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Sample records for beagle dogs inheritance

  1. Penis Allotransplantation in Beagle Dog.

    Science.gov (United States)

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

    2016-01-01

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

  2. Penis Allotransplantation in Beagle Dog

    Directory of Open Access Journals (Sweden)

    Yongbin Zhao

    2016-01-01

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

  3. Penis Allotransplantation in Beagle Dog

    National Research Council Canada - National Science Library

    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...

  4. 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.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2015-07-01

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

  8. Pharmacokinetic Study on Hyperoside in Beagle's Dogs

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  10. 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.

  11. 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.

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

    Science.gov (United States)

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

    2013-08-01

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

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

    OpenAIRE

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rodríguez Sosa

    2011-11-01

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

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

    Science.gov (United States)

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

    2009-09-01

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Pascale M Y Smets

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

  2. 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.

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2011-10-01

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

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

    Science.gov (United States)

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

    2017-03-14

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    OpenAIRE

    2015-01-01

    The objective of the study was to assess the effects of a dog-appeasing pheromone (DAP) collar in reducing sound-induced fear and anxiety in a laboratory model of thunderstorm simulation. Twenty-four beagle dogs naïve to the current test were divided into two treatment groups (DAP and placebo) balanced on their fear score in response to a thunderstorm recording. Each group was then exposed to two additional thunderstorm simulation tests on consecutive days. Dogs were video-assessed by a train...

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

    Directory of Open Access Journals (Sweden)

    Lim Chung-San

    2010-09-01

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

  11. 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.

  12. N-dephenylation of CERM 3517 (mociprazine) in beagle dogs. A mass spectrometric determination.

    Science.gov (United States)

    Pognat, J F; Enreille, A; Chabard, J L; Busch, N; Berger, J A

    1986-01-01

    CERM 3517 (mociprazine), a new antiemetic compound, was administered orally at 10 mg/kg twice a day for 4 days to six Beagle dogs in order to identify the major metabolite. Mass spectrometric comparison of this metabolite and a synthesized reference compound (CERM 4082) showed that both had identical structures. The metabolite originated from cleavage of the aromatic moiety. After iv administration of CERM 3517 (0.9 mg/kg) and CERM 4082 (0.6 mg/kg) to five beagle dogs, 13% and 56% of the dose, respectively, were eliminated in the urine as CERM 4082 compound. It can be calculated that at least 25% of CERM 3517 was biotransformed by N-dephenylation.

  13. Ten inherited disorders in purebred dogs by functional breed groupings

    OpenAIRE

    Oberbauer, A. M.; Belanger, J. M.; Bellumori, T.; Bannasch, D.L.; Famula, T. R.

    2015-01-01

    Background Analysis of 88,635 dogs seen at the University of California, Davis Veterinary Medical Teaching Hospital from 1995 to 2010 identified ten inherited conditions having greater prevalence within the purebred dog population as compared to the mixed-breed dog population: aortic stenosis, atopy/allergic dermatitis, gastric dilatation volvulus (GDV), early onset cataracts, dilated cardiomyopathy, elbow dysplasia, epilepsy, hypothyroidism, intervertebral disk disease (IVDD), and hepatic po...

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

    Directory of Open Access Journals (Sweden)

    Jie Zhao

    2015-11-01

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

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

    Science.gov (United States)

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

    2015-11-06

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

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

    Science.gov (United States)

    2011-01-01

    In dogs Helicobacter spp. are found in all gastric regions usually localized in the surface mucus, gastric glands and parietal cells. The aim of this study was to detail the distribution of Helicobacter spp. in the fundic mucosa of asymptomatic Beagle dogs and their intracellular localization within parietal cells, in order to evaluate species-specific pathogenetic effects on gastric cells. The presence of Helicobacter spp. was investigated by immunohistochemistry, TEM, and PCR in the fundic mucosa of six Beagle dogs. Helicobacter spp. were found in all dogs examined, and H. bizzozeronii and H. felis were identified by PCR and confirmed by TEM. In the lumen of the fundic glands, co-localization was common. H. bizzozeronii was present in larger numbers than H. felis in both intraluminal and intraparietal localization. The amounts of H. bizzozeronii were similar in superficial and basal portions of the glands. H. felis was predominantly localized in the superficial portions of gastric glands but almost absent from the base. Within parietal cells, most Helicobacter organisms were intracanalicular, but intact and degenerate Helicobacter organisms were also visualized free in the cytoplasm or in secondary lysosomes. No specific degenerative lesions were found in infected parietal cells. Helicobacter organisms were also observed within macrophages in the lamina propria. In conclusion, there is a differential distribution of H. bizzozeronii and H. felis in the fundic mucosa of Beagle dogs, and their intracellular localization in parietal cells and macrophages suggests novel pathogenic scenarios for the development of immune response and maintenance of chronic gastritis in dogs. PMID:21366900

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

    Directory of Open Access Journals (Sweden)

    Lanzoni Anna

    2011-03-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Wang Wusan

    2016-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2017-02-04

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

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

    Science.gov (United States)

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

    2011-04-15

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

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

    Science.gov (United States)

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

    2011-12-01

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

  4. Antibody responses to Borrelia burgdorferi outer surface proteins C and F in experimentally infected Beagle dogs.

    Science.gov (United States)

    Callister, Steven M; LaFleur, Rhonda L; Jobe, Dean A; Lovrich, Steven D; Wasmoen, Terri L

    2015-07-01

    Antibody levels to outer surface proteins C and F (OspC and OspF, respectively) in sera collected from laboratory Beagle dogs at 1, 2, and 4 months after challenge with infected black-legged ticks (Ixodes scapularis) were determined. Each dog was confirmed by culture to harbor Borrelia burgdorferi in the skin (n = 10) or the skin and joints (n = 14). Significant levels of immunoglobulin M (Ig)M or IgG anti-OspC antibodies were detected in single serum samples from only 3 (13%) dogs. Similarly, IgM anti-OspF antibodies were detected in only 1 (4%) serum sample collected from a dog with B. burgdorferi in the skin and joints. In contrast, 4 (29%) dogs with skin and joint infections produced IgG anti-OspF antibodies after 2 months, and the response expanded to include 2 (20%) dogs with skin infection and 4 additional dogs with skin and joint infections (overall sensitivity = 62%) after 4 months. The findings failed to support the utility of OspC-based antibody tests for diagnosing canine Lyme disease, but demonstrated that dogs with B. burgdorferi colonizing joint tissue most often produced significant levels of IgG anti-OspF antibodies. Therefore, additional studies to more thoroughly evaluate the clinical utility of OspF-based antibody tests are warranted. © 2015 The Author(s).

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

    Directory of Open Access Journals (Sweden)

    Zhenbao Li

    2016-10-01

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

  6. Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Chih-Hsien Chang

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

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    Hye-Chul, Yoon

    2010-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    1986-03-01

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

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

    Institute of Scientific and Technical Information of China (English)

    陈伟平; 刘运忠; 罗甜义

    2003-01-01

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

  14. [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

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

    Directory of Open Access Journals (Sweden)

    Yuqiao Zhang

    2016-10-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

  19. Study on surgical approaches and electrode implantation of oculomotor nerve and inferior obliquus in beagle dogs.

    Science.gov (United States)

    Zhu, Ning-Xi; Meng, You-Qiang; Feng, Bao-Hui; Wang, Xu-Hui; Li, Xin-Yuan; Yang, Min; Zhu, Shu-Gan; Li, Shi-Ting

    2009-03-01

    To study the surgical anatomy and approaches of intracranial oculomotor nerve (OMN) and inferior obliquus (IO), and the methods of their electrode implantation in dogs. The research was performed on 30 adult beagle dogs at Shanghai Jiaotong University Medical College, Shanghai, China from November 2007 to August 2008. All animals were subjected to a right transfrontotemperal approach to intracranial OMN, a transconjunctival route to IO, and the neuro-stimulating and recording electrode implantation under general anaesthesia. The OMN was stimulated and the electromyography of IO recorded and analyzed with the Powerlab System. The security and reliability of the implanted electrodes were investigated. The surgical anatomy and approaches of both the OMN from its exit from midbrain to the entrance into cavernous sinus and the IO were described. Moreover, the implantation methods of OMN stimulating electrode and the electromyographic recording electrode of IO were displayed. The implanted electrodes were safe and reliable. Some electrophysiologic data of IO were obtained in the healthy dogs. Also, some perioperative precautions for intracranial and ophthalmic surgical procedures in dog were exhibited. The mortality rate of the dogs was 0%, and no operative complications were observed. With the data provided, these surgical approaches and the methods of electrode implantation offer a choice to construct an animal model for studying various aspects of OMN regeneration.

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-05-10

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

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

    Science.gov (United States)

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

    1986-02-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Yan-teng LI

    2017-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Jae-Seuk Park

    2010-12-01

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

  7. Inherited disorders of hemostasis in dogs and cats.

    Science.gov (United States)

    Barr, James W; McMichael, Maureen

    2012-05-01

    Inherited disorders of hemostasis encompass abnormalities in primary hemostasis, coagulation, and fibrinolysis resulting from genetic mutations. There is significant variation in the phenotype expressed ranging from life limiting to the absence of overt clinical signs. Von Willebrand disease is the most common primary hemostatic disorder in dogs, and hemophilia A is the most common coagulation factor disorder. The diagnosis of inherited bleeding disorders is made by functional and/or quantitative evaluation. Genetic testing has added to the knowledge base, allowing prevention through targeted breeding. Avoidance of trauma and injury is paramount in the prevention of bleeding in animals diagnosed with inherited hemostatic disorders. Current therapeutic options include platelet transfusions, broad replacement of coagulation factors (e.g., plasma), targeted factor replacement (e.g., cryoprecipitate), antifibrinolytic agents and specific factor replacement, and treatment of the symptoms (i.e., bleeding) with blood transfusions.

  8. Evaluation of spectral entropy to measure anaesthetic depth and antinociception in sevoflurane-anaesthetised Beagle dogs.

    Science.gov (United States)

    Morgaz, Juan; Granados, María del Mar; Domínguez, Juan Manuel; Navarrete, Rocío; Fernández, Andrés; Galán, Alba; Muñoz, Pilar; Gómez-Villamandos, Rafael J

    2011-06-01

    The use of spectral entropy to determine anaesthetic depth and antinociception was evaluated in sevoflurane-anaesthetised Beagle dogs. Dogs were anaesthetised at each of five multiples of their individual minimum alveolar concentrations (MAC; 0.75, 1, 1.25, 1.5 and 1.75 MAC), and response entropy (RE), state entropy (SE), RE-SE difference, burst suppression rate (BSR) and cardiorespiratory parameters were recorded before and after a painful stimulus. RE, SE and RE-SE difference did not change significantly after the stimuli. The correlation between MAC-entropy parameters was weak, but these values increased when 1.75 MAC results were excluded from the analysis. BSR was different to zero at 1.5 and 1.75 MAC. It was concluded that RE and RE-SE differences were not adequate indicators of antinociception and SE and RE were unable to detect deep planes of anaesthesia in dogs, although they both distinguished the awake and unconscious states. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Tooth movement with light continuous and discontinuous forces in beagle dogs.

    Science.gov (United States)

    van Leeuwen, E J; Maltha, J C; Kuijpers-Jagtman, A M

    1999-12-01

    In orthodontics, no consensus exists on how to move teeth most efficiently. The aim of the present study was to investigate the effect of two different force regimes and two different force magnitudes on tooth displacement. A split mouth design study was conducted in young adult beagle dogs. In each dog, both mandibular third premolars were extracted, and orthodontic appliances were placed for bodily distalization of the second premolars. The forces (10 cN or 25 cN) were applied, either continuously (24 h a day) or discontinuously (active 16 h daily from 17.00 till 9.00). Individual time-displacement curves of the second premolars were constructed. Four phases of tooth movement could be distinguished. Statistical analysis showed that the choice of regime had an influence on the duration of the hyalinisation phase, while force magnitude had not. The rate of tooth movement in the linear phase was mainly regime dependent. However, force magnitude also appeared to have some influence. The individual tissue response in each dog appeared to have an influence on both the duration of the second phase and the rate in the fourth phase. It was concluded that under these experimental conditions, force regime has more influence on the rate of orthodontic tooth movement than force magnitude.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  12. 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.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2015-09-12

    The objective of the study was to assess the effects of a dog-appeasing pheromone (DAP) collar in reducing sound-induced fear and anxiety in a laboratory model of thunderstorm simulation. Twenty-four beagle dogs naïve to the current test were divided into two treatment groups (DAP and placebo) balanced on their fear score in response to a thunderstorm recording. Each group was then exposed to two additional thunderstorm simulation tests on consecutive days. Dogs were video-assessed by a trained observer on a 6-point scale for active, passive and global fear and anxiety (combined). Both global and active fear and anxiety scores were significantly improved during and following thunder compared with placebo on both test days. DAP significantly decreased global fear and anxiety across 'during' and 'post' thunder times when compared with baseline. There was no significant improvement in the placebo group from baseline on the test days. In addition, the DAP group showed significantly greater use of the hide box at any time with increased exposure compared with the placebo group. The DAP collar reduced the scores of fear and anxiety, and increased hide use in response to a thunder recording, possibly by counteracting noise-related increased reactivity.

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-09-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-08-12

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

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

    OpenAIRE

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

    2011-01-01

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

  20. 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.

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

    Science.gov (United States)

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

    2010-11-15

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

  2. Anatomical and ultrasonographic study of the femoral nerve within the iliopsoas muscle in beagle dogs and cats.

    Science.gov (United States)

    Mogicato, Giovanni; Layssol-Lamour, Catherine; Mahler, Stephan; Charrouin, Maxime; Boyer, Guillaume; Verwaerde, Patrick; Jourdan, Géraldine

    2015-07-01

    An ultrasound (US)-guided ventral suprainguinal approach to block the femoral nerve (FN) within the iliopsoas muscle (IPM) has recently been described in dogs. The goal of the present study was to provide the operator with additional information to locate the FN within the IPM in dogs and cats using US. The study was carried out in three phases: a dissection of the FN (phase 1); an in vivo US-assisted nerve study (phase 2), and an anatomical cross-sectional study (phase 3). Nine healthy adult beagle dogs and nine healthy adult cats. Dissections were performed to investigate the anatomical characteristics of the FN and its related structures in one dog and one cat. Ultrasound scans of the left and right FN were performed in eight dogs and eight cats. The FN diameter and the distance between the FN and the external iliac artery (EIA) in US images and in anatomical cryosections were measured. The median FN diameter did not differ significantly between cats and dogs (1.1 mm versus 1.0 mm) or between the two techniques (US versus anatomical cross-sectional study) (1.1 mm versus 1.1 mm in dogs; 1.0 mm versus 1.1 mm in cats). The US and anatomical measurements of the median distances between the FN and EIA differed significantly between dogs and cats (8.2 mm versus 5.8 mm by US; 5.7 mm versus 4.8 mm in the anatomical study). The distance between the EIA and FN is reproducible in beagle dogs and cats and can be used in locating the FN within the IPM. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

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

    Science.gov (United States)

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

    1996-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Nívia Carolina Nogueira-Paiva

    2014-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

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

    2015-01-30

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

  8. 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.

  9. 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.

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-05-01

    Secreted phospholipase A2 inhibitor (sPLA2i) has been reported to have an anti-inflammatory function by blocking the production of inflammatory mediators. Obesity is characterized by low-grade inflammation and oxidative stress. The aim of this study was to investigate the effects of dietary supplementation of sPLA2i on inflammation, oxidative stress and serum fatty acid profile in dogs. Seven obese and seven lean Beagle dogs were used in a 28-day double blind cross-over design. Dogs were fed a control diet without supplemental sPLA2i or an sPLA2i supplemented diet. The sPLA2i diet decreased plasma fibrinogen levels and increased the protein:fibrinogen ratio in obese dogs to levels similar to those of lean dogs fed the same diet. Obese dogs had a higher plasma concentration of the lipophilic vitamin A with potential antioxidative capacity and a lower ratio of retinol binding protein 4:vitamin A compared to lean dogs, independent of the diets. A higher proportion of myristic acid (C14:0) and a lower proportion of linoleic acid (C18:2n-6) were observed in the dogs fed with the sPLA2i diet compared to dogs fed with the control diet. Furthermore, a higher ratio of n-6 to n-3, a lower proportion of n-3 polyunsaturated fatty acids and lower omega-3 index were observed in obese compared to lean dogs. The results indicate that obese dogs are characterized by a more 'proinflammatory' serum fatty acid profile and that diet inclusion of sPLA2i may reduce inflammation and alter fatty acid profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Schaeppi, U; Krinke, G

    1982-10-01

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

  14. 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 (t1/2 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.

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    1998-10-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Science.gov (United States)

    Wang, Lanlei; Guan, Aizhong; Shi, Han; Chen, Yangxi; Liao, Yunmao

    2009-09-01

    The aim of the present study was to investigate the effect of porous biphasic calcium phosphate nanocomposite (nanoBCP) scaffolds bioceramic. Alveolar bone defects were surgically created bilaterally at the buccal aspects of the upper second premolar in fourteen beagle dogs. After root conditioning with ethylenediaminetetraacetate (EDTA), nanoBCP was randomly filled in the defects and nothing was put into the contralaterals as controls. Dogs were killed at the 12th weeks. Histological observations were processed through a light microscopy. The results revealed that a great amount of functional periodontal fissures formed in the defects in the nanoBCP groups while minimal bone took shape in the controls. In this study, nanoBCP has proved to work well as a biocompatible and osteoconductive scaffold material to promote periodontal regeneration effectively.

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

    Science.gov (United States)

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

    2013-04-15

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

  3. Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs

    Directory of Open Access Journals (Sweden)

    Wang CL

    2015-05-01

    Full Text Available Chunling Wang,1 Xiaobo Cheng,2 Yuqing Su,1 Ying Pei,3 Yanzhi Song,1 Jiao Jiao,1 Zhenjun Huang,1 Yanfei Ma,1 Yinming Dong,1 Ying Yao,1 Jingjing Fan,1 Han Ta,1 Xinrong Liu,1 Hui Xu,1 Yihui Deng1 1College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Deli Wei Biological Technology Co, Ltd, Beijing, People’s Republic of China; 3Shenyang Women’s and Children’s Hospital, Shenyang, People’s Republic of China Abstract: The cross-administration of nanocarriers modified by poly(ethylene glycol (PEG, named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers. In this study, we investigated the ABC phenomenon induced by the intravenous cross-administration of various PEGylated nanocarriers, including PEGylated liposomes (PL, PEG micelles (PM, PEGylated solid lipid nanoparticles (PSLN, and PEGylated emulsions (PE, in beagle dogs. The results indicated that the magnitude of the immune response elicited by the cross-administration was in the following order (from the strongest to the weakest: PL, PE, PSLN, PM. It is specifically PEG in the brush structure that elicits a significant immune response, in both the induction phase and the effectuation phase. Furthermore, the present study suggests that there is a considerable difference between the effect of repeated injections and

  4. Exocrine pancreatic insufficiency in the Eurasian dog breed - inheritance and exclusion of two candidate genes

    DEFF Research Database (Denmark)

    Proschowsky, Helle Friis; Fredholm, Merete

    2007-01-01

    Exocrine pancreatic insufficiency is considered an inherited disease in several dog breeds. Affected dogs show polyphagia, weight loss and voluminous faeces of light colour due to the lack of pancreatic enzymes. In the study described herein, we performed a segregation analysis using the SINGLES ...

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Ko-Ning Ho

    2016-03-01

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

  8. Distribution of /sup 14/C-labelled acrylamide and betaine in foetuses of rats, rabbits, beagle dogs and miniature pigs

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, G.J.; Miller, E.; Sapienza, P.P.; Michel, T.C.; King, M.T.; Turner, V.A.; Blumenthal, H.; Jackson, W.E.; Levin, S.

    1983-02-01

    (/sup 14/C)Acrylamide and (/sup 14/C)betaine hydrochloride were administered in a single iv dose to pregnant rats, rabbits, beagle dogs and miniature pigs late in gestation (1-2 days before expected parturition). Dosages used were 10 mg/kg for rats and 5 mg/kg for the other species. The compounds were allowed to equilibrate in the animal (for 1 hr in rats and for 2 hr in the other species); the dam was then killed and the foetuses were removed by caesarean section. Each foetus was weighed and analysed for radioactivity, either by homogenization of the whole foetus (rat and rabbit) or by determining separately the radioactivity in individual organs and tissues (dog and pig). Foetal uptake of the polar compound betaine hydrochloride was much lower than that of the more lipophilic acrylamide. The sex of the foetus did not appear to affect uptake of either compound. There were no significant differences in total uptake of isotope attributable to the position of the foetus within the uterus in any of the four species given either acrylamide or betaine. Similarly, uterine position did not affect the uptake of acrylamide or betaine by individual tissues of foetal dogs or pigs. Since the distributions of /sup 14/C-labelled acrylamide and betaine hydrochloride were essentially uniform throughout a litter, it would not be necessary to sample all of the members of a litter to obtain a representative picture of foetal distribution.

  9. Radiologic study of the healing process of the extracted socket of beagle dogs using cone beam CT

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Bong Won; Lee, Won; Lee, Byung Do [Department of Oral and Maxillofacial Radiology, School of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Kim, De Sok [Department of Electrical Engineering, Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2009-03-15

    To longitudinally observe the healing process of extracted socket and the alterations of the residual ridge in healthy adult dogs using cone beam CT (CBCT). The mandibular premolars of two beagle dogs were removed and the extraction sites were covered with the gingival tissue. CBCTs (3D X-ray CT scanner, Alphard vega, Asahi Co.) were taken at baseline and at 1 week interval for 12 weeks. Radiographic density of extracted wounds was measured on normalized images with a custom-made image analysis program. The amount of alveolar crestal resorption after the teeth extraction was measured with a reformatted three-dimensional image using CBCT. Bony healing pattern of extracted wound of each group was also longitudinally observed and analyzed. Dimensional changes occurred during the first 6 weeks following the extraction of dogs' mandibular premolars. The reduction of the height of residual ridge was more pronounced at the buccal than at the lingual aspect of the extraction socket. Radiographic density of extracted wounds increased by week 4, but the change in density stabilized after week 6. New bone formation was observed at the floor and the peripheral side of extracted socket from week 1. The entrance of extracted socket was sealed by a hard-tissue bridge at week 5. The healing process of extracted wound involved a series of events including new bone formation and residual ridge resorption.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-11-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

  12. Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles

    Directory of Open Access Journals (Sweden)

    Jie Lai

    2009-12-01

    Full Text Available Jie Lai1,2, Yi Lu1, Zongning Yin2, Fuqiang Hu3, Wei Wu11School of Pharmacy, Fudan University, Shanghai, China, 2West China School of Pharmacy, Sichuan University, Chengdu, China, 3School of Pharmacy, Zhejiang University, Hangzhou, ChinaAbstract: Efforts to improve the oral bioavailability of cyclosporine A (CyA remains a challenge in the field of drug delivery. In this study, glyceryl monooleate (GMO/poloxamer 407 cubic nanoparticles were evaluated as potential vehicles to improve the oral bioavailability of CyA. Cubic nanoparticles were prepared via the fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by sonication and homogenization. The cubic inner structure formed was verified using Cryo-TEM. The mean diameters of the nanoparticles were about 180 nm, and the entrapment efficiency of these particles for CyA was over 85%. The in vitro release of CyA from these nanoparticles was less than 5% at 12 h. The results of a pharmacokinetic study in beagle dogs showed improved absorption of CyA from cubic nanoparticles as compared to microemulsion-based Neoral®; higher Cmax (1371.18 ± 37.34 vs 969.68 ± 176.3 ng mL-1, higher AUC0–t (7757.21 ± 1093.64 vs 4739.52 ± 806.30 ng h mL-1 and AUC0–∞ (9004.77 ± 1090.38 vs 5462.31 ± 930.76 ng h mL-1. The relative oral bioavailability of CyA cubic nanoparticles calculated on the basis of AUC0–∞ was about 178% as compared to Neoral®. The enhanced bioavailability of CyA is likely due to facilitated absorption by cubic nanoparticles rather than improved release.Keywords: nanoparticles, cubosomes, cyclosporine A, glyceryl monooleate, oral drug delivery, bioavailability, beagle dogs

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-12

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

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

    Science.gov (United States)

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

    2009-04-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

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

    2015-06-16

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

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

    Science.gov (United States)

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

    2014-10-01

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

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

    Science.gov (United States)

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

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs=1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species.

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

    Science.gov (United States)

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

    2016-12-01

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

  20. N-dephenylated and N-phenyl urinary metabolites of mociprazine (CERM 3517) in beagle dogs after oral administration. A mass spectrometric determination.

    Science.gov (United States)

    Enreille, A; Pognat, J F; Galmier, M J; Lartigue-Mattei, C; Chabard, J L; Busch, N; Berger, J A

    1991-01-01

    CERM 3517 (mociprazine), a new anti-emetic compound, was administered orally to six beagle dogs at 10 mg/kg b.i.d. for four days. Unconjugated urinary metabolites were identified by GC-MS analysis against synthesized reference compounds, after solvent extraction, purification by TLC and concentration. Twenty one metabolites were identified indicating the following biotransformations: N-dephenylation followed by reactions on the exposed secondary amine such as methylation acetylation; and parahydroxylation on the phenyl ring, and monohyrdoxylation on the cyclohexyl ring in different positions. The parahydroxylation on the phenyl ring was confirmed by NMR analysis. Some reactions on the secondary amine were unexpected, such as N-formylation. N-dephenylation and N-formylation were confirmed not to be artifacts. The role of the para-hydroxyl intermediate was proved to be essential for the N-dephenylation after intravenous administration of meta- and para-hydroxylated derivatives of CERM 3517 to five beagle dogs.

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

    Directory of Open Access Journals (Sweden)

    Jie Li

    2017-06-01

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

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

    Science.gov (United States)

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

    2011-09-05

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  6. 26-week repeated oral dose toxicity study of UP446, a combination of defined extracts of Scutellaria baicalensis and Acacia catechu, in beagle dogs.

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Christopher E.; Wilson, Dulaney A.; Brooks, Antone L.; McCord, Stacey; Dagle, Gerald E.; James, Anthony C.; Tolmachev, Sergei Y.; Thrall, Brian D.; Morgan, William F.

    2012-11-01

    The long-term retention of inhaled soluble forms of plutonium raises concerns as to the potential health effects in persons working in nuclear energy or the nuclear weapons program. The distributions of long-term retained inhaled plutonium-nitrate [239Pu (NO3)4] deposited in the lungs of an accidentally exposed nuclear worker (Human Case 0269) and in the lungs of experimentally exposed beagle dogs with varying initial lung depositions were determined via autoradiographs of selected histological lung, lymph node, trachea, and nasal turbinate tissue sections. These studies showed that both the human and dogs had a non-uniform distribution of plutonium throughout the lung tissue. Fibrotic scar tissue effectively encapsulated a portion of the plutonium and prevented its clearance from the body or translocation to other tissues and diminished dose to organ parenchyma. Alpha radiation activity from deposited plutonium in Human Case 0269 was observed primarily along the sub-pleural regions while no alpha activity was seen in the tracheobronchial lymph nodes of this individual. However, relatively high activity levels in the tracheobronchial lymph nodes of the beagles indicated the lymphatic system was effective in clearing deposited plutonium from the lung tissues. In both the human case and beagle dogs, the appearance of retained plutonium within the respiratory tract was inconsistent with current biokinetic models of clearance for soluble forms of plutonium. Bound plutonium can have a marked effect on the dose to the lungs and subsequent radiation exposure has the potential increase in cancer risk.

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Science.gov (United States)

    Nielsen, Christopher E; Wilson, Dulaney A; Brooks, Antone L; McCord, Stacey L; Dagle, Gerald E; James, Anthony C; Tolmachev, Sergei Y; Thrall, Brian D; Morgan, William F

    2012-11-01

    The long-term retention of inhaled soluble forms of plutonium raises concerns as to the potential health effects in persons working in nuclear energy or the nuclear weapons program. The distributions of long-term retained inhaled plutonium-nitrate [(239)Pu (NO(3))(4)] deposited in the lungs of an accidentally exposed nuclear worker (Human Case 0269) and in the lungs of experimentally exposed beagle dogs with varying initial lung depositions were determined via autoradiographs of selected histologic lung, lymph node, trachea, and nasal turbinate tissue sections. These studies showed that both the human and dogs had a nonuniform distribution of plutonium throughout the lung tissue. Fibrotic scar tissue effectively encapsulated a portion of the plutonium and prevented its clearance from the body or translocation to other tissues and diminished dose to organ parenchyma. Alpha radiation activity from deposited plutonium in Human Case 0269 was observed primarily along the subpleural regions while no alpha activity was seen in the tracheobronchial lymph nodes of this individual. However, relatively high activity levels in the tracheobronchial lymph nodes of the beagles indicated the lymphatic system was effective in clearing deposited plutonium from the lung tissues. In both the human case and beagle dogs, the appearance of retained plutonium within the respiratory tract was inconsistent with current biokinetic models of clearance for soluble forms of plutonium. Bound plutonium can have a marked effect on the dose to the lungs and subsequent radiation exposure has the potential to increase cancer risk.

  11. Genetic variances, trends and mode of inheritance for hip and elbow dysplasia in Finnish dog populations

    NARCIS (Netherlands)

    Mäki, K.; Groen, A.F.; Liinamo, A.E.; Ojala, M.

    2002-01-01

    The aims of this study were to assess genetic variances, trends and mode of inheritance for hip and elbow dysplasia in Finnish dog populations. The influence of time-dependent fixed effects in the model when estimating the genetic trends was also studied. Official hip and elbow dysplasia screening

  12. Why do people buy dogs with potential welfare problems related to extreme conformation and inherited disease?

    DEFF Research Database (Denmark)

    Sandøe, Peter; Kondrup, Sara Vincentzen; Bennett, P.C.

    2017-01-01

    number of dog breeds suffer from welfare problems due to extreme phenotypes and high levels of inherited diseases but the popularity of such breeds is not declining. Using a survey of owners of two popular breeds with extreme physical features (French Bulldog and Chihuahua), one with a high load...

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiaobing [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China); Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Li, Bo, E-mail: libo@nifdc.org.cn [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China)

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species. - Highlights: • Urinary NGAL, clusterin and NAG levels were significantly elevated in canine AKI. • NGAL and clusterin gene expression were increased following treatment with gentamicin. • NGAL and clusterin have high specificity and sensitivity for detection of AKI.

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

    Science.gov (United States)

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

    2008-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Samjhana Kashaju; Yarning Chen; Ting Chen

    2008-01-01

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

  16. Trypanosoma cruzi: blood parasitism kinetics and their correlation with heart parasitism intensity during long-term infection of Beagle dogs

    Directory of Open Access Journals (Sweden)

    Vanja M Veloso

    2008-09-01

    Full Text Available The goals of the present study were to evaluate the kinetics of blood parasitism by examination of fresh blood, blood culture (BC and PCR assays and their correlation with heart parasitism during two years of infection in Beagle dogs inoculated with the Be-78, Y and ABC Trypanosoma cruzi strains. Our results showed that the parasite or its kDNA is easily detected during the acute phase in all infected animals. On the other hand, a reduced number of positive tests were verified during the chronic phase of the infection. The frequency of positive tests was correlated with T. cruzi strain. The percentage of positive BC and blood PCR performed in samples from animals inoculated with Be-78 and ABC strains were similar and significantly larger in relation to animals infected with the Y strain.Comparison of the positivity of PCR tests performed using blood and heart tissue samples obtained two years after infection showed two different patterns associated with the inoculated T. cruzi strain: (1 high PCR positivity for both blood and tissue was observed in animals infected with Be-78 or ABC strains; (2 lower and higher PCR positivity for the blood and tissue, respectively, was detected in animals infected with Y strains. These data suggest that the sensitivity of BC and blood PCR was T. cruzi strain dependent and, in contrast, the heart tissue PCR revealed higher sensitivity regardless of the parasite stock.

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

    Science.gov (United States)

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

    2012-03-01

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

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

    Science.gov (United States)

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

    2000-01-01

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

  19. Pharmacokinetics and metabolism of cyadox and its main metabolites in beagle dogs following oral, intramuscular and intravenous administration

    Directory of Open Access Journals (Sweden)

    Adeel Sattar

    2016-08-01

    Full Text Available Cyadox (Cyx is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO, intramuscular (IM and intravenous (IV routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females were administered Cyx through PO (40 mg kg-1 b.w., IM (10 mg kg-1 b.w. and IV (10 mg kg-1 b.w. routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1, cyadox-1-monoxide (Cy2, N-(quinoxaline-2-methyl-cyanide acetyl hydrazine (Cy4 and quinoxaline-2-carboxylic acid (Cy6 in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC of Cyx after PO, IM and IV administration were 1.22 h×µg mL-1, 6.3 h×µg mL-1, and 6.66 h×µg mL-1, while mean resident times (MRT were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology.

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

    Science.gov (United States)

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

    2016-01-01

    Cyadox (Cyx) is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO), intramuscular (IM), and intravenous (IV) routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females) were administered Cyx through PO (40 mg kg(-1) b.w.), IM (10 mg kg(-1) b.w.), and IV (10 mg kg(-1) b.w.) routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1), cyadox-1-monoxide (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), and quinoxaline-2-carboxylic acid (Cy6) in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC) of Cyx after PO, IM and IV administration were 1.22 h × μg mL(-1), 6.3 h × μg mL(-1), and 6.66 h × μg mL(-1), while mean resident times (MRT) were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

    AIM: To evaluate the pharmaceutical safety of a Chinese herbal formula, Chunggan extract (CGX), traditionally prescribed as a hepatotherapeutic drug via systemic acute and subacute toxicological study.METHODS: Twenty male dogs and 20 female dogs were fed doses 50 times and 4 times greater than the clinically-recommended drug dosages in an acute and a subacute toxicological study, respectively. Adverse effects were examined by comparing the differences between normal and drug-administered groups using clinical signs, necropsies, histopathologic findings, haematology,urinalysis, and biochemical analysis.RESULTS: In the acute study no change in the body weight, diarrhoea, apetite, mortality rate and histopathology of major organs was observed in male or female dogs with a single administration of CGX at 5 g/kg. No drug-induced abnormalities at analysis of histopathology,haematology, urinalysis, and biochemistry were found with any dose of this drug.CONCLUSION: CGX is supposed to be very safe when used in a clinical application with a wide therapeutic index.

  2. Capromorelin oral solution (ENTYCE®) increases food consumption and body weight when administered for 4 consecutive days to healthy adult Beagle dogs in a randomized, masked, placebo controlled study.

    Science.gov (United States)

    Zollers, Bill; Rhodes, Linda; Heinen, Ernst

    2017-01-05

    Dogs can suffer from inappetence caused by a variety of medical conditions. This may present as anorexia (complete loss of appetite), hyporexia (decreased appetite) or dysrexia (change in food preferences). A drug with a new mechanism of action, capromorelin, has potential to stimulate appetite in dogs. Capromorelin is a ghrelin receptor agonist, which mimics the action of endogenous ghrelin. It is a member of the growth hormone secretagogue (GHS) class of drugs. Capromorelin oral solution (ENTYCE®) was tested in healthy adult male and female Beagle dogs (n = 6 males and 6 females per group) for its effect on food consumption and body weight. A randomized, masked, placebo controlled study was conducted to measure the effects of a daily 3 mg/kg oral dose given over 4 days. Dogs were observed for clinical signs, physical examinations were completed prior to and at the end of treatment, and blood was drawn before and after treatment for evaluation of serum chemistry and hematology parameters. Capromorelin was well-tolerated, with no abnormalities seen on physical examination or clinical pathology. Some dogs showed increased salivation. Capromorelin treated dogs had increased mean (±SD) food consumption compared to placebo treated dogs (60.55 ± 39.87% versus -11.15 ± 14.23% respectively, P dogs also had increased mean body weights compared to placebo treated dogs (5.96 ± 1.76% versus 0.053 ± 1.14% respectively, P dogs. Treatment with the oral solution resulted in dramatic increases in appetite, as measured by food consumption, of over 60% compared to placebo. The drug was well tolerated. Capromorelin is the first ghrelin receptor agonist developed for appetite stimulation in any species, and represents a novel mechanism of action for this clinical use.

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Hongcheng Hu

    2015-10-01

    Full Text Available A plastic and biodegradable bone substitute consists of poly (l-lactic-co-glycolic acid and 30 wt % β-tricalcium phosphate has been previously fabricated, but its osteogenic capability required further improvement. We investigated the use of globular adiponectin (gAPN as an anabolic agent for tissue-engineered bone using this scaffold. A qualitative analysis of the bone regeneration process was carried out using μCT and histological analysis 12 weeks after implantation. CBCT (Cone Beam Computed Tomography superimposition was used to characterise the effect of the different treatments on bone formation. In this study, we also explored adiponectin’s (APN influence on primary cultured human jaw bone marrow mesenchymal stem cells gene expressions involved in the osteogenesis. We found that composite scaffolds loaded with gAPN or bone morphogenetic protein 2 (BMP2 exhibited significantly increased bone formation and mineralisation following 12 weeks in the extraction sockets of beagle dogs, as well as enhanced expression of osteogenic markers. In vitro investigation revealed that APN also promoted osteoblast differentiation of primary cultured human jaw bone marrow mesenchymal stem cells (h-JBMMSCs, accompanied by increased activity of alkaline phosphatase, greater mineralisation, and production of the osteoblast-differentiated genes osteocalcin, bone sialoprotein and collagen type I, which was reversed by APPL1 siRNA. Therefore, the composite scaffold loaded with APN exhibited superior activity for guided bone regeneration compared with blank control or Bio-Oss® (a commercially available product. The composite scaffold with APN has significant potential for clinical applications in bone tissue engineering.

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

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    Jun Anzai

    Full Text Available The long-term stability and qualitative characteristics of periodontium regenerated by FGF-2 treatment were compared with normal physiological healing tissue controls in a Beagle dog 2-wall periodontal defect model 13 months after treatment by assessing tissue histology and three-dimensional microstructure using micro-computed tomography (μCT. After FGF-2 (0.3% or vehicle treatment at the defect sites, serial changes in the bone mineral content (BMC were observed using periodic X-ray imaging. Tissues were harvested at 13 months, evaluated histomorphometrically, and the cortical bone volume and trabecular bone structure of the newly formed bone were analyzed using μCT. FGF-2 significantly increased the BMC of the defect area at 2 months compared with that of the control group, and this difference was unchanged through 13 months. The cortical bone volume was significantly increased by FGF-2, but there was no difference between the groups in trabecular bone structure. Bone maturation was occurring in both groups because of the lower cortical volume and denser trabecular bone than what is found in intact bone. FGF-2 also increased the area of newly formed bone as assessed histomorphometrically, but the ratios of trabecular bone in the defect area were similar between the control and FGF-2 groups. These results suggest that FGF-2 stimulates neogenesis of alveolar bone that is of similar quality to that of the control group. The lengths of the regenerated periodontal ligament and cementum, measured as the distance from the defect bottom to the apical end of the gingival epithelium, and height and area of the newly formed bone in the FGF-2 group were larger than those in the control group. The present study demonstrated that, within the limitation of artificial periodontal defect model, the periodontal tissue regenerated by FGF-2 was maintained for 13 months after treatment and was qualitatively equivalent to that generated through the physiological

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

    Directory of Open Access Journals (Sweden)

    Toshie Nagayasu-Tanaka

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

    The long-term stability and qualitative characteristics of periodontium regenerated by FGF-2 treatment were compared with normal physiological healing tissue controls in a Beagle dog 2-wall periodontal defect model 13 months after treatment by assessing tissue histology and three-dimensional microstructure using micro-computed tomography (μCT). After FGF-2 (0.3%) or vehicle treatment at the defect sites, serial changes in the bone mineral content (BMC) were observed using periodic X-ray imaging. Tissues were harvested at 13 months, evaluated histomorphometrically, and the cortical bone volume and trabecular bone structure of the newly formed bone were analyzed using μCT. FGF-2 significantly increased the BMC of the defect area at 2 months compared with that of the control group, and this difference was unchanged through 13 months. The cortical bone volume was significantly increased by FGF-2, but there was no difference between the groups in trabecular bone structure. Bone maturation was occurring in both groups because of the lower cortical volume and denser trabecular bone than what is found in intact bone. FGF-2 also increased the area of newly formed bone as assessed histomorphometrically, but the ratios of trabecular bone in the defect area were similar between the control and FGF-2 groups. These results suggest that FGF-2 stimulates neogenesis of alveolar bone that is of similar quality to that of the control group. The lengths of the regenerated periodontal ligament and cementum, measured as the distance from the defect bottom to the apical end of the gingival epithelium, and height and area of the newly formed bone in the FGF-2 group were larger than those in the control group. The present study demonstrated that, within the limitation of artificial periodontal defect model, the periodontal tissue regenerated by FGF-2 was maintained for 13 months after treatment and was qualitatively equivalent to that generated through the physiological healing process.

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

    Science.gov (United States)

    Hu, Hongcheng; Pu, Yinfei; Lu, Songhe; Zhang, Kuo; Guo, Yuan; Lu, Hui; Li, Deli; Li, Xuefen; Li, Zichen; Wu, Yuwei; Tang, Zhihui

    2015-10-20

    A plastic and biodegradable bone substitute consists of poly (L-lactic-co-glycolic) acid and 30 wt % β-tricalcium phosphate has been previously fabricated, but its osteogenic capability required further improvement. We investigated the use of globular adiponectin (gAPN) as an anabolic agent for tissue-engineered bone using this scaffold. A qualitative analysis of the bone regeneration process was carried out using μCT and histological analysis 12 weeks after implantation. CBCT (Cone Beam Computed Tomography) superimposition was used to characterise the effect of the different treatments on bone formation. In this study, we also explored adiponectin's (APN) influence on primary cultured human jaw bone marrow mesenchymal stem cells gene expressions involved in the osteogenesis. We found OPEN ACCESS Int. J. Mol. Sci. 2015, 16 24947 that composite scaffolds loaded with gAPN or bone morphogenetic protein 2 (BMP2) exhibited significantly increased bone formation and mineralisation following 12 weeks in the extraction sockets of beagle dogs, as well as enhanced expression of osteogenic markers. In vitro investigation revealed that APN also promoted osteoblast differentiation of primary cultured human jaw bone marrow mesenchymal stem cells (h-JBMMSCs), accompanied by increased activity of alkaline phosphatase, greater mineralisation, and production of the osteoblast-differentiated genes osteocalcin, bone sialoprotein and collagen type I, which was reversed by APPL1 siRNA. Therefore, the composite scaffold loaded with APN exhibited superior activity for guided bone regeneration compared with blank control or Bio-Oss® (a commercially available product). The composite scaffold with APN has significant potential for clinical applications in bone tissue engineering.

  11. Pharmacokinetics of ketamine and three metabolites in Beagle dogs under sevoflurane vs. medetomidine comedication assessed by enantioselective capillary electrophoresis.

    Science.gov (United States)

    Sandbaumhüter, Friederike A; Theurillat, Regula; Bektas, Rima N; Kutter, Annette P N; Bettschart-Wolfensberger, Regula; Thormann, Wolfgang

    2016-10-07

    Ketamine is often used for anesthesia in veterinary medicine. One possible comedication is the sedative α2-agonist medetomidine. Advantages of that combination are the compensation of side effects of the two drugs and the anesthetic-sparing effect of medetomidine. In vitro studies showed that medetomidine has an inhibitive effect on the formation of norketamine. Norketamine is the first metabolite of ketamine and is also active. It is followed by others like 6-hydroxynorketamine and 5,6-dehydronorketamine (DHNK). In an in vivo pharmacokinetic study Beagle dogs under sevoflurane anesthesia (mean end-tidal concentration 3.0±0.2%) or following medetomidine sedation (450μg/m(2)) received 4mg/kg racemic ketamine or 2mg/kg S-ketamine. Blood samples were collected between 0 and 900min after drug injection. 50μL aliquots of plasma were pretreated by liquid-liquid extraction prior to analysis of the reconstituted extracts with a robust enantioselective capillary electrophoresis assay using highly sulfated γ-cyclodextrin as chiral selector and electrokinetic sample injection of the analytes from the extract across a short buffer plug without chiral selector. Levels of S- and R-ketamine, S- and R-norketamine, (2S,6S)- and (2R,6R)-hydroxynorketamine and S- and R-DHNK were determined. Data were analyzed with compartmental pharmacokinetic models which included two compartments for the ketamine and norketamine enantiomers and a single compartment for the DHNK and 6-hydroxynorketamine stereoisomers. Medetomidine showed an effect on the formation and elimination of all metabolites. Stereoselectivities were detected for 6-hydroxynorketamine and DHNK, but not for ketamine and norketamine. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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    Chen Peng

    2011-04-01

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

  13. Safety and toxicology of cyclosporine in propylene glycol after 9-month aerosol exposure to beagle dogs.

    Science.gov (United States)

    Niven, Ralph; Lynch, Maryellen; Moutvic, Ronald; Gibbs, Seth; Briscoe, Crystal; Raff, Howard

    2011-08-01

    Cyclosporine inhalation solution (CIS) delivered via nebulization is under evaluation for the prevention of chronic rejection post-lung transplant. A 300-patient randomized, controlled clinical trial (CYCLIST) is expected to be completed late in 2011. In support of this trial, a chronic inhalation toxicology study in dogs has been completed. To mimic the clinical setting, animals (four/sex/dose plus two/sex/dose in the control and high dose recovery groups) were exposed to aerosolized CIS, via nose-only exposure, three times per week for 9 months at targeted inhaled doses of 0 (air), 4, 12, and 24 mg/kg. In addition, the potential for persistence or reversibility of any toxic effects were assessed after a 6-week recovery period. The toxicological endpoints included clinical observations, body-weight, food consumption, toxicokinetics, clinical chemistry, and histopathology. All dogs receiving CIS completed the study with the only consistent observations being excessive salivation and changes in minute ventilation. There was no limiting lung or systemic toxicity associated with exposure to CIS, and the only possible drug-related effect was an observation of benign fibroadenoma tissue in the mammary glands of the high-dose female recovery group. Toxicokinetic data showed that cyclosporine is initially absorbed rapidly with little drug remaining in lung tissue or blood 24 h after the end of dosing. The study supports the pulmonary and systemic safety of aerosolized CIS at expected lung dose levels/kg of up to 12 times greater than the average dose patients are receiving in the CYCLIST trial.

  14. Determination of morphological, biometric and biochemical susceptibilities in healthy Eurasier dogs with suspected inherited glaucoma.

    Science.gov (United States)

    Boillot, Thomas; Rosolen, Serge G; Dulaurent, Thomas; Goulle, Frédéric; Thomas, Philippe; Isard, Pierre-François; Azoulay, Thierry; Lafarge-Beurlet, Stéphanie; Woods, Mike; Lavillegrand, Sylvie; Ivkovic, Ivana; Neveux, Nathalie; Sahel, José-Alain; Picaud, Serge; Froger, Nicolas

    2014-01-01

    In both humans and dogs, the primary risk factor for glaucoma is high intraocular pressure (IOP), which may be caused by iridocorneal angle (ICA) abnormalities. Oxidative stress has also been implicated in retinal ganglion cell damage associated with glaucoma. A suspected inherited form of glaucoma was recently identified in Eurasier dogs (EDs), a breed for which pedigrees are readily available. Because of difficulties in assessing ICA morphology in dogs with advanced glaucoma, we selected a cohort of apparently healthy dogsfor the investigation of ICA morphological status, IOP and plasma concentrations of oxidative stress biomarkers. We aimed to establish correlations between these factors, to identify predictive markers of glaucoma in this dog breed. A cohort of 28 subjects, volunteered for inclusion by their owners, was selected by veterinary surgeons. These dogs were assigned to four groups: young males, young females (1-3 years old), adult males and adult females (4-8 years old). Ocular examination included ophthalmoscopy, tonometry, gonioscopy, biometry and ultrasound biomicroscopy (UBM), and the evaluation of oxidative stress biomarkers consisting of measurements of plasma glutathione peroxidase (GP) activity and taurine and metabolic precursor (methionine and cysteine) concentrations in plasma. The prevalence of pectinate ligament abnormalities was significantly higher in adult EDs than in young dogs. Moreover, in adult females, high IOP was significantly correlated with a short axial globe length, and a particularly large distance between Schwalbe's line and the anterior lens capsule. GP activity levels were significantly lower in EDs than in a randomized control group of dogs, and plasma taurine concentrations were higher. Hence, ICA abnormalities were associated with weaker antioxidant defenses in EDs, potentially counteracted by higher plasma taurine concentrations. This study suggests that EDs may constitute an appropriate canine model for the

  15. Determination of morphological, biometric and biochemical susceptibilities in healthy Eurasier dogs with suspected inherited glaucoma.

    Directory of Open Access Journals (Sweden)

    Thomas Boillot

    Full Text Available In both humans and dogs, the primary risk factor for glaucoma is high intraocular pressure (IOP, which may be caused by iridocorneal angle (ICA abnormalities. Oxidative stress has also been implicated in retinal ganglion cell damage associated with glaucoma. A suspected inherited form of glaucoma was recently identified in Eurasier dogs (EDs, a breed for which pedigrees are readily available. Because of difficulties in assessing ICA morphology in dogs with advanced glaucoma, we selected a cohort of apparently healthy dogsfor the investigation of ICA morphological status, IOP and plasma concentrations of oxidative stress biomarkers. We aimed to establish correlations between these factors, to identify predictive markers of glaucoma in this dog breed. A cohort of 28 subjects, volunteered for inclusion by their owners, was selected by veterinary surgeons. These dogs were assigned to four groups: young males, young females (1-3 years old, adult males and adult females (4-8 years old. Ocular examination included ophthalmoscopy, tonometry, gonioscopy, biometry and ultrasound biomicroscopy (UBM, and the evaluation of oxidative stress biomarkers consisting of measurements of plasma glutathione peroxidase (GP activity and taurine and metabolic precursor (methionine and cysteine concentrations in plasma. The prevalence of pectinate ligament abnormalities was significantly higher in adult EDs than in young dogs. Moreover, in adult females, high IOP was significantly correlated with a short axial globe length, and a particularly large distance between Schwalbe's line and the anterior lens capsule. GP activity levels were significantly lower in EDs than in a randomized control group of dogs, and plasma taurine concentrations were higher. Hence, ICA abnormalities were associated with weaker antioxidant defenses in EDs, potentially counteracted by higher plasma taurine concentrations. This study suggests that EDs may constitute an appropriate canine model for

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

    Science.gov (United States)

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

    2016-10-01

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

  17. Why do people buy dogs with potential welfare problems related to extreme conformation and inherited disease? A representative study of Danish owners of four small dog breeds

    DEFF Research Database (Denmark)

    Sandøe, Peter; Kondrup, Sara Vincentzen; Bennett, P.C.

    2017-01-01

    number of dog breeds suffer from welfare problems due to extreme phenotypes and high levels of inherited diseases but the popularity of such breeds is not declining. Using a survey of owners of two popular breeds with extreme physical features (French Bulldog and Chihuahua), one with a high load...... of inherited diseases not directly related to conformation (Cavalier King Charles Spaniel), and one representing the same size range but without extreme conformation and with the same level of disease as the overall dog population (Cairn Terrier), we investigated this seeming paradox. We examined planning...... and motivational factors behind acquisition of the dogs, and whether levels of experienced health and behavior problems were associated with the quality of the owner-dog relationship and the intention to re-procure a dog of the same breed. Owners of each of the four breeds (750/breed) were randomly drawn from...

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

    Science.gov (United States)

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

    2016-10-27

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

  19. Development and validation of an LC-MS/MS method for the determination of mesalazine in beagle dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Qin, Juan; Di, Xin; Wang, Xin; Liu, Youping

    2015-02-01

    A simple, specific and sensitive LC-MS/MS method was developed and validated for the determination of mesalazine in beagle dog plasma. The plasma samples were prepared by protein precipitation, then the separation of the analyte was achieved on a Waters Spherisorb C6 column (150 × 4.6 mm, 5 µm) with a mobile phase consisting of 0.2% formic acid in water-methanol (20:80, v/v). The flow rate was set at 1.0 mL/min with a split ratio of 3:2. Mass spectrometric detection was achieved by a triple-quadrupole mass spectrometer equipped with an electrospray source interface in positive ionization mode. Quantitation was performed using selected reaction monitoring of precursor-product ion transitions at m/z 154 → m/z 108 for mesalazine and m/z 285 → m/z 193 for diazepam (internal standard). The linear calibration curve of mesalazine was obtained over the concentration range 50-30,000 ng/mL. The matrix effect of mesalazine was within ±9.8%. The intra- and inter-day precisions were beagle dogs after rectal administration of mesalazine suppository.

  20. Development and validation of an enantioselective SFC-MS/MS method for simultaneous separation and quantification of oxcarbazepine and its chiral metabolites in beagle dog plasma.

    Science.gov (United States)

    Yang, Zhichao; Xu, Xueyu; Sun, Lingxia; Zhao, Xue; Wang, Hao; Fawcett, John Paul; Yang, Yan; Gu, Jingkai

    2016-05-01

    A rapid and sensitive assay based on supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) has been developed and validated for the determination of oxcarbazepine (OXC) and its chiral metabolite licarbazine (Lic) in beagle dog plasma using carbamazepine as internal standard. Chiral analysis in a run time of only 3 min was performed on an ACQUITY UPC(2) ™ Trefoil™ CEL2 column (3.0 × 150 mm, 2.5 μm) at 50 °C by isocratic elution with a mobile phase of supercritical carbon dioxide (purity ≥ 99.99%) and methanol (60:40, v/v) at a flow rate of 2.3 mL/min. The assay was linear over the concentration ranges 5-1000 ng/mL for OXC and 0.5-100 ng/mL for the enantiomers of Lic with corresponding lower limits of quantitation of 5 ng/mL and 0.5 ng/mL. Intra- and inter-day precisions were in the range 0.78-14.14% with accuracies in the range -10.80% to 0.42%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of 16 mg/kg OXC as Trileptal(@) tablets to beagle dogs.

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

    Science.gov (United States)

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

    2016-01-21

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Yuqing Cao

    2016-01-01

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

  4. The Effect of Hierarchical Micro/Nanotextured Titanium Implants on Osseointegration Immediately After Tooth Extraction in Beagle Dogs.

    Science.gov (United States)

    Fu, Qian; Bellare, Anuj; Cui, Yajun; Cheng, Bingkun; Xu, Shanshan; Kong, Liang

    2017-06-01

    Owing to simplify the operation and shorten the overall duration of treatment, immediate implantation earned much satisfactory from patients and dentists. The results of immediate implantation determined by osseointegration, we fabricated a micro/nanotextured titanium implants to improve osseointegration immediately after tooth extraction. The aim of this study was to investigate the effect of hierarchical micro/nanotextured titanium implant on osseointegration immediately after tooth extraction. The micro/nanotextured titanium implants were fabricated by etching with 0.5 wt% hydrofluoric (HF) acid followed by anodization in HF electrolytes. Implants with a machined surface as well as implants a microtextured surface prepared by 0.5 wt% HF etching served as control groups. The machined, microtextured, and micro/nanotextured implants were inserted into fresh sockets immediately after tooth extraction in beagle dogs. Twelve weeks after implantation, the animals were sacrificed for micro-CT scanning, histological analysis and biomechanical test. The micro-CT imaging revealed that the bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th) in the micro/nanotextured group was significantly higher than that in the machined group and microtextured group, and the trabecular separation (Tb.Sp) in the micro/nanotextured group was significantly lower than that in the other groups. For the histological analysis, the bone-to-implant contact in the machined, micro and micro/nanotextured groups were 47.13 ± 6.2%, 54.29 ± 4.18%, and 63.38 ± 7.63%, respectively, and the differences significant. The maximum pull-out force in the machined, micro, and micro/nanotextured groups were 216.58 ± 38.71 N, 259.42 ± 28.93 N, and 284.73 ± 47.09 N, respectively. The results indicated that implants with a hierarchical micro/nanotextured can promote osseointegration immediately after tooth extraction. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Arencibia Arrebola, Daniel Francisco

    2009-11-01

    pathological alterations of the hydrosaline balance, the water and sodium balance, they are known as contractions and expansions of the extracellular space volume. One of the fundamental causes of weight decrease, the appearance of animals with anemia and unfavorable physical state in the dogs of the beagle breed constitutes of diarrheas, vomits, inappetence for other illnesses mainly in the quarantine stage orduring our biomedical research which prevent that are used capable andhealthy animals. The aim of this work is to carry out a practical guide to classify, to diagnose and to treat the dogs beagle dehydration, for to arrive at the final studies with the biggest quality and quantity of animals required, assuring the speed with to counteract it cause the unfavorable dehydration effects. For a good diagnosis, prognosis and treatment is fundamental to know the dehydration type, quantity of lost liquid, state of integral health ofthe animal and existent fluids.

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

    Directory of Open Access Journals (Sweden)

    Longshan Zhao

    2012-01-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Science.gov (United States)

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

    2007-06-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

    Gong, Xue-Lian; Gao, Ting-Ting; Zhao, Li-Jun; Zhu, Hai; Xia, Zhen-Na; Lu, Wen; Lu, Guo-Cai

    2014-08-01

    CMS-1, mainly composed of imperatorin as its active compound, is a partially purified fraction of a Chinese herbal medicine, Semen Cnidium monnieri. CMS-1 has the potential to be further developed as a new treatment for hypertension. Thus, we studied its toxicity in both Sprague-Dawley rats and beagle dogs. Rats (0-900mg/kg/day) and dogs (0-450mg/kg/day) received CMS-1 orally for 30 consecutive days, followed by a 15-day recovery period. The major target organs of CMS-1 toxicity are the GI (inappetence), liver (hepatocellular necrosis, enzyme elevation), thymus (atrophy), cardiovascular (hypotension), changes in ECG T and P waveforms, elevation of nitrous oxide levels and hematological (RBC parameters disturbances) systems. Most treatment-induced adverse effects were reversible or showed a progressive recovery upon discontinuation of the treatment. The No Observed Adverse Effect Level (NOAEL) was 100mg/kg/day for rats and 50mg/kg/day for dogs. This non-clinical study suggests that clinical monitoring of CMS-1 in patients should focus on the gastrointestinal system, blood tests for liver functions, electrolytes, and blood homeostasis, cardiovascular functions, and immune functions.

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

    Science.gov (United States)

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

    2015-10-10

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

  13. Digging for known genetic mutations underlying inherited bone and cartilage characteristics and disorders in the dog and cat.

    Science.gov (United States)

    Haase, Bianca; Mazrier, Hamutal; Wade, Claire M

    2016-07-19

    Gene mapping projects for many traits in both dogs and cats have yielded new knowledge. Both researchers and the public alike have been fascinated by the inheritance of breed characteristic phenotypes and sporadic disorders. It has been proposed that selective breeding practices have on occasion generated alterations in structure that might be harmful. In this review, simply inherited disorders and characteristics affecting bone and cartilage for which a putative mutation is known are collected. A better understanding of the known inherited basis of skeletal conditions and disorders will assist veterinarians to improve their diagnoses and increase their effectiveness on advising clients on the prevention, management, prognosis and possible treatment of the conditions.

  14. Effects of concomitant use of fibroblast growth factor (FGF)-2 with beta-tricalcium phosphate ({beta}-TCP) on the beagle dog 1-wall periodontal defect model

    Energy Technology Data Exchange (ETDEWEB)

    Anzai, Jun, E-mail: anzai_jun@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Kitamura, Masahiro, E-mail: kitamura@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nozaki, Takenori, E-mail: tnozaki@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nagayasu, Toshie, E-mail: nagayasu_toshie@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Terashima, Akio, E-mail: terashima_akio@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Asano, Taiji, E-mail: asano_taiji@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Murakami, Shinya, E-mail: ipshinya@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2010-12-17

    Research highlights: {yields} Concomitant use of FGF-2 and {beta}-TCP (an osteo-conductive scaffold) significantly promotes periodontal regeneration in the severe periodontitis model (1-wall defect model) of beagle dog. {yields} FGF-2 enhanced new bone formation via {beta}-TCP at the defects. {yields} In particular, FGF-2 dramatically regenerated new periodontal ligament and cementum formations at the defects, that is one of the most important healing outcomes during the process of periodontal regeneration. {yields} Epithelial downgrowth (undesirable wound healing) was decreased by administration of FGF-2. {yields} This manuscript indicates for the first time that concomitant use of FGF-2 and {beta}-TCP is efficacious in regenerating periodontal tissue following severe destruction of the tissue by progression of periodontitis. -- Abstract: The effects of concomitant use of fibroblast growth factor-2 (FGF-2) and beta-tricalcium phosphate ({beta}-TCP) on periodontal regeneration were investigated in the beagle dog 1-wall periodontal defect model. One-wall periodontal defects were created in the mesial portion of both sides of the mandibular first molars, and 0.3% FGF-2 plus {beta}-TCP or {beta}-TCP alone was administered. Radiographic evaluation was performed at 0, 3, and 6 weeks. At 6 weeks, the periodontium with the defect site was removed and histologically analyzed. Radiographic findings showed that co-administration of FGF-2 significantly increased bone mineral contents of the defect sites compared with {beta}-TCP alone. Histologic analysis revealed that the length of the regenerated periodontal ligament, the cementum, distance to the junctional epithelium, new bone height, and area of newly formed bone were significantly increased in the FGF-2 group. No abnormal inflammatory response or ankylosis was observed in either group. These findings indicate the efficacy of concomitant use of FGF-2 and {beta}-TCP as an osteoconductive material for periodontal

  15. Development of a rapid and sensitive UPLC-MS/MS assay for the determination of TM-2 in beagle dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Lin, Hongli; Zhao, Yunli; Men, Lei; Yang, Mingjing; Liu, Hui; Shao, Yanjie; Wang, Pei; Tang, Xing; Yu, Zhiguo

    2015-01-01

    A simple and sensitive method based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of TM-2, which was a novel semi-synthetic taxane derivative in beagle dog plasma. Cabazitaxel was chosen as internal standard. Following extraction by methyl tert-butyl ether, the chromatographic separation was achieved on a Thermo Syncronis C18 column (50 × 2.1 mm, 1.7 µm) by gradient elution within a runtime of 3.5 min. The mobile phase consisted of (A) acetonitrile and (B) 2 mmol/L ammonium acetate in water. The detection was accomplished using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 812.39 → 551.35 for TM-2 and 836.36 → 555.26 for IS, respectively. The method was linear for TM-2 (r = 0.9924) ranging from 2.5 to 1000 ng/mL. The intra-day and inter-day precisions (relative standard deviation) were within 8.0 and 17.6%, respectively, and the accuracy (relative error) was less than 2.3%. The extraction recovery ranged from 83.1 to 97.1%. The reliable method was successfully applied to a pharmacokinetic study of TM-2 in beagle dogs after intravenous drip with different doses of 0.6, 1.2, and 2.4 mg/kg, respectively.

  16. Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs.

    Science.gov (United States)

    Marsella, Rosanna; Ahrens, Kim; Sanford, Rachel

    2017-10-06

    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.

  17. Why do people buy dogs with potential welfare problems related to extreme conformation and inherited disease? A representative study of Danish owners of four small dog breeds.

    Science.gov (United States)

    Sandøe, P; Kondrup, S V; Bennett, P C; Forkman, B; Meyer, I; Proschowsky, H F; Serpell, J A; Lund, T B

    2017-01-01

    A number of dog breeds suffer from welfare problems due to extreme phenotypes and high levels of inherited diseases but the popularity of such breeds is not declining. Using a survey of owners of two popular breeds with extreme physical features (French Bulldog and Chihuahua), one with a high load of inherited diseases not directly related to conformation (Cavalier King Charles Spaniel), and one representing the same size range but without extreme conformation and with the same level of disease as the overall dog population (Cairn Terrier), we investigated this seeming paradox. We examined planning and motivational factors behind acquisition of the dogs, and whether levels of experienced health and behavior problems were associated with the quality of the owner-dog relationship and the intention to re-procure a dog of the same breed. Owners of each of the four breeds (750/breed) were randomly drawn from a nationwide Danish dog registry and invited to participate. Of these, 911 responded, giving a final sample of 846. There were clear differences between owners of the four breeds with respect to degree of planning prior to purchase, with owners of Chihuahuas exhibiting less. Motivations behind choice of dog were also different. Health and other breed attributes were more important to owners of Cairn Terriers, whereas the dog's personality was reported to be more important for owners of French Bulldogs and Cavalier King Charles Spaniels but less important for Chihuahua owners. Higher levels of health and behavior problems were positively associated with a closer owner-dog relationship for owners of Cavalier King Charles Spaniels and Chihuahuas but, for owners of French Bulldogs, high levels of problems were negatively associated with an intention to procure the same breed again. In light of these findings, it appears less paradoxical that people continue to buy dogs with welfare problems.

  18. Higher neonatal growth rate and body condition score at 7 months are predictive factors of obesity in adult female Beagle dogs.

    Science.gov (United States)

    Leclerc, Lucie; Thorin, Chantal; Flanagan, John; Biourge, Vincent; Serisier, Samuel; Nguyen, Patrick

    2017-04-13

    The risks during early growth on becoming overweight in adulthood are widely studied in humans. However, early-life predictive factors for canine adult overweight and obesity have not yet been studied. To identify factors that may help explain the development of overweight and obesity at adulthood in dogs, a longitudinal study of 2 years was conducted in 24 female Beagle dogs of the same age, sexual status, and raised under identical environmental conditions. By means of a hierarchical classification on principal components with the following quantitative values: fat-free mass (FFM), percentage fat mass and pelvic circumference at 2 years of age, three groups of dogs were established and were nominally named: ideal weight (IW, n = 9), slightly overweight (OW1, n = 6) and overweight (OW2, n = 9). With the aim of identifying predictive factors of development of obesity at adulthood parental characteristics, growth pattern, energy balance and plasma factors were analysed by logistic regression analysis. At 24 months, the group compositions were in line with the body condition scores (BCS 1-9) values of the IW (5 or 6/9), the OW1 (6/9) and the OW2 (7 or 8/9) groups. Logistic regression analysis permitted the identification of neonatal growth rate during the first 2 weeks of life (GR2W) and BCS at 7 months as predictors for the development of obesity at adulthood. Seventy percent of dogs with either GR2W >125% or with BCS > 6/9 at 7 months belonged to the OW2 group. Results from energy intake and expenditure, corrected for FFM, showed that there was a greater positive energy imbalance between 7 and 10 months for the OW2, compared to the IW group. This study expands the understanding of previously reported risk factors for being overweight or obese in dogs, establishing that (i) 15 out of 24 of the studied dogs became overweight and (ii) GR2W and BCS at 7 months of age could be used as predictive factors as overweight adult dogs in the OW2 group

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

    Science.gov (United States)

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

    2008-09-01

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

  20. Why do people buy dogs with potential welfare problems related to extreme conformation and inherited disease? A representative study of Danish owners of four small dog breeds

    Science.gov (United States)

    Kondrup, S. V.; Bennett, P. C.; Forkman, B.; Meyer, I; Proschowsky, H. F.; Serpell, J. A.; Lund, T. B.

    2017-01-01

    A number of dog breeds suffer from welfare problems due to extreme phenotypes and high levels of inherited diseases but the popularity of such breeds is not declining. Using a survey of owners of two popular breeds with extreme physical features (French Bulldog and Chihuahua), one with a high load of inherited diseases not directly related to conformation (Cavalier King Charles Spaniel), and one representing the same size range but without extreme conformation and with the same level of disease as the overall dog population (Cairn Terrier), we investigated this seeming paradox. We examined planning and motivational factors behind acquisition of the dogs, and whether levels of experienced health and behavior problems were associated with the quality of the owner-dog relationship and the intention to re-procure a dog of the same breed. Owners of each of the four breeds (750/breed) were randomly drawn from a nationwide Danish dog registry and invited to participate. Of these, 911 responded, giving a final sample of 846. There were clear differences between owners of the four breeds with respect to degree of planning prior to purchase, with owners of Chihuahuas exhibiting less. Motivations behind choice of dog were also different. Health and other breed attributes were more important to owners of Cairn Terriers, whereas the dog’s personality was reported to be more important for owners of French Bulldogs and Cavalier King Charles Spaniels but less important for Chihuahua owners. Higher levels of health and behavior problems were positively associated with a closer owner-dog relationship for owners of Cavalier King Charles Spaniels and Chihuahuas but, for owners of French Bulldogs, high levels of problems were negatively associated with an intention to procure the same breed again. In light of these findings, it appears less paradoxical that people continue to buy dogs with welfare problems. PMID:28234931

  1. Inherited retinal diseases in dogs: advances in gene/mutation discovery.

    Science.gov (United States)

    Miyadera, Keiko

    1. Inherited retinal diseases (RDs) are vision-threatening conditions affecting humans as well as many domestic animals. Through many years of clinical studies of the domestic dog population, a wide array of RDs has been phenotypically characterized. Extensive effort to map the causative gene and to identify the underlying mutation followed. Through candidate gene, linkage analysis, genome-wide association studies, and more recently, by means of next-generation sequencing, as many as 31 mutations in 24 genes have been identified as the underlying cause for canine RDs. Most of these genes have been associated with human RDs providing opportunities to study their roles in the disease pathogenesis and in normal visual function. The canine model has also contributed in developing new treatments such as gene therapy which has been clinically applied to human patients. Meanwhile, with increasing knowledge of the molecular architecture of RDs in different subpopulations of dogs, the conventional understanding of RDs as a simple monogenic disease is beginning to change. Emerging evidence of modifiers that alters the disease outcome is complicating the interpretation of DNA tests. In this review, advances in the gene/mutation discovery approaches and the emerging genetic complexity of canine RDs are discussed.

  2. 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.

  3. 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.

  4. 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.

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

    Science.gov (United States)

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

    2017-04-01

    This study's objective was to determine the effects in dogs of oral capromorelin, a ghrelin agonist, at different doses for 7 days on food consumption, body weight and serum concentrations of growth hormone (GH), insulin-like growth factor 1 (IGF-1), and cortisol. Adult Beagles (n = 6) were dosed with placebo BID, capromorelin at 3.0 mg/kg SID, 4.5 mg/kg SID, or 3.0 mg/kg BID. Food consumption, body weight, serum capromorelin, GH, IGF-1, and cortisol were measured at intervals on days 1, 4, 7, and 9. Capromorelin increased food consumption and body weight compared to placebo and caused increased serum GH, which returned to the baseline by 8 h postdose. The magnitude of the GH increase was less on days 4 and 7 compared to Day 1. IGF-1 concentrations increased on Day 1 in capromorelin-treated dogs and this increase was sustained through Day 7. Serum cortisol increased postdosing and returned to the baseline concentrations by 8 h. The magnitude of the increase was less on days 4 and 7 compared to Day 1. A dose of 3 mg/kg was chosen for further study in dogs based on this dose causing increased food consumption and sustained IGF-1 serum concentrations that may increase lean muscle mass when administered over extended periods. © 2016 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Kim JS

    2016-06-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

  8. The occurrence and suspected mode of inheritance of congenital subaortic stenosis and tricuspid valve dysplasia in Dogue de Bordeaux dogs.

    Science.gov (United States)

    Ohad, D G; Avrahami, A; Waner, T; David, L

    2013-08-01

    The Dogue de Bordeaux (DdB) breed has gone through several genetic 'bottle necks' and has a relatively small effective population size. Importing new stock into Israel has been limited, further narrowing the already restricted local gene-pool and increasing the chances of inherited defects. In 56 DdB dogs examined between 2003 and 2010, the authors sought to study the proportion congenital subaortic stenosis (SAS) and tricuspid valve dysplasia (TVD). The aim was also to identify a probable mode of inheritance (MOI) using segregation and pedigree analyses of genealogical data available from 13/21 DdB dogs diagnosed with these conditions between 2004 and 2007. Among all breeds in the country, TVD was highest in the DdB breed, which also displayed the second highest proportion of SAS. Echocardiographic measurements and selected physical examination findings from 26 normal DdB dogs, 18 DdB dogs with SAS, and 12 DdB dogs with TVD are reported. Based on pedigree and segregation analyses, the most probable MOI appeared to be autosomal recessive. Pedigree analyses helped to identify three ancestors that might have introduced these two congenital heart defects into the local DdB population. Excluding those three dogs and their progeny from future mating could therefore reduce the prevalence of these diseases in the DdB population in Israel. The unusual local breeding circumstances may offer a unique opportunity to identify associated SAS and TVD genes in the DdB, as well as in other dog breeds. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2014-09-01

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

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

    Institute of Scientific and Technical Information of China (English)

    张毅; 陈霞; 周凌云; 王旭东; 虞昊

    2015-01-01

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

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

    Science.gov (United States)

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

    2014-05-01

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

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

    Science.gov (United States)

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

    2007-09-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-12-15

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

  15. Cloning of the short-tailed Gyeongju Donggyeong dog via SCNT: conserving phenotypic inheritance.

    Science.gov (United States)

    Choi, Yoo Bin; Kim, Geon A; Oh, Hyun Ju; Kim, Min Jung; Jo, Young Kwang; Setyawan, Erif Maha Nugraha; Lee, Seok Hee; Lee, Byeong Chun

    2016-02-01

    Somatic cell nuclear transfer is a useful tool to maintain genetic information of animals. The Gyeongju Donggyeong dog is a breed registered as natural monument in Korea. The unique feature of the Donggyeong dog is its tail, as the Donggyeong dog can be classified as either short tailed or tailless. The aim of this study was to preserve the Donggyeong dog's unique feature by cloning. Fibroblasts were obtained from a short-tailed Donggyeong dog. In vivo matured oocytes were enucleated, microinjected with a donor cell and fused electrically. Reconstructed embryos were transferred to six recipient dogs. One surrogate became pregnant, and one short-tailed Donggyeong dog was delivered. This study demonstrated that the phenotype of the Donggyeong dog could be conserved by somatic cell nuclear transfer.

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

    Science.gov (United States)

    Christiansen, Martin Lau; Holm, Rene; Kristensen, Jakob; Kreilgaard, Mads; Jacobsen, Jette; Abrahamsson, Bertil; Müllertz, Anette

    2014-06-16

    To elucidate if a SNEDDS approach can eliminate the food-effect on cinnarizine absorption and to, investigate if a nutritional drink, Fresubin energy, could mimic food effect in dogs for the poorly soluble compound cinnarizine. A conventional tablet, a SNEDDS capsule or a SNEDDS tablet, containing cinnarizine, were dosed to beagles dogs in fed or fasted state (n=5), with a one week wash-out period between dosing. Dogs were pre-treated with pentagastrin. Fed state was induced by a nutritional drink (Fresubin Energy®). The food-effect was evaluated by comparing Tmax, Cmax and Bioavailability (F) for the different formulations. Food effect was observed on all three parameters for the conventional tablet; Tmax was delayed 2.5times and bioavailability increased in fed state (from 20.9±5.7 to 53.8±30.1). Apart from an extended Tmax (2.5 and 3.3 times longer in fed state compared to fasted state for the SNEDDS tablets and SNEDDS capsules respectively), food effect on absorption for the SNEDDS capsules and SNEDDS tablets was not observed. The SNEDDS capsules had a higher bioavailability in both fed and fasted state compared to SNEDDS tablets (Ffasted=58.1±16.7, vs. 32.7±11.5), (Ffed=79.3±14.7 vs. 43.7±6.7) There were no significant differences in bioavailability between the conventional tablet in fed state and the SNEDDS capsules. Food effect was observed when dosing cinnarizine with ingestion of the nutritional drink Fresubin Energy. Food effect on cinnarizine could be significantly reduced by dosing either as a SNEEDS capsule or a SNEDDS tablet, however, the SNEDDS tablet resulted in an overall lower absorption than the SNEDDS capsules in both fed and fasted state. The delay in fed state absorption could not be changed by dosing with SNEDDS formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Rickert, D E; Dingley, K H; Ubick, E; Dix, K J; Molina, L

    2004-07-02

    Administration of {sup 14}C-Moli1901 (duramycin, 2622U90), a 19 amino acid polycyclic peptide by intratracheal instillation (approximately 100 {micro}g) into the left cranial lobe of the lung of beagle dogs resulted in retention of 64% of the dose in the left cranial lobe for up to 28 days. In this study, we used accelerator mass spectrometry (AMS) to quantify Moli901 following administration of only 0.045 {micro}Ci of {sup 14}C-Moli901 per dog. Limits of quantitation of AMS were 0.03 (urine) to 0.3 (feces) ng equiv. Moli1901/g. Whole blood and plasma concentrations of {sup 14}C were <5ng/ml at all times after the dose. Concentrations of {sup 14}C in whole blood and plasma declined over the first day after the dose and rose thereafter, with the rise in plasma concentrations lagging behind those in whole blood. During the first 3 days after the dose, plasma accounted for the majority of {sup 14}C in whole blood, but after that time, plasma accounted for only 25-30% of the {sup 14}C in whole blood. Tissue (left and right caudal lung lobe, liver, kidney, spleen, brain) and bile concentrations were low, always less than 0.25% the concentrations found in the left cranial lung lobe. Approximately 13% of the dose was eliminated in urine and feces in 28 days, with fecal elimination accounting for about 10% of the dose. The data presented here are consistent with that obtained in other species. Moli1901 is slowly absorbed and excreted from the lung, and it does not accumulate in other tissues. Moli1901 is currently in the clinic and has proven to be safe in single dose studies in human volunteers and cystic fibrosis patients by the inhalation route. No information on the disposition of the compound in humans is available. This study in dogs demonstrates the feasibility of obtaining that information using {sup 14}C-Moli1901 and AMS.

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

    Institute of Scientific and Technical Information of China (English)

    马大勇; 韩振蕴; 范吉平

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    康纪平; 李秋波; 冯晓科; 廖婷彬; 杨杰

    2011-01-01

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

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

    Science.gov (United States)

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

    2014-10-23

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    王亚辉; 胡斌; 那丽; 丁国臣

    2012-01-01

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

  3. Rapid and Sensitive LC-MS/MS Method for the Determination of Metoprolol in Beagle Dog Plasma with a Simple Protein Precipitation Treatment and Its Pharmacokinetic Applications

    Directory of Open Access Journals (Sweden)

    Aihua Hong

    2012-03-01

    Full Text Available : A rapid LC-MS/MS method with good accuracy and sensitivity was developed and validated for the pharmacokinetics study of metoprolol (MP in beagle dogs. The plasma samples were simply precipitated by methanol and then analyzed by LC-MS/MS. An Ultimate XB-C18 column (150 × 2.1 mm ID, 5 μm was used for separation, with methanol-water containing 0.2% formic acid (65:35, v/v as the mobile phase at a flow rate of 0.2 mL/min. Monitoring ions of MP and internal standard (hydroxypioglitazone were m/z 268.1/115.6 and m/z 373.1/150.2, respectively. The linear range was 3.03–416.35 ng/mL with an average correlation coefficient of 0.9996, and the limit of quantification was 3.03 ng/mL. The intra- and inter-day precision was less than 15%. At low, middle and high concentrations, the recovery, the matrix effect and the accuracy was in the range of 76.06%–95.25%, 93.67%–104.19% and 95.20%–99.96% respectively. The method was applied for the pharmacokinetics study of MP tartrate tablets (50 mg. The AUC0-t, Tmax and Cmax were respectively 919.88 ± 195.67 μg/L·h, 0.96 ± 0.33 h, 349.12 ± 78.04 ng/mL.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

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    Hannah L Bader

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

  7. Sustained-release of Cyclosporin A pellets: preparation, in vitro release, pharmacokinetic studies and in vitro-in vivo correlation in beagle dogs.

    Science.gov (United States)

    Jiang, Dongmei; Zeng, Jin; Zhu, Yuan; Zhou, Guanghui; Deng, Wenwen; Xu, Ximing; Yu, Jiangnan

    2016-01-01

    The aim of this study was to develop Cyclosporin A (CsA) sustained-release pellets which could maintain CsA blood concentration within the therapeutic window throughout dosing interval and to investigate the in vitro-in vivo correlation (IVIVC) in beagle dogs. The CsA sustained-release pellets (CsA pellets) were prepared by a double coating method and characterized in vitro as well as in vivo. Consequently, the CsA pellets obtained were spherical in shape, with a desirable drug loading (7.18 ± 0.17 g/100 g), good stability and showed a sustained-release effect. The Cmax, Tmax and AUC0-24 of CsA pellets from the in vivo pharmacokinetics evaluation was 268.22 ± 15.99 ng/ml, 6 ± 0 h and 3205.00 ± 149.55 ng·h/ml, respectively. Compared with Neoral®, CsA pellets significantly prolonged the duration of action, reduced the peak blood concentration and could maintain a relatively high concentration level till 24 h. The relative bioavailability of CsA pellets was 125.68 ± 5.37% that of Neoral®. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the pellets. In conclusion, CsA pellets which could ensure a constant systemic blood concentration within the therapeutic window for 24 h were prepared successfully. Meanwhile, this formulation possessed a good IVIVC.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  9. Cloning of the short-tailed Gyeongju Donggyeong dog via SCNT: conserving phenotypic inheritance

    OpenAIRE

    Choi, Yoo Bin; Kim, Geon A; Oh, Hyun Ju; Kim, Min Jung; Jo, Young Kwang; SETYAWAN, Erif Maha Nugraha; Lee, Seok Hee; Lee, Byeong Chun

    2015-01-01

    Somatic cell nuclear transfer is a useful tool to maintain genetic information of animals. The Gyeongju Donggyeong dog is a breed registered as natural monument in Korea. The unique feature of the Donggyeong dog is its tail, as the Donggyeong dog can be classified as either short tailed or tailless. The aim of this study was to preserve the Donggyeong dog’s unique feature by cloning. Fibroblasts were obtained from a short-tailed Donggyeong dog. In vivo matured oocytes were enucleated, microin...

  10. Simultaneous determination of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside, senkyunolide I in Beagle dogs plasma by UPLC-MS/MS and its application to a pharmacokinetic study after Oral Administration of Shaofu Zhuyu Decoction.

    Science.gov (United States)

    Huang, Xiaochen; Su, Shulan; Cui, Wenxia; Liu, Pei; Duan, Jin-ao; Guo, Jianming; Li, Zhenhao; Shang, Erxin; Qian, Dawei; Huang, Zhijun

    2014-07-01

    In this present study, a sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside and senkyunolide I in Beagle dog plasma after oral administration of the Shao-Fu-Zhu-Yu Decoction. Chloramphenicol and clarithromycin were used as internal standards. Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100mm×2.1mm, 1.7μm) at a flow-rate of 0.4mL/min, using 0.1% formic acid-acetonitrile as mobile phase. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. After validation, this method was successfully applied to a pharmacokinetic study. The results showed that the apparent plasma clearance of paeoniflorin, albiflorin, typhaneoside and senkyunolide I were significantly higher than others. Double peak was observed in plasma concentration curves of tetrahydropalmatine, the ferulic acid had a good absorption in Beagle dog plasma, and senkyunolide I was detected in plasma from the first blood sampling time (15min) and rapidly reached Tmax. The compound of typhaneoside has a low bioavailability according to the results.

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

    Science.gov (United States)

    Kenward, Hannah; Pelligand, Ludovic; Elliott, Jonathan

    2014-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

    高国义; 刘志东; 解江纯

    2009-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    宋玉琴; 张雪; 董艳红; 代良萍; 彭成; 谢晓芳

    2015-01-01

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

  14. An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs.

    Directory of Open Access Journals (Sweden)

    Kari J Ekenstedt

    2014-10-01

    Full Text Available An inherited polyneuropathy (PN observed in Leonberger dogs has clinical similarities to a genetically heterogeneous group of peripheral neuropathies termed Charcot-Marie-Tooth (CMT disease in humans. The Leonberger disorder is a severe, juvenile-onset, chronic, progressive, and mixed PN, characterized by exercise intolerance, gait abnormalities and muscle atrophy of the pelvic limbs, as well as inspiratory stridor and dyspnea. We mapped a PN locus in Leonbergers to a 250 kb region on canine chromosome 16 (Praw = 1.16×10-10, Pgenome, corrected = 0.006 utilizing a high-density SNP array. Within this interval is the ARHGEF10 gene, a member of the rho family of GTPases known to be involved in neuronal growth and axonal migration, and implicated in human hypomyelination. ARHGEF10 sequencing identified a 10 bp deletion in affected dogs that removes four nucleotides from the 3'-end of exon 17 and six nucleotides from the 5'-end of intron 17 (c.1955_1958+6delCACGGTGAGC. This eliminates the 3'-splice junction of exon 17, creates an alternate splice site immediately downstream in which the processed mRNA contains a frame shift, and generates a premature stop codon predicted to truncate approximately 50% of the protein. Homozygosity for the deletion was highly associated with the severe juvenile-onset PN phenotype in both Leonberger and Saint Bernard dogs. The overall clinical picture of PN in these breeds, and the effects of sex and heterozygosity of the ARHGEF10 deletion, are less clear due to the likely presence of other forms of PN with variable ages of onset and severity of clinical signs. This is the first documented severe polyneuropathy associated with a mutation in ARHGEF10 in any species.

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

    Institute of Scientific and Technical Information of China (English)

    李庆新; 郑军; 张世范; 孟辉; 杨俊峰; 高炜; 刘传兰

    2012-01-01

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

  16. Simultaneous determination of triamcinolone acetonide palmitate and triamcinolone acetonide in beagle dog plasma by UPLC-MS/MS and its application to a long-term pharmacokinetic study of triamcinolone acetonide palmitate lipid emulsion injection.

    Science.gov (United States)

    Liu, Hui; Yang, Mingjing; Wu, Panpan; Guan, Jiao; Men, Lei; Lin, Hongli; Tang, Xing; Zhao, Yunli; Yu, Zhiguo

    2015-02-01

    In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid-liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C18 column (50 mm × 2.1mm, 1.7 μm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5→397.3, 435.3→415.3 and 393.3→355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1-1,000 ng/ml for TAP and 0.5-500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of -8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7-104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs.

  17. Development and validation of a rapid and high-sensitivity liquid chromatography-tandem mass spectrometry assay for the determination of neostigmine in small-volume beagle dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Cao, Di; Li, Wenxue; Zhao, Xin; Ye, Xiaolan; Sun, Fanlu; Li, Jinying; Song, Fenyun; Fan, Guorong

    2014-03-01

    A simple, rapid and high sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of neostigmine in small-volume beagle dog plasma was developed to assess the plasma pharmacokinetics of neostigmine. After protein precipitation in a Sirocco 96-well filtration plate, the filtrate was directly injected into the LC-MS/MS system. The analytes were separated on a Hanbon Hedera CN column (100 × 4.6 mm, 5 µm) with a mobile phase composed of methanol-water (60:40, v/v) and the water containing 0.01% formic acid at a flow rate of 0.6mL/min, with a split ratio of 1:1 flowing 300 μL into the mass spectrometer. The run time was 3 min. Detection was accomplished by electrospray ionization source in multiple reactions monitoring mode with the precursor-to-product ion transitions m/z 223.0 → 72.0 and 306.0 → 140.0 for neostigmine and anisodamine (internal standard), respectively. The method was sensitive with a lower limit of quantitation of 0.1 ng/mL, and good linearity in the range 0.1-100ng/mL for neostigmine (r ≥ 0.998). All the validation data, such as accuracy, intra-run and inter-run precision, were within the required limits. The method was successfully applied to pharmacokinetic study of neostigmine methylsulfate injection in beagle dogs.

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

    Institute of Scientific and Technical Information of China (English)

    郑朝; 李洪发; 赵艳红; 林姝慧

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    刘飞; 刘阳; 戴姗姗; 马宁虎; 张林; 郭青玉

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    贾栗; 王以美; 张利军; 李利忠; 彭双清

    2016-01-01

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

  1. Progressive axonopathy: an inherited neuropathy of boxer dogs. 2. The nature and distribution of the pathological changes.

    Science.gov (United States)

    Griffiths, I R; McCulloch, M C; Abrahams, S

    1985-01-01

    This report describes the neuropathology of progressive axonopathy (PA), an autosomal recessive inherited neuropathy of Boxer dogs, which affects CNS and PNS. The nerve roots contain numerous myelin bubbles and proximal paranodal axonal swellings containing vesicles, vesiculo-tubular profiles and disorganized neurofilaments. The myelin sheath overlying such swellings is often attenuated. As the disease develops there are progressive changes in the myelin sheath with thinning at paranodal and internodal locations, loss of myelin from lengths of axon and the formation of short internodes with disproportionately thin sheaths. The abnormalities show a very definite selectivity for nerve roots and proximal nerves. Conversely, the frequency of degeneration and regeneration is greater distally except in the cervical ventral roots which contain numerous regenerating clusters. In the CNS numerous axonal spheroids are found in the lateral and ventral columns of the spinal cord and in various brain stem nuclei, particularly the superior olives, accessory cuneate nuclei and lateral lemniscus and its nucleus. Axonal degeneration which occurs mainly in the cord shows no obvious tract or proximal/distal selectivity. The optic pathways are also involved, predominantly adjacent to the chiasma. The autonomic nervous system is affected and distal limb muscles show varying, but usually minor, degrees of neurogenic atrophy. The condition, which has no obvious direct parallel in human or veterinary medicine, shows gross disturbances of axon-glial inter-relationships in both CNS and PNS.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    To elucidate if a SNEDDS approach can eliminate the food-effect on cinnarizine absorption and to, investigate if a nutritional drink, Fresubin energy, could mimic food effect in dogs for the poorly soluble compound cinnarizine....

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

    Institute of Scientific and Technical Information of China (English)

    林若勤; 傅晓晴; 杨朝阳; 朱龙; 李慧勇

    2011-01-01

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

  5. Mitochondrial transcription factor A (Tfam) gene sequencing and mitochondrial evaluation in inherited retinal dysplasia in miniature schnauzer dogs

    OpenAIRE

    Bauer, Bianca S.; Forsyth, George W.; Sandmeyer, Lynne S.; Grahn, Bruce H.

    2011-01-01

    Mitochondrial transcription factor A (Tfam) has been implicated in the pathogenesis of retinal dysplasia in miniature schnauzer dogs and it has been proposed that affected dogs have altered mitochondrial numbers, size, and morphology. To test these hypotheses the Tfam gene of affected and normal miniature schnauzer dogs with retinal dysplasia was sequenced and lymphocyte mitochondria were quantified, measured, and the morphology was compared in normal and affected dogs using transmission elec...

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

    Science.gov (United States)

    1983-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

    董妮; 宋锦璘; 冯格; 刘珉懿; 邓锋

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    付唆林; 朱惠明; 郑丽

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    常会超; 陈山乔; 关晓多; 钱忠直; 范国荣; 毕开顺

    2013-01-01

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

  10. Life-span effects of ionizing radiation in the beagle dog: A summary account of four decades of research funded by the US Department of Energy and its predecessor agencies

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, R.C.

    1989-01-01

    Nearly 40 years ago, the US Atomic Energy Commission made a far- reaching commitment to the support of life-span radiation-effects studies in a relatively long-lived animal, the beagle dog. Something in the range of 200 million dollars has already been spent on a group of closely related experiments, many of which are only now coming to fruition. Responsible fiscal management of these studies, directed toward securing an optimum return from past investments, and toward creative planning of future directions, requires a comprehensive view of this total effort. This report is designed to provide that comprehensive view. This is primarily intended as a research management document. Evaluation and interpretation are tasks for those directly involved in conducting these experiments. The limited objective of the present document is to describe what has been done, to give some of the background for why it was done, to describe results already realized and applications that have been made of these results -- all in a manner designed to display the total effort rather than piecemeal details. While proposing no specific answers to the questions ''Where do we go from here.''it is hoped that the document will provide a basis for approaching that question in an informed manner. The maintenance of a continuity of scientific understanding and direction in these experiments, which often continue beyond the initiating investigators' working life, is no small part of the problem involved in conducting these experiments.

  11. XLPRA: A canine retinal degeneration inherited as an X-linked trait

    Energy Technology Data Exchange (ETDEWEB)

    Acland, G.M.; Blanton, S.H.; Hershfield, B.; Aguirre, G.D.

    1994-08-01

    Breeding studies are reported of a previously undescribed hereditary retinal degeneration identified in the Siberian Husky breed of dog. This disorder clinically resembles the previously reported autosomal recessive canine hereditary retinal degenerations collectively termed progressive retinal atrophy (PRA). However, the pedigree of the propositus, a male Siberian Husky, exhibited an X-linked pattern of transmission. This dog was outcrossed to three phenotypically normal female laboratory Beagles and two of their F1 daughters were bred to a phenotypically normal male Beagle, producing affected males in the F2 generation. Subsequent inbreedings produced further affected males and affected females as well. X-linked transmission was established by exclusion of alternative modes of inheritance and, consequently, the disease has been termed X-linked progressive retinal atrophy (XLPRA). This is the first reported X-linked retinal degeneration in an animal. Because of the many similarities of PRA in dogs to retinitis pigmentosa (RP) in humans, this new disease may not only represent the first animal model of X-linked RP (XLRP) but may well be a true homolog of one of the XLRP loci (RP2, RP3, RP6). It is the first retinal degeneration in dogs that can be assigned to an identified canine chromosome, and the first for which linkage mapping offers a realistic approach to proceed by positional cloning towards identifying the responsible gene. 58 refs., 1 fig., 3 tabs.

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    潘永明; 陈亮; 何欢; 徐孝平; 陈民利

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    杨大龙; 狄斌; 林荣锦; 尤淋君

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    李玉谷; 张媛; 孔小明; 程树军; 黄韧

    2003-01-01

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

  19. The effect of low doses of zearalenone and its metabolites on progesterone and 17β-estradiol concentrations in peripheral blood and body weights of pre-pubertal female Beagle dogs.

    Science.gov (United States)

    Gajęcka, Magdalena; Zielonka, Łukasz; Dąbrowski, Michał; Mróz, Magdalena; Gajęcki, Maciej

    2013-12-15

    The experiment involved 30 clinically healthy female Beagle dogs aged approximately 70 days with estimated initial body weight (BW) of 8 kg. The animals were randomly divided into two experimental groups (EI and EII) and a control group of 10 animals each. Group EI was intoxicated with 50 μg zearalenone/kg BW per os for 42 days, group EII received 75 μg zearalenone/kg BW per os for 42 days, and the control group was administered placebo per os for 42 days. The animals were weighed, and blood samples for analyses of the concentrations of zearalenone, its metabolites, progesterone and 17β-estradiol were collected seven times at seven-day intervals, one hour after mycotoxin administration. Biotransformation of zearalenone was observed in all groups throughout the experiment, and the highest percentage share of α-zearalenol was reported in group EII on the last five sampling dates (0.637-0.788 ng/ml, i.e. percentage share of 57.96-73.64%). The above had a significant influence on the non-physiological concentrations of progesterone and 17β-estradiol in both experimental (E) groups throughout the experiment. The lowest progesterone levels (0.131 ng/ml) were observed in group EII during the last test, and high concentrations of 17β-estradiol were found in group EII on the last two sampling dates (17.434 and 21.581 ng/ml, respectively) in comparison with control. Inhibited proliferation, manifested by a slower rate of body weight gain, was observed on the last but one day of zearalenone administration in both experimental groups. Our results indicate that NOAEL doses have stimulating/adaptive effects, whereas doses above NOAEL values suggest that even very low zearalenone doses can act as endocrine disruptors with regard to progesterone and 17β-estradiol. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Institute of Scientific and Technical Information of China (English)

    伍衢; 王悦; 王永禄; 李学明; 毛利娟

    2011-01-01

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

  1. Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed.

    Directory of Open Access Journals (Sweden)

    Oliver P Forman

    2012-01-01

    Full Text Available The domestic dog (Canis familiaris segregates more naturally-occurring diseases and phenotypic variation than any other species and has become established as an unparalled model with which to study the genetics of inherited traits. We used a genome-wide association study (GWAS and targeted resequencing of DNA from just five dogs to simultaneously map and identify mutations for two distinct inherited disorders that both affect a single breed, the Cavalier King Charles Spaniel. We investigated episodic falling (EF, a paroxysmal exertion-induced dyskinesia, alongside the phenotypically distinct condition congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID, commonly known as dry eye curly coat syndrome. EF is characterised by episodes of exercise-induced muscular hypertonicity and abnormal posturing, usually occurring after exercise or periods of excitement. CKCSID is a congenital disorder that manifests as a rough coat present at birth, with keratoconjunctivitis sicca apparent on eyelid opening at 10-14 days, followed by hyperkeratinisation of footpads and distortion of nails that develops over the next few months. We undertook a GWAS with 31 EF cases, 23 CKCSID cases, and a common set of 38 controls and identified statistically associated signals for EF and CKCSID on chromosome 7 (P(raw 1.9×10(-14; P(genome = 1.0×10(-5 and chromosome 13 (P(raw 1.2×10(-17; P(genome = 1.0×10(-5, respectively. We resequenced both the EF and CKCSID disease-associated regions in just five dogs and identified a 15,724 bp deletion spanning three exons of BCAN associated with EF and a single base-pair exonic deletion in FAM83H associated with CKCSID. Neither BCAN or FAM83H have been associated with equivalent disease phenotypes in any other species, thus demonstrating the ability to use the domestic dog to study the genetic basis of more than one disease simultaneously in a single breed and to identify multiple novel candidate genes in

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

    Directory of Open Access Journals (Sweden)

    Thiago Ignácio Wakoff

    2013-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

    蒋飞荣; 马丽; 曾贵荣; 邓青; 邓友田; 姜德建

    2016-01-01

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

  4. In Vivo Performance of Fenofibrate Formulated With Ordered Mesoporous Silica Versus 2-Marketed Formulations: A Comparative Bioavailability Study in Beagle Dogs.

    Science.gov (United States)

    Bukara, Katarina; Schueller, Laurent; Rosier, Jan; Daems, Tinne; Verheyden, Loes; Eelen, Siemon; Martens, Johan A; Van den Mooter, Guy; Bugarski, Branko; Kiekens, Filip

    2016-08-01

    The present study aims to evaluate the in vitro and in vivo performance of ordered mesoporous silica (OMS) as a carrier for the poorly water-soluble compound fenofibrate. Fenofibrate was loaded into OMS via incipient wetness impregnation to obtain a 29% drug load and formulated into capsules. Two capsule dosage forms (containing 33.5 and 16.75 mg fenofibrate, respectively) were compared with the commercially available forms-Lipanthyl(®) (fenofibrate microcrystals) and Tricor(®) (fenofibrate nanocrystals). In vitro dissolution tests showed that the amount of fenofibrate released from Lipanthyl(®) and Tricor(®) was approximately 30%, whereas approximately 66% and 60% of the drug was released from OMS capsules containing 33.5 and 16.75 mg of fenofibrate, respectively. Storage of OMS capsules loaded with 33.5 mg of fenofibrate at 25°C/60% relative humidity (RH) or 40°C/75% RH did not alter the release kinetics, nor the physical state of the compound, pointing the stability of the present formulation. The in vivo study in dogs confirmed satisfying level of safety and tolerability of fenofibrate-OMS formulation (eq. 33.5 mg) with the potential to improve the absorption of fenofibrate. Though some variability in the data, this formulation is promising to be further investigated in a clinical trial setting. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

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

    Institute of Scientific and Technical Information of China (English)

    胡晓乐; 李会恩; 李斌; 王恩力; 冯中; 赵涛

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    方颖颖; 陈爱瑛; 叶小弟; 程敏; 缪云萍; 董文彬; 郑高利

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    冯利; 孙文霞; 毛旭东; 程强

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    蔡飞; 朱宏辉; 孙亮; 高守红; 王维泓; 陈万生

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    老东辉; 严东明; 马璟

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    何平; 高翔; 宋锦?; 邓锋; 赵纯亮; 王智彪; 李娜

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    吴敏; 谢佳; 曾建; 刘洪; 李德银

    2013-01-01

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

  12. Dogs

    Science.gov (United States)

    ... Dogs Farm Animals Backyard Poultry Ferrets Fish Horses Reptiles and Amphibians Turtles Kept as Pets Key Messages ... transmitted by sandflies and is uncommon in North America. The two forms of the disease are visceral ...

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

    Institute of Scientific and Technical Information of China (English)

    张建明; 吴江; 方晓玲

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    郭怡丹; 张笋

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    黄闯; 宋镜明; 宋扬; 刘佳; 王丽颖; 金作林

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Walaa I. Mohamaden

    2014-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

    潘永明; 何欢; 陈亮; 徐孝平; 杨玉伟; 朱科燕; 陈民利

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    阚淑玲; 谢卫锋; 周永强

    2012-01-01

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

  20. Acute monocytic leukemia in an irradiated beagle

    Energy Technology Data Exchange (ETDEWEB)

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

    1979-01-01

    A purebred female Beagle dog that had received 2,000 R of protracted whole-body ..gamma..-irradiation from /sup 60/Co when 14 months old had hematologic changes consistent with a myeloproliferative disorder 3 years after the termination of radiation exposure. Peripheral blood and bone marrow findings during the 7-month period before death showed progressive anemia with increased numbers of platelets; immature granulocytes, monocytes and promonocytes. A period of partial remission occurred during which time the peripheral blood was aleukemic, although there was marked thrombocytosis and abnormal erythropoiesis which was evidenced by bizarre circulating nucleated red cells, anisocytosis, poikilocytosis and Howell-Jolly bodies. The dog had a terminal crisis with marked leukocytosis, most cells in the peripheral blood being bizarre monocytes and promonocytes. Tissues obtained at necroscopy showed diffuse as well as focal infiltration of the spleen, liver, lymph nodes, heart, kidney and gastrointestinal wall with immature neoplastic cells resembling monocytes and monocytic precursors. The monocytic differentiation of the invasive cell population was confirmed by morphological, cytochemical, histological, ultrastructural and in vitro cell culture studies.

  1. Inherited Thrombophilia

    Institute of Scientific and Technical Information of China (English)

    包承鑫

    2007-01-01

    @@ The term thrombophilia includes any inherited and acquired disorders associated with an increased tendency to venous thromboembolism(VTE), the presence of inherited thrombophilic defects exposed carriers to increased risks for VTE compared with noncarriers.

  2. Mars Express releases Beagle 2

    Science.gov (United States)

    2003-12-01

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

  3. 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.

  4. The Legacy of Beagle 2

    Science.gov (United States)

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

    2015-04-01

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

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

    Institute of Scientific and Technical Information of China (English)

    殷健; 冯岩; 卢骏; 刘志东; 师健鑫

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    黄平; 何春柏; 赵子明; 唐翠

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-01

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

  8. Lunar Beagle and Lunar Astrobiology

    Science.gov (United States)

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

    2010-12-01

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

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

    Science.gov (United States)

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

    1985-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-10-01

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

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

    Institute of Scientific and Technical Information of China (English)

    李欣; 姜庆伟; 杜丽娜

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  13. To inherit heritage or to inherit inheritance?

    Directory of Open Access Journals (Sweden)

    Vladimir Krivošejev

    2016-02-01

    Full Text Available The Republic of Serbia is one of the few, if not the only country in the world that, at ratification and translation of the term „baština“– heritage which appears in two significant and related international conventions of UNESCO, used different terms: „baština“– „heritage“, with regard to the Convention Concerning the Protection of the World Cultural and Natural Heritage, and „nasledje“ –inheritance in the Convention for the Safeguarding of the Intangible Cultural Heritage. One of the reasons for the subsequent rejection of the term heritage could lay in the opinion that it was the case of (end of 20th and beginning of the 21st century political bureaucratic introduction of an old, forgotten word, which also contains the notion of gender incorrectness based on pointing out the inheritance through the male line, which could be in conflict with international law. The views expressed in this paper suggest the unsustainability of these claims, as well as greater suitability of the term „baština“– heritage. Namely, the ratification of the Convention Concerning the Protection of the World Cultural and Natural Heritage was done as early as in 1974, and since then the term „baština“– heritage was used, its new introduction into use on the basis of recent daily political aspirations cannot be the case. At the same time inheritance through the male line is encountered with the use of the Latin word „patrimonium“, which is the basis for the terms used in the official translation of the UNESCO-listed conventions in French and Spanish: „patrimoine“ and „patrimonio“ (and other Roman languages so that the use of the term „baština“ –heritage cannot be a violation of international legal norms. Finally, bearing in mind the fact that, in general, use of languages is impossible to achieve complete gender purism, it is necessary to emphasize that in contrast to the term „nasledje“ – inheritance, the

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    马银玲; 赵锋; 金晓利; 王静; 曹德英

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    郑鸿; 卢礼; 宋锦璘; 高翔; 邓锋; 王智彪

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    许蕾; 李家锋; 唐巍; 韩建国; 孙晋虎

    2015-01-01

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

  18. Subchronic (13-week) oral toxicity study of α-cyclodextrin in dogs

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    2004-01-01

    The oral toxicity of α-cyclodextrin (α-CD) was examined in a 13-week feeding study in which groups of Beagle dogs received α-CD in the diet at concentrations of 0 (control), 5, 10, or 20% (4dogs/sex/group). No treatment-related changes were noted in behavior or appearance of the dogs and no mortalit

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

    Institute of Scientific and Technical Information of China (English)

    张晓梅; 朱梅; 孙天慧; 王明新; 刘津爱; 赵怀清

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  1. 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).

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

    Institute of Scientific and Technical Information of China (English)

    肖慧娟; 柳忠豪; 杨云东; 许胜

    2014-01-01

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

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

    Science.gov (United States)

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

    2006-10-01

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

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

    Institute of Scientific and Technical Information of China (English)

    高翔; 宋锦璘; 邓锋; 赵纯亮; 王智彪

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    申文晋; 宋紫辉; 范明源; 项宗尚; 蔡永明; 张宗鹏

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    王格; 吴文惠; 王小雨; 张朝燕; 包斌

    2015-01-01

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

  7. Beagle-2 landing site atlas

    Science.gov (United States)

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

    2003-04-01

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

  8. Beagle 2: Mission to Mars - Current Status

    Science.gov (United States)

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

    2004-01-01

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

  9. Subchronic (13-week) oral toxicity study of y-cyclodextrin in dogs

    NARCIS (Netherlands)

    Til, H.P.; Bär, A.

    1998-01-01

    The oral toxicity of γ-cyclodextrin (γ- CD) was examined in a 13-week feeding study in which four groups of four male and four female Beagle dogs received γ-CD in the diet at concentrations of 0 (control), 5, 10, or 20%. No treatment-related changes were noted in behavior or appearance of the dogs a

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

    Institute of Scientific and Technical Information of China (English)

    宋玉乔; 廖杰; 刘华伟; 艾常虹; 张峰

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    陈雪珊; 滕亮; 贺鑫韬; 马桂芝

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-02-01

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

  13. Screening for periodontal disease in research dogs - a methodology study

    DEFF Research Database (Denmark)

    Kortegaard, Hanne E; Eriksen, Thomas; Bælum, Vibeke

    2014-01-01

    BackgroundIt has been shown that the prevalence of both clinical attachment loss (CAL) >1 mm and pocket probing depth (PPD) >4 mm is relatively high even in younger dogs, but also that only a minority of the dogs have such clinical signs of periodontal disease (PD) in more than a few teeth. Hence...... is the central variable in assessing PD extent and severity while PPD is the central variable used in treatment planning which make these two variables obvious in a screening protocol with the dual aim of disease identification and treatment planning. The main purpose of the present study in 98 laboratory Beagle.......2% of all teeth positive for CAL ¿1mm. The results presented here only pertain to the present study population.ConclusionsThis screening protocol is suitable for examination of larger groups of laboratory Beagle dogs for PD and our findings indicate that diseased dogs are identified with a high degree...

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

    Directory of Open Access Journals (Sweden)

    Cabrera García, Alexei

    2012-01-01

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

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

    Science.gov (United States)

    Nishita, Toshiho; Miyazaki, Rui; Miyazaki, Takae; Ochiai, Hideharu; Orito, Kensuke

    2016-06-01

    IgGs to carbonic anhydrase isozymes (CA-I and CA-II) and albumin were identified in dog serum. IgG titers were determined in the sera of asymptomatic dogs, and in dogs with atopic dermatitis, diarrhea and/or vomiting, diabetes and/or pancreatitis, kidney disease, hepatic disease, and thyroid gland disease, using ELISA. Low titres of IgG-reactive CA-I, CA-II, BSA, and CSA were found in the sera of healthy beagles. Compared with healthy beagles, there was a significant difference in the titers of antibodies against CA-I in asymptomatic dogs, dogs with diabetes and/or pancreatitis, or thyroid gland disease, or hepatic disease. Compared with healthy beagles, there was a significant difference in the antibody titer of anti-CA-II IgG in asymptomatic dogs and in those with hepatic disease. There was a significant difference in the antibody titer of anti-BSA IgG between healthy beagles and dogs with hepatic disease.

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

    Science.gov (United States)

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

    2014-01-01

    We evaluated adverse events, biodistribution and shedding of oncolytic vaccinia virus encoding CD40 ligand in two Beagles, in preparation for a phase 1 trial in canine cancer patients. Dog 1 received one dose of vaccinia virus and was euthanized 24 hours afterwards, while dog 2 received virus four times once weekly and was euthanized 7 days after that. Dogs were monitored for adverse events and underwent a detailed postmortem examination. Blood, saliva, urine, feces, and organs were collected for virus detection. Dog 1 had mild fever and lethargy while dog 2 experienced a possible seizure 5.5 hours after first virus administration. Viral DNA declined quickly in the blood after virus administration in both dogs but was still detectable 1 week later by quantitative polymerase chain reaction. Only samples taken directly after virus infusion contained infectious virus. Small amounts of viral DNA, but no infectious virus, were detected in a few saliva and urine samples. Necropsies did not reveal any relevant pathological changes and virus DNA was detected mainly in the spleen. The dogs in the study did not have cancer, and thus adverse events could be more common and viral load higher in dogs with tumors which allow viral amplification.

  17. Thrombin-activatable fibrinolysis inhibitor activity in healthy and diseased dogs

    DEFF Research Database (Denmark)

    Jessen, Lisbeth Rem; Wiinberg, Bo; Kjelgaard-Hansen, Mads

    2010-01-01

    Background: In people, increased thrombin-activatable fibrinolysis inhibitor (TAFI) antigen has been associated with increased risk of thrombosis, and decreased TAFI may contribute to bleeding diathesis. TAFI activity in dogs has been described in experimental models, but not in dogs...... with spontaneous disease. Objective: The aim of this study was to compare TAFI activity in healthy dogs with TAFI activity in dogs with spontaneous disease. Methods: Plasma samples from 20 clinically healthy Beagles and from 35 dogs with various diseases were analyzed using a commercial chromogenic assay...... that measured TAFI activity relative to activity in standardized pooled human plasma. Results: Median TAFI activity for the 20 Beagles was 46.1% (range 32.2-70.8%) compared with 62.6% (29.1-250%) for the 35 diseased dogs, and 14/35 (40%) had TAFI activities >the upper limit for controls. The highest individual...

  18. 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.

  19. Use of imidacloprid-permethrin to prevent transmission of Anaplasma phagocytophilum from naturally infected Ixodes scapularis ticks to dogs.

    Science.gov (United States)

    Blagburn, Byron L; Spencer, Jennifer A; Billeter, Sarah A; Drazenovich, Nicole L; Butler, Jamie M; Land, Tracey M; Dykstra, Christine C; Stafford, Kirby C; Pough, Margaret B; Levy, Steven A; Bledsoe, David L

    2004-01-01

    One group of eight beagles was treated with a combination of imidacloprid and permethrin 7 days before exposure to Ixodes scapularis ticks that were naturally infected with Anaplasma phagocytophilum. A second group of eight beagles was not treated and was also exposed to infected ticks. Seven of eight non-treated dogs--but none of the treated dogs--developed specific antibodies to A. phagocytophilum. Results of this study indicate that a combination of imidacloprid and permethrin can prevent transmission of A. phagocytophilum to dogs if administered before exposure to infected ticks.

  20. Effect of short-term scrotal hyperthermia on spermatological parameters, testicular blood flow and gonadal tissue in dogs

    NARCIS (Netherlands)

    Henning, H; Masal, C; Herr, A; Wolf, K; Urhausen, C; Beineke, A; Beyerbach, M; Kramer, S; Günzel-Apel, A-R

    2014-01-01

    The objective was to assess the effect of a short-term scrotal hyperthermia in dogs on quantitative and qualitative ejaculate parameters, testicular blood flow and testicular and epididymal histology. After a control period, the scrotum of seven normospermic adult beagle dogs was insulated with a se

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

    Directory of Open Access Journals (Sweden)

    Jing-xiang Zhao

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

  2. The effect of frequency and duration of training sessions on acquisition and long-term memory in dogs

    DEFF Research Database (Denmark)

    Demant, Helle; Ladewig, Jan; Balsby, Thorsten Johannes Skovbjerg

    2011-01-01

    dogs such as guide dogs and police dogs, also the training of family dogs can benefit from this knowledge. We studied the effect of frequency and duration of training sessions on acquisition and on long-term memory. Forty-four laboratory Beagles were divided into 4 groups and trained by means...... of the learned task; all groups had a high level of retention after 4 weeks. The results of the study can be used to optimize training in dogs, which is important since the number of training sessions often is a limiting factor in practical dog training. The results also suggest that, once a task is learned...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1978-01-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

  5. Experimental infection of dogs with various Bartonella species or subspecies isolated from their natural reservoir.

    Science.gov (United States)

    Chomel, Bruno B; Ermel, Richard W; Kasten, Rickie W; Henn, Jennifer B; Fleischman, Drew A; Chang, Chao-Chin

    2014-01-10

    Dogs can be infected by a wide variety of Bartonella species. However, limited data is available on experimental infection of dogs with Bartonella strains isolated from domestic animals or wildlife. We report the inoculation of six dogs with Bartonella henselae (feline strain 94022, 16S rRNA type II) in three sets of two dogs, each receiving a different inoculum dose), four dogs inoculated with B. vinsonii subsp. berkhoffii type I (ATCC strain, one mongrel dog) or type II (coyote strain, two beagles and one mongrel) and B. rochalimae (coyote strain, two beagles). None of the dogs inoculated with B. henselae became bacteremic, as detected by classical blood culture. However, several dogs developed severe necrotic lesions at the inoculation site and all six dogs seroconverted within one to two weeks. All dogs inoculated with the B. v. berkhoffii and B. rochalimae strains became bacteremic at levels comparable to previous experimental infections with either a dog isolate or a human isolate. Our data support that dogs are likely accidental hosts for B. henselae, just like humans, and are efficient reservoirs for both B. v. berkhoffii and B. rochalimae.

  6. Glucose and lipid profile of obese dogs fed with different starchy sources

    Directory of Open Access Journals (Sweden)

    Mariana Lorenção Feitosa

    Full Text Available ABSTRACT: Among the health disorders caused by obesity in dogs stand out hyperglycemia and hyperlipidemia. Glycemic responses are directly related to the amount and type of starch. Thus, this study aimed to evaluate the effect of different sources of starch on glycemic and lipid levels in obese dogs. These dogs were distributed in a completely randomized design in a factorial 3x2x2 (three sources starchy - corn (60%, sorghum (60% and corn: sorghum (30:30%, two breeds - Beagle and Dachshund and males and females. After 28 days of experiment, dogs fed with corn had higher amounts of glucose (93.79A mg dL-1 (P0.05. Thus, dogs that consumed corn had a higher glycemic peak in a shorter time compared with dogs that ingested sorghum. Furthermore, the dogs fed with diet containing sorghum showed lower levels of fructosamine that dogs that ingested corn diet (P<0.05 demonstrating that the diet containing sorghum maintained blood glucose over a longer time period that reduces the fluctuation of glucose in dogs. At 56 and 112 days of the experiment, a positive correlation between glucose levels and body weight (P<0.05 was also observed. At 28, 56, 84 and 112 days, Beagle dogs showed higher serum concentrations of total cholesterol compared with Dachshund dogs (P<0.05. It was concluded that the starchy source and breed can interfere with metabolic rates of obese dogs.

  7. Gender affiliation and inheritance

    Directory of Open Access Journals (Sweden)

    Đorđević Jadranka Đ.

    2005-01-01

    Full Text Available Looking at the inheritance matter in the socialist period, the author concludes that it was based solely on gender. This paper explains the relationship between gender, inheritance, ownership and possessions among kinsmen in the Vranje district. During the socialist period so called customary law of inheritance (a right to inherit a deceased father, that is, a mother was socially and legislatively accepted. The women from the Vranje district are aware of their unfair position in matters of inheritance, but also they know that even if they are to inherit a property they will not become equal to men. It is obvious that it was an illusion that a socialist organization with its legislative system (or any other, as a mater of fact could establish the gender equality in inheritance and thus solve the dualism between the customary law and the law.

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

    Science.gov (United States)

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

    2007-01-01

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

  9. 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.

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  12. Candidate genes for idiopathic epilepsy in four dog breeds

    Directory of Open Access Journals (Sweden)

    Mickelson James R

    2011-04-01

    Full Text Available Abstract Background Idiopathic epilepsy (IE is a naturally occurring and significant seizure disorder affecting all dog breeds. Because dog breeds are genetically isolated populations, it is possible that IE is attributable to common founders and is genetically homogenous within breeds. In humans, a number of mutations, the majority of which are genes encoding ion channels, neurotransmitters, or their regulatory subunits, have been discovered to cause rare, specific types of IE. It was hypothesized that there are simple genetic bases for IE in some purebred dog breeds, specifically in Vizslas, English Springer Spaniels (ESS, Greater Swiss Mountain Dogs (GSMD, and Beagles, and that the gene(s responsible may, in some cases, be the same as those already discovered in humans. Results Candidate genes known to be involved in human epilepsy, along with selected additional genes in the same gene families that are involved in murine epilepsy or are expressed in neural tissue, were examined in populations of affected and unaffected dogs. Microsatellite markers in close proximity to each candidate gene were genotyped and subjected to two-point linkage in Vizslas, and association analysis in ESS, GSMD and Beagles. Conclusions Most of these candidate genes were not significantly associated with IE in these four dog breeds, while a few genes remained inconclusive. Other genes not included in this study may still be causing monogenic IE in these breeds or, like many cases of human IE, the disease in dogs may be likewise polygenic.

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

    Science.gov (United States)

    Domestic dog breeds are hosts for the tick Rhipicephalus sanguineus sensu lato, but infestation levels vary among breeds. Beagles are less susceptible to tick infestations than English cocker spaniels due to enhanced production of 2-hexanone and benzaldehyde that act as tick repellents. We report th...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-03-01

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

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

    Directory of Open Access Journals (Sweden)

    ChangKui Liu

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

  17. Clinical Phenotype of Musladin-Lueke Syndrome in 2 Beagles.

    Science.gov (United States)

    Packer, R A; Logan, M A; Guo, L T; Apte, S S; Bader, H; O'Brien, D P; Johnson, G; Shelton, G D

    2017-03-01

    Musladin-Lueke syndrome (MLS), previously termed Chinese Beagle syndrome, is an autosomal-recessive connective tissue disorder characterized by extensive fibrosis of the skin and joints that was first identified in Beagles in the 1970s. Recent research identified a founder mutation (c.660C>T; p.R221C) in the ADAMTSL2 gene in Beagles with MLS. Here, we report the detailed clinical phenotype and laboratory findings in 2 Beagles affected with MLS. We discuss these findings in relation to the human disorder geleophysic dysplasia (GD), which also arises from recessive ADAMTSL2 mutations, and recent findings in Adamtsl2-deficient mice. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  18. Biochemical and immunological investigations on hypothyroidism in dogs.

    Science.gov (United States)

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

    1980-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Kirberger Robert M

    2012-08-01

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

  20. Relaxing Behavioural Inheritance

    Directory of Open Access Journals (Sweden)

    Nuno Amálio

    2013-05-01

    Full Text Available Object-oriented (OO inheritance allows the definition of families of classes in a hierarchical way. In behavioural inheritance, a strong version, it should be possible to substitute an object of a subclass for an object of its superclass without any observable effect on the system. Behavioural inheritance is related to formal refinement, but, as observed in the literature, the refinement constraints are too restrictive, ruling out many useful OO subclassings. This paper studies behavioural inheritance in the context of ZOO, an object-oriented style for Z. To overcome refinement's restrictions, this paper proposes relaxations to the behavioural inheritance refinement rules. The work is presented for Z, but the results are applicable to any OO language that supports design-by-contract.

  1. Multi-Dimensional Inheritance

    CERN Document Server

    Erbach, G

    1994-01-01

    In this paper, we present an alternative approach to multiple inheritance for typed feature structures. In our approach, a feature structure can be associated with several types coming from different hierarchies (dimensions). In case of multiple inheritance a type has supertypes from different hierarchies. We contrast this approach with approaches based on a single type hierarchy where a feature structure has only one unique most general type, and multiple inheritance involves computation of greatest lower bounds in the hierarchy. The proposed approach supports current linguistic analyses in constraint-based formalisms like HPSG, inheritance in the lexicon, and knowledge representation for NLP systems. Finally, we show that multi-dimensional inheritance hierarchies can be compiled into a Prolog term representation, which allows to compute the conjunction of two types efficiently by Prolog term unification.

  2. Minimum Alveolar Concentration for Blunting Adrenergic Responses (MAC-BAR) of Sevoflurane in Dogs

    OpenAIRE

    YAMASHITA, Kazuto; FURUKAWA, Erika; ITAMI, Takaharu; ISHIZUKA, Tomohito; TAMURA, Jun; MIYOSHI, Kenjirou

    2012-01-01

    It is well known that heart rate or arterial blood pressure may increase in response to surgical stimulation despite the absence of a purposeful movement. However, there is limited information regarding anesthetic requirement for blunting adrenergic response in dogs. This study was designed to compare the minimum alveolar concentrations of sevoflurane required to prevent autonomic response (MAC-BAR) and purposeful movement (MAC) in dogs. Sevoflurane MAC-BAR and MAC were determined in 5 beagle...

  3. Avian Influenza (H5N1) Susceptibility and Receptors in Dogs

    OpenAIRE

    Maas,; Tacken, M.G.J.; Ruuls-van Stalle, E.M.F.; G. Koch; Rooij, De; Stockhofe-Zurwieden, N.

    2007-01-01

    Inoculation of influenza (H5N1) into beagles resulted in virus excretion and rapid seroconversion with no disease. Binding studies that used labeled influenza (H5N1) showed virus attachment to higher and lower respiratory tract tissues. Thus, dogs that are subclinically infected with influenza (H5N1) may contribute to virus spread.

  4. Cardiovascular effects of tramadol in dogs anesthetized with sevoflurane.

    Science.gov (United States)

    Itami, Takaharu; Tamaru, Naomichi; Kawase, Kodai; Ishizuka, Tomohito; Tamura, Jun; Miyoshi, Kenjirou; Umar, Mohammed A; Inoue, Hiroki; Yamashita, Kazuto

    2011-12-01

    Cardiovascular effects of tramadol were evaluated in dogs anesthetized with sevoflurane. Six beagle dogs were anesthetized twice at 7 days interval. The minimum alveolar concentration (MAC) of sevoflurane was earlier determined in each dog. The dogs were then anesthetized with sevoflurane at 1.3 times of predetermined individual MAC and cardiovascular parameters were evaluated before (baseline) and after an intravenous injection of tramadol (4 mg/kg). The administration of tramadol produced a transient and mild increase in arterial blood pressure (ABP) (P=0.004) with prolonged increase in systemic vascular resistance (SVR) (Ppressure, right atrial pressure and pulmonary capillary wedge pressure. In conclusion, the administration of tramadol produces a prolonged peripheral vascular constriction in dogs anesthetized with sevoflurane, which is accompanied with a transient and mild increase in arterial blood pressure. It also indicated that the degree of vasoconstriction might depend on the plasma concentration of tramadol.

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

    Science.gov (United States)

    Chevallard, Jacopo; Charlot, Stéphane

    2016-10-01

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

  6. Dominantly Inherited Nemaline Myopathy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-08-01

    Full Text Available A locus on chromosome 15q21-23 for a dominantly inherited nemaline myopathy with core-like lesions is reported in two unrelated families evaluated at University Medical Center, Nijmegen, The Netherlands.

  7. Absorption and pharmacokinetics of green tea catechins in beagles.

    Science.gov (United States)

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

    2008-09-01

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

  8. Positive affect and learning: exploring the "Eureka Effect" in dogs.

    Science.gov (United States)

    McGowan, Ragen T S; Rehn, Therese; Norling, Yezica; Keeling, Linda J

    2014-05-01

    Animals may experience positive affective states in response to their own achievements. We investigated emotional responses to problem-solving in dogs, separating these from reactions to rewards per se using a yoked control design. We also questioned whether the intensity of reaction would vary with reward type. We examined the response (behavior and heart rate) of dogs as they learned to gain access to different rewards: (1) food (2) human contact, and (3) dog contact. Twelve beagles were assigned to matched pairs, and each dog served as both an experimental and a control animal during different stages of the experiment. We trained all dogs to perform distinct operant tasks and exposed them to additional devices to which they were not trained. Later, dogs were tested in a new context. When acting as an experimental dog, access to the reward was granted immediately upon completion of trained operant tasks. When acting as a control, access to the reward was independent of the dog's actions and was instead granted after a delay equal to their matched partner's latency to complete their task. Thus, differences between the two situations could be attributed to experimental dogs having the opportunity to learn to control access to the reward. Experimental dogs showed signs of excitement (e.g., increased tail wagging and activity) in response to their achievements, whereas controls showed signs of frustration (e.g., chewing of the operant device) in response to the unpredictability of the situation. The intensity of emotional response in experimental dogs was influenced by the reward type, i.e., greatest response to food and least to another dog. Our results suggest that dogs react emotionally to problem-solving opportunities and that tail wagging may be a useful indicator of positive affective states in dogs.

  9. Evaluation of nanoparticle delivered cisplatin in beagles

    Science.gov (United States)

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

    2015-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-12-31

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

  11. R-R interval variations influence the degree of mitral regurgitation in dogs with myxomatous mitral valve disease

    DEFF Research Database (Denmark)

    Reimann, M. J.; Moller, J. E.; Haggstrom, J.

    2014-01-01

    Mitral regurgitation (MR) due to myxomatous mitral valve disease (MMVD) is a frequent finding in Cavalier King Charles Spaniels (CKCSs). Sinus arrhythmia and atrial premature complexes leading to R-R interval variations occur in dogs. The aim of the study was to evaluate whether the duration...... of the RR interval immediately influences the degree of MR assessed by echocardiography in dogs. Clinical examination including echocardiography was performed in 103 privately-owned dogs: 16 control Beagles, 70 CKCSs with different degree of MR and 17 dogs of different breeds with clinical signs...

  12. Safe Dynamic Multiple Inheritance

    DEFF Research Database (Denmark)

    Ernst, Erik

    2002-01-01

    Multiple inheritance and similar mechanisms are usually only supported at compile time in statically typed languages. Nevertheless, dynamic multiple inheritance would be very useful in the development of complex systems, because it allows the creation of many related classes without an explosion...... in the size and level of redundancy in the source code. In fact, dynamic multiple inheritance is already available. The language gbeta is statically typed and has supported run-time combination of classes and methods since 1997, by means of the combination operator '&'. However, with certain combinations...... of operands the '&' operator fails; as a result, dynamic creation of new classes and methods was considered a dangerous operation in all cases. This paper presents a large and useful category of combinations, and proves that combinations in this category will always succeed....

  13. Organs as inheritable property?

    Science.gov (United States)

    Voo, Teck Chuan; Holm, Soren

    2014-01-01

    It has been argued that organs should be treated as individual tradable property like other material possessions and assets, on the basis that this would promote individual freedom and increase efficiency in addressing the shortage of organs for transplantation. If organs are to be treated as property, should they be inheritable? This paper seeks to contribute to the idea of organs as inheritable property by providing a defence of a default of the family of a dead person as inheritors of transplantable organs. In the course of discussion, various succession rules for organs and their justifications will be suggested. We then consider two objections to organs as inheritable property. Our intention here is to provoke further thought on whether ownership of one's body parts should be assimilated to property ownership.

  14. Levying Inheritance Tax Now?

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Whether China should levy inheritance tax has become a hot topic of discussion. One survey about levying such a tax on high-income earners conducted by a consultancy agency of China Youth Daily shows 48.46 percent of 11,203 respondents thought it was not yet the right time while 34.03 percent of them said it was and 17.51 percent were not sure. The survey also shows 52.6 percent of the respondents thought affluent Americans’ giving of money to charity was related to inheritance tax.

  15. Inherited Peripheral Neuropathies

    Science.gov (United States)

    Saporta, Mario A.; Shy, Michael E.

    2013-01-01

    SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725

  16. Genetic evaluation of Addison's disease in the Portuguese Water Dog

    Directory of Open Access Journals (Sweden)

    Belanger JM

    2006-05-01

    Full Text Available Abstract Background Addison's disease, also known as hypoadrenocorticism, has been reported in many individual dogs, although some breeds exhibit a greater incidence than the population as a whole. Addison's is presumed to be an autoimmune mediated hereditary defect but the mode of inheritance remains unclear. In particular, the heritability and mode of inheritance have not been defined for the Portuguese Water Dog although Addison's is known to be prevalent in the breed. Results The analyses present clear evidence that establishes Addison's disease as an inherited disorder in the Portuguese Water Dog with an estimate of heritability of 0.49 (± 0.16; there were no differences in risk for disease across sexes (p > 0.49. Further, the complex segregation analysis provides suggestive evidence that Addison's disease in the Portuguese Water Dog is inherited under the control of a single, autosomal recessive locus. Conclusion The high heritability and mode of inheritance of Addison's disease in the Portuguese Water Dog should enable the detection of segregating markers in a genome-wide scan and the identification of a locus linked to Addison's. Though the confirmation of Addison's disease as an autosomal recessive disorder must wait until the gene is identified, breeders of these dogs may wish to keep the present findings in mind as they plan their breeding programs to select against producing affected dogs.

  17. Genetic evaluation of Addison's disease in the Portuguese Water Dog.

    Science.gov (United States)

    Oberbauer, A M; Bell, J S; Belanger, J M; Famula, T R

    2006-05-02

    Addison's disease, also known as hypoadrenocorticism, has been reported in many individual dogs, although some breeds exhibit a greater incidence than the population as a whole. Addison's is presumed to be an autoimmune mediated hereditary defect but the mode of inheritance remains unclear. In particular, the heritability and mode of inheritance have not been defined for the Portuguese Water Dog although Addison's is known to be prevalent in the breed. The analyses present clear evidence that establishes Addison's disease as an inherited disorder in the Portuguese Water Dog with an estimate of heritability of 0.49 (+/- 0.16); there were no differences in risk for disease across sexes (p > 0.49). Further, the complex segregation analysis provides suggestive evidence that Addison's disease in the Portuguese Water Dog is inherited under the control of a single, autosomal recessive locus. The high heritability and mode of inheritance of Addison's disease in the Portuguese Water Dog should enable the detection of segregating markers in a genome-wide scan and the identification of a locus linked to Addison's. Though the confirmation of Addison's disease as an autosomal recessive disorder must wait until the gene is identified, breeders of these dogs may wish to keep the present findings in mind as they plan their breeding programs to select against producing affected dogs.

  18. Digestibility and behavior of dogs housed in kennels or metabolic cages

    Directory of Open Access Journals (Sweden)

    Tabyta Tamara Sabchuk

    2012-01-01

    Full Text Available The objective of the present study was to compare the apparent digestibility coefficients of a commercial dog food, fecal consistency and behavior of dogs housed in kennels and metabolic cages. Six adult Beagle dogs were distributed in cross-over experimental design, with six replicates per treatment. Dogs were housed in two environments: metabolic cages and in masonry kennels with solarium. Dogs were fed for a five-day adaptation period, and the five following days were used for total feces collection. Dogs behavior was recorded during a 48-h period, with 10-min intervals. Apparent digestibility coefficients were not different between treatments. However, dogs housed in metabolic cages produced lower weight and more consistent feces as compared with dogs housed in kennels. Dogs spent most of the time sleeping in both housing systems; however, dogs housed in the metabolic cages slept more than those in kennels. Stress-related behaviors (barking, whimpering, stereotypies, etc were observed for no longer than 15 minutes per day, and were not different between dogs in kennels or in cages. There is no difference in food digestibility evaluated in dogs housed in metabolic cages or kennels; however, dogs kept in metabolic cages eliminate drier feces and spend more time inactive than those kept in kennels.

  19. Bone reactions at implants subjected to experimental peri-implantitis and static load. A study in the dog

    DEFF Research Database (Denmark)

    Gotfredsen, K; Berglundh, T; Lindhe, J

    2002-01-01

    AIM: The aim of the present experiment was to study peri-implant tissue reactions to lateral static load at implants subjected to experimental mucositis or peri-implantitis. MATERIAL AND METHODS: 5 beagle dogs were used. The mandibular premolars were extracted. After 12 weeks, 3 implants were ins...

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, Darrell R.; Weller, Richard E.

    2010-09-01

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

  2. Serum Glial Fibrillary Acidic Protein as a Specific Marker for Necrotizing Meningoencephalitis in Pug Dogs

    Science.gov (United States)

    MIYAKE, Hizuru; INOUE, Akiko; TANAKA, Miho; MATSUKI, Naoaki

    2013-01-01

    ABSTRACT To evaluate the ability of serum glial fibrillary acidic protein (GFAP) concentration as a diagnostic marker for canine central nervous system (CNS) disorders, sera from dogs with various CNS (n=47) and non-CNS (n=56) disorders were measured for GFAP by using an ELISA kit. Healthy Beagles (n=15) and Pug dogs (n=12) were also examined as controls. Interestingly, only Pug dogs with necrotizing meningoencephalitis (NME) showed elevated serum GFAP concentrations (<0.01 to 1.14 ng/ml), while other breeds of dogs with NME did not. Among the Pug dogs with NME, serum GFAP concentrations did not correlate with their clinical features, such as ages or survival times. Our data indicate the usefulness of serum GFAP as a novel marker for Pug dogs with NME. PMID:23856761

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

    Science.gov (United States)

    Swab, Janice C.

    2010-01-01

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

  4. 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).

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

    Science.gov (United States)

    Swab, Janice C.

    2010-01-01

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

  6. Association between nasal shedding and fever that influenza A (H3N2 induces in dogs

    Directory of Open Access Journals (Sweden)

    Oh Jinsik

    2011-01-01

    Full Text Available Abstract Background Avian origin canine influenza virus was reported in Korea. The dog to dog contact transmission of the avian origin canine influenza virus (CIV H3N2 and CIV H3N8 was shown by experimental contact transmission. This study was focused on viral excretion and fever in order to elucidate the epidemiological associations which might be helpful to control the disease transmissions in CIV outbreak in dogs. Methods An influenza seronegative 10-week-old Beagle dog was experimentally inoculated with the canine influenza virus A/canine/01/2007, subtype H3N2. Eight hours after inoculation, the infected dog was cohoused with seven uninfected Beagle dogs. Clinical signs including fever were recorded for 14 days post inoculation. Results The infected dog and four of seven contact dogs in the study showed clinical signs (sneezing, nasal discharge and coughing during the study. Viral shedding occurred in all of the animals tested and began on 1 to 6 DPI in dogs with clinical signs. Elevated body temperatures above 39.5°C (geometric mean temperature of 39.86°C±0.49 were observed in all symptomatic dogs. The mean viral titer during fever was 2.99 log EID50/ml, which was significantly higher than the viral titer detected in the non fever. Conclusions The data show that contact dogs with a canine influenza infected dog shed different levels of virus in their nasal excretions and demonstrate that clinical signs, including fever, significantly correlate with the viral shedding.

  7. Evaluating the toxicity of novel Zn-DTPA tablet formulation in dogs and rats.

    Science.gov (United States)

    Shankar, Gita N; Potharaju, Suresh; Green, Carol E

    2014-02-01

    The purpose of this research work is to evaluate toxicity of diethylenetriamine pentaacetic acid zinc trisodium salt (Zn-DTPA) tablets, a novel oral solid dosage form containing permeation enhancers in beagle dogs and Sprague Dawley rats. (Zn-DTPA) in tablet dosage form was administered once daily for 7 days to beagle dogs at low (840 mg/dog/day), mid (2520 mg/dog/day), or high (7560 mg/dog/day). On day 8, all treated and control groups were necropsied. The novel Zn-DTPA tablet formulation showed rapid absorption with the T(max) at 1 h. Plasma concentrations as high as 270 μg/mL were observed after 7 days of administration. Exposure to DTPA, based on area under the curve (AUC(last)) and maximum concentration (C(max)), was dose dependent but not dose proportional. No biologically relevant changes in hematology or clinical chemistry that were related to DTPA exposure were observed, and there were no changes in body weight in treated dogs compared with controls. Zn-DTPA was well tolerated, with minor toxicological effects of emesis and diarrhea, following oral tablet administration for 7 consecutive days. Based on the endpoints evaluated in this study, the maximum tolerated dose is considered to be greater than 7560 mg/dog/day (2535 μmol/kg/day, 1325 mg/kg/day), and the no-observed-adverse-effect level (NOAEL) is considered to be approximately 1325 mg/kg/day per oral when given to male and female beagle dogs. For rats, the NOAEL was estimated to be greater than 1000 mg/kg/day when administered by oral gavage of the crushed Zn-DTPA tablets as suspension once daily (qd) to male and female Sprague Dawley rats. © 2013 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Frank, Diane; Gauthier, Audrey; Bergeron, Renée

    2006-11-01

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

  9. Levying Inheritance Tax Now?

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Whether China should levy inheritance tax has become a hot topic of discussion. One survey about levying such a tax on high-income earners conducted by a consul-tancy agency of China Youth Daily shows 48.46 percent of 11,203 respondents thought it was not yet the right time while 34.03 per-cent of them said it was and 17.51 percent were not sure.

  10. Dog models of naturally occurring cancer.

    Science.gov (United States)

    Rowell, Jennie L; McCarthy, Donna O; Alvarez, Carlos E

    2011-07-01

    Studies using dogs provide an ideal solution to the gap in animal models for natural disease and translational medicine. This is evidenced by approximately 400 inherited disorders being characterized in domesticated dogs, most of which are relevant to humans. There are several hundred isolated populations of dogs (breeds) and each has a vastly reduced genetic variation compared with humans; this simplifies disease mapping and pharmacogenomics. Dogs age five- to eight-fold faster than do humans, share environments with their owners, are usually kept until old age and receive a high level of health care. Farseeing investigators recognized this potential and, over the past decade, have developed the necessary tools and infrastructure to utilize this powerful model of human disease, including the sequencing of the dog genome in 2005. Here, we review the nascent convergence of genetic and translational canine models of spontaneous disease, focusing on cancer.

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

    Science.gov (United States)

    Kohno, T; Ohnishi, Y

    1989-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-01-01

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

  13. 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.

  14. [Establishment of prostatic hyperplasia model with castration beagle canines].

    Science.gov (United States)

    Wu, Jian-Hui; Sun, Zu-Yue; Zhu, Yan; Zhong, En-Hong; He, Gui-Lin; Liu, Gui-Ming

    2003-09-01

    To establish a prostatic hyperplasia model with Beagle canines. Twenty-four two-year-old male Beagle canines were divided into treatment and control groups at random and were administrated testosterone propionate (TP) through intramuscular injection two months after castration. Three treatment groups were given 0.8, 2.5 and 7.5 mg/kg TP respectively, and the control was given the same volume of vehicle. Two months later, half of the animals were killed and the serum and prostate were prepared. After the wet weight and volume of prostate were measured, the dihydrotestosterone (DHT) level of serum and prostate were detected with DHT radioimmunoassay (RIA) kit, and paraffine section from canine prostate was stained by the HE methods. Pictures were taken by digital camera under microscope, and all the pictures were analyzed by computer for epithelial cell height and acinar luminal area of prostate with micro image analysis software. The canine prostate volume was measured with ultrasonic diagnosis instrument before castration, at two months after castration and at two months after being given TP. The ultrasonic results showed that the prostate volumes of all the canines were smaller at two months after castration than before castration (P canines became higher with the increase of TP dose. The results of micro image analysis showed that the acinar luminal area of prostate was enlarged, and the epithelial cell height increased with larger dose of TP. It is practicable to establish prostatic hyperplasia model in Beagle canines after two months of TP administration.

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

    Directory of Open Access Journals (Sweden)

    Kyung Hoon Lee

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

  16. A Dog

    Institute of Scientific and Technical Information of China (English)

    韩选文

    2004-01-01

    A dog can't speak words, but it can "talk", It has feelings just as you do. At times it may feel angry or afraid. Watching a dog closely, you can find out what it feels. You can see what it is trying to tell you.

  17. Dominantly-inherited lop ears.

    Science.gov (United States)

    Leung, Alexander K C; Kong, Albert Y F; Robson, W Lane M; McLeod, D Ross

    2007-10-01

    We describe a four-generation Chinese family that included five members who had an isolated bilateral lop ear anomaly. The presentation suggested a dominant mode of inheritance. The absence of male-to-male transmission does not exclude an X-linked dominant mode of inheritance. Since the phenotypic anomaly of the male proband was no more severe than the affected female members, an autosomal dominant mode of inheritance is most likely. 2007 Wiley-Liss, Inc

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

    Science.gov (United States)

    Nelson, L W; Kelly, W A

    1976-01-01

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

  19. A mathematical model of inheritance

    Institute of Scientific and Technical Information of China (English)

    瞿裕忠; 王志坚; 徐家福

    1996-01-01

    Inheritance is regarded as the hallmark of object-oriented programming languages.A mathematical model of inheritance is presented.In this model,the graph-sorted signature is introduced to represent the algebraic structure of the program,and an extension function on the graph-sorted signatures is used to formally describe the semantics of inheritance.The program’s algebraic structure reflects the syntactic constraints of the language and the corresponding extension function exposes the character of the language’s inheritance.

  20. Inherited autonomic neuropathies.

    Science.gov (United States)

    Axelrod, Felicia B; Hilz, Max J

    2003-12-01

    Inherited autonomic neuropathies are a rare group of disorders associated with sensory dysfunction. As a group they are termed the "hereditary sensory and autonomic neuropathies" (HSAN). Classification of the various autonomic and sensory disorders is ongoing. In addition to the numerical classification of four distinct forms proposed by Dyck and Ohta (1975), additional entities have been described. The best known and most intensively studied of the HSANs are familial dysautonomia (Riley-Day syndrome or HSAN type III) and congenital insensitivity to pain with anhidrosis (HSAN type IV). Diagnosis of the HSANs depends primarily on clinical examinations and specific sensory and autonomic assessments. Pathologic examinations are helpful in confirming the diagnosis and in differentiating between the different disorders. In recent years identification of specific genetic mutations for some disorders has aided diagnosis. Replacement or definitive therapies are not available for any of the disorders so that treatment remains supportive and directed toward specific symptoms.

  1. Inherited mitochondrial optic neuropathies

    Science.gov (United States)

    Yu-Wai-Man, P; Griffiths, P G; Hudson, G; Chinnery, P F

    2009-01-01

    Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited. PMID:19001017

  2. Influence of pneumoperitoneum and postural change on the cardiovascular and respiratory systems in dogs

    OpenAIRE

    2015-01-01

    We investigated the influence of pneumoperitoneum#(PP) and postural change under inhalation anesthesia with isoflurane, which is routinely used in dogs, on the cardiovascular and respiratory systems. As test animals, 6 adult beagles were used. To induce anesthesia, atropine, butorphanol and propofol were intravenously injected. Anesthesia was maintained with 1.3 MAC (1.7%) isoflurane. The following were the experiment conditions: I:E ratio, 1:1.9; tidal air exchange, 20 ml/kg; and ventilation...

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

    Science.gov (United States)

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

    2017-01-01

    Although the rehoming of laboratory dogs has gained popularity, a scientific evaluation of the process is lacking. The behavior of 145 laboratory beagles was tested before leaving a research facility (Test 1). The new owners were then surveyed using a standardized telephone interview 1 week (n = 143) and 12 weeks (n = 126) after adoption. The behavior test was repeated with 68 dogs in their new homes 6 weeks after adoption (Test 2). The predictive power of Test 1 or Interview 1 on Test 2 or Interview 2, respectively, as well as the relevance of various factors was analyzed. We found no significant differences between Tests 1 and 2 regarding the behavior reactions. However, body language scores and heart rates changed significantly, indicating a more relaxed state of the dogs in their new homes. The interviews revealed a significant change toward desired behavior in most dogs within the 11 week period (p dogs returned the animals, resulting in a rehoming success rate of 94%. Test 1 revealed a significant age effect (p = 0.0066), with younger and older dogs reaching higher scores than dogs who were approximately 2 years old. Dogs that had been born and reared in the research facility scored higher than dogs that had originally been acquired from a commercial breeder (p = 0.0257). The predictive power of Test 1 on Test 2 or Interview 1 on Interview 2 was moderate to low, respectively. Altogether, rehoming of laboratory dogs is a valuable alternative to euthanasia.

  4. Astaxanthin uptake in domestic dogs and cats

    Directory of Open Access Journals (Sweden)

    Massimino Stefan

    2010-06-01

    Full Text Available Abstract Background Research on the uptake and transport of astaxanthin is lacking in most species. We studied the uptake of astaxanthin by plasma, lipoproteins and leukocytes in domestic dogs and cats. Methods Mature female Beagle dogs (18 to 19 mo old; 11 to 14 kg BW were dosed orally with 0, 0.1, 0.5, 2.5, 10 or 40 mg astaxanthin and blood taken at 0, 3, 6, 9, 12, 18 and 24 h post-administration (n = 8/treatment. Similarly, mature domestic short hair cats (12 mo old; 3 to 3.5 kg body weight were fed a single dose of 0, 0.02, 0.08, 0.4, 2, 5, or 10 mg astaxanthin and blood taken (n = 8/treatment at the same interval. Results Both dogs and cats showed similar biokinetic profiles. Maximal astaxanthin concentration in plasma was approximately 0.14 μmol/L in both species, and was observed at 6 h post-dosing. The plasma astaxanthin elimination half-life was 9 to 18 h. Astaxanthin was still detectable by 24 h in both species. In a subsequent study, dogs and cats were fed similar doses of astaxanthin daily for 15 to 16 d and astaxanthin uptake by plasma, lipoproteins, and leukocytes studied. In both species, plasma astaxanthin concentrations generally continued to increase through d 15 or 16 of supplementation. The astaxanthin was mainly associated with high density lipoprotein (HDL. In blood leukocytes, approximately half of the total astaxanthin was found in the mitochondria, with significant amounts also associated with the microsomes and nuclei. Conclusion Dogs and cats absorb astaxanthin from the diet. In the blood, the astaxanthin is mainly associated with HDL, and is taken up by blood leukocytes, where it is distributed to all subcellular organelles. Certain aspects of the biokinetic uptake of astaxanthin in dogs and cats are similar to that in humans.

  5. Serum alpha-1-acid glycoprotein concentration in clinically healthy puppies and adult dogs and in dogs with various diseases.

    Science.gov (United States)

    Yuki, Masashi; Itoh, Hiroshi; Takase, Katsuaki

    2010-03-01

    alpha-1-acid glycoprotein (AGP) is an acute-phase protein and a serum marker of inflammation and neoplasia in humans. AGP concentrations in diseased dogs and the potential effects of age, breed, and sex have not been elucidated. The purpose of this study was to examine differences in AGP concentration based on age, sex, and breed in a large population of clinically healthy dogs and to compare AGP concentrations in dogs with various diseases. Serum was obtained from clinically healthy puppies (n=74) and adults (n=172) of both sexes, and included mongrels (n=205) and Beagles (n=41). Serum also was obtained from 192 dogs with various diseases, including 8 with pyometra that were sampled before, and 1, 2, 3, and 10 days after surgery. AGP concentration was measured by single radial immunodiffusion. Statistical comparisons were made among age, sex, breed, and disease groups. Serum AGP in healthy adult mongrels was 364+/-106 mg/L (reference interval, 152-576 mg/L). AGP was lowest in newborns (n=11, 122+/-54 mg/L) and gradually increased to adult levels by 3 months of age. Median AGP concentration was highest in dogs with parvovirus (n=17, 2100 mg/L), distemper (n=7, 1250 mg/L), and pyometra (n=18, 2480 mg/L) and was also significantly higher in dogs with acute filariasis, renal failure, urolithiasis, pancreatitis, hepatitis, trauma, hyperadrenocorticism, and immune-mediated hemolytic anemia. Dogs with acute filariasis and acute hepatopathy had significantly higher AGP concentrations than dogs with chronic filariasis and chronic hepatopathy. Serum AGP concentration decreased gradually following surgery for pyometra but remained increased after 10 days (896+/-175 mg/L). Because of significantly lower AGP in puppies, the age of dogs should be considered when using AGP as a marker of disease. Serum AGP may be a useful marker of inflammatory disease in dogs and may help differentiate acute and chronic stages of disease.

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

    Science.gov (United States)

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

    2012-06-01

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

  7. Cat and Dog Bites

    Science.gov (United States)

    ... Prevention and Wellness Staying Healthy Pets and Animals Cat and Dog Bites Cat and Dog Bites Pets and AnimalsPrevention and WellnessStaying Healthy Share Cat and Dog Bites Cat and dog bites are ...

  8. Allegheny County Dog Licenses

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — A list of dog license dates, dog breeds, and dog name by zip code. Currently this dataset does not include City of Pittsburgh dogs.

  9. The effect of water and shampooing on the efficacy of a pyriprole 12.5% topical solution against brown dog tick (Rhipicephalus sanguineus) and cat flea (Ctenocephalides felis) infestations on dogs.

    Science.gov (United States)

    Schuele, G; Barnett, S; Bapst, B; Cavaliero, T; Luempert, L; Strehlau, G; Young, D R; Moran, C; Junquera, P

    2008-02-14

    The efficacy of a single treatment with a 12.5% pyriprole spot-on formulation against induced infestations with R. sanguineus ticks and cat fleas (C. felis) as well as its persistence after repeated washing and shampooing was investigated in four separate studies. In a first study on R. sanguineus involving 32 beagle dogs, the efficacy at various time-points during the 30 days that followed treatment assessed 48 h after re-infestation ranged from 100% to 99.3%. No engorged ticks, alive or dead, were found in the treated animals. Shampooing 2 days after treatment and weekly washings did not affect the efficacy. In a second study on R. sanguineus involving 32 beagle dogs, the efficacy at various time-points during the 30 days that followed treatment assessed 48 h after re-infestation ranged from 100% to 96.8%. Single washing 8h after treatment and single shampooing 24 h after treatment had no negative impact on the efficacy of the product. In a third study on C. felis involving 28 beagle dogs, the efficacy at various time-points during the 30 days that followed treatment assessed 48 h after re-infestation was always 100% and weekly washings did not diminish the efficacy. In a last study on C. felis involving 24 beagle dogs, the efficacy at various time-points during the 5 weeks that followed treatment assessed 48 h after re-infestation ranged from 100% to 99.8%, and shampooing 24 h after treatment did not reduce the efficacy. The product was well tolerated by the dogs.

  10. Subchronic oral administration of acemannan in the rat and dog.

    Science.gov (United States)

    Fogleman, R W; Shellenberger, T E; Balmer, M F; Carpenter, R H; McAnalley, B H

    1992-04-01

    Acemannan is the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed O-acetyl groups, with a mannose monomer/acetyl ratio of approximately 1:1. This complex polysaccharide is extracted from Aloe vera (barbadensis Miller); the technical material contains approximately 78% acemannan. Technical grade acemannan was administered po to rats for 14 d at 5% of the diet and for 6 mo at up to 2,000 mg/kg/d, and to beagle dogs for 90 d at up to 1,500 mg/kg/d without significant effect on any parameter measured in either species.

  11. Preliminary study: voluntary food intake in dogs during tryptophan supplementation.

    Science.gov (United States)

    Fragua, Víctor; González-Ortiz, Gemma; Villaverde, Cecilia; Hervera, Marta; Mariotti, Valentina Maria; Manteca, Xavier; Baucells, María Dolores

    2011-10-01

    Tryptophan, a precursor of important molecules such as serotonin, melatonin and niacin, is an essential amino acid for dogs. In pigs, tryptophan supplementation has been shown to induce a significant increase in food intake. The aim of the present study was to assess whether long-term tryptophan supplementation increases voluntary food intake in dogs and to observe whether this was accompanied by a change in serum ghrelin. In the present study, sixteen adult Beagle dogs were used, with four male and four female dogs fed diets supplemented with tryptophan (1 g/dog per d) during 81 d (Trp) and four male and four female dogs that were not supplemented (control). A voluntary food intake test was performed during 5 d following the supplementation period. The Trp group tended to show a higher food intake during the voluntary food intake test (58.0 (SE 5.37) v. 77.5 (SE 3.65) g/kg metabolic weight per d; P = 0.074). No significant differences were found for serum ghrelin concentrations.

  12. Inherited epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Fine Jo-David

    2010-05-01

    Full Text Available Abstract Inherited epidermolysis bullosa (EB encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Each EB subtype is known to arise from mutations within the genes encoding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis. EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis. Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct whenever possible the extracutaneous complications. Prognosis varies considerably and is based on both EB subtype and the overall health of the patient.

  13. Dog Ecology and Dog Rabies Control

    OpenAIRE

    Wandeler, A I; Budde, A.; Capt, S.; Kappeler, A.; Matter, H.

    2017-01-01

    Dog populations, like other populations, depend on the availability of resources (food, water, and shelter). Humans either make available or deliberately withhold resources for varying proportions of dog populations. Dog-keeping practices and the duties of responsible ownership vary with the cultural setting. Dog populations often attain densities that allow the species to be a main host of rabies. The epidemiology of dog rabies is not well understood, despite the easy access to dog populatio...

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

    Science.gov (United States)

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

    2011-10-01

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

  15. Evaluation of a calculolytic diet in female dogs with induced struvite urolithiasis.

    Science.gov (United States)

    Abdullahi, S U; Osborne, C A; Leininger, J R; Fletcher, T F; Griffith, D P

    1984-08-01

    The calculolytic effect of a diet designed to reduce the urine concentration of urea, P, and Mg was evaluated in female Beagles with induced urease-positive urinary tract infections and struvite urolithiasis and in female Beagles with induced sterile struvite urolithiasis. The reduced-protein calculolytic diet induced urolith dissolution in 5 of 6 infected dogs with struvite urolithiasis in 2 to 5 months (means = 14.4 weeks). At the end of 6 months, uroliths in comparable control dogs fed a maintenance diet were 5 times larger and 14 times heavier than at the beginning of the study. The calculolytic diet induced urolith dissolution in 6 of 6 noninfected dogs with struvite uroliths in 2 to 4 weeks (means = 3.3 weeks). Four uroliths in noninfected dogs fed the maintenance diet dissolved over a period of 2 to 5 months (means = 14 weeks). Urolith dissolution in dogs fed the calculolytic diet was associated with diet-induced diuresis, reduction in urine pH, reduction in urine concentration of urea ammonia, P, and Mg, and increase in urine titratable acidity. Consumption of the calculolytic diet was also associated with significant (P = less than 0.01) reduction in the serum concentration of urea and albumin and a significant (P = less than 0.01) increase in serum hepatic alkaline phosphatase activity. Concomitant occurrence of hydropic degeneration of hepatocytes indicated that these biochemical and morphologic changes were associated with dietary protein restriction.

  16. Genomic Regions Associated With Interspecies Communication in Dogs Contain Genes Related to Human Social Disorders.

    Science.gov (United States)

    Persson, Mia E; Wright, Dominic; Roth, Lina S V; Batakis, Petros; Jensen, Per

    2016-09-29

    Unlike their wolf ancestors, dogs have unique social skills for communicating and cooperating with humans. Previously, significant heritabilities for human-directed social behaviors have been found in laboratory beagles. Here, a Genome-Wide Association Study identified two genomic regions associated with dog's human-directed social behaviors. We recorded the propensity of laboratory beagles, bred, kept and handled under standardized conditions, to initiate physical interactions with a human during an unsolvable problem-task, and 190 individuals were genotyped with an HD Canine SNP-chip. One genetic marker on chromosome 26 within the SEZ6L gene was significantly associated with time spent close to, and in physical contact with, the human. Two suggestive markers on chromosome 26, located within the ARVCF gene, were also associated with human contact seeking. Strikingly, four additional genes present in the same linkage blocks affect social abilities in humans, e.g., SEZ6L has been associated with autism and COMT affects aggression in adolescents with ADHD. This is, to our knowledge, the first genome-wide study presenting candidate genomic regions for dog sociability and inter-species communication. These results advance our understanding of dog domestication and raise the use of the dog as a novel model system for human social disorders.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    毕甜甜; 张晋; 文润来; 韩杰; 富强; 王小珂; 卢胜明

    2011-01-01

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

  19. Evaluation of the efficacy of afoxolaner against Haemaphysalis longicornis on dogs.

    Science.gov (United States)

    Kondo, Yumi; Kinoshita, Gen; Drag, Marlene; Chester, Theodore S; Larsen, Diane

    2014-04-02

    A controlled study to assess the acaricidal efficacy of afoxolaner in dogs after a single oral administration was conducted against Haemaphysalis longicornis ticks. The study was characterized by a negative controlled randomized block design and included sixteen beagle dogs of both sexes. Starting two days before treatment, each dog was infested weekly with 50 ticks over 4 weeks. The number of live ticks was determined 48 h after treatment and then 48 h after each infestation. The mean dose of afoxolaner received by dogs was 3.0mg/kg (range: 2.5-3.1mg/kg). Afoxolaner rapidly eliminated pre-existing tick infestations (100% ticks killed within 48 h of treatment) and controlled weekly re-infestations (91.9% prophylactic efficacy at Day 30).

  20. Comparison of regional gene expression differences in the brains of the domestic dog and human

    Directory of Open Access Journals (Sweden)

    Kennerly Erin

    2004-11-01

    Full Text Available Abstract Comparison of the expression profiles of 2,721 genes in the cerebellum, cortex and pituitary gland of three American Staffordshire terriers, one beagle and one fox hound revealed regional expression differences in the brain but failed to reveal marked differences among breeds, or even individual dogs. Approximately 85 per cent (42 of 49 orthologue comparisons of the regional differences in the dog are similar to those that differentiate the analogous human brain regions. A smaller percentage of human differences were replicated in the dog, particularly in the cortex, which may generally be evolving more rapidly than other brain regions in mammals. This study lays the foundation for detailed analysis of the population structure of transcriptional variation as it relates to cognitive and neurological phenotypes in the domestic dog.

  1. Total lymphoid irradiation assessed for possible enhancement of immunosuppression in hyperimmunized dogs receiving renal allografts

    Energy Technology Data Exchange (ETDEWEB)

    Sonoda, Kazuhiko (Yamato Seiwa Hospital, Kanagawa (Japan)); Rapaport, F.T.

    1992-12-01

    With performed antibodies to human leukocyte antigens (HLA) appearing in an increasing number of patients today, hyperimmunization constitutes a major problem in clinical transplantation. In adult beagle dogs hyperimmunized with skin allografts and buffy coat injection, we performed renal allograft transplantation to assess the efficacy of total lymphoid irradiation (TLI) employed as a preoperative measure in combination with cyclosporine (CyA) and methyl-prednisolone (MPL) in effecting immunosuppression. The mean survival period were 6.5 days in dogs withheld preliminary treatment, 9.0 days in the dogs receiving CyA and MPL, 26.7 days in those administered one-stage TLI, and 68 days (terminated by euthanasia) of the dogs given two-stage TLI. TLI administered two stages is considered an effective method of enhancing immunosuppression sufficiently to enable the attenuation of adverse reaction to renal allograft in hyperimmunized recipients. (author).

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

    Science.gov (United States)

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

    2001-12-01

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

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

    CERN Document Server

    Chevallard, Jacopo

    2016-01-01

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

  4. Beagle 2: The Next Exobiology Mission to Mars

    Science.gov (United States)

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

    2001-01-01

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

  5. Influence of experimental distemper infection on the distribution of lead in dogs previously subacutely intoxicated with lead carbonate

    Energy Technology Data Exchange (ETDEWEB)

    White, D.J.; Marshall, A.J.; McLeod, S.

    1975-01-01

    The ability of experimental canine distemper infection to mobilize body lead deposits has been studied in Beagle dogs previously subacutely intoxicated with lead carbonate. For comparative purposes dogs were included which had either received lead only or distemper only or remained undosed. It was found that in dogs predosed with lead, distemper infection resulted in a significant increase in lead levels in blood and urine; this coincided with the peak body temperatures reached on the third day post infection. It was also found that the lead content of the liver and bone of these dogs was considerably higher than that of dogs receiving lead alone; at the same time bone phosphorus showed a marked decrease while bone calcium values remained similar to undosed controls.

  6. Inherited thrombophilia and pregnancy complications

    NARCIS (Netherlands)

    de Jong, P.G.

    2015-01-01

    The research presented in this thesis addresses several aspects of the association between inherited thrombophilia and pregnancy complications. Antithrombotic therapy is prescribed to women with recurrent miscarriage and antiphospholipid syndrome to increase their chance of live birth in a subsequen

  7. Inherited thrombophilia and pregnancy complications

    NARCIS (Netherlands)

    de Jong, P.G.

    2015-01-01

    The research presented in this thesis addresses several aspects of the association between inherited thrombophilia and pregnancy complications. Antithrombotic therapy is prescribed to women with recurrent miscarriage and antiphospholipid syndrome to increase their chance of live birth in a

  8. Oral absorption and bioavailability of fenbendazole in the dog and the effect of concurrent ingestion of food.

    Science.gov (United States)

    McKellar, Q A; Galbraith, E A; Baxter, P

    1993-06-01

    Fenbendazole was administered orally without food to six beagle dogs at 2.5, 5.0, 10, 20, 40 and 80 mg/kg of body weight. Increasing the dose rate did not significantly increase the amount of fenbendazole absorbed. In a separate study fenbendazole was administered to the same six beagle dogs at a dose rate of 20 mg/kg of bodyweight in food with high, medium and low fat content. The food provided 1.52, 0.70 or 0.34 g of fat per kg of body weight. Administration of fenbendazole in food with different fat contents did not affect its relative bioavailability. Administration of fenbendazole at a dose rate of 20 mg/kg in food, irrespective of fat content, did however significantly increase its bioavailability when compared to administration of the same dose as a bolus on an empty stomach.

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

    OpenAIRE

    2016-01-01

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

  10. PULMONARY IMMUNITY TO RAGWEED IN A BEAGLE DOG MODEL OF ALLERGIC ASTHMA. (R826442)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

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

    Science.gov (United States)

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

    2007-07-01

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

  12. 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.

  13. Efficacy of afoxolaner against Dermacentor variabilis ticks in dogs.

    Science.gov (United States)

    Mitchell, Elizabeth B; Dorr, Paul; Everett, William R; Chester, Theodore S; Larsen, Diane

    2014-04-02

    Efficacy of afoxolaner, a novel isoxazoline insecticide/acaricide, against Dermacentor variabilis ticks was confirmed in two laboratory studies. Each study utilized a controlled, randomized block design. One day prior to treatment, beagle dogs were infested with 50 unfed adult ticks. Repeat infestations were performed weekly for four weeks. The number of live ticks remaining on each dog was determined 48 h after treatment and after each subsequent infestation. A single oral treatment with a dose approaching the minimum effective dose of afoxolaner (2.5mg/kg) eliminated the pre-existing infestations by D. variabilis ticks and controlled weekly re-infestations with 99.7-100% efficacy up to Day 23 and >97% efficacy at Day 30.

  14. Efficacy of afoxolaner against Ixodes scapularis ticks in dogs.

    Science.gov (United States)

    Mitchell, Elizabeth B; McCall, John W; Theodore Chester, S; Larsen, Diane

    2014-04-02

    Efficacy of afoxolaner, a novel isoxazoline insecticide/acaricide, against Ixodes scapularis was evaluated in a laboratory study. One day prior to treatment, beagle dogs (n=16) were infested with 50 unfed wild adult ticks. Repeat infestations were performed weekly for four additional weeks. The number of live ticks remaining on each dog was determined 48 h after treatment and after each subsequent infestation. A single oral treatment with a dose approaching the minimum effective dose of afoxolaner (2.5mg/kg) eliminated the pre-existing infestations of I. scapularis ticks and controlled weekly re-infestations, with efficacy between 98% and 100% recorded until Day 23 and 94% at Day 30.

  15. Comparison of two techniques for diagnosis of giardiasis in dogs

    Directory of Open Access Journals (Sweden)

    Decock C.

    2003-03-01

    Full Text Available Giardiasis is an intestinal parasitosis affecting dogs and able to infect human beings. Its diagnosis can not be done with the only clinical signs, the main of which is non characteristic diarrhoea. It implicates to perform further tests to detect the parasite. The zinc sulfate concentration technique (ZSCT is the more effective one if performed on two or three successive days. Fecal ELISA kits have been developed to detect Giardia in humans and were found to be less sensitive than the ZSCT in dogs. In this study, we used 30 infected Beagles to compare the sensitivity of one, two or three fecal examinations following ZSCT and one or two ELISA tests. We conclude that if a single ZSCT is insufficient, two or three ZSCT and one or two ELISA using the commercial kit ProSpecT® Giardia have almost the same sensitivity.

  16. Weight loss effect of dietary diacylglycerol in obese dogs.

    Science.gov (United States)

    Umeda, T; Bauer, J E; Otsuji, K

    2006-06-01

    Obesity in dogs and cats have been increasingly recognized in recent years. Because obesity underlies various diseases, pet owners and veterinarians have an important responsibility to help animals lose weight and maintain their health. Diet therapy, however, is typically based on limited calorie intake and animals may suffer stress from hunger and this is also a concern to animal owners. For this reason, many clients drop out of weight control programmes. In the present study, we focused on dietary diacylglycerol (DAG) as a potentially effective ingredient for canine weight control without caloric restriction. We replaced a portion of the fat in dog food with either DAG or triacylglycerol (TAG), referred to as DAG or TAG diets here, and fed overweight beagle dogs (body condition score of 4 or higher) with either the DAG or TAG diet for a 6-week period. Results indicated that, even though the food composition other than fat type were identical, dogs fed the DAG diet showed a statistically significant reduction in body weight averaging a 2.3% reduction within 6 weeks while the TAG-fed dogs maintained their obese body weights. In addition, the DAG group also showed a reduction in body fat content, serum triglyceride and total cholesterol concentrations. These results suggest the possibility of developing a pet food using DAG to control weight and serum lipid levels without compromising caloric intake.

  17. Hero Dog

    Institute of Scientific and Technical Information of China (English)

    Dorine; Houston

    1997-01-01

    Today a dog in the neighborhood is getting showered with packages of beefsteak!He deserves every bite, too! He is a hero. He rescued his family from a terrible fire. Do you remember looking over my balcony at the rowhouses down on Spruce

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

    Institute of Scientific and Technical Information of China (English)

    朱奎成; 刘娜; 王纯耀; 金树兴

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Segura Alejandro

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gustavo Bujalesky

    2004-03-01

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

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

    Science.gov (United States)

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

    2008-07-01

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

  2. Genomic Regions Associated With Interspecies Communication in Dogs Contain Genes Related to Human Social Disorders

    Science.gov (United States)

    Persson, Mia E.; Wright, Dominic; Roth, Lina S. V.; Batakis, Petros; Jensen, Per

    2016-01-01

    Unlike their wolf ancestors, dogs have unique social skills for communicating and cooperating with humans. Previously, significant heritabilities for human-directed social behaviors have been found in laboratory beagles. Here, a Genome-Wide Association Study identified two genomic regions associated with dog’s human-directed social behaviors. We recorded the propensity of laboratory beagles, bred, kept and handled under standardized conditions, to initiate physical interactions with a human during an unsolvable problem-task, and 190 individuals were genotyped with an HD Canine SNP-chip. One genetic marker on chromosome 26 within the SEZ6L gene was significantly associated with time spent close to, and in physical contact with, the human. Two suggestive markers on chromosome 26, located within the ARVCF gene, were also associated with human contact seeking. Strikingly, four additional genes present in the same linkage blocks affect social abilities in humans, e.g., SEZ6L has been associated with autism and COMT affects aggression in adolescents with ADHD. This is, to our knowledge, the first genome-wide study presenting candidate genomic regions for dog sociability and inter-species communication. These results advance our understanding of dog domestication and raise the use of the dog as a novel model system for human social disorders. PMID:27685260

  3. Expression of caveolin-1 in the early phase of beta-TCP implanted in dog mandible.

    Science.gov (United States)

    Chou, Cherng-Tzeh; Bhawal, Ujjal K; Watanabe, Nobuyuki; Kuboyama, Noboru; Chang, Wei-Jen; Lee, Sheng-Yang; Abiko, Yoshimitsu

    2013-07-01

    Caveolin is an essential and signature protein of caveolae. Caveolin-1 participates in signal transduction processes by acting as a scaffolding protein that concentrates, organizes and functional regulates signalling molecules within caveolar membranes. Beta-tricalcium phosphate (β-TCP) has been widely used for scaffold in tissue engineering due to its high biodegradability, osteoconductivity, easy manipulation, and lack of histotoxicity. To better understand the role of caveolin-1 in bone homeostasis and response to β-TCP scaffold, β-TCP was implanted into the dog mandible defects in beagle dogs, and gene expression profiles were examined focused on the molecular components involved in caveolin-1 regulation. Here we showed the quantitative imageology analysis characterized using in vivo micro-computed tomography (CT) images at 4 and 7 days after β-TCP implanted in dog mandibles. The bone reformation by using the β-TCP scaffolds began within 4 days of surgery, and was healing well at 7 days after surgery. Higher mRNA level of caveolin-1 was observed in β-TCP-implanted Beagle dog mandibles compared with controls at day 4 and day 7 post-surgery. The enhancement of caveolin-1 by β-TCP was further confirmed by immunohistochemistry and immunofluorescence analysis. We further revealed increased Smad7 and Phospho Stat3 expression in β-TCP-implanted specimens. Taken together, these results suggest that the enhancement of caveolin-1 play an important role in accelerating bone formation by β-TCP.

  4. Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

    Institute of Scientific and Technical Information of China (English)

    付琳; 代宗顺; 侯淑贤; 万元胜

    2004-01-01

    This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet, TP; sustained-release capsule, TJ and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. Tmax , Cmax and MRT revealed significant difference (P<0.05). Relative bioavailability was 111. 5 ± 16. 9 % (TP) and 110.4% ± 9.6%(TJ). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, Tmax Cmax MRT and DF had significant difference (P<0. 05); Cav, Cmin and AUC0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.

  5. From Neo-Darwinism to Epigenetic Inheritance

    OpenAIRE

    Axholm, Ida; Ranum, Kasper; Al-Makdisi Razeeghi, Redaa

    2014-01-01

    Transgenerational epigenetic inheritance is at variance with the neo-Darwinian theory of inheritance, and this possibly has important implications for how we view evolution, since it could allow for a kind of inheritance of acquired characteristics. We have applied Imre Lakatos and Thomas Kuhn’s models of scientific change and investigated if they can accurately describe the change in the view on inheritance from neo-Darwinism to a view that includes transgenerational epigenetic inheritance, ...

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

    Science.gov (United States)

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

    2016-01-01

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

  7. Dog Bite Emergencies

    Science.gov (United States)

    ... Emergency Care Animal Welfare Veterinary Careers Public Health Dog bite emergencies What do I do if I’ ... vaccination records. What do I do if my dog bites someone? Dog bites are scary for everyone ...

  8. Mechanisms of inherited cancer susceptibility

    Institute of Scientific and Technical Information of China (English)

    Shirley HODGSON

    2008-01-01

    A small proportion of many cancers are due to inherited mutations in genes, which result in a high risk to the individual of developing specific cancers. There are several classes of genes that may be involved: tumour suppressor genes, oncogenes, genes encoding proteins involved in DNA repair and cell cycle control, and genes involved in stimulating the angiogenic pathway. Alterations in susceptibility to cancer may also be due to variations in genes involved in carcinogen metabolism. This review discusses examples of some of these genes and the associated clinical conditions caused by the inheritance of mutations in such genes.

  9. The inheritance of groin hernia

    DEFF Research Database (Denmark)

    Burcharth, J; Pommergaard, H C; Rosenberg, Jacob

    2013-01-01

    Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias.......Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias....

  10. Inherited ataxia with slow saccades

    Directory of Open Access Journals (Sweden)

    R T Chakor

    2012-01-01

    Full Text Available Ataxia is a symptom of cerebellar dysfunction. Slowly progressive ataxia, dysarthria in an adult with a positive family history suggests an inherited cerebellar ataxia. We present an adult with gradually progressive ataxia and slow saccades. There was history of similar illness in his son. Genetic testing for spinocerebellar ataxia 2 was positive. We discuss the various inherited ataxias, causes of acute, progressive ataxia syndromes, episodic ataxias and ataxia associated with other neurological signs like peripheral neuropathy, pyramidal features, movement disorders and cognitive decline.

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

    Science.gov (United States)

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

    2012-05-01

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

  12. Care for Dogs

    Institute of Scientific and Technical Information of China (English)

    孙犁

    2015-01-01

    <正>I choose dog issue as the starting point of my paper,for I have seen many stray dogs everywhere and also some domestic dogs have no suitable place to live,enjoy little care and have little rights.As to those stray dogs,there are many stray dogs one can see on the street.These dogs are running across roads,sidewalks even highways.Many stray dogs’dead bodies are seen on the

  13. Ventricular arrhythmias in Rhodesian Ridgebacks with a family history of sudden death and results of a pedigree analysis for potential inheritance patterns.

    Science.gov (United States)

    Meurs, Kathryn M; Weidman, Jess A; Rosenthal, Steven L; Lahmers, Kevin K; Friedenberg, Steven G

    2016-05-15

    OBJECTIVE To evaluate a group of related Rhodesian Ridgebacks with a family history of sudden death for the presence of arrhythmia and to identify possible patterns of disease inheritance among these dogs. DESIGN Prospective case series and pedigree investigation. ANIMALS 25 Rhodesian Ridgebacks with shared bloodlines. PROCEDURES Pedigrees of 4 young dogs (1 female and 3 males; age, 7 to 12 months) that died suddenly were evaluated, and owners of closely related dogs were asked to participate in the study. Dogs were evaluated by 24-hour Holter monitoring, standard ECG, echocardiography, or some combination of these to assess cardiac status. Necropsy reports, if available, were reviewed. RESULTS 31 close relatives of the 4 deceased dogs were identified. Of 21 dogs available for examination, 8 (2 males and 6 females) had ventricular tachyarrhythmias (90 to 8,700 ventricular premature complexes [VPCs]/24 h). No dogs had clinical signs of cardiac disease reported. Echocardiographic or necropsy evaluation for 7 of 12 dogs deemed affected (ie, with frequent or complex VPCs or sudden death) did not identify structural lesions. Five of 6 screened parents of affected dogs had 0 to 5 VPCs/24 h (all singlets), consistent with a normal reading. Pedigree evaluation suggested an autosomal recessive pattern of inheritance, but autosomal dominant inheritance with incomplete penetrance could not be ruled out. CONCLUSIONS AND CLINICAL RELEVANCE Holter monitoring of Rhodesian Ridgebacks with a family history of an arrhythmia or sudden death is recommended for early diagnosis of disease. An autosomal recessive pattern of inheritance in the studied dogs was likely, and inbreeding should be strongly discouraged.

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

    Science.gov (United States)

    Wucherer, Katja L; Wilke, Vicki

    2010-01-01

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

  15. Skinny Dog

    Institute of Scientific and Technical Information of China (English)

    谢贵贤

    2007-01-01

    <正>I’ve been saving money for a new guitar.It took me over a year,but now I have enough to buy the one I want.Nothside Music has a Pindari Super Twanger on sale this week and I’m going to buy one tomorrow.I can hardly wait! I think the guitar is really going to help the sound of our band.We call the band Skinny Dog because of the skinny dog that lives near our practice hall.Our band sounds very good now.Mr Walton,the music teacher,heard us practicing today at school,and he came in to listen for a while.He seemed to enjoy it.When we finished,he said we should try to have a gig at a party or something.

  16. Gender Differences in Baseline Levels of Vascular Endothelial Growth Factor in the Plasma of Alaskan Sled Dogs

    Directory of Open Access Journals (Sweden)

    Scott W. Kemp

    2005-01-01

    Full Text Available Angiogenesis and vasculogenesis are two very important processes in the development and maintenance of mammalian health. In sled dogs, the angiogenic role is to supply and support tissue with ample vasculature, thus providing a route of access for the transportation of essential nutrients, including oxygen and the removal of waste in a sustained fashion. VEGF has been shown to be a key mediating factor in the underlying cascade of chemical events leading to angiogenesis, which makes it a very important precursor molecule for both muscle development and early neoplasia detection. The overall purpose of this study was to establish circulatory baseline VEGF levels in healthy dogs to develop an alternative mammalian model. Mean VEGF levels were 19 pg mL‾1 in sled dogs (n=20 and 5 pg mL‾1 in beagles (n=4. There were significant baseline VEGF-ir differences between male and female dogs and exercising males and exercising females. In addition preliminary data on beagles suggest that breed may play a role in baseline VEGF-ir levels. This study is the first step in the biotechnological development of a diagnostic VEGF assay in dogs.

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

    Science.gov (United States)

    Chapagain, Durga; Virányi, Zsófia; 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 breeds) divided into three age groups [late adulthood (6- food on the floor. In the first task, results revealed a significant effect of age but no effect of lifelong training on latency to orient to the stimuli. Duration of looking decreased with age and increased with lifelong training. In the second task, while lifelong training decreased the latency of dogs to form eye contact, aged dogs needed longer to find food. BC did not differ from other dogs in any measures of attention except latency to find food. In conclusion, aged dogs showed a decline in attentional capture and sustained attention demonstrating that these tests are sensitive to detect aging of attentiveness in older pet dogs. Importantly, selective attention remained unchanged with age and lifelong training seemed to delay or reduce the aging of attentiveness, further highlighting the importance of lifelong training in retaining general cognitive functions.

  18. Inherited or acquired metabolic disorders.

    Science.gov (United States)

    Eichler, Florian; Ratai, Eva; Carroll, Jason J; Masdeu, Joseph C

    2016-01-01

    This chapter starts with a description of imaging of inherited metabolic disorders, followed by a discussion on imaging of acquired toxic-metabolic disorders of the adult brain. Neuroimaging is crucial for the diagnosis and management of a number of inherited metabolic disorders. Among these, inherited white-matter disorders commonly affect both the nervous system and endocrine organs. Magnetic resonance imaging (MRI) has enabled new classifications of these disorders that have greatly enhanced both our diagnostic ability and our understanding of these complex disorders. Beyond the classic leukodystrophies, we are increasingly recognizing new hereditary leukoencephalopathies such as the hypomyelinating disorders. Conventional imaging can be unrevealing in some metabolic disorders, but proton magnetic resonance spectroscopy (MRS) may be able to directly visualize the metabolic abnormality in certain disorders. Hence, neuroimaging can enhance our understanding of pathogenesis, even in the absence of a pathologic specimen. This review aims to present pathognomonic brain MRI lesion patterns, the diagnostic capacity of proton MRS, and information from clinical and laboratory testing that can aid diagnosis. We demonstrate that applying an advanced neuroimaging approach enhances current diagnostics and management. Additional information on inherited and metabolic disorders of the brain can be found in Chapter 63 in the second volume of this series.

  19. Transgenerational epigenetic inheritance in plants.

    Science.gov (United States)

    Hauser, Marie-Theres; Aufsatz, Werner; Jonak, Claudia; Luschnig, Christian

    2011-08-01

    Interest in transgenerational epigenetic inheritance has intensified with the boosting of knowledge on epigenetic mechanisms regulating gene expression during development and in response to internal and external signals such as biotic and abiotic stresses. Starting with an historical background of scantily documented anecdotes and their consequences, we recapitulate the information gathered during the last 60 years on naturally occurring and induced epialleles and paramutations in plants. We present the major players of epigenetic regulation and their importance in controlling stress responses. The effect of diverse stressors on the epigenetic status and its transgenerational inheritance is summarized from a mechanistic viewpoint. The consequences of transgenerational epigenetic inheritance are presented, focusing on the knowledge about its stability, and in relation to genetically fixed mutations, recombination, and genomic rearrangement. We conclude with an outlook on the importance of transgenerational inheritance for adaptation to changing environments and for practical applications. This article is part of a Special Issue entitled "Epigenetic control of cellular and developmental processes in plants".

  20. Inherited myopathies and muscular dystrophies

    NARCIS (Netherlands)

    Cardamone, Michael; Darras, Basil T.; Ryan, Monique M.

    The inherited myopathies and muscular dystrophies are a diverse group of muscle diseases presenting with common complaints and physical signs: weakness, motor delay, and respiratory and bulbar dysfunction. The myopathies are caused by genetic defects in the contractile apparatus of muscle, and

  1. Brown dog tick, Rhipicephalus sanguineus sensu lato, infestation of susceptible dog hosts is reduced by slow release of semiochemicals from a less susceptible host.

    Science.gov (United States)

    de Oliveira Filho, Jaires Gomes; Ferreira, Lorena Lopes; Sarria, André Lucio Franceschini; Pickett, John A; Birkett, Michael A; Mascarin, Gabriel Moura; de León, Adalberto A Pérez; Borges, Lígia Miranda Ferreira

    2017-01-01

    Domestic dog breeds are hosts for the brown dog tick, Rhipicephalus sanguineus sensu lato, but infestation levels vary among breeds. Beagles are less susceptible to tick infestations than English cocker spaniels due to enhanced production of 2-hexanone and benzaldehyde that act as volatile tick repellents. We report the use of prototype slow-release formulations of these compounds to reduce the burden of R. sanguineus s. l. on English cocker spaniel dogs. Twelve dogs were randomly assigned to two groups with six dogs each. The treated group received collars with slow-release formulations of the compounds attached, while the control group received collars with clean formulations attached. Five environmental infestations were performed, with the number of ticks (at all stages) on the dogs being counted twice a day for 45days. The counts on the number of tick stages found per dog were individually fitted to linear mixed effects models with repeated measures and normal distribution for errors. The mean tick infestation in the treated group was significantly lower than in the control group. For larvae and nymphs, a decrease in tick infestation was observed at the fifth count, and for adults, lower average counts were observed in all counts. The compounds did not interfere with the distribution of the ticks on the body of the dogs, as a similar percentage of ticks was found on the anterior half of the dogs (54.5% for the control group and 56.2% for the treated group). The biological and reproductive parameters of the ticks were not affected by the repellents. This study highlights for the first time the potential use of a novel allomone (repellent)-based formulation for reduction of tick infestation on susceptible dogs. Copyright © 2016 Elsevier GmbH. All rights reserved.

  2. Comparative acaricidal efficacy of the topically applied combinations fipronil/(S-methoprene, permethrin/imidacloprid and metaflumizone/ amitraz against Dermacentor reticulatus, the European dog tick (ornate dog tick, Fabricius, 1794 in dogs*

    Directory of Open Access Journals (Sweden)

    Tielemans E.

    2010-12-01

    Full Text Available The acaricidal efficacy against Dermacentor reticulatus in dogs of the commercial topical combinations fipronil/(S-methoprene (FRONTLINE Combo® spot-on dog, imidacloprid/permethrin (Advantix® and metaflumizone/amitraz (ProMeris Duo® was evaluated and compared. Three treatment groups and one untreated control group of six adult Beagle dogs each were randomly formed. Each treatment was administered topically once on Day-0, according to the recommended label dose and instructions for use. All dogs were infested weekly with approximately 50 adult unfed D. reticulatus over a period of seven weeks. Ticks were removed and counted approximately 48 hours after each infestation. The percent reduction in numbers of ticks for fipronil/(S-methoprene was ≥ 97 % compared to untreated controls for all seven weekly infestations. The percent reductions for imidacloprid/permethrin and metaflumizone/amitraz were satisfactory initially but fell and stayed below 90 % after three weeks. From the third week onwards, fipronil/(S-methoprene treated dogs had significantly fewer ticks than imidacloprid/ permethrin or metaflumizone/amitraz treated dogs (p < 0.05.

  3. The effect of food on the pharmacokinetics of oral fluralaner in dogs.

    Science.gov (United States)

    Walther, Feli M; Allan, Mark J; Roepke, Rainer K A; Nuernberger, Martin C

    2014-03-05

    Fluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. The pharmacokinetics of orally administered drugs may be influenced by feeding. This study investigated the influence of concurrent feeding on fluralaner pharmacokinetics. Twelve fasted or fed beagles received a single oral administration of 25 mg fluralaner/kg body weight in a chewable tablet. Plasma samples were collected at multiple post-treatment time points for fluralaner concentration analysis. Clinical observations were performed on all dogs at regular intervals throughout the study. Fluralaner was readily absorbed in fasted and fed dogs administered at a dose of 25 mg/kg BW with a similar mean tmax for both groups. In fed dogs, AUC and C(max) were increased compared to fasted dogs by a factor of 2.5 and 2.1 respectively. The difference in AUC and C(max) between the fed and fasted groups was statistically significant. No adverse events were observed following oral fluralaner administration to fasted and fed dogs. Fluralaner is absorbed to a considerable extent in fasted and fed dogs. Administration of fluralaner chewable tablets with food significantly increases bioavailability.

  4. Early changes of dog esophageal mucosa induced by N-ethyl-N'-nitro-N-nitrosoguanidine.

    Science.gov (United States)

    Takubo, K; Shisa, H; Futatsuki, K; Sasajima, K

    1981-12-01

    Early changes in the esophageal mucosa of dogs induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) were studied. Seven one-year-old beagle dogs were given a solution of 250 micrograms ENNG/ml to drink ad libitum for 4 months. Three different kinds of lesions (10 erosive carcinomas, 4 slightly elevated microcarcinomas and 19 leukoplakias) were recognized. These three kinds of lesions were not located adjacent to one another, and were surrounded by almost normal stratified squamous epithelium. The foci of the carcinomas revealed an abrupt transition to normal epithelium and were considered to have arisen abruptly from normal esophageal epithelium. The histogenesis of squamous cell carcinomas of the esophagus in dogs may differ from that in man.

  5. Bone reactions adjacent to titanium implants subjected to static load. A study in the dog (I)

    DEFF Research Database (Denmark)

    Gotfredsen, K; Berglundh, T; Lindhe, J

    2001-01-01

    The aim of the study was to evaluate the effect of lateral static load induced by an expansion force on the bone/implant interface and adjacent peri-implant bone. In 3 beagle dogs, the 2nd, 3rd and 4th mandibular premolars were extracted bilaterally. Twelve weeks later 8 implants of the ITI Dental...... Implant System were placed in each dog. Crowns connected in pairs were screwed on the implants 12 weeks after implant installation. The connected crowns contained an orthodontic expansion screw yielding 4 loading units in each dog. Clinical registrations, standardized radiographs and fluorochrome labeling...... were carried out during the 24-week loading period. Biopsies were harvested and processed for ground sectioning. The sections were subjected to histological examination. No evident marginal bone loss was observed at either test or control sites. The bone density and the mineralized bone-to-implant...

  6. Factors influencing measurement of serum iron concentration in dogs: diurnal variation and hyperferritinemia.

    Science.gov (United States)

    Chikazawa, Seishiro; Hori, Yasutomo; Kanai, Kazutaka; Ito, Naoyuki; Hoshi, Fumio; Orino, Koichi; Watanabe, Kiyotaka; Higuchi, Seiichi

    2013-12-30

    We evaluated diurnal variation and hyperferritinemia as factors that influence the values of serum iron concentration in dogs, using the International Committee for Standardization in Hematology (ICSH) colorimetric method. Serum iron levels were significantly higher in the morning than in the evening in 6 clinically healthy beagle dogs, and the maximum decrease in serum iron concentration was 47.3%. Moreover, the change in serum iron concentrations in 22 clinical canine cases with various serum ferritin levels was evaluated by immunoprecipitation of ferritin. The rate of decline in the serum iron concentrations positively correlated with serum ferritin levels (r=0.48, P=0.024). These results show that it is necessary to consider the sampling time and serum ferritin level for accurate interpretation of serum iron concentrations in dogs.

  7. Effect of Frequency of Brushing Teeth on Plaque and Calculus Accumulation, and Gingivitis in Dogs.

    Science.gov (United States)

    Harvey, Colin; Serfilippi, Laurie; Barnvos, Donald

    2015-01-01

    The efficacy of brushing the teeth of beagle dogs in a randomized, controlled, blinded study design using a clearly-defined brushing technique was evaluated for 4 brushing frequencies: brushing daily, brushing every other day, brushing weekly and brushing every other week, compared with no brushing in a control group of dogs. All dogs were fed a standard dry kibble diet during the study. Standard plaque, calculus, and gingivitis indices were used to score the teeth. A 'clean tooth' model was used. No gingival or non-gingival lacerations or other signs of injury to oral tissues were found at the end of the 28 day trial period. Brushing more frequently had greater effectiveness in retarding accumulation of plaque and calculus, and reducing the severity of pre-existing gingivitis. Brushing daily or every other day produced statistically significant improved results compared with brushing weekly or every other week. Based on the results of this study, daily brushing is recommended.

  8. Selecting shelter dogs for service dog training.

    Science.gov (United States)

    Weiss, Emily

    2002-01-01

    Service dogs are an essential aid to persons with disabilities, providing independence, mobility, and improved self-esteem. Because of these proven benefits, the growing se of service dogs is creating a demand and supply crisis. One major cause is the 50% verage dropout rate for dogs selected for training. Weiss and Greenber (1997) re-cently found that a dog, successful on the most commonly used selection test items, was as likely to be either a poor or a good candidate for service work. The experiment presented here evaluated test items developed by the author in 15 years of experience with dogs. The test items were administered to 75 dogs from the Kansas Humane So-ciety. Once tested, the dogs received obedience and retrieval training. The experiment assessed each dog on behavior over 5 weeks of training versus performance on each selection test item. A subset of the selection items, combined in a regression analysis, accounted for 36.4% of the variance with R = 0.603. This research also revealed a reli-able test for dog aggression without risking injury to dog or tester. Items for testing in-cluded fear, motivation, and submission. Another set of selection items reliably pre-dicted the trait of "high energy" commonly described as "high strung." Future research should involve investigating the effectiveness of both cortisol levels and blood pressure in predicting traits to help strengthen the predictive value of the tool and then testing on dogs trained to be full service dogs.

  9. The repeatability and characteristics of right ventricular longitudinal strain imaging by speckle-tracking echocardiography in healthy dogs.

    Science.gov (United States)

    Morita, T; Nakamura, K; Osuga, T; Yokoyama, N; Khoirun, N; Morishita, K; Sasaki, N; Ohta, H; Takiguchi, M

    2017-08-01

    To assess the repeatability and characteristics of echocardiographic indices of the right ventricular (RV) function derived from speckle-tracking echocardiography. Fourteen laboratory Beagles and 103 privately owned dogs without cardiac disease were involved in this study. Right ventricular longitudinal strain, strain rate, and a strain-related index for assessing RV dyssynchrony derived from speckle-tracking echocardiography were obtained by two different observers using five Beagles. Within-day, between-day, and interobserver coefficients of variation and the intraclass correlation coefficient of speckle-tracking echocardiography indices were determined. Both speckle-tracking echocardiography and conventional indices of RV function, including the peak velocity of systolic tricuspid annular motion, tricuspid annulus plane systolic excursion, fractional area change, and the Tei index, were obtained from 14 Beagles and 103 privately owned dogs. Relationships between echocardiographic indices and the body weight, heart rate, age, and sex were estimated by regression analysis. Speckle-tracking echocardiographic indices showed good within-day repeatability, between-day and interobserver repeatability were moderate to good. In large dogs, RV longitudinal strain, strain rate, and fractional area change were significantly decreased, while the index of RV dyssynchrony, systolic tricuspid annular motion, tricuspid annulus plane systolic excursion, and the Tei index were increased. All speckle-tracking and conventional echocardiographic indices were correlated with the body weight. The speckle-tracking echocardiography indices were highly repeatable and body weight affected speckle-tracking echocardiography indices in dogs. Further studies are needed to apply speckle-tracking echocardiography indices in dogs with cardiac disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs

    Science.gov (United States)

    Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We ...

  11. Our Friends—Dogs

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Many people love keeping dogs.They feed and clean their dogs every day,and they even build comfortable houses for them.In their eyes,dogs are not different from their family members.What’s more,dogs can understand theirs owners and usually listen to their instructions.

  12. Dog bites

    OpenAIRE

    Muñoz Leyva, Felipe; Pontificia Universidad Javeriana

    2011-01-01

    Introduction: Although no official data exists for Colombia, dog bites are not infrequent consults to the emergency department on a global scale. In the urban or rural setting, it is likely that Colombian emergency department physicians face patients with such consults in their clinical practice. It is imperative that those physicians become familiar with the current national guidelines and protocols for the attention of such patients, since he/she must act pertinently according to the resour...

  13. Dog bites

    OpenAIRE

    Muñoz Leyva, Felipe; Pontificia Universidad Javeriana

    2011-01-01

    Introduction: Although no official data exists for Colombia, dog bites are not infrequent consults to the emergency department on a global scale. In the urban or rural setting, it is likely that Colombian emergency department physicians face patients with such consults in their clinical practice. It is imperative that those physicians become familiar with the current national guidelines and protocols for the attention of such patients, since he/she must act pertinently according to the resour...

  14. My Dog

    Institute of Scientific and Technical Information of China (English)

    蔡任

    2004-01-01

    My favorite animal is a dog.Its name is Dolly.Dolly has white fur.It has two big eyes and two small ears.My mother knits a blue "sweater" for it.Dolly likes eating meat and bones.It likes playing ball on the grassland.I often play with Dolly on Sundays.Dolly is very naughty.I "hate" and love it.One day,I didmy homework.It was very dirty.It came here and tread my notebook.I was angry

  15. DogPulse

    DEFF Research Database (Denmark)

    Skovgaard, Christoffer; Thomsen, Josephine Raun; Verdezoto, Nervo;

    2015-01-01

    This paper presents DogPulse, an ambient awareness system to support the coordination of dog walking among family members at home. DogPulse augments a dog collar and leash set to activate an ambient shape-changing lamp and visualize the last time the dog was taken for a walk. The lamp gradually...... changes its form and pulsates its lights in order to keep the family members aware of the dog walking activity. We report the iterative prototyping of DogPulse, its implementation and its preliminary evaluation. Based on our initial findings, we present the limitations and lessons learned as well...

  16. Inheriting geodesic flows

    Indian Academy of Sciences (India)

    D B Lortan; S D Maharaj; N K Dadhich

    2001-06-01

    We investigate the propagation equations for the expansion, vorticity and shear for perfect fluid space-times which are geodesic. It is assumed that space-time admits a conformal Killing vector which is inheriting so that fluid flow lines are mapped conformally. Simple constraints on the electric and magnetic parts of the Weyl tensor are found for conformal symmetry. For homothetic vectors the vorticity and shear are free; they vanish for nonhomothetic vectors. We prove a conjecture for conformal symmetries in the special case of inheriting geodesic flows: there exist no proper conformal Killing vectors ( ≠ 0) for perfect fluids except for Robertson–Walker space-times. For a nonhomothetic vector field the propagation of the quantity ln () along the integral curves of the symmetry vector is homogeneous.

  17. CZ: Multiple Inheritance Without Diamonds

    Science.gov (United States)

    2008-12-01

    be solved by allowing renaming (e.g., Eiffel [24]) or by linearizing the class hierarchy [33, 32]. However, there is still no satisfactory solution to...desirable semantics; it is supported in languages such as Scala, Eiffel , and C++ (the last through virtual inheritance) [28, 24, 18]. Next, diamond...Languages that attempt to solve the object initialization problem include Eiffel [24], C++ [18], Scala [28] and Smalltalk with stateful traits [8

  18. Epigenetic Inheritance Across the Landscape

    Directory of Open Access Journals (Sweden)

    Amy Vaughn Whipple

    2016-10-01

    Full Text Available The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome-environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype.

  19. Utilizing inheritance in requirements engineering

    Science.gov (United States)

    Kaindl, Hermann

    1994-01-01

    The scope of this paper is the utilization of inheritance for requirements specification, i.e., the tasks of analyzing and modeling the domain, as well as forming and defining requirements. Our approach and the tool supporting it are named RETH (Requirements Engineering Through Hypertext). Actually, RETH uses a combination of various technologies, including object-oriented approaches and artificial intelligence (in particular frames). We do not attempt to exclude or replace formal representations, but try to complement and provide means for gradually developing them. Among others, RETH has been applied in the CERN (Conseil Europeen pour la Rechereche Nucleaire) Cortex project. While it would be impossible to explain this project in detail here, it should be sufficient to know that it deals with a generic distributed control system. Since this project is not finished yet, it is difficult to state its size precisely. In order to give an idea, its final goal is to substitute the many existing similar control systems at CERN by this generic approach. Currently, RETH is also tested using real-world requirements for the Pastel Mission Planning System at ESOC in Darmstadt. First, we outline how hypertext is integrated into a frame system in our approach. Moreover, the usefulness of inheritance is demonstrated as performed by the tool RETH. We then summarize our experiences of utilizing inheritance in the Cortex project. Lastly, RETH will be related to existing work.

  20. Epigenetic inheritance, prions and evolution

    Indian Academy of Sciences (India)

    JOHANNES MANJREKAR

    2017-07-01

    The field of epigenetics has grown explosively in the past two decades or so. As currently defined, epigenetics deals with heritable, metastable and usually reversible changes that do not involve alterations in DNA sequence, but alter the way that information encoded inDNAis utilized.The bulk of current research in epigenetics concerns itself with mitotically inherited epigenetic processes underlying development or responses to environmental cues (as well as the role of mis-regulation or dys-regulation of such processes in disease and ageing), i.e., epigenetic changes occurring within individuals. However, a steadily growing body of evidence indicates that epigenetic changes may also sometimes be transmitted from parents to progeny, meiotically in sexually reproducingorganisms or mitotically in asexually reproducing ones. Such transgenerational epigenetic inheritance (TEI) raises obvious questions about a possible evolutionary role for epigenetic ‘Lamarckian’ mechanisms in evolution, particularly when epigenetic modifications are induced by environmental cues. In this review I attempt a brief overview of the periodically reviewed and debated ‘classical’ TEI phenomena and their possible implications for evolution. The review then focusses on a less-discussed, unique kind of protein-onlyepigenetic inheritance mediated by prions. Much remains to be learnt about the mechanisms, persistence and effects of TEI. The jury is still out on their evolutionary significance and how these phenomena should be incorporated into evolutionary theory, but the growing weight of evidence indicates that likely evolutionary roles for these processes need to be seriously explored.

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

    Science.gov (United States)

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

    2000-01-01

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

  2. Evaluating the Strange Situation Procedure (SSP to assess the bond between dogs and humans.

    Directory of Open Access Journals (Sweden)

    Therese Rehn

    Full Text Available The Strange Situation Procedure (SSP is increasingly being used to study attachment between dogs and humans. It has been developed from the Ainsworth Strange Situation Procedure, which is used extensively to investigate attachment between children and their parents. In this experiment, 12 female beagle dogs were tested in two treatments to identify possible order effects in the test, a potential weakness in the SSP. In one treatment (FS, dogs participated together with a 'familiar person' and a 'stranger'. In a control treatment (SS, the same dogs participated together with two unfamiliar people, 'stranger A' and 'stranger B'. Comparisons were made between episodes within as well as between treatments. As predicted in FS, dogs explored more in the presence of the familiar person than the stranger. Importantly, they also explored more in the presence of stranger A (who appeared in the same order as the familiar person and followed the same procedure than stranger B in SS. Furthermore, comparisons between treatments, where a familiar person was present in FS and stranger A was present in SS, showed no differences in exploration. In combination, these results indicate that the effect of a familiar person on dogs' exploratory behaviour, a key feature when assessing secure attachment styles, could not be tested reliably due to the order in which the familiar person and the stranger appear. It is proposed that in the future only counterbalanced versions of the SSP are used. Alternatively, since dogs reliably initiated more contact with the familiar person compared to the strangers, it is suggested that future studies on attachment in dogs towards humans should focus either on the behaviour of the dog in those episodes of the SSP when the person returns, or on reunion behaviour in other studies, specially designed to address dog-human interactions at this time.

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

    Science.gov (United States)

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

    2015-02-01

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

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

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    Chapagain, Durga; Virányi, Zsófia; 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 breeds) divided into three age groups [late adulthood (6- dogs in order to explore if prior results in BC are generalizable and to evaluate the influence of lifelong training on measures of attention. Each dog’s lifelong training score (ranging from 0 to 52) was calculated from a questionnaire filled in by the owners listing what kinds of training the dog participated in during its entire life. Dogs were tested in two tasks; the first, measuring attentional capture and sustained attention toward two stimuli (toy and human); and the second, measuring selective attention by means of clicker training for eye contact and finding food on the floor. In the first task, results revealed a significant effect of age but no effect of lifelong training on latency to orient to the stimuli. Duration of looking decreased with age and increased with lifelong training. In the second task, while lifelong training decreased the latency of dogs to form eye contact, aged dogs needed longer to find food. BC did not differ from other dogs in any measures of attention except latency to find food. In conclusion, aged dogs showed a decline in attentional capture and sustained attention demonstrating that these tests are sensitive to detect aging of attentiveness in older pet dogs. Importantly, selective attention remained unchanged with age and lifelong training seemed to delay or reduce the aging of attentiveness, further highlighting the importance of lifelong training in retaining general cognitive

  5. Akita dogs possess GLUT1 in erythrocytes, and Na,K-ATPase activity enables more efficient ascorbic acid recycling.

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    Ogawa, Eri; Neo, Sakurako

    2016-11-01

    We investigated hematologic characteristics of healthy Akita dogs. All were found to contain glucose transporters, GLUT1 and GLUT4, in erythrocyte membrane, whereas Beagle and any other Western dogs have only GLUT4. Of 47 Akitas, ten showed high K and low Na concentrations with elevated glutathione (GSH) in erythrocytes due to Na,K-ATPase activity in the membrane (HK). Akitas showed increased capacity for recycling vitamin C or ascorbic acid (AA) from oxidized ascorbic acid (DHA) compared to Beagle dogs. Particularly, HK Akitas performed even greater AA recycling and ferricyanide reduction than normal Akitas which have normal GSH, low K and high Na concentrations (LK). All HK Akitas also had stomatin in erythrocyte membrane, while half of LK Akitas had it at lower levels than HK Akitas. Stomatin did not have any influence on AA recycling. GLUT1, Na,K-ATPase and stomatin in erythrocytes are characteristics of Akita dogs, and the high prevalence of these proteins suggests their positive roles in biological efficiency.

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

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    Jean A Hall

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

  7. Use of the pentagastrin dog model to explore the food effects on formulations in early drug development.

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    Zane, P; Guo, Z; MacGerorge, D; Vicat, P; Ollier, C

    2014-06-16

    The ability to extrapolate dosage performance from in vitro to in vivo situations has an important role in early drug development. In parallel, the Beagle dog has come to represent a useful animal model for extrapolation to humans especially when drugs formulated for humans are to be tested. In this article, the pentagastrin-induced Beagle dog model was validated internally to show that in the colony the dogs were generally responsive to known doses of pentagastrin that produces effects similar to gastrin in the stomach, i.e., increasing gastric acid production and lowering gastric pH. The effect was observed with a short time course, maximum pH lowering was observed between 0.5 and 1h with return to baseline at 2-4h. The dog stomach pH is a better representative of the human fasted stomach with this pretreatment. The ultimate goal was to use these animals in a food effect studies to predict the behavior of formulations in humans. The results for 4 compounds were provided in the dog and a clear relationship between the effect of food in the dog and the effect of food in humans was observed. While the directionality (positive or negative) of the effect could be adequately predicted, the extent of the effect could not be predicted for all the tested formulations of the 4 compounds. The data will be used to generate a database of known compounds from which a correlation can be drawn to make future predictions using the pentagastrin dog model. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Increased immunoreactivity of c‑Fos in the spinal cord of the aged mouse and dog.

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    Ahn, Ji Hyeon; Shin, Myoung Chul; Park, Joon Ha; Kim, In Hye; Lee, Jae-Chul; Yan, Bing Chun; Hwang, In Koo; Moon, Seung Myung; Ahn, Ji Yun; Ohk, Taek Geun; Lee, Tae Hun; Cho, Jun Hwi; Shin, Hyung-Cheul; Won, Moo-Ho

    2015-02-01

    Expression of c‑Fos in the spinal cord following nociceptive stimulation is considered to be a neurotoxic biomarker. In the present study, the immunoreactivity of c‑Fos in the spinal cord was compared between young adult (2‑3 years in dogs and 6 months in mice) and aged (10‑12 years in dogs and 24 months in mice) Beagle dogs and C57BL/6J mice. In addition, changes to neuronal distribution and damage to the spinal cord were also investigated. There were no significant differences in neuronal loss or degeneration of the spinal neurons observed in either the aged dogs or mice. Weak c‑Fos immunoreactivity was observed in the spinal neurons of the young adult animals; however, c‑Fos immunoreactivity was markedly increased in the nuclei of spinal neurons in the aged dogs and mice, as compared with that of the young adults. In conclusion, c‑Fos immunoreactivity was significantly increased without any accompanying neuronal loss in the aged spinal cord of mice and dogs, as compared with the spinal cords of the young adult animals.

  9. Gene expression profiles of colonic mucosa in healthy young adult and senior dogs.

    Directory of Open Access Journals (Sweden)

    Dong Yong Kil

    Full Text Available BACKGROUND: We have previously reported the effects of age and diet on nutrient digestibility, intestinal morphology, and large intestinal fermentation patterns in healthy young adult and senior dogs. However, a genome-wide molecular analysis of colonic mucosa as a function of age and diet has not yet been performed in dogs. METHODOLOGY/PRINCIPAL FINDINGS: Colonic mucosa samples were collected from six senior (12-year old and six young adult (1-year old female beagles fed one of two diets (animal protein-based vs. plant protein-based for 12 months. Total RNA in colonic mucosa was extracted and hybridized to Affymetrix GeneChip® Canine Genome Arrays. Results indicated that the majority of gene expression changes were due to age (212 genes rather than diet (66 genes. In particular, the colonic mucosa of senior dogs had increased expression of genes associated with cell proliferation, inflammation, stress response, and cellular metabolism, whereas the expression of genes associated with apoptosis and defensive mechanisms were decreased in senior vs. young adult dogs. No consistent diet-induced alterations in gene expression existed in both age groups, with the effects of diet being more pronounced in senior dogs than in young adult dogs. CONCLUSION: Our results provide molecular insight pertaining to the aged canine colon and its predisposition to dysfunction and disease. Therefore, our data may aid in future research pertaining to age-associated gastrointestinal physiological changes and highlight potential targets for dietary intervention to limit their progression.

  10. Stratum corneum removal facilitates experimental sensitization to mite allergens in atopic dogs.

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    Olivry, Thierry; Wofford, Jessica; Paps, Judy S; Dunston, Stanley M

    2011-04-01

    In humans with atopic dermatitis and in mouse models of IgE-mediated allergic diseases, evidence is mounting that the stratum corneum (SC) provides an important barrier against environmental allergens. At this time, it is not known whether the SC has a similar role in dogs, especially in those with atopic dermatitis. The objectives of this pilot study were to determine whether SC removal led to earlier and stronger sensitization of atopic dogs to Dermatophagoides farinae (Df) house dust mites. Five Maltese-beagle atopic (MBA) dogs were sensitized epicutaneously after the SC was removed with ten tape strips (TS group), while sensitization was done without tape strips in five other MBA dogs (nontape stripping; NTS group). During this 16 week study, sensitization was assessed with allergen-specific IgE serology, intradermal testing with Df allergens and determination of stimulation indices of blood mononuclear cells cultured with Df and stained for CD4 and the activation markers CD25 or CD30. Compared with dogs from the NTS group, those of the TS group exhibited earlier rises in Df-specific IgE serum levels, usually had higher allergen-specific IgE titres, showed higher intradermal test reactivity and had earlier increases and higher percentages of CD25- or CD30-positive activated allergen-specific peripheral CD4-positive T lymphocytes. These observations implicate a role of the SC as a barrier limiting sensitization to exogenous allergens in this experimental atopic dog model.

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

    Directory of Open Access Journals (Sweden)

    Gustavo Bujalesky

    2004-03-01

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

  12. Plate tectonics, damage and inheritance.

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    Bercovici, David; Ricard, Yanick

    2014-04-24

    The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The reason for this time lag is unknown but fundamental to understanding the origin of plate tectonics. Here we suggest that when sufficient lithospheric damage (which promotes shear localization and long-lived weak zones) combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of weak plate boundaries and eventually to fully formed tectonic plates driven by subduction alone. We simulate this process using a grain evolution and damage mechanism with a composite rheology (which is compatible with field and laboratory observations of polycrystalline rocks), coupled to an idealized model of pressure-driven lithospheric flow in which a low-pressure zone is equivalent to the suction of convective downwellings. In the simplest case, for Earth-like conditions, a few successive rotations of the driving pressure field yield relic damaged weak zones that are inherited by the lithospheric flow to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even though flow is driven only by subduction. But for hotter surface conditions, such as those on Venus, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which corresponds to observations. After plates have developed, continued changes in driving forces, combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor plates.

  13. Evaluation of 3D printed PCL/PLGA/β-TCP versus collagen membranes for guided bone regeneration in a beagle implant model.

    Science.gov (United States)

    Won, J-Y; Park, C-Y; Bae, J-H; Ahn, G; Kim, C; Lim, D-H; Cho, D-W; Yun, W-S; Shim, J-H; Huh, J-B

    2016-10-07

    Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PCL/PLGA/β-TCP) membranes with the widely used collagen membranes for guided bone regeneration (GBR) in beagle implant models. For mechanical property comparison in dry and wet conditions and cytocompatibility determination, we analyzed the rate and pattern of cell proliferation of seeded fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning electron microscopy. Osteogenic differentiation was verified using alizarin red S staining. At 8 weeks following implantation in vivo using beagle dogs, computed tomography and histological analyses were performed after sacrifice. Cell proliferation rates in vitro indicated that early cell attachment was higher in collagen than in PCL/PLGA/β-TCP membranes; however, the difference subsided by day 7. Similar outcomes were found for osteogenic differentiation, with approximately 2.5 times greater staining in collagen than PCL/PLGA/β-TCP, but without significant difference by day 14. In vivo, bone regeneration in the defect area, represented by new bone formation and bone-to-implant contact, paralleled those associated with collagen membranes. However, tensile testing revealed that whereas the PCL/PLGA/β-TCP membrane mechanical properties were conserved in both wet and dry states, the tensile property of collagen was reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo that PCL/PLGA/β-TCP membranes have similar levels of biocompatibility and bone regeneration as collagen membranes. In particular, considering that GBR is always applied to a wet environment (e.g. blood, saliva), we demonstrated that PCL/PLGA/β-TCP membranes maintained their form more reliably than collagen membranes in a wet setting, confirming their appropriateness as a GBR membrane.

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

    Science.gov (United States)

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

    2005-10-01

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

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

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    Amin, O; Ferrer, L; Marcovecchio, J

    1996-07-01

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

  16. Origins of the Domestic Dog and the Rich Potential for Gene Mapping

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    Jeremy R. Shearman

    2011-01-01

    Full Text Available The unique breeding structure of the domestic dog makes canine genetics a useful tool to further the understanding of inherited diseases and gene function. Answers to the questions of when and where the dog was domesticated from the wolf are uncertain, but how the modern diversity of dog breeds was developed is documented. Breed development has resulted in many genetically isolated populations which are segregating for different alleles for disease and morphological and behavioral traits. Many genetic tools are available for dog research allowing investigation into the genetic basis of these phenotypes. Research into causes of diseases in dogs is relevant to humans and other species; comparative genomics is being used to transfer genetic information to them, including some studies on morphological and behavioral phenotypes. Because of the unique breed structure and well-maintained pedigrees, dogs represent a model organism containing a wealth of genetic information.

  17. Atypical mitochondrial inheritance patterns in eukaryotes.

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    Breton, Sophie; Stewart, Donald T

    2015-10-01

    Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

  18. Paternal inheritance of mitochondria in Chlamydomonas.

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    Nakamura, Soichi

    2010-03-01

    To analyze mitochondrial DNA (mtDNA)inheritance, differences in mtDNA between Chlamydomonas reinhardtii and Chlamydomonas smithii, respiration deficiency and antibiotic resistance were used to distinguish mtDNA origins. The analyses indicated paternal inheritance. However, these experiments raised questions regarding whether paternal inheritance occurred normally.Mitochondrial nucleoids were observed in living zygotes from mating until 3 days after mating and then until progeny formation. However, selective disappearance of nucleoids was not observed. Subsequently, experimental serial backcrosses between the two strains demonstrated strict paternal inheritance. The fate of mt+ and mt- mtDNA was followed using the differences in mtDNA between the two strains. The slow elimination of mt+ mtDNA through zygote maturation in darkness was observed, and later the disappearance of mt+ mtDNA was observed at the beginning of meiosis. To explain the different fates of mtDNA, methylation status was investigated; however, no methylation was detected. Variously constructed diploid cells showed biparental inheritance. Thus, when the mating process occurs normally, paternal inheritance occurs. Mutations disrupting mtDNA inheritance have not yet been isolated. Mutations that disrupt maternal inheritance of chloroplast DNA (cpDNA) do not disrupt inheritance of mtDNA. The genes responsible for mtDNA inheritance are different from those of chloroplasts.

  19. Mitochondrial DNA inheritance after SCNT.

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    Hiendleder, Stefan

    2007-01-01

    Mitochondrial biogenesis and function is under dual genetic control and requires extensive interaction between biparentally inherited nuclear genes and maternally inherited mitochondrial genes. Standard SCNT procedures deprive an oocytes' mitochondrial DNA (mtDNA) of the corresponding maternal nuclear DNA and require it to interact with an entirely foreign nucleus that is again interacting with foreign somatic mitochondria. As a result, most SCNT embryos, -fetuses, and -offspring carry somatic cell mtDNA in addition to recipient oocyte mtDNA, a condition termed heteroplasmy. It is thus evident that somatic cell mtDNA can escape the selective mechanism that targets and eliminates intraspecific sperm mitochondria in the fertilized oocyte to maintain homoplasmy. However, the factors responsible for the large intra- and interindividual differences in heteroplasmy level remain elusive. Furthermore, heteroplasmy is probably confounded with mtDNA recombination. Considering the essential roles of mitochondria in cellular metabolism, cell signalling, and programmed cell death, future experiments will need to assess the true extent and impact of unorthodox mtDNA transmission on various aspects of SCNT success.

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

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    Rebecca A. Mullis

    2015-02-01

    Full Text Available Despite their important role in security, little is known about the energy requirements of working dogs such as odor, explosive and human detection dogs. Previous researchers have evaluated the energy requirements of individual canine breeds as well as dogs in exercise roles such as sprint racing. This study is the first to evaluate the energy requirements of working dogs trained in odor, explosive and human detection. This retrospective study evaluated twenty adult dogs who maintained consistent body weights over a six month period. During this time, the average energy consumption was $136\\pm 38~\\mathrm{kcal}\\cdot {\\mathrm{BW}}_{\\mathrm{kg}}^{0.75}$136±38kcal⋅BWkg0.75 or two times the calculated resting energy requirement ($\\mathrm{RER}=70~\\mathrm{kcal}\\cdot {\\mathrm{BW}}_{\\mathrm{kg}}^{0.75}$RER=70kcal⋅BWkg0.75. No statistical differences were found between breeds, age or sex, but a statistically significant association (p = 0.0033, R-square = 0.0854 was seen between the number of searches a dog performs and their energy requirement. Based on this study’s population, it appears that working dogs have maintenance energy requirements similar to the 1974 National Research Council’s (NRC maintenance energy requirement of $132~\\mathrm{kcal}\\cdot {\\mathrm{BW}}_{\\mathrm{kg}}^{0.75}$132kcal⋅BWkg0.75 (National Research Council (NRC, 1974 and the $139\\pm 42~\\mathrm{kcal}\\cdot {\\mathrm{BW}}_{\\mathrm{kg}}^{0.75}$139±42kcal⋅BWkg0.75 reported for young laboratory beagles (Rainbird & Kienzle, 1990. Additional research is needed to determine if these data can be applied to all odor, explosive and human detection dogs and to determine if other types of working dogs (tracking, search and rescue etc. have similar energy requirements.

  1. Evaluation of a commercial in-clinic point-of-care polymerase chain reaction test for Ehrlichia canis DNA in artificially infected dogs.

    Science.gov (United States)

    Waner, Trevor; Nachum-Biala, Yaarit; Harrus, Shimon

    2014-12-01

    A novel in-clinic point-of-care (ICPOC) polymerase chain reaction (PCR) test was evaluated for its ability to detect Ehrlichia canis DNA in artificially infected dogs compared to a real-time PCR assay. Six Beagle dogs negative for E. canis antibodies and PCR negative were artificially infected with an Israeli E. canis strain (611). All dogs developed IgG antibodies 8 days post infection (PI), and clinical and hematological abnormalities on day 10 PI. Only the real-time PCR detected E. canis DNA in the blood of five dogs at days 3 and 5 PI. At day 12 PI during the acute phase of the disease, 1 day after the initiation of doxycycline treatment,