两种妥曲珠利混悬液口服给药在仔猪的药动学比较研究

16只体重较一致的健康断奶仔猪随机分成2组,采用单剂量平行随机对照试验设计,分别单剂量(20 mg/kg体重,以妥曲珠利计)经口内服国产(受试品)和进口(对照品)妥曲珠利混悬液。结果表明,与妥曲珠利混悬液对照品相比较,妥曲珠利触变混悬液受试品单剂量内服给药吸收和消除较慢,但药物吸收完全。给药后按预定时间采集血样,血浆中妥曲珠利含量采用HPLC紫外检测器进行分析。实测血药浓度-时间数据采用Winnonlin5.2药动学分析软件计算药代动力学参数。结果显示,妥曲珠利混悬液对照品单剂量内服后,其平均消除半衰期(T1/2β)约为40.806 h,达峰时间(Tmax)和峰值浓度(Cmax)分别为16.500 h和27.494 mg/L,平均药时曲线下面积(AUC)为1 375.738(μg/m L/h),平均滞留时间(MRT)为50.677 h;妥曲珠利触变混悬液受试品单剂量内服后,其T1/2β约为51.642 h,Tmax和Cmax分别为37.500 h和21.452mg/L,AUC为1 843.842μg/m L/h,MRT为64.058 h,相对生物利用度为134.02%。与妥曲珠利混悬液对照品相比,妥曲珠利触变混悬液受试品口服吸收AUC(P=0.020)、Tmax(P=0.001)、MRT(P=0.019)有显著性差异;但两种混悬剂的其他药动学参数,如T1/2β(P=0.224)、Cmax(P=0.146)无显著差异。     

帕托珠利混悬液对靶动物仔猪的安全性评价

为研究帕托珠利混悬液对靶动物仔猪的安全性,本试验选取32只3～5日龄哺乳仔猪,分为4个剂量组,每组8头,公母各半。其中各剂量组按体重给药剂量分别为1倍(15 mg/kg)、3倍(45 mg/kg)和5倍(75 mg/kg)最大推荐剂量,经口灌服5%帕托珠利混悬液,连用3次,每次间隔3 d;另一组为空白对照组,给予相当于5倍最大推荐剂量体积的生理盐水,试验周期为17 d。试验期间除进行一般临床健康状况观察外,还进行体重增重、体温、血常规和血液生化指标检测,以及大体剖检和组织病理学检查。结果显示,试验期间试验组和对照组临床表现正常,帕托珠利混悬液各剂量组对仔猪的精神状态、生长性能、血常规、血液生化指标均无明显影响,均处正常范围内。对5倍推荐剂量组及对照组的仔猪进行剖检,主要脏器和显微结构未见明显异变,未出现中毒及死亡。研究表明,推荐剂量下帕托珠利混悬液口服给药对靶动物仔猪有较大安全性。     

海南霉素钠预混剂在鸡体内的药动学及生物利用度研究

为研究海南霉素钠预混剂在鸡体内的药代动力学特征和生物利用度,将16只健康AA鸡随机分成2组,每组8只,采用平行试验设计对两组鸡分别进行单剂量口服给药和静脉注射给药药动学研究,给药量均为1.5 mg/kg bw(相当于7.5 mg/kg混饲给药)。按预定时间点采集血样,血样中海南霉素的含量采用高效液相色谱-串联质谱法(HPLC-MS/MS)测定,流动相为乙腈-0.1%甲酸水溶液(90:10,V/V)。实测血药浓度-时间数据使用Winnonlin 5.2药动学分析软件拟合药动学参数。鸡口服给药的药动学参数如下:平均消除半衰期为(T_(1/2β))约为30.44 h,平均滞留时间(MRT)约为36.40 h,在血浆中的达峰时间(T_(max))约为0.5 h,达峰浓度(C_(max))约为68.87 ng/mL,平均药时曲线下面积(AUC)约为654.95 ng·h/mL,平均生物利用度(F)约为32.82%。鸡静脉注射给药的药动学参数如下:平均消除半衰期约为(T_(1/2β))为46.40 h,平均滞留时间(MRT)约为30.91 h,平均血浆清除率(CL)约为1.59 L/(kg·h),平均表观分布容积(V_d)约为116.05 L/kg。结果表明海南霉素进入鸡体后分布广泛,消除缓慢,半衰期长;口服海南霉素钠预混剂吸收迅速,但吸收不完全。     

酒石酸泰万菌素预混剂在仔猪体内的药代动力学研究

为研究酒石酸泰万菌素预混剂在仔猪体内的药物动力学特征,采用平行试验设计方法,将12头28日龄健康仔猪随机分为两组,每组6头（公猪）,第1组口服沈阳伟嘉生物技术有限公司的酒石酸泰万菌素预混剂,第2组口服英国伊科拜克动物保健品有限公司的酒石酸泰万菌素预混剂。两组给药剂量相同均为125mg/kg,所有仔猪给药前禁食12h,给药6h后恢复正常饮食。给药后按照预定的采血点采集血样,用液相色谱-质谱法（LC/MS-MS）测定酒石酸泰万菌素预混剂的血浆浓度,用DAS 2.1.1 软件计算药动学参数。结果显示：口服沈阳伟嘉生物技术有限公司的酒石酸泰万菌素预混剂在仔猪体内主要药动学参数如下：平均最高血药浓度（Cmax）为247.3 ng/ml,平均药时曲线下面积（AUC）为1899.0 ng/ml*h,平均达峰时间（Tmax）为1 h;口服英国伊科拜克动物保健品有限公司的酒石酸泰万菌素预混剂主要药动学参数如下：平均最高血药浓度（Cmax）为159.8 ng/ml,平均药时曲线下面积（AUC）为986.0 ng/ml*h,平均达峰时间（Tmax）为1.5 h;结果表明,沈阳伟嘉生物技术有限公司的酒石酸泰万菌素预混剂平均最高血药浓度（Cmax）是参比制剂的1.55倍,平均药时曲线下面积（AUC）是参比制剂的1.93倍,生物利用度是参比制剂的193%;沈阳伟嘉生物技术有限公司的酒石酸泰万菌素预混剂相比参比制剂（英国伊科拜克动物保健品有限公司）具有给药后仔猪体内分布迅速,血药浓度高,药时曲线下面积（AUC）高,生物利用度高,吸收和代谢速度快,药物残留时间短,休药期短,对减少抗生素残留具有重要意义。     

乳炎消在奶牛体内的药代动力学研究

给乳牛单剂量肌注0.73mg/kg乳炎消后不同时间采集血样，采用紫外分光光度法测定血药浓度。应用MCPKP药动学程序自动拟合处理血药浓度－时间数据，并求出药动学参娄。血药浓度－时间曲线符合一级吸收－一室开放模型。最佳药时方程Ci=17.8(e^-0.333t-e^-1.57t)。主要药动学参数：t1/2Ka为0.441h,t1/2K为2.082h,tmax为1.395h,Cmax为11.671μg/mL，AUC53．477mg/lh,Tcp为12.733h。根据单剂量给药参数计算出多剂量给药参数：г为12h,D^*为0.mL/kg,D（维持剂量）为0.08mL/kg。     

妥曲珠利微晶体的制备及其在家兔体内的药动学

采用反溶剂法制备妥曲珠利微晶体,利用显微镜观察妥曲珠利微晶体与妥曲珠利原药显微特征差异,并在25℃条件下测定两者体外溶出速率差异。将12只家兔随机分为2组,每组6只,分别按药物剂量10mg/kg灌胃,单剂量给药,采用HPLC检测血药浓度;用DAS2.0药代动力学程序计算药代动力学参数。结果显示,成功制备了妥曲珠利微晶体,微晶体与原药的显微特征差异明显,体外溶出速率明显加快;家兔单剂量灌胃妥曲珠利和微晶体后,主要药动学参数Cmax分别为（8.925±0.360）mg/L和（12.510±0.525）mg/L,tmax均为24h,AUC（0-∞）分别为（411.605±20.918）mg/（L·h）和（578.650±11.664）mg/（L·h）,相对生物利用度为140.6%,药时数据符合一级吸收二室模型。结果表明,HPLC法适用于妥曲珠利血浆浓度的测定;妥曲珠利微晶体与妥曲珠利原药相比,体内吸收速率和吸收程度有较大的提高。     

氟苯尼考混悬剂与常规制剂在猪体内药动学的比较研究

长效制剂能够使药物在动物体内缓慢释放,使有效药物浓度维持较长时间,实现方便给药的目的,同时也克服常规制剂多次给药造成的波峰波谷现象,更好地发挥药效。氟苯尼考混悬剂和常规制剂按20mg/kg体重肌注给药,用高效液相色谱法测定血药浓度。试验所得的血浆浓度-时间数据采用非房室模型统计距原理处理。氟苯尼考混悬剂的主要药动学参数:AUC=44.99μg/(mL.h),MRT=26.62h,t1/2β=16.5h;氟苯尼考常规制剂的主要药动学参数:AUC=54.3μg/(mL.h),MRT=12.97h,t1/2β=11h。试验结果表明氟苯尼考混悬剂在体内吸收缓慢,能够延长药物在体内作用时间。     

两种磺胺氯吡嗪钠溶液剂灌服给药在鸡体中的比较药动学研究

24只健康肉鸡随机分成2组,每组12只(公母各半),采用单周期平行设计,分别进行单剂量(60 mg/kg bw,以磺胺氯吡嗪钠计)经口灌服复方和单方磺胺氯吡嗪钠溶液的药动学研究.给药后按预定时间采集血样,采用HPLC法测定血浆中药物含量.实测血药浓度-时间数据,采用Kinetica药动学分析软件计算药动学参数.结果显示,鸡单剂量灌服磺胺氯吡嗪钠溶液后,主要药动学参数如下:T1/2β为9.39 h,MRT为26.57 h,Tm.和Cm.分别为7.33 h和64.69 μg/mL,ClB为0.52 mL/(min · kg),Vz为0.43 L/kg,AUC为1954.28 μg/mL·h.鸡单剂量灌服复方磺胺氯吡嗪钠溶液后,主要药动学参数如下:T1/2β为8.24 h,MRT为26.37 h;Tmmax和Cmax15.50 h和71.43 μg/mL;ClB为0.51 mL/(min·kg),Vz为0.36 L/kg,AUC为2125.81 μg/mL·h,相对生物利用度为108.78％.结果表明,与磺胺氯吡嗪钠溶液相比,复方磺胺氯吡嗪钠溶液灌服后,除达峰时间和峰浓度明显延长或增高(P＜0.01)外,其他药动学参数均无显著差异(P＞0.05).     

特比萘芬在比格犬体内的药动学和绝对生物利用度

8只健康比格犬采用随机交叉试验设计,盐酸特比萘芬注射液按5 mg/kg单剂量静注,盐酸特比萘芬片按20mg/kg单剂量口服给药,洗脱期为2周。采用高效液相色谱法测定犬血浆中特比萘芬的浓度,以药动学分析软件WinNonlin5.2的非房室模型分析方法处理血药浓度-时间数据。结果显示,犬静注盐酸特比萘芬注射液的药动学参数分别为:Tmax(0.083±0.000)h,Cmax(3.334±0.185)mg/L,T1/2β(15.158±8.558)h,MRT(2.443±1.132)h,AUClast(1.803±0.374)h·mg/L,Vd(49 778.164±25 594.370)mL/kg,CLB(2 414.907±577.369)kg·mL/h。犬口服盐酸特比萘芬片的主要药动学参数为:Tmax(1.875±0.791)h,Cmax(0.324±0.126)mg/L,T1/2β(18.150±10.557)h,MRT(5.019±1.591)h,AUClast(1.094±0.588)h·mg/L,Vd(395 321.202±236 694.989)mL/kg,CLB(14 340.535±3 560.508)kg·mL/h,Flast(16.589±11.495)%,F0~∞(18.236±8.114)%。结果表明,特比萘芬片剂在犬体内吸收迅速,保留时间更长,消除更为缓慢,有长效抑菌效果。     

健康仔猪口服亚硒酸钠的血液中药代动力学的研究

本实验按0.6mg/kgBW单剂量对健康仔猪口服亚硒酸钠溶液后，首次系统地研究了其在血液中药物代谢动力学。实验结果表明，血液动力学特征符合一级吸收二室开放模型，其理论方程为：C＝0.0820e^-0.0421t 0.1050e^-0.0014t-0.1870e^-2.2541t。主要动力学参数为：吸收半衰期（t1/2Ka)为0.3075h，达峰时间（tmax)为2.1517h；消除半衰期（t1/2β）为510.2706h，曲线下面积（AUC）为75.1460mg/L.h；表观分布容积（Vd)为5.5742L/kg。根据单剂量药动学参数，计算多剂量给药参数，为临床治疗制订给药方案，先导剂量（D^*)为1.2262mg/kg BW，维持剂量（D0）为0.6mg/kgBW，给药间隔（τ）为480h，平均稳态血药浓度（c)为0.1566μg/ml。     

白术、微米白术和白术多糖对断奶仔猪生长性能和肠道形态及微生态区系的影响

试验选用96头平均体重14.82 kg左右的杜×长×大断奶仔猪,随机分成4组,每组3栏,每栏8头(公母各半)。对照组饲喂基础日粮,试验1、2、3组分别添加1%80目白术、0.2%白术多糖和1%微米白术。试验期30 d。结果表明:在生长性能方面,与对照组相比,1%微米白术添加组可显著提高日增重(P0.05)、降低饲料增重比和腹泻率,而且效果优于1%80目白术组和0.2%白术多糖组,在肠道形态和肠道微生态区系方面,与对照组相比,日粮添加1%80目白术、0.2%白术多糖、1%微米白术均可不同程度的提高十二指肠和空肠的绒毛高度,加深十二指肠和空肠的隐窝深度,并且增加肠道微生态区系的多样性,其中以1%微米白术添加组的效果最佳。     

Prevalence and seasonal incidence of nematode parasites and fluke infections of sheep and goats in eastern Ethiopia

Sissay, M.M., Uggla, A. and Waller, P.J., XXXX. Prevalence and seasonal incidence of nematode parasites and fluke infections of sheep and goats in eastern Ethiopia. Tropical Animal Health and Production, XXXX. A 2-year abattoir survey was carried out to determine the prevalence, abundance and seasonal incidence of gastro-intestinal (GI) nematodes and trematodes (flukes) of sheep and goats in the semi-arid zone of eastern Ethiopia. During May 2003 to April 2005, viscera including liver, lungs and GI tracts were collected from 655 sheep and 632 goats slaughtered at 4 abattoirs located in the towns of Haramaya, Harar, Dire Dawa and Jijiga in eastern Ethiopia. All animals were raised in the farming areas located within the community boundaries for each town. Collected materials were transported within 24 h to the parasitology laboratory of Haramaya University for immediate processing. Thirteen species belonging to 9 genera of GI nematodes (Haemonchus contortus, Trichostrongylus axei, T. colubriformis, T. vitrinus, Nematodirus filicollis, N. spathiger, Oesophagostomum columbianum, O. venulosum, Strongyloides papillosus, Bunostomum trigonocephalum, Trichuris ovis, Cooperia curticei and Chabertia ovina), and 4 species belonging to 3 genera of trematodes (Fasciola hepatica, F. gigantica, Paramphistomum {Calicohoron} microbothrium and Dicrocoelium dendriticum) were recorded in both sheep and goats. All animals in this investigation were infected with multiple species to varying degrees. The mean burdens of adult nematodes were generally moderate in both sheep and goats and showed patterns of seasonal abundance that corresponded with the bi-modal annual rainfall pattern, with highest burdens around the middle of the rainy season. In both sheep and goats there were significant differences in the mean worm burdens and abundance of the different nematode species between the four geographic locations, with worm burdens in the Haramaya and Harar areas greater than those observed in the Dire Dawa and Jijiga locations. Similar seasonal variations were also observed in the prevalence of flukes. But there were no significant differences in the prevalence of each fluke species between the four locations. Overall, the results showed that Haemonchus, Trichostrongylus, Nematodirus, Oesophagostomum, Fasciola and Paramphistomum species were the most abundant helminth parasites of sheep and goats in eastern Ethiopia.     

Internal Parasites and Haematological Values in Cattle Slaughtered in Buea Subdivision of Cameroon

Tropical Animal Health and Production -     

Phase I evaluation of CCNU (lomustine) in tumor-bearing cats

1-(2-Chloroethyl)3-cyclohexyl-1-nitrosourea (CCNU) is an alkylating agent in the nitrosourea subclass. A prospective evaluation of CCNU was done to determine the maximally tolerated dosage of CCNU in tumor-bearing cats. Response data were obtained when available. Twenty-five cats were treated with CCNU at a dosage of 50-60 mg/m3 body surface area. Complete hematologic data were available for 13 cats. Neutropenia was the acute dose-limiting toxicity. The median neutrophil count at the nadir was 1,000 cells/microL (mean, 2,433 cells/microL; range, 0-9,694 cells/microL). The time of neutrophil nadir was variable, occurring 7-28 days after treatment, and counts sometimes did not return to normal for up to 14 days after the nadir. Based on these findings, a 6-week dosing interval and weekly hematologic monitoring after the 1st treatment with CCNU are recommended. The nadir of the platelet count may occur 14-21 days after treatment. The median platelet count at the nadir was 43,500 cells/microL. No gastrointestinal, renal, or hepatic toxicities were observed after a single CCNU treatment, and additional studies to evaluate the potential for cumulative toxicity should be performed. Five cats with lymphoma and 1 cat with mast cell tumor had measurable responses to CCNU. Phase II studies to evaluate antitumor activity should be completed with a dosing regimen of 50-60 mg/m3 every 6 weeks.     

Chemotaxis of macrophage in inflammation

Our particular attention in this article was given to natural mediators for macrophages isolated from the sites of tissue injury. A number of chemotactic factors, which may satisfy many criteria making them acceptable as inflammatory leucocyte chemotactic factors, has been separated. Among them, our laboratory has isolated three macrophage (monocyte) chemotactic factors (MCF-a, -b and -c). Their purification, characterization and functional specificity are discussed.     

Prevalence of gastric lesions in racing Alaskan sled dogs

Human and equine athletes are reported to have a high prevalence of gastric disease, and anecdotal evidence suggests a similar phenomenon applies to racing sled dogs. To investigate the prevalence of gastric disease in racing sled dogs, we conducted 2 gastroscopy studies on dogs competing in the annual Iditarod Sled Dog Race. A pilot study of dogs that were either dropped from the 2000 Iditarod Sled Dog Race because of illness or that finished the race indicated that, approximately 5 days after competing, 10 of 28 dogs (35%) had endoscopic evidence of gastric ulceration, erosion, or hemorrhage. The next year, an endoscopic study of 73 dogs participating in the 2001 Iditarod race was performed in order to evaluate a larger population of dogs. Data from 70 of these dogs could be used; 34 (48.5%) had ulceration, erosion, gastric hemorrhage, or some combination of these findings. When this group of 70 dogs was compared retrospectively to a control group of 87 dogs presented to the Texas A&M University (TAMU) Veterinary Medical Teaching Hospital, the Iditarod sled dogs had a significantly higher prevalence (P = .049) of gastric lesions. These findings suggest that, similar to athletes of other species, elite canine athletes have an increased prevalence of gastric disease compared to the canine population at large.     

Furosemide continuous rate infusion in the horse: evaluation of enhanced efficacy and reduced side effects

Continuous rate infusion (CRI) of furosemide in humans is considered superior to intermittent administration (IA). This study examined whether furosemide CRI, compared with IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse. Five mares were used in a crossover-design study. During a 24-hour period, each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1 mg/kg IV q8h). There was not a statistically significant difference in urine volume over 24 hours between methods; however, urine volume was significantly greater after CRI compared with IA during the first 8 hours ([median 25th percentile, 75th percentile]: 9.6 L [8.9, 14.4] for CRI versus 5.9 L [5.3, 6.0] for IA). CRI produced a more uniform urine flow, decreased fluctuations in plasma volume, and suppressed renal concentrating ability throughout the infusion period. Potassium, Ca, and Cl excretion was greater during CRI than IA (1,133 mmol [1.110, 1,229] versus 764 mmol [709, 904], 102.7 mmol [96.0, 117.2] versus 73.3 mmol [65.0, 73.5], and 1,776 mmol [1,657, 2.378] versus 1,596 mmol [1,457, 1,767], respectively). Elimination half-lives of furosemide were 1.35 and 0.47 hours for CRI and IA, respectively. The area under the excretion rate curve was 1,285.7 and 184.2 mL x mg/mL for CRI and IA, respectively. Furosemide CRI (0.12 mg/kg/h) for 8 hours, preceded by a loading dose (0.12 mg/kg), is recommended when profound diuresis is needed acutely in horses.     

Y‐chromosomal variation of local goat breeds of Turkey close to the domestication centre

Genetic variations in chromosome Y are enabling researchers to identify paternal lineages, which are informative for introgressions and migrations. In this study, the male‐specific region markers, sex‐determining region‐Y (SRY), amelogenin (AMELY) and zinc finger (ZFY) were analysed in seven Turkish native goat breeds, Angora, Kilis, Hair, Honaml?, Norduz, Gürcü and Abaza. A SNP in the ZFY gene defined a new haplotype Y2C. All domestic haplogroups originate from Capra aegagrus, while the finding of Y1A, Y1B, Y2A and Y2C in 32, 4, 126 and 2 Turkish domestic goats, respectively, appears to indicate a predomestic origin of the major haplotypes. The occurrence of four haplotypes in the Hair goat and, in contrast, a frequency of 96% of Y1A in the Kilis breed illustrate that Y‐chromosomal variants have a more breed‐dependent distribution than mitochondrial or autosomal DNA. This probably reflects male founder effects, but a role in adaptation cannot be excluded.     

Changes in proportion of canine urinary calculi composed of calcium oxalate or struvite in specimens analyzed from 1981 through 2001

The objective of this report was to characterize 20-year changes in proportion of calcium oxalate (CaOx) calculi and struvite calculi in dogs, and associations with breed, age, and sex. In this retrospective study, results of analysis of urinary calculi from dogs were reviewed for specimens received between July 1, 1981, and December 31, 2001. Breed, sex, age, year of submission of the specimen, and mineral type(s) were analyzed statistically. CaOx or Struvite or both were contained in 18,966 of 20,884 (91%) specimens. For both sexes, a 20-year statistically significant increase was observed in the proportion of calculus specimens that contained CaOx. The increase in this proportion was greater in females (1% to 31%) than in males (18% to 82%). From 1998 to 2001, when proportions may have plateaued, the odds of specimens containing CaOx were markedly higher in 18 breeds, markedly lower in 5 breeds, and not significantly different in 13 breeds compared with crossbreds. For both sexes, a 20-year statistically significant decrease was observed in the proportion of calculus specimens that contained struvite. This decrease in proportion was greater for males (79-16%) than for females (97-68%). From 1998 to 2001, when proportions plateaued, the odds of calculi containing struvite were markedly lower in 20 breeds, markedly higher in 1 breed, and not significantly different in 15 breeds when compared with crossbreds. Breed, age, and sex were associated statistically with CaOx or struvite urolithiasis. In conclusion, there appears to have been a long-term increase in the proportion of specimens of canine urinary calculi that contain CaOx as well as a long-term decrease in the proportion of specimens of calculi that contain struvite for both male and female dogs. The rate of change appeared to begin leveling off in the period 1998 to 2001. The recent proportion of dogs with either CaOx- or struvite-associated urolithiasis may depend on breed, age, and sex, and on interactions among these 3 factors.     

Smart Phone Assisted City-scale Wireless Sensor Network Deployment for Transportation System Monitoring

<正>1.INTRODUCTION Ensuring transportation network security is one Of the most daunting challenges confronting homeland security agencies today.Significant research has been dedicated.To model and analyze the vulnerability of transportation systems,while notably fewer studies propose specific strategies for deploying defensive technologies to safeguard these systems.