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Sample records for aged ovariectomized beagles

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-12-31

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

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

    International Nuclear Information System (INIS)

    Our purpose was to evaluate the effects of ovariectomy in conjunction with cadmium (Cd) exposure on bone. Aged female beagles with 45Ca-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 45Ca content and 45Ca/dry and 45Ca/ash ratios were observed in long bones and vertebrae of OV- and OV+ groups. In contrast, intact ribs showed significantly decreased Ca/dry and Ca/ash ratios compared to the SO-group. Quartered ribs demonstrated regional responses to specific treatment; decreases in total Ca content were greatest in the mid-rib region (-36 to -46%). Results suggest that in the aged female beagle, bone mineral loss associated with estrogen depletion is not only related to bone type (trabecular versus cortical) but also to bone Ca pools. Our results also suggest that a regional heterogeneity of bone plays a role in responsiveness to ovariectomy and Cd exposure. These aspects suggest that Cd is an exogenous factor affecting bone mineral loss independently of estrogen depletion. However, estrogen depletion primes bone for responsiveness to Cd-induced bone mineral loss

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-08-01

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

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

    International Nuclear Information System (INIS)

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

  6. Voluntary Exercise Impairs Initial Delayed Spatial Alternation Performance in Estradiol Treated Ovariectomized Middle-Aged Rats

    OpenAIRE

    Neese, Steven L.; Korol, Donna L.; Schantz, Susan L.

    2013-01-01

    Estrogens differentially modulate behavior in the adult female rodent. Voluntary exercise can also impact behavior, often reversing age associated decrements in memory processes. Our research group has published a series of papers reporting a deficit in the acquisition of an operant working memory task, delayed spatial alternation (DSA), following 17β-estradiol treatment to middle-aged ovariectomized (OVX) rats. The current study examined if voluntary exercise could attenuate the 17β-estradio...

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-01-01

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

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

    International Nuclear Information System (INIS)

    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 45Ca labeled skeletons were divided into four groups: sham controls (SO-); ovariectomized (OV-); shams exposed to Cd (SO+); ovariecomized exposed to Cd (OV+). Total Cd exposure period was 7 months, including 1 month by capsules and 6 months by drinking H2O. 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 45Ca content, were determined for each quarter. Analysis of ribs from control animals demonstrated that a given rib is heterogeneous in composition. One end appears to be less mineralized and more metabolically active than other regions. The OV- and OV+ mid-rib regions had significantly lower dry and ash weights than SO-. Total Ca contents of these same regions were also decreased in the OV- and OV+. The only significant change in Ca/dry and Ca/ash was observed when comparing OV+ to SO-. Analysis of treatment suggests that there are regional effects following ovariectomy increased the loss of bone mineral occurring as a result of ovariectomy. 30 refs., 1 fig

  10. Age incidence and site distribution of mammary dysplasias in young beagle bitches

    Energy Technology Data Exchange (ETDEWEB)

    Warner, M.R.

    1976-07-01

    The age incidence and site distribution of 2,142 mammary dysplasias were documented for 39 beagle bitches 6 months to 4 years of age. Lesion onset was at 2-3 years of age, at which time more than 50 percent of the females had dysplasias. Dysplasias appeared before palpable tumors. Posterior mammae developed more lesions than did anterior mammae. Thus the gradient for early onset of lesions coincided with the gradient for tumor frequency reported previously; a preneoplastic potential is suggested for (some) dysplasias. Problems of defining normal tissue are discussed.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    The influence of age at exposure on the metabolism, dosimetry, and biological effects of inhaled 239PuO2 particles is being studied in aged Beagle dogs (8.0-10.5 yr of age at exposure). Forty-eight dogs inhaled 239PuO2 particles with an activity median aerodynamic diameter of 1.5 mm to achieve graded levels of initial pulmonary burdens (IPB) ranging from 0.02-0.66 μCi 239Pu/kg body weight (0.75-24 kBq/kg). Twelve other dogs were exposed to the aerosol diluent only. All forty-eight exposed dogs have died, including two in the past year. The twelve control dogs have also died, including one in the past year. Radiation pneumonitis and pulmonary fibrosis have been the primary causes of death in these aged dogs exposed to 239PuO2. (author)

  13. Effect of Age and Level of Cognitive Function on Spontaneous and Exploratory Behaviors in the Beagle Dog

    OpenAIRE

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

    2001-01-01

    Cognitively characterized young and aged beagle dogs were administered six different spontaneous behavior tests, which provided measures of locomotion, exploration, and social interaction. Consistent with our previous findings, we obtained no overall effect of age on locomotion. We did find, however, that for the aged dogs locomotion correlated with level of cognitive function, being lowest in age-unimpaired dogs and highest in impaired dogs. Exploratory behavior, as measured by response to n...

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

    OpenAIRE

    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 w...

  15. Gross and surgical pathologic findings in beagles receiving gamma radiation during development and sacrificed at 5 or 8 years of age

    International Nuclear Information System (INIS)

    Gross necropsy examinations have been completed on each of the 140 beagles scheduled for sacrifice at 5 years of age and on 28 of 140 beagles for sacrifice at 8 years of age. To date, the only major gross pathologic changes that are correlated with radiation treatment are an unusual number of testicular tumors occurring in irradiated dogs, especially in those receiving 100R at 55 days postcoitus and sacrificed at 5 years of age

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

    International Nuclear Information System (INIS)

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

  17. The GABAA antagonist bicuculline attenuates progesterone-induced memory impairments in middle-aged ovariectomized rats

    Directory of Open Access Journals (Sweden)

    B. Blair Braden

    2015-08-01

    Full Text Available In women, high levels of natural progesterone have been associated with detrimental cognitive effects via the “maternal amnesia” phenomenon as well as in controlled experiments. In aged ovariectomized (Ovx rats, progesterone has been shown to impair cognition and impact the GABAergic system in cognitive brain regions. Here, we tested whether the GABAergic system is a mechanism of progesterone’s detrimental cognitive effects in the Ovx rat by attempting to reverse progesterone-induced impairments via concomitant treatment with GABAA antagonist, bicuculline. Thirteen month old rats received Ovx plus daily vehicle, progesterone, bicuculline, or progesterone+bicuculline injections beginning two weeks prior to testing. The water radial-arm maze was used to evaluate spatial working and reference memory. During learning, rats administered progesterone made more working memory errors than those administered vehicle, and this impairment was reversed by the addition of bicuculline. The progesterone impairment was transient and all animals performed similarly by the end of regular testing. On the last day of testing, a six-hour delay was administered to evaluate memory retention. Progesterone-treated rats were the only group to increase working memory errors with the delay; the addition of bicuculline prevented the progesterone-induced impairment. The vehicle, bicuculline, and progesterone+bicuculline groups were not impaired by the delay. The current rodent findings corroborate prior research reporting progesterone-induced detriments on cognition in women and in the aging Ovx rat. Moreover, the data suggest that progesterone-induced cognitive impairment is, in part, related to the GABAergic system. Given that progesterone is included in numerous clinically-prescribed hormone therapies and contraceptives (e.g. micronized, and as synthetic analogs, further research is warranted to better understand the parameters and mechanism(s of progesterone

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

    Science.gov (United States)

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

    2016-03-01

    AstraZeneca ran a bespoke study to generate age-matched clinical pathology and histopathology data from a cohort of Beagle dogs aged between 25 and 37 months to support the use of these older animals in routine preclinical toxicology studies. As the upper age range of Beagle dogs routinely used in toxicology studies does not normally exceed 24 months, there is an absence of appropriate age-matched historical control data. The generation of such data was crucial to understand whether age-related differences in spontaneous findings might confound the interpretation of toxicology study data. While the majority of the histopathology findings in all the older dogs occurred at a similar prevalence as those expected in young adult dogs (<24 months), a number of differences were observed in the thymus (involution), bone marrow (increased adiposity), testes (degenerative changes), and lung (fibrosis, pigment and alveolar hyperplasia) that could be misinterpreted as a test article effect. Minor differences in some clinical pathology values (hemoglobin, alkaline phosphatase, absolute reticulocytes) were of a small magnitude and considered unlikely to affect the interpretation of study data. PMID:26553522

  19. The effects of strength training and raloxifene on bone health in aging ovariectomized rats.

    Science.gov (United States)

    Stringhetta-Garcia, Camila Tami; Singulani, Monique Patrício; Santos, Leandro Figueiredo; Louzada, Mário Jefferson Quirino; Nakamune, Ana Cláudia Stevanato; Chaves-Neto, Antonio Hernandes; Rossi, Ana Cláudia; Ervolino, Edilson; Dornelles, Rita Cássia Menegati

    2016-04-01

    The aim of this study was to investigate the effects of strength training (ST) and raloxifene (Ral), alone or in combination, on the prevention of bone loss in an aging estrogen-deficient rat model. Aging Wistar female rats were ovariectomized at 14months and allocated to four groups: (1) non-trained and treated with vehicle, NT-Veh; (2) strength training and treated with vehicle, ST-Veh; (3) non-trained and treated with raloxifene, NT-Ral; and (4) strength training and treated with raloxifene, ST-Ral. ST was performed on a ladder three times per week and Ral was administered daily by gavage (1mg/kg/day), both for 120days. Areal bone mineral density (aBMD), strength, microarchitecture, and biomarkers (osteocalcin, OCN; osteoprotegerin, OPG; and tartrate-resistant acid phosphatase, TRAP) were assessed. Immunohistochemistry was performed for runt-related transcription factor 2 (RUNX2), osterix (OSX), OCN, OPG, TRAP, and receptor activator of nuclear factor kappa-B ligand (RANKL). The rats that performed ST (ST-Veh) or were treated with Ral (NT-Ral) showed significant improvements in aBMD (p=0.001 and 0.004), bone strength (p=0.001), and bone microarchitecture, such as BV/TV (%) (p=0.001), BS/TV (mm(2)/mm(3)) (p=0.023 and 0.002), Conn.Dn (1/mm(3)) (p=0.001), Tb.N (1/mm) (p=0.012 and 0.011), Tb.Th (1/mm) (p=0.001), SMI (p=0.001 and 0.002), Tb.Sp (p=0.001), and DA (p=0.002 and 0.007); there was also a significant decrease in plasma levels of OCN (p=0.001 and 0.002) and OPG (p=0.003 and 0.014), compared with animals in the NT-Veh group. Ral, with or without ST, promoted an increased immunolabeling pattern for RUNX2 (p=0.0105 and p=0.0006) and OSX (p=0.0105), but a reduced immunolabeling pattern for TRAP (p=0.0056) and RANKL (p=0.033 and 0.004). ST increased the immunolabeling pattern for RUNX2 (p=0.0105), and association with Ral resulted in an increased immunolabeling pattern for OPG (p=0.0034) and OCN (p=0.0024). In summary, ST and Ral administration in aged, estrogen

  20. Sequential treatment with basic fibroblast growth factor and parathyroid hormone restores lost cancellous bone mass and strength in the proximal tibia of aged ovariectomized rats

    DEFF Research Database (Denmark)

    Wronski, T.J.; Ratkus, A.M.; Thomsen, Jesper Skovhus; Vulcan, Q.; Mosekilde, Lis

    2001-01-01

    This study was designed to determine whether sequential treatment with basic fibroblast growth factor (bFGF) and parathyroid hormone (PTH) can restore lost cancellous bone mass and strength at a severely osteopenic skeletal site in aged ovariectomized (OVX) rats. Female Sprague-Dawley rats were s...

  1. Long-Term Estrogen Receptor Beta Agonist Treatment Modifies the Hippocampal Transcriptome in Middle-Aged Ovariectomized Rats.

    Science.gov (United States)

    Sárvári, Miklós; Kalló, Imre; Hrabovszky, Erik; Solymosi, Norbert; Rodolosse, Annie; Liposits, Zsolt

    2016-01-01

    Estradiol (E2) robustly activates transcription of a broad array of genes in the hippocampal formation of middle-aged ovariectomized rats via estrogen receptors (ERα, ERβ, and G protein-coupled ER). Selective ERβ agonists also influence hippocampal functions, although their downstream molecular targets and mechanisms are not known. In this study, we explored the effects of long-term treatment with ERβ agonist diarylpropionitrile (DPN, 0.05 mg/kg/day, sc.) on the hippocampal transcriptome in ovariectomized, middle-aged (13 month) rats. Isolated hippocampal formations were analyzed by Affymetrix oligonucleotide microarray and quantitative real-time PCR. Four hundred ninety-seven genes fulfilled the absolute fold change higher than 2 (FC > 2) selection criterion. Among them 370 genes were activated. Pathway analysis identified terms including glutamatergic and cholinergic synapse, RNA transport, endocytosis, thyroid hormone signaling, RNA degradation, retrograde endocannabinoid signaling, and mRNA surveillance. PCR studies showed transcriptional regulation of 58 genes encoding growth factors (Igf2, Igfb2, Igf1r, Fgf1, Mdk, Ntf3, Bdnf), transcription factors (Otx2, Msx1), potassium channels (Kcne2), neuropeptides (Cck, Pdyn), peptide receptors (Crhr2, Oprm1, Gnrhr, Galr2, Sstr1, Sstr3), neurotransmitter receptors (Htr1a, Htr2c, Htr2a, Gria2, Gria3, Grm5, Gabra1, Chrm5, Adrb1), and vesicular neurotransmitter transporters (Slc32a1, Slc17a7). Protein-protein interaction analysis revealed networking of clusters associated with the regulation of growth/troph factor signaling, transcription, translation, neurotransmitter and neurohormone signaling mechanisms and potassium channels. Collectively, the results reveal the contribution of ERβ-mediated processes to the regulation of transcription, translation, neurogenesis, neuromodulation, and neuroprotection in the hippocampal formation of ovariectomized, middle-aged rats and elucidate regulatory channels responsible for

  2. Long-Term Estrogen Receptor Beta Agonist Treatment Modifies the Hippocampal Transcriptome in Middle-Aged Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Miklós Sárvári

    2016-06-01

    Full Text Available Estradiol (E2 robustly activates transcription of a broad array of genes in the hippocampal formation of middle-aged ovariectomized rats via estrogen receptors (ERα, ERβ and G protein-coupled ER. Selective ERβ agonists also influence hippocampal functions, although their downstream molecular targets and mechanisms are not known. In this study, we explored the effects of long-term treatment with ERβ agonist diarylpropionitrile (DPN, 0.05 mg/kg/day, sc. on the hippocampal transcriptome in ovariectomized, middle-aged (13 month rats. Isolated hippocampal formations were analyzed by Affymetrix oligonucleotide microarray and quantitative real-time PCR. Four hundred ninety-seven genes fulfilled the absolute fold change higher than 2 (FC>2 selection criterion. Among them 370 genes were activated. Pathway analysis identified terms including glutamatergic and cholinergic synapse, RNA transport, endocytosis, thyroid hormone signaling, RNA degradation, retrograde endocannabinoid signaling and mRNA surveillance. PCR studies showed transcriptional regulation of 58 genes encoding growth factors (Igf2, Igfb2, Igf1r, Fgf1, Mdk, Ntf3, Bdnf, transcription factors (Otx2, Msx1, potassium channels (Kcne2, neuropeptides (Cck, Pdyn, peptide receptors (Crhr2, Oprm1, Gnrhr, Galr2, Sstr1, Sstr3, neurotransmitter receptors (Htr1a, Htr2c, Htr2a, Gria2, Gria3, Grm5, Gabra1, Chrm5, Adrb1 and vesicular neurotransmitter transporters (Slc32a1, Slc17a7. Protein-protein interaction analysis revealed networking of clusters associated with the regulation of growth/troph factor signaling, transcription, translation, neurotransmitter and neurohormone signaling mechanisms and potassium channels. Collectively, the results reveal the contribution of ERβ-mediated processes to the regulation of transcription, translation, neurogenesis, neuromodulation and neuroprotection in the hippocampal formation of ovariectomized, middle-aged rats and elucidate regulatory channels responsible for

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-01

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

  4. Age-related pharmacokinetic changes of acetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys and beagle dogs.

    Science.gov (United States)

    Koyanagi, Takashi; Yamaura, Yoshiyuki; Yano, Koji; Kim, Soonih; Yamazaki, Hiroshi

    2014-10-01

    1. The pharmacokinetics of acetaminophen (marker of gastric emptying), antipyrine (marker of hepatic metabolic activity and total body water), diazepam (lipophilic and highly distributed), diphenhydramine (hepatic blood flow-limited and alpha-1 acid glycoprotein bound) and ofloxacin (renally eliminated) were evaluated in cynomolgus monkeys (3-18 years old) and beagle dogs (2-11 years old) as models in elderly persons. 2. Gastric pH fluctuated with aging in monkeys and dogs. The concentration of alpha-1 acid glycoprotein appeared to be increased by aging. There were no age-related differences in the absorption rates of the drugs under the conditions used in the study. Total body fat increased and water decreased in monkeys, but these parameters did not change in dogs. 3. Hepatic blood flow decreased in both species, but a significant decrease of hepatic clearance was only seen in monkeys. Renal clearance decreased significantly with age in monkeys and showed a tendency to decrease in dogs. 4. Age-related alterations of physiological parameters in monkeys are in agreement with clinical observations in humans, except for the lack of a change in the plasma albumin concentration. Therefore, this study suggests that monkey might be a suitable animal model for prediction of age-related changes in pharmacokinetics in humans. PMID:24650193

  5. Acute effects of 17 β-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats.

    Science.gov (United States)

    Alonso, Ana; González-Pardo, Héctor; Garrido, Pablo; Conejo, Nélida M; Llaneza, Plácido; Díaz, Fernando; Del Rey, Carmen González; González, Celestino

    2010-12-01

    Aging is characterized by decline in metabolic function and insulin resistance, and both seem to be in the basis of neurodegenerative diseases and cognitive dysfunction. Estrogens prevent age-related changes, and phytoestrogens influence learning and memory. Our hypothesis was that estradiol and genistein, using rapid-action mechanisms, are able to modify insulin sensitivity, process of learning, and spatial memory. Young and aged ovariectomized rats received acute treatment with estradiol or genistein. Aged animals were more insulin-resistant than young. In each age, estradiol and genistein-treated animals were less insulin-resistant than the others, except in the case of young animals treated with high doses of genistein. In aged rats, no differences between groups were found in spatial memory test, showing a poor performance in the water maze task. However, young females treated with estradiol or high doses of genistein performed well in spatial memory task like the control group. Only rats treated with high doses of genistein showed an optimal spatial memory similar to the control group. Conversely, acute treatment with high doses of phytoestrogens improved spatial memory consolidation only in young rats, supporting the critical period hypothesis for the beneficial effects of estrogens on memory. Therefore, genistein treatment seems to be suitable treatment in aged rats in order to prevent insulin resistance but not memory decline associated with aging. Acute genistein treatment is not effective to restore insulin resistance associated to the early loss of ovarian function, although it can be useful to improve memory deficits in this condition. PMID:20467821

  6. Toxicity of inhaled 144Ce in fused aluminosilicate particles in aged beagle dogs. V

    International Nuclear Information System (INIS)

    The toxicity of 144Ce in fused aluminosilicate particles inhaled by 8- to 10.5-yr-old dogs is being investigated to provide information on age-related differences in the response of older members of the human population to accidental inhalation of radioactive aerosols. These data on aged dogs will be compared to the results of similar studies of dogs exposed at approximately 3 mo or 12 to 14 mo of age. Six blocks of five female dogs each have been divided into four exposure levels with mean initial lung burdens of 7.2, 14, 28 and 57 μCi 144Ce/kg body weight. Six blocks of four male dogs have been divided into three exposure levels with mean initial lung burdens of 7.2, 14 and 28 μCi 144Ce/kg body weight. Controls in each block were exposed to fused aluminosilicate particles containing stable cerium. Fifteen dogs with initial lung burdens ranging from 20 to 75 μCi 144Ce/kg body weight and cumulative doses to lung of from 22,000 to 74,000 rads have died or were euthanized 197 to 1207 days after exposure with clinicopathologic findings of radiation pneumonitis and pulmonary fibrosis.Pulmonary retention of the inhaled 144Ce was similar to that observed previously in dogs exposed at 18 to 22 mo of age in a radiation dose pattern study. Serial observations are continuing on the 19 surviving 144Ce-exposed and eight control dogs

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

    International Nuclear Information System (INIS)

    The toxicity of 144Ce inhaled in fused aluminosilicate particles by 8 to 10.5-year-old dogs is being investigated to provide information on age-related differences in the response of older members of the human population to accidental inhalation of radioactive aerosols. These data on aged dogs will be compared to the results of similar studies of dogs exposed at approximately 3 months or 12 to 14 months of age. Six blocks of five female dogs each have been divided into four exposure levels with mean initial lung burdens of 7.2, 14, 28 and 57 μCi 144Ce/kg body weight. Six blocks of four male dogs each have been divided into three exposure levels with mean initial lung burdens of 7.2, 14 and 28 μCi 144Ce/kg body weight. Controls in each block were exposed to fused aluminosilicate particles containing stable cerium. Eighteen dogs with initial lung burdens ranging from 14 to 75 μCi 144Ce/kg body weight and cumulative doses to lung of from 22,000 to 74,000 rads have died or were euthanized 197 to 1207 days after exposure with clinicopathologic findings of radiation pneumonitis and pulmonary fibrosis

  8. Soybean isoflavones alter parvalbumin in hippocampus of mid-aged normal female, ovariectomized female, and normal male rats

    Institute of Scientific and Technical Information of China (English)

    In Koo HWANG; Moo Ho WON; Yoon-bok LEE; Ki-yeon YOO; Tae-cheon KANG; Soon Sung LIM; Sang Moo KIM; Heon-soo SOHN; Woo-jung KIM; Hyun Kyung SHIN

    2006-01-01

    Aim: To investigate the long-term effect of soybean isoflavones on changes in parvalbumin (PV) immunoreactivity in the hippocampus in normal female, ovariectomized (OVX) female and normal male rats. Methods: Ten-month-old rats were assigned to one of 9 groups (n=7 in each group) based on body weight using arandomized complete-block design. The groups were: control diet-treated females,OVX females, and males; 0.3 g/kg isoflavone-treated females, OVX females, and males; and 1.2 g/kg isoflavone-treated females, OVX females, and males. The PV immunostaining was conducted by using the standard avidin-biotin complex method. Results: PV immunoreactivity and the number of PV-immunoreactive neurons in all the groups after isoflavone treatment were significantly changed in the hippocampal CA1 region and in the dentate gyrus, but not in the hippocampal CA2/3 region. PV immunoreactivity and the number of PV-immunoreactive neurons in the control diet OVX females were similar to those in the control diet, and were greater than those in the control diet normal females. PV immunoreactivity and the number of PV-immunoreactive neurons in all the isoflavone-treated groups decreased dose-dependently after isoflavone treatment. Conclusion: Long-term administration of isoflavones may induce a reduction of PV in interneurons in the hippocampal CA1 region and in the dentate gyrus. The reduction of PV in these regions suggests that the long-term administration of isoflavones may cause a change in calcium homeostasis in the hippocampal CA1 region and in the dentate gyrus.

  9. Age-related effects of estrogen on the expression of estrogen receptor (ER) α and β mRNA in the ovariectomized (OVX) monkey hypothalamus

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In the present study, we reported distribution of ERα and ER β mRNAs in the hypothalamus of young and old ovariectomized (OVX) rhesus macaques. The ERα were detected in all six major vestiblular nuclei which included arcuate nucleus (ARC) , paraventricularis nucleus (PVN) , periventricular nucleus (PeriV) , supraoptic nucleus (SON) ,medial prioptic nucleus (MPN) and lateral hypothalamus area (LHA). However, the ERβ mRNA can also detected in those nuclei excerpt SON, but the signals of ERβ mRNA were weaker than those of ERα mRNA. We observed that the degree of expression of ERs mRNA were different in most nucleus of old and young monkeys. The ERα mRNAs were highly expressed in ARC and SON in young monkeys compared with old monkeys. Moderate amount of ERα mRNAs hybridization signals and weak signals were observed in LHA, and MPN both in young and old monkeys. In contrast, only lower level of ERα hybridization signal were observed in PVN and PeriV in young monkeys, and the signals of ERα were very low in those nucleus of old monkeys. In general, the expression of ERβ mRNA were weaker than that of ERα mRNA in above nucleus excerpt LHA. The relatively higher density of ERβ hybridization signals have been observed in the LHA in young monkey compared with old monkeys. Low amount of ERβ mRNA hybridization signals were observed in the ARC, PVN and MPN, and no age differences were seen in PVN and MPN of those monkeys. In PeriV, we observed some signals in young monkey and a few signals in old monkeys. It was different from the rodent in which we did not found ERβ hybridization signal in SON. This study showed that both of the two estrogen receptors not only had the same pattern of expression but also had many different patterns of expression. The different expression of ERα and ERβ mRNAs in the young and old monkey brain may imply diverse functions in different regions of the monkey brain.

  10. Mamary neoplasia in a closed beagle colony

    International Nuclear Information System (INIS)

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

  11. Penis Allotransplantation in Beagle Dog

    OpenAIRE

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

    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 leve...

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

    International Nuclear Information System (INIS)

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

  13. 226Ra-induced dental changes: a comparative microradiographic study of human and beagle dog

    International Nuclear Information System (INIS)

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

  14. BeagleBone media center

    CERN Document Server

    Lewin, David

    2015-01-01

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

  15. The Legacy of Beagle 2

    Science.gov (United States)

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

    2015-04-01

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

  16. Exercise Effects on Menopause-Induced Changes in Heart of Ovariectomized Rats

    OpenAIRE

    Necip Fazil Kishali

    2011-01-01

    The menopause is characterized by the progressive decrease in estrogenic secretion and associated with bio-psycho and social changes which in turn impairs quality of life. This experiment was conducted to determine if exercise training has a protective role against the deleterious effects of aging in ovariectomized rats. Control rats and ovariectomized rats 12 weeks after surgery were subjected to a 4 weeks treadmill-running program. Subgroups established were young animals, old animals, ovar...

  17. Pathology in a lifespan study of x-irradiated female beagles

    International Nuclear Information System (INIS)

    Clinical records, gross necropsy records, slides, and stored tissues of x-irradiated beagles were reviewed. Tables are presented to show preliminary determinations of causes of death, neoplasms found, and number of dogs at risk in relation to age and dose level. Mammary and ovarian tumors were more numerous in irradiated beagles and were partially responsible for shortening of lifespan. Neoplasms of the urogenital system were also increased in irradiated groups

  18. UK and ESA announce Beagle 2 inquiry

    CERN Multimedia

    2004-01-01

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

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

    International Nuclear Information System (INIS)

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

  20. The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats

    OpenAIRE

    Norazlina Mohamed; Sharon Gwee Sian Khee; Ahmad Nazrun Shuid; Norliza Muhammad; Farihah Suhaimi; Faizah Othman; Abdul Salam Babji; Ima-Nirwana Soelaiman

    2012-01-01

    Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja), a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham) while group two was ovariectomized. These two groups were given ionized water b...

  1. Effect of exercise training on livers of young, old, and ovariectomized rats

    OpenAIRE

    SELLİ, Jale; Kara, Adem; AKARAS, Nurhan; PARLAK, Seçil; YETİM, Zeliha; Aksak, Selina; KHOSHVAGHTİ, Habib; Ünal, Deniz; Ünal, Bünyami

    2013-01-01

    The menopause is a mid life event, characterized by estrogenic deficiency and associated with bio-psycho and social changes which impair quality of life. In addition, exercise can be described as a body activity that enhances or maintains physical fitness and overall life quality. This experiment was conducted to determine if exercise training has a protective role against the deleterious effects of aging in ovariectomized rats. In this study, thirty-six Wistar albino rats were used. The rats...

  2. BeagleBone for secret agents

    CERN Document Server

    Datko, Josh

    2014-01-01

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

  3. Physical exercise neuroprotects ovariectomized 3xTg-AD mice through BDNF mechanisms.

    Science.gov (United States)

    García-Mesa, Yoelvis; Pareja-Galeano, Helios; Bonet-Costa, Vicent; Revilla, Susana; Gómez-Cabrera, M Carmen; Gambini, Juan; Giménez-Llort, Lydia; Cristòfol, Rosa; Viña, José; Sanfeliu, Coral

    2014-07-01

    Postmenopausal women may be more vulnerable to cognitive loss and Alzheimer's disease (AD) than premenopausal women because of their deficiency in estrogens, in addition to their usually older age. Aerobic physical exercise has been proposed as a therapeutic approach for maintaining health and well-being in postmenopausal women, and for improving brain health and plasticity in populations at high risk for AD. To study the neuroprotective mechanisms of physical exercise in a postmenopausal animal model, we submitted previously ovariectomized, six-month old non-transgenic and 3xTg-AD mice to three months of voluntary exercise in a running wheel. At nine months of age, we observed lower grip strength and some exacerbation of the behavioral and psychological symptoms of dementia (BPSD)-like involving active exploratory activities. A similar major cognitive impairment was observed of ovariectomized 3xTg-AD mice in comparison with sham-operated 3xTg-AD mice. A reduction of bodily fitness and lack of retention of memory were observed in the ovariectomized non-transgenic mice. Physical exercise protected against all deleterious behaviors and normalized learning and memory. It also protected against body frailty, as expected. Analyses of hippocampal key markers of antioxidant and neuroplasticity signaling pathways, showed that ovariectomy impairs the activation of CREB through physical exercise. Furthermore, molecular and behavioral correlates suggested a central role of BDNF in the neuroprotection mediated by physical exercise therapy against apathy and memory loss induced by ovariectomy and the AD-genotype. PMID:24845186

  4. Retention and distribution of 226Ra in beagles: a comparison between multiple and single injections

    International Nuclear Information System (INIS)

    Skeletal uptake, retention, and distribution of 226Ra were studied in 330 beagles administered eight semi-monthly i.v. injections of radium starting at 2, 4, and 14 months of age. Skeletal uptake, the ratio of body burden at 35 days post-injection (A35) to the total injected dose (A0) was 71.7 percent, 78.1 percent and 38.5 percent, for a dose of 10 μCi/kg body weight administered starting at 2, 4, and 14 months of age, respectively. Skeletal retention of radium 350 days post-injection (A350/A0) was 67.2 percent, 73.3 percent, and 27.7 percent. Comparison of 226Ra retention from single and multiple injections of radium shows that at dose level 6.064 μCi/kg the retention functions for periods 35 days after injection are identical; for dose level 10 μCi/kg, a larger retention is observed for multiple-injection groups. Comparison of 226Ra retention in man with that in beagles shows that within a period between 35 days and 6000 days post--injection, the body burden in dog decreases by about 6 times in contrast with 43 times in man. Regional distribution of 226Ra in bone matrix at proximal, midshaft, and distal humeri from 21 beagles shows the highest concentration of the radionuclide at proximal regions. Radium distribution on autoradiograms shows a uniform distribution in 4-month-old beagles in contrast to ''hot spots'' superimposed on a diffuse background for the 14-month age group. Radium in the latter group is located mostly on periosteum and endosteum surfaces

  5. Development of the canine tooth in the beagle

    International Nuclear Information System (INIS)

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

  6. Sexual differences in glomerular ultrafiltration: effect of androgen administration in ovariectomized rats.

    Science.gov (United States)

    Blantz, R C; Peterson, O W; Blantz, E R; Wilson, C B

    1988-03-01

    The glomerular ultrafiltration rate varies as a function of age and sex. To further elucidate the basis for the sexual difference, an androgen [Deca-Durabolin (DECA)] was administered to female ovariectomized rats, and glomerular hemodynamics were evaluated by renal micropuncture after 6 and 16 weeks of therapy. Results were compared to those in control ovariectomized female rats injected with vehicle. Therapy did not produce significant differences in body weight, but kidney size was modestly increased in DECA-treated rats at 6 weeks (0.68 +/- 0.03 vs. 0.86 +/- 0.03 g wet weight; P less than 0.05); at 16 weeks major differences in renal size were documented (0.69 +/- 0.03 vs. 1.18 +/- 0.05 g wet weight; P less than 0.01). The increase in size was primarily due to tubular hypertrophy, with more modest increases in glomerular size. After 6 weeks of therapy, the single nephron glomerular filtration rate (SNGFR) was increased in DECA-treated ovariectomized rats (24.8 +/- 1.0 vs. 32.9 +/- 1.1 nl/min; P less than 0.01). Whole kidney glomerular filtration rate also rose in proportion to increases in kidney size. The greater SNGFR was attributed to higher rates of nephron plasma flow and a numerical increase in the glomerular ultrafiltration coefficient. However, after 16 weeks of androgen therapy, in spite of marked renal hypertrophy, SNGFR did not further rise in proportion to renal size, and the rate of nephron plasma flow and the glomerular ultrafiltration coefficient actually fell relative to those in control untreated rats. Light microscopic evaluation of renal tissue revealed no abnormalities in DECA-treated rats. Thus, 6-week androgen therapy to ovariectomized female rats increased both glomerular ultrafiltration rates and renal size. However, with prolonged administration a glomerular dysfunction may have ensued whereby glomerular ultrafiltration was dissociated from increases in renal size. PMID:3342752

  7. 224Ra toxicity from a pilot study in beagles

    International Nuclear Information System (INIS)

    Toxicity data are reported for 20 beagles given single intravenous injections of 224Ra in 1963 or 1968. The injection of 1 μCi 224Ra/kg gave an average skeletal dose of about 54 rad in young adult beagles. Two dogs died of acute radiation sickness, 6 with bone sarcomas, 6 from other causes, and 6 were still alive on 31 March 1977. The acutely lethal dosage (LD/sub 50/30)/ for a single injection of 224 Ra in young adult beagles seems to lie between 10 and 20 μCi 224Ra/kg, with an average skeletal dose between 500 and 1000 rad

  8. Pathology associated with inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    The pathology associated with the inhalation of plutonium was studied in beagle dogs given a single exposure to aerosols of 239PuO2, 238PuO2, or 239Pu(NO3)4. The temporal-spatial relationships between plutonium deposition and the development of lesions in dogs were evaluated up to 11 years, 8 years, or 5 years, respectively, after exposures, resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Exposure of the lung to high dose levels produced a spectrum of progressively more severe morphological changes, ranging from radiation pneumonitis to fibrosis. Lung tumors occurred at exposure levels that did not result in early death from radiation pneumonitis or fibrosis. Bronchiolar-alveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and combined epidermoid and adenocarcinomas were observed. Sclerosing tracheobronchial lymphadenitis, radiation osteodystrophy, osteosarcoma, and hepatic adenomatous hyperplasia were the principal extrapulmonary lesions resulting from translocation of plutonium. 15 refs., 2 tabs

  9. Conjugated linoleic acid reduces body weight gain in ovariectomized female C57BL/6J mice

    OpenAIRE

    Kanaya, Noriko; Chen, Shiuan

    2010-01-01

    Estrogen is an important protective factor against obesity in females. Therefore, postmenopausal women have a higher rate of obesity than premenopausal women, which is associated with age-related loss of ovary function. It has been reported that a diet containing conjugated linoleic acid (CLA) reduced body weight and body fat mass in the animal model as well as in human trials. We hypothesized that ingestion of CLA would reduce body weight gain in ovariectomized (OVX) female C57BL/6J mice whi...

  10. Effects of treadmill exercise training on cerebellar estrogen and estrogen receptors, serum estrogen, and motor coordination performance of ovariectomized rats

    OpenAIRE

    Saidah Rauf; Sri Kadarsih Soejono; Ginus Partadiredja

    2015-01-01

    Objective(s): The present study aims at examining the motor coordination performance, serum and cerebellar estrogen, as well as ERβ levels, of ovariectomized rats (as menopausal model) following regular exercise. Materials and Methods: Ten female Sprague Dawley rats aged 12 weeks old were randomly divided into two groups; all of which underwent ovariectomy. The first group was treated with regular exercise of moderate intensity, in which the rats were trained to run on a treadmill for 60 min ...

  11. Antiapoptotic effect of exercise training on ovariectomized rat hearts.

    Science.gov (United States)

    Huang, Chih-Yang; Lin, Yi-Yuan; Hsu, Chih-Chao; Cheng, Shiu-Min; Shyu, Woei-Cherng; Ting, Hua; Yang, Ai-Lun; Ho, Tsung-Jung; Lee, Shin-Da

    2016-08-01

    The purpose of this study was to evaluate the effects of exercise training on cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways in ovariectomized rats. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from three groups of Sprague-Dawley rats, which were divided into a sham-operated group, a bilaterally ovariectomized group (OVX), and a bilaterally ovariectomized group that underwent treadmill running exercise for 60 min/day, 5 sessions/wk, for 10 wk (OVX-EX). The abnormal myocardial architecture, cardiac trichome-stained fibrosis and cardiac TUNEL-positive apoptotic cells in ovariectomized rats improved after exercise training. The protein levels of tumor necrosis factor-α, tumor necrosis factor receptor 1, Fas ligand, Fas receptors, Fas-associated death domain, activated caspase-8 and activated caspase-3 (Fas receptor-dependent apoptotic pathways), as well as t-Bid, Bad, Bak, Bax, cytosolic cytochrome c, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) were decreased in the OVX-EX group compared with the OVX group. Exercise training suppressed ovariectomy-induced cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways in ovariectomized rat models. These findings might indicate a new therapeutic effect for exercise training to prevent cardiac apoptosis in menopausal or bilaterally oophorectomized women. PMID:27339185

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

    International Nuclear Information System (INIS)

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

  13. Cysteine Prevents Menopausal Syndromes in Ovariectomized Mouse.

    Science.gov (United States)

    Han, Na-Ra; Kim, Na-Rae; Kim, Hyung-Min; Jeong, Hyun-Ja

    2016-05-01

    Cysteine (Cys) is well known to be involved in oxidation-reduction reactions, serving as a source of sulfides in the body. Amino acids are known to improve menopausal symptoms and significantly reduce morbidity. This study aims to find an unrevealed effect of Cys with estrogenic and osteogenic actions. Ovariectomized (OVX) mice were treated with Cys daily for 8 weeks. Estrogen-related and osteoporosis-related factors were analyzed in the vagina, serum, and tibia. Cys was treated in estrogen receptor (ER)-positive human osteoblast-like MG-63 cells and ER-positive human breast cancer Michigan Cancer Foundation-7 (MCF-7) cells. Cysteine administration ameliorated overweightness of the body and vaginal atrophy in the OVX mice. Cysteine increased the levels of alkaline phosphatase (ALP) and 17β-estradiol in the serum of the OVX mice and improved the bone mineral density in the OVX mice. In MG-63 cells, Cys increased the proliferation, ERβ messenger RNA (mRNA) expression, and estrogen response element (ERE) activity. Cysteine increased the ALP activity and the phosphorylation of extracellular signal-regulated kinase. In MCF-7 cells, Cys also increased the proliferation, ERβ mRNA expression, and ERE activity. Taken together, these results demonstrated that Cys has estrogenic and osteogenic activities in OVX mice, MG-63 cells, and MCF-7 cells. The novel insights gained here strongly imply the potential use of Cys as a new agent for postmenopausal women. PMID:26494699

  14. Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

    International Nuclear Information System (INIS)

    Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17β-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca2+ delaying the opening of the permeability transition pore. The presence of 25 μM E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H2O2 in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered

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

    International Nuclear Information System (INIS)

    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 60Co 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

  16. Evaluation of nanoparticle delivered cisplatin in beagles

    Science.gov (United States)

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

    2015-08-01

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

  17. Hematologic effects of inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Beagle dogs were exposed, by inhalation, 5 to 11 years ago, to aerosols of 239PuO2, 238PuO2, or 239Pu(NO3)4, at six dose levels resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Translocation of the plutonium to extrapulmonary sites was related to the physical-chemical characteristics of the plutonium compound. The highly insoluble 239PuO2 was retained primarily in the lung and associated lymph nodes, whereas 239Pu(NO3)4 was much more soluble and translocated relatively rapidly to the skeleton and other extrapulmonary tissues. The 238PuO2 was intermediate in solubility and translocation characteristics. The hematologic effects of plutonium inhalation were most pronounced on lymphocyte populations. Evidence suggests that these effects result from irradiation of lymphocytes via the pulmonary lymph nodes with insoluble 239PuO2, and via these same lymph nodes, extrapulmonary lymph nodes, and bone marrow lymphocytes with the more soluble forms, i.e., 238PuO2 and 239Pu(NO3)4. There is no evidence suggesting that these exposures increase the risk of developing myeloid or lymphoid neoplasia. 8 refs., 4 figs., 3 tabs

  18. Allocation of nutrients to somatic tissues in young ovariectomized grasshoppers.

    Science.gov (United States)

    Judd, Evan T; Hatle, John D; Drewry, Michelle D; Wessels, Frank J; Hahn, Daniel A

    2010-11-01

    The disposable soma hypothesis predicts that when reproduction is reduced, life span is increased because more nutrients are invested in the soma, increasing somatic repair. Rigorously testing the hypothesis requires tracking nutrients from ingestion to allocation to the soma or to reproduction. Fruit flies on life-extending dietary restriction increase allocation to the soma "relative" to reproduction, suggesting that allocation of nutrients can be associated with extension of life span. Here, we use stable isotopes to track ingested nutrients in ovariectomized grasshoppers during the first oviposition cycle. Previous work has shown that ovariectomy extends life span, but investment of protein in reproduction is not reduced until after the first clutch of eggs is laid. Because ovariectomy does not affect investment in reproduction at this age, the disposable soma hypothesis would predict that ovariectomy should also not affect investment in somatic tissues. We developed grasshopper diets with distinct signatures of ¹³C and ¹⁵N, but that produced equivalent reproductive outputs. These diets are, therefore, appropriate for the reciprocal switches in diet needed for tracking ingested nutrients. Incorporation of stable isotopes into eggs showed that grasshoppers are income breeders, especially for carbon. Allocation to the fat body of nitrogen ingested as adults was slightly increased by ovariectomy; this was our only result that was not consistent with the disposable soma hypothesis. In contrast, ovariectomy did not affect allocation of nitrogen to femoral muscles. Further, allocation of carbon to the fat body or femoral muscles did not appear to be affected by ovariectomy. Total anti-oxidant activities in the hemolymph and femoral muscles were not affected by ovariectomy. These experiments showed that allocation of nutrients was altered little by ovariectomy in young grasshoppers. Additional studies on older individuals are needed to further test the disposable

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

    International Nuclear Information System (INIS)

    The authors are completing a 30-year study of the biologic effects of 90Sr and 226Ra 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 90Sr, (b) a single intravenous injection of 90Sr, or (c) a series of eight intravenous injections of 226Ra. Although administration of 90Sr and 226Ra 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 90Sr and in exposures that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with 90Sr. 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

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

    International Nuclear Information System (INIS)

    The authors are completing a 30-year study of the biological effects of 90Sr and 226Ra 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 90Sr, (b) a single intravenous injection of 90Sr, or (c) a series of eight intravenous injections of 226Ra. Although administration of 90Sr and 226Ra 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 90Sr and in exposures that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with 90Sr. 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

  1. Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats

    Science.gov (United States)

    Nofrey, Barbara S.; Ben-Shahar, Osnat M.; Brake, Wayne G.

    2008-01-01

    Estrogen is frequently prescribed as a method of birth control and as hormone replacement therapy for post-menopausal women with varied effects on cognition. Here the effects of estrogen on attention were examined using the latent inhibition (LI) behavioral paradigm. Ovariectomized (OVX) female rats were given either estrogen benzoate (EB, 10 or…

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

    Directory of Open Access Journals (Sweden)

    Rodríguez Sosa

    2011-11-01

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

  3. Methanol Extract of the Fruits of Morinda citrifolia Linn., Restores Bone Loss in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    V. Parmar

    2011-01-01

    Full Text Available The objective of this study was to evaluate the effect of methanol extract of the fruits of Morinda citrifolia Linn., on osteoporosis induced by ovariectomy in female albino rats at two different dose levels of 500 and 750 mg/kg/day. Healthy female albino rats in the age group of 90 days were selected and randomized into five groups of six animals each. Group 1 was sham operated and served as control while all the remaining groups were ovariectomized. Group 2 was fed with an equivolume of saline and served as ovariectomized control. Group 3 was orally treated with standard Raloxifene (5.4 mg kg-1 whereas the methanol extract of Morinda citrifolia (500 and 750 mg kg-1 was administered to the groups 4 and 5. The findings assessed on the basis of biomechanical, biochemical and histopathological parameters, showed that the methanol extract significantly reduced bone loss, as evidenced by a reduction in Tartrate Resistant Acid Phosphatase (TRAP and urine Hydroxyproline (Hp levels while simultaneously increasing bone formation [high serum Alkaline Phosphatase (ALP levels], thereby restoring bone mineralization. The restoration of bone strength was confirmed by biomechanical parameters viz., the three point bending of tibia, load testing of femoral head and compression of IV lumbar vertebra and it was further endorsed by histopathological findings i.e., bone microarchitecture. The extract significantly increased the osteoblastic activity on one hand while on the other it retarded the osteoclastic function thereby contributing to a positive bone balance and hence enhanced mineralization.

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

    International Nuclear Information System (INIS)

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

  5. Monstrilloida (Crustacea: Copepoda) from the Beagle Channel, South America

    NARCIS (Netherlands)

    Suárez-Morales, E.; Ramírez, F.C.; Derisio, C.

    2008-01-01

    Monstrilloid copepods were collected during zooplankton surveys in the Beagle Channel at the southernmost end of South America. These specimens represent two species of Monstrillopsis, one of them undescribed, and one new species of Monstrilla. Monstrillopsis igniterra n. sp. is related to forms of

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

    Science.gov (United States)

    Swab, Janice C.

    2010-01-01

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

  7. Mars orbiter redirected in bid to find Beagle

    CERN Multimedia

    2003-01-01

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

  8. Decreased bioavailability of nitric oxide in aorta from ovariectomized senescent mice. Role of cyclooxygenase.

    Science.gov (United States)

    Vidal-Gómez, Xavier; Novella, Susana; Pérez-Monzó, Isabel; Garabito, Manel; Dantas, Ana Paula; Segarra, Gloria; Hermenegildo, Carlos; Medina, Pascual

    2016-04-01

    This study investigates the effects of aging and/or ovariectomy on vascular reactivity to thromboxane A2 (TXA2) receptor stimulation with U46619, and the modulation by nitric oxide (NO) and cyclooxygenase (COX) in aorta from female senescence-accelerated mice (SAMP8) and from senescence resistant mice (SAMR1). Five-month-old female SAMR1 and SAMP8 were divided into three groups: sham-operated, ovariectomized and ovariectomized plus estradiol. Twenty-eight days after surgery, thoracic aortic rings were mounted for isometric recording of tension and concentration-response curves for U46619 (10(-10)-3×10(-7)M) were performed in the absence and in the presence of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME, 10(-4)M) and/or COX inhibitor indomethacin (10(-5)M). Vascular superoxide production was detected by dihydroethidium staining on sections of thoracic aorta. NO bioavailability in response to U46619 was suppressed by estrogen withdrawn in young and senescent mice and was restored by the administration of estradiol. In the presence of indomethacin, contractions to U46619 decreased in all groups indicating an aging- and estrogen-dependent modulation of contractile prostanoids. The simultaneous incubation of L-NAME and indomethacin did not change the maximal responses and sensitivities to TXA2 in any group in comparison with untreated aortic segments. The superoxide generation induced by TXA2 was greater in aorta from SAMP8 than in SAMR1. Moreover, in ovariectomized groups superoxide production was further increased and treatment with 17β-estradiol reverted the effects of the ovariectomy. Inhibition of COX with indomethacin prevented the U46619-induced increase in superoxide formation. Our results indicate that NO bioavailability in response to TP receptor activation is both estrogen- and aging-dependent. TXA2 induced contractions are partially mediated by COX activation. Both aging and ovariectomy enhanced COX-dependent component of the TXA2

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

    International Nuclear Information System (INIS)

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

  10. Effects of genistein and 17 beta-estradiol on hippocampal synaptophysin expression in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Ru Chen; Liming Tan; Bo Jiang

    2008-01-01

    BACKGROUND:Phytoestrogen,derived from plants,is an estrogen-like element,and is effective and safe for estrogen replacement.OBJECTIVE:To compare the interventional effects of genistein and 17 β-estradiol on learning and memory and synaptophysin(SYN)expression in the hippocampus of ovariectomized rats.DESIGN:Randomized controlled animal study.SETTING:Department of Neurology,the Third Affiliated Hospital,Xiangya Medical College,Central South University. MATERIALS:130 healthy female Sprague Dawley(SD)rats,6 months old and weighing(293.1±10.2)g,were provided by the Second Xiangya Hospital of Central South University.This animal experiment received confirmed consent from the local ethics committee.All rats were randomly divided into 5 groups,including baseline group(n=10),sham operation group(n=30),ovariectomlzed group(n=30),genistein group(n= 30),and 17 β-estradiol group(n=30).Rats in the latter four groups were observed for 3 weeks(n=10)and for 15 weeks(n=20)after model establishment.METHODS:This study was performed at the Department of Endocrinology,the Second Affiliated Hospital,Xiangya Medical College,Central South University from August 2005 to January 2006.Animals were not submitted to any treatment in the baseline group,but anesthetized and sacrificed at the 7 months of age.After anesthesia in the ovariectomized,genistein,and 17 β-estradiol groups,both ovaries were separated and resected to establish an ovariectomized model.The same volume of fat was resected in the sham operation group.After surgery,rats were intraperitoneally injected with 5 mg/kg genistein in the genistein group,10 μ g/kg 17 β-estradiol in the 17 β-estradiol group,and 0.1 mL/100 g dimethyl sulfoxide (DMSO)/polyethylene glycol(PEG)-200 stock solution in the sham peration and ovariectomized groups once a day until one day before sacrifice.MAIN OUTCOME MEASURES:①Learning and memory changes of SD rats were detected using water maze behavioral testing 3 and 15 weeks after

  11. Possible antiosteoporotic mechanism of Cicer arietinum extract in ovariectomized rats

    OpenAIRE

    Fahmy, Sohair R; Amel M. Soliman; Sayed, Amany A; Marzouk, Mohamed

    2015-01-01

    Objective: The present study aimed to throw the light on the anti-osteoprotic mechanism of Cicer arietinum extract (CAE) seeds against ovariectomized (OVX) rats. Methods: Seventy female rats were divided into two groups. The first group (14 rats/group) represented normal rats (Sham operated) while the second group (56 rats/group) underwent bilateral ovariectomy (OVX). After one week of recovery from ovariectomy surgery, the second group was randomly subdivided into 4 subgroups (14 rats/ each ...

  12. Whey Protein Concentrate Hydrolysate Prevents Bone Loss in Ovariectomized Rats.

    Science.gov (United States)

    Kim, Jonggun; Kim, Hyung Kwan; Kim, Saehun; Imm, Ji-Young; Whang, Kwang-Youn

    2015-12-01

    Milk is known as a safe food and contains easily absorbable minerals and proteins, including whey protein, which has demonstrated antiosteoporotic effects on ovariectomized rats. This study evaluated the antiosteoporotic effect of whey protein concentrate hydrolysate (WPCH) digested with fungal protease and whey protein concentrate (WPC). Two experiments were conducted to determine (1) efficacy of WPCH and WPC and (2) dose-dependent impact of WPCH in ovariectomized rats (10 weeks old). In Experiment I, ovariectomized rats (n=45) were allotted into three dietary treatments of 10 g/kg diet of WPC, 10 g/kg diet of WPCH, and a control diet. In Experiment II, ovariectomized rats (n=60) were fed four different diets (0, 10, 20, and 40 g/kg of WPCH). In both experiments, sham-operated rats (n=15) were also fed a control diet containing the same amount of amino acids and minerals as dietary treatments. After 6 weeks, dietary WPCH prevented loss of bone, physical properties, mineral density, and mineral content, and improved breaking strength of femurs, with similar effect to WPC. The bone resorption enzyme activity (tartrate resistance acid phosphatase) in tibia epiphysis decreased in response to WPCH supplementation, while bone formation enzyme activity (alkaline phosphatase) was unaffected by ovariectomy and dietary treatment. Bone properties and strength increased as the dietary WPCH level increased (10 and 20 g/kg), but there was no difference between the 20 and 40 g/kg treatment. WPCH and WPC supplementation ameliorated bone loss induced by ovariectomy in rats. PMID:26367331

  13. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil); Irigoyen, M.C. [Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); De Angelis, K. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil)

    2015-03-27

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.

  14. Standardization of resistance exercise training: effects in diabetic ovariectomized rats.

    Science.gov (United States)

    Sanches, I C; Conti, F F; Sartori, M; Irigoyen, M C; De Angelis, K

    2014-04-01

    This study was carried out with a 3-fold aim: 1) to standardize a maximal load test (MLT) on ladders for prescription of resistance exercise training (RET) in rats, 2) to prescribe moderate-intensity RET based on this MLT and 3) to test the effect of this RET in diabetic ovariectomized rats. Female Wistar rats were divided into control (C), diabetic ovariectomized sedentary (DOS) and trained (DOT) groups. The MLT was standardized with increased load applied to the rat tail for each climb, and blood lactate was measured to identify lactate threshold in C rats. MLT was applied in the 1st, 4th and 8th week of the protocol. After 8 weeks of RET, the arterial pressure was directly recorded. DOS group reduced performance in MLT, body weight, left ventricular, plantar and soleus muscles mass (vs. C). DOT rats showed an improvement in MLT associated with plantar muscle mass increased (vs. C and DOS), with attenuation of hypotension and bradycardia (vs. DOS). In conclusion, the results provide a useful method for determining the maximal load and applying RET in rats. Moreover, this study showed that moderate intensity RET improves hemodynamic status in diabetic ovariectomized rats, thereby reinforcing the role of RET in diabetes management. PMID:24022577

  15. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation

  16. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

    Directory of Open Access Journals (Sweden)

    G.L. Shimojo

    2015-06-01

    Full Text Available The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC, sedentary hypertensive (SH, sedentary hypertensive ovariectomized (SHO, and resistance-trained hypertensive ovariectomized (RTHO. Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR responses to methylatropine (3 mg/kg, iv and propranolol (4 mg/kg, iv. Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg, as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm. Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05. The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.

  17. The effects of Vigna unguiculata on cardiac oxidative stress and aorta estrogen receptor-β expression of ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Etik Khusniyati

    2014-12-01

    Conclusions: V. unguiculata is an alternative therapy in decreasing cardiac oxidative stress in ovariectomized rats. Besides, high dose of V. unguiculata also able to increase aorta estrogen receptor-β expression in ovariectomized rats.

  18. Expression of intestinal transporter genes in beagle dogs

    OpenAIRE

    Cho, Soo-Min; Park, Sung-Won; Kim, Na-Hyun; Park, Jin-A; YI, HEE; CHO, Hee-Jung; PARK, KI-HWAN; HWANG, INGYUN; Shin, Ho-Chul

    2012-01-01

    This study was performed to produce a transcriptional database of the intestinal transporters of beagle dogs. Total RNA was isolated from the duodenum and the expression of various mRNAs was measured using GeneChip® oligonucleotide arrays. A total of 124 transporter genes were detected. Genes for fatty acid, peptide, amino acid and glucose and multidrug resistance/multidrug resistance-associated protein (MDR/MRP) transport were expressed at relatively higher levels than the other transporter ...

  19. Building networks and servers using BeagleBone

    CERN Document Server

    Pretty, Bill

    2015-01-01

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

  20. Absorption and pharmacokinetics of grapefruit flavanones in beagles

    OpenAIRE

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

    2007-01-01

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

  1. L-Carnitine, but not coenzyme Q10, enhances the anti-osteoporotic effect of atorvastatin in ovariectomized rats

    OpenAIRE

    Murad, Hussam A. S.

    2016-01-01

    Objective: Statins’ therapy in osteoporosis can aggravate muscle damage. This study was designed to assess which agent, L-carnitine or coenzyme Q10, could enhance the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats. Methods: Forty-eight female Sprague Dawley rats were used; forty rats were ovariectomized while eight were sham-operated. Eight weeks post-ovariectomy, rats were divided into ovariectomized-untreated group and four ovariectomized-treated...

  2. Atlas of experimentally-induced neoplasia in beagle dogs

    International Nuclear Information System (INIS)

    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

  3. Atlas of experimentally-induced neoplasia in beagle dogs

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-10-01

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

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

    International Nuclear Information System (INIS)

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

  5. Toxicity of 239PuO2 in immature Beagle dogs. X

    International Nuclear Information System (INIS)

    Immature beagles have been exposed by inhalation to a monodisperse aerosol of 239PuO2 (1.5 μm AMAD) to compare the biological effects with those being observed in dogs exposed to a similar aerosol when they were young or aged adults. The study includes 96 dogs exposed to 239PuO2 and 12 controls. A total of 66 experimental and 11 control dogs are still alive. Six dogs died during the past year, all of radiation-related causes. Five dogs died from lung carcinomas and the sixth dog died of pneumonia/fibrosis, but with a lung tumor. With the large number of dogs still alive in this study, it is still premature to compare the cancer dose-response relationships for the immature and adult dogs. (author)

  6. Toxicity of inhaled 239PuO2 in immature beagle dogs

    International Nuclear Information System (INIS)

    Immature beagle dogs have been exposed by inhalation to a 1.5 μm aerodynamic diameter monodisperse aerosol of 239PuO2 to compare the biological effects with those seen in young adult and aged dogs exposed to a similar aerosol. To date, 18 dogs have been exposed to the aerosol, resulting in graded initial lung burdens ranging from 0.003 to 0.38 μCi/kg body weight. Two dogs have been exposed to the aerosol diluent and serve as controls. Two of the 18 exposed animals were sacrificed 8 days after exposure to provide information on initial deposition and distribution. All other exposed animals are alive 400 days after exposure. No dogs were exposed during the past year because of an outbreak of canine parvovirus enteritis which caused death in 8 to 10 week-old dogs

  7. Response of the genital tract to gonadotropin stimulation of the afollicular (x-irradiated) ovary in the beagle

    International Nuclear Information System (INIS)

    The morphologic response of the genital system in 16 beagles with afollicular (x-irradiated) ovaries has been examined following follicle and luteinizing hormone treatment. The dogs received a single brief exposure of 5 R daily or 10 R on alternate days from birth to 60 days of age (total 300 R). When the dogs were 7 months or older, the hormone treatment caused enlargement of the afollicular ovary and specific changes resembling proestrus in the oviduct and uterus; the vagina and vulva did not respond to the treatment

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

    International Nuclear Information System (INIS)

    We are completing a 30-year study of the biological effects of 90Sr and 226Ra 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 90Sr, (b) a single intravenous injection of 90Sr, or (c) a series of eight intravenous injections of 226Ra. Although administration of 90Sr and 226Ra 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 90Sr and in exposure that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with 90Sr. 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

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

    International Nuclear Information System (INIS)

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

  10. Nutrigenomic effects of edible bird’s nest on insulin signaling in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Hou ZP

    2015-08-01

    Full Text Available Zhiping Hou,1,2 Mustapha Umar Imam,1 Maznah Ismail,1,3 Der Jiun Ooi,1 Aini Ideris,4 Rozi Mahmud5 1Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia; 2Department of Pathology, Chengde Medical University, Chengde, People’s Republic of China; 3Department of Nutrition and Dietetics, Universiti Putra Malaysia, Serdang, Malaysia; 4Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia; 5Department of Imaging, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia Abstract: Estrogen deficiency alters quality of life during menopause. Hormone replacement therapy has been used to improve quality of life and prevent complications, but side effects limit its use. In this study, we evaluated the use of edible bird’s nest (EBN for prevention of cardiometabolic problems in rats with ovariectomy-induced menopause. Ovariectomized female rats were fed for 12 weeks with normal rat chow, EBN, or estrogen and compared with normal non-ovariectomized rats. Metabolic indices (insulin, estrogen, superoxide dismutase, malondialdehyde, oral glucose tolerance test, and lipid profile were measured at the end of the experiment from serum and liver tissue homogenate, and transcriptional levels of hepatic insulin signaling genes were measured. The results showed that ovariectomy worsened metabolic indices and disrupted the normal transcriptional pattern of hepatic insulin signaling genes. EBN improved the metabolic indices and also produced transcriptional changes in hepatic insulin signaling genes that tended toward enhanced insulin sensitivity, and glucose and lipid homeostasis, even better than estrogen. The data suggest that EBN could meliorate estrogen deficiency-associated increase in risk of cardiometabolic disease in rats, and may in fact be useful as a functional food for the prevention of such a problem in

  11. Proteomic study of periovarian adipose tissue in 17β-estradiol-treated and untreated ovariectomized rats.

    Science.gov (United States)

    Amengual-Cladera, Emilia; Capllonch-Amer, Gabriela; Lladó, Isabel; Gianotti, Magdalena; Proenza, Ana M

    2016-04-01

    Taking into account the sexual dimorphism previously found in white adipose tissue (WAT) regarding mitochondrial function and biogenesis, as well as insulin sensitivity, the aim of this study was to go further into the role of sex hormones in this dimorphism. To achieve this objective, we used ovariectomized rats and performed a screening by means of proteomic analyses of the periovarian WAT, combined with a study of the protein levels of specific factors involved in mitochondrial function. Rats were ovariectomized at 5 weeks of age and subcutaneously injected every 48 h with corn-oil (OVX group) or with 17β-estradiol (E2, 10 μg/kg body mass; OVX + E2 group) for 4 weeks prior to sacrifice. Beside proteomic analysis, protein levels of Transcription Factor A, Mitochondrial (TFAM), cytochrome oxidase (COX)II, and COXIV were determined by Western blot, and mRNA levels of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, ERα, ERβ, lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPARγ), and adiponectin were quantified by real-time PCR. Our results show that ovariectomy leads to an increase in anabolic processes and inflammatory protein levels as well as to a decrease in some of the markers of mitochondrial function, which are restored, at least in part, by E2 supplementation. Indeed, this E2 supplementation seems to be counteracted by a decline in ERα and in the ERα to ERβ ratio values that could be directed to avoid an over-stimulation of the E2 signaling pathway, given the possibility of an activation of extra-gonadal steroid biosynthetic pathways. PMID:26914441

  12. Supplementation with pumpkin seed oil improves plasma lipid profile and cardiovascular outcomes of female non-ovariectomized and ovariectomized Sprague-Dawley rats.

    Science.gov (United States)

    Gossell-Williams, M; Lyttle, K; Clarke, T; Gardner, M; Simon, O

    2008-07-01

    Pumpkin (Cucurbita species) seed oil (PSO) is a rich source of phytoestrogens and the aim of this study was to examine the effect of PSO supplementation on the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides, high density lipoprotein cholesterol (HDL-C), systolic and diastolic blood pressure in non-ovariectomized and ovariectomized Sprague-Dawley rats. Female rats weighing 220-300 g were divided into non-ovariectomized rats for supplementation with corn oil (control CO; n = 6) or PSO (control PSO; n = 5) and ovariectomized rats for supplementation with corn oil (OVX/CO; n = 6) or PSO (OVX/PSO; n = 5) for 5 days per week for 12 weeks (corn oil 40 mg/kg or PSO 40 mg/kg given orally). Systolic and diastolic blood pressures were measured weekly. Blood was collected at the end of the period for plasma lipid assays. Control PSO had lower TC, LDL-C, triglycerides and higher HDL-C than the control CO. The OVX/CO had higher TC, LDL-C, triglycerides and lower HDL-C than the control CO and these changes were prevented in the OVX/PSO rats. PSO supplementation also resulted in lower systolic and diastolic blood pressures in both non-ovariectomized and ovariectomized rats. It is concluded that PSO supplementation can prevent changes in plasma lipids and blood pressure associated with inadequate oestrogen availability. PMID:18567058

  13. Pleiotropic effects of simvastatin in physically trained ovariectomized rats

    International Nuclear Information System (INIS)

    This study tested the hypothesis that simvastatin treatment can improve cardiovascular and autonomic functions and membrane lipoperoxidation, with an increased effect when applied to physically trained ovariectomized rats. Ovariectomized rats were divided into sedentary, sedentary+simvastatin and trained+simvastatin groups (n = 8 each). Exercise training was performed on a treadmill for 8 weeks and simvastatin (5 mg/kg) was administered in the last 2 weeks. Blood pressure (BP) was recorded in conscious animals. Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses to BP changes. Cardiac vagal and sympathetic effects were determined using methylatropine and propranolol. Oxidative stress was evaluated based on heart and liver lipoperoxidation using the chemiluminescence method. The simvastatin-treated groups presented reduced body weight and mean BP (trained+simvastatin = 99 ± 2 and sedentary+simvastatin = 107 ± 2 mmHg) compared to the sedentary group (122 ± 1 mmHg). Furthermore, the trained group showed lower BP and heart rate compared to the other groups. Tachycardic and bradycardic responses were enhanced in both simvastatin-treated groups. The vagal effect was increased in the trained+simvastatin group and the sympathetic effect was decreased in the sedentary+simvastatin group. Hepatic lipoperoxidation was reduced in sedentary+simvastatin (≈21%) and trained+simvastatin groups (≈57%) compared to the sedentary group. Correlation analysis involving all animals demonstrated that cardiac lipoperoxidation was negatively related to the vagal effect (r = -0.7) and positively correlated to the sympathetic effect (r = 0.7). In conclusion, improvement in cardiovascular and autonomic functions associated with a reduction of lipoperoxidation with simvastatin treatment was increased in trained ovariectomized rats

  14. Pleiotropic effects of simvastatin in physically trained ovariectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Bernardes, N. [Universidade Nove de Julho (UNINOVE), São Paulo, SP (Brazil); Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Brito, J.O. [Universidade Nove de Julho (UNINOVE), São Paulo, SP (Brazil); Fernandes, T.G. [Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universdade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Llesuy, S.F. [University of Buenos Aires, Buenos Aires (Argentina); Irigoyen, M.C. [Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Belló-Klein, A. [Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universdade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); De Angelis, K. [Universidade Nove de Julho (UNINOVE), São Paulo, SP (Brazil)

    2013-05-24

    This study tested the hypothesis that simvastatin treatment can improve cardiovascular and autonomic functions and membrane lipoperoxidation, with an increased effect when applied to physically trained ovariectomized rats. Ovariectomized rats were divided into sedentary, sedentary+simvastatin and trained+simvastatin groups (n = 8 each). Exercise training was performed on a treadmill for 8 weeks and simvastatin (5 mg/kg) was administered in the last 2 weeks. Blood pressure (BP) was recorded in conscious animals. Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses to BP changes. Cardiac vagal and sympathetic effects were determined using methylatropine and propranolol. Oxidative stress was evaluated based on heart and liver lipoperoxidation using the chemiluminescence method. The simvastatin-treated groups presented reduced body weight and mean BP (trained+simvastatin = 99 ± 2 and sedentary+simvastatin = 107 ± 2 mmHg) compared to the sedentary group (122 ± 1 mmHg). Furthermore, the trained group showed lower BP and heart rate compared to the other groups. Tachycardic and bradycardic responses were enhanced in both simvastatin-treated groups. The vagal effect was increased in the trained+simvastatin group and the sympathetic effect was decreased in the sedentary+simvastatin group. Hepatic lipoperoxidation was reduced in sedentary+simvastatin (≈21%) and trained+simvastatin groups (≈57%) compared to the sedentary group. Correlation analysis involving all animals demonstrated that cardiac lipoperoxidation was negatively related to the vagal effect (r = -0.7) and positively correlated to the sympathetic effect (r = 0.7). In conclusion, improvement in cardiovascular and autonomic functions associated with a reduction of lipoperoxidation with simvastatin treatment was increased in trained ovariectomized rats.

  15. Effects of short-term swimming exercise on bone mineral density, geometry, and microstructural properties in sham and ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Foong Kiew Ooi

    2014-12-01

    Full Text Available Little information exists about the effects of swimming exercise on bone health in ovariectomized animals with estrogen deficiency, which resembles the postmenopausal state and age-related bone loss in humans. This study investigated the effects of swimming exercise on tibia and femur bone mineral density (BMD, geometry, and microstructure in sham and ovariectomized rats. Forty 3-month-old female rats were divided into four groups: sham operated-sedentary control (Sham-control, sham operated with swimming exercise group (Sham-Swim, ovariectomy-sedentary control (OVx-control, and ovariectomy and swimming exercise (OVx-Swim groups. Swimming sessions were performed by the rats 90 minutes/day for 5 days/week for a total of 8 weeks. At the end of the study, tibial and femoral proximal volumetric total BMD, midshaft cortical volumetric BMD, cross-sectional area, and cross-sectional moment of inertia (MOI, and bone microstructural properties were measured for comparison. Data were analyzed using one-way analysis of variance (ANOVA. The Sham-Swim group exhibited significantly (p < 0.05; one-way ANOVA greater values in bone geometry parameters, that is, tibial midshaft cortical area and MOI compared to the Sham-control group. However, no significant differences were observed in these parameters between the Ovx-Swim and Ovx-control groups. There were no significant differences in femoral BMD between the Sham-Swim and Sham-control groups. Nevertheless, the Ovx-Swim group elicited significantly (p < 0.05; one-way ANOVA higher femoral proximal total BMD and improved bone microstructure compared to the Ovx-Sham group. In conclusion, the positive effects of swimming on bone properties in the ovariectomized rats in the present study may suggest that swimming as a non- or low-weight-bearing exercise may be beneficial for enhancing bone health in the postmenopausal population.

  16. TAHU MENGHAMBAT KEHILANGAN TULANG LUMBAR TIKUS BETINA OVARIEKTOMI [Tofu Attenuates Lumbar Bone Loss of Ovariectomized Female Rats

    Directory of Open Access Journals (Sweden)

    Suyanto Pawiroharsono 4

    2002-12-01

    Full Text Available The objectives of this research were to examine the efeects of feed containing soybean tofu and tempeh on lumbar bone density and mass of ovariectomized female rats. Twenty four 17 weeks-old Sprague-Dawley rats were randomly assigned to four group, i.e.: (1 non-ovariectomized rats fed casein based diet (NonOvx, (2 ovariectomized rats fed casein based diet (OvxC, (3 ovariectomized rats fed diet containing soybean tofu (OvxH, and (4 ovariectomized rats fed diet containing soybean tempeh (OvxT; in three block based on their body weight. The result show that body weight gram of ovariectomized rats was greater than nonovariectomized. Ovariectomy caused atrophy of the uterus, and resulted in higher serum calcium level. The lower lumbar vertebrae density of ovariectomized rats was observed and the decrease was prevented by tofu.

  17. Pulmonary lesions induced by inhaled plutonium in beagles

    International Nuclear Information System (INIS)

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

  18. Pulmonary lesions induced by inhaled plutonium in beagles

    International Nuclear Information System (INIS)

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

  19. Radix Achyranthis Bidentatae improves learning and memory capabilities in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Yuefen Wang; Ya Xu; Yanshu Pan; Weihong Li; Wei Zhang; Yang Liu; Jing Jia; Pengtao Li

    2013-01-01

    Kidney-tonifying recipe can reduce the accumulation of advanced glycation end products, prevent neuronal degeneration and improve cognitive functions in ovariectomized rats. Radix Achyranthis Bidentatae alcohol extracts may dose-dependently inhibit non-enzymatic saccharification in vitro. This study aimed to examine the effect of Radix Achyranthis Bidentatae on advanced glycation end products and on learning and memory capabilities in ovariectomized rats. Ovariectomized rats were treated with Radix Achyranthis Bidentatae alcohol extracts (containing 1.5 g/kg crude drug) or 0.1% aminoguanidine for 12 weeks and behavioral testing was performed with the Y-electrical maze. This test revealed that Radix Achyranthis Bidentatae and aminoguanidine could improve the learning and memory capabilities of ovariectomized rats. Results of competitive enzyme-linked immunosorbent assay showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine reduced the accumulation of advanced glycation end products in the frontal cortex of ovariectomized rats, while increasing content in the blood and urine. Biochemical tests showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine decreased superoxide dismutase activity in the serum and frontal cortex, and increased serum levels of glutathione peroxidase in ovariectomized rats. In addition, there was no apparent effect on malondialdehyde levels. These experimental findings indicate that Radix Achyranthis Bidentatae inhibits production of advanced glycation end products and its accumulation in brain tissue, and improves learning and memory capabilities in ovariectomized rats. These effects may be associated with an anti-oxidative action of the extract.

  20. Vitamin E suppresses ex vivo osteoclastogenesis in ovariectomized rats.

    Science.gov (United States)

    Johnson, Sarah A; Feresin, Rafaela G; Soung, Do Y; Elam, Marcus L; Arjmandi, Bahram H

    2016-03-16

    Postmenopausal osteoporosis may be caused, in part, by oxidative stress and inflammation. Vitamin E is a strong antioxidant which has been shown to have anti-inflammatory and bone-protective effects. The objective of this study was to investigate the effects of various doses of supplemental vitamin E on osteoclastogenesis in ovariectomized rats. Sixty 12-month-old female Sprague-Dawley rats were sham-operated (Sham) or ovariectomized (Ovx; 4 groups) and fed a diet containing basal levels of vitamin E (75 mg d-α tocopherol acetate per kg diet) for 220 days. Rats in three of the Ovx groups were given supplemental doses of vitamin E (300, 525, and 750 mg d-α tocopherol acetate per kg diet) for the last 100 days. Femoral bone marrow cells were isolated, cultured, and osteoclasts were counted and normalized to 1000 total bone marrow cells. Blood monocyte and lymphocyte counts were also determined. Osteoclast number was significantly higher in the Ovx control group and was suppressed by all three doses of vitamin E, although more effectively in the Ovx group that received 300 mg per kg diet vitamin E. Additionally, vitamin E suppressed the Ovx-induced increase in monocyte and lymphocyte production. The results of this study suggest that vitamin E supplementation suppresses osteoclastogenesis, possibly by inhibiting monocyte and lymphocyte production. PMID:26923532

  1. ZP2307, a novel cyclic PTH(1-17) analog, reversed established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Vääräniemi, Jukka; Morko, Jukka; Peng, ZhiQi;

    -17) analog, ZP2307, with a high efficacy and potency on the human PTH receptor in vitro. This study characterized the effects of intermittent treatment with ZP2307 on established osteopenia in adult ovariectomized (OVX) rats. Female Sprague-Dawley rats were ovariectomized at 6 months of age. After 6 weeks...... treated with vehicle. Treatment with ZP2307 reversed the OVX-induced reduction in Tb.BMD and bone volume (BV/TV) in tibial metaphysis and lumbar vertebra at all doses in a dose-dependent manner. ZP2307 enhanced an OVX-induced increase in bone formation rate (BFR/BS) at 200 µg/kg/d and reversed an OVX......-induced increase in the number of osteoclasts (N.Oc/B.Pm) at 2-200 µg/kg/d. As a functional consequence in lumbar vertebra, ZP2307 reversed an OVX-induced reduction in maximal load at 6-200 µg/kg/d and increased modulus at 20-200 µg/kg/d. Furthermore, ZP2307 increased cortical thickness and enhanced endocortical...

  2. Hematological effects of inhaled plutonium dioxide in beagles

    International Nuclear Information System (INIS)

    A life-span study indicated that plutonium activity in the thoracic lymph nodes is a contributor to development of lymphopenia in beagles exposed to 239PuO2. Significant lymphopenia was found in 67 (58%) beagles given a single nose-only exposure to 239PuO2 to result in mean initial lung depositions ranging from 0.69 to 213.3 kBq. Lymphoid atrophy and sclerosis of the thoracic lymph nodes and lymphopenia were observed in exposure-level groups with initial lung depositions ≥2.5 kBq. Those dogs with final plutonium concentrations in the thoracic lymph nodes ≥0.4 kBq/g and dose rates ≥0.01 Gy/day developed lymphopenia. Marked differences existed between chronically lymphopenic dogs and intermittently lymphopenic dogs with regard to initial lung deposition, time to lymphopenic events and absolute lymphocyte concentrations. Linear regression analysis revealed moderate correlation between reduction in lymphocyte values and initial lung deposition, in both magnitude and time of appearance after exposure. Cumulative dose and dose rate appeared to act together to produce initial effects on lymphocyte populations, while dose rate alone appeared to be responsible for the maintenance and subsequent cycles of lymphopenia seen over the life span. No primary tumors were associated with the thoracic lymph nodes in this study, although 70% of the lymphopenic dogs developed lung tumors. 28 refs., 2 figs., 7 tabs

  3. Beagle 2: The Next Exobiology Mission to Mars

    Science.gov (United States)

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

    2001-01-01

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

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

    CERN Document Server

    Chevallard, Jacopo

    2016-01-01

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

  5. Planetary Protection for the Beagle2 Mars Lander Mission

    Science.gov (United States)

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

    Following ejection from the Mars Express orbiter on 19th December 2003, the Beagle 2 probe of mass 68kg headed for the martian surface. The fact that no communications were established with the Beagle 2 lander, and thus neither its location nor fate are currently known, heightens the relevance of the planetary protection aspects of the project. Payload configuration requirements and stringent mass constraints in the design did not allow the whole spacecraft to be terminally sterilised by a single processing method, due to material incompatibility issues. The lander was therefore integrated aseptically in a specially designed and constructed Class 10 cleanroom facility, following appropriate sterilisation processing at sub-assembly level utilising one of several different sterilisation technologies. Additional further cleanliness precautions were taken to ensure the integrity of the science package. The project demonstrates that the COSPAR requirements for a category IVA mission can be met or exceeded using this approach. The data show that, even in the event of a non-nominal landing, the martian environment is protected through the precautionary and conservative approach adopted in the planetary protection strategy.

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

    Science.gov (United States)

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

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

  7. 26-week repeated oral dose toxicity study of UP446, a combination of defined extracts of Scutellaria baicalensis and Acacia catechu, in beagle dogs.

    Science.gov (United States)

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

    2016-07-01

    The needs for relatively safe botanical alternatives to relieve symptoms associated to arthritis have continued to grow in parallel with the ageing population. UP446, a standardized bioflavonoid composition from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, has been used as over the counter joint care dietary supplements and a prescription medical food. Significant safety data have been documented in rodents and human for this composition. Here we evaluated the potential adverse effects of orally administered UP446 in beagle dogs following a 26-week repeated oral dose toxicity study. UP446 at doses of 250, 500 and 1000 mg/kg/day were administered orally to beagle dogs for 26 weeks. A 4-week recovery group from the high dose (1000 mg/kg) and vehicle treated groups were included. No morbidity or mortality was observed for the duration of the study. No significant differences between groups in body weights, food consumption, ophthalmological examinations, electrocardiograms, urinalysis, hematology, clinical chemistry, organ weights, gross pathology and histopathology were documented. Emesis, loose feces and diarrhea were noted in both genders at the 1000 mg/kg treatment groups. These clinical signs were considered to be reversible as they were not evident in the recovery period. In conclusion, the no-observed-adverse-effect-level (NOAEL) of UP446 was considered to be 500 mg/kg/day both in male and female beagle dogs. PMID:27125835

  8. Flemingia macrophylla Extract Ameliorates Experimental Osteoporosis in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Hui-Ya Ho

    2011-01-01

    Full Text Available Flemingia macrophylla (Leguminosae, a native plant of Taiwan, is used as folk medicine. An in vitro study showed that a 75% ethanolic extract of F. macrophylla (FME inhibited osteoclast differentiation of cultured rat bone marrow cells, and the active component, lespedezaflavanone A (LDF-A, was isolated. It was found that oral administration of FME for 13 weeks suppressed bone loss in ovariectomized rats, an experimental model of osteoporosis. In addition, FME decreased urinary deoxypyridinoline concentrations but did not inhibit serum alkaline phosphatase activities, indicating that it ameliorated bone loss via inhibition of bone resorption. These results suggest that FME may represent a useful remedy for the treatment of bone resorption diseases, such as osteoporosis. In addition, LDF-A could be used as a marker compound to control the quality of FME.

  9. Calcium and caffeine interaction in increased calcium balance in ovariectomized rats

    OpenAIRE

    Sandra Tavares da Silva; Neuza Maria Brunoro Costa; Frederico Souzalima Caldoncelli Franco; Antônio José Natali

    2013-01-01

    OBJECTIVE: This study investigated the effects of caffeine intake associated with inadequate or adequate calcium intake in laparotomized or ovariectomized rats by means of the calcium balance. Forty adults Wistar rats were ovariectomized or laparotomized. METHODS: The animals (n=40) were randomly placed in eight groups receiving the AIN-93 diet with 100% or 50% of the recommended calcium intake with or without added caffeine (6mg/kg/day). The animals were kept in individuals metabolic cages a...

  10. Effects of taurine supplementation on bone mineral density in ovariectomized rats fed calcium deficient diet

    OpenAIRE

    Choi, Mi-Ja

    2009-01-01

    Taurine supplementation has been shown to have a beneficial effect on femur bone mineral content in ovariectomized rats. It therefore seemed desirable to find out whether the beneficial effect of taurine on ovariectomized rats fed calcium deficient diet could also be reproduced. Forty female Sprague-Dawley rats were divided into two groups. One group was OVX and the other group received sham operation (SHAM), and received either control diet or a taurine supplemented diet for 6 weeks. All rat...

  11. TROPISETRON INCREASES THE INHIBITORY EFFECT OF MILD RESTRAINT ON LORDOSIS BEHAVIOR OF HORMONALLY PRIMED, OVARIECTOMIZED RATS

    OpenAIRE

    Uphouse, Lynda; Heckard, Danyeal; Hiegel, Cindy; Guptarak, Jutatip; Maswood, Sharmin

    2011-01-01

    Ovariectomized rats, hormonally primed with 10 μg estradiol benzoate and 500 μg progesterone are resistant to the lordosis-inhibiting effects of a 5 min restraint experience. However, modulation of the serotonergic (5-HT) system alters this resistance to stress. In the following experiment, ovariectomized Fischer inbred rats were hormonally primed with 10 μg estradiol benzoate and 500 μg progesterone. The effect of 5 min restraint on sexual behavior was examined after bilateral hypothalamic i...

  12. Radioprotective effect of sodium selenite on bone repair in the tibia of ovariectomized rats

    International Nuclear Information System (INIS)

    This study evaluated protection by selenium (Se) in the bone repair process in ovariectomized rats after irradiation. For such purpose, 80 ovariectomized female Wistar rats were randomly divided into 4 experimental groups: ovariectomized (Ov), Ov/Se, Ov/irradiated (Irr) and Ov/ Se/Irr. A bone defect was created on the tibia of all animals 40 days after ovariectomy. Two days after surgery, only the Ov/Se and Ov/Se/Irr rats received 0.8 mg Se/kg. Three days after surgery, only the Ov/Irr and Ov/Se/Irr rats received 10 Gy of x-rays on the lower limb region. The animals were euthanized at 7, 14, 21 and 28 days after surgery to assess the repair process, which was evaluated by analysis of trabecular bone number (Masson Trichrome) and birefringence analysis (Picrosirius). It was possible to observe a delay in the bone repair process in the ovariectomized/irradiated group and similarity between the ovariectomized, Ov/Se and Ov/Se/Irr groups. In conclusion, sodium selenite exerted a radioprotective effect in the bone repair of tibia of ovariectomized rats without toxicity. (author)

  13. Radioprotective effect of sodium selenite on bone repair in the tibia of ovariectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, Deborah Queiroz de; Neves, Ellen Gaby; Boscolo, Frab Norberto; Almeida, Solange Maria de [University of Campinas (UNICAMP), Piracicaba, SP (Brazil). Piracicaba Dental School. Department of Oral Diagnosis. Oral Radiology Area; Ramos-Perez, Flavia Maria de Moraes [Federal University of Pernambuco, Recife, PE (Brazil). Department of Clinical and Preventive Dentistry; Marques, Marcelo Rocha [University of Campinas (UNICAMP), Piracicaba, SP (Brazil). Piracicaba Dental School. Division of Histology. Department of Morphology

    2012-07-01

    This study evaluated protection by selenium (Se) in the bone repair process in ovariectomized rats after irradiation. For such purpose, 80 ovariectomized female Wistar rats were randomly divided into 4 experimental groups: ovariectomized (Ov), Ov/Se, Ov/irradiated (Irr) and Ov/ Se/Irr. A bone defect was created on the tibia of all animals 40 days after ovariectomy. Two days after surgery, only the Ov/Se and Ov/Se/Irr rats received 0.8 mg Se/kg. Three days after surgery, only the Ov/Irr and Ov/Se/Irr rats received 10 Gy of x-rays on the lower limb region. The animals were euthanized at 7, 14, 21 and 28 days after surgery to assess the repair process, which was evaluated by analysis of trabecular bone number (Masson Trichrome) and birefringence analysis (Picrosirius). It was possible to observe a delay in the bone repair process in the ovariectomized/irradiated group and similarity between the ovariectomized, Ov/Se and Ov/Se/Irr groups. In conclusion, sodium selenite exerted a radioprotective effect in the bone repair of tibia of ovariectomized rats without toxicity. (author)

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

    International Nuclear Information System (INIS)

    The metabolism, dosimetry, and biological effects of inhaled 91YCl3 in Beagle dogs are being studied. Forty-two dogs with initial 91Y body burdens from 14 to 1300 μCi/kg body weight and 12 control dogs were observed during their life spans. Four additional dogs with a mean initial body burden of 180 μCi 91Y/kg body weight were placed in a sacrifice study. All 46 of the exposed dogs and all 12 of the control dogs have died. Dogs with the highest initial body burdens died with bone marrow damage and pancytopenia. Three dogs died with nasal cavity carcinomas, three died with pulmonary carcinomas, and one died with hepatic hemangiosarcoma. These cancers all appeared to be related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases

  15. Toxicity of inhaled 91YCl3 in beagle dogs

    International Nuclear Information System (INIS)

    The metabolism, dosimetry and effects of inhaled 91YCl3 in beagle dogs are being studied. Forty-two dogs with 91Y initial body burdens from 14 to 1300 μCi/kg body weight and 12 control dogs are being maintained for lifetime observation. Four additional dogs with a mean initial body burden of 180 μCi/kg body weight were placed in a sacrifice study. Thirty-six of the exposed dogs and 7 of the control dogs have died. Dogs with the highest activity levels died with bone marrow damage and pancytopenia. Three dogs died with nasal cavity carcinomas and three with pulmonary carcinomas and one with hepatic hemangiosarcoma that all appear related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases. Observations are continuing on 10 surviving exposed dogs and six surviving unexposed dogs

  16. Toxicity of inhaled 91YCl3 in Beagle dogs. XVI

    International Nuclear Information System (INIS)

    The metabolism, dosimetry and biological effects of inhaled 91YCl3 in Beagle dogs are being studied. Forty-two dogs with initial 90Y body burdens from 14 to 1300 μCi per kilogram body weight and 12 control dogs are being maintained for lifetime observation. Four additional dogs with a mean initial body burden of 180 μCi 91Y per kilogram body weight were placed in a sacrifice study. Forty-four of the exposed dogs and all 12 of the control dogs have died. Dogs with the highest initial body burdens died with bone marrow damage and pancytopenia. Three dogs died with nasal cavity carcinomas, three dogs died with pulmonary carcinomas and one dog died with hepatic hemangiosarcoma; these cancers all appeared to be related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases. Observations are continuing on the two surviving exposed dogs

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

    International Nuclear Information System (INIS)

    Beagle dogs given single exposure to 239PuO2 or 238Pu16O2 aerosols are being observed for life-span dose-effect relationships. The 239Pu body burden of the nine dogs dying due to respiratory insufficiency during the first 3 years after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor. None of the dogs exposed to 238Pu died during the first postexposure year. After inhalation of 239PuO2 or 238PuO2 lymphocytopenia was the earliest observed effect, occurring 0.5 to 2 years after deposition of greater than or equal to 80 nCi plutonium in the lungs. (U.S.)

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

    International Nuclear Information System (INIS)

    Beagle dogs given a single exposure to 239PuO2 or 238PuO2 aerosols are being observed for life-span dose-effect relationships. The 239Pu body burden of the nine dogs that died of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor. Five additional dogs with body burdens of 0.7 to 1.8 μCi died due to pulmonary neoplasia 3 to 5 yr after exposure. None of the dogs exposed to 238Pu have died during the first 3 postexposure yr. Lymphocytopenia was the earliest observed effect after inhalation of 239PuO2 or 238PuO2, occurring 0.5 to 2 yr after deposition of greater than or equal to 80 nCi plutonium in the lungs

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

    International Nuclear Information System (INIS)

    Beagle dogs given single exposure to 239PuO2 or 238PuO2 aerosols are being observed for life-span dose-effect relationships. The 239Pu body burden of the nine dogs dying due to pulmonary fibrosis-induced insufficiency during the first 3 years after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor. Three additional dogs with body burdens of 0.7 to 1.8 μCi died due to pulmonary neoplasia 4-1/2 years after exposure. None of the dogs exposed to 238Pu have died during the first two postexposure years. After inhalation of 239PuO2 or 238PuO2 lymphocytopenia was the earliest observed effect, occuring 0.5 to 2 years after deposition of greater than or equal to 80 nCi plutonium in the lungs

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

    Directory of Open Access Journals (Sweden)

    Gustavo Bujalesky

    2004-03-01

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

  1. Restricted dog leucocyte antigen (DLA) class II haplotypes and genotypes in Beagles

    OpenAIRE

    Soutter, Francesca; Kennedy, Lorna J; Ollier, William E R; Solano-Gallego, Laia; Catchpole, Brian

    2015-01-01

    Beagles are commonly used in vaccine trials as part of the regulatory approval process. Genetic restriction within this breed and the impact this might have on vaccine responses are rarely considered. This study was designed to characterise diversity of dog leucocyte antigen (DLA) class II genes in a breeding colony of laboratory Beagles, whose offspring are used in vaccine studies. DLA haplotypes were determined by PCR and sequence-based typing from genomic DNA extracted from blood. Breeding...

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

    International Nuclear Information System (INIS)

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

  3. Tissue reactions to suture materials in the oral mucosa of beagle dogs

    OpenAIRE

    Kim, Jae-Seok; Shin, Seung-Il; Herr, Yeek; Park, Joon-Bong; Kwon, Young-Hyuk; Chung, Jong-Hyuk

    2011-01-01

    Purpose The objective of this study was to compare and evaluate the inflammatory responses of three widely used suture materials in the keratinized gingiva and buccal mucosa of beagle dogs. Methods Silk, polyglycolic acid, and nylon sutures were placed within the mandibular keratinized gingiva and maxillary buccal mucosa of four male beagle dogs. Biopsies were taken 3, 7, and 14 days after suturing. Specimens were prepared with hematoxylin-eosin stain for evaluation under a light microscope. ...

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

    International Nuclear Information System (INIS)

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

  5. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model.

    Science.gov (United States)

    Britton, Robert A; Irwin, Regina; Quach, Darin; Schaefer, Laura; Zhang, Jing; Lee, Taehyung; Parameswaran, Narayanan; McCabe, Laura R

    2014-11-01

    Estrogen deficiency is a major risk factor for osteoporosis that is associated with bone inflammation and resorption. Half of women over the age of 50 will experience an osteoporosis related fracture in their lifetime, thus novel therapies are needed to combat post-menopausal bone loss. Recent studies suggest an important role for gut-bone signaling pathways and the microbiota in regulating bone health. Given that the bacterium Lactobacillus reuteri ATCC PTA 6475 (L. reuteri) secretes beneficial immunomodulatory factors, we examined if this candidate probiotic could reduce bone loss associated with estrogen deficiency in an ovariectomized (Ovx) mouse menopausal model. Strikingly, L. reuteri treatment significantly protected Ovx mice from bone loss. Osteoclast bone resorption markers and activators (Trap5 and RANKL) as well as osteoclastogenesis are significantly decreased in L. reuteri-treated mice. Consistent with this, L. reuteri suppressed Ovx-induced increases in bone marrow CD4+ T-lymphocytes (which promote osteoclastogenesis) and directly suppressed osteoclastogenesis in vitro. We also identified that L. reuteri treatment modifies microbial communities in the Ovx mouse gut. Together, our studies demonstrate that L. reuteri treatment suppresses bone resorption and loss associated with estrogen deficiency. Thus, L. reuteri treatment may be a straightforward and cost-effective approach to reduce post-menopausal bone loss. PMID:24677054

  6. Partial hepatectomy induces delayed hepatocyte proliferation and normal liver regeneration in ovariectomized mice

    Directory of Open Access Journals (Sweden)

    Umeda M

    2015-07-01

    Full Text Available Makoto Umeda,1 Masaki Hiramoto,1,2 Takeshi Imai1 1Department of Aging Intervention, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan; 2Department of Biochemistry, Tokyo Medical University, Tokyo, Japan Abstract: Estrogens play central roles in sexual development, reproduction, and hepatocyte proliferation. The ovaries are one of the main organs for estradiol (E2 production. Ovariectomies (OVXs were performed on the female mice, and hepatocyte proliferation was analyzed. The ovariectomized mice exhibited delayed hepatocyte proliferation after partial hepatectomy (PH and also exhibited delayed and reduced E2 induction. Both E2 administration and PH induced the gene expression of estrogen receptor α (ERα. The transcripts of ERα were detected specifically in periportal hepatocytes after E2 administration and PH. Moreover, the E2 concentrations and hepatocyte proliferation rates were highest in the proestrus period of the estrous cycle. Taken together, these findings indicate that E2 accelerated ERα expression in periportal hepatocytes and hepatocyte proliferation in the female mice.Keywords: estrogen, ER, estrous cycle, hepatocyte proliferation, liver regeneration

  7. Estrogen modulates the mRNA levels for cancellous bone protein of ovariectomized rats.

    Science.gov (United States)

    Salih, M A; Liu, C C; Arjmandi, B H; Kalu, D N

    1993-12-01

    This study was undertaken to examine the effects of ovariectomy and 17 beta-estradiol (E2) on the gene expression of type 1 collagen, osteocalcin and the protooncogen, c-myc, in cancellous bone. Female Sprague-Dawley rats, aged 95 days, were divided into 4 groups. Group 1 was sham operated and Groups 2-4 were ovariectomized. Groups 3 and 4 received daily injections of 160 ng and 1600 ng E2/kg body weight, respectively. Groups 1 and 2 received the solvent vehicle. All animals were sacrificed after 14 days. The femurs were dissected out and cancellous bone scraped from the distal metaphysis. RNA was isolated from the cancellous bone, immobilized on filters or size-fractionated by agarose gel electrophoresis and adsorbed on filters which were then hybridized with specific cDNA probes. Ovariectomy resulted in a significant increase in the mRNAs of type 1 collagen, osteocalcin and c-myc. The increase was suppressed in animals that received 17 beta-estradiol injections. In addition, ovariectomy caused the expected decrease in cancellous bone in the proximal tibia and increased osteoclast and osteoblast numbers. The ovariectomy-induced changes were prevented by 17 beta-estradiol administration. These findings suggest that the lack of ovarian hormones shortly after ovariectomy up-regulates and estrogen administration down-regulates the expression of important cancellous bone matrix proteins as well as the protooncogen, c-myc. PMID:8148671

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  11. Histomorphometry of the organic matrix of the femur in ovariectomized rats treated with sodium alendronate

    Directory of Open Access Journals (Sweden)

    Patricia Tanios Haddad

    2015-02-01

    Full Text Available OBJECTIVE: To evaluate the effect of two different concentrations of sodium alendronate on the quantity of organic matrix in the femur of rats with estrogen suppression caused by ovariectomy.METHODS: Sixty-days-old Wistar rats (Rattus norvegicus were subjected to bilateral laparotomy to remove the ovaries. The animals were divided into a control group, in which they only underwent laparotomy; an ovariectomized group (OVX; an ovariectomized group treated with 1 mg/kg of alendronate (OVX 1 mg; and an ovariectomized group treated with 2 mg/kg of alendronate (OVX 2 mg. The rats received alendronate twice a week for 90 days. The left femur was then removed, fixed and processed for embedding in paraffin. Semi-serial sections stained with hematoxylin and eosin were used to determine the area occupied by organic bone matrix, by means of image analysis software. The animals' weights were obtained at the beginning and end of the experiment.RESULTS: The ovariectomized animals and those treated with 1 mg/kg of alendronate presented significant increases in body weight (p 0.05 to that of the non-ovariectomized control animals (2,04,800 ± 9590, which indicates that this medication had a preventive effect with regard to bone mass loss.CONCLUSION: The higher concentration of the medication, administered twice a week for 90 days, was more effective than the dose of 1 mg/kg over the same period.

  12. EFFECT OF GLABRIDIN AND GLYCYRRHIZIC ACID ON HISTOMORPHOMETRIC PARAMETERS OF BONES IN OVARIECTOMIZED RATS.

    Science.gov (United States)

    Klasik-Ciszewska, Sylwia; Kaczmarczyk-Sedlak, Ilona; Wojnar, Weronika

    2016-01-01

    Licorice is a medicinal plant showing many therapeutic activities. Its roots contain numerous pharmacologically active compounds such as a triterpenoid saponin--glycyrrhizic acid and an isoflavan--glabridin. There are reports indicating that glabridin exhibits estrogen-like activity, therefore it can be classified into phytoestrogens, which may soothe menopause symptoms including postmenopausal osteoporosis. Due to this fact, the aim of the presented study was to evaluate the effect of glabridin and glycyrrhizic acid on histomorphometric parameters of bones in rats with ovariectomy-induced osteoporosis. The animals were divided into 6 group: (C)--control rats, (OVX)--ovariectomized rats, (OVX + E)--ovariectomized rats receiving estradiol at a dose of 0.1 mg/kg p.o., (OVX + G)--ovariectomized rats receiving genistein at a dose of 5 mg/kg p.o., (OVX + GL --ovariectomized rats treated with glabridin at a dose of 5 mg/kg p.o. and (OVX + GA)--ovariectomized rat administered with glycyrrhizic acid at a dose of 15 mg/kg p.o. Estradiol and genistein served as the positive controls in the study. Several macrometric and histomorphometric parameters were analyzed in the bones of tested rats. Obtained results indicate that glabridin shows slightly positive effect on osteoporotically changed bone tissue, and glycyrrhizic acid reveals meager influence on skeletal system with no preventive significance. PMID:27180445

  13. Estrogen deficiency in ovariectomized rats: can resistance training re-establish angiogenesis in visceral adipose tissue?

    Science.gov (United States)

    do Valle Gomes-Gatto, Camila; Duarte, Fernanda Oliveira; Stotzer, Uliana Sbeguen; Rodrigues, Maria Fernanda Cury; de Andrade Perez, Sérgio Eduardo; Selistre-de-Araujo, Heloisa Sobreiro

    2016-01-01

    OBJECTIVE: The purpose of this study was to investigate the effects of resistance training on angiogenesis markers of visceral adipose tissue in ovariectomized rats. METHOD: Adult Sprague-Dawley female rats were divided into four groups (n=6 per group): sham-sedentary, ovariectomized sedentary, sham-resistance training and ovariectomized resistance training. The rats were allowed to climb a 1.1-m vertical ladder with weights attached to their tails and the weights were progressively increased. Sessions were performed three times per week for 10 weeks. Visceral adipose tissue angiogenesis and morphology were analyzed by histology. VEGF-A mRNA and protein levels were analyzed by real-time PCR and ELISA, respectively. RESULTS: Ovariectomy resulted in higher body mass (p=0.0003), adipocyte hypertrophy (p=0.0003), decreased VEGF-A mRNA (p=0.0004) and protein levels (p=0.0009), and decreased micro-vascular density (p=0.0181) in the visceral adipose tissue of the rats. Resistance training for 10 weeks was not able to attenuate the reduced angiogenesis in the visceral adipose tissue of the ovariectomized rats. CONCLUSION: Our findings indicate that the resistance training program used in this study could not ameliorate low angiogenesis in the visceral adipose tissue of ovariectomized rats.

  14. Effects of salmon calcitonin on fracture healing in ovariectomized rats

    International Nuclear Information System (INIS)

    Objective was to explore the effects of salmon calcitonin on the healing process of osteoporotic fractures in ovariectomized rats. We performed this study in the First Affiliated Hospital of Guangzhaou Medical College, Guangzhaou, China during the period March 2002 to December 2004. We used 120 female adult Wistar rats in this experiment, among which 90 underwent ovariectomy (OVX) and the other 30 had shamoperation. All rats had their left tibias fractured 3 months later. The 90 OVX rats were randomly divided into 3 groups with 30 in each, while the 30 shamoperated rats served as control group. After the fracture rats had subcutaneous injection of normal saline, salmon calcitonin and estrogen, respectively. X-ray film, histological examination, bone mineral density (BMD) measurement and biomechanics testing were carried out to evaluate the fracture healing. Compared with OVX rats treated normal saline, the rats with salmon calcitonin had significantly higher BMD values in the left tibia, higher max torque, shear stress of the left tibia 8 weeks after fracture (p<0.05), and presented with stronger callus formation, shorter fracture healing time and faster normalization of microstructure of bone trabeculae. Salmon calcitonin can, not only increase in osteoporotic bone biomechanical properties and improve the process of fractured osteoporotic bone. (author)

  15. Effect of Kiwifruit on Bone Resorption in Ovariectomized Mice.

    Science.gov (United States)

    Katsumata, Shinichi; Wolber, Frances M; Tadaishi, Miki; Tousen, Yuko; Ishimi, Yoshiko; Kruger, Marlena C

    2015-01-01

    Kiwifruit is a good source of dietary components and has beneficial effects for health. In this study, we investigated the effects of two types of kiwifruit, green kiwifruit (GRK) and gold kiwifruit (GOK), on bone metabolism in ovariectomized (OVX) mice. Seven-week-old female Balb/c-strain mice were divided into four groups: sham-operated (sham) group, OVX group, and OVX mice that were fed a GRK-supplemented diet or GOK-supplemented diet. Freeze-dried GRK and GOK were prepared and added in the diet at a concentration of 3 g/100 g. After 9 wk, the mice were sacrificed, and the serum, uterus, and femurs were obtained. Final body weight did not differ significantly among the four groups. Compared to the sham group, uterine weight was significantly lower and serum C-terminal telopeptide of type I collagen (CTx) levels and receptor activator of NF-κB ligand (RANKL) mRNA expression of the whole femur were significantly higher in the OVX group. Compared to the OVX group, GRK, but not GOK, reduced serum CTx concentrations and RANKL mRNA expression of the whole femur without changes in uterine weight. These results suggest that the GRK inhibited bone resorption, which might be due to a decrease in RANKL mRNA expression in OVX mice. PMID:26440641

  16. Regular exercise modulates cardiac mast cell activation in ovariectomized rats.

    Science.gov (United States)

    Phungphong, Sukanya; Kijtawornrat, Anusak; Wattanapermpool, Jonggonnee; Bupha-Intr, Tepmanas

    2016-03-01

    It is well accepted that regular exercise is a significant factor in the prevention of cardiac dysfunction; however, the cardioprotective mechanism is as yet not well defined. We have examined whether regular exercise can modulate the activity of cardiac mast cells (CMC) after deprivation of female sex hormones, as well as the density and percentage degranulation of mast cells, in ventricular tissue of ovariectomized (OVX) rats after an 11-week running program. A significant increase in CMC density with a greater percentage degranulation was induced after ovarian sex hormone deprivation. Increased CMC density was prevented by estrogen supplements, but not by regular training. To the contrary, increased CMC degranulation in the OVX rat heart was attenuated by exercise training, but not by estrogen supplement. These findings indicate a significant correlation between the degree of CMC degranulation and myocyte cross-section area. However, no change in the expression of inflammatory mediators, including chymase, interleukin-6, and interleukin-10, was detected. Taken together, these results clearly indicate one of the cardioprotective mechanisms of regular aerobic exercise is the modulation of CMC activation. PMID:26467449

  17. Estradiol release kinetics determine tissue response in ovariectomized rats.

    Science.gov (United States)

    Otto, Christiane; Kantner, Ingrid; Nubbemeyer, Reinhard; Schkoldow, Jenny; Fuchs, Iris; Krahl, Elisabeth; Vonk, Richardus; Schüler, Christiane; Fritzemeier, Karl-Heinrich; Erben, Reinhold G

    2012-04-01

    Estrogen replacement is an effective therapy of postmenopausal symptoms such as hot flushes, bone loss, and vaginal dryness. Undesired estrogen effects are the stimulation of uterine and mammary gland epithelial cell proliferation as well as hepatic estrogenicity. In this study, we examined the influence of different estradiol release kinetics on tissue responsivity in ovariectomized (OVX) rats. Pulsed release kinetics was achieved by ip or sc administration of estradiol dissolved in physiological saline containing 10% ethanol (EtOH/NaCl) whereas continuous release kinetics was achieved by sc injection of estradiol dissolved in benzylbenzoate/ricinus oil (1+4, vol/vol). Initial 3-d experiments in OVX rats showed that pulsed ip estradiol administration had profoundly reduced stimulatory effects on the uterus and the liver compared with continuous release kinetics. On the other hand, both administration forms prevented severe vaginal atrophy. Based on these results, we compared the effects of pulsed (sc in EtOH/NaCl) vs. continuous (sc in benzylbenzoate/ricinus oil) estradiol release kinetics on bone, uterus, mammary gland, and liver in a 4-month study in OVX rats. Ovariectomy-induced bone loss was prevented by both administration regimes. However, pulsed estradiol resulted in lower uterine weight, reduced induction of hepatic gene expression, and reduced mammary epithelial hyperplasia relative to continuous estradiol exposure. We conclude that organ responsivity is influenced by different hormone release kinetics, a fact that might be exploited to reduce undesired estradiol effects in postmenopausal women. PMID:22334713

  18. The reproductive cycle of Eurhomalea exalbida (Chemnitz, 1795) (Bivalvia: Veneridae) in Ushuaia Bay (54°50′ S), Beagle Channel (Argentina)

    OpenAIRE

    Morriconi, E.; Lomovasky, B.; Calvo, J.; Brey, Thomas

    2002-01-01

    The reproductive cycle of Eurhomalea exalbida (Chemnitz, 1795) in Ushuaia Bay, Beagle Channel, was studied from October 1998 to December 1999. Clams were collected monthly by SCUBA diving at 3 to 5 m water depth. The degree of sexual maturity was determined histologically (n=318). The sex ratio was 1:1 (Chi-squared p > 0.05). First sexual maturity occurred at 39 mm shell heigth in males and 40 mm in females (i.e. 4 years of age).Five distinct histological stages of sexual maturity could be es...

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

    International Nuclear Information System (INIS)

    Immature Beagle dogs (approximately equal to 3 months of age at exposure) have been exposed by inhalation to a relatively insoluble form of 144Ce (in fused aluminosilicate particles) to compare the resulting patterns of metabolism, dosimetry and biological effects with those seen in dogs exposed at 12 and 14 months of age and at 8 to 10.5 years of age. Five blocks of longevity animals, each consisting of 10 exposed dogs and one control, are currently on experiment. The initial lung burdens of the 144Ce-exposed dogs range from 0.004 to 140 μCi 144Ce/kg body weight. Three dogs with initial lung burdens of 73 to 120 μCi 144Ce/kg body weight died at 66 to 121 days after exposure with pulmonary injury and congestive heart failure. One dog with an initial lung burden of 140 μCi 144Ce/kg body weight died at 91 days after exposure with severe radiation pneumonitis and minimal pulmonary fibrosis and another dog whose initial lung burden was 70 μCi 144Ce/kg body weight died at 511 days after exposure with pulmonary injury that was mainly fibrotic in nature. Two dogs with initial lung burdens of 52 and 64 μCi 144Ce/kg body weight had primary pulmonary hemangiosarcomas and died at 618 and 689 days, respectively, with cumulative average absorbed beta doses to lung of 23,000 and 29,000 rads. One dog with an initial lung burden of 28 μCi 144Ce/kg body weight was euthanized at 1227 days after exposure with a hemangiosarcoma of the mediastinum, and another dog with an initial lung burden of 12 μCi 144Ce/kg body weight died at 1520 days after exposure from epilepsy. Serial observations are continuing on the surviving 40 exposed and five control dogs

  20. Inhibitory effects of Leonurus sibiricus on weight gain after menopause in ovariectomized and high-fat diet-fed mice.

    Science.gov (United States)

    Kim, Jangseon; Kim, Mi Hye; Choi, You Yeon; Hong, Jongki; Yang, Woong Mo

    2016-07-01

    Leonurus sibiricus, also called motherwort, is a well-known functional food and medicinal herb. It has been known to possess beneficial properties for women's health, especially for aged women. Estrogen deficiency in the menopause could induce lipid metabolic abnormalities in body fat, resulting in obesity. In this study, the inhibitory effects of L. sibiricus on obesity after the menopause were investigated. Female C57BL/6 mice were ovariectomized and fed high-fat diet (HFD) for 12 weeks. Following an induction period, aqueous extracts of L. sibiricus (LS) were orally administrated for 6 weeks. The body, uterine, and visceral fat weights were measured immediately after the animals were killed. Histological analysis was performed to monitor fat and liver. Serum levels of glucose, triglyceride, total cholesterol, and LDL-cholesterol were evaluated. In addition, the expression of lipases was analyzed. Total body weight was significantly decreased by LS treatment. Histological changes in adipocyte size were shown along with a decrease of visceral fat weight in the LS-treated group. In addition, the fat infiltration of liver was reduced by LS administration. LS-treated mice experienced decreases of serum triglyceride, total cholesterol, and LDL-cholesterol levels. The expression of HSL and ATGL was significantly increased by LS treatment. These results suggest that LS could regulate the lipid metabolism via an increase of lipases expression in ovariectomized and HFD-fed mice. LS might be a novel candidate for a functional food to inhibit weight gain after the menopause. PMID:26899238

  1. Investigation of strontium accumulation on ovariectomized Sprague–Dawley rat tibia by micro-PIXE

    Energy Technology Data Exchange (ETDEWEB)

    Li, X.; Li, Y. [Institute of Modern Physics, Fudan University, Shanghai 200433 (China); Jin, W. [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China); Zheng, Y.; Rong, C.; Lyu, H. [Institute of Modern Physics, Fudan University, Shanghai 200433 (China); Shen, H., E-mail: haoshen@fudan.edu.cn [Institute of Modern Physics, Fudan University, Shanghai 200433 (China)

    2014-08-01

    Strontium ranelate is a newly developed drug effective in osteoporosis treatment by depressing bone resorption and maintaining bone formation. Strontium accumulation and distribution are determined in bones of rat after strontium ranelate administration by using micro-PIXE. The investigated rats are divided into four groups: (A) control, (B) ovariectomized, (C) ovariectomized followed with strontium chloride, (D) ovariectomized followed with strontium ranelate. It was found that strontium ranelate would result in increasing trabecular volume and decreasing bone resorption to treat osteoporosis. There are similar contours of calcium and strontium in two-dimensional images, while the strontium is not evenly distributed in the bone. It supports the conclusion that strontium has an affinity for bone and it is capable of replacing calcium atoms as a part of the strontium mechanism in the osteoporosis treatment. The results related to biochemistry are also discussed.

  2. Dynamic changes of beta-amyloid protein deposition in hippocampus of female ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Huiqing Xie; Jianda Zhou; Shaodan Sun; Xuhong Li; Liming Deng; Fengmei Li

    2008-01-01

    BACKGROUND: To evaluate and summarize the effects of cerebral perfusion and vascular reserve on the treatment of SICAS. Recently, research on β-amyloid protein has focused on the regulatory effects of es-trogen or phytoestrogen on its deposition. However, there have been only a few reports on dynamic changes of β-amyloid protein deposition in hippocampus of ovariectomized rats.OBJECTIVE: To measureβ-amyloid protein deposition in the hippocampal formation of ovariectomized rats by using immunohistochemistry; to observe time-dependent dynamic changes. DESIGN: Randomized controlled animal study.SETTING: Third Xiangya Hospital of Central South University.MATERIALS: The experiment was carried out in the Central Laboratory of the Third Xiangya Hospital of Central South University from November 2005 to December 2006. Fifty healthy female Sprague Dawley (SD) rats, weighing (293 ± 10) g, were provided by the Animal Laboratory of Xiangya Medical College, Central South University. All rats had neither a childbearing history nor hepatic or renal disease, or skeletal deformity. Β-amyloid protein immunohistochemical kit was provided by Wuhan Boster Company. The ex-periment was in accordance with animal ethics standards.METHODS: All rats were randomly divided into five groups, including normal control group (n = 10), sham operation group (n = 10), and ovariectomized group (n = 30). After anesthesia in the ovariectomized group, the bilateral ovaries were separated and resected. The same volume of fat was resected in the sham operation group. Rats from the normal control group, however, did not receive any surgical treatments. Rats in the normal control group and sham operation group were sacrificed by anesthesia 7 weeks after surgery. Every ten rats from the ovariectomized group was respectively sacrificed at 7, 15, and 30 weeks after surgery. Immunohistochemistry was used to detectβ-amyloid protein deposition in hippocampal sections. Cell counting and gray value

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

    International Nuclear Information System (INIS)

    Beagle dogs given a single exposure to 239PuO2 and 238PuO2 aerosols are being observed for life-span dose-effect relationships. The 239Pu body burden of the nine dogs that died of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor; nine additional dogs with body burdens of 0.6 to 1.8 μCi died due to pulmonary neoplasia 3 to 6 yr after exposure. Two of the dogs exposed to 238Pu have died during the first 4 yr postexposure, due to bone and lung tumors, with body burdens at death of 10 μCi. Lymphocytopenia was the earliest observed effect after inhalation of 239PuO2 or 238PuO2, occurring 0.5 to 2 yr after deposition of equal to or greater than 80 nCi plutonium in the lungs

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

    International Nuclear Information System (INIS)

    Beagle dogs given a single exposure to 239PuO2 and 238PuO2 aerosols are being observed for life-span dose-effect relationships. The 239Pu body burden of the nine dogs that dies of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi; one of these dogs had a pulmonary tumor. Eleven additional dogs with body burdens of 0.6 to 1.8 μCi died due to pulmonary neoplasia 3 to 7 yr after exposure. Four of the dogs exposed to 238Pu have died during the first 4 1/2 yr postexposure due to bone and/or lung tumors; the body burden at death ranged from 6 to 10 μCi. Lymphopenia was the earliest observed effect after inhalation of 239PuO2 or 238PuO2, occurring 0.5 to 2 yr after deposition of greater than or equal to 80 nCi plutonium in the lungs

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

    International Nuclear Information System (INIS)

    The metabolism, dosimetry, and biological effects of inhaled 91YCl3 were studied in Beagle dogs. Forty-two dogs with initial 91Y body burdens from 14 to 1300 μCi/kg (0.52-48 MBq/kg) body weight and 12 control dogs were observed during their life spans. Four additional dogs with a mean initial body burden of 180 μCi 91Y/kg (6.7 MBq/kg) body weight were placed in a sacrifice study. All 46 of the exposed dogs and all 12 of the control dogs have died. Dogs with the highest initial body burdens died with bone marrow damage and pancytopenia. Of the dogs dying of late-occurring effects, three died with nasal cavity carcinomas, three died with pulmonary carcinomas, and one died with hepatic hemangiosarcoma. These cancers all appeared to be related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases. 1 reference, 1 figure, 3 tables

  6. Retention of plutonium in the beagle after gastrointestinal absorption

    International Nuclear Information System (INIS)

    A 0.01 M bicarbonate solution containing 130 nCi (approx. 5 kBq) of 237Pu (90% hexavalent, 93% ultrafilterable) was administered via gelatin capsule to six adult male beagles following a 21-hr fast. The dogs were sacrificed after 5-6 weeks and the percentage of the administered plutonium retained in the liver plus skeleton and its distribution within the skeleton were determined. The mean amount retained in these tissues was (0.063 +- 0.006)% of the administered dose. The mean amounts of plutonium in the liver and the skeleton were approximately equal, and the distribution within the skeleton was similar to that observed by other workers following either intravenous injection or inhalation. The value for plutonium retention by the dog is about a factor of three less than the values the authors have reported for rodents. It is a factor of 7 greater than the product of the values for gastrointestinal absorption (f1) and fractional retention (f2) recommended by the ICRP for man

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

    International Nuclear Information System (INIS)

    Beagle dogs given a single exposure to 239PuO2 and 238PuO2 aerosols are being observed for life-span dose-effect relationships. The 239Pu body burden of the nine dogs that died of pulmonary-fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi; one of these dogs had a pulmonary tumor. Seventeen additional dogs, with body burdens of 0.2 to 1.8 μCi, died due to pulmonary neoplasia 3 to 8 yr after exposure. Ten of the dogs exposed to 238Pu have died during the first 5 1/2 yr postexposure due to bone and/or lung tumors; the body burden at death ranged from 1.5 to 10 μCi. Lymphopenia was the earliest observed effect after inhalation of 239PuO2 or 238PuO2, occurring 0.5 to 2 yr after deposition of >80 nCi plutonium in the lungs

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

    Science.gov (United States)

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

    2000-01-01

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

  9. Role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice.

    Directory of Open Access Journals (Sweden)

    Karol Kaminski

    2011-04-01

    Full Text Available Postmenopausal women frequently develop hypothyroidism. Estrogen depletion is accompanied by an increase of IL-6, accelerating bone turnover. The influence of hypothyroidism on bone metabolism in postmenopausal women is poorly understood. The aim of the study was an attempt to clarify the role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT and C57BL/6JIL6-/-Kopf (IL-6 knock-out; IL6KO. The mice were randomly divided into 8 groups with 7 mice in each one: 1/ WT controls, 2/ IL6KO controls, 3/ WT hypothyroid mice, 4/ IL6KO hypothyroid mice, 5/ WT ovariectomized, 6/ IL6KO ovariectomized, 7/ WT ovariectomized hypothyroid mice and 8/ IL6KO ovariectomized hypothyroid mice. Experimental model of menopause was produced by bilateral ovariectomy carried out in 8-9 weeks old mice. Experimental model of hypothyroidism was induced by propylthiouracyl administration in driking water. The serum levels of TRACP 5b, osteocalcin, OPG and RANKL were determined by ELISA. Serum RANKL concentrations were elevated significantly in all groups of ovariectomized mice as compared to respective controls, but in a minor degree in IL6KO hypothyroid mice as compared to wild-type animals. Moreover sRANKL values were significantly lower in IL6KO as compared to WT controls and IL6KO PTU injected mice. Osteoprotegerin serum levels were decreased in all IL-6 deficient mice and in a highest degree in sham-operated hypothyroid mice. To sum up, the results of the present study suggest that estrogens deficit is a strong stimulus for RANKL-RANK/OPG pathway that breaks an inhibitory influence of hypothyroidism even in IL-6 deficient mice.

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

    Science.gov (United States)

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

  11. Quantification of brown dog tick repellent, 2-hexanone and benzaldehyde, release from tick-resistant Beagle dogs, Canis lupus familiaris

    Science.gov (United States)

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

  12. Effects of Kalsis, A Dietary Supplement, on Bone Metabolism in the Ovariectomized Rats

    OpenAIRE

    Mercedes Montero.; Manuel Díaz-Curiel; David Guede; Jose Ramón Caeiro; Marta Martín-Fernández; Mercedes Rubert; Daisy Navarro; Concepción de la Piedra

    2012-01-01

    We studied the ability of Kalsis, a food supplement that contains selenium, citric acid, and vitamin E, to prevent the effects of ovariectomy on bone loss. Six-month-old, Wistar female rats were studied. Groups (n = 12): SHAM: sham-operated rats; OVX: ovariectomized rats, treated with vehicle; OVX + Kalsis: ovariectomized rats treated with Kalsis (25 mg/kg/day) for 3 months. Bone mineral density (BMD) was determined by DXA in lumbar spine and femur. Computerized microtomography (μCT) in femur...

  13. Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats

    OpenAIRE

    Ma, Hai-rong; Wang, Jie; Qi, Hong-xue; Gao, Yan-hua; Pang, Li-Juan; Yang, Yi(Department of Electrophysics, National Chiao-Tung University, Hsinchu, Taiwan, ROC); Wang, Zhen-Hua; Duan, Ming-jun; Chen, Hua; Cao, Xu; Aisa, Haji Akber

    2013-01-01

    Aim: Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats. Methods: Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg−1·d−1) for 5 weeks. Their uterine weight and serum levels of 17β-estradiol (E2), follicle stimulating hormone (FSH)...

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  16. Estradiol-induced object memory consolidation in middle-aged female mice requires dorsal hippocampal ERK and PI3K activation

    OpenAIRE

    Fan, Lu; Zhao, Zaorui; Orr, Patrick T.; Chambers, Cassie H.; Michael C. Lewis; Frick, Karyn M.

    2010-01-01

    We previously demonstrated that dorsal hippocampal extracellular signal-regulated kinase (ERK) activation is necessary for 17β-estradiol (E2) to enhance novel object recognition in young ovariectomized mice (Fernandez et al., 2008). Here, we asked whether E2 has similar memory-enhancing effects in middle-aged and aged ovariectomized mice, and whether these effects depend on ERK and phosphatidylinositol 3-kinase (PI3K)/Akt activation. We first demonstrated that intracerebroventricular (ICV) E2...

  17. Black Cohosh Ameliorates Metabolic Disorders in Female Ovariectomized Rats.

    Science.gov (United States)

    Sun, Yu; Yu, Qiuxiao; Shen, Qiyang; Bai, Wenpei; Kang, Jihong

    2016-06-01

    Estrogen deficiency is associated with metabolic derangements in menopausal women. Black cohosh has been widely used as an alternative therapy in the treatment of menopausal syndrome. However, its role in metabolism needs to be defined. The aim of the present study was to investigate the long-term effect of black cohosh on glucose and lipid metabolism in a rat model of post-menopause. Adult female Sprague-Dawley rats were sham operated (SHAM), ovariectomized (OVX), OVX with the treatment of estradiol valerate (OVX + E), or OVX with the treatment of isopropanolic black cohosh extract (OVX + iCR). Body weight, body composition, and blood glucose levels of the animals were monitored. The rats were then sacrificed after 3 months of the treatments. At the end of the experiment, OVX + iCR and OVX + E rats exhibited a significant decrease in body weight gain, body and abdominal fat mass, serum triglycerides levels, hepatic fat accumulation, and adipocyte hypertrophy compared with OVX rats. In addition, insulin resistance and glucose intolerance were improved in OVX + iCR but not in OVX + E rats. No hepatotoxicity was detected in OVX + iCR animals. Furthermore, western blot analysis suggested the increased lipolysis in adipose tissue of OVX + iCR and OVX + E rats. Data from in vitro experiments using cultured primary rat adipocytes also showed that black cohosh could affect lipolysis of adipocytes. In conclusion, the long-term treatment of black cohosh at a proper dosage ameliorated metabolic derangements in OVX rats. Thus, this drug is promising for the treatment of metabolic disorders in menopausal and post-menopausal women. PMID:26414761

  18. Effects of chronic testosterone administration on body weight and food intake differ among pre-pubertal, gonadal-intact, and ovariectomized female rats.

    Science.gov (United States)

    Iwasa, Takeshi; Matsuzaki, Toshiya; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Yiliyasi, Mayila; Kato, Takeshi; Kuwahara, Akira; Irahara, Minoru

    2016-08-01

    In females, estrogens play pivotal roles in preventing excessive body weight gain. On the other hand, the roles of androgen in female appetite and body weight regulation have not been fully studied. In this study, whether the roles of androgen in the regulation of body weight and appetite were different among ages and/or the estrogen milieu in females was evaluated. Body weight gain and food intake were increased by chronic testosterone administration in pre-pubertal and gonadal-intact female rats, but not in ovariectomized female rats. Testosterone administration also affected the serum leptin level and adipose leptin gene expression levels differently in each experimental condition. Hypothalamic mRNA levels of ERα, which plays pivotal roles in regulation of body weight and metabolism, were decreased by chronic testosterone administration in pre-pubertal and gonadal-intact female rats, but not in ovariectomized female rats. These results indicate that the effects of testosterone on body weight and appetite differed among ages and/or estrogen milieu in female rats, and that attenuation of estrogens' actions on the hypothalamus might be partly involved in the androgen-induced increases of body weight gain and food intake in females. PMID:27139935

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2011-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Gustavo Bujalesky

    2004-03-01

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

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

    International Nuclear Information System (INIS)

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

  3. Complement activation associated with polysorbate 80 in beagle dogs.

    Science.gov (United States)

    Qiu, Shidong; Liu, Zhaohua; Hou, Li; Li, Yuanyuan; Wang, Jiao; Wang, Hong; Du, Wu; Wang, Wenfang; Qin, Yizhuo; Liu, Zhaoping

    2013-01-01

    Polysorbate 80 (Tween® 80) is the most extensively used surfactant in parenteral drug formulation. Its application as an adjunct for intravenous drug administration is approved by the Food and Drug Administration. However, severe hypersensitive reactions, which are typical non-immune anaphylactic reactions (pseudoallergy) characterized by the release of histamine and unvaried IgE antibodies, have been associated with Tween® 80. In order to explore the non-immune anaphylactic mechanisms of Tween® 80, we performed in vivo experiments to assess the changes in physiological and hematologic indicators after intravenous injection of Tween® 80 into dogs. Tween® 80 induced the release of histamine, and a 2-fold increase in SC5b-9, 2.5-fold increase in C4d, 1.3-fold increase in Bb, while IgE remained unchanged. It also produced changes in pulmonary pressure, systemic pressure and ECG. In in vitro experiments, Tween® 80 was incubated with dog serum in the presence of an inhibitor of complement activation (EGTA/Mg(2+)). Under these conditions, Tween® 80 increased the contents of C4d and Bb. The results of this study reveal that Tween® 80 can cause cardiopulmonary distress in dogs and activate the complement system through classical and alternative pathways as indicated in both in vivo and in vitro preparations. Moreover, they demonstrate the utility of the beagle dog as an animal model for the study of complement activation-related pseudoallergy. These findings raise concerns with regard to the indiscriminate use of Tween® 80 in clinical applications. PMID:23159336

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

    International Nuclear Information System (INIS)

    Studies on the metabolism, dosimetry and effects of inhaled 91YCl3 in Beagle dogs are being continued to provide information that will aid in assessing the biological consequences of nuclear accidents in which 91Y or other radionuclides that produce a similar radiation dose pattern may be released. Forty-two dogs with 91Y initial body burdens from 64 to 1300 μCi/kg body weight was placed in four groups with mean lung burdens of 310, 180, 75 and 40 μCi/kg body weight. These dogs and 12 control dogs are being maintained for lifetime observation. An additional group of four dogs with a mean initial 91Y body burden of 180 μCi/kg body weight was placed in a sacrifice study. Twenty-six of the exposed dogs and four of the control dogs have died. Eleven dogs within the highest activity level groups died or were euthanized at 12 to 33 days after inhalation of 91Y with changes related to severe bone marrow damage and associated pancytopenia. Two dogs died approximately one year after 91Y inhalation with convulsive seizures that were presumed to be unrelated to the 91Y exposure. Nine 91Y-exposed dogs died or were euthanized due to neoplasms 2012 to 4115 days after exposure. Three dogs had nasal squamous cell carcinomas, one had a bronchioloalveolar carcinoma, one a mast cell sarcoma, one a mammary adenocarcinoma, one a malignant lymphoma, one a melanosarcoma in the mouth and one heart base tumor. Two dogs died of renal failure 2663 and 4086 days after exposure. One dog died with autoimmune hemolytic anemia 3888 days after exposure and one died with congestive heart failure 4042 days after inhalation exposure. One control dog died of empyema, another control dog died with a mammary adenocarcinoma, one died with congestive heart failure and one with malabsorption syndrome. Serial observations are continuing on all surviving dogs

  5. Aging.

    Science.gov (United States)

    Park, Dong Choon; Yeo, Seung Geun

    2013-09-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  6. Modulation of phase-II enzyme activities in benzene treated ovariectomized rats.

    Science.gov (United States)

    Verma, Yeshvandra; Rana, S V S

    2011-05-01

    The aim of the study was to determine the influence of ovariectomy on phase II enzymes viz. glutathione-S-transferase (GST), glutathione peroxidase (GPX) and catalase (CAT) in liver and kidney of female rats treated with benzene. The results showed the significant decrease of the GST and GPX activity in benzene treated rats after ovariectomy. However progesterone supplementation stimulated the activity of GST and GPX in liver and kidney of benzene treated non ovariectomized and ovariectomized rats. Progesterone supplementation to benzene treated ovariectomized rats helps to gain in CAT activity. Our results on DNA damage using single cell gel electrophoresis also confirmed our findings on antioxidant enzymes. The results showed that lack of protective progesterone against benzene toxicity is reflected in alterations in antioxidant enzyme activities. However progesterone therapy to benzene treated ovariectomized rats results in activating the antioxidant defence system. Since female workers are engaged in industrial sector, these results are important from occupational health point of view. Benzene exposure affects their reproductive health. Nevertheless, it could be modulated by suitable hormonal therapy. PMID:21787707

  7. Termination of Pregnancy with Cloprostenol and Dexamethasone in Intact or Ovariectomized Cows

    OpenAIRE

    Johnson, W H; Manns, J. G.; Adams, W. M.; Mapletoft, R. J.

    1981-01-01

    Termination of pregnancy in cows was investigated using sham-operated (SH) or ovariectomized (OV) cows treated with either a saline vehicle (V), cloprostenol (PG), dexamethasone (DEX) or dexamethasone and cloprostenol (DEX+PG). Surgery was done at 210 days of pregnancy and treatment was administered 72 hours later.

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

    International Nuclear Information System (INIS)

    This paper reviews 19 studies conducted by the Lovelace ITRI on the toxicity of inhaled radionuclides in beagle dogs. These studies provide information to estimate potential health effects in accidentally exposed people. Specific radionuclides (90Sr, 90Y, 91Y, 137Cs, 144Ce, 238Pu, and 239Pu), chemical forms, and particle sizes were selected for study because they are abundant in nuclear operations and deliver a wide range of radiation dose patterns. Depending upon the aerosol, one or more of the following organs or tissues received the significant irradiation: lung, nasal cavity, lung-associated lymph nodes, whole body, liver, or skeleton, with the radiation dose delivered over durations of time ranging from a few days to several years. In eight studies monodisperse particles of either 238PuO2 or 239PuO2 were used to evaluate the influence of particle number and total dose on lung cancer induction. Most studies involved single, brief exposures of young adult dogs, but two studies used immature dogs, two used aged dogs, and two studies involved repeated brief exposures. For each aerosol two types of studies were conducted. One was used to evaluate the time course of retention of radioactivity in various tissues of the body for calculating radiation doses. The second was used to determine health effects in animals exposed to achieve different initial lung burdens and observed for the remainder of their life spans. Initial lung burdens were selected to produce early morbidity and mortality at the highest levels and an excess of late-occurring diseases such as cancer at the lowest levels. The latter dogs have had an excess incidence of cancer, especially of the lung, lung-associated lymph nodes, nasal cavity, skeleton, and liver. Relationships between radiation doses to various tissues and effects have been evaluated for individual studies

  9. Effects of chitosan oligosaccharides on the femur trabecular structure in ovariectomized rats

    International Nuclear Information System (INIS)

    Drugs used to treat osteoporosis are taken long-term and ideally have no adverse effects. Recent interest has focused on chitosan oligosaccharides as a bone-inducing substance for use as bone graft material. The present study was designed to investigate the effects of chitosan oligosaccharides on the femur trabecular structure in ovariectomized rats by three-dimensional imaging analysis using micro-computed tomography (CT). Female 12-week-old Wistar rats were divided into three groups, which underwent ovariectomy (two groups) or sham surgery (one group). After 12 weeks, rats of one of the ovariectomized groups began treatment with chitosan oligosaccharides (500 mg/kg bodyweight) three times per week for 8 weeks. Then, the femurs of all rats were resected for bone analysis by micro-CT, and three-dimensional images of the femur were reconstructed from the axial CT images to evaluate the following parameters: bone volume tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.sp), trabecular bone pattern factor (TBPf), structure model index (SMI), number of nodes per unit tissue volume, number of termini per unit tissue volume, and the total strut length per unit tissue volume. The BV/TV, Tb.Th, and Tb.N were significantly higher in the ovariectomized and treated (OVX+C) group versus the ovariectomized, untreated (OVX) group. Tb.Sp, TBPf, and SMI were significantly lower in the OVX+C group versus the OVX group. Our findings demonstrate that chitosan oligosaccharides prevent decreases in bone volume, trabecular number, trabecular thickness, and trabecular connectivity in the femurs of ovariectomized rats. (author)

  10. RNA-sequencing data analysis of uterus in ovariectomized rats fed with soy protein isolate, 17β-estradiol and casein.

    Science.gov (United States)

    Ronis, Martin J; Gomez-Acevedo, Horacio; Blackburn, Michael L; Cleves, Mario A; Singhal, Rohit; Badger, Thomas M

    2016-06-01

    This data file describes the bioinformatics analysis of uterine RNA-seq data comparing genome wide effects of feeding soy protein isolate compared to casein to ovariectomized female rats age 64 days relative to treatment of casein fed rats with 5 μg/kg/d estradiol and relative to rats treated with estradiol and also fed soy protein isolate. Complete raw data files were deposited in the gene Expression Omnibus (GEO) at NCBI (http:/www.ncbi.nlm.nih.gov.geo/) under the GEO accession number GEO: GSE69819. Data presented here incudes a summary of the differential expression analysis with top 30 genes up- and down-regulated by soy protein isolate (SPI), estradiol (E2) and SPI+E2. Additional functional annotation analysis of KEGG pathways is also presented for each treatment, together with networks of interaction between those pathways. Further interpretation and discussion of this data can be found in the article "Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats" Ronis et al. (2016) [1]. PMID:27182546

  11. Angiopoietin-1 mRNA expression in estradiol-treated ovariectomized rats with focal cerebral ischemia after reperfusion

    Institute of Scientific and Technical Information of China (English)

    Ling Tang; Jun Zuo; Yonghong Wang; Yuanda Zhou; Haixia He

    2008-01-01

    BACKGROUND: Epidemiologic studies have indicated that the incidence of stroke in premenopausal females is lower than in males at the same age, but it significantly rises in postmenopausal females. Estrogen is used clinically to alleviate injury caused by cerebral ischemia. It has been hypothesized that the neuroprotective role of estrogen relates to angiopoietin (Angpt), which plays an important role in vascularization, vascular remodeling and maturation.OBJECTIVE: To observe and validate the effect of estradiol on angiopoietin-1 (Angpt1) mRNA expression in ovariectomized rats with focal cerebral ischemia alter reperfusion, so as to explore the molecular mechanisms of estradiol-mediated protection from cerebral ischemic damage.DESIGN, TIME AND SETTING: Randomized, controlled, molecular biology, prospective animal study. The experiment was performed at the Central Laboratory of Chongqing Medical University from September to December 2005.MATERIALS: Fifty healthy female wild type (WT) rats aged 6 months and fifty female rats aged 6 months with knockout of the estrogen-alpha receptor gene (ERKO).METHODS: WT rats and ERKO rats were divided into estradiol and control groups (n = 25), and injected intramuscularly with estradiol benzoate (100 μg/kg per day) or corn oil (1 mL/kg per day) for 7 days, 30 days after bilateral ovariectomy. Rat models of cerebral ischemia/reperfusion were established with the middle cerebral artery occlusion method. After 30 minutes of middle cerebral artery occlusion, rats from the estradiol and control groups were injected intramuscularly with estradiol benzoate or corn oil at the above dose.MAIN OUTCOME MEASURES: We used radio-immunity analysis and laser-Doppler flowmetry to measure plasma estradiol levels and changes in cerebral blood flow. We used immunohistochemical staining of CD34 epitopes to measure changes in the capillary density in brain following cerebral ischemia/reperfusion, and quantitative RT-PCR analysis to assess m

  12. Life-span radiation effects studies in prenatally and postnatally exposed beagle dogs at Colorado State University

    International Nuclear Information System (INIS)

    The lifetime hazards associated with exposure to ionizing radiation during development are studied in 1680 beagle dogs given whole-body exposures to 60Co gamma radiation. Eight groups of 120 dogs each received 20-R or 100-R exposures at 8, 28, or 55 days postcoitus (dpc) or at 2 days postpartum (dpp). In addition, exposures of 100 R were given to 120 dogs at 70 dpp and to 240 dogs at 365 dpp. An additional 360 dogs were sham exposed. Smaller groups of dogs were used to identify organs and tissues of particular sensitivity to radiation injury during development and to evaluate mechanisms of radiation injury. The research is concerned primarily with evaluating the role of age at exposure as a factor influencing response to radiation injury. As of December 31, 1982, of the 1680 dogs, 1058 were dead. Survivors ranged from 9.9 to 15 years of age. Through 10 years of age, no differences in survival were evident in any exposure groups. A variety of clinical, pathophysiologic, and pathologic responses have been studied. Irradiation during development has been found to be associated with abnormalities of skeletal, dental, and central nervous system development. Irradiation during ocular development has induced dysplastic and atrophic retinal lesions. Perinatal irradiation of the kidney has resulted in dysplasia, and, in animals receiving higher doses, significant chronic renal disease. The thymus gland, particularly thymic epithelium, has been found to be highly radiosensitive during fetal development

  13. Preliminary considerations for an in-depth investigation of thyroid disease in the CRHL beagle colony

    International Nuclear Information System (INIS)

    This report describes preliminary results of evaluation of selected clinical laboratory data from hypothroid and euthyroid beagles as an initial step in an in-depth study of hypothyroidism in the CRHL colony. Both hyperchloesterolemia and a decreased hematocrit were present in dogs with clinically diagnosed or pathologically confirmed thyroid disease

  14. Late effects of inhaled 238PuO2 in beagles

    International Nuclear Information System (INIS)

    Osteosarcomas were the primary cause of death in beagle dogs 4 to 8 years after inhalation of 238PuO2. The plutonium body burden at death ranged from 0.4 to 2.6 μCi with 32 to 55 percent of the plutonium in the skeleton. Pulmonary neoplasia was observed in three of the bone-tumor-bearing dogs

  15. Effects of inhaled 239PuO2 on the primary immune response of beagle dogs

    International Nuclear Information System (INIS)

    Effects of inhaled 239PuO2 on the humoral component of the immune system were measured by intravenous immunizations of beagle dogs with keyhole limpet hemocyanin (KLH). With this T-cell-dependent antigen, a significant decrease in primary antibody response was observed in exposed versus unexposed dogs

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

    International Nuclear Information System (INIS)

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

  17. Reference Intervals, Intraindividual and Interindividual Variability, and Reference Change Values for Hematologic Variables in Laboratory Beagles

    OpenAIRE

    Bourgès-Abella, Nathalie H; Gury, Thierry D; Geffré, Anne; Concordet, Didier; Thibault-Duprey, Kevin C; Dauchy, Arnaud; Trumel, Catherine

    2015-01-01

    In research and development studies for human and veterinary medicine, relevant comparators for interpreting clinical pathology results are matched with concurrent control animals. However, reference intervals (RI) provide a comparator database and important aids for interpreting clinical pathology data, especially in laboratory beagle dogs. Furthermore, RI incorporate biologic variation, which includes analytical, intraindividual, and interindividual variation. No studies to date have establ...

  18. Disposition of 241AmO2 following inhalation by beagle dogs

    International Nuclear Information System (INIS)

    Translocation of 241Am from the lungs of beagles following inhalation of AmO2 was fairly rapid, roughly equal quantities being found in the liver and skeleton at all postexposure times to 810 days. Less than 16 percent of the initial body burden was excreted, more than two-thirds of this in the feces

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

    International Nuclear Information System (INIS)

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

  20. Toxicity of 144Ce inhaled in a relatively insoluble form by immature Beagle dogs. VII

    International Nuclear Information System (INIS)

    Immature Beagle dogs (approx. = 3 months of age at exposure) have been exposed by inhalation to a relatively insoluble form of 144Ce (in fused aluminosilicate particles) to compare the resulting patterns of metabolism, dosimetry and biological effects with those seen in dogs exposed at 12 and 14 months of age and at 8 to 10.5 years of age. Five blocks of longevity animals, each consisting of 10 exposed dogs and one control, are currently being studied. The initial lung burdens of the 144Ce-exposed dogs range from 0.004 to 140 μCi 144Ce/kg body weight. Three dogs with initial lung burdens of 73 to 120 μCi 144Ce/kg body weight died at 66 to 121 days after exposure with pulmonary injury and congestive heart failure. One dog with an initial lung burden of 140 μCi 144Ce/kg body weight died at 91 days after exposure with severe radiation pneumonitis and minimal pulmonary fibrosis and another dog whose initial lung burden was 70 μCi 144Ce/kg body weight died at 511 days after exposure with pulmonary injury that was mainly fibrotic in nature. Four dogs with initial lung burdens of 52 to 79 μCi/kg body weight had primary pulmonary hemangiosarcomas and died between 618 and 738 days, with cumulative average absorbed beta doses to lung of 23,000 to 31,000 rads. Two of these dogs, 1027S and 1024D, died within the past year. One dog with an initial lung burden of 28 μCi/kg body weight was euthanized at 1227 days after exposure with an hemangiosarcoma of the mediastinum. Within the past year, Dog 627S, with an initial lung burden of 48 μCi/kg body weight, died 1732 days after exposure with hemangiosarcoma primary in the liver or spleen. A dog with an initial lung burden of 12 μCi/kg body weight died from epilepsy at 1520 days after exposure. Serial observations are continuing on the surviving 37 exposed and five control dogs

  1. Acupuncture and Auricular Acupressure in Relieving Menopausal Hot Flashes of Bilaterally Ovariectomized Chinese Women: A Randomized Controlled Trial

    OpenAIRE

    Jue Zhou; Fan Qu; Xisheng Sang; Xiaotong Wang; Rui Nan

    2011-01-01

    The objective of this study is to explore the effects of acupuncture and auricular acupressure in relieving menopausal hot flashes of bilaterally ovariectomized Chinese women. Between May 2006 and March 2008, 46 bilaterally ovariectomized Chinese women were randomized into an acupuncture and auricular acupressure group (n = 21) and a hormone replacement therapy (HRT) group (Tibolone, n = 25). Each patient was given a standard daily log and was required to record the frequency and severity of ...

  2. The cerebrovascular structure and brain tissue volume: a comparative study between beagle dogs and mongrel dogs

    International Nuclear Information System (INIS)

    Objective: To compare the differences of cerebrovascular structure and brain tissue volume between beagle and mongrel dogs by using angiography and MR scanning. Methods: A total of 40 dogs, including 20 beagle dogs (beagle group) and 20 mongrel dogs (mongrel group), were enrolled in this study. Under general anesthesia, all dogs were examined with cerebral angiography and MR scanning. The cerebrovascular structure was evaluated with angiography via selective catheterization of aortic arch, bilateral external cerebral arteries (ECA), maxillary arteries, internal cerebral arteries (ICA) and vertebral arteries separately. The diameters of the ICA, middle cerebral artery (MCA), rostral cerebral artery (RCA), the anastomosis channel ICA and ECA, and basilar artery (BA) were measured at the similar point of each dog. Meanwhile the volumes of the brain tissue were calculated in coronal T2 view of MR scanning. The statistical analysis was performed among the weight of dogs, the diameter of arteries and the volume of brain tissue. The differences in the diameters and brain tissue volume were compared between the two groups. Results: No obvious variations in the cerebrovascular structure and brain tissue volume were found in these dogs. One mongrel dog was excluded from this study because of the severe stenosis of ICA. The mean weight of 20 beagle dogs and 19 mongrel dogs was (12.81±1.29) kg and (12.85±1.12) kg, respectively. The diameters of the ICA, MCA, RCA, the anastomosis channel between ICA and ECA and BA in beagle group were (1.26±0.07) mm, (0.90±0.05) mm, (0.58±0.07) mm, (0.55±0.07) mm and (0.95±0.06) mm, respectively. These parameters in mongrel group were (1.27±0.07) mm, (0.92±0.05) mm, (0.59±0.06) mm, (0.67±0.07) mm and (0.94±0.05) mm, respectively. The volume of brain in two groups was (76232.33±5018.51) mm3 and (71863.96±4626.87) mm3, respectively. There were no obvious correlation among the body weight, the cerebrovascular diameters and brain

  3. Ethnoarchaeology of hunter‐fisher‐gatherers societies in the Beagle Channel (Tierra del Fuego): ethnographical sources and social simulation

    OpenAIRE

    Briz i Godino, Ivan; Izquierdo Millán, Luis Rodrigo; Álvarez, Myrian; Caro, Jorge; Galán Ordax, José Manuel; Santos Martín, José Ignacio; Zurro, Débora

    2014-01-01

    Research from the Beagle Channel (Tierra del Fuego) offers a rich ethnographic and historical record produced by the late inclusion of Tierra del Fuego in the industrial world (the Beagle Channel was discovered by R. Fitz- Roy in 1830). This is an interesting frame for using new techniques (social simulation by Agent Based Modelling (ABM)) to generate new hypotheses in archaeology. In this case, the hypothesis is focused on the role of social cooperation in Yámana hunter-fisher-ga...

  4. Inhibitory effects of morinda officinalis extract on bone loss in ovariectomized rats.

    Science.gov (United States)

    Li, Nan; Qin, Lu-Ping; Han, Ting; Wu, Yan-Bin; Zhang, Qiao-Yan; Zhang, Hong

    2009-01-01

    The present study was undertaken to investigate the protective effects of ethanol extract from the root of Morinda Officinalis (RMO) on ovariectomy-induced bone loss. Administration of RMO extract increased trabecular bone mineral content and bone mineral density of tibia, improved the levels of phosphorus (P), calcium (Ca) and OPG, decreased the levels of DPD/Cr, TRAP, ACTH and corticosterone, but did not reverse the levels of ALP, TNF-alpha and IL-6 in serum of ovariectomized rats. These findings demonstrated that RMO extract reduced bone loss in ovariectomized rats, probably via the inhibition of bone resorption, but was not involved with bone formation. Anthraquinones and polysaccharides from Morinda officinals could be responsible for their antiosteoporotic activity, and the action mechanism of these constituents needs to be further studied. Therefore, RMO has the potential to develop a clinically useful antiosteoporotic agent. PMID:19513005

  5. Inhibitory Effects of Morinda officinalis Extract on Bone Loss in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Qiao-Yan Zhang

    2009-06-01

    Full Text Available The present study was undertaken to investigate the protective effects of ethanol extract from the root of Morinda Officinalis (RMO on ovariectomy-induced bone loss. Administration of RMO extract increased trabecular bone mineral content and bone mineral density of tibia, improved the levels of phosphorus (P, calcium (Ca and OPG, decreased the levels of DPD/Cr, TRAP, ACTH and corticosterone, but did not reverse the levels of ALP, TNF-α and IL-6 in serum of ovariectomized rats. These findings demonstrated that RMO extract reduced bone loss in ovariectomized rats, probably via the inhibition of bone resorption, but was not involved with bone formation. Anthraquinones and polysaccharides from Morinda officinals could be responsible for their antiosteoporotic activity, and the action mechanism of these constituents needs to be further studied. Therefore, RMO has the potential to develop a clinically useful antiosteoporotic agent.

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

    Directory of Open Access Journals (Sweden)

    Lim Chung-San

    2010-09-01

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

  7. Therapeutic Advantages of Treatment of High-Dose Curcumin in the Ovariectomized Rat

    OpenAIRE

    Cho, Dae-Chul; Jung, Hyun-Sik; Kim, Kyoung-Tae; Jeon, Younghoon; Sung, Joo-Kyung; Hwang, Jeong-Hyun

    2013-01-01

    Objective Although curcumin has a protective effect on bone remodeling, appropriate therapeutic concentrations of curcumin are not well known as therapeutic drugs for osteoporosis. The purpose of this study was to compare the bone sparing effect of treatment of low-dose and high-dose curcumin after ovariectomy in rats. Methods Forty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed...

  8. Pycnogenol® treatment inhibits bone mineral density loss and trabecular deterioration in ovariectomized rats

    OpenAIRE

    Huang, Gangyong; Wu, Jianguo; Wang, Siqun; Wei, Yibing; Chen, FeiYan; Chen, Jie; Shi, JingSheng; Xia, Jun

    2015-01-01

    Context: Pycnogenol® extracted from French maritime pine bark (Pinus pinaster Ait. subsp. atlantica) is functional for its antioxidant activity. Objective: To investigate the effects of Pycnogenol® on bone mineral density (BMD), trabecular microarchitecture and bone metabolism in ovariectomized (OVX) rats. Materials and methods: Thirty Sprague-Dawley rats were randomized into 3 groups: SHAM group (sham-operated rats), OVX group (OVX rats), and treatment group (OVX rats supplemented with 40 mg...

  9. The effects of Cordyceps sinensis phytoestrogen on estrogen deficiency-induced osteoporosis in Ovariectomized rats

    OpenAIRE

    Zhang, Da-Wei; Wang, Zhen-lin; Qi, Wei; Zhao, Guang-Yue

    2014-01-01

    Background Isoflavones are naturally occurring plant chemicals belonging to the “phytoestrogen” class. The aim of the present study was to examine the effects of isoflavones obtained from Cordyceps sinensis (CSIF) on development of estrogen deficiency-induced osteoporosis in ovariectomized rats. Methods After the rats were treated orally with CSIF, serum alkaline phosphatase (ALP), tartarate resistant acid phosphatase (TRAP), serum osteocalcin (OC), homocysteine (HCY), C-terminal crosslinked ...

  10. Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice

    OpenAIRE

    Jackson, Kathryn C.; Wohlers, Lindsay M.; Richard M. Lovering; Schuh, Rosemary A.; Maher, Amy C.; Bonen, Arend; Koves, Timothy R.; Ilkayeva, Olga; Thomson, David M.; Muoio, Deborah M.; Spangenburg, Espen E.

    2012-01-01

    Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism coupled with altered mitochondrial function may also develop. The objective of this study was to use an integrative metabolic approach to identify potential areas of dysfunction that develop in skeletal muscle from ovariectomized (OVX) femal...

  11. Locally Administrated Perindopril Improves Healing in an Ovariectomized Rat Tibial Osteotomy Model

    OpenAIRE

    Zhao, Xiong; Wu, Zi-Xiang; Zhang, Yang; Gao, Ming-xuan; Yan, Ya-bo; Cao, Peng-Chong; Zang, Yuan; Lei, Wei

    2012-01-01

    Angiotensin-converting enzyme inhibitors are widely prescribed to regulate blood pressure. High doses of orally administered perindopril have previously been shown to improve fracture healing in a mouse femur fracture model. In this study, perindopril was administered directly to the fracture area with the goal of stimulating fracture repair. Three months after being ovariectomized (OVX), tibial fractures were produced in Sprague–Dawley rats and subsequently stabilized with intramedullary wir...

  12. Fermented soybeans by Rhizopus oligosporus reduce femoral bone loss in ovariectomized rats

    OpenAIRE

    Yoo, Hyun-Wook; Chang, Moon-Jeong; Kim, Sun-Hee

    2014-01-01

    BACKGROUND/OBJECTIVES Soy isoflavones are structurally similar to estrogen and bind to estrogen receptors, suggesting that they exhibit estrogenic activities; therefore, they are referred to as phytoestrogens. Fermentation may affect the bioavailability of isoflavones altering soy isoflavone glycosides in the form of aglycones. Thus, this study investigated the effects of fermented soybeans by Rhizopus oligosporus on bone metabolism in both young rats as a pilot test and in ovariectomized (ov...

  13. The Effects of Combined Treatment with Naringin and Treadmill Exercise on Osteoporosis in Ovariectomized Rats

    OpenAIRE

    Sun, Xiaolei; Li, Fengbo; Ma, Xinlong; MA, JIANXIONG; Zhao, Bin; Zhang, Yang; Li, Yanjun; Lv, Jianwei; Xinmin MENG

    2015-01-01

    Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increased the risk of fracture. Previous studies have demonstrated the effect of naringin (NG) or treadmill exercise (EX) on osteoporosis, however, reports about effects of NG plus EX on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with naringin and treadmill exercise on osteoporosis in ovariectomized (OVX) rats. Three m...

  14. Induced lactation with a dopamine antagonist in mares: different responses between ovariectomized and intact mares.

    Science.gov (United States)

    Guillaume, D; Chavatte-Palmer, P; Combarnous, Y; Duchamp, G; Martinat, N; Nagy, P; Daels, P F

    2003-10-01

    The aim of this study was to compare the effects of treatment with repeated injections of sulpiride (a dopamine D2 antagonist) on prolactin secretion and induced lactation in ovariectomized and intact adult mares and to verify if this induction was possible at the beginning and at the end of the birth season. Two experiments were carried out in September [experiment (expt) 1], and in March (expt 2), in France (48 degrees N). In expt 1, three groups of five mares were tested: intact-control, intact-treated and ovariectomized-treated mares. In expt 2, mares previously subjected to artificial photoperiod were assigned in two groups: four intact-control and five intact-treated mares. The cyclicity of intact mares was previously synchronized with PGF2alpha injections, then all the mares were in the follicular phase at the beginning of treatment. Sulpiride was intramuscularly injected (0.5 mg/kg of BW), twice a day. Mares were milked at 7:30, 11:45, 16:00 and 20:15 hours. Blood samples were collected every day during the treatment for progesterone, total oestrogen and prolactin assays. In the two experiments, only treated intact mares produced milk, with a large inter-animal variability. Prolactin increase after sulpiride treatment was not so great in the ovariectomized-treated mares as in the intact-treated mares. The total correlations between prolactin, progesterone, oestrogen plasma concentrations and daily milk production were significant (0.57, 0.25, 0.17 respectively). This induction of lactation can be performed during the entire birth season in intact mares, but not in ovariectomized mares, indicating that steroids are necessary for this induction in mares treated by dopamine D2 antagonist. PMID:12950692

  15. Inhibitory Effects of Morinda officinalis Extract on Bone Loss in Ovariectomized Rats

    OpenAIRE

    Qiao-Yan Zhang; Hong Zhang; Yan-Bin Wu; Ting Han; Lu-Ping Qin; Nan Li

    2009-01-01

    The present study was undertaken to investigate the protective effects of ethanol extract from the root of Morinda Officinalis (RMO) on ovariectomy-induced bone loss. Administration of RMO extract increased trabecular bone mineral content and bone mineral density of tibia, improved the levels of phosphorus (P), calcium (Ca) and OPG, decreased the levels of DPD/Cr, TRAP, ACTH and corticosterone, but did not reverse the levels of ALP, TNF-α and IL-6 in serum of ovariectomized rats. These findin...

  16. Ovarian steroids enhance object recognition in naturally cycling and ovariectomized, hormone-primed rats

    OpenAIRE

    Walf, Alicia A.; Rhodes, Madeline E.; Frye, Cheryl A.

    2006-01-01

    Learning and memory processes may be influenced by fluctuations in steroid hormones, such as estrogens and progestins. In this study, we have used an animal model to investigate the effects of endogenous fluctuations in ovarian steroids in intact female rats and effects of administration of ovarian steroids to ovariectomized rats for non-spatial, working memory using the object recognition task. Performance in this task relies on cortical and hippocampal function. As such, serum, cortical, an...

  17. The Effect of Estrogen on the Restoration of Bone Mass and Bone Quality in Ovariectomized Rats

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To evaluate the effect of estrogen on its ability to restore the bone mass and bone quality in ovariectomized rats by examining the changes of bone morphology and histomorphometry, 3month-old rats were divided randomly into 4 groups: normal control, ovariectomized (OVX), shamoperated (Sham-O) and OVX plus estrogen (OVX+E2). Treatment initiated from the day 8 weeks after operation and continued for 12 weeks. Bone morphology and histomorphometry were examined afterwards. Results showed that comparing to control group, the trabecular bone in OVX appeared thinner and reduced in the amount. The connectivity between trabecula was decreased and the structure disordered. The free-end of trabecula was increased. The cavity of bone marrow enlarged. After treatment with estrogen, above changes improved remarkably by different degree, although did not reach the normal face. The bone histomorphometry results damonstrated that estrogen treatment increased bone mass and the amount of trabecula by 129% and 132% respectively (P<0. 05). The activity of bone resorption decreased significantly and the rate of bone formation increased to 203 %. These results suggest that treatment of ovariectomized rats with estrogen can not only increase bone mass, also improve the bone structure and enhance the property of bone mechanics.

  18. Effect of Different Doses of Soy Isoflavones on Spatial Learning and Memory in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Ahmad Zand Moghaddam

    2011-08-01

    Full Text Available Introduction: Several studies indicate that estrogen use increase performance on some tests of cognition especially in postmenopausal women. These steroids have many side effects, thus, other estrogenic agents with fewer side effects are needed to develop alternative treatment strategies. The main objection of this study was to evaluate the effects of different doses of dietary soy meals (with or without isoflavone on spatial learning and memory in ovariectomized (OVX rats. Methods: Female Wistar rats with the exception of intact group were ovariectomized at the first line of study. Subjects were divided into six groups. The control group rats (c were gonadally intact, while the others were OVX. OVX groups received normal diet (0, treated with 10 gr soy (10, 20 gr soy (20, 10 gr isoflavone free soy (-10 or 20 gr isoflavone free soy (-20 in daily diet for four weeks. The spatial learning and memory were tested using Morris water maze. Rats were trained in water maze to find a hidden escape Platform. Rats received 6 blocks that each block consisted of 3 trials. Following acquisition trials, one probe trial were conducted in which the platform was removed. Results: Soy meal diet (with or without isoflavone in ovariectomized rats caused improvement of performance across 18 trials of Acquisition. Discussion: Our results suggest that soy consumption apart from containing isoflavone or not is a potential alternative to estrogen in the improvement of cognition.

  19. Toxicity of inhaled 144Ce fused clay particles in beagle dogs. VII

    International Nuclear Information System (INIS)

    The metabolism, dosimetry, and effects of inhaled 144Ce in fused clay particles are being investigated in the Beagle dog to aid in assessing the biological consequences of release of 144Ce in a relatively insoluble form such as might occur in certain types of nuclear accidents. The toxicity of inhaled 144Ce fused clay is also of general interest since it is representative of intermediate-lived beta-emitting radionuclides. Two major studies with young adult dogs (12 to 14 months of age at exposure) are involved: (1) a metabolism and dosimetry study in which 24 dogs were serially sacrificed over an extended period of time, and (2) a longevity study with 2 series of dogs; Series I with 15 dogs exposed to aerosols of 144Ce in fused clay particles to yield initial lung burdens of 11 to 210 μCi/kg body weight and 3 control dogs exposed to nonradioactive fused clay particles and Series II with 96 dogs exposed to aerosols of 144Ce in fused clay particles to yield initial lung burdens of 0.0024 to 66 μCi/kg body weight and 12 control dogs exposed to nonradioactive fused clay particles. Twenty-eight dogs died or were euthanized at 143 to 2396 days after inhalation of 144Ce. The prominent findings were radiation pneumonitis in 17 dogs that died or were euthanized at early time periods and neoplastic disease in 10 of the 11 dogs that died or were euthanized at 750 days or later; 5 with hemangiosarcoma of the lung, 1 with both a hemangiosarcoma and a fibrosarcoma of the lung, 1 with both a bronchiolo-alveolar carcinoma and a hemangiosarcoma of lung, 1 with a hemangiosarcoma of lung, bronchiolo-alveolar carcinoma, and a bronchiogenic adenocarcinoma, and 1 each with a hemangiosarcoma of the mediastinum and of the spleen. The cumulative radiation dose to the lung at time of death has ranged from 22,000 to 140,000 rads. Serial observations are continuing on the 83 survivors and 15 controls. (U.S.)

  20. Digenea in notothenioid fish in the Beagle Channel (Magellanic sub-region, sub-Antarctica).

    Science.gov (United States)

    Jeżewski, Witold; Zdzitowiecki, Krzysztof; Laskowski, Zdzisław

    2014-03-01

    Fish of five species of Notothenioidei (104 specimens), Cottoperca trigloides, Patagonotothen brevicauda, P. longipes, P. tessellata and Champsocephalus esox, caught in the Beagle Channel (Magellanic sub-region, sub-Antarctica) were infected with Digenea of nine species (1130 specimens). Faunistic data on the occurrence of all nine parasites are provided. The most abundant digenean species was Macvicaria magellanica found in the intestine of three host species of the genus Patagonotothen. The second most abundant digenean species was Elytrophalloides oatesi found in the stomach of four host species, with exception of P. brevicauda. Three digenean species: Stenakron kerguelense, Whitegonimus ozoufae and Genolinea bowersi, were more abundant in fish caught at the harbor of Ushuaia (depth 7-9 m), remaining six species: M. magellanica, Neolepidapedoides subantarcticus, Postmonorchis variabilis, Derogenes varicus, E. oatesi and Lecithaster macrocotyle, in the eastern mouth of the Beagle Channel (depth 30 m). PMID:24570049

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

    Science.gov (United States)

    Amin, O; Ferrer, L; Marcovecchio, J

    1996-07-01

    For the first time the concentration of trace metals (Fe, Pb, Cu, Zn, Cd and total Hg) of sediments from the coastal zone of the Beagle Channel (Tierra del Fuego, in Southern Argentina) were measured. Atomic absorption spectrophotometry was utilized in order to determine the metal contents. The level of metals as observed in the sediments was recognized as the natural background, even though the use of normalization of lead, copper, and zinc to iron allowed the identification of the main sources of metal pollution for this environment. In order to develop future environmental monitoring programmes for the area of Ushuaia city and the Beagle Channel, the present results need to be considered. PMID:24193396

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    Beagle dogs given a single inhalation exposure to 239Pu(NO3)4, and observed for life-span dose-effect relationship, died from radiation pneumonitis (4 of 5) at the highest dosage level, 14 to 25 mo postexposure. There were also indications in these dogs of radiation osteosis, characterized by peritrabecular fibrosis. Leukopenia, lymphopenia, neutropenia and decreased numbers of circulating monocytes and eosinophils occurred at the two highest dosage levels, as previously reported

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

    OpenAIRE

    Kim, Dong-Seok; Kim, Dae-Gon; Park, Chan-Jin; Cho, Lee-Ra

    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 incl...

  5. Tissue Doppler and strain imaging of left ventricle in Beagle dogs with iatrogenic hypercortisolism

    OpenAIRE

    OUI, Heejin; JEON, Sunghoon; LEE, Gahyun; Park, Seungjo; Cho, Kyoung-Oh; Choi, Jihye

    2015-01-01

    Changes in radial and longitudinal left ventricular (LV) function were investigated in beagles with iatrogenic hypercortisolism. A total of 11 normal dogs were used, and 2 mg/kg prednisone was administered per oral q12 h for 28 days to 7 out of 11 dogs to induce iatrogenic hypercortisolism. Body weight, blood pressure, conventional echocardiography and tissue Doppler imaging (TDI) of normal and iatrogenic hypercortisolism groups were conducted. The myocardial wall velocity of the LV was measu...

  6. Late effects of inhaled 238PuO2 in beagles

    International Nuclear Information System (INIS)

    Bone tumors were the primary cause of death in beagle dogs 4 to 6 years after inhalation of 238PuO2. The plutonium body burden at death ranged from 0.5 to 2.6 μCi with 32 to 55 percent of the plutonium in the skeleton. Pulmonary neoplasia was observed in three of the bone-tumor-bearing dogs. (U.S.)

  7. Identification of Matrix Metalloproteinase-2 and -9 Activities within Intestinal Mucosa of Clinically Healthy Beagle Dogs

    OpenAIRE

    Hanifeh, Mohsen; Rajamäki, Minna M.; MÄKITALO, Laura; Syrjä, Pernilla; Sankari, Satu; Kilpinen, Susanne; Spillmann, Thomas

    2014-01-01

    ABSTRACT Matrix metalloproteinases (MMPs) 2 and 9 are zinc-dependent endopeptidases that contribute to the control of breakdown and reconstitution of extracellular matrix under both normal and pathological conditions. The main objective of this study was to identify the presence of MMP-2 and -9 in the mucosa of the small and large intestines of clinically healthy beagle dogs using gelatin zymography technique. Intestinal mucosa samples from four different parts of the intestine (duodenum, jej...

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

    Directory of Open Access Journals (Sweden)

    Jie Zhao

    2015-11-01

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

  9. Survey of blood pressure in 226Ra- and 90Sr-treated beagles

    International Nuclear Information System (INIS)

    Multiple blood pressure measurements on a total of 407 beagles with a non-invasive method showed the greatest frequency of mean pressures to be in the normal 101-120 mm Hg range. Another major group of dogs were hypertensive, with mean pressures of 120-140 mm Hg. Future correlation of canine blood pressures with diseases should prove useful in both veterinary and human medical research

  10. Radionuclide distribution dynamics in skeletons of beagles fed 90Sr: Correlation with injected 226Ra and 239Pu

    International Nuclear Information System (INIS)

    Data for the bone-by-bone redistribution of 90Sr in the beagle skeleton are reported for a period of 4000 d following a midgestation-to-540-d-exposure by ingestion. The partitioned clearance model (PCM) that was originally developed to describe bone-by-bone radionuclide redistribution of 226Ra after eight semimonthly injections at ages 435-535 d has been fitted to the 90Sr data. The parameter estimates for the PCM that describe the distribution and clearance of 226Ra after deposition on surfaces following injection and analogous parameter estimates for 90Sr after uniform deposition in the skeleton as a function of Ca mass are given. Fractional compact bone masses per bone group (mi,COM) are also predicted by the model and compared to measured values; a high degree of correlation (r = 0.84) is found. Bone groups for which the agreement between the model and experimental values of mi,COM was poor had tissue-to-calcium weight ratios about 1.5 times those for bones that agreed well. Metabolically defined surface in PCM is initial activity fraction per Ca fraction in a given skeletal component for intravenously injected alkaline earth (Sae) radionuclides; comparisons are made to similarly defined surface (Sact) values from 239Pu injection studies. The patterns of Sae and Sact distribution throughout the skeleton are similar

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

    Science.gov (United States)

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

    2016-06-01

    A pharmacokinetic comparison and conformational stability study of S-oxiracetam (S-ORT) and R-oxiracetam (R-ORT) in beagle dogs was used to investigate the possible mechanism of different effects of two oxiracetam enantiomers through a random crossover design. After drug administration to beagle dogs, blood samples were collected at different time points for pharmacokinetic analysis using the UPLC-ESI-MS/MS method. Parts of plasma samples were used for conformation transformation studies using a normal phase high performance liquid chromatographic (NP HPLC) method. The study showed that oxiracetam enantiomers maintained their original conformation when administered orally to beagle dogs. Concentrations of S-ORT were significantly higher than R-ORT 1.5 and 2 h after administration; the AUC0-∞ of S-ORT after oral administration tended to be higher than that of R-ORT, which showed that the different effects between S-ORT and R-ORT may be partly associated with their distinctive absorption at least. PMID:27279070

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

    Science.gov (United States)

    Brinkman, Paul D

    2010-01-01

    The prevailing view among historians of science holds that Charles Darwin became a convinced transmutationist only in the early spring of 1837, after his Beagle collections had been examined by expert British naturalists. With respect to the fossil vertebrate evidence, some historians believe that Darwin was incapable of seeing or understanding the transmutationist implications of his specimens without the help of Richard Owen. There is ample evidence, however, that he clearly recognized the similarities between several of the fossil vertebrates he collected and some of the extant fauna of South America before he returned to Britain. These comparisons, recorded in his correspondence, his diary and his notebooks during the voyage, were instances of a phenomenon that he later called the "law of the succession of types." Moreover, on the Beagle, he was following a geological research agenda outlined in the second volume of Charles Lyell's Principles of Geology, which implies that paleontological data alone could provide an insight into the laws which govern the appearance of new species. Since Darwin claims in On the Origin of Species that fossil vertebrate succession was one of the key lines of evidence that led him to question the fixity of species, it seems certain that he was seriously contemplating transmutation during the Beagle voyage. If so, historians of science need to reconsider both the role of Britain's expert naturalists and the importance of the fossil vertebrate evidence in the development of Darwin's ideas on transmutation. PMID:20665232

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2012-05-01

    With the aim to evaluate the mollusk Nacella (P)magellanica as biomonitor of elemental pollution in seawater of the Beagle Channel, more than one hundred individuals of the gastropod were sampled, separated in viscera and muscle, and then examined with respect to the accumulation of Cd, Cr, Cu, Ni, Pb and Zn. Collection was performed in seven strategic locations along 170 km of the coastal area of the Beagle Channel (Tierra del Fuego, Argentina) in two campaigns during 2005 and 2007. Samples of surrounding seawater in the different sites were obtained and tested for the same metals as well. The accumulation capacity of Nacella (P)magellanica and thus its aptitude as biomonitor, was evaluated through the calculus of the preconcentration factors of the metals assayed. A discussion involving the comparison with other mollusks previously tested will be given. Several statistical approaches able to analyze data with environmental purposes were applied. Non parametric univariate tests such as Kruskal-Wallis and Mann-Whitney were carried out to assess the changes of the metal concentrations with time (2005 and 2007) in each location. Multivariate methods (linear discriminant analysis on PCA factors) were also applied to obtain a more reliable site classification. Johnson's probabilistic method was carried out for comparison between different geographical areas. The possibility of employing these results as heavy metals' background levels of seawater from the Beagle Channel will be debated. PMID:22350107

  15. Analysis of acamprosate in beagle dog plasma by LC-MS-MS.

    Science.gov (United States)

    Rhee, Yun-Seok; Park, Jeong-Hwa; Park, Seok; Park, Chun-Woong; Ha, Jeong-Myung; Jeong, Ki-Woo; Lee, Dong-Soo; Park, Eun-Seok

    2008-08-01

    A rapid, sensitive, and specific analytical method was developed and validated to quantify acamprosate calcium in beagle dog plasma. The method employs a single plasma protein precipitation, and the analytes are separated by chromatography on an Acquity UPLC HSS T3 column and analyzed by mass spectrometry in the multiple reaction monitoring (MRM) mode. The method has a chromatographic run time of 1.25 min and a linear calibration curve over the range 200-10000 ng/mL (r(2)>0.9994). The intra-day and inter-day accuracy and precision were within 10.0% for the analyte. Acamprosate was stable during all sample storage, preparation, and analytical periods. This method was employed in a pharmacokinetic study of an acamprosate 333 mg enteric-coated tablet in 8 male beagle dogs that received single 666 mg doses (333 mg x 2 tablets). The proposed method enables identification and quantification in pharmacokinetic studies of acamprosate in beagle dog plasma. PMID:18787794

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  17. Sodium Valproate Enhances the Urethane-Induced Lung Adenomas and Suppresses Malignization of Adenomas in Ovariectomized Female Mice

    Directory of Open Access Journals (Sweden)

    Donatas Stakisaitis

    2015-01-01

    Full Text Available In the present study, the possible effect of sodium valproate (NaVP on urethane-induced lung tumors in female mice has been evaluated. BALB/c mice (n=60; 4–6 weeks old, females were used in the following groups: (1 urethane-treated; (2 urethane-NaVP-treated; (3 only NaVP-treated; (4 control. In the same groups, ovariectomized female mice (n=60 were investigated. Urethane was given intraperitoneally, with a total dose of 50 mg/mouse. In NaVP-treated mice groups, 0.4% aqueous solution of NaVP was offered to mice ad libitum. The duration of the experiment was 6 months. The number of tumors per mouse in ovariectomized mice and in those treated with urethane and NaVP was significantly higher than in mice treated with urethane only (8.29±0.58 versus 6.0±0.63, p<0.02. No significant difference in the number of tumors per mouse was revealed while comparing the nonovariectomized urethane- and urethane-NaVP-treated groups (p=0.13. A significant decrease of adenocarcinoma number in ovariectomized mice treated with a urethane-NaVP as compared with ovariectomized mice treated with urethane only was found (p=0.031. NaVP together with low estrogen may have a protective effect on the malignization of adenomas in ovariectomized mice.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-12-31

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

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

    CERN Document Server

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

  3. Influence of dynorphin on estradiol- and cervical stimulation-induced prolactin surges in ovariectomized rats.

    Science.gov (United States)

    Stathopoulos, Andrea M; Helena, Cleyde V; Cristancho-Gordo, Ruth; Gonzalez-Iglesias, Arturo E; Bertram, Richard

    2016-08-01

    Prolactin is an anterior pituitary hormone necessary for fertility, pregnancy maintenance, lactation, and aspects of maternal behavior. In rodents, there is a surge of prolactin on the afternoon of proestrus, and a semi-circadian pattern of prolactin surges during early pregnancy, with a diurnal and nocturnal surge every day. Both of these patterns can be replicated in ovariectomized rats. A prior study demonstrated that central antagonism of κ-opioid receptors, the target of dynorphin, largely abolished the nocturnal prolactin surge in pregnant rats. We build on this to determine whether dynorphin, perhaps from the arcuate population that co-express kisspeptin, neurokinin B, and dynorphin (KNDy neurons), also contributes to the estradiol- or cervical stimulation-induced surges in ovariectomized rats. Ovariectomized rats were treated with either estradiol or cervical stimulation to induce prolactin surge(s). Blood samples were taken around the expected surge time to determine the effect of either acute κ-opioid receptor antagonism or previous chemical ablation of the KNDy population on prolactin levels. Dynorphin antagonism does significantly disrupt the nocturnal prolactin surge, but it does not contribute to the estradiol-induced surge. Chemical ablation of KNDy neurons had opposite effects; ablation of 40 % of the KNDy neurons had no impact on the nocturnal prolactin surge, while a somewhat larger ablation significantly reduced the size of the estradiol-induced surge. We conclude that dynorphin is likely a controlling factor for the nocturnal surge induced by cervical stimulation, and that other KNDy neuron products must play a role in the estradiol-induced surge. PMID:27038317

  4. Preventive Effects of Flaxseed and Sesame Oil on Bone Loss in Ovariectomized Rats

    OpenAIRE

    S. Boulbaroud; Mesfioui, A.; A. Arfaoui; A. Ouichou; A. El Hessni

    2008-01-01

    A study was designed to examine the effects of dietary flaxseed oil (FO) and sesame oil (SO) which are rich successively in n-3 and (n-9 and n-6) on biochemical parameters and histological status of bone. Sixty-four 90-day-old female wistar rats were randomly assigned to 6 groups: sham-operated rat (sham)+ control diets, ovariectomized rat (OVX))+ control diets, OVX+ 7% FO, OVX+ 7% SO, OVX+ 10% FO, OVX+ 10% SO. After 4 weeks of treatments, rats were euthanized; blood and tissues were c...

  5. Role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice.

    OpenAIRE

    Karol Kaminski; Andrzej Taranta; Piotr Mysliwiec; Agnieszka Nikolajuk; Robert Zbucki; Janusz Mysliwiec; Zofia Bondyra; Jacek Dadan; Maria Gorska; Maria M Winnicka

    2011-01-01

    Postmenopausal women frequently develop hypothyroidism. Estrogen depletion is accompanied by an increase of IL-6, accelerating bone turnover. The influence of hypothyroidism on bone metabolism in postmenopausal women is poorly understood. The aim of the study was an attempt to clarify the role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6JIL6-/-Kopf (IL...

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

    Directory of Open Access Journals (Sweden)

    Jorge Rabassa

    2009-12-01

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

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

    Science.gov (United States)

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

    2016-06-01

    We have recently shown that repellency of the tick Rhipicephalus sanguineus sensu lato by the tick resistant dog breed, the beagle, is mediated by volatile organic compounds (VOCs) 2-hexanone and benzaldehyde present in beagle odour. Ectoparasite location of animal hosts is affected by variation in these odour components and their ratios. The aim of this study was to quantify the release rate, and the ratio, of 2-hexanone and benzaldehyde from beagles. The odour of three beagles was collected, for four days, over one week (day 0, day 1, day 4 and day 7). The compounds were identified using coupled high-resolution gas chromatography-mass spectrometry (GC-MS), and authentic standards of compounds were used to generate external calibration curves for quantification. Both compounds were found in all dogs on all days. The amount of benzaldehyde was always higher than that of 2-hexanone and so their ratio varied from unity, on average (over time) being 3.128±0.365, 1.902±0.390, 1.670±0.671ngmL(-1) for beagle 1, 2 and 3, respectively. There was no significant (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. PMID:27085013

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

    International Nuclear Information System (INIS)

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

  9. Ovariectomized rats as a model of postmenopausal osteoarthritis

    DEFF Research Database (Denmark)

    Høegh-Andersen, Pernille; Tankó, László B; Andersen, Thomas L;

    2004-01-01

    , aged 5 and 7 months. In a third cohort, the effect of exogenous estrogen and a selective estrogen receptor modulator was analyzed. Knee joints were assessed by histological analysis of the articular cartilage after 9 weeks. Cartilage turnover was measured in urine by an immunoassay specific for.......008). Ovariectomy also significant increased CTX-I and CTX-II. Both the absolute levels of CTX-II and the relative changes from baseline seen at week 4 correlated strongly with the severity of cartilage surface erosion at termination (r = 0.74, P < 0.01). Both estrogen and the selective estrogen receptor modulator...... inhibited the ovariectomy-induced acceleration of cartilage and bone turnover and significantly suppressed cartilage degradation and erosion seen in vehicle-treated OVX rats. The study indicates that estrogen deficiency accelerates cartilage turnover and increases cartilage surface erosion. OVX rats provide...

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

    Directory of Open Access Journals (Sweden)

    Hye-Chul, Yoon

    2010-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Lanzoni Anna

    2011-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-15

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

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

    Science.gov (United States)

    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. PMID:23888699

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

    International Nuclear Information System (INIS)

    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

  15. BEAGLE: An Application Programming Interface and High-Performance Computing Library for Statistical Phylogenetics

    Science.gov (United States)

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

    2012-01-01

    Phylogenetic inference is fundamental to our understanding of most aspects of the origin and evolution of life, and in recent years, there has been a concentration of interest in statistical approaches such as Bayesian inference and maximum likelihood estimation. Yet, for large data sets and realistic or interesting models of evolution, these approaches remain computationally demanding. High-throughput sequencing can yield data for thousands of taxa, but scaling to such problems using serial computing often necessitates the use of nonstatistical or approximate approaches. The recent emergence of graphics processing units (GPUs) provides an opportunity to leverage their excellent floating-point computational performance to accelerate statistical phylogenetic inference. A specialized library for phylogenetic calculation would allow existing software packages to make more effective use of available computer hardware, including GPUs. Adoption of a common library would also make it easier for other emerging computing architectures, such as field programmable gate arrays, to be used in the future. We present BEAGLE, an application programming interface (API) and library for high-performance statistical phylogenetic inference. The API provides a uniform interface for performing phylogenetic likelihood calculations on a variety of compute hardware platforms. The library includes a set of efficient implementations and can currently exploit hardware including GPUs using NVIDIA CUDA, central processing units (CPUs) with Streaming SIMD Extensions and related processor supplementary instruction sets, and multicore CPUs via OpenMP. To demonstrate the advantages of a common API, we have incorporated the library into several popular phylogenetic software packages. The BEAGLE library is free open source software licensed under the Lesser GPL and available from http://beagle-lib.googlecode.com. An example client program is available as public domain software. PMID:21963610

  16. Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats.

    Science.gov (United States)

    Cui, Zhuang; Xu, Changpeng; Li, Xue; Song, Jinqi; Yu, Bin

    2015-05-01

    Osteoarthritis (OA) is a most commonly multifactorial degenerative joint disease along with the aging population, particularly in postmenopausal women. During the onset of OA, articular cartilage and subchondral bone act in concert as a functional unit. This present study is to investigate the effects of early or late treatment with recombinant lubricin on the onset of osteoarthritis (OA) in ovariectomized (OVX) rats. We found that both early and late recombinant lubricin treatments attenuated the onset of OA by positive feedback loop between articular cartilage and subchondral bone, although late treatment contributed to a lesser effect compared with early treatment. Specifically, treatment with recombinant lubricin protected articular cartilage from degeneration, demonstrated by lower proteoglycan loss, lower OARSI scores, less calcification cartilage zone and reduced immunostaining for collagen X (Col X) and matrix metalloproteinase (MMP-13) but increased the expression of lubricin, in comparison with vehicle-treated OVX rat group. Further, chondroprotective effects of lubricin normalized bone remodeling in subchondral bone underneath. It's suggested that treatment with recombinant lubricin inhibited the elevation of TRAP and Osterix positive cells in OVX rats and led to the normalization of subchondral bone microarchitectures with the suppression of subsidence of bone volume ratio (BV/TV) and trabecular thickness (Tb.Th) and the increase of trabecular separation (Tb.Sp) in vehicle-treated OVX rats. What's more, the normalization of subchondral bone in turn attenuated the articular cartilage erosion by inhibiting vascular invasion from subchondral bone to calcified cartilage zone, exemplified by inhibiting the elevation of CD31 positive cells in calcified cartilage and angiography in subchondral bone. Together, these results shed light that both early and late recombinant lubricin treatments attenuate the onset of OA by balancing the interplay between articular

  17. A comparison of Ca-DTPA and Zn-DTPA for chelating 241Am in beagles

    International Nuclear Information System (INIS)

    Results of a comparative study of the efficiency of removing body burdens of 241Am in beagles subjected to chelation therapy with either Ca-DTPA or Zn-DTPA are given. It is shown that on an equimolar basis the efficacy of the calcium salt is not greater than the zinc salt for treatments begun 2 weeks after radionuclide injection. The authors suggest that due to the much greater toxicity which has been shown for Ca-DTPA, it appears that Zn-DTPA should replace Ca-DTPA as treatment of choice in human cases. (U.K.)

  18. Liver tumors in Beagle dogs exposed by inhalation to 144CeCl3

    International Nuclear Information System (INIS)

    Primary malignant hepatic neoplasms developed in 9 of 55 Beagle dogs (16 percent) exposed to 144CeCl3 in CsCl aerosol (seven primary hepatic hemangiosarcomas, one hepatocellular carcinoma and one intrahepatic bile duct carcinoma). Cerium-144 was rapidly translocated from the lung to the liver and skeleton; the liver received the highest cumulative beta dose. The latent periods of hepatic hemangiosarcomas appeared to be dose-related; death from hepatic hemangiosarcoma occurred earlier in dogs which received higher beta doses

  19. Accuracy of sonographic diagnosis of pneumoperitoneum using the enhanced peritoneal stripe sign in beagle dogs

    OpenAIRE

    Kim, Song Yeon; Park, Ki Tae; Yeon, Seong Chan; Lee, Hee Chun

    2014-01-01

    The objective of this study was to evaluate the feasibility and accuracy of estimating the smallest amount of abdominal free gas detectible in a large population of beagles by ultrasonography. Healthy dogs were randomly divided into three groups: group A that received 0.1 mL of air injected into the peritoneal cavity, group B that received 0.2 mL of air injected into the peritoneal cavity, and group C that received 0.5 mL of intraperitoneal air. Randomly, some dogs in each group did not recei...

  20. Growth and production of the venerid bivalve Eurhomalea exalbida in the Beagle Channel, Tierra del Fuego

    OpenAIRE

    Lomovasky, B.; Brey, Thomas; Morriconi, E.; Calvo, J.

    2002-01-01

    Growth, mortality and productivity of the hard clam E. exalbida from Ushuaia Bay, Beagle Channel were investigated. The parameters of the von Bertalanffy growth function were estimated to be H = 73.98 mm, K = 0.180 y 1, t0 = 0.147 y. Maximum individual production amounted to 2.742 g shell free wet mass (SFWM) at 49.5 mm shell height. Animals between 40 mm and 70 mm shell height contribute most to overall population somatic production P of 133.89 g SFWM m-2 y-1. Mean annual biomass B amounted ...

  1. Exploraciones osteológicas de la salud de las poblaciones humanas del Canal Beagle

    OpenAIRE

    Suby, Jorge A.; Zangrando, Francisco Atilio; Piana, Ernesto Luis

    2011-01-01

    Algunas evidencias acerca de la salud de las poblaciones aborígenes han comenzado a ser reportadas en varias regiones de Patagonia Austral. Por el contrario, hasta el momento carecemos de información comparable para la región del canal Beagle. El objetivo de este trabajo es comunicar los resultados de las investigaciones bioarqueológicas y paleopatológicas de los restos humanos recuperados en excavaciones realizadas en la margen norte del canal durante la primera década del siglo XXI. Estos e...

  2. Mischiuen III, un contexto funerario singular en el Canal Beagle (Tierra del Fuego)

    OpenAIRE

    Vila-Mitjà, Assumpció; Casas, Alicia; Oriol Vicente, Campos

    2006-01-01

    (ESP)Presentamos aquí los trabajos realizados en un contexto funerario singular, Mischiuen III, así como los primeros resultados obtenidos. Este estudio aporta nuevos datos para la comprensión de las sociedades cazadoras- recolectoras de Tierra del Fuego, y se enmarca en los proyectos de investigación etnoarqueológica que venimos desarrollando en la costa argentina del canal Beagle desde finales de los años 80. Al mismo tiempo se presentan los resultados de la aplicación de nuevas metodología...

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

    International Nuclear Information System (INIS)

    Beagle dogs were exposed once or semi-annually for 10 yr by inhalation to aerosols of 239PuO2 to study the relative doses and effects of these two types of exposures. All exposures have been completed. Dogs exposed at high levels died predominantly of radiation pneumonitis and pulmonary fibrosis. Dogs exposed at lower levels, either once or repeatedly, are dying of a variety of causes including lung cancer. Dogs have survived up to 11 yr after their first exposure. Preliminary results suggest that single and repeated exposures cause similar health effects for equal accumulated radiation doses. (author)

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  6. Effects of estradiol on norepinephrine and prostaglandin efflux in medial basal hypothalamus of ovariectomized rats

    International Nuclear Information System (INIS)

    The spontaneous and K+-stimulated efflux of norepinephrine (NE) and the release of PGE2 and PGF2α were examined in medial basal hypothalamus (MBH) of ovariectomized rats killed before and during the LH release that follows estradiol treatment. As compared to vehicle-treated, ovariectomized rats, estradiol-primed rats exhibited a 60% more increase in K+-stimulated 3H-overflow of MBH slices preloaded with 3H-NE at morning hours (1000 hours). Estradiol treatment did not result in further increase of K+-induced 3H release from MBH slices at the time of LH release (1700 hours), nor affected labelled NE release in occipital cortex slices. A significant difference between K+-stimulated NE release of vehicle-treated spayed rats killed at 1000 and 1700 hours was observed, the latter showing 54% more release upon stimulus. PGE2 efflux was time-dependent being highest at the evening in both vehicle- and estradiol-treated animals. The MBH of estrogenized rats released significantly more PGE2 at the evening as compared to the controls. The release of PGF2α remained essentially unchanged regardless of estradiol treatment or time of day. The present results offer additional support to the involvement of MBH catecholamines and prostaglandins in the mechanism of LH secretion in the rat. (author)

  7. Locally administrated perindopril improves healing in an ovariectomized rat tibial osteotomy model.

    Directory of Open Access Journals (Sweden)

    Xiong Zhao

    Full Text Available Angiotensin-converting enzyme inhibitors are widely prescribed to regulate blood pressure. High doses of orally administered perindopril have previously been shown to improve fracture healing in a mouse femur fracture model. In this study, perindopril was administered directly to the fracture area with the goal of stimulating fracture repair. Three months after being ovariectomized (OVX, tibial fractures were produced in Sprague-Dawley rats and subsequently stabilized with intramedullary wires. Perindopril (0.4 mg/kg/day was injected locally at the fractured site for a treatment period of 7 days. Vehicle reagent was used as a control. Callus quality was evaluated at 2 and 4 weeks post-fracture. Compared with the vehicle group, perindopril treatment significantly increased bone formation, increased biomechanical strength, and improved microstructural parameters of the callus. Newly woven bone was arranged more tightly and regularly at 4 weeks post-fracture. The ultimate load increased by 66.1 and 76.9% (p<0.01, and the bone volume over total volume (BV/TV increased by 29.9% and 24.3% (p<0.01 at 2 and 4 weeks post-fracture, respectively. These findings suggest that local treatment with perindopril could promote fracture healing in ovariectomized rats.

  8. Green tea polyphenols supplementation improves bone microstructure in orchidectomized middle-Aged rats

    Science.gov (United States)

    Our recent study shows that green tea polyphenols (GTP) attenuate trabecular bone loss in ovariectomized middle-aged female rats. To investigate whether GTP prevents bone loss in male rats, 40 rats with and without oriectomy (ORX) were assigned to 4 groups in a 2 (sham vs. ORX)× 2 (no GTP and 0.5% G...

  9. Clinical Efficacy of Sustained-Release Buprenorphine with Meloxicam for Postoperative Analgesia in Beagle Dogs Undergoing Ovariohysterectomy

    Science.gov (United States)

    Nunamaker, Elizabeth A; Stolarik, DeAnne F; Ma, Junli; Wilsey, Amanda S; Jenkins, Gary J; Medina, Chris L

    2014-01-01

    The goal of the current study was to compare the efficacy, adverse effects, and plasma buprenorphine concentrations of sustained-release buprenorphine (SRB) and buprenorphine after subcutaneous administration in dogs undergoing ovariohysterectomy. In a prospective, randomized, blinded design, 20 healthy adult female Beagle dogs underwent routine ovariohysterectomy and received multimodal analgesia consisting of meloxicam and one of two buprenorphine formulations. Dogs were randomly assigned to receive either SRB (0.2 mg/kg SC, once) or buprenorphine (0.02 mg/kg SC every 12 h for 3 d). Blinded observers assessed all dogs by using sedation scores, pain scores, temperature, HR, RR, and general wellbeing. Dogs were provided rescue analgesia with 0.02 mg/kg buprenorphine SC if the postoperative pain score exceeded a predetermined threshold. Blood samples were collected, and mass spectrometry was used to determine plasma buprenorphine concentrations. Data were analyzed with a linear mixed model and Tukey–Kramer multiple comparison. Age, body weight, anesthetic duration, surgical duration, sevoflurane concentration, and cardiorespiratory variables did not differ significantly between groups. Dogs in both formulation groups had comparable postoperative sedation and pain scores. One dog from each formulation group had breakthrough pain requiring rescue analgesia. Plasma buprenorphine concentrations remained above a hypothesized therapeutic concentration of 0.6 ng/mL for 136.0 ± 11.3 and 10.67 ± 0.84 h for SRB and buprenorphine, respectively. Based on the results of this study, multimodal analgesic regimens consisting of meloxicam and either buprenorphine or SRB are equally efficacious in managing pain associated with an ovariohysterectomy and show comparable side effects. PMID:25255072

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    The efficacy of bronchopulmonary lavage and chelatan therapy for removing 239Pu from beagle dogs after inhalation of 239Pu aerosols having different solubilities has been investigated. The four aerosols used were nebulized from a solution of 239PuCl4 and heat treated at temperatures of 325, 600, 900 and 11500C. Groups of six beagle dogs were exposed to each of the aerosols. Subsequently, three dogs in each group were treated by lavage and intravenous injections of DTPA. The remaining three dogs in each group served as untreated controls. It was found that bronchopulmonary lavage treatment was effective in removing nearly half of the 239Pu activity from the lung regardless of the aerosol production temperature. This early removal of 239Pu activity resulted in a significant reduction in daily dose rate and therefore cumulative α dose to lung. The effectiveness of DTPA treatment depended on aerosol production temperature, and was effective in reducing accumulation of 239Pu in liver and skeleton of the dogs that inhaled aerosols produced at 3250 and 6000C by enhancing urinary excretion of 239Pu. (U.K.)

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

    Science.gov (United States)

    Jergovic, B.; Miller, S.

    2008-05-01

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

  13. Effects of dietary protein and ethanol intake on pregnant beagles fed purified diets.

    Science.gov (United States)

    Switzer, B R; Anderson, J J; Pick, J R

    1986-04-01

    Maternal weight gain of beagles was approximately 50% lower when ethanol was given twice daily at a dose of 1.8 g/kg body weight with either control protein (17% energy from protein) or low protein (8.5%) diet as compared to isocalorically sucrose-treated animals. Similarly, pup birth weights were about 27% lower from beagles given ethanol with either diet when compared to those from sucrose-treated bitches. Two weeks after beginning ethanol treatment, pregnant bitches fed either diet had higher hematocrit values and lower plasma concentrations of albumin and calcium as compared to sucrose-treated animals. Low dietary protein treatment, rather than ethanol, lowered maternal concentrations of red blood cell folate during pregnancy. As compared to sucrose-treated bitches, ethanol prevented folate levels in red blood cells from returning to the normal range by the 9th wk of pregnancy in animals fed low dietary protein. These data show that ethanol consumption and low dietary protein intake, independently of each other, significantly depress maternal weight gain, pup birth weight and some nutritionally related parameters of the mother. PMID:3958813

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

    International Nuclear Information System (INIS)

    To determine the life-span dose-effect relationships of inhaled plutonium, we gave 124 beagle dogs a single exposure of 239PuO2 2 to 3 years ago at six different levels, i.e., 4, 20, 80, 300, 1100, or 5800 nCi mean initial alveolar depositions. Another group (20 dogs) served as controls. All dogs were about 18 months old. At the four highest exposure levels, a chronic lymphocytopenia developed which correlated with the initial alveolar plutonium burden in regard to magnitude of depression and time of development after exposure. The nadir occurred near 10 months after exposure in dogs receiving 5800, 1100, and 300 nCi, with corresponding lymphocyte levels 40, 55, and 75 percent, respectively, of those observed in control dogs. In the 80-nCi level the nadir occurred about 2 years after exposure at approximately 80 percent of control values. At the two lowest doses, i.e., 4 and 20 nCi, no effect on lymphocyte concentrations was noted 3 years after exposure. The persistent lymphocytopenia related to plutonium inhalation may be of significance in the subsequent development of pulmonary neoplasms previously observed in beagles at this laboratory 8 to 11 years after initial lung depositions of 200 to 1000 nCi of 239Pu

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2012-06-20

    A rapid and sensitive postcolumn fluorescence derivatization method was developed for microanalysis of antidiabetic oligosaccharide HS203 in beagle dog plasma. After plasma protein was removed by a simple and fast ultrafiltration method, chromatographic separation was performed on an Asahipak GS-320 HQ column with a mobile phase of 50 mmol/L phosphate buffer (pH 6.7) and acetonitrile (83/17, v/v). The column effluent was monitored by fluorescence detection at 249 nm (excitation) and 435 nm (emission) using guanidine hydrochloride as a postcolumn derivatizing reagent. A satisfactory resolution of the analyte was achieved and the limit of detection was found to be 4 ng (more sensitive than silver staining of HS203 in polyacrylamide gel electrophoresis). The method described above was successfully applied to a pharmacokinetic study of HS203 and to monitor blood glucose level simultaneously in beagle dog. It is also possible to be applied for microanalysis of other oligosaccharides in biological samples. PMID:24750771

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    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. PMID:26548565

  19. A comparison of the effects of estrogen and Cimicifuga racemosa on the lacrimal gland and submandibular gland in ovariectomized rats.

    Science.gov (United States)

    Da, Yunmeng; Niu, Kaiyu; Wang, Ke; Cui, Guangxia; Wang, Wenjuan; Jin, Biao; Sun, Yu; Jia, Jing; Qin, Lihua; Bai, Wenpei

    2015-01-01

    This study aims to observe the effects of estradiol and Cimicifuga racemosa on the lacrimal gland and submandibular gland of ovariectomized rats. We randomly divided 20 adult female SD rats into four groups-a sham-operated group (SHAM), ovariectomized (OVX) group, ovariectomized group treated with estradiol (OVX+ E), and ovariectomized group treated with the isopropanolic extract of Cimicifuga racemosa (OVX+ iCR). The SHAM group and OVX group used distilled water to instead the drugs. Two weeks after ovariectomy, the estradiol and iCR were administered for 4 weeks. Next, we used H&E staining and electron microscopy to observe any histological changes in the lacrimal and submandibular glands and immunohistochemical staining to observe the expressions of cleaved caspase-3 (Casp-3) and Cu-Zn SOD (superoxide dismutase). The H&E staining find that both drugs can prevent the cells of area from shrinkage in the two kinds of gland. But under the electron microscopy, estradiol and iCR have different efficacy. Estradiol is more effective at protecting mitochondria in lacrimal gland acinar cells than iCR, and iCR is more effective at suppressing endoplasmic reticulum expansion than estradiol. Both estradiol and iCR have a similar protective function on mitochondria in the submandibular gland. The protective function of the two glands may inhibit apoptosis by suppressing the expression of Casp-3. In addition, iCR increases the expression of Cu-Zn SOD in duct system of submandibular gland. The results suggest that both estradiol and iCR confer a protective effect on the lacrimal and submandibular glands of ovariectomized rats via different mechanisms. PMID:25793872

  20. Initial deposition and early clearance of inhaled 239Pu(NO3)4 aerosols in beagle dogs

    International Nuclear Information System (INIS)

    Data from exposures of 113 beagle dogs to 239Pu(NO3)4 aerosols were analyzed for effects of aerosol properties on deposition and early clearance. The percent of inhaled aerosols deposited was not significantly dependent on particle size or aerosol concentration. The early clearance rate was significantly slower at the highest exposure levels than at medium and low levels

  1. Effects of plutonium on the immune system: IgG in beagle dogs exposed to plutonium and in nonexposed controls

    International Nuclear Information System (INIS)

    Serum IgG levels in plutonium-oxide-exposed and unexposed beagle dogs was assayed with the Mancini system. With this system, there was no significant difference between IgG levels of exposed dogs and controls, nor among exposed dogs with different degrees of lymphopenia. (U.S.)

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27160397

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

    Science.gov (United States)

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

    2016-05-01

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

  4. Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Hai-rong MA; Jie WANG; Hong-xue QI; Yan-hua GAO; Li-juan PANG; Yi YANG; Zhen-hua WANG

    2013-01-01

    Aim:Chickpea (Cicer arietinum L) is a traditional Uighur herb.In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats.Methods:Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX).The rats were administered via intragastric gavage 3 different doses of ICS (20,50,or 100 mg·kg-1.d-1) for 5 weeks.Their uterine weight and serum levels of 17β-estradiol (E2),follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured.The epithelial height,number of glands in the uterus,and number of osteoclasts in the femur were histologically quantified,and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically.Bone structural parameters,including bone mineral density (BMD),bone volume/tissue volume (BV/TV),trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning.Results:Treatments of OVX rats with ICS (50 or 100 mg·kg-1.d-1) produced significant estrogenic effects on the uteruses,including the increases in uterine weight,epithelial height and gland number,as well as in the expression of the cell proliferation marker PCNA.The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins:serum E2 level was significantly increased,while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats.Furthermore,the treatments significantly attenuated the bone loss,increased BMD,BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts.Treatment of OVX rats with the positive control drug E2 (0.25 mg·kg-1.d-1) produced similar,but more prominent effects.Conclusion:ICS exhibits moderate estrogenic activities as compared to E2 in ovariectomized rats,suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.

  5. Distribución batimétrica, espacial y temporal del macrozoobentos en el Canal Beagle, Tierra del Fuego, Argentina

    OpenAIRE

    Diez, M.

    2006-01-01

    El Canal Beagle (Tierra del Fuego, Argentina) se encuentra en el sistema de canales fueguinos que representa el ambiente marino subantártico costero más estrechamente relacionado con la Antártida. Además, el Canal Beagle constituye una vía de intercambio de fauna y flora ente los océanos Pacífico y Atlántico. El objetivo de este trabajo fue determinar la composición, abundancia y biomasa del macrozoobentos en el Canal Beagle como también la producción secundaria de los ensambles bentónicos. D...

  6. Improvements of insulin resistance in ovariectomized rats by a novel phytoestrogen from Curcuma comosa Roxb

    Directory of Open Access Journals (Sweden)

    Prasannarong Mujalin

    2012-03-01

    Full Text Available Abstract Background Curcuma comosa Roxb. (C. comosa is an indigenous medicinal herb that has been used in Thailand as a dietary supplement to relieve postmenopausal symptoms. Recently, a novel phytoestrogen, (3R-1,7-diphenyl-(4E,6E-4,6-heptadien-3-ol or compound 049, has been isolated and no study thus far has investigated the role of C. comosa in preventing metabolic alterations occurring in estrogen-deprived state. The present study investigated the long-term effects (12 weeks of C. comosa hexane extract and compound 049 on insulin resistance in prolonged estrogen-deprived rats. Methods Female Sprague-Dawley rats were ovariectomized (OVX and treated with C. comosa hexane extract (125 mg, 250 mg, or 500 mg/kg body weight (BW and compound 049 (50 mg/kg BW intraperitoneally three times per week for 12 weeks. Body weight, food intake, visceral fat weight, uterine weight, serum lipid profile, glucose tolerance, insulin action on skeletal muscle glucose transport activity, and GLUT-4 protein expression were determined. Results Prolonged ovariectomy resulted in dyslipidemia, impaired glucose tolerance and insulin-stimulated skeletal muscle glucose transport, as compared to SHAM. Treatment with C. comosa hexane extract and compound 049, three times per week for 12 weeks, markedly reduced serum total cholesterol and low-density lipoprotein levels, improved insulin sensitivity and partially restored uterine weights in ovariectomized rats. In addition, compound 049 or high doses of C. comosa hexane extract enhanced insulin-mediated glucose uptake in skeletal muscle and increased muscle GLUT-4 protein levels. Conclusions Treatment with C. comosa and its diarylheptanoid derivative improved glucose and lipid metabolism in estrogen-deprived rats, supporting the traditional use of this natural phytoestrogen as a strategy for relieving insulin resistance and its related metabolic defects in postmenopausal women.

  7. Differences in vertebral, tibial, and iliac cancellous bone metabolism in ovariectomized rats.

    Science.gov (United States)

    Takakura, Aya; Takao-Kawabata, Ryoko; Isogai, Yukihiro; Kajiwara, Makoto; Murayama, Hisashi; Ejiri, Sadakazu; Ishizuya, Toshinori

    2016-05-01

    Bone histomorphometry is usually performed on the iliac bone in humans and the tibia or vertebrae in rats. Bone metabolism differences among skeletal sites may be problematic when translating experimental results from rats to humans, but data on such differences in rats are lacking. Therefore, we examined the differences in bone structure and metabolism among skeletal sites using the lumbar vertebra (LV), tibia, and iliac bone obtained from ovariectomized or sham-operated rats preoperatively and at various times from 3 days to 26 weeks postoperatively. The trabeculae were thicker in the LV, where bone metabolism was less active than at other sites, and numerous fine trabeculae were observed in the tibia, where bone metabolism was more active. The iliac bone structure and metabolism were intermediate between those of the tibia and LV. Ovariectomy induced lower bone volume and higher bone metabolism in all skeletal sites, but the changes were greatest and occurred earliest in the tibia, followed by the iliac bone and then LV. Ovariectomy caused changes in bone metabolic markers, which occurred earlier than those in bone tissue. Activation frequency (Ac.f) increased after ovariectomy. At week 26 in ovariectomized rats, Ac.f was highest in the tibia (3.13 N/year) but similar between iliac bone (0.87 N/year) and LV (1.39 N/year). Ac.f is reportedly 0.3-0.4 N/year in the iliac bone of postmenopausal women, suggesting that bone turnover in rats is several times higher than in humans. The reference values reported here are useful for translating experimental results from rats to humans. PMID:26082076

  8. Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Urmila Aswar; Mayuri Gurav; Ganesh More; Khaled Rashed; Manoj Aswar

    2014-01-01

    OBJECTIVE: Solanum xanthocarpum Schrad.&Wendl. (Solanaceae) is present in many Ayurveda compound formulations including Chavanaprasha and Dasamoolarishta. The whole plant is used in conditions such as inflammation, constipation and promoting conception in females. In the present study, we carried out different tests to evaluate the effect of aqueous extract of Solanum xanthocarpum (SXE) in postmenopausal syndrome. METHODS: The study was carried out in bilaterally ovariectomized one-month-old Wistar rats (40-50 g). Bilaterally ovariectomized (OVX) Wistar rats were divided into four groups (n=6) receiving different treatments, consisting of a vehicle (distilled water), aqueous extract of Solanum xanthocarpum at two different doses (200 and 400 mg/kg) administered orally daily for 90 d and standard drugβestradiol at a dose of 1 mg/kg administered subcutaneously biweekly for 90 d. Estrogenic activity was assessed by vaginal corniifcation, sexual behavior, serum estradiol and uterine weight to body weight ratio. Antiosteoporotic activity was assessed on the basis of biomechanical and biochemical parameters followed by histopathological studies, and antidepressant activity was assessed by forced swim test. RESULTS:SXE showed presence of steroids. At the dose of 200 mg/kg, it signiifcantly improved all the parameters of sexual behavior (P<0.01), caused vaginal corniifcation, and increased serum estradiol and uterine weight (P<0.01). It also significantly improved all the parameters of bone strength as well as depression (P<0.01). Histopathology of bones conifrmed the above ifndings. CONCLUSION:The study indicated that SXE may provide an effective treatment in the prevention of postmenopausal symptoms.

  9. Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice

    Directory of Open Access Journals (Sweden)

    Naoto Tokuyama

    2015-06-01

    Full Text Available We examined the individual and combined effects of teriparatide and anti-RANKL (receptor activator of nuclear factor κB ligand monoclonal antibody in ovariectomized mice. Three-month-old female C57BL/6 mice were ovariectomized (OVX or sham operated. Four weeks after OVX, they were assigned to 3 different groups to receive anti-RANKL monoclonal antibody (Ab alone (5 mg/kg single injection at 4 weeks after OVX, Ab group, teriparatide alone (80 μg/kg daily injection for 4 weeks from 4 weeks after OVX, PTH group, or mAb plus teriparatide (Ab + PTH group. Mice were sacrificed 8 weeks after OVX. Bone mineral density (BMD was measured at the femur and lumbar spine. Hind limbs were subjected to histological and histomorphometric analysis. Serum osteocalcin and CTX-I levels were measured to investigate the bone turnover. Compared with Ab group, Ab + PTH group showed a significant increase in BMD at distal femur and femoral shaft. Cortical bone volume was significantly increased in PTH and Ab + PTH groups compared with Ab group. Bone turnover in Ab + PTH group was suppressed to the same degree as in Ab group. The number of TRAP-positive multinucleated cells was markedly reduced in Ab and Ab + PTH groups. These results suggest that combined treatment of teriparatide with anti-RANKL antibody has additive effects on BMD in OVX mice compared with individual treatment.

  10. Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman

    Directory of Open Access Journals (Sweden)

    Peano Bryan J

    2008-06-01

    Full Text Available Abstract Background Vaginal atrophy (VA is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause. Some of the consequences of VA include increased susceptibility to bacterial infection, pain during sexual intercourse, and vaginal burning or itching. Although estrogen treatment is highly effective, alternative therapies are also desired for women who are not candidates for post-menopausal hormone therapy (HT. The ovariectomized (OVX rat is widely accepted as an appropriate animal model for many estrogen-dependent responses in humans; however, since reproductive biology can vary significantly between mammalian systems, this study examined how well the OVX rat recapitulates human biology. Methods We analyzed 19 vaginal biopsies from human subjects pre and post 3-month 17β-estradiol treated by expression profiling. Data were compared to transcriptional profiling generated from vaginal samples obtained from ovariectomized rats treated with 17β-estradiol for 6 hrs, 3 days or 5 days. The level of differential expression between pre- vs. post- estrogen treatment was calculated for each of the human and OVX rat datasets. Probe sets corresponding to orthologous rat and human genes were mapped to each other using NCBI Homologene. Results A positive correlation was observed between the rat and human responses to estrogen. Genes belonging to several biological pathways and GO categories were similarly differentially expressed in rat and human. A large number of the coordinately regulated biological processes are already known to be involved in human VA, such as inflammation, epithelial development, and EGF pathway activation. Conclusion At the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples.

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

    Directory of Open Access Journals (Sweden)

    Jae-Seuk Park

    2010-12-01

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

  12. Resistance training associated with the administration of anabolic-androgenic steroids improves insulin sensitivity in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Urtado CB

    2011-11-01

    Full Text Available Christiano Bertoldo Urtado1,2, Guilherme Borges Pereira3, Marilia Bertoldo Urtado4, Érica Blascovi de Carvalho2, Gerson dos Santos Leite1, Felipe Fedrizzi Donatto1, Claudio de Oliveira Assumpção1, Richard Diego Leite3, Carlos Alberto da Silva1, Marcelo Magalhães de Sales5, Ramires Alsamir Tibana5, Silvia Cristina Crepaldi Alves1, Jonato Prestes51Health Sciences, Methodist University of Piracicaba, Piracicaba, SP, 2Center for Investigation in Pediatrics, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, 3Department of Physiological Sciences, Federal University of São Carlos, São Carlos, SP, 4Laboratory of Orofacial Pain, Division of Oral Physiology, Piracicaba Dental School, State University of Campinas, Campinas, SP, 5Graduation Program in Physical Education, Catholic University of Brasilia, Brasilia, DF, BrazilAbstract: The aim of the present study was to investigate the effects of anabolic-androgenic steroids and resistance training (RT on insulin sensitivity in ovariectomized rats. Adult female Wistar rats were divided into ten experimental groups (n = 5 animals per group: (1 sedentary (Sed-Intact; (2 sedentary ovariectomized (Sed-Ovx; (3 sedentary nandrolone (Sed-Intact-ND; (4 sedentary ovariectomized plus nandrolone (Sed-Ovx-ND; (5 trained (TR-Intact; (6 trained nandrolone (TR-Intact-ND; (7 trained ovariectomized (TR-Ovx; (8 trained ovariectomized plus nandrolone; (9 trained sham; and (10 trained ovariectomized plus sham. Four sessions of RT were used, during which the animals climbed a 1.1 m vertical ladder with weights attached to their tails. The sessions were performed once every 3 days, with between four and nine climbs and with eight to twelve dynamic movements per climb. To test the sensitivity of insulin in the pancreas, glucose and insulin tolerance tests were performed. For insulin sensitivity, there was a statistically significant interaction for the TR-Ovx group, which presented higher sensitivity

  13. Effects of chronic estrogen treatment on modulating age-related bone loss in female mice.

    Science.gov (United States)

    Syed, Farhan A; Mödder, Ulrike Il; Roforth, Matthew; Hensen, Ira; Fraser, Daniel G; Peterson, James M; Oursler, Merry Jo; Khosla, Sundeep

    2010-11-01

    While female mice do not have the equivalent of a menopause, they do undergo reproductive senescence. Thus, to dissociate the effects of aging versus estrogen deficiency on age-related bone loss, we sham-operated, ovariectomized, or ovariectomized and estrogen-replaced female C57/BL6 mice at 6 months of age and followed them to age 18 to 22 months. Lumbar spines and femurs were excised for analysis, and bone marrow hematopoietic lineage negative (lin-) cells (enriched for osteoprogenitor cells) were isolated for gene expression studies. Six-month-old intact control mice were euthanized to define baseline parameters. Compared with young mice, aged/sham-operated mice had a 42% reduction in lumbar spine bone volume/total volume (BV/TV), and maintaining constant estrogen levels over life in ovariectomized/estrogen-treated mice did not prevent age-related trabecular bone loss at this site. By contrast, lifelong estrogen treatment of ovariectomized mice completely prevented the age-related reduction in cortical volumetric bone mineral density (vBMD) and thickness at the tibial diaphysis present in the aged/sham-operated mice. As compared with cells from young mice, lin- cells from aged/sham-operated mice expressed significantly higher mRNA levels for osteoblast differentiation and proliferation marker genes. These data thus demonstrate that, in mice, age-related loss of cortical bone in the appendicular skeleton, but not loss of trabecular bone in the spine, can be prevented by maintaining constant estrogen levels over life. The observed increase in osteoblastic differentiation and proliferation marker gene expression in progenitor bone marrow cells from aged versus young mice may represent a compensatory mechanism in response to ongoing bone loss. PMID:20499336

  14. Effects of pulsed electromagnetic fields on the mRNA expression of RANK and CAII in ovariectomized rat osteoclast-like cell.

    Science.gov (United States)

    Chen, Jian; He, Hong-Cheng; Xia, Qing-Jie; Huang, Li-Qun; Hu, Yu-Jun; He, Cheng-qi

    2010-01-01

    This study was designed to determine the effects of pulsed electromagnetic fields (PEMF) on the mRNA expression of the receptor activator of NF-kappa-B (RANK) and carbonic anhydrase II (CA II) in ovariectomized rat osteoclast-like cells. Marrow cells were harvested from femora and tibiae of rats, from which the ovaries had been totally excised, and cultured in 6-well chamber slides. After 1 day of incubation, the marrow cells were exposed to PEMF for 3 days with 3.8 mT, 8 Hz, and 40 min per day. Osteoclast-like cells were confirmed by both tartrate resistant acid phosphatase (TRAP) stain and bone resorption assay. The expression of RANK and CA II mRNA was determined with real-time fluorescent-nested quantitative polymerase chain reaction. Compared with the sham group, the level of serum estradiol in the ovariectomized group was significantly decreased ( p invitro study, the expression of RANK and CA II were measured in sham, ovariectomized without PEMF, and ovariectomized with PEMF treatment. Compared with the ovariectomized (PEMF) experimental group and sham group, CA II mRNA expression was significantly increased in the ovariectomized control group ( p culture system. PMID:20067410

  15. Toxicity of 90Sr inhaled in a relatively insoluble form by beagle dogs

    International Nuclear Information System (INIS)

    Beagle dogs were exposed by inhalation to 90Sr in a relatively insoluble form to study long-term health effects. Lung burdens ranged from 0.12 to 96 μCi of 90Sr per kilogram of body weight. High levels of exposure have caused pulmonary fibrosis and radiation pneumonitis; lower level exposures caused long-term effects which included cancer of the lung, heart and tracheobronchial lymph nodes. Most of these tumors were hemangiosarcomas. Six dogs died during the past year and two of them had hemangiosarcoma primary to a tracheobronchial lymph node. This was a new finding in this study and indicates the importance of considering the radiation dose to thoracic lymph nodes which continually accumulate radioactive particles after inhalation exposure to relatively insoluble radioactive aerosols

  16. Toxicity of 90Sr inhaled in a relatively insoluble form by Beagle dogs. XIII

    International Nuclear Information System (INIS)

    Beagle dogs were exposed by inhalation to 90Sr in a relatively insoluble form to study long-term health effects. Lung burdens ranged from 0.02 to 96 μCi of 90Sr per kilogram of body weight. High levels of exposure resulted in radiation pneumonitis and pulmonary fibrosis; lower level exposures caused long-term effects which included cancer of the lung, heart and tracheobronchial lymph nodes. Most of these tumors were hemangiosarcomas. Three control dogs and two 90Sr-exposed dogs died or were euthanized during the past year. One exposed dog died with hemangiosarcoma of the liver; the other exposed dog died with hemangiosarcoma of the tracheobronchial lymph nodes. One control dog died during routine anesthesia, one died with hepatocellular carcinoma and the third died with transitional cell carcinoma of the bladder

  17. Bioavailability of water-soluble CoQ10 in beagle dogs.

    Science.gov (United States)

    Prosek, Mirko; Butinar, Janos; Lukanc, Barbara; Fir, Maja Milivojevic; Milivojevic, Luka; Krizman, Mitja; Smidovnik, Andrej

    2008-08-01

    The bioavailability of a novel water-soluble inclusion complex of CoQ10, prepared in our laboratory was determined and compared with the bioavailability of commercially available oil-based form of CoQ10. Experimental work consisted of single dose comparative bioavailability study on seven beagle dogs, with a 14-day washout period between treatments. Identification and quantification of CoQ10 was done with HPLC-MS method using positive APCI ionization and SIM mode, M+ m/z 863.4. The bioavailability results confirm that the water-soluble formulation has nearly three times higher AUC(0-48 h), two times higher Cmax, and Tmax is shortened from 6 to 4 h. PMID:18495407

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

    International Nuclear Information System (INIS)

    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

  19. Biomarkers and heavy metal bioaccumulation in mussels transplanted to coastal waters of the Beagle Channel.

    Science.gov (United States)

    Giarratano, Erica; Duarte, Claudia A; Amin, Oscar A

    2010-03-01

    Mussels coming from a mussel farm at Brown Bay (Beagle Channel) were transplanted to four sites inside Ushuaia Bay for 2 and 4 weeks. The objective of this study was to assess the quality of coastal waters of Ushuaia Bay by measuring catalase activity, lipid peroxidation, total lipid content, bioaccumulation of heavy metals and condition index in transplanted mussel Mytilus edulis chilensis. Biomarkers except condition index showed significant differences among exposure times as well as among tissues. Digestive gland presented the highest catalase activity, malondialdehyde level and total lipid content. Digestive gland also was the main target tissue of accumulation of iron and copper, while gill accumulated the highest levels of zinc. A principal component analyzes with the whole set of data allowed to separate stations based on physicochemical conditions and biochemical responses of each studied area. PMID:19913913

  20. Growth and production of the venerid bivalve Eurhomalea exalbida in the Beagle Channel, Tierra del Fuego

    Science.gov (United States)

    Lomovasky, Betina J.; Brey, Thomas; Morriconi, Elba; Calvo, Jorge

    2002-11-01

    Growth, mortality and productivity of the hard clam Eurhomalea exalbida from Ushuaia Bay, Beagle Channel, were investigated. The parameters of the von Bertalanffy growth function were estimated to be H ∞ = 74 mm, K = 0.18 y -1, t 0 = 0.15 y. Maximum individual production amounted to 2.74 g shell-free wet mass (SFWM) at 49.5 mm shell height. Animals between 40 mm and 70 mm shell height contributed most to overall population somatic production P of 134 g SFWM m -2 y -1. Mean annual biomass B amounted to 1123 g SFWM m -2 y -1. Annual P/B ratio and mortality rate Z were estimated to be 0.12 y -1 and 0.14 y -1, respectively. Slow growth and low turnover make this population less suitable for sustainable commercial exploitation.

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

    Science.gov (United States)

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

    2011-06-01

    The occurrence of biomarker variations linked to environmental factors makes it difficult to distinguish the effect of pollution. In an attempt to evaluate spatial and seasonal effects of environmental parameters on biomarker responses, mussels Mytilus edulis chilensis coming from an aquaculture farm were transplanted to several points within Ushuaia Bay (Beagle Channel) for 6 weeks in summer and winter. Activities of superoxide dismutase, catalase, glutathione-S-transferase and levels of lipid peroxidation were measured in gills and digestive gland. Cu, Zn, Fe, Cd and Pb concentrations were also assessed. Results indicated a significant effect of seasons on biological responses as well as in metal bioaccumulation showing the influence of natural factors such as dissolved oxygen, temperature and food availability. The interdependence of those environmental factors is important for the homeostasis of thermoconformers, especially regarding their oxidative metabolism and should also be taken into consideration to distinguish natural from pollution-induced variations. PMID:21550069

  2. Radium-226-induced bone lesions in beagle dogs treated by amputation: clinical, radiological, and histologic observations

    International Nuclear Information System (INIS)

    Within a colony of beagle dogs that had received intravenous injections of 226Ra there was a subgroup of dogs, each of which developed a painful lesion of a long bone. These bone lesions had their inception in bizarre, progressively expansile resorption cavities in which the process of normal bone tissue replacement was defective. On occasion, bone sarcomas arose in some of the sites of perturbed bone repair. This radiation-induced disturbance of the normal bone remodeling process with its preneoplastic spectrum of radiographic and histologic lesions was termed radiation-osteodystrophy. Lesions were studied by sequential radiography prior to the onset of clinical signs. Because of the painful nature of the lesion and difficulty experienced by the dogs in walking, full leg amputations were performed. This not only provided relief from clinical signs, but also permitted the dog to continue to live, allowing study of subsequently identified radiation-induced lesions

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

    Directory of Open Access Journals (Sweden)

    Cabrera García, Alexei

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    Labeled cDNA synthesized from RNA extracted from 238PuO2-, 239PuO2-, and 90Sr-induced lung tumors in Beagle dogs, from nontumor tissue from 239PuO2-exposed dogs, and from unexposed dog lung and liver tissue produces strong hybridization signals with a plasmid (pKSma) that contains Kirsten murine sarcoma virus (KMSV) sequences. At least 90 percent of the KMSV sequences are expressed in these dog tissues, including sequences corresponding to p21 K-ras, qp70 envelope glycoprotein, and at least one other proviral sequence. The expression of Kirsten ras and other sarcoma virus sequences may have important implications for the interpretation of carcinogenesis studies in these dogs. (author)

  8. Toxicity of 91Y inhaled in a relatively insoluble form by Beagle dogs. XVI

    International Nuclear Information System (INIS)

    Beagle dogs were exposed by inhalation to aerosols of 91Y in fused aluminosilicate particles, resulting in initial lung burdens ranging from 11 to 360 μCi (0.4-13 MBq) 91Y/kg body weight. These 96 dogs, plus 12 controls, were maintained for life-span observation of toxic and carcinogenic effects. Dogs with the highest lung burdens died at early times with radiation pneumonitis. At later times, tumors were seen in lungs, nasal cavity, heart, and tracheobronchial lymph nodes; these organs received the highest radiation doses. Observations are continuing on the 5 exposed and 3 control dogs that remain alive 5120 to 5605 days after exposure. 2 figures, 1 table

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    Young-adult beagles were exposed continuously (22 hours/day) to 60Co γ rays in a specially constructed facility. The exposure rates were either 5, 10, 17, or 35 R/day, and the exposures were terminated at either 600, 1400, 2000, or 4000 R. A total of 354 dogs were irradiated; 221 are still alive as long-term survivors, some after more than 2000 days. The data on survival of these dogs, coupled with data from similar preliminary experiments, allow an estimate of the LD50 for γ-ray exposures given at a number of exposure rates. They also allow comparison of the relative importance of dose rate and total dose, and the interaction of these two variables, in the early and late effects after protracted irradiation. The LD50 for the beagle increases from 258 rad delivered at 15 R/minute to approximately 3000 rad at 10 R/day. Over this entire range, the LD50 is dependent upon hematopoietic damage. At 5 R/day and less, no meaningful LD50 can be determined; there is nearly normal continued hematopoietic function, survival is prolonged, and the dogs manifest varied individual responses in other organ systems. Although the experiment is not complete, interim data allow several important conclusions. Terminated exposures, while not as effective as radiation continued until death, can produce myelogenous leukemia at the same exposure rate, 10 R/day. More importantly, at the same total accumulated dose, lower exposure rates are more damaging than higher rates on the basis of the rate and degree of hematological recovery that occurs after termination of irradiation. Thus, the rate of hematologic depression, the nadir of the depression, and the rate of recovery are dependent upon exposure rate; the latter is inversely related and the former two are directly related to exposure rate

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-09-15

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

  14. Physical Activity Differentially Affects the Cecal Microbiota of Ovariectomized Female Rats Selectively Bred for High and Low Aerobic Capacity.

    Directory of Open Access Journals (Sweden)

    Tzu-Wen Liu

    Full Text Available The gut microbiota is considered a relevant factor in obesity and associated metabolic diseases, for which postmenopausal women are particularly at risk. Increasing physical activity has been recognized as an efficacious approach to prevent or treat obesity, yet the impact of physical activity on the microbiota remains under-investigated. We examined the impacts of voluntary exercise on host metabolism and gut microbiota in ovariectomized (OVX high capacity (HCR and low capacity running (LCR rats. HCR and LCR rats (age = 27 wk were OVX and fed a high-fat diet (45% kcal fat ad libitum and housed in cages equipped with (exercise, EX or without (sedentary, SED running wheels for 11 wk (n = 7-8/group. We hypothesized that increased physical activity would hinder weight gain, increase metabolic health and shift the microbiota of LCR rats, resulting in populations more similar to that of HCR rats. Animals were compared for characteristic metabolic parameters including body composition, lipid profile and energy expenditure; whereas cecal digesta were collected for DNA extraction. 16S rRNA gene-based amplicon Illumina MiSeq sequencing was performed, followed by analysis using QIIME 1.8.0 to assess cecal microbiota. Voluntary exercise decreased body and fat mass, and normalized fasting NEFA concentrations of LCR rats, despite only running one-third the distance of HCR rats. Exercise, however, increased food intake, weight gain and fat mass of HCR rats. Exercise clustered the gut microbial community of LCR rats, which separated them from the other groups. Assessments of specific taxa revealed significant (p<0.05 line by exercise interactions including shifts in the abundances of Firmicutes, Proteobacteria, and Cyanobacteria. Relative abundance of Christensenellaceae family was higher (p = 0.026 in HCR than LCR rats, and positively correlated (p<0.05 with food intake, body weight and running distance. These findings demonstrate that exercise differentially

  15. Protection of Trabecular Bone in Ovariectomized Rats by Turmeric (Curcuma longa L.) is Dependent on Extract Composition

    OpenAIRE

    Wright, Laura E; Frye, Jennifer B.; Timmermann, Barbara N.; Funk, Janet L.

    2010-01-01

    Extracts prepared from turmeric (Curcuma longa L., [Zingiberaceae]) containing bioactive phenolic curcuminoids were evaluated for bone-protective effects in a hypogonadal rat model of postmenopausal osteoporosis. Three-month female Sprague Dawley rats were ovariectomized (OVX) and treated with a chemically complex turmeric fraction (41% curcuminoids by weight) or a curcuminoid-enriched turmeric fraction (94% curcuminoids by weight), both dosed at 60mg/kg 3x per week, or vehicle alone. Effects...

  16. Energy Status Determines Hindbrain Signal Transduction Pathway Transcriptional Reactivity to AMPK in the Estradiol-Treated Ovariectomized Female Rat

    OpenAIRE

    Ibrahim, Baher A.; Alenazi, Fahaad S.H.; Briski, Karen P.

    2014-01-01

    Dorsal vagal complex (DVC) AMPK regulation of food intake in the estradiol-treated ovariectomized (OVX) female rat is energy state-dependent. Here, RT-PCR array technology was used to identify estradiol-sensitive AMPK-regulated DVC signal transduction pathways that exhibit differential reactivity to sensor activation during energy balance versus imbalance. The AMP mimetic AICAR correspondingly reduced or stimulated cDVC phosphoAMPK (pAMPK) and estrogen receptor-beta (ERβ) proteins in full-fed...

  17. Acute effect of high-dose isoflavones from Pueraria lobata (Willd.) Ohwi on lipid and bone metabolism in ovariectomized mice.

    Science.gov (United States)

    Cho, Hee Joon; Jun, Hee-jin; Lee, Ji Hae; Jia, Yaoyao; Hoang, Minh Hien; Shim, Jae-Hoon; Park, Kwan-Hwa; Lee, Sung-Joon

    2012-12-01

    We investigated the acute metabolic effects of isoflavones from Pueraria lobata (Willd.) Ohwi (IPL) in ovariectomized (OVX) mice. After 4 weeks of IPL feeding at 500 mg/day/kg body weight (OVX500), plasma 17β-estradiol concentrations were significantly higher (+25%, p menopausal symptoms in mice. Further studies will confirm the effects of IPL in humans. PMID:22422661

  18. Effect of high soy diet on the cerebrovasculature and endothelial nitric oxide synthase in the ovariectomized rat

    OpenAIRE

    Schreihofer, Derek A.; Deutsch, Christian; Lovekamp-Swan, Tara; Sullivan, Jennifer C.; Dorrance, Anne M.

    2010-01-01

    High soy (HS) diets are neuroprotective and promote vascular dilatation in the periphery. We hypothesized that a HS diet would promote vascular dilatation in the cerebrovasculature by mimicking estradiol's actions on the endothelial nitric oxide synthase (eNOS) system including increasing eNOS expression and decreasing caveolin-1 expression to increase nitric oxide (NO) production. Ovariectomized rats were fed HS or a soy-free diet (SF) ± low physiological estradiol (E2) for 4 weeks. Neither ...

  19. The Effects of Puerariae Flos on Stress-induced Deficits of Learning and Memory in Ovariectomized Female Rats

    OpenAIRE

    Park, Hyun-Jung; Han, Seung-Moo; Yoon, Won Ju; Kim, Kyung-Soo; Shim, Insop

    2009-01-01

    Puerariae flos (PF) is a traditional oriental medicinal plant and has clinically been prescribed for a long time. The purpose of the present study was to examine the effect of PF on repeated stress-induced alterations of learning and memory on a Morris water maze (MWM) test in ovariectomized (OVX) female rats. The changes in the reactivity of the cholinergic system were assessed by measuring the immunoreactive neurons of choline acetyltransferase (ChAT) in the hippocampus after behavioral tes...

  20. The effects of different exercise modes for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats

    OpenAIRE

    Park, Jonghoon; Omi, Naomi

    2014-01-01

    [Purpose] Several epidemiological studies have demonstrated that there are positive correlations between vascular disorders and bone loss in postmenopausal women. The aim of the present study was to examine the effect of different types of exercise (e.g., climbing and swimming) for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats. [Methods] Twenty Sprague-Dawley female rats were randomly divided into three groups: ovariectomy (OVX) plus treatment with vitami...

  1. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

    Science.gov (United States)

    Westerlind, K. C.; Wronski, T. J.; Ritman, E. L.; Luo, Z. P.; An, K. N.; Bell, N. H.; Turner, R. T.

    1997-01-01

    Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

  2. Ad libitum feeding following ovariectomy in female Beagle dogs: effect on maintenance energy requirement and on blood metabolites.

    Science.gov (United States)

    Jeusette, I; Detilleux, J; Cuvelier, C; Istasse, L; Diez, M

    2004-04-01

    The aim of this study was (i) to evaluate the effect of ovariectomy on daily energy requirement in Beagle dogs, and (ii) to evaluate the effects of ad libitum feeding with a high energy diet on energy consumption, body weight gain and blood metabolites in these spayed dogs. Four young adult female Beagle dogs were used. Ovariectomy induced a significant decrease of daily energy requirement in dogs. Ad libitum feeding, initiated 6 months after spaying, induced a significant increase in consumption in spayed dogs. This overconsumption was greatest during the first month of ad libitum feeding but continued for the entire 4 months of this period. When fed ad libitum, dogs gained excess body weight without significant effect on plasma cholesterol, triglycerides, glucose and insulin, at short term. These data suggest that energy intake should be strictly controlled to avoid excess weight gain in spayed dogs. PMID:15059235

  3. Experimental therapeutic effect of combined cytokines on beagle dogs exposed to 4.5 Gy γ-rays

    International Nuclear Information System (INIS)

    Objective: To evaluate the effects of combined administration of recombinant human interleukin-11 (rhIL-11), recombinant human G-CSF (rhG-CSF) and recombinant human interleukin-2 (rhIL-2) on acute radiation sickness (ARS) beagles. Methods: Sixteen beagle were irradiated with 4.5 Gy 60Co γ-rays to establish ARS models, and were divided into irradiation control group, supportive care group and combined cytokines treatment group. After irradiation irradiation control group was given no treatment, the dogs in supportive care group received purely symptomatic treatment, while combined cytokines treatment group received rhIL-11 50 μg/(kg·d) subcutaneously (0-14 d) and rhIL-2 1 x 106 U/d(29-43 d) besides symptomatic treatment. Manifestation and characteristics of ARS (authors)

  4. Effects of estrogen on cerebrovascular function: age-dependent shifts from beneficial to detrimental in small cerebral arteries of the rat.

    Science.gov (United States)

    Deer, Rachel R; Stallone, John N

    2016-05-15

    In the present study, interactions of age and estrogen in the modulation of cerebrovascular function were examined in small arteries vasoconstriction was attenuated in ovariectomized + estrogen-replaced, multigravid adult rats (5-6 mo; MAE) but potentiated in older ovariectomized + estrogen-replaced, reproductively senescent rats (12-14 mo; RSE). SC560 and NS398 reduced reactivity similarly in ovariectomized multigravid adult rats (5-6 mo; MAO) and ovariectomized reproductively senescent rat (12-14 mo; RSO). In MAE, reactivity to VP was reduced to a greater extent by SC560 than by NS398; however, in RSE, this effect was reversed. VP-stimulated PGI2 was increased by estrogen, yet reduced by age. VP-stimulated TXA2 was increased by estrogen and age in RSE but did not differ in MAO and RSO. Taken together, these data reveal that the vascular effects of estrogen are distinctly age-dependent in F rats. In younger MA, beneficial and protective effects of estrogen are evident (decreased vasoconstriction, increased dilator prostanoid function). Conversely, in older RS, detrimental effects of estrogen begin to be manifested (enhanced vasoconstriction and CP function). These findings may lead to age-specific estrogen replacement therapies that maximize beneficial and minimize detrimental effects of this hormone on small cerebral arteries that regulate blood flow. PMID:26993224

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

    OpenAIRE

    Hyung-Joo Choi; Dong-Yeol Lee; Tae-Woo Kim

    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...

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

    OpenAIRE

    LIU, HUI; Wang, Ya-Jing; YANG, Lei; Zhou, Mei; Jin, Man-Wen; Xiao, Guo-Sheng; Wang, Yan; Sun, Hai-Ying; Li, Gui-Rong

    2016-01-01

    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 effic...

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

    OpenAIRE

    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...

  8. Age-Dependent Reductions in Mitochondrial Respiration are Exacerbated by Calcium in the Female Rat Heart

    OpenAIRE

    Hunter, J. Craig; Machikas, Alexandra M.; Korzick, Donna H.

    2012-01-01

    Cardiovascular disease mortality increases rapidly following menopause by poorly defined mechanisms. Since mitochondrial function and Ca2+ sensitivity are important regulators of cell death following myocardial ischemia, we sought to determine if aging and/or estrogen deficiency (ovx) increased mitochondrial Ca2+ sensitivity. Mitochondrial respiration was measured in ventricular mitochondria isolated from adult (6mo; n=26) and aged (24mo; n=25), intact or ovariectomized female rats using the ...

  9. Absorbed dose distribution patterns in the beagle thorax after inhalation of 90Sr--90Y fused clay particles. II

    International Nuclear Information System (INIS)

    This experiment was designed to examine absorbed dose patterns in the Beagle dog thorax after inhalation of polydisperse fused montmorillonite clay particles labeled with 90Sr-90Y. Sixteen dogs were exposed nose-only to achieve initial lung burdens of 91 to 200 μCi. Dogs are being serially sacrificed and photographic data and autoradiographic data produced for a series of parallel planes approximately 1 cm apart through the thorax. Data analysis will include definition of absorbed dose patterns in the Beagle thorax at 8 days, 64 days, 1 year, 2 years, and 3 years post-exposure. To date, 8-day, 64-day, and 1-year animals have been sacrificed and partially analyzed. The result of this experiment will be a better understanding of deposition and absorbed dose patterns and allow a better correlation between absorbed dose and biological response for Beagle dogs exposed to relatively insoluble aerosols contaminated by energetic beta-emitting radionuclides. In addition, results will allow quantitating anomalies in deposition patterns, such as the striated pattern near ribs previously observed in this laboratory. (U.S.)

  10. Preventive Effects of Flaxseed and Sesame Oil on Bone Loss in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    S. Boulbaroud

    2008-01-01

    Full Text Available A study was designed to examine the effects of dietary flaxseed oil (FO and sesame oil (SO which are rich successively in n-3 and (n-9 and n-6 on biochemical parameters and histological status of bone. Sixty-four 90-day-old female wistar rats were randomly assigned to 6 groups: sham-operated rat (sham+ control diets, ovariectomized rat (OVX+ control diets, OVX+ 7% FO, OVX+ 7% SO, OVX+ 10% FO, OVX+ 10% SO. After 4 weeks of treatments, rats were euthanized; blood and tissues were collected for analyses. Markers of bone formation which is alkaline phosphatase activity and markers of bone resorption which is tartrate resistant acid phosphatase activity were measured. Present results showed that OVX increased significantly ALP and TRAP activity and the examination of bone tissue showed disruptive and lytic bone trabeculae. Animals fed 10% FO and 10% SO of fat reduced these parameters and improved bone microarchitecture. Whereas, there was no improvement in biochemical and histological states in OVX rats that received 7% of PUFAs successively provided from FO and SO diets. In conclusion, our results are encouraging because they suggest that PUFAs intake may help to prevent osteoporosis associated with estrogens deficiency. However, further studies are needed to determine the mechanism by which a diet rich in n-3 or lignans modulate bone tissue.

  11. Adenoviral vector-mediated overexpression of osteoprotegerin accelerates osteointegration of titanium implants in ovariectomized rats.

    Science.gov (United States)

    Yin, G; Chen, J; Wei, S; Wang, H; Chen, Q; Lin, Y; Hu, J; Luo, E

    2015-08-01

    This study investigated the efficacy of human osteoprotegerin (hOPG) transgene to accelerate osteointegration of titanium implant in ovariectomized (OVX) rats. Bone marrow stromal cells transduced with Ad-hOPG-EGFP could sustainedly express hOPG. Osteoclast precursor RAW264.7 cells treated by the hOPG were examined by tartrate-resistant acid phosphatase (TRAP) staining and bone slice resorption assay. The results showed differentiation and function of osteoclasts were significantly suppressed by hOPG in vitro. Ad-hOPG-EGFP was locally administered to the bone defect prior to implant placement in OVX and sham rats. After 3, 7, 28 days of implantation, the femurs were harvested for molecular and histological analyses. Successful transgene expression was confirmed by western blot and cryosectioning. A significant reduction in TRAP+ numbers was detected in Ad-hOPG-EGFP group. Real-time reverse transcriptase-PCR examination revealed that hOPG transgene markedly diminished the expression of cathepsin K and receptor activator for nuclear factor-κ B ligand in vivo. The transgene hOPG modification revealed a marked increasing osteointegration and restored implant stability in OVX rats (Prats. Osteoprotegerin gene therapy may be an effective strategy to osteointegration of implants under osteoporotic conditions. PMID:25871826

  12. Estrogen Replacement Reduces Oxidative Stress in the Rostral Ventrolateral Medulla of Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Fan Hao

    2016-01-01

    Full Text Available Cardiovascular disease prevalence rises rapidly after menopause, which is believed to be derived from the loss of estrogen. It is reported that sympathetic tone is increased in postmenopause. The high level of oxidative stress in the rostral ventrolateral medulla (RVLM contributes to increased sympathetic outflow. The focus of this study was to determine if estrogen replacement reduces oxidative stress in the RVLM and sympathetic outflow in the ovariectomized (OVX rats. The data of this study showed that OVX rat increased oxidative stress in the RVLM and sympathetic tone; estrogen replacement improved cardiovascular functions but also reduced the level of oxidative stress in the RVLM. These findings suggest that estrogen replacement decreases blood pressure and sympathoexcitation in the OVX rats, which may be associated with suppression in oxidative stress in the RVLM through downregulation of protein expression of NADPHase (NOX4 and upregulation of protein expression of SOD1. The data from this study is beneficial for our understanding of the mechanism of estrogen exerting cardiovascular protective effects on postmenopause.

  13. Pomegranate seed hydroalcoholic extract improves memory deficits in ovariectomized rats with permanent cerebral hypoperfusion /ischemia

    Directory of Open Access Journals (Sweden)

    Alireza Sarkaki

    2014-12-01

    Full Text Available Objective: Estrogen deficit following menopause results in cognitive behaviors impairment. Severity of these impairments in menopause women suffer with cerebral hypo perfusion/ischemia (HI cause the brain damage and neuronal death. This study aimed to evaluate the effects of pomegranate seed extract (PGSE on avoidance memories after permanent bilateral common carotid arteries occlusion (2CCAO in ovariectomized (OVX rats. Materials and Methods: Adult female Wistar rats were divided randomly into eight groups with 8 rats in each group: 1 Sham-operated for ovaries and 2CCAO (ShO; 2 OVX and sham operated for ischemia (OShI; 3-7 OVX with 2CCAO (OI received PGSE (100, 200, 400 and 800 mg/2ml/kg or normal saline, orally for 14 days (OI+E100, 200, 400, 800 or OI+Veh; 8 OShI received most effective dose of PGSE (200 and 400 mg/kg for passive and active avoidance memories respectively. Active and passive avoidance tasks were measured in Y-maze and two-way shuttle box respectively. Data were analyzed with one-way and RM-ANOVA followed by HSD post-hoc test. Results: Sensorimotor impaired in OShI+Veh and OI+Veh (P

  14. Pycnogenol® treatment inhibits bone mineral density loss and trabecular deterioration in ovariectomized rats

    Science.gov (United States)

    Huang, Gangyong; Wu, Jianguo; Wang, Siqun; Wei, Yibing; Chen, Feiyan; Chen, Jie; Shi, Jingsheng; Xia, Jun

    2015-01-01

    Context: Pycnogenol® extracted from French maritime pine bark (Pinus pinaster Ait. subsp. atlantica) is functional for its antioxidant activity. Objective: To investigate the effects of Pycnogenol® on bone mineral density (BMD), trabecular microarchitecture and bone metabolism in ovariectomized (OVX) rats. Materials and methods: Thirty Sprague-Dawley rats were randomized into 3 groups: SHAM group (sham-operated rats), OVX group (OVX rats), and treatment group (OVX rats supplemented with 40 mg/kg Pycnogenol® by oral gavage). Serum levels of procollagen type I N-terminal propeptide (PINP), alkaline phosphatase (ALP) and minerals were detected at the end of 9 weeks of gavage. Deoxypyridinoline/creatinine (DPYD/Cr) and N-telopeptide of type I collagen/creatinine (NTX/Cr) rate in urine were also calculated. Left femora were collected for BMD determination, and the right distal femora were made into undecalcified specimens for histomorphometry analysis. Results: At the end of study, PINP level, DPYD/Cr and NTX/Cr rate were significantly increased, and femoral BMD were dramatically decreased in OVX group compared with SHAM group (P Pycnogenol® (40 mg/kg) can inhibit aggravated bone resorption, prevent BMD loss, and restore the impaired trabecular microarchitecture in OVX rats after 9-week-intervention. PMID:26379883

  15. Effects of diet-induced hypercholesterolemia on amyloid accumulation in ovariectomized mice

    Indian Academy of Sciences (India)

    V Kaliyamurthi; V Thanigavelan; G Victor Rajamanickam

    2012-12-01

    A central hypothesis in the study of Alzheimer’s disease (AD) is the accumulation and aggregation of -amyloid peptide (A). Recent epidemiological studies suggest that patients with elevated cholesterol and decreased estrogen levels are more susceptible to AD through A accumulation. To test the above hypothesis, we used ovariectomized with diet-induced hypercholesterolemia (OVX) and hypercholesterolemia (HCL) diet alone mouse models. HPLC analysis reveals the presence of beta amyloid in the OVX and HCL mice brain. Congo red staining analysis revealed the extent of amyloid deposition in OVX and hypercholesterolemia mice brain. Overall, A levels were higher in OVX mice than in HCL. Secondly, estrogen receptors (ER) were assessed by immunohistochemistry and this suggested that there was a decreased expression of ER in OVX animals when compared to hypercholesterolemic animals. A was quantified by Western blot and ELISA analysis. Overall, Aβ levels were higher in OVX mice than in HCL mice. Our experimental results suggested that OVX animals were more susceptible to AD with significant increase in A peptide.

  16. The Effect of Weight-Bearing Exercise on the Strength of Femur Bone in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    GH Sharifi

    2011-08-01

    Full Text Available Introduction & Objective: Fractures due to osteoporosis after menopause in women is widespread. Osteoporosis may occur in case of inadequate lack of physical activity .The aim of this study was to determine the effect of running training on femur bone strength in ovariectomized rats. Materials & Methods Forty matured Sprague Dawley rats were chosen for this study. A group of 10 were killed randomly to measure their initial femur strength. The remaining rats had ovarian surgery. After three months, in order to reach menopause period, they were randomly divided into 3 groups, including pre test, running training and control groups. The running training program was carried out for one hour a day, five days a week, for eight weeks. Femur bone strength was measured by HOUNSFIELD system. Data was analyzed by using one-way analysis of variance and dependent T- tests by the SPSS software. Results: Results of this study showed that ovariectomy leads to significant decrease of femur bone strength. On the other hand the eight weeks running training lead to significant increase of femur bone strength. Conclusion: The results of this study suggest that life style is important factors in preventing of osteoporosis and running training program had an inhibitory or reversal effect on decrease of menopause-induced femur bone strength.

  17. The Effects of Combined Treatment with Naringin and Treadmill Exercise on Osteoporosis in Ovariectomized Rats.

    Science.gov (United States)

    Sun, Xiaolei; Li, Fengbo; Ma, Xinlong; Ma, Jianxiong; Zhao, Bin; Zhang, Yang; Li, Yanjun; Lv, Jianwei; Meng, Xinmin

    2015-01-01

    Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increased the risk of fracture. Previous studies have demonstrated the effect of naringin (NG) or treadmill exercise (EX) on osteoporosis, however, reports about effects of NG plus EX on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with naringin and treadmill exercise on osteoporosis in ovariectomized (OVX) rats. Three months after bilateral ovariectomy, Seventy-five rats were randomly assigned to the following treatment groups: OVX, sham-operated (SHAM), NG, EX, or NG plus EX treatment. Treatments were administered for 60 days. Bone metabolism, bone mineral density, trabecular bone parameters, immunohistochemistry, and the bone strength were evaluated. Compared to the OVX groups, all treatments increased bone volume (BV/TV), trabecula number (Tb.N), trabecula thickness (Tb.Th), bone mineral density (BMD), and mechanical strength. NG + EX showed the strongest effects on BV/TV, Tb.Th, and biomechanical strength. Additionally, decreased C-terminal telopeptides of type I collagen (CTX-1) and enhanced osteocalcin (OCN) expression were observed in the NG + EX group. The present study demonstrates that the NG + EX may have a therapeutic advantage over each monotherapy for the treatment of osteoporosis. PMID:26260240

  18. Effects of Obesity on Bone Mass and Quality in Ovariectomized Female Zucker Rats

    Directory of Open Access Journals (Sweden)

    Rafaela G. Feresin

    2014-01-01

    Full Text Available Obesity and osteoporosis are two chronic conditions that have been increasing in prevalence. Despite prior data supporting the positive relationship between body weight and bone mineral density (BMD, recent findings show excess body weight to be detrimental to bone mass, strength, and quality. To evaluate whether obesity would further exacerbate the effects of ovariectomy on bone, we examined the tibiae and fourth lumbar (L4 vertebrae from leptin receptor-deficient female (Leprfa/fa Zucker rats and their heterozygous lean controls (Leprfa/+ that were either sham-operated or ovariectomized (Ovx. BMD of L4 vertebra was measured using dual-energy X-ray absorptiometry, and microcomputed tomography was used to assess the microstructural properties of the tibiae. Ovariectomy significantly (P<0.001 decreased the BMD of L4 vertebrae in lean and obese Zucker rats. Lower trabecular number and greater trabecular separation (P<0.001 were also observed in the tibiae of lean- and obese-Ovx rats when compared to sham rats. However, only the obese-Ovx rats had lower trabecular thickness (Tb.Th (P<0.005 than the other groups. These findings demonstrated that ovarian hormone deficiency adversely affected bone mass and quality in lean and obese rats while obesity only affected Tb.Th in Ovx-female Zucker rats.

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

    International Nuclear Information System (INIS)

    During 1963-1968, 20 young adult Beagle dogs were given a single intravenous injection of 224Ra that was unintentionally contaminated with 210Pb and 228Th. All of these dogs have died, eight with bone sarcomas. In addition, 128 Beagle dogs were given purified 224Ra in one, ten or fifty weekly injections during 1977-1979. The acute lethal dosage (LD50) for a single injection was about 400 kBq 224Ra/kg (11 μCi 224Ra/kg). As of September 14, 1987, at the highest skeletal dose of 3 Gy from purified 224Ra, bone sarcomas occurred in 5 of 6 dogs at an average ± SD of 2069 ± 302 days after the start of injections (no survivors), in 4 of 6 dogs at 2485 ± 1,110 days after the start of 10 injections (healthy survivor) and in 1 of 8 dogs at 3066 days after a single injection (3 healthy survivors). At 3 Gy the toxicity of 224Ra relative to 239Pu, based on the ratio of skeletal doses at equal tumor appearance times, was 1.0 for 50 injections of 224Ra, 0.7 for 10 injections, and 0.4 for one injection. In contrast, the effectiveness per Gy of a 224Ra-equivalent dose from a single injection of 224Ra contaminated with 228Th and 210Pb was equal to that from 239Pu, assuming that the 224Ra-equivalent dose equaled the 224Ra dose plus the 228Th dose pus 0.1 of the 210Pb dose. A possible explanation is that protracted irradiation from the 1.91-yr half-life 228Th and the 22.3-yr half-life 210Pb may have 'activated' residual damage from the short-lived, 3.62 day half-life 224Ra, possibly by stimulating the division of damaged stem cells to replace the bone cells killed by the protracted alpha particle irradiation. An important spin off from the study is experimental support for the assumption that the bone sarcoma effectiveness for 210Pb is similar to that from long-lived, 1600 yr half-life 226Ra. (author)

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

    International Nuclear Information System (INIS)

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

  1. Effect of moderate treadmill exercise on some physiological parameters in untrained Beagle dogs.

    Science.gov (United States)

    Piccione, Giuseppe; Casella, Stefania; Panzera, Michele; Giannetto, Claudia; Fazio, Francesco

    2012-01-01

    The aim of the present study was to evaluate the modifications of some physiological parameters during moderate treadmill exercise in seven healthy Beagle dogs. All animals were submitted to treadmill exercise consisting of walking (15 min), trotting (20 min) and walking (10 min). At every step, rectal temperature (RT) was measured, and the mean heart rate (HR) was assessed. Venous blood samples were collected immediately before starting the treadmill exercise session (at rest), after the end of walking (15 min), trotting (20 min) and walking (10 min), and after 30 min of passive recovery. For immediate assessment of lactate and glucose concentration, blood was analyzed with portable blood lactate and blood glucose analyzers, respectively. Blood was also transferred into sterile glass tubes containing K(3)-ethylenediaminetetraacetic acid (K(3)-EDTA) for evaluation of red blood cells (RBC), white blood cells (WBC), platelets (PLT), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). One-way repeated measures analysis of variance (ANOVA) showed a significant effect of treadmill exercise (P<0.05) on RT, HR, lactate, glucose, RBC and Hct. Considering these significant variations, the knowledge of RT, HR, glucose and lactate concentrations, RBC, and Hct, the most suitable and sensitive indicators of response to treadmill exercise in untrained dogs, is essential in order to evidence the individual levels of exercise tolerance, to investigate exercise-related problems and to design specific and individual treadmill protocols. PMID:23095814

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  5. Nasal carcinomas in beagle dogs after inhalatioon of relatively soluble forms of beta-emitting radionuclides

    International Nuclear Information System (INIS)

    Beagle dogs were exposed by inhalation to relatively soluble forms of three beta-emitting radionuclides and are being held for life span observation to evaluate hazards associated with nuclear power production. Dogs were exposed to graded activity levels of 91YCl3, 144CeCl3 or 90SrCl2. With 91YCl3 and 144CeCl3, significant radiation dose was delivered to liver, respiratory tract, and skeleton. With 90SrCl2, the dose was essentially to skeleton. Nasal cavity squamous cell carcinomas have been the most frequent neoplasms in the 91Y and one of the most frequent in the 144Ce study while relatively few have been seen after 90Sr exposure. Also one nasal cavity hemangiosarcoma was seen in the 144Ce study. The 90Sr-exposed dogs have survived longer after exposure and have higher skeletal radiation doses than do the dogs exposed to 91Y or 144Ce. The greater incidence of nasal carcinomas can be explained by the finding of high concentrations of the lanthanides, 91Y and 144Ce, associated with the nasal turbinate epithelium

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

    International Nuclear Information System (INIS)

    Beagles that inhaled 239PuO2, 238PuO2, or 239Pu(NO3)4, in dose-level groups of 20 dogs, with initial lung burdens of ∼2, 15, 70, 300, 1100, or 5500 nCi, are now 11, 9, or 5 years postexposure. Lung tumors, bone tumors, and radiation pneumonitis, the plutonium-exposure-related causes of death observed to date, have occurred in the two, three, and four highest dose-level groups exposed to 238PuO2, 239Pu(NO3)4, and 239PuO2, respectively. No plutonium-exposure-related deaths have thus far been observed in dose-level groups exposed to less than ∼40 times the current maximum permissible lung dose for a plutonium worker. Plutonium-exposure-related effects not directly related to the cause of death include chronic lymphopenia, chronic neutropenia, sclerosis of the tracheobronchial lymph nodes, focal radiation pneumonitis, adenomatous hyperplasia in the liver, and dystrophic osteolytic lesions in the skeleton. No plutonium-exposure-related effects have thus far been observed in dose-level groups that received less than ∼15 times the current maximum permissible lung dose for a plutonium worker. 10 refs., 5 figs., 4 tabs

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

    International Nuclear Information System (INIS)

    The temporal and spatial distributions of 238Pu have been measured during the course of a dose-response study of the biological effects of inhaled 238PuO2 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 238PuO2 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 238Pu 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

  8. Study on toxicity of danshensu in beagle dogs after 3-month continuous intravenous infusion.

    Science.gov (United States)

    Li, Guisheng; Gao, Yonglin; Li, Shenjun; Li, Chunmei; Zhu, Xiaoyin; Li, Min; Liu, Zhifeng

    2009-09-01

    Danshensu (3-(3,4-dihydroxyphenyl) lactic acid), a natural phenolic acid, is isolated from root of Salvia miltiorrhiza, and is widely used as a traditional Chinese medicine for treatment of various cardiovascular diseases. In the present study, toxicity of danshensu was evaluated in male and female dogs after 3-month continuous intravenous infusion. Beagle dogs were treated with danshensu at doses of 17, 50, and 150 mg/kg/day, and observed for 90 days followed by recovery periods. Measurements included clinical observations, body weight, food consumption, temperature, electro-cardiography (EGC), hematology, blood chemistry, urinalysis, gross necropsy, organ weight, and histopathology. No significant adverse effects on these parameters were observed. The only treatment-related finding was a hard knot at injection site observed in the 150 mg/kg group after 2-3 weeks continuous administration, and returned to normal after 3-4 days withdrawal. From these results, it might be concluded that danshensu did not produce any significant cumulative toxicity at the doses administered, as reflected by the various parameters investigated. PMID:19778246

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

    Science.gov (United States)

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

    2016-08-01

    Aralia elata Seem. (A. elata) is a traditional Chinese medicine to treat some diseases. This investigation aims to evaluate the pharmaceutical safety of the ethanol extract of A. elata leaves, namely ethanol leaves extract (ELE), in Beagle dogs. In sub-chronic oral toxicity study, dogs were treated with the ELE at doses of 50, 100 and 200 mg/kg for 12 weeks and followed by 4 weeks recovery period. During experimental period, clinical signs, mortality, body temperature, food consumption and body weight were recorded. Analysis of electrocardiogram, urinalysis, ophthalmoscopy, hematology, serum biochemistry, organ weights and histopathology were performed. The results showed that both food consumption and body weight significantly decreased in high-dose group. Treatment-related side effects and mortality were observed in high-dose female dogs. Some parameters showed significant alterations in electrocardiogram, urinalysis, serum biochemistry and relative organ weights. These alterations were not related to dose or consistent across gender, which were ascribed to incidental and biological variability. The findings in this study indicated that the no-observed adverse effect level (NOAEL) of the ELE was 100 mg/kg in dogs and provided a vital reference for selecting a safe application dosage for human consumption. PMID:27156779

  10. Effect of inhaled 90Y in fused clay particles on the gastrointestinal tract of beagle dogs

    International Nuclear Information System (INIS)

    Ten Beagle dogs were exposed by inhalation to aerosols of 90Y in fused clay particles to study the radiation dose to the gastrointestinal (GI) tract and effects resulting from clearance of the upper respiratory tract after the deposition of high initial body burdens of inhaled 90Y. Focal colonic lesions were found in 2 dogs, 8 and 12 days after inhalation of 90Y which resulted in transient GI burdens (GIB) of 18 and 34 mCi. Similar, but less severe, lesions were found in 2 dogs sacrificed 27 days after exposure with GIBs of 18 and 32 mCi. No GI lesions were found in 6 dogs with GIBs of 9 to 18 mCi. Two of the 10 dogs had thermoluminescent dosimeters surgically implanted in the GI tract lumen and submucosa. Highest radiation doses were measured in the colon. One dog, with measured doses to the colon of 3200 to 5700 rads, had focal colitis when sacrificed 8 days after exposure. The other dog, with doses to colon of 1000 to 2800 rads had no GI lesions at sacrifice 8 days after exposure. Although focal colitis was found, no dogs died due primarily to GI injury. Other significant findings were nasal dermatitis and radiation pneumonitis. The latter was more severe and life threatening than the GI injury. (U.S.)

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

    International Nuclear Information System (INIS)

    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 μm, a CMD of 0.25 μm and a CML < 5 μm. 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 μm, a CMD of 0.15 μm and a CML of 5.4 μ. 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

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

    A 10-year-old castrated male Beagle dog was presented with a 2-month history of intermittent vomiting and abdominal pain. The dog was referred to the Veterinary Teaching Hospital at Iwate University for further evaluation, and a splenic tumour was suspected on the basis of ultrasonography and computed tomography. Surgery identified a large, solid, light-pink mass on the greater omentum with blood-coloured ascites in the abdominal cavity, and resection was performed. Microscopically, the mass comprised spindle-shaped tumour cells and scattered osteoclast-like giant cells. Most spindle-shaped cells were positive for vimentin, desmin, and smooth muscle actin (α-SMA), whereas osteoclast-like giant cells were positive only for vimentin. On the basis of histopathological and immunohistochemical findings, a diagnosis of leiomyosarcoma was made. To the best of our knowledge, this represents the first report of leiomyosarcoma associated with osteoclast-like giant cells developing from the greater omentum in a dog. PMID:27342093

  15. The effects of raloxifene treatment on oxidative status in brain tissues and learning process of ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Süreyya Osmanova

    2011-01-01

    Full Text Available Background: The effects of estrogene on central nervous system are still controversial. Objective: We aimed to investigate the effects of raloxifene on the antioxidant enzyme [superoxide dismutase (SOD and catalase (CAT] activities and malondialdehyde (MDA levels in brain homogenates of ovariectomized female rats and its effect on cognitive process of learning.Materials and Methods: Female Sprague Dawley rats (n=24 were divided into three groups. Three weeks after ovariectomy; nonovariectomized group (control group (n=8 was given physiological saline (SP as placebo. First ovariectomized group (n=8 received raloxifene 1mg/kg dissolved in a 1% solution of carboxymethylcellulose (CMC subcutaneusly (sc and second group of ovariectomized rats were given 1 % CMC 1mg/kg (sc every day for 14 days. Learning behaviors of rats were evaluated in active avoidence cage with using sound and electrical stimulation. The levels of oxidative stress (MDA and antioxidant enzymes (SOD, CAT in different regions of the brain homogenates were compared between three groups of decapitated rats.Results: Raloxifene had a significant attenuating effect on the levels of MDA in brain tissues suggesting raloxifene’s effect against lipid peroxidation at the end of training days. With the comparison of brain regions, cortex showed the highest average activity of SOD and CAT and cerebellum had the lowest average levels for both. Its effects on learning and cognitive process with active avoidence task were considered insignificant.Conclusion: Raloxifene treatment may have preventive effects for the brain against oxidative stress and lipid peroxidation in rats

  16. Effect of 17beta-estradiol or alendronate on the bone densitometry, bone histomorphometry and bone metabolism of ovariectomized rats.

    Science.gov (United States)

    da Paz, L H; de Falco, V; Teng, N C; dos Reis, L M; Pereira, R M; Jorgetti, V

    2001-08-01

    The objective of the present study was to evaluate the effect of 17beta-estradiol or alendronate in preventing bone loss in 3-month-old ovariectomized Wistar rats. One group underwent sham ovariectomy (control, N = 10), and the remaining three underwent double ovariectomy. One ovariectomized group did not receive any treatment (OVX, N = 12). A second received subcutaneous 17beta-estradiol at a dose of 30 microg/kg for 6 weeks (OVX-E, N = 11) and a third, subcutaneous alendronate at a dose of 0.1 mg/kg for 6 weeks (OVX-A, N = 8). Histomorphometry, densitometry, osteocalcin and deoxypyridinoline measurements were applied to all groups. After 6 weeks there was a significant decrease in bone mineral density (BMD) at the trabecular site (distal femur) in OVX rats. Both alendronate and 17beta-estradiol increased the BMD of ovariectomized rats, with the BMD of the OVX-A group being higher than that of the OVX-E group. Histomorphometry of the distal femur showed a decrease in trabecular volume in the untreated group (OVX), and an increase in the two treated groups, principally in the alendronate group. In OVX-A there was a greater increase in trabecular number. An increase in trabecular thickness, however, was seen only in the OVX-E group. There was also a decrease in bone turnover in both OVX-E and OVX-A. The osteocalcin and deoxypyridinoline levels were decreased in both treated groups, mainly in OVX-A. Although both drugs were effective in inhibiting bone loss, alendronate proved to be more effective than estradiol at the doses used in increasing bone mass. PMID:11471040

  17. Long-term effects of alendronate on fracture healing and bone remodeling of femoral shaft in ovariectomized rats

    OpenAIRE

    Fu, Ling-jie; Tang, Ting-ting; Hao, Yong-qiang; Dai, Ke-Rong

    2013-01-01

    Aim: To investigate the long-term effects of alendronate (Aln), a widely used oral bisphosphonate, on fracture healing and bone remodeling in ovariectomized rats. Methods: Adult female SD rats underwent ovariectomy, and then bilateral femoral osteotomy at 12 weeks post-ovariectomy. From d 2 post-ovariectomy, the animals were divided into 3 groups, and treated with Aln (3 mg·kg−1·d−1, po) for 28 weeks (Aln/Aln), Aln for 12 weeks and saline for 16 weeks (Aln/Saline) or saline for 28 weeks (Sali...

  18. A Kampo Medicine, Boi-ogi-to, Inhibits Obesity in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Jun-ichi Yamakawa

    2010-01-01

    Full Text Available In women facing menopause, end of menstrual activity is accompanied by lower levels of estrogen and gradual weight gain. Postmenopausal weight gain sounds an alarm for women's health and may lead to hyperlipidemia, a lipid increase and glucose intolerance. These phenomena are connected to lifestyle-related diseases such as hypertension, type II diabetes mellitus, arteriosclerosis and metabolic syndrome, making it essential to prevent weight gain in women. A Kampo medicine, Boi-ogi-to, is traditionally used to treat obese conditions, but the mechanism has not yet been investigated. In this experiment, we tested the antiobesity properties of Boi-ogi-to in ovariectomized rats by measuring changes of serum cytokine levels and adipocytokines in fat cells. After treatment with this extract for 6 weeks (20-week-old rats, we found that there was a significant weight decrease in rats treated with Boi-ogi-to as compared with that in the control group. Serum tumor necrosis factor (TNF-α levels increased significantly in a dose-dependent manner. Gene expression of adipose tissue in uterus also dose dependently showed a significant increase of TNF-α levels, suggesting that secretion of TNF-α by fat cells might play a role in the ability of Boi-ogi-to to inhibit weight gain. While peroxisome proliferators-activated receptor-γ and adiponectin levels did not show a significant difference as compared with those in the control, levels of mRNA expression showed a tendency to increase dose dependently. Resistin did not show any significant change. These results suggest that Boi-ogi-to might be useful for the prevention of obesity that occurs in women with reduction of estrogen.

  19. Effects of multi-deficiencies-diet on bone parameters of peripheral bone in ovariectomized mature rat.

    Directory of Open Access Journals (Sweden)

    Thaqif El Khassawna

    Full Text Available Many postmenopausal women have vitamin D and calcium deficiency. Therefore, vitamin D and calcium supplementation is recommended for all patients with osteopenia and osteoporosis. We used an experimental rat model to test the hypothesis that induction of osteoporosis is more efficiently achieved in peripheral bone through combining ovariectomy with a unique multi-deficiencies diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus. 14-week-old Sprague-Dawley rats served as controls to examine the initial bone status. 11 rats were bilaterally ovariectomized (OVX and fed with multi-deficiencies diet. Three months later the treated group and the Sham group (n = 8 were euthanized. Bone biomechanical competence of the diaphyseal bone was examined on both, tibia and femur. Image analysis was performed on tibia via µCT, and on femur via histological analysis. Lower torsional stiffness indicated inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal metaphyseal region of the tibia showed a diminished bone tissue portion to total tissue in the µCT despite the increased total area as evaluated in both µCT and histology. Cortical bone showed higher porosity and smaller cross sectional thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area and elevated serum level of RANKL exhibited the unbalanced cellular interaction in bone remodeling in the OVX+Diet rat after 3 month of treatment. Interestingly, more adipose tissue area in bone marrow indicated an effect of bone loss similar to that observed in osteoporotic patients. Nonetheless, the presence of osteoid and elevated serum level of PTH, BGP and Opn suggest the development of osteomalacia rather than an osteoporosis. As the treatment and fracture management of both osteoporotic and osteomalacia patients are clinically overlapping, this study provides a preclinical animal model to be utilized in local supplementation of minerals, drugs

  20. Sclerostin antibody prevented progressive bone loss in combined ovariectomized and concurrent functional disuse.

    Science.gov (United States)

    Zhang, Dongye; Hu, Minyi; Chu, Timothy; Lin, Liangjun; Wang, Jingyu; Li, Xiaodong; Ke, Hua Zhu; Qin, Yi-Xian

    2016-06-01

    Osteoporosis is characterized by low bone mass and compromised trabecular architecture, and is commonly occurred in post-menopausal women with estrogen deficiency. In addition, prolonged mechanical unloading, i.e., long term bed rest, can exaggerate the bone loss. Sclerostin is a Wnt signaling antagonist and acts as a negative regulator for bone formation. A sclerostin-neutralizing antibody (Scl-Ab) increased bone mineral density in women with postmenopausal osteoporosis and healthy men. The objective of this study was to characterize the condition of bone loss in ovariectomized (OVX) rats with concurrent mechanical unloading and evaluate the effect of sclerostin antibody treatment in mitigating the prospective severe bone loss conditions in this model. Four-month-old OVX- or sham-operated female SD rats were used in this study. They were subjected to functional disuse induced by hind-limb suspension (HLS) or free ambulance after 2days of arrival. Subcutaneous injections with either vehicle or Scl-Ab at 25mg/kg were made twice per week for 5weeks from the time of HLS. μCT analyses demonstrated a significant decrease in distal metaphyseal trabecular architecture integrity with HLS, OVX and HLS+OVX (bone volume fraction decreased by 29%, 71% and 87% respectively). The significant improvements of various trabecular bone parameters (bone volume fraction increased by 111%, 229% and 297% respectively as compared with placebo group) with the administration of Scl-Ab are associated with stronger mechanical property and increased bone formation by histomorphometry. These results together indicate that Scl-Ab prevented the loss of trabecular bone mass and cortical bone strength in OVX rat model with concurrent mechanical unloading. The data suggested that monoclonal sclerostin-neutralizing antibody represents a promising therapeutic approach for severe osteoporosis induced by estrogen deficiency with concurrent mechanical unloading. PMID:26868528

  1. Effect of swimming exercise on three-dimensional trabecular bone microarchitecture in ovariectomized rats.

    Science.gov (United States)

    Ju, Yong-In; Sone, Teruki; Ohnaru, Kazuhiro; Tanaka, Kensuke; Fukunaga, Masao

    2015-11-01

    Swimming is generally considered ineffective for increasing bone mass in humans, at least compared with weight-bearing sports. However, swimming exercise has sometimes been shown to have a strong positive effect on bone mass in small animals. This study investigated the effects of swimming on bone mass, strength, and microarchitecture in ovariectomized (OVX) rats. OVX or sham operations were performed on 18-wk-old female Fisher 344 rats. Rats were randomly divided into four groups: sham sedentary (Sham-CON), sham swimming exercised (Sham-SWI), OVX sedentary (OVX-CON), and OVX swimming exercised (OVX-SWI). Rats in exercise groups performed swimming in a water bath for 60 min/day, 5 days/wk, for 12 wk. Bone mineral density (BMD) in right femurs was analyzed using dual-energy X-ray absorptiometry. Three-dimensional trabecular architecture at the distal femoral metaphysis was analyzed using microcomputed tomography (μCT). Geometrical properties of diaphyseal cortical bone were evaluated in the midfemoral region using μCT. The biomechanical properties of femurs were analyzed using three-point bending. Femoral BMD was significantly decreased following ovariectomy. This change was suppressed by swimming. Trabecular bone thickness, number, and connectivity were decreased by ovariectomy, whereas structure model index (i.e., ratio of rod-like to plate-like trabeculae) increased. These changes were also suppressed by swimming exercise. Femurs displayed greater cortical width and maximum load in SWI groups than in CON groups. Together, these results demonstrate that swimming exercise drastically alleviated both OVX-induced decreases in bone mass and mechanical strength and the deterioration of trabecular microarchitecture in rat models of osteoporosis. PMID:26338454

  2. The determination of apoptosis rates on articular cartilages of ovariectomized rats with and without alendronate treatment.

    Science.gov (United States)

    Acar, Nuray; Balkarli, Huseyin; Soyuncu, Yetkin; Ozbey, Ozlem; Celik-Ozenci, Ciler; Korkusuz, Petek; Ustunel, Ismail

    2016-06-01

    Osteoporosis (OP) is a major health problem characterized by compromised bone strength. Osteoarthritis (OA) is a joint disease that progresses slowly and is characterized by breakdown of the cartilage matrix. Alendronate (ALN), a nitrogen-containing bisphosphonate (BIS), inhibits bone loss and increases bone mineralization, and has been used clinically for the treatment of OP. It is still controversial whether BIS is effective in inhibiting the progression of OA. Chondrocyte apoptosis has been described in both human and experimentally induced OA models. In our study we aimed to detect whether ALN could protect articular cartilage from degeneration and reduce apoptosis rates in experimentally OA induced rats. For this rats were ovariectomized (ovex), nine weeks after operation rats were injected 30 µg/kg/week ALN subcutaneously for six weeks. After six weeks articular cartilages were obtained. We did Safranin O staining and Mankin and Pritzker scorings to evaluate degeneration and investigated the expressions of p53, cleaved caspase 3, Poly ADP-ribose (PAR), Poly ADP-ribose polymerase 1 (PARP 1), and applied TUNEL technique to determine apoptotis rates. We found a significant decrease in glycosaminoglycan (GAG) amount and increased apoptosis which indicates damage on articular cartilages of ovex rats. GAG amount was higher and apoptosis rate was lower on articular cartilages of ALN treated ovex rats compared to the ovex group. In contrary to studies showing that early ALN treatment has a protective effect, our study shows late ALN treatment has a chondroprotective effect on articular cartilage since we treated rats nine weeks after ovariectomy. PMID:26631351

  3. Calcium phosphate cement delivering zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats

    International Nuclear Information System (INIS)

    Patients sustaining bony fractures frequently require the application of bone graft substitutes to fill the bone defects. In the meantime, anti-osteoporosis drugs may be added in bone fillers to treat osteoporosis, especially in postmenopausal women and the elderly. The effects of zoledronate-impregnated calcium phosphate cement (ZLN/CPC) on ovariectomized (OVX) rats were evaluated. OVX rats were implanted with ZLN/CPC, containing 0.025 mg ZLN in the greater omentum. Afterward the clinical sign of toxicity was recorded for eight weeks. The rats were sacrificed and blood samples were collected for hematology and serum bone turnover markers analyses. The four limbs of the rats were harvested and micro-computer tomography (micro-CT) scanning and bone ash analyses were performed. No clinical toxicity was observed in the treated rats. Compared to the OVX rats, levels of bone resorption markers (fragments of C-telopeptides of type I collagen) and bone formation markers (alkaline phosphatase and osteocalcin) decreased significantly in the treated rats. Osteopontin, which mediates the anchoring of osteoclasts to the mineral matrix of bones, also decreased significantly. Micro-CT scanning and histologic examinations of the distal femoral metaphyses showed that the cancellous bone architectures were restored, with a concomitant decrease in bone porosity. The bone mineral content in the bone ashes also increased significantly. This study indicates that ZLN-impregnated CPC reduces bone turnover rate and restores bone architecture in OVX rats. CPC may be an appropriate carrier to deliver drugs to treat osteoporosis, and this approach may also reduce rates of post-dosing symptoms for intravenous ZLN delivery. (paper)

  4. The Effect of Different Doses of Vitamin D Supplementation on Insulin Resistance in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Rastegar Hoseini

    2016-04-01

    Full Text Available Background and Aim: Type 2 diabetes mellitus (T2DM and vitamin D deficiency are both too common during menopause. Since the effect of different doses of vitamin D supplements on blood sugar, insulin concentration  and insulin resistance are unknown, the present study aimed at investigating the effects of different doses of the vitamin D supplements on visceral fat, blood sugar, insulin concentration,  and insulin resistance in ovariectomized rats. Materials and Methods: In this randomized experimental study, 32 female Wistar rats were divided into 4 equal groups  as follows: three groups . that received vitamin D supplements (high, moderate, and low dose and one control group. After 8 weeks of different doses of vitamin D supplementation plasma concentration of glucose, insulin and HOMA-IR were measured  in the three groups. The obtained data  was statistically analyzed by means of dependent t-test and ANOVA . at the significance level of P<0.05. Results: After a period of eight-week  intervention, body weight, BMI, waist circumference, visceral fat, insulin, blood glucose and HOMA-IR at high, moderate, and low doses of vitamin D supplementation were significantly lower than those in the control group (P<0.05. High dose of vitamin D compared with moderate and low doses significantly caused reduction in insulin, blood glucose, and HOMA-IR (P<0.001 for all three variables. Conclusion: The findings of the current study showed that a high dose of vitamin D causes significant improvements in FPG, insulin, and insulin resistance  evaluated by HOMA-IR. It was also found that adding vitamin D supplements can improve glucose control in menopause model of rats.

  5. Exercise training is an effective alternative to estrogen supplementation for improving glucose homeostasis in ovariectomized rats.

    Science.gov (United States)

    MacDonald, Tara L; Ritchie, Kerry L; Davies, Sarah; Hamilton, Melissa J; Cervone, Daniel T; Dyck, David J

    2015-11-01

    The irreversible loss of estrogen (specifically 17-β-estradiol; E2) compromises whole-body glucose tolerance in women. Hormone replacement therapy (HRT) is frequently prescribed to treat estrogen deficiency, but has several deleterious side effects. Exercise has been proposed as an HRT substitute, however, their relative abilities to treat glucose intolerance are unknown. Thirty ovariectomized (OVX) and 20 SHAM (control) rats underwent glucose tolerance tests (GTT) 10 weeks post surgery. Area under the curve (AUC) for OVX rats was 60% greater than SHAM controls (P = 0.0005). Rats were then randomly assigned to the following treatment groups: SHAM sedentary (sed) or exercise (ex; 60 min, 5×/weeks), OVX sed, ex, or E2 (28 μg/kg bw/day) for 4 weeks. OVX ex rats experienced a ~45% improvement in AUC relative to OVX sed rats, whereas OVX E2 underwent a partial reduction (17%; P = 0.08). Maximal insulin-stimulated glucose uptake in soleus and EDL was not impaired in OVX rats, or augmented with exercise or E2. Akt phosphorylation did not differ in soleus, EDL, or liver of any group. However, OVX ex and OVX E2 experienced greater increases in p-Akt Ser473 in VAT and SQ tissues compared with SHAM and OVX sed groups. Mitochondrial markers CS, COXIV, and core1 were increased in soleus posttraining in OVX ex rats. The content of COXIV was reduced by 52% and 61% in SQ of OVX sed and E2 rats, compared to SHAM controls, but fully restored in OVX ex rats. In summary, exercise restores glucose tolerance in OVX rats more effectively than E2. This is not reflected by alterations in muscle maximal insulin response, but increased insulin signaling in adipose depots may underlie whole-body improvements. PMID:26603453

  6. Micro-morphologic changes around biophysically-stimulated titanium implants in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Chang Ting-Ling

    2007-07-01

    Full Text Available Abstract Background Osteoporosis may present a risk factor in achievement of osseointegration because of its impact on bone remodeling properties of skeletal phsiology. The purpose of this study was to evaluate micro-morphological changes in bone around titanium implants exposed to mechanical and electrical-energy in osteoporotic rats. Methods Fifteen 12-week old sprague-dowley rats were ovariectomized to develop osteoporosis. After 8 weeks of healing period, two titanium implants were bilaterally placed in the proximal metaphyses of tibia. The animals were randomly divided into a control group and biophysically-stimulated two test groups with five animals in each group. In the first test group, a pulsed electromagnetic field (PEMF stimulation was administrated at a 0.2 mT 4 h/day, whereas the second group received low-magnitude high-frequency mechanical vibration (MECHVIB at 50 Hz 14 min/day. Following completion of two week treatment period, all animals were sacrificed. Bone sites including implants were sectioned, removed en bloc and analyzed using a microCT unit. Relative bone volume and bone micro-structural parameters were evaluated for 144 μm wide peri-implant volume of interest (VOI. Results Mean relative bone volume in the peri-implant VOI around implants PEMF and MECHVIB was significantly higher than of those in control (P P > .05 while the difference in trabecular-number among test and control groups was significant in all VOIs (P Conclusion Biophysical stimulation remarkably enhances bone volume around titanium implants placed in osteoporotic rats. Low-magnitude high-frequency MECHVIB is more effective than PEMF on bone healing in terms of relative bone volume.

  7. Effects of traditional Chinese medicines on serum lipid profiles and homocysteine in the ovariectomized rats.

    Science.gov (United States)

    Lee, Su-Chen; Chang, Shun-Jen; Tsai, Li-Yu

    2004-01-01

    To investigate the effects of the traditional Chinese medicines, kuei-lu-erh-hsien-chiao and chia-wei-hsiao-yao-san, on the cardiovascular systems of mimic menopausal rats, five groups were formed: group 1 (the control group) was given a sham operation and received distilled water, while groups 2, 3, 4 and 5 were ovariectomized and received distilled water, kuei-lu-erh-hsien-chiao, chia-wei-hsiao-yao-san and 17-beta-estradiol, respectively, for4 months. Our results demonstrated that the mean differences of the estrogen levels in groups 3 or 5 were significantly higher than those of group 2. These data suggest that there might be some estrogen-like substances in kuei-lu-erh-hsien-chiao. However, the function of these estrogen-like substances was unknown. The mean differences of the triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-C) levels, low-density lipoprotein cholesterol (LDL-C) levels, and the ratios of TC/HDL-C and LDL-C/HDL-C in groups 1, 3, 4 and 5 were not significantly different from those in group 2. The mean differences of the total cholesterol (TC) levels in group 5 were significantly higher than those in group 2 (p chia-wei-hsiao-yao-san declines the Hcy levels in OVX rats and does not affect the TC levels in these animals. In conclusion, our results indicate that chia-wei-hsiao-yao-san shows a more profound effect than 17-beta-estradiol in the prevention of atherosclerosis in these OVX rats. PMID:15481644

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    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

  10. Exercise training in ovariectomized rats stimulates estrogenic-like effects on expression of genes involved in lipid accumulation and subclinical inflammation in liver.

    Science.gov (United States)

    Pighon, Abdolnaser; Gutkowska, Jolanta; Jankowski, Marek; Rabasa-Lhoret, Remi; Lavoie, Jean-Marc

    2011-05-01

    We hypothesized that the reduction in liver fat accumulation known to occur with exercise training in ovariectomized (Ovx) rats is associated with reduced expression of genes involved in lipogenesis while favoring the expression of transcription factors regulating lipid oxidation. We also tested the hypothesis that liver fat accumulation in Ovx rats is associated with an increased gene expression of several inflammatory biomarkers and that exercise training would attenuate this response. Sprague-Dawley female rats (14 weeks of age) were randomly divided into 4 groups of sedentary sham-operated (Sham), Ovx, Ovx with 17β-estradiol (E2) supplementation using a pellet (0.72 mg; 0.012 mg/d) with a biodegradable carrier binder, and Ovx trained with endurance exercise. Endurance exercise training consisted of continuous running on a motor-driven rodent treadmill 5 times per week for 5 weeks. Fat accumulation in liver as well as in adipose fat depots was higher (P exercise training. Liver gene expressions of sterol regulatory element-binding protein 1-c, stearoyl coenzyme A desaturase 1 (and its protein content), carbohydrate response element binding protein, and acetyl-coenzyme A carboxylase were increased with estrogen withdrawal (P hepatic peroxisome proliferator-activated receptor α messenger RNA levels were lower (P hepatic peroxisome proliferator-activated receptor α messenger RNA levels in Ovx rats were reincreased by E2 replacement or by exercise training. Gene expression of proinflammatory cytokines including inhibitor-κB kinase β and interleukin-6, as well as protein content of nuclear factor-κB, was higher (P exercise training prevented the expression of the proinflammatory markers. It is concluded that exercise training reduces fat accumulation in liver of Ovx rats possibly through regulation of key molecules involved in lipogenesis and lipid oxidation. Exercise training also acts as estrogens in properly regulating the expression of inflammatory

  11. Effect of Concurrent Use of Whole-Body Vibration and Parathyroid Hormone on Bone Structure and Material Properties of Ovariectomized Mice.

    Science.gov (United States)

    Matsumoto, Takeshi; Itamochi, Shinya; Hashimoto, Yoshihiro

    2016-05-01

    This study was designed to determine the effectiveness of whole-body vibration (WBV) and intermittent parathyroid hormone (iPTH) in combination against estrogen deficiency-induced osteoporosis. Female C57BL/6J mice were bilaterally ovariectomized (OVX, n = 40) or sham-operated (sham-OVX, n = 8) at 9 weeks of age. Two weeks later, the OVX mice were randomly divided into four groups (n = 10 each): the control group (c-OVX) and groups treated with iPTH (p-OVX), WBV (w-OVX) and both (pw-OVX). The p-OVX and pw-OVX groups were given human PTH (1-34) at a dose of 30 µg/kg/day. The w-OVX and pw-OVX groups were exposed to WBV at an acceleration of 0.3 g and 45 Hz for 20 min/day. All mice were euthanized after the 18-day treatment, and the left tibiae were harvested. The proximal metaphyseal region was µCT-scanned, and its cortical bone cross-section was analyzed by Fourier transform infrared microspectroscopy and nanoindentation testing. A single application of iPTH or WBV to OVX mice had no effect on bone structure or material properties of cortical bone, which were compromised in comparison to those in sham-OVX mice. The combination of iPTH and WBV improved trabecular bone volume, thickness, and connectivity in OVX mice. Although the combined treatment failed to improve cortical bone structure, its mineral maturity and hardness were restored to the levels observed in sham-OVX mice. There was no evidence of interaction between the two treatments, and the combined effects seemed to be additive. These results suggest combining WBV with iPTH has great potential for treating postmenopausal osteoporosis. PMID:26746476

  12. Effects of Odanacatib on bone mineralization density distribution in thoracic spine and femora of ovariectomized adult rhesus monkeys: a quantitative backscattered electron imaging study.

    Science.gov (United States)

    Fratzl-Zelman, Nadja; Roschger, Paul; Fisher, John E; Duong, Le T; Klaushofer, Klaus

    2013-03-01

    Odanacatib (ODN) has been developed as a selective inhibitor of cathepsin K, the major cysteine protease in osteoclasts. In adult rhesus monkeys, treatment with ODN prevents ovariectomy-induced bone loss in lumbar vertebrae and hip. In this study, we evaluate the effects of ODN on bone mineralization density distribution (BMDD) by quantitative backscattered electron imaging in vertebral spongiosa, distal femoral metaphyseal and cortical shaft from monkeys (aged 16-23 years), treated with vehicle (n=5) or ODN (6 mg/kg, n=4 or 30 mg/kg, n=4, PO daily) for 21 months. Dual-energy X-ray absorptiometry was measured in a subset of distal femoral samples. In lumbar vertebrae there was a shift to higher mineralization in samples from ODN-treated groups, compared to vehicle: CaMean (+4%), CaPeak (+3%), CaWidth (-9%), CaLow (-28%) in the 6 mg/kg group and CaMean (+5.1%, p<0.023), CaPeak (+3.4%, p<0.046), CaWidth (-15.7%, p=0.06) and CaLow (-38.2%, p<0.034) in the 30 mg/kg group. In distal femoral metaphyseal cancellous bone, there was a clear tendency toward a dose-dependent increase in matrix mineralization, as in the spine. However, primary and osteonal bone of the distal cortical diaphyses showed no significant change in BMDD, whereas bone mineral density was significantly increased after treatment. In ovariectomized monkeys, this study shows that ODN treatment increased trabecular BMDD, consistent with its previously reported ability to reduce cancellous remodeling. Here, ODN also showed no changes in BMDD in cortical bone sites, consistent with its actions on maintaining endocortical and stimulating periosteal bone formation. PMID:23179105

  13. Bovine Colostral Antibody Against Verotoxin 2 Derived from Escherichia coli O157:H7: Resistance to Proteases and Effects in Beagle Dogs

    OpenAIRE

    Kuribayashi, Takashi; Seita, Tetsuro; Matsumoto, Mariko; Furuhata, Katsunori; Tagata, Kazutoshi; Yamamoto, Shizuo

    2009-01-01

    A bovine colostral antibody against verotoxin (VT) 2 of Escherichia coli O157:H7 was administered orally to beagle dogs. The antibody remained in the dogs’ small intestine for at least 2 h, whereas little serum antibody remained 1.5 h after administration. Furthermore, the antibody activity of secretory IgA did not change until 2 h after administration; however, the activity of IgG and IgM antibodies decreased by approximately 60% and 40% at 2 h after administration, respectively. Seven beagl...

  14. Chov psů plemene beagle v ČR a některé etologické aspekty reprodukce

    OpenAIRE

    Šabatová, Jitka

    2013-01-01

    Beagle is one of favourite dog breeds in the world. Beagle is bred in the Czech Republic for only 20 years but despite this fact it became very popular not only as hunting breed but mainly as family breed. Reproduction of bred animal is for breeders one of the most important function of the organism. Ethological aspects of dogs´ reproduction are related to successful breeding. Dog has been domesticated for very long time, despite this fact its social behaviour has not changed n...

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

    Directory of Open Access Journals (Sweden)

    Hyung-Joo Choi

    2014-01-01

    Full Text Available 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.

  16. Dynamics of alloplastic bone grafts on an early stage of corticotomy-facilitated orthodontic tooth movement in beagle dogs.

    Science.gov (United States)

    Choi, Hyung-Joo; Lee, Dong-Yeol; 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

  17. Study of bone formation in the mandibular alveolar process of the young adult beagle by tetracycline label analysis

    International Nuclear Information System (INIS)

    The mandibular alveolar processes of young, adult beagles were observed to determine several aspects of tissue-level bone turnover. The animals had been previously labeled with a double tetracycline (TC) regimen, and analysis carried out on the resulting label distributions and patterns. Analysis of the fraction of bone surface incorporating TC showed that about 1.5 percent of surfaces are double labeled, 16 percent are single labeled, and 75 percent of surfaces are bare of label. The apposition rate for formation sites was found to be approximately 1.54 μm/day

  18. Population dynamics of the venerid bivalve, Tawera gayi (Hupé, 1854) in the Ushuaia Bay, Beagle Channel

    OpenAIRE

    Lomovasky, B.; Brey, Thomas; Morriconi, E.

    2005-01-01

    Growth, productivity and potential for exploitation of the clam Tawera gayi from shallow waters (3 to 5 m) of Ushuaia Bay, Beagle Channel were investigated. Mean abundance and biomass in the study area were 1091 ± 737 ind m^-2 and 901.83 g SFWM m^-2 (shell free wet mass) respectively. Individual growth was described best by the von Bertalanffy growth model with the parameter values H? = 28.03 mm, K = 0.288 y^1, t0 = -0.34 (r^2 = 0.83). Annual production of the population was estimated to be 1...

  19. Artes y métodos de pesca desarrollados en el Canal de Beagle, Tierra del Fuego, Argentina.

    OpenAIRE

    Izzo, A.; Isla, M.; Salvini, L; Bartozzetti, J.D.; Garcia, J.C. (Juan); Roth, R.R.; Prado, L.; Ercoli, R.

    2000-01-01

    This paper deals with the design and application of different fishing gears tested in the Beagle Channel (Tierra del Fuego, Argentina) with the supervision of the technical personnel of INIDEP Fishing Gear Group, the support of the General Directorate of Natural Resources (known today as SRNyAH) of Tierra del Fuego, Antártida e Islas del Atlántico Sur Province and the participation of local fishermen. Activities started as a result of an agreement between the INIDEP and the SRNyAH ratified i...

  20. RhPTH(1-34)和双磷酸盐交替联合应用对去势大鼠骨质疏松模型治疗的实验研究%Curative Effects of Sequential Application of RhPTH1-34 and Bisphosphonates on Osteoporosis in Ovariectomized Rats

    Institute of Scientific and Technical Information of China (English)

    窦志; 景士忠; 白峰; 刘剑; 范少地; 周凤金

    2013-01-01

    目的:研究联合应用重组人甲状旁腺素(1-34)和双磷酸盐对双侧卵巢切除(OVX)骨质疏松大鼠模型的治疗作用.方法:选用3月龄健康SD雌性大白鼠40只作为实验动物,随机分为五组:假手术组(S组)、卵巢切除组(o组)、OVX +RhPTH(1-34)组(R组)、OVX+阿仑磷酸钠组(A组)、OVX+联合用药组(RA组).术后12周开始给药,持续给药6周.给药后6周取血行相关生化指标检测,取股骨进行骨密度测定、骨组织形态计量学分析.结果:O组的大鼠股骨骨密度值较假手术组有明显减少,血清磷、骨钙素和血清雌二醇水平减少(P<0.01),血清碱性磷酸酶水平增加(P<0.01),使用甲状旁腺素和阿仑膦酸钠治疗后,大鼠股骨骨密度值、血清磷、骨钙素和血清雌二醇水平增加,血清碱性磷酸酶水平相应下降,尤其是两种药物联合应用后效果更为明显(P<0.01);荧光双标显示,O组骨形成速率较R组及RA组低(P<0.05),S组、O组、A组骨形成速率无明显差别(P>0.05).结论:联合应用RhPTH(1-34)和双磷酸盐可以减少去卵巢大鼠骨量的丢失,预防骨质疏松的发生.%Objective:To investigate the effect of sequential application of rhPTH1-34 and bisphosphonates on osteoporosis in ovariectomized rats in order to provide evidence for its clinical application.Methods:Forty SD female rats at the age of 3 months were randomly divided into 5 groups:sham operation group (S group),ovariectomized group (O group),ovariectomized +RhPTH1-34 (R group),ovariectomized +Alendronate Sodium (A group),ovariectomized +RhPTH1-34 and Alendronate Sodium (RA group).The rats were given drugs after 12 weeks.Bone mineral density (BMD),biochemical indexes,and bone histomorphometry parameters were measured with computer image analysis in tetracycline bone double labeling fluorescence were measured after treatment 6 weeks later.Results:The bone mineral density of femur and concentration of P iron,E2,BGP in group O decreased

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

    International Nuclear Information System (INIS)

    An experiment was conducted in 15 adult Beagle dogs to evaluate lung lavage and chelation therapy for the removal of inhaled particles of mixed actinide oxides. The dogs were divided into three groups of five dogs each. Each group was exposed to an aerosol from a different industrial process. Group 1 was exposed to mixed oxide material which had been calcined at 7500C collected from a ball milling process. Group 2 was exposed to mixed oxide material from a centerless grinding operation which had been previously heat treated to 17500C. The third group was exposed to 239PuO2 not containing uranium from a V-blending procedure which had been heat treated at 8500C. After exposure, three dogs in each group were given ten lung lavages and 18 intravenous injections of calcium trisodium diethylenetriaminepentaacetate (DTPA). All dogs were sacrificed 64 days after inhalation exposure. The tissues were radioanalyzed for plutonium and americium. Fluorimetric analyses for uranium in the tissues are in progress. The urine, feces and lavage fluid are also being analyzed for plutonium, americium and uranium. The distribution of plutonium and americium expressed as percentages of the sacrifice body burden was similar in the tissues of the treated and unteated dogs. The lungs contained most of the radionuclides with a small amount in the liver, skeleton and tracheobronchial lymph nodes. The percentage of the sacrifice body burden of americium and plutonium that was present in the lung was less in the treated dogs and was higher in the TBLN's and skeleton than in the untreated dogs. The ratio of Pu/Am was higher in the lungs than in the original material obtained from the industrial sites suggesting a shorter retention time for americium than plutonium to 64 days in the dog

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

    Science.gov (United States)

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

    2015-12-01

    The pharmacokinetics and bioavailability of cefquinome in Beagle dogs were determined by intravenous (IV), intramuscular (IM) or subcutaneous (SC) injection at a single dose of 2 mg/kg body weight (BW). The minimum inhibitory concentrations (MIC) of cefquinome against 217 Escherichia coli isolated from dogs were also investigated. After IV injection, the plasma concentration-time curve of cefquinome was analyzed using a two-compartmental model, and the mean values of t1/2α (h), t1/2β (h), Vss (L/kg), ClB (L/kg/h) and AUC (μg·h/mL) were 0.12, 0.98, 0.30, 0.24 and 8.51, respectively. After IM and SC administration, the PK data were best described by a one-compartmental model with first-order absorption. The mean values of t1/2Kel , t1/2Ka , tmax (h), Cmax (μg/mL) and AUC (μg·h/mL) were corresponding 0.85, 0.14, 0.43, 4.83 and 8.24 for IM administration, 0.99, 0.29, 0.72, 3.88 and 9.13 for SC injection. The duration of time that drug levels exceed the MIC (%T > MIC) were calculated using the determined MIC90 (0.125 μg/mL) and the PK data obtained in this study. The results indicated that the dosage regimen of cefquinome at 2 mg/kg BW with 12-h intervals could achieve %T > MIC above 50% that generally produced a satisfactory bactericidal effect against E. coli isolated from dogs in this study. PMID:25776615

  3. Studies of the effects of FK506 on renal allografting in the beagle dog.

    Science.gov (United States)

    Ochiai, T; Nagata, M; Nakajima, K; Suzuki, T; Sakamoto, K; Enomoto, K; Gunji, Y; Uematsu, T; Goto, T; Hori, S

    1987-12-01

    The immunosuppressive activities of a newly discovered macrolide extracted from Streptomyces tsukubaensis, FK506, were examined using 38 renal allografts in the beagle dog. The median survival time was 15.5 days in dogs without treatment, 61 days with a dose of 0.08 mg/kg/day and 176 days with a dose of 0.16 mg/kg/day of intramuscularly administered FK506. Prolongation of survival was statistically significant when compared with controls (P = 0.02, 0.0044, respectively). None of 6 recipient dogs receiving the agent at a dose of 0.16 mg/kg/day encountered rejection during the treatment course. Three of them survived over 200 days. Oral administration of FK506 at a dose of 0.32 mg/kg/day did not prolong the median survival time (20.5 days) compared with the placebo treated control (16.5 days), but oral treatment with 1.0 mg/kg/day resulted in all of the recipient dogs surviving over 130 days. Histological studies of 7 kidney graft biopsy specimens of the dogs surviving over 3 months revealed no cell infiltration or only some degree of reversible interstitial cell infiltration, but vascular and glomerular changes were not observed in any of the specimens. Irregularity of nuclear shape and cytoplasmic vacuolation of the pars recta of the proximal tubules were observed in one dog each. Liver biopsy specimens showed no consistent evidence of hepatocellular damage. Three dogs died of intussusception 2-3 weeks posttransplant. The dogs treated intramuscularly with 0.32 mg/kg/day suffered from anorexia. Two dogs receiving oral treatment at a dose of 1.0 mg/kg developed papilloma of the skin around day 60, but the tumors disappeared by day 120. We conclude that FK506 is a powerful immunosuppressant in the dog with tolerable side effects. PMID:2447688

  4. Toxicity of inhaled 144CeCl3 in beagle dogs. XI

    International Nuclear Information System (INIS)

    Studies on the metabolism, dosimetry and effects of inhaled 144CeCl3 in Beagle dogs are being conducted to assess the biological consequences of inhaling 144Ce such as might be released in certain nuclear accidents. Studies on the organ distribution of inhaled 144CeCl3 have shown that the 144Ce deposited in the lung is translocated at a moderately rapid rate to liver and skeleton and that significant radiation doses are accumulated by all three organs. Fifty-five dogs that inhaled 144CeCl3 and 15 control dogs are being observed for their life span. The 144Ce dogs have long-term retained burdens with values ranging from 20 to 2900 μCi. Forty-five of the dogs exposed to 144CeCl3 have died; eight from 21 to 44 days after inhalation with severe bone marrow damage and associated pancytopenia; two at 138 and 144 days with radiation pneumonitis; three from 309 to 874 days with hepatic necrosis; one at 510 days with marrow aplasia; one at 375 days with pulmonary fibrosis; and 30 from 799 to 4085 days, most with neoplasms or myeloproliferative disorders. In this last group, one dog had an osteosarcoma, five had squamous cell carcinomas of the nasal cavity (two also having primary pulmonary neoplasms), six had hemangiosarcomas of the liver, one had a hemangiosarcoma of the nasal cavity, two had myelogenous leukemia, one had myelofibrosis with myeloid metaplasia, one had spinal cord ependymomas, one had a malignant melanoma (also an ependymoma) and two had mammary adenocarcinomas. Three dogs had primary pulmonary neoplasms including two with bronchogenic adenocarcinomas and one with an adenoma. Seven did not have malignant neoplasms. Two of these had severe myelomalacia, one had pulmonary edema, three had congestive heart failure and one had diffuse hepatic lipidosis with severe hepatic degeneration

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

    International Nuclear Information System (INIS)

    Studies on the metabolism, dosimetry, and effects of inhaled 90SrCl2 in the Beagle dog are continuing in an effort to provide a basis for assessing the consequences of inhaling 90Sr such as might be released in certain nuclear accidents. Seventy-two dogs were exposed to aerosols containing 90Sr resulting in initial body burdens ranging from 2.5 to 250 μCi 90Sr/kg body weight. Forty-eight of these dogs are being maintained for lifetime observation. Twenty-five unexposed dogs serve as controls. The long-term retained burden (LTRB) in these dogs ranged from 1 to 120 μCi 90Sr/kg. Twenty-four dogs with a mean LTRB of 38 μCi 90Sr/kg have been assigned to a sacrifice study. Two of these dogs and one control dog were sacrificed at five days, one month and one year after inhalation of 90Sr. To date, 51 90Sr-exposed dogs have died or have been euthanized, six during the first 31 days after inhalation of 90Sr with bone marrow aplasia and 45 between 585 and 4236 days after inhalation of 90Sr. The latter group includes 12 dogs with bone-related hemangiosarcomas, 16 with osteosarcomas, three with fibrosarcomas, three with osteochondrosarcomas, one with osteochondrofibrosarcoma, two with leukemia, one with a baso-squamous carcinoma of the skull, one with a squamous cell carcinoma of the maxilla, one with a squamous cell carcinoma of the frontal sinus, one with a hemangiosarcoma of the heart, one with a myxosarcoma of the skull, one with transitional cell carcinoma, one with bronchioalveolar carcinoma, one with an epileptic seizure, one with pneumonia, one with cerebellar hemorrhage and three with a malabsorption syndrome

  6. Toxicity of inhaled 144CeCl3 in beagle dogs. VIII

    International Nuclear Information System (INIS)

    Studies on the metabolism, dosimetry, and effects of inhaled 144CeCl3 in the Beagle dog are continuing to provide information that will aid in assessing the biological consequences of inhaling 144Ce such as might be released in certain nuclear accidents. Studies on the tissue distribution of inhaled 144CeCl3 have shown that the 144Ce deposited in lung is translocated at a moderately rapid rate to liver and skeleton and that significant radiation doses are accumulated by all three organs. Fifty-five dogs that inhaled 144CeCl3 and 15 control dogs were placed in a longevity study and are being observed for their lifespan. The 144Ce dogs had long-term retained burdens with values ranging from 20 to 2900 μCi. Thirty-one of the dogs exposed to 144CeCl3 have died; 8 at 21 to 44 days after inhalation with signs attributed to severe bone marrow damage and associated pancytopenia; 2 at 138 and 144 days with radiation pneumonitis; 3 at 309 to 874 days with hepatic necrosis; 1 at 510 days with marrow aplasia; 1 at 375 days with pulmonary fibrosis; and 16 at 799 to 3081 days, most with neoplasms or myeloproliferative disorders. In this last group, 1 dog had an osteosarcoma, 3 had squamous cell carcinomas of the maxilla, 2 of the latter also having primary pulmonary neoplasms, 5 had hemangiosarcomas of the liver, 1 had a hemangiosarcoma of the nasal cavity, 2 had myelogenous leukemia, 1 had myelofibrosis with myeloid metaplasia, 1 had spinal cord ependymomas, and 2 did not have neoplasms. One of these had severe myelomalacia and the other diffuse hepatic lipidosis with severe degeneration. Two controls died; 1 with a thyroid carcinoma and 1 with aspiration pneumonia. Serial observations are continuing on the 24 surviving 144CeCl3 dogs and 13 control dogs. (U.S.)

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

    International Nuclear Information System (INIS)

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

  8. Toxicity of 91Y inhaled in a relatively insoluble form by beagle dogs. VIII

    International Nuclear Information System (INIS)

    Studies of the radiation hazards due to inhalation of 91Y in fused aluminosilicate particles have been undertaken in Beagle dogs to assess the biological consequences of inhaling a relatively insoluble, energetic beta emitter with an intermediate effective half-life in the lung. A radiation-dose pattern study in which 30 dogs were serially sacrificed from 0 to 320 days after inhalation exposure to 91Y in fused aluminosilicate particles has been completed. A longevity study is in progress in which 96 dogs were exposed to achieve initial lung burdens ranging from 11 to 300 μCi 91Y in fused aluminosilicate particles/kg body weight and 12 dogs were exposed to stable yttrium in fused aluminosilicate particles. To date, 52 dogs have died in the longevity study between 113 and 2514 days after exposure. Forty of these dogs, with cumulative radiation doses to lung between 8,300 and 60,000 rads, died with clinicopathologic findings of radiation pneumonitis and/or pulmonary fibrosis at 113 to 1011 days after exposure. Eleven dogs that died between 1115 and 2376 days after exposure with cumulative doses to lung ranging from 16,000 to 25,000 rads had pulmonary carcinomas. One of these dogs also had a mediastinal hemangiosarcoma. One dog that died at 1847 days after exposure with a cumulative dose to lung of 9,700 rads, had a hemangiosarcoma of the spleen. Four exposed dogs, alive from 2206 and 2669 days after exposure with doses to lung of 15,000 to 17,000 rads, have radiographic lesions suggestive of lung tumors. Forty-four exposed dogs with doses to lung of 2,400 to 18,000 rads and 12 control dogs remain alive from 2198 to 2751 days after inhalation exposure and will continue to be studied throughout the remainder of their life span with attention directed toward determining the relationship between radiation dose, dose rate and biologic effects

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

    International Nuclear Information System (INIS)

    Studies to determine the life-span dose-effect relationship of inhaled 238PuO2 in dogs require an estimate of initial lung deposition (ILD) to calculate the radiation dose to several organs. Ideally, this estimate of ILD is obtained by a summation of plutonium body burden at death plus all the plutonium excreted during the life of the dog. However, the high costs of excreta collection and of plutonium analyses for all excreta from each dog made it necessary to approximate the ILD by other less expensive methods. These methods could introduce error into the estimate of ILD and, consequently, into the radiation dose calculation. The objective of this work was to evaluate the potential error for several methods of estimating ILD. Thirteen beagle dogs were given a single 5- to 30-min exposure to 238PuO2 aerosols, resulting in estimated ILD of 0.85 to 11.7 μCi of plutonium-238. Plutonium analyses of the tissues at death and of all excreta from these dogs were used for this evaluation. The estimate of ILD, obtained by summation of the plutonium body burden at death plus all the plutonium excreted, was compared to the estimated ILD obtained by the plutonium whole-body retention function for each dog, using all excreta data; the mean plutonium whole-body retention function for each dog, using all excreta data; the plutonium whole-body retention function for each dog, using partial excreta data; and a mean plutonium whole-body retention function for all dogs, using partial excreta data. 4 refs., 3 figs., 4 tabs

  10. Toxicity of injected 137CsCl in beagle dogs. IX

    International Nuclear Information System (INIS)

    Studies on the metabolism, dosimetry and effects of intravenously administered 137CsCl in the Beagle dog are being conducted to aid in assessing the biologic consequences of exposure to 137Cs such as occurs in the event of certain nuclear accidents. Effects of the chronic, relatively uniform whole-body exposure produced by 137Cs are being compared with other diverse radiation dose patterns resulting from inhalation of radioactive aerosols. Sixty-six dogs were entered into the study: six with a mean initial 137Cs body burden of 3780 μCi/kg and five groups of 12 dogs each with mean initial 137Cs body burdens of 2820, 1940, 1420, 970 and 0 μCi/kg. Seventeen of the dogs injected with 137CsCl have died: 11 at 19 to 81 days after injection and cumulative whole-body doses of 860 to 1400 rads died with severe bone marrow damage and resultant pancytopenia; two at 2471 and 2707 days after injection and cumulative doses of 690 and 1800 rads with a neurofibrosarcoma of the liver and a mast cell tumor of the skin; four at 693 to 2148 days after injection and cumulative doses of 840 to 2000 rads with shock, aspiration pneumonia, severe arthritis and renal amyloidosis. Two control dogs died; one at 647 days with auto-immune hemolytic anemia and one at 2442 days with renal amyloidosis. Serial observations are continuing on the 37 137CsCl dogs and 10 control dogs. The 137CsCl dogs now alive have cumulative whole-body doses of 550 to 2200 rads at 2777 to 3031 days after injection

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  13. Effect of glucocorticoid administration on adrenal gland size and sonographic appearance in beagle dogs.

    Science.gov (United States)

    Pey, Pascaline; Daminet, Sylvie; Smets, Pascale M Y; Duchateau, Luc; Travetti, Olga; Saunders, Jimmy H

    2012-01-01

    Our aim was to evaluate the influence of glucocorticoids on the adrenal gland using ultrasonography. Eleven healthy beagles were used in a prospective placebo-controlled study. All dogs received hydrocortisone at 10 mg/kg twice a day per os for 4 months or a gelatin capsule twice a day per os as a placebo. Clinical and endocrinologic examination of the dogs and ultrasonographic evaluation of adrenal echogenicity, shape, and measurement of the length and height of the cranial and caudal pole were performed at baseline (TO), at 1 (T1) and 4 months (T4) after the beginning of treatment, and 2 months after the end of the treatment including 1 month of tapering and 1 month without treatment (T6). The dogs were assigned randomly to the glucocorticoid (n = 6) and placebo groups (n = 5). At T1, the difference between the two groups for the height of the cranial and caudal pole was not ultrasonographically remarkable despite a statistically significant difference (P = 0.0165 and P = 0.0206). Decreased height and length of entire gland were observed at T4 (P < 0.0001, P = 0.0015, and P = 0.0035, respectively). Percentages of atrophy were variable between dogs. Both adrenal glands regained normal size and shape 1 month after cessation of glucocorticoid administration. As not all dogs developed marked adrenal gland atrophy and the degree of atrophy varied widely between individuals, ultrasonography cannot be the technique of choice to detect iatrogenic hypercortisolism. Ultrasonographic changes are reversible within 1 month after the end of glucocorticoid administration. PMID:22092685

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  16. Effects of live yeast dietary supplementation on nutrient digestibility and fecal microflora in beagle dogs.

    Science.gov (United States)

    Stercova, E; Kumprechtova, D; Auclair, E; Novakova, J

    2016-07-01

    The effects of live yeast (strain CNCM I-4407; Actisaf Sc 47; Phileo Lesaffre Animal Care, Marcq-en-Baroeul, France) administration on nutrient digestibility and fecal microflora in dogs were investigated. The study included 24 young beagle dogs. They were allocated in control and live yeast (LY) groups (6 males and 6 females in each). During the Adaptation (d 1 to 28) and Trial (d 29 to 70) periods, the dogs received a standard dry pelleted diet. In the Trial period, the LY dogs were given capsuled Actisaf Sc 47 at 1 g/kg live weight with at 2.9 × 10 cfu/g. The control dogs received empty capsules. Live weight and feed consumption were recorded. Blood samples for complete blood count (CBC) and serum biochemistry (urea, creatinine, alkaline phosphatase, and alanine aminotransferase) and fecal samples for pH, microbiology, DM, lactic acid, and ammonia and digestibility evaluation were collected during the Trial period from each dog. The LY dogs had a higher ( < 0.05) weight gain during the Trial period than the control ones. Feed consumption was not adversely affected by LY. The CBC values and urea, creatinine, alkaline phosphatase, and alanine aminotransferase were not adversely affected by LY. Live yeast did not significantly influence pH of fresh feces. Fecal lactic acid and ammonia concentrations were not affected. The LY dogs showed lower ( < 0.05) Escherichia coli and fecal enterococci counts in feces than the control ones. Lactic acid bacteria, Clostridium perfringens, and total coliforms did not show any significant differences between the treatments. The LY dogs showed a higher ( < 0.05) apparent digestibility of NDF. Digestibilities of DM, ash, crude fiber, CP, and fat were not influenced. PMID:27482677

  17. Toxicity of injected 137CsCl in Beagle dogs. XI

    International Nuclear Information System (INIS)

    Studies of the metabolism, dosimetry and effects of intravenously administered 137CsCl in the Beagle dog are being conducted to aid in assessing the biologic consequences of exposure to 137Cs that might occur in the event of certain nuclear accidents. Effects of the chronic, relatively uniform whole-body exposure produced by 137Cs are being compared with other diverse radiation dose patterns resulting from inhalation of radioactive aerosols. Sixty-six dogs were entered into the study: six with a mean initial 137Cs body burden of 3780 μCi/kg and five groups of 12 dogs each with mean initial 137Cs body burdens of 2820, 1940, 1420, 970 and 0 μCi/kg. Twenty-two of the dogs injected with 137CsCl have died: 11 with cumulative whole-body doses of 860 to 1400 rads died from 19 to 81 days after injection with severe bone marrow damage and resultant pancytopenia; four with cumulative whole-body doses of 690 to 1900 rads have died between 2471 and 3386 days post injection with neurofibrosarcoma of the liver, dermal mast cell tumor, hemangiosarcoma of the right atrium, and squamous cell carcinoma of the maxillary sinus and soft palate; seven with cumulative doses of 840 to 2200 rads from 693 to 3529 days after injection with shock, aspiration pneumonia, severe arthritis, renal amyloidosis, congestive heart failure, leiomyoma of bladder and urethra, and brain and spinal cord edema. Four control dogs have died: one at 647 days with auto-immune hemolytic anemia, one at 2442 days with renal amyloidosis, one at 3088 days with disseminated complex mammary adenocarcinoma and one at 3265 days with chronic interstitial nephritis. Serial observations are continuing on the 32 137CsCl injected dogs and eight control dogs. The 137CsCl injected dogs now alive have cumulative whole-body doses of 550 to 1500 rads from 3508 to 3762 days after injection

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

    International Nuclear Information System (INIS)

    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 14C]PEA, the urine contained 61% and 88% of the dose in 4 and 24 hr, respectively. [14C]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 [14C]PEA and 7.9 hr for [14C]EEA. Only trace amounts of 14CO2 (14C]PEA or [14C]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 [14C]PEA being excreted more rapidly than [14C]EEA. 15 references, 4 figures, 4 tables

  19. Estrogenic Effect of 70% Ethanol Turmeric (Curcuma domestica Val. Extract on Ovariectomized Female Mice (Mus musculus L.

    Directory of Open Access Journals (Sweden)

    A.N. Dewi

    2007-11-01

    Full Text Available The influence of extract turmeric (Curcuma domestica Val. on endometrium thickness, vaginal epithelium, mammary gland, and protein of estrogen receptor of ovariectomized mice was examined. Twenty five ovariectomized mice which were divided into five groups, were treated by ethynilestradiol (8,4 x 10-3 g, aquades (10 ml, and turmeric extract at doses 230 mg/kg b.w.; 310 mg/kg b.w.; and 390 mg/kg b.w. for eight days. At the end of experiments the mice were killed, then the uterus, vagina, and mammae were removed and the wet weight of uterus was recorded. Uterus, vagina, and mammae were examined histologically. Estrogen receptor protein from uterus were analized by using SDS-PAGE. One way anava test showed that turmeric extract at doses 310 mg/kg b.w. and 390 mg/kg b.w give estrogenic effect on vaginal ephitelium, endometrium thickness, and diametre of mammary glands. SDS-PAGE analysis showed there were differences in protein concentration between control and treatment groups which were seen in the thickness of the bands. Estrogen receptor band could be detected in sampel of treatment groups at molecular weight 45 kDa.

  20. Effects of treadmill exercise training on cerebellar estrogen and estrogen receptors, serum estrogen, and motor coordination performance of ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Saidah Rauf

    2015-06-01

    Full Text Available Objective(s: The present study aims at examining the motor coordination performance, serum and cerebellar estrogen, as well as ERβ levels, of ovariectomized rats (as menopausal model following regular exercise. Materials and Methods:Ten female Sprague Dawley ratsaged 12 weeks old were randomly divided into two groups; all of which underwent ovariectomy. The first group was treated with regular exercise of moderate intensity, in which the rats were trained to run on a treadmill for 60 min per day for 12 weeks. The second group served as control. Rotarod test was carried out before and after exercise treatment. All rats were euthanized thereafter, and blood and cerebellums of the rats were collected. The serum and cerebellar estrogen as well as cerebellar ERβ levels were measured using ELISA assays. Results: The number of falls in the rotarod task of the exercise group was significantly lower than that of control group. The cerebellar estrogen level of the exercise group was significantly higher than that of control group. Accordingly, there was a significantly negative correlation between the number of falls and cerebellar estrogen level in the exercise group. Conclusion:The present study shows that a lengthy period of regular exercise improves the cerebellar estrogen level and motor coordination performance in ovariectomized rats.

  1. Stress-induced sensitization of the limbic system in ovariectomized rats is partly restored by cyclic 17 beta-estradiol administration

    NARCIS (Netherlands)

    Gerrits, M; Bakker, PL; Koch, T; Ter Horst, GJ

    2006-01-01

    Chronic stress induces neurobiological alterations which have consequences for subsequent stress handling. In the current experiment, ovariectomized rats were subjected daily to a stressor for 21 days. Thereafter, the rats were treated for 21 days with 17 beta-estradiol benzoate (10 mu g/250 g, once

  2. Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Lund, Claus O.; Mortensen, Alicja; Nilas, Lisbeth;

    2007-01-01

    -six female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomised to treatment with 17 beta-estradiol (17 beta-E-2), SoyLife 150(R) or control for 16 weeks. Ring segments of basilar artery (BA) and posterior cerebral artery (PCA) were mounted in myographs for isometric tension...

  3. Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Lund, Claus Otto; Mortensen, A; Nilas, Lisbeth;

    2007-01-01

    -six female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomised to treatment with 17beta-estradiol (17beta-E(2)), SoyLife 150 or control for 16 weeks. Ring segments of basilar artery (BA) and posterior cerebral artery (PCA) were mounted in myographs for isometric tension recordings...

  4. Age and Diet Affect Gene Expression Profile in Canine Skeletal Muscle

    OpenAIRE

    Middelbos, Ingmar S.; Brittany M Vester; Lisa K Karr-Lilienthal; Schook, Lawrence B; Swanson, Kelly S.

    2009-01-01

    We evaluated gene transcription in canine skeletal muscle (biceps femoris) using microarray analysis to identify effects of age and diet on gene expression. Twelve female beagles were used (six 1-year olds and six 12-year olds) and they were fed one of two experimental diets for 12 months. One diet contained primarily plant-based protein sources (PPB), whereas the second diet contained primarily animal-based protein sources (APB). Affymetrix GeneChip Canine Genome Arrays were used to hybridiz...

  5. Bovine lactoferrin improves bone mass and microstructure in ovariectomized rats via OPG/RANKL/RANK pathway

    Institute of Scientific and Technical Information of China (English)

    Jian-ming HOU; Ying XUE; Qing-ming LIN

    2012-01-01

    Aim:Lactoferrin (LF),an 80-kDa iron-binding glycoprotein,is a pleiotropic factor found in colostrum,milk,saliva and epithelial cells of the exocrine glands.The aim of this study was to evaluate the effects of LF on the bones in ovariectomized (Ovx) rats and to identify the pathways that mediate the anabolic action of LF on the bones.Methods:Female Sprague-Dawley rats (6-month-old) underwent ovariectomy,and were treated with different doses of LF (10,100,1000,and 2000 mg·kg-1·d-1,po) or with 7β-estradiol (0.1 mg·kg-1,im,each week) as the positive control.By the end of 6 month-treatments,the bone mass and microstructure in the rats were scanned by micro-computed tomography (micro-CT),and the bone metabolism was evaluated with specific markers,and the mRNA levels of osteoprotegerin (OPG) and the receptor-activator of nuclear factor kB ligand (RANKL) in femur were measured using qRT-PCR.Results:LF treatment dose-dependently elevated the bone volume (BV/TV),trabecular thickness (TbTh) and trabecular number (TbN),and reduced the trabecular separation (TbSp) in Ovx rats.Furthermore,higher doses of LF (1000 and 2000 mg·kg-1·d-1) significantly increased the bone mineral density (BMD) compared with the untreated Ovx rats.The higher doses of LF also significantly increased the serum levels of OC and BALP,and decreased the serum levels of β-CTx and NTX.LF treatment significantly increased the OPG mRNA levels,and suppressed the RANKL mRNA levels,and the RANKL/OPG mRNA ratio in Ovx rats.Conclusion:Oral administration of LF preserves the bone mass and improves the bone microarchitecture.LF enhances bone formation,reduces bone resorption,and decreases bone mass loss,possibly through the regulation of OPG/RANKL/RANK pathway.

  6. Effects of low doses of hydrochloride tetracycline on bone metabolism and uterus in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    LIQing-Nan; HUBin; HUANGLian-Fang; CHENYan; WENGLin-Ling; ZhengHu; CHENHuai-Qing

    2003-01-01

    AIM:To study the effects of low doses of hydrochloride tetracycline (Tc) on bone metabolism and uterus in the ovariectomized (Ova) rats. METHODS:Forty 3-month-old rats were randomly divided into 5 groups: sham group, Ova group, Tc1 group (1.2mg·kg-1·d-1), Tc2 group (4.8mg·kg-1·d-1), and estrone group (1.48 mg·kg-1·d-1),oral fed for 3 months. The proximal tibia metaphyses were processed undecalcified for quantitative bone histomorphometry and the soft tissues were processed in paraffin for pathological observation. RESULTS: Placebo-treated (lactose) Ova rats were characterized by trabecular area (TA) decreasing and their architecture worsening compared with sham controls, and bone resorption was over formation with high bone turnover. The uteri were atrophy. (2)In estrone-treated group, TA and trabecular numbers were significantly increased and the trabecular separation decreased vs Ova group. Estrone slowed down Ova-inducing bone high turnover. But the size, weight, and the endometrium of the uteri in this group were increased vs Ova group. (3) TA was increased in both Tc1 and Tc2 groups compared with Ova rats. Tc maintained bone formation indices almost at Ova level, and only decreased mineral apposition rate (MAR) in Tc1 group, and declined bone resorption perimeter. The uteri and the cell of liver and kidney almost maintained at Ova level; Tc2 decreased labeling perimeter and increased MAR in comparison with Tc1 group. The uteri were atrophy, whose size maintained at Ova level; yellow labeling was not found in bone with these doses of Tc, while yellow labeling could be seen with the doses of 30mg·kg-1·d-1 of Tc for bone marker. CONCLUSION:The two doses of Tc have similar effects on preventing bone loss in Ova rats while the bone formation and uterus are not affected. However, Tc2 does not have more effects on increasing bone mass, Tc2 causes less mild damages to the liver and kidneys.

  7. Neuroprotective effect of estrogen after chronic spinal cord injury in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: At present, there is still lack of effective drugs for chronic spinal cord injury, whereas it is found recently that estrogen has a neuroprotective effect on brain and spinal cord injuries.OBJECTIVE: To observe the effect of estrogen on the apoptosis of nerve cells after gradual chronic spinal cord injury in ovariectomized rats.DESIGN: A randomized controlled animal trial.SETTING: Institute of Orthopaedics, the Second Hospital of Lanzhou University.MATERIALS: Sixty-five female Wistar rats of common degree, weighing 220 - 250 g, were provided by the experimental animal center of Lanzhou University. The rats were randomly divided into sham-operated group (n =5), estrogen-treated group (n =30) and saline control group (n =30), and the latter two groups were observed at 1, 3, 7, 14, 28 and 60 days respectively, and 5 rats for each time point.METHODS: All the rats were treated with bilateral oophorectomy 2 weeks before the experiment. T10 vertebral lamina was revolved into using plastic screw. The spinal canal impingement was not induced initially. After that, the original incision was opened to expose the screw every 7 - 10 days.MAIN OUTCOME MEASURES: The apoptosis and Caspase-3 positive cells in the damaged spinal cord were detected using terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and Caspase-3 immunohistochemical staining at 1, 3, 7, 14, 28 and 60 days after chronic spinal cord injury respectively.RESULTS: Totally 65 rats were used, and the deleted ones during the experiment were supplemented by others. Changes of Caspase-3 expression after spinal cord injury: In the sham-operated group, only a small amount of Caspase-3 proteins were observed in the rat spinal cord, mainly located in motor neurons of spinal cord anterior horn. In the estrogen-treated group and saline control group, positive cells expressed occasionally at 1 day postoperatively, began to increase obviously at 7 days after injury, strongly

  8. Different effects of L-arginine on morphine tolerance in sham and ovariectomized female mice

    Institute of Scientific and Technical Information of China (English)

    Reza KARAMI; Mahmoud HOSSEINI; Fatimeh KHODABANDEHLOO; Leila KHATAMI; Zahra TAIARANI

    2011-01-01

    Objective: The roles of gonadal hormones and nitric oxide (NO) on the analgesic effects of morphine,tolerance to morphine,and their interactions have been widely investigated.In the present study,the effect of L-arginine (an NO precursor) on morphine tolerance in sham and ovariectomized (OVX) female mice was investigated.Methods: Forty mice were divided into sham and OVX groups.On the first day,a hot plate test ((55±0.2) ℃; cut-off 30 s)was carried out as a base record 15 min before injection of morphine (10 mg/kg,subcutaneously (s.c.)) and was repeated every 15 min after injection.The sham group was then divided into two subgroups: sham-toleranceL-arginine (Sham-ToI-LA) and sham-tolerance-saline (Sham-ToI-Sal) which received either L-arginine 50 mg/kg (intraperitoneally (i.p.)) or saline 10 mi/kg (i.p.),respectively,three times in a day for three consecutive days.Morphine tolerance was induced in animals by injecting 30 mg/kg morphine (s.c.) three times/day for three days.This treatment was also used for OVX subgroups.On the fifth day,the hot plate test was repeated.The analgesic effect of morphine was calculated as the maximal percent effect (MPE).The results were compared using repeated measure analysis of variance (ANOVA).Results: There was no significant difference in MPE between the OVX and sham groups.The MPEs in both the Sham-ToI-Sal and OVX-ToI-Sal groups were lower than those in both the sham and OVX groups (P<0.01).The MPE in the OVX-ToI-Sal group was greater than that in the Sham-ToI-Sal group (P<0.01).The MPE in the Sham-ToI-LA group was higher than that in the Sham-ToI-Sal group (P<0.01).However,there was no significant difference between the Sham-ToI-LA and sham groups or between the OVX-ToI-LA and OVX-ToI-Sal groups.Conclusions: The results of the present study showed that repeated administration of morphine causes tolerance to the analgesic effect of morphine.L-Arginine could prevent tolerance to morphine but its effect was different in

  9. Radiation dose patterns in beagle dogs following inhalation of monodisperse and polydisperse aerosols of 238PuO2. II

    International Nuclear Information System (INIS)

    The radiation dose patterns in organs and tissues of the Beagle dog are being determined after inhalation of monodisperse or polydisperse aerosols of 238PuO2. Aerosols employed in the study were 0.7, 1.4 and 2.7 μm aerodynamic diameter (AD) monodisperse aerosols and 1.4 μm activity median aerodynamic diameter (AMAD) polydisperse aerosol. Twenty-six Beagle dogs received inhalation exposure to each aerosol to achieve initial lung burdens (ILB) of 0.07 μCi/kg body weight with sacrifice of two animals at 4 hours, 4, 8, 16, 32, 64, 128, 365, 512 and 730 days and 4, 6 and 8 years after inhalation exposure. Excreta collections were performed on all animals for the first 21 days after inhalation exposure and then three-day collections were taken at 6, 12, 18 and 24 weeks and at six-month intervals thereafter. Information derived from this study will be instrumental in developing a description of the radiation dose to tissues and organs as related to particle size of the inhaled aerosol and will provide a basis for interpretation of biological response being measured in a companion dose-response study. The radiation dose pattern study is in progress with data now available on 238Pu in tissues of animals sacrificed through 64 days after inhalation. Work is continuing on radiochemical analysis of tissues and excreta preparatory to expression of the data in terms of initial lung burden for each animal

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

    Directory of Open Access Journals (Sweden)

    Ko-Ning Ho

    2016-03-01

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

  11. Trace quantification of 1-triacontanol in beagle plasma by GC-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Wang, Chunfeng; Fan, Ali; Zhu, Xiaojie; Lu, Yang; Deng, Shuhua; Gao, Wenchao; Zhang, Wei; Liu, Qi; Chen, Xijing

    2015-05-01

    1-Triacontanol (TA), a member of long chain fatty alcohol, has recently been received great attention owing to its antitumor activity. In this study, an accurate, sensitive and selective gas chromatography-tandem mass spectrometry method was developed and validated for the quantification of TA in beagle plasma using 1-octacosanal as the internal standard (IS) for the first time. With temperature programming, chromatographic separation was carried out on an HP-5MS column, using helium as carrier gas and argon as collision gas, both at a flow rate of 1 mL/min. TA was analyzed using positive ion electrospray ionization in multiple-reaction monitoring mode, with the precursor to product ion transitions of m/z 495.6 → 97.0 and m/z 467.5 → 97.0 for TA and the IS, respectively. The lower limit of quantitation, linearity, intra- and interday precision, accuracy, stability, extraction recovery and matrix effect of TA were within the acceptable limits. The validated method was successfully applied to a pharmacokinetic study of TA in beagles. PMID:25331188

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

    Science.gov (United States)

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

    2016-06-01

    Extensive safety evaluation of UP446, a botanical composition comprised of standardized extracts from roots of Scutellaria baicalensis and heartwoods of Acacia catechu, has been reported previously. Here we carried out additional studies to assess the effect of UP446 on respiratory, cardiovascular and central nervous (CNS) systems. A Functional observational battery (FOB) and whole body plethysmography system in rats and implanted telemetry in dogs were utilized to evaluate the potential CNS, respiratory and cardiovascular toxicity, respectively. UP446 was administered orally at dose levels of 800, 2000 and 5000 mg/kg to SpragueDawley rats and at 4 ascending dose levels (0, 250, 500 and 1000 mg/kg) to beagle dogs. No abnormal effects were observed on the cage side, open field, hand held, and sensori-motor observations suggestive of toxicity in respiratory, cardiovascular and central nervous (CNS) systems. Rectal temperatures were comparable for each treatment groups. Similarly, respiratory rate, tidal volume and minute volume were unaffected by any of the treatment groups. No UP446 related changes were observed on blood pressure, heart rate and electrocardiogram in beagle dogs at dose levels of 250, 500 and 1000 mg/kg. Some minor incidental, non-dose correlated changes were observed in the FOB assessment. These data suggest that UP446 has minimal or no pharmaco-toxicological effect on the respiratory, cardiovascular and central nervous systems. PMID:27012374

  13. Contact heat thermal threshold testing in beagle dogs: baseline reproducibility and the effect of acepromazine, levomethadone and fenpipramide

    Directory of Open Access Journals (Sweden)

    Hoffmann Marina Verena

    2012-10-01

    Full Text Available Abstract Background In this methodology article a thermal threshold testing device designed to test nociception in cats was assessed in six dogs. The purpose of this study was to investigate baseline reproducibility of thermal thresholds obtained by the contact heat testing device, to assess the influence of acepromazine and levomethadone and fenpipramide in dogs. The relationship between change in nociceptive thermal threshold and the opioid′s plasma concentration was determined. Six adult beagle dogs received levomethadone (0.2 mg/kg, acepromazine (0.02 mg/kg or saline placebo by intramuscular injection (IM in a randomized cross-over design. Three baseline nociceptive thermal threshold readings were taken at 15 minutes intervals prior to treatment. Further readings were made at 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360, 420 and 480 minutes after injection. A sedation score was assigned at every reading. Four saline placebo treatments were performed to assess baseline reproducibility. Levomethadone serum concentrations were measured prior and 0.5, 1, 2, 4, 8, 12 and 24 hours after drug dosing in a separate occasion. Results Acepromazine did not seem to increase the thermal threshold at any time. After levomethadone there was a significant rise of the thermal threshold between 15 to 120 minutes at serum concentrations between 22.6-46.3 ng/mL. Baseline reproducibility was stable in adult beagle dogs. Conclusion The thermal threshold testing system is a suitable device for nociceptive threshold testing in dogs.

  14. The impact of ovariectomy on calcium homeostasis and myofilament calcium sensitivity in the aging mouse heart.

    Directory of Open Access Journals (Sweden)

    Elias Fares

    Full Text Available This study determined whether deficiency of ovarian estrogen starting very early in life promoted age-associated Ca(2+ dysregulation and contractile dysfunction in isolated ventricular myocytes. Myocytes were isolated from anesthetized C57BL/6 female mice. Animals received an ovariectomy or sham-operation at one month and were aged to ~24 months. Excitation-contraction coupling parameters were compared in fura-2 loaded myocytes (37°C. While Ca(2+ transients were larger and faster in field-stimulated myocytes from ovariectomized mice, ovariectomy had no effect on peak fractional shortening. Similarly, ovariectomy had no effect on fractional shortening measured in vivo by echocardiography (values were 60.5 ± 2.9 vs. 60.3 ± 2.5% in sham and ovariectomized, respectively; n=5 mice/group. Ovariectomy did decrease myofilament Ca(2+ sensitivity, as evidenced by a 26% increase in the Ca(2+ required to activate actomyosin MgATPase in ovariectomized hearts. Larger Ca(2+ transients were attributable to a 48% increase in peak Ca(2+ current, along with an increase in the amplitude, width and frequency of Ca(2+ sparks measured in fluo-4 loaded myocytes. These changes in Ca(2+ handling were not due to increased expression of Ca(2+ channels (Cav1.2, sarcoplasmic reticulum Ca(2+ ATPase (SERCA2 or Na(+-Ca(2+ exchanger in ovariectomized hearts. However, ovariectomy increased sarcoplasmic reticulum Ca(2+ stores by ~90% and promoted spontaneous Ca(2+ release from the sarcoplasmic reticulum when compared to sham controls. These observations demonstrate that long-term ovariectomy promotes intracellular Ca(2+ dysregulation, reduces myofilament Ca(2+ sensitivity and increases spontaneous Ca(2+ release in the aging female heart.

  15. Toxicity of inhaled 90SrCl2 in beagle dogs. VIII

    International Nuclear Information System (INIS)

    Studies on the metabolism, dosimetry, and effects of inhaled 90SrCl2 in the Beagle dog are continuing in an effort to provide a basis for assessing the consequences of inhaling 90Sr such as might be released in certain nuclear accidents. Seventy-two dogs have been exposed to aerosols containing 90Sr resulting in initial body burdens ranging from 2.5 to 250 μCi 90Sr/kg. Forty-eight of these dogs are being maintained for lifetime observation. Twenty-five unexposed dogs served as controls. The long-term retained burdens in these dogs range from 1 to 120 μCi 90Sr/kg. Twenty-four dogs with a mean long-term retained burden of 38 μCi 90Sr/kg have been assigned to a sacrifice study. Two of these dogs and 1 control dog were sacrificed at 5 days, 1 month, and 1 year after inhalation of 90Sr. To date, 44 90Sr dogs have died or have been euthanized, 6 during the first 31 days after inhalation of 90Sr with bone marrow aplasia and 38 between 585 and 3473 days after inhalation of 90Sr. The latter group includes 12 dogs with hemangiosarcomas, 15 with osteosarcomas, 3 with fibrosarcomas, 3 with osteochondrosarcomas, 1 with osteochondrofibrosarcoma, 2 with leukemia, 1 with a baso-squamous carcinoma, 1 with a malignant giant cell tumor, 1 with a myxosarcoma, 1 with a transitional cell carcinoma, 1 with an epileptic seizure, 1 with pneumonia, and 1 with cerebellar hemorrhage (5 dogs had both a hemangiosarcoma and an osteosarcoma). The skeletons of the dogs dying with neoplasms received initial radiation dose rates of 4 to 55 rads/day and cumulative doses to death of 3300 to 22,000 rads. Six control dogs have died, 3 during the last year. One had renal amyloidosis, 1 had atheromatosis and arteriosclerosis, and 1 had aspiration pneumonia. Serial observations are continuing on the 22 surviving 90Sr dogs and 16 controls. (U.S.)

  16. Toxicity of 90Sr inhaled in a relatively insoluble form by Beagle dogs. IX

    International Nuclear Information System (INIS)

    Studies on the biological effects of 90Sr inhaled in a relatively insoluble form by Beagle dogs are being conducted to define the biological consequences of inhaling this radionuclide in a form which has a long retention time in the lung. One hundred and six dogs were exposed to a polydisperse aerosol (AMAD 1.4 to 2.8 μm and sigma/sub g/ 1.4 to 2.7) of fused aluminosilicate particles labeled with 90Sr. Initial lung burdens ranged from 0.21 to 94 μCi 90Sr per kilogram of body weight (μCi/kg). Eighteen control dogs were exposed to an aerosol of stable strontium in fused aluminosilicate particles. To date, 34 dogs having initial lung burdens of 8.9 to 94 μCi 90Sr/kg and cumulative doses to lung of 33,000 to 96,000 rads have died from radiation pneumonitis and/or pulmonary fibrosis between 159 and 2596 days after exposure. Twenty-nine dogs with initial lung burdens of 3.7 to 36 μCi 90Sr/kg and cumulative doses to lung of 13,000 to 68,000 rads have died from hemangiosarcomas in the lung, heart or mediastinum between 644 and 2565 days after exposure. In addition, one dog developed a bronchioloalveolar carcinoma, another developed epidermoid carcinoma of the lung, another died of pneumonia while recovering from anesthesia, one dog died at 1821 days after exposure with an hemangiosarcoma of the spleen and two dogs developed squamous cell carcinomas in the nasal cavity. During the past year one dog was euthanized 2753 days after exposure (34,000 rads lung dose) as a result of an hemangiosarcoma which developed in a rib and spread widely. Another dog died 2830 days after exposure (35,000 rads lung dose) with a squamous cell carcinoma in the lung. An additional dog was euthanized 2636 days after exposure (12,000 rads lung dose) with widespread hemangiosarcoma of unknown origin. The remaining 36 exposed dogs and 18 controls are surviving at 1387 to 3168 days after exposure

  17. Pharmacokinetics and pharmacodynamics of a nitric oxide-releasing derivative of enalapril in male beagles.

    Science.gov (United States)

    Okuyama, Cristina E; Mendes, Gustavo Duarte; Faro, Renato; Rezende, Vinicius M; Lagos, Rodolfo Monaco; Astigarraga, Rafael E B; Antunes, Edson; De Nucci, Gilberto

    2007-04-01

    1. Pharmacological compounds that release nitric oxide (NO) have been useful tools in the evaluation of the broad role of NO in physiopathology and therapeutics. The present study compared the pharmacokinetics and pharmacodynamics of enalapril and an NO-releasing enalapril molecule (NCX899) in conscious male beagles. The effects of both enalapril and NCX899 in the arterial hypertension and bradycardia induced by acute NO inhibition in anaesthetized dogs were also investigated. 2. Dogs received either NCX899 (4 micromol/kg, i.v.) or enalapril (4 micromol/kg, i.v.), after which plasma concentrations of the analytes and metabolites were quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). 3. In the NCX899 group, the area under the time-course curve (AUC(0-24h)) was 29.18 +/- 4.72, 229.37 +/- 51.32 and 5159.23 +/- 514.88 microg.h/L for the analytes nitro-enalapril, enalapril and enalaprilat, respectively. In the enalapril group, the AUC(0-24h) was 704.53 +/- 158.86 and 4149.27 +/- 847.30 microg.h/L for the analytes enalapril and enalaprilat, respectively. Statistical analysis of data from both groups showed a significant difference for the analyte enalapril, but not for enalaprilat. Moreover, NCX899 and enalapril were equally effective in inhibiting the activity of serum angiotensin-converting enzyme. 4. In anaesthetized dogs, i.v. administration of the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME; 0.1-10 mg/kg) significantly elevated arterial blood pressure, with concomitant bradycardia. The compound NCX899 significantly attenuated both arterial hypertension and bradycardia, whereas enalapril had no significant effect. 5. In conclusion, the present results showed that the NO-releasing derivative of enalapril NCX899 presents a pharmacokinetic/pharmacodynamic relationship similar to its parent compound enalapril. Moreover, NCX899 (but not enalapril) was effective in protecting against the cardiovascular changes

  18. Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs

    Directory of Open Access Journals (Sweden)

    Wang CL

    2015-05-01

    Full Text Available Chunling Wang,1 Xiaobo Cheng,2 Yuqing Su,1 Ying Pei,3 Yanzhi Song,1 Jiao Jiao,1 Zhenjun Huang,1 Yanfei Ma,1 Yinming Dong,1 Ying Yao,1 Jingjing Fan,1 Han Ta,1 Xinrong Liu,1 Hui Xu,1 Yihui Deng1 1College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Deli Wei Biological Technology Co, Ltd, Beijing, People’s Republic of China; 3Shenyang Women’s and Children’s Hospital, Shenyang, People’s Republic of China Abstract: The cross-administration of nanocarriers modified by poly(ethylene glycol (PEG, named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers. In this study, we investigated the ABC phenomenon induced by the intravenous cross-administration of various PEGylated nanocarriers, including PEGylated liposomes (PL, PEG micelles (PM, PEGylated solid lipid nanoparticles (PSLN, and PEGylated emulsions (PE, in beagle dogs. The results indicated that the magnitude of the immune response elicited by the cross-administration was in the following order (from the strongest to the weakest: PL, PE, PSLN, PM. It is specifically PEG in the brush structure that elicits a significant immune response, in both the induction phase and the effectuation phase. Furthermore, the present study suggests that there is a considerable difference between the effect of repeated injections and

  19. Toxicity of injected 137CsCl in the beagle dog. VII

    International Nuclear Information System (INIS)

    Studies on the metabolism, dosimetry, and effects of intravenously administered 137CsCl in the Beagle dog are being conducted to aid in assessing the biologic consequences of exposure to 137Cs such as might occur in the event of certain nuclear accidents. Effects of the chronic, relatively uniform whole-body exposure produced by 137Cs are being compared with other diverse radiation dose patterns resulting from inhalation of radioactive aerosols. Sixty-six dogs were entered into the study; 6 with a mean initial 137Cs body burden of 3780 μCi/kg, and 5 groups of 12 dogs each with mean initial 137Cs body burdens of 2820, 1940, 1420, 970, and 0 μCi/kg. All six of the highest level dogs died 19 to 33 days post-injection with cumulative whole-body doses of 950 to 1400 rads. Three dogs in the 2820 μCi/kg level died at 24 to 27 days post-injection with cumulative whole-body doses of 860 to 910 rads. One dog in the 2820 μCi/kg level and one dog in the 1940 μCi/kg level died at 77 and 81 days after injection with cumulative whole-body doses of 1300 to 1400 rads. These early deaths were attributed to severe bone marrow damage which was reflected in an early dose related pancytopenia. A dog injected with 1900 μCi/137Cs/kg died 693 days post-injection with necropsy findings attributed to shock. A dog injected with 2800 μCi/kg died 1594 days post-injection with aspiration pneumonia and a dog with 2900 μCi/kg was euthanized 1704 days post-injection with severe arthritis. A control dog died 647 days after initiation of the study with clinicopathological manifestations of auto-immune hemolytic anemia. Forty 137Cs dogs and 11 controls are surviving at 2047 to 2301 days after being placed on experiment. The surviving 137Cs dogs had initial body burdens that ranged from 880 to 3000 μCi/kg and received cumulative whole-body doses of 550 to 2200 rads. Serial observations are continuing on all survivors. (U.S.)

  20. Toxicity of inhaled 91Y fused clay in beagle dogs. IV

    International Nuclear Information System (INIS)

    Studies of the radiological hazards due to inhalation of 91Y in fused clay particles are being conducted in Beagle dog to aid in assessing the biological consequences of inhaling a relatively insoluble, energetic β-emitter with a short-to-intermediate effective half-life in the lung. These consist of two parallel efforts involving inhalation of 91Y in fused clay particles: (1) a radiation dose pattern study in which 30 dogs were serially sacrificed from 0 to 320 days post-exposure, and (2) a longevity study in which 96 dogs received initial lung burdens ranging from 11 to 360 μCi 91Y/kb body weight and 12 control dogs were exposed to stable yttrium in fused clay. The aerosols ranged in size from 1.5 to 2.6 μm AMAD. Total body deposition of 91Y ranged between 40 and 50 percent of the inhaled activity with about 22 percent deposited in the alveolar region of the lung. The 91Y deposited in the alveolar region was retained with a mean effective half-life of 50 days whereas the whole-bo effective half-life was 53 days. Small quantities of 91Y were translocated to the tracheobronchial lymph nodes, liver, and skeleton. Concentration in the tracheobronchial lymph nodes exceeded that of the lung by 50 days after exposure. To date, 42 dogs have died in the longevity study between 113 and 1388 days post-exposure. Forty of these dogs with cumulative radiation doses to lung from 8300 to 60,000 rads died with clinico-pathologic findings of radiation pneumonitis and/or pulmonary fibrosis at 113 to 1011 days post-exposure. Two dogs that died at 1115 and 1388 days p/st-exposure, respectively, with cumulative doses to lung of 23,000 and 25,000 rads had primary malignant pulmonary epithelial neoplasms. All survivors will be observed over their total lifespan with particular attention directed toward relating the radiation dose distribution with the resulting clinico-pathologic effects. (U.S.)

  1. Removal of ovarian hormones affects the ageing process of acetate metabolism

    Directory of Open Access Journals (Sweden)

    Yoshihisa Urita

    2009-01-01

    Full Text Available Background : Despite a close association between gastrointestinal motility and sex hormones, it has been unknown whether ovarian hormones affect absorption and metabolism of nutrients. The aim of this study is, therefore, to evaluate metabolism of acetate in rats with age and the influence of ovariectomy on its change. M ethods : Fourteen female rats of the F344 strain were used, and 13C-acetate breath test was performed at 2, 7 and 13 months of age. Seven rats were ovariectomized at three weeks of age (ovariectomy group and the remaining seven rats were studied as control group. After 24-hr fasting, rats are orally administrated 1ml of water containing sodium 13C-acetate (100mg/kg and housed in an animal chamber. The expired air in the chamber is collected in a breath-sampling bag using a aspiration pump. The 13CO2 concentration is measured using an infrared spectrometer for 120 min and expressed as delta per mil. Results : The breath 13CO2 excretion increased with time and peaked 30 min in control rats. In ovariectomized rats, thee peak time of 13CO2 excretion was prolonged to 40 min at 7 and 13 months of age. Cmax was significantly higher at 2 months of age but lower at 4 months of age in ovariectomized rats than in control rats. Those of two groups became equal at 7 months of age. Conclusions : From the viewpoint of acetate metabolism, removal of ovarian hormones might make rats to be precocious ones and accelerate ageing. (Urita Y, Watanabe T, Imai T, Yasuyuki Miura Y, Washizawa N, Masaki Sanaka M, Nakajima H, Sugimoto M. Removal of ovarian hormones affects the ageing process of acetate metabolism.

  2. Hawthorn Fruit Extract Elevates Expression of Nrf2/HO-1 and Improves Lipid Profiles in Ovariectomized Rats.

    Science.gov (United States)

    Yoo, Jeong-Hyun; Liu, Yanan; Kim, Hyun-Sook

    2016-01-01

    The purpose of this study was to investigate the effects of hawthorn (Crataegus pinnatifida Bunge) extract on the lipid profiles and antioxidant properties in ovariectomized (OVX) rats. After ovariectomy, the rats were randomly divided into four groups: the non-OVX control (Sham), the OVX-control (OVX), the OVX + 100 mg/kg b.w. of hawthorn extract (OL), and the OVX + 200 mg/kg b.w. of hawthorn extract (OH). The final body weights of the OVX group were significantly increased, but the increment was significantly decreased in hawthorn groups (p hawthorn groups showed a significant decrease in these levels (p hawthorn groups compared with the OVX group (p hawthorn groups exhibited a significant increase in expression (p hawthorn extract reversed the suppression of protein levels. These results suggest that hawthorn extract could have protective effects in OVX rats by improving lipid profiles, decreasing oxidative stress, and improving the antioxidant defense system. PMID:27187458

  3. Ethanolic extract of Coelogyne cristata Lindley (Orchidaceae) and its compound coelogin promote osteoprotective activity in ovariectomized estrogen deficient mice.

    Science.gov (United States)

    Sharma, Chetan; Mansoori, Mohd Nizam; Dixit, Manisha; Shukla, Priyanka; Kumari, Tejaswita; Bhandari, S P S; Narender, T; Singh, Divya; Arya, K R

    2014-10-15

    Coelogyne cristata Lindley (CC) family Orchidaceae is an Indian medicinal plant used for the treatment of fractured bones in folk-tradition of Kumaon region, Uttarakhand, India. In continuation of our drug discovery program, feeding of ethanolic extract to ovariectomized estrogen deficient mice led to significant restoration of trabecular micro architecture in both femoral and tibial bones, better bone quality and also devoid of any uterine estrogenicity. Subsequently, coelogin, a pure compound was isolated from ethyl acetate fraction of C. cristata and evaluated in in vitro osteoblast cell cultures. Treatment of coelogin to osteoblasts led to enhanced ALP activity (a marker of osteoblast differentiation), mineral nodule formation and mRNA levels of osteogenic markers like BMP-2, Type 1 Collagen and RUNX-2. Based on these results, we propose that ethanolic extract of C. cristata and its pure compound coelogin have potential in the management of post menopausal osteoporosis. PMID:25442280

  4. THE EFFECT OF OESTROGEN AND OR CALCIUM VITAMIN D3 ON THE MANDIBULAR HEIGHT OF POST OVARIECTOMIZED WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Henri D. Henri

    2015-07-01

    Full Text Available One of the major health problems in elderly women is osteoporosis post menopause. Dentists must be aware of the disease since its involvement on the jaw. Nowadays, there are a lot of researches on correlation of osteopororsis and mandible but only few concentrate on hormonal substitution therapy and/or Calcium-vitamin D3 (Ca-Vit D3. This research is to evaluate the effect of hormonal substitiution therapy and/or Ca-vit D3 on mandibular height. Forty five rats used in this research and divided into nine groups: one control group, two ovariectomized (OVX groups, two OVX groups treated with estrogen, two OVC groups treated with Ca-vit D3, two OVC groups treated with estrogen and Ca-vit D3. All of the rats except the control group were ovariectomized as model for postmenopausal estrogen deficiency state. The treatment was done in two or four weeks. The animals were killed with cervical dislocation, the mandible were excised and soaked on Hydrogen Peroxide 10%. Then the mandible's heights on right buccal side were measured from the manduble base to the alveolar crest. It is concluded that hormonal substitution therapy and combination of the hormonal substitution therapy and Ca-vit D3 can maintain the normal mandibular height. Mandibular height of groups with therapy using Ca-vit D3 have slightly lower means compared to control group but without significant difference statistically. The best therapy is combination of hormonal substitution therapy and Ca-vit D3.

  5. Anti-osteoporotic Activity of the Petroleum Ether Extract of Cissus quadrangularis Linn. in Ovariectomized Wistar Rats

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    Huban Thomas

    2010-06-01

    Full Text Available Background: The plant Cissus quadrangularis (CQ is used as an osteoprotective agent inAyurveda, the Indian system of alternative medicine. The present study wasdone to validate the anti-osteoporotic role of the petroleum ether extract ofCQ on ovariectomy-induced osteoporosis in rats.Methods: Female wistar rats were divided into five groups of six rats each; (1 TheNormal control (NC group (n = 6 received no surgery and no treatment,(2. The Sham control (SHAM group (n = 6 received sham surgery but notreatment, (3 the Ovariectomized (OVX group (n = 6 received an ovariectomyand normal saline treatment for 90 days, (4 the Ovariectomized +raloxifene (OVX + RAL group (n = 6 received an ovariectomy and treatmentwith raloxifene, a known anti-osteoporotic agent for 90 days commencingfrom 22nd post ovariectomy day and (5 the Ovariectomy + Cissus quadrangularis(OVX + CQ group (n = 6 received an ovariectomy, and treatmentwith the petroleum ether extract of CQ 500 mg/kg body weight dailyfor 90 days commencing from 22nd post ovariectomy day. At the end of thetreatment period, rats in all groups were sacrificed and the right femur wasused for biomechanical analysis, and the left femur for histomorphometricalanalysis.Results: CQ significantly increased the force required to break the femur (p < 0.001and significantly increased the thickness of both cortical (p < 0.001 and trabecularbone (p < 0.001. This action of CQ was comparable to the action ofraloxifene.Conclusions: The petroleum ether extract of CQ stem seems to possess anti-osteoporoticactivity in rats.

  6. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yuehua, E-mail: yuesjtu@126.com; Zheng, Xinfeng, E-mail: zxf272@126.com; Li, Bo, E-mail: libo@126.com; Jiang, Shengdan, E-mail: jiangsd@126.com; Jiang, Leisheng, E-mail: leisheng_jiang@126.com

    2014-08-15

    Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) and bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss.

  7. Long-term effects of alendronate on fracture healing and bone remodeling of femoral shaft in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Ling-jie FU; Ting-ting TANG; Yong-qiang HAO; Ke-rong DAI

    2013-01-01

    Aim:To investigate the long-term effects of alendronate (Aln),a widely used oral bisphosphonate,on fracture healing and bone remodeling in ovariectomized rats.Methods:Adult female SD rats underwent ovariectomy,and then bilateral femoral osteotomy at 12 weeks post-ovariectomy.From d 2 post-ovariectomy,the animals were divided into 3 groups,and treated with Aln (3 mg·kg-1d-1,po) for 28 weeks (Aln/Aln),Aln for 12 weeks and saline for 16 weeks (Aln/Saline) or saline for 28 weeks (Saline/Saline).At 6 and 16 weeks post-fracture,the fracture calluses were examined with X-ray radiography,and biomechanical testing and histological analysis were performed.The calluses were labeled with tetracycline and calcein to evaluate the mineral apposition rate (MAR).Results:The fracture line was less distinct in the 2 Aln-treated groups at 6 weeks post-fracture,and disappeared in all the 3 groups at 16 weeks post-fracture.The size of the callus and radiographic density of the femora in the Aln/Aln group were the highest among the 3 groups at 6 and 16 weeks post-fracture.Similar results were observed in the ultimate load at failure and energy absorption.However,the treatment with Aln delayed endochondral ossification of the callus,and significantly increased the total sagittal-sectional area,percentage callus area and callus thickness,and decreased the MAR at 6 and 16 weeks post-fracture.Conclusion:In the ovariectomized rat model,Aln is beneficial for the mechanical properties of the callus,but delays callus remodeling by suppressing the remodeling of woven bone into lamellar bone.

  8. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

    International Nuclear Information System (INIS)

    Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) and bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss

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

    Directory of Open Access Journals (Sweden)

    Arencibia Arrebola, Daniel Francisco

    2009-11-01

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

  10. Removal of ovarian hormones affects the ageing process of acetate metabolism

    Directory of Open Access Journals (Sweden)

    Tsunehiko Imai

    2009-07-01

    Full Text Available Background: Despite a close association between gastrointestinal motility and sex hormones, it has been unknown whether ovarian hormones affect absorption and metabolism of nutrients. The aim of this study is, therefore, to evaluate metabolism of acetate in rats with age and the influence of ovariectomy on its change. Methods: Fourteen female rats of the F344 strain were used, and 13C-acetate breath test was performed at 2, 7 and 13 months of age. Seven rats were ovariectomized at three weeks of age (ovariectomy group and the remaining seven rats were studied as control group. After 24-hr fasting, rats are orally administrated 1ml of water containing sodium 13C-acetate (100mg/kg and housed in an animal chamber. The expired air in the chamber is collected in a breath-sampling bag using a aspiration pump. The 13CO2 concentration is measured using an infrared spectrometer for 120 min and expressed as delta per mil. Results: The breath 13CO2 excretion increased with time and peaked 30 min in control rats. In ovariectomized rats, thee peak time of 13CO2 excretion was prolonged to 40 min at 7 and 13 months of age. Cmax was significantly higher at 2 months of age but lower at 4 months of age in ovariectomized rats than in control rats. Those of two groups became equal at 7 months of age. Conclusions: From the viewpoint of acetate metabolism, removal of ovarian hormones might make rats to be precocious ones and accelerate ageing.

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

    Science.gov (United States)

    Lee, Jongsung; Suh, Sangil; Choi, Ran; Hyun, Changbaig

    2016-01-01

    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

  12. Tissue characteristics of high- and low-incidence plutonium-induced osteogenic sarcoma sites in life-span beagles

    International Nuclear Information System (INIS)

    On the basis of information gathered from the 239Pu life-span study in beagles at the University of Utah, the tissue features were found to be characteristic of high-incidence bone-tumor sites compared to low-incidence sites included more hematopoietic tissues in the bone marrow; greater trabecular bone mass; greater bone remodeling rates; greater mineral apposition rates; greater density and activity of bone surface cells; greater density of putative bone-cell precursors; greater initial uptake of plutonium on bone surfaces; and greater marrow vascular volumes and a venous sinusoidal bed. Although most of these studies are not yet complete, the information being collected should contribute to our understanding of the mechanisms of radiation-induced osteogenic sarcomas. This should aid in predicting the types and characteristics of osseous tissues where radiation-induced osteogenic sarcomas may arise in humans. 25 refs., 4 figs., 3 tabs

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

    OpenAIRE

    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-d...

  14. In vivo distribution and excretion studies and in vitro blood studies on the kinetics of lead-203 in beagle dogs

    International Nuclear Information System (INIS)

    Studies on the kinetics of the distribution of lead-203 in body fluids have been carried out in vitro, and in animal studies using beagle dogs. In vitro, the distribution of carrier free lead-203 between plasma and cells of canine blood at 370C was measured after the addition of isotope. In animal studies, activity in plasma was measured for about 150 hours, and activity in blood cells, urine and feces measured for about 400 hours after exposure to lead-203. Linear compartmental models for distribution of the isotope are presented for both in vitro and in vivo experimental systems. The models contain compartments for both untransformed lead, for isotope added in saline or citric acid, and transformed lead, as obtained by lead-203 incubation in plasma

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-11-01

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

  16. Cutaneous mastocytosis with a mutation in the juxtamembrane domain of c-kit in a young laboratory beagle dog.

    Science.gov (United States)

    Kato, Yuki; Kashiwagi, Emi; Masuno, Koichi; Fujisawa, Kae; Tsuchiya, Noriko; Matsushima, Shuuichi; Torii, Mikinori; Takasu, Nobuo

    2016-01-01

    Cutaneous mastocytosis, which resembles a subset of urticaria pigmentosa in humans, is rare in dogs. We herein report unrepresentative neoplastic proliferation of mast cells in ventral skin removed routinely from a nine-month-old female laboratory beagle dog at necropsy. A histological examination revealed diffuse extensive cellular infiltration from the superficial to deep dermis in most parts of the skin around the fourth and fifth mammary papilla without nodule formation. Tumor cells were fairly monomorphic, well-differentiated mast cells with round nuclei of small distinct nucleoli and moderate to abundant, slightly eosinophilic and granular cytoplasm. A perivascular arrangement of mast cells was noted at the margin of the lesions. Infiltration of eosinophils and degeneration of collagen were not observed in the dermis. Cutaneous mastocytosis was diagnosed based on these features. A sequence analysis of lesions revealed the deletion of Gln555 to Ile570 within the juxtamembrane domain of c-kit (exon 11). PMID:26989302

  17. [Pharmacokinetics of 6beta-naltrexol after single and multiple intramuscular injections in Beagle dogs].

    Science.gov (United States)

    Yan, Ling-Di; Liu, Jun; Dong, Hua-Jin; Cui, Meng-Xun; Yao, Xia-Jun; Liu, Yong-Shao; Gong, Zheng-Hua; Gong, Ze-Hui

    2009-07-01

    The pharmacokinetics of 6beta-naltrexol (6beta-NOL) following single intramuscular administration and multiple intramuscular injection once per day for seven days was studied in 4 Beagle dogs. Plasma concentration of 6beta-NOL in dogs was analyzed by a combination of high performance liquid chromatography (HPLC) and electrochemical detection with naloxone (NLX) as internal standard. After single intramuscular injection of 0.2 mg x kg(-1) 6beta-NOL, the plasma concentration-time curve of the drug was found to fit to a two compartment model with first-order absorption. The main parameters of single dosing were as follows: t1/2alpha was (0.26 +/- 0.23) h, t1/2beta was (4.77 +/- 1.65) h, C(max) was (81.65 +/- 5.61) ng x mL(-1), t(peak) was (0.27 +/- 0.07) h, CL(s) was (1.20 +/- 0.06) L x kg(-1) x h(-1), V/F(c) was (1.94 +/- 0.15) L x kg(-1), and AUC(0-t) was (166.82 +/- 7.68) ng x h x mL(-1), separately. After multiple intramuscular injection of 0.2 mg x kg(-1) 6beta-NOL once per day for seven days, the plasma concentration-time curve of the drug fitted to a two compartment model with first-order absorption too. The main parameters of the last dosing were as follows: t1/2alpha was (0.19 +/- 0.18) h, t1/2beta was (5.79 +/- 1.50) h, C(max) was (79.82 +/- 10.5) ng x mL(-1), t(peak) was (0.18 +/- 0.08) h, CL(s) was (1.12 +/- 0.07) L x kg(-1) x h(-1), V/F(c) was (2.10 +/- 0.27) L x kg(-1), and AUC(0-t) was (173.23 +/- 9.49) ng x h x mL(-1), separately. The difference of the parameters between the first and the last dosing was not significant, showing that the plasma kinetics of 6beta-naltrexol was not changed after multiple administrations. In the course of multiple administration, the peak and valley concentration of plasma 6beta-naltrexol were (79.03 +/- 10.3) and (1.50 +/- 0.93) ng x mL(-1), respectively. No clear adverse events were noted during this study. These results showed that plasma 6beta-naltrexol fits to a two compartment model with first-order absorption in

  18. Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles

    Directory of Open Access Journals (Sweden)

    Jie Lai

    2009-12-01

    Full Text Available Jie Lai1,2, Yi Lu1, Zongning Yin2, Fuqiang Hu3, Wei Wu11School of Pharmacy, Fudan University, Shanghai, China, 2West China School of Pharmacy, Sichuan University, Chengdu, China, 3School of Pharmacy, Zhejiang University, Hangzhou, ChinaAbstract: Efforts to improve the oral bioavailability of cyclosporine A (CyA remains a challenge in the field of drug delivery. In this study, glyceryl monooleate (GMO/poloxamer 407 cubic nanoparticles were evaluated as potential vehicles to improve the oral bioavailability of CyA. Cubic nanoparticles were prepared via the fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by sonication and homogenization. The cubic inner structure formed was verified using Cryo-TEM. The mean diameters of the nanoparticles were about 180 nm, and the entrapment efficiency of these particles for CyA was over 85%. The in vitro release of CyA from these nanoparticles was less than 5% at 12 h. The results of a pharmacokinetic study in beagle dogs showed improved absorption of CyA from cubic nanoparticles as compared to microemulsion-based Neoral®; higher Cmax (1371.18 ± 37.34 vs 969.68 ± 176.3 ng mL-1, higher AUC0–t (7757.21 ± 1093.64 vs 4739.52 ± 806.30 ng h mL-1 and AUC0–∞ (9004.77 ± 1090.38 vs 5462.31 ± 930.76 ng h mL-1. The relative oral bioavailability of CyA cubic nanoparticles calculated on the basis of AUC0–∞ was about 178% as compared to Neoral®. The enhanced bioavailability of CyA is likely due to facilitated absorption by cubic nanoparticles rather than improved release.Keywords: nanoparticles, cubosomes, cyclosporine A, glyceryl monooleate, oral drug delivery, bioavailability, beagle dogs

  19. Pu and Am decorporation in beagles: effects of magnitude of initial Ca-DTPA injection upon chelation efficacy

    International Nuclear Information System (INIS)

    To investigate the effects of magnitude of initial DTPA injection upon chelation efficacy, five young adult beagles were each given an intravenous injection of 237+239Pu(IV) citrate + 241Am(III) citrate, followed by a single intravenous injection of Ca-DTPA 0.5 hr later. Amounts of this chelating agent administered were 3, 10, 30, 100, and 300 μmole Ca-DTPA/kg body mass. Animals were sacrificed 7 days later. Total-body retention of both plutonium and americium was influenced strongly by the amount of DTPA administered, although the removal of Pu by DTPA was less pronounced than that of Am; and in the range of 30 μmole/kg, an increase of DTPA administration by a factor of 2 resulted in only a 25% decrease in residual body content. Plutonium retention at 7 days was reduced from about 77% in the dog given 3 μmole/kg to 14% in the animal injected with 300 μmole/kg. Corresponding values for americium were 40 and 9%. Also, liver content of both Pu and Am was reduced significantly by larger amounts of administered DTPA, decreasing from 18 to 2% for Pu with increasing levels of DTPA, and from 21 to 1% for Am. If there is a level of Ca-DTPA administration at 30 min after injection in a beagle at which no additional chelation of Pu or Am is produced with increasing dosage, it is greater than 300 μmole/kg. In a 70-kg human, this would be equivalent to the injection of 10 g Ca-DTPA

  20. Scintigraphic tracking of mesenchymal stem cells after portal, systemic intravenous and splenic administration in healthy beagle dogs.

    Science.gov (United States)

    Spriet, Mathieu; Hunt, Geraldine B; Walker, Naomi J; Borjesson, Dori L

    2015-01-01

    Mesenchymal stem cells have been proposed to treat liver disease in the dog. The objective of this study was to compare portal, systemic intravenous and splenic injections for administration of mesenchymal stem cells to target the liver in healthy beagle dogs. Four healthy beagle dogs were included in the study. Each dog received mesenchymal stem cells via all three delivery methods in randomized order, 1 week apart. Ten million fat-derived allogeneic mesenchymal stem cells labeled with Technetium-99m (99mTc)-hexamethyl-propylene amine oxime(HMPAO) were used for each injection. Right lateral, left lateral, ventral, and dorsal scintigraphic images were obtained with a gamma camera equipped with a low-energy all-purpose collimator immediately after injection and 1, 6, and 24 h later. Mesenchymal stem cells distribution was assessed subjectively using all four views. Pulmonary, hepatic, and splenic uptake was quantified from the right lateral view, at each time point. Portal injection resulted in diffuse homogeneous high uptake through the liver, whereas the systemic intravenous injection led to mesenchymal stem cell trapping in the lungs. After splenic injection, mild splenic retention and high homogeneous diffuse hepatic uptake were observed. Systemic injection of mesenchymal stem cells may not be a desirable technique for liver therapy due to pulmonary trapping. Splenic injection represents a good alternative to portal injection. Scintigraphic tracking with 99mTc-HMPAO is a valuable technique for assessing mesenchymal stem cells distribution and quantification shortly after administration. Data obtained at 24 h should be interpreted cautiously due to suboptimal labeling persistence. PMID:25582730

  1. In vitro release and in vivo absorption in beagle dogs of meloxicam from Eudragit FS 30 D-coated pellets.

    Science.gov (United States)

    Gao, Chunsheng; Huang, Jian; Jiao, Yan; Shan, Li; Liu, Yan; Li, Ying; Mei, Xingguo

    2006-09-28

    The objective of this study was to develop meloxicam-loaded colon-specific pellets coated with Eudragit FS 30 D and further evaluate their in vitro release and in vivo absorption in beagle dogs. Meloxicam-loaded cores (drug loading, 4.8%, w/w) were prepared by layering drug-binder (HPMC)-solubilizer (beta-cyclodextrin) solution onto nonpareils (710-850 microm) and then coated with a copolymer of methyl acrylate, methyl methacrylate and methacrylic acid (Eudragit FS 30 D). The obtained pellets with 15% (w/w) coating level had a spherical form and a smooth surface with coating thickness approximately 28 microm. The in vitro drug release from the pellets was pH-dependent with sufficient gastric resistance (pH 1.2: no release; pH 6.8: 6%; pH 7.0: 52%; pH 7.2: 100%; pH 7.4: 100%, after 3 h incubation). In vivo study was carried out using pentagastrin-pretreated beagle dogs. The onset of meloxicam absorption from the coated pellets with 15% (w/w) Eudragit FS 30 D (3.0+/-0.8 h) was significantly delayed (pmeloxicam plasma concentration-time curve (AUC(0-->96)(h) was not significantly different between the two preparations (p>0.05), although AUC(0-->96)(h) obtained after oral administration of coated pellets (142.5+/-59.6 microg h/ml) was lower than that obtained after administration of uncoated drug-layered cores (180.8+/-61.9 microg h/ml). These results suggested that meloxicam could be delivered to the colon with 15% (w/w) coating level of Eudragit FS 30 D and this polymer coating had no significant influence on the relative bioavailability of meloxicam of the pellets. PMID:16806752

  2. Novel fenofibric acid-loaded controlled release pellet bioequivalent to choline fenofibrate-loaded commercial product in beagle dogs.

    Science.gov (United States)

    Kim, Kyung Soo; Jin, Sung Giu; Mustapha, Omer; Yousaf, Abid Mehmood; Kim, Dong Wuk; Kim, Young Hun; Kim, Jong Oh; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon

    2015-07-25

    The objective of this study was to develop a novel fenofibric acid-loaded controlled release pellet showing enhanced, or equivalent to, bioavailability compared with two commercially available products containing fenofibrate or choline fenofibrate. The effect of solubilizing agents on drug solubility and the impact of fillers on core properties were investigated. Among them, magnesium carbonate most improved drug solubility, and κ-carrageenan provided the best spherical cores. The fenofibric acid-loaded pellet was prepared with magnesium carbonate and κ-carrageenan employing the extrusion/spheronizing technique followed by coating with ethylcellulose. Furthermore, dissolution and pharmacokinetic study in beagle dogs were performed compared to the fenofibrate-loaded commercial tablet (FCT) and choline fenofibrate-loaded commercial mini-tablet (CFCM). This fenofibric acid-loaded pellet showed controlled release of the drug in phosphate buffer (pH 6.8) and 0.025 M sodium laurylsulfate within 4h. Furthermore, this pellet and CFCM exhibited similar dissolution profiles. Plasma concentrations greater than 1,000 ng/ml were maintained from 30 min to 8h, suggesting a sustained release pattern. Also, the fenofibric acid-loaded pellet gave significantly higher AUC and Cmax values than FCT, indicating that it improved the bioavailability of fenofibrate due to enhanced solubility and sustained release. In addition, this pellet and CFCM were not significantly different in terms of pharmacokinetic parameters including AUC, Cmax and Tmax. Thus, this pellet was bioequivalent to CFCM in beagle dogs. In conclusion, this fenofibric acid-loaded controlled release pellet would be a potential alternative to the choline fenofibrate-loaded commercial product. PMID:26024820

  3. The combination therapy with alfacalcidol and risedronate improves the mechanical property in lumbar spine by affecting the material properties in an ovariectomized rat model of osteoporosis

    Directory of Open Access Journals (Sweden)

    Ito Masako

    2009-06-01

    Full Text Available Abstract Background We conducted the present study to investigate the therapeutic effects of a combination treatment of alfacalcidol (ALF and risedronate (RIS on the bone mechanical properties of bone and calcium (Ca metabolism using an ovariectomized (OVX rat model of osteoporosis. Methods Female Wistar rats were OVX- or sham-operated at 40 weeks of age. Twelve weeks post-surgery, rats were randomized into seven groups: 1 sham + vehicle, 2 OVX + vehicle, 3 OVX + ALF 0.025 μg/kg/day, 4 OVX + ALF 0.05 μg, 5 OVX + RIS 0.3 mg, 6 OVX + RIS 3.0 mg, 7 OVX + ALF 0.025 μg + RIS 0.3 mg. Each drug was administered orally five times a week for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral midshaft. In the lumbar vertebra, structural and material analyses were performed using micro-computed tomography (micro-CT and microbeam X-ray diffraction (micro-XRD, respectively. Biochemical markers in serum and urine were also determined. Results (1 With respect to improvement in the mechanical strength of the lumbar spine and the femoral midshaft, the combination treatment of ALF and RIS at their sub-therapeutic doses was more effective than each administered as a monotherapy; (2 In the suppression of bone resorption and the amelioration of microstructural parameters, the effects of ALF and RIS were considered to be independent and additive; (3 The improvement of material properties, such as microstructural parameters and the biological apatite (Bap c-axis orientation, contributed to the reinforcement of spinal strength; and (4 The combination treatment of ALF and RIS normalized urinary Ca excretion, suggesting that this treatment ameliorated the changes in Ca metabolism. Conclusion These results demonstrate that the combination treatment of ALF and RIS at their sub-therapeutic doses can improve the mechanical properties of the spine as well as the femur and ameliorate changes in Ca metabolism in an animal

  4. The Preventive Effect of Biochanin A on Bone Loss in Ovariectomized Rats: Involvement in Regulation of Growth and Activity of Osteoblasts and Osteoclasts

    OpenAIRE

    Shu-Jem Su; Yao-Tsung Yeh; Huey-Wen Shyu

    2013-01-01

    Biochanin A (BCA) is a major isoflavone abundant in red clover (Trifolium pretense). The protective effect of BCA on bone loss in an ovariectomized (OVX) animal model has never been clarified. The objective of this study was to investigate the biological effects of BCA on bone loss in OVX rats in vivo and on the development of osteoblasts and osteoclasts in vitro. Ovariectomy resulted in a marked increase in body weight and a decrease in femoral bone mineral density and trabecular bone volume...

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Christopher E.; Wilson, Dulaney A.; Brooks, Antone L.; McCord, Stacey; Dagle, Gerald E.; James, Anthony C.; Tolmachev, Sergei Y.; Thrall, Brian D.; Morgan, William F.

    2012-11-01

    The long-term retention of inhaled soluble forms of plutonium raises concerns as to the potential health effects in persons working in nuclear energy or the nuclear weapons program. The distributions of long-term retained inhaled plutonium-nitrate [239Pu (NO3)4] deposited in the lungs of an accidentally exposed nuclear worker (Human Case 0269) and in the lungs of experimentally exposed beagle dogs with varying initial lung depositions were determined via autoradiographs of selected histological lung, lymph node, trachea, and nasal turbinate tissue sections. These studies showed that both the human and dogs had a non-uniform distribution of plutonium throughout the lung tissue. Fibrotic scar tissue effectively encapsulated a portion of the plutonium and prevented its clearance from the body or translocation to other tissues and diminished dose to organ parenchyma. Alpha radiation activity from deposited plutonium in Human Case 0269 was observed primarily along the sub-pleural regions while no alpha activity was seen in the tracheobronchial lymph nodes of this individual. However, relatively high activity levels in the tracheobronchial lymph nodes of the beagles indicated the lymphatic system was effective in clearing deposited plutonium from the lung tissues. In both the human case and beagle dogs, the appearance of retained plutonium within the respiratory tract was inconsistent with current biokinetic models of clearance for soluble forms of plutonium. Bound plutonium can have a marked effect on the dose to the lungs and subsequent radiation exposure has the potential increase in cancer risk.

  8. Accelerated immune senescence and reduced response to vaccination in ovariectomized female rhesus macaques

    OpenAIRE

    Engelmann, Flora; Barron, Alex; Urbanski, Henryk; Neuringer, Martha; Kohama, Steven G.; Park, Byung; Messaoudi, Ilhem

    2010-01-01

    Aging is associated with a general dysregulation in immune function, commonly referred to as “immune senescence”. Several studies have shown that female sex steroids can modulate the immune response. However, the impact of menopause-associated loss of estrogen and progestins on immune senescence remains poorly understood. To help answer this question, we examined the effect of ovariectomy on T-cell homeostasis and function in adult and aged female rhesus macaques. Our data show that in adult ...

  9. Preformulation characterization and in vivo absorption in beagle dogs of JFD, a novel anti-obesity drug for oral delivery.

    Science.gov (United States)

    Fan, Yunzhou; Yang, Meiyan; Wang, Yuli; Li, Yanyou; Zhou, Yuanda; Chen, Xiaoping; Shan, Li; Wei, Jun; Gao, Chunsheng

    2015-05-01

    JFD (N-isoleucyl-4-methyl-1,1-cyclopropyl-1-(4-chlorine)phenyl-2-amylamine·HCl) is a novel investigational anti-obesity drug without obvious cardiotoxicity. The objective of this study was to characterize the key physicochemical properties of JFD, including solution-state characterization (ionization constant, partition coefficient, aqueous and pH-solubility profile), solid-state characterization (particle size, thermal analysis, crystallinity and hygroscopicity) and drug-excipient chemical compatibility. A supporting in vivo absorption study was also carried out in beagle dogs. JFD bulk powders are prismatic crystals with a low degree of crystallinity, particle sizes of which are within 2-10 μm. JFD is highly hygroscopic, easily deliquesces to an amorphous glass solid and changes subsequently to another crystal form under an elevated moisture/temperature condition. Similar physical instability was also observed in real-time CheqSol solubility assay. pK(a) (7.49 ± 0.01), log P (5.10 ± 0.02) and intrinsic solubility (S0) (1.75 μg/ml) at 37 °C of JFD were obtained using potentiometric titration method. Based on these solution-state properties, JFD was estimated to be classified as BCS II, thus its dissolution rate may be an absorption-limiting step. Moreover, JFD was more chemically compatible with dibasic calcium phosphate, mannitol, hypromellose and colloidal silicon dioxide than with lactose and magnesium stearate. Further, JFD exhibited an acceptable pharmacokinetic profiling in beagle dogs and the pharmacokinetic parameters T(max), C(max), AUC(0-t) and absolute bioavailability were 1.60 ± 0.81 h, 0.78 ± 0.47 μg/ml, 3.77 ± 1.85 μg·h/ml and 52.30 ± 19.39%, respectively. The preformulation characterization provides valuable information for further development of oral administration of JFD. PMID:24694186

  10. Therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles

    International Nuclear Information System (INIS)

    Objective: To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy 60Co γ-rays irradiation in beagles, and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness (ARS). Methods: 16 beagles were given 4.5 Gy 60Co γ-rays total body irradiation, and then randomly assigned into irradiation control group, supportive care group and cytokines group. In addition to supportive care, recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human interleukin-11 (rhIL-11) and recombinant human interleukin-2 (rhIL-2) were administered subcutaneouly to dogs in cytokines group. Peripheral blood hemogram was examined once every two days. Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation. Conventional histopathological sections sternum were prepared to observe the histomorphology changes. Results: After irradiation, the population of all kinds of cells in peripheral blood declined sharply. WBC nadir was elevated (1.04 x 109 /L, but 0.28 x 109 /L and 0.68 x 109 /L for the irradiation control group and the supportive care group separately), the duration of thrombocytopenia was shortened (24 days, but 33 days for the supportive care group) and red blood cell counts were maintained in the range of normal values after cytokines treatment in combination. The colony forming efficiency of haemopoietic stem cells (HSCs) in bone marrow and peripheral blood decreased obviously 1 d post irradiation, but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment. Hematopoietic cells disappeared in bone marrow of animals in irradiation control group, but hematopoietic functions were recovered after cytokines were administrated. Conclusions: RhG-CSF, rhIL-11 and rhIL-2 used in combination could elevate WBC nadir, accelerate the

  11. Citrus reticulata’s Peels Modulate Blood Cholesterol Profile and IncreaseBone Density of Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Rosa Adelina

    2015-11-01

    Full Text Available Hormon Replacement Therapy is a common therapy for estrogen deficiency but in other side it will increase the risk of cardiovascular disease. Another alternative therapy which relatively more safe is using phytoestrogen. The Citrus reticulata’s peel contain flavanone and polimethoxyflavone which are suspected to give estrogenic effect, therefore it is potential to be used as phytoestrogen.The purpose of this study was to examine the estrogenic effect of Citrus reticulata’s peel extract in modulation of bone density and blood cholesterol profile of ovariectomized rats (OVX, an animal model of postmenopausal osteoporosis. Thirty six 7-weeks-old female Sprague Dawley rats were assigned to six groups: a SO group, an OVX group, an OVX+CMCNa group, an OVX+extract dose 500 mg/kgBW group, an OVX+extract dose 1000 mg/kgBW group, and an OVX+estradiol group. After 7 weeks, the rats were killed then blood and femoral were collected immediately. The rontgenogram indicated that extract and estradiol administration increase the bone density. And the data analysis with Oneway ANOVA test ,followed by Shceffé test (P 0.05 showed that extract can improve blood cholesterol profile in dose depend manner. These results suggest a possible role of Citrus reticulata’s peel extract as women’s health agent because of its beneficial effects on bone and lipids.

  12. DHEA supplementation in ovariectomized rats reduces impaired glucose-stimulated insulin secretion induced by a high-fat diet

    Directory of Open Access Journals (Sweden)

    Katherine Veras

    2014-01-01

    Full Text Available Dehydroepiandrosterone (DHEA and the dehydroepiandrosterone sulfate (DHEA-S are steroids produced mainly by the adrenal cortex. There is evidence from both human and animal models suggesting beneficial effects of these steroids for obesity, diabetes mellitus, hypertension, and osteoporosis, conditions associated with the post-menopausal period. Accordingly, we hypothesized that DHEA supplementation in ovariectomized (OVX female rats fed a high-fat diet would maintain glucose-induced insulin secretion (GSIS and pancreatic islet function. OVX resulted in a 30% enlargement of the pancreatic islets area compared to the control rats, which was accompanied by a 50% reduction in the phosphorylation of AKT protein in the pancreatic islets. However, a short-term high-fat diet induced insulin resistance, accompanied by impaired GSIS in isolated pancreatic islets. These effects were reversed by DHEA treatment, with improved insulin sensitivity to levels similar to the control group, and with increased serine phosphorylation of the AKT protein. These data confirm the protective effect of DHEA on the endocrine pancreas in a situation of diet-induced overweight and low estrogen concentrations, a phenotype similar to that of the post-menopausal period.

  13. Anti-Osteoporotic Effects of Angelica sinensis (Oliv. Diels Extract on Ovariectomized Rats and Its Oral Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Dong Wook Lim

    2014-10-01

    Full Text Available Angelica sinensis root is one of the herbs most commonly used in China; it is also often included in dietary supplements for menopause in Europe and North America. In the present study, we examined the anti-osteoporotic effects of A. sinensis extract in an ovariectomized (OVX rat model of osteoporosis as well as toxicity of the extract after repeated oral administration. The OVX rats were treated with 17β-estradiol (10 μg/kg i.p. once daily or A. sinensis extract (30, 100, and 300 mg/kg, p.o. once daily for four weeks. The bone (femur mineral density (BMD of rats treated with the extract (300 mg/kg was significantly higher than that of the OVX-control, reaching BMD of the estradiol group. Markers of bone turnover in osteoporosis, serum alkaline phosphatase, collagen type I C-telopeptide and osteocalcin, were significantly decreased in the extract group. The body and uterus weight and serum estradiol concentration were not affected, and no treatment-related toxicity was observed during extract administration in rats. The results obtained indicate that A. sinensis extract can prevent the OVX-induced bone loss in rats via estrogen-independent mechanism.

  14. EFFECTS OF XW630 ON BONE FORMATION IN OVARIECTOMIZED RATS AND IN HUMAN OSTEOBLAST-LIKE CELLS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective. To study the effects of XW630 on bone formation in overiectomized(OVX) rats and in human osteoblast-like cell line TE85.Method. Bone histomorphometric analysis was performed with undecalcified bone sections and tetracycline intraperitoneally labeling.Results. Compared with that of OVX rats, the static data of trabecular bone volume(TBV)/ total tissue volume(TTV), TBV/sponge bone volume(SBV) and mean trabecular plate density (MTPD) were enhanced while mean trabecular plate spacing(MTPS) decreased after treated with XW630 for 13w. The dynamic data of single-labeled surface [Sfract(s)], double-labeled surface[Sfract(d)],Sfract(d+1/2s),trabecular osteoid surface(TOS), and bone formation rate in tissue level (Svf) were increased and osteoid maturation period (OMP) shortened in XW630 group. In osteoblast-like cells, both 3H-thymidine incorporation and cell count increased after treated with XW630 for 48. Treated with XW630 for 12~18h,inducible nitric oxide synthase(iNOS) activity and cGMP content increased in time-dependent manners.Conclusions. XW630 enhanced bone activation frequency and increased trabecular connectivity, stability, and strength. The cellular mechanism related to effects of XW630 on bone formation in ovariectomized rats.

  15. Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats.

    Science.gov (United States)

    Ronis, Martin J; Gomez-Acevedo, Horacio; Blackburn, Michael L; Cleves, Mario A; Singhal, Rohit; Badger, Thomas M

    2016-04-15

    There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 μg/kg/d 17β-estradiol (E2) or vehicle. E2 increased uterine wet weight (Pestrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (Pselective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens. PMID:26945725

  16. Vitex agnus-castus L. (Verbenaceae Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Franciele Neves Moreno

    2015-01-01

    Full Text Available Vitex agnus-castus (VAC is a plant that has recently been used to treat the symptoms of menopause, by its actions on the central nervous system. However, little is known about its actions on disturbances in lipid metabolism and nonalcoholic fat liver disease (NAFLD, frequently associated with menopause. Ovariectomized (OVX rats exhibit increased adiposity and NAFLD 13 weeks after ovary removal and were used as animal models of estrogen deficiency. The rats were treated with crude extract (CE and a butanolic fraction of VAC (ButF and displayed the beneficial effects of a reduction in the adiposity index and a complete reversion of NAFLD. NAFLD reversion was accompanied by a general improvement in the liver redox status. The activities of some antioxidant enzymes were restored and the mitochondrial hydrogen peroxide production was significantly reduced in animals treated with CE and the ButF. It can be concluded that the CE and ButF from Vitex agnus-castus were effective in preventing NAFLD and oxidative stress, which are frequent causes of abnormal liver functions in the postmenopausal period.

  17. Trabecular bone response to mechanical loading in ovariectomized Sprague-Dawley rats depends on baseline bone quantity.

    Science.gov (United States)

    Ko, Chang-Yong; Jung, Young Jin; Park, Ji Hyung; Seo, Donghyun; Han, Paul; Bae, Kiho; Schreiber, Jürgen; Kim, Han Sung

    2012-07-26

    Mechanical loading is one of the determining factors for bone modulation, and is therefore frequently used to treat or prevent bone loss; however, there appears to be no data on the effects of baseline bone quantity on this response. This study aimed to verify whether baseline bone quantity affects osteoporotic trabecular bone adaptive response to mechanical stimulation. Twenty-four female Sprague-Dawley (SD) rats were ovariectomized (OVX). After 3 weeks of OVX, rats were divided into a high bone quantity and a low bone quantity group, and rats in each group were then subdivided into 4 groups that were exposed to different loading strategies. In the loading groups, tibiae were stimulated through axial loading at 2000με of strain, for 1500 cycles each of 75s, 150s, or 250s. The sham treatment groups received no loading. Changes in BV/TV for trabecular bone in the tibia were measured at the baseline (before loading), and at 3 weeks and 6 weeks after loading. BV/TVs in loading groups of the low baseline bone quantity group were significantly increased at 6 weeks, compared with those in the no-loading groups (p0.05). A significant negative correlation was observed between baseline BV/TV and its relative variations at 3 weeks or 6 weeks (p<0.05). These results indicate that adaptive responses of osteoporotic trabecular bone to mechanical loading depend on baseline bone quantity. PMID:22663762

  18. Labisia pumila extract down-regulates hydroxysteroid (11-beta) dehydrogenase 1 expression and corticosterone levels in ovariectomized rats.

    Science.gov (United States)

    Fazliana, Mansor; Gu, Harvest F; Östenson, Claes-Göran; Yusoff, Mashitah Mohd; Wan Nazaimoon, W M

    2012-04-01

    We evaluated the effects of a standardized Labisia pumila var. alata (LPva) extract on body weight change, hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) expressions and corticosterone (CORT) level in ovariectomized (OVX) rats. The decoction of LPva has been used for generations among Malay women in Malaysia to maintain a healthy reproductive system.Thirty-six Sprague-Dawley OVX rats were treated orally with LPva extract (10, 20 or 50 mg/kg/day) or estrogen replacement (ERT) for 30 days. Sham operated rats were used as controls. Compared to untreated OVX rats, LPva-treated rats showed less weight gain and had significantly down-regulated HSD11B1 mRNA in liver tissues. HSD11B1 mRNA in adipose tissues increased by 55% (p rats but normalized in rats treated with LPva. Similarly, there was significant down-regulation (p rats. This is the first study ever conducted to evaluate the beneficial effects of LPva in relation to weight gain caused by estrogen insufficiency. Results implied that the bioactive components in LPva extract affect not only HSD11B1 expressions in both adipose and liver tissues but also decrease circulating CORT. The extract should be explored for its potential use as a natural remedy for weight management. PMID:21833773

  19. Role of Mas receptor in renal blood flow response to angiotensin-(1-7 in ovariectomized estradiol treated rats

    Directory of Open Access Journals (Sweden)

    Shadan Saberi

    2016-01-01

    Full Text Available The angiotensin 1-7 (Ang 1-7, is abundantly produced in kidneys and antagonizes the function of angiotensin II through Mas receptor (MasR or other unknown mechanisms. In the current study, the role of MasR and steroid hormone estrogen on renal blood flow response to Ang 1-7 administration was investigated in ovariectomized (OV female rats. OV female Wistar-rats received estradiol (500 μg/kg/week or vehicle for two weeks. In the day of the experiment, the animals were anesthetized, cannulated, and the responses including mean arterial pressure, renal blood flow (RBF, and renal vascular resistance at the constant level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300 ng/kg/min were determined in OV and OV estradiol-treated (OVE rats, treated with vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose-dependently in vehicle (P dose <0.001 and A779-treated (P dose<0.01 animals. However, when MasR was blocked, the RBF response to Ang 1-7 significantly increased in OV animals compared with OVE rats (P<0.05. When estradiol was limited by ovariectomy, A779 increased RBF response to Ang 1-7 administration, while this response was attenuated in OVE animals.

  20. Impact of Actinomyces naeslundii on bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats with periodontitis.

    Science.gov (United States)

    Li, Chun Lei; Seneviratne, Chaminda Jayampath; Huo, Lei; Lu, Weijia William; Zheng, Li Wu

    2015-10-01

    Bisphosphonates-related osteonecrosis of the jaws (BRONJ) is a severe complication of BPs therapy with unknown pathogenesis. This study aimed to evaluate the impact of Actinomyces naeslundii (A. naeslundii) on the progression of BRONJ in ovariectomized (OVX) rat model with periodontal diseases. Sixty rats were randomly assigned into four groups. All rats underwent bilateral ovariectomy. Six weeks after surgery, animals with periodontitis induced by ligature placement were administrated with normal saline (NS), NS &A. naeslundii inoculation, zolecdronic acid (ZA) and ZA &A. naeslundii inoculation for 12 weeks, respectively. Loads of total bacteria and A. naeslundii in the mouth were assessed by real time PCR. After sacrifice, the mandibles were harvested for micro-computed tomography (micro-CT) and histological examination. Real-time PCR demonstrated that A. naeslundii was not routinely found in the rats and ZA treatment did not promote its accumulation. Micro-CT examination disclosed that ligature placement induced significant alveolar bone loss, which was greatly attenuated by ZA treatment and aggravated by A. naeslundii. Histological assessment demonstrated that ZA treatment increased the risk of developing BRONJ-like disease but this condition was not worsen with the presence of A. naeslundii. Our study suggested that oral A. naeslundii inoculation aggravated periodontal disease but not BRONJ in our animal model. PMID:26293192

  1. IgG isotype profile is correlated with cardiomegaly in Beagle dogs infected with distinct Trypanosoma cruzi strains.

    Science.gov (United States)

    Guedes, Paulo M M; Veloso, Vanja M; Gollob, Kenneth J; Afonso, Luis C C; Caldas, Ivo S; Vianna, Priscila; de Lana, Marta; Chiari, Egler; Bahia, Maria T; Galvão, Lúcia M C

    2008-07-15

    A systematic study following infection by various strains of the protozoan parasite, Trypanosoma cruzi, and the simultaneous monitoring of the humoral immune response together with the elicited cellular response, could add greatly to our understanding of differences between strains of this important human pathogen. In that sense, acute and chronic infections with distinct T. cruzi strains (Y, Berenice-78 and ABC) in Beagle dogs were studied through a longitudinal evaluation of immunoglobulin G (IgG), IgG1 and IgG2 isotypes (by ELISA and flow cytometry (FC)), as well as measurements of peripheral blood mononuclear cell (PBMC) proliferation over a 100-week period, and their correlation with cardiomegaly. Our results show that infected animals presenting cardiomegaly showed lower or absent levels of IgG1 during the chronic phase of the infection, when compared to those that did not show an increase in heart weight. In that manner, our results suggest that IgG1 could be used as a marker for cardiac pathogenicity in Chagas disease. PMID:18439688

  2. Removal of inhaled 241Am oxide particles of various sizes from beagle dogs using lung lavage and chelation treatment

    International Nuclear Information System (INIS)

    The combined treatments of lung lavage and chelation therapy were evaluated for the removal of inhaled 241AmO2 aerosols in Beagle dogs. Groups 1 to 3 were exposed to monodisperse particles of 241AmO2 of 0.75, 1.5 and 3.0 μm aerodynamic diameter (AD) respectively; a fourth group was exposed to polydisperse particles of 241AmO2 with an activity median aerodynamic diameter (AMAD) of 1.8 μm. Treatment consisted of 5 lung lavages of the right and left lungs. Treated dogs were also given 18 intravenous injections of DTPA. The dogs were sacrificed 64 days after inhalation exposure. The amount of 241Am removed from lung in the lavage fluid for Groups 1 to 4 represented 41, 46, 42 and 33 % of the initial lung burden, respectively. The amount of 241Am excreted in the urine from the treated dogs in excess of that excreted by the untreated dogs for Groups 1 to 4 was 20, 19, 8 and 26 %, respectively. More 241Am was excreted in the urine from dogs that inhaled smaller particle sized aerosols. As a result of the removal of 241Am activity, the 64-day cumulative absorbed radiation doses to lung, liver and skeleton were reduced by 50, 90 and 85 %, respectively. (author)

  3. Removal of inhaled 241Am oxide of various particle sizes from beagle dogs by lung lavage and chelation treatment

    International Nuclear Information System (INIS)

    The removal of 241Am oxide aerosols of various particle sizes from the lung was studied in 24 Beagle dogs. There were four groups of dogs with six dogs per group and each group inhaled an aerosol of 241Am oxide of a different particle size or particle size distribution. The four aerosols had sizes of: 0.75 μm AD, sigma/sub g/ 1.1; 1.5 μm AD, sigma/sub g/ 1.1; 3.0 μm AD, sigma/sub g/ 1.1; or 1.5 μm AMAD and sigma/sub g/ of 1.6. Three of the dogs in each group were treated with 10 lung lavages, the first lavage performed 2 days after exposure and the last lavage on day 49 after exposure. Each of these treated dogs was also given 100 mg diethylenetriaminepentaacetic acid (DTPA) intravenously daily for 4 days after 241Am exposure and twice per week thereafter to the end of the study. Daily excreta collections were made on each of the dogs until sacrifice at 64 days after exposure. The sacrifice body burden (SBB) was much lower for all of the treated dogs compared to the untreated dogs. The 241Am activity found in the recovered lavage fluid was two to four times greater than the sacrifice body burden. These results suggest that the treatment procedures were effective in reducing the lung and body burden of 241Am

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

    Science.gov (United States)

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

    2014-01-01

    We evaluated adverse events, biodistribution and shedding of oncolytic vaccinia virus encoding CD40 ligand in two Beagles, in preparation for a phase 1 trial in canine cancer patients. Dog 1 received one dose of vaccinia virus and was euthanized 24 hours afterwards, while dog 2 received virus four times once weekly and was euthanized 7 days after that. Dogs were monitored for adverse events and underwent a detailed postmortem examination. Blood, saliva, urine, feces, and organs were collected for virus detection. Dog 1 had mild fever and lethargy while dog 2 experienced a possible seizure 5.5 hours after first virus administration. Viral DNA declined quickly in the blood after virus administration in both dogs but was still detectable 1 week later by quantitative polymerase chain reaction. Only samples taken directly after virus infusion contained infectious virus. Small amounts of viral DNA, but no infectious virus, were detected in a few saliva and urine samples. Necropsies did not reveal any relevant pathological changes and virus DNA was detected mainly in the spleen. The dogs in the study did not have cancer, and thus adverse events could be more common and viral load higher in dogs with tumors which allow viral amplification. PMID:27119092

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

    Directory of Open Access Journals (Sweden)

    Juan Carlos Fernicola

    2009-04-01

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

  6. The pharmacokinetics of the β2-adrenoceptor agonist, tulobuterol, in Beagle dogs following transdermal and intravenous administration.

    Science.gov (United States)

    Kim, J H; Kim, T H; Park, H J; Choi, Y J; Kang, J H; Song, K H; Koo, T S; Seo, K W

    2016-02-01

    Tulobuterol is a β2-adrenergic agonist that was the first bronchodilator approved as a transdermal patch for humans. Previous studies have examined the pharmacokinetics of tulobuterol in humans but not in the veterinary species. In this study, the pharmacokinetics of tulobuterol was examined in healthy Beagle dogs after transdermal and intravenous administration. The Cmax was 2.09 ng/mL at 16.0 h for a 0.2 mg/kg patch and 4.85 ng/mL at 13.6 h for a 0.4 mg/kg patch. The effective blood level in humans is 1-3 ng/mL, a concentration achieved using the 0.2 mg/kg patch in dogs. In conclusion, application of a 0.2 mg/kg tulobuterol patch to healthy dogs led to an apparently effective blood concentration for 24 h. PMID:26639828

  7. Screw- vs cement-implant-retained restorations: an experimental study in the Beagle. Part 1. Screw and abutment loosening.

    Science.gov (United States)

    Assenza, Bartolomeo; Scarano, Antonio; Leghissa, Giulio; Carusi, Giorgio; Thams, Ulf; Roman, Fidel San; Piattelli, Adriano

    2005-01-01

    The causes of implant failures can be biological or mechanical. The mechanical causes include fracture of the implant, fracture of the abutment, and loosening of the abutment. Numerous studies show that abutment loosening constitutes one of the marked implant postsurgery complications requiring clinical intervention. The aim of the present study was to evaluate the incidence of the screw loosening in screwed or cemented abutments. Six adult male Beagles were used. In each dog, the first molars and 2 premolars were extracted. The sutures were removed after 7 days. After 3 months, 10 implants were placed in each dog, 5 in the right mandible and 5 in the left mandible. The abutments either were screwed in (n=30) by applying a total strength of 30 N/cm or were cemented (n=30). After 12 months, 8 (27%) loosened screws were present in screwed abutments, whereas no abutment loosening was observed in cemented abutments (P = .0001). Screwed abutments are often submitted to nonaxial loads that determine screw and abutment loosening. PMID:16265854

  8. Trace metal content in sediments and autochthonous intertidal organisms from two adjacent bays near Ushuaia, Beagle Channel (Argentina).

    Science.gov (United States)

    Duarte, Claudia Alejandra; Giarratano, Erica; Gil, Mónica N

    2012-08-01

    The aim of this work was to monitor levels of Cd, Cu, Pb, Zn and Fe in sediments, mussels (Mytilus edulis chilensis) and limpets (Nacella magellanica) from the Industrial zone (IZ); fuel dock (FD) and Ushuaia Peninsula (UP) on the Beagle Channel. In sediments, seasonal variations showed high values of Cu and Pb in spring and Zn in autumn. Comparing among sites, Cd concentration was superior in UP (2.07 μg/g); while Pb was maximum in FD (41.00 μg/g). In mussels, a higher bioaccumulation in winter was found. Mussels from UP showed the highest bioaccumulation of Cu (5.95 μg/g) and those from FD presented the highest of Zn (170.15 μg/g). A seasonal trend was not found for limpets, while differences among sites were observed for Cd being the highest at IZ (3.02 μg/g). Although pollution level found was low, anthropic activities at the studied sites could result in deterioration, further monitoring is recommended. PMID:22681905

  9. Retention patterns in beagle dogs repeatedly exposed to aerosols of 137Cs-labeled fused clay particles. II

    International Nuclear Information System (INIS)

    To provide an experimental evaluation of the adequacy of extrapolating single inhalation exposure kinetics to the repeated exposure situation, 12 Beagle dogs were given 10, 20, or 40 weekly, 10-min inhalation exposures to 137Cs in fused clay particles. Whole-body counting immediately before and after each exposure and at other intervals has been used to assess the kinetics of buildup and retention of the deposited material. Current analyses indicate that neither the deposition percentage nor the rate of buildup of 137Cs in the lung was affected by the number of exposures. Two dogs each were sacrificed at 7 days after 10, 20, or 40 inhalation exposures. Tissue analyses indicated that 96 percent of the body burden was in the lung, 0.3 to 1 percent in the tracheobronchial lymph nodes, and the remainder mainly in other soft tissues. Preliminary analysis of the whole-body retention data obtained after the last inhalation exposure for the six remaining living dogs indicates that the 137Cs is being retained somewhat more tenaciously than was observed in dogs that received a single inhalation exposure to a similar aerosol. Observations are continuing on these six dogs. (U.S.)

  10. Biological effects of repeated inhalation exposure of beagle dogs to aerosols of 144Ce in fused clay particles I

    International Nuclear Information System (INIS)

    This experiment was initiated to study the biological behavior and long-term effects of repeated inhalation exposures to 144Ce in fused clay particles compared with those seen in Beagle dogs that received a single exposure as young adults. The 36 dogs, divided into four equal groups, are exposed every 8 weeks to achieve the following: to maintain lung burdens of 9 and 4.5 μCi 144Ce/kg body weight in the first and second groups, respectively; to increase the lung burden by 2.5 μCi 144Ce/kg body weight in the third group with each exposure and to expose controls (fourth group) to fused clay containing stable cerium. With these exposure sequences, the 144Ce-exposed dogs will receive increasing or maintained β dose rates in contrast to the steadily decreasing dose rate seen after a single inhalation exposure. Exposures to the first and third groups will produce a cumulative absorbed dose to lung of approximately equal to 35,000 rads and those to the second group will yield approximately equal to 17,000 rads within 2 yr after the first exposure. Single exposure dogs that had died with pulmonary neoplasia when this experiment was initiated had cumulative doses to death of 29,000 to 61,000 rads. Six of the planned 13 exposures have been completed to date. All exposed dogs are surviving and will be maintained for lifespan observation. (U.S.)

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

    Science.gov (United States)

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

    2014-01-01

    We evaluated adverse events, biodistribution and shedding of oncolytic vaccinia virus encoding CD40 ligand in two Beagles, in preparation for a phase 1 trial in canine cancer patients. Dog 1 received one dose of vaccinia virus and was euthanized 24 hours afterwards, while dog 2 received virus four times once weekly and was euthanized 7 days after that. Dogs were monitored for adverse events and underwent a detailed postmortem examination. Blood, saliva, urine, feces, and organs were collected for virus detection. Dog 1 had mild fever and lethargy while dog 2 experienced a possible seizure 5.5 hours after first virus administration. Viral DNA declined quickly in the blood after virus administration in both dogs but was still detectable 1 week later by quantitative polymerase chain reaction. Only samples taken directly after virus infusion contained infectious virus. Small amounts of viral DNA, but no infectious virus, were detected in a few saliva and urine samples. Necropsies did not reveal any relevant pathological changes and virus DNA was detected mainly in the spleen. The dogs in the study did not have cancer, and thus adverse events could be more common and viral load higher in dogs with tumors which allow viral amplification. PMID:27119092

  12. Effect of posture and anaesthesia on the distribution of pulmonary perfusion and lung configuration in beagle dogs

    International Nuclear Information System (INIS)

    To investigate the effect of posture and anaesthesia on the topographical distribution of pulmonary perfusion in canine lungs, the changes in lung shape, configuration and regional perfusion were assessed in healthy beagle dogs, using a repeated 99mTc perfusion scintigraphic procedure. The general shape of the lung images was similar in standing and prone postures, except for a relative increase of the more ventral zone in the prone posture, ascribed to vertical flattening of the lung associated with enlargement of the ventral zones. Configuration changes revealed a shift of the parenchyma towards the more caudal parts in the prone posture, which suggests a parenchymal compression of the paradiaphragmatic lung zones. The prone posture induced a decreased perfusion to the caudal third of the lung. Anaesthesia induced significant changes in lung shape without an obvious direction. The perfusion to the more ventral as well as to the more cranial zones was reduced. Differences in the perfusion distribution are thought to be mainly due to the pressure exerted by the abdominal content through the diaphragm and to the shift of the blood towards better ventilated lung regions

  13. Analysis of the toxicity and radioprotective effect of the chemical radioprotector WR 2721 in dogs (beagles). Pt. 2

    International Nuclear Information System (INIS)

    In order to examine the efficacy of the radioprotective agent Aminopropylamino-enthylthiophosphate (WR 2721) in larger animals, 43 adult male dogs (beagles) were exposed to gamma rays. The LD50sub(/)30 values were determined by probit analysis. The LD50sub(/)30 value for unprotected control animals has been found to be around 274 rd, while for animals pretreated with 150 mg WR 2721/kg body weight this value lay at about 632 rd. Hence the DRF due to WR 2721 is 2.3, i.e. the midlethal dose of irradiation for protected animals was higher by the 2.3 fold against control animals. The protective action of WR 2721 could also be observed at the lesser post-irradiation decrease of thrombocytes, leucocytes and lymphocytes and at the quick recovery of bone-marrow. The symptoms of radiation sickness were observed in the protected dogs only after exposure to high doses (650 and 750 rd). All data on clinical-chemical parameters of sera were subjected to variance and discriminant analyses. On the bases of these clinical data the animals could be classified with 90% certainty into their exposure doses. The discriminant analyses of these data allowed the prediction whether an experimental animal would die before or after the 10th day p.r. or survive the assault. These clinical data have obvious relevance to the problem of biological dosimetry. (orig.)

  14. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model

    OpenAIRE

    Britton, Robert A.; Irwin, Regina; Quach, Darin; Schaefer, Laura; Zhang, Jing; Lee, Taehyung; Parameswaran, Narayanan; McCabe, Laura R.

    2014-01-01

    Estrogen deficiency is a major risk factor for osteoporosis that is associated with bone inflammation and resorption. Half of women over the age of 50 will experience an osteoporosis related fracture in their lifetime, thus novel therapies are needed to combat post-menopausal bone loss. Recent studies suggest an important role for gut-bone signaling pathways and the microbiota in regulating bone health. Given that the bacterium Lactobacillus reuteri ATCC PTA 6475 (L. reuteri) secretes benefic...

  15. The stimulation of respiration by progesterone in ovariectomized cat is mediated by an estrogen-dependent hypothalamic mechanism requiring gene expression.

    Science.gov (United States)

    Bayliss, D A; Cidlowski, J A; Millhorn, D E

    1990-01-01

    The central site of action and the cellular mechanism by which progesterone stimulates respiration were studied in ovariectomized cats that were anesthetized, paralyzed, and ventilated and in which respiratory sensory feedback mechanisms were either eliminated or controlled. Phrenic nerve activity served as an index of central respiratory output. Progesterone did not stimulate respiration in ovariectomized cats not pretreated with estrogen. In contrast, repeated doses of progesterone (0.1-1.0 microgram/kg, iv, cumulative) caused a sustained (greater than 45 min) dose-dependent facilitation of phrenic nerve activity in animals primed 3 days before study with 17 beta-estradiol (20 micrograms/kg, sc). Estrogen exposure is, therefore, a prerequisite for the respiratory response to progesterone in ovariectomized cats. This estrogen-dependent respiratory response to progesterone was attenuated in animals pretreated with either the estrogen receptor antagonist CI628 or the progesterone receptor antagonist RU486, indicating that the respiratory response is mediated by both estrogen and progesterone receptors. Inhibitors of protein (anisomycin) and RNA (actinomycin-D) synthesis caused a diminution of the respiratory response to progesterone, implicating a requirement for gene expression in the response. Midcollicular decerebration (which removed the diencephalon) attenuated, whereas decortication (which spared the diencephalon) did not affect the respiratory response to progesterone. Thus, the diencephalon appears to be a critical neuroanatomical substrate for the response. These results indicate that the respiratory response to progesterone is mediated, at a hypothalamic site, via a genomic mechanism with characteristics consistent with the prototypic mechanism for progesterone actions. PMID:2294002

  16. Hawthorn Fruit Extract Elevates Expression of Nrf2/HO-1 and Improves Lipid Profiles in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Jeong-Hyun Yoo

    2016-05-01

    Full Text Available The purpose of this study was to investigate the effects of hawthorn (Crataegus pinnatifida Bunge extract on the lipid profiles and antioxidant properties in ovariectomized (OVX rats. After ovariectomy, the rats were randomly divided into four groups: the non-OVX control (Sham, the OVX-control (OVX, the OVX + 100 mg/kg b.w. of hawthorn extract (OL, and the OVX + 200 mg/kg b.w. of hawthorn extract (OH. The final body weights of the OVX group were significantly increased, but the increment was significantly decreased in hawthorn groups (p < 0.05. The serum total and low-density lipoprotein (LDL cholesterol levels were significantly elevated in the OVX group, whereas the hawthorn groups showed a significant decrease in these levels (p < 0.05. The hepatic triglyceride (TG and malondialdehyde (MDA levels were significantly reduced in the hawthorn groups compared with the OVX group (p < 0.05. The mRNA expression of nuclear factor erythroid 2–related factor (Nrf2, heme oxygenase-1 (HO-1, and glutathione peroxidase (GPx were significantly decreased in the OVX group, whereas the hawthorn groups exhibited a significant increase in expression (p < 0.05. The protein expressions of Nrf2, HO-1, and GPx were lower in the OVX group than the Sham group (p < 0.05. The oral administration of hawthorn extract reversed the suppression of protein levels. These results suggest that hawthorn extract could have protective effects in OVX rats by improving lipid profiles, decreasing oxidative stress, and improving the antioxidant defense system.

  17. Comparative temporal and dose-dependent morphological and transcriptional uterine effects elicited by tamoxifen and ethynylestradiol in immature, ovariectomized mice

    Directory of Open Access Journals (Sweden)

    Burgoon Lyle D

    2007-06-01

    Full Text Available Abstract Background Uterine temporal and dose-dependent histopathologic, morphometric and gene expression responses to the selective estrogen receptor modulator tamoxifen (TAM were comprehensively examined to further elucidate its estrogen receptor-mediated effects. These results were systematically compared to the effects elicited by the potent estrogen receptor ligand 17α-ethynylestradiol (EE to identify pathways similarly and uniquely modified by each compound. Results Three daily doses of 100 μg/kg TAM elicited a dose-dependent increase in uterine wet weight (UWW in immature, ovariectomized C57BL/6 mice at 72 hrs with concurrent increases in luminal epithelial cell height (LECH, luminal circumference and glandular epithelial tubule number. Significant UWW and LECH increases were detected at 24 hrs after a single dose of 100 μg/kg TAM. cDNA microarray analysis identified 2235 differentially expressed genes following a single dose of 100 μg/kg TAM at 2, 4, 8, 12, 18 and 24 hrs, and at 72 hrs after three daily doses (3 × 24 hrs. Functional annotation of differentially expressed genes was associated with cell growth and proliferation, cytoskeletal organization, extracellular matrix modification, nucleotide synthesis, DNA replication, protein synthesis and turnover, lipid metabolism, glycolysis and immunological responses as is expected from the uterotrophic response. Comparative analysis of TAM and EE treatments identified 1209 common, differentially expressed genes, the majority of which exhibited similar profiles despite a temporal delay in TAM elicited responses. However, several conserved and treatment specific responses were identified that are consistent with proliferation (Fos, Cdkn1a, Anapc1, and water imbibition (Slc30a3, Slc30a5 responses elicited by EE. Conclusion Overall, TAM and EE share similar gene expression profiles. However, TAM responses exhibit lower efficacy, while responses unique to EE are consistent with the

  18. Protective effects of white button mushroom (Agaricus bisporus against hepatic steatosis in ovariectomized mice as a model of postmenopausal women.

    Directory of Open Access Journals (Sweden)

    Noriko Kanaya

    Full Text Available Nonalcoholic fatty liver disease (NAFLD includes various hepatic pathologies ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH, fibrosis and cirrhosis. Estrogen provides a protective effect on the development of NAFLD in women. Therefore, postmenopausal women have a higher risk of developing NAFLD. Hepatic steatosis is an early stage of fatty liver disease. Steatosis can develop to the aggressive stages (nonalcoholic steatohepatitis, fibrosis and cirrhosis. Currently, there is no specific drug to prevent/treat these liver diseases. In this study, we found that white button mushroom (WBM, Agaricus Bisporus, has protective effects against liver steatosis in ovariectomized (OVX mice (a model of postmenopausal women. OVX mice were fed a high fat diet supplemented with WBM powder. We found that dietary WBM intake significantly lowered liver weight and hepatic injury markers in OVX mice. Pathological examination of liver tissue showed less fat accumulation in the livers of mice on WBM diet; moreover, these animals had improved glucose clearance ability. Microarray analysis revealed that genes related to the fatty acid biosynthesis pathway, particularly the genes for fatty acid synthetase (Fas and fatty acid elongase 6 (Elovl6, were down-regulated in the liver of mushroom-fed mice. In vitro mechanistic studies using the HepG2 cell line showed that down-regulation of the expression of FAS and ELOVL6 by WBM extract was through inhibition of Liver X receptor (LXR signaling and its downstream transcriptional factor SREBP1c. These results suggest that WBM is protective against hepatic steatosis and NAFLD in OVX mice as a model for postmenopausal women.

  19. Combined effects of exercise and soy isoflavone diet on paraoxonase, nitric oxide and aortic apoptosis in ovariectomized rats.

    Science.gov (United States)

    Lee, Jin; Cho, Hyung-Sook; Kim, Dae-Young; Cho, Joon-Yong; Chung, Jae-Soon; Lee, Han-Kyung; Seong, Nak-Hun; Kim, Won Kyu

    2012-04-01

    Menopause is associated with an increased risk of cardiovascular disease (CVD). Exercise and soy isoflavone diets have been suggested to reduce the risk of CVD in postmenopausal women. We investigated the effects of exercise, or combined exercise and soy isoflavone diet, on plasma lipid profiles, paraoxonase (PON), nitric oxide (NO) and apoptosis in the aorta of ovariectomized (OVX) rats. Thirty-two female Sprague-Dawley rats were divided into four groups: OVX with general diet (OVX-GD), OVX with isoflavone diet (OVX-ISO), OVX-GD with exercise training (OVX-ET) and OVX-ISO with exercise training (OVX-ISO+ET). The experimental rats undertook treadmill training (30 min/day, 4 days/week) and/or were supplied a soy isoflavone diet (added to the experimental diet at 2.39 mg/g protein) for 12 weeks. Body weight and levels of total cholesterol (TC), triglyceride (TG), LDL-cholesterol (LDL-C) increased in the OVX rats and HDL-C decreased. These effects were reduced by exercise and/or soy isoflavone supplementation. PON and NO activities were higher in the OVX-ISO+ET group than in the OVX-GD group. In addition, this group had lower caspase-9 and -3 and higher Bcl-2 expression, and there was less aortic apoptotic cell death. These results suggest that a combination of exercise and a soy isoflavone diet has beneficial effects in terms of protecting against cardiovascular risk factors by controlling lipid profiles and the related enzyme, PON, as well as NO activity and apoptosis of the aorta in OVX rats. PMID:22227066

  20. Effects of Long-Term Treatment with Estradiol and Estrogen Receptor Subtype Agonists on Serotonergic Function in Ovariectomized Rats.

    Science.gov (United States)

    Benmansour, Saloua; Adeniji, Opeyemi S; Privratsky, Anthony A; Frazer, Alan

    2016-01-01

    Acute estradiol treatment was reported to slow the clearance of serotonin via activation of estrogen receptors (ER)β and/or GPR30 and to block the ability of a selective serotonin reuptake inhibitor (SSRI) to slow serotonin clearance via activation of ERα. In this study, the behavioral consequences of longer-term treatments with estradiol or ER subtype-selective agonists and/or an SSRI were examined in the forced swim test (FST). Ovariectomized rats were administered the following for 2 weeks: estradiol, ERβ agonist (diarylpropionitrile, DPN), GPR30 agonist (G1), ERα agonist (PPT), and/or the SSRI sertraline. Similar to sertraline, longer-term treatment with estradiol, DPN or G1 induced an antidepressant-like effect. By contrast, PPT did not, even though it blocked the antidepressant-like effect of sertraline. Uterus weights, used as a peripheral measure of estrogenic activity, were increased by estradiol and PPT but not DPN or G1 treatment. A second part of this study investigated, using Western blot analyses in homogenates from hippocampus, whether these behavioral effects are accompanied by changes in the activation of specific signaling pathways and/or TrkB. Estradiol and G1 increased phosphorylation of Akt, ERK and TrkB. These effects were similar to those obtained after treatment with sertraline. Treatment with DPN increased phosphorylation of ERK and TrkB, but it did not alter that of Akt. Treatment with PPT increased phosphorylation of Akt and ERK without altering that of TrkB. In conclusion, activation of at least TrkB and possibly ERK may be involved in the antidepressant-like effect of estradiol, ERβ and GPR30 agonists whereas Akt activation may not be necessary. PMID:26159182

  1. Dried Pomegranate Potentiates Anti-Osteoporotic and Anti-Obesity Activities of Red Clover Dry Extracts in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Su Jin Kang

    2015-04-01

    Full Text Available Red clover (RC shows potential activity against menopausal symptoms and pomegranates have antioxidative and beneficial effects on postmenopausal symptoms; thus, we investigated whether the anti-climacteric activity of RC could be enhanced by the addition of dried pomegranate concentrate powder (PCP extracts in ovariectomized (OVX rats. Regarding the anti-osteoporotic effects, bone mineral density increased significantly in OVX induced rats treated with 60 and 120 mg/kg of an RC:PCP 2:1 mixture, respectively, compared with OVX control rats. Additionally, femoral, tibia, and L4 bone resorption was decreased in OVX induced control rats treated with the RC:PCP 2:1 mixture (60 and 120 mg/kg, respectively, compared with OVX control rats. Regarding anti-obesity effects, the OVX induced rats treated with 60 and 120 mg/kg of the RC:PCP 2:1 mixture showed a decrease in total fat pad thickness, the mean diameters of adipocytes and the body weights gain compared with OVX induced control rats. The estradiol and bone-specific alkaline phosphatase levels were significantly increased in OVX induced rats treated with the RC:PCP 2:1 mixture (120 mg/kg compared with OVX induced control rats, also, the uterine atrophy was significantly inhibited in 60 and 120 mg/kg of the RC:PCP 2:1 mixture treatment compared with OVX control rats. In conclusion, our results indicate that PCP enhanced the anti-climacteric effects of RC in OVX rats. The RC:PCP 2:1 mixture used in this study may be a promising new potent and protective agent for relieving climacteric symptoms.

  2. Effects of Long-Term Odanacatib Treatment on Bone Gene Expression in Ovariectomized Adult Rhesus Monkeys: Differentiation From Alendronate.

    Science.gov (United States)

    Muise, Eric S; Podtelezhnikov, Alexei A; Pickarski, Maureen; Loboda, Andrey; Tan, Yejun; Hu, Guanghui; Thomspon, John R; Duong, Le T

    2016-04-01

    Similar efficacy of the cathepsin K inhibitor odanacatib (ODN) and the bisphosphonate alendronate (ALN) in reducing bone turnover markers and increasing bone mineral density in spine and hip were previously demonstrated in ovariectomized (OVX)-monkeys treated for 20 months in prevention mode. Here, we profiled RNA from tibial metaphysis and diaphysis of the same study using Affymetrix microarrays, and selected 204 probe sets (p < 0.001, three-group ANOVA) that were differentially regulated by ODN or ALN versus vehicle. Both drugs produced strikingly different effects on known bone-related genes and pathways at the transcriptional level. Although ALN either reduced or had neutral effects on bone resorption-related genes, ODN significantly increased the expression of osteoclast genes (eg, APC5, TNFRSF11A, CTSK, ITGB3, and CALCR), consistent with previous findings on the effects of this agent in enhancing the number of nonresorbing osteoclasts. Conversely, ALN reduced the expression of known bone formation-related genes (eg, TGFBR1, SPP1, RUNX2, and PTH1R), whereas ODN either increased or had neutral effects on their expression. These differential effects of ODN versus ALN on bone resorption and formation were highly correlative to the changes in bone turnover markers, cathepsin K (Catk) target engagement marker serum C-terminal cross-linked telopeptide (1-CTP) and osteoclast marker tartrate resistant acid phosphatase isoform 5b (TRAP5b) in the same monkeys. Overall, the molecular profiling results are consistent with the known pharmacological actions of these agents on bone remodeling and clearly differentiate the molecular mechanisms of ODN from the bisphosphonates. © 2016 American Society for Bone and Mineral Research. PMID:26587671

  3. Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats.

    Science.gov (United States)

    Pinkham, Maximilian I; Whalley, Gillian A; Guild, Sarah-Jane; Malpas, Simon C; Barrett, Carolyn J

    2015-07-15

    There is controversy regarding whether the arterial baroreflex control of renal sympathetic nerve activity (SNA) in heart failure is altered. We investigated the impact of sex and ovarian hormones on changes in the arterial baroreflex control of renal SNA following a chronic myocardial infarction (MI). Renal SNA and arterial pressure were recorded in chloralose-urethane anesthetized male, female, and ovariectomized female (OVX) Wistar rats 6-7 wk postsham or MI surgery. Animals were grouped according to MI size (sham, small and large MI). Ovary-intact females had a lower mortality rate post-MI (24%) compared with both males (38%) and OVX (50%) (P < 0.05). Males and OVX with large MI, but not small MI, displayed an impaired ability of the arterial baroreflex to inhibit renal SNA. As a result, the male large MI group (49 ± 6 vs. 84 ± 5% in male sham group) and OVX large MI group (37 ± 3 vs. 75 ± 5% in OVX sham group) displayed significantly reduced arterial baroreflex range of control of normalized renal SNA (P < 0.05). In ovary-intact females, arterial baroreflex control of normalized renal SNA was unchanged regardless of MI size. In males and OVX there was a significant, positive correlation between left ventricle (LV) ejection fraction and arterial baroreflex range of control of normalized renal SNA, but not absolute renal SNA, that was not evident in ovary-intact females. The current findings demonstrate that the arterial baroreflex control of renal SNA post-MI is preserved in ovary-intact females, and the state of left ventricular dysfunction significantly impacts on the changes in the arterial baroreflex post-MI. PMID:25994953

  4. Addition of Fructooligosaccharides and Dried Plum to Soy-Based Diets Reverses Bone Loss in the Ovariectomized Rat

    Directory of Open Access Journals (Sweden)

    Catherine D. Johnson

    2011-01-01

    Full Text Available Dietary bioactive components that play a role in improving skeletal health have received considerable attention in complementary and alternative medicine practices as a result of their increased efficacy to combat chronic diseases. The objectives of this study were to evaluate the additive or synergistic effects of dried plum and fructooligosaccharides (FOS and to determine whether dried plum and FOS or their combination in a soy protein-based diet can restore bone mass in ovarian hormone deficient rats. For this purpose, 72 3-month-old female Sprague-Dawley rats were divided into six groups (n = 12 and either ovariectomized (Ovx, five groups or sham-operated (sham, one group. The rats were maintained on a semipurified standard diet for 45 days after surgery to establish bone loss. Thereafter, the rats were placed on one of the following dietary treatments for 60 days: casein-based diet (Sham and Ovx, soy-based diet (Ovx + soy or soy-based diet with dried plum (Ovx + soy + plum, FOS (Ovx + soy + FOS and combination of dried plum and FOS (Ovx + soy + plum + FOS. Soy protein in combination with the test compounds significantly improved whole-body bone mineral density (BMD. All test compounds in combination with soy protein significantly increased femoral BMD but the combination of soy protein, dried plum and FOS had the most pronounced effect in increasing lumbar BMD. Similarly, all of the test compounds increased ultimate load, indicating improved biomechanical properties. The positive effects of these test compounds on bone may be due to their ability to modulate bone resorption and formation, as shown by suppressed urinary deoxypyridinoline excretion and enhanced alkaline phosphatase activity.

  5. Effects of treatment with estrogen and progesterone on the methamphetamine-induced cognitive impairment in ovariectomized rats.

    Science.gov (United States)

    Ghazvini, Hamed; Khaksari, Mohammad; Esmaeilpour, Khadijeh; Shabani, Mohammad; Asadi-Shekaari, Majid; Khodamoradi, Mehdi; Sheibani, Vahid

    2016-04-21

    Methamphetamine (METH) is one of the most powerful psychostimulant that leads to long lasting cognitive impairment. Earlier researches demonstrated that ovarian hormones including estrogen and progesterone ameliorate cognitive function against various central nervous system disorders. Moreover, recent studies demonstrate a neuroprotective role against methamphetamine toxicity. In current study the effects of estrogen and progesterone alone or in combination, on spatial learning and memory in METH-exposed ovariectomized (OVX) rats are investigated. Three weeks after ovariectomy, the animals were treated by estrogen (1mg/kg, i.p.) and progesterone (8mg/kg, i.p.) alone and in combination or vehicle during 14 consecutive days. On the 28th day, rats were exposed to a single-day METH regimens (four injections of 6mg/kg, s.c, at 2h intervals) 30min after the hormones treatment. Finally, spatial learning and memory were examined using the Morris water maze 2days after the last treatment. The findings showed that estrogen and progesterone did not have significant effect on spatial learning and memory in non METH-exposed OVX rats. The treatment with estrogen and progesterone alone in METH-exposed rats, significantly improved spatial learning and memory impairment. On the other hand, the cognitive performance of animals that received combination of estrogen plus progesterone in METH-exposed rats did not significantly differ from that of METH-exposed animals that received vehicle injections. Taken together, the present findings suggest that treatment with ovarian hormones can partially improve spatial learning and memory deficits induced by methamphetamine in OVX rats. PMID:26944454

  6. Effects of genistein on cognitive dysfunction and hippocampal synaptic plasticity impairment in an ovariectomized rat kainic acid model of seizure.

    Science.gov (United States)

    Khodamoradi, Mehdi; Asadi-Shekaari, Majid; Esmaeili-Mahani, Saeed; Esmaeilpour, Khadije; Sheibani, Vahid

    2016-09-01

    The major objective of this study was to investigate the probable effects of genistein (one of the most important soy phytoestrogens-SPEs) on seizure-induced cognitive dysfunction, hippocampal early long-term potentiation (E-LTP) impairment and morphological damage to CA1 neurons in ovariectomized (OVX) rats. Three weeks after ovariectomy, cannulae were implanted over the left lateral ventricle. After a 7-day recovery period, animals were injected by genistein (0.5 or 5mg/kg) or vehicle during four consecutive days, each 24h. One h after the last treatment, kainic acid (KA) or vehicle was perfused into the left lateral ventricle to induce generalized tonic-clonic seizures. Finally, 7 days later, spatial learning and memory of animals were examined using the Morris water maze (MWM) task, hippocampal E-LTP was assessed using in-vivo field potential recordings and the morphology of hippocampal CA1 area was examined using Fluoro-Jade C staining. KA-induced generalized seizures resulted in spatial learning and memory impairment, E-LTP deficit and CA1 cell injury. Seizure-induced abnormalities improved partially only by the lower dose of genistein (0.5mg/kg). However, genistein at the higher dose (5mg/kg) did not have any beneficial effects. Also, genistein did not affect seizure activity. It is concluded that genistein may have partially preventive effects against seizure-induced cognitive impairment in OVX rats. Also, it seems that such effects of genistein are correlated with its beneficial effects on hippocampal synaptic plasticity and morphology. PMID:27235295

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

    OpenAIRE

    Thiago Ignácio Wakoff; Rodrigo Mencalha; Natália Soares Souza; Carlos Augusto dos Santos Sousa; Mariana do Desterro Inácio e Sousa; Paulo Oldemar Scherer

    2013-01-01

    The brachial plexus block (BPB) is a regional anesthesia technique which enables the attainment of surgical procedures distal scapulohumeral articulation. This study aimed to compare the efficacy of ropivacaine and bupivacaine 0.25% without vasoconstrictor in BPB guided by electrical stimulation in dogs. Thirteen male and female beagle dogs underwent a BPB using bupivacaine and ropivacaine 0.25% (4mg/kg), both alone and in different times. The anesthesic block was performed in the right forel...

  8. Individual and combined effects of noise-like whole-body vibration and parathyroid hormone treatment on bone defect repair in ovariectomized mice.

    Science.gov (United States)

    Matsumoto, Takeshi; Sato, Daisuke; Hashimoto, Yoshihiro

    2016-01-01

    The effectiveness of intermittent administration of parathyroid hormone and exposure to whole-body vibration on osteoporotic fracture healing has been previously investigated, but data on their concurrent use are lacking. Thus, we evaluated the effects of intermittent administration of parathyroid hormone, whole-body vibration, and their combination on bone repair in osteoporotic mice. Noise-like whole-body vibration with a broad frequency range was used instead of conventional sine-wave whole-body vibration at a specific frequency. Mice were ovariectomized at 9 weeks of age and subjected to drill-hole surgery in the right tibial diaphysis at 11 weeks. The animals were divided into four groups (n = 12 each): a control group, and groups treated with intermittent administration of parathyroid hormone, noise-like whole-body vibration, and both. From postoperative day 2, the groups treated with intermittent administration of parathyroid hormone and groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration were subcutaneously administered parathyroid hormone at a dose of 30 µg/kg/day. The groups treated with noise-like whole-body vibration and groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration were exposed to noise-like whole-body vibration at a root mean squared acceleration of 0.3g and frequency components of 45-100 Hz for 20 min/day. Following 18 days of interventions, the right tibiae were harvested, and the regenerated bone was analyzed by micro-computed tomography and nanoindentation testing. Compared with the control group, callus volume fraction was 40% higher in groups treated with intermittent administration of parathyroid hormone and 73% higher in groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration, and callus thickness was 35% wider in groups treated with both

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

    Science.gov (United States)

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

    2016-10-01

    The objective of this study was to develop a novel prasugrel base microsphere-loaded tablet (PBMST) with enhanced stability as a bioequivalent to the commercial prasugrel hydrochloride-loaded tablet. Numerous prasugrel base-loaded microspheres were prepared with hydroxypropylmethyl cellulose (HPMC), colloidal silica and various acidifying agents using a spray-drying process, and the physicochemical properties, solubility and stability were investigated. The PBMSTs were prepared and their dissolution, pharmacokinetics in beagle dogs and stability were evaluated compared to commercial prasugrel hydrochloride-loaded tablets. Among the acidifying agents tested, phosphoric acid provided the greatest increase in drug solubility, by as much as 110-fold. The prasugrel base-loaded microspheres composed of prasugrel base, HPMC, colloidal silica and phosphoric acid at a weight ratio of 10/10/5/2.5 provided an amorphous drug and reduced particle size of about 11.3μm. Moreover, it exhibited excellent solubility and improved stability compared to prasugrel base and hydrochloride. Moreover, PBMST drug dissolution was improved in comparison to the prasugrel base-loaded tablet (PBT), with similar dissolution to the commercial prasugrel hydrochloride-loaded tablet at pH 1.2 and 4.0. PBMST provided significantly higher plasma concentrations of AUC and Cmax in beagle dogs compared to PBT. In particular, the AUC of PBMST was approximately four times greater than PBT, leading to improved oral bioavailability. There were no significant differences observed for all pharmacokinetic parameters between PBMST and the commercial prasugrel hydrochloride-loaded tablet, suggesting their bioequivalence in beagle dogs. Furthermore, the prepared PBMSTs were stable for at least six months. Therefore, this novel prasugrel base microsphere-loaded tablet could be a potential alternative for enhancing the stability and bioavailability of prasugrel. PMID:27451362

  10. The effect of gamma irradiation on the biological properties of intervertebral disc allografts: in vitro and in vivo studies in a beagle model.

    Directory of Open Access Journals (Sweden)

    Yu Ding

    Full Text Available STUDY DESIGN: An animal experiment about intervertebral disc allograft. OBJECTIVE: To explore the feasibility to decellularize disc allografts treated by 6°Co Gamma Irradiation, and simultaneously, to assess the possibility to make use of the decellularized natural disc scaffold for disc degeneration biotherapy. SUMMARY OF BACKGROUND DATA: Studies of both animal and human disc allograft transplantation indicated that the disc allograft may serve as a scaffold to undertake the physiological responsibility of the segment. METHODS: Experiment in vitro: 48 discs of beagles were harvested and divided randomly into four groups including a control group and three irradiated groups. Immediate cell viability and biomechanical properties of the discs were checked and comparisons were made among these groups. Experiment in vivo: 24 beagles accepted single-level allografted disc treated with different doses of gamma irradiation. Plain X-rays and MRIs were taken before and after surgery. Then, the spinal columns were harvested en bloc from the sacrificed beagles and were examined morphologically. RESULTS: There were significant differences of both the annulus fibrosus and nucleus pulposus immediate cell viabilities among the various groups. There were no obvious differences of the biomechanical properties among the four groups. The disc height and range of motion decreased significantly in all groups as time went on. The observed indexes in irradiated groups were much smaller than those in the control group, but the indexes in 18-kGy group were larger than those in 25-kGy and 50-kGy groups. Both MRI and macroscopic findings showed that the segmental degeneration in the control and 18-kGy group was less severe than that in 25-kGy and 50-kGy groups. CONCLUSION: Gamma Irradiation can decellularize disc allograft successfully to provide natural scaffold for the study of degenerative disc disease therapy, and also can be used as an effective method to produce

  11. Effect of exogenous estradiol on plasma concentrations of somatotropin, insulin-like growth factor-I, insulin-like growth factor binding protein activity, and metabolites in ovariectomized Angus and Brahman cows.

    Science.gov (United States)

    Simpson, R B; Chase, C C; Spicer, L J; Carroll, J A; Hammond, A C; Welsh, T H

    1997-11-01

    To determine the effect of breed and estradiol-17 beta on selected hormones and metabolites, ovariectomized (> or = 3 mo) Angus (n = 14) and Brahman (n = 12) cows were paired by age and body weight and randomly assigned as either nonimplanted controls (CON) or implanted with estradiol (E2) for 45 d. After Day 7 and through Day 42, plasma concentration of somatotropin was greater for E2 than CON cows (treatment x day, P 0.10) by E2 treatment. The effect of breed was apparent on Day 36 as Brahman cows had greater (P Angus cows. Overall, plasma concentration of IGF-I was greater (P Brahman than Angus cows (164.1 vs. 98.4 ng/ml). However, there was a trend (P x breed x day interaction for IGF-I (i.e., the magnitude of increase in IGF-I concentration was greater in E2-Angus than E2-Brahman cows). After Day 7 and through Day 42, total plasma IGF binding protein (IGFBP) activity was greater (P Brahman cows had greater (P Angus cows. After Day 14 and through Day 42, concentration of urea nitrogen (PUN) was greater (P x day, P Brahman had greater (P Angus cows (16.6 vs. 14.2 mg/dl). Plasma concentration of glucose was greater (P 0.10) by breed. In summary, these data suggest that some, but not all, of the positive effects of estradiol on peripheral concentration of IGF-I and IGFBP activity can be attributed to increased somatotropin. Moreover, breed influenced basal and E2-induced secretion of somatotropin and IGF-I such that differences between Brahman and Angus cows in plasma IGF-I concentrations were abated within 3 wk of estradiol implantation. Thus, breed influences the metabolite and hormonal response of cattle to estrogenic implants. PMID:9437573

  12. Isótopos estables del carbono en restos humanos de Península Mitre y del Canal Beagle, Tierra del Fuego

    OpenAIRE

    Kozameh, Livia Febes; Panarello, Héctor; Tessone, Augusto; Testa, N; Valencio, Susana; Zangrando, Francisco Atilio

    2003-01-01

    El objetivo de este trabajo es realizar un análisis comparativo de los valores isotópicos del carbono (δ13C) medidos sobre gelatina ósea extraída de restos humanos procedentes de Península Mitre y del canal Beagle, Tierra del Fuego. Paralelamente, se discute esta información con aquella recabada a partir de otros estudios referidos a rastros fisiológicos y patológicos del esqueleto y del aparato masticatorio efectuados en ambas regiones. Los resultados señalan que, si bien en los análisis de ...

  13. Isótopos estables del carbono en restos óseos humanos de la región del canal Beagle, Isla Grande de Tierra del Fuego

    OpenAIRE

    Tessone, Augusto; Zangrando, Francisco Atilio; Valencio, Susana; Panarello, Héctor

    2003-01-01

    El objetivo de este trabajo es conocer las particularidades de la dieta de grupos cazadores-recolectores, que habitaron la región del canal Beagle durante el Holoceno medio y tardío, mediante el análisis de isótopos estables del carbono sobre el colágeno de sus restos óseos. Se dan a conocer los valores de la 8¹³C obtenidos en cinco individuos. Seis determinaciones efectuadas previamente por otros autores en la misma región señalaron una variación mayor que la esperada en base a la informació...

  14. Establishment of a Method to Measure Length of the Ulnar Nerve and Standardize F-wave Values in Clinically Normal Beagles

    OpenAIRE

    HIRASAWA, Shun; Shimizu, Miki; MARUI, Yuumi; KISHIMOTO, Miori; OKUNO, Seiichi

    2014-01-01

    We designed a new method of measuring the length of the ulnar nerve and determining standard values for F-wave parameters of the ulnar nerve in clinically normal beagles. Nerve length must be precisely measured to determine F-wave latency and conduction velocity. The length of the forelimb has served as the length of the ulnar nerve for F-wave assessments, but report indicates that F-wave latency is proportional to the length of the pathway traveled by nerve impulses. Therefore, we measured t...

  15. Development and validation of a rapid and sensitive UHPLC–MS/MS method for the determination of paliperidone in beagle dog plasma

    OpenAIRE

    Hongming Chen; Longshan Zhao; Guangjing Li; Donglei Leng; Panqin Ma; Lijin Tong; Tianhong Zhang

    2014-01-01

    In order to evaluate the pharmacokinetic profile of paliperidone extended-release tablets in vivo, a simple and rapid ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was developed and validated for the determination of paliperidone in beagle dog plasma. Paliperidone and diazepam (internal standard) were extracted from plasma samples with diethyl ether, and then separated on a C18 column (2.1 × 50 mm, 2.6 μm) under gradient elution with methanol–0.1% ...

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

    Science.gov (United States)

    Symonds, Martin

    2002-07-01

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

  17. Chronic effects of maternal ethanol and low-protein intake on growth and blood measurements of beagle pups

    International Nuclear Information System (INIS)

    Pups used in this study were born to nulliparous, purebred female beagles fed either 17% control (CP) or 8.5% low protein (LP) diets and were given twice daily either 1.8 g/kg ethanol (E) or an equivalent isocaloric dose of sucrose (S) throughout pregnancy. After parturition, all mothers were fed the CP diet and no E or S. On day 1 and each week up to 4 weeks, the weight (WT), crown-rump length (LT) and head circumference (HC) of the pups were measured. These measurements were taken for a post-weaning subset at 6, 8 and 10 weeks. Blood samples were collected each week. At birth, mean WT, LT and HC were significantly lower in pups from E-mothers as compared to S-mothers with either CP or LP diets. The birth WT, LT and HC were significantly lower when mothers were fed LP as compared to the CP diet with either S or E. The prenatal effects of E and LP were significantly associated with lower pup WT, HT and hematocrit values, but not HC up to 4 weeks. At 10 weeks, the growth measurements and hematocrits were significantly lower with prenatal E exposure but not with LP. Pup red cell levels of folate were significantly lower with prenatal E during the first 4 weeks, whereas the effect of prenatal LP but not E was significant at 10 weeks. These data suggest that growth parameters and hematocrit values of pups prenatally exposed to E do not catch up to those of pups from S-mothers fed either diet

  18. Biological effects of repeated inhalation exposure of Beagle dogs to relatively insoluble aerosols of 144Ce. VI

    International Nuclear Information System (INIS)

    Beagle dogs were exposed repeatedly to a relatively insoluble form of 144Ce (in fused aluminosilicate particles) to study the deposition, retention and long-term biological effects for comparison with data from dogs that were exposed only once to a similar aerosol. Four groups of nine dogs each were exposed once every 8 weeks for 2 years (13 exposures) to achieve specified exposure goals. These goals were: to increase the lung burden by 2.5 μCi 144Ce/kg body weight with each exposure; to reestablish lung burdens of 9 or 4.5 μCi 144Ce/kg body weight and to expose controls to fused aluminosilicate particles containing nonradioactive cerium. With these exposure sequences, the 144Ce-exposed dogs received increasing or relatively constant beta radiation dose rates in contrast to the steadily decreasing dose rate seen after a single inhalation exposure. Following completion of the exposure series, the dogs are being observed for the development of long-term biological effects. To date, 11 dogs have died or were euthanized, nine exposed dogs and two controls. Although pulmonary hemangiosarcomas were a prominent finding in dogs exposed once to the same aerosol at a level that led to cumulative doses to lung similar to these repeatedly exposed dogs, only one has been observed in the repeatedly exposed dogs. Other effects of note to date include three pulmonary carcinomas, two hemangiosarcomas of the tracheobronchial lymph nodes and one splenic hemangiosarcoma. Observations are continuing on the surviving 18 exposed and seven control dogs

  19. Mesozooplankton assemblages and their relationship with environmental variables: a study case in a disturbed bay (Beagle Channel, Argentina).

    Science.gov (United States)

    Biancalana, Florencia; Dutto, M Sofía; Berasategui, Anabela A; Kopprio, Germán; Hoffmeyer, Mónica S

    2014-12-01

    This study focused on the seasonal and spatial analysis of the mesozooplankton community in a human-impacted subantarctic bay in Argentina and aimed to detect assemblages associated with environmental variability. Mesozooplankton samples and environmental data were obtained in the Ushuaia Bay (UB) seasonally, from August 2004 to June 2005, and spatially, from coastal (more polluted), middle (less influenced) and open sea water (free polluted) sampling stations. Remarkable seasonal changes on the mesozooplankton community were observed. Nitrogenated nutrients, chlorophyll a, salinity and temperature were the prevailing environmental conditions likely associated with the different mesozooplankton assemblages found in the bay. The copepods Eurytemora americana, Acartia tonsa, Podon leuckarti and Nematoda were particularly observed on the northwest coast of the bay, characterized by the highest level of urban pollution, eutrophicated by sewage and freshwater inputs from the Encerrada Bay which is connected to it. The stations situated in the northeast area, mostly influenced by freshwater input from rivers and glacier melting, showed low mesozooplankton abundances and an important contribution of adventitious plankton. The copepods Ctenocalanus citer, Clausocalanus brevipes and Drepanopus forcipatus were mostly observed at the stations located near the Beagle Channel, characterized by open sea and free polluted waters. Our findings suggest that the variations observed in the mesozooplankton assemblages in the UB seem to be modulated by environmental variables associated with the anthropogenic influence, clearly detected on the coast of the bay. Certain opportunistic species such as A. tonsa and E. americana could be postulated as potential bioindicators of water quality in subantarctic coastal ecosystems. PMID:25204897

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiaobing [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China); Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Li, Bo, E-mail: libo@nifdc.org.cn [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China)

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species. - Highlights: • Urinary NGAL, clusterin and NAG levels were significantly elevated in canine AKI. • NGAL and clusterin gene expression were increased following treatment with gentamicin. • NGAL and clusterin have high specificity and sensitivity for detection of AKI.

  1. The comparison of bolus tracking and test bolus techniques for computed tomography thoracic angiography in healthy beagles

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    Nicolette Cassel

    2013-02-01

    Full Text Available Computed tomography thoracic angiography studies were performed on five adult beagles using the bolus tracking (BT technique and the test bolus (TB technique, which were performed at least two weeks apart. For the BT technique, 2 mL/kg of 300 mgI/mL iodinated contrast agent was injected intravenously. Scans were initiated when the contrast in the aorta reached 150 Hounsfield units (HU. For the TB technique, the dogs received a test dose of 15% of 2 mL/kg of 300 mgI/mL iodinated contrast agent, followed by a series of low dose sequential scans. The full dose of the contrast agent was then administered and the scans were conducted at optimal times as identified from time attenuation curves. Mean attenuation in HU was measured in the aorta (Ao and right caudal pulmonary artery (rCPA. Additional observations included the study duration, milliAmpere (mA, computed tomography dose index volume (CTDI[vol] and dose length product (DLP. The attenuation in the Ao (BT = 660 52 HU ± 138 49 HU, TB = 469 82 HU ± 199 52 HU, p = 0.13 and in the rCPA (BT = 606 34 HU ± 143 37 HU, TB = 413 72 HU ± 174.99 HU, p = 0.28 did not differ significantly between the two techniques. The BT technique was conducted in a significantly shorter time period than the TB technique (p = 0.03. The mean mA for the BT technique was significantly lower than the TB technique (p = 0.03, as was the mean CTDI(vol (p = 0.001. The mean DLP did not differ significantly between the two techniques (p = 0.17. No preference was given to either technique when evaluating the Ao or rCPA but the BT technique was shown to be shorter in duration and resulted in less DLP than the TB technique.

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

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    Hongcheng Hu

    2015-10-01

    Full Text Available A plastic and biodegradable bone substitute consists of poly (l-lactic-co-glycolic acid and 30 wt % β-tricalcium phosphate has been previously fabricated, but its osteogenic capability required further improvement. We investigated the use of globular adiponectin (gAPN as an anabolic agent for tissue-engineered bone using this scaffold. A qualitative analysis of the bone regeneration process was carried out using μCT and histological analysis 12 weeks after implantation. CBCT (Cone Beam Computed Tomography superimposition was used to characterise the effect of the different treatments on bone formation. In this study, we also explored adiponectin’s (APN influence on primary cultured human jaw bone marrow mesenchymal stem cells gene expressions involved in the osteogenesis. We found that composite scaffolds loaded with gAPN or bone morphogenetic protein 2 (BMP2 exhibited significantly increased bone formation and mineralisation following 12 weeks in the extraction sockets of beagle dogs, as well as enhanced expression of osteogenic markers. In vitro investigation revealed that APN also promoted osteoblast differentiation of primary cultured human jaw bone marrow mesenchymal stem cells (h-JBMMSCs, accompanied by increased activity of alkaline phosphatase, greater mineralisation, and production of the osteoblast-differentiated genes osteocalcin, bone sialoprotein and collagen type I, which was reversed by APPL1 siRNA. Therefore, the composite scaffold loaded with APN exhibited superior activity for guided bone regeneration compared with blank control or Bio-Oss® (a commercially available product. The composite scaffold with APN has significant potential for clinical applications in bone tissue engineering.

  3. Biological effects of repeated inhalation exposure of Beagle dogs to relatively insoluble aerosols of 144Ce. V

    International Nuclear Information System (INIS)

    The behavior and long-term biological effects in Beagle dogs of 144Ce inhaled in fused aluminosilicate particles in repeated inhalation exposures are being studied for comparison with data from dogs that were exposed only once to a similar aerosol. Four groups of nine dogs each were exposed once every 8 weeks for 2 years (13 exposures) to achieve specified exposure goals. These goals were: to increase the lung burden by 2.5 μCi 144Ce/kg body weight with each exposure in the first group; to reestablish lung burdens of 9 or 4.5 μCi 144Ce/kg body weight in the second and third groups, respectively; and to expose controls (fourth group) to fused aluminosilicate particles containing stable cerium. With these exposure sequences, the 144Ce-exposed dogs received increasing or relatively constant beta radiation dose rates in contrast to the steadily decreasing dose rate seen after a single inhalation exposure. Exposures in the first and second groups were planned to yield a cumulative absorbed dose to lung of approx. = 35,000 rads and those in the third group approx. = 17,000 rads within two years after the first exposure. All 13 exposures have been completed. During the past year, one dog in the 9.0 μCi 144Ce/kg body weight group died at 1558 days after the first exposure with autoimmune hemolytic anemia. The remaining 24 144Ce-exposed and seven control dogs generally appear to be in good physical condition with exception of a persistent lymphopenia at approx. = 5 years after the first exposure. They are continuing to be maintained for life span observations

  4. Insights into radionuclide-induced lung cancer in people from life-span studies in beagle dogs

    International Nuclear Information System (INIS)

    In life-span studies, beagle dogs were exposed one time by inhalation to an aerosol containing a beta- or alpha-emitting radionuclide in a relatively soluble or insoluble chemical form. After exposure dogs were observed for late-occurring biological effects. Lung cancer has been a predominant observation for radionuclides inhaled in a relatively insoluble form because most of the absorbed dose was delivered to the lung and contiguous tissues. Approximately 130 lung cancers were observed in dogs exposed to inhaled beta-emitting radionuclides; tumors occurred with absorbed doses to lung ranging from 1100 to 68,000 rads. With inhaled alpha emitters lung tumors occurred at doses between 530 and 8400 rads. Dose rate pattern was shown to be an important factor in the induction of lung cancer by inhaled beta emitters. Doses of low-LET irradiation delivered in a matter of days can be as much as 8 times more effective per unit of dose than radiation doses delivered over a more protracted period of time. Tumors also have occurred in tracheobronchial lymph nodes of dogs that inhaled relatively insoluble forms of beta emitters. From these studies, the risk of lung cancer from inhaled beta- or alpha-emitting radionuclides was compared to determine the importance of LET and other dose-effect modifying factors on resulting risks and on extrapolation to human inhalation exposure. Attention also was given to the risk of cancer in tracheobronchial lymph nodes, on the basis of the results of these studies and the current ICRP computational method in which lymph nodes are included with lung for purposes of dose and risk calculation. 12 refs., 3 figs., 4 tabs

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

    International Nuclear Information System (INIS)

    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

  6. Neoplastic and other pathologic effects of fractionated fast neutrons or photons on the thorax and anterior abdomen of beagles

    International Nuclear Information System (INIS)

    Thirty-nine adult male beagle dogs received either fast-neutron or photon irradiation to the right hemithorax and right rostral abdomen. Twenty-four dogs (six per group) received fast neutrons (15 MeV) to total doses of 1000, 1500, 2250, or 3375 cGy in four fractions per week for six weeks. Fifteen dogs received 3000, 4500, or 6750 cGy of photons in an identical fractionation pattern. One photon-irradiated dog and 13 neutron-irradiated dogs died or were euthanatized because of hepatic and gastrointestinal disturbances 47 to 708 days after irradiation; 20 dogs died of other causes. These 34 dogs were necropsied and have been studied microscopically; the remaining five dogs are still alive seven years after irradiation. Neutron-induced lesions included hemorrhage, necrosis, fibrosis, and atrophy of the heart, liver, pancreas, pylorus, duodenum, and kidney. All lesions were associated with degenerative and occlusive vascular changes including coronary arteriosclerosis. The relative biological effectiveness (RBE) of fast neutrons, assessed by clinical signs and by gross and microscopic pathology, is between 3 and 4.5 for pancreas, ∼4.5 for heart, pylorus, duodenum, and kidney, and greater than 6.75 for liver. Ten malignancies and two benign tumors developed in the irradiated field of six of 12 neutron-exposed dogs that survived over one year after irradiation. Two malignancies and one benign tumor arose in three of 12 photon-exposed dogs surviving over one year postirradiation. Only one neoplasm developed in the same field in 11 nonirradiated controls or in 62 dogs irradiated at sites other than the thorax or abdomen. The neutron RBE for neoplasia is approximately 6.75. 85 refs., 8 figs., 3 tabs

  7. Sialoglycoproteins prepared from the eggs of Carassius auratus prevent bone loss by inhibiting the NF-κB pathway in ovariectomized rats.

    Science.gov (United States)

    Xia, Guanghua; Wang, Jingfeng; Sun, Shuhong; Zhao, Yanlei; Wang, Yiming; Yu, Zhe; Wang, Shanshan; Xue, Changhu

    2016-02-17

    In this study, we investigated the improvement of osteoporosis by sialoglycoproteins isolated from the eggs of Carassius auratus (Ca-SGP) in ovariectomized rats. Ca-SGP was supplemented to ovariectomized Sprague-Dawley rats for 90 days. The results showed that Ca-SGP treatment remarkably prevented the reduction of bone mass, improved cancellous bone structure and biochemical properties. Ca-SGP also significantly decreased the serum contents of TRAP, Cath-K, MMP-9, DPD, CTX-1, Ca, and P. Mechanism investigation revealed that Ca-SGP significantly increased the OPG/RANKL ratio in mRNA expression, protein expression and serum content. Further research suggested that NF-κB signaling pathways were inhibited by suppressing the mRNA and protein expressions of NFATc1 and TRAF6, diminishing the mRNA expression and phosphorylation of NF-κB p65, three key transcription factors in NF-κB pathways. These results suggest that Ca-SGP can improve osteoporosis by inhibiting bone resorption via suppressing the activation of osteoclastogenesis related NF-κB pathways. PMID:26765587

  8. Effects of butorphanol on luteinizing hormone and follicle stimulating hormone levels in ovariectomized rats: comparison with the effects of morphine sulphate

    International Nuclear Information System (INIS)

    The effects of the synthetic morphine derivative, butorphanol, which was claimed to be a potent analgesic with few side effects, in comparison to the effects of the naturally occurring alkaloid, morphine on pituitary gonadotrophic hormones was investigated in ovariectomized rats. For this purpose 3 groups of ovariectomized rats were used. Rats of the first group were injected with butorphanol at 2 dose levels (1 or 2 mg/Kg b.w). Those of the second group were injected with morphine sulphate -(10 or 20 mg/Kg b.w). The third group was injected with saline and served as control. Blood samples were collected from theorbital sinus puncture just before treatment and then one hour post injection. Luteinizing hormone and follicle stimulating hormone levels were determined in blood sera of rats by radioimmunoassay. The results revealed that, the two dose levels used of morphine produced more than 90% decrease in serum LH concentration, whereas butorphanol produced more than 70% decrease in serum LH levels. Both morphine and butorphanol, at the two doses used produced more than 76% decrease in serum FSH concentration. It is concluded that butorphanol, the morphine derivative has a depressant effect on the synthesis and/or release of gonadotrophic hormones. This inhibitory effect, however, was nearly as potent as that produced by morphine sulphate.2 fig., 1 tab

  9. Bone mass density estimation: Archimede’s principle versus automatic X-ray histogram and edge detection technique in ovariectomized rats treated with germinated brown rice bioactives

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    Muhammad SI

    2013-10-01

    Full Text Available Sani Ismaila Muhammad,1,2 Ismail Maznah,1,3 Rozi Binti Mahmud,4 Maher Faik Esmaile,5 Zuki Abu Bakar Zakaria6 1Laboratory of Molecular Biomedicine, Institute of Bioscience, 2Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, Sokoto, Nigeria; 3Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, 4Department of Radiology, Faculty of Medicine and Health Sciences, 5Department of Electrical and Electronic Engineering, Faculty of Engineering, 6Department of Pre-clinical Studies, Faculty of Veterinary Medicine, University Putra Malaysia, Selangor, Malaysia Background: Bone mass density is an important parameter used in the estimation of the severity and depth of lesions in osteoporosis. Estimation of bone density using existing methods in experimental models has its advantages as well as drawbacks. Materials and methods: In this study, the X-ray histogram edge detection technique was used to estimate the bone mass density in ovariectomized rats treated orally with germinated brown rice (GBR bioactives, and the results were compared with estimated results obtained using Archimede’s principle. New bone cell proliferation was assessed by histology and immunohistochemical reaction using polyclonal nuclear antigen. Additionally, serum alkaline phosphatase activity, serum and bone calcium and zinc concentrations were detected using a chemistry analyzer and atomic absorption spectroscopy. Rats were divided into groups of six as follows: sham (nonovariectomized, nontreated; ovariectomized, nontreated; and ovariectomized and treated with estrogen, or Remifemin®, GBR-phenolics, acylated steryl glucosides, gamma oryzanol, and gamma amino-butyric acid extracted from GBR at different doses. Results: Our results indicate a significant increase in alkaline phosphatase activity, serum and bone calcium, and zinc and ash content in the treated groups compared with the ovariectomized

  10. Effect of an isoflavones-containing red clover preparation and alkaline supplementation on bone metabolism in ovariectomized rats

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    S Kawakita

    2009-02-01

    Full Text Available S Kawakita1, F Marotta2, Y Naito3, U Gumaste4, S Jain5, J Tsuchiya1, E Minelli21Biokenkyusho Research Laboratory, Shizuoka, Japan; 2WHO-cntr for Biotechnology and Natural Medicine, University of Milan, Milan, Italy; 3Immunology Research Institute and Clinic, Nagoya, Japan; 4Agharkar Research Institute, Pune, Maharashtra, India; 5Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, IL, USA Abstract: The aim of this study was to test the combined effect of a quality-controlled red clover extract (RCE standardized to contain 40% isoflavones by weight (genistein, daidzein, biochanin A, and formononetin present as hydrolyzed aglycones together with a modified alkaline supplementation on bone metabolic and biomechanical parameters in an experimental model of surgically-induced menopause. Sprague–Dawley female rats were maintained under controlled standard conditions of light and fed with conventional food of standard calcium content and no alfalfa or soybean components. Rats were randomized into four groups: Group A represented normal rats (sham operated while three other groups were ovariectomized (OVX and fed for three months as follows: standard food (group B, 6 mg/kg/day food mixed with RCE (Group C, or given 6 mg/kg/day of RCE plus a modified alkaline supplementation (BP through a nasogastric tube at a dose of 16 mg (group D. The animals were killed 90 days after surgery. As compared to group B, RCE or RCE + BP treatments brought about significantly higher level of estradiol and mitigated the weight loss of the uterus and improved maximum load of the femoral neck. Osteocalcin level showed an over 65% increase in group B but both RCE and RCE + BP treatments prevented such abnormality with a significantly better result in RCE + BP group which virtually normalized such parameter as well as urinary excretion of DPD. Group C and D reduced the over 20% loss of bone mineral density and bone mineral content

  11. Effects of estradiol benzoate, raloxifen and an ethanolic extract of Cimicifuga racemosa in nonclassical estrogen regulated organs of ovariectomized rats.

    Science.gov (United States)

    Seidlova-Wuttke, Dana; Jarry, Hubertus; Wuttke, Wolfgang

    2009-10-01

    The special extract of Cimicifuga racemosa (CR) BNO 1055 was shown to have bone protective effects without exerting estrogenic effects in the uterus or mammary gland. Whether the effects of CR BNO 1055 would be exerted in other organs that also express estrogen receptors (ERs) but in which the effects of estrogens and of the selective estrogen receptor modulator raloxifen (Ral) were not thoroughly studied was therefore investigated in the present contribution. Rats were ovariectomized (ovx) and their food immediately substituted with estradiol benzoate (EB), Ral or 2 doses of CR BNO 1055 for 3 months. Expressions of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta) and of insulin-like growth factor-1 (IGF-1) genes were determined in the vagina, liver, thyroid gland, lung, spleen, colon and kidney by means of quantitative RT-PCRs. Body weights in all treatment groups were significantly reduced and uterine weights in the EB treated animals were largely and in the Ral treated animals slightly but significantly increased. CR BNO 1055 was without effects in the uterus. We tested 3 genes: ERalpha gene expression was significantly reduced in the vagina, liver and kidney and remained unaffected in all other organs with the exception of the thyroid gland where ERalpha gene expression was stimulated by EB, Ral had--if any--similar effects in these organs. The CR extract BNO 1055 was devoid of any effect on ERalpha gene expression. ERbeta gene expression was suppressed in the vagina and colon by EB and this effect was shared by Ral in the colon. In the thyroid, EB and Ral stimulated ERbeta gene expression. Expression of IGF-1 gene was stimulated by EB and CR BNO 1055 in the vagina and kidney and inhibited by EB and Ral in the liver. No effects were observed by CR BNO 1055 in these organs. The effects of Ral, if occurring, were similar to those of EB while CR BNO 1055 was ineffective in all organs but the vagina. In the colon, reduced ERbeta gene activity may

  12. Effect of zoledronate acid treatment on osseointegration and fixation of implants in autologous iliac bone grafts in ovariectomized rabbits.

    Science.gov (United States)

    Qi, Mengchun; Hu, Jing; Li, Jianping; Li, Jinyuan; Dong, Wei; Feng, Xiaojie; Yu, Jing

    2012-01-01

    One main problem associated with alveolar bone augmentation in implant dentistry is resorption of grafted bone, which may be further compromised by systemic skeletal disorders such as osteoporosis. Zoledronate acid (ZOL) is the most potent bisphosphonate to treat osteoporosis and therefore it is hypothesized to be able to invert the negative effect of osteoporosis on osseointegration and fixation of dental implants in autologous bone grafts. In this study, 56 rabbits received bilateral ovariectomy (OVX) (40 rabbits) or sham operation (16 rabbits). Three months later, 8 animals from each group were sacrificed for bone mineral density (BMD) examination. Then the remaining animals underwent bilateral autologous iliac bone grafting with simultaneous implantation of titanium implants in tibiae and were divided into 5 groups (n=8): Sham, OVX, Loc-ZOL (local treatment), Sys-ZOL (systemic treatment) and Loc+Sys-ZOL (local plus systemic) group. At 3 months after implantation, all animals were sacrificed and specimens were harvested for examinations. Both BMD and histological examinations of femurs showed osteoporotic changes after ovariectomy, while systemic treatment with ZOL restored mineralized bone. Micro-CT examination demonstrated that OVX group showed significant decrease of mineralized bone and implant-bone contact when compared with sham control, whereas both systemic and local treatments of ZOL significantly increased mineralized bone and implant-bone contact in ovariectomized animals. However, the best effects were observed in Loc+Sys-ZOL group (combined use of ZOL) and most of bone indices were similar to (IBCR, p>0.05) or higher than (BV/TV, Conn.D and Tb.N) (peffects were also confirmed by histomorphometric analysis of bone indices on implant-bone contact and mineralized bone. In addition, biomechanical testing further supported the beneficial effect of ZOL treatment and maximal removal torque of titanium implants was observed in Loc+Sys-ZOL group. In

  13. The supplementation of Korean mistletoe water extracts reduces hot flushes, dyslipidemia, hepatic steatosis, and muscle loss in ovariectomized rats.

    Science.gov (United States)

    Kim, Min Jung; Park, Jong-Heum; Kwon, Dae Young; Yang, Hye Jeong; Kim, Da Sol; Kang, Suna; Shin, Bae Keun; Moon, Na Rang; Song, Beom-Seok; Kim, Jae-Hun; Park, Sunmin

    2015-04-01

    Since Korean mistletoe (Viscum album) has been used for alleviating metabolic diseases, it may also prevent the impairment of energy, glucose, lipid, and bone metabolisms in an estrogen-deficient animal model. We determined that long-term consumption of Korean mistletoe water extract (KME) can alleviate menopausal symptoms such as hot flush, increased abdominal fat mass, dyslipidemia, hyperglycemia, and decreased bone mineral density in ovariectomized (OVX) rats fed a high-fat diet, and explored the mechanisms of the effects. OVX rats were divided into four groups and fed high-fat diets supplemented with either 0.6% dextrin (control), 0.2% lyophilized KME + 0.4% dextrin (KME-L), or 0.6% lyophilized KME (KME-H). Sham rats were fed with the high-fat diets with 0.6% dextrin as a normal-control without estrogen deficiency. After eight weeks, OVX rats exhibited impaired energy, glucose and lipid metabolism, and decreased uterine and bone masses. KME-L did not alleviate energy dysfunction. However, KME-H lowered serum levels of total-, LDL-cholesterol, and triglycerides and elevated serum HDL-cholesterol levels in OVX rats with dyslipidemia, to similar levels as normal-control rats. Furthermore, KME-H improved HOMA-IR, an indicator of insulin resistance, in OVX rats. Surprisingly, KME-H fed rats had greater lean mass in the abdomen and leg without differences in fat mass but neither dosage of KME altered bone mineral density in the lumbar spine and femur. The increased lean mass was related to greater phosphorylation of mTOR and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in the quadriceps muscles. Hepatic triglyceride contents were lowered with KME-H in OVX rats by increasing carnitine palmitoyltransferase-1 (CPT-1) expression and decreasing fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) expression. In conclusion, KME may be useful for preventing some menopausal symptoms such as hot flushes, dyslipidemia

  14. Metabolic effects of estrogen substitution in combination with targeted exercise training on the therapy of obesity in ovariectomized Wistar rats.

    Science.gov (United States)

    Zoth, Nora; Weigt, Carmen; Zengin, Sinan; Selder, Oliver; Selke, Nadine; Kalicinski, Michael; Piechotta, Marion; Diel, Patrick

    2012-05-01

    Postmenopausal women tend to have a higher risk in developing obesity and thus metabolic syndrome. Recently we could demonstrate that physical activity and estrogen replacement are effective strategies to prevent the development of nutritional induced obesity in an animal model. The aim of this study was to determine the combined effects of estrogen treatment and exercise training on already established obesity. Therefore ovariectomized (OVX) and sham-operated (SHAM) female Wistar rats were exposed to a high fat diet for ten months. After this induction period obese SHAM and OVX rats either remained sedentary or performed treadmill training for six weeks. In addition OVX rats were treated with 17β-Estradiol (E(2)) alone, or in combination with training. Before and after intervention effects on lipid and glucose metabolism were investigated. Training resulted in SHAM and OVX rats in a significant decrease of body weight, subcutaneous and visceral body fat, size of adipocytes and the serum levels of leptin, cholesterol, low-density lipoprotein and triglycerides. In OVX animals E(2) treatment resulted in similar effects. Often the combination of E(2) treatment and training was most effective. Analysis of the respiratory quotient indicates that SHAM animals had a better fat burning capacity than OVX rats. There was a tendency that training in SHAM animals and E(2) treatment in OVX animals could improve this capacity. Analysis of glucose metabolism revealed that obese SHAM animals had higher glucose tolerance than OVX animals. Training improved glucose tolerance in SHAM and OVX rats, E(2) treatment in OVX rats. The combination of both was most effective. Our results indicate that even after a short intervention period of six weeks E(2) treatment and exercise training improve parameters related to lipid as well as glucose metabolism and energy expenditure in a model of already established obesity. In conclusion a combination of hormone replacement therapy and exercise

  15. Changes of microRNA profile and microRNA-mRNA regulatory network in bones of ovariectomized mice.

    Science.gov (United States)

    An, Jee Hyun; Ohn, Jung Hun; Song, Jung Ah; Yang, Jae-Yeon; Park, Hyojung; Choi, Hyung Jin; Kim, Sang Wan; Kim, Seong Yeon; Park, Woog-Yang; Shin, Chan Soo

    2014-03-01

    Growing evidence shows the possibility of a role of microRNAs (miRNA) in regulating bone mass. We investigated the change of miRNAs and mRNA expression profiles in bone tissue in an ovariectomized mice model and evaluated the regulatory mechanism of bone mass mediated by miRNAs in an estrogen-deficiency state. Eight-week-old female C3H/HeJ mice underwent ovariectomy (OVX) or sham operation (Sham-op), and their femur and tibia were harvested to extract total bone RNAs after 4 weeks for microarray analysis. Eight miRNAs (miR-127, -133a, -133a*, -133b, -136, -206, -378, -378*) were identified to be upregulated after OVX, whereas one miRNA (miR-204) was downregulated. Concomitant analysis of mRNA microarray revealed that 658 genes were differentially expressed between OVX and Sham-op mice. Target prediction of differentially expressed miRNAs identified potential targets, and integrative analysis using the mRNA microarray results showed that PPARγ and CREB pathways are activated in skeletal tissues after ovariectomy. Among the potential candidates of miRNA, we further studied the role of miR-127 in vitro, which exhibited the greatest changes after OVX. We also studied the effects of miR-136, which has not been studied in the context of bone mass regulation. Transfection of miR-127 inhibitor has enhanced osteoblastic differentiation in UAMS-32 cells as measured by alkaline phosphatase activities and mRNA expression of osteoblast-specific genes, whereas miR-136 precursor has inhibited osteoblastic differentiation. Furthermore, transfection of both miR-127 and miR-136 inhibitors enhanced the osteocyte-like morphological changes and survival in MLO-Y4 cells, whereas precursors of miR-127 and -136 have aggravated dexamethasone-induced cell death. Both of the precursors enhanced osteoclastic differentiation in bone marrow macrophages, indicating that both miR-127 and -136 are negatively regulating bone mass. Taken together, these results suggest a novel insight into the

  16. Combined Effects of Rosuvastatin and Exercise on Gene Expression of Key Molecules Involved in Cholesterol Metabolism in Ovariectomized Rats

    Science.gov (United States)

    Ngo Sock, Emilienne Tudor; Mayer, Gaétan; Lavoie, Jean-Marc

    2016-01-01

    The purpose of this study was to investigate the effects of three weeks of rosuvastatin (Ros) treatment alone and in combination with voluntary training (Tr) on expression of genes involved in cholesterol metabolism (LDLR, PCSK9, LRP-1, SREBP-2, IDOL, ACAT-2 and HMGCR) in the liver of eight week-old ovariectomized (Ovx) rats. Sprague Dawley rats were Ovx or sham-operated (Sham) and kept sedentary for 8 weeks under a standard diet. Thereafter, rats were transferred for three weeks in running wheel cages for Tr or kept sedentary (Sed) with or without Ros treatment (5mg/kg/day). Six groups were formed: Sham-Sed treated with saline (Sal) or Ros (Sham-Sed-Sal; Sham-Sed-Ros), Ovx-Sed treated with Sal or Ros (Ovx-Sed-Sal; Ovx-Sed-Ros), Ovx trained treated with Sal or Ros (Ovx-Tr-Sal; Ovx-Tr-Ros). Ovx-Sed-Sal rats depicted higher (P < 0.05) body weight, plasma total cholesterol (TC) and LDL-C, and liver TC content compared to Sham-Sed-Sal rats. In contrast, mRNA levels of liver PCSK9, LDLR, LRP-1 as well as plasma PCSK9 concentrations and protein levels of LRP-1 were reduced (P < 0.01) in Ovx-Sed-Sal compared to Sham-Sed-Sal rats. However, protein levels of LDLR increased (P < 0.05) in Ovx-Sed-Sal compared to Sham-Sed-Sal rats. Treatment of Ovx rats with Ros increased (P < 0.05) mRNA and protein levels of LRP-1 and PCSK9 but not mRNA levels of LDLR, while its protein abundance was reduced at the level of Sham rats. As a result, plasma LDL-C was not reduced. Exercise alone did not affect the expression of any of these markers in Ovx rats. Overall, Ros treatment corrected Ovx-induced decrease in gene expression of markers of cholesterol metabolism in liver of Ovx rats, but without reducing plasma LDL-C concentrations. Increased plasma PCSK9 levels could be responsible for the reduction of liver LDLR protein abundance and the absence of reduction of plasma LDL-C after Ros treatment. PMID:27442011

  17. Inhibition of cathepsin K increases modeling-based bone formation, and improves cortical dimension and strength in adult ovariectomized monkeys.

    Science.gov (United States)

    Pennypacker, Brenda L; Chen, Charles M; Zheng, Helen; Shih, Mei-Shu; Belfast, Mary; Samadfam, Rana; Duong, Le T

    2014-08-01

    Treatment with the cathepsin K (CatK) inhibitor odanacatib (ODN) protects against bone loss and maintains normal biomechanical properties in the spine and hip of ovariectomized (OVX) preclinical models. Here, we characterized the effects of ODN on the dynamics of cortical modeling and remodeling, and dimension and strength of the central femur in adult OVX-rhesus monkeys. Animals were treated with vehicle or ODN (6 or 30 mg/kg, once per day [q.d., p.o.]) in prevention mode for 21 months. Calcein and tetracycline double-labeling were given at 12 and 21 months, and the femoral cross-sections were subjected to dynamic histomorphometric and cement line analyses. ODN treatment significantly increased periosteal and endocortical bone formation (BFR/BS), accompanied with an increase in endocortical mineralizing surface (102%, p < 0.01) with the 6 mg/kg dose. ODN at both doses reduced remodeling hemiosteon numbers by 51% and 66% (p < 0.05), respectively, and ODN 30 mg/kg numerically reduced activation frequency without affecting wall thickness. On the same endocortical surface, ODN increased all modeling-based parameters, while reducing intracortical remodeling, consistent with the observed no treatment effects on cortical porosity. ODN 30 mg/kg markedly increased cortical thickness (CtTh, p < 0.001) and reduced marrow area (p < 0.01). Lastly, ODN treatment increased femoral structural strength (p < 0.001). Peak load was positively correlated with the increases in bone mineral content (BMC) (r(2)  = 0.9057, p < 0.0001) and CtTh (r2  = 0.6866, p < 0.0001). Taken together, by reducing cortical remodeling-based and stimulating modeling-based bone formation, ODN significantly improved cortical dimension and strength in OVX monkeys. This novel mechanism of CatK inhibition in stimulating cortical formation suggests that ODN represents a novel therapeutic approach for the treatment of osteoporosis. PMID:24591096

  18. Bioequivalence evaluation of two brands of rivastigmine of different salt forms, an acetylcholinesterase inhibitor for the treatment of Alzheimer's disease, in healthy Beagle dogs.

    Science.gov (United States)

    Shen, Cidan; Yang, Bei; Zhou, Tao; Duan, Gengli; Yu, Yingjia

    2011-08-01

    The bioequivalence of two brands of rivastigmine capsules, of different salt forms, was demonstrated in six healthy beagle dogs after a single oral dose in a randomized cross-over study. Reference (Rivastigmine hydrochloride, Sunve, CN) and test (Rivastigmine tartrate, Novartis, CH) products were administered to fasting beagles on two treatment days separated by a two-day washout period; blood samples were collected at specified time intervals, and the plasma was separated and analyzed for rivastigmine using a validated GC-MS method. The pharmacokinetic parameters AUC(0-t), AUC(0-infinity), C(max), T(max) and t1/2 were compared statistically to evaluate bioequivalence between the two brands, using the statistical modules recommended by the State Food and Drug Administration (SFDA) of China. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable ranges for bioequivalence. Based on these statistical inferences it was concluded that the two brands exhibited comparable pharmacokinetic profiles and that Sanwei's Rivastigmine hydrochloride was bioequivalent to Rivastigmine tartrate of Novartis, CH. PMID:21901981

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-12

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

  20. Development and validation of a rapid and sensitive UHPLC–MS/MS method for the determination of paliperidone in beagle dog plasma

    Directory of Open Access Journals (Sweden)

    Hongming Chen

    2014-10-01

    Full Text Available In order to evaluate the pharmacokinetic profile of paliperidone extended-release tablets in vivo, a simple and rapid ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS method was developed and validated for the determination of paliperidone in beagle dog plasma. Paliperidone and diazepam (internal standard were extracted from plasma samples with diethyl ether, and then separated on a C18 column (2.1 × 50 mm, 2.6 μm under gradient elution with methanol–0.1% formic acid at a flow rate of 0.3 ml/min. The compounds were detected using a triple-quadrupole mass spectrometer equipped with an electrospray ionization (ESI source. The validated method was linear over the concentration range of 1.00–1000.00 ng/ml and the lower limit of quantitation was 1.00 ng/ml. The intra-day and inter-day precision values were not more than 15% (relative standard deviation < 20% at low levels, while the accuracy was within ±10% of nominal values. The validated UHPLC–MS/MS method was successfully applied to an oral pharmacokinetic study of paliperidone extended-release tablets in a beagle dog.