Beagle犬灌胃厄多司坦盐酸氨溴索混合物的急性和亚慢性毒性研究

目的 观察Beagle犬给予厄多司坦盐酸氨溴索混合物后出现的急性和亚慢性毒性反应,为临床安全用药剂量的设计和毒副反应监测提供参考.方法 选用Beagle犬进行急性和13周亚慢性毒性试验.急性试验中,设置厄多司坦盐酸氨溴索混合物剂量组(5.04 g/kg)、厄多司坦组(4.80 g/kg)、盐酸氨溴索组(0.24 g/k...     

注射用紫杉醇脂肪乳和普通紫杉醇注射液在比格犬体内的药动学比较

目的:建立测定比格犬血浆中紫杉醇浓度的方法,并将其应用于比格犬体内注射用紫杉醇脂肪乳和普通紫杉醇注射液的药动学比较研究。方法:将注射用紫杉醇脂肪乳和普通紫杉醇注射液静脉给药1.5mg/kg后,测定比格犬血浆中的药物浓度,估算并比较药动学数据。血浆样品及内标多西他赛置于96孔板中,进行高通量的液液萃取。结果:紫杉醇的线性范围为2～500ng/ml,最低定量下限为2ng/ml,批内、批间精密度(RSD%)均<15%。分别静脉注射两种制剂后,在比格犬血浆中,紫杉醇的t1/2分别为(4.72±0.53)和(4.50±0.81)h,MRT为(2.46±0.38)和(1.82±0.59)h,AUC0～12h为(388.90±63.39)和(711.74±33.70)ng.h.ml-1,AUC0～∞为(411.89±68.44)和(738.35±45.54)ng.h.ml-1,CL为(3.71±0.46)和(2.04±0.11)L.h-1.kg-1,Vd为(9.07±1.35)和(3.65±0.91)L/kg。结论:该方法灵敏、准确、专一、简便并且实现高通量分析,适用于注射用紫杉醇脂肪乳和普通紫杉醇注射液在比格犬体内的药动学比较研究。两种制剂的主要药动学参数中c0、AUC、CL、Vd存在显著性差异(P<0.05),用梯形面积法(AUC)估算紫杉醇脂肪乳对于紫杉醇普通制剂的相对生物利用度为(54.93±10.82)%。     

Tissue reactions to sutures in the presence and absence of anti-infective therapy

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.     

Periodontal repair in dogs: evaluation of the natural disease model

Abstract Animal models are frequently consulted for histometric analysis of periodontal reconstructive therapy. Such models include surgical, periodontitis-simulating and natural disease defects in canines or non-human primates. Our studies suggest that homogeneity in defect height is critical for sensitivity of surgical and periodontitis-simulating supraalveolar defect models in discriminating treatment effects. We herein evaluate this model aspect for natural disease defects. Buccal-lingual histologic sections from the 2nd, 3rd, and 4th mandibular premolar teeth (P2, P3, P4) from 6 aged beagle dogs with advanced natural periodontal disease were used. Defect heights from the reduced alveolar bone to the cemento-enamel junction were recorded in central step-serial sections at the buccal and lingual surfaces of the mesial and distal roots for the premolar teeth. Mean defect height, standard deviation and coefficient of variation were calculated for tooth types and jaw quadrants, separately, and for all teeth. Confidence intervals were calculated for teeth in left and right jaw quadrants. Mean defect height and standard deviation for left and right jaw quadrants was 3.6±0.9 and 3.3±0.6 mm for P2. 3.3±.9 and 2.3±0.9 mm for P3, and 3.3±1.0 and 4.5±1.6 mm for P4. respectively. Coefficient of variation for defects for left and right jaw quadrants was 26 and 40%, respectively. Using confidence intervals for mean differences between jaw quadrants, it was determined that a mean treatment effect may be as large as 0.8, 1.1 and 1.9 mm for P2. P3 and P4, respectively, before being detected as statistically significant (p≤0.05, N=6). With the apparent variation in defect baseline, it is suggested that natural disease defects have limited potential in discriminating treatment effects following periodontal reconstructive therapy.     

Dental pulp exposed to the CO2 laser beam

Traumatic inflammation due to application of CO2 laser beam on teeth (dentin and pulp) of Beagle dogs and Macaca Monkeys, stimulate in dentino-pulpal tissue morphological phenomena studied after 5 days, 1, and 3 months by microscopy and microradiography. After a dentin exposure to a density of energy from 2 X 10(3) J/cm2, the first cell layers of the pulp tissue show a rarefaction and a cellular degeneration, followed by a neoformation of calcified dentin, of about 300 microns thick in 3 months, due to the excitation of odontoblasts or produced by pulpal cells functioning before. A density of energy of 10(3) J/cm2 order applied to the pulp beads to its partial necrosis, to various inflammatory aspects and to a quasi-constant regeneration by a neo-dentin bridge of 200 microns at 1 month. The analysis of cell activity seems able to be investigated from this method.     

蒿甲醚肌注对beagle犬外用血淋巴细胞的影响

本文用细胞化学方法研究了im蒿甲醚对beagle犬外周血T,B,T_μ及T_γ淋巴细胞的作用。im6,19及32 mg/(kg·d)(MKD)蒿甲醚。连续7d后32MKD组出现明显的T,B及T_μ淋巴细胞下降;连续15d则可使19和32MKD组T,B及T_μ淋巴细胞显著降低,3个剂量组的T_γ淋巴细胞皆降低至零;停药28d后3个剂量组的T,T_μ及T_γ淋巴细胞皆恢复至对照组水平,而19及32 MKD组B淋巴细胞仍明显低于对照组。     

Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs

Several growth factors (or cytokines) have been recently investigated for their use as potential therapeutics for periodontal tissue regeneration. The objective of this study was to evaluate periodontal tissue regeneration, including new bone and cementum formation, following topical application of recombinant basic fibroblast growth factor (bFGF, FGF-2) to furcation class II defects. Twelve furcation class II bone defects were surgically created in six beagle dogs, then recombinant bFGF (30 micro g/site) + gelatinous carrier was topically applied to the bony defects. Six weeks after application, periodontal regeneration was analyzed. In all sites where bFGF was applied, periodontal ligament formation with new cementum deposits and new bone formation was observed histomorphometrically, in amounts greater than in the control sites. Basic FGF-applied sites exhibited significant regeneration as represented by the new bone formation rate (NBR) (83.6 +/- 14.3%), new trabecular bone formation rate (NTBR) (44.1 +/- 9.5%), and new cementum formation rate (NCR) (97.0 +/- 7.5%). In contrast, in the carrier-only sites, the NBR, NTBR, and NCR were 35.4 +/- 8.9%, 16.6 +/- 6.2%, and 37.2 +/- 15.1%, respectively. Moreover, no instances of epithelial down growth, ankylosis, or root resorption were observed in the bFGF-applied sites examined. The present results indicate that topical application of bFGF can enhance considerable periodontal regeneration in artificially created furcation class II bone defects of beagle dogs.     

再生的牙周组织在正畸压应力下破骨相关因子表达的研究

目的 研究应用改良的双相磷酸钙(biaphasic calcium phosphate,BCP)复合骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)行犬牙周组织再生后,对再生的牙周组织施加正畸压应力,比较与健康牙周组织受力后破骨相关因子表达的异同,从而探讨牙周再生后进行正畸牙移动的可行性。方法 取6只成年雄性比格犬,拔除其双侧上下颌第一前磨牙,随机分为1周组、2周组和4周组,每组2只犬,实验组于每只犬右上、左下象限第二前磨牙牙根的近中侧制造牙周缺损,并将体外培养的犬BMSCs与BCP的共培物植入缺损区,牙周再生20周后施加正畸力,以1.47 N左右的力值拉第二前磨牙向近中方向移动;以自身为对照,另两象限交替作为牙周再生术后加力0周组和空白对照组。分别于加力1周、2周及4周后处死2只比格犬并取组织块。通过Real-Time PCR及Western-Blot印迹法检测破骨相关因子活化T细胞转化因子-1（NFATc-1）和组织蛋白酶K（Cath-K）的表达。结果 实验组NFATc-1和Cath-K的mRNA和蛋白表达趋势一致:从0周到2周呈上升趋势,2周至4周下降,但仍高于0周时;实验组与对照组阳性表达情况无明显差异（P>0.05)。结论 再生的牙周组织中破骨细胞相关因子的表达情况及变化趋势与正常牙周组织相似,应用改良的BCP用于牙周组织缺损的再生及再生后的正畸牙移动是可行的。     

THEOPHYLLINE CONTROLLED-RELEASE FORMULATIONS: IN VIVO--IN VITRO CORRELATIONS

Four experimental controlled-release oral solid dosage formulations were developed and the in vitro dissolution characteristics of theophylline from these formulations were studied in USP apparatus I. Pharmacokinetic evaluation of these formulations was carried out in eight beagle dogs under fasting conditions. Theophylline in a 5% dextrose injection USP, oral solution, and Slo-Phyllin® were used as controls to estimate the in vivo dissolution of these four formulations in the GI tract. The percentage cumulative amounts of drug absorbed and the percentage cumulative amounts of drug released into the GI tract from these four controlled-release formulations were obtained by numerical deconvolution methods. The in vivo and in vitro dissolution data demonstrated good correlation indicating that in vitro dissolution tests can be used to optimize the further design of controlled drug release oral solid dosage formulations for theophylline.     

模拟灾害搜救条件下禁水禁食比格犬主要生命体征变化规律研究

本文旨在通过研究禁水禁食条件下比格犬的生命体征变化规律及特点,为灾后受困人员生命状态非接触识别技术研究提供基础,以便搜救人员提前探测并掌握受困人员生命状态和伤情进而开展科学施救.实验对比分析了禁水禁食条件下两只比格犬在呼吸率、心率、体温、体重方面的变化趋势,发现了呼吸、心跳等生理信号在不同时期的变化具有一定规律,中后期...