dogs, a negative correlation was found between aging and testicular P450arom mRNA levels. Based on the rapid testicular growth observed during puberty, these results suggested that total testis gene expression for steroidogenesis-related factors, in particular for P450arom, increases during puberty in dogs. In addition, the decline in P450arom gene expression during aging may affect the ability to synthesize steroids in canine testes.

  10. A cloned toy poodle produced from somatic cells derived from an aged female dog.

    PubMed

    Jang, G; Hong, S G; Oh, H J; Kim, M K; Park, J E; Kim, H J; Kim, D Y; Lee, B C

    2008-03-15

    To date, dogs have been cloned with somatic cell nuclear transfer (SCNT), using donor cells derived from large-breed dogs 2 months to 3 years of age. The objective of the present study was to use SCNT to produce a small-breed dog from ear fibroblasts of an aged poodle, using large-breed oocyte donors and surrogate females, and to determine the origin of its mitochondrial DNA (mtDNA) and the length of its telomeres. Oocytes were derived from large-breed donors, matured in vivo, collected by flushing oviducts, and reconstructed with somatic cells derived from an aged (14-year-old) female toy poodle. Oocytes and donor cells were fused by electric stimuli, activated chemically, and transferred into the oviducts of large-breed recipient females. Overall, 358 activated couplets were surgically transferred into the oviducts of 20 recipient dogs. Two recipients became pregnant; only one maintained pregnancy to term, and a live puppy (weighing 190 g) was delivered by Caesarean section. The cloned poodle was phenotypically and genetically identical to the nuclear donor dog; however, its mtDNA was from the oocyte donor, and its mean telomere length was not significantly different from that of the nuclear donor. In summary, we demonstrated that a small-breed dog could be cloned by transferring activated couplets produced by fusion of somatic cells from a small-breed, aged donor female with enucleated in-vivo-matured oocytes of large-breed females, and transferred into the oviduct of large-breed recipient female dogs.

  11. An Age-Associated Decline in Thymic Output Differs in Dog Breeds According to Their Longevity

    PubMed Central

    Holder, Angela; Mella, Stephanie; Palmer, Donald B.; Aspinall, Richard; Catchpole, Brian

    2016-01-01

    The age associated decline in immune function is preceded in mammals by a reduction in thymic output. Furthermore, there is increasing evidence of a link between immune competence and lifespan. One approach to determining thymic output is to quantify signal joint T cell receptor excision circles (sj-TRECs), a method which has been developed and used in several mammalian species. Life expectancy and the rate of aging vary in dogs depending upon their breed. In this study, we quantified sj-TRECs in blood samples from dogs of selected breeds to determine whether there was a relationship between longevity and thymic output. In Labrador retrievers, a breed with a median expected lifespan of 11 years, there was an age-associated decline in sj-TREC values, with the greatest decline occurring before 5 years of age, but with sj-TREC still detectable in some geriatric animals, over 13 years of age. In large short-lived breeds (Burnese mountain dogs, Great Danes and Dogue de Bordeaux), the decline in sj-TREC values began earlier in life, compared with small long-lived breeds (Jack Russell terriers and Yorkshire terriers), and the presence of animals with undetectable sj-TRECs occurred at a younger age in the short-lived breeds. The study findings suggest that age-associated changes in canine sj-TRECs are related to breed differences in longevity, and this research highlights the use of dogs as a potential model of immunosenescence. PMID:27824893

  12. Comparing supervised learning methods for classifying sex, age, context and individual Mudi dogs from barking.

    PubMed

    Larrañaga, Ana; Bielza, Concha; Pongrácz, Péter; Faragó, Tamás; Bálint, Anna; Larrañaga, Pedro

    2015-03-01

    Barking is perhaps the most characteristic form of vocalization in dogs; however, very little is known about its role in the intraspecific communication of this species. Besides the obvious need for ethological research, both in the field and in the laboratory, the possible information content of barks can also be explored by computerized acoustic analyses. This study compares four different supervised learning methods (naive Bayes, classification trees, [Formula: see text]-nearest neighbors and logistic regression) combined with three strategies for selecting variables (all variables, filter and wrapper feature subset selections) to classify Mudi dogs by sex, age, context and individual from their barks. The classification accuracy of the models obtained was estimated by means of [Formula: see text]-fold cross-validation. Percentages of correct classifications were 85.13 % for determining sex, 80.25 % for predicting age (recodified as young, adult and old), 55.50 % for classifying contexts (seven situations) and 67.63 % for recognizing individuals (8 dogs), so the results are encouraging. The best-performing method was [Formula: see text]-nearest neighbors following a wrapper feature selection approach. The results for classifying contexts and recognizing individual dogs were better with this method than they were for other approaches reported in the specialized literature. This is the first time that the sex and age of domestic dogs have been predicted with the help of sound analysis. This study shows that dog barks carry ample information regarding the caller's indexical features. Our computerized analysis provides indirect proof that barks may serve as an important source of information for dogs as well.

  13. Effects of age and dietary beta-carotene on immunological variables in dogs.

    PubMed

    Massimino, Stefan; Kearns, Robert J; Loos, Kathleen M; Burr, John; Park, Jean Soon; Chew, Boon; Adams, Scott; Hayek, Michael G

    2003-01-01

    beta-Carotene is a naturally occurring carotenoid reported to have health-promoting effects in several species. Advancing age is known to have a negative impact on various immune variables in several species. This study was conducted in order to assess the effect of age on immune response in dogs and to determine whether beta-carotene is able to reverse this age-associated decline. To test this hypothesis, young and old dogs (n = 36) were fed either a control diet or experimental diets containing supplemental beta-carotene for 2-month periods. Age significantly (P < .05) lowered CD4+ T cell populations (47.2% versus 33.7%; young-control versus old-control, respectively) and beta-carotene restored percent distributions in old dogs to nonsignificance versus younger controls (41.0%). T cell proliferation was lower in old dogs (30,254 +/- 2,248 versus 14,811 +/- 2,497 cCPM; young-control versus old-control, respectively; P < .05), and beta-carotene supplementation significantly improved responses in this age group (21,329 +/- 2,275 cCPM). Although B cell proliferation was depressed with age (17,967 +/- 1,384 versus 7,535 +/- 1,469 cCPM; young-control versus old-control, respectively; P < .05), beta-carotene supplementation improved B cell proliferation in young dogs (23,500 +/- 1,339 cCPM). Old dogs displayed lower delayed-type hypersensitivity test (DTH) responses versus younger controls to both phytohemagglutinin-P (PHA; 11.1 +/- 0.95 versus 7.57 +/- 1.15 mm; young-control versus old-control, respectively; P < .05) and sheep red blood cell (RBC; 9.12 +/- 0.62 versus 8.08 +/- 0.75 mm; young-control versus old-control, respectively; P < .10). beta-Carotene improved these responses, mostly within the first 24-48 hours after injection. In summary, older dogs have lower immunological responses compared with younger controls. beta-Carotene supplementation significantly restored immune responses in older dogs when compared with their age-matched controls and younger

  14. Neoplasms in young dogs after perinatal irradiation

    SciTech Connect

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

    1986-08-01

    For a study of the life-time effects of irradiation during development, 1,680 beagles were given single, whole-body exposures to /sup 60/Co gamma-radiation at one of three prenatal (preimplantation, embryonic, and fetal) or at one of three postnatal (neonatal, juvenile, and young adult) ages. Mean doses were 0, 0.16, or 0.83 Gy. For comparison with data on childhood cancer after prenatal irradiation, examination was made of tumors occurring in young dogs in this life-span experiment. Up to 4 years of age, 18 dogs had neoplasms diagnosed, 2 of these being in controls. Four dogs that were irradiated in the perinatal (late fetal or neonatal) period died of cancers prior to 2 years of age. This risk was of significant increase compared to the risks for other experimental groups and for the canine population in general. Overall, 71% (5 of 7) of all cancers and 56% (10 of 18) of all benign and malignant neoplasms seen in the first 4 years of life occurred in 29% (480 of 1680) of the dogs irradiated in the perinatal period. These data suggest an increased risk for neoplasia after perinatal irradiation in dogs.

  15. Immunohistochemical analysis of constituents of senile plaques and cerebro-vascular amyloid in aged dogs.

    PubMed

    Uchida, K; Nakayama, H; Tateyama, S; Goto, N

    1992-10-01

    Immunohistochemical analysis of constituents of senile plaques and cerebro-vascular amyloid in the brain of aged dogs was performed using antisera against beta protein, cystatin C, ubiquitin, tau, and neurofilament (NF). All types of senile plaques and cerebro-vascular amyloid in aged dogs were labeled by anti-beta protein serum. Cystatin C immunoreactivity was detected in neuronal cell bodies, primitive or classical plaques, and amyloid deposited around cerebral capillaries, but not in diffuse plaques and amyloid deposited in the media tunica of cerebro-meningeal arterioles. Ubiquitin-positive granules distributed widely in both gray and white matter of aged dogs, while they were very small in number in young dogs. Swollen neurites-like materials in primitive plaques or classical plaques were immunoreactive for anti-ubiquitin serum. Tau immunostaining labeled commonly axons and several neuronal or glial cells after hydrate autoclave pretreatment. Tau-positive components were observed very rarely in the corona of classical plaques. Most of swollen neurites-like structures of primitive or classical plaques were not reactive for anti-NF serum, and only a few plaques contained small numbers of NF-positive elements.

  16. Old Dogs, New Tricks: Training Mature-Aged Manufacturing Workers

    ERIC Educational Resources Information Center

    Smith, Erica; Smith, Andrew; Smith, Chris Selby

    2010-01-01

    Purpose: This paper aims to examine the employment and training of mature-aged workers, so that suggestions for improving training for mature-aged workers may be offered. Design/methodology/approach: Six expert interviews were carried out by telephone, and three case studies involving company site visits were completed. Each company case study…

  17. Identification of the most common cutaneous neoplasms in dogs and evaluation of breed and age distributions for selected neoplasms.

    PubMed

    Villamil, J Armando; Henry, Carolyn J; Bryan, Jeffrey N; Ellersieck, Mark; Schultz, Loren; Tyler, Jeff W; Hahn, Allen W

    2011-10-01

    OBJECTIVE-To identify the most common cutaneous neoplasms in dogs and evaluate breed and age distributions for selected neoplasms. DESIGN-Retrospective epidemiological study. SAMPLE-Records available through the Veterinary Medical Database of dogs examined at veterinary teaching hospitals in North America between 1964 and 2002. PROCEDURES-Information on tumor type and patient breed and age was collected. Incidence and odds ratios with 95% confidence intervals were calculated. RESULTS-Records of 1,139,616 dogs were reviewed. Cutaneous neoplasms were diagnosed in 25,996 of these dogs; records for the remaining 1,113,620 dogs did not indicate that cutaneous neoplasms had been diagnosed, and these dogs were considered controls. The most frequent age range for dogs with cutaneous neoplasms was 10 to 15 years. Lipoma, adenoma, and mast cell tumor were the most common skin tumor types. CONCLUSIONS AND CLINICAL RELEVANCE-Results supported previously reported data regarding cutaneous neoplasia in dogs but provided updated information on the most common skin tumors and on age and breed distributions.

  18. Alterations in immune responses in prenatally irradiated dogs

    SciTech Connect

    Nold, J.B.; Benjamin, S.A.; Miller, G.K.

    1988-09-01

    Immunologic responses were studied in beagle dogs following prenatal (35 days gestation) irradiation to evaluate the effects of ionizing radiation on the developing immune system. Each dog received 1.5 Gy /sup 60/Co gamma irradiation or sham irradiation. Prenatally irradiated dogs exhibited a significant reduction in primary humoral antibody responses to inoculated sheep red blood cells, a T-dependent antigen, and a concurrent decrease in T-helper lymphocyte subpopulations in the peripheral blood at 3 to 4 months of age. Similarly, irradiated fetuses have been shown to have defects in epitheliostromal development of the thymus. It is suggested that the postnatal immunologic deficits may relate to the prenatal thymic injury.

  19. BDNF increases with behavioral enrichment and an antioxidant diet in the aged dog.

    PubMed

    Fahnestock, Margaret; Marchese, Monica; Head, Elizabeth; Pop, Viorela; Michalski, Bernadeta; Milgram, William N; Cotman, Carl W

    2012-03-01

    The aged canine (dog) is an excellent model for investigating the neurobiological changes that underlie cognitive impairment and neurodegeneration in humans, as canines and humans undergo similar pathological and behavioral changes with aging. Recent evidence indicates that a combination of environmental enrichment and antioxidant-fortified diet can be used to reduce the rate of age-dependent neuropathology and cognitive decline in aged dogs, although the mechanisms underlying these changes have not been established. We examined the hypothesis that an increase in levels of brain-derived neurotrophic factor (BDNF) is one of the factors underlying improvements in learning and memory. Old, cognitively impaired animals that did not receive any treatment showed a significant decrease in BDNF mRNA in the temporal cortex when compared with the young group. Animals receiving either an antioxidant diet or environmental enrichment displayed intermediate levels of BDNF mRNA. However, dogs receiving both an antioxidant diet and environmental enrichment showed increased levels of BDNF mRNA when compared with untreated aged dogs, approaching levels measured in young animals. BDNF receptor TrkB mRNA levels did not differ between groups. BDNF mRNA levels were positively correlated with improved cognitive performance and inversely correlated with cortical Aβ((1-42)) and Aβ((1-40)) levels. These findings suggest that environmental enrichment and antioxidant diet interact to maintain brain levels of BDNF, which may lead to improved cognitive performance. This is the first demonstration in a higher animal that nonpharmacological changes in lifestyle in advanced age can upregulate BDNF to levels approaching those in the young brain.

  20. FOLLICULAR CELL CARCINOMA OF THE THYROID GLAND IN THREE CAPTIVE AGED RACCOON DOGS (NYCTEREUTES PROCYONOIDES).

    PubMed

    Kido, Nobuhide; Itagaki, Iori; Ono, Kaori; Omiya, Tomoko; Matsumoto, Rei

    2015-12-01

    The clinical and histologic features of thyroid carcinoma in raccoon dogs have not been previously reported. Three of four raccoon dogs (Nyctereutes procyonoides) over 8 yr of age at the Nogeyama Zoological Gardens developed thyroid follicular cell carcinomas that were detected at necropsy. The affected raccoon dogs were rescued from the wild and were housed at the Nogeyama Zoological Gardens for 8 yr 8 mo, 8 yr 10 mo, and 10 yr 3 mo, respectively. Although all of them appeared lethargic and developed partial alopecia or desquamation of their skin, they did not display any other specific clinical signs associated with a thyroid lesion. Serum thyroid hormone values were examined in two of the affected raccoon dogs and the average and standard deviation values (free-thyroxin [FT4]: 0.078 ± 0.077 pM/L and 0.062 ± 0.0039 pM/L; free-triiodothyronine [FT3]: 3.261 ± 0.765 pM/L and 3.407 ± 0.919 pM/L) were lower than the reference range (FT4: 0.141 ± 0.117 pM/L; FT3: 5.139 ± 2.412 pM/L) derived from a clinically normal raccoon dog. On necropsy, the thyroid lobes were markedly enlarged bilaterally. Histopathologically, the neoplastic cells in the thyroid gland appeared round or oval and columnar or cuboidal with minimal heteromorphism. Moreover, mostly small (but occasionally large) follicles were identified, and the neoplastic cells had infiltrated into the surrounding capsule and blood vessels. The histopathologic features of the thyroid tumors in the raccoon dogs revealed that the tumors were derived from follicular cells.

  1. Hematological effects of inhaled plutonium dioxide in beagles

    SciTech Connect

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

    1995-07-01

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

  2. Comparison of age- and sex-specific incidence rate patterns of the leukemia complex in the cat and the dog.

    PubMed

    Schneider, R

    1983-05-01

    Data on cancer cases in cats and dogs were collected systematically by the Animal Neoplasm Registry of Alameda and Contra Costa Counties, Calif., a population-based animal tumor registry. Etiologic relationships were evaluated on the basis of comparisons of age-specific, sex-specific, and age-neutered-specific incidence rate patterns of the leukemias. Age-adjusted annual incidence rates for all leukemias per 100,000 cats or dogs were 224.3 and 30.5, respectively. The cat had 6.1 times more malignant lymphomas and 15.7 times more myeloproliferative disease than the dog. Feline age-specific rates indicated a bimodal age pattern for all leukemias and for malignant lymphoma alone and a single early peak for myeloproliferative disease. In the dog, all age-specific patterns increased with age and peaked later in life. Feline sex-specific, age-adjusted rates showed that the neutered female was at lowest risk, followed by the neutered male, entire female, and entire male. In the dog, the neutered male was at lowest risk while the other three sex categories were clustered. However, the magnitude of expression within each species separately was the same for the neutered male, entire male, and entire female, but not for the neutered female. Neutering decreased the risk of leukemias in the female cat by approximately one-half but did not affect the risk of leukemias in the female dog.

  3. Increase in Trx2/Prx3 redox system immunoreactivity in the spinal cord and hippocampus of aged dogs.

    PubMed

    Ahn, Ji Hyeon; Choi, Jung Hoon; Song, Ju Min; Lee, Choong Hyun; Yoo, Ki-Yeon; Hwang, In Koo; Kim, Jin Sang; Shin, Hyung-Cheul; Won, Moo-Ho

    2011-11-01

    We previously reported that no distinct neuronal loss occurred in the aged dog spinal cord, although oxidative stress was increased in the aged dog spinal cord. Thioredoxin 2 (Trx2)/peroxiredoxin 3 (Prx3) redox system is a major route for removing H(2)O(2) in the central nervous system. In the present study, we compared the distribution and immunoreactivity of thioredoxin reductase 2 (TrxR2), Trx2 and Prx3 and their protein levels in the spinal cord and hippocampus between the adult (2-3 years) and aged (10-12 years) dogs. The number of TrxR2-immunoreactive neurons was slightly increased; however, its immunoreactivity was significantly increased in the aged spinal cord compared to that in the adult spinal cord. On the other hand, the number and immunoreactivity of both Trx2- and Prx3-immunoreactive neurons were significantly increased in the spinal cord of the aged dog. Similarly, in the hippocampus of the aged dog, TrxR2, Trx2 and Prx3 immunoreactivity and protein levels were markedly increased compared to those in the adult dog. These results indicate that the increases of TrxR2, Trx2 and Prx3 immunoreactivity and their protein levels in the aged spinal cord and hippocampus may contribute to reducing neuronal damage against oxidative stresses during normal aging.

  4. Topographic relationship between senile plaques and cerebrovascular amyloidosis in the brain of aged dogs.

    PubMed

    Shimada, A; Kuwamura, M; Awakura, T; Umemura, T; Takada, K; Ohama, E; Itakura, C

    1992-02-01

    The distributions of senile plaques (SP) and cerebrovascular amyloidosis (CA) were studied by employing thioflavin S and modified Bielschowsky stains, and beta-protein immunohistochemistry on serial sections of the brains of aged dogs older than 10 years. Mature and perivascular plaques, both of which contained compact amyloid deposits, always showed a close topographic relationship to CA. In contrast, the majority of diffuse plaques showed no topographic relationship to CA. Cell bodies of neurons and/or glia were almost always involved in the diffuse plaques. In addition, beta-protein immunohistochemistry demonstrated amyloid deposits on the periphery of occasional neurons. These findings suggest that different mechanisms may be involved in the development of the different subtypes of SP in the brains of aged dogs.

  5. Endoparasite prevalence and recurrence across different age groups of dogs and cats.

    PubMed

    Gates, Maureen C; Nolan, Thomas J

    2009-12-03

    The apparent prevalence of endoparasite infections across different age groups was calculated from 6555 dogs and 1566 cats that had a fecal examination performed upon presentation to the Veterinary Hospital of the University of Pennsylvania between 1997 and 2007. Based on notations from the medical history indicating prior parasite infections, estimates of recurrence were generated for each common group of parasites, including Trichuris, Giardia, ascarids, hookworms, Cystoisospora, and tapeworms. Endoparasitism was predominantly a disease of younger animals, with peak prevalence observed almost uniformly in dogs under 6 months old, with the exception of Trichuris with its longer pre-patent period, and in cats less than 18 months old. Furthermore, nearly 50% of dogs under 6 months old with a history of parasites, were diagnosed with at least one species of parasite on subsequent fecal examination. The percentage dropped to 18.4% in animals aged 1-4 years, but again increased to 31.5% in animals over 10 years old. There was no reported recurrence of Giardia or Cystoisospora from canine or feline patients older than 1 year. The recurrence of whipworm rose steadily with age, while hookworm and roundworm recurrence peaked in patients 1-4 years old. Findings from the study emphasize the importance of follow up fecal examinations and treatments in patients diagnosed with endoparasites.

  6. Endoparasite prevalence and recurrence across different age groups of dogs and cats

    PubMed Central

    Gates, Maureen C.; Nolan, Thomas J.

    2009-01-01

    The apparent prevalence of endoparasite infections across different age groups was calculated from 6,555 dogs and 1,566 cats that had a fecal examination performed upon presentation to the Veterinary Hospital of the University of Pennsylvania between 1997 and 2007. Based on notations from the medical history indicating prior parasite infections, estimates of recurrence were generated for each common group of parasites, including Trichuris, Giardia, ascarids, hookworms, Cystoisospora, and tapeworms. Endoparasitism was predominantly a disease of younger animals, with peak prevalence observed almost uniformly in dogs under 6 months old, with the exception of Trichuris with its longer pre-patent period, and in cats less than 18 months old. Furthermore, nearly 50% of dogs under 6 months old with a history of parasites, were diagnosed with at least one species of parasite on subsequent fecal examination. The percentage dropped to 18.4% in animals aged 1 – 4 years, but again increased to 31.5% in animals over 10 years old. There was no reported recurrence of Giardia or Cystoisospora from canine or feline patients older than 1 year. The recurrence of whipworm rose steadily with age, while hookworm and roundworm recurrence peaked in patients 1 - 4 years old. Findings from the study emphasize the importance of follow up fecal examinations and treatments in patients diagnosed with endoparasites. PMID:19709815

  7. Maintenance energy requirements of odor detection, explosive detection and human detection working dogs.

    PubMed

    Mullis, Rebecca A; Witzel, Angela L; Price, Joshua

    2015-01-01

    Despite their important role in security, little is known about the energy requirements of working dogs such as odor, explosive and human detection dogs. Previous researchers have evaluated the energy requirements of individual canine breeds as well as dogs in exercise roles such as sprint racing. This study is the first to evaluate the energy requirements of working dogs trained in odor, explosive and human detection. This retrospective study evaluated twenty adult dogs who maintained consistent body weights over a six month period. During this time, the average energy consumption was [Formula: see text] or two times the calculated resting energy requirement ([Formula: see text]). No statistical differences were found between breeds, age or sex, but a statistically significant association (p = 0.0033, R-square = 0.0854) was seen between the number of searches a dog performs and their energy requirement. Based on this study's population, it appears that working dogs have maintenance energy requirements similar to the 1974 National Research Council's (NRC) maintenance energy requirement of [Formula: see text] (National Research Council (NRC), 1974) and the [Formula: see text] reported for young laboratory beagles (Rainbird & Kienzle, 1990). Additional research is needed to determine if these data can be applied to all odor, explosive and human detection dogs and to determine if other types of working dogs (tracking, search and rescue etc.) have similar energy requirements.

  8. Mars Express releases Beagle 2

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    Westermarck, Elias; Frias, Rafael; Skrzypczak, Teresa

    2005-01-01

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

  10. The Canine Sand Maze: an Appetitive Spatial Memory Paradigm Sensitive to Age-Related Change in Dogs

    PubMed Central

    Salvin, Hannah E; McGreevy, Paul D; Sachdev, Perminder S; Valenzuela, Michael J

    2011-01-01

    Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter circular pool was filled with a sand and powdered food reward mix to a depth of 10 cm. Dogs were given 4 habituation and 16 learning trials which alternated a food reward being half (control trials) or fully-buried (acquisition trials) in a fixed location. After a 90-min break, a probe trial was conducted. Cognitively normal, aged (> 8 years, n  =  11) and young (1–4 years, n  =  11), breed-matched dogs were compared. After correction for differences in control trials, average probe times were 2.97 and 10.81 s for young and aged dogs, respectively. In the probe trial, both groups spent significantly more time in the target quadrant but there was a trend for young dogs to cross a 1 m2 annulus zone around the buried reward more frequently (2.6 times) than aged dogs (1.5 times). Test–retest reliability in a subset of young dogs (n  =  5) was high. On the basis of these findings, the Canine Sand Maze is presented as a quick, sensitive and nonaversive tool for assessing spatial learning and reference memory in dogs. PMID:21541168

  11. Thyroid cancer in dogs: an update based on 638 cases (1995-2005).

    PubMed

    Wucherer, Katja L; Wilke, Vicki

    2010-01-01

    The goal of this study was to update the descriptive statistics of thyroid cancer by using data from multiple institutions collected through the Veterinary Medical Database (VMDB). Information was collected and reported from cases of canine thyroid cancer submitted to the VMDB between January 1, 1995 and December 31, 2005. Odds ratio (OR) analysis was performed on breeds that had > or =3% of the total number of dogs with thyroid cancer; ORs for each age category were also determined. Thyroid cancer represented 1.1% of all neoplasms during the time period of interest. Golden retrievers, beagles, and Siberian huskies all had significantly increased ORs for developing thyroid cancer. No sex predisposition was evident, but dogs between 10 and 15 years of age had a significantly increased chance of developing thyroid disease. Carcinomas and adenocarcinomas represented 90% of thyroid cancers, while adenomas represented 9.3%. Thyroid carcinoma and adenocarcinoma continue to be uncommon in our canine population. Older dogs are still more commonly affected, and this study is in agreement with previous studies that golden retrievers and beagles are overrepresented. A new finding is that Siberian huskies are also overrepresented. Carcinomas represent a much higher proportion of thyroid cancers than previously reported, and adenomas are likely incidental findings on necropsy. Thyroid cancer should be high on the list of differentials for a neck mass in older, large-breed dogs, as they make up 1.1% of the cancer cases reported. The overwhelming majority of thyroid cancers are carcinomas, and they are most common in golden retrievers, beagles, and Siberian huskies.

  12. The Legacy of Beagle 2

    NASA Astrophysics Data System (ADS)

    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.

  13. 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

    SciTech Connect

    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 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.

  14. A pharmacokinetic study of Isatin in Beagles' bodies

    PubMed Central

    REN, AILING; SU, BENHUA; YE, SIYONG; WEI, XIA; FANG, ZHAOGUO; WANG, QIAN; ZHANG, JIAN; XU, WEN; YUE, WANG; YIN, LEI; LIU, ZHANTAO; LI, XIAOLING; DING, BO

    2016-01-01

    Isatin are marine active drugs that exert anti-cancer effects, have a cancer-prevention function, and possess many pharmacological activities. The study aimed to examine the pharmacokinetics of a single intravenous injection and oral medication of Isatin given to Beagles. Nine male and nine female Beagles were injected with 30 mg/kg of 2,3-indole quinones. The animals were divided into 3 groups (n=6 per group) and lavaged with a dose of 15, 30 and 60 mg/kg, respectively. Blood samples were collected prior to the medicine delivery (0 h) and 0.083, 0.25, 0.5, 1, 2, 4, 6, 8 and 24 h post-medicine delivery. The blood plasma samples were analyzed using the liquid chromatography-mass spectrometry (MS)/MS method following pretreatment for the protein precipitation. Pharmacokinetics software was applied to calculate relevant pharmacokinetic parameters through the atrioventricular model. The drug concentration in plasma decreased rapidly following the intravenous injection of Isatin. After 8 h, the prototype drugs could not be tested in the plasma and only trace amounts of drugs were tested in one dog, which was considered to be an endogenous drug. Indole quinone was absorbed following lavage into Beagles and peaked in <1 h, and the drug concentration in the plasma decreased rapidly. After 8 h, the prototype drugs could not be tested in the plasma. The elimination of the two drugs in the body had no evident gender differences. In conclusion, Isatin is rapidly absorbed in bodies of Beagles. Within the dose range of 15–60 mg/kg, no linear relationship was observed for the increase in Cmax and AUC0-t values with the increased dose. PMID:27284305

  15. Lunar Beagle and Lunar Astrobiology

    NASA Astrophysics Data System (ADS)

    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.

  16. Domestic dogs (Canus familiaris) as sentinels of environmental health hazards: The use of canine bioassays to determine alterations in immune system function following exposure to polychlorinated biphenyl aroclor 1248

    SciTech Connect

    Fadden, M.F.K.

    1994-12-31

    The principle objective of this study was to determine if domestic dogs could be used as human surrogates to monitor the immunotoxic effects of environmental toxicants such as polychlorinated biphenyls (PCBs). Our first objective was to determine if PCBs, which are commonly found as pollutants in the environment, have specific and identifiable effects on the function of immunocompetent cells in the dog. Our second aim was to explore the pathogenesis of any defects and to determine the cellular and molecular basis for observed changes. Our third objective was to compare immune function in normal laboratory beagles to dogs living contiguous to a US EPA Superfund site located near the Mohawk Nation community of Akwesasne and to correlate any observed immunologic abnormalities to plasma levels of specific congeners of PCBs. To elucidate the effects of PCBs on the canine immune system, laboratory beagles were fed 20 ppm (n = 2), 25 ppm (n =9) and 50 ppm (n = 2) PCB Aroclor 1248 in their diet and compared with age/sex matched controls (n = 8). Peripheral blood mononuclear cells (PBMCs) were isolated from all dogs and submitted to in vitro testing. Within 8 weeks, many significant changes were seen in PCB fed dogs including: excessive lacrimation (p < .001), weight loss, decreased serum thyroxine (p < .004), increased serum alkaline phosphatase and increased blood leukocyte count (p < .01). In addition, PCB fed dogs had altered in vitro T and B cell proliferative response (p < .004) and serum immunoglobulin levels (p < .01). Following thyroxine supplementation (wk 8-16) many, but not all, immunologic abnormalities improved. Necropsy examination revealed decreased thymus (p < .02) and lymph node (p < .004) weight; all other organs appeared normal. Many of the immunologic abnormalities documented in PCB fed beagles were similar to those observed in dogs residing in the Mohawk Nation Community of Akwesasne.

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

    SciTech Connect

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

    1985-01-01

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

  18. The management of dog bite injuries of genitalia in paediatric age.

    PubMed

    Bertozzi, Mirko; Appignani, Antonino

    2013-01-01

    Dog bite injuries are common in children and represent an important health-care problem. Most dog bite injuries involve the face or an extremity. Victims tend to seek medical care quickly. Dog bites to the external genitalia are rarely reported, but they potentially result in morbidity if improperly managed. Morbidity is also directly related to the severity of initial wound. Guidelines for the management of dog bites include irrigation, debridement, antibiotic therapy, consideration of tetanus and rabies immunisation and suture of wounds or surgical reconstruction. Literature review was conducted and focused to analyze the management of dog bite lesions involving external genitalia.

  19. The Canine Sand Maze: An Appetitive Spatial Memory Paradigm Sensitive to Age-Related Change in Dogs

    ERIC Educational Resources Information Center

    Salvin, Hannah E.; McGreevy, Paul D.; Sachdev, Perminder S.; Valenzuela, Michael J.

    2011-01-01

    Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter…

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

    PubMed

    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.

  1. Lithofacies, age, and geochemistry of the Otuk Formation (Triassic) in the Red Dog District, northwest Alaska

    USGS Publications Warehouse

    Dumoulin, Julie A.; Burruss, Robert A.; Blome, Charles D.

    2011-01-01

    A complete penetration of the Otuk Fm. in continuous drill core (DH 927) from the Red Dog District illuminates the facies, age, source rock potential, and isotope stratigraphy of this unit in northwest Alaska. The section, in the Wolverine Creek plate of the Endicott Mountains Allochthon, is ~82 m thick. It gradationally overlies undated gray siliceous mudstone of the Siksikpuk Fm. and underlies undated black organic-rich mudstone of the Kingak(?) Shale. Shale, chert, and limestone members of the Otuk are recognized in DH 927 but the Blankenship Member is absent. The lower (shale) member consists of 28 m of variegated, silty shale with up to 6.9 wt % TOC; thin limy layers near the base contain bivalve fragments (Claraia sp.?) consistent with an Early Triassic (Griesbachian-early Smithian) age. Gray radiolarian chert dominates the middle member (25 m thick) and yields radiolarians of Middle Triassic (Anisian, Ladinian) and Late Triassic (Carnian-Norian) ages; a distinctive, ~2.5-m-thick interval of black shale and calcareous radiolarite ~6 m below the top has 9.8 wt % TOC. The upper (limestone) member (29 m thick) is lime mudstone with monotid bivalves and late Norian radiolarians, overlain by gray chert that contains the first Rhaetian (latest Triassic) radiolarians recognized in the Otuk. Rare black shale interbeds have up to 3.4 wt % TOC. Regional correlations indicate that Otuk lithofacies vary with both structural and geographic position.

  2. Cognitive and behavioral assessment in dogs and pet food market applications.

    PubMed

    Zicker, Steven C

    2005-03-01

    A multi-disciplinary program was developed to assess the efficacy of antioxidant inclusion in a canine pet food on cognitive decline in aged beagles. A systematic approach to development of the food was used prior to beginning the cognitive studies. Comprehensive evaluation of antioxidant ingredients included assessments of commodities with naturally occurring antioxidants and synthetic antioxidants not commonly utilized, or at different concentrations than what was commonly utilized, in commercial pet foods. Studies were conducted to insure stability through processing, absorption from the gastrointestinal tract, safety, and tests for potential antioxidant biological benefit by ex vivo tests. Testing of the antioxidant-fortified food in aged beagles slowed the rate of cognitive decline in aged dogs. In addition, environmental enrichment also slowed the rate of cognitive decline. Importantly, the combination of dietary antioxidants and environmental enrichment was synergistic and resulted in the least amount of cognitive decline over the 30-month study period. Finally, a clinical study showed that antioxidant fortified food improved age-related behavioral changes in older pet dogs at in-home situations.

  3. Tooth brushing inhibits oral bacteria in dogs.

    PubMed

    Watanabe, Kazuhiro; Hayashi, Kotaro; Kijima, Saku; Nonaka, Chie; Yamazoe, Kazuaki

    2015-10-01

    In this study, scaling, polishing and daily tooth brushing were performed in 20 beagle dogs, and the number of oral bacteria was determined using a bacterial counter. The dogs were randomized into the scaling (S), scaling + polishing (SP), scaling + tooth daily brushing (SB) and scaling + polishing + tooth daily brushing (SPB) groups. Samples were collected from the buccal surface of the maxillary fourth premolars of the dogs immediately after scaling and every week thereafter from weeks 1 to 8. Throughout the study, the number of bacteria was significantly lower in the SB and SPB groups compared with the S group. The findings suggest that daily tooth brushing inhibited oral bacterial growth in the dogs.

  4. Autonomic, endocrine and behavioural responses to thunder in laboratory and companion dogs.

    PubMed

    Franzini de Souza, Carla Caroline; Maccariello, Carolina Elisabetta Martins; Dias, Daniel Penteado Martins; Almeida, Norma Aparecida Dos Santos; Medeiros, Magda Alves de

    2017-02-01

    Dogs are highly sensitive to sound stimuli, especially fireworks, firearms, and thunder, and therefore these sounds are used as models of stress reactivity in dogs. Companion and laboratory dogs may respond differently to stressful stimuli, due to differences in management and their relationship with humans. Therefore, the reactivity of beagle dogs (laboratory) and companion dogs to an acute acoustic stress model was studied by analysing the heart rate variability (HRV; cardiac interval values), serum cortisol levels and various behavioural parameters. Eight beagles and six privately owned dogs with no history of phobia to thunder were used. The sound stimulus consisted of a standardized recording of thunder for 2.5min with a maximum intensity of 103-104dB. To evaluate the HRV, cardiac intervals were recorded using a frequency meter (Polar RS800CX model), and later the data were analysed using CardioSeries 2.4.1 software. In both laboratory and companion dogs, thunder promoted an increase in the power of the LF band of the cardiac interval spectrum, in the LF/HF ratio and in the HR, and a decrease in the power of the HF band of the cardiac interval spectrum. Companion dogs showed higher cortisol levels, than beagles, independently of the time point studied and a significant increase in the cortisol levels 15min after acoustic stress, while beagles did not show any alterations in their cortisol levels in response to the sound. On the other hand, beagles showed higher scores in the trembling, hiding, vigilance, running, salivation, bolting and startle parameters than companion dogs. Our results showed that independently of the sound stimulus, companion dogs had higher cortisol levels than laboratory dogs. Furthermore, the sound stimulus induced a marked autonomic imbalance towards sympathetic predominance in both laboratory and companion dogs. However a significant increase in the cortisol was observed only in companion dogs. On the other hand, in general the

  5. Behavior of laboratory dogs before and after rehoming in private homes.

    PubMed

    Döring, Dorothea; Nick, Ophelia; Bauer, Alexander; Küchenhoff, Helmut; Erhard, Michael H

    2017-01-01

    Although the rehoming of laboratory dogs has gained popularity, a scientific evaluation of the process is lacking. The behavior of 145 laboratory beagles was tested before leaving a research facility (Test 1). The new owners were then surveyed using a standardized telephone interview 1 week (n = 143) and 12 weeks (n = 126) after adoption. The behavior test was repeated with 68 dogs in their new homes 6 weeks after adoption (Test 2). The predictive power of Test 1 or Interview 1 on Test 2 or Interview 2, respectively, as well as the relevance of various factors was analyzed. We found no significant differences between Tests 1 and 2 regarding the behavior reactions. However, body language scores and heart rates changed significantly, indicating a more relaxed state of the dogs in their new homes. The interviews revealed a significant change toward desired behavior in most dogs within the 11 week period (p < 0.0001). The main behavior problems included separation problems (28%; n = 126), destroying objects (24%), and not being housebroken (39%). Owners of 9 dogs returned the animals, resulting in a rehoming success rate of 94%. Test 1 revealed a significant age effect (p = 0.0066), with younger and older dogs reaching higher scores than dogs who were approximately 2 years old. Dogs that had been born and reared in the research facility scored higher than dogs that had originally been acquired from a commercial breeder (p = 0.0257). The predictive power of Test 1 on Test 2 or Interview 1 on Interview 2 was moderate to low, respectively. Altogether, rehoming of laboratory dogs is a valuable alternative to euthanasia.

  6. Aging and Veterinary Care of Cats, Dogs, and Horses through the Records of Three University Veterinary Hospitals

    PubMed Central

    Cozzi, Bruno; Ballarin, Cristina; Mantovani, Roberto; Rota, Ada

    2017-01-01

    The present article examines over 63,000 medical records belonging to the Veterinary Hospitals of the Universities of Bologna, Torino, and Padova, all in Northern Italy, and relative to dogs (approximately 50,000), cats (approximately 12,000), and companion horses (slightly less than 1,000). The animals of the three species were divided into age classes and categorized per sex into males, females, and neutered individuals. The mean age at visit and the effects of age classes and category (analyzed via ANOVA) are presented and discussed. The data indicate that many animals are presented to the hospitals either in the early phases of their life (presumably for vaccination and, in cats and dogs, gonadectomy) or in the advanced age (over 10 years in dogs, over 15 years in cats, and over 17 years in horses). The records of very old individuals of the three species are also reported. On the whole, the results suggest that a growing population of mature to old domestic carnivores or companion horses reaches ages that were considered exceptional only a few years ago. The data also testify an evolution in the animal–owner relationship and a renewed respect for the value of life in companion domestic mammals. PMID:28261586

  7. In vivo evaluation of the cornea and conjunctiva of the normal laboratory beagle using Time- and Fourier-domain optical coherence tomography and ultrasound pachymetry

    PubMed Central

    Strom, Ann R.; Cortés, Dennis E.; Rasmussen, Carol A.; Thomasy, Sara M.; McIntyre, Kim; Lee, Shwu-Fei; Kass, Philip H.; Mannis, Mark J.; Murphy, Christopher J.

    2015-01-01

    Objective To obtain normative data for the canine cornea and conjunctiva using high-resolution Time- and Fourier-Domain optical coherence tomography (TD-OCT and FD-OCT) and ultrasound pachymetry (USP). Animals One hundred sixty-eight eyes of 133 healthy, young, intact laboratory beagles. Procedures The cornea and conjunctiva of 16 eyes of 8 healthy young intact female intact beagles were imaged using FD-OCT. Corneal thickness was measured with FD-OCT and USP, while corneal and conjunctival epithelial thickness was measured with FD-OCT. The central corneal thickness (CCT) was determined in 152 eyes of 125 healthy young adult intact female (35) and male (90) beagles using TD-OCT. Mixed effects linear regression was used for statistical analysis. Results The CCT was (mean ± standard deviation) 497.54 ± 29.76, 555.49 ± 17.19 and 594.81 ± 33.02 μm as measured by FD-OCT, USP and TD-OCT, respectively. The central, superior paraxial, superior perilimbal corneal epithelial thickness and superior bulbar conjunctival epithelial thickness was 52.38 ± 7.27, 56.96 ± 6.47, 69.06 ± 8.84 and 42.98 ± 6.17 μm, respectively. When comparing techniques used for measuring CCT (USP versus FD-OCT and FD-OCT versus TD-OCT), USP and TD-OCT generated significantly greater values in comparison to FD-OCT (both P < 0.001). For all dogs CCT increased with increasing age and body weight (both P < 0.001) and was higher in intact males versus females using TD-OCT (P = 0.034). Conclusion High-resolution FD-OCT and TD-OCT provide detailed non-invasive evaluation of in vivo canine anterior segment structures. Normative values of the canine cornea and conjunctiva are reported. PMID:25676065

  8. Evaluation of the effects of hypergravity exposure and caging restraint on bone mineralization in the Beagle by in vivo photon absorptiometry

    NASA Technical Reports Server (NTRS)

    Fisher, G. L.; Berding, K. L.; Goldman, M.

    1975-01-01

    Photon absorptiometry was used to evaluate bone mineral kinetics associated with normal development and the possible perturbations to bone development resulting from hypergravity exposure over a period of six months in developing Beagles. A series of seven measurements were performed at specific times with the first measurement prior to treatment and subsequent measurements at 2, 5, 9, 14, 20 and 26 weeks from the onset of the experiment. Four groups of six male Beagle pups, ranging in age from 85 to 92 days were studied. Two groups were chronically exposed to hypergravity treatments by centrifugation of 2.0 G (18.0 RPM, 11.7 ft radius) and 2.6 G (18.0 RPM, 19.8 ft radius) for the 26 week period. A third group of six dogs served as a caged control to evaluate possible changes due to confinement in small plexiglass cages similar to those of the centrifuge. Thus this control group was subjected to limited exercise due to caging restraint. The fourth group of animals was housed in open runs to allow exercise without the spatial confinement of the smaller plexiglass cages. Results show highly significant differences in body weight, bone length, increase in bone density of control group relative to other groups, and a decrease in bone mineral content in the two gravity treated groups.

  9. /sup 228/Th retention and dosimetry in beagles

    SciTech Connect

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

    1984-06-01

    Total-body and skeletal retention of /sup 228/Th were determined in a group of 104 young adult male and female beagles for about the first 7 years after the injection of 0.00159 to 2.76 ..mu..Ci/kg. Ratios of /sup 224/Ra//sup 228/Th, /sup 212/Pb//sup 228/Th, and /sup 212/Bi//sup 228/Th in the skeleton and in soft tissues of 20 beagles were measured as a function of time after injection. A humerus, femur, and ulna from 20 dogs dying 7 to 554 days after injection were sectioned, and the /sup 228/Th concentration was obtained for each piece. Ratios of daughter-to-parent activity in soft tissue showed no definite trend with dose level or time and averaged Ra/Th = 0.56, Pb/Th = 0.83, and Bi/Th = 0.91, whereas the ratios for the skeleton varied with both dose level and time. Retained /sup 228/Th was deposited most heavily in parts of the skeleton with much trabecular bone, much bone surface area, and high bone remodeling rates. No changes in this deposition pattern could be discerned during the 554 days over which the measurements of sectioned long bones were made.

  10. Soft tissue tumors among beagles injected with 90Sr, 228Ra, OR 228Th.

    PubMed

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

    1995-08-01

    The occurrence of soft-tissue tumors in beagles given 90Sr (88 dogs), 228Ra (76 dogs), or 228Th (81 dogs) as young adults and followed throughout their lifespans was compared with that of 133 control beagles given no radioactivity. For animals injected with 228Ra, tumors of the eye were more prominent (p < 0.05) than in the controls, and soft-tissue tumors of cavities in the head (excluding the brain, mouth, and eye) were more prominent in dogs given 90Sr than in the controls (p < 0.05). There was some indication that eye tumors in animals given about 0.56 kBq 228Th kg-1 were associated with their radionuclide exposure. For tumors at a few other locations, the relative occurrence was greater (p < 0.05) in the controls. These included malignant tumors of the testis and malignant plus benign tumors of the mammae and vagina in 228Th dogs; both malignant and malignant plus benign tumors of the mouth and testis, and malignant plus benign tumors of the mammae and vagina in 228Ra dogs; and malignant plus benign tumors of the mammae in 90Sr dogs (p > 0.05 by Odds Ratio Chi Square analysis but p < 0.05 by Fisher's Exact Test). Differences in relative occurrence between radioactive dogs and controls of all other tumor types that appeared in any of the animals (notably lymphosarcoma, lymph node tumors, leukemia, mast cell tumors, liver tumors, etc.) were not statistically significant (p > 0.05). Intercurrent mortality, mainly from bone cancer, was higher in the radioactive dogs than in the controls. Mean survival was reduced in the dogs given 90Sr, 228Ra, or 228Th (13.17 +/- 2.64 y in controls, 10.95 +/- 4.06 y in 90Sr dogs, 9.07 +/- 3.61 y in 228Ra dogs, and 9.20 +/- 4.15 y in 228Th dogs). Attenuated lifespans could account, at least in part, for the relative paucity of soft-tissue tumors not induced by radiation among the groups of dogs given radioactivity and occurring near the end of life for control animals.

  11. Macroscopic and histological variations in the cellular tapetum in dogs.

    PubMed

    Yamaue, Yasuhiro; Hosaka, Yoshinao Z; Uehara, Masato

    2014-08-01

    We aimed to document macroscopic variations in the cellular tapetum in the dog, to provide a histologic description of the macroscopic results and to evaluate the correlation between the macroscopic appearance and aging. Fifty three dogs including 5 beagles, 1 Chihuahua and 47 mixed breeds of each gender were used. For a macroscopic study, the fresh tapetal fundi were photographed using digital camera. For a histological study, the glutaraldehyde-formalin fixed eyes were embedded in nitrocellulose and stained with hematoxylin-eosin or thionine. The normal tapetum was triangular with the rounded angles and the smooth contour. The atypical tapetum was smaller and more variable in shape, contour and color than the normal one. In severe cases, the fundus was devoid of the tapetum. The atypical tapetum tended to increase in frequency with aging. Retinal pigment epithelial cells on the normal tapetum were unpigmented. In the eye with the atypical tapetum, regardless of tapetal size and shape, unpigmented retinal pigment epithelial cells showed a similar distribution to that on the normal tapetum, even in a dog without a tapetum. Although there is a congenitally hypoplastic tapetum, the atypical tapetum tends to increase in incidence and severity with aging.

  12. Imidacloprid plus moxidectin topical solution for the prevention of heartworm disease (Dirofiloria immitis) in dogs.

    PubMed

    Arther, R G; Bowman, D D; Slone, R L; Travis, L E

    2005-10-01

    A topically applied formulation containing 10% imidacloprid+2.5% moxidectin (Advocate/Advantage multi) has been developed for monthly application to dogs for the prevention of canine heartworm (HW) disease caused by Dirofilaria immitis; and for the treatment and control of flea infestations, mite infestations, and intestinal nematode infections. The efficacy of this formulation to prevent canine HW disease was confirmed at three study locations which included the use of 88 purpose-bred beagles 6-8 months of age. Two of these studies also evaluated the effects of post-treatment water exposure or shampooing on product performance. Each dog was infected with 50 third-stage D. immitis larvae on test days -30 to -45. Dogs were blocked according to gender and body weight on test day -1. Topically applied test articles were administered once on test day 0 as follows: 10% imidacloprid+2.5% moxidectin (52 dogs); 2.5% moxidectin mono solution (eight dogs); 10% imidacloprid mono solution (16 dogs); and placebo solution (12 dogs). Treatment dosages were applied to provide a minimum of 10 mg/kg imidacloprid and/or 2.5 mg/kg moxidectin. Subgroups of dogs were exposed to water to simulate swimming/rain exposure at designated post-treatment intervals. Additional dogs were shampooed at 90 min, 4 h, or 24 h post-treatment. All dogs were necropsied 110-119 days post-treatment for recovery of adult D. immitis. No adult D. immitis were recovered at necropsy from any of the dogs receiving 10% imidacloprid+2.5% moxidectin or 2.5% moxidectin mono solution, demonstrating 100% efficacy for prevention of D. immitis infection. A total of 701 adult D. immitis were recovered at necropsy from dogs receiving 10% imidacloprid mono solution or placebo (range of 11-40 D. immitis/dog). The efficacy of 10% imidacloprid+2.5% moxidectin treatment for the prevention of HW disease was not decreased when dogs were shampooed as early as 90 min post-treatment, or when dogs immersed in water 5 times post

  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.

    PubMed

    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., < 1.8 microg/kg/d) to not excessively down-regulate spontaneous pre-ovulatory surge release of gonadotropin or be removed shortly before or at the time when the LH surges typically occurred (10-13 days after initiation of treatment). The 1.8 microg dose was compared to saline to assess the time course of its down-regulation action on serum LH in six ovariohysterectomized bitches compared to four saline-related controls. Results in intact bitches receiving the 1.8-microg doses demonstrated an LH-releasing effect for 10-11 days that overlapped a period of obvious down-regulation seen with the same dose after 3 days in the ovariohysterectomized bitches. In the latter, however, complete down-regulation to anestrus-like values did not occur until after 18-21 days of treatment. A dose of 0.6 microg/kg/d for 12 days yielded the best estrus-induction results, including pregnancy rates of 100% in six bitches

  14. Soft-tissue tumors among beagles injected with {sup 226}Ra

    SciTech Connect

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

    1994-03-01

    A total of 409 primary soft-tissue tumors (189 malignant) occurred among 87 of 120 young adult beagles (72.5%) injected with {sup 226}Ra in eight dose levels ranging from 0.2-440 kBq kg{sup -1} body mass, while a total of 565 primary soft-tissue tumors (208 of them malignant) were seen among 117 of 133 control beagles not given radioactivity (88%). Because the p-value for the difference in these two percentages was >0.05, further comparisons were not made of all tumor locations or types taken together but only of the individual tumor locations or types. There was a clear excess of malignant tumors and all tumors (benign plus malignant) in the eye among dogs injected with radium (p < 0.05, p < 0.01, respectively), but the occurrence of all the other types of soft-tissue tumors was not greater in irradiated vs. control dogs (p > 0.05). This was also true for hematopoietic tumor types (including just one leukemia in a control and none in irradiated dogs) in which there was no difference between controls and dogs given radium. 25 refs., 7 tabs.

  15. Establishment of reference intervals for kaolin-activated thromboelastography in dogs including an assessment of the effects of sex and anticoagulant use.

    PubMed

    Bauer, Natali; Eralp, Oya; Moritz, Andreas

    2009-09-01

    Tissue factor (TF)- and kaolin-activated thromboelastography (TEG) have been performed in a small number of healthy dogs, but reference intervals have not been assessed in a larger number of dogs. The goal of the current study was to establish reference intervals and assess intra-assay repeatability for kaolin-activated TEG in dogs. Additionally, the impact of sex and the influence of anticoagulant (native blood vs. recalcified citrate anticoagulated blood) were evaluated. Thromboelastography analyses were performed in 56 healthy dogs including German Shepherd Dogs (n = 19), Beagles (n = 15), and others (n = 22). Median age was 2 years (range: 1-6 years) and sex was evenly distributed (31 males and 25 females). To establish reference intervals, citrated whole-blood samples were collected, and TEG was performed 1 hr after sampling. Five TEG variables (R = reaction time; K = clot formation time; alpha = angle alpha; MA = maximal amplitude; G-value reflecting clot stability) were evaluated, and reference intervals were defined as the mean +/- 1.96-fold standard deviation. Intra-assay repeatability was assessed by calculating the pooled variance estimate in duplicate measurements of 6 healthy dogs. The effect of anticoagulant was assessed in 17 specimens. Reference intervals were as follows: R = 1.8-8.6 min; angle alpha = 36.9-74.6 degrees; K = 1.3-5.7 min; MA = 42.9-67.9 mm, and G = 3.2-9.6 Kdyn/cm(2). Coefficients of variation for R, K, angle alpha, MA, and G were 7.6%, 17.7%, 7.4%, 2.9%, and 6.6%, respectively. There was no significant impact of sex or anticoagulant on results. Interindividual variation was higher in native samples than in citrated whole blood. A limitation of the current study was that most of the samples were obtained from Beagles and German Shepherd Dogs. This study provides useful reference intervals for kaolin-activated TEG.

  16. An Antioxidant Dietary Supplement Improves Brain-Derived Neurotrophic Factor Levels in Serum of Aged Dogs: Preliminary Results

    PubMed Central

    Sechi, Sara; Chiavolelli, Francesca; Spissu, Nicoletta; Di Cerbo, Alessandro; Canello, Sergio; Guidetti, Gianandrea; Fiore, Filippo; Cocco, Raffaella

    2015-01-01

    Biological aging is characterized by a progressive accumulation of oxidative damage and decreased endogenous antioxidant defense mechanisms. The production of oxidants by normal metabolism damages proteins, lipids, and nucleotides, which may contribute to cognitive impairment. In this study 36 dogs were randomly divided into four groups and fed croquettes of different compositions for 6 months. We monitored derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potential (BAP) levels in dogs' plasma samples as well as brain-derived neurotrophic factor (BDNF) serum levels at the beginning and at the end of the dietary regime. Our results showed that a dietary regime, enriched with antioxidants, induced a significant decrease of plasma levels of dROMs (p < 0.005) and a significant increase in BDNF serum levels (p < 0.005) after six months. Thus, we hypothesized a possible role of the diet in modulating pro- and antioxidant species as well as BDNF levels in plasma and serum, respectively. In conclusion the proposed diet enriched with antioxidants might be considered a valid alternative and a valuable strategy to counteract aging-related cognitive decline in elderly dogs. PMID:26464952

  17. Review of idiopathic eosinophilic meningitis in dogs and cats, with a detailed description of two recent cases in dogs.

    PubMed

    Williams, J H; Köster, L S; Naidoo, V; Odendaal, L; Van Veenhuysen, A; de Wit, M; van Wilpe, E

    2008-12-01

    Eosinophilic meningoencephalitis (EME) has been described in various species of animals and in humans. In dogs it has been associated with protozoal infections, cuterebral myiasis and various other aetiologies. Ten cases of idiopathic eosinophilic meningoencephalitis have been reported in dogs and one in a cat where the origin was uncertain or unknown. The dogs were all males, of various breeds but with a predominance of Golden Retrievers and Rottweilers; they generally had a young age of onset. Two cases with no apparent underlying aetiology were diagnosed on post mortem examination. The 18-month-old, male Boerboel presented with sudden onset of cerebellar ataxia, as well as various asymmetrical cranial nerve deficits of 2 weeks' duration and without progression. Haematology revealed a peripheral eosinophilia. Necropsy showed extreme generalised congestion especially of the meninges and blood smear and histological sections of various tissues showed intravascular erythrocyte fragmentation with the formation of microcytes. Histopathology revealed severe diffuse cerebrocortical subarachnoidal meningitis and submeningeal encephalitis, the exudate containing variable numbers of eosinophils together with neutrophils and mononuclear cells. There was also deeper white matter and hippocampal multifocal perivascular mononuclear encephalitis and multifocal periventricular malacia, gliosis and phagocytosis of white matter. The cerebellum, brain stem and spinal c showed only mild multifocal oedema or scattered occasional axon and myelin degeneration respectively, with no inflammation. Immunohistochemical staining of central nervous tissue for Toxoplasma gondii failed to show any antigen in the central nervous tissue. Ultrastructure of a single submeningeal suspected parasitic cyst showed it to be chromatin clumping within a neuron nucleus indicating karyorrhexis. Gram stain provided no evidence of an aetiological agent. The 3-year-old Beagle bitch had a Caesarian section

  18. Retinal dysplasia and progressive atrophy in dogs irradiated during ocular development

    SciTech Connect

    Schweitzer, D.J.; Benjamin, S.A.; Lee, A.C.

    1987-08-01

    Beagle dogs were given a single, whole-body gamma-radiation exposure at various stages during ocular development and were evaluated for the presence of ocular lesions. Dogs were exposed during middle or late pregnancy at 28 or 55 days postcoitus (dpc) or as neonates at 2 days postpartum (dpp). Mean whole-body and ocular doses ranged from 1.0 to 3.8 Gy. Dogs were sacrificed and ocular lesions were evaluated at 70 days, 2 years, or 4 years of age. Retinal dysplasias and atrophy were the most striking lesions related to radiation exposure. These lesions were bilateral and focal to diffuse in nature, and they increased in severity with increasing radiation dose. The stage of development at irradiation had a marked effect on the distribution of retinal lesions, with the most severe changes being present in that portion of the retina undergoing differentiation at the time of the insult. In dogs sacrificed at 70 days of age the lesions were primarily dysplasias consisting of ectopic nuclear aggregates in the photoreceptor layer, retinal folds, and retinal rosettes. With increasing age (up to 4 years), there appeared to be progression of the extent of the clinically evident lesions, and there was a change in the nature of the lesions from dysplasia to atrophy. This was accompanied by marked attenuation of the retinal vasculature.

  19. Motivational Factors Underlying Problem Solving: Comparing Wolf and Dog Puppies' Explorative and Neophobic Behaviors at 5, 6, and 8 Weeks of Age.

    PubMed

    Marshall-Pescini, Sarah; Virányi, Zsófia; Kubinyi, Enikő; Range, Friederike

    2017-01-01

    Background: Wolves have been shown to be better in independent problem-solving tasks than dogs, however it is unclear whether cognitive or motivational factors underlie such differences. In a number of species problem solving has been linked to both persistence in exploration and neophobia, suggesting both these aspects may underlie dog-wolf differences in problem solving. Indeed adult wolves have been shown to be more likely to approach a novel object and more persistent in their investigation of it, but also slower in making contact with it and more fearful of it than dogs. Methods: In the current study we investigated potential differences in equally-raised dogs' and wolves' explorative and neophobic behaviors in a novel environment and with novel objects at 5, 6, and 8 weeks of age. Results: Results showed that wolves were more persistent in exploring both the environment and the objects than dogs, and this was the case at all ages. There were no differences in the frequency of fear-related behaviors and time spent in proximity to humans. Stress-related behaviors were similarly expressed at 5 and 6 weeks, although wolves showed a higher frequency of such behaviors at 8 weeks. Discussion: Overall, results with puppies confirm those with adult animals: wolves appear to be more explorative than dogs. Such motivational differences need to be taken into account when comparing dogs and wolves in cognitive tasks.

  20. Motivational Factors Underlying Problem Solving: Comparing Wolf and Dog Puppies' Explorative and Neophobic Behaviors at 5, 6, and 8 Weeks of Age

    PubMed Central

    Marshall-Pescini, Sarah; Virányi, Zsófia; Kubinyi, Enikő; Range, Friederike

    2017-01-01

    Background: Wolves have been shown to be better in independent problem-solving tasks than dogs, however it is unclear whether cognitive or motivational factors underlie such differences. In a number of species problem solving has been linked to both persistence in exploration and neophobia, suggesting both these aspects may underlie dog-wolf differences in problem solving. Indeed adult wolves have been shown to be more likely to approach a novel object and more persistent in their investigation of it, but also slower in making contact with it and more fearful of it than dogs. Methods: In the current study we investigated potential differences in equally-raised dogs' and wolves' explorative and neophobic behaviors in a novel environment and with novel objects at 5, 6, and 8 weeks of age. Results: Results showed that wolves were more persistent in exploring both the environment and the objects than dogs, and this was the case at all ages. There were no differences in the frequency of fear-related behaviors and time spent in proximity to humans. Stress-related behaviors were similarly expressed at 5 and 6 weeks, although wolves showed a higher frequency of such behaviors at 8 weeks. Discussion: Overall, results with puppies confirm those with adult animals: wolves appear to be more explorative than dogs. Such motivational differences need to be taken into account when comparing dogs and wolves in cognitive tasks. PMID:28232814

  1. Human-directed social behaviour in dogs shows significant heritability.

    PubMed

    Persson, M E; Roth, L S V; Johnsson, M; Wright, D; Jensen, P

    2015-04-01

    Through domestication and co-evolution with humans, dogs have developed abilities to attract human attention, e.g. in a manner of seeking assistance when faced with a problem solving task. The aims of this study were to investigate within breed variation in human-directed contact seeking in dogs and to estimate its genetic basis. To do this, 498 research beagles, bred and kept under standardized conditions, were tested in an unsolvable problem task. Contact seeking behaviours recorded included both eye contact and physical interactions. Behavioural data was summarized through a principal component analysis, resulting in four components: test interactions, social interactions, eye contact and physical contact. Females scored significantly higher on social interactions and physical contact and age had an effect on eye contact scores. Narrow sense heritabilities (h(2) ) of the two largest components were estimated at 0.32 and 0.23 but were not significant for the last two components. These results show that within the studied dog population, behavioural variation in human-directed social behaviours was sex dependent and that the utilization of eye contact seeking increased with age and experience. Hence, heritability estimates indicate a significant genetic contribution to the variation found in human-directed social interactions, suggesting that social skills in dogs have a genetic basis, but can also be shaped and enhanced through individual experiences. This research gives the opportunity to further investigate the genetics behind dogs' social skills, which could also play a significant part into research on human social disorders such as autism.

  2. CSU-FDA (Colorado State Univ. -Food and Drug Administration) Collaborative Radiological Health Laboratory. Annual report - 1982: health effects of prenatal and postnatal whole-body exposure to ionizing radiation in the beagle dog

    SciTech Connect

    Benjamin, S.A.

    1984-09-01

    The Collaborative Radiological Health Laboratory was established in 1962 by the U.S. Public Health Service and Colorado State University for the purpose of determining in a carefully controlled animal experiment the life-time hazards associated with prenatal and early postnatal exposure to ionizing radiation. The CRHL study is designed to provide information that will facilitate the evaluation of risks to human beings from medical exposure during early development. The study is a long-term (lifespan) study of a moderately large and long-lived mammal exposed at one of several times during development to a relatively small and discrete dose of external radiation. Ages at irradiation selected for comparison reflect the primary concern with medical exposures during the development period. This annual report summarizes the current status of the study for the reporting period of January 1 through December 31, 1982.

  3. Evaluation of respiratory function by barometric whole-body plethysmography in healthy dogs.

    PubMed

    Talavera, Jesús; Kirschvink, Nathalie; Schuller, Simone; Garrérès, Alain Le; Gustin, Pascal; Detilleux, Johanne; Clercx, Cécile

    2006-07-01

    The objective of the present study was to assess the validity of barometric whole-body plethysmography (BWBP), to establish reference values, and to standardise a bronchoprovocative test to investigate airway responsiveness using BWBP in healthy dogs. BWBP measurements were obtained from six healthy beagle dogs using different protocols: (1) during three consecutive periods (3.5min each) in two morning and two evening sessions; (2) before and after administration of two protocols of sedation; (3) before and after nebulisation of saline and increasing concentrations of carbachol and histamine both in conscious dogs and in dogs under both protocols of sedation. Enhanced pause (PENH) was used as index of bronchoconstriction. Basal BWBP measurements were also obtained in 22 healthy dogs of different breeds, age and weight. No significant influence of either time spent in the chamber or daytime was found for most respiratory variables but a significant dog effect was detected for most variables. A significant body weight effect was found on tidal volume and peak flow values (P<0.05). Response to carbachol was not reproducible and always associated with side effects. Nebulisation of histamine induced a significant increase in respiratory rate, peak expiratory flow, peak expiratory flow/peak inspiratory flow ratio and PENH (P<0.05). The response was reproduced in each dog at different concentrations of histamine. Sedation with acepromazine+buprenorphine had little influence on basal measurements and did not change the results of histamine challenge. It was concluded that BWBP is a safe, non invasive and reliable technique of investigation of lung function in dogs which provides new opportunities to characterise respiratory status, to evaluate airway hyperresponsiveness and to assess therapeutic interventions.

  4. Hepatic effects of inhaled plutonium dioxide in beagles

    SciTech Connect

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

    1995-10-01

    The effects of inhaled {sup 238}PuO{sub 2} deposited in the liver of dogs were studied in beagles exposed to initial lung depositions ranging from 5.7 to 2979.7 Bq/g lung. Approximately 20% of the initial lung deposition was translocated to the liver by 1500 days after exposure. Life-span observations revealed that the liver contained 40% of the final body burden of plutonium, second only to the skeleton. Elevated serum liver enzyme activities were observed in dogs with final liver depositions of {ge}0.4 Bq/g, cumulative dose to the liver of {ge}0.18 Gy and annual dose rate {ge}0.02 Gy/year. Enzyme elevations were seen at one dose level lower than that in which bone or lung tumors were observed. Linear regression analysis revealed strong to moderate correlation between cumulative dose and dose rate and time to observed increases in liver enzyme activities. Liver tumors were late occurring neoplasms observed at lower exposure levels where life span was not shortened by lung and bone tumors. 22 refs., 4 figs., 9 tabs.

  5. Beagle 2: Mission to Mars - Current Status

    NASA Technical Reports Server (NTRS)

    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.

  6. Age at vaccination may influence response to sylvatic plague vaccine (SPV) in Gunnison’s prairie dogs (Cynomys gunnisoni)

    USGS Publications Warehouse

    Rocke, Tonie E.; Tripp, Daniel W.; Lorenzsonn, Faye; Falendysz, Elizabeth A.; Smith, Susan; Williamson, Judy L.; Abbott, Rachel C.

    2015-01-01

    Gunnison’s prairie dogs (Cynomys gunnisoni) have been considered at greater risk from Yersinia pestis (plague) infection in the montane portion of their range compared to populations at lower elevations, possibly due to factors related to flea transmission of the bacteria or greater host susceptibility. To test the latter hypothesis and determine whether vaccination against plague with an oral sylvatic plague vaccine (SPV) improved survival, we captured prairie dogs from a C. g. gunnisoni or “montane” population and a C. g. zuniensis or “prairie” population for vaccine efficacy and challenge studies. No differences (P = 0.63) were found in plague susceptibility in non-vaccinated animals between these two populations; however, vaccinates from the prairie population survived plague challenge at significantly higher rates (P < 0.01) than those from the montane population. Upon further analysis, we determined that response to immunization was most likely associated with differences in age, as the prairie group was much younger on average than the montane group. Vaccinates that were juveniles or young adults survived plague challenge at a much higher rate than adults (P < 0.01 and P = 0.02, respectively), but no difference (P = 0.83) was detected in survival rates between control animals of different ages. These results suggest that host susceptibility is probably not related to the assumed greater risk from plague in the C. g. gunnisoni or “montane” populations of Gunnison’s prairie dogs, and that SPV could be a useful plague management tool for this species, particularly if targeted at younger cohorts.

  7. Age at Vaccination May Influence Response to Sylvatic Plague Vaccine (SPV) in Gunnison's Prairie Dogs (Cynomys gunnisoni).

    PubMed

    Rocke, Tonie E; Tripp, Dan; Lorenzsonn, Faye; Falendysz, Elizabeth; Smith, Susan; Williamson, Judy; Abbott, Rachel

    2015-06-01

    Gunnison's prairie dogs (Cynomys gunnisoni) have been considered at greater risk from Yersinia pestis (plague) infection in the montane portion of their range compared to populations at lower elevations, possibly due to factors related to flea transmission of the bacteria or greater host susceptibility. To test the latter hypothesis and determine whether vaccination against plague with an oral sylvatic plague vaccine (SPV) improved survival, we captured prairie dogs from a C. g. gunnisoni or "montane" population and a C. g. zuniensis or "prairie" population for vaccine efficacy and challenge studies. No differences (P = 0.63) were found in plague susceptibility in non-vaccinated animals between these two populations; however, vaccinates from the prairie population survived plague challenge at significantly higher rates (P < 0.01) than those from the montane population. Upon further analysis, we determined that response to immunization was most likely associated with differences in age, as the prairie group was much younger on average than the montane group. Vaccinates that were juveniles or young adults survived plague challenge at a much higher rate than adults (P < 0.01 and P = 0.02, respectively), but no difference (P = 0.83) was detected in survival rates between control animals of different ages. These results suggest that host susceptibility is probably not related to the assumed greater risk from plague in the C. g. gunnisoni or "montane" populations of Gunnison's prairie dogs, and that SPV could be a useful plague management tool for this species, particularly if targeted at younger cohorts.

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

    SciTech Connect

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

    1996-12-01

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

  9. Antibodies reacting to carbonic anhydrase isozymes (I and II) and albumin in sera from dogs.

    PubMed

    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.

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

    PubMed

    Kubinyi, Eniko; Turcsán, Borbála; Miklósi, Adám

    2009-07-01

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

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:27119092

  13. Age and sex distribution of Dirofilaria immitis among dogs in Meshkin-Shahr, northwest Iran and molecular analysis of the isolates based on COX1 gene

    PubMed Central

    Zarei, Zabiholah; Kia, Eshrat Beigom; Heidari, Zahra; Mikaeili, Fattaneh; Mohebali, Mehdi; Sharifdini, Meysam

    2016-01-01

    Dirofilaria immitis is an important filarial nematode in dogs. In this study, age and sex distribution of this zoonotic nematode among dogs were investigated in northwest of Iran in Meshkin-Shahr city. Molecular characteristics of the isolates, based on cytochrome oxidase subunit 1 (COX1) gene were compared to the isolates from other areas of the world.Blood samples were collected from 91 dogs which were selected by simple classified accidental sampling. Thin and thick blood smear examinations were used to find out infectivity with D. immitis. DNA extraction was performed from adult D. immitis recovered from heart of infected dogs. The COX1 gene was amplified and sequenced. Phylogenetic analysis was carried out using sequences obtained in this study along with relevant sequences deposited in the GenBank. Phylogenetic analysis and sequence variation was performed using MEGA software in comparison with those COX1 sequences deposited in GenBank. Out of 91 dogs, 19 (20.87%) were found positive for infection with D. immitis. There was no statistically significant difference between males and females of dogs in terms of D. immitis infection. However, the rate of infection in dogs more than 2 years old was significantly higher than those with lower age. Both sequences analyzed in this study showed 100% homology to each other. Intra-species variation of these isolates with those from other areas of the world amounted to 0 to 0.50%. Phylogenetic analysis of the COX1 gene suggested that it is conserved, and can be used for study on genetic diversity and classification of filarial nematodes. PMID:28144425

  14. Human-dog interactions in a guide-dog training program.

    PubMed

    Koda, N; Shimoju, S

    1999-06-01

    We analyzed dyadic interactions between 12 neutered dogs (6 females and 6 males) and 44 humans (20 women, 14 men, and 10 girls) who were unfamiliar with each other. We also examined the effect of sex differences in dogs and humans as well as age differences in humans on human-dog interactions in a guide-dog training program. Female dogs more actively regulated their distance from humans than male dogs. Dogs made contact with women more frequently than with men, and men made contact with dogs more frequently than women. Girls initiated interactions with dogs more frequently than women; girls formed reciprocal interactions with dogs less frequently than women.

  15. Soft tissue tumors among beagles injected with {sup 90}Sr, {sup 228}Ra, or {sup 228}Th

    SciTech Connect

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

    1995-08-01

    The occurrence of soft-tissue tumors in beagles given {sup 90}Sr (88 dogs), {sup 228}Ra (76 dogs), or {sup 228}Th (81 dogs) as young adults and followed throughout their lifespans was compared with that of 133 control beagles given no radioactivity. For animals injected with {sup 228}Ra, tumors of the eye were more prominent (p<0.05) than in the controls, and soft-tissue tumors of cavities in the head (excluding the brain, mouth, and eye) were more prominent in dogs given {sup 90}Sr than in the controls (p<0.05). There was some indication that eye tumors in animals given about 0.56 kBq {sup 228}Th kg{sup {minus}1} were associated with their radionuclide exposure. For tumors at a few other locations, the relative occurrence was greater (p<0.05) in the controls. These included malignant tumors of the testis, and malignant plus benign tumors of the mammae and vagina in {sup 228}Ra dogs; and malignant plus benign tumors of the mammae in {sup 90}Sr dogs (p>0.05 by Odds Ratio Chi Square analysis but p<0.05 by Fiosher`s Exact Test). Differences in relative occurrence between radioactive dogs and controls of all other tumor types that appeared in any of the animals (notably lymphosarcoma, lymph node tumors, leukemia, mast cell tumors, liver tumors, etc.) were not statistically significant (p > 0.05). Intercurrent mortality, mainly from bone cancer, was higher in the radioactive dogs than in the controls. Mean survival was reduced in the dogs given {sup 90}Sr, {sup 228}Ra, or {sup 228}Th(13.17 {plus_minus} 2.64 y in controls, 10.95 {plus_minus} 4.06 y in {sup 90}Sr dogs, 9.07 {plus_minus} 3.61 y in {sup 228}Ra dogs, and 9.20 {plus_minus}4.15 y in {sup 228}Th dogs). Attenuated lifespans could account, at least in part, for the relative paucity of soft-tissue tumors not induced by radiation among the groups of dogs given radioactivity and occurring near the end of life for control animals. 24 refs., 3 tabs.

  16. Age-related changes in the articular cartilage of the stifle joint in non-working and working German Shepherd dogs.

    PubMed

    Francuski, J V; Radovanović, A; Andrić, N; Krstić, V; Bogdanović, D; Hadzić, V; Todorović, V; Lazarević Macanović, M; Sourice Petit, S; Beck-Cormier, S; Guicheux, J; Gauthier, O; Kovacević Filipović, M

    2014-11-01

    The aims of this study were to define age-related histological changes in the articular cartilage of the stifle joint in non-chondrodystrophic dogs and to determine whether physical activity has a positive impact on preservation of cartilage structure during ageing. Twenty-eight German shepherd dogs were included in the study. These dogs had no evidence of joint inflammation as defined by clinical assessment, radiology and synovial fluid analysis (specifically absence of synovial fluid serum amyloid A). The dogs were grouped as young working (n ¼ 4), young non-working (n ¼ 5), aged working (n ¼ 13) and aged non-working (n ¼ 6) animals. Gross changes in the stifle joints were recorded and biopsy samples of femoral and tibial articular cartilage were evaluated for thickness; chondrocyte number, density, surface area and morphology; isogenous group morphology; tidemark integrity; subchondral bone structure; presence of proteoglycans/ glycosaminoglycans; and expression of type I, II and X collagens. The major age-related changes, not related to type of physical activity, included elevated chondrocyte density and thinning of tibial cartilage and increased chondrocyte surface area in the superficial and intermediate zone of the femoral cartilage. There was also expression of type X collagen in the femoral and tibial calcified and non-calcified cartilage; however, type X collagen was not detected in the superficial zone of old working dogs. Therefore, ageing, with or without physical activity, leads to slight cartilage degeneration, while physical activity modulates the synthesis of type X collagen in the superficial cartilage zone, partially preserving the structure of hyaline cartilage.

  17. Young to Middle-Aged Dogs with High Amyloid-β Levels in Cerebrospinal Fluid are Impaired on Learning in Standard Cognition tests

    PubMed Central

    Borghys, Herman; Van Broeck, Bianca; Dhuyvetter, Deborah; Jacobs, Tom; de Waepenaert, Katja; Erkens, Tim; Brooks, Melissa; Thevarkunnel, Sandy; Araujo, Joseph A.

    2016-01-01

    Understanding differences in Alzheimer’s disease biomarkers before the pathology becomes evident can contribute to an improved understanding of disease pathogenesis and treatment. A decrease in amyloid-β (Aβ)42 in cerebrospinal fluid (CSF) is suggested to be a biomarker for Aβ deposition in brain. However, the relevance of CSF Aβ levels prior to deposition is not entirely known. Dogs are similar to man with respect to amyloid-β protein precursor (AβPP)-processing, age-related amyloid plaque deposition, and cognitive dysfunction. In the current study, we evaluated the relation between CSF Aβ42 levels and cognitive performance in young to middle-aged dogs (1.5–7 years old). Additionally, CSF sAβPPα and sAβPPβ were measured to evaluate AβPP processing, and CSF cytokines were measured to determine the immune status of the brain. We identified two groups of dogs showing consistently low or high CSF Aβ42 levels. Based on prior studies, it was assumed that at this age no cerebral amyloid plaques were likely to be present. The cognitive performance was evaluated in standard cognition tests. Low or high Aβ concentrations coincided with low or high sAβPPα, sAβPPβ, and CXCL-1 levels, respectively. Dogs with high Aβ concentrations showed significant learning impairments on delayed non-match to position (DNMP), object discrimination, and reversal learning compared to dogs with low Aβ concentrations. Our data support the hypothesis that high levels of CSF Aβ in dogs coincide with lower cognitive performance prior to amyloid deposition. Further experiments are needed to investigate this link, as well as the relevance with respect to Alzheimer’s disease pathology progression. PMID:28035921

  18. Young to Middle-Aged Dogs with High Amyloid-β Levels in Cerebrospinal Fluid are Impaired on Learning in Standard Cognition tests.

    PubMed

    Borghys, Herman; Van Broeck, Bianca; Dhuyvetter, Deborah; Jacobs, Tom; de Waepenaert, Katja; Erkens, Tim; Brooks, Melissa; Thevarkunnel, Sandy; Araujo, Joseph A

    2017-01-01

    Understanding differences in Alzheimer's disease biomarkers before the pathology becomes evident can contribute to an improved understanding of disease pathogenesis and treatment. A decrease in amyloid-β (Aβ)42 in cerebrospinal fluid (CSF) is suggested to be a biomarker for Aβ deposition in brain. However, the relevance of CSF Aβ levels prior to deposition is not entirely known. Dogs are similar to man with respect to amyloid-β protein precursor (AβPP)-processing, age-related amyloid plaque deposition, and cognitive dysfunction. In the current study, we evaluated the relation between CSF Aβ42 levels and cognitive performance in young to middle-aged dogs (1.5-7 years old). Additionally, CSF sAβPPα and sAβPPβ were measured to evaluate AβPP processing, and CSF cytokines were measured to determine the immune status of the brain. We identified two groups of dogs showing consistently low or high CSF Aβ42 levels. Based on prior studies, it was assumed that at this age no cerebral amyloid plaques were likely to be present. The cognitive performance was evaluated in standard cognition tests. Low or high Aβ concentrations coincided with low or high sAβPPα, sAβPPβ, and CXCL-1 levels, respectively. Dogs with high Aβ concentrations showed significant learning impairments on delayed non-match to position (DNMP), object discrimination, and reversal learning compared to dogs with low Aβ concentrations. Our data support the hypothesis that high levels of CSF Aβ in dogs coincide with lower cognitive performance prior to amyloid deposition. Further experiments are needed to investigate this link, as well as the relevance with respect to Alzheimer's disease pathology progression.

  19. Experimental pharmacodynamics and analgesic efficacy of liposome-encapsulated hydromorphone in dogs.

    PubMed

    Krugner-Higby, Lisa; Smith, Lesley; Schmidt, Brynn; Wunsch, Laura; Smetana, Andrea; Brown, Carolyn; Heath, Timothy D

    2011-01-01

    The purpose of this study was to determine the experimental side effects of liposome-encapsulated hydromorphone (LE-Hydro) in beagles and to evaluate LE-Hydro analgesia in dogs undergoing ovariohysterectomies (OVH). Beagles were injected subcutaneously with 1-3 mg/kg LE-Hydro or 0.1 mg/kg hydromorphone. Dogs were evaluated for sedation, temperature, respiratory rate, and heart rate. OVH dogs were injected with 2 mg/kg LE-Hydro subcutaneously or 0.2 mg/kg morphine and 0.05 mg/kg acepromazine intramuscularly. Side effects of LE-Hydro were within clinically acceptable limits. The analgesic efficacy was superior in dogs administered LE-Hydro at 12 hr postsurgically. LE-Hydro provided adequate, durable analgesia in dogs undergoing OVH.

  20. Isolation and immunisation studies of a canine parco-like virus from dogs with haemorrhagic enteritis.

    PubMed

    Appel, M J; Scott, F W; Carmichael, L E

    1979-08-25

    A newly recognised canine parvo like virus was isolated from faeces of dogs with haemorrhagic enteritis. Cell cultures from several species were susceptible to it. Virus infected cells could be demonstrated by staining with fluorescent antibody reagents (prepared against canine virus or feline panleucopenia virus) or by haemagglutination with pig or rhesus monkey red blood cells. Inhibition of haemagglutination by specific antiserum prepared in specific-pathogen-free beagles provided a convenient method for viral identification. Experimental inoculation of specific-pathogen-free beagles resulted in elevated body temperatures and caused lymphopenia lasting one to three days. Feline panleucopenia virus vaccines protected dogs against challenge with virulent canine parvo-like virus.

  1. Tooth brushing inhibits oral bacteria in dogs

    PubMed Central

    WATANABE, Kazuhiro; HAYASHI, Kotaro; KIJIMA, Saku; NONAKA, Chie; YAMAZOE, Kazuaki

    2015-01-01

    In this study, scaling, polishing and daily tooth brushing were performed in 20 beagle dogs, and the number of oral bacteria was determined using a bacterial counter. The dogs were randomized into the scaling (S), scaling + polishing (SP), scaling + tooth daily brushing (SB) and scaling + polishing + tooth daily brushing (SPB) groups. Samples were collected from the buccal surface of the maxillary fourth premolars of the dogs immediately after scaling and every week thereafter from weeks 1 to 8. Throughout the study, the number of bacteria was significantly lower in the SB and SPB groups compared with the S group. The findings suggest that daily tooth brushing inhibited oral bacterial growth in the dogs. PMID:25994486

  2. Distribution of skeletal malignancies in beagles injected with {sup 239}Pu citrate

    SciTech Connect

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

    1994-04-01

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

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

    PubMed Central

    You, Guo-xing; Wang, Ying; Chen, Gan; Wang, Quan; Zhang, Xi-gang; Zhao, Lian; Zhou, Hong; He, Yue-zhong

    2015-01-01

    Objective 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. Methods 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. Results 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. Conclusions 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

  4. Imaging diagnosis--hyperostosis associated with meningioma in a dog.

    PubMed

    Mercier, Miyu; Heller, Heidi L Barnes; Bischoff, Matthew G; Looper, Jayme; Bacmeister, Cynthia X

    2007-01-01

    A 5-year-old neutered male Beagle mix dog had a 5-day history of generalized tonic-clonic seizures. Before the seizures, the dog had a 1-2-month history of progressive right hemiparesis. In computed tomography images, a presumed extraaxial mass with hyperostosis and destruction of the skull covering the mass were identified. Surgical excision was performed and the histopathologic diagnosis was meningioma. Hyperostosis is frequently associated with feline meningioma, but this report documents that hyperostosis may also occur secondary to meningioma in the dog.

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  6. Prevalence of ultrasound-determined cystic endometrial hyperplasia and the relationship with age in dogs.

    PubMed

    Moxon, Rachel; Whiteside, Helen; England, Gary C W

    2016-09-01

    To investigate the potential relationship between age and diagnosis of cystic endometrial hyperplasia (CEH) in the bitches, 348 ultrasound examinations from 240 bitches (Labradors, Golden Retrievers, German Shepherds, Flat Coated Retrievers, or crosses of those breeds aged between 1.6 and 7.2 years at examination) were examined. A subpopulation of 32 bitches that had completed their breeding careers at 6 years or more of age was also identified. Of all, 18.3% of the bitches were diagnosed with CEH; these cases were newly diagnosed when bitches were between 2.5 years and 7.3 years of age. The proportion of ultrasound examinations in which CEH was identified increased from 6.8% of examinations on 2-year-old breeding bitches to 60.0% of examinations on 6-year-old bitches. Logistic regression identified a positive correlation between mean age at the examination and presence of CEH (χ(2) = 30.74, degrees of freedom = 1, P < 0.001). For 32 bitches that had completed their breeding career, the prevalence of CEH was 56.3%, age at the diagnosis ranged from 3.8 to 7.3 years, and the proportion of bitches affected with CEH increased from 6.3% at 3 years of age to 56.3% at 7 years of age. These data support the contention that the prevalence of CEH increases with age.

  7. Soft tissue tumors in beagles injected with {sup 241}Am citrate

    SciTech Connect

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

    1995-02-01

    The occurrence of soft tissue tumors has been studied in 117 beagles assigned to 8 dosage groups of between 2 and 26 animals each and injected with 0.07 to 104 kBq {sup 241}Am kg{sup -1} as the citrate. In addition, 133 control beagles given no radioactivity were used as a comparison group. All 250 dogs were maintained under identical conditions and were observed for their entire lifespans. An important competing risk for the appearance of soft tissue tumors appeared to be the occurrence of skeletal malignancy, and at the highest injected activity (104) kBq kg{sup -1}, kidney and liver failure brought about the death of both of the two dogs in this group. Thyroid and liver were the only soft tissues that exhibited greater concentrations of {sup 241}Am than the skeleton. Liver tumors were associated {sup 241}Am exposure (p < 0.001), but the thyroid tumor rate was not increased significantly in the irradiated animals (p > 0.10) as compared with the occurrence in controls. There was a greater relative occurrence of all vaginal tumors in control animals than in dogs given {sup 241}Am, a situation also found for all tumors of the pancreas, skin, testis, and mammary glands and for malignant ovarian tumors. All of these differences were statistically significant. The survival of animals given 0.07 to 0.59 kBq {sup 241}Am Kg{sup -1} could not be established (p > 0.10) as significantly different from controls, but the survival of all groups given 1.8 to 104 kBq kg{sup -1} was decreased (p < 0.05). There was no indication in our studies of a positive association between relative exposure to {sup 241}Am and the occurrence of mammary tumors, mast cell sarcomas originating outside the liver, lymphosarcoma or tumors of marrow, including leukemia. 20 refs., 1 fig., 8 tabs.

  8. [Dog bites].

    PubMed

    Horn, Benedikt

    2015-01-01

    In Switzerland 10'000 people are bitten by a dog annualy. Dog bites are notifiable incidents. Defensive and offensive aggression of dogs (why does a dog bite?), history, signs, treatment and prevention are discussed. Finally a short psychogram of dog owner and victim emphasizes the role of avoiding any escalation.

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

    NASA Technical Reports Server (NTRS)

    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.

  10. Brown dog tick, Rhipicephalus sanguineus sensu lato, infestation ofsusceptible dog hosts is reduced by slow release of semiochemicalsfrom a less susceptible host

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  11. Pharmacokinetics of ammonium sulfate gradient loaded liposome-encapsulated oxymorphone and hydromorphone in healthy dogs

    PubMed Central

    Smith, Lesley J.; Kukanich, Butch K.; Krugner-Higby, Lisa A.; Schmidt, Brynn H.; Heath, Timothy D.

    2013-01-01

    Objective To evaluate the pharmacokinetics, in dogs, of liposome-encapsulated oxymorphone and hydromorphone made by the ammonium sulfate gradient loading technique (ASG). Animals Four healthy purpose-bred Beagles aged 9.5 ± 3.2 months and weighing 13.4 ± 2.3 kg. Study Design Randomized cross-over design. Methods Each dog was given either 4.0 mg kg−1 of ASG-oxymorphone or 8.0 mg kg−1 of ASG-hydromorphone SC on separate occasions with a 3-month washout period. Blood was collected at baseline and at serial time points up to 1032 hours (43 days) after injection for determination of serum opioid concentrations. Serum opioid concentrations were measured with HPLC-MS and pharmacokinetic parameters were calculated using commercial software and non-compartmental methods. Results Serum concentrations of oxymorphone remained above the limit of quantification for 21 days, while those for hydromorphone remained above the limit of quantification for 29 days. Cmax for ASG-oxymorphone was 7.5 ng mL−1; Cmax for ASG-hydromorphone was 5.7 ng mL−1. Conclusions and clinical relevance Oxymorphone and hydromorphone, when encapsulated into liposomes using the ammonium sulfate gradient loading technique, result in measureable serum concentrations for between 3 to 4 weeks. This formulation may have promise in the convenient use of opioids for clinical treatment of chronically painful conditions in dogs. PMID:23601353

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

    NASA Astrophysics Data System (ADS)

    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 < 10 Myr), the 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.

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

    SciTech Connect

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

    2013-07-15

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

  14. Biochemical and immunological investigations on hypothyroidism in dogs.

    PubMed Central

    Gosselin, S J; Capen, C C; Martin, S L; Targowski, S P

    1980-01-01

    Circulating antibody titers (1:20 to 1:2560) against thyroglobulin were demonstrated in 48% of pet dogs with hypothyroidism by the chromic chloride passive hemagglutination test. Four of six dogs with acanthosis nigricans (1:20) and one of six male dogs with hyperestrogenism (1:40) had low titers of antibody against thyroglobulin whereas clinically normal pet dogs and dogs with other selected endocrinopathies (hypoadrenocorticism, cortisol-excess, diabetes mellitus) or obesity were consistently negative. Circulating immune complexes evaluated by the mastocytoma cell-assay were present in the sera of 20% of pet dogs with hypothyroidism but were absent in clinically normal dogs. Although variations in dose significantly altered the quantitative response of the thyroid gland to thyrotropin the qualitative pattern of response was similar for T3 but not T4 in clinically normal laboratory beagles. The peak increases for serum triiodothyronine and thyroxine were observed either at eight (0.1 and 0.2 I.U bTSH/5 lbs) or 12 (1.0 I.U. bTYSH/5 lbs) hours postthyrotropin. Dogs with naturally occurring hypothyroidism had a decreased serum T3 and T4 at baseline and eight hours postthyrotropin (1.0 I.U. bTSH/5 lbs) compared to clinically normal pet dogs, laboratory beagles and dogs with other clinical endocrinopathies. The consistent lack of a significant increase of serum T3 and T4 in response to thyrotropin was necessary for the separation of certain hypothyroid from euthyroid pet dogs in which the baseline level of thyroid hormones were equivocal. PMID:7407688

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

    PubMed

    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.

  16. PiB Fails to Map Amyloid Deposits in Cerebral Cortex of Aged Dogs with Canine Cognitive Dysfunction.

    PubMed

    Fast, Rikke; Rodell, Anders; Gjedde, Albert; Mouridsen, Kim; Alstrup, Aage K; Bjarkam, Carsten R; West, Mark J; Berendt, Mette; Møller, Arne

    2013-01-01

    Dogs with Canine Cognitive Dysfunction (CCD) accumulate amyloid beta (Aβ) in the brain. As the cognitive decline and neuropathology of these old dogs share features with Alzheimer's disease (AD), the relation between Aβ and cognitive decline in animal models of cognitive decline is of interest to the understanding of AD. However, the sensitivity of the biomarker Pittsburgh Compound B (PiB) to the presence of Aβ in humans and in other mammalian species is in doubt. To test the sensitivity and assess the distribution of Aβ in dog brain, we mapped the brains of dogs with signs of CCD (n = 16) and a control group (n = 4) of healthy dogs with radioactively labeled PiB ([(11)C]PiB). Structural magnetic resonance imaging brain scans were obtained from each dog. Tracer washout analysis yielded parametric maps of PiB retention in brain. In the CCD group, dogs had significant retention of [(11)C]PiB in the cerebellum, compared to the cerebral cortex. Retention in the cerebellum is at variance with evidence from brains of humans with AD. To confirm the lack of sensitivity, we stained two dog brains with the immunohistochemical marker 6E10, which is sensitive to the presence of both Aβ and Aβ precursor protein (AβPP). The 6E10 stain revealed intracellular material positive for Aβ or AβPP, or both, in Purkinje cells. The brains of the two groups of dogs did not have significantly different patterns of [(11)C]PiB binding, suggesting that the material detected with 6E10 is AβPP rather than Aβ. As the comparison with the histological images revealed no correlation between the [(11)C]PiB and Aβ and AβPP deposits in post-mortem brain, the marked intracellular staining implies intracellular involvement of amyloid processing in the dog brain. We conclude that PET maps of [(11)C]PiB retention in brain of dogs with CCD fundamentally differ from the images obtained in most humans with AD.

  17. Modeling lung cancer risks in laboratory dogs exposed to inhaled plutonium

    SciTech Connect

    Gilbert, E.S.; Park, J.F.; Buschbom, R.L.

    1990-06-01

    These analyses are based on data from a lifespan study of beagle dogs exposed to inhaled plutonium being conducted at Pacific Northwest Laboratory. An important goal of this study is to increase understanding of health risk resulting from this exposure, with particular attention to lung cancer risks. Data on humans exposed to plutonium are inadequate for achieving this goal.

  18. [A survey on intestinal parasites of livestock guardian dogs and herding dogs in Switzerland].

    PubMed

    Frey, C F; Regotz, J; Rosenberg, G; Gottstein, B; Kohler, S

    2010-12-01

    The present study describes the occurrence of intestinal parasite infections in livestock guardian dogs and herding dogs. A total of 71 guardian dogs (more than half of the total number of guardian dogs in Switzerland) and 21 herding dogs were coprologically examined, using a combined sedimentation-flotation method. In 21 (23 %) of the dogs intestinal parasites were detected, and 8 (8.7 %) of these dogs shed either sporocysts of Sarcocystis sp. (n = 6) or taeniid eggs (n = 2). The evaluation of questionnaires providing data on age, origin and deworming schemes of the dogs completed the study.

  19. Intra- and interobserver variability of ultrasonographic measurements of the adrenal glands in healthy Beagles.

    PubMed

    Barberet, Virginie; Pey, Pascaline; Duchateau, Luc; Combes, Anais; Daminet, Sylvie; Saunders, Jimmy H

    2010-01-01

    The aim of the present study was to establish which adrenal gland measurement was characterized by the least variations. To do this, we quantified the variability of seven different size measurements of the canine adrenal gland (maximal length, maximal height at the cranial and caudal poles on longitudinal and transverse images, and maximal width of the cranial and caudal poles) within observer, between observer, and between dogs based on three different measurements made by each of the three observers in six healthy Beagle dogs. The height of the caudal pole of both adrenal glands measured on longitudinal images had the lowest intra- and interobserver variability, while measurements of the length had the highest intra- and interobserver variability. Other measurements that were characterized by low intra- and interobserver variability were: height and width of the caudal pole on transverse images and height of the cranial pole on longitudinal images only. These results provide a basis for further study of the changes in adrenal gland size in dogs with pituitary-dependent hyperadrenocorticism.

  20. Occurrence of metastases in beagles with skeletal malignancies induced by internal irradiation

    SciTech Connect

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

    1994-03-01

    Metastases from malignant bone tumors often are responsible for the fatal effects of these cancers. Characteristics of primary skeletal malignancies in beagles injected with bone-seeking radionuclides were studied by Thurman (1971) and summarized by Thurman et al. (1971). There were 212 tumors in 186 of these dogs for which we subsequently received information on bone tumor metastases. Evaluation of bone and soft tissue slides from these animals allowed us to compare parameters reported previously with the occurrence of grossly apparent bone tumor metastases. Data included growth-rate of the primary tumor, volume of the primary tumor at death, sex of the animal, growth period of the primary tumor, degree of calcification of the primary tumor, skeletal location of the primary tumor, cumulative radiation dose to the skeleton, dose equivalent to the skeleton, and year of death. For most of the comparisons, no significant differences could be established between dogs with and without metastases. However, tumor volume at death appeared to be correlated with probability of metastasis (p < 0.05), with the larger tumors being associated with higher rates of metastasis. Comparisons of dogs with and without metastases as a function of tumor growth-rate did not, for the most part, yield significantly different results between groups. 10 refs., 11 tabs.

  1. Studies on the erythron and the ferrokinetic responses in beagles adapted to hypergravity

    NASA Technical Reports Server (NTRS)

    Beckman, D. A.; Evans, J. W.; Oyama, J.

    1978-01-01

    Red cell survival, ferrokinetics, and hematologic parameters were investigated in beagle dogs exposed to chronic hypergravity (2.6 Gx). Ineffective erythropoiesis, red cell mass, plasma volume, and Cr-51-elution were significantly increased; maximum Fe-59 incorporation was decreased; and there was no change in the mean erythrocyte life span following autologous injection of Cr-51-labeled red cells and Fe-59-labeled transferrin. Red cell count, F(cells), total body hemoglobin (Hb), susceptability to osmotic lysis, and differential reticulocyte count were increased. White blood cell count, venous blood %Hb, mean cell volume, mean cell Hb, mean cell Hb concentration, and serum iron were decreased. No changes were observed for body mass, mg Fe per g Hb, iron binding capacity, percent saturation of iron carrying capacity, or the electrophoretic mobility of purified Hb. This study indicated that chronic exposure to hypergravity induced changes in red cell size, volume, total mass, and membrane permeability.

  2. Lithofacies, age, depositional setting, and geochemistry of the Otuk Formation in the Red Dog District, northwestern Alaska

    USGS Publications Warehouse

    Dumoulin, Julie A.; Burruss, Robert A.; Blome, Charles D.

    2013-01-01

    Complete penetration of the Otuk Formation in a continuous drill core (diamond-drill hole, DDH 927) from the Red Dog District illuminates the facies, age, depositional environment, source rock potential, and isotope stratigraphy of this unit in northwestern Alaska. The section, in the Wolverine Creek plate of the Endicott Mountains Allochthon (EMA), is ~82 meters (m) thick and appears structurally uncomplicated. Bedding dips are generally low and thicknesses recorded are close to true thicknesses. Preliminary synthesis of sedimentologic, paleontologic, and isotopic data suggests that the Otuk succession in DDH 927 is a largely complete, albeit condensed, marine Triassic section in conformable contact with marine Permian and Jurassic strata. The Otuk Formation in DDH 927 gradationally overlies gray siliceous mudstone of the Siksikpuk Formation (Permian, based on regional correlations) and underlies black organic-rich mudstone of the Kingak(?) Shale (Jurassic?, based on regional correlations). The informal shale, chert, and limestone members of the Otuk are recognized in DDH 927, but the Jurassic Blankenship Member is absent. The lower (shale) member consists of 28 m of black to light gray, silty shale with as much as 6.9 weight percent total organic carbon (TOC). Thin limy layers near the base of this member contain bivalve fragments (Claraia sp.?) consistent with an Early Triassic (Griesbachian-early Smithian) age. Gray radiolarian chert dominates the middle member (25 m thick) and yields radiolarians of Middle Triassic (Anisian and Ladinian) and Late Triassic (Carnian-late middle Norian) ages. Black to light gray silty shale, like that in the lower member, forms interbeds that range from a few millimeters to 7 centimeters in thickness through much of the middle member. A distinctive, 2.4-m-thick interval of black shale and calcareous radiolarite ~17 m above the base of the member has as much as 9.8 weight percent TOC, and a 1.9-m-thick interval of limy to cherty

  3. Normal canine prostate gland: repeatability, reproducibility, observer-dependent variability of ultrasonographic measurements of the prostate in healthy intact beagles.

    PubMed

    Leroy, C; Conchou, F; Layssol-Lamour, C; Deviers, A; Sautet, J; Concordet, D; Mogicato, G

    2013-10-01

    Most prostatic diseases in dogs are associated with prostatomegaly, and transabdominal ultrasonography has become the imaging modality of choice for evaluation of the prostate gland in the dog. The aim of the present study was to assess the reproducibility, the repeatability and interobserver variations of sonographic measurements of prostate and to determine which measurement had the lowest variability. Length and height of prostate gland were measured on longitudinal views, width of the prostate gland and height of left and right lobes of the gland on transversal views. The within-day and between-day variabilities of the prostatic parameters were determined by performing 1350 (270 length, 270 height, 270 width, 270 height of right lobe and 270 height of left lobe) examinations on ten healthy intact beagle dogs on six different days, in a two-week period (three days for the five dogs, three different days for the five others). Three observers with different levels of experience in ultrasonography performed the examinations. The lowest within-day and between-day standard deviation and coefficient of variation values were observed for the width of the prostate. The width of the gland measured on transverse frozen images seems to be the most reliable measurement for evaluating size of prostate glands in healthy dogs, although the shape, position, outline, and echogenicity of the prostate should also be assessed.

  4. Opportunity Approaches the Bowl of Beagle Crater (False Color)

    NASA Technical Reports Server (NTRS)

    2006-01-01

    NASA's Mars Exploration Rover Opportunity acquired this false-color image of the rim of the 35-meter (115-foot) diameter Beagle Crater on Martian day, or sol, 894 (July 30, 2006) using the panoramic camera's 753-nanometer, 535-nanometer, and 432-nanometer filters. At the time the rover was about 25 meters (82 feet) from Beagle Crater, looking east-southeast. The image reveals ejecta blocks near the rover, the largest of which is about 50 centimeters (20 inches) across. The image also shows a portion of the eastern interior rim of Beagle Crater, which appears composed of jumbled, angular blocks of brighter and darker outcrop rocks. The rover will drive to the rim of Beagle and acquire an extensive color panorama of the crater rim and interior in the coming sols.

  5. [Effect of rhG-CSF on blood coagulation in beagles irradiated by 2.3 Gy neutron].

    PubMed

    Li, Ming; Han, Qin-Fang; Liu, Xiao-Lan; Xing, Shuang; Xiong, Guo-Lin; Xie, Ling; Zhao, Yan-Fang; Yu, Zu-Yin; Ding, Yi-Bo; Zhao, Zhen-Hu; Cong, Yu-Wen; Luo, Qing-Liang

    2010-12-01

    The aim of this study was to investigate the effect of recombinant human granulocyte stimulating factor (rhG-CSF) on blood coagulation of beagles irradiated by 2.3 Gy neutron so as to provide new therapy for blood coagulation disorder after neutron irradiation. 10 beagles were exposed to 2.3 Gy neutron, and then randomly assigned into supportive care group and rhG-CSF-treated group. The rhG-CSF-treated cohorts were injected subcutaneously with rhG-CSF (10 µg/kg·d) beginning at the day of exposure for 21 consecutive days. Peripheral blood platelet counts were examined once every two days. In vitro platelet aggregation test, thromboelastography and blood clotting tetrachoric tests were also performed. The results indicated that the blood clotting system of irradiated dogs was in hypercoagulable state in the early days after 2.3 Gy neutron irradiation, and became hypocoagulable at crisis later and were mainly on intrinsic coagulation pathway. Blood fibrinogen increased markedly during the course of disease, while platelet counts and aggregation function were decreased remarkably. rhG-CSF administered daily could correct hypercoagulable state induced by 2.3 Gy neutron irradiation at the early time post exposure, shortened the thromboplastin generation time and clotting formation, down-regulated the abnormal high fibrinogen in blood, and improved platelet aggregation function. It is concluded that rhG-CSF can improve coagulation disorders of irradiated dogs.

  6. Short-term inhalation of particulate transition metals has little effect on the electrocardiograms of dogs having preexisting cardiac abnormalities.

    PubMed

    Muggenburg, B A; Benson, J M; Barr, E B; Kubatko, J; Tilley, L P

    2003-04-11

    There is growing epidemiological evidence for statistical associations between increases in air pollution, especially particulate matter, and increases in cardiovascular morbidity and mortality. Laboratory studies have shown that transition metals contribute strongly to the effects of high lung doses of model particles on changes in the electrocardiograms of animals. The present study evaluated the effects of short-term inhalation exposure to respirable particles of specific oxide and sulfate forms of transition metals on heart rate and the electrocardiogram of old dogs having preexisting cardiac abnormalities. Conscious beagle dogs were exposed by oral inhalation for 3 h on each of 3 successive days to aerosols of manganese, nickel, vanadium, iron, and copper oxides, and nickel and vanadium sulfates as single compounds at concentrations of 0.05 mg/m(3). Electrocardiograms were recorded and evaluated for exposure-related changes in heart rate, heart rate variability, and abnormalities of waveforms. Although the electrocardiograms of this population of dogs having potential age and cardiovascular susceptibility factors reflected their underlying clinical abnormalities, no significant effect of exposure to the transition metal aerosols was observed.

  7. Microsatellite loci analysis for the genetic variability and the parentage test of five dog breeds in South Korea.

    PubMed

    Kang, Byeong-Teck; Kim, Kyung-Seok; Min, Mi-Sook; Chae, Young-Jin; Kang, Jung-Won; Yoon, Junghee; Choi, Jihye; Seong, Je-Kyung; Park, Han-Chan; An, Junghwa; Lee, Mun-Han; Park, Hee-Myung; Lee, Hang

    2009-06-01

    To investigate the population structure of five dog breeds in South Korea and to validate polymorphic microsatellite markers for the parentage test, microsatellite loci analyses were conducted for two Korean native dog breeds, Poongsan and Jindo, and three imported dog breeds, German Shepherd, Beagle and Greyhound. Overall genetic diversity was high across all dog breeds (expected heterozygosity range: 0.71 to 0.85), although breeds differed in deviations from Hardy-Weinberg equilibrium (HWE). Significant reduction of heterozygosity in the Poongsan and Greyhound breeds was caused by non-random mating and population substructure within these breeds (the Wahlund effects). The close relationship and high degree of genetic diversity for two Korean native dog breeds were substantial. The mean polymorphism information content value was highest in Jindos (0.82) and Poongsans (0.81), followed by Beagles (0.74), Greyhounds (0.72), and German Shepherds (0.66). Accumulated exclusion power values, as an indication of marker validity for parentage tests, were varied but very high across breeds, 0.9999 for Jindos, Poongsans, and Beagles, 0.9997 for Greyhounds, and 0.9995 for German Shepherds. Taken together, the microsatellite loci investigated in this study can serve as suitable markers for the parentage test and as individual identification to establish a reliable pedigree verification system of dog breeds in South Korea. This study also stresses that the population subdivision within breeds can become an important cause of deviation from HWE in dog breeds.

  8. Lessons learned from cloning dogs.

    PubMed

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

    2012-08-01

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

  9. An epidemiological study of gastrointestinal parasites of dogs from Southern Greater Buenos Aires (Argentina): age, gender, breed, mixed infections, and seasonal and spatial patterns.

    PubMed

    Fontanarrosa, María F; Vezzani, Darío; Basabe, Julia; Eiras, Diego F

    2006-03-31

    A total of 2193 fecal samples from owned dogs were collected during the 2003-2004 period in Southern Greater Buenos Aires, and were evaluated for the presence of intestinal parasites by a flotation-centrifugation method. The overall prevalence was 52.4%, and the 11 species found were: Ancylostoma caninum (13%), Isospora ohioensis complex (12%), Toxocara canis (11%), Trichuris vulpis (10%), Sarcocystis sp. (10%), Giardia duodenalis (9%), Isospora canis (3%), Hammondia-Neospora complex (3%), Dipilydium caninum (18 cases), Cryptosporidium sp. (5 cases), and Toxascaris leonina (1 case). There was no significant difference in the overall prevalence between genders (female = 50.4%, male = 54.6%), and breeds (pure = 52.3%, mixed = 53%), but prevalence in puppies (<1 year) was higher than in adult dogs (62.7% versus 40.8%, respectively). Only the prevalence of A. caninum differed between genders, with higher values for males. The prevalences of six of the parasite species showed a decreasing trend with increasing host age, and an inverse pattern was found for two other species. The prevalences of three protozoa were significantly higher in pure-breed dogs, and those of two nematodes were significantly higher in mixed-breed dogs. The prevalences of T. canis, A. caninum, and T. vulpis were spatially heterogeneous with a clear Southwest-Northeast gradient. Only prevalences of Sarcocystis sp. and G. duodenalis showed seasonal variation. The frequency distribution of the number of species per fecal sample did not differ from a random distribution. Results obtained throughout the world were discussed.

  10. The canine model of human cognitive aging and dementia: pharmacological validity of the model for assessment of human cognitive-enhancing drugs.

    PubMed

    Studzinski, Christa M; Araujo, Joseph A; Milgram, Norton W

    2005-03-01

    For the past 15 years we have investigated the aged beagle dog as a model for human aging and dementia. We have shown that dogs develop cognitive deficits and neuropathology seen in human aging and dementia. These similarities increase the likelihood that the model will be able to accurately predict the efficacy of Alzheimer's disease (AD) treatments as well as detect therapeutics with limited or no efficacy. Better predictive validity of cognitive-enhancing therapeutics (CETs) could lead to enormous cost savings by reducing the number of failed human clinical trials and also may reduce the likelihood of negative outcomes such as those recently observed in the AN-1792 clinical trials. The current review assesses the pharmacological validity of the canine model of human aging and dementia. We tested the efficacy of (1) CP-118,954 and phenserine, two acetylcholinesterase inhibitors, (2) an ampakine, (3) selegiline hydrochloride, two drugs that have failed human AD trials, and (4) adrafinil, a putative CET. Our research demonstrates that dogs not only develop isomorphic changes in human cognition and brain pathology, but also accurately predict the efficacy of known AD treatments and the absence or limited efficacy of treatments that failed clinical trials. These findings collectively support the utilization of the dog model as a preclinical screen for identifying novel CETs for both age-associated memory disorder and dementia.

  11. Age-associated and breed-associated variations in haematological and biochemical variables in young labrador retriever and miniature schnauzer dogs

    PubMed Central

    Brenten, Thomas; Morris, Penelope J.; Salt, Carina; Raila, Jens; Kohn, Barbara; Schweigert, Florian J.; Zentek, Jürgen

    2016-01-01

    Breed, sex and age effects on haematological and biochemical variables were investigated in 24 labrador retriever and 25 miniature schnauzer dogs during the first year of life. Blood samples were taken regularly between weeks 8 and 52. White blood cell and red blood cell counts, haemoglobin concentration, haematocrit, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, platelet count as well as total protein, albumin, calcium, phosphate, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, total cholesterol, triglycerides, creatine and urea were evaluated. For all haematological and biochemical parameters, there were significant effects of age on test results. Statistically significant effects for breed and the breed×age interaction on test results were observed for most of the parameters with the exception of haemoglobin. Variations in test results illustrate growth related alterations in body tissue and metabolism leading to dynamic and marked changes in haematological and biochemical parameters, which have to be considered for the interpretation of clinical data obtained from dogs in the first year of life. PMID:27252875

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

    PubMed

    Szánthó, Flóra; Miklósi, Ádám; Kubinyi, Enikő

    2017-01-01

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

  13. Antibody responses to Bordetella bronchiseptica in vaccinated and infected dogs

    PubMed Central

    Ellis, John; Rhodes, Carrie; Lacoste, Stacey; Krakowka, Steven

    2014-01-01

    Bordetella bronchiseptica (Bb) whole cell bacterins have been replaced with acelluar vaccines. We evaluated the response to the acellular Bb vaccines in Bb-seropositive commingled laboratory beagles and client-owned dogs with various lifestyles and vaccination histories. A single parenteral dose of the acellular Bb vaccine resulted in consistent anamnestic IgG, and to a lesser, but notable extent, IgA, Bb-reactive antibody responses in the seropositive beagles. Associated with the increase in antibodies measured by enzyme-linked immunosorbent assay (ELISA) was an increase in the complement (C)-dependent IgG antibody mediated bactericidal effect on Bb in vitro. Antibody responses in client-owned dogs were more variable and were dependent upon the vaccination history and serological evidence of previous Bb exposure. Antibodies from vaccinated dogs recognized several Bb proteins, notably P68 (pertactin) and P220 (fimbrial hemagglutinin), the response to which has been shown to be disease-sparing in Bp infections. These antibody responses were similar to those in experimentally infected dogs and in dogs that had received a widely used whole cell bacterin. PMID:25183893

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Hypodontia in the beagle after perinatal whole-body /sup 60/Co gamma irradiation

    SciTech Connect

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

    1989-06-01

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

  16. Absorption and pharmacokinetics of green tea catechins in beagles.

    PubMed

    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.

  17. Beagle 2: lessons learned and the way forward

    NASA Astrophysics Data System (ADS)

    2004-05-01

    The Mars Express spacecraft, carrying the Beagle 2 lander, was launched on 2 June last year, arriving in the vicinity of Mars in December. The separation of Beagle 2 from Mars Express took place flawlessly on 19 December. The satellite continued its mission with its successful insertion into a Mars orbit on 25 December, the day on which Beagle 2 was due to land. The first radio contact with Beagle 2 was expected shortly after the scheduled landing time but no signal was received. Many radio contacts were attempted over the following days and weeks, but without result. By early February it became clear that there was no prospect of communicating with Beagle 2 and a joint ESA/UK inquiry was set up to investigate the circumstances and possible reasons that prevented completion of the Beagle 2 mission. The Commission of Inquiry, including senior managers and experts from Europe and also from NASA and Russia held several meetings in the UK and at ESA, interviewed the key players -directors, managers, scientists, and engineers - involved in the development of Beagle 2, and has submitted its findings, assessments and recommendations. The report was submitted to the UK Minister for Science and Innovation and the Director General of ESA on 21 April and accepted. No single technical failure or shortcoming was unambiguously identified but a few credible causes for Beagle 2 loss were highlighted. More importantly, the Board made it clear that there were programmatic and organisational reasons that significantly increased the risk of Beagle 2 failure. The outcome of the review carried out by the Commission of Inquiry is summarized in 19 recommendations to the British Authorities and ESA. These constitute the basis of lessons learned for the future. Both parties have accepted them fully. ESA will undertake a course of action to ensure their implementation. On Monday 24 May, BNSC invites media representatives to attend a press conference at: The Department of Trade and Industry

  18. Coat and claws as new matrices for noninvasive long-term cortisol assessment in dogs from birth up to 30 days of age.

    PubMed

    Veronesi, M C; Comin, A; Meloni, T; Faustini, M; Rota, A; Prandi, A

    2015-09-15

    The last stage of fetal development and the neonatal period represent the most critical phases for the mammals' offspring. In the dog, the knowledge about the final intrauterine fetal development and biology, as well as about the neonatal physiology, remains scarce. Hormonal changes occurring in the last intrauterine fetal phase and during the early neonatal age are still not completely clear, probably because of the invasiveness related to the collection of the more common biological matrix, represented by circulating blood. Toward term of pregnancy, during parturition, and after birth, the hypothalamic-pituitary-adrenal axis is a key system regulating several physiological processes, and its activity was previously investigated by blood analysis, considered an invasive procedure providing a single-point measurement. In respect to animal welfare, and for a more correct long-term retrospective investigation, noninvasive hormonal studies were performed firstly on the hair of humans and coat of animals and, more recently, in the nails of human beings. This study was aimed to assess cortisol (COR) in coat and claws of newborn puppies and to evaluate the possible influence of the newborn gender, breed body size, and age on coat and claws COR concentrations. The results obtained from 165 newborn puppies evidenced that coat and claws COR levels were highly correlated each other (P < 0.0001), although the COR accumulation in the two matrices was different in relation to the class of age. Moreover, the puppies age influenced both coat and claws COR concentrations (P < 0.05), with premature puppies showing higher values when compared to term born-dead puppies or puppies dead between 1 and 30 days of age. The present study reported that COR is quantifiable in coat and claws of newborn dogs. Moreover, both matrices appear as useful tools for new, noninvasive, long-term perinatal and neonatal researches also in canine species.

  19. Histopathology of Incidental Findings in Beagles Used in Toxicity Studies

    PubMed Central

    Sato, Junko; Doi, Takuya; Wako, Yumi; Hamamura, Masao; Kanno, Takeshi; Tsuchitani, Minoru; Narama, Isao

    2012-01-01

    The purpose of our publication is to widely communicate the pictures of spontaneous findings occurring in beagles. Spontaneous arteritis occurs commonly in beagles. Frequent sites of arteritis are the heart, spleen, pancreas, epididymis and spinal cord. Morphological similarities between spontaneous and drug-induced arterial lesions may cause confusion when evaluating vascular toxicity of chemicals such as vasodilating agents. Focal and minimal inflammatory lesions are occasionally seen in the lung and may be associated with aspiration of food particles or of unknown causes. A cystic change with copious mucin production occurs occasionally in the mucosal epithelium of the gall bladder. Nesidioblastosis is seen rarely in the pancreas of beagles. C-cell complex and lymphocytic thyroiditis are common thyroid lesions. Spontaneous focal hypospermatogenesis and lobular Sertoli-cell-only seminiferous tubules occurring frequently in beagles must be distinguished from drug-induced damage of the seminiferous tubules in toxicity studies. The morphological differences of the female genital system in each cycle need to be understood; therefore, we present the normal features of the cyclic changes of the female genital organs. Further, we provide more information on spontaneous findings in beagles for exact diagnoses in toxicity studies. PMID:22481862

  20. Evaluation of nanoparticle delivered cisplatin in beagles

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed

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

    2017-01-11

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

  2. Opportunity Approaches the Bowl of Beagle Crater (True Color)

    NASA Technical Reports Server (NTRS)

    2006-01-01

    NASA's Mars Exploration Rover Opportunity took this approximate true-color image of Beagle Crater from a distance of about 25 meters (82 feet). The crater is thought to be relatively young based on its prominent, raised rim and surrounding ejecta that have not been eroded away or buried by sand. The image also shows a portion of the eastern interior rim of Beagle Crater, which appears composed of jumbled, angular blocks of brighter and darker outcrop rocks. The rover will drive to the rim of the crater and acquire an extensive color panorama in the coming sols.

  3. Bone sarcoma characteristics and distribution in beagles injected with radium-226

    SciTech Connect

    White, R.G.; Raabe, O.G.; Culbertson, M.R.; Parks, N.J.; Samuels, S.J.; Rosenblatt, L.S. )

    1994-03-01

    A total of 155 primary bone sarcomas were found in 131 of the 246 beagles injected with [sup 226]Ra and 5 primary bone sarcomas were found in 4 of the 158 unexposed controls. Of these 155 bone sarcomas, 146 (94%) were osteosarcomas and 9 were nonosteosarcomas. An additional 31 primary bone sarcomas (28 osteosarcomas) developed in 44 dogs terminated from the main study because of limb amputation for bone sarcoma. Nonosteosarcomas predominated in both the controls and the second lowest of six logarithmically increasing dose levels (there were no bone sarcomas in the lowest dose group). Osteosarcomas predominated at the higher dose levels, and incidence tended to increase as dose increased. The 146 osteosarcomas were distributed quite evenly between males and females (72:74). Of the 9 nonosteosarcomas, 6 occurred in males and 3 in females. The ratio of bone sarcomas of the appendicular skeleton to those in the axial skeleton was 110:45, with osteosarcomas occurring more often in the appendicular skeleton (108:38). Cases of multiple primary bone sarcomas in dogs injected with [sup 226]Ra were found only in the four highest dose groups. Amputations were performed on 44 of the 96 dogs (94 injected and 2 unexposed) that developed appendicular bone sarcomas. A statistical study of the distribution of bone sarcomas among 16 separate bone groups showed a statistically significant correlation to cancellous skeletal surface, but the variability among bone groups was too large for this relationship to be of real predictive value. it is postulated that the distribution of bone sarcomas reflects primarily the relative cell division rates in the bone groups and secondarily the radiation dose distribution, with the highest occurrence of bone sarcoma in the humeri, pelvis, femora and tibiae/fibular tarsal, and no occurrence in the coccygeal vertebrae, sternum, forepaws or hindpaws. 16 refs., 5 figs., 4 tabs.

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

    SciTech Connect

    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

  5. Preference for sugars and nonnutritive sweeteners in young beagles.

    PubMed

    Ferrell, F

    1984-01-01

    Two-bowl choice tests were used to examined preference of puppies aged two to four months for compounds tasting sweet to humans. Puppies found many, but not all of the compounds highly palatable, and were sensitive to both type and amount of sugar or nonnutritive sweetener contained in a semi-moist dog food recipe. Lactose, fructose, and sucrose were well accepted, whereas maltose elicited indifference or rejection. Sodium cyclamate, but not sodium saccharin, was preferred at some concentrations to 15 percent sucrose sweetened semi-moist food used as the standard. Solutions of lactose, fructose, glucose and galactose were preferred to plain tap water.

  6. Fungal rhinitis in dogs.

    PubMed

    Ostrzeszewicz, M; Sapierzyński, R

    2015-01-01

    Fungal rhinitis and sinusitis in dogs are quite common reasons of chronic nasal discharge and rhinoscopy in such cases is commonly suggested. Forty three dogs were examined using rhinoscopy because of the presence of chronic airway symptoms. Clinical examination, routine hematology and serum biochemistry profiles, nasal and frontal sinus radiographs were made in all animals. Additionally, computed tomography in one dog was performed. Samples for histopathology were taken from 9 patients during rhinoscopy, additionally, from 8 of these patients samples for cytopathology were collected by blind nasal swab technique. In 9 of 43 dogs (20,5%), all males aged 1 to 13 years, examinations led to a diagnosis of fungal rhinitis. In 2 cases a diagnosis of fungal rhinitis was obtained based solely on cytopathology, while in 7 cases - mycosis of nasal mucosa was confirmed by histopathology. The present study revealed that cytopathological examination of nasal swabs has a low diagnostic value in the case of nasal infections in dogs. Although, in some dogs cytopathology, together with other widely available diagnostic techniques was sufficient to reliably diagnose fungal rhinitis, histopathology of samples collected during rhinoscopy is still the gold standard in such cases.

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

    PubMed Central

    Szánthó, Flóra; Miklósi, Ádám; Kubinyi, Enikő

    2017-01-01

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

  8. Effects of the Dietary Protein and Carbohydrate Ratio on Gut Microbiomes in Dogs of Different Body Conditions

    PubMed Central

    Lauber, Christian L.; Czarnecki-Maulden, Gail; Pan, Yuanlong; Hannah, Steven S.

    2017-01-01

    ABSTRACT Obesity has become a health epidemic in both humans and pets. A dysbiotic gut microbiota has been associated with obesity and other metabolic disorders. High-protein, low-carbohydrate (HPLC) diets have been recommended for body weight loss, but little is known about their effects on the canine gut microbiome. Sixty-three obese and lean Labrador retrievers and Beagles (mean age, 5.72 years) were fed a common baseline diet for 4 weeks in phase 1, followed by 4 weeks of a treatment diet, specifically, the HPLC diet (49.4% protein, 10.9% carbohydrate) or a low-protein, high-carbohydrate (LPHC) diet (25.5% protein, 38.8% carbohydrate) in phase 2. 16S rRNA gene profiling revealed that dietary protein and carbohydrate ratios have significant impacts on gut microbial compositions. This effect appeared to be more evident in obese dogs than in lean dogs but was independent of breed. Consumption of either diet increased the bacterial evenness, but not the richness, of the gut compared to that after consumption of the baseline diet. Macronutrient composition affected taxon abundances, mainly within the predominant phyla, Firmicutes and Bacteroidetes. The LPHC diet appeared to favor the growth of Bacteroides uniformis and Clostridium butyricum, while the HPLC diet increased the abundances of Clostridium hiranonis, Clostridium perfringens, and Ruminococcus gnavus and enriched microbial gene networks associated with weight maintenance. In addition, we observed a decrease in the Bacteroidetes to Firmicutes ratio and an increase in the Bacteroides to Prevotella ratio in the HPLC diet-fed dogs compared to these ratios in dogs fed other diets. Finally, analysis of the effect of diet on the predicted microbial gene network was performed using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). PMID:28119466

  9. VARIABILITY IN THE ULTRASONOGRAPHIC APPEARANCE OF THE PANCREAS IN HEALTHY DOGS COMPARED TO DOGS WITH HYPERADRENOCORTICISM.

    PubMed

    Granger, L Abbigail; Hilferty, Michael; Francis, Taylor; Steiner, Jörg M; Gaschen, Lorrie

    2015-01-01

    Anecdotally, an unusually hyperechoic pancreas can be found in seemingly healthy dogs on ultrasound examination and the prevalence and clinical significance of this finding is unknown. The objective of this study was to describe the prevalence of a hyperechoic and/or heterogenous pancreas in healthy dogs and correlate these findings to weight, age, and body condition score (BCS). An additional objective was to describe the prevalence of a hyperechoic and/or heterogenous pancreas in dogs with hyperadrenocorticism and compare this to the healthy dogs. Pancreata of 74 healthy dogs were evaluated prospectively and pancreatic echogenicity and echotexture were graded. Each dog's age, BCS, and weight were recorded. Dogs were screened for health by physical examination, serum chemistry panel, urine specific gravity, and a canine pancreatic lipase immunoreactivity assay. Pancreatic images for 92 dogs having hyperadrenocorticism were also reviewed and pancreatic echogenicity and echotexture were recorded. The prevalence of pancreatic hyperechogenicity in normal dogs was 7% (5 of 74) and heterogeneity was 40% (30 of 74). No correlation existed between pancreatic echogenicity and weight, age, or BCS (P > 0.1 for all sets). A statistically significant increase in the proportion of dogs having a hyperechoic pancreas was found in the hyperadrenocorticism sample of dogs (40%, 37 of 92, P < 0.0001). The underlying cause of pancreatic variability in the few healthy dogs and in dogs with hyperadrenocorticism is unknown and the varying appearance of the pancreas in these samples confounds interpretation of diseases such as chronic pancreatitis.

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

    ERIC Educational Resources Information Center

    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.

  11. Astrovirus-like, coronavirus-like, and parvovirus-like particles detected in the diarrheal stools of beagle pups.

    PubMed

    Williams, F P

    1980-01-01

    Astrovirus-like, coronavirus-like, and parvovirus-like particles were detected through electron microscopic (EM) examination of loose and diarrheal stools from a litter of beagle pups. Banding patterns obtained from equilibrium centrifugations in CsCl supported the EM identification. Densities associated with the identified particles were: 1.34 g/ml for astrovirus, 1.39 g/ml for "full" parvovirus and 1.24-1.26 g/ml for "typical" coronavirus. Convalescent sera from the pups aggregated these three particle types as observed by immunoelectron microscopy (IEM). Only coronavirus-like particles were later detected in formed stools from these same pups. Coronavirus and parvo-like viruses are recognized agents of canine viral enteritis, however, astrovirus has not been previously reported in dogs.

  12. Lifetime carcinogenicity study of 1- and 2-naphthylamine in dogs.

    PubMed Central

    Purchase, I. F.; Kalinowski, A. E.; Ishmael, J.; Wilson, J.; Gore, C. W.; Chart, I. S.

    1981-01-01

    Groups of male and female beagle dogs were given daily doses of 400 mg of various mixtures of naphthylamines for up to 109 months. Survivors were killed at 128 months. A variety of pathological conditions was diagnosed, but the only effect related to treatment was the induction of bladder neoplasms. All dogs which received pure 2-naphthylamine developed transitional-cell carcinomas of the bladder within 34 months. Two of 8 dogs receiving 6% 2-naphthylamine in 1-naphthylamine developed early carcinoma and 2/8 dogs receiving 0.5% 2-naphthylamine in 1-naphthylamine developed haemangioma of the bladder. Some of the dogs receiving 1-naphthylamine (total dose 950 g) and the controls had focal cystitis or hyperplasia, but no neoplasia of the bladder. These results confirm the carcinogenicity of 2-naphthylamine to dogs. No carcinogenic effect of 1-naphthylamine was observed, indicating that it is at least 200 times less potent as a carcinogen than 2-naphthylamine. The incidence of bladder cancer in dogs fed mixtures of both naphthylamines explains why previous experimental and epidemiological studies of impure 1-naphthylamine have revealed carcinogenicity. Images Fig. 1 Fig. 2 PMID:7326199

  13. Effect of a prolonged stay in a locked environment on the microbial flora in dogs

    NASA Technical Reports Server (NTRS)

    Balish, E.; Shih, C.-N.; Yale, C. E.; Mandel, A. D.

    1974-01-01

    Ten purebred Beagle dogs (all males) were used to determine the effect of a prolonged stay in a locked environment (i.e., no exogenous microbial contamination) on the microbial flora. At monthly intervals the microbial profile (feces, nose, and throat) of each dog was assessed. After 12 months it was found there was no drastic alteration or simplification of the microbial profile of isolated or control dogs. Although isolated dogs had slightly higher levels of anaerobic bacteria and somewhat lower levels of enterococci, the major groups of anaerobic, aerobic, and facultative bacteria remained qualitatively and quantitatively similar for the 12-month study period. Although they were only minor components of the fecal flora, Candida albicans and Shigella sonnei were consistently isolated in larger numbers from the dogs in the locked environment.

  14. Immunohistochemical analysis of collagen types I, III, IV and alpha-actin in the urethra of sexually intact and ovariectomized beagles.

    PubMed

    Augsburger, Heinz R; Oswald, Marianne

    2007-09-01

    Urinary incontinence is a widespread problem in both postmenopausal women and ovariectomized dogs. The objective of this study was to investigate the influence of ovariectomy on the immunoreactivity and the distribution pattern of collagens I, III, IV and alpha-actin in the canine urethra. The immunohistochemical results were evaluated in five sexually intact and five ovariectomized beagles. The immunostaining of both collagens I and III delineated urethral connective tissue fibres and co-localized within in the fibres of both groups. The basement membranes of smooth muscle cells and sinusoids showed marked type IV collagen expression, whereas only faint immunoreactivity was present at the urothelial-stromal interface. No differences could be detected in the expression or distribution of the assessed collagen types and actin between ovariectomized and control animals. In conclusion, ovariectomy does not appear to have an effect on urethral collagens I, III, IV and smooth muscle actin in the dog, as ascertained by immunohistochemistry.

  15. A Combination Cocktail Improves Spatial Attention in a Canine Model of Human Aging and Alzheimer's disease

    PubMed Central

    Head, Elizabeth; Murphey, Heather L.; Dowling, Amy L.S.; McCarty, Katie L.; Bethel, Samuel R.; Nitz, Jonathan A.; Pleiss, Melanie; Vanrooyen, Jenna; Grossheim, Mike; Smiley, Jeffery R.; Murphy, M. Paul; Beckett, Tina L.; Pagani, Dieter; Bresch, Frederick; Hendrix, Curt

    2014-01-01

    Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of beta-amyloid (Aβ) plaques. We hypothesized that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits and oxidative damage in the brain. Thus, 9 aged beagles (98-115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) an extract of green tea containing 50% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t(11)=4.3, p=0.001) and were more accurate across all distances (F(1,9)=20.7, p=0.001), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and CSF Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD. PMID:22886019

  16. Human behavior preceding dog bites to the face.

    PubMed

    Rezac, P; Rezac, K; Slama, P

    2015-12-01

    Facial injuries caused by dog bites pose a serious problem. The aims of this study were to determine human behavior immediately preceding a dog bite to the face and to assess the effects of victim age and gender and dog sex and size on the location of the bite to the face and the need for medical treatment. Complete data on 132 incidents of bites to the face were analysed. A human bending over a dog, putting the face close to the dog's face, and gazing between victim and dog closely preceded a dog bite to the face in 76%, 19% and 5% of cases, respectively. More than half of the bites were directed towards the central area of the victim's face (nose, lips). More than two thirds of the victims were children, none of the victims was an adult dog owner and only adult dogs bit the face. Victim's age and gender and dog's sex and size did not affect the location of the bite on the face. People who were bitten by large dogs sought medical treatment more often than people who were bitten by small dogs (P <0.01). Risk factors such as bending over the dog, putting the face close to the dog's face and gazing between human and dog should be avoided, and children should be carefully and constantly supervised when in the presence of dogs.

  17. Effect of 30 months in a locked environment on the microbial flora of dogs

    NASA Technical Reports Server (NTRS)

    Balish, E.; Shih, C.-N.; Yale, C. E.; Mandel, A. D.

    1977-01-01

    It has been proposed that the microbial flora of mammals would simplify to a few microbial species if the host animal was confined to a 'locked' environment and provided with sterile food, water, and air. This paper updates information on the microbial profile (feces, nose and throat) of purebred beagles housed in the above-mentioned conditions through a 30-month study period and demonstrates that no drastic decrease or simplification of the microbial profile occurred in isolated or control dogs.

  18. Perinatal radiation-induced renal damage in the beagle

    SciTech Connect

    Jaenke, R.S.; Angleton, G.M. )

    1990-04-01

    The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated.

  19. Plutonium- or americium-induced liver tumors and lesions in beagles

    SciTech Connect

    Taylor, G.N.; Lloyd, R.D.; Mays, C.W.; Angus, W.; Miller, S.C.; Shabestari, L.; Hahn, F.F. )

    1991-09-01

    Plutonium-239 or 241Am administered intravenously in the monomeric citrate form was initially deposited in beagle livers principally in the hepatocytes and to a much lesser extent in the sinusoidal macrophages and connective tissues. The initial distribution was quite uniform throughout the hepatic parenchyma; however, at later postinjection intervals, depending on the amount of injected activity, the liver burden became increasingly more focal due to: (1) a progressive shift of the radionuclide from the hepatic epithelium to the macrophages; (2) the movement of such macrophages toward the portal or central regions of the lobule; and (3) the displacement of the older more radioactive tissue by regenerating hepatocytes, which generally have a much lower radionuclide content. The hepatic lesions produced by Pu or Am included: (1) necrosis and degenerative changes that were clinically serious or fatal in some of the animals injected with approximately 107 kBq kg-1; (2) marked structural and circulatory changes resulting from necrosis and focal hepatocyte hyperplasia; (3) a significant incidence of both benign and malignant primary liver tumors. In both Pu- and Am-treated dogs, the most frequently appearing neoplasm was the bile duct adenoma, followed by the cholangiocarcinoma. The most obvious difference between Pu- and Am-induced liver neoplasia was the greater frequency of fibrosarcomas and mast cell sarcomas in the Am-treated groups. Hepatomas were of relatively low frequency in animals with Pu or Am burdens. Although the incidence of bone neoplasia was high among the dogs in these studies, the risk of liver tumors, especially in the Am-treated animals, exceeded that of the skeleton in some of the lower dosage levels where the survival times were long.

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

    PubMed

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

    2016-02-01

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

  1. Cat and Dog Bites

    MedlinePlus

    ... Prevention and Wellness Staying Healthy Pets and Animals Cat and Dog Bites Cat and Dog Bites Pets and AnimalsPrevention and WellnessStaying Healthy Share Cat and Dog Bites Cat and dog bites are ...

  2. The effect of water and shampooing on the efficacy of a pyriprole 12.5% topical solution against brown dog tick (Rhipicephalus sanguineus) and cat flea (Ctenocephalides felis) infestations on dogs.

    PubMed

    Schuele, G; Barnett, S; Bapst, B; Cavaliero, T; Luempert, L; Strehlau, G; Young, D R; Moran, C; Junquera, P

    2008-02-14

    The efficacy of a single treatment with a 12.5% pyriprole spot-on formulation against induced infestations with R. sanguineus ticks and cat fleas (C. felis) as well as its persistence after repeated washing and shampooing was investigated in four separate studies. In a first study on R. sanguineus involving 32 beagle dogs, the efficacy at various time-points during the 30 days that followed treatment assessed 48 h after re-infestation ranged from 100% to 99.3%. No engorged ticks, alive or dead, were found in the treated animals. Shampooing 2 days after treatment and weekly washings did not affect the efficacy. In a second study on R. sanguineus involving 32 beagle dogs, the efficacy at various time-points during the 30 days that followed treatment assessed 48 h after re-infestation ranged from 100% to 96.8%. Single washing 8h after treatment and single shampooing 24 h after treatment had no negative impact on the efficacy of the product. In a third study on C. felis involving 28 beagle dogs, the efficacy at various time-points during the 30 days that followed treatment assessed 48 h after re-infestation was always 100% and weekly washings did not diminish the efficacy. In a last study on C. felis involving 24 beagle dogs, the efficacy at various time-points during the 5 weeks that followed treatment assessed 48 h after re-infestation ranged from 100% to 99.8%, and shampooing 24 h after treatment did not reduce the efficacy. The product was well tolerated by the dogs.

  3. Beagle 2: the exobiological lander of Mars Express

    NASA Astrophysics Data System (ADS)

    Pullan, D.; Sims, M. R.; Wright, I. P.; Pillinger, C. T.; Trautner, R.

    2004-08-01

    In late 2003, the Beagle 2 lander component of the Mars Express mission is planned to touch down in the Isidis Planitia region of Mars (265.0°W, 11.6°N). Once safely deployed on the surface, Beagle 2 will conduct an intensive and exhaustive programme of surface operations for about 180 sols (equivalent to about 6 months on Earth). The principal objective is the detection of extinct and/or extant life, or at least to establish if the conditions at the landing site were ever suitable for life to have evolved in the planet's history. To achieve this goal, a systematic set of experiments using a complemetary suite of instruments will perform in situ geochemical, mineralogical and petrological analysis of selected rocks and soils. Studies of the martian environment will also be conducted via chemical analysis of the atmosphere, local geomorphological assessment of the landing site and measurement/monitoring of dynamic environmental processes, including transient events such as "dust devils". Further studies, unique to Beagle 2, include analysis of the subsurface regime using a ground penetration tool and the first attempt at in situ isotopic dating of rocks on another planet. The complete experiment package weights less than 9 kg and requires less than 40 W of power. With a probe mass limit of 69 kg, imposed by mission constraints, and a landed mass of 33 kg, Beagle 2 thus aims to fly the highest mass ratio of payload-to-support systems of any mission to Mars. This is achievable only by adopting an integrated design approach and employing minimal or zero redundancy.

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

    SciTech Connect

    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.

  5. Genomic Regions Associated With Interspecies Communication in Dogs Contain Genes Related to Human Social Disorders.

    PubMed

    Persson, Mia E; Wright, Dominic; Roth, Lina S V; Batakis, Petros; Jensen, Per

    2016-09-29

    Unlike their wolf ancestors, dogs have unique social skills for communicating and cooperating with humans. Previously, significant heritabilities for human-directed social behaviors have been found in laboratory beagles. Here, a Genome-Wide Association Study identified two genomic regions associated with dog's human-directed social behaviors. We recorded the propensity of laboratory beagles, bred, kept and handled under standardized conditions, to initiate physical interactions with a human during an unsolvable problem-task, and 190 individuals were genotyped with an HD Canine SNP-chip. One genetic marker on chromosome 26 within the SEZ6L gene was significantly associated with time spent close to, and in physical contact with, the human. Two suggestive markers on chromosome 26, located within the ARVCF gene, were also associated with human contact seeking. Strikingly, four additional genes present in the same linkage blocks affect social abilities in humans, e.g., SEZ6L has been associated with autism and COMT affects aggression in adolescents with ADHD. This is, to our knowledge, the first genome-wide study presenting candidate genomic regions for dog sociability and inter-species communication. These results advance our understanding of dog domestication and raise the use of the dog as a novel model system for human social disorders.

  6. Efficacy of fipronil, amitraz and (S)-methoprene combination spot-on for dogs against adult dog fleas (Ctenocephalides canis, Curtis, 1826).

    PubMed

    Bouhsira, Emilie; Yoon, Stephen S; Roques, Martine; Manavella, Coralie; Vermot, Solange; Cramer, Luiz G; Ollagnier, Catherine; Franc, Michel

    2011-07-15

    A novel spot-on formulation combining fipronil, amitraz and (S)-methoprene (CERTIFECT™, Merial Limited, GA, USA) was evaluated in adult Beagle dogs in a study to determine its adulticidal efficacy against the dog flea (Ctenocephalides canis, Curtis, 1826). Sixteen dogs were randomly allocated to treatment groups: 8 dogs served as untreated controls, and 8 dogs were treated once. Treatment consisted of applying a new combination formulation to deliver at least 6.7mg fipronil/kg body weight (bw), 8.0mg amitraz/kg bw, and 6.0mg (S)-methoprene/kg bw. The combination was designed to enhance the efficacy against ticks of the original fipronil/(S)-methoprene combination. Each dog was infested with 100 adult unfed dog fleas within 24h prior to treatment and then at weekly intervals for 8 weeks after treatment. At 24h after treatment or after each subsequent infestation, each dog was combed thoroughly to remove live fleas to be counted. A single treatment with CERTIFECT provided excellent knock-down of fleas within 24h after treatment and controlled re-infestations for up to 7 weeks (efficacy ≥96.5%, p<0.05).

  7. Titanium implants in irradiated dog mandibles

    SciTech Connect

    Schweiger, J.W. )

    1989-08-01

    The use of osseointegrated titanium implants has been a great benefit to selected cancer patients who otherwise would not be able to wear conventional and/or maxillofacial prostheses. Cognizant of the risk of osteoradionecrosis, we used an animal model to seek experimental evidence for successful osseointegration in bone irradiated to tumoricidal levels. Five healthy male beagle dogs received 60 gray to a previously edentulated and healed area of the right hemimandible. The left hemimandible was kept as a nonirradiated control. After 9 months, titanium implants were placed and allowed an additional 5 1/2 months to osseointegrate. At that time, block specimens were obtained, radiographed, photographed, and analyzed histologically. Although statistical significance cannot be attached to the results, osseointegration was achieved in half of the irradiated specimens.

  8. Primary ciliary dyskinesia in Newfoundland dogs.

    PubMed

    Watson, P J; Herrtage, M E; Peacock, M A; Sargan, D R

    1999-06-26

    Primary ciliary dyskinesia was diagnosed in three Newfoundland dogs with histories of chronic rhinitis and bronchopneumonia from an early age. Thoracic radiographs of two of them showed severe, dependent bronchopneumonia and right displacement of the cardiac apex but normal positioning of other organs. Histopathological examination of sections of lung from the other dog showed severe bronchopneumonia. A semen sample from one dog had a high percentage of spermatozoa with abnormal tails and poor progressive motility. Transmission electron microscopy of nasal brushings from all three dogs showed consistent ultrastructural defects in the cilia, including an absence of outer and inner dynein arms, disorganisation of peripheral doublets, occasional supernumerary doublets and singlets, and consistently disorganised basal bodies and foot processes; sections of trachea from one dog also had disorganised basal bodies. Pedigree analysis was consistent with a monogenic autosomal recessive pattern of inheritance for the defect. One dog is still alive, one dog died aged five years two months, and one dog was euthanased aged nine months. This is the first time primary ciliary dyskinesia has been reported in Newfoundland dogs.

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

    NASA Astrophysics Data System (ADS)

    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.

  10. Histocompatibility studies in a closely bred colony of dogs. V. Mechanisms of cellular adaptation in long-term DL-A identical radiation chimeras

    PubMed Central

    1975-01-01

    20 Cooperstown beagles of known DL-A genotypes (B" dogs) were exposed to supralethal total body irradiation and received a bone marrow allograft from a DL-A identical donor (A" dog); the resulting chimeras have survived uneventfully for 882, 1466 days, with no evidence of secondary disease, and have been tolerant to kidney and skin allografts obtained from the donor of marrow. Treatment of "A" dogs with serum obtained from their long-term "B" chimeras had no significant effect upon the ability of the recipients to reject "B" skin allografts... PMID:1097570

  11. [Juvenile sterile granulomatous dermatitis and lymphadenitis in the dog].

    PubMed

    Weingart, C; Eule, C; Welle, M; Kohn, B

    2011-04-01

    Juvenile sterile granulomatous dermatitis and lymphadenitis is a rare immune-mediated skin disease in young dogs. History, signalment, diagnostics, treatment, and outcome in 10 dogs are described. The age ranged from 8 - 36 weeks. The lymph nodes were enlarged in all dogs, especially the mandibular and prescapular lymph nodes. Systemic signs including fever were present in 8 dogs. Seven dogs suffered from blepharitis and painful edema of the muzzle with hemorrhagic discharge, pustules and papules. Cytology of pustules and lymph node aspirates revealed a pyogranulomatous inflammation. In 7 cases the diagnosis of juvenile sterile granulomatous dermatitis and lymphadenitis was confirmed by histology. Nine dogs were treated with prednisolone (0.5 - 1.25 mg/kg BID), H2-receptor antagonists and analgetics; all dogs were treated with antibiotics. Four dogs were treated with eye ointment containing antibiotics and glucocorticoids. The prednisolone dosage was tapered over 3 - 8 weeks. One dog had a relapse.

  12. Dog Fights

    ERIC Educational Resources Information Center

    Taylor, Kelley R.

    2010-01-01

    Bringing service animals into schools raises serious questions about how to meet one student's special needs while ensuring the educational well-being of all. This article discusses how schools grapple with the practical and legal questions involved in allowing service dogs on campus. The author cites a case in 2009 called "Kalbfleisch v. Columbia…

  13. The biological effects of radium-224 injected into dogs

    SciTech Connect

    Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.

    1996-08-01

    A life-span study was conducted in 128 beagle dogs to determine the biological effects of intravenously injected {sup 224}Ra chloride. The {sup 224}Ra chloride was prepared by the same method used for intravenous injections in humans who were treated for ankylosing spondylitis and tuberculosis. Thus the results obtained from dogs can be compared directly to the population of treated humans, both for the elucidation of the effect of exposure rate and for comparison with other radionuclides for which data for humans are unavailable. Using equal numbers of males and females, the dogs were injected with one of four levels of {sup 224}Ra resulting in initial body burdens of approximately 13, 40, 120 or 350 kBq of {sup 224}Ra kg{sup -1} body mass. A control group of dogs was injected with diluent only. All dogs were divided further into three groups for which the amount of injected {sup 224}Ra (half-life of 3.62 days) or diluent was given in a single injection or divided equally into 10 or 50 weekly injections. As a result of these three injection schedules, the accumulation of dose from the injected {sup 224}Ra was distributed over approximately 1, 3 or 12 months. Each injection schedule included four different injection levels resulting in average absorbed {alpha}-particle doses to bone of 0.1, 0.3, 1 and 3 Gy, respectively. The primary early effect observed was a hematological dyscrasia in the dogs receiving either of the two highest injection levels. The effect was most severe in the dogs receiving a single injection of {sup 224}Ra and resulted in the death of three dogs injected at the highest level. The late-occurring biological effects were tumors. Bone tumors were the most common followed by tumors in the nasal mucosa. 52 refs., 8 figs., 8 tabs.

  14. Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium, antimony, selenium, and lead in the liver and kidneys of dogs according to age, gender, and the occurrence of chronic kidney disease.

    PubMed

    Passlack, Nadine; Mainzer, Barbara; Lahrssen-Wiederholt, Monika; Schafft, Helmut; Palavinskas, Richard; Breithaupt, Angele; Zentek, Jürgen

    2015-01-01

    This study was conducted to measure the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se), and lead (Pb) in canine liver, renal cortex, and renal medulla, and the association of these concentrations with age, gender, and occurrence of chronic kidney disease (CKD). Tissues from 50 dogs were analyzed using inductively coupled plasma mass spectrometry. Cu, Zn, and Mn levels were highest in the liver followed by the renal cortex and renal medulla. The highest Sr, Cd, and Se concentrations were measured in the renal cortex while lower levels were found in the renal medulla and liver. Female dogs had higher tissue concentrations of Sr (liver and renal medulla), Cd (liver), Zn (liver and renal cortex), Cr (liver, renal cortex, and renal medulla), and Pb (liver) than male animals. Except for Mn and Sb, age-dependent variations were observed for all element concentrations in the canine tissues. Hepatic Cd and Cr concentrations were higher in dogs with CKD. In conclusion, the present results provide new knowledge about the storage of specific elements in canine liver and kidneys, and can be considered important reference data for diagnostic methods and further investigations.

  15. Health effects of low-level irradiation during development: experimental design and prenatal and early neonatal mortality in beagles exposed to /sup 60/Co gamma rays

    SciTech Connect

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

    1988-07-01

    As part of a long-term study of the effects of irradiation during development, prenatal and early neonatal mortality were evaluated for beagles exposed in utero at 8 days postcoitus (dpc), 28 dpc, 55 dpc, or 2 days postpartum. Mean doses used were 0,0.16, or 0.83 Gy. A decrease in whelping rates was observed for female breeders irradiated at 8 dpc. There was a significant decrease in litter sizes from female breeders irradiated at 8 and 28 dpc. Both of these findings are indicative of increased embryonic mortality. There was a significant decrease in the percentage of females born after exposures given at 28 dpc, indicating a differential radiosensitivity by sex. A significant increase in early neonatal mortality up to 14 days of age was observed for beagles exposed 8 or 28 dpc, again with an excess mortality in females.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS

    PubMed Central

    Rapaport, Felix T.; Boyd, Arthur D.; Spencer, Frank C.; Lower, Richard R.; Dausset, Jean; Cannon, Florence D.; Ferrebee, Joseph W.

    1971-01-01

    The DL-A system of histocompatibility plays an important role in conditioning the survival of cardiac allografts in the unmodified canine host. The mean survival time of six cardiac allografts performed in DL-A-compatible littermate dogs obtained from a closely bred colony of beagles was 53.2 days, while the MST of transplants performed in seven DL-A-incompatible animals was 7.3 days. The MST of cardiac allografts performed in nine DL-A-compatible nonlittermate beagles was 26.3 days, as compared with 6.3 days in six DL-A-incompatible nonlittermate transplants. The results did not appear to be affected by Swisher erythrocyte-group incompatibilities. The MST of 28 cardiac allografts performed in randomly selected mongrel dogs was 10.0 days. Incompatibilities for DL-A antigens e, f, g, l, and m may constitute major barriers to transplantation, but antigens b, c, d, and k appeared to act as weak histocompatibility antigens. Under controlled conditions of donor-recipient DL-A compatibility, cardiac allografts may be less immunogenic than renal transplants. Heart transplants performed across major donor-recipient DL-A incompatibilities appeared, however, to be more vulnerable to the events of allograft rejection than renal allografts performed under similar conditions. The selection of optimally compatible donor-recipient combinations for organ transplantation may be aided materially by genetic studies of the transmission of DL-A antigens to the animals under consideration. PMID:4943931

  18. Comparison of behavioral characteristics of dogs in the United States and Japan.

    PubMed

    Nagasawa, Miho; Kanbayashi, Shunichi; Mogi, Kazutaka; Serpell, James A; Kikusui, Takefumi

    2016-02-01

    This study examined the difference in dog owning between Japan and the United States, and the effect of these differences on dogs' behavioral characteristics. Behavioral evaluations of privately-owned dogs were obtained by using online questionnaire. We compared background and demographic information from the two countries and analyzed the effects of these differences on behavioral characteristics in dogs. The results indicated that there was a bias in the dog breeds kept in Japan compared to the United States and that Japanese dogs' body weight was lower than the US dogs. The main source of dog acquisition was pet stores in Japan and breeders and/or shelters in the United States. Multiple linear regression analysis found that Japanese dogs showed more aggression to household members and higher energy, restlessness and fear of non-social stimuli than US dogs, while US dogs showed more fear of unfamiliar persons, separation-related behavior and excitability. US dogs also showed higher levels of trainability and attachment to owners. The lower dog's body weight was, the higher the behavioral scores except for trainability were. When dogs that were obtained under 3 months of age were analyzed, the younger the dogs were when their owners obtained them, the higher the scores on some behavioral problem factors were. The higher rates of problem behaviors among Japanese dogs compared with US dogs suggest that the preference for small breed dogs and poor early development environment influenced the behavioral characteristics of dogs.

  19. Dog bite risk: an assessment of child temperament and child-dog interactions.

    PubMed

    Davis, Aaron L; Schwebel, David C; Morrongiello, Barbara A; Stewart, Julia; Bell, Melissa

    2012-08-01

    Annually approximately 400,000 American children receive treatment for dog bites. Young children are at greatest risk and are frequently bitten following behavior that provokes familiar dogs. This study investigated the effects of child temperament on children's interaction with dogs. Eighty-eight children aged 3.5-6 years interacted with a live dog. Dog and child behaviors were assessed through observational coding. Four child temperament constructs-impulsivity, inhibitory control, approach and shyness-were assessed via the parent-report Children's Behavioral Questionnaire. Less shy children took greater risks with the dog, even after controlling for child and dog characteristics. No other temperament traits were associated with risk-taking with the dog. Based on these results, children's behavior with unfamiliar dogs may parallel behavior with other novel or uncertain situations. Implications for dog bite intervention programs include targeting at-risk children and merging child- and parent-oriented interventions with existing programs geared toward the physical environment and the dog.

  20. [Keeping dogs indoor aggravates infantile atopic dermatitis].

    PubMed

    Endo, K; Hizawa, T; Fukuzumi, T; Kataoka, Y

    1999-12-01

    We had a two-month-old girl with severe dermatitis since birth. Her serum RAST to HD, Df and Dp were 1.06, 0.03 and 0.01 Ua/ml respectively. A Yorkshire terrier were kept at her mother's parents' home where the patient had lived for a month since birth. Her eczema, which became markedly aggravated whenever she visited there, improved after the elimination of the dog. We investigated the relationship between keeping dogs and infantile atopic dermatitis. We studied 368 patients under the age of two years (211 boys and 157 girls). Skin symptoms were graded globally mild, moderate or severe. Total serum IgE and specific antibody titer to dog dander were measured. We asked them whether they kept dogs and specifically, where they kept dogs, outdoor, indoor, in their own house, or in their grandparents' house. 197 patients had no contact with dogs, 90 patients kept dogs outdoor and 81 patients did indoor. The positive rate of RAST (> or = 0.7 Ua/ml) to dog dander was 6.1%, 17.8% and 46.9% respectively in these three groups. There were strong statistical differences between three groups. On the other hand, among the 81 patients who kept indoor, the RAST positive rates were almost same regarding where the dogs were kept, in their own house or their grandparents' house. Interestingly this difference happens only with patients under the age of 3 months. Patients older than 4 months showed no significant differences in the positive RAST rates, whether they kept dogs indoor or outdoor. This suggests the sensitization occurs before the age of 3 months. Speaking of symptoms, patients who kept dogs indoor showed significantly more severe symptoms than patients who had no contact with dogs and patients who kept dogs outdoor. There was no significant difference between the symptoms of patients who had no contact with dogs and those of patients who kept dogs outdoor. This implies the patient's symptom will improve only by moving the dog out of the house.

  1. Microdistribution and local dosimetry of /sup 226/Ra in trabecular bone of the beagle

    SciTech Connect

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

    1988-11-01

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

  2. Dog Bite Emergencies

    MedlinePlus

    ... Emergency Care Animal Welfare Veterinary Careers Public Health Dog bite emergencies What do I do if I’ ... vaccination records. What do I do if my dog bites someone? Dog bites are scary for everyone ...

  3. Transmission of avian influenza virus (H3N2) to dogs.

    PubMed

    Song, Daesub; Kang, Bokyu; Lee, Chulseung; Jung, Kwonil; Ha, Gunwoo; Kang, Dongseok; Park, Seongjun; Park, Bongkyun; Oh, Jinsik

    2008-05-01

    In South Korea, where avian influenza virus subtypes H3N2, H5N1, H6N1, and H9N2 circulate or have been detected, 3 genetically similar canine influenza virus (H3N2) strains of avian origin (A/canine/Korea/01/2007, A/canine/Korea/02/2007, and A/canine/Korea/03/2007) were isolated from dogs exhibiting severe respiratory disease. To determine whether the novel canine influenza virus of avian origin was transmitted among dogs, we experimentally infected beagles with this influenza virus (H3N2) isolate. The beagles shed virus through nasal excretion, seroconverted, and became ill with severe necrotizing tracheobronchitis and bronchioalveolitis with accompanying clinical signs (e.g., high fever). Consistent with histologic observation of lung lesions, large amounts of avian influenza virus binding receptor (SAalpha 2,3-gal) were identified in canine tracheal, bronchial, and bronchiolar epithelial cells, which suggests potential for direct transmission of avian influenza virus (H3N2) from poultry to dogs. Our data provide evidence that dogs may play a role in interspecies transmission and spread of influenza virus.

  4. Expression of caveolin-1 in the early phase of beta-TCP implanted in dog mandible.

    PubMed

    Chou, Cherng-Tzeh; Bhawal, Ujjal K; Watanabe, Nobuyuki; Kuboyama, Noboru; Chang, Wei-Jen; Lee, Sheng-Yang; Abiko, Yoshimitsu

    2013-07-01

    Caveolin is an essential and signature protein of caveolae. Caveolin-1 participates in signal transduction processes by acting as a scaffolding protein that concentrates, organizes and functional regulates signalling molecules within caveolar membranes. Beta-tricalcium phosphate (β-TCP) has been widely used for scaffold in tissue engineering due to its high biodegradability, osteoconductivity, easy manipulation, and lack of histotoxicity. To better understand the role of caveolin-1 in bone homeostasis and response to β-TCP scaffold, β-TCP was implanted into the dog mandible defects in beagle dogs, and gene expression profiles were examined focused on the molecular components involved in caveolin-1 regulation. Here we showed the quantitative imageology analysis characterized using in vivo micro-computed tomography (CT) images at 4 and 7 days after β-TCP implanted in dog mandibles. The bone reformation by using the β-TCP scaffolds began within 4 days of surgery, and was healing well at 7 days after surgery. Higher mRNA level of caveolin-1 was observed in β-TCP-implanted Beagle dog mandibles compared with controls at day 4 and day 7 post-surgery. The enhancement of caveolin-1 by β-TCP was further confirmed by immunohistochemistry and immunofluorescence analysis. We further revealed increased Smad7 and Phospho Stat3 expression in β-TCP-implanted specimens. Taken together, these results suggest that the enhancement of caveolin-1 play an important role in accelerating bone formation by β-TCP.

  5. Genomic Regions Associated With Interspecies Communication in Dogs Contain Genes Related to Human Social Disorders

    PubMed Central

    Persson, Mia E.; Wright, Dominic; Roth, Lina S. V.; Batakis, Petros; Jensen, Per

    2016-01-01

    Unlike their wolf ancestors, dogs have unique social skills for communicating and cooperating with humans. Previously, significant heritabilities for human-directed social behaviors have been found in laboratory beagles. Here, a Genome-Wide Association Study identified two genomic regions associated with dog’s human-directed social behaviors. We recorded the propensity of laboratory beagles, bred, kept and handled under standardized conditions, to initiate physical interactions with a human during an unsolvable problem-task, and 190 individuals were genotyped with an HD Canine SNP-chip. One genetic marker on chromosome 26 within the SEZ6L gene was significantly associated with time spent close to, and in physical contact with, the human. Two suggestive markers on chromosome 26, located within the ARVCF gene, were also associated with human contact seeking. Strikingly, four additional genes present in the same linkage blocks affect social abilities in humans, e.g., SEZ6L has been associated with autism and COMT affects aggression in adolescents with ADHD. This is, to our knowledge, the first genome-wide study presenting candidate genomic regions for dog sociability and inter-species communication. These results advance our understanding of dog domestication and raise the use of the dog as a novel model system for human social disorders. PMID:27685260