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。     

亲和吸附材料应用于血液灌流治疗外源性内毒素血症的安全性研究

目的 评估课题组研发的亲和吸附材料特异清除外源性内毒素的安全性。方法 15 只比格犬静脉输注内毒素（Sigma）复制内毒素血症模型,随机分为治疗组（n =10）和对照组（n =5）,治疗组用课题组研发的一次性血液灌流器进行干预,对照组不用该灌流器。实验前后监测生命体征并于灌流开始、灌流60 及120 min 采集血液标本检测生化、血常规和凝血功能。结果 治疗组体温及呼吸在灌流后逐步下降,对照组则上升。灌流开始、灌流120 min 治疗组血小板（PLT）为（222.50±14.19）×109/L、（199.00±18.18）×109/L,对照组为（233.91±12.22）×109/L、（222.07±7.62）×109/L,两组比较,差异有统计学意义（P <0.05）;灌流开始、灌流120 min 治疗组白细胞（WBC）为（7.14±0.10）×109/L、（6.10±0.19）×109/L,对照组为（7.17±0.11）×109/L、（5.52±0.54）×109/L,两组比较,差异有统计学意义（P <0.05）。谷丙转氨酶（ALT）、谷草转氨酶（AST）、碱性磷酸酶（ALP）、总蛋白（TP）、球蛋白（GLO）治疗组灌流120 min与灌流开始比较,均差异有统计学意义（P <0.05）,灌流120 min 均下降;对照组灌流120 min 与灌流开始比较,均差异有统计学意义（P <0.05）,灌流120 min 均上升。尿素（Urea）、肌酐（Cr）、尿酸（UA）治疗组灌流120 min 后呈下降趋势,对照组则轻微上升。结论 该亲和吸附材料清除实验犬血液中的内毒素具有安全性。     

锥形束CT与根尖片对实验性根尖周炎根管治疗结果的评估

目的：???观察一次法根管治疗的短期临床疗效,并比较锥形束CT（CBCT）与根尖片在根管治疗结果评估中的差异。方法??选择4只比格犬的24颗上颌前磨牙（56个根管）为研究对象,所有牙齿形成实验性根尖周炎后,随机分为2组,一组采用一次法根管治疗,另一组采用两次法根管治疗,术后6个月应用CBCT和根尖片评估根管治疗疗效。结果 CBCT显示：一次法根管治疗成功率为28.57%,二次法根管治疗成功率为53.57%,两组间的成功率差异无统计学意义（P=0.057）。根尖片显示：一次法根管治疗成功率为67.86%,二次法成功率为78.57%,两组间差别无统计学意义（P=0.365）。CBCT显示的根管治疗总成功率为41.07%,根尖片显示的总成功率为73.21%, CBCT与根尖片在根管治疗后疗效评估中的差异有统计学意义（P=0.001）。结论??在针对实验性根尖周炎的治疗中,一次法根管治疗的近期治愈率与两次法根管治疗的近期治愈率相比较,其差异无统计学意义;然而,CBCT与根尖片的检查结果,在根管治疗后的疗效评估上,存在着一定差异。由此可见,CBCT这种三维检查手段相较于根尖片的二维影像来说,在根管治疗后对疾病的诊断评估中的准确性以及灵敏度更高。     

以氘代利伐沙班为内标物的UHPLC-MS/MS法测定Beagle犬血浆中利伐沙班及其药动学研究

摘要： 目的 建立测定Beagle犬血浆中利伐沙班浓度的超高效液相色谱-串联质谱(UPLC-MS/MS) 法。 方法 以甲基叔丁基醚：二氯甲烷(2:1)沉淀蛋白处理血浆样品,D4-利伐沙班为内标, 采用 Thermo BDS HYPERSI L C18色谱柱（100×4.6 mm,2.4 μm）;流动相：A相为甲醇溶液（含0.015 mol/L甲酸铵和0.1%甲酸）; B相为水/甲醇(90/10)溶液（含0.015 mol/L甲酸铵和0.1%甲酸）,梯度洗脱。质谱条件为电喷雾离子源,正离子模式检测,扫描方式为多反应离子监测。用于定量检测的离子反应分别为 [M+H]+ m/z 436@30eV→m/z144.900（利伐沙班）和 [M+H]+ m/z 440@24eV→m/z144.900（D4-利伐沙班）。结果 血浆利伐沙班浓度在0.5-400 ng·mL-1范围内线性关系良好（r=0.9961）,定量下限为0.5ng/ml,批内批间精密度均<13%,提取回收率89.4%-96.5%,基质效应94.7%-97.2%。血浆样品冻存（-80℃）33d稳定性良好,反复冻融3次及提取后室温放置12h条件下,样品浓度均无显著变化。将本法应用于Beagle犬口服给予利伐沙班片后的药动学考察,主要药动学参数如下：tmax(2.11±1.133) h,Cmax(179.3±50.65) ng/ml, t1/2(10.05±4.34) h,AUC0-t(1161.6±339.74) h·ng·ml-1。结论 试验结果表明本法操作简单,灵敏度高,重现性良好,结果准确可靠,可用于测定Beagle犬血浆中利伐沙班浓度和其体内的药动学研究。     

New Water-Soluble Pilocarpine Derivatives with Enhanced and Sustained Muscarinic Activity

The synthesis of an homologous series of new water-soluble derivatives of pilocarpine is described. The new compounds, referred to as soft quaternary salts, are water soluble by virtue of a cationic ammonium head and their lipophilicity can be modulated by manipulating the size and the nature of the substituent in the inactive portion of the molecule. The miotic activity of the compounds was evaluated after administration to normotensive New Zealand White rabbits. Changes in pupil size indicated a substantial cholinergic effect on the iridal sphincter musculature. The best candidate, compound 20, which has a 16-carbon side chain, was evaluated for reduction of the intraocular pressure in genetically glaucomatous Beagles. Compound 20 is superior to pilocarpine in both tests, with a potency 10 to 20 times that of the parent compound and a longer duration of action. It is suggested that the new compounds are pro-drug forms of pilocarpine which greatly enhance the corneal bio-availability of the parent compound.     

A histologic comparative study of the midpalatal suture and periodontal ligament tissue in the beagle dog

Abstract — The present investigation describes the morphological difference between. the suture and the periodontal ligament in beagie dogs. Specimens from fivs beagle dogs, 2 yr old, containing the anterior portion of the maxilla were used. Following routine histologic preparations frontal sections were cut with the microtome. The sections were stained and studied in the light microscope. The fibers in the midpaiatal suture seemed coarser and less organized than the fibers in the periodontal ligament tissue. The vessels in the suture had thicker walls than the vessels in the periodontal ligament. A probable reason for the morphologica differences between the two tissues is discussed.     

The Effect of Whole- and Partial-body X-irradiation on the Metabolism of Collagen in Polyethylene Sponges and the Urinary Excretion of Pyrrole-2-carboxylic Acid

Summary

1. The incorporation of glycine-2-¹⁴C into sponge collagen is of the same magnitude in two different sponges implanted at different sites in the same animal.

2. Partial-body, in contrast to whole-body x-irradiation, had no effect on the incorporation of ¹⁴C-labelled proline, hydroxyproline and glycine into sponge collagen. Similar observations were made with respect to the specific activity of urinary PCA.

3. Evidence has been presented indicating the possible interference of ionizing radiation with the conversion of proline to hydroxyproline.

4. Whole-body x-irradiation had no effect on the metabolism of collagen from rat-tail tendon although in these same animals the specific activity of urinary PCA did undergo radiation-induced changes.     

LC/MS法测定犬血浆中的水飞蓟宾浓度

目的建立犬血浆中水飞蓟宾浓度的LC-MS测定方法。方法取犬血浆400μl,加200μl磷酸氢二钠(0.1mol.L-1)和50μl内标萘酚(10mg·mL-1),3ml乙醚萃取后取上清液挥干,100μl甲醇复溶,离心并取10μl进行LC-MS测定。色谱条件:色谱柱为ODS-C18柱(2.1mm×150mm,5μm,Phenomenex,USA),流动相为甲醇:2%乙酸水=55∶45,流速为0.2ml.min-1;质谱条件:电喷雾离子化(ESI)方式,以选择性负离子方式检测,水飞蓟宾和内标萘酚的选择检测离子质荷比分别为m/z481.00([M-H]-)和m/z142.92([M-H]-)。结果水飞蓟宾的线性范围为25～8000μg.L-1,定量下限(LOQ)为25μg.L-1。准确度、精密度及回收率均符合有关要求。结论本方法专属性强,检测限低,灵敏度高,线性关系良好,方法简便快捷、经济,适用于水飞蓟宾药代及毒代动力学研究。     

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.     

Effectiveness of hydroxyethyl starch (HES) on purification of pancreatic islets

BACKGROUND: The isolation of large-scale and high-quality islets from the pancreas is essential for a successful islet transplantation. We developed a hydroxyethyl starch (HES)-Collins solution as the purification medium and evaluated its usefulness on islet isolation from the pancreas of beagle dogs. MATERIALS AND METHODS: The pancreas of beagle dog was digested using our original 2-step automated technique. Islets were purified by discontinuous purification method on HES-Collins solution (group 1, n = 10) or Euro-Ficoll solution (group 2, n = 16) with a COBE2991 cell processor. Islet yield and purity, changes in islet number during 3-day cultures, static incubation, perifusion study, and insulin content were examined. In addition, the islets were autotransplanted into the liver via the portal vein. RESULTS: Although no significant differences were detected, yield and purity were higher in group 1. After 3 days of culture, the islet number decreased less in group 1. Both under static incubation and in the perifusion study, stimulation indices were 4.50 +/- 1.82 and 6.02 +/- 1.05, which were significantly higher than the 2.18 +/- 0.67 and 3.32 +/- 1.46 observed in group 2. Also, insulin content of the islets was significantly higher in group 1 than in group 2. Fasting blood glucose levels were maintained at values below 100 mg/dl for 100 days in group 1 and around 200 mg/dl in group 2. CONCLUSIONS: The use of HES-Collins solution was associated with an improvement of islet yield and purity. Also, islet viability and function were preserved longer during culture. Accordingly, islet purification using HES-Collins solution might be recommended for clinical islet transplantation.