Comparative pharmacokinetics of marbofloxacin in healthy and Mannheimia haemolytica infected calves

The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.     

肌肉注射硫酸安普霉素在猪体内的药代动力学和生物利用度研究

对6头健康猪单剂量静脉注射、肌肉注射国产硫酸安普霉素,研究其在猪体内的药代动力学和生物利用度.用微生物法测定血清药物浓度,结果平均回收率为99.03%,血清最低检测浓度为0.05μg/ml,日内日间变异系数为2.2%～5.1%,且血清浓度在0.05～3μg/ml范围呈良好线性关系(r＝0.9965).对猪静注、肌注硫酸安普霉素20mg/kg后,经MCPKP药代动力学计算机程序处理,体内药物运转符合开放型二室模型,肌肉注射0.856h后达峰药浓度Cmax为36.09±1.22μg/ml;t1/2分别为1.58±0.67h、1.06±0.11h,CLB分别为0.15L/kg/h、0.17 L/kg/h,V1分别为0.71L/kg、0.1L/kg,绝对生物利用度为AUC i.m/AUC i.v＝88.47%±3.32%,上述药代动力学数据为动物临床用药提供有价值的理论依据.     

Binding of phenthoate to bovine serum albumin and reduced inhibition on acetylcholinesterase

Organophosphorus pesticides (OPs) are of environmental significance due to their high toxicity to animals. Binding to plasma proteins may effective influence the toxicological properties of xenobiotics. In an attempt to evaluate the affinity of phenthoate (PTA) to bovine serum albumin (BSA) and inhibitory ability of bound PTA to acetylcholinesterase (AChE), we investigated the interactions between phenthoate (PTA) and bovine serum albumin (BSA) using tryptophan fluorescence quenching and subsequent inhibition on AChE activity by PTA. The results showed that PTA caused the fluorescence quenching of BSA because of the formation of a PTA-BSA complex. Quenching constants (K_sv), determined using the Sterns-Volmer equation to provide a measure of the binding affinity between PTA and BSA at 303, 306, 310 and 313 K were (3.4295 ± 0.0763) × 10⁻⁴, (3.2446 ± 0.0635) × 10⁻⁴, (3.0434 ± 0.0856) × 10⁻⁴ and (2.8262 ± 0.0569) × 10⁻⁴ M⁻¹, respectively. The thermodynamic parameters, ΔH and ΔS were −25.04 kJ mol⁻¹ and 168.94 J mol⁻¹ K⁻¹, respectively, which indicated that the electrostatic interactions played a major role in PTA-BSA association. The presence of BSA consistently reduced the inhibitory ability of PTA on AChE, with the relative activity being increased from 46.98 to 61.71% for the concentration range of BSA between 0 and 4.0 g L⁻¹.     

Pharmacokinetics of oxolinic acid and oxytetracycline in kuruma shrimp, Penaeus japonicus

The pharmacokinetics of oxolinic acid and oxytetracycline were examined in kuruma shrimp (Penaeus japonicus) after intra-sinus (10 and 25 mg/kg, respectively) and oral (50 mg/kg) administration. The shrimp were kept in tanks with recirculated artificial seawater at a salinity of 22–23 ppt. The water temperature was maintained at 25±0.6 °C. The hemolymph concentrations of both drugs after intra-sinus dosing were best described by a two-compartment open model. The distribution and elimination half-lives (t_1/2 and t_1/2β) were found to be 0.59 and 33.2 h for oxolinic acid and 0.45 and 24.7 h for oxytetracycline, respectively. The apparent volume of distribution at a steady state (V_ss) and total body clearance (CL_b) were estimated to be 1309 ml/kg and 28.8 ml/kg/h for oxolinic acid and 748 ml/kg and 22.7 ml/kg/h, respectively. The hemolymph concentration–time curves after oral administration did not fit by the nonlinear least squares method using one- and two-compartment model with first-order absorption in either of the drugs. The peak hemolymph concentration (C_max), the time to peak hemolymph concentration (t_max) and the elimination half-life were found to be 17.8 μg/ml, 7 h and 34.3 h for oxolinic acid and 24.3 μg/ml, 10 h and 33.6 h for oxytetracycline, respectively. The bioavailability (F) after oral administration was 32.9% for oxolinic acid and 43.2% for oxytetracycline. The hemolymph protein binding in vivo was determined to be 36.7±8.5% for oxolinic acid and 22.9±4.8% for oxytetracycline.     

氟苯尼考PEG6000固体分散体在大鼠体内的生物利用度研究

[目的]研究氟苯尼考PEG6000固体分散体在大鼠体内的生物利用度.[方法]建立大鼠血浆中氟苯尼考的HPLC检测方法.用灌喂药物水溶液的方法,通过高效液相分析技术对氟苯尼考PEG6000固体分散体的血药浓度进行测定,与氟苯尼考原粉进行对照.[结果]氟苯尼考PEG6000固体分散体在大鼠体内吸收及代谢良好,氟苯尼考固体分散体和氟苯尼考原药的最高血药浓度分别为13.44和3.88 μ.g/ml,提高了3.46倍;药-时曲线下面积分别为：氟苯尼考原粉AUC0-8h=20.12 25 μg/（ml·h）、氟苯尼考固体分散体AUC0-8h=23.22μg/（ml·h）,氟苯尼考-PEG6000固体分散体口服生物利用度与氟苯尼考原粉相比提高了15.39％.[结论]氟苯尼考-PEG6000固体分散体能显著提高氟苯尼考的生物利用度.     

除草剂污染堆肥用量对黄瓜生物有效性的影响

化学除草已成为确保现代农业生产不可或缺的技术，但因除草剂会在非靶标植物中残留，进
而导致堆肥和有机肥料产品被除草剂污染，为避免堆肥及其产品在不合理应用时对后茬植物的生长产生不
良影响，造成不可挽回的损失，本试验采用市售基质、普通堆肥和受除草剂污染的堆肥为试材，设置无污
染堆肥处理（C1）、氯氨吡啶酸污染堆肥处理（C2）和二氯吡啶酸污染堆肥处理（C3）3 个处理，在0、5%、
10% 和20% 堆肥不同用量条件下，以黄瓜的出苗率和播种后45 d 时植株的节间距、株高、茎粗、植株干质量、
叶片数、叶面积、叶片卷曲情况和壮苗指数为评价指标。结果表明，受除草剂污染的堆肥对黄瓜种子的萌
发有抑制作用，且堆肥用量越大，出苗率越低，而且黄瓜幼苗表现出严重的除草剂药害症状，植株纤弱，
叶片狭小、卷曲。两种除草剂污染堆肥对黄瓜的影响呈现不同的规律，在堆肥用量相同的条件下，氯氨吡
啶酸比二氯吡啶酸对黄瓜的药害严重，这表明越高效的除草剂随堆肥或有机肥的施用对后茬敏感植物的药
害风险越大。     

Hydrolase activity, microbial biomass and community structure in long-term Cd-contaminated soils

Long-term effects of high Cd concentrations on enzyme activities, microbial biomass and respiration and bacterial community structure of soils were assessed in sandy soils where Cd was added between 1988 and 1990 as Cd(NO₃)₂ to reach concentrations ranging from 0 to 0.36 mmol Cd kg⁻¹ dry weight soil. Soils were mantained under maize and grass cultivation, or ‘set-aside’ regimes, for 1 year. Solubility of Cd and its bioavailability were measured by chemical extractions or by the BIOMET bacterial biosensor system. Cadmium solubility was very low, and Cd bioavailability was barely detectable even in soils polluted with 0.36 mmol Cd kg⁻¹. Soil microbial biomass carbon (B_C) was slightly decreased and respiration was increased significantly even at the lower Cd concentration and as a consequence the metabolic quotient (qCO₂) was increased, indicating a stressful condition for soil microflora. However, Cd-contaminated soils also had a lower total organic C (TOC) content and thus the microbial biomass C-to-TOC ratio was unaffected by Cd. Alkaline phosphomonoesterase, arylsulphatase and protease activities were significantly reduced in all Cd-contaminated soils whereas acid phosphomonoesterase, β-glucosidase and urease activites were unaffected by Cd. Neither changes in physiological groups of bacteria, nor of Cd resistant bacteria could be detected in numbers of the culturable bacterial community. Denaturing gradient gel electrophoresis analysis of the bacterial community showed slight changes in maize cropped soils containing 0.18 and 0.36 mmol Cd kg⁻¹ soil as compared to the control. It was concluded that high Cd concentrations induced mainly physiological adaptations rather than selection for metal-resistant culturable soil microflora, regardless of Cd concentration, and that some biochemical parameters were more sensitive to stress than others.     

Critical body residues (CBRs) for ecotoxicological soil quality assessment: copper in earthworms

The term ‘critical body residue’ (CBR) was defined as the lowest observed total body concentration of a contaminant in an organism, which is associated with the occurrence of adverse toxic effects in either individuals or populations of a defined age or stage of development. In this study, internal toxicity thresholds were determined for copper in the clitellated adult stage of earthworms (Lumbricus rubellus and Aporrectodea caliginosa). The objective was to assess the applicability of CBRs as a practical tool in soil quality assessment of contaminated sites and as a means of a sustainable protection of earthworm fauna. Laboratory studies showed that body concentrations of Cu were generally in agreement with the chemically available CaCl₂-extractable fraction in soil, but that there was also some evidence of internal pH-related homeostatic regulation. Toxicological correlates of body Cu concentrations with adverse effects on cocoon production (fecundity) suggested an approximate sublethal internal threshold of about 40 mg kg⁻¹, with mortality occurring at about 60 mg kg⁻¹. Adult L. rubellus sampled from areas with a wide range of metal pollution showed body Cu concentrations with a minimum of 8 mg kg⁻¹ and a maximum of 60 mg kg⁻¹. Beyond this apparent physiological tolerance range, environmental management directed at optimal earthworm population survival may not be sustainable in contaminated fields. Studies of L. rubellus colonizing a metal-contaminated experimental sludge-treated field showed that a reduced rate of colonization can already be associated with an average body Cu concentration of 25 mg kg⁻¹. However, in this particular field situation mixture effects of other metals that were also present in the soil and the occurrence of avoidance behaviour during colonization may have contributed to this low internal toxicity threshold. It is concluded that the CBR approach seems to be a feasible option for use as a tool in a bioavailability-based soil quality assessment, even for essential trace metals like copper, but that further insight may be needed to establish the uncertainty and reliability of the application in environmental quality assessment and decision making.     

潮间带沉积物中重金属污染评价及生物有效性研究进展

潮间带是一个典型的环境脆弱带和敏感带,极易受到人类活动的破坏.潮间带重金属除了直接对潮间带生物有影响外,还可以通过过食物链的富集和放大作用影响人类健康,同时由于潮间带水动力和生物活动的影响,造成重金属的重新分布和释放,产生重金属的"二次污染",直接危害近岸环境.开展重金属元素在潮间带沉积物中含量、赋存形态、污染评价及其生物有效性已成为目前环境科学领域中十分重要的研究内容和任务,国内外学者均对河流沉积物重金属污染开展了大量的研究.文章从这4个方面阐述了潮间带沉积物重金属研究进展,以期为潮间带沉积物重金属研究提供一定的参考.     

Effects of modified Pb-, Zn-, and Cd- availability on the microbial communities and on the degradation of isoproturon in a heavy metal contaminated soil

The effects of modified heavy metal (HM) availability on the microbial community structure and on the microbe-mediated degradation of herbicide isoproturon (IPU) were evaluated in soil with a long-term HM contamination. The fate of ¹⁴C-ring labelled IPU was investigated for over 60 days under controlled microcosm conditions. Phosphate mineral apatite and a water solution of Pb, Zn, and Cd salts were previously homogeneously mixed into the soil material to reduce and to increase the proportion of bioavailable HM, respectively. The availability of Pb, Zn, and Cd was determined by HM fractionation and plant uptake 110 days after the addition of amendments, shortly before IPU addition. Apatite treatment reduced the availability of HM, but did not affect the microbial biomass and the microbial community structure on the genotype level (total soil DNA-RAPD). However, it changed the microbial community structure on the phenotype level, based on the composition of phospholipid fatty acids (PLFA) at the end of the degradation experiment. The degradation of IPU did not change. In contrast to apatite treatment, HM supplementation increased the bioavailability of Pb, Zn and Cd, which resulted in biomass reduction and changes of microbial community structure on the genotypic (total soil DNA-RAPD) and phenotypic (PLFA) level. Increased bioavailability of HM also significantly reduced the rate of IPU degradation and mineralisation. The total mineralisation over a period of 60 days decreased from 12 to 5% of initial ¹⁴C. Increased HM bioavailability did not influence the degradation pathways and kinetics of IPU.