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Beagle Dogs (beagle + dog)
Kinds of Beagle Dogs Selected AbstractsQuantitative Assessment of Regional Right Ventricular Myocardial Velocities in Awake Dogs by Doppler Tissue Imaging: Repeatability, Reproducibility, Effect of Body Weight and Breed, and Comparison with Left Ventricular Myocardial VelocitiesJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2005Valérie Chetboul Right ventricular myocardial (RVM) motion is poorly documented. The objective of this study was to determine the variability of RVM velocities by tissue Doppler imaging (TDI) in healthy dogs (study 1), to analyze RVM motion in a large healthy canine population (study 2), and to compare the results with those obtained for the left ventricular free wall. Six healthy Beagle Dogs were monitored in study 1, and 64 healthy dogs of 14 different breeds were monitored in study 2. Velocities were recorded in 2 segments (basal and apical) of the right and left myocardial walls. In study 1, 36 TDI examinations were performed for 4 days, whereas a single TDI examination was performed on each dog in study 2. All velocity profiles included 1 positive systolic wave and 2 negative diastolic waves. The lowest intraday and interday coefficient of variation values of the right TDI variables were observed at the base (3.5,16.1%). The variability of the right apical velocities was much higher, with most coefficient of variation values >15%. RVM velocities were higher in the basal than in the apical segments (P < .001) and were higher than the left velocities of the corresponding segment (P < .01). Body weight and breed had an effect on only a few right and left TDI variables. TDI provides a repeatable and reproducible method for evaluating basal RV function in the dog. These data also demonstrate the heterogeneity of the myocardial velocities between the left and the right ventricles and between the base and the apex. [source] Investigational New Drug-Directed Toxicology and Pharmacokinetic Study of 4-[3-(2-Nitro-1-Imidazolyl)-Propylamino]-7-Chloroquinoline Hydrochloride (NLCQ-1, NSC 709257) in Beagle DogsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2010Maria V. Papadopoulou The present study is one of several pre-clinical toxicology studies conducted in support of an ,investigational new drug' (IND) application to test this agent as an adjuvant to radio/chemotherapy for the treatment of cancer in humans. Twenty-four dogs were each assigned to one vehicle control group or to one of three test article-treated groups (three dogs/sex/treatment group). Intravenous (i.v.) doses of 0, 2.74, 5.48 and 10.95 mg/kg/day (54.8, 109.6 or 219 mg/m2/day) were administered on a per day × 5 days (qd × 5) schedule. NLCQ-1 was formulated as a solution in sterile saline at 1.5 mg/ml. None of the dogs died during this 33-day study. With few exceptions, most of the clinical signs of toxicity were noted within 2 hr following dosing in the 10.95 mg/kg/day dose group. These observations included aggressive behaviour, ataxia, tachypnea, emesis, hypoactivity, excessive salivation, tremors, and involuntary urination and defecation. Aggressive behaviour was judged to be dose-limiting. No clinical signs of toxicity were noted during the 28-day observation period that followed the 5-day dose period. Findings in a functional observation battery examination were consistent with the clinical observations. No drug-related effects were noted on the body weight or food consumption values, and no drug-related changes were noted during ocular examinations made on these animals prior to scheduled necropsy or during examination of electrocardiogram recordings made at 15 min. and 2 hr after dosing on days 1 and 5. No definitive changes in haematology, clinical chemistry or coagulation values were noted in dogs treated with NLCQ-1. NLCQ-1 was detected in the plasma of treated dogs on days 1 and 5, up to 60 min. after dosing (2.74 and 5.48 mg/kg/day) and up to 8 hr after dosing (10.95 mg/kg/day). There was a dose-related increase in maximum plasma concentration of NLCQ-1 at 5 min. after dosing; comparable concentrations were noted on days 1 and 5. No definitive test article-related lesions were noted during microscopic evaluation of tissues from dogs in this study, although lesions noted at the injection site and in the vascular tissue, lungs, thymus, prostate gland, muscle, adrenal cortex and tongue may have resulted from treatment with this drug. Any drug-related toxicity noted was readily reversible and not cumulative. No sex difference was detected in the susceptibility to NLCQ-1-induced toxicity. [source] Pyometra with inguinal herniation of the left uterine horn and omentum in a Beagle dogJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 1 2007Christopher G. Byers DVM Abstract Objective: To describe a unique case of pyometra with inguinal herniation of the left uterine horn and omentum. Case summary: A 7-year-old, 19 kg, intact female Beagle dog presented for surgical treatment of presumptive pyometra and biopsy of a caudal abdominal mass in the left inguinal mammary gland region. Ventral midline celiotomy was performed, and a distended, fluid-filled uterus with passage of the distal aspect of the left uterine horn through the left vaginal process into the inguinal canal was identified. The patient recovered uneventfully following ovariohysterectomy and left inguinal herniorrhaphy. New or unique information provided: This is the first documented report of inguinal herniation of a uterine horn associated with a pyometra. [source] Metabolism of cholesterol ester of apolipoprotein B100-containing lipoproteins in dogs: evidence for disregarding cholesterol ester transferEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2004E. Bailhache Abstract Background, It has been shown that dogs exhibit no cholesterol ester transfer protein (CETP) activity in vitro, in contrast to humans. The aim of our study was to determine modalities of in vivo plasma cholesterol ester turnover in this species, using a kinetic approach with stable isotopes. Materials and methods, Kinetics of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) were studied in seven adult male Beagle dogs using a dual isotope approach through endogenous labelling of both their cholesterol moiety and their protein moiety. A primed constant infusion of both [1,213C]acetate and [5,5,5- 2H3]leucine enabled us to obtain measurable deuterium enrichments by gas chromatography-mass spectrometry for plasma leucine and apoB100, as well as measurable 13C enrichment by gas chromatography-combustion-isotopic ratio mass spectrometry for unesterified cholesterol and cholesterol ester in the VLDL and LDL. Two identical multicompartmental models (SAAM II) were used together for the analysis of tracer kinetics' data of proteins and cholesterol. Results, Characterization of the apoB100-containing lipoprotein cholesterol ester model allowed determination of kinetic parameters of VLDL and LDL cholesterol ester metabolism. We succeeded in modelling VLDL and LDL cholesterol ester metabolism and apoB100 metabolism simultaneously. Fractional catabolic rate (FCR) of apoB100 and CE had the same values. Introducing cholesterol ester transfer between lipoproteins in the model did not significantly improve the fit. Total VLDL FCR was 2·97 ± 01·47 h,1. Approximately one-quarter corresponded to the direct removal of VLDL (0·81 ± 00·34 h,1) and the remaining three-quarters corresponded to the fraction of VLDL converted to LDL, which represented a conversion of VLDL into LDL of 2·16 ± 01·16 h,1. Low-density lipoproteins were produced exclusively from VLDL conversion and were then removed (0·031 ± 0·004 h,1) from plasma. Conclusion, These kinetic data showed that VLDL cholesterol ester and LDL cholesterol ester metabolism followed VLDL and LDL apoB100 metabolism, and that consequently there is no in vivo transfer of cholesterol ester in dogs. [source] Effect of ovariectomy and ad libitum feeding on body composition, thyroid status, ghrelin and leptin plasma concentrations in female dogs,JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2006I. Jeusette Summary The objective of this study was to evaluate the effects of ovariectomy (i) and ad libitum feeding (ii) on energy intake, body weight (BW), body composition, thyroid status, leptin and ghrelin plasma concentrations. Four young adult female Beagle dogs were fed a maintenance diet for 6 weeks prior to ovariectomy, then 6 months after. Food allowance was adjusted in order to maintain optimal BW. Then, a diet slightly higher in energy concentration was fed ad libitum for 4 months. The maintenance diet was then fed ad libitum for one additional month. The maintenance of optimal BW after ovariectomy required a significant decrease in energy allowance. No increase in fat mass was observed. Ghrelin concentration remained unchanged. During the first month of ad libitum feeding, plasma ghrelin concentration and energy intake increased, then they decreased. Mean BW, plasma leptin, thyrotropin (TSH), total triiodothyronine (TT3) and total thyroxine (TT4) concentrations significantly increased over the study. The BW increase was exclusively due to an increase in body fat. In conclusion, energy allowance should be strictly controlled in spayed female dogs. The results suggest that in dogs, thyroid hormones, leptin and ghrelin concentrations change in response to a positive energy balance in an attempt to limit weight gain. However, the significant weight gain shows that this goal was not achieved. [source] Evolution of blood parameters during weight loss in experimental obese Beagle dogsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2004M. Diez Summary The effects of weight loss on hormonal and biochemical blood parameters were measured monthly [carnitine, creatinine, urea, free T4 (fT4), total T4 (TT4), plasma alkaline phosphatases (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), potassium and total proteins] or bimonthly [cholesterol, triglycerides, non-esterified fatty acids (NEFA), insulin-like growth factor I (IGF-I), glucose, insulin] in eight obese Beagles dogs fed either a high protein dry diet, DP (crude protein 47.5%, on dry matter basis) or a commercial high fibre diet, HF (crude protein 23.8%, crude fibre 23.3%). The dogs were allotted to two groups according to sex and body weight (BW) and they were respectively fed with the DP or the control HF diet during 12,26 weeks, until they reach their optimal BW. The plasma basal triglycerides and cholesterol concentrations were decreased by the two diets but the difference was only significant for the DP diet. The plasma mean NEFA concentration increased regularly over the period with the HF diet, without significant difference between the two diets. No effect of diet or weight loss was observed on plasma carnitine, urea, creatinine, ALP, AST, ALT, potassium, TT4, FT4, IGF-I, glucose and insulin. Weight loss induced a decrease in fT4 plasma concentration (p < 0.001). The high protein diet allowed a safe weight loss. [source] Tissue reactions to sutures in the presence and absence of anti-infective therapyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2 2005Knut N. Leknes Abstract Background: In the oral cavity, sutures are placed within tissues of high vascularity in a moist environment with infectious potential. The objective of this study was to evaluate tissue reactions at silk and expanded polytetrafluoroethylene (ePTFE) sutures in the presence and absence of anti-infective therapy (AT). Methods: Thirty-six sutures were placed within the mandibular keratinized gingiva in six Beagle dogs. Each animal received one braided silk (4-0) and one ePTFE (CV-5) suture in contra-lateral jaw quadrants at 14, 7, and 3 days prior to biopsy. Three animals received daily AT including topical 2% chlorhexidine solution and a systemic broad-spectrum antibiotic. Biopsy specimens allowed histometric analysis of tissue reactions along the central part of the suture loop including the area of perisutural epithelium, ratio inflammatory cells (ICs)/epithelial cells and IC/fibroblasts, and presence/absence of bacterial plaque in the suture track. Results: A perisutural epithelial sheath was forming within 3 days. The cross-sectional area of the epithelium increased with time for both suture materials (p=0.003) but was particularly pronounced for the silk sutures in the absence of AT. Clusters of IC were present in the perisutural connective tissue and epithelium. Over time, a more prominent increase in IC/fibroblasts was evident for the silk sutures in the absence of AT. The pooled material revealed a significantly higher IC/fibroblast ratio for silk compared with ePTFE sutures (p=0.017). Bacterial plaque influx was detected in 6/9 silk and 0/9 ePTFE suture channels in the presence, and 6/6 and 3/6 suture channels, respectively, in the absence of AT. Conclusions: AT may reduce biofilm formation and inflammation along the suture track. Braided silk, however, elicits more severe tissue reactions than ePTFE regardless of infection control. [source] Design and evaluation of compound metformin/glipizide elementary osmotic pump tabletsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2005Defang Ouyang A simple elementary osmotic pump (EOP) system that could deliver metformin hydrochloride (MT) and glipizide (GZ) simultaneously for extended periods of time was developed in order to reduce the problems associated with multidrug therapy of type 2 non-insulin-dependent diabetes mellitus. In general, both highly and poorly water-soluble drugs are not good candidates for elementary osmotic delivery. However, MT is a highly soluble drug with a high dose (500 mg) while GZ is a water-insoluble drug with a low dose (5 mg) so it is a great challenge to pharmacists to provide satisfactory extended release of MT and GZ. In this paper sodium carbonate was used to modulate the solubility of GZ within the core and MT was not only one of the active ingredients but also the osmotic agent. The optimal EOP was found to deliver both drugs at a rate of approximately zero order for up to 10h in pH 6.8, independent of environment media. In-vivo evaluation was performed relative to the equivalent dose of conventional MT tablet and GZ tablet by a cross-study in six Beagle dogs. The EOP had a good sustained effect in comparison with the conventional product. The prototype design of the system could be applied to other combinations of drugs used for cardiovascular diseases, diabetes, etc. [source] Actions of melatonin mixed with collagenized porcine bone versus porcine bone only on osteointegration of dental implantsJOURNAL OF PINEAL RESEARCH, Issue 3 2010José Luis Calvo-Guirado Abstract:, This study evaluated the effect of the topical application of melatonin mixed with collagenized porcine bone on the osteointegration on the rough discrete calcium deposit (DCD) surface implants in Beagle dogs 3 months after their insertion. In preparation for subsequent insertion of dental implants, lower molars were extracted from 12 Beagle dogs. Each mandible received two parallel wall expanded platform implants with a DCD surface of 4 mm in diameter and 10 mm in length. The implants were randomly assigned to the distal sites on each mandible in the molar area and the gaps were filled with 5 mg lyophilized powdered melatonin and porcine bone and collagenized porcine bone alone. Ten histological sections per implant were obtained for histomorphometric studies. After a 4-wk treatment period, melatonin plus porcine bone significantly increased the perimeter of bone that was in direct contact with the treated implants (P < 0.0001), bone density (P < 0.0001), and new bone formation (P < 0.0001) in comparison with porcine bone alone around the implants. Melatonin plus collagenized porcine bone on DCD surface may act as a biomimetic agent in the placement of endo-osseous dental implants and enhance the osteointegration. Melatonin combined with porcine bone on DCD implants reveals more bone in implant contact at 12 wk (84.5 ± 1.5%) compared with porcine bone alone treated area (67.17 ± 1.2%). [source] Comparative pharmacokinetics of amikacin in Greyhound and Beagle dogsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2008B. KUKANICH The purpose of the study was to compare the pharmacokinetics of amikacin administered i.v., to Greyhound and Beagle dogs and determine amikacin pharmacokinetics administered subcutaneously to Greyhounds. Amikacin was administered i.v. at 10 mg/kg to six healthy Greyhounds and six healthy Beagles. The Greyhounds also received amikacin, 10 mg/kg s.c. Plasma was sampled at predetermined time points and amikacin concentrations determined by a fluorescence polarization immunoassay (FPIA). The volume of distribution was significantly smaller in Greyhounds (mean = 176.5 mL/kg) compared to Beagles (234.0 mL/kg). The C0 and AUC were significantly larger in Greyhounds (86.03 ,g/mL and 79.97 h·,g/mL) compared to Beagles (69.97 ,g/mL and 50.04 h·,g/mL). The plasma clearance was significantly lower in Greyhounds (2.08 mL/min/kg) compared to Beagles (3.33 mL/min/kg). The fraction of the dose absorbed after s.c. administration to Greyhounds was 0.91, the mean absorption time was 0.87 h, and the mean maximum plasma concentration was 27.40 ,g/mL at 0.64 h. Significant differences in the pharmacokinetics of amikacin in Greyhounds indicate it should be administered at a lower dose compared to Beagles. The dose in Greyhounds to achieve a Cmax:AUC , 8 for bacteria (with an MIC , 4 ,g/mL) is 12 mg/kg q24 h compared to 22 mg/kg q24 in Beagles. [source] Estimation of absolute oral bioavailability of moxidectin in dogs using a semi-simultaneous method: influence of lipid co-administrationJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2007E. LALLEMAND Moxidectin is a long-acting anthelmintic drug for which little is known about its kinetic behaviour in dogs and its oral absolute bioavailability has never been reported. We studied the pharmacokinetics of moxidectin in dogs, with a special emphasis on oral bioavailability and the influence of lipid co-administration, by using a semi-simultaneous method of administration. Ten Beagle dogs were dosed orally and then intravenously (i.v.) with 0.2 mg/kg moxidectin. The oral application was conducted with or without corn oil co-administration. Moxidectin concentration,time profiles in plasma were analysed using a compartmental modelling approach, designed to fit the oral and i.v. kinetic disposition curves simultaneously. In contrast to what happens in other species, our study indicates that the bioavailability of orally given moxidectin in dogs is nearly total (90.2 ± 7.4%), and is not enhanced by lipid co-administration. The clearance, the volume of distribution, the mean residence time and the terminal half-life were similar to what was already described for other species. Finally our trial suggests that the body condition (degree of obesity) is likely to be a major determinant of moxidectin kinetics in dogs because of its modulation of the volume of distribution that indirectly controls the terminal half-life of the drug. [source] Effect of tepoxalin on renal function in healthy dogs receiving an angiotensin-converting enzyme inhibitorJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2005M. FUSELLIER The objective of this study was to investigate renal function in clinically normal dogs receiving tepoxalin, a nonsteroidal inflammatory drug, either in association with or without an angiotensin-converting enzyme inhibitor (ACEI). Ten adult female Beagle dogs were used in the three phases of the study. The dogs were administered the drugs once daily for 7 days (experiment 1: placebo/tepoxalin/tepoxalin and benazepril; experiment 2: enalapril/tepoxalin and enalapril) or for 28 days (experiment 3: tepoxalin and benazepril together). Renal function was assessed by measurement of glomerular filtration rate (GFR) by renal scintigraphy [(renal uptake of 99mTc-diethylenetriaminepentacetic acid (DTPA)] and plasma clearance of 99mTc-DTPA. Compared with the placebo group, renal uptake and plasma clearance of 99mTc-DTPA were not significantly modified after a 7-day period of treatment with tepoxalin or enalapril alone, tepoxalin and benazepril or tepoxalin and enalapril together. No significant change was obtained in GFR after a 28-day period of dosing with tepoxalin and benazepril together. Therefore, it was concluded that tepoxalin did not alter renal function in healthy Beagle dogs receiving ACEI. [source] Variable absorption of clavulanic acid after an oral dose of 25 mg/kg of Clavubactin® and Synulox® in healthy dogsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2003T. B. Vree The aims of this investigation were to calculate the pharmacokinetic parameters and to identify parameters, based on individual plasma concentration,time curves of amoxicillin and clavulanic acid in dogs, that may govern the observed differences in absorption of both drugs. The evaluation was based on the data from plasma concentration,time curves obtained following a single dose in an open, randomized, two-way crossover study involving 24 male Beagle dogs treated with two Amoxi,Clav formulations (A Clavubactin® and B Synulox®, each with 200/50 mg). Plasma amoxicillin and clavulanic acid concentrations were determined using validated bioassay methods. The half-life of elimination of amoxicillin was 1.5 h (t1/2 = 1.52 ± 0.19 h, Cmax = 11.4 ± 2.74 ,g/mL), and that of clavulanic acid 0.76 h (t1/2 = 0.71 ± 0.23 h, Cmax = 2.06 ± 1.05 ,g/mL). There was a fivefold variation in the AUCt of clavulanic acid for both formulations, while the AUCt of amoxicillin varied by a factor of 2. The mean ratio of the AUCt amoxicillin : clavulanic acid was 12.7 ± 3.65 for formulation A and 11.8 ± 5.22 for formulation B (P = 0.51). [source] Pharmacokinetics of ibafloxacin following intravenous and oral administration to healthy Beagle dogsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2002M. COULET The pharmacokinetics of ibafloxacin, a new veterinary fluoroquinolone antimicrobial agent, was studied following intravenous (i.v.) and oral administration to healthy dogs. The mean absolute bioavailability of ibafloxacin after oral doses of 7.5, 15 and 30 mg/kg ranged from 69 to 81%, indicating that ibafloxacin was well absorbed by dogs. Ibafloxacin was also absorbed rapidly [time of maximum concentration (tmax) 1.5 h], reaching a mean maximum concentration (Cmax) of 6 ,g/mL at 15 mg/kg, well distributed in the body [large volume of distribution at steady state (Vss) and Varea of 1.1 L/kg and 4 L/kg, respectively], and exhibited an elimination half-life of 5.2 h and a low total body clearance (8.7 mL/min/kg). Both Cmax and area under the concentration,time curve (AUC) showed dose proportionality over the dose range tested (7.5,30 mg/kg). The pharmacokinetics of ibafloxacin was similar following single and repeated dosage regimens, implying no significant accumulation in plasma. Food promoted the absorption of ibafloxacin by increasing Cmax and AUC, but did not change tmax. High amounts of the metabolites, mainly 8-hydroxy- and, 7-hydroxy-ibafloxacin were excreted in urine and faeces, either unchanged or as glucuronide conjugates. Following oral administration of 15 mg ibafloxacin/kg, the total recovery of ibafloxacin, its metabolites and conjugates in urine and faeces was 61.9,99.9% of the dose within 48 h. [source] Comparative serum pharmacokinetics of the fluoroquinolones enrofloxacin, difloxacin, marbofloxacin, and orbifloxacin in dogs after single oral administrationJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2002E. HEINEN The pharmacokinetics after oral application of the fluoroquinolones (FQs), enrofloxacin, difloxacin, marbofloxacin and orbifloxacin were compared in independent crossover studies in Beagle dogs. Commercially available tablet formulations were given at common dosage recommended by the manufacturers which were 2.0 mg/kg body weight (bw) for marbofloxacin, 2.5 mg/kg bw for orbifloxacin and 5.0 mg/kg bw for enrofloxacin and difloxacin. Analysis was performed by an agar diffusion assay. Pharmacokinetic parameters were calculated by noncompartmental methods. All FQs were rapidly absorbed and achieved average peak serum concentrations of 1.41, 1.11, 1.47 and 1.37 ,g/mL for enrofloxacin, difloxacin, marbofloxacin and orbifloxacin, respectively. Enrofloxacin was eliminated at a terminal half-life (t½) of 4.1 h, difloxacin at 6.9 h, orbifloxacin at 7.1 h and marbofloxacin at 9.1 h. While the area under the serum concentration,time curve of the 24-h dosing interval (AUC0,24) for marbofloxacin and orbifloxacin were similar (approximately 13 ,g · h/mL), enrofloxacin attained an AUC0,24 of 8.7 and difloxacin of 9.3 ,g · h/mL. Because of its favourable pharmacokinetics combined with excellent in vitro activity, enrofloxacin exhibited superior pharmacodynamic predictors of in vivo antimicrobial activity as Cmax/MIC (maximum serum concentration/minimum inhibitory concentration) and AUC0,24/MIC (area under the 24-h serum concentration,time curve/minimum inhibitory concentration) compared with other FQs. [source] Evolution of blood parameters during weight loss in experimental obese Beagle dogsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2004M. Diez Summary The effects of weight loss on hormonal and biochemical blood parameters were measured monthly [carnitine, creatinine, urea, free T4 (fT4), total T4 (TT4), plasma alkaline phosphatases (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), potassium and total proteins] or bimonthly [cholesterol, triglycerides, non-esterified fatty acids (NEFA), insulin-like growth factor I (IGF-I), glucose, insulin] in eight obese Beagles dogs fed either a high protein dry diet, DP (crude protein 47.5%, on dry matter basis) or a commercial high fibre diet, HF (crude protein 23.8%, crude fibre 23.3%). The dogs were allotted to two groups according to sex and body weight (BW) and they were respectively fed with the DP or the control HF diet during 12,26 weeks, until they reach their optimal BW. The plasma basal triglycerides and cholesterol concentrations were decreased by the two diets but the difference was only significant for the DP diet. The plasma mean NEFA concentration increased regularly over the period with the HF diet, without significant difference between the two diets. No effect of diet or weight loss was observed on plasma carnitine, urea, creatinine, ALP, AST, ALT, potassium, TT4, FT4, IGF-I, glucose and insulin. Weight loss induced a decrease in fT4 plasma concentration (p < 0.001). The high protein diet allowed a safe weight loss. [source] Temporal kinetics and concentration,response relationships for induction of CYP1A, CYP2B, and CYP3A in primary cultures of beagle dog hepatocytesJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2006Richard A. Graham Abstract Compared to other species, little information is available on the xenobiotic-induced regulation of cytochrome P450 enzymes in the beagle dog. Dogs are widely used in the pharmaceutical industry for many study types, including those that will impact decisions on compound progression. The purpose of this study was (1) to determine the temporal kinetics of drug-induced changes in canine CYP1A, CYP2B, and CYP3A mRNA and enzymatic activity, and (2) to characterize concentration,response relationships for CYP1A2, CYP2B11, and CYP3A12 using primary cultures of canine hepatocytes treated with ,-naphthoflavone (BNF), phenobarbital (PB), and rifampin (RIF), respectively. CYP1A1 and CYP1A2 mRNA exhibited maximal expression (12,700-fold and 206-fold, respectively) after 36 h of treatment with BNF. PB treatment, but not RIF treatment, caused maximal induction of CYP2B11 mRNA (149-fold) after 48 h of treatment. CYP3A12 and CYP3A26 mRNA levels were increased maximally after 72 h of treatment with PB and RIF (CYP3A12, 35-fold and 18-fold, and CYP3A26, 72-fold and 22-fold with PB and RIF treatment, respectively). Concentration,response relationships for BNF induced 7-ethoxyresorufin O -dealkylation (EROD) (EC50 = 7.8 ± 4.2 ,M), PB induced 7-benzyloxyresorufin O -dealkylation (BROD) (EC50 = 123 ± 30 ,M), and PB and RIF induced testosterone 6,-hydroxylation (EC50 = 132 ± 28 ,M and 0.98 ± 0.16 ,M) resembled the relationship for human CYP induction compared to that of rodent. Interestingly, RIF had no effect on CYP2B11 expression, which represents a species difference overlooked in previous investigations. Overall, the induction of dog CYP1A, CYP2B, and CYP3A exhibits characteristics that are intermediate to those of rodent and human. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:69,78, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20118 [source] Hard tissue alterations after socket preservation with additional buccal overbuilding: a study in the beagle dogJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2009Stefan Fickl Abstract Objectives: The aim of this study was to histometrically assess alterations of the ridge following socket preservation alone and socket preservation with additional buccal overbuilding. Material and Methods: In five beagle dogs four extraction sites were randomly subjected to one of the following treatments: Tx 1: The socket was filled with BioOss Collagen® and covered with a free gingival graft from the palate. Tx 2: The buccal bone plate was augmented using the GBR-technique, the socket was filled with BioOss Collagen® and covered with a free gingival graft. Tx 3: The buccal bone plate was forced into a buccal direction using a manual bone spreader. The socket was filled with BioOss Collagen® and covered with a free gingival graft from the palate. Tx 4: The socket was filled with BioOss Collagen® and a combined free gingival/connective tissue graft was used to cover the socket and for buccal tissue augmentation. For each experimental site, two histological sections were subjected to histometric analysis and evaluated for (i) vertical bone dimensions and (ii) horizontal bone dimensions. Results: All treatment groups showed horizontal and vertical bone loss. The mean vertical bone loss of the buccal bone plate was significantly lower in Tx 4 than in the other groups, while no statistical significant differences could be detected among the groups in the horizontal dimension. Conclusion: Overbuilding the buccal aspect in combination with socket preservation does not seem to be a suitable technique to compensate for the alterations after tooth extraction. [source] Early healing of implants placed into fresh extraction sockets: an experimental study in the beagle dog.JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 3 2009De novo bone formation Abstract Objectives: Describe the early phases of tissue integration in implants placed into fresh extraction sockets and test whether a new implant surface nano-topography (DCD nano-particles, NanotiteÔ) promotes early osseointegration when compared with minimally rough surface implants (DAE, Osseotite®). Material and Methods: Sixteen beagle dogs received 64 test and control implants randomly installed into the distal socket of 3P3 and 4P4. Histomorphometric analysis of bone to implant contact (BIC) and bone area was performed at 4 h, 1, 2, 4 and 8 weeks. Results: Wound healing initiated with a coagulum that was substituted by a provisional matrix at 1 week. Bone formation started concomitant to a marked bone resorption. At 2 weeks, woven bone formation was evident and gradually remodelled into lamellar bone at 4 and 8 weeks. BIC increased similarly throughout the study in both groups with a tendency to higher percentages for the test devices at 2 and 4 weeks. The influence of the DCD nano-particles was more evident at the fourth premolar site. Conclusion: Osseointegration occurred similarly at both implant groups, although the socket dimension appeared to influence bone healing. It is suggested that the enhanced nano-topography has a limited effect in the immediate implant surgical protocol. [source] Tissue alterations after tooth extraction with and without surgical trauma: a volumetric study in the beagle dogJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2008Stefan Fickl Abstract Objectives: The aim of this study is to evaluate whether tooth extraction without the elevation of a muco-periosteal flap has advantageous effects on the resorption rate after tooth extraction. Material and Methods: In five beagle dogs polyether impressions were taken before the surgery. The roots of the first and second pre-molars (P1 and P2) were extracted and the sites were assigned to one of the following treatments: treatment group (Tx) 1, no treatment; Tx 2, surgical trauma (flap elevation and repositioning); Tx 3, the extraction socket was filled with BioOss Collagen® and closed with a free soft-tissue graft; Tx 4, after flap elevation and repositioning, the extraction socket was treated with BioOss Collagen® and a free soft-tissue graft. Impressions were taken 2 and 4 months after surgery. The casts were scanned, matched together with baseline casts and evaluated with digital image analysis. Results: The "flapless groups" demonstrated significant lower resorption rates both when using socket-preservation techniques and without. Furthermore, socket-preservation techniques yielded better results compared with not treating the socket. Conclusion: The results demonstrate that leaving the periosteum in place decreases the resorption rate of the extraction socket. Furthermore, the treatment of the extraction socket with BioOss Collagen® and a free gingival graft seems beneficial in limiting the resorption process after tooth extraction. [source] Preclinical experiment of auxiliary partial orthotopic liver transplantation as a curative treatment for hemophiliaLIVER TRANSPLANTATION, Issue 5 2005Saiho Ko The cause of hemophilia is deficiency of coagulation factor VIII production in the liver, which can be cured by liver transplantation. Because the hepatic function of hemophilia patients is quite normal except for production of factor VIII, auxiliary partial orthotopic liver transplantation (APOLT) is beneficial in that patient survival is secured by preserving native liver even in the event of graft loss. However, it is not known whether the graft of APOLT would be enough to cure hemophilia. We evaluated the efficacy and feasibility of APOLT for hemophilia in a canine hemophilia A model that we established. Partial left liver graft was taken from the normal donor (blood factor VIII activity > 60%). The graft was transplanted to the hemophilia beagle dog (blood factor VIII activity < 5%) after resection of the left lobe preserving native right lobe. Changes in time of blood factor VIII activity and liver function parameters were observed after APOLT. APOLT and perioperative hemostatic management were successfully performed. The blood factor VIII activity increased to 30% after APOLT, and was sustained at least 6 weeks throughout the observation period without symptoms of bleeding. The result demonstrated sustained production of factor VIII in the hemophilia recipient after APOLT. Transplantation of approximately one third of whole liver resulted in cure of hemophilia. In conclusion, it is suggested that APOLT would be feasible as a curative treatment of hemophilia A to improve quality of life of the patients. (Liver Transpl 2005;11:579,584.) [source] Comparative study of PSMA expression in the prostate of mouse, dog, monkey, and human,THE PROSTATE, Issue 9 2006Saurabh Aggarwal Abstract BACKGROUND Intraprostatic PSMA targeted prodrugs/protoxins are under development in our laboratory. Future toxicologic studies of these therapies require identification of animal models that express PSMA within the prostate. METHOD PSMA enzymatic activity and protein expression was determined. PSMA expression in the prostates of mouse, dog, and monkey were compared to humans by real-time PCR analysis. RESULTS No substrate hydrolysis was observed in dog or monkey prostate homogenates. Monkey prostate was negative for PSMA protein expression. No significant PSMA mRNA levels were detected by real time PCR in mouse, dog, or monkey prostate tissue compared to PSMA negative tissues. CONCLUSIONS PSMA is not expressed in any significant amount in the prostates of mouse, beagle dog, or macaque monkeys in this study but is expressed in high levels by human prostate. These non-human species, therefore, are not suitable toxicologic models to assess prostate damage from PSMA-activated intraprostatic prodrug/protoxin therapies. Prostate 66: 903,910, 2006. © 2006 Wiley-Liss, Inc. [source] Development of a New Tissue-Engineered Sheet for Reconstruction of the StomachARTIFICIAL ORGANS, Issue 10 2009Masato Araki Abstract We have developed tissue-engineered digestive tracts composed of collagen scaffold and an inner silicon sheet and successfully used it to repair defects in parts of the esophagus, stomach, and small intestine. However, some improvements were demanded for clinical usage because the silicon sheet presented technical difficulties for suturing and endoscopic removal. New tissue-engineered sheet (New-sheet) was composed of a single-piece and reinforced collagen scaffold with biodegradable copolymer. One beagle dog was used to evaluate whether New-sheet could withstand suturing in comparison with native digestive tracts using a tensile tester. Seven beagle dogs had a 5-cm circular defect created in the stomach. New-sheet soaked with autologous peripheral blood or bone marrow aspirate was sutured to the gastric wall. Endoscopic, histological, and immunohistochemical assessment was performed to evaluate regeneration of the stomach up to 16 weeks. Tensile strength testing showed that the mucosal side of New-sheet had strength almost equivalent to the mucosa of the esophagus (P = 0.61). Endoscopically, regeneration of the mucosa started from the circumference after 4 weeks, but a small linear ulcer was still evident at 16 weeks. The regenerated stomach shrank by 60,80% of its original size and histologically showed villous mucosa and underlying dense connective tissue. Immunohistochemically, the regenerated area expressed ,-smooth-muscle actin but was negative for basic calponin, irrespective of the source of soaked blood. New-sheet shows sufficient strength for suturing, no dehiscence, and better biocompatibility for clinical use, although further examination will be necessary to create a functional digestive tract. [source] Liquid chromatography,mass spectrometry for analysis of a novel ,2 -adrenoceptor agonist trantinterol and its metabolites in beagle dog urineBIOMEDICAL CHROMATOGRAPHY, Issue 3 2010Yanjuan Wang Abstract A liquid chromatography,tandem mass spectrometry method was developed for the identification of metabolites of trantinterol, a novel ,2 -adrenoceptor agonist, in beagle dog urine. The separation of metabolites was performed on a reversed-phase C8 column using 0.1% formic acid in water and methanol (70 : 30, v/v) as the mobile phase. The structural information and elemental information of metabolites were acquired by an electrospray ionization tandem mass spectrometer and a quadrupole time-of-flight mass spectrometer, respectively. A total of 13 metabolites were detected and characterized on the basis of their tandem MS/MS fragmentation patterns. The accurate masses of nine metabolites were determined and two metabolites were further confirmed by comparing with reference standards. The metabolic pathways of trantinterol in beagle dog are proposed. Copyright © 2009 John Wiley & Sons, Ltd. [source] Nonclinical pharmacokinetics of BMS-292655, a water-soluble prodrug of the antifungal ravuconazoleBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2008Jay O. Knipe Abstract The phosphate ester, BMS-292655, was developed as a water-soluble prodrug of the antifungal agent, ravuconazole (BMS-207147). BMS-292655 was comparatively stable in rat, beagle dog, cynomolgus monkey and human plasma, but was hydrolysed upon incubation with liver S9 preparations from all species. The major product in rat, monkey and human S9 was BMS-207147, while in dog S9, the intermediate ester, BMS-300043, predominated. BMS-300043 itself was more stable in dog S9 than in S9 preparations from the other species. Intravenous administration of BMS-292655 to rats, beagle dogs and cynomolgus monkeys indicated species differences in the extent of formation of BMS-207147 (monkeys>rats>dogs). The lower overall generation of BMS-207147 in dogs was consistent with the presence of circulating plasma levels of BMS-300043. BMS-300043 was present in monkey plasma but not detectable in rat plasma. The conversion of BMS-292655 to BMS-207147 in the presence of human S9 indicated the potential for BMS-292655 to function as a BMS-207147 prodrug in humans. The similarity in the hydrolysis of BMS-292655 when incubated with human and monkey S9 in vitro, coupled with the effective release of BMS-207147 from BMS-292655 upon i.v. administration to monkeys, is consistent with this conclusion. Copyright © 2008 John Wiley & Sons, Ltd. [source] Metabolism of high density lipoprotein apolipoprotein A-I and cholesteryl ester in insulin resistant dog: a stable isotope studyDIABETES OBESITY & METABOLISM, Issue 1 2007F. Briand Aims:, In reverse cholesterol transport (RCT), hepatic Scavenger Receptor class B type I (SR-BI) plays an important role by mediating the selective uptake of high-density lipoprotein cholesteryl ester (HDL-CE). However, little is known about this antiatherogenic mechanism in insulin resistance. HDL-CE selective uptake represents the main process for HDL-CE turnover in dog, a species lacking cholesteryl ester transfer protein activity. We therefore investigate the effects of diet induced insulin resistance on RCT. Methods:, Five beagle dogs, in healthy and insulin resistant states, underwent a primed constant infusion of [1,213C2]acetate and [5,5,5- 2H3]leucine, as labelled precursors of CE and apolipoprotein (apo) A-I, respectively. Data were analysed using modelling methods. Results:, HDL-apo A-I concentration did not change in insulin resistant state but apo A-I absolute production rate (APR) and fractional catabolic rate (FCR) were both higher (2.2- and 2.4-fold, respectively, p < 0.05). HDL-CE levels were lower (1.2-fold, p < 0.05). HDL-CE APR and FCR were both lower (2.3- and 2-fold, respectively, p < 0.05), as well as selective uptake (2.6-fold, p < 0.05). Conclusions:, Lower HDL-CE selective uptake suggests that RCT is impaired in obese insulin resistant dog. [source] Pharmacodynamics and pharmacokinetics of YM128, a GPIIb/IIIa antagonist prodrugDRUG DEVELOPMENT RESEARCH, Issue 3 2002Ken-ichi Suzuki Abstract We examined the biochemical properties of YM-57029 ({4-[4-(4-Carbamimidoylphenyl)-3-oxopiperazin-1-yl]piperidino}acetic acid monohydrochloride trihydrate) and the pharmacodynamics and pharmacokinetics of its prodrug, YM128 (Ethyl (Z)-(4-{4-[4-(N2 -hydroxycarbamimidoyl)phenyl]-3-oxopiperazin-1-yl}piperidino)acetate), an orally-active glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist. YM-57029 strongly inhibited aggregation of human platelets induced by various agonists, with IC50 values ranging from 3.6 to 51 nM. YM-57029 specifically inhibited fibrinogen binding to purified GPIIb/IIIa about 1,000-fold more potently than Arg-Gly-Asp-Ser (RGDS). Moreover, YM-57029 effectively inhibited an Arg-Gly-Asp (RGD) peptide binding to platelets, suggesting that YM-57029 competed with the RGD sequence of ligand. YM-57029 or YM128 dose-dependently inhibited ex vivo platelet aggregation after iv bolus injection or oral administration to beagle dogs and cynomolgus monkeys. However, YM128 exerted more potent and prolonged inhibitory effects on platelet aggregation than YM-57029 after oral administration to cynomolgus monkeys. Furthermore, YM-57029 prolonged template bleeding time at a dose that inhibited ex vivo platelet aggregation during cumulative iv infusion to cynomolgus monkeys. Metabolic and pharmacokinetic studies showed that YM128 effectively converted into YM-57029 in liver microsomes from humans as well as dogs and monkeys, and that bioavailabilities of YM128 in dogs and monkeys were 32.3 and 22.2%, respectively. These results suggest that YM128, a prodrug of YM-57029, may be a valuable GPIIb/IIIa antagonist with good bioavailability in humans. Drug Dev. Res. 55:149,161, 2002. © 2002 Wiley-Liss, Inc. [source] Adhesive, Flexible, and Robust Polysaccharide Nanosheets Integrated for Tissue-Defect RepairADVANCED FUNCTIONAL MATERIALS, Issue 16 2009Toshinori Fujie Abstract Recent developments in nanotechnology have led to a method for producing free-standing polymer nanosheets as a macromolecular organization. Compared with bulk films, the large aspect ratio of such nanosheets leads to unique physical properties, such as transparency, noncovalent adhesion, and high flexibility. Here, a biomedical application of polymer nanosheets consisting of biocompatible and biodegradable polysaccharides is reported. Micro-scratch and bulge tests indicate that the nanosheets with a thickness of tens of nanometers have sufficient physical adhesiveness and mechanical strength for clinical use. A nanosheet of 75,nm thickness, a critical load of 9.1,×,104,N m,1, and an elastic modulus of 9.6,GPa is used for the minimally invasive repair of a visceral pleural defect in beagle dogs without any pleural adhesion caused by wound repair. For the first time, clinical benefits of sheet-type nano-biomaterials based on molecular organization are demonstrated, suggesting that novel therapeutic tools for overlapping tissue wounds will be possible without the need for conventional surgical interventions. [source] One-year dog toxicity study of D-002, a mixture of aliphatic alcoholsJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2001Celia Alemán Abstract D-002 is a mixture of high-molecular-weight aliphatic alcohols, obtained from bees wax (Apis mellifera), with mild anti-inflammatory properties and effective anti-ulcer activities demonstrated in experimental models. This study investigated the oral toxicity of D-002 administered for 1 year to beagle dogs. Twenty-four beagle dogs (12 males and 12 females) were distributed randomly in three experimental groups (four animals per group): a control and two treated groups received D-002 at 50 and 250 mg kg,1 (7 days/week) by gastric gavage. Overall, D-002 was well tolerated throughout the study. No signs or symptoms of toxicity were observed, and no mortality occurred during the study. All groups showed similar weight gain and food consumption. No hematological, blood biochemical or histopathological disturbances attributable to treatment were observed. This study shows no drug-related toxicity induced by long-term administration of up to 250 mg kg,1 D-002 to beagle dogs. Copyright © 2001 John Wiley & Sons, Ltd. [source] In vitro change in mechanical strength of ,-tricalcium phosphate/copolymerized poly- L -lactide composites and their application for guided bone regenerationJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2002Masanori Kikuchi Abstract Novel composites of bioactive ,-tricalcium phosphate [Ca3(PO4)2] and biodegradable copolymerized poly- L -lactide (CPLA) were prepared by a heat-kneading method. The mechanical and chemical changes of the composites were evaluated in vitro by soaking in physiological saline and Dulbecco's phosphate buffered saline. When soaked in physiological saline, the 3-point mechanical strength decreased rapidly from 60 to 30 MPa in the initial 4 weeks and then gradually reached a plateau; the initial decrease in the mechanical strength was ascribed to the dissolution of ,-tricalcium phosphate from the surface. The mechanical properties evident at 8,12 weeks were sufficient for the composites to be used as a biodegradable material for regeneration of bone because the hydrolysis of CPLA was inhibited in both physiological saline and phosphate-buffered saline as a result of a pH-buffering effect. Composite membranes 250-,m thick were used to regenerate large bone defects in beagle dogs: 10 × 10 × 10 mm3 in volume in the mandible and 20 mm in length in the tibia. The afflicted areas covered with the composite membranes were almost perfectly filled with new bone 12 weeks after the operation, whereas those covered with a CPLA membrane or without any membranes were invaded by soft tissue. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 265,272, 2002 [source] | ||||||||||||||||||||||||||||||||||||||||