氟苯尼考在鸡体内的药动学及其体内抗菌后效应研究

为探讨氟苯尼考的药动学特征及抗菌后效应(PAE),制订临床给药方案,用微生物法测定鸡血清中氟苯尼考浓度。建立鸡组织笼感染模型,以菌落计数法测定氟苯尼考的体内PAE。结果显示内服给药后药-时数据符合一级吸收一室开放式模型,其药动学方程为C=4.7804(e-0.1096t-e-2.5858t),主要药动学参数:t1/2Ke=(6.42±0.83)h、Cmax=(3.96±0.42)μg/mL、AUC=(42.41±7.50)(μg/mL).h-1、Vd=(6.63±0.68)L/kg;氟苯尼考浓度在2MIC、4MIC和8MIC时,作用1h的体内PAE分别为0.35、1.20和1.48h,同时测定的体外PAE为0.23、0.93和1.17h。鸡内服氟苯尼考的给药方案为1日1次,维持剂量30mg/kg体重。     

单诺沙星对大肠杆菌和金葡球菌的体外抗茵后效应

采用菌落计数法测定了单诺沙星在三种不同浓度下对大肠杆菌和金黄色葡萄球菌 (金葡球菌 )的体外抗菌后效应 (PAE)。当药物浓度为 0 .5MIC、2MIC、4MIC时 ,对大肠杆菌的PAE值为 (0 .6 4 6 4± 0 .0 2 94 )h、(1.2 0 77± 0 .0 2 84 )h、(1.6 5 2 9± 0 .0 4 96 )h ;对金葡球菌的PAE值为 (0 .5 6 6 0± 0 .0 0 75 )h、(1.174 6± 0 .0 0 5 7)h、(1.4 913± 0 .0 2 5 7)h。这表明单诺沙星对大肠杆菌、金葡球菌均有不同程度的较强的PAE ,且PAE值与药物浓度呈正相关     

单诺沙星在雏鸡体内的药动学特征及生物利用度研究

以高效液相色谱法为定量手段研究了单诺沙星内服给药在雏鸡体内的药动学特征及生物利用度。 12 0只雏鸡静注或内服单诺沙星 (5mg/kg)后 ,血药浓度时间数据分别符合无吸收二室模型和一级吸收二室模型。静注给药的主要动力学参数为t1/ 2α0 .34h ,t1/ 2 β为 7.3184h ,VB 为 16 .0 6 31L/kg ,AUC为 3.2 872mg/L·h ,Tcp为 2 5 .0 1h。内服给药的主要动力学参数如下 :t1/ 2ka为 0 .2 42 8h ,t1/ 2α为 0 .8917h ,t1/ 2 β为 8.7936h ,Tp 为 0 .9377h ,Cmax为 0 .5 487μg/mL ,AUC为3 .0 5 2 3mg/L·h ,Tcp为 31.115h。内服生物利用度为 92 .85 %。     

单诺沙星在支原体一大肠杆菌感染鸡体内的药动学与生物利用度的研究

以高效液相色谱法为定量手段研究了单诺沙星内服给药在支原体与大肠杆菌合并感染鸡体内的药动学特征及生物利用度。 12 0只合并感染雏鸡静注或内服单诺沙星 (5mg/kg)后 ,血药浓度时间数据分别符合无吸收二室模型和一级吸收二室模型。静注给药的主要动力学参数为t1/ 2α0 .5 0 34h,t1/ 2 β为 6 .8485h,VB 为 12 .16 0 3L/kg,AUC为 40 6 33mg/L·h ,Tcp为 2 5 .2 43h。内服给药的主要动力学参数如下 :t1/ 2ka为 0 .3182h ,t1/ 2α为 1.5 5 0 2h ,t1/ 2 β为 12 .6 2 0 0h ,Tp 为 1.110 7h ,Cmax为 0 .5 10 6 μg/mL ,AUC为 3.6 6 2mg/Lh ,Tcp为 39.18h。内服生物利用度为 90 .0 8%。     

肌注马波沙星在犊黄牛体内的药动学及半体内抗菌后效应研究

旨在研究单次肌内注射马波沙星在犊黄牛体内的药动学及马波沙星对多杀性巴氏杆菌的抗菌后效应。选用5头健康犊黄牛按体重以2mg·kg-1的剂量给药,用高效液相色谱法测定马波沙星的血药浓度,使用WinNolin6.2药物动力学软件提供的非房室模型处理血药浓度-时间数据。并测定马波沙星对多杀性巴氏杆菌在预定时间点收集血清中的抗菌后效应(PAE)。马波沙星在犊牛血清中的主要药动学参数:Cmax2.04μg·mL-1、Tmax0.83h、AUC15.03h·μg·mL-1、AUMC138.67h·h·μg·mL-1、MRT9.17h、t1/2β9.00h、Vd1.80L·kg-1、CL/F0.14L·(h·kg)-1。当血清中马波沙星浓度大约在2MIC、4MIC、8MIC时,其PAE的值分别为1.90、2.65、3.50h。结果表明,犊牛肌注马波沙星后,吸收相对较为迅速,分布广泛,消除缓慢;对多杀性巴氏杆菌在血清中具有较长的抗菌后效应,且与暴露药物呈明显的浓度依赖性。     

盐酸沙拉沙星在兔体内的药物动力学及生物利用度研究

选用24只健康哈白兔，分3组，每组8只，进行药物动力学研究。静注、内服和肌注剂量均为10mg/kg。以反相高效液相色谱法，测定了血清中的药物浓度，所得药时数据用MCPKP程序处理，得出了药动学参数，拟合方程及肌注和内服的生物利用度。结果表明，哈白兔静注盐酸沙拉沙星后的药时数据符合无吸收因素二室模型，主要药动学参数如下Vd4.67±0.75L/kg，t1/2α0.54±0.12h，t1/2β4.43±0.186h，AUC13.86±2.63μg/ml*h，ClB0.75±0.16L/kg*h。兔内服盐酸沙拉沙星后，药时数据符合一级吸收一室开放式模型，主要药动学参数如下t1／2ka0.36±0.08h，t1/2Kel5.94±1.09h，tmax1.53±0.15h，cmax0.41±0.09μg/ml,AUC4.19±0.86μg/ml*h，生物利用度为30.22%。兔肌注盐酸沙拉沙星后，药时数据符合一级吸收二室开放式模型，主要药动学参数如下t1/2ka0.06±0.01h，t1/2α0.83±0.16h，t1/2β5.01±1.14h，AUC10.75±1.38μg/ml*h，tmax0.27±0.02h，cmax3.52±0.38μg/ml，生物利用度为77.58%。     

单诺沙星在鲫鱼体内的药物代谢动力学研究

以15 mg/kg的剂量肌肉注射单诺沙星,研究其在鲫鱼体内的药物动力学代谢规律。取给药后不同时间的鲫鱼血浆,采用反相高效液相色谱法测定血浆中单诺沙星的质量浓度,用MPTCP软件进行数据处理和分析。结果表明,健康鲫鱼肌注给药的药时数据符合二室开放模型,主要药物动力学参数为:表观分布容积(V)为5.099 0 L±0.061 5 L,分布半衰期(t1/2α)为0.527 5 h±0.008 1 h,消除半衰期(t1/2β)为286.944 0 h±18.595 0 h,药时曲线下面积(AUC)为387.767 7/(mg/L).h±23.779 3/(mg/L).h。单诺沙星在鲫鱼体内的主要药物动力学特征为分布快且完全,消除缓慢,作用时间长。     

单诺沙星脂质体在蛋雏鸡血浆的药代动力学

分别采用静脉注射和内服两种给药途径给予健康蛋雏鸡甲磺酸单诺沙星溶液和甲磺酸单诺沙星脂质体混悬液(剂量为5 mg/kg).结果显示,两种剂型静注给药的药时数据均符合无吸收二室开放模型,主要药动学参数分别为T1/2α 0.349 6、0.351 8 h;T1/2β6.411 4、8.193 2 h;AUC3.799 7、5.066 0 mg/(L·h);CLβ1.723 2、1.131 7 L/(kg·h).两种剂型内服给药的药时数据均符合一级吸收一室开放模型,主要药动学参数分别为T1/2 Ka0.301 7、0.524 4 h;T1/2K 4.479 2、5.021 7 h;AUC 3.284 4、4.610 6 mg/(L·h);Cmax 0.483 8、1.054 8 mg/L;Tp 1.287 3、1.936 2 h;生物利用度分别为86.44%、91.01%.可见这两种剂型的静注与内服给药的体内药动学特征不同.与甲磺酸单诺沙星溶液相比,甲磺酸单诺沙星脂质体血浆半衰期延长,达峰浓度高,有效浓度维持时间持久,内服生物利用度提高.     

沙拉沙星及与安普霉素联用的体外抗菌后效应研究

本次实验采用试管溶液二倍稀释法测得沙拉沙星对大肠杆菌和金黄色葡萄球菌的最小抑菌浓度(MIC)分别为0.25μg/m L和1.0μg/m L,安普霉素对两种菌的MIC值为2.5μg/m L和0.63μg/m L。试验分别以1MIC、2MIC、4MIC并设置一组空白对照组,然后将大肠杆菌和金黄色葡萄球菌与不同浓度的抗生素短暂接触后1.5h,采用千倍稀释法清除抗生素,然后与未处理的对照组比较细菌恢复再生长时间,按公式PAE=T-C计算结果。结果显示在1MIC时,单用沙拉沙星对大肠杆菌和金黄色葡萄球菌的PAE分别为0.92士0.28h、1.15士0.31h,而沙拉沙星与安普霉素联合应用在1MIC对大肠杆菌和金黄色葡萄球菌的PAE分别为1.68士0.26h,1.45士0.25h,比较可以得出,两种药联合应用可有效延长PAE。再者,两种药联用对大肠杆菌和金黄色葡萄球菌在药物浓度为2MIC和4MIC的PAE分别为为2.05±0.35h、2.13±0.27h和3.47±0.32h、2.47±0.34h。可得PAE大小与药物浓度呈正相关,并推测其最佳接触时间为4h左右。     

六氢β-酸月桂酸酯在鸡体内的药动学研究

文中进行了六氢β-酸月桂酸酯在鸡体内的药动学研究。将12只健康鸡随机分为2组,分别单剂量每千克体重40 mg/kg灌胃给药和1 mg/kg静注给药。在给药前后不同时间点从前腔静脉采集血样,分离血浆,用高效液相色谱法测定血浆中六氢β-酸月桂酸酯的浓度。用Winnon-lin5.2.1的非房室模型处理血浆药物浓度-时间数据。单剂量口服六氢β-酸月桂酸酯的主要药动学参数:Cmax(0.04±0.01)μg/ml,Tmax(1.00±0.15)h,T1/2(2.35±0.17)h,AUC(0.13±0.01)(h·μg)/ml,V(1 024.1±98.4)L/kg,CLB(302.2±7.6)L/(kg·h),MRT(3.55±0.27)h;单剂量静注六氢β-酸月桂酸酯的主要药动学参数:C0(1.25±0.17)μg/ml,T1/2(1.10±0.25)h,AUC(0.82±0.14)(h·μg)/ml,V(1.93±0.13)L/kg,CLB(1.25±0.21)L/(kg·h),MRT(1.27±0.31)h。结果表明:灌胃六氢β-酸月桂酸酯[40mg/(kg·bw)]与静脉注射六氢β-酸月桂酸酯[1 mg/(kg·bw)]相比,鸡灌胃给药的生物利用度为0.4%,灌胃给药后吸收极少,静注浓度较高,消除半衰期均较短。     

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.     

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.     

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.     

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

Tropical Animal Health and Production -     

The Epidemiology of Gastrointestinal Nematodes of Dairy Cattle in Central Kenya

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.     

Diversity of Ectoparasites in Sheep Flocks in Sa~o Paulo,Brazil

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.     

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.     

Evaluation of biohydrogenation rate of canola vs. soya bean seeds as unsaturated fatty acids sources for ruminants in situ

An experiment was conducted to study disappearance of C14 to C18 fatty acids, lag times and biohydrogenation (BH) rates of C18 fatty acids of ground soya bean and canola seeds in situ. Three ruminally fistulated Dallagh sheep were used to determine ruminal BH of unsaturated fatty acids (UFAs). Differences in the disappearance of fatty acids through the bags and lag times were observed between the oilseeds. We saw that the longer the incubation time of the oilseeds in the rumen, the lower the content of C18:2 and C18:3. Significantly higher lag times for both C18:2 and C18:3 were observed in ground canola compared to ground soya bean. BH rates of C18:2 and C18:3 fatty acids in soya bean were three times higher than those of canola. These results suggest that the fatty acid profile of fat source can affect the BH of UFAs by rumen micro‐organisms. So that UFAs of canola had higher ability to escape from ruminal BH. It seems that fatty acid profile of ruminant products is more affected by canola seed compared to soya bean seed.     

Serum biochemical values and mineral element contents of tissues in yaks

Serum biochemical values and the wet weight to dry weight ratios of tissues were determined in yaks in Shandan county of Gansu province. The liver, kidney, heart and muscle contents of seven elements in yaks were also analysed. Most serum biochemical values were similar to those of cattle, camels and sheep, but the calcium concentration was considerably above the normal range for other ruminants. The liver contained the highest concentrations of copper, manganese and cobalt and the kidney of selenium, iron and calcium.Abbreviations Alb albumin - ALT alanine aminotransferase - AST aspartate aminotransferase - BUN blood urea nitrogen - Chol cholesterol - Glob globulin - -GT -glutamyl transpeptidase - IP inorganic phosphorus - TP total protein