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1.
恩诺沙星长效注射液肌注后在猪体内的药动学研究   总被引:2,自引:0,他引:2  
研究了恩诺沙星长效注射液给猪肌注后的药物动力学特征。将12只白猪随机分成两组,每组6只,分别肌注恩诺沙星注射液(5mg/kg)和长效恩诺沙星注射液(18.75mg/kg),并于给药后0.1, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 60h, 从前腔静脉采取5ml血,用HPLC分析各血浆样品中的药物浓度,用MCPKP软件计算药动学参数。结果表明:长效恩诺沙星注射液肌注后,经5.64h达到4.86μg/ml的最高浓度,吸收半衰期和消除半衰期分别为2.42h和19.47h,有效浓度维持时间为128.73h, AUC为166.96mg/L.h。吸收半衰期显著延长(p<0.05),达峰时间极显著推迟(p<0.01),消除半衰期也显著长于恩诺沙星注射液。  相似文献   

2.
对7头健康猪随机交叉设计进行单剂量肌肉注射国产30%长效土霉素注射液和进口20%长效土霉素注射液药动学试验,给药剂量以土霉素计均为20mg/kg体重。用高效液相色谱法测定血药浓度,血药浓度一时间数据用MCPKP计算机程序处理。30%长效土霉素注射液和20%长效土霉素注射液主要药动学参数分别为:吸收半衰期(t1/2ka)为(0.088±0.016)、(0.140±0.076)h;消除半衰期(t1/2β)为(52.499±22.885)、(36.481±21.673)h;达峰时间(Lmax)为(0.609±0.100)、(0.832±0.373)h;峰浓度(Cmax)为(4.956±1.171)、(5.0184-0.948)μg/mL;药时曲线下面积(AUG)为(112.483±18.135)、(109.877±19.949)mg/L·h;以20%长效土霉素注射液为对照物,30%长效土霉素注射液的相对生物利用度(F)为(105.368±26.027)%。结果表明,国产30%长效土霉素注射液与进口20%长效土霉素注射液相比,主要药动学参数无显著差异。此结论为临床合理使用该剂型提供了依据和指导。  相似文献   

3.
为研究"一针肥"注射液中硒元素在山羊体内的血硒水平及药动学变化规律,采用单剂量肌肉注射"一针肥"注射液0.2mL/kg(相当于硒用量6μg/kg),用原子荧光法测定血硒浓度,通过3p97药物动力学程序软件分析药时数据。结果显示,肌注"一针肥"注射液后,血硒的药时数据符合二室开放模型,主要的药代动力学参数分别为:t1/2Ka(0.148 4±0.051 0)h,t1/2α(6.832 4±0.397 7)h,t1/2β(362.324 3±17.789 5)h,Kel(0.004 3±0.000 3)h,AUC(22 414.233 5±2 512.959 8)(μg/L).h。结果表明,肌注"一针肥"注射液后硒在山羊体内吸收迅速,消除缓慢。  相似文献   

4.
本文描述了阿维菌素长效注射液与阿维菌素普通注射液(阿福丁注射液)药物动力学的比较研究。绵羊血浆经提取、纯化、真空干燥和荧光衍生化后,用荧光高效液相色谱法进行检测。用3P87药代动力学分析软件对所测得的结果进行分析,得出以下药代动力学结果:阿维菌素长效注射液和阿福丁注射液在绵羊体内均呈二室代谢模型。长效注射液以1mg/kg体重进行颈部皮下注射得到以下药动学参数:吸收半衰期t1/2α=9.59h,消除半衰期t1/2β=292.97h,达峰时间tmax=47.46h,最大血药浓度Cmax=13.91ng/mL,曲线下面积AUC=6235.48ng/(mL·h),消除率ClB=0.034L/(kg·h),表观分布容积Vd=13.7L/kg。将阿福丁注射液以0.2mg/kg体重进行颈部皮下注射得到以下药动学参数:吸收半衰期t1/2α=9.05h,消除半衰期t1/2β=144.34h,达峰时间tmax=12.63h,最大血药浓度Cmax=8.52ng/mL,曲线下面积AUC=1017.35ng/(mL·h),消除率ClB=0.22L/(kg·h),表观分布容积Vd=14.5L/kg。研究结果表明:阿维菌素长效注射液比普通注射液吸收慢、消除慢,在体内维持有效血药浓度的时间长,长效注射液维持有效血药浓度(0.5ng/mL血浆)的时间长于49d,而阿福丁注射液不足21d。  相似文献   

5.
36只黄羽肉鸡,随机均分为3组,每组12只,分别进行恩诺沙星、恩诺沙星钠和盐酸恩诺沙星的药动学试验,高致液相色谱法测定鸡只血浆中恩诺沙星浓度,MCPKP程序处理药-时数据。恩诺沙星、恩诺沙星钠和盐酸恩诺沙星溶液经内服给药后在鸡体内最佳药动学模型为一级吸收一室模型,峰浓度高(峰浓度分别为2.39、2.04和2.37μg/mL),吸收快(吸收半衰期t1/2Ka分别为1.15h、0.76h和1.55h),消除缓慢(消除半衰期t1/2K分别为8.39h、12.19h和10.95h)。以恩诺沙星做对照,恩诺沙星钠和盐酸恩诺沙星内服给药后吸收完全,其相对生物利用度高,分别为103.2%和126.8%。恩诺沙星钠和盐酸恩诺沙星内服给药后主要药动学参数与恩诺沙星给药后的药动学参数相比均无显著性差异.  相似文献   

6.
研究了氧氟沙星缓释注射液肌注给药后在猪体内的药物动力学特征,给药剂量为10mg/kg,采用反相高效液相色谱荧光检测法(HPLC-FLD)测定血浆中氧氟沙星浓度。采用3p97药物动力学程序软件处理药-时数据,得出相关药物动力学参数。静注氧氟沙星注射液在猪体内的药物动力学过程符合无吸收一室开放式模型,肌注氧氟沙星注射液、缓释注射液在猪体内的药物动力学过程均符合一级吸收一室开放式模型。氧氟沙星缓释注射液的吸收半衰期(t1/2ka)为(0.292 0±0.102 4)h,消除半衰期(t1/2ke)为(6.902 2±0.901 9)h,达峰时间(Tmax)为(1.379 5±0.373 2)h,达峰浓度(Cmax)为(2.148 1±0.296 1)μg/mL,生物利用度为(95.70±12.56)%,在猪体内的持效时间(MIC=0.5μg/mL)为(15.736 4±1.854 2)h,与氧氟沙星注射液相比,该制剂的吸收半衰期延长,消除半衰期延长,达峰时间延迟,峰浓度降低,生物利用度提高,持效时间延长。  相似文献   

7.
本文描述了阿维菌素长效注射液与阿维菌素普通注射液(阿福丁注射液)药物动力学的比较研究。绵羊血浆经提取、纯化、真空干燥和荧光衍生化后,用荧光高效液相色谱法进行检测。用3P87药代动力学分析软件对所测得的结果进行分析,得出以下药代动力学结果;阿维菌素长效注射液和阿福丁注射液在绵羊体内均呈二室代谢模型。长效注射液以1mg/kg体重进行颈部皮下注射得到以下药动学参数;吸收半衰期t_(1 2α)=9.59h,消除半衰期t_(1 2β)=292.97h,达峰时间t_(max)=47.46h,最大血药浓度C_(max)=13.91ng/mL,曲线下面积AUC=6235.48ng/(mL·h),消除率CLB=(0.034L/(kg·h),表观分布容积V_d=13.7L/kg。将阿福丁注射液以0.2mg/kg体重进行颈部皮下注射得到以下药动学参数:吸收半衰期t_(1 2α)=9.05h,消除半衰期t_(1 2β)=144.34h,达峰时间t_(max)=12.63h,最大血药浓度C_(max)=8.52ng/mL,曲线下面积AUC=1017.35ng/(mL·h),消除率CL_B=0.22L/(kg·h),表现分布容积V_d=14.5L/kg。研究结果表明:阿维菌素长效注射液比普通注射液吸收慢、消除慢,在体内维持有效血药浓度的时间长,长效注射液维持有效血药浓度(0.5ng/mL血浆)的时间长于49d,而阿福丁注射液不足21d。  相似文献   

8.
恩诺沙星混悬液在猪体内的药动学及生物利用度   总被引:6,自引:0,他引:6  
本文比较了恩诺沙星混悬液和恩诺沙星溶液在猪体内的药动学特征和生物利用度。选用 7头健康猪按拉丁方设计进行静注、肌注恩诺沙星溶液和肌注恩诺沙星混悬液在猪体内的药物动力学研究。 3种给药方法的剂量均为 10mg/kg。猪静注给药的药时数据符合二室开放模型 ,主要药动学参数为 :t1/ 2α0 6 4± 0 15h ,t1/ 2 β9 0 6± 2 47h ,Vd(area) 4 40± 0 88L/kg ,ClB0 35± 0 0 6L·kg-1·h-1,AUC2 9 85± 4 11L·kg-1·h。猪肌注恩诺沙星溶液和恩诺沙星混悬液的药时数据符合一级吸收一室模型 ,其主要药动学参数分别为t1/ 2ka0 2 4± 0 10h和 1 2 5± 1 0 9h(P <0 0 5 ) ;t1/ 2ke8 90± 2 0 2h和 18 95± 4 5 5h(P <0 0 1) ;Tmax1 2 5± 0 41h和 5 14± 2 95h(P <0 0 1) ;Cmax1 5 4± 0 2 5 μg/ml和 0 87± 0 2 1μg/ml;AUC2 1 49± 4 94mg·L-1·h和 2 8 97± 10 80mg·L-1·h ;F72 0 %±17 4%和 97 7%± 35 0 %。比较肌注恩诺沙星混悬液和恩诺沙星溶液的主要药动学参数 ,二者有显著差异 ,前者的t1/ 2ka、Tmax、t1/ 2ke和Cmax分别为后者的 5 2、4 1、2 1和 0 6倍。这些差异说明恩诺沙星混悬液肌注后吸收缓慢 ,消除半衰期延长 ,临床应用 48h给药 1次仍能维持对常见病原菌的有效血药  相似文献   

9.
两种盐酸多西环素注射液在猪体内的药代动力学研究   总被引:1,自引:1,他引:0  
研究制备了两种稳定的20%盐酸多西环素注射液,按10 mg/kg的剂量分别给猪肌肉注射,观察两个制剂在猪体内单剂量肌注的药代动力学特征.结果表明,多西环素在猪体内的药物动力学特征均符合一级吸收二室开放模型,其主要的药物代谢动力学参数:消除半衰期(T1/2β)分别为(3.246±1.04)和(9.631±1.12)h,药时曲线下面积(AUC)为(10.462±0.28)和(17.525±0.14)(μg/mL)*h,达峰时间(Tpeak)及达峰浓度(Cmax)分别为(1.427±0.16)h、(1.465±0.20) μg/mL和(1.694±0.15)h、(1.058±0.09) μg/mL.其中制剂一的血药浓度在给药2h后迅速降低,为普通注射液;与制剂一相比,制剂二能够缓慢释放药物,为长效缓释盐酸多西环素注射液.  相似文献   

10.
研究了两种头孢噻呋注射液给猪肌注后的比较药物动力学特征。选用12头健康猪随机分为两组,每组6头,分别肌注上海公谊兽药厂生产的长效盐酸头孢噻呋注射液和美国辉瑞生产的盐酸头孢噻呋注射液(速解灵注射液),每头5mg/kg。采用超高效液相色谱法测定猪血浆中头孢噻呋的的药物浓度,用Winnonlin5.2药动学分析软件非房室模型处理药时数据,模型200处理肌注给药后的药代动力学参数。结果表明:健康猪肌注两种注射液后,参数MRT、Cmax、tmax统计差异极显著(P〈0.01),长效盐酸头孢噻呋注射液单剂量肌注给药较速解灵注射液吸收慢,达峰时间显著延迟,达峰浓度显著降低,平均驻留时间显著延长;参数AUC、Kel、t1/2允统计无显著性差异(P〉0.05),长效盐酸头孢噻呋注射液的相对生物利用度为98.41%,与速解灵注射液的生物利用度相当。本研究可为头孢噻呋注射液的临床合理用药提供参考。  相似文献   

11.
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。  相似文献   

12.
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.  相似文献   

13.
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.  相似文献   

14.
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.  相似文献   

15.
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.  相似文献   

16.
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.  相似文献   

17.
The purpose of this study was to determine the frequency of different tumor types within a large cohort of cats with intracranial neoplasia and to attempt to correlate signalment, tumor size and location, and survival time for each tumor. Medical records of 160 cats with confirmed intracranial neoplasia evaluated between 1985 and 2001 were reviewed. Parameters evaluated included age, sex, breed, FeLV/FIV status, clinical signs, duration of signs, number of tumors, tumor location(s), imaging results, treatment, survival times, and histopathologic diagnosis. Most of the cats were older (11.3 +/- 3.8 years). Primary tumors accounted for 70.6% of cases. Metastasis and direct extension of secondary tumors accounted for only 5.6 and 3.8% of cases, respectively. Twelve cats (7.5%) had 2 or more discrete tumors of the same type, whereas 16 cats (10.0%) had 2 different types of intracranial tumors. The most common tumor types were meningioma (n = 93, 58.1%), lymphoma (n = 23, 14.4%), pituitary tumors (n = 14, 8.8%), and gliomas (n = 12, 7.5%). The most common neurological signs were altered consciousness (n = 42, 26.2%), circling (n = 36, 22.5%), and seizures (n = 36, 22.5%). Cats without specific neurological signs were common (n = 34, 21.2%). The tumor was considered an incidental finding in 30 (18.8%) cats. In addition to expected relationships (eg, meninges and meningioma, pituitary and pituitary tumors), we found that lesion location was predictive of tumor type with diffuse cerebral or brainstem involvement predictive of lymphoma and third ventricle involvement predictive of meningioma.  相似文献   

18.
The epidemiology of H. placei and of other gastrointestinal nematodes in yearling dairy cattle was examined on two farms in Kiambu District, central Kenya during each of 13 one-month periods from April 1993 to April 1994. On each farm, 32 newly weaned dairy calves were given a single dose of albendazole and then placed on experimental pastures. Twelve of the animals were designated for bi-monthly slaughter (n = 2) and analysis of worm population characteristics and 20 were designated for blood and faecal collection and for weighing. Two parasite-free tracer calves were grazed alongside the weaner calves each month throughout the study period and were also slaughtered for analysis of worm populations. Faecal egg counts, haematological and serum pepsinogen determinations, herbage larval counts, and animal live weight changes were recorded monthly. The study revealed that Haemonchus placei, Trichostrongylus axei, Cooperia spp. and Oesophagostomum radiatum were responsible for parasitic gastroenteritis and that H. placei was the predominant nematode present in the young cattle on both farms. Faecal egg counts from resident cattle and necropsy worm counts revealed that pasture larval levels were directly related to the amount of rainfall. The total worm burdens in the animals were highest during the rainy season (March–June and October–December) and lowest during the dry seasons (July–September and January–February). The very low recovery of immature larvae of H. placei from the tracer calves indicated that arrested development is not a feature of the life cycle of this parasite in central Kenya. The maintenance of the parasite population depended on continuous cycling of infection between the host and the pasture. The agroclimatic conditions of the study area were such that, in general, favourable weather conditions for the development and survival of the free-living stages of gastrointestinal nematodes existed all year round.  相似文献   

19.
The occurrence of ectoparasites in sheep flocks is frequently reported but seldom quantified. Sheep production used to be a predominantly family activity in the state of Sa~o Paulo (Brazil), but it began to become a commercial activity in the past decade. Thus, information about the ectoparasites existing in sheep flocks has become necessary. The present data were obtained by means of questionnaires sent to all sheep breeders belonging to the `Associaça~o Paulista de Criadores de Ovinos' (ASPACO; Sa~o Paulo State Association of Sheep Breeders). Response reliability was tested by means of random visits paid to 10.6% of the respondents. Most of the properties (89.5%) reported the presence of one or more ectoparasites. Screw-worm (Cochliomyia hominivorax) was the most frequent ectoparasite (72.5%), followed by bot fly larvae (Dermatobia hominis, 45.0%), ticks (Amblyomma cajennense) and Boophilus microplus, 31.3%) and finally lice (Damalinia ovis, 13.8%). Combined infestations also occurred, the most common one being screw-worm with bot fly larvae (36.0%) followed by bot fly larvae with ticks (13.9%), screw-worm with ticks (9.3%), bot fly larvae with lice (6.9%), and ticks with lice (5.0%). The most common triple combination was screw-worm, bot fly larvae and ticks (12.8%). Breeds raised for meat or wool were attacked by bot fly larvae and ticks more often than other breeds. Lice were only absent from animals of indigenous breeds. The relationships among these ectoparasites are discussed in terms of sheep breeds, flock size, seasonality and the ectoparasitic combinations on the host.  相似文献   

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