氚标记小牛胸腺DNA在大鼠和犬体内的药动学研究

目的:研究氚标记小牛胸腺DNA(3H-小牛胸腺DNA)在大鼠和Beagle犬体内的药动学特征。方法:采用氚水交换法制备3H-小牛胸腺DNA。取大鼠尾静脉注射高、中、低剂量(15、5、1.67 mg/kg,n=5)的3H-小牛胸腺DNA,中、高剂量组大鼠连续给药7d(第1、7天给予3H-小牛胸腺DNA,其余时间给予未标记小牛胸腺DNA),低剂量大鼠仅单次给药;另取犬前肢静脉注射高、中、低剂量(1.5、0.5、0.167 mg/kg,n=3)的3H-小牛胸腺DNA,中剂量犬连续给药7 d,低、高剂量犬仅单次给药。分别于第1、7天给药后0.033、0.25、1、2、4、6、8、12、24 h取血,分离血浆后加入闪烁液并使用液闪计数仪分析,以WinNonlin软件计算药动学参数。结果:高、中、低剂量3H-小牛胸腺DNA在大鼠体内的药动学参数分别为:单次给药的AUC0-24 h为(11 742±2 245)、(3 571±851)、(727±202)ng-Eq·h/g,t1/2为(21.4±5.08)、(13±6.0)、(6.8±1.76)h;重复给药高、中剂量的AUC0-24 h为(5 706±1 009)、(7 601±1 861)ng-Eq·h/g,t1/2为(16.0±10.13)、(9±2.7)h。高、中、低剂量3H-小牛胸腺DNA在犬体内的药动学参数分别为:单次给药的AUC0-24 h为(4 444±999)、(2 719±139)、(501±101)ng-Eq·h/g,t1/2为(17.6±7.57)、(14.0±1.76)、(16.4±2.39)h;重复给药中剂量的AUC0-24 h为(3 073±200)ng-Eq·h/g,t1/2为(20.6±6.62)h。结论:3H-小牛胸腺DNA在大鼠与Beagle犬体内单次给药和重复给药均可被快速消除。     

The Role of Waste Management in Control of Rabies: A Neglected Issue

Despite being vaccine preventable, the global burden of dog rabies remains significant, and historically it is the rural and marginalized communities in developing countries of Africa and Asia that are most threatened by the disease. In recent years, the developing world has been experiencing unprecedented increases in urbanization, with a correspondingly massive increase in municipal solid waste generation, among other things. Inefficient and inadequate waste collection and management, due to lack of resources and planning, led to significant increases in the volumes of waste on the streets and in open dumps, where it serves as food sources for free-roaming dogs. In this commentary, we discuss examples of poor waste management and the likely impact on rabies control efforts through the sustenance of free-roaming dogs in some dog rabies-endemic countries. We aim to stress the importance of implementing strategies that effectively address this particular issue as an important component of humane dog population management, as it relates to aspirations for the control and elimination of dog rabies per se.     

Dogs as Sentinels for Flavivirus Exposure in Urban,Peri-Urban and Rural Hanoi,Vietnam

Diseases caused by flaviviruses, including dengue fever and Japanese encephalitis, are major health problems in Vietnam. This cross-sectional study explored the feasibility of domestic dogs as sentinels to better understand risks of mosquito-borne diseases in Hanoi city. A total of 475 dogs serum samples from 221 households in six districts of Hanoi were analyzed by a competitive enzyme-linked immunosorbent assay (cELISA) for antibodies to the pr-E protein of West Nile virus and other flaviviruses due to cross-reactivity. The overall flavivirus seroprevalence in the dog population was 70.7% (95% CI = 66.4–74.8%). At the animal level, significant associations between seropositive dogs and district location, age, breed and keeping practice were determined. At the household level, the major risk factors were rural and peri-urban locations, presence of pigs, coil burning and households without mosquito-borne disease experience (p < 0.05). Mosquito control by using larvicides or electric traps could lower seropositivity, but other measures did not contribute to significant risk mitigation of flavivirus exposure in dogs. These results will support better control of mosquito-borne diseases in Hanoi, and they indicate that dogs can be used as sentinels for flavivirus exposure.     

盐酸伊伐布雷定对单硝酸异山梨酯在比格犬体内的药动学影响

目的 研究盐酸伊伐布雷定对单硝酸异山梨酯在比格犬体内的药动学影响.方法 采用HPLC法测定单硝酸异山梨酯单独给药或联合盐酸伊伐布雷定给药后不同时间比格犬体内的血药浓度,采用非房室模型计算单硝酸异山梨酯药动学参数.结果 单硝酸异山梨酯单独给药及与盐酸伊伐布雷定联合使用后,在比格犬体内单硝酸异山梨酯的主要药动学参数差异无统计学意义(P<0.05).单硝酸异山梨酯联合盐酸伊伐布雷定给药相对单硝酸异山梨酯单独给药的生物利用度为100%.结论 盐酸伊伐布雷定与单硝酸异山梨酯联合用药后对单硝酸异山梨酯在比格犬体内的药动学过程无影响.     

Cardiovascular Safety Pharmacology of Sibutramine

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC₅₀ of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD₅₀, and 9% and 17% decreases in APD₉₀, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.     

国产镍钛记忆合金房间隔封堵器的实验研究

目的:通过外科创建的房间隔缺损动物模型评价国产镍钛记忆合金封堵器的封堵效果和组织学反应。方法:将犬房间隔造口建立房间隔缺损动物模型后,利用国产镍钛记忆合金房间隔封堵器进行封堵,术后4h、15h、1、2、3个月分别进行大体解剖和光镜、电镜检查。结果:5只犬成功建立了动物模型并1次封堵成功,完成4h～3个月随访。动物生长发育正常,无严重并发症出现。15d～3个月大体解剖可见封堵器与房间隔组织紧密嵌合,表面完全被一层半透明、光滑的新生组织所覆盖,光镜及透射电镜检查证实为内皮样细胞。结论:国产镍钛记忆合金封堵器封堵外科创建的房间隔缺损动物模型是可行的。     

Histomorphologic and histomorphometric evaluation of various endosseous implant healing chamber configurations at early implantation times: a study in dogs

Aim: The objective of this study was to evaluate the early healing of endosseous implants presenting various healing chamber configurations in a beagle dog mandible model. Methods: The four premolars of 12 beagle dogs were extracted and allowed to heal for a period of 8 weeks. Implants allowing six different healing chamber configurations were placed in each dog (three per side, six configurations per dog). The animals were sacrificed after 3 and 5 weeks in vivo (n=6 per time in vivo), and the implants were non‐decalcified processed to slides of ～30 μm thickness. Bone‐to‐implant contact (BIC) and bone area fraction occupied (BAFO) within the healing chamber were quantified. Statistical analysis was performed by a GLM ANOVA model at 5% significance level. Results: Osseointegration and healing with woven bone filling throughout all healing chambers was observed. Replacement of woven bone by lamellar bone showing primary osteonic structures was observed at 5 weeks. BIC was significantly affected by healing chamber configuration (P<0.001) and was not affected by time in vivo (P>0.42) at 3 and 5 weeks in vivo. BAFO was not affected by healing chamber configuration (P>0.14) however significantly increased over implantation time (P<0.001). Conclusion: Regardless of healing chamber design and dimensions considered, healing allowed the devices osseointegration. However, healing chamber configuration significantly affected osseointegration measurable parameters such as BIC. To cite this article:
Marin C, Granato R, Suzuki M, Gil JN, Janal, MN Coelho PG. Histomorhpologic and histomorphometric evaluation of various endosseous implant healing chamber configurations at early implantation times: a study in dogs.
Clin. Oral Impl. Res. 21 , 2010; 577–583.
doi: 10.1111/j.1600‐0501.2009.01853.x     

Effects of Calcium Infusion on Gastric Secretion in Heidenhain Pouch Dogs

Calcium salts were infused against a background of stimulation by histamine or porcine gastrin or against the release of endogenous gastrin (feeding test). Raising the plasma calcium to values noted in clinical chronic hyperparathyroidism did not influence histamine-stimulated secretion but had a strong inhibitory action on gastrin-stimulated secretion. In the feeding tests (endogenous gastrin) the onset of secretion was delayed by calcium infusion.

The results of these experiments cannot be related directly to the problem of hyperparathyroidism, hypercalcemia, and peptic ulcer. The results do, however, indicate a difference in the stimulant actions of gastrin and histamine.     

犬心房肌细胞的分离及外向钾通道电流的记录

目的：探讨犬心房肌细胞的分离方法及其通道电流记录.方法：采用冠状动脉灌流、酶解技术分离犬心房肌细胞,应用膜片钳全细胞记录技术,记录细胞膜快速延迟整流钾电流（Ikr）、缓慢延迟整流钾电流（Iks）、超快延迟整流钾电流（Ikur）及瞬时外向钾电流（Ito）.结果：获得具有正常电生理活性的单个心房肌细胞,成功记录了Ikr、Iks、Ikur及Ito.结论：此方法分离的单个心房肌细胞具有正常的电生理活性,可用于研究心房肌细胞离子通道特征.