Early retention of 237Pu + 239Pu in mature beagles

International Nuclear Information System (INIS)

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

1978-01-01

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

Relative radiosensitivity of bone tumor induction among beagles as a function of age at injection of 239Pu or 226Ra

International Nuclear Information System (INIS)

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

1999-01-01

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

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

International Nuclear Information System (INIS)

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

1985-01-01

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

Atrophic thyroiditis in long-term Segment III beagles

International Nuclear Information System (INIS)

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

1981-01-01

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

The Effect of Low Calcium Diet on Bone in Ovariectomized Mice

OpenAIRE

Minematsu, Akira; Yoshimura, Osamu; Yotsuji, Hirofumi; Ichigo, Hirozo; Takayanagi, Kiyomi; Kobayashi, Ryuji; Hosoda, Masataka; Sasaki, Hisato; Maejima, Hiroshi; Matsuda, Yuichi; Tanaka, Sachiko; Kanemura, Naohiko; Matsuo, Akihisa

2000-01-01

This study investigates the effects of Ca on bone in the ovariectomized mice. Twenty-six female ICR mice aged 5 weeks were used. They were ovariectomized (OVX) or sham-operated (SHAM) and fed standard mouse diet (SF) or special low calcium diet (L.Ca), respectively. All animals were sacrificed at day 100 after operation. Mechanical strength of the left femur and tibia was measured by the three-point bending strength test. The bones were dried, weighed and burned to ash. Correlation between me...

Prussian Blue decorporation of 137Cs in beagles of different ages

International Nuclear Information System (INIS)

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

1996-01-01

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

Radium rentention and dosimetry in juvenile beagles

International Nuclear Information System (INIS)

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

1983-01-01

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

Working memory in bisphenol-A treated middle-aged ovariectomized rats.

Science.gov (United States)

Neese, Steven L; Bandara, Suren B; Schantz, Susan L

2013-01-01

Over 90% of the U.S. population has detectable bisphenol-A (BPA) in their urine according to recent biomonitoring data. BPA is best known for its estrogenic properties, and most rodent research on the nervous system effects of BPA has focused on determining if chronic exposures during pre- and perinatal development have organizational effects on brain development and behavior. Estrogens also have important impacts on brain and behavior during adulthood, particularly in females during aging, but the impact of BPA on the adult brain is less studied. We have published a series of studies documenting that chronic exposure to various estrogens including 17β-estradiol, ERβ selective SERMs and soy phytoestrogens impairs performance of middle-aged female rats on an operant working memory task. The purpose of this study was to determine if chronic oral exposure to BPA would alter working memory on this same task. Ovariectomized (OVX) middle-aged Long Evans rats were tested on an operant delayed spatial alternation (DSA) task. Rats were treated for 8-10 weeks with either a 0 (vehicle control), 5 or 50 μg/kg bw/day oral bolus of BPA. A subset of the vehicle control rats was implanted with a Silastic implant containing 17β-estradiol (low physiological range) to serve as a positive control. All rats were tested for 25 sessions on the DSA task. BPA treatment did not influence performance accuracy on the DSA task, whereas 17β-estradiol significantly impaired performance, as previously reported. The results of this study suggest that chronic oral exposure to BPA does not alter working memory processes of middle-aged OVX rats assessed by this operant DSA task. Copyright © 2013. Published by Elsevier Inc.

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

Science.gov (United States)

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

2008-12-01

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

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

International Nuclear Information System (INIS)

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

1984-01-01

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

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

International Nuclear Information System (INIS)

Momeni, M.H.

1979-01-01

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

Osteoprotective effects of Fructus Ligustri Lucidi aqueous extract in aged ovariectomized rats

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Fung Kwok

2010-11-01

Full Text Available Abstract Background Fructus Ligustri Lucidi (FLL is a commonly used herb for treating bone disorders in Chinese medicine. The present study investigates the anti-osteoporotic activity of FLL aqueous extract in the model of postmenopausal bone loss in aged ovariectomized (OVX female rats. Methods After eight weeks of treatment of FLL or water, the lumbar spine was scanned by peripheral quantitative computed tomography (pQCT. Effects of FLL water extract on osteogenic and adipogenic differentiations in rat mesenchymal stem cells (MSCs were assessed by biochemical methods and staining. Results FLL aqueous extract significantly inhibited bone mineral density (BMD loss in total, trabecular and cortical bones without affecting body weight and uterus wet weight. FLL extract significantly promoted osteogenesis and suppressed adipogenesis in MSCs as indicated by the elevated alkaline phosphatase activity, calcium deposition levels and decreased adipocyte number in a dose-dependent manner without cytotoxic effects. Real-time PCR analysis revealed significant increase of osteoprotegerin (OPG-to-receptor activator for nuclear factor-κB ligand (RANKL mRNA, indicating a decrease in osteoclastogenesis. Conclusion The present study demonstrates the osteoprotective effects of FLL aqueous extract on aged OVX rats, stimulation of osteogenesis, inhibition of adipogenesis and osteoclastogenesis in MSCs.

Age-related effects on the disposition and dosimetry of inhaled 239Pu or 144Ce in immature or aged beagle dogs

International Nuclear Information System (INIS)

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

1987-01-01

Immature (90 days of age), young adult (18 months of age), and aged (8-10.5 years of age) male and female beagle dogs received a single brief pernasal inhalation exposure to an aerosol of 144 Ce in an insoluble fused aluminosilicate matrix or 239 PuO 2 . These isotopes were selected to represent low- and high-LET emitters, respectively. No age-related differences in the retention of Pu in the lungs of dogs have been observed, nor have there been any detectable differences in the uptake and retention of Pu in the tracheobronchial lymph nodes. Age-related effects have been seen in the uptake of Pu in the skeleton, with the amount of Pu being greatest in the skeleton of immature dogs. For the dogs exposed to the 144 Ce aerosol, there was a statistically significant difference in the retention of 144 Ce in the lungs of immature dogs compared to young adults. Increased uptake of 144 Ce in the immature dog skeleton was also noted. 14 refs.; 4 figs

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

International Nuclear Information System (INIS)

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

1976-01-01

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

Mamary neoplasia in a closed beagle colony

International Nuclear Information System (INIS)

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

1975-01-01

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

The effects of age at time of exposure on the distribution and toxicity of radium 226 in the beagle dog

International Nuclear Information System (INIS)

Bruenger, F.W.; Lloyd, R.D.; Egger, M.J.

1989-01-01

The influence of age at time of injection of radium 226 on its skeletal deposition, retention and distribution, the pattern of bone tumour formation and the post-injection survival has been studied in beagles. Dogs received a single intravenous injection of radium 226 at an age of 3 months (juveniles), 17-19 months (young adults) or 60 months (mature), respectively. In spite of large differences in distribution and retention of the nuclide, the influence of age on bone tumour induction was moderate and the post-injection survivals were not significantly different, although a larger skeletal dose combined with a longer survival indicated a trend to a lower overall toxicity in the juvenile age group. (author)

Penis Allotransplantation in Beagle Dog.

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

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

2011-05-01

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

Radiation injury of the developing immune system in the beagle dog

International Nuclear Information System (INIS)

Miller, G.K.

1982-01-01

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

Estrogen restores brain insulin sensitivity in ovariectomized non-obese rats, but not in ovariectomized obese rats.

Science.gov (United States)

Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2014-06-01

We previously demonstrated that obesity caused the reduction of peripheral and brain insulin sensitivity and that estrogen therapy improved these defects. However, the beneficial effect of estrogen on brain insulin sensitivity and oxidative stress in either ovariectomy alone or ovariectomy with obesity models has not been determined. We hypothesized that ovariectomy alone or ovariectomy with obesity reduces brain insulin sensitivity and increases brain oxidative stress, which are reversed by estrogen treatment. Thirty female rats were assigned as either sham-operated or ovariectomized. After the surgery, each group was fed either a normal diet or high-fat diet for 12 weeks. At week 13, rats in each group received either the vehicle or estradiol for 30 days. At week 16, blood and brain were collected for determining the peripheral and brain insulin sensitivity as well as brain oxidative stress. We found that ovariectomized rats and high-fat diet fed rats incurred obesity, reduced peripheral and brain insulin sensitivity, and increased brain oxidative stress. Estrogen ameliorated peripheral insulin sensitivity in these rats. However, the beneficial effect of estrogen on brain insulin sensitivity and brain oxidative stress was observed only in ovariectomized normal diet-fed rats, but not in ovariectomized high fat diet-fed rats. Our results suggested that reduced brain insulin sensitivity and increased brain oxidative stress occurred after either ovariectomy or obesity. However, the reduced brain insulin sensitivity and the increased brain oxidative stress in ovariectomy with obesity could not be ameliorated by estrogen treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Longitudinal as well as age-matched assessments of bone changes in the mature ovariectomized rat model

NARCIS (Netherlands)

Leitner, M.M.; Tami, A.E.; Montavon, P.M.; Ito, K.

2009-01-01

In the past, bone loss in the ovariectomized (OVX) osteoporotic rat model has been monitored using in vitro micro-computed tomography (micro-CT) to assess bone structure (bone volume/total volume, BV/TV). The purpose of this study was to assess the importance of baseline control and sham groups in

Rabbiteye blueberry prevents osteoporosis in ovariectomized rats.

Science.gov (United States)

Li, Tao; Wu, Shou-Mian; Xu, Zhi-Yuan; Ou-Yang, Sheng

2014-08-08

It has been forecasted that the rabbiteye blueberry could inhibit osteoporosis. However, the inhibition and prevention of osteoporosis via rabbiteye blueberry are still elusive. This study was aim to evaluate the anti-osteoporosis effects of rabbiteye blueberry in ovariectomized rats. Thirty rats were randomly divided into three groups of ten rats each as follows: sham-operated group (SG), ovariectomized model control group (OMG), and ovariectomized rabbiteye blueberry treatment group (OBG). The blood mineral levels, the alkaline phosphatase (ALP) activity, and osteoprotegerin (OPG) level were determined. The expression analyses of type I collagen, integrin-β1, and focal adhesion kinase (FAK) were performed. Besides, the bone mineral density (BMD) and bone histomorphometry (BH) were measured. The ALP activity in SG and OBG was significantly lower than that in OMG. For the OPG level, the significant increase of OPG level in OBG was indicated compared with the other groups. The mRNA expression levels of type I collagen, integrin-β1, and FAK in OMG were significantly lower than those in other groups. The BMD in OMG were all significantly lower than those in SG and OBG. For BH, blueberry significantly improved the trabecular bone volume fraction, trabecular thickness, mean trabecular bone number, and bone formation rate, and decreased the trabecular separation, the percent of bone resorption perimeter, and mean osteoclast number in OBG compared with OMG. The rabbiteye blueberries had an effective inhibition in bone resorption, bone loss, and reduction of bone strength of ovariectomized rats and could improve the BMD, osteogenic activity, and trabecular bone structure.

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

International Nuclear Information System (INIS)

Miller, S.C.

1985-01-01

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

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.

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Piper sarmentosum enhances fracture healing in ovariectomized osteoporotic rats: a radiological study

Directory of Open Access Journals (Sweden)

Mohamed Abdalla Estai

2011-01-01

Full Text Available INTRODUCTION: Osteoporotic fractures are common during osteoporotic states. Piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties. OBJECTIVES: To observe the radiological changes in fracture calluses following administration of a Piper sarmentosum extract during an estrogen-deficient state. METHODS: A total of 24 female Sprague-Dawley rats (200-250 g were randomly divided into 4 groups: (i the sham-operated group; (ii the ovariectomized-control group; (iii the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy group, which was supplemented with estrogen (100 μg/kg/day; and (iv the ovariectomized + Piper sarmentosum (ovariectomized + Piper sarmentosum group, which was supplemented with a water-based Piper sarmentosum extract (125 mg/kg. Six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a K-wire was inserted. Each group of rats received their respective treatment for 6 weeks. Following sacrifice, the right femora were subjected to radiological assessment. RESULTS: The mean axial callus volume was significantly higher in the ovariectomized-control group (68.2 + 11.74 mm³ than in the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups (20.4 + 4.05, 22.4 + 4.14 and 17.5 + 3.68 mm³, respectively. The median callus scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups had median (range, minimum - maximum value as 1.0 (0 - 2, 1.0 (1 - 2 and 1.0 (1 - 2, respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3. The median fracture scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups were 3.0 (3 - 4, 3.0 (2 - 3 and 3.0 (2 - 3, respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2 (p<0.05. CONCLUSION: The Piper sarmentosum extract improved

Piper sarmentosum enhances fracture healing in ovariectomized osteoporotic rats: a radiological study.

Science.gov (United States)

Estai, Mohamed Abdalla; Suhaimi, Farihah Haji; Das, Srijit; Fadzilah, Fazalina Mohd; Alhabshi, Sharifah Majedah Idrus; Shuid, Ahmad Nazrun; Soelaiman, Ima-Nirwana

2011-01-01

Osteoporotic fractures are common during osteoporotic states. Piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties. To observe the radiological changes in fracture calluses following administration of a Piper sarmentosum extract during an estrogen-deficient state. A total of 24 female Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: (i) the sham-operated group; (ii) the ovariectomized-control group; (iii) the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy) group, which was supplemented with estrogen (100 μg/kg/day); and (iv) the ovariectomized + Piper sarmentosum (ovariectomized + Piper sarmentosum) group, which was supplemented with a water-based Piper sarmentosum extract (125 mg/kg). Six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a K-wire was inserted. Each group of rats received their respective treatment for 6 weeks. Following sacrifice, the right femora were subjected to radiological assessment. The mean axial callus volume was significantly higher in the ovariectomized-control group (68.2 ± 11.74 mm³) than in the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups (20.4 ± 4.05, 22.4 ± 4.14 and 17.5 ± 3.68 mm³, respectively). The median callus scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups had median (range, minimum - maximum value) as 1.0 (0 - 2), 1.0 (1 - 2) and 1.0 (1 - 2), respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3). The median fracture scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups were 3.0 (3 - 4), 3.0 (2 - 3) and 3.0 (2 - 3), respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2) (pPiper sarmentosum extract improved fracture healing, as assessed by the reduced callus volumes and

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

International Nuclear Information System (INIS)

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

1981-01-01

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

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)

A grape-enriched diet increases bone calcium retention and cortical bone properties in ovariectomized rats.

Science.gov (United States)

Hohman, Emily E; Weaver, Connie M

2015-02-01

Grapes and their associated phytochemicals have been investigated for beneficial effects on cardiovascular health, cancer prevention, and other chronic diseases, but the effect of grape consumption on bone health has not been fully determined. We previously found short-term benefits of grape products on reducing bone turnover in ovariectomized rats. The objective of this study was to determine the long-term benefits of a grape-enriched diet on bone in ovariectomized rats. Rats were ovariectomized at 3 mo of age and were administered a single dose of (45)Ca to prelabel bones at 4 mo of age. After a 1-mo equilibration period, baseline urinary (45)Ca excretion was determined. Rats (n = 22/group) were then randomly assigned to a modified AIN93M diet containing 25% freeze-dried grape powder or to a control diet for 8 wk. Urinary (45)Ca excretion was monitored throughout the study to determine changes in bone (45)Ca retention. Calcium balance was assessed after 1 and 8 wk of consuming the experimental diets, and a calcium kinetic study was performed at 8 wk. After 8 wk, femurs were collected for micro-computed tomographic imaging, 3-point bending, and reference point indentation. Rats fed the grape-enriched diet had 44% greater net bone calcium retention than did rats fed the control diet. There were no differences in calcium balance due to diet at either week 1 or week 8, but there was a significant increase in net calcium absorption (10.6%) and retention (5.7%) from week 1 to week 8 in the grape-enriched diet group only. Grape-enriched diet-fed rats had 3% greater cortical thickness and 11% greater breaking strength. There were no differences in femur bone mineral density, trabecular microarchitecture, or reference point indentation variables due to diet. This study of ovariectomized rats indicates that the consumption of grape products may improve calcium utilization and suppress bone turnover, resulting in improvements in bone quality. © 2015 American Society for

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

African Journals Online (AJOL)

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

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

International Nuclear Information System (INIS)

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

1980-01-01

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

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

International Nuclear Information System (INIS)

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

1983-01-01

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

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

International Nuclear Information System (INIS)

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

1984-01-01

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

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.

Swimming training prevents coronary endothelial dysfunction in ovariectomized spontaneously hypertensive rats

Directory of Open Access Journals (Sweden)

E.R.G. Claudio

Full Text Available Estrogen deficiency and hypertension are considered major risk factors for the development of coronary heart disease. On the other hand, exercise training is considered an effective form to prevent and treat cardiovascular diseases. However, the effects of swimming training (SW on coronary vascular reactivity in female ovariectomized hypertensive rats are not known. We aimed to evaluate the effects of SW on endothelium-dependent coronary vasodilation in ovariectomized hypertensive rats. Three-month old spontaneously hypertensive rats (SHR, n=50 were divided into four groups: sham (SH, sham plus swimming training (SSW, ovariectomized (OVX, and ovariectomized plus swimming training (OSW. The SW protocol (5 times/week, 60 min/day was conducted for 8 weeks. The vasodilatory response was measured in isolated hearts in the absence and presence of a nitric oxide synthase inhibitor (L-NAME, 100 µM. Cardiac oxidative stress was evaluated in situ by dihydroethidium fluorescence, while the expression of antioxidant enzymes (SOD-2 and catalase and their activities were assessed by western blotting and spectrophotometry, respectively. Vasodilation in SHR was significantly reduced by OVX, even in the presence of L-NAME, in conjunction with an increased oxidative stress. These effects were prevented by SW, and were associated with a decrease in oxidative stress. Superoxide dismutase 2 (SOD-2 and catalase expression increased only in the OSW group. However, no significant difference was found in the activity of these enzymes. In conclusion, SW prevented the endothelial dysfunction in the coronary bed of ovariectomized SHR associated with an increase in the expression of antioxidant enzymes, and therefore may prevent coronary heart disease in hypertensive postmenopausal women.

Retention and distribution of 241AmIII in neonatal beagles

International Nuclear Information System (INIS)

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

1977-01-01

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

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

International Nuclear Information System (INIS)

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

1987-01-01

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

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

Science.gov (United States)

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

1985-12-01

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

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

International Nuclear Information System (INIS)

Moreira, Paula I.; Custodio, Jose B.A.; Nunes, Elsa; Moreno, Antonio; Seica, Raquel; Oliveira, Catarina R.; Santos, Maria S.

2007-01-01

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 Ca 2+ 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 H 2 O 2 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

Thyroid neoplasia in beagles receiving whole-body irradiation during development

International Nuclear Information System (INIS)

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

1979-01-01

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

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

International Nuclear Information System (INIS)

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

1982-01-01

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

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

International Nuclear Information System (INIS)

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

1995-01-01

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

External scintigraphy in measuring rate of gastric emptying in beagles

Energy Technology Data Exchange (ETDEWEB)

Theodorakis, M.C.

1980-07-01

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

Primary joint disease in the shoulder of the beagle dog

International Nuclear Information System (INIS)

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

1985-01-01

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

Atlas of experimentally-induced neoplasia in beagle dogs

International Nuclear Information System (INIS)

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

1996-10-01

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

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.

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.

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

Science.gov (United States)

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

2011-01-01

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

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

Science.gov (United States)

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 ug/kg/d estradiol and relative to rats treated with e...

[Effect of red maca (Lepidium meyenii) on INF-γ levels in ovariectomized rats].

Science.gov (United States)

Leiva-Revilla, Johanna; Guerra-Castañon, Félix; Olcese-Mori, Paola; Lozada, Iván; Rubio, Julio; Gonzales, Carla; Gonzales, Gustavo F

2014-01-01

Compare the effect of different doses of red maca on gamma interferon (IFN-γ) levels in ovariectomized rats (OVX). Adult female rats were randomly divided into the following six groups: Group 1: pseudo-ovariectomized rats (PO); Group 2: OVX rats; Group 3: OVX rats treated with 4 ug/kg estradiol; and Group 4, 5 and 6: OVX rats treated with red maca extracts with 2.15, 4.3 and 8.6 mg polyphenols/body weight kilogram, respectively. OVX rats showed low levels of IFN-γ compared to PO rats. Estradiol and red maca reversed the effect of ovariectomy on the IFN-γ levels. A positive dose-response effect of red maca on IFN-γ levels was shown (r = 0.57, p maca administration increases levels of IFN-γ in ovariectomized rats.

Development of the canine tooth in the beagle

International Nuclear Information System (INIS)

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

1993-01-01

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

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).

Life-span studies of inhaled plutonium in beagle dogs

International Nuclear Information System (INIS)

Bair, W.J.

1990-04-01

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

EFFECTS OF PHYSICAL TRAINING ON THE MYOCARDIUM OF FEMALE LDL KNOCKOUT OVARIECTOMIZED MICE

OpenAIRE

Brianezi, Ledimar; Marques, Mara Rubia; Cardoso, Clever Gomes; Miranda, Maria Luiza de Jesus; Fonseca, Fernando Luiz Affonso; Maifrino, Laura Beatriz Mesiano

2017-01-01

ABSTRACT Introduction: The emergence of coronary heart disease increases with menopause, physical inactivity and with dyslipidemia. It is known that physical training promotes the improvement of cardiovascular functions. Objective: The purpose of this study was to investigate the effects of aerobic physical training on the left ventricle in female LDL knockout ovariectomized mice. Methods: Thirty animals were divided into 6 groups (n=5), namely, sedentary non-ovariectomized control; sedentary...

Radiation-induced erythroleukemia in the beagle dog

International Nuclear Information System (INIS)

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

1977-01-01

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

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

International Nuclear Information System (INIS)

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

1990-01-01

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

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

International Nuclear Information System (INIS)

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

1991-01-01

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

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.

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.

Hormone therapy alters the composition of the vaginal microflora in ovariectomized rats.

Science.gov (United States)

Bezirtzoglou, E; Voidarou, Ch; Papadaki, A; Tsiotsias, A; Kotsovolou, O; Konstandi, M

2008-05-01

The aim of the present study was to evaluate the alterations that may take place in the bacterial genital tract flora in the absence of ovarian hormones. The role of hormone replacement therapy was also assessed. For this purpose, various bacteria were identified from the vaginal flora of ovariectomized and sham operated female rats, following the Bergey's manual criteria. The data of this study showed that substantial differences exist in the vaginal bacterial microflora between ovariectomized and normal cyclic rats. Ovariectomy was associated with a lower total bacterial load that may be due mainly to the absence of Lactobacillus. Anaerobic bacteria were also absent. Streptococcus and Enterococcus were also not favored in an environment lacking the ovarian hormones. In contrast, C. perfringens, Bacteroides, S. epidermidis, and S. aureus were detected in high numbers in ovariectomized rats. In terms of the impact of hormone replacement therapy on vaginal flora, only estradiol (EE2) restored Lactobacillus levels in ovariectomized rats, whereas all hormonal schemes used brought Streptococcus, Clostridium lec (-), and C. perfringens, the spore and vegetative forms, close to those detected in normal cyclic female rats. In conclusion, ovarian hormones appeared to be regulatory factors that favor the presence of a broad variety of bacteria, which are members of the normal genital tract flora. On the other hand, ovariectomy modifies the vaginal microbial profile, and hormone replacement therapy based mainly on schemes containing EE2 could alleviate this disturbance.

Resistance training and hormone replacement increase MMP-2 activity, quality and quantity of bone in ovariectomized rats

Directory of Open Access Journals (Sweden)

Markus V.C Souza

2017-12-01

Full Text Available Abstract AIMS The aim of the present study was to investigate the influence of resistance training (RT and hormone replacement (HR on MMP-2 activity, biomechanical and physical properties bone of ovariectomized (OVX rats. METHODS Sprague-Dawley female rats were grouped into six experimental groups (n = 11 per group: sham-operated sedentary (SHAM Sed, ovariectomized sedentary (OVX Sed, sham-operated resistance training (SHAM RT, ovariectomized resistance training (OVX RT, ovariectomized sedentary hormone replacement (OVX Sed-HR, and ovariectomized resistance training hormone replacement (OVX RT-HR. HR groups received implanted silastic capsules with a 5% solution of 17β-estradiol (50 mg 17β-estradiol/ml of sunflower oil. In a 12-week RT period (27 sessions; 4-9 climbs the animals climbed a 1.1 m vertical ladder with weights attached to their tails. Biomechanical and physical bone analyses were performed using a universal testing machine, and MMP-2 activity analysis was done by zymography. RESULTS Bone density and bone mineral content was higher in the RT and HR groups. The MMP-2 activity was higher in the RT and HR groups. The biomechanical analysis (stiffness, fracture load and maximum load demonstrated better bone tissue quality in the RT associated with HR. CONCLUSION The RT alone as well as when it is associated with HR was efficient in increasing MMP-2 activity, biomechanical and biophysical properties bone of ovariectomized rats.

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

International Nuclear Information System (INIS)

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

1989-01-01

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

Effect of Itraconazole on the Pharmacokinetics of Diclofenac in Beagle Dogs

OpenAIRE

AL-JENOOBI, Fahad

2010-01-01

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

The Ovariectomized Rat as a Model for Studying Alveolar Bone Loss in Postmenopausal Women

Directory of Open Access Journals (Sweden)

Bryan D. Johnston

2015-01-01

Full Text Available In postmenopausal women, reduced bone mineral density at the hip and spine is associated with an increased risk of tooth loss, possibly due to a loss of alveolar bone. In turn, having fewer natural teeth may lead to compromised food choices resulting in a poor diet that can contribute to chronic disease risk. The tight link between alveolar bone preservation, tooth retention, better nutritional status, and reduced risk of developing a chronic disease begins with the mitigation of postmenopausal bone loss. The ovariectomized rat, a widely used preclinical model for studying postmenopausal bone loss that mimics deterioration of bone tissue in the hip and spine, can also be used to study mineral and structural changes in alveolar bone to develop drug and/or dietary strategies aimed at tooth retention. This review discusses key findings from studies investigating mandible health and alveolar bone in the ovariectomized rat model. Considerations to maximize the benefits of this model are also included. These include the measurement techniques used, the age at ovariectomy, the duration that a rat is studied after ovariectomy and habitual diet consumed.

The Effect of Fenugreek (Trigonella foenum-graecum Seed and 17-β Estradiol on Serum Apelin, Glucose, Lipids, and Insulin in Ovariectomized Rats

Directory of Open Access Journals (Sweden)

Abedinzade

2015-08-01

Full Text Available Background Menopause, a natural phenomenon, is defined by the fall of ovarian hormones mainly estrogens causing major problems such as insulin resistance. Fenugreek (Trigonella foenum-graecum is known to have some useful properties such as insulin sensitizing effect. Apelin is an adipokine, which has several roles such as regulation of insulin secretion. Objectives The objective of the present study was to evaluate the effect of fenugreek seed and 17-β estradiol on serum Apelin along with glucose, lipids and insulin in ovariectomized rats. Materials and Methods Forty-nine adult female Wistar rats were randomly divided to seven groups: normal control, ovariectomized control, ovariectomized treated with ethanolic and hexanic extract of fenugreek seed (50 and 150 mg/kg/daily for each, and ovariectomized treated with 17-β estradiol (10 µg/kg/daily for 42 days. Serum Apelin, glucose, lipids and insulin were measured. Results Serum Apelin, glucose, lipids and insulin significantly increased in ovariectomized controls in comparison with normal controls (P < 0.05. Serum glucose, lipids and insulin in ovariectomized rats treated with fenugreek seed extract and 17-β estradiol were remarkably lower than ovariectomized controls (P < 0.05. Furthermore, 17-β estradiol caused a significant decrease (P < 0.05 in serum Apelin in ovariectomized rats. Conclusions It appears that fenugreek seed might be effective against hyperglycemia, hyperlipidemia and insulin resistance in ovariectomized rats without impact on serum Apelin. Furthermore, 17-β estradiol could have similar effects along with possible inhibitory effects on serum Apelin. The complicated role of Apelin in menopause needs to be further explored.

Clotting mechanism in beagles irradiated by 4.5 Gy γ-rays

International Nuclear Information System (INIS)

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

2010-01-01

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

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

International Nuclear Information System (INIS)

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

1991-01-01

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

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

International Nuclear Information System (INIS)

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

1977-01-01

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

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.

Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

International Nuclear Information System (INIS)

Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C.; Irigoyen, M.C.; De Angelis, K.

2015-01-01

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

Toxicity of 239PuO2 in immature Beagle dogs. III

International Nuclear Information System (INIS)

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

1981-01-01

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

Plutonium-induced lymphadenitis in beagles

International Nuclear Information System (INIS)

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

1976-01-01

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

The Cooccurrence of Obesity, Osteoporosis, and Sarcopenia in the Ovariectomized Rat: A Study for Modeling Osteosarcopenic Obesity in Rodents

Directory of Open Access Journals (Sweden)

Zahra Ezzat-Zadeh

2017-01-01

Full Text Available Background. Obesity, osteoporosis, and sarcopenia may individually occur due to age-related gradual alterations in body composition. This study investigates the cooccurrence of these age-related diseases in female animals with low levels of ovarian hormone in the absence of complex multifactorial process of chronological aging. Methods. Thirty-six 5- and 10-month-old female rats were chosen to model pre- and postmenopausal women, respectively. Rats were divided into three treatment groups in each age category—sham, ovariectomized (ovx, and ovx + E2 (17β-estradiol, 10 μg/kg—and were pair-fed. Volunteer wheel running activity, body composition, bone microstructure, serum C-telopeptides of type I collagen, bone specific alkaline phosphatase, E2, and gastrocnemius and soleus muscles were analyzed. Results. The cooccurrence of osteoporosis, sarcopenia, and obesity was observed in the older ovx rats associated with a significant (p<0.05 increased fat mass (30%, bone loss (9.6%, decreased normalized muscle mass-to-body-weight ratio (10.5%, and a significant decrease in physical activity (57%. The ratio of tibial bone mineral density to combined muscle mass was significantly decreased in both ovx age categories. Conclusion. Ovariectomized rat could be used as an experimental model to examine the effect of loss of ovarian hormones, while controlling for energy intake and expenditure, to conduct obesity and body composition translational research in females without the confounding effect of genetic background.

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.

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

International Nuclear Information System (INIS)

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

1988-01-01

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

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

Directory of Open Access Journals (Sweden)

Lisa Frank

2018-02-01

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

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

Science.gov (United States)

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

2015-07-01

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

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.

Occurrence of bone cancer among young adult Beagles given 239Pu

International Nuclear Information System (INIS)

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

1991-01-01

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

Pleiotropic effects of simvastatin in physically trained ovariectomized rats

International Nuclear Information System (INIS)

Bernardes, N.; Brito, J.O.; Fernandes, T.G.; Llesuy, S.F.; Irigoyen, M.C.; Belló-Klein, A.; De Angelis, K.

2013-01-01

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

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.

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

International Nuclear Information System (INIS)

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

1989-01-01

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

The influence of age at time of exposure to 239Pu or 226Ra on retention, distribution, survival and tumor induction in Beagles

International Nuclear Information System (INIS)

Bruenger, F.W.; Miller, S.C.; Lloyd, R.D.

1991-01-01

The influence of age at injection of 226 Ra or 239 Pu on skeletal deposition and local distribution, the pattern of bone tumor formation and post-injection survival were studied in parallel short-term mechanistic and lifetime toxicity experiments. Beagles received a single intravenous injection of 226 Ra or 239 Pu at age 3 months (juveniles), 17-19 months (young adults) or 60 months (mature). Data from short-term mechanistic-dosimetric studies and from one dosage level (41 kBq 226 Ra/kg or 11 kBq 239 Pu/kg body mass) of each of the toxicity experiments were compared. Skeletal growth and turnover produced differential initial deposition and distribution patterns typical for each age group. The highest bone tumor incidence was seen in the young adult groups. Differences were observed in bone tumor location between dogs in the same age group given radium or plutonium and among age groups injected with either radionuclide, and some of these could be explained by differences in local dose distributions (e.g., trabecular vs. cortical bone). Cox regression indicated no significant differences in post-injection survivals (uncorrected for the different pre-injection periods) of Ra-injected groups, but there was a statistically significant difference among the Pu-injected groups. Neutron-induced autoradiography showed that differences in the effects of Pu in the three age groups were due primarily to the age- and time-dependent local distribution of the nuclide

Role of Pitavastatin in Prevention of Osteopenic Changes in Ovariectomized Rats

International Nuclear Information System (INIS)

Qadir, F.; Alam, S. M.; Siddiqi, A. Q.

2016-01-01

Objective: To determine the effect of pitavastatin, a third generation statin, on development of osteopenia in ovariectomized rats. Study Design: Experimental study. Place and Duration of Study: Department of Pharmacology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Center, Karachi, from January to July 2013. Methodology: Forty female Sprague Dawley rats were divided into ovariectomized (OVX), Sham OVX and OVX given pitavastatin 0.4 mg/kg/day, 0.8 mg/kg/day, for 8 weeks. Bone density measurements using CT scan and Archimedes principle were made on femora and tibiae. Blood samples were analyzed for acid phosphatase (ACP) and alkaline phosphatase (ALP) levels. Results: Ovariectomy-induced osteopenic changes were indicated by significant decrease in bone densities and Hounsfield (HU) index of distal femoral and proximal tibial metaphyses and elevation of ACP and ALP levels. 0.4 mg/kg pitavastatin did not significantly alter the evaluated parameters. 0.8 mg/kg produced a restoration of HU of lower femur and femoral density comparable to Sham. HU of upper tibia and tibial density following 0.8 mg/kg was significantly higher than OVX but was not approximate to Sham. ALP and ACP with 0.8 mg/kg were comparable to Sham. Conclusion: Supra-therapeutic dose of pitavastatin was effective in preventing estrogen deficiency-induced decrease in bone density of ovariectomized rates, over an 8-week period. (author)

Executive function is less sensitive to estradiol than spatial memory: performance on an analog of the card sorting test in ovariectomized aged rhesus monkeys.

Science.gov (United States)

Lacreuse, A; Chhabra, R K; Hall, M J; Herndon, J G

2004-09-30

Functions supported by the frontal lobes are particularly sensitive to the detrimental effects of aging. Recent studies on postmenopausal women find that estrogen replacement therapy benefits performance on tasks dependent on the frontal lobes. To determine whether estrogen has a similar influence in a rhesus monkey model of menopause, we tested five aged, long-term ovariectomized rhesus monkeys in a modified version of the Wisconsin Card Sort test which had been adapted to the nonhuman primate. In this test, monkeys had to select 3-D objects based either on color (blue, red, yellow) or shape (block, tube, cup) and had to be able to switch their response as a function of reinforcement contingencies. The monkeys were treated with placebo and ethinyl estradiol (EE2, 450 ng/kg/day) in alternation with each successive test. Contrary to our hypothesis, estradiol treatment did not affect performance. Because previous studies in the same monkeys [Neurobiol. Aging 23 (2002) 589] had shown that EE2 improves performance on a spatial memory task dependent on the hippocampus, but not on another task dependent upon the frontal lobes (the delayed response), we conclude that executive processes may be less sensitive to the effects of estradiol than hippocampal-dependent tasks.

Effects of Herbal-Acupuncture with Rosae Laevigatae Fructus Extract at KI10(Umgok on Osteoporosis in Ovariectomized Mice

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Kim Dong-soo

2009-12-01

Full Text Available Objective & Methods : The purpose of this study was to observe the effects of herbal-acupuncture with Rosae Laevigatae Fructus extact(RLF-HA at KI10(Umgok on osteoporosis in ovariectomized(OVX ddy mice. We carried out several experimental items to analyze the changes in body weight, uterine weight, uterus index, tibial length, the ash bone weight, tibial BMD, serum ALP, serum osteocalcin, serum Ca, and the levels of Ca, P, Ca/P ratio in tibia, and we performed histological and histomorphological analysis as well. Results : 1. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok and saline injection at KI10(Umgok significantly inhibited the reduction of tibial calcium level in ovariectomized mice. 2. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok significantly inhibited the increase of tibial osteoclast cells in ovariectomized mice. 3. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok significantly inhibited the reduction of tibial trabecular bone thickness(TBT in ovariectomized mice. 4. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok significantly inhibited the overgrowth of tibial growth plate length(GPL in ovariectomized mice. Conclusion : These results suggested that herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok has a therapeutic effect on osteoporosis, and to be put to practical use in the future osteoporosis clinic.

Decorporation of 241Am in beagles by DTPA

International Nuclear Information System (INIS)

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

1975-01-01

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

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

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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.

Meiofauna communities from the Straits of Magellan and the Beagle Channel

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G. C. Chen

1999-12-01

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

The effects of acute and chronic estrogen deficiency on glucose and lipid profile in ovariectomized rats

OpenAIRE

Rabie P; Namjoo AR

2017-01-01

Background and aims: Ovariectomy is a standard experimental model of menopause in rodent to investigate postmenopausal women. The aim of this study was to evaluate effects acute and chronic estrogen deficiency on lipid profile and glucose serum in ovariectomized (OVX) rats. Methods: In this experimental study, Twenty-four adult female Wistar rats were divided into three groups of eight rats. The first group: sham-control, Second group: ovariectomized rats (for five weeks), Third group: Ova...

Computational segmentation of collagen fibers in bone matrix indicates bone quality in ovariectomized rat spine.

Science.gov (United States)

Daghma, Diaa Eldin S; Malhan, Deeksha; Simon, Paul; Stötzel, Sabine; Kern, Stefanie; Hassan, Fathi; Lips, Katrin Susanne; Heiss, Christian; El Khassawna, Thaqif

2018-05-01

Bone loss varies according to disease and age and these variations affect bone cells and extracellular matrix. Osteoporosis rat models are widely investigated to assess mechanical and structural properties of bone; however, bone matrix proteins and their discrepant regulation of diseased and aged bone are often overlooked. The current study considered the spine matrix properties of ovariectomized rats (OVX) against control rats (Sham) at 16 months of age. Diseased bone showed less compact structure with inhomogeneous distribution of type 1 collagen (Col1) and changes in osteocyte morphology. Intriguingly, demineralization patches were noticed in the vicinity of blood vessels in the OVX spine. The organic matrix structure was investigated using computational segmentation of collagen fibril properties. In contrast to the aged bone, diseased bone showed longer fibrils and smaller orientation angles. The study shows the potential of quantifying transmission electron microscopy images to predict the mechanical properties of bone tissue.

Age validation and growth of yolked larvae of Patagonotothen tessellata (Richardson, 1845 (Pisces: Nototheniidae from the rocky littoral of the Beagle Channel, Argentina

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Gustavo Alfredo Rae

1999-12-01

Full Text Available Age and growth estimation of Patagonotothen tessellata larvae over the endogenous period was estimated by examining their otolith microstructure and the associated increment deposition rate. Analyzed specimens were incubated from egg-masses collected in Lapataia Bay, Beagle Channel, Argentina. Validation was performed by monitoring reared larvae of known ages. Actual age and increment count were regressed suggesting a daily deposition of one ring in the otolith, which began at hatching time and continued until larvae reached sixteen days old (time of massive mortality. Mean lengths at each age were estimated using Richards´ growth function; their constant (m attained a value close to zero indicating that the data fitted to the von Bertalanffy model. Absolute growth rate was 0.55 mm*d-1of total length at hatching, dropped near zero on the fifth day after hatching and afterwards, there was no growth. Yolk absorption rate (expressed as a ratio between minor axis/major axis of the vitelline-sac showed a similar variation as that observed in absolute growth rate during the endogenous period. The total yolk absorption took five days in the unfed larvae group and seven days in the fed larvae group. The rapid absorption of the yolk and the observed growth pattern suggest that Patagonotothen tessellata larvae have a short endogenous period, reaching the state of first food uptake five days after hatching.

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).

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

International Nuclear Information System (INIS)

Liu Sheng; Shi Haibin; Hu Weixing; Zu Qingquan; Lu Shanshan; Xu Xiaoquan; Sun Lei; Li Linsun

2011-01-01

Objective: To compare the differences of cerebrovascular structure and brain tissue volume between beagle and mongrel dogs by using angiography and MR scanning. Methods: A total of 40 dogs, including 20 beagle dogs (beagle group) and 20 mongrel dogs (mongrel group), were enrolled in this study. Under general anesthesia, all dogs were examined with cerebral angiography and MR scanning. The cerebrovascular structure was evaluated with angiography via selective catheterization of aortic arch, bilateral external cerebral arteries (ECA), maxillary arteries, internal cerebral arteries (ICA) and vertebral arteries separately. The diameters of the ICA, middle cerebral artery (MCA), rostral cerebral artery (RCA), the anastomosis channel ICA and ECA, and basilar artery (BA) were measured at the similar point of each dog. Meanwhile the volumes of the brain tissue were calculated in coronal T2 view of MR scanning. The statistical analysis was performed among the weight of dogs, the diameter of arteries and the volume of brain tissue. The differences in the diameters and brain tissue volume were compared between the two groups. Results: No obvious variations in the cerebrovascular structure and brain tissue volume were found in these dogs. One mongrel dog was excluded from this study because of the severe stenosis of ICA. The mean weight of 20 beagle dogs and 19 mongrel dogs was (12.81±1.29) kg and (12.85±1.12) kg, respectively. The diameters of the ICA, MCA, RCA, the anastomosis channel between ICA and ECA and BA in beagle group were (1.26±0.07) mm, (0.90±0.05) mm, (0.58±0.07) mm, (0.55±0.07) mm and (0.95±0.06) mm, respectively. These parameters in mongrel group were (1.27±0.07) mm, (0.92±0.05) mm, (0.59±0.06) mm, (0.67±0.07) mm and (0.94±0.05) mm, respectively. The volume of brain in two groups was (76232.33±5018.51) mm 3 and (71863.96±4626.87) mm 3 , respectively. There were no obvious correlation among the body weight, the cerebrovascular diameters and brain

Focal hyalinization during experimental tooth movement in beagle dogs.

NARCIS (Netherlands)

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

2004-01-01

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

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.

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

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Martin J. Ronis

2016-06-01

Full Text Available 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].

Genistein preserves the lungs of ovariectomized diabetic rats: addition to apoptotic and inflammatory markers in the lung

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Faeze Daghigh

2017-12-01

Full Text Available Objective(s: The role of isoflavones in pulmonary structure and function during menopause is not well studied. Moreover, the important role of estrogen in the physiological function of respiratory system has been revealed. Genistein, as an isoflavone, mimics estrogenic in diabetic and ovariectomized rats. Here, we hypothesized that genistein would reverse changes in the protein expression levels related to estrogen deficiency in the lung of ovariectomized diabetic rats. Materials and Methods: Wistar female rats were assigned to four experimental groups (n=10 in each group: sham, rats underwent laparotomy without removing the ovaries; OVX, rats that underwent ovariectomy; OVX.D, rats underwent bilateral ovariectomy and were fed a high-fat diet (HFD; OVX.D.G, ovariectomized diabetic rats with genistein administration (1 mg/kg /day. After ovariectomy, rats continued to feed HFD for a 4-week period. After 4 weeks of HFD feeding, a single dose of 30 mg/kg of streptozotocin was administered in the diabetic group. Genistein was administered for eight weeks. At the end of the experiment, lung tissue was removed and Western blotting technique and hematoxylin-eosin staining were used for evaluation of the lung. Results: Treatment with genistein significantly decreased inflammatory and apoptotic biomarkers in the ovariectomized diabetic rats compared to non-treated animals (P

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

Science.gov (United States)

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

2010-01-01

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

Quantitative Ultrasound Assessment of Cartilage Degeneration in Ovariectomized Rats with Low Estrogen Levels.

Science.gov (United States)

Wang, Qing; Liu, Zhiwei; Wang, Yinong; Pan, Qingya; Feng, Qianjin; Huang, Qinghua; Chen, Wufan

2016-01-01

The aim of this study was to assess quantitatively the site-specific degeneration of articular cartilage in ovariectomized rats with low estrogen levels using a high-frequency ultrasound system. Fourteen female Sprague-Dawley rats were randomly divided into two groups (n = 7 per group): a sham group in which only the peri-ovarian fatty tissue was exteriorized and an ovariectomized group that underwent bilateral ovariectomy to create a menopause model with low estrogen levels. All animals were sacrificed at the end of the third week after ovariectomy. Hindlimbs were harvested. The articular cartilage from five anatomic sites (i.e., femoral caput [FC], medial femoral condyle [MFC], lateral femoral condyle [LFC], medial tibial plateau [MTP] and lateral tibial plateau [LTP]) was examined with ultrasound. Four parameters were extracted from the ultrasound radiofrequency data: reflection coefficient of the cartilage surface (RC1), reflection coefficient of the cartilage-bone interface (RC2), ultrasound roughness index (URI) and thickness of the cartilage tissue. The results indicated significant (p reduction induces morphologic and acoustic alterations in the articular cartilage of the hip and knee joints in ovariectomized rats. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Identification of the Beagle 2 lander on Mars

Science.gov (United States)

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

2017-10-01

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

Identification of the Beagle 2 lander on Mars.

Science.gov (United States)

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

2017-10-01

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

Beagle 2: Seeking the signatures of life on Mars

OpenAIRE

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

2003-01-01

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

Biomechanical and microstructural benefits of physical exercise associated with risedronate in bones of ovariectomized rats.

Science.gov (United States)

Shimano, Roberta Carminati; Macedo, Ana Paula; Falcai, Maurício José; Ervolino, Edilson; Shimano, Antônio Carlos; Issa, João Paulo Mardegan

2014-06-01

Several treatments have been developed aiming the prevention of bone loss. There are discussions about the best prophylactic and therapeutic procedures for osteoporosis. This study evaluated the effects of physical exercise associated with risedronate as a prophylactic and therapeutic procedure in osteopenic bones of rats submitted to ovariectomy. We used 48 Wistar rats divided into: ovariectomized or subjected to sham surgery. Ovariectomized rats were divided into the following sub-groups: OVX, 12 weeks sedentary; OVX-EX, treadmill training for 12 weeks; OVX-RA, 12 weeks with risedronate administration; and OVX-EX-RA, 12 weeks with risedronate administration and treadmill training. Rats subjected to sham surgery were divided into the following sub-groups: SH, 12 weeks sedentary; SH-EX, treadmill training for 12 weeks; SH-RA, 12 weeks with risedronate administration; and SH-EX-RA, 12 weeks with risedronate administration and training on the treadmill. The effectiveness of the treatment was evaluated in tibias using biomechanical, radiological, histomorphometric, and immunohistochemical analyses. Data were analyzed by statistical tests, with significance level of P bones of ovariectomized rats. © 2014 Wiley Periodicals, Inc.

Toxicity of 239PuO2 in immature Beagle dogs. VIII

International Nuclear Information System (INIS)

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

1986-01-01

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

Effect of Cistanches Herba Aqueous Extract on Bone Loss in Ovariectomized Rat

Directory of Open Access Journals (Sweden)

Zaiguo Huang

2011-08-01

Full Text Available To assess the ability of traditional Chinese medicine Cistanches Herba extract (CHE to prevent bone loss in the ovariectomized (OVX rat, Cistanches Herba extract (CHE was administered intragastrically to the rats. Female rats were anesthetized with pentobarbital sodium (40 mg kg−1, i.p., and their ovaries were removed bilaterally. The rats in the sham-operated group were anesthetized, laparotomized, and sutured without removing their ovaries. After 1 week of recovery from surgery, the OVX rats were randomly divided into three groups and orally treated with H2O (OVX group or CHE (100 or 200 mg kg−1 daily for 3 months. The sham-operated group (n = 8 was orally treated with H2O. After 3 months, the total body bone mineral density (BMD, bone mineral content (BMC, Bone biomechanical index, blood mineral levels and blood antioxidant enzymes activities were examined in sham-operated, ovariectomized and Cistanches Herba extract treated rats. Results showed that Cistanches Herba extract treatment significantly dose-dependently enhanced bone mineral density (BMD, bone mineral content (BMC, maximum load, displacement at maximum load, stress at maximum load, load at auto break, displacement at auto break, and stress at auto break, and blood antioxidant enzymes activities, decreased blood Ca, Zn and Cu levels compared to the OVX group. This experiment demonstrates that the administration of Cistanches Herba extract to ovariectomized rats reverses bone loss and prevents osteoporosis.

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

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...... intravenously (iv) daily with bFGF for 14 days at a dose of 200 microg/kg body weight. At the end of bFGF treatment, one group was killed whereas the other group was subjected to 8 weeks of treatment with synthetic human PTH 1-34 [hPTH(1-34)] consisting of subcutaneous (sc) injections 5 days/week at a dose...... of 80 microg/kg. Another group of OVX rats was treated iv with vehicle for 2 weeks followed by treatment with PTH alone for 8 weeks. Other groups of sham-operated control rats and OVX rats were treated iv and sc with vehicle alone. The right proximal tibia from each rat was processed undecalcified...

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

African Journals Online (AJOL)

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

Effects of Low-Intensity Pulsed Ultrasound on Orthodontic Tooth Movement and Orthodontically Induced Inflammatory Root Resorption in Ovariectomized Osteoporotic Rats.

Science.gov (United States)

Dahhas, Feras Y; El-Bialy, Tarek; Afify, Ahmed R; Hassan, Ali H

2016-03-01

This study investigated the effects of low-intensity pulsed ultrasound (LIPUS) on orthodontic tooth movement (OTM) and orthodontically induced inflammatory root resorption (OIRR) in ovariectomized osteoporotic rats. Forty-eight 28-d-old female Wistar rats were divided into ovariectomized and intact groups. In both groups, animals were left untreated; treated with 50 g mesially directed orthodontic force on the maxillary first molars using nickel-titanium closed-coil springs for 28 d; or treated with the same orthodontic protocol along with a 20-min LIPUS application on alternate days for 28 d. Extent of OTM and amount of OIRR of mesial roots were measured on three-dimensionally reconstructed micro-computed tomography images. Ovariectomy increased OIRR (p root volumetric loss regardless of ovariectomy status (p < 0.05); only ovariectomized animals had decreased OTM (p < 0.05). LIPUS normalizes OTM and attenuates OIRR in ovariectomized osteoporotic rats. It may therefore be beneficial in women with postmenopausal osteoporosis. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Extending the BEAGLE library to a multi-FPGA platform.

Science.gov (United States)

Jin, Zheming; Bakos, Jason D

2013-01-19

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

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

Science.gov (United States)

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

2014-01-01

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

Effect of antiresorptive drugs in the alveolar bone healing. A histometric and immunohistochemical study in ovariectomized rats.

Science.gov (United States)

Ramalho-Ferreira, Gabriel; Faverani, Leonardo Perez; Momesso, Gustavo Antonio Correa; Luvizuto, Eloá Rodrigues; de Oliveira Puttini, Igor; Okamoto, Roberta

2017-06-01

The aim of this study is to evaluate the alendronate and raloxifene influence in the alveolar healing process of osteoporotic rats. Sixty-four female rats were divided in four groups: sham rats (SHAM), ovariectomized rats and no medical treatment (OVX NT), ovariectomized rats and submitted to alendronate treatment (OVX ALE), and ovariectomized and submitted to raloxifene treatment (OVX RAL). The histomorphometrical and immunohistochemical analysis was performed. The quantitative data were analyzed through Kruskal-Wallis and Dunn tests (α = 0.05). In the longest period, SHAM and OVX RAL groups showed the better bone formation responses (P alveolar healing process in osteoporotic rats, but not enough to achieve the histometrical and protein expression values that were observed in the SHAM group. Alendronate is largely used as a potent antiresorptive agent. Otherwise, considering the undesirable effects in relation to the alveolar healing, other antiosteoporosis medications should be studied. Raloxifene seems to be a good candidate once its action mechanism involves the activation of osteoblasts.

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

International Nuclear Information System (INIS)

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

2002-01-01

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

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

Science.gov (United States)

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

2015-07-01

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

Differentiation of peripheral lymphocyte population in Pu-exposed beagle dogs

International Nuclear Information System (INIS)

Morris, J.E.

1977-01-01

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

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

International Nuclear Information System (INIS)

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

1983-01-01

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

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

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...

2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice.

Science.gov (United States)

Pingili, Ajeeth K; Davidge, Karen N; Thirunavukkarasu, Shyamala; Khan, Nayaab S; Katsurada, Akemi; Majid, Dewan S A; Gonzalez, Frank J; Navar, L Gabriel; Malik, Kafait U

2017-06-01

Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and end-organ damage in intact Cyp1b1 -/- , ovariectomized female, and Cyp1b1 +/+ male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II-induced increases in systolic blood pressure, water consumption, urine output, and proteinuria in intact female Cyp1b1 -/- and ovariectomized mice. 2-Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water intake, urine output, and proteinuria in Cyp1b1 +/+ male mice. Treatment with 2-methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice and Cyp1b1 +/+ male mice. 2-Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of angiotensinogen in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice but not in Cyp1b1 +/+ male mice. The G protein-coupled estrogen receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood pressure and renal function in Cyp1b1 +/+ female mice. These data suggest that 2-methoxyestradiol reduces Ang II-induced hypertension and associated end-organ damage in intact Cyp1b1 -/- , ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice, and Cyp1b1 +/+ male mice independent of G protein-coupled estrogen receptor 1. Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating hypertension and associated pathogenesis in postmenopausal females, and in males. © 2017 American Heart Association, Inc.

Effects of chronic estradiol treatment on the thyroid gland structure and function of ovariectomized rats

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Elgendy Mohamed S

2009-08-01

Full Text Available Abstract Background Estrogen therapy is widely used nowadays in women to treat many postmenopausal symptoms but it may have some undesirable effects due to multiple organs affection. So, the aim of this study was to determine the effects of chronic estradiol treatment on the structure and function of the thyroid gland in ovarictomized rats as a model simulating menopause. Findings Thirty adult female Wistar rats divided into three groups were used in this study; the first group was sham-operated, while the second and third groups were ovariectomized. The first and second groups were injected with olive oil while the third group was injected with estradiol dipropionate daily for three months, after that; hormonal assay for T3, T4, TSH and specimens of the thyroid were taken and processed to be examined by light and electron microscopy. The results of this study revealed that serum levels of T3 and T4 decreased in ovariectomized animals and significantly increased after estradiol treatment, while TSH increased in ovariectomized animals and decreased with estradiol treatment. Histological and morphometric study in ovariectomized group revealed marked accumulation of colloid in follicular lumens with decreased epithelial height in addition to increased connective tissue amount. After estradiol treatment the follicles became smaller in size, having small amount of colloid with increased epithelial height in addition to decreased connective tissue content. Ultrastructural study supported these results in addition to the presence of large amount of intracytoplasmic colloid vesicles after estradiol treatment. Conclusion Low estrogen level may lead to mild thyroidal hypofunction while estradiol treatment may lead to hyperactivity so it should be used very cautiously in the treatment of postmenopausal symptoms to avoid its undesirable stimulatory effect on the thyroid.

Effect of dietary soy isoflavones on bone loss in ovariectomized rats ...

African Journals Online (AJOL)

Purpose: To determine the effect of dietary soy isoflavone supplementation on bone loss in ovariectomized (OVX) rats. Methods: Forty-eight rats were assigned randomly to groups of OVX rats receiving soy isoflavones (20, 30, or 40 mg/kg of body weight daily), untreated OVX rats, or untreated intact rats. After 8 weeks, bone ...

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.

The variation of cancellous bones at lumbar vertebra, femoral neck, mandibular angle and rib in ovariectomized sheep.

Science.gov (United States)

Zhang, Yongqiang; Li, Yongfeng; Gao, Qi; Shao, Bo; Xiao, Jianrui; Zhou, Hong; Niu, Qiang; Shen, Mingming; Liu, Baolin; Hu, Kaijin; Kong, Liang

2014-07-01

This study aimed to compare the variation of cancellous bones at four skeletal sites: lumbar vertebra, femoral neck, mandibular angle and rib in ovariectomized sheep. Sixteen adult sheep were randomly divided into two groups: eight sheep were ovariectomized served as experimental group; the other eight untreated sheep were served as control group. Bone mineral density was assessed by dual-energy X-ray absorptiometry on lumbar vertebrae at baseline and twelve months after ovariectomy. After 12 months, lumbar vertebrae L3 and L4, femoral necks, mandibular angles and the fourth ribs were harvested for micro-CT scanning, histological analysis and biomechanical test. The results showed that bone mineral density of lumbar vertebra decreased significantly in twelfth month (pbone volume/total volume decreased by 45.6%, 36.1% 21.3% and 18.7% in lumbar vertebrae, femoral necks, mandibular angles and ribs in experimental group (pbones to oestrogen deficiency in ovariectomized sheep was site-specific on a pattern as follows: lumbar vertebra, femoral neck, mandibular angle and rib. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of whole body vibration therapy on circulating serotonin levels in an ovariectomized rat model of osteoporosis.

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Wei, Qiu-Shi; Huang, Li; Chen, Xian-Hong; Wang, Hai-Bin; Sun, Wei-Shan; Huo, Shao-Chuan; Li, Zi-Qi; Deng, Wei-Min

2014-01-01

Studies have reported that whole body vibration (WBV) played a vital role in bone remodeling. Circulating serotonin is also involved in negative regulating bone mass in rodents and humans. However, both WBV and inhibition of serotonin biosynthesis may suppress receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis in vitro. The purpose of the current study was to investigate the effect of WBV therapy on the levels of serum serotonin in ovariectomized rats. Thirty-six-month-old female Sprague Dawley rats weighing 276.15±37.75 g were ovariectomized to induce osteoporosis, and another ten rats underwent sham operation to establish sham control (SHAM) group. After 3 months, ovariectomized rats were divided into three subgroups and then separately treated with WBV, Alendronate (ALN) and normal saline (OVX), SHAM group was given normal saline. After 6 weeks of treatment, rats were sacrificed. Serum serotonin, RANKL, bone turnover markers, and bone mineral density (BMD), bone strength were evaluated. The serum serotonin level was significantly lower in WBV group than OVX and ALN groups (P<0.05 and P<0.001). RANKL levels significantly decreased in WBV and ALN groups compared to OVX group (P<0.001 for both). BMD and biomechanical parameters of femur significantly increased (P<0.05 for both) and bone turnover levels decreased (P<0.001 for both) in WBV group compared to OVX group. These data indicated that WBV enhanced the bone strength and BMD in ovariectomized rats most likely by reducing the levels of circulating serotonin.

Cardiac Hypertrophy and Brain Natriuretic Peptide Levels in an Ovariectomized Rat Model Fed a High-Fat Diet

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Goncalves, Gleisy Kelly; de Oliveira, Thiago Henrique Caldeira; de Oliveira Belo, Najara

2017-01-01

Background Heart failure in women increases around the time of menopause when high-fat diets may result in obesity. The heart produces brain natriuretic peptide (BNP), also known as B-type natriuretic peptide. This aims of this study were to assess cardiac hypertrophy and BNP levels in ovariectomized rats fed a high-fat diet. Material/Methods Forty-eight female Wistar rats were divided into four groups: sham-operated rats fed a control diet (SC) (n=12); ovariectomized rats fed a control diet (OC) (n=12); sham-operated rats fed a high-fat diet (SF) (n=12); and ovariectomized rats fed a high-fat diet (OF) (n=12). Body weight and blood pressure were measured weekly for 24 weeks. Rats were then euthanized, and plasma samples and heart tissue were studied for gene expression, hydroxyproline levels, and histological examination. Results A high-fat diet and ovariectomy (group OF) increased the weight body and the systolic blood pressure after three months and five months, respectively. Cardiomyocyte hypertrophy was associated with increased expression of ventricular BNP, decreased natriuretic peptide receptor (NPR)-A and increased levels of hydroxyproline and transforming growth factor (TGF)-β. The plasma levels of BNP and estradiol were inversely correlated; expression of estrogen receptor (ER)β and ERα were reduced. Conclusions The findings of this study showed that, in the ovariectomized rats fed a high-fat diet, the BNP-NPR-A receptor complex was involved in cardiac remodeling. BNP may be a marker of cardiac hypertrophy in this animal model. PMID:29249795

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

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Mathis, Justin C; Campbell, Vicki L

2015-07-01

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

Toxicity of inhaled 239PuO2 in immature beagle dogs

International Nuclear Information System (INIS)

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

1980-01-01

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

Absorption and pharmacokinetics of grapefruit flavanones in beagles

OpenAIRE

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

2007-01-01

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

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

International Nuclear Information System (INIS)

Luciani, A.; Polig, E.

2007-01-01

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

Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

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Nelson, Britta S; Black, Katelyn L; Daniel, Jill M

2016-01-01

Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

Absorption of DTPA from the respiratory tracts of Beagle dogs

International Nuclear Information System (INIS)

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

1978-01-01

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

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

OpenAIRE

Garneau, Christine Elise

2012-01-01

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

Effect of dietary γ-aminobutyric acid on the nerve growth factor and the choline acetyltransferase in the cerebral cortex and hippocampus of ovariectomized female rats.

Science.gov (United States)

Tujioka, Kazuyo; Thanapreedawat, Panicha; Yamada, Takashi; Yokogoshi, Hidehiko; Horie, Kenji; Kim, Mujo; Tsutsui, Kazumi; Hayase, Kazutoshi

2014-01-01

The brain protein synthesis and the plasma concentration of growth hormone (GH) is sensitive to the dietary γ-aminobutyric acid (GABA) in ovariectomized female rats; however, the role of dietary GABA on biomarkers including nerve growth factor (NGF) and choline acetyltransferase for the function of cholinergic neurons remains unknown in ovariectomized female rats. The purpose of this study was to determine whether the dietary GABA affects the concentration and mRNA level of NGF, and the activity of choline acetyltransferase in the brains of ovariectomized female rats. Experiments were done on two groups of 24-wk-old ovariectomized female rats given 0 or 0.5% GABA added to a 20% casein diet. The concentrations of NGF and activities of choline acetyltransferase in the cerebral cortex and hippocampus, and mRNA level of NGF in the hippocampus increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone. In the hippocampus, the mRNA level of NGF significantly correlated with the NGF concentration (r=0.714, pGABA to ovariectomized female rats is likely to control the mRNA level and concentration of NGF and cause an increase in the activity of choline acetyltransferase in the brains.

Late effects of inhaled 238PuO2 in beagles

International Nuclear Information System (INIS)

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

1976-01-01

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

The Protective Effect of γ-aminobutyric Acid on Kidney Injury Induced by Renal Ischemia-reperfusion in Ovariectomized Estradiol-treated Rats.

Science.gov (United States)

Talebi, Nahid; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Vafapour, Marzieh

2016-01-01

Renal ischemia-reperfusion injury (IRI) is one of the most important causes of kidney injury, which is possibly gender-related. This study was designed to investigate the role of γ-aminobutyric acid (GABA) against IRI in ovariectomized estradiol-treated rats. Thirty-five ovariectomized Wistar rats were used in six experimental groups. The first three groups did not subject to estradiol treatment and assigned as sham-operated, control, and GABA-treated groups. GABA (50 μmol/kg) and saline were injected in the treated and control groups 30 min before the surgery, respectively. The second three groups received the same treatments but received estradiol valerate (500 μg/kg, intramuscularly) 3 days prior to the surgery. The IRI was induced in the control and treated groups by clamping the renal artery for 45 min and then 24 h of reperfusion. All animals were sacrificed for the measurements. The serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score significantly increased in the IRI rats (P GABA significantly decreased the aforementioned parameters (P levels of nitrite (nitric oxide metabolite) did not alter significantly. Serum level of malondialdehyde increased significantly in the ovariectomized rats exposed to IRI (P GABA improved IRI in ovariectomized rats. Estradiol was also nephroprotective against IRI. However, co-administration of estradiol and GABA could not protect the kidney against IRI.

Hematological effects of inhaled plutonium dioxide in beagles

International Nuclear Information System (INIS)

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

1995-01-01

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

Subchronic feeding study of carnauba wax in beagle dogs.

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

1983-02-01

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

The Cooccurrence of Obesity, Osteoporosis, and Sarcopenia in the Ovariectomized Rat: A Study for Modeling Osteosarcopenic Obesity in Rodents.

Science.gov (United States)

Ezzat-Zadeh, Zahra; Kim, Jeong-Su; Chase, P Bryant; Arjmandi, Bahram H

2017-01-01

Obesity, osteoporosis, and sarcopenia may individually occur due to age-related gradual alterations in body composition. This study investigates the cooccurrence of these age-related diseases in female animals with low levels of ovarian hormone in the absence of complex multifactorial process of chronological aging. Thirty-six 5- and 10-month-old female rats were chosen to model pre- and postmenopausal women, respectively. Rats were divided into three treatment groups in each age category-sham, ovariectomized (ovx), and ovx + E 2 (17 β -estradiol, 10  μ g/kg)-and were pair-fed. Volunteer wheel running activity, body composition, bone microstructure, serum C-telopeptides of type I collagen, bone specific alkaline phosphatase, E 2 , and gastrocnemius and soleus muscles were analyzed. The cooccurrence of osteoporosis, sarcopenia, and obesity was observed in the older ovx rats associated with a significant ( p obesity and body composition translational research in females without the confounding effect of genetic background.

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

Energy Technology Data Exchange (ETDEWEB)

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

1969-11-15

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

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

Science.gov (United States)

Smith, Louis M.

1987-01-01

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

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

International Nuclear Information System (INIS)

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

1976-01-01

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

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

Directory of Open Access Journals (Sweden)

Maryam Safahani

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.

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

International Nuclear Information System (INIS)

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

1975-01-01

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

Dietary phosphorus exacerbates bone loss induced by cadmium in ovariectomized rats.

Science.gov (United States)

Bakhshalian, Neema; Johnson, Sarah A; Hooshmand, Shirin; Feresin, Rafaela G; Elam, Marcus L; Soung, Do Y; Payton, Mark E; Arjmandi, Bahram H

2014-12-01

Postmenopausal bone loss can be exacerbated by environmental contaminants, including the heavy metal cadmium (Cd). We hypothesized that incorporating phosphorus (P) into the diet would lead to the chelation of Cd into P, preventing its absorption and subsequent bone loss. To test this hypothesis, we used ovariectomized rats as a model of postmenopausal osteoporosis to examine the deleterious effects of Cd on bone with and without added P. Fifty 3-month-old ovariectomized Sprague-Dawley rats were assigned to five treatment groups (n = 10 per group) for 3 months as follows: (1) control; (2) 50 ppm Cd; (3) 50 ppm Cd plus 1.2% P; (4) 200 ppm Cd; and (5) 200 ppm Cd plus 1.2% P. Cd plus P caused a significant loss of whole body (P = 0.0001 and P properties, 50 ppm Cd plus 1.2% P caused an increase in trabecular separation, whereas 200 ppm Cd plus 1.2% P caused a decrease in bone volume-to-total volume ratio, a decrease in trabecular number, and an increase in trabecular separation and structural model index. Our findings indicate that Cd exposure, along with high intake of P, may be a public health hazard with respect to bone health.

The effects of honey (Apis dorsata) supplements on increased bone strength in ovariectomized rat as animal model of osteoporosis

Science.gov (United States)

Yudaniayanti, Ira Sari; Primarizky, Hardany; Nangoi, Lianny

2018-04-01

Osteoporosis is a chronic skeletal disease characterized by low bone mass and microarchitectural deterioration with a consequent increase in bone fragility and fracture risk. The aim of the study was to evaluate the effects of honey (Apis dorsata) supplements on increased bone strength in ovariectomized rat as animal models of osteoporosis. Twenty female rats at 3 months of age, weighing 150-200 g were used in the study. The rats were divided into five groups (n=4) : Sham operation group (SH); ovariectomy group no treatment(OVX); ovariectomy with treatment Apis dorsata 1g/Kg BW (AD-1); ovariectomy with treatment Apis dorsata 2g/Kg BW (AD-2); ovariectomy with treatment Apis dorsata 4g/Kg BW (AD-3). The treatment started to be given the next day after ovariectomy operation for 12 weeks. The Rats were sacrified within 12 weeks, and then the right femur were taken bone strength test. Based on the statistical analysis of the bone strength test, the greatest score belongs to the Sham operation group (SH) that have significant difference (p0,05). In conclusion, honey (Apis dorsata) supplements has the effect of increasing bone strength in ovariectomized rat as animal models of osteoporosis, so that honey (Apis dorsata) supplements has the potential to be used as an alternative treatment for osteoporosis.

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

Science.gov (United States)

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

2014-02-01

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

Skeletal lesions from inhaled plutonium in beagles

International Nuclear Information System (INIS)

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

1984-10-01

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

Relationships between bone strength and bone quality. Three-dimensional imaging analysis in ovariectomized mice

International Nuclear Information System (INIS)

Wakabayashi, Suguru; Sakurai, Takashi; Kashima, Isamu

2004-01-01

Low-energy trauma resulting in fractures of the distal femur is often observed in elderly patients with osteoporosis; such fractures are often associated with treatment difficulties and poor prognosis. The purpose of this study was to clarify the factors that affect the bone strength of the distal femur. We used ovariectomized mice to demonstrate bone quality factors associated with deterioration of the strength of the distal femur. Ten-week old ICR-strain mice were ovariectomized or sham-ovariectomized. Total bone mineral density (BMD), total bone area, cortical BMD, cortical thickness, and trabecular BMD were measured by peripheral quantitative computed tomography in the distal metaphyseal region of the femora. As three-dimensional architectural parameters, the trabecular number, trabecular thickness (Tb.Th), trabecular separation, and connectivity density were measured in the same region by micro-computed tomography. The maximum load measured by compression testing of the distal metaphyseal region was regarded as the bone strength of each sample. No significant differences in total bone area or in cortical BMD were found between the groups. Bone strength showed the closest relationship with total BMD (r=0.834). Multiple regression analysis demonstrated that total BMD greatly depended on cortical thickness. The addition of Tb.Th to trabecular BMD markedly reflected bone strength (R=0.857), suggesting that Tb.Th affected bone strength more significantly than trabecular BMD. These findings suggested that deterioration of bone strength of the distal femur (metaphysis) was not caused by a reduction in cortical BMD, but was related to reduced cortical thickness, which reduced total BMD, and to trabecular BMD and architecture, in particular to reduced Tb.Th. (author)

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

Science.gov (United States)

Zeng, Ruixia; Zhang, Yibo; Du, Peng

2014-01-01

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

The influence of age at time of exposure to 226Ra or 239Pu on distribution, retention, postinjection survival, and tumor induction in beagle dogs

International Nuclear Information System (INIS)

Bruenger, F.W.; Lloyd, R.D.; Miller, S.C.

1991-01-01

The influence of age at injection of 226Ra or 239Pu on skeletal deposition and local distribution, the pattern of bone tumor formation, and postinjection survival was assessed in parallel short-term studies of mechanisms and lifetime toxicity. Beagles received a single intravenous injection of 226Ra or 239Pu at 3 months (juveniles), 17-19 months (young adults) or 60 months (mature). Data from short-term studies of mechanisms and dosimetry and from one dosage level of each of the toxicity experiments were compared. Skeletal growth and turnover produced differential initial deposition and distribution patterns typical for each age group. At 1 week after injection, skeletal retention of 226Ra or 239Pu was 68 and 68%, respectively, in the juveniles, 32 and 46% in the young adults, and 31 and 43% in the mature dogs. Comparing individual bones in the juveniles, gradients in the concentration of 239Pu were small since all bones were actively growing, but substantial gradients, corresponding to centers of ossification, were present within individual bones. In other age groups, local concentration gradients were less pronounced, but much larger differences were present among the various bones. In the toxicity study all animals injected with either 41 kBq 226Ra/kg or 11 kBq 239Pu/kg have died. The cumulative average skeletal doses to the presumed time of start of tumor growth (1 year before death) were 25 and 4 Gy, respectively, for the juveniles, 22 and 5 Gy for the young adults, and 15 and 4 Gy for the mature dogs. The highest bone tumor incidence was seen in the young adult groups. Differences were observed in location of bone tumors between dogs in the same age group given radium or plutonium and among age groups injected with either radionuclide, some of which could be explained by differences in local dose distributions

SERUM CONCENTRATIONS OF MATRIX METALLOPROTEINASE-9, -13 AND TIMP-1 IN AN OVARIECTOMIZED WISTAR RAT MODEL OF OSTEOPOROSIS

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Armine V. Grigoryan

2017-12-01

Full Text Available Introduction. Osteoporosis is a disease characterized by decreased bone density and destruction of the microarchitectonics of the bone structure. This leads to increased bone fragility and risk of fracture, particularly of the hip, spine, wrist and shoulder. Osteoporosis is known as „The Silent Epidemic of the Century“ because bone loss occurs without symptoms. An altered ovarian function is one of the most common causes of osteoporosis. Indicators for altered bone homeostasis are the changes in serum levels of matrix metalloproteinases (MMPs and their tissue inhibitors (TIMPs. Objective. The aim of current study was to determine the activity of alkaline phosphatase (ALP and serum concentrations of MMP-9, MMP-13 and TIMP-1 in the ovariectomized rats. Materials and Methods. An experiment was performed on 35 female Wistar rats at reproductive age – 2 months divided into 2 groups: group 1 (G1-20 animals were sham-operated (sham and group 2 (G2-15 were ovariectomized (ovx. Results. The concentrations of ALP, MMP-9, MMP-13 and TIMP-1 in G2 were significantly increased compared to G1 (p<0.05. Conclusion. Our study confirmed that the serum activity of ALP, which is a marker of bone formation, was elevated in rats with OVX-induced osteoporosis. Although the level of TIMP-1 is increased, the level of MMP 9 in G2 is also increased, that confirms the thesis that MMP-9 may be a marker for osteoclast activity.

Tetracycline treatment of periodontal disease in the beagle dog

Energy Technology Data Exchange (ETDEWEB)

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

1982-01-01

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

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

Science.gov (United States)

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

2013-11-01

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

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

International Nuclear Information System (INIS)

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

1982-01-01

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

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

International Nuclear Information System (INIS)

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

1979-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1983-01-01

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

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Brenda Lía Doti

2005-12-01

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

Myelopoiesis in whole-body-irradiated beagles

International Nuclear Information System (INIS)

Stevenson, A.F.G.

1985-01-01

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

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

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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.

Pulmonary lesions induced by inhaled plutonium in beagles

International Nuclear Information System (INIS)

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

1975-01-01

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

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.

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

International Nuclear Information System (INIS)

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

1985-01-01

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

Evaluation of fixation of expandable implants in the mandibles of ovariectomized sheep.

Science.gov (United States)

Xiao, Jian-Rui; Li, De-Hua; Chen, Yu-Xuan; Chen, Shu-Jun; Guan, Su-Min; Kong, Liang

2013-04-01

This study aimed to investigate the effects of an expandable implant (EI) in ovariectomized sheep. The EI and taper implant (control group) were produced and placed in mandibles of ovariectomized sheep. Twelve weeks after implantation, resonance frequency analysis, biomechanical tests, histomorphometry, and micro-computed tomography were applied to detect the osseointegration in the 2 groups. The implant stability quotient values, maximal pullout forces, and bone-implant contact (BIC) were 60.3 ± 7.9, 511.0 ± 18.7 N, and 53.14% ± 4.56%, respectively, in the EI group and 58.3 ± 8.9, 394.5 ± 54.5 N, and 46.85% ± 5.04%, respectively, in the control group. There was no significant difference between the 2 groups in implant stability quotient values (P > .05); however, in the EI group the maximal pullout force and BIC were increased significantly (P bone volume/total volume ratio and trabecular number increased significantly (P < .01) and trabecular separation decreased significantly (P < .05) in the EI group. EI could improve osseointegration in osteoporosis after 12 weeks of implantation by increasing BIC around the implant and by supplying an extra osseointegration surface. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

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

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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.

Toxicity of inhaled 239PuO2 in immature Beagle dogs. VII

International Nuclear Information System (INIS)

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

1985-01-01

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

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

Science.gov (United States)

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

2012-01-01

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

Comparative element analysis on femur of antler hemo-treated ovariectomized wistar rats by SRXRF

International Nuclear Information System (INIS)

Yang Jianhong; Fei Yurong; Wang Ruilin; Cao Yi; Huang Yuying; He Wei

2007-01-01

To investigate the relationship between bone element contents and bone m/neral density (BMD), left femur of sham-operated rats (SHAM, n=5), ovariectomized rats (OVX, n=5) and antler hemo-treated ovariectomized rats (OVX + antler hemo, n=5) were analyzed by synchrotron radiation X-ray fluorescence (SRXRF) microprobe. The results showed that there were very good positive correlations among contents of Ca, P, Zn and Sr. In comparison to the SHAM group, decreased relative intensities of Ca, P, Zn and Sr (especially Ca and P, p<0.05) were observed in femur of the OVX group, which showed significant decrease (p<0.05) of the BMD. The results indicate that loss of Ca and P in bone will cause osteoporosis. On the other hand, increased relative intensities of Ca, P and Zn in femur, and the BMD (p<0.05), of the anlter hemo-treated OVX group were found, in comparison to the OVX group. This suggests that anlter hemo may help cure osteoporosis through maintaining bone contents of Zn, Ca and P, and increasing the BMD. (authors)

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

International Nuclear Information System (INIS)

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

2004-01-01

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

High-intensity interval training beneficial effects on body mass, blood pressure, and oxidative stress in diet-induced obesity in ovariectomized mice.

Science.gov (United States)

Pimenta, Marcel; Bringhenti, Isabele; Souza-Mello, Vanessa; Dos Santos Mendes, Iara Karise; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A

2015-10-15

To investigate the possible beneficial effect of high-intensity interval training (HIIT) on skeletal muscle oxidative stress, body mass (BM) and systolic blood pressure (SBP) in ovariectomized mice fed or not fed a high-fat diet. Three-month-old female C57BL/6 mice were bilaterally ovariectomized (OVX group) or submitted to surgical stress without ovariectomy (SHAM group) and separated into standard chow (SHAM-SC; OVX-SC) and high-fat diet (SHAM-HF; OVX-HF) groups. After 13 weeks, an HIIT program (swimming) was carried out for 8 weeks in non-trained (NT) and trained (T) groups. The significant reduction of uterine mass and the cytological examination of vaginal smears in the OVX group confirmed that ovariectomy was successful. Before the HIIT protocol, the ovariectomized groups showed a greater BM than the SHAM group, irrespective of the diet they received. The HIIT minimized BM gain in animals fed an HF diet and/or ovariectomized. SBP and total cholesterol were increased in the OVX and HF animals compared to their counterparts, and the HIIT efficiently reduced these factors. In the HF and OVX mice, the muscular superoxide dismutase and catalase levels were low while their glutathione peroxidase and glutathione reductase levels were high and the HIIT normalized these parameters. Diet-induced obesity maximizes the deleterious effects of an ovariectomy. The HIIT protocol significantly reduced BM, SBP and oxidative stress in the skeletal muscle indicating that HIIT diminishes the cardiovascular and metabolic risk that is inherent to obesity and menopause. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of Social Housing on Hippocampal Dendrites and Behavior in Ovariectomized Rats

OpenAIRE

Leedy, Gail M.; Burrows, Lorraine F.; Clark, Suzanne

2012-01-01

Social stress is both species and gender specific. For female rats, individual housing and social instability housing conditions are associated with behavioral indicators of stress and depression. The present study directly compared the effects of six weeks of individual housing, social instability and mixed sex, semi-crowded housing in a visible burrow system (VBS) on ovariectomized female rats. Paired, stable housing was used as the control. Behavioral tests were conducted two, four and six...

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.

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

International Nuclear Information System (INIS)

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

1988-01-01

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

Effects of high-intensity swimming training on the bones of ovariectomized rats

OpenAIRE

Oh, Taewoong; Tanaka, Sakura; Naka, Tatsuki; Igawa, Shoji

2016-01-01

[Purpose] This study was performed to assess the effects of high-intensity intermittent swimming training(HIT) on bone in ovariectomized rats. [Methods] Six-week-old female Sprague-Dawley rats were randomly assigned to either sham operation or bilateral ovariectomy. After surgery, they were divided into the following four groups: 1) sham-operated sedentary (S), 2) sham-operated exercise training (SE), 3) OVX sedentary (O), 4) OVX exercise training (OE) 5) OVX given 17?-estradiol (OE2) and 6) ...

Pulmonary lesions induced by inhaled plutonium in beagles

International Nuclear Information System (INIS)

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

1976-01-01

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

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

International Nuclear Information System (INIS)

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

1986-01-01

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

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1990-12-31

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

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.

Favorable effect of moderate dose caffeine on the skeletal system in ovariectomized rats.

Science.gov (United States)

Folwarczna, Joanna; Pytlik, Maria; Zych, Maria; Cegieła, Urszula; Kaczmarczyk-Sedlak, Ilona; Nowińska, Barbara; Sliwiński, Leszek

2013-10-01

Caffeine, a methylxanthine present in coffee, has been postulated to be responsible for an increased risk of osteoporosis in coffee drinkers; however, the data are inconsistent. The aim of the present study was to investigate the effects of a moderate dose of caffeine on the skeletal system of rats with normal and decreased estrogen level (developing osteoporosis due to estrogen deficiency). The experiments were carried out on mature nonovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving caffeine once daily, 20 mg/kg p.o., for 4 wk. Serum bone turnover markers, bone mass, mass of bone mineral, calcium and phosphorus content, histomorphometric parameters, and bone mechanical properties were examined. Caffeine favorably affected the skeletal system of ovariectomized rats, slightly inhibiting the development of bone changes induced by estrogen deficiency (increasing bone mineralization, and improving the strength and structure of cancellous bone). Moreover, it favorably affected mechanical properties of compact bone. There were no significant effects of caffeine in rats with normal estrogen levels. In conclusion, results of the present study indicate that low-to-moderate caffeine intake may exert some beneficial effects on the skeletal system of mature organisms. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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

Science.gov (United States)

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

2012-06-20

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

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice.

Science.gov (United States)

Han, Tae-Kyung; Lee, Jang-Kyu; Leem, Yea-Hyun

2015-06-01

We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

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

International Nuclear Information System (INIS)

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

1974-01-01

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

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.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Excessive Vitamin E Intake Does Not Cause Bone Loss in Male or Ovariectomized Female Mice Fed Normal or High-Fat Diets.

Science.gov (United States)

Ikegami, Hiroko; Kawawa, Rie; Ichi, Ikuyo; Ishikawa, Tomoko; Koike, Taisuke; Aoki, Yoshinori; Fujiwara, Yoko

2017-10-01

Background: Animal studies on the effects of vitamin E on bone health have yielded conflicting and inconclusive results, and to our knowledge, no studies have addressed the effect of vitamin E on bone in animals consuming a high-fat diet (HFD). Objective: This study aimed to evaluate the effect of excessive vitamin E on bone metabolism in normal male mice and ovariectomized female mice fed a normal diet (ND) or HFD. Methods: In the first 2 experiments, 7-wk-old male mice were fed an ND (16% energy from fat) containing 75 (control), 0 (vitamin E-free), or 1000 (high vitamin E) mg vitamin E/kg (experiment 1) or an HFD (46% energy from fat) containing 0, 200, 500, or 1000 mg vitamin E/kg (experiment 2) for 18 wk. In the third experiment, 7-wk-old sham-operated or ovariectomized female mice were fed the ND (75 mg vitamin E/kg) or HFD containing 0 or 1000 mg vitamin E/kg for 8 wk. At the end of the feeding period, blood and femurs were collected to measure bone turnover markers and analyze histology and microcomputed tomography. Results: In experiments 1 and 2, vitamin E intake had no effect on plasma alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activity, or bone formation, resorption, or volume in femurs in mice fed the ND or HFDs. In experiment 3, bone volume was significantly reduced (85%) in ovariectomized mice compared with that in sham-operated mice ( P vitamin E/kg. Conclusions: The results suggest that excess vitamin E intake does not cause bone loss in normal male mice or in ovariectomized or sham-operated female mice, regardless of dietary fat content. © 2017 American Society for Nutrition.

Estrogen receptor-immunoreactive neurons in the lumbosacral cord projecting to the periaqueductal gray in the ovariectomized female cat

NARCIS (Netherlands)

VanderHorst, Veronique G.J.M.; Meijer, Ellie; Schasfoor, Fabienne C.; Leeuwen, Fred W. van; Holstege, Gert

1997-01-01

The periaqueductal gray (FAG) plays a crucial role in reproductive behavior. The present study investigates whether lumbosacral FAG-projecting neurons contain estrogen receptors. In four ovariectomized adult female cats, injections with cholera toxin subunit (CTb) were made into the FAG to

Determination of rat vertebral bone compressive fatigue properties in untreated intact rats and zoledronic-acid-treated, ovariectomized rats

NARCIS (Netherlands)

Brouwers, J.E.M.; Ruchselman, M.; Rietbergen, van B.; Bouxsein, M.L.

2009-01-01

Summary Compressive fatigue properties of whole vertebrae, which may be clinically relevant for osteoporotic vertebral fractures, were determined in untreated, intact rats and zoledronic-acid-treated, ovariectomized rats. Typical fatigue behavior was found and was similar to that seen in other

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

Science.gov (United States)

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

1980-09-01

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

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.

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

International Nuclear Information System (INIS)

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

1980-01-01

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

Glabridin and glycyrrhizic acid show no beneficial effect on the chemical composition and mechanical properties of bones in ovariectomized rats, when administered in moderate dose.

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

2016-10-01

One of the major causes of osteoporosis and bone fracture in postmenopausal women is estrogen deficiency. To prevent the fractures, and avoid the side effects of hormone replacement therapy, phytoestrogens including the isoflavonoids are used. In the presented study two constituents occurring in the licorice root-the isoflavane glabridin and triterpenoid saponin glycyrrhizic acid were examined on the skeletal system of ovariectomized rats. The female Wistar rats were divided into five groups: control group, ovariectomized group as well as three ovariectomized groups treated with estradiol (0.2mg/kg), glabridin (5mg/kg) or glycyrrhizic acid (15mg/kg). All substances were administered orally for 4 weeks. The estradiol served as a positive control. The mechanical properties of femoral diaphysis, tibial metaphysis and femoral neck were assessed using bending and compression tests. Moreover the chemical composition of the femur, tibia and L-4 vertebra - content of water, organic substances and minerals - was determined. Ovariectomy induced unfavorable changes in the skeletal system of the rats. Administration of glabridin and glycyrrhizic acid to the ovariectomized rats did not improve analyzed parameters of the bones. Obtained results indicate, that the tested substances revealed no beneficial effect on the mechanical properties and chemical composition of the tested bones, thus they cannot be used as the osteoporosis protective agents. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Low-intensity aerobic exercise training: inhibition of skeletal muscle atrophy in high-fat-diet-induced ovariectomized rats.

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Kim, Hye Jin; Lee, Won Jun

2017-09-30

Postmenopausal women are highly susceptible to diseases, such as obesity, type 2 diabetes, osteoporosis, or skeletal muscle atrophy and many people recognize the need for regular physical activity. Aerobic exercise training is known to improve the oxidative capacity and insulin sensitivity of skeletal muscles. This study aimed to investigate the role of low-intensity aerobic exercise training on skeletal muscle protein degradation or synthesis in the plantaris muscles of high-fat-fed ovariectomized rats. Ovariectomized female rats were divided into two groups: a high-fat diet-sedentary group (HFD), and a high-fat diet-aerobic exercise group (HFD+EX). The exercise group exercised aerobically on a treadmill 5 days/week for 8 weeks. The rats progressively ran 30 min/day at 15 m/min, up to 40 min/day at 18 m/min, 0% slope, in the last 4 weeks. Although aerobic exercise led to significantly increased AMP-activated protein kinase (AMPK) phosphorylation at Thr172, phosphorylation of the mammalian target of rapamycin (mTOR) substrate Thr389 S6K1 level did not decrease. Additionally, even though Akt activity did not increase at Ser473, the atrogin-1 level significantly decreased in the exercise group compared to the non-exercise group. Immunohistochemical staining revealed that high-fat-induced TSC2 protein expression was eliminated in response to aerobic exercise. These results suggest that aerobic exercise can inhibit skeletal muscle protein degradation, but it cannot increase protein synthesis in the plantaris muscle of high-fat-fed ovariectomized rats. Our findings have implications in understanding skeletal muscle mass maintenance with low intensity aerobic exercise in post-menopausal women. ©2017 The Korean Society for Exercise Nutrition

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

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Jue Zhou

2011-01-01

Full Text Available 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 hot flashes and side effects of the treatment felt daily, from 1 week before the treatment started to the fourth week after the treatment ended. The serum levels of follicle stimulating hormone (FSH, LH and E2 were detected before and after the treatment. After the treatment and the follow-up, both the severity and frequency of hot flashes in the two groups were relieved significantly when compared with pre-treatment (P   .05, while after the follow-up, the severity of hot flashes in the HRT group was alleviated more. After the treatment and the follow-up, the frequency of menopausal hot flashes in the HRT group was reduced more (P <  .05. After treatment, the levels of FSH decreased significantly and the levels of E2 increased significantly in both groups (P <  .05, and they changed more in the HRT group (P <  .05. Acupuncture and auricular acupressure can be used as alternative treatments to relieve menopausal hot flashes for those bilaterally ovariectomized women who are unable or unwilling to receive HRT.

The Effect of Methanolic Soy Extract on Heart Tissue Changes in Ovariectomized Rats

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Mohammad Reza Nasirzadeh

2012-04-01

Full Text Available Background & Objectives: Following to estrogen depletion in postmenopausal womens, its cardioprotective effect decreases. Stroke usually occurs in women during the menopause years. Estrogen hormone therapy is still controversial. Epidemiological data suggest that phytoestrogens have a preventive effect on various estrogen-related diseases/symptoms such as menopausal symptoms, cardiovascular diseases. Some studies suggest that genistein as an important component of soy have cardioprotection effects but its role on inflammation and cardiomyocte injury remained to be elucidated. So, this study was goaled to investigate the cardioprotective effect of methanolic soy extract on heart tissue injures.   Method: In this study 40 female rats were randomly allocated into 4 groups: 1 Control (intact animals, 2 sham surgery (without ovarictomy, 3 ovariectomized (ovx, and 4 treatment (ovx and soy gavage group that received 60mg/kg per day soy extract in drinking water for 28days (4 weeks. At the end of experiments, the rat heart tissue was processed histologically and the sections were stained with hematoxylin and eosin to examine under light microscope. Statistical analysis was performed using the wilcoxon test.   Results: The results showed that ovariectomy significantly increased inflammation and cardiomyocte injury and soy extract significantly promoted heart tissue recovery (p<0.05.   Conclosions: This study indicated that oral administration of soy extract has a positive effect on attenuation of inflammation and myocyte injury in ovariectomized rat.

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

International Nuclear Information System (INIS)

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

1985-01-01

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

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

International Nuclear Information System (INIS)

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

1976-01-01

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

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

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

2013-09-01

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

Modulatory effects of caffeine on oxidative stress and anxiety-like behavior in ovariectomized rats.

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Caravan, Ionut; Sevastre Berghian, Alexandra; Moldovan, Remus; Decea, Nicoleta; Orasan, Remus; Filip, Gabriela Adriana

2016-09-01

Menopause is accompanied by enhanced oxidative stress and behavioral changes, effects attenuated by antioxidants. The aim of this study was to evaluate the effects of caffeine on behavior and oxidative stress in an experimental model of menopause. Female rats were divided into the following groups: sham-operated (CON), sham-operated and caffeine-treated (CAF), ovariectomized (OVX), ovariectomized and caffeine-treated (OVX+CAF). Caffeine (6 mg/kg) and vehicle were administered for 21 days (subchronic) and 42 days (chronic), using 2 experimental subsets. Behavioral tests and oxidative stress parameters in the blood, whole brain, and hippocampus were assessed. The subchronic administration of caffeine decreased the lipid peroxidation and improved the antioxidant defense in the blood and brain. The GSH/GGSG ratio in the brain was improved by chronic administration, with reduced activities of antioxidant enzymes and enhanced nitric oxide and malondialdehyde levels. In particular, the lipid peroxidation in the hippocampus decreased in both experiments. The rats became hyperactive after 21 days of treatment, but no effect was observed after chronic administration. In both experimental subsets, caffeine had anxiolytic effects as tested in elevated plus maze. The administration of low doses of caffeine, for a short period of time, may be a new therapeutic approach to modulating the oxidative stress and anxiety in menopause.

Lymphocytopenia induced in beagle dogs by inhalation of 239PuO2

International Nuclear Information System (INIS)

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

1976-01-01

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

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

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

2011-10-01

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

Evaluation of nanoparticle delivered cisplatin in beagles

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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

Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats.

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Fabricio, Victor; Oishi, Jorge Camargo; Biffe, Bruna Gabriele; Ruffoni, Leandro Dias Gonçalves; Silva, Karina Ana da; Nonaka, Keico Okino; Rodrigues, Gerson Jhonatan

2017-02-01

Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats. Apesar de se saber que o resveratrol apresenta efeitos sobre a pressão arterial e os vasos sanguíneos, e que os fitoestrógenos podem melhorar o relaxamento/vasodilatação dependente do endotélio, não há relatos do efeito direto do resveratrol sobre a pressão arterial e a função endotelial em animais com deficiência de estrógeno (mimetizando a pressão arterial aumentada pós-menopausa). Verificar o efeito de dois diferentes períodos de tratamento preventivo com resveratrol sobre a

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

Energy Technology Data Exchange (ETDEWEB)

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

1988-12-01

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

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

OpenAIRE

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

2006-01-01

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

Flemingia macrophylla Extract Ameliorates Experimental Osteoporosis in Ovariectomized Rats

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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.

Vitex Agnus Castus Extract Improves Learning and Memory and Increases the Transcription of Estrogen Receptor α in Hippocampus of Ovariectomized Rats.

Science.gov (United States)

Allahtavakoli, Mohammad; Honari, Najmeh; Pourabolli, Iran; Kazemi Arababadi, Mohammad; Ghafarian, Hossein; Roohbakhsh, Ali; Esmaeili Nadimi, Ali; Shamsizadeh, Ali

2015-07-01

Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormone-dependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline. 24 female Wistar rats weighing 180-220 g were used in this study. The animals were ovariectomized and randomly divided into four groups including, control and two groups which received 8 and 80 mg/kg Vitex agnus castus (VAC) ethanolic extract orally. The last groups were treated with 40 μg/kg of estradiol valerat. Step-through passive avoidance (STPA) test was used for the evaluation of learning and memory. The hippocampal estrogen receptor α (ERα) expression was measured using Real-Time PCR. The results demonstrated that VAC extract or estradiol had better performance on step-through passive avoidance test than control group (all P<0.05). Moreover, administration of either estradiol or VAC extract increased the hippocampal mRNA level of ERα and prevented the decrease in uterine weight of ovariectomized rats. Based on our data, VAC extract improves learning and memory in ovariectomized rats. The positive effect of VAC extract on learning and memory is possibly associated with an increase in ERα gene expression in the hippocampal formation.

Effects of dihydrotestosterone administration on the expression of reproductive and body weight regulatory factors in ovariectomized and estradiol-treated female rats.

Science.gov (United States)

Iwasa, Takeshi; Matsuzaki, Toshiya; Yano, Kiyohito; Mayila, Yiliyasi; Irahara, Minoru

2018-01-01

To clarify the direct effects of androgens, the changes in the hypothalamic levels of reproductive and appetite regulatory factors induced by chronic dihydrotestosterone (DHT) administration were evaluated in female rats. DHT treatment increased the BW and food intake of the ovariectomized rats, but not the estradiol (E2)-treated rats. DHT administration suppressed the expression of a hypothalamic anorexigenic factor. Although the kisspeptin (Kiss1) mRNA levels of the anterior hypothalamic block (the anteroventral periventricular nucleus, AVPV) were increased in the E2-treated rats, DHT administration did not affect the Kiss1 mRNA levels of the AVPV in the ovariectomized or E2-treated rats. Conversely, DHT administration reduced the Kiss1 mRNA levels of the posterior hypothalamic block (the arcuate nucleus, ARC) in the ovariectomized rats. Although the Kiss1 mRNA levels of the posterior hypothalamic block (ARC) were decreased in the E2-treated rats, DHT administration did not affect the Kiss1 mRNA levels of the ARC in these rats. Serum luteinizing hormone levels of these groups exhibited similar patterns to the Kiss1 mRNA levels of the ARC. These results showed that DHT affects the production of hypothalamic reproductive and appetite regulatory factors, and that these effects of DHT differ according to the estrogen milieu.

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

Science.gov (United States)

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

2015-12-01

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

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

OpenAIRE

Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

2015-01-01

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

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

International Nuclear Information System (INIS)

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

1986-01-01

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

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

International Nuclear Information System (INIS)

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

1994-01-01

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

Influence of ferutinin on bone metabolism in ovariectomized rats. II: Role in recovering osteoporosis

Science.gov (United States)

Ferretti, Marzia; Bertoni, Laura; Cavani, Francesco; Zavatti, Manuela; Resca, Elisa; Carnevale, Gianluca; Benelli, Augusta; Zanoli, Paola; Palumbo, Carla

2010-01-01

The aim of the present investigation, which represents an extension of a previous study, was to investigate the effect of ferutinin in recovering severe osteoporosis due to estrogen deficiency after rat ovariectomy and to compare phytoestrogen effects with those of estrogens commonly used in hormone replacement therapy (HRT) by women with postmenopausal osteoporosis. The animal model used was the Sprague–Dawley ovariectomized rat. Ferutinin was orally administered (2 mg kg−1 per day) for 30 or 60 days starting from 2 months after ovariectomy (i.e. when osteoporosis was clearly evident) and its effects were compared with those of estradiol benzoate (1.5 μg per rat twice a week, subcutaneously injected) vs. vehicle-treated ovariectomized (OVX) and sham-operated (SHAM) rats. Histomorphometric analyses were performed on trabecular bone of lumbar vertebrae (4th and 5th) and distal femoral epiphysis, as well as on cortical bone of femoral diaphysis. Bone histomorphometric analyses showed that ferutinin seems to display the same effects on bone mass recorded with estradiol benzoate, thus suggesting that it could enhance the recovery of bone loss due to severe estrogen deficiency in OVX rats. On this basis, the authors propose listing ferutinin among the substances representing a potential alternative for the treatment of postmenopausal osteoporosis, which occurs as a result of estrogen deficiency. PMID:20492429

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

International Nuclear Information System (INIS)

Cardinali, D.P.; Fernandez Pardal, J.; Gimeno, M.F.; Gimeno, A.L.

1982-01-01

The spontaneous and K + -stimulated efflux of norepinephrine (NE) and the release of PGE 2 and PGF 2 α 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 3 H-overflow of MBH slices preloaded with 3 H-NE at morning hours (1000 hours). Estradiol treatment did not result in further increase of K + -induced 3 H 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. PGE 2 efflux was time-dependent being highest at the evening in both vehicle- and estradiol-treated animals. The MBH of estrogenized rats released significantly more PGE 2 at the evening as compared to the controls. The release of PGF 2 α 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)

A Novel Self-Expandable, Radioactive Airway Stent Loaded with 125I Seeds: A Feasibility and Safety Study in Healthy Beagle Dog.

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Wang, Yong; Guo, Jin-He; Zhu, Guang-Yu; Zhu, Hai-Dong; Chen, Li; Lu, Jian; Wang, Chao; Teng, Gao-Jun

2017-07-01

Airway stent placement is an effective treatment for the immediate palliation of malignant airway obstruction. However, restenosis caused by tumor ingrowth and/or overgrowth after stenting is common. The purpose of this study was to investigate the feasibility and safety of a novel self-expandable stent loaded with 125 I seeds in healthy beagle dog. Under fluoroscopic guidance, forty-eight self-expandable airway stents loaded with 125 I seeds were perorally placed in the main trachea of 48 healthy beagle dogs, who were randomly divided into four groups (Group A: 0.3 mCi; Group B: 0.6 mCi; Group C: 0.9 mCi; Control group: 0 mCi). The estimated radiation dose was calculated using the isotropic point source approximation. Radiological follow-up examinations and histopathological examinations of stented tracheal segments and their adjacent organs and tissues were performed at 2, 4, 8, and 16 weeks following the stenting. All stents were successfully deployed in the targeted tracheal segment in the beagle dogs without procedure-related complications. Tracheal stenosis became severe gradually in all the four groups, which was not associated with the radioactivity of 125 I seeds (p > 0.05). The tracheal injury scores increased along with the higher dose of radioactive seeds which reached peak at 8 weeks and then turned back slightly at 16 weeks. The adjacent tissue did not show pathohistological changes under microscope, while mild and reversible ultrastructure changes were showed under electronic microscope. This study demonstrates that it is feasible and safe to insert this novel self-expandable airway stent loaded with 125 I seeds in healthy beagle dog.

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

International Nuclear Information System (INIS)

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

1985-01-01

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

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Therapeutic Effect of Cistanoside A on Bone Metabolism of Ovariectomized Mice

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Xiaoxue Xu

2017-01-01

Full Text Available Cistanoside A (Cis A, an active phenylethanoid glycoside isolated from Cistanche deserticola Y. C. Ma, has received our attention because of its possible role in the treatment of osteoporosis. In the present study, we evaluated the effects of Cis A on an ovariectomized (OVX mice model and investigated its underlying molecular mechanisms of action. After 12 weeks of orally-administrated intervention, Cis A (20, 40 and 80 mg/kg body weight/day exhibited significant antiosteoporotic effects on OVX mice, evidenced by enhanced bone strength, bone mineral density and improved trabecular bone microarchitecture. Meanwhile, the activities of bone resorption markers, including tartrate-resistant acid phosphatase (TRAP, deoxypyridinoline (DPD and cathepsin K, were decreased, and the bioactivity of bone formation marker alkaline phosphatase (ALP was increased. Mechanistically, Cis A inhibited the expression of TNF-receptor associated factor 6 (TRAF6, an upstream molecule that is shared by both nuclear factor kappa-light chain enhancer of activated B cells (NF-κB and phosphatidylinositol 3-kinase (PI3K/Akt pathways and subsequently suppressed the levels of receptor activators of nuclear factor kappaB ligand (RANKL, downregulated the expression of NF-κB and upregulated osteoprotegerin (OPG, PI3K and Akt, which means Cis A possessed antiosteoporotic activity in ovariectomized mice via TRAF6-mediated NF-kappaB inactivation and PI3K/Akt activation. Put together, we present novel findings that Cis A, by downregulating TRAF6, coordinates the inhibition of NF-κB and stimulation of PI3K/Akt pathways to promote bone formation and prevent bone resorption. These data demonstrated the potential of Cis A as a promising agent for the treatment of osteoporosis disease.

Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress

Science.gov (United States)

Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2016-01-01

Objective The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Methods Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Results Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=−0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=−0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=−0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction

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

Science.gov (United States)

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

2015-11-06

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Science.gov (United States)

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

2016-10-18

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

Development of tissue-engineered self-expandable aortic stent grafts (Bio stent grafts) using in-body tissue architecture technology in beagles.

Science.gov (United States)

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

2015-02-01

In this study, we aimed to describe the development of tissue-engineered self-expandable aortic stent grafts (Bio stent graft) using in-body tissue architecture technology in beagles and to determine its mechanical and histological properties. The preparation mold was assembled by insertion of an acryl rod (outer diameter, 8.6 mm; length, 40 mm) into a self-expanding nitinol stent (internal diameter, 9.0 mm; length, 35 mm). The molds (n = 6) were embedded into the subcutaneous pouches of three beagles for 4 weeks. After harvesting and removing each rod, the excessive fragile tissue connected around the molds was trimmed, and thus tubular autologous connective tissues with the stent were obtained for use as Bio stent grafts (outer diameter, approximately 9.3 mm in all molds). The stent strut was completely surrounded by the dense collagenous membrane (thickness, ∼150 µm). The Bio stent graft luminal surface was extremely flat and smooth. The graft wall of the Bio stent graft possessed an elastic modulus that was almost two times higher than that of the native beagle abdominal aorta. This Bio stent graft is expected to exhibit excellent biocompatibility after being implanted in the aorta, which may reduce the risk of type 1 endoleaks or migration. © 2014 Wiley Periodicals, Inc.

The effects of orbital spaceflight on bone histomorphometry and messenger ribonucleic acid levels for bone matrix proteins and skeletal signaling peptides in ovariectomized growing rats

Science.gov (United States)

Cavolina, J. M.; Evans, G. L.; Harris, S. A.; Zhang, M.; Westerlind, K. C.; Turner, R. T.

1997-01-01

A 14-day orbital spaceflight was performed using ovariectomized Fisher 344 rats to determine the combined effects of estrogen deficiency and near weightlessness on tibia radial bone growth and cancellous bone turnover. Twelve ovariectomized rats with established cancellous osteopenia were flown aboard the space shuttle Columbia (STS-62). Thirty ovariectomized rats were housed on earth as ground controls: 12 in animal enclosure modules, 12 in vivarium cages, and 6 killed the day of launch for baseline measurements. An additional 18 ovary-intact rats were housed in vivarium cages as ground controls: 8 rats were killed as baseline controls and the remaining 10 rats were killed 14 days later. Ovariectomy increased periosteal bone formation at the tibia-fibula synostosis; cancellous bone resorption and formation in the secondary spongiosa of the proximal tibial metaphysis; and messenger RNA (mRNA) levels for the prepro-alpha2(1) subunit of type 1 collagen, osteocalcin, transforming growth factor-beta, and insulin-like growth factor I in the contralateral proximal tibial metaphysis and for the collagen subunit in periosteum pooled from tibiae and femora and decreased cancellous bone area. Compared to ovariectomized weight-bearing rats, the flight group experienced decreases in periosteal bone formation, collagen subunit mRNA levels, and cancellous bone area. The flight rats had a small decrease in the cancellous mineral apposition rate, but no change in the calculated bone formation rate. Also, spaceflight had no effect on cancellous osteoblast and osteoclast perimeters or on mRNA levels for bone matrix proteins and signaling peptides. On the other hand, spaceflight resulted in an increase in bone resorption, as ascertained from the diminished retention of a preflight fluorochrome label. This latter finding suggests that osteoclast activity was increased. In a follow-up ground-based experiment, unilateral sciatic neurotomy of ovariectomized rats resulted in cancellous

Pathology associated with inhaled plutonium in beagles

International Nuclear Information System (INIS)

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

1986-01-01

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

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

International Nuclear Information System (INIS)

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

1979-01-01

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

Toxicity of injected 137CsCl in Beagle dogs. XVI

International Nuclear Information System (INIS)

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

1983-01-01

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

Toxicity of injected 137CsCl in Beagle dogs. XVIII

International Nuclear Information System (INIS)

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

1984-01-01

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

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

International Nuclear Information System (INIS)

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

1978-01-01

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

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

International Nuclear Information System (INIS)

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

1996-01-01

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

Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.

Science.gov (United States)

Bowman, R E; Ferguson, D; Luine, V N

2002-01-01

Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid. In summary, the current

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

International Nuclear Information System (INIS)

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

1979-01-01

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

Bovine Colostral Antibody Against Verotoxin 2 Derived from Escherichia coli O157:H7: Resistance to Proteases and Effects in Beagle Dogs

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Kuribayashi, Takashi; Seita, Tetsuro; Matsumoto, Mariko; Furuhata, Katsunori; Tagata, Kazutoshi; Yamamoto, Shizuo

2009-01-01

A bovine colostral antibody against verotoxin (VT) 2 of Escherichia coli O157:H7 was administered orally to beagle dogs. The antibody remained in the dogs’ small intestine for at least 2 h, whereas little serum antibody remained 1.5 h after administration. Furthermore, the antibody activity of secretory IgA did not change until 2 h after administration; however, the activity of IgG and IgM antibodies decreased by approximately 60% and 40% at 2 h after administration, respectively. Seven beagle dogs inoculated with Escherichia coli O157:H7 producing VT2 were administered bovine colostral antibody or bovine colostral whey without antibody. With administration of bovine colostral whey without antibody, the amount of VT2 in feces decreased gradually after administration and increased again at 5 d after inoculation, whereas bovine colostral antibody significantly reduced the amount of VT2 in feces on the day after administration. In addition, 9 beagle dogs were given bovine colostral antibody, bovine plasma antibody, or saline. The amount of VT2 in feces again decreased significantly more rapidly after administration of bovine colostral antibody than after administration of bovine plasma antibody or saline. PMID:19389308

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.

The Effects of Antioxidants and Experience on the Development of Age Dependent Cognitive Dysfunction and Neuropathology in Canines

National Research Council Canada - National Science Library

Muggenburg, Bruce

2002-01-01

Progression of individual rates of age-dependent cognitive dysfunction and the potential for antioxidants and environmental enrichment to slow the rate of decline are being evaluated over a 3-year span in beagle dogs...

The Effects of Antioxidants and Experience on the Development of Age Dependent Cognitive Dysfunction and Neuropathology in Canines

National Research Council Canada - National Science Library

Muggenburg, Bruce

2003-01-01

Progression of individual rates of age-dependent cognitive dysfunction and the potential for antioxidants and environmental enrichment to slow the rate of decline are being evaluated over a 3-year span in beagle dogs...

The Effects of Antioxidants and Experience on the Development of Age Dependent Cognitive Dysfunction and Neuropathology in Canines

National Research Council Canada - National Science Library

Muggenburg, Bruce

2001-01-01

Progression of individual rates of age-dependent cognitive dysfunction and the potential for antioxidants and environmental enrichment to slow the rate of decline are being evaluated over a 3-year span in beagle dogs...

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

International Nuclear Information System (INIS)

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

1982-01-01

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

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

Directory of Open Access Journals (Sweden)

Melisa Daiana Fernández-Severini

2005-12-01

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

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

International Nuclear Information System (INIS)

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

1976-01-01

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

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Kefir improves bone mass and microarchitecture in an ovariectomized rat model of postmenopausal osteoporosis.

Science.gov (United States)

Chen, H-L; Tung, Y-T; Chuang, C-H; Tu, M-Y; Tsai, T-C; Chang, S-Y; Chen, C-M

2015-02-01

Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel. Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities. The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line. A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased

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

Science.gov (United States)

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

2017-01-01

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

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

International Nuclear Information System (INIS)

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

1984-01-01

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

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

International Nuclear Information System (INIS)

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

1983-01-01

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

[Characteristics of sublingual vein and expressions of vascular endothelial growth factor and hypoxia-inducible factor 1alpha proteins in sublingual tissues of Beagle dogs with portal hypertension].

Science.gov (United States)

Li, Bai-yu; Wang, Li-na; Yue, Xiao-qiang; Li, Bai

2009-05-01

To observe sublingual vein characteristics and the expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha) proteins in sublingual tissues of Beagle dogs with cirrhotic portal hypertension. Twelve Beagle dogs were randomly divided into normal control group and cirrhotic portal hypertension group. There were 6 dogs in each group. A canine model of cirrhosis portal hypertension was established by injecting dimethylnitrosamine (DMN) into portal vein once a week for 7 weeks. The characteristics of sublingual vein were observed. Portal venous pressure was measured by using bioelectric recording techniques. The expressions of VEGF and HIF-1alpha proteins in sublingual vein were detected by immunohistochemical method. The shape and color of sublingual vein in beagle dogs in the cirrhotic portal hypertension group changed obviously as compared with the normal control group. Immunohistochemical results showed that there were almost no expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the normal control group; however, the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the cirrhotic portal hypertension group significantly increased. Changes of portal pressure may lead to the formation of the abnormal sublingual vein by increasing the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in Beagle dogs with portal hypertension.

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...

Vitex agnus-castus L. (Verbenaceae) Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats

OpenAIRE

Moreno, Franciele Neves; Campos-Shimada, Lilian Brites; da Costa, Silvio Claudio; Garcia, Ros?ngela Fernandes; Cecchini, Alessandra Louren?o; Natali, Maria Raquel Mar?al; Vitoriano, Adriana de Souza; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

2015-01-01

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 (...

The effect of hierarchical micro/nanosurface titanium implant on osseointegration in ovariectomized sheep.

Science.gov (United States)

Xiao, J; Zhou, H; Zhao, L; Sun, Y; Guan, S; Liu, B; Kong, L

2011-06-01

Hydrofluoric etching and anodized hierarchical micro/nanotextured surface titanium implant was placed in mandibles of ovariectomized sheep for 12 weeks, and it showed improved osseointegration by resonance frequency analysis (RFA), microcomputed tomography (micro-CT) evaluation, histomorphometry, and biomechanical test. This study aimed to investigate the effects of micro/nanotextured titanium implant on osseointegration in ovariectomized (OVX) sheep. The hierarchical micro/nanotextured surface of titanium implant was fabricated by acid in 0.5% (w/v) hydrofluoric (HF) and anodized in HF acid electrolytes with a DC power of 20 V, and the machined surface implants with no treatment served as control group. The implants were placed in mandibles of OVX sheep, respectively. Twelve weeks after implantation, RFA, microcomputed tomography, histomorphometry, and biomechanical tests were applied to detect the osseointegration of the two groups. The implant stability quotient (ISQ) values, the maximum pull-out forces, and the bone-implant contact (BIC) were 65.5 ± 6.3, 490.6 ± 72.7 N, and 58.31 ± 5.79% in the micro/nanogroup and 58.3 ± 8.9, 394.5 ± 54.5 N, and 46.85 ± 5.04% in the control group, respectively. There was no significant difference between the two groups in ISQ values (p > 0.05), but in the micro/nanogroup, the maximal pull-out force and the BIC were increased significantly (p Micro-CT analysis showed that the bone volume ratio and the trabecular number increased significantly (p micro/nanogroup. Implant modification by HF acid etching and anodization to form a hierarchical micro/nanotextured surface could improve titanium implant osseointegration in OVX sheep 12 weeks after implantation.

Honokiol Improves Liver Steatosis in Ovariectomized Mice

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Yeon-Hui Jeong

2018-01-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common liver disease, and is associated with the development of metabolic syndrome. Postmenopausal women with estrogen deficiency are at a higher risk of progression to NAFLD. Estrogen has a protective effect against the progression of the disease. Currently, there are no safe and effective treatments for these liver diseases in postmenopausal women. Honokiol (Ho, a bioactive natural product derived from Magnolia spp, has anti-inflammatory, anti-angiogenic, and anti-oxidative properties. In our study, we investigated the beneficial effects of Ho on NAFLD in ovariectomized (OVX mice. We divided the mice into four groups, as follows: SHAM, OVX, OVX+β-estradiol (0.4 mg/kg of bodyweight, and OVX+Ho (50 mg/kg of diet. Mice were fed diets with/without Ho for 12 weeks. The bodyweight, epidermal fat, and weights of liver tissue were lower in the OVX group than in the other groups. Ho improved hepatic steatosis and reduced proinflammatory cytokine levels. Moreover, Ho markedly downregulated plasma lipid levels. Our results indicate that Ho ameliorated OVX-induced fatty liver and inflammation, as well as associated lipid metabolism. These findings suggest that Ho may be hepatoprotective against NAFLD in postmenopausal women.

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

International Nuclear Information System (INIS)

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

1977-01-01

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

Tissue Selective Androgen Receptor Modulators (SARMs) Increase Pelvic Floor Muscle Mass in Ovariectomized Mice.

Science.gov (United States)

Ponnusamy, Suriyan; Sullivan, Ryan D; Thiyagarajan, Thirumagal; Tillmann, Heather; Getzenberg, Robert H; Narayanan, Ramesh

2017-03-01

Stress urinary incontinence (SUI), a prevalent condition, is represented by an involuntary leakage of urine that results, at least in part, from weakened or damaged pelvic floor muscles and is triggered by physical stress. Current treatment options are limited with no oral therapies available. The pelvic floor is rich in androgen receptor and molecules with anabolic activity including selective androgen receptor modulators (SARMs) may serve as therapeutic options for individuals with SUI. In this study, two SARMs (GTx-024 and GTx-027) were evaluated in a post-menopausal animal model in order to determine their effect on pelvic floor muscles. Female C57BL/6 mice were ovariectomized and their pelvic muscles allowed to regress. The animals were then treated with vehicle or doses of GTx-024 or GTx-027. Animal total body weight, lean body mass, and pelvic floor muscle weights were measured along with the expression of genes associated with muscle catabolism. Treatment with the SARMs resulted in a restoration of the pelvic muscles to the sham-operated weight. Coordinately, the induction of genes associated with muscle catabolism was inhibited. Although a trend was observed towards an increase in total lean body mass in the SARM-treated groups, no significant differences were detected. Treatment of an ovariectomized mouse model with SARMs resulted in an increase in pelvic floor muscles, which may translate to an improvement of symptoms associated with SUI and serves as the basis for evaluating their clinical use. J. Cell. Biochem. 118: 640-646, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

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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.

Serial ultrasonographic appearance of postpartum uterine involution in beagle dogs.

Science.gov (United States)

Yeager, A E; Concannon, P W

1990-09-01

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

241Am induced thyroid lesions in the beagle: interim observations

International Nuclear Information System (INIS)

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

1976-01-01

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

Evaluation of a hydrophilic gingival dental sealant in beagle dogs.

Science.gov (United States)

Sitzman, Clarence

2013-01-01

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

Skeletal dosimetry of injected 226RA in young adult beagles

International Nuclear Information System (INIS)

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

1986-01-01

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

Dose-effect studies with inhaled plutonium oxide in beagles

International Nuclear Information System (INIS)

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

1976-01-01

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

Toxicity of inhaled 91YCl3 in beagle dogs

International Nuclear Information System (INIS)

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

1980-01-01

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

Dietary fibers from mushroom sclerotia. 4. In vivo mineral absorption using ovariectomized rat model.

Science.gov (United States)

Wong, Ka-Hing; Katsumata, Shin-Ichi; Masuyama, Ritsuko; Uehara, Mariko; Suzuki, Kazuharu; Cheung, Peter C K

2006-03-08

The effect of three novel dietary fibers (DFs) prepared from mushroom sclerotia, namely, Pleurotus tuber-regium, Polyporus rhinocerus, and Wolfiporia cocos, on calcium and magnesium absorption was evaluated in ovariectomized (OVX) rats fed with sclerotial DF based and low Ca (0.3%) diets for 14 days. The animals in the W. cocos DF diet group possessed significantly (p cocos DF group were also significantly (p cocos DF could improve the overall Ca and Mg absorptions of the OVX rats fed a low Ca diet. The potential use of sclerotial DFs as a functional food ingredient for enhancing mineral absorption is also discussed.

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

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Zhenbao Li

2016-10-01

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

Interaction between estradiol and 5-HT1A receptors in the median raphe nucleus on acquisition of aversive information and association to the context in ovariectomized rats

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Telma Gonçalves Carneiro Spera de Andrade

2017-12-01

Full Text Available The median raphe nucleus (MRN is related to stress resistance and defensive responses, a crucial source of serotonergic neurons that project to prosencephalic structures related to stress and anxiety. Estrogen receptors were identified in this mesencephalic structure. It is possible that the estrogen action is related to serotonin effect on somatodendritic 5-HT1A receptors, inhibiting the function of serotonergic neurons and thus preventing of the stress effect and inducing anxiolysis. So, in order to evaluate these aspects, female Wistar rats were ovariectomized and 21 days later were given a direct microinjection of estradiol benzoate (EB (1200 ng into the MRN, preceded by microinjections of saline or WAY100.635 (100 ng, a 5-HT1A receptor antagonist. Immediately after the two microinjections, the ovariectomized rats were conditioned with an aversive event (foot shock session in a Skinner box. Twenty-four hours later, they were exposed to the same context in a test session for 5 min for behavioral assessment: freezing, rearing, locomotion, grooming, and autonomic responses (fecal boluses and micturition. EB microinjection in the MRN prior to the exposure of animals to the foot shocks in the conditioning session did not alter their behavior in this session, but neutralized the association of the aversive experience to the context: there was a decrease in the expression of freezing and an increased rearing activity in the test session. This effect was reversed by prior microinjection of WAY100.635. In conclusion, EB acted on serotonergic neurons in the MRN of the ovariectomized rats, impairing the association of the aversive experience to the context, by co-modulating the functionality of somatodendritic 5-HT1A. Keywords: Contextual conditioning, Median raphe nucleus, Estradiol benzoate, 5-HT1A receptors, WAY100.635, Ovariectomized rats, Anxiety

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

International Nuclear Information System (INIS)

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

1986-01-01

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

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

International Nuclear Information System (INIS)

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

1981-01-01

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

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Expression of Kirsten murine sarcoma virus sequences in Beagle dog tissues

International Nuclear Information System (INIS)

Kerkof, P.R.; Kelly, G.

1988-01-01

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

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

Science.gov (United States)

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

2002-01-01

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

Life-span studies of inhaled plutonium in beagle dogs

International Nuclear Information System (INIS)

Bair, W.J.

1991-01-01

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

Toxicity of inhaled 91YCl3 in Beagle dogs. XVII

International Nuclear Information System (INIS)

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

1983-01-01

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

Effect of phytooestrogen - coumestrol and estrone on some aspects of carbohydrate metabolism in ovariectomized female rats

International Nuclear Information System (INIS)

Nogowski, L.; Nowak, K.W.; Mackowiak, P.

1992-01-01

The purpose of the presented study is a comparison of phytooestrogen -coumestrol and estrone effects on carbohydrate metabolism in ovariectomized female rats and to examine the partition of pancreatic hormones in changes of this metabolism. Administration of coumestrol diminished muscle glycogen in investigated animals. There were no significant changes in insulin and glucagon blood level but decrease in the specific insulin binding in the insulin receptor activity in this tissue and it could be a cause of glycogen deficiency. (author). 28 refs, 4 tabs

Dose-effect studies with inhaled plutonium oxide in beagles

International Nuclear Information System (INIS)

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

1977-01-01

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

Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of ERK activity in ovariectomized mice.

Science.gov (United States)

Wang, Shiquan; Wei, Haidong; Cai, Min; Lu, Yan; Hou, Wugang; Yang, Qianzi; Dong, Hailong; Xiong, Lize

2014-01-01

Stroke has severe consequences in postmenopausal women. As replacement therapy of estrogen have various adverse effects and the undermined outcomes. Genistein, a natural phytoestrogen, has been suggested to be a potential neuroprotective agent for such stroke patients. However, the role of genistein and its underlying mechanism in ovariectomized mice has not yet been evaluated. In the present study, ovariectomized mice were treated with genistein (10 mg/kg) or vehicle daily for two weeks before developing transient cerebral ischemia (middle cerebral artery occlusion). The neurological manifestation was evaluated, and infarct volumes were demonstrated by 2,3,5-triphenyltetrazolium chloride staining at 24 h after reperfusion. In addition, phosphorylation of extracellular signal-regulated kinase (ERK) was detected by Western blotting and immunofluorescence staining, and cellular apoptosis was evaluated in the ischemic penumbra. We found that treatment with genistein reduced infarct volumes, improved neurological outcomes and attenuated cellular apoptosis at 24 h after reperfusion. ERK1/2 showed increased phosphorylation by genistein treatment after reperfusion, and an ERK1/2 inhibitor U0126 abolished this protective effect of genistein in terms of infarct volumes, neurological scores and cellular apoptosis. Our findings indicate that treatment with genistein can reduce the severity of subsequent stroke episodes, and that this beneficial function is associated with ERK activation.

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

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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

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.

2010-01-01

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

Orthodontic tooth movement and root resorption in ovariectomized rats treated by systemic administration of zoledronic acid.

Science.gov (United States)

Sirisoontorn, Irin; Hotokezaka, Hitoshi; Hashimoto, Megumi; Gonzales, Carmen; Luppanapornlarp, Suwannee; Darendeliler, M Ali; Yoshida, Noriaki

2012-05-01

The effect of zoledronic acid, a potent and novel bisphosphonate, on tooth movement and orthodontically induced root resorption in osteoporotic animals systemically treated with zoledronic acid as similarly used in postmenopausal patients has not been elucidated. Therefore, this study was undertaken. Fifteen 10-week-old female Wistar rats were divided into 3 groups: ovariectomy, ovariectomy + zoledronic acid, and control. Only the ovariectomy and ovariectomy + zoledronic acid groups underwent ovariectomies. Two weeks after the ovariectomy, zoledronic acid was administered only to the ovariectomy + zoledronic acid group. Four weeks after the ovariectomy, 25-g nickel-titanium closed-coil springs were applied to observe tooth movement and orthodontically induced root resorption. There were significant differences in the amounts of tooth movement and orthodontically induced root resorption between the ovariectomy and the control groups, and also between the ovariectomy and the ovariectomy + zoledronic acid groups. There was no statistically significant difference in tooth movement and orthodontically induced root resorption between the ovariectomy + zoledronic acid and the control groups. Zoledronic acid inhibited significantly more tooth movement and significantly reduced the severity of orthodontically induced root resorption in the ovariectomized rats. The ovariectomy + zoledronic acid group showed almost the same results as did the control group in both tooth movement and orthodontically induced root resorption. Zoledronic acid inhibits excessive orthodontic tooth movement and also reduces the risk of severe orthodontically induced root resorption in ovariectomized rats. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

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

International Nuclear Information System (INIS)

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

1985-01-01

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

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

International Nuclear Information System (INIS)

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

1981-01-01

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

Renal function changes associated with aging and ionizing radiation

International Nuclear Information System (INIS)

Miller, C.W.; Norrdin, R.W.; Sawyer, S.S.; Nealeigh, R.C.

1978-01-01

Renal function testing of irradiated and unirradiated beagles at CRHL has been carried out for the past 7 years using a simultaneous estimation of sodium sulfanilate and sodium iodohippurate 131 I clearance. Evidence has been cited that the beagle kidney is markedly sensitive to whole-body ionizing radiation delivered in the perinatal period. The objectives of this continuing study are to determine the nature of the progression of chronic renal disease, its possible association to hypertension, the impact of unilateral nephrectomy upon an already compromised renal parenchyma, and the age-related changes in renal function. Thus far, data seem to indicate the following conclusions: sulfanilate clearance appears to be a sensitive indicator of impending renal failure, exhibiting earlier and more obvious indicators than BUN (blood urea nitrogen) levels; hypertension does not appear to be a factor in radiation-induced renal failure in the adult dogs studied here, since the average arterial blood pressure was as high in normal control dogs as in irradiated dogs suffering from renal failure; unilateral nephrectomy affected unirradiated dogs less than irradiated animals with mild renal insufficiency. The BUN levels returned to prenephrectomy levels in 8 weeks in the unirradiated group, but required up to 1 year in the dogs with renal insufficiency; and an age related decrease inrenal function was observed in a group of unirradiated dogs studied from 0 to 2 through 13 years of age

The antidepressant-like effects of topiramate alone or combined with 17β-estradiol in ovariectomized Wistar rats submitted to the forced swimming test.

Science.gov (United States)

Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

2014-09-01

There is a significant delay in the clinical response of antidepressant drugs, and antidepressant treatments produce side effects. We examined the relationship between 17β-estradiol and topiramate in ovariectomized Wistar rats submitted to the forced swimming test (FST). Topiramate was administered alone or combined with 17β-estradiol to ovariectomized rats submitted to the FST. Topiramate (20 mg/kg, P swimming; these effects were antagonized by finasteride (50 mg/kg). In interaction experiments, topiramate (10 mg/kg) plus 17β-estradiol (5 micrograms per rat; P swimming behavior. Besides, 17β-estradiol (2.5 micrograms per rat) shortened the onset of the antidepressant-like effects of topiramate (P < 0.05). In the open field test, topiramate alone or combined with 17β-estradiol (P < 0.05) reduced locomotion. Topiramate alone or combined with 17β-estradiol produced antidepressant-like actions; and 17β-estradiol shortened the onset of the antidepressant-like effects of topiramate.

Expression of Kirsten murine sarcoma virus sequences in Beagle dog tissues

Energy Technology Data Exchange (ETDEWEB)

Kerkof, P R; Kelly, G

1988-12-01

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

[Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration of Ajuga decumbens extract in beagle dog].

Science.gov (United States)

Wen, Bin-Yu; Li, Jian-Rong

2013-06-01

8-O-acetylharpagide and harpagide are two kinds of effective component of Ajuga decumbens extract. A sensitive LC-MS/MS method has been established for pharmacokinetics of 8-O-acetylharpagide and harpagide in beagle dog after oral administration of from A. decumbens extract. Female beagle dogs received orally 12.9, 25.7 mg x kg(-1) p. o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartment analysis. The mobile phase consisted of 0.1% formic acid in water (A) and acetonitrile (B), which was run at a flow rate of 0.3 mL x min(-1). Chromatographic separation was achieved on an Agilent ZORBAX XDB-C18 column (2.1 mm x 50 mm, 3.5 microm) using a gradient elution of 5% B at 0-2 min, 95% B at 2. 1-5 min and 5% B at 5. 1-10 min. All analytes, including the IS, were monitored under positive ionization conditions and quantified in MRM mode with transitions of m/z 429.2-369.2 for 8-O-acetylharpagide, m/z 387.2-207.2 for harpagide, and m/z 149.2-103.1 for IS. High purity nitrogen was employed as both the nebulizing and drying gas. Other parameters of the mass spectrometer were optimized as follows: drying gas flow 10.0 L x min(-1); drying gas temperature 300 degrees C; capillary voltage 4 000 V. Results showed that 8-O-acetylharpagide and harpagide showed a dose-dependence profile. T(max) of 8-O-acetylharpagide is 1.7 h, and T(max) of harpagide is 1.57 h, which was higher than T(max) of 8-O-acetylharpagide and harpagide after oral administration of from A. decumbens extract in rats. The different pharmacokinetic parameters may be due to the species differences of rat and beagle dog.

Aging of Attentiveness in Border Collies and Other Pet Dog Breeds: The Protective Benefits of Lifelong Training

OpenAIRE

Chapagain, Durga; Vir?nyi, Zs?fia; Wallis, Lisa J.; Huber, Ludwig; Serra, Jessica; Range, Friederike

2017-01-01

Aging of attentiveness affects cognitive functions like perception and working memory, which can seriously impact communication between dogs and humans, potentially hindering training and cooperation. Previous studies have revealed that aged laboratory beagles and pet Border collies (BC) show a decline in selective attention. However, much less is known about the aging of attentiveness in pet dogs in general rather than in specific breeds. Using 185 pet dogs (75 BC and 110 dogs of other breed...

Dose-effect studies with inhaled plutonium oxide in beagles

International Nuclear Information System (INIS)

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

1978-01-01

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

Dose-effect studies with inhaled plutonium oxide in beagles

International Nuclear Information System (INIS)

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

1980-01-01

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

Dose-effect studies with inhaled plutonium oxide in beagles

International Nuclear Information System (INIS)

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

1979-01-01

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

Toxicity of inhaled 144CeCl3 in beagle dogs

International Nuclear Information System (INIS)

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

1980-01-01

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

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

International Nuclear Information System (INIS)

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

1974-01-01

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

Ovariectomy increases the age-induced hyperphosphorylation of Tau at hippocampal CA1.

Science.gov (United States)

Picazo, O; Espinosa-Raya, J; Briones-Aranda, A; Cerbón, M

2016-11-01

One of the main hallmarks of Alzheimer's disease includes the neurofibrillary tangles formation produced by hyperphosphorylation of the Tau protein, whose expression is putatively regulated by the ovarian hormones estradiol and progesterone. Hippocampus is a brain region that participates in many functions related to learning and memory; in addition, it is abundant in both estradiol and progesterone receptors. In this study, we explore the expression of Tau hyperphosphorylation at hippocampus and the performance of rats in an autoshaping learning task at 5, 10 and 15 months after the ovaries removal. In these animals, ovariectomy was performed at 3 months of age. These data were compared with those derived from intact rats at 8, 13 and 18 months old. A clear decrease in the number of conditioned responses of both intact and ovariectomized rats in the autoshaping learning task was observed. The interaction of both factors confirms that, in this test, learning varies depending on aging and the presence or absence of ovaries. A progressive increase in hippocampal Tau phosphorylation at Ser-396 was observed in either intact or ovariectomized rats. Interestingly, an interaction between the analyzed factors shows that such hyperphosphorylation was potentiated by the absence of ovaries. These results emphasize the importance of aging and the lack of ovarian hormones for an associative learning test and for the expression of one of the most important hallmarks of Alzheimer's disease.

Hematologic effects of inhaled plutonium in beagles

International Nuclear Information System (INIS)

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

1986-01-01

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

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

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Jie Li

2017-06-01

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

Blackcurrant Anthocyanins Increase the Levels of Collagen, Elastin, and Hyaluronic Acid in Human Skin Fibroblasts and Ovariectomized Rats

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Naoki Nanashima

2018-04-01

Full Text Available Blackcurrants (Ribes nigrum L. contain high levels of anthocyanin polyphenols, which have beneficial effects on health, owing to their antioxidant and anticarcinogenic properties. Phytoestrogens are plant-derived substances with estrogenic activity, which could have beneficial effects on the skin. Estradiol secretion decreases during menopause, reducing extracellular matrix (ECM component production by skin fibroblasts. Using a normal human female skin fibroblast cell line (TIG113 and ovariectomized rats, the present study investigated whether an anthocyanin-rich blackcurrant extract (BCE and four blackcurrant anthocyanins have novel phytoestrogenic activities that could benefit the skin in menopausal women. In TIG113 cells, a microarray and the Ingenuity® Pathway Analysis showed that 1.0 μg/mL of BCE upregulated the expression of many estrogen signaling-related genes. A quantitative RT-PCR analysis confirmed that BCE (1.0 or 10.0 μg/mL and four types of anthocyanins (10 μM altered the mRNA expression of ECM proteins and enzymes involved in ECM turnover. Immunofluorescence staining indicated that the anthocyanins stimulated the expression of ECM proteins, such as collagen (types I and III and elastin. Dietary administration of 3% BCE to ovariectomized rats for 3 months increased skin levels of collagen, elastin, and hyaluronic acid. This is the first study to show that blackcurrant phytoestrogens have beneficial effects on skin experimental models.

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

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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.

Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress

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Machi JF

2016-03-01

Full Text Available Jacqueline Freire Machi,1,2 Danielle da Silva Dias,3 Sarah Cristina Freitas,3 Oscar Albuquerque de Moraes,1 Maikon Barbosa da Silva,1 Paula Lázara Cruz,1 Cristiano Mostarda,4 Vera M C Salemi,1 Mariana Morris,2 Kátia De Angelis,3 Maria-Cláudia Irigoyen1 1Hypertension Unit, Heart Institute (InCor, School of Medicine, University of Sao Paulo, São Paulo, Brazil; 2Institute of Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA; 3Laboratory of Translational Physiology, Universidade Nove de Julho (UNINOVE, São Paulo, 4Health Adult and Child, Federal University of Maranhao (UFMA, São Luiz, Maranhão, Brazil Objective: The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX. Methods: Female Wistar rats (3 or 22 months old were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal. After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Results: Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG was reduced in young ovariectomized, old controls, and old ovariectomized

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

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

2005-07-01

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

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

Science.gov (United States)

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

2015-12-01

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

Toxicity of inhaled 91YCl3 in Beagle dogs. XV

International Nuclear Information System (INIS)

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

1981-01-01

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

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

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

2018-01-01

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

Selective estrogen receptor modulator promotes weight loss in ovariectomized female rhesus monkeys (Macaca mulatta) by decreasing food intake and increasing activity.

Science.gov (United States)

Sullivan, Elinor L; Shearin, Jean; Koegler, Frank H; Cameron, Judy L

2012-04-01

The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone (P Physical activity increased during the 3rd mo of treatment (P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment (P = 0.02). Metabolic rate did not change (P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.

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

International Nuclear Information System (INIS)

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

1988-01-01

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

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

International Nuclear Information System (INIS)

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

1988-01-01

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

Effect of age on the efficacy of Zn-diethylenetriaminepentaacetic acid therapy for removal of Am and Pu from beagles

International Nuclear Information System (INIS)

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

1985-01-01

Decorporation of intravenously injected monomeric 241 Am and /sup 237+239/Pu by the administration of 30 μmole Zn-diethylenetriaminepentaacetic acid (DTPA)/kg each day beginning 2 weeks after radionuclide injection was compared in beagles entered into the experiment when 3 months (juveniles), 1.9 years (young adults), or 10 years (mature adults) old and studied for about 5 months. DTPA therapy was most effective in the juvenile dogs and least effective in the mature adults. Retention of 241 Am in the liver decreased from a pretreatment value for adults of about 50% of the injected activity to about 10% in the mature adults and less than 1% in the young adults at 140 days of treatment, while the liver retention of juveniles decreased from pretreatment values of about 16% to undetectable levels by 28 days of treatment. Plutonium retention in the liver decreased from adult pretreatment levels of about 30% to near 10% in the mature adults and 6% in the young adults at 140 days of treatment, while juvenile liver retention decreased from pretreatment values near 15% to undetectable levels by 56 days of treatment. Nonliver Am retention (mainly skeleton) decreased in mature adults from pretreatment values of about 45% of the injected activity to near 25%, in young adults from 35 to 20%, and in juveniles from roughly 70 to 9% by 140 days of DTPA administration. Nonliver Pu retention decreased from pretreatment values of about 50% for mature and young adults to about 30% by 140 days and from 75 to 16% in juveniles over the same period

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

International Nuclear Information System (INIS)

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

1980-01-01

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

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

Science.gov (United States)

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

1989-01-01

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

Sexual dimorphism in development of kidney damage in aging Fischer-344 rats.

Science.gov (United States)

Sasser, Jennifer M; Akinsiku, Oladele; Moningka, Natasha C; Jerzewski, Katie; Baylis, Chris; LeBlanc, Amanda J; Kang, Lori S; Sindler, Amy L; Muller-Delp, Judy M

2012-08-01

Aging kidneys exhibit slowly developing injury and women are usually protected compared with men, in association with maintained renal nitric oxide. Our purpose was to test 2 hypotheses: (1) that aging intact Fischer-344 (F344) female rats exhibit less glomerular damage than similarly aged males, and (2) that loss of female ovarian hormones would lead to greater structural injury and dysregulation of the nitric oxide synthase (NOS) system in aging F344 rat kidneys. We compared renal injury in F344 rats in intact, ovariectomized, and ovariectomized with estrogen replaced young (6 month) and old (24 month) female rats with young and old intact male rats and measured renal protein abundance of NOS isoforms and oxidative stress. There was no difference in age-dependent glomerular damage between young or old intact male and female F344 rats, and neither ovariectomy nor estrogen replacement affected renal injury; however, tubulointerstitial injury was greater in old males than in old females. These data suggest that ovarian hormones do not influence these aspects of kidney aging in F344 rats and that the greater tubulointerstitial injury is caused by male sex. Old males had greater kidney cortex NOS3 abundance than females, and NOS1 abundance (alpha and beta isoforms) was increased in old males compared with both young males and old females. NOS abundance was preserved with age in intact females, ovariectomy did not reduce NOS1 or NOS3 protein abundance, and estrogen replacement did not uniformly elevate NOS proteins, suggesting that estrogens are not primary regulators of renal NOS abundance in this strain. Nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production and nitrotyrosine immunoreactivity were increased in aging male rat kidneys compared with females, which could compromise renal nitric oxide production and/or bioavailability. The kidney damage expressed in aging F344 rats is fairly mild and is not related to loss of renal cortex NOS3

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

International Nuclear Information System (INIS)

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

1979-01-01

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

Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs

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Chih-Hsien Chang

2014-01-01

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

Retention of plutonium in the beagle after gastrointestinal absorption

International Nuclear Information System (INIS)

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

1985-01-01

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

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

International Nuclear Information System (INIS)

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

1978-01-01

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

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

International Nuclear Information System (INIS)

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

1977-01-01

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

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

International Nuclear Information System (INIS)

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

1978-01-01

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

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

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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.

High-Throughput Determination of Sodium Danshensu in Beagle Dogs by the LCMS/MS Method, Employing Liquid-Liquid Extraction Based on 96-Well Format Plates

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Jingjing Jiang

2017-04-01

Full Text Available Sodium Danshensu (sodium d-(+-β-(3,4-dihydroxyphenyl lactate, one of the water-soluble ingredients in Salvia miltiorrhiza, exhibits potent relaxation of the coronary artery and anticoagulation effection. A high-throughput, rapid, and sensitive method combining liquid chromatography with electrospray ionization tandem mass spectrometry to determine the sodium danshensu in beagle dog plasma was developed and validated, using gallic acid as an internal standard (IS. Acidified plasma samples were extracted using 96-well liquid-liquid extraction, and were eluted on a CNW Athena C18 column (3 μm, 2.1 × 100 mm by using a gradient mobile phase system of methanol and water (containing 0.2% formic acid. The mass spectrometric detection was achieved using negative ion electrospray ionization mode and monitoring the precursor→production combinations of m/z 197→135 for sodium danshensu and 169→125 for IS, in multiple reaction monitoring modes. Good linearity was achieved, and the linear range was 10–1000 ng/mL (R2 > 0.996 with a quantification limit of 10 ng/mL for sodium danshensu in beagle dog plasma. The intra- and inter-day precision (RSD ranged from 2.1% to 9.0%. The accuracy (RE was between −8.6% and 5.7% at all quality control levels. The validated method was successfully applied to the pharmacokinetics study of sodium danshensu in beagle dog plasma after intravenous injection and oral administration of sodium danshensu.

High-Throughput Determination of Sodium Danshensu in Beagle Dogs by the LCMS/MS Method, Employing Liquid-Liquid Extraction Based on 96-Well Format Plates.

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Jiang, Jingjing; Zhao, Xin; Li, Xiuxiu; Wu, Shengyuan; Yu, Shidan; Lou, Yuefen; Fan, Guorong

2017-04-25

Sodium Danshensu (sodium d-(+)-β-(3,4-dihydroxyphenyl) lactate), one of the water-soluble ingredients in Salvia miltiorrhiza , exhibits potent relaxation of the coronary artery and anticoagulation effection. A high-throughput, rapid, and sensitive method combining liquid chromatography with electrospray ionization tandem mass spectrometry to determine the sodium danshensu in beagle dog plasma was developed and validated, using gallic acid as an internal standard (IS). Acidified plasma samples were extracted using 96-well liquid-liquid extraction, and were eluted on a CNW Athena C18 column (3 μm, 2.1 × 100 mm) by using a gradient mobile phase system of methanol and water (containing 0.2% formic acid). The mass spectrometric detection was achieved using negative ion electrospray ionization mode and monitoring the precursor→production combinations of m / z 197→135 for sodium danshensu and 169→125 for IS, in multiple reaction monitoring modes. Good linearity was achieved, and the linear range was 10-1000 ng/mL (R² > 0.996) with a quantification limit of 10 ng/mL for sodium danshensu in beagle dog plasma. The intra- and inter-day precision (RSD) ranged from 2.1% to 9.0%. The accuracy (RE) was between -8.6% and 5.7% at all quality control levels. The validated method was successfully applied to the pharmacokinetics study of sodium danshensu in beagle dog plasma after intravenous injection and oral administration of sodium danshensu.

Toxicity of inhaled 91YCl3 in Beagle dogs. XVIII

International Nuclear Information System (INIS)

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

1984-01-01

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

[Pharmacokinetics of (-)-clausenamide and its major metabolite 6-hydroxyl-clausenamide in beagle dogs by HPLC/MS].

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Song, Min; Qian, Wen; Hang, Tai-Jun; Zhang, Zheng-Xing

2005-10-01

To establish a sensitive and accurate method to study the pharmacokinetics of (-)-clausenamide [(-)-clau] and its major metabolite 6-hydroxyl-clausenamide (6-OH-clau) in the plasma of the Beagle dog. (-)-Clau was orally administered to six Beagle dogs at the dose of 30 mg x kg(-1), venous blood from front leg was sampled and plasma was separated for analysis. After extraction with ethyl acetate, the plasma samples were analyzed by HPLC/MS and the mobile phase was a mixture of methanol-water-acetic acid (60: 40: 0. 8) at the flow rate of 1.0 mL x min(-1). The API-ES positive ion SIM detection was carried out for the detection of both (-)-clau ([M + H] (+), m/z 298 ) and 6-OH-clau ([M + H - H2 O](+), m/z 296) with glipzide (glip) ([M + H](+), m/z 446) as internal standard. The pharmacokinetic parameters were calculated by 3P97 software. There was good linear relationship ( r > 0. 999) between the SIM responses and the concentrations for (-)-clau and 6-OH-clau at the range from 1.0 to 200 ng x mL(-1) and 0.2 to 40.0 ng x mL(-1), respectively. The absolute recovery was greater than 85%. The plasma concentration-time curves of (-)-clau and 6-OH-clau were both best fitted to a two-compartment model. The C(max) of (-)-clau and 6-OH-clau were (21 +/- 10) ng x mL(-1) and (3.9 +/- 2.2) ng x mL(-1), T(max) were (0.8 +/- 0.5) h and (1.3 +/- 0.5) h, T 1/2 alpha were (0.9 +/- 0.6) hand (1.4 +/- 0.6) h, T 1/2 beta were (19 +/- 23) hand (13 +/- 12) h, AUC(0-24 h) were (69 +/- 14) h x ng x mL(-1) and (12 +/- 7) h x ng x mL(-1) respectively. The established HPLC/MS method was sensitive and specific for the determination of (-)-clau. It was shown that the absorption and first phase elimination of (-)-clau were very quick in Beagle dogs, but the terminal elimination was very slow. The plasma concentration profile of its major metabolite 6-OH-clau was similar to (-)-clau and the AUC was relatively small in comparison with (-)-clau.

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

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Aleš Jerin

2009-01-01

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

Detection of myocardial metabolic abnormalities by 18F-FDG PET/CT and corresponding pathological changes in beagles with local heart irradiation

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Yan, Rul [Nursing College of Shanxi Medical University, Taiyuan (China); Song, Jianbo; Wu, Zhi Fang; Liu, Jian Zhang; Hao, Xin Zhong; Li, Sijin [Dept. of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan (China); Guo, Min [Dept. of Cardiology, First Hospital of Shanxi Medical University, Taiyuan (China); Li, Jianguo [Dept. of Radiological and Environmental Medicine, China Institute for Radiation Protection, Taiyuan (China)

2015-08-15

To determine the efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of radiation-induced myocardial damage in beagles by comparing two pre-scan preparation protocols as well as to determine the correlation between abnormal myocardial FDG uptake and pathological findings. The anterior myocardium of 12 beagles received radiotherapy locally with a single X-ray dose of 20 Gy. 18F-FDG cardiac PET/CT was performed at baseline and 3 months after radiation. Twelve beagles underwent two protocols before PET/CT: 12 hours of fasting (12H-F), 12H-F followed by a high-fat diet (F-HFD). Regions of interest were drawn on the irradiation and the non-irradiation fields to obtain their maximal standardized uptake values (SUVmax). Then the ratio of the SUV of the irradiation to the non-irradiation fields (INR) was computed. Histopathological changes were identified by light and electron microscopy. Using the 12H-F protocol, the average INRs were 1.18 ± 0.10 and 1.41 ± 0.18 before and after irradiation, respectively (p = 0.021). Using the F-HFD protocol, the average INRs were 0.99 ± 0.15 and 2.54 ± 0.43, respectively (p < 0.001). High FDG uptake in irradiation field was detected in 33.3% (4/12) of 12H-F protocol and 83.3% (10/12) of F-HFD protocol in visual analysis, respectively (p = 0.031). The pathology of the irradiated myocardium showed obvious perivascular fibrosis and changes in mitochondrial vacuoles. High FDG uptake in an irradiated field may be related with radiation-induced myocardial damage resulting from microvascular damage and mitochondrial injury. An F-HFD preparation protocol used before obtaining PET/CT can improve the sensitivity of the detection of cardiotoxicity associated with radiotherapy.

Determination of antazoline hydrochloride in Beagle dog plasma by HPLC-UV and its application to pharmacokinetics.

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Li, Xiaotian; Chu, Yanle; Ke, Yu; Wang, Linxi; Yu, Tong; Hao, Lianqi

2013-06-15

In order to evaluate the pharmacokinetics characteristic of antazoline hydrochloride in Beagle dogs, a sensitive and specific HPLC method was developed and validated using phenacetin as the internal standard (IS). The analyte and the IS were extracted from dog plasma by ethyl acetate under the basic condition. The analyte was separated by a C18 column and detected with a variable wavelength UV-detector. The mobile phase consisted of methanol-5mmolL(-1) tetrabutyl ammonium bromide (45:55, v/v) containing 0.5% glacial acetic acid in a flow rate of 1.0mLmin(-1). Standard calibration graph for antazoline was linear over a curve range of 20-1600ngmL(-1) (R>0.99) and the lower limit of quantification was 20ngmL(-1) using a plasma sample of 500μL. The intra- and inter-day precision values were less than 14.3% relative standard deviation (RSD). The intra-day assay accuracy was in the range of 98.1-100.6% and the inter-day assay accuracy in the range of 99.2-101.1%. The extraction recoveries were on the average of 88.4% for antazoline and 76.8% for IS. Plasma samples were stable at least for 1 month at -20°C. This method was successfully applied to pharmacokinetics study of antazoline after intravenous administration to Beagle dogs. Copyright © 2013 Elsevier B.V. All rights reserved.

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

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Yuqiao Zhang

2016-10-01

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

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

International Nuclear Information System (INIS)

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

1988-01-01

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

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

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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.

Development and validation of a liquid chromatography-tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study.

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Ye, Ling; Shi, Jian; Wan, Shanhe; Yang, Xiaoshan; Wang, Ying; Zhang, Jiajie; Zheng, Dayong; Liu, Zhongqiu

2013-11-01

Topotecan (TPT) is an important anti-cancer drug that inhibits topoisomerase I. A sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that potentially determines TPT in beagle dog plasma is needed for a bioequivalence study of TPT formulations. We developed and validated LC-MS/MS to evaluate TPT in beagle dog plasma in terms of specificity, linearity, precision, accuracy, stability, extraction recovery and matrix effect. Plasma samples were treated with an Ostro(TM) sorbent plate (a robust and effective tool) to eliminate phospholipids and proteins before analysis. TPT and camptothecin (internal standard) were separated on an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 50 mm) with 0.1% formic acid and methanol as the mobile phase at a flow rate of 0.25 mL/min. TPT was analyzed using positive ion electrospray ionization in multiple-reaction monitoring mode. The obtained lower limit of quantitation was 1 ng/mL (signal-to-noise ratio > 10). The standard calibration curve for TPT was linear (correlation coefficient > 0.99) at the concentration range of 1-400 ng/mL. The intra-day and inter-day precision, accuracy, stability, extraction recovery and matrix effect of TPT were within the acceptable limits. The validated method was successfully applied in a bioequivalence study of TPT in healthy beagle dogs. Copyright © 2013 John Wiley & Sons, Ltd.

Cutaneous papillomatous hyperplasia in cyclosporine-A treated beagles.

Science.gov (United States)

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

1989-08-01

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

Multiple whole body hyperthermia treatments on normal beagles

International Nuclear Information System (INIS)

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

1985-01-01

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

Biological effects of inhaled 144CeCl3 in beagle dogs

International Nuclear Information System (INIS)

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

1997-01-01

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

Late biological effects of 137CsCl injected in beagle dogs

International Nuclear Information System (INIS)

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

1994-01-01

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

Spontaneous cell-mediated cytolysis by peripheral blood cells obtained from whole-body chronically irradiated beagle dogs

International Nuclear Information System (INIS)

Dyck, J.A.; Shifrine, M.; Klein, A.K.; Rosenblatt, L.S.; Kawakami, T.

1986-01-01

The level of natural killer (NK) activity of continuously gamma-irradiated (whole body) beagle dogs and their nonirradiated controls was studied. For analytical purposes, irradiated dogs were segregated into groups according to their clinical status: clinically normal, hypocellular, or with acute non-lymphocytic leukemia. Since unirradiated control animals exhibited a wide range of NK responses, the data from each irradiated animal were compared to its own age-matched or litter-matched unirradiated control. Of the eight clinically normal irradiated dogs (median = 146% activity of control) only one animal had a NK activity lower than that of its control. The hypocellular group (n = 5, median = 21.8% of control) and the leukemic group (n = 4, median = 52.5% of control) each contained one responder with higher activity than its control. The difference between the percentage of control of the clinically normal and clinically abnormal dogs was found to be significant (P less than 0.05). There is a negative correlation between the NK results obtained and the total accumulated dose of radiation at the time of sampling (correlation coefficient = -0.739, P less than 0.01), suggesting a radiation effect upon natural killer activity, which is evidence by enhancement at lower doses and depression at higher doses of irradiation

Alcohol consumption negates estrogen-mediated myocardial repair in ovariectomized mice by inhibiting endothelial progenitor cell mobilization and function.

Science.gov (United States)

Mackie, Alexander R; Krishnamurthy, Prasanna; Verma, Suresh K; Thorne, Tina; Ramirez, Veronica; Qin, Gangjian; Abramova, Tatiana; Hamada, Hiromichi; Losordo, Douglas W; Kishore, Raj

2013-06-21

We have shown previously that estrogen (estradiol, E2) supplementation enhances voluntary alcohol consumption in ovariectomized female rodents and that increased alcohol consumption impairs ischemic hind limb vascular repair. However, the effect of E2-induced alcohol consumption on post-infarct myocardial repair and on the phenotypic/functional properties of endothelial progenitor cells (EPCs) is not known. Additionally, the molecular signaling of alcohol-estrogen interactions remains to be elucidated. This study examined the effect of E2-induced increases in ethanol consumption on post-infarct myocardial function/repair. Ovariectomized female mice, implanted with 17β-E2 or placebo pellets were given access to alcohol for 6 weeks and subjected to acute myocardial infarction. Left ventricular functions were consistently depressed in mice consuming ethanol compared with those receiving only E2. Alcohol-consuming mice also displayed significantly increased infarct size and reduced capillary density. Ethanol consumption also reduced E2-induced mobilization and homing of EPCs to injured myocardium compared with the E2-alone group. In vitro, exposure of EPCs to ethanol suppressed E2-induced proliferation, survival, and migration and markedly altered E2-induced estrogen receptor-dependent cell survival signaling and gene expression. Furthermore, ethanol-mediated suppression of EPC biology was endothelial nitric oxide synthase-dependent because endothelial nitric oxide synthase-null mice displayed an exaggerated response to post-acute myocardial infarction left ventricular functions. These data suggest that E2 modulation of alcohol consumption, and the ensuing EPC dysfunction, may negatively compete with the beneficial effects of estrogen on post-infarct myocardial repair.

Combination treatment with whole body vibration and a kidney-tonifying herbal Fufang prevent osteoporosis in ovariectomized rats.

Science.gov (United States)

Wei, Qiu-shi; Wang, Hai-bin; Wang, Jun-ling; Fang, Bin; Zhou, Guang-quan; Tan, Xin; He, Wei; Deng, Wei-min

2015-02-01

To assess the ability of whole body vibration (WBV) with the kidney-tonifying herbal Fufang (Bushen Zhuanggu Granules, BZG) to prevent osteoporosis in ovariectomized rats. Fifty 6-month-old female Sprague Dawley rats were divided into five groups: sham-operated (SHAM), ovariectomized (OVX), OVX with WBV (OVX + WBV), OVX with BZG (OVX + BZG), OVX with both WBV and BZG (OVX + WBV + BZG). The SHAM group received normal saline. After 12 weeks of treatment, the rats were killed, their serum concentrations of osteopontin (OPN), receptor activator of nuclear factor kappa-B ligand RANKL and bone turnover markers assayed and bone mineral density (BMD), histomorphometry and bone strength evaluated. Concentrations of OPN were significantly lower in the SHAM, OVX + WBV and OVX + WBV + BZG groups at 12 weeks, whereas concentrations of RANKL had decreased significantly in the SHAM, OVX + WBV, OVX + BZG and OVX + WBV + BZG groups. In the OVX + WBV, OVX + BZG and OVX + WBV + BZG groups the amount of bone turnover had been significantly antagonized. Compared with OVX group, BMD, % trabecular area (Tb.Ar), number of trabeculae (Tb.N) and assessed biomechanical variables were higher in OVX+WBV group, whereas and BMD, %Tb.Ar, Tb.N, maximal load and yield load were higher in the OVX + BZG group. All tested indices were significantly lower in the OVX + WBV and OVX + BZG groups than in the OVX + WBV + BZG group. Either WBV or BZG alone prevents OVX-induced bone loss. However, BZG enhances the effect of WBV by further enhancing BMD, bone architecture and strength. © 2015 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

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

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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.

The synergistic effect of TiO2 nanoporous modification and platelet-rich plasma treatment on titanium-implant stability in ovariectomized rats

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Jiang N

2016-09-01

Full Text Available Nan Jiang,1,2 Pinggong Du,2 Weidong Qu,2 Lin Li,2 Zhonghao Liu,2 Songsong Zhu1 1State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 2Yantai City Stomatological Hospital, Yantai, People’s Republic of China Abstract: For several decades, titanium and its alloys have been commonly utilized for endosseous implantable materials, because of their good mechanical properties, chemical resistance, and biocompatibility. But associated low bone mass, wear and loss characteristics, and high coefficients of friction have limited their long-term stable performance, especially in certain abnormal bone-metabolism conditions, such as postmenopausal osteoporosis. In this study, we investigated the effects of platelet-rich plasma (PRP treatment and TiO2 nanoporous modification on the stability of titanium implants in osteoporotic bone. After surface morphology, topographical structure, and chemical changes of implant surface had been detected by scanning electron microscopy (SEM, atomic force microscopy, contact-angle measurement, and X-ray diffraction, we firstly assessed in vivo the effect of PRP treatment on osseointegration of TiO2-modified implants in ovariectomized rats by microcomputed tomography examinations, histology, biomechanical testing, and SEM observation. Meanwhile, the potential molecular mechanism involved in peri-implant osseous enhancement was also determined by quantitative real-time polymerase chain reaction. The results showed that this TiO2-modified surface was able to lead to improve bone implant contact, while PRP treatment was able to increase the implant surrounding bone mass. The synergistic effect of both was able to enhance the terminal force of implants drastically in biomechanical testing. Compared with surface modification, PRP treatment promoted earlier osteogenesis with increased expression of the RUNX2 and COL1 genes and

Sequential treatment with basic fibroblast growth factor and PTH is more efficacious than treatment with PTH alone for increasing vertebral bone mass and strength in osteopenic ovariectomized rats

DEFF Research Database (Denmark)

Iwaniec, U.T.; Mosekilde, Li.; Mitova-Caneva, N.G.

2002-01-01

The study was designed 1) to determine whether treatment with basic fibroblast growth factor (bFGF) and PTH is more efficacious than treatment with PTH alone for increasing bone mass and strength and improving trabecular microarchitecture in osteopenic ovariectomized rats, and 2) to assess whethe...

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

International Nuclear Information System (INIS)

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

1994-01-01

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

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

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Yan-teng LI

2017-04-01

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

Effect of diet and tylosin on chronic diarrhea in beagles.

Science.gov (United States)

Westermarck, Elias; Frias, Rafael; Skrzypczak, Teresa

2005-01-01

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

Re-induction of obese body weight occurs more rapidly and at lower caloric intake in beagles.

Science.gov (United States)

Nagaoka, D; Mitsuhashi, Y; Angell, R; Bigley, K E; Bauer, J E

2010-06-01

For the purpose of investigating the mechanism of obesity-induction/re-induction including weight-cycling in beagles, a study was conducted using commercially available dog food combined with human food to mimic at home-snacking and diet-supplementation behaviours. Adult female beagles, which had free access to water and exercise, were used (n = 9). All dogs were initially offered two times their daily calculated number of calories using a dry extruded diet plus blend of canola and soybean oils and allowed to eat ad libitum. After 3 weeks, Pecan shortbread cookies were added to the diet mixture. Obesity was induced during a 19-week period with 1875-2250 kcal/day consumed, on average, during this period. The dogs were then subjected to a weight-loss regimen while consuming 490-730 kcal/day. After weight loss, a similar degree of obesity was re-induced for 17 weeks even though dogs consumed only 1125-1250 kcal/day. Body weight, body condition scores, kcal consumption and food efficiency were recorded. Results indicated that less time and fewer kcal were required to re-induce the same degree of obesity compared with the initial obesity induction. Human snack foods appeared to stimulate appetite and thus contribute to the obese state. Food efficiency was also increased during the obesity-reinduction period compared with the induction period. This information may help pet owners better understand the need to limit table scraps and human-type food snacks in dogs prone to obesity as well as weight maintenance after weight loss.

Osteogenic actions of metoprolol in an ovariectomized rat model of menopause.

Science.gov (United States)

Zang, Yuan; Tan, Quanchang; Ma, Xiangyu; Zhao, Xiong; Lei, Wei

2016-09-01

Osteoporosis and hypertension are age-related chronic diseases with increased morbidity rates among postmenopausal women. Clinical epidemiological investigations have demonstrated that hypertensive patients treated with β1-selective β-blockers have a higher bone mineral density (BMD) and lower fracture risk. Nevertheless, no fundamental studies have examined the relationships between β1-selective β-blockers and these effects. The present study explored the effects and mechanisms of metoprolol in the in vitro treatment of osteoblasts and the in vivo treatment of ovariectomy-induced osteoporosis in rats. Primary osteoblasts were obtained by digestion of the cranial bones of 24-hour-old Sprague-Dawley rats. After metoprolol treatment, cell proliferation and differentiation capacities were assessed at the corresponding time points. In addition, 3-month-old female Sprague-Dawley rats (200-220 g) were divided into a sham-operated group (n = 8) and three ovariectomized (OVX) (bilateral removal of ovaries) groups as follows: vehicle (OVX; n = 8), low-dose metoprolol (L-M, oral, 120 mg/kg/d; n = 8), and high-dose metoprolol (H-M, oral, 240 mg/kg/d; n = 8). After 12 weeks of metoprolol treatment, BMD, microarchitecture, and biomechanical properties were evaluated. The results indicated that the treatments with 0.01 to 0.1 μM metoprolol increased osteoblast proliferation, alkaline phosphatase activity, and calcium mineralization, and promoted the expression of osteogenic genes. The in vivo study indicated that administration of metoprolol to OVX rats resulted in maintenance of the BMDs of the L4 vertebrae. Moreover, amelioration of trabecular microarchitecture deterioration and preservation of bone biomechanical properties were detected in the trabecular bones of the OVX rats. Our findings indicate that metoprolol prevents estrogen deficiency-induced bone loss by increasing the number and enhancing the biological functions of osteoblasts, implying

Vitamin D is associated with metabotropic but not neurotrophic effects of exercise in ovariectomized rats

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Parvin Babaei

2017-11-01

Full Text Available Abstract Purpose Here, we studied the beneficial effects of aerobic exercise on metabolic syndrome components, cognitive performance, brain derived neurotrophic factor (BDNF and irisin in ovariectomized rats with different serum vitamin D (Vit D status. Methods Eighty female wistar rats were divided into 2 groups of sham operated (sham, n = 8, and ovariectomized (OVX, n = 72. Then OVX were divided into 9 groups of receiving combination of exercise protocol with low dose of Vit D (OVX + EXE + LD, high dose of Vit D (OVX + EXE + HD, Vit D deficiency (OVX + EXE − D, and (OVX + EXE + Veh. Also non exercised groups of OVX receiving high dose of Vit D (OVX + HD, low dose of Vit D (OVX + LD, Vit D deficiency (OVX − D, and Veh (OVX + Veh were included. After 2 months of related interventions, spatial memory was assessed using Morris water maze (MWM, and then metabolic syndrome components were measured. Results High dose of Vit D supplementation showed significant reduction in weight (p = 0.001, lipid profiles (p = 0.001, visceral fat (p = 0.001 and waist circumference (p = 0.001 regardless of exercising or not, with no change in cognitiive function. Serum BDNF level was significantly higher in Vit D deficient group (p = 0.001, and was decreased in the OVX + HD. In contrary, irisin did not show any significant relationship with serum concentration of Vit D, while it was significantly elevated in the exercised groups compared with non-exercised counterparts. Conclusion Vit D insufficiency deteriorates metabolic syndrome components, and elevates serum BDNF as a compensatory metabotropic factor, and further supplementation significantly attenuates these components parallel with reduction in BDNF. In addition, aerobic exercise successfully induces various metabolic benefits, provided optimum serum level of Vit D.

Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

International Nuclear Information System (INIS)

Savergnini, S.Q.; Reis, A.M.; Santos, R.A.S.; Santos, P.E.B.; Ferreira, A.J.; Almeida, A.P.

2012-01-01

Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E 2 ; 5 µg·100 g −1 ·day −1 ) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E 2 treatment caused an increase in uterine weight. Although E 2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E 2 -treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval

Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

Energy Technology Data Exchange (ETDEWEB)

Savergnini, S.Q.; Reis, A.M. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Santos, R.A.S. [1Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Santos, P.E.B. [Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ferreira, A.J. [Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Almeida, A.P. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

2012-11-01

Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E{sub 2}; 5 µg·100 g{sup −1}·day{sup −1}) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E{sub 2} treatment caused an increase in uterine weight. Although E{sub 2} administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E{sub 2}-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

Effects of salmon calcitonin on fracture healing in ovariectomized rats.

Science.gov (United States)

Li, Xiaolin; Luo, Xinle; Yu, Nansheng; Zeng, Bingfang

2007-01-01

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 Guangzhou Medical College, Guangzhou, 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 sham-operation. 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 sham-operated rats served as control group. After the fracture the 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 with 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 (pnormalization of microstructure of bone trabeculae. Salmon calcitonin can, not only increase BMD in osteoporotic bone, but also enhance the bone biomechanical properties and improve the process of fracture healing in fractured osteoporotic bone.

Effects of salmon calcitonin on fracture healing in ovariectomized rats

International Nuclear Information System (INIS)

Li, Xiaolin; Zeng, Bingfang; Luo, Xinle; Yu, Nansheng

2007-01-01

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)

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

International Nuclear Information System (INIS)

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

1978-01-01

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

Effects of lifetime ingestion of 90Sr in beagle dogs

International Nuclear Information System (INIS)

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

1982-01-01

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

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

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Yuqing Cao

2016-01-01

Full Text Available A rapid and sensitive capillary zone electrophoresis (CZE method with field enhanced sample injection (FESI was developed and validated for the determination of quetiapine fumarate in beagle dog plasma, with a sample pretreatment by LLE in 96-well deep format plate. The optimum separation was carried out in an uncoated 31.2 cm × 75 μm fused-silica capillary with an applied voltage of 13 kV. The electrophoretic analysis was performed by 50 mM phosphate at pH 2.5. The detection wavelength was 210 nm. Under these optimized conditions, FESI with acetonitrile enhanced the sensitivity of quetiapine about 40–50 folds in total. The method was suitably validated with respect to stability, specificity, linearity, lower limit of quantitation, accuracy, precision and extraction recovery. Using mirtazapine as an internal standard (100 ng/mL, the response of quetiapine was linear over the range of 1–1000 ng/mL. The lower limit of quantification was 1 ng/mL. The intra- and inter-day precisions for the assay were within 4.8% and 12.7%, respectively. The method represents the first application of FESI-CZE to the analysis of quetiapine fumarate in beagle dog plasma after oral administration.

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

International Nuclear Information System (INIS)

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

1995-01-01

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

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

International Nuclear Information System (INIS)

Day, P.A.

1988-01-01

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

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

Science.gov (United States)

Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

2015-07-01

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

Transcranial direct current stimulation (tDCS) neuromodulatory effects on mechanical hyperalgesia and cortical BDNF levels in ovariectomized rats.

Science.gov (United States)

da Silva Moreira, Sônia Fátima; Medeiros, Liciane Fernandes; de Souza, Andressa; de Oliveira, Carla; Scarabelot, Vanessa Leal; Fregni, Felipe; Caumo, Wolnei; Torres, Iraci L S

2016-01-15

Epidemiological studies show that painful disorders are more prevalent in women than in men, and the transcranial direct current stimulation (tDCS) technique has been tested in chronic pain states. We explored the effect of tDCS on pain behavior and brain-derived neurotrophic factor (BDNF) levels in ovariectomized rats. Forty-five female Wistar adult rats were distributed into five groups: control (CT), ovariectomy + tDCS (OT), ovariectomy + sham tDCS (OS), sham ovariectomy + tDCS (ST), and sham ovariectomy+shamtDCS (SS). The rats were subjected to cathodal tDCS. The vaginal cytology and the estradiol levels confirmed the hormonal status. In addition, nociceptive behavior was evaluated using the tail-flick, von Frey, and hot-plate tests, as well as the BDNF levels in the serum, hypothalamus, hippocampus, spinal cord, and cerebral cortex. One-way analysis of variance (ANOVA) or two-way ANOVA was used for statistical analysis, followed by the Bonferroni, and P-value b 0.05 was considered significant. The ovariectomized animals presented a hypersensitivity response in the hot-plate (P b 0.01) and von Frey (P b 0.05) tests, as well as increased serum BDNF (P b 0.05) and decreased hypothalamic BDNF (P b 0.01) levels. The OT, OS, ST, and SS groups showed decreased hippocampal BDNF levels as compared with the control group (P b 0.001). The interaction between tDCS and ovariectomy on the cortical BDNF levels (P b 0.01) was observed. The ovariectomy induced nociceptive hypersensitivity and altered serum and hypothalamic BDNF levels. The cathodal tDCS partially reversed nociceptive hypersensitivity.

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

International Nuclear Information System (INIS)

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

1982-01-01

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

Dietary supplementation of soy germ phytoestrogens or estradiol improves spatial memory performance and increases gene expression of BDNF, TrkB receptor and synaptic factors in ovariectomized rats

Directory of Open Access Journals (Sweden)

Li Zhuoneng

2010-09-01

Full Text Available Abstract Background Estrogen or phytoestrogens treatment has been suggested to improve cognitive function of the brain in postmenopausal women. However, there is lack of information on the mechanism of such treatment on the central nervous system. The present study aimed to determine the effects of estradiol and soy germ phytoestrogens on spatial memory performance in ovariectomized rats and to explore the underlying mechanisms affecting the central nervous system. Methods Ovariectomized Sprague-Dawley rats were fed a basic diet supplemented with soy germ phytoestrogens (0.4 g/kg or 1.6 g/kg or 17β-estradiol (0.15 g/kg for 12 weeks. At the end of the experiment, animals were evaluated for their spatial learning and memory performance by the Morris Water Maze task. The expressions of brain-derived neurotrophic factor (BDNF and synaptic formation proteins in the hippocampal tissue were estimated using RT-PCR and ELISA. Results It was found that rats supplemented with soy germ phytoestrogens or estradiol performed significantly better in spatial memory acquisition and retention when compared to the rats fed on the control diet. Estradiol or the high dose of phytoestrogens treatment significantly increased BDNF concentration and the mRNA levels for BDNF and its TrkB receptors as well as the synaptic formation proteins, synaptophysin, spinophilin, synapsin 1 and PSD-95, in the hippocampal tissue of the experimental animals. It was also found that phytoestrogens, in contrast to estradiol, did not show any significant effect on the vaginal and uteri. Conclusion Soy germ phytoestrogens, which may be a substitute of estradiol, improved spatial memory performance in ovariectomized rats without significant side-effects on the vaginal and uteri. The memory enhancement effect may relate to the increase in BDNF and the synaptic formation proteins expression in the hippocampus of the brain.

Biomedical risks of multiple lung lavages in beagle dogs

International Nuclear Information System (INIS)

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

1976-01-01

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

Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ: electrocardiographic, echocardiographic, and morphologic studies

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Machida Noboru

2006-12-01

Full Text Available Abstract Background Cardiac mortality in Duchenne muscular dystrophy (DMD has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. The cardiac involvement is characterized by distinctive electrocardiographic abnormalities or dilated cardiomyopathy, but the pathogenesis has remained obscure. In research on DMD, Golden retriever-based muscular dystrophy (GRMD has attracted much attention as an animal model because it resembles DMD, but GRMD is very difficult to maintain because of their severe phenotypes. We therefore established a line of dogs with Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ and examined the cardiac involvement. Methods The cardiac phenotypes of eight CXMDJ and four normal male dogs 2 to 21 months of age were evaluated using electrocardiography, echocardiography, and histopathological examinations. Results Increases in the heart rate and decreases in PQ interval compared to a normal littermate were detected in two littermate CXMDJ dogs at 15 months of age or older. Distinct deep Q-waves and increase in Q/R ratios in leads II, III, and aVF were detected by 6–7 months of age in all CXMDJ dogs. In the echocardiogram, one of eight of CXMDJ dogs showed a hyperechoic lesion in the left ventricular posterior wall at 5 months of age, but the rest had not by 6–7 months of age. The left ventricular function in the echocardiogram indicated no abnormality in all CXMDJ dogs by 6–7 months of age. Histopathology revealed myocardial fibrosis, especially in the left ventricular posterobasal wall, in three of eight CXMDJ dogs by 21 months of age. Conclusion Cardiac involvement in CXMDJ dogs is milder and has slower progression than that described in GRMD dogs. The distinct deep Q-waves have been ascribed to myocardial fibrosis in the posterobasal region of the left ventricle, but our data showed that they precede the lesion on echocardiogram and

Development of a UPLC-ESI-MS/MS method for the determination of larotaxel in beagle dog plasma: application to the pharmacokinetic study.

Science.gov (United States)

Liu, Zhenzhen; Zhang, Bo; Liu, Zhihong; Li, Song; Li, Guofei; Geng, Lulu; Zhao, Xu; Bi, Kaishun; Tang, Xing; Chen, Xiaohui

2012-04-01

A UPLC-ESI-MS/MS method has been developed and validated for the determination of larotaxel in beagle dog plasma. After addition of the internal standard, plasma samples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a 50×2.1 mm ACQUITY 1.7 μm C18 column (Waters, USA), with acetonitrile and 5 mM ammonium acetate as mobile phase, within a runtime of 3.0 min. The analytes were detected without interference in Multiple Reaction Monitoring mode with positive electrospray ionization. The linear range was 2.5-5,000 ng/mL. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 9.3% and 10.2%, respectively, and the accuracy (relative error, RE, %) was less than 11.5%. The validated method was successfully applied to a pharmacokinetic study of larotaxel in beagle dogs after intravenous administration of larotaxel-loaded lipid microsphere with different doses of 0.4, 0.8, and 1.6 mg/kg. The area under the concentration-time curve and the peak concentration of larotaxel seemed to increase with increasing dose proportionally, suggesting linear pharmacokinetics.

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Impact of four different recumbencies on the distribution of ventilation in conscious or anaesthetized spontaneously breathing beagle dogs: An electrical impedance tomography study.

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Tamas D Ambrisko

Full Text Available The aim was to examine the effects of recumbency and anaesthesia on distribution of ventilation in beagle dogs using Electrical Impedance Tomography (EIT. Nine healthy beagle dogs, aging 3.7±1.7 (mean±SD years and weighing 16.3±1.6 kg, received a series of treatments in a fixed order on a single occasion. Conscious dogs were positioned in right lateral recumbency (RLR and equipped with 32 EIT electrodes around the thorax. Following five minutes of equilibration, two minutes of EIT recordings were made in each recumbency in the following order: RLR, dorsal (DR, left (LLR and sternal (SR. The dogs were then positioned in RLR, premedicated (medetomidine 0.01, midazolam 0.1, butorphanol 0.1 mg kg-1 iv and pre-oxygenated. Fifteen minutes later anaesthesia was induced with 1 mg kg-1 propofol iv and maintained with propofol infusion (0.1-0.2 mg kg-1 minute-1 iv. After induction, the animals were intubated and allowed to breathe spontaneously (FIO2 = 1. Recordings of EIT were performed again in four recumbencies similarly to conscious state. Centre of ventilation (COV and global inhomogeneity (GI index were calculated from the functional EIT images. Repeated-measures ANOVA and Bonferroni tests were used for statistical analysis (p < 0.05. None of the variables changed in the conscious state. During anaesthesia left-to-right COV increased from 46.8±2.8% in DR to 49.8±2.9% in SR indicating a right shift, and ventral-to-dorsal COV increased from 49.8±1.7% in DR to 51.8±1.1% in LLR indicating a dorsal shift in distribution of ventilation. Recumbency affected distribution of ventilation in anaesthetized but not in conscious dogs. This can be related to loss of respiratory muscle tone (e.g. diaphragm and changes in thoracic shape. Changing position of thoraco-abdominal organs under the EIT belt should be considered as alternative explanation of these findings.

/sup 144/Ce in tissue of beagle dogs after inhalation of CeCl/sub 3/ with special emphasis on endocrine glands and reproductive organs

Energy Technology Data Exchange (ETDEWEB)

Cuddihy, R G; Boecker, B B; McClellan, R O; Kanapilly, G M [Lovelace Foundation for Medical Education and Research, Albuquerque, N.Mex. (USA)

1976-01-01

Beagle dogs inhaled aerosols containing /sup 144/CeCl/sub 3/. Deposition of /sup 144/Ce in tissues was determined in serially sacrificed dogs to characterize radiation dose patterns at early times after exposure. Uptakes of /sup 144/Ce in endocrine glands and reproductive organs were also measured; radiation doses were calculated and those doses were compared with the doses to the major organs of deposition - lung, liver and skeleton. Integrated radiation doses in pituitary and adrenal glands, pancreas, ovaries, testes, prostate and uterus were less than 2 % of those in lung and liver, while the thyroid dose was about 30 % of the dose in liver. These findings were consistent with previously reported biological responses in beagle dogs exposed to high levels of /sup 144/CeCl/sub 3/ wherein no radiation effects related to endocrine glands or the reproductive system have been observed. Use of these results in predicting the dosimetry of /sup 144/Ce in exposed humans re-emphasized the importance of radiation damage to lung, liver, skeleton and gastrointestinal tract compared to other organ systems.

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

International Nuclear Information System (INIS)

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

1978-01-01

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

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

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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.

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

International Nuclear Information System (INIS)

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

1981-01-01

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

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.

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

International Nuclear Information System (INIS)

Whittemore, A.S.; McMillan, A.

1980-03-01

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

The influence of alendronate on the healing of extraction sockets of ovariectomized rats assessed by in vivo micro-computed tomography.

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Jee, Jeong-Hyun; Lee, Wan; Lee, Byung Do

2010-08-01

Many dental patients take bisphosphonates to reduce the risk of hip and vertebral fractures. In vivo micro-computed tomography (micro-CT) was used to examine the longitudinal inhibitory effect of alendronate on the healing of extraction sockets in ovariectomized rats. Twenty 5-week-old Sprague-Dawley rats were assigned randomly to 1 of 3 groups: sham-operated (n = 5), and 2 ovariectomized (OVX) groups: saline treated (0.1 mL/100 g/d, n = 7) and alendronate treated (1 mg/kg/d, n = 8). Before micro-CT scanning, the left maxillary first molars of the rats were extracted. In vivo micro-CT (spatial resolution 50 x 50 mum) of the jaw was performed at baseline and at 2-week intervals for 6 weeks. Alveolar-bone radiographic densities and dimensions were analyzed with repeated measures analysis of variance. The bony healing patterns of the extraction sockets were also evaluated in each group. The radiographic socket densities of the sham-treated and OVX-alendronate groups significantly increased during the first 4 weeks after extraction (P sockets in the OVX-saline group increased, but the increase was significantly lower than for the other groups at 4 weeks (P sockets in all groups 2 to 6 weeks after extraction. There was a significant loss of alveolar ridge height at the second week postextraction compared with baseline, and at the fourth week compared with the second week (P sockets in estrogen-deficient rats and helps resist the loss of alveolar bone adjacent to extraction sockets. Copyright 2010 Mosby, Inc. All rights reserved.

Therapeutic Efficacy of Fenugreek Extract or/and Choline with Docosahexaenoic Acid in Attenuating Learning and Memory Deficits in Ovariectomized Rats

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Anjaneyulu K

2018-04-01

Full Text Available Background: Studies have demonstrated that estradiol influences cognitive functions. Phytoestrogens and many other estrogen-like compounds in plants have beneficial effects on cognitive performance in postmenopausal women. However, there is no evident report of fenugreek and choline-Docosahexaenoic Acid (DHA on cognition in ovariectomized rats. Aim and Objectives: The present study was aimed to evaluate the therapeutic efficacy of fenugreek extract or/and choline- DHA in attenuating ovariectomy-induced memory impairment, brain antioxidant status and hippocampal neural cell deficits in the rat model. Material and Methods: Female Wistar 9-10 months old rats were grouped (n=12/group as - (1 Normal Control (NC, (2 Ovariectomized (OVX, (3 OVX+FG (hydroalcoholic seed extract of fenugreek, (4 OVX+C-DHA,(5 OVX+FG+C-DHA and (6 OVX+Estradiol. Groups 2- 6 were bilaterally OVX. FG, C-DHA was supplemented orally for 30 days, 14 days after ovariectomy. Assessment of learning and memory was performed by passive avoidance test. Oxidative stress and antioxidant markers were assessed by standard methods. Nissl stained hippocampal sections were analyzed to determine alterations in neural cell numbers in CA1, CA3 and dentate gyrus. Results: Supplementation of FG or/and choline with DHA to OVX rats, caused significant improvement in learning and memory as well as decreased neural cell deficits compared to the same in OVX rats. Further, significantly reduced levels of brain Malondialdehyde (MDA and increased levels of Glutathione (GSH were observed. Conclusion: Therapeutic supplementation of FG with choline-DHA significantly attenuates ovariectomy-induced neurocognitive deficits in rats.

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

International Nuclear Information System (INIS)

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

1997-01-01

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

Effect of dioxin exposure on aromatase expression in ovariectomized rats

International Nuclear Information System (INIS)

Ye Lan; Leung, Lai K.

2008-01-01

Because of their persistence in the environment dioxins are one of the most concerned classes of carcinogens. Displaying both pro- and anti-agonistic properties to some hormone receptors, the pollutants are also known to be endocrine disruptors. Humans can be exposed to this pollutant through contaminated food, air, drinking water, etc. The female hormone estrogen may initiate various physiological functions, and excessive exposure to this hormone is a documented risk factor for carcinogenesis. Cyp19 (aromatase) catalyses the last step of estrogen biosynthesis, while cyp1a1 can hydroxylate and deactivate the hormone. In the present study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) on aromatase expression in the brain and adipose tissue in ovariectomized Sprague Dawley rats. Female rats were given 2.5 μg/kg TCDD p.o. before and after ovariectomy. Real-time PCR and western blot analysis indicated that pre-ovariectomy administration of TCDD could significantly reduce aromatase expression in the brain but increase the expression in the adipose tissue. In addition, increased plasma estrogen level and uterine weight were observed in these rats. These parameters did not change in rats with post-ovariectomy TCDD treatment. Our results suggested that the timing of exposure to the toxicant could determine the estrogenicity of TCDD. No correlation between cyp1a1 and cyp19 expression was observed

The effects of yellow soybean, black soybean, and sword bean on lipid levels and oxidative stress in ovariectomized rats.

Science.gov (United States)

Byun, Jae Soon; Han, Young Sun; Lee, Sang Sun

2010-04-01

Soy isoflavones have been reported to decrease the risk of atherosclerosis in postmenopausal women. However, the effects of dietary consumption of soybean have not been explored. In this study, we evaluated the effects of consuming yellow soybeans, black soybeans (Glycine max), or sword beans (Canavalia gladiate) on lipid and oxidative stress levels in an ovariectomized rat model. Forty-seven nine-week-old female rats were ovariectomized, randomly divided into four groups, and fed one of the following diets for 10 weeks: a diet supplemented with casein (NC, n = 12), a diet supplemented with yellow soybean (YS, n = 12), a diet supplemented with black soybean (BS, n = 12), or a diet supplemented with sword bean (SB, n = 11). Plasma triglyceride (TG) levels in the BS and SB groups were significantly lower than that in the NC group. Notably, the BS group had significantly lower plasma total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels than the other groups. Hepatic total lipid levels were significantly lower in the YS and SB groups, and cholesterol levels were significantly lower in the SB group than in the NC group. Superoxide dismutase (SOD) and catalase (CAT) activities were significantly higher in the groups fed beans compared to the NC group. Hepatic thiobarbituric acid reactive substances (TBARS) levels were also significantly lower in the BS and SB groups than the NC group. In conclusion, our results suggest that consumption of various types of beans may inhibit oxidative stress in postmenopausal women by increasing antioxidant activity and improving lipid profiles. Notably, intake of black soybean resulted in the greatest improvement in risk factors associated with cardiovascular disease.

Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

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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.

Effects of different varieties of Maca (Lepidium meyenii) on bone structure in ovariectomized rats.

Science.gov (United States)

Gonzales, Carla; Cárdenas-Valencia, Isaias; Leiva-Revilla, Johanna; Anza-Ramirez, Cecilia; Rubio, Julio; Gonzales, Gustavo F

2010-01-01

This study was designed to determine the effect of different varieties of maca (Lepidium meyenii) on bone structure in ovariectomized (OVX) rats. 36 female rats were randomly divided into 6 groups: sham and OVX rats treated with vehicle, estradiol (40 microg/kg), black, yellow or red maca (63 mg/ml) for 4 weeks. At the end of the treatment, uterine weight, femoral bone and lumbar vertebra histomorphology were assessed. Ovariectomy reduced weight, diameter and width of the femoral bone. Estradiol, black and red maca treatment reduced the effect of ovariectomy on these variables. Histological analyses revealed that estradiol, black and red maca treatments reversed the effect of ovariectomy by increasing the trabecular bone area in the second lumbar vertebra. Uterine weight was reduced in OVX rats, and estradiol but neither black nor red maca increased uterine weight. Red and black maca have protective effects on bone architecture in OVX rats without showing estrogenic effects on uterine weight. 2010 S. Karger AG, Basel.

Agonistic activity of tamoxifen, a selective estrogen-receptor modulator (SERM), on arthritic ovariectomized mice

Science.gov (United States)

Silva, L.A.S.; Felix, F.B.; Araujo, J.M.D.; Souza, E.V.; Camargo, E.A.; Grespan, R.

2017-01-01

Arthritis is positively associated with the decline of sex hormones, especially estrogen. Tamoxifen (TMX) is a selective estrogen receptor modulator, possessing agonist or antagonistic activity in different tissues. Thus, the objective of this study was to investigate the effect of TMX on the zymosan-induced arthritis model. Female Swiss normal and ovariectomized (OVX) mice were divided into groups and treated for five days with TMX (0.3, 0.9 or 2.7 mg/kg) or 17-β-estradiol (E2, 50 µg/kg). On the fifth day, arthritis was induced and 4 h later, leukocyte migration into joint cavities was evaluated. The neutrophil migration in OVX animals, but not in normal mice, treated with TMX (all tested doses) was significantly decreased compared with mice that received the vehicle (P≤0.05). Similarly, this effect was also demonstrated in the E2-treated group. Therefore, the present study demonstrates that TMX presented agonist effects in inhibiting neutrophil migration and preventing arthritis progression in OVX mice. PMID:29160416

Quantitative response of bone marrow colony-forming units (CFU-C and PFU-C) in weaning beagles exposed to acute whole-body γ irradiation

International Nuclear Information System (INIS)

Wilson, F.D.; Stitzel, K.A.; Klein, A.K.; Shifrine, M.; Graham, R.; Jones, M.; Bradley, E.; Rosenblatt, L.S.

1978-01-01

Using a methylcellulose-supported bone marrow culture system, the dose-response relationships of suspended granulocyte-monocyte colonies (CFU-C) and adherent fibroblastic colonies (PFU-C) were investigated in 2- to 3-month-old beagles exposed to acute whole-body γ irradiation. Groups of weanling beagles were exposed at a rate of 140 R/hr delivered from a 60 Co γ source achieving total exposures ranging from 0 to 586 R. Twenty-four hours following irradiation, bone marrow was collected, plated into methylcellulose, and after 1 week of incubation both colony types were quantitated. In addition, bone marrow cellularity determinations were made for a variety of bones using an 59 Fe-labeling technique. The results show a D 37 for the linear part of the slope of 70 R for CFU-C. Although within the limits of the experiment a D 37 could not be established for the fibroblastic populations, the results indicate a substantial degree of radioresistance for these elements supporting our previous studies on PFU-C, performed on mice, which suggested a D 37 of approximately 400 R for the progenitors of these fibroblastic elements

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

International Nuclear Information System (INIS)

1988-09-01

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

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

Science.gov (United States)

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

2004-08-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1988-12-01

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

Enhanced therapeutic benefit of quercetin-loaded phytosome nanoparticles in ovariectomized rats.

Science.gov (United States)

Abd El-Fattah, Abeer I; Fathy, Mohamed M; Ali, Zeinab Y; El-Garawany, Abd El-Rahman A; Mohamed, Ehsan K

2017-06-01

Quercetin, a dietary flavonol phytoestrogen, has many health benefits but it is poorly absorbed when administered orally. To improve its bioavailability, we prepared quercetin-loaded phytosome nanoparticles (QP) using the thin film hydration method. The prepared nano-formulations were characterized using different techniques. Transmission electron microscopy revealed the homogeneously spherical, well and uniformly dispersed, nano-sized nature of QP. Dynamic light scattering measurements of QP (70 ± 7.44 nm) also confirmed this. Stability of the formed nanoparticles was established via zeta potential determination. The prepared QP exhibited very high encapsulation efficiency (98.4%). The estrogenic activity of QP, concerning inflammation, oxidative stress, bone, lipid profile, blood glucose level and weight gain, was investigated in ovariectomized rat model using 10 and 50 mg/kg/day oral doses for 4 weeks. Treatment with QP showed significant increase in serum calcium, inorganic phosphorus and glutathione content. Whereas, it significantly decreased serum alkaline phosphatase, acid phosphatase, malondialdehyde level, tumor necrosis factor-alpha and glucose level and improved lipid profile. Consequently, the results obtained confirm the superiority of QP over free quercetin at the same doses as a promising hormone replacement therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

1988-12-01

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

Peri-implant and Paracrestal Inflammatory Biomarkers at Failing Versus Surviving Implant Sites in a Beagle Dog Study.

Science.gov (United States)

Montero, Javier; Aragón, Fernando; Blanco, Leticia A; Guadilla, Yasmina; García-Cenador, Begona; López-Valverde, Antonio

This study sought to quantify three biochemical mediators of inflammation (tumor necrosis factor alpha [TNF-α], superoxide anion [SOA], and myeloperoxidase [MPO]) by analyzing crestal (peri-implants) and paracrestal gingival biopsy samples obtained from an experimental study on beagle dogs treated with implants inserted immediately into fresh sockets with circumferential defects. In 10 beagle dogs, 4 roughened titanium implants (3.8 mm wide × 8 mm high) were placed in the distal sockets of the third and fourth premolars, where a circumferential defect (5 mm wide and 5 mm deep) had been previously created by trephination. After varying follow-up periods, ranging from 80 to 190 days, the dogs were explored clinically to assess implant survival, peri-implant pocket depth, and implant stability. The levels of three biochemical mediators of inflammation (MPO, TNF-α, and SOA) were investigated using the crestal and paracrestal gingival biopsy samples with ELISA tests. It was found that 37.5% of the implants were either absent or mobile. Higher levels of the inflammatory mediators were found in the crestal samples than in the paracrestal samples. The final implant stability values were significantly correlated with the final probing depth (r = -0.83, P < .01), but neither of the clinical measures were significantly correlated with any biochemical marker. The risk of implant failure was significantly proportional to the level of MPO (odds ratio: 1.1) and TNF-α (odds ratio: 1.1) in both the crestal and paracrestal regions. All the inflammatory mediators studied were higher in the crestal areas than in the paracrestal regions, but only the values of MPO and TNF-α were significant predictors of implant failure.

Application of collagen hydrogel/sponge scaffold facilitates periodontal wound healing in class II furcation defects in beagle dogs.

Science.gov (United States)

Kosen, Y; Miyaji, H; Kato, A; Sugaya, T; Kawanami, M

2012-10-01

A three-dimensional scaffold may play an important role in periodontal tissue engineering. We prepared bio-safe collagen hydrogel, which exhibits properties similar to those of native extracellular matrix. The aim of this study was to examine the effect of implantation of collagen hydrogel/sponge scaffold on periodontal wound healing in class II furcation defects in dogs. The collagen hydrogel/sponge scaffold was prepared by injecting collagen hydrogel, cross-linked to the ascorbate-copper ion system, into a collagen sponge. Class II furcation defects (of 5 mm depth and 3 mm width) were surgically created in beagle dogs. The exposed root surface was planed and demineralized with EDTA. In the experimental group, the defect was filled with collagen hydrogel/sponge scaffold. In the control group, no implantation was performed. Histometric parameters were evaluated 2 and 4 wk after surgery. At 2 wk, the collagen hydrogel/sponge scaffold displayed high biocompatibility and biodegradability with numerous cells infiltrating the scaffold. In the experimental group, reconstruction of alveolar bone and cementum was frequently observed 4 wk after surgery. Periodontal ligament tissue was also re-established between alveolar bone and cementum. Volumes of new bone, new cementum and new periodontal ligament were significantly greater in the experimental group than in the control group. In addition, epithelial down-growth was suppressed by application of collagen hydrogel. The collagen hydrogel/sponge scaffold possessed high tissue compatibility and degradability. Implantation of the scaffold facilitated periodontal wound healing in class II furcation defects in beagle dogs. © 2012 John Wiley & Sons A/S.

Influence of X-ray irradiation on the mandible of ovariectomized rats

International Nuclear Information System (INIS)

Ikoma, Kazuyuki; Iwata, Hiroshi; Yosue, Takashi

2004-01-01

The aim of the present study was to investigate the influence of irradiation on the mandible of ovariectomized (OVX) rats. Female rats were subject to OVX or a sham operation (SHAM) at the age of 14 weeks. Ten Gy doses of X-ray were applied to the mandibles twelve weeks after the operation. The experimental animals were divided into four groups: the OVX non-irradiation group, the OVX irradiation group, SHAM non-irradiation group and SHAM irradiation group. Four, eight and twelve weeks after irradiation, the animals were sacrificed and the mandibles removed. The mandibles were investigated using μCT and pQCT, and from the images obtained, the rate of mineralized tissue in the bone as well as the bone mineral content (BMC) were evaluated. The rate of mineralized tissue in the bone as determined from the images of μCT was significantly (P<0.05) lower in the OVX non-irradiation group than in the SHAM non-irradiation group at four weeks after irradiation. Similarly, the rate in the OVX irradiation group was lower than that in the SHAM irradiation group at twelve weeks after irradiation. In both the SHAM and OVX groups, there was no difference between the non-irradiation and irradiation groups. From the pQCT images, the change in the BMC in the cortical bone was negligible when the BMC was measured in the mandibles. In the OVX non-irradiation group, the trabecular BMC of the mandibles was significantly lower than that in the SHAM non-irradiation group at four and twelve weeks after irradiation. The trabecular BMC of the mandibles in the SHAM and OVX irradiation groups were significantly lower than that of the SHAM and OVX non-irradiation groups respectively throughout the experimental period. In the rate of mineralized tissue in the mandibles, the influence of OVX was recognized, but the influence of irradiation was not. On the other hand, the BMC in the cortical bone was not significant through out the experiment. The influence of irradiation on the OVX group was

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

International Nuclear Information System (INIS)

1989-09-01

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

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

International Nuclear Information System (INIS)

1986-07-01

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

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

International Nuclear Information System (INIS)

1987-08-01

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

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

International Nuclear Information System (INIS)

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

1983-01-01

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

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

International Nuclear Information System (INIS)

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

1989-01-01

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

Preclinical evaluation of intravenously administered 111In-and 90Y-labeled B72.3 immunoconjugate (GYK-DTPA) in beagle dogs

International Nuclear Information System (INIS)

Quadri, S.M.; Vriesendorp, H.M.; Yi Shao; Blum, J.E.; Leichner, P.K.; Williams, J.R.

1993-01-01

B72.3, a monoclonal antibody with reactivity against human adenocarcinomas was obtained from the Cytogen Corporation in the form of an immunoconjugate coupled with linker-chelator GYK-DTPA by using proprietary carbohydrate directed site specific chemistry. The immunoconjugate was radiolabeled with indium-111 or yttrium-90. A preclinical analysis was performed in 10 normal beagle dogs. The pharmacokinetics of intravenously administered indium- and yttrium-labeled immunoconjugates were compared serially in blood, bone marrow and urine samples. Compared to 90 Y less of the 111 In label ended up in urine and more was found in blood and bone marrow. Indium-labeled B72.3 GYK-DTPA had relatively higher uptake in most glandular tissues than 111 In-labeled antiferritin immunoconjugate. Bone marrow toxicity was the dose limiting side effect after intravenous infusion of 90 Y-labeled B72.3 GYK-DTPA. Toxicity was also observed in the liver but not in other organ systems. Recently other investigators obtained similar results with these immunoconjugates in human patients. A preclinical pharmacokinetic analysis of radioimmunoconjugates in beagle dogs provided useful information regarding bone marrow toxicity, liver toxicity and in vivo instability of the immunoconjugate. Data suggest that for future trials in human patients, a more stable chelated immunoconjugate for yttrium is needed to achieve less liver uptake and a better correlation with the 111 In-labeled product than the 90 Y-labeled B72.3 GYK-DTPA used in this investigation. (Author)

Deposition of 0.1 μm chain aggregate aerosols in beagle dogs

International Nuclear Information System (INIS)

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

1981-01-01

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

Anatomical and ultrasonographic study of the femoral nerve within the iliopsoas muscle in beagle dogs and cats.

Science.gov (United States)

Mogicato, Giovanni; Layssol-Lamour, Catherine; Mahler, Stephan; Charrouin, Maxime; Boyer, Guillaume; Verwaerde, Patrick; Jourdan, Géraldine

2015-07-01

An ultrasound (US)-guided ventral suprainguinal approach to block the femoral nerve (FN) within the iliopsoas muscle (IPM) has recently been described in dogs. The goal of the present study was to provide the operator with additional information to locate the FN within the IPM in dogs and cats using US. The study was carried out in three phases: a dissection of the FN (phase 1); an in vivo US-assisted nerve study (phase 2), and an anatomical cross-sectional study (phase 3). Nine healthy adult beagle dogs and nine healthy adult cats. Dissections were performed to investigate the anatomical characteristics of the FN and its related structures in one dog and one cat. Ultrasound scans of the left and right FN were performed in eight dogs and eight cats. The FN diameter and the distance between the FN and the external iliac artery (EIA) in US images and in anatomical cryosections were measured. The median FN diameter did not differ significantly between cats and dogs (1.1 mm versus 1.0 mm) or between the two techniques (US versus anatomical cross-sectional study) (1.1 mm versus 1.1 mm in dogs; 1.0 mm versus 1.1 mm in cats). The US and anatomical measurements of the median distances between the FN and EIA differed significantly between dogs and cats (8.2 mm versus 5.8 mm by US; 5.7 mm versus 4.8 mm in the anatomical study). The distance between the EIA and FN is reproducible in beagle dogs and cats and can be used in locating the FN within the IPM. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Choline acetyltransferase and TrkA expression, as well as the improvement in cognition produced by E2 and P4 in ovariectomized rats, are blocked by ICI 182 780 and RU486.

Science.gov (United States)

Espinosa-Raya, Judith; Cruz-Raya, Ulises; López-Martínez, Margarita; Picazo, Ofir

2018-01-09

Treatment with 17-β estradiol and progesterone improves the performance of ovariectomized rats in an autoshaping learning task, representing cognitive improvement. To test whether this is attributable to genomic mechanisms, the antiestrogen ICI 182 780 or antiprogesterone RU486 was injected into ovariectomized animals primed previously with estrogen or progesterone, respectively. Compared with the vehicle control, each hormone administered alone produced an elevated expression of choline acetyltransferase and TrkA, along with an improvement in performance on the behavioral test. E2+ICI reverted the increase in these two proteins. However, RU alone elicited higher ChAT expression. With this exception, there was a clear linear regression between the number of conditioned responses and the level of ChAT and TrkA in the basal forebrain. The results suggest that TrkA may be more important than ChAT for regulating autoshaping learning tasks, and that genomic mechanisms in the basal forebrain could possibly underlie hormonal improvement of cognition.

Theoretical consideration of metabolic and histomorphometric data for alkaline earth and actinide distribution dynamics in the beagle skeleton

International Nuclear Information System (INIS)

Parks, N.J.

1989-01-01

The beagle has been used for thirty years as a putative model for human skeletal dynamics in terms of metabolic behaviour and response to in situ radiation insults. The partitioned clearance model (PCM) is a bone by bone description of radionuclide redistribution in the beagle skeleton after the end of exposure to 226 Ra by eight semi-monthly injections at 435-535 days or by continuous ingestion of 90 Sr from in utero to 540 days. The PCM describes both the clearance of radium after deposition on surfaces following injection and the clearance of 90 Sr after uniform deposition in the skeleton as a function of Ca mass. The PCM relates the metabolically determined time-zero deposition fraction (% A) per skeletal component to the calcium fraction (%Ca) per component. The ratio of these two fractions is defined as an estimator of relative 'surface',S, in PCM for the alkaline earths (ae). A comparison is made of 'surface' as defined, in PCM, by activity fraction per mass fraction in a given skeletal component for bone seeking alkaline earths (S ae ), to similarly defined 'surface' (S act ) for injected plutonium citrate. For inhaled soluble plutonium nitrate that translocates to bone, the S act values are very similar to the S ae values for injected radium. The physiochemical determinants of Pu deposition in bone after inhalation appear to be similar to those for alkaline earths. Histomorphometric data from actual bone surfaces marked in vivo with fluorescent labels given to a juvenile dog and then 13 years later give direct evidence that actinides not removed metabolically may never be removed by remodelling processes. (author)

Effect of ovarian hormones on the phagocytic response of ovariectomized mares.

Science.gov (United States)

Ganjam, V K; McLeod, C; Klesius, P H; Washburn, S M; Kwapien, R; Brown, B; Fazeli, M H

1982-01-01

The reaction between ovarian hormones and experimental uterine infection (Streptococcus zooepidemicus) was investigated in 3 groups, each containing 6 ovariectomized mares. Group 1 served as controls ('anoestrus'), Group 2 mares were injected with oestrogen ('oestrus') and Group 3 with progesterone ('dioestrus') over a period of 5 weeks. All mares received an intrauterine inoculation of the bacteria 1 week after the start of hormonal treatment, and the results of the challenge were examined by endometrial biopsy and swabs once weekly. At the end of Week 1 no bacteria were recovered from the mares in Group 2. Group 1 mares were free of bacteria at the end of Week 2 but all Group 3 mares remained infected at least for the total period examined. Streptococcal phagocytosis was quantitated by chemiluminescence. Before the challenge-inoculation, phagocytosis was not significantly different in the 3 groups of mares. Bacterial cultures were negative for all three groups. However, within 48 h after infection, there was a significant increase (P less than 0.01) in phagocytosis in Group 2 and a significant suppression (P less than 0.05) in Group 3 mares. Patterns of streptococcal clearance from the uterus closely paralleled the changes in the magnitude of chemiluminescence response. The results suggest that ovarian hormonal status can modulate the phagocytic response in episodes of streptococcal-induced endometritus in mares.

Effects of Velvet Antler with Blood on Bone in Ovariectomized Rats

Directory of Open Access Journals (Sweden)

Ching-Chiung Wang

2012-09-01

Full Text Available In traditional Chinese medicine (TCM, both velvet antlers (VA and VA blood can tonify qi, essence, and marrow, nourish the blood, and invigorate bones and tendons. In TCM, the combination of VA and VA blood is believed to have superior pharmacological effects. Scientific evidence supporting the traditional therapeutic preference for redder antler is needed. The effectiveness of the combination therapy of VA middle sections (VAMs and VA blood (VAM-B was first examined in promoting proliferation of mouse osteoblastic cells (MC3T3-E1. The anti-osteoporotic activity of VAM-B (ratio of VAM:VA blood = 1:0.2 was evaluated with ovariectomized (OVX rats at a dose of 0.2 g/kg. In VAM-B-treated OVX rats, the body weight decreased 10.7%, and the strength of vertebrae and the femur respectively increased 18.1% and 15.4%, compared to the control. VAM-B treatment also recovered the estrogen-related loss of the right tibial trabecular bone microarchitecture. Alkaline phosphatase (ALP significantly decreased, but estradiol did not significantly change in serum of VAM-B-treated OVX rats. We also provide an effective strategy to enhance the anti-osteoporotic activity of VAM. In conclusion, our results provide scientific evidence supporting the traditional therapeutic preference of redder antler and indicate that VAM-B is a potential therapeutic agent for managing osteoporosis.

Heart sounds analysis via esophageal stethoscope system in beagles.

Science.gov (United States)

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

2013-10-01

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

Unopposed Estrogen Supplementation/Progesterone Deficiency in Post-Reproductive Age Affects the Secretory Profile of Resident Macrophages in a Tissue-Specific Manner in the Rat.

Science.gov (United States)

Stanojević, Stanislava; Kovačević-Jovanović, Vesna; Dimitrijević, Mirjana; Vujić, Vesna; Ćuruvija, Ivana; Blagojević, Veljko; Leposavić, Gordana

2015-11-01

The influence of unopposed estrogen replacement/isolated progesterone deficiency on macrophage production of pro-inflammatory/anti-inflammatory mediators in the post-reproductive age was studied. Considering that in the rats post-ovariectomy the circulating estradiol, but not progesterone level rises to the values in sham-operated controls, 20-month-old rats ovariectomized at the age of 10 months served as an experimental model. Estrogen and progesterone receptor expression, secretion of pro- and anti-inflammatory cytokines, and arginine metabolism end-products were examined in splenic and peritoneal macrophages under basal conditions and following lipopolysaccharide (LPS) stimulation in vitro. Almost all peritoneal and a subset of splenic macrophages expressed the intracellular progesterone receptor. Ovariectomy diminished cytokine production by splenic (IL-1β) and peritoneal (TNF-α, IL-1β, IL-10) macrophages and increased the production of IL-10 by splenic and TGF-β by peritoneal cells under basal conditions. Following LPS stimulation, splenic macrophages from ovariectomized rats produced less TNF-α and more IL-10, whereas peritoneal macrophages produced less IL-1β and TGF-β than the corresponding cells from sham-operated rats. Ovariectomy diminished urea production in both subpopulations of LPS-stimulated macrophages. Although long-lasting isolated progesterone deficiency in the post-reproductive age differentially affects cytokine production in the macrophages from distinct tissue compartments, in both subpopulations, it impairs the pro-inflammatory/anti-inflammatory cytokine secretory balance. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oxidative Stress in Aging: Advances in Proteomic Approaches

Directory of Open Access Journals (Sweden)

Daniel Ortuño-Sahagún

2014-01-01

Full Text Available Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual’s Quality of Life (QOL. Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS], which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8, naked mole-rat (Heterocephalus glaber, and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS and oxidative stress in aging.

Estrogen Replacement Therapy in Ovariectomized Nonpregnant Ewes Stimulates Uterine Artery Hydrogen Sulfide Biosynthesis by Selectively Up-Regulating Cystathionine β-Synthase Expression.

Science.gov (United States)

Lechuga, Thomas J; Zhang, Hong-hai; Sheibani, Lili; Karim, Muntarin; Jia, Jason; Magness, Ronald R; Rosenfeld, Charles R; Chen, Dong-bao

2015-06-01

Estrogens dramatically dilate numerous vascular beds with the greatest response in the uterus. Endogenous hydrogen sulfide (H2S) is a potent vasodilator and proangiogenic second messenger, which is synthesized from L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). We hypothesized that estrogen replacement therapy (ERT) selectively stimulates H2S biosynthesis in uterine artery (UA) and other systemic arteries. Intact and endothelium-denuded UA, mesenteric artery (MA), and carotid artery (CA) were obtained from ovariectomized nonpregnant ewes (n = 5/group) receiving vehicle or estradiol-17β replacement therapy (ERT). Total RNA and protein were extracted for measuring CBS and CSE, and H2S production was determined by the methylene blue assay. Paraffin-embedded UA rings were used to localize CBS and CSE proteins by immunofluorescence microscopy. ERT significantly stimulated CBS mRNA and protein without altering CSE mRNA or protein in intact and denuded UA. Quantitative immunofluorescence microscopic analyses showed CBS and CSE protein localization in endothelium and smooth muscle and confirmed that ERT stimulated CBS but not CSE protein expression in UA endothelium and smooth muscle. ERT also stimulated CBS, but not CSE, mRNA and protein expression in intact and denuded MA but not CA in ovariectomized ewes. Concomitantly, ERT stimulated UA and MA but not CA H2S production. ERT-stimulated UA H2S production was completely blocked by a specific CBS but not CSE inhibitor. Thus, ERT selectively stimulates UA and MA but not CA H2S biosynthesis by specifically up-regulating CBS expression, implicating a role of H2S in estrogen-induced vasodilation and postmenopausal women's health.

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

International Nuclear Information System (INIS)

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

1974-01-01

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

Beagle puppy model of intraventricular hemorrhage: ethamsylate studies.

Science.gov (United States)

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

1984-02-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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

International Nuclear Information System (INIS)

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

1985-01-01

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

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

International Nuclear Information System (INIS)

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

1994-01-01

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

Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats

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Aghdas Dehghani

2015-01-01

Full Text Available Background. The accompanied role of Mas receptor (MasR, bradykinin (BK, and female sex hormone on renal blood flow (RBF response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779 and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE or vehicle (OV for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP, RBF, and renal vascular resistance (RVR responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1 were determined. Results. Percentage change of RBF (%RBF in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P<0.05. Infusion of 300 ng kg−1 min−1 Ang 1-7 increased RBF by 6.9±1.9% in OVE group versus 0.9±1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly. Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

Lifetime radiation risks from low-dose rate radionuclides in beagles

International Nuclear Information System (INIS)

Goldman, M.; Rosenblatt, L.S.

1985-01-01

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

Changes of auditory event-related potentials in ovariectomized rats injected with d-galactose: Protective role of rosmarinic acid.

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Kantar-Gok, Deniz; Hidisoglu, Enis; Er, Hakan; Acun, Alev Duygu; Olgar, Yusuf; Yargıcoglu, Piraye

2017-09-01

Rosmarinic acid (RA), which has multiple bioactive properties, might be a useful agent for protecting central nervous system against age related alterations. In this context, the purpose of the present study was to investigate possible protective effects of RA on mismatch negativity (MMN) component of auditory event-related potentials (AERPs) as an indicator of auditory discrimination and echoic memory in the ovariectomized (OVX) rats injected with d-galactose combined with neurochemical and histological analyses. Ninety female Wistar rats were randomly divided into six groups: sham control (S); RA-treated (R); OVX (O); OVX+RA-treated (OR); OVX+d-galactose-treated (OD); OVX+d-galactose+RA-treated (ODR). Eight weeks later, MMN responses were recorded using the oddball condition. An amplitude reduction of some components of AERPs was observed due to ovariectomy with or without d-galactose administiration and these reduction patterns were diverse for different electrode locations. MMN amplitudes were significantly lower over temporal and right frontal locations in the O and OD groups versus the S and R groups, which was accompanied by increased thiobarbituric acid reactive substances (TBARS) and hydroxy-2-nonenal (4-HNE) levels. RA treatment significantly increased AERP/MMN amplitudes and lowered the TBARS/4-HNE levels in the OR and ODR groups versus the O and OD groups, respectively. Our findings support the potential benefit of RA in the prevention of auditory distortion related to the estrogen deficiency and d-galactose administration at least partly by antioxidant actions. Copyright © 2017 Elsevier B.V. All rights reserved.

Cobalt-60 oxide aerosols: methods of production and short-term retention and distribution kinetics in the beagle dog

International Nuclear Information System (INIS)

Barnes, J.E.; Kanapilly, G.M.; Newton, G.J.

1976-01-01

Cobalt-60 has been used extensively in nuclear applications and has been considered for use in nuclear auxiliary power devices. The most common chemical form used is the oxide. This study of the retention and distribution of two differnt exoides of cobalt when administered by inhalation was conducted to assess the potential inhalation hazard associated with its use. Cobaltosic oxide (Co 3 O 4 ) was formed by passing a cobalt nitrate aerosol through a heating column at 850 0 C before delivery to the dog. Cobaltous oxide (CoO) was formed by raising the heating column temperature to 1400 0 C. Three beagle dogs were exposed to 60 Co 3 O 4 and sacrificed singly at 8, 64 and 128 days. Three beagle dogs were exposed to 60 CoO and sacrificed at 8, 16 and 64 days after exposure. Whole-body retention patterns showed that 60 CoO left the body with a shorter effective half-life than 60 Co 3 O 4 . The concentration of 60 Co detected in the blood was at least an order of magnitude higher in the dogs exposed to 60 CoO than in the dogs exposed to 60 Co 3 O 4 . Cobalt-60 translocated from the lung accumulated predominantly in the kidney, liver, skeleton and cartilagenous structures such as the trachea. Higher concentrations were reached earlier in the dogs exposed to 60 CoO. After early fecal excretion of material deposited in the upper respiratory tract, excretion was greatest via the urine. The higher solubility of the 60 CoO formed at 1400 0 C relative to 60 Co 3 O 4 formed at 850 0 C is noteworthy considering that generally aerosols formed at higher temperatures are more insoluble than aerosols formed at lower temperatures. (author)

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

Science.gov (United States)

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

2011-12-15

A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma has been developed and validated. Following liquid-liquid extraction, the analytes were separated on a reversed-phase C(18) column (150 mm × 2.0 mm, 3 μm) using formic acid:10 mM ammonium acetate:methanol (0.2:62:38, v/v/v) as mobile phase at a flow rate of 0.2 mL/min and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode. The method was linear for all analytes over the following concentration (ng/mL) ranges: codeine 0.08-16; ephedrine 0.8-160; guaiphenesin 80-16,000; chlorpheniramine 0.2-40. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method was successfully applied to a bioequivalence study in 6 healthy beagle dogs. Copyright © 2011 Elsevier B.V. All rights reserved.

Alpinumisoflavone and abyssinone V 4'-methylether derived from Erythrina lysistemon (Fabaceae) promote HDL-cholesterol synthesis and prevent cholesterol gallstone formation in ovariectomized rats.

Science.gov (United States)

Mvondo, Marie A; Njamen, Dieudonné; Kretzschmar, Georg; Imma Bader, Manuela; Tanee Fomum, Stephen; Wandji, Jean; Vollmer, Günter

2015-07-01

Erythrina lysistemon was found to improve lipid profile in ovariectomized rats. Alpinumisoflavone (AIF) and abyssinone V 4'-methylether (AME) derived from this plant induced analogous effects on lipid profile and decreased atherogenic risks. To highlight the molecular mechanism of action of these natural products, we evaluated their effects on the expression of some estrogen-sensitive genes associated with cholesterol synthesis (Esr1 and Apoa1) and cholesterol clearance (Ldlr, Scarb1 and Cyp7a1). Ovariectomized rats were subcutaneously treated for three consecutive days with either compound at the daily dose of 0.1, 1 and 10 mg/kg body weight (BW). Animals were sacrificed thereafter and their liver was collected. The mRNA of genes of interest was analysed by quantitative real-time polymerase chain reaction. Both compounds downregulated the mRNA expression of Esr1, a gene associated with cholesterogenesis and cholesterol gallstone formation. AME leaned the Apoa1/Scarb1 balance in favour of Apoa1, an effect promoting high-density lipoprotein (HDL)-cholesterol formation. It also upregulated the mRNA expression of Ldlr at 1 mg/kg/BW per day (25%) and 10 mg/kg/BW per day (133.17%), an effect favouring the clearance of low-density lipoprotein (LDL)-cholesterol. Both compounds may also promote the conversion of cholesterol into bile acids as they upregulated Cyp7a1 mRNA expression. AIF and AME atheroprotective effects may result from their ability to upregulate mechanisms promoting HDL-cholesterol and bile acid formation. © 2015 Royal Pharmaceutical Society.

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

International Nuclear Information System (INIS)

Miyabayashi, T.; Morgan, J.P.

1991-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

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

Directory of Open Access Journals (Sweden)

Liping Pan

2015-01-01

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

The effect of dose protraction on the incidence of lung carcinomas in beagle dogs with internally deposited β-emitting radionuclides

International Nuclear Information System (INIS)

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

1992-01-01

Studies using Beagle dogs were conducted to understand health effects when lung is the primary organ irradiated after inhaling insoluble radioactive particles containing one of four β-emitting radionuclides, 90 Y, 91 Y, 144 Ce, or 90 Sr. The low-LET β irradiation was delivered over a wide range of total doses and dose rate patterns that protracted the dose to lung from about 1 wk to several years. The tumor incidence rates for lung carcinomas were estimated using a proportional hazard rate model. These studies suggest that dose protraction only affects production of lung carcinomas at doses above 50 Gy

Anti-obesity activity of Yamabushitake (Hericium erinaceus) powder in ovariectomized mice, and its potentially active compounds.

Science.gov (United States)

Hiraki, Eri; Furuta, Shoko; Kuwahara, Rika; Takemoto, Naomichi; Nagata, Toshiro; Akasaka, Taiki; Shirouchi, Bungo; Sato, Masao; Ohnuki, Koichiro; Shimizu, Kuniyoshi

2017-07-01

Hericium erinaceus (H. erinaceus) improves the symptoms of menopause. In this study, using ovariectomized mice as a model of menopause, we investigated the anti-obesity effect of this mushroom in menopause. Mice fed diets containing H. erinaceus powder showed significant decreases in the amounts of fat tissue, plasma levels of total cholesterol, and leptin. To determine the mechanism, groups of mice were respectively fed a diet containing H. erinaceus powder, a diet containing ethanol extract of H. erinaceus, and a diet containing a residue of the extract. As a result, H. erinaceus powder was found to increase fecal lipid levels in excreted matter. Further in vitro investigation showed that ethanol extract inhibited the activity of lipase, and four lipase-inhibitory compounds were isolated from the extract: hericenone C, hericenone D, hericenone F, and hericenone G. In short, we suggest that H. erinaceus has an anti-obesity effect during menopause because it decreases the ability to absorb lipids.

"My appointment received the sanction of the Admiralty": why Charles Darwin really was the naturalist on HMS Beagle.

Science.gov (United States)

van Wyhe, John

2013-09-01

For decades historians of science and science writers in general have maintained that Charles Darwin was not the 'naturalist' or 'official naturalist' during the 1831-1836 surveying voyage of HMS Beagle but instead Captain Robert FitzRoy's 'companion', 'gentleman companion' or 'dining companion'. That is, Darwin was primarily the captain's social companion and only secondarily and unofficially naturalist. Instead, it is usually maintained, the ship's surgeon Robert McCormick was the official naturalist because this was the default or official practice at the time. Although these views have been repeated in countless accounts of Darwin's life, this essay aims to show that they are incorrect. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

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

1984-01-01

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

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

International Nuclear Information System (INIS)

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

1988-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1988-12-01

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

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

Science.gov (United States)

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

2016-02-01

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

Absorption and pharmacokinetics of grapefruit flavanones in beagles.

Science.gov (United States)

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

2007-07-01

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

Reproductive ability of female dogs (beagles) surviving a single, midlethal, whole-body x-ray exposure

International Nuclear Information System (INIS)

Andersen, A.C.; Rosenblatt, L.S.

1976-01-01

The ability of 82 irradiated and sham-treated female beagles to whelp and wean pups was tested over a major portion of their reproductive life span. The dogs were exposed to 290 or 300 R of x rays (250 kVp) either as young pups, prior to puberty, or at puberty. Although all of the irradiated dogs were fertile and produced approximately the same number of litters as controls, litters of the pup irradiated and prepubertal irradiated dams surviving throughout the study were smaller than those of controls by 17 and 9 percent, respectively. Pup survival was also reduced relative to controls; the number of pups weaned was 38 percent lower in the pup irradiated group and 18 percent lower in the prepubertal irradiated group, as compared with controls. The overall reproductive ability of dogs irradiated at puberty was similar to that of sham-treated controls

Fos Expression in the Olfactory Pathway of High- and Low-Sexually Performing Rams Exposed to Urine from Estrous or Ovariectomized Ewes

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Mirto, AJ; Austin, KJ; Uthlaut, VA; Roselli, CE; Alexander, BM

2015-01-01

Exposure to estrous ewe urine stimulates investigation and mounting activity in sexually active but not sexually inactive rams. It was hypothesized sexual indifference may result from an inability to detect olfactory cues or an interruption of the pathway from detection of the olfactory stimulus to the motor response. Sexually active (n=4) and inactive (n=3) rams were exposed to urine from estrous ewes. An additional group of sexually active rams (n=3) were exposed to urine from ovariectomized ewes. Rams were exsanguinated following 1 h of exposure to stimulus. Neural activity was determined in tissues of interest by the presence of fos and fos-related proteins detected by immunohistochemistry procedures. Sexually active rams exposed to urine from ovariectomized ewes had more (P ≤ 0.05) fos-positive cells in the olfactory bulb, but fewer (P = 0.03) fos-positive cells in the cortical amygdala compared to sexually active rams exposed to urine from estrous ewes. Sexually inactive rams had similar (P ≥ 0.13) numbers of fos positive neurons in the olfactory bulb and medial amygdala but fewer (P ≤ 0.04) in the central amygdala, bed nucleus of the stria terminalis and the medial preoptic area compared to sexually active rams exposed to urine from estrous ewes. Sexual inactivity was not associated with decreased hypothalamic function since fos activity was similar (P ≥ 0.14) among groups in the suprachiasmatic and ventral medial nucleus. Sexual inactivity is not likely due to an impaired ability to detect or process olfactory stimuli by the main olfactory bulb and medial-cortical amygdala. Sexually inactive rams may have reduced attentiveness to sexual stimuli and/or decreased responsiveness of regions in the brain which regulate reproductive behaviors. PMID:28348447

Anti-Inflammatory Activity of Water-Soluble Polysaccharide of Agaricus blazei Murill on Ovariectomized Osteopenic Rats

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Peng Wang

2013-01-01

Full Text Available In the present study, we investigated the anti-inflammatory activity of water-soluble polysaccharide of Agaricus blazei Murill (WSP-AbM on ovariectomized osteopenic rats. The rats were administered orally WSP-AbM (200 mg/kg BW for 8 weeks. Subsequent serum maleic dialdehyde (MDA level, total antioxidant status (TAOS, nuclear factor kappa B (NF-κB level, polymorphonuclear (PMN cells level, interleukin-1β (IL-1β level, inducible nitric oxide synthase (iNOS level, tumor necrosis factor-α (TNF-α level, adhesion molecule (ICAM-1, and cyclooxygenase-2 (COX-2 were determined by enzyme linked immunosorbent assay (ELISA and immunohistochemistry, respectively. WSP-AbM administration markedly (P<0.05 decreased serum IL-1β and TNF-α levels and the expressions of ICAM-1, COX-2, and iNOS NF-κB compared with OVX rats. WSP-AbM administration alsomarkedly (P<0.05 decreased PMN infiltration. In conclusion, we observed that WSP-AbM supplementation had anti-inflammatory effects in a model of osteoporosis disease.

Effect of Low-Magnitude Whole-Body Vibration Combined with Alendronate in Ovariectomized Rats: A Random Controlled Osteoporosis Prevention Study

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Zhong, Zhao-Ming; Wu, Xiu-Hua; Huang, Zhi-Ping; Li, Wei; Ding, Ruo-Ting; Yu, Hui; Chen, Jian-Ting

2014-01-01

Background Alendronate (ALE) is a conventional drug used to treat osteoporosis. Low-magnitude whole-body vibration (WBV) exercise has been developed as a potential treatment for osteoporosis. The aim of this study was to investigate whether low-magnitude WBV could enhance the protective effect of ALE on bone properties in ovariectomized rats. Methods A total of 128 Sprague-Dawley rats were randomly divided into five groups (SHAM, OVX+VEH, OVX+WBV, OVX + ALE, OVX+WBV+ALE). The level of WBV applied was 0.3 g at 45–55 Hz for 20 min/day, 5 day/week and for 3 months. ALE was administered in dose of 1 mg/Kg once a week. Every four weeks eight rats from each group were sacrificed and their blood and both tibiae were harvested. The expression of osteocalcin and CTX in serum was measured by enzyme-linked immunosorbent assay (ELISA) and the tibiae were subjected to metaphyseal three-point bending and μCT analysis. Results Osteocalcin rose after ovariectomy and was not appreciably changed by either alendronate or WBV alone or in combination. Alendronate treatment significantly prevented an increase in CTX. WBV alone treatment did not alter this effect. Compared with the OVX+WBV group, nearly all tested indices such as the BV/TV, TV apparent, Tb.N, Tb.Th, and Conn.D were higher in the OVX+ALE group at week 12.Compared with the OVX+WBV group, certain tested indices such as BV/TV, TV apparent, Tb.N, and Con.D, were higher in the OVX+WBV+ALE group at week 12. At week 12, tibiae treated with WBV+ALE exhibited a significantly higher Fmax compared to the OVX+VEH group, and a significant difference was also found in energy absorption between the OVX+WBV+ALE and OVX+VEH groups. Conclusions Compared with the WBV, ALE was more effective at preventing bone loss and improved the trabecular architecture. However, WBV enhanced the effect of alendronate in ovariectomized rats by inducing further improvements in trabecular architecture. PMID:24796785

Development and validation of an enantioselective SFC-MS/MS method for simultaneous separation and quantification of oxcarbazepine and its chiral metabolites in beagle dog plasma.

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Yang, Zhichao; Xu, Xueyu; Sun, Lingxia; Zhao, Xue; Wang, Hao; Fawcett, John Paul; Yang, Yan; Gu, Jingkai

2016-05-01

A rapid and sensitive assay based on supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) has been developed and validated for the determination of oxcarbazepine (OXC) and its chiral metabolite licarbazine (Lic) in beagle dog plasma using carbamazepine as internal standard. Chiral analysis in a run time of only 3 min was performed on an ACQUITY UPC(2) ™ Trefoil™ CEL2 column (3.0 × 150 mm, 2.5 μm) at 50 °C by isocratic elution with a mobile phase of supercritical carbon dioxide (purity ≥ 99.99%) and methanol (60:40, v/v) at a flow rate of 2.3 mL/min. The assay was linear over the concentration ranges 5-1000 ng/mL for OXC and 0.5-100 ng/mL for the enantiomers of Lic with corresponding lower limits of quantitation of 5 ng/mL and 0.5 ng/mL. Intra- and inter-day precisions were in the range 0.78-14.14% with accuracies in the range -10.80% to 0.42%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of 16 mg/kg OXC as Trileptal(@) tablets to beagle dogs. Copyright © 2016. Published by Elsevier B.V.

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

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Hui Liu

2016-02-01

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

Effects of β-estradiol on cold-sensitive receptor channel TRPM8 in ovariectomized rats.

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Kubo, Takuro; Tsuji, Shunichiro; Amano, Tsukuru; Yoshino, Fumi; Niwa, Yoko; Kasahara, Kyoko; Yoshida, Saori; Mukaisho, Ken-Ichi; Sugihara, Hiroyuki; Tanaka, Sachiko; Kimura, Fuminori; Takahashi, Kentaro; Murakami, Takashi

2017-10-30

Transient receptor potential cation channel subfamily M member 8 (TRPM8) is associated with sensitivity to cold sensation in mammals. A previous study demonstrated that TRPM8 was overexpressed in the skin of ovariectomized (OVX) rats due to the loss of estrogen. In the present study, we investigated whether estrogen replacement restricts overexpression of the TRPM8 channel in the skin of OVX rats. We divided 15 Sprague Dawley rats into three groups: a non-operated group (NON-OPE), an ovariectomy group (OVX), and a group subjected to estrogen replacement during 4 weeks beginning 7 days after ovariectomy (OVX + E2). Five weeks later, TRPM8 channel mRNA and protein in lumbar skin were quantified by real-time RT-PCR, protein ELISA, and immunohistochemistry. The OVX + E2 group exhibited a trend for decreased expression of the TRPM8 channel in the lumbar skin in comparison with the OVX group, whereas ELISA data and immunohistochemistry data and immunohistochemistry graphs relating to TRPM8 protein did not show any obvious differences between the OVX group and the OVX + E2 group. Estrogen replacement may restrict the overexpression of TRPM8 in the dermis of OVX rats.

Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture

International Nuclear Information System (INIS)

Bhattacharyya, M.H.; Whelton, B.D.; Stern, P.H.; Peterson, D.P.

1988-01-01

Loss of bone mineral after ovariectomy was studied in mice exposed to dietary cadmium at 0.25, 5, or 50 ppm. Results show that dietary cadmium at 50 ppm increased bone mineral loss to a significantly greater extent in ovariectomized mice than in sham-operated controls. These results were obtained from two studies, one in which skeletal calcium content was determined 6 months after ovariectomy and a second in which 45 Ca release from 45 Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with 45 Ca-prelabeled fetal rat limb bones in culture demonstrated that Cd at 10 nM in the medium, a concentration estimated to be in the plasma of mice exposed to 50 ppm dietary Cd, strikingly increased bone resorption. These in vitro results indicate that cadmium may enhance bone mineral loss by a direct action on bone. Results of the in vivo studies are consistent with a significant role of cadmium in the etiology of Itai-Itai disease among postmenopausal women in Japan and may in part explain the increased risk of postmenopausal osteoporosis among women who smoke

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

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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.

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

International Nuclear Information System (INIS)

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

1978-01-01

The toxicity of 144 Ce inhaled in fused aluminosilicate particles by 8- 10.5-year-old dogs is being investigated to provide information on age-related differences in the response of older members of the human population to accidental inhalation of radioactive aerosols. These data on aged dogs will be compared to the results of similar studies of dogs exposed at approximately 3 months or 12 to 14 months of age. Six blocks of five female dogs each have been divided into four exposure levels with mean initial lung burdens of 7.2, 14, 28, and 57 μCi 144 Ce/kg body weight. Six blocks of four male dogs each have been divided into three exposure levels with mean initial lung burdens of 7.2, 14, and 28 μCi 144 Ce/kg body weight. Controls in each block were exposed to fused aluminosilicate particles containing stable cerium. Nineteen dogs with initial lung burdens ranging from 14 to 75 μCi 144 Ce/kg body weight and cumulative doses to lung of from 20,000 to 74,000 rads have died or were euthanized 197 to 1849 days after exposure with clinicopathologic findings of radiation pneumonitis and pulmonary fibrosis. Eight control dogs have died. Pulmonary retention of the inhaled 144 Ce was similar to that observed previously in dogs exposed at 18 to 22 months of age in a radiation dose pattern study. Serial observations are continuing on the nine surviving 144 Ce-exposed and four control dogs

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

International Nuclear Information System (INIS)

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

1979-01-01

The toxicity of relatively insoluble 144 Ce inhaled by 8- to 10.5-year-old dogs is being investigated to provide information on age-related differences in the response of dogs to lung burdens of this fission product. These data on aged dogs will be compared to the results of similar studies of dogs exposed at approximately 3 months or 12 to 14 months of age. Forty-two dogs were exposed, nose only, to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 2.2 to 75 μCi/kg body weight and 12 control dogs were exposed to nonradioactive fused aluminosilicate particles. To date, 37 dogs have died or were euthanized 197 to 2375 days after inhalation of 144 Ce. The prominent findings were radiation pneumonitis in 19 dogs that died at early times with cumulative doses to lung of 20 000 to 74 000 rads and neoplastic disease in six of 14 dogs that died 943 days after exposure or later. Pulmonary tumors were found in four of these dogs. However, only one of these tumors killed the dog. No hemangiosarcomas have been observed in this study. This result is in contrast to the results with immature or young adult dogs exposed to 144 Ce. The difference may be a dose-related phenomenon since dogs which developed hemangiosarconomas had greater initial lung burdens of 144 Ce. Aged dogs with similar burdens died at earlier times with radiation pneumonitis. Observations are continuing on the five surviving 144 Ce-exposed and four control dogs

Toxicity of inhaled 91YCl3 in beagle dogs. VII

International Nuclear Information System (INIS)

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

1974-01-01

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

Toxicity of inhaled 91YCl3 in beagle dogs. X

International Nuclear Information System (INIS)

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

1976-01-01

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

Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles

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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

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

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Wang, Lanlei; Guan, Aizhong; Shi, Han; Chen, Yangxi; Liao, Yunmao

2009-09-01

The aim of the present study was to investigate the effect of porous biphasic calcium phosphate nanocomposite (nanoBCP) scaffolds bioceramic. Alveolar bone defects were surgically created bilaterally at the buccal aspects of the upper second premolar in fourteen beagle dogs. After root conditioning with ethylenediaminetetraacetate (EDTA), nanoBCP was randomly filled in the defects and nothing was put into the contralaterals as controls. Dogs were killed at the 12th weeks. Histological observations were processed through a light microscopy. The results revealed that a great amount of functional periodontal fissures formed in the defects in the nanoBCP groups while minimal bone took shape in the controls. In this study, nanoBCP has proved to work well as a biocompatible and osteoconductive scaffold material to promote periodontal regeneration effectively.

Antagonism of brain insulin-like growth factor-1 receptors blocks estradiol effects on memory and levels of hippocampal synaptic proteins in ovariectomized rats

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Nelson, Britta S.; Springer, Rachel C.; Daniel, Jill M.

2013-01-01

Rationale Treatment with estradiol, the primary estrogen produced by the ovaries, enhances hippocampus-dependent spatial memory and increases levels of hippocampal synaptic proteins in ovariectomized rats. Increasing evidence indicates that the ability of estradiol to impact the brain and behavior is dependent upon its interaction with insulin-like growth factor-1 (IGF-1). Objectives The goal of the current experiment was to test the hypothesis that the ability of estradiol to impact hippocampus-dependent memory and levels of hippocampal synaptic proteins is dependent on its interaction with IGF-1. Methods Adult rats were ovariectomized and implanted with estradiol or control capsules and trained on a radial-maze spatial memory task. After training, rats were implanted with intracerebroventricular cannulae attached to osmotic minipumps (flow rate 0.15 μl/hr). Half of each hormone treatment group received continuous delivery of JB1 (300 μg/ml), an IGF-1 receptor antagonist, and half received delivery of aCSF vehicle. Rats were tested on trials in the radial-arm maze during which delays were imposed between the 4th and 5th arm choices. Hippocampal levels of synaptic proteins were measured by western blotting. Results Estradiol treatment resulted in significantly enhanced memory. JB1 blocked that enhancement. Estradiol treatment resulted in significantly increased hippocampal levels of postsynaptic density protein 95 (PSD-95), spinophilin, and synaptophysin. JB1 blocked the estradiol-induced increase of PSD-95 and spinophilin and attenuated the increase of synaptophysin. Conclusions Results support a role for IGF-1 receptor activity in estradiol-induced enhancement of spatial memory that may be dependent on changes in synapse structure in the hippocampus brought upon by estradiol/IGF-1 interactions. PMID:24146138

Estrogen replacement avoids the decrease of bladder innervations in ovariectomized adult virgin rats: in vivo stereological study.

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de Fraga, Rogerio; Palma, Paulo; Dambros, Miriam; Riccetto, Cassio L Z; Mandarim-de-Lacerda, Carlos; Miyaoka, Ricardo

2009-05-01

The authors quantified the nerve fibers in the bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old). Group 1: remained intact; Group 2: underwent bilateral ovariectomy, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 3: sham-operated, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 4: bilateral ovariectomy, and after 30 days was started on subcutaneous injection of 17β-estradiol (10 μg/kg body weight) for 90 days. S-100 was used to stain nerves myelinized fibers on paraffin rat bladder sections. The G-50 grid system was used to quantitatively analyze the fibers. Long-term estrogen deprivation caused significant changes in bladder innervations, which can be characterized by a decreased number of nerve fibers by 65% (p < 0.001).

Toxicity of inhaled 90SrCl2 in Beagle dogs. XIII

International Nuclear Information System (INIS)

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

1979-01-01

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

Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS.

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Paris, Jason J; Fenwick, Jason; McLaughlin, Jay P

2014-05-01

Increased anxiety is co-morbid with human immunodeficiency virus (HIV) infection. Actions of the neurotoxic HIV-1 regulatory protein, Tat, may contribute to affective dysfunction. We hypothesized that Tat expression would increase anxiety-like behavior of female GT-tg bigenic mice that express HIV-1 Tat protein in the brain in a doxycycline-dependent manner. Furthermore, given reports that HIV-induced anxiety may occur at lower rates among women, and that the neurotoxic effects of Tat are ameliorated by sex steroids in vitro, we hypothesized that 17β-estradiol and/or progesterone would ameliorate Tat-induced anxiety-like effects. Among naturally-cycling proestrous and diestrous mice, Tat-induction via 7days of doxycycline treatment significantly increased anxiety-like responding in an open field, elevated plus maze and a marble-burying task, compared to treatment with saline. Proestrous mice demonstrated less anxiety-like behavior than diestrous mice in the open field and elevated plus maze, but these effects did not significantly interact with Tat-induction. Among ovariectomized mice, doxycycline-induced Tat protein significantly increased anxiety-like behavior in an elevated plus maze and a marble burying task compared to saline-treated mice, but not an open field (where anxiety-like responding was already maximal). Co-administration of progesterone (4mg/kg), but not 17β-estradiol (0.09mg/kg), with doxycycline significantly ameliorated anxiety-like responding in the elevated plus maze and marble burying tasks. When administered together, 17β-estradiol partially antagonized the protective effects of progesterone on Tat-induced anxiety-like behavior. These findings support evidence of steroid-protection over HIV-1 proteins, and extend them by demonstrating the protective capacity of progesterone on Tat-induced anxiety-like behavior of ovariectomized female mice. Copyright © 2014 Elsevier Inc. All rights reserved.

Upregulation of adipose 11-beta-hydroxysteroid dehydrogenase type 1 expression in ovariectomized rats is due to obesity rather than lack of estrogen.

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Paulsen, Søren K; Nielsen, Maria P; Richelsen, Bjørn; Bruun, Jens M; Flyvbjerg, Allan; Pedersen, Steen B

2008-04-01

Increased tissue activity of cortisol induced by the activation of inert cortisone to active cortisol through 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) may play a role in the metabolic syndrome. We recently found that 11beta-HSD1 in subcutaneous adipose tissue (AT) was lower in lean women compared with lean men. Estrogen suppresses hepatic and renal 11beta-HSD1 in rats; hence we investigated the in vitro effect of estrogen on human and rat AT, and the in vivo effects on rat AT 11beta-HSD1 expression. Wistar rats were divided into four groups of eight animals. One group was sham-operated (controls) and others were ovariectomized (OVX). One OVX group was left untreated (OVX-E), another (OVX+E) received estrogen treatment, and one received a hypo-caloric diet (OVX-E+D), matching the weight gain of the control group. AT from women undergoing liposuction or surgery and from killed male and female rats were incubated with estrogen alone or in the presence of IL-1beta. Gene expressions were determined by real-time reverse transcriptase PCR. Ovariectomy resulted in a 280% increase in adipose 11beta-HSD1 expression P < 0.05). 11beta-HSD1 expression in the (OVX+E)-group was significantly reduced compared with the nonsubstituted group (P < 0.05). 11beta-HSD1 expression in the (OVX-E+D)-group was reduced significantly (P < 0.05) when compared with the level of the estrogen-substituted group. No significant differences between the control group, the (OVX+E)-group, and the (OVX-E+D)-group were found. In the in vitro studies, no direct effect of estrogen on adipose 11beta-HSD1 was found. The upregulation of 11beta-HSD1 in ovariectomized rats was most likely due to changes in body composition rather than lack of estrogen.

Quantification of a Novel Photosensitizer of Chlorin e6-C15-Monomethyl Ester in Beagle Dog Plasma Using HPLC: Application to Pharmacokinetic Studies

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Xiuxiu Li

2017-04-01

Full Text Available Chlorin e6-C15-monomethyl ester (CMME is a novel photosensitizer, which is synthetized from the degradation products of silkworm excrement. Preclinical studies on the promising photosensitizer CMME are necessary to determine its therapeutic efficacy and druglikeness. A high-performance liquid chromatography with UV detection (HPLC–UV method was established for the determination of CMME in beagle dog plasma. The sample preparation involved a protein-precipitation method with acetonitrile after the addition of tanshinone IIA as an internal standard (IS. CMME and the IS were separated on a Diamonsil C18 (2 column (100 mm × 4.6 mm, 5 μm with a isocratic system of methanol–water containing 20 mM ammonium acetate with 0.3% glacial acetic acid (85:15, v/v. The flow rate was 1.0 mL/min with UV detection using a wavelength of 400 nm. The method was sensitive enough with a lower limit of quantitation (LLOQ of 0.05 μg/mL and had a good linearity (r2 > 0.999 over the linear range of 0.05–5.00 μg/mL. The intra-day and inter-day accuracies ranged from 98.5% to 102.8% and precisions (RSD were within 6.8%. The validated method was successfully applied to the pharmacokinetic study of CMME after intravenous administration of single and multiple doses in beagle dogs.

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

International Nuclear Information System (INIS)

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

1977-01-01

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

The folic acid combined with 17-β estradiol produces antidepressant-like actions in ovariectomized rats forced to swim.

Science.gov (United States)

Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

2011-01-15

Folic acid or 17-β estradiol produces antidepressant effects, either alone or combined with several antidepressants. However, the antidepressant-like actions of folic acid combined with 17-β estradiol in the forced swimming test (FST) have not been tested before. Thus, in the present study, ovariectomized female rats received folic acid (5.0 nmol/i.c.v., Pfluoxetine (20.0mg/kg, Pswimming behavior when they were tested in the FST. Combination of subthreshold doses of folic acid (2.5 nmol/i.c.v.; or 25.0mg/kg, p.o.) with subthreshold doses of 17-β estradiol (5.0 μg/rat, Pfluoxetine (15.0mg/kg, Pfluoxetine in the FST reduced immobility in the FST. These antidepressant-like actions probably were due to modifications of the serotonergic system since swimming behavior was increased and these effects were cancelled by ketanserin. Copyright © 2010 Elsevier Inc. All rights reserved.

DOE life-span radiation effects studies in experimental animals at University of Utah Division of Radiobiology

International Nuclear Information System (INIS)

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

1986-01-01

The Radiobiology Laboratory at the University of Utah compared the long-term biological effects of 226 Ra and 239 Pu in adult beagles. The program includes the investigation of other radionuclides. More recently, groups of juvenile and aged beagles were added to the study to investigate the influence of age at exposure. These studies involved single intravenous injection of radionuclides to small groups of beagles, in graded doses from levels at which no effects were expected up to levels where a 100% incidence of bone tumors was sometimes found. Some of the principal effects were bone tumors, fractures, and other skeletal alterations observed radiographically and histologically; emphasis was placed on the detection of precancerous changes, hematological changes, and changes related to aging. Emphasis was also placed on metabolic and autoradiographic studies necessary for good radiation dosimetry

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

International Nuclear Information System (INIS)

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

1986-01-01

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

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

International Nuclear Information System (INIS)

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

1986-01-01

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

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

OpenAIRE

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

2017-01-01

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

Tissue characteristics of high- and low-incidence plutonium-induced osteogenic sarcoma sites in life-span beagles

International Nuclear Information System (INIS)

Miller, S.C.; Jee, W.S.S.; Smith, J.M.; Wronski, T.J.

1986-01-01

On the basis of information gathered from the 239 Pu life-span study in beagles at the University of Utah, the tissue features were found to be characteristic of high-incidence bone-tumor sites compared to low-incidence sites included more hematopoietic tissues in the bone marrow; greater trabecular bone mass; greater bone remodeling rates; greater mineral apposition rates; greater density and activity of bone surface cells; greater density of putative bone-cell precursors; greater initial uptake of plutonium on bone surfaces; and greater marrow vascular volumes and a venous sinusoidal bed. Although most of these studies are not yet complete, the information being collected should contribute to our understanding of the mechanisms of radiation-induced osteogenic sarcomas. This should aid in predicting the types and characteristics of osseous tissues where radiation-induced osteogenic sarcomas may arise in humans. 25 refs., 4 figs., 3 tabs

Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (I) Biochemical and Pharmacodynamic Study on Maca using Clinical Laboratory Model on Ovariectomized Rats.

Science.gov (United States)

Meissner, H O; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Mscisz, A; Kedzia, B; Lowicka, A; Reich-Bilinska, H; Kapczynski, W; Barchia, I

2006-09-01

Ovariectomized rats were used in a model laboratory study to examine biochemical and pharmacodynamic effects of pre-gelatinized organic preparation of Lepidium peruvianum Chacon (Maca-GO). Biochemical and Pharmacodynamic effects of Maca-GO (250 mg Maca-GO per kg body weight (bw) administered by intubation twice daily) were assessed in a 28 day model laboratory study on ovariectomized (by laparoscopy) Wistar rats with pharmacodynamic tests performed at the conclusion of the trial followed by blood collection for morphology and biochemical tests. Toxicity of Maca-GO used in the study was determined in bioassay on mice and rats. Anti-depressive function (Porsolt's test) and anxiolytic sedative and cognitive effects (using elevated-plus maze, locomotor activity and passive avoidance tests) were assessed against control (laparotomized female rats with intact ovaries). In addition to blood morphology, the following blood serum constituents were analyzed: Estrogen (E2), Progesterone (PGS), Cortisol (CT), Adrenocorticotropic Hormone (ACTH), Thyroid Hormones (TSH, T3, and T4), Iron (Fe) and lipid profile (Triglycerides, Total Cholesterol, LDL, HDL). Analytically-determined non-toxic status of Maca-GO was confirmed in bioassays when applied to mice and rats at levels of 0.5 and up to 15mg/kg bw which shows it safe use in humans with the LD50>15 mg/kg bw. Maca-GO showed a distinctive, (PMaca-GO on sex hormone levels show its potential as a safe preparation for use in correcting physiological symptoms characteristic in postmenopausal stage with an indication of potentially even more value for its use in pre-menopausal women.

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

Science.gov (United States)

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

2006-08-01

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

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

International Nuclear Information System (INIS)

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

1980-01-01

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

A tricalcium phosphate/polyether ether ketone anchor bionic fixation device for anterior cruciate ligament reconstruction: Safety and efficacy in a beagle model.

Science.gov (United States)

Mao, Genwen; Qin, Zili; Li, Zheng; Li, Xiang; Qiu, Yusheng; Bian, Weiguo

2018-05-02

The goal of this study was to develop a bionic fixation device based on the use of a tricalcium phosphate/polyether ether ketone anchor and harvesting of the ulnar carpal flexor muscle tendon for application as a ligament graft in a beagle anterior cruciate ligament (ACL) reconstruction model, with the goal of accelerating the ligament graft-to-bone tunnel healing and providing a robust stability through exploration of this new kind of autologous ligament graft. The safety and efficacy of this fixation device were explored 3 and 6 months after surgery in a beagle ACL reconstruction model using biomechanical tests and comprehensive histological observation. The data were compared using a two-tailed Student's t test and a paired t test. A p value <0.05 was defined as statistically significant. All the models were successfully established. This fixation device possessed the excellent mechanical properties for ACL reconstruction. A comprehensive histological observation revealed that a cartilage layer was visible in the transition zone between the tendon and bone interface at both 3 and 6 months postoperation. The trabecular of the new bone was observed six months after surgery and was found to be similar to a direct connection. This fixation technique provided not only a robust primary mechanical fixation but also a bionic fixation for long-term knee joint stability by accelerating the healing of the tendon to the bone tunnel, showing a high potential for use in clinical practice. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

Vitex agnus-castus L. (Verbenaceae) Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats.

Science.gov (United States)

Moreno, Franciele Neves; Campos-Shimada, Lilian Brites; da Costa, Silvio Claudio; Garcia, Rosângela Fernandes; Cecchini, Alessandra Lourenço; Natali, Maria Raquel Marçal; Vitoriano, Adriana de Souza; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

2015-01-01

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.

Vitex agnus-castus L. (Verbenaceae Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats

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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.

Vitex agnus-castus L. (Verbenaceae) Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats

Science.gov (United States)

Moreno, Franciele Neves; Campos-Shimada, Lilian Brites; da Costa, Silvio Claudio; Garcia, Rosângela Fernandes; Cecchini, Alessandra Lourenço; Natali, Maria Raquel Marçal; Vitoriano, Adriana de Souza; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

2015-01-01

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. PMID:25954315

Retaining Residual Ovarian Tissue following Ovarian Failure Has Limited Influence on Bone Loss in Aged Mice

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Zelieann R. Craig

2010-01-01

Full Text Available Previous work showed that retaining residual ovarian tissue protects young mice from accelerated bone loss following ovarian failure. The present study was designed to determine whether this protection is also present in aged animals. Aged (9–12 months C57BL/6Hsd female mice were divided into: CON (vehicle, VCD (160 mg/kg; 15d, or OVX (ovariectomized. Lumbar BMD was monitored by DXA and μCT used to assess vertebral microarchitecture. BMD was not different between VCD and CON at any time point but was lower (P<.05 than baseline, starting 1 month after ovarian failure in VCD and OVX mice. Following μCT analysis there were no differences between CON and VCD, but OVX mice had lower bone volume fraction, trabecular thickness, and a trend for decreased connectivity density. These findings provide evidence that retention of residual ovarian tissue may protect aged follicle-depleted mice from accelerated bone loss to a lesser extent than that observed in young mice.

Transsphenoidal hypophysectomy in beagle dogs: evaluation of a microsurgical technique

Energy Technology Data Exchange (ETDEWEB)

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

1997-07-15

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

Transsphenoidal hypophysectomy in beagle dogs: evaluation of a microsurgical technique

International Nuclear Information System (INIS)

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

1997-01-01

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

Distraction-like phenomena in maxillary bone due to application of orthodontic forces in ovariectomized rats

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Apostolos I Tsolakis

2012-01-01

Full Text Available Background: Orthodontic forces may not only influence the dentoalveolar system, but also the adjacent and surrounding cortical bone. Aim: Since there is very limited information on this issue, we aimed to study the possible changes in maxillary cortical bone following the application of heavy orthodontic forces in mature normal and osteoporotic rats. Materials and Methods: Twenty-four 6-month-old female rats were selected and divided into an ovariectomized group and a normal group. In both groups, the rats were subjected to a 60 grFNx01 orthodontic force on the upper right first molar for 14 days. Results: In both groups, histological sections showed that the application of this force caused hypertrophy and fatigue failure of the cortical maxillary bone. The osteogenic reaction to distraction is expressed by the formation of subperiosteal callus on the outer bony side, resembling that seen in distracted bones. Conclusion: From this study we concluded that heavy experimental orthodontic forces in rats affect the maxillary cortical bone. The osteogenic reaction to these forces, expressed histologically by subperiosteal callus formation, is similar to that seen in distraction osteogenesis models.

The effects of hyaluronic acid vaginal gel on the vaginal epithelium of ovariectomized rats.

Science.gov (United States)

Liu, Shuai-Bin; Liu, Shao-Li; Gan, Xiao-Ling; Zhou, Qin; Hu, Li-Na

2015-03-01

Hyaluronic acid is one of the best materials of water retention which can be used in vaginal atrophy. This study is to evaluate the role and mechanism of the hyaluronic acid vaginal gel (Hyalofemme) in the vaginal epithelium of ovariectomized rats. Sixty SD rats were randomly divided into control group (Sham ovariectomy, Sham-OVX), tendency group (ovariectomy, OVX), and experiment group (ovariectomy+Hyalofemme, OVX+Hyalofemme). The hyaluronic acid vaginal gel was administered local vaginal therapy to the experiment group with cytologicaly confirmed vaginal atrophy. The doses were adjusted by animal weight according to human dosage. After daily treatment for 14 days, VEGF and P-AKT activations were detected by Western blot in the experiment group. The hyaluronic acid vaginal gel proved to be very effective in the cytological reversal of vaginal atrophy but did not increase uterine weight. Vaginal microecosystem indicators were negative in the control group and the experiment group. By contrast, the indicators were positive in the tendency group. Hyaluronic acid vaginal gel is effective in the reversal of vaginal atrophy and is beneficial for improving vaginal microecosystem in the postmenopausal rat model. The hyaluronic acid vaginal gel can also improve the repair capacity of the vaginal epithelium.

Characterisation of tramadol, morphine and tapentadol in an acute pain model in Beagle dogs.

Science.gov (United States)

Kögel, Babette; Terlinden, Rolf; Schneider, Johannes

2014-05-01

To evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive pain, the tail-flick model in dogs. Prospective part-randomized pre-clinical research trial. Fifteen male Beagle dogs (HsdCpb:DOBE), aged 12-15 months. On different occasions separated by at least 1 week, dogs received intravenous (IV) administrations of tramadol (6.81, 10.0 mg kg(-1) ), tapentadol (2.15, 4.64, 6.81 mg kg(-1) ) or morphine (0.464, 0.681, 1.0 mg kg(-1) ) with subsequent measurement of tail withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1). Tapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg(-1) and 0.71 mg kg(-1) , respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociceptive effect of tramadol in this experimental pain model in dogs. Different breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting. This contrasts to many clinical situations described in the literature, where tramadol appears to provide useful analgesia in dogs for post-operative pain relief and in more chronically pain states. © 2014 Association of Veterinary

The effects of soy and tamoxifen on apoptosis in the hippocampus and dentate gyrus in a pentylenetetrazole-induced seizure model of ovariectomized rats.

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Ebrahimzadeh-Bideskan, Ali Reza; Mansouri, Somaieh; Ataei, Mariam Lale; Jahanshahi, Mehrdad; Hosseini, Mahmoud

2018-03-01

The effects of tamoxifen and soy on apoptosis of the hippocampus and dentate gyrus of ovariectomized rats after repeated seizures were investigated. Female rats were divided into: (1) Control, (2) Sham, (3) Sham-Tamoxifen (Sham-T), (4) Ovariectomized (OVX), (5) OVX-Tamoxifen (OVX-T), (6)OVX-Soy(OVX-S) and (7) OVX-S-T. The animals in the OVX-S, OVX-T and OVX-S-T groups received soy extract (60 mg/kg; i.p.), tamoxifen (10 mg/kg) or both for 2 weeks before induction of seizures. The animals in these groups additionally received the mentioned treatments before each injection of pentylenetetrazole (PTZ; 40 mg/kg) for 6 days. The animals in the Sham and OVX groups received a vehicle of tamoxifen and soy. A significant decrease in the seizure score and TUNEL-positive neurons was seen in the OVX group compared to the Sham (P < 0.001). The animals in both the OVX-T and OVX-S groups had a significantly higher seizure score as well as number of TUNEL-positive neurons compared to the OVX group (P < 0.01-P < 0.001). Co-treatment of the OVX rats by the extract and tamoxifen decreased the seizure score and number of TUNEL-positive neurons compared to OVX-S (P < 0.001). Treatment of the OVX rats by either soy or tamoxifen increased the seizure score as well as the number of TUNEL-positive neurons in the hippocampal formation. Co-administration of tamoxifen and soy extract inhibited the effects of the soy extract and tamoxifen when they were administered alone. It might be suggested that both soy and tamoxifen have agonistic effects on estrogen receptors by changing the seizure severity.

Genistein induces estrogen-like effects in ovariectomized rats but fails to increase cardiac GLUT4 and oxidative stress.

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Al-Nakkash, Layla; Markus, Brandon; Batia, Lyn; Prozialeck, Walter C; Broderick, Tom L

2010-12-01

This study aimed to determine whether a 2-week genistein treatment induced estrogen-like effects in ovariectomized (OVX) Sprague-Dawley rats, after 2 weeks of subcutaneous genistein injections (250 mg/kg of body weight/day). Uterine weight, uterine-to-body weight ratio, femur weight, and femur-to-body weight ratio were all significantly increased with genistein in OVX rats. Body weight was significantly decreased with genistein in OVX rats. Genistein had no effect on the weights of heart, heart-to-body ratio, and fat pad but significantly decreased heart rate and pulse pressure. Genistein had no effect on cardiac GLUT4 protein, oxidative stress, plasma glucose, nonesterified fatty acids, or low-density lipoprotein levels; however, plasma insulin levels were significantly increased. Our results show that a 2-week genistein treatment produced favorable estrogen-like effects on some physical and physiological characteristics in OVX rats. However, based on our experimental conditions, the effects of genistein were not associated with changes in cardiac GLUT4 or oxidative stress.

The effect of steroid hormones on the mRNA expression of oct4 and sox2 in uterine tissue of the ovariectomized mice model of menopause

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Marzieh Davoudi

2016-07-01

Full Text Available Background: The uterus is a dynamic tissue responding to hormonal changes during reproductive cycles. As such, uterine stem cells have been studied in recent years. Transcription factors oct4 and sox2 are critical for effective maintenance of pluripotent cell identity. Objective: The present research evaluated the mRNA expression of oct4 and sox2 in the uterine tissues of ovariectomized mice treated with steroid hormones. Materials and Methods: In this experimental study, adult virgin female mice were ovariectomized and treated with estradiol 17β (E2, progesterone (P4, and a combination of E2 and P4 (E2 & P4 for 5 days. Uterine tissues were removed, and immunofluorescent (IF staining and quantitative real-time PCR of oct4 and sox2 markers were performed. Results: IF showed oct4 and sox2 expression in the uterine endometrium and myometrium among all groups. The mRNA expression of oct4 (p=0.022 and sox2 (p=0.042 in the E2-treated group significantly were decreased compared to that in the control group. By contrast, the mRNA expression of oct4 and sox2 in the P4 (p=0.641 and 0.489 respectively and E2 & P4-treated groups (p=0.267 and 0.264 respectively did not show significant differences compared to the control group. Conclusion: The results indicate ovarian steroid hormones change the expression of oct4 and sox2 in the mice uterine tissues, which suggest the involvement of steroid hormonal regulation in uterine stem cells.

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

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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.

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

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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.

Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs.

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Marsella, Rosanna; Ahrens, Kim; Sanford, Rachel

2018-02-01

IL-31 is a cytokine that is believed to play an important role in atopic dermatitis (AD). IL-31 levels positively correlate with disease severity in children with AD. Currently, there is no study that has investigated such a correlation in atopic dogs. The purpose of this study was to evaluate the correlation between IL-31 serum levels and severity of dermatitis. It was hypothesized that a positive correlation exists between severity of AD and circulating levels of IL-31. Sixteen atopic beagles experimentally sensitized to house dust mites. Atopic beagles were exposed to dust mites epicutaneously twice weekly for four weeks. Severity of dermatitis was scored by the Canine Atopic Dermatitis and Extent Severity Index, 3 rd iteration (CADESI-03) on days 0 and 28. Blood samples were taken on days 0 and 28 to measure serum IL-31 using a commercially available ELISA. Correlation between CADESI-03 scores and serum IL-31 levels was not detected on day 0 (Pearson, r = -0.2609, P = 0.3291). After flare-up of dermatitis was induced with allergen exposure, a significant positive correlation was detected between serum IL-31 and CADESI-03 on Day 28 (r = 0.6738, P = 0.004). Positive correlation was detected in active disease between severity of dermatitis and circulating levels of IL-31. Additional studies are needed to investigate this correlation in other breeds of dogs and to test whether circulating levels of IL-31 may predict clinical response to biological agents aimed at IL-31. © 2017 ESVD and ACVD.

GMP-grade α-TEA lysine salt: a 28-Day oral toxicity and toxicokinetic study with a 28-Day recovery period in Beagle dogs

International Nuclear Information System (INIS)

Guerrouahen, Bella S.; Hahn, Tobias; Alderman, Zefora; Curti, Brendan; Urba, Walter; Akporiaye, Emmanuel T.

2016-01-01

Alpha-tocopheryloxyacetic acid (α-TEA) is a semi-synthetic derivative of naturally occurring vitamin E (alpha-tocopherol) that can be delivered via an oral route. Preclinical in vitro and in vivo data demonstrated that α-TEA is a potent anti-tumor agent with a safe toxicity profile in mice. We report a comprehensive study to evaluate the toxokinetics of good manufacturing practice (GMP)-grade α-TEA in dogs after daily oral administration for 28 days, followed by a 28-day recovery period. Male and female beagle dogs received capsules of α-TEA Lysine Salt at doses of 100, 300, 1500 mg/kg/day. α-TEA plasma levels were determined by high-performance liquid chromatography (HPLC) with mass spectrometric detection. During the treatment, animals were observe for clinical signs, food consumption, body weight, and subjected to ophthalmoscopic, and electrocardiographic assessments. At the end of the dosing period, blood was taken and toxicokinetic analyses and histopathology assessments were performed when animals were necropsied. Our findings showed that there was no α-TEA-related mortality or moribundity. At the highest dose, increases in white blood cells and fibrinogen levels were observed. These levels returned to normal at the end of the recovery period. Histopathological evaluation of major organs revealed no significant lesions related to α-TEA-treatment. We demonstrate that for designing clinical trials in patients, the highest non-severely toxic dose (HNSTD) of α-TEA is 1500 mg/kg/day in Beagle dogs and this data informed the design of dose-escalation studies of α-TEA in patients with advanced cancer

Development of a supercritical fluid chromatography-tandem mass spectrometry method for the determination of lacidipine in beagle dog plasma and its application to a bioavailability study.

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Geng, Yajie; Zhao, Longshan; Zhao, Juanhang; Guo, Bei; Ma, Panqin; Li, Yuanyuan; Zhang, Tianhong

2014-01-15

A simple, novel, rapid and sensitive supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method was developed and validated for the determination of lacidipine in beagle dog plasma with nimodipine as internal standard. The method involved a simple liquid-liquid extraction method with tert-butyl methyl ether. The analytes were analyzed on an Acquity UPC(2) with a HSS C18 SB column (3mm×100mm, 1.8μm) set at 50°C. The mobile phase was carbon dioxide (≥99.99%) and methanol (92:8, v/v) at a flow rate of 2ml/min, the compensation solvent was methanol with 2% formic acid at a flow rate of 0.2ml/min and a total analysis time of 1.5min for each sample. The multiple reaction-monitoring mode was used for quantification of ion transitions at m/z 473.32→354.10 and 419.00→343.10 for lacidipine and internal standard, respectively. The linearity range of proposed method was 0.10-100ng/ml) (r(2)≥0.9990). The intra- and inter-day precision values were less than 15% and accuracy was from -0.83% to 3.27% at all quality control levels. The proposed method was successfully applied to a pharmacokinetic study of lacidipine in beagle dogs. Copyright © 2013 Elsevier B.V. All rights reserved.

Circannual changes in progesterone secretion in intact ewes, luteinizing hormone secretion in ovariectomized estradiol-implanted ewes, and prolactin secretion in three sheep breeds anticipated to differ in seasonality of reproduction.

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Goff, Katherine J; Knight, James W; Pelzer, Kevin D; Akers, R Michael; Notter, David R

2013-05-01

Changes in progesterone secretion in intact ewes (7 or 9 per breed) and luteinizing hormone secretion in ovariectomized, estradiol-implanted ewes (9 or 10 per breed) were monitored for 12 mo in Suffolk, tropically adapted St. Croix, and OOS ewes. The OOS line is a composite population of 50% Dorset, 25% Rambouillet, and 25% Finnish Landrace breeding that was selected for 10 yr for ability to lamb in October and early November. Ewes were isolated from rams, and blood samples were collected twice weekly. Circulating prolactin concentrations were also determined from blood samples collected near the summer and winter solstice and vernal and autumnal equinox. Intact OOS ewes entered anestrus later, began the subsequent breeding season sooner, and had a shorter seasonal anestrus than Suffolk and St. Croix ewes (P ≤ 0.005). St. Croix ewes did not differ from Suffolk ewes in date of onset or cessation of breeding or duration of anestrus (P ≥ 0.06). Breed differences in duration of luteinizing hormone inhibition in ovariectomized ewes were essentially identical to those observed for duration of anestrous. Prolactin concentrations varied during the year: annual changes were larger in relatively seasonal Suffolk ewes than in tropically-derived St. Croix ewes (Psheep did not have a shorter seasonal anestrus than Suffolk sheep under temperate conditions and ram isolation. Copyright © 2013 Elsevier B.V. All rights reserved.

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

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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.

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

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

1984-07-01

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

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

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

2003-12-01

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

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

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

2017-07-01

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