去势比格犬腹部脂肪与相关血清学指标及骨密度的变化关系

目的通过建立去势比格犬模型,观察绝经早期腹部脂肪变化规律,并通过对脂肪与骨代谢相关血清学指标的测量与分析,探讨脂肪及骨代谢的关键影响因素。方法选取6只成年雌性比格犬进行去势术,分别在术前、术后4个月、6个月、10个月进行腰椎定量CT(quantatitive computed tomography,QCT)腹部脂肪面积、骨密度(bone mineral density,BMD)、MRI腰椎骨髓脂肪含量及血清学指标的检测,比较不同时间各指标的变化趋势及关系。结果比格犬腹内脂肪面积(visceral fat area,VFA)、皮下脂肪面积(subcutaneous fat area,SFA)、腹部总脂肪面积(total fat area,TFA)在术后6个月、10个月均增加(P0.05),术后10个月VFA增加百分比均值为84.39%,且为三者中最大;术后比格犬BMD并未明显降低。体重、BMD、瘦素(leptin,LP)、VFA、高密度脂蛋白(high-density lipoprotein,HDL)与SFA相关。SFA、体重、低密度脂蛋白(low-density lipoprotein,LDL)、内脏脂肪素(visfatin,VFN)与BMD相关。结论去势比格犬模型可用于研究绝经后雌激素缺乏所引起的脂肪代谢变化,但短期内BMD并未明显丢失,骨、脂肪代谢之间存在交互作用。     

Establishment of a prostatic hyperplasia model with beagle dogs

Objective: To establish a prostatic hyperplasia model with beagle dogs. Methods: Twenty-four male beagle dogs, 2 years of age, were divided into the treatment and control groups at random and were administrated testosterone propionate (TP) i.m. two months after castration. Three treatment groups were set with the doses of TP at 0.8 mg/kg, 2.5 mg/kg and 7.5 mg/kg, respectively, and the control was given the same volume of vehicle. Two months later, half of the animals were killed and sera samples were obtained. The wet weight and volume of prostate were measured. The dihydro testosterone (DHT) level of the serum and prostate were determined with the commercial radioimmunoassay (RIA) kit. The prostate was sectioned, fixed and stained with hematoxylin and eosin. Pictures were taken with a digital camera under the microscope and were analyzed with a computer for the epithelial cell height and the acinar luminal area with micro image analysis software. The prostate volume was measured with ultrasonic diagnost     

Pharmacokinetics of the antitumor antibiotic n-pentyl-sparsomycin in beagle dogs

Summary N-pentyl-sparsomycin (PSm) is a lipophilic analogue of sparsomycin (Sm), which is a well known inhibitor of protein synthesis. This compound was selected for preclinical pharmacokinetic studies because of its high in vitro and in vivo antitumor activity. In this study in which the drug was evaluated in beagle dogs under anaesthesia, the drug concentrations in plasma, urine and bile samples were determined using high performance liquid chromatography (HPLC). Plasma protein binding was approximately 54%. The mean t1/2 was 0.2 hours (12 minutes) and t1/2 was 0.75 ± 0.1 hours (45 ± 6 minutes). During continuous infusions up to 5.25 hours, the steady state was reached in 3 out of 6 experiments, suggesting that in some cases the real t1/2 was longer than measured. PSm was actively reabsorbed from the renal tubuli. This process was saturable at the higher doses. Tubular reabsorption played only a minor role in pharmacokinetics as most of the drug (67%) was eliminated by the non-renal clearance. The non-renal clearance was saturable at higher doses of PSm and was the reason for non-linearity of pharmacokinetics.     

口腔种植体Beagle犬动物模型的建立

目的:以延期和即刻两种方式建立种植体植入Beagle犬下颌骨的动物模型,用以比较研究延期与即刻两种种植方式的种植体周围组织状况差异。方法:选用纯系动物Beagle犬四只,分为两组:延期种植(A组),即刻种植(B组),分别以延期和即刻两种方式将种植体植入Beagle犬下颌骨,并对两种方式植入的种植体进行mPLI、PD、松动度、GI及骨吸收量的比较。结果:种植体植入顺利,种植体植入后均稳固,各项临床检测指标无统计学差异。结论:成功建立延期种植与即刻种植的口腔种植体Beagle犬动物模型,尚不能定论即刻与延期哪种种植方式更好,临床种植方式的选择还需结合临床具体情况,严格控制适应症。     

普萘洛尔致犬急性心衰模型的方法学研究

目的探讨普萘洛尔对比格犬诱导急性心力衰竭模型的可行性。方法静脉推注普萘洛尔诱导急性心力衰竭,静脉滴注普萘洛尔维持心衰,股动脉插管监测血流动力学指标变化,电磁流量计测量心输出量。结果与造模前基础值相比,普萘洛尔造模后心率、动脉收缩压、动脉舒张压、平均动脉压、左室内压下降速度和左室收缩压均下降(P<0.05~0.01),左室舒张末期压上升(P<0.01),左室内压上升速度和心输出量分别下降51.7%、41.1%(P<0.01),达到心衰标准,且上述指标在2 h内保持稳定。结论普萘洛尔建立急性心力衰竭模型稳定可行。     

葛根总黄酮缓释片药动学研究

目的：考察葛根总黄酮缓释片体内缓释效果。方法：建立HPLC法测定葛根素的血药浓度，以市售愈风宁心片、自制葛根总黄酮普通片作为参比制剂，采用比格犬进行了缓释片的药动学研究及体内验证实验。结果：与愈风宁心片、自制葛根总黄酮普通片相比，葛根总黄酮缓释片在体内外具有明显的缓释作用。结论：葛根总黄酮缓释片达到了设计要求。     

丹参葡萄糖注射液对Beagle犬的长期毒性研究

目的　在动物体内验证丹参葡萄糖注射液 (丹参 )临床毒副反应及性质。方法　以丹参 0 .8、2 .0、5 .0 g/(kg·d)对Beagle犬连续静脉缓慢注射 15 0d及 180d ,观察用药期间毒性反应及停药 2 1d期间恢复情况。结果　丹参高剂量组用药 30～ 15 0d、中剂量组 4 5d、135d及 15 0d动物体重增长明显减慢 (P <0 .0 1,P <0 .0 5 ) ;用药期及恢复期各组动物进食量、心电图、血液学、尿液等各项指标均在正常值范围内 ;丹参高剂量组用药 180d ,凝血时间延长 ,高、中剂量组用药 180d ,AST明显升高 ,白蛋白降低 ;高剂量组部分动物有不同程度的肝脂肪变性及肝细胞水肿 ,但停药 2 1d基本恢复正常。结论　丹参高剂量长期应用对Beagle犬肝细胞有一定毒性 ;其无毒反应剂量大约为 2 .0g/ (kg·d)     

Hormonal regulation of cytoplasmic estrogen and progesterone receptors in the beagle uterus and oviduct

The hormonal regulation of uterine and oviductal cytoplasmic estrogen and progesterone receptors was studied in immature beagles that were untreated, treated with estradiol-17β, or treated sequentially with estradiol and progesterone. Estradiol treatment increased the concentration of estrogen receptors in both tissues. Progesterone receptors were not detectable in the reproductive tract of untreated animals, but increased dramatically under the influence of estradiol. Estrogen withdrawal following estrogen stimulation, concomitant estrogen plus progesterone administration, and estrogen withdrawal plus progesterone administration all caused significant reductions in both estrogen and progesterone receptors in uterine and oviductal cytosols when compared to estrogen treatment alone. Estrogen withdrawal resembled estrogen plus progesterone administration in reducing both estrogen and progesterone receptor levels, although estrogen withdrawal plus progesterone administration resulted in a further reduction in both receptor concentrations. The same positive and negative relationships between estrogen and progesterone receptor content were observed in uterine cytosols from cycling and ovariectomized adults. These data suggest that estrogen and progesterone regulate their respective receptors and that tissue sensitivity to both steroids may be controlled by mechanisms involving fluctuations in receptor concentration in the reproductive tract of the beagle.     

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

Background and purpose:

Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.

Experimental approach:

Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).

Key results:

Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K₁ treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.

Conclusions and implications:

Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients.