肌注和口服药饵麻保沙星在日本对虾体内的药代动力学比较

在水温(25±0.6)℃条件下,分别以10、10和30 mg/kg剂量给健康日本对虾血窦注射、肌注和口服药饵麻保沙星后,用高效液相色谱法测定药物浓度,采用DAS2.0药动学软件对血药浓度进行分析,主要比较了肌注和口服药饵两种给药方式下麻保沙星在日本对虾体内的药代动力学差异。结果显示,血窦注射给药后,麻保沙星在日本对虾体内药物动力学最佳模型为无级吸收二室开放模型,表达方程为:C血窦注射=13.373e–1.396 t+8.28e–0.062 t;肌注和口服药饵麻保沙星后,在日本对虾体内的代谢过程均符合一级吸收二室开放模型,表达方程为C肌肉注射=15.521e–1.153t+7.90e–0.059t-23.421e–11.73t,C口服药饵=17.486e–0.33t+3.01e–0.051t-20.496e–0.408t。与口服药饵给药后药代动力学参数比较,肌注给药后的tmax(0.25 h)、t1/2Ka(0.059 h)、t1/2α(0.601 h)和t1/2β(11.769 h)均小于口服药饵给药的tmax(0.5 h)、t1/2Ka(1.697 h)、t1/2α(2.103 h)和t1/2β(13.535 h),且Cmax(20.7858 mg/L)和F(99.56%)均大于口服药饵给药Cmax(12.4774mg/L)、F(69.68%)。结果表明,肌注麻保沙星在日本对虾体内的吸收、分布和消除均快于口服药饵给药,且比口服给药吸收较完全。本实验将药动学参数与抗菌后效应(PAE)和最小抑菌浓度(MIC)相结合来探讨麻保沙星的给药方案,建议在治疗日本对虾细菌性疾病时,肌注14.30 mg/kg,每隔13.6 h一次;口服19.17 mg/kg,每隔11.8 h一次。     

噁喹酸在大菱鲆体内的药代动力学研究

采用高效液相色谱法,研究了(24.5±0.2)℃水温条件下单次静注和口服给药后噁喹酸在健康大菱鲆体内的代谢动力学规律.结果显示,大菱鲆单次口服嗯喹酸(20mg/kg)后,药物在血浆中经时过程符合一级吸收二室开放模型,表达方程为C口服 =2.059e-0.062t +0.645e-0.023t-2.704e-0.202t,单次静注嗯喹酸(10mg/kg)后,药物在血浆经时过程符合无级吸收二室开放模型,表达方程为C静注=12.284e-0.144 +0.284e-0.027t.血浆中的主要药动学参数,静注的t1/2α (4.813 h)、t1/2β(25.441h)、tmax(0.083 h)均小于口服给药(11.26、30.212、6h).结果表明,静注嗯喹酸在大菱鲆体内的吸收、消除速度,达峰时间均快于口服给药.根据本实验的结果,嗯喹酸的合理给药方案为:建议口服给药按鱼体重21.41mg/kg,每日1次给药,连用5～7 d.     

氟苯尼考在中国对虾体内消除规律的研究

采用口服药饵的方法研究氟苯尼考在中国对虾体内的代谢动力学和残留规律,用反相高效液相色谱测定氟苯尼考在对虾组织中的含量。结果表明:中国对虾连续5 d口服氟苯尼考药饵,高、低2种剂量(16 mg/kg.d和8 mg/kg.d)组的药物代谢动力学变化趋势相似,高剂量组的组织中药物含量远高于低剂量组,肝脏中的药物浓度远大于肌肉中的药物浓度,氟苯尼考在对虾体内的消除速度较快,低剂量组的消除速度比高剂量组快,2种剂量的药物在对虾肌肉中的消除曲线方程分别为C(t)高=0.247 3 e-0.015 5 t和C(t)低=0.118 2 e-0.043 2 t,消除半衰期分别为44.71 h和16.04 h。在本试验条件下,高、低2种剂量的氟苯尼考在肌肉组织中降到0.01,0.05,和0.1μg/g不同浓度水平的理论时间为:207,103,58,57,20和4 h。     

诺氟沙星2种不同给药方式在中国对虾体内的残留及消除规律

在水温(28±1)℃条件下,诺氟沙星药浴给药(10 mg·L-1)和药饵给药(30 mg·kg-1)连续5 d后,利用反相高效液相色谱法(RP-HPLC)分析诺氟沙星在中国对虾体内的残留及消除规律。结果表明,2种给药方式下,诺氟沙星在中国对虾肝胰腺、肌肉等组织中的分布和消除差别较大。药浴给药后中国对虾肝胰腺和肌肉中药物达峰时间分别为9和24 h,药峰浓度分别为1.36,0.25μg.g-1,消除半衰期分别为29.87和40.19 h;药饵给药后中国对虾肝胰腺和肌肉中药物达峰时间均为4 h,药峰浓度分别为0.79,0.113μg.g-1。2种给药方式下药物在对虾肌肉中的消除曲线分别为C(t)浴=0.2449e-0.4138t和C(t)饵=0.4066e-0.5364t;消除半衰期分别为40.19和31.01 h。根据诺氟沙星在水产品中的残留限量标准(50μg·kg-1),2种给药方式下,肌肉中诺氟沙星浓度均在给药后24 h低于此残留限量;肝胰腺中浓度经药浴给药后216 h低于此残留限量,药饵给药后96 h低于此残留限量。药浴给药和药饵给药后,肌肉中药物浓度达到此残留限量的休药期分别为3.84和3.90 d。     

恩诺沙星在菲律宾蛤仔体内的消除规律研究

以5mg/L恩诺沙星浸浴菲律宾蛤仔(Ruditapes philippinarum)24h,取血液、鳃、内脏团、足、闭壳肌5种组织,反相高效液相色谱法测定其中的药物浓度。结果表明,恩诺沙星按一级动力学过程从体内消除,在5种组织中消除速率快慢不一,其在菲律宾蛤仔血液、鳃、内脏团、足、闭壳肌中的消除曲线方程分别为c=6.995e-0.0853t,c=2.7957e-0.1177t,c=1.539e-0.1013t,c=1.7015e-0.1535t,c=2.010e-0.1414t,消除半衰期T1/2分别为6.284,5.889,6.483,4.516,3.679h。恩诺沙星在水产品中的最大残留限量为50μg/kg,在本实验条件下,建议临床休药期不小于2d。     

氟苯尼考在九孔鲍体内的药代动力学初步研究

初步研究了新型抗菌兽药氟苯尼考(florfenicol)在健康九孔鲍体内的药代动力学特征;建立了高效液相色谱法(HPLC)检测鲍血淋巴中氟苯尼考含量的可靠方法,平均回收率为85.69%,最低检测限0.05μg/cm3.以20×10-6(m/m)剂量对九孔鲍腹足单次肌注,血药浓度-时间数据用非房室模型的统计矩原理(SMT)处理后的主要药代动力学参数为:血药浓度-时间曲线下面积(AUC)为21.25mg/(h.dm3),平均滞留时间(MRT)为2.41h,清除率(C lB)为0.94dm3/(kg.h),稳态表观分布容积[Vd(ss)]为2.27dm3/kg,消除半衰期(t1/2β)为3.61h.结果显示氟苯尼考在九孔鲍体内吸收良好,分布广泛,代谢消除快.     

不同温度下氟苯尼考在大菱鲆体内的药代动力学研究

研究了14和17℃2种不同养殖温度下,氟苯尼考在健康大菱鲆(Scophthalmus maximus)体内的药代动力学特征。以15mg/kg BW的剂量经静注和口灌2种方式给药后,于0.25、0.5、1、2、4、6、8、12、16、24、48和96h采集血液样品,采用Agilent1200型高效液相色谱仪测定样品中药物的含量,药时数据采用DAS2.0自动药动学软件进行分析。研究显示,14和17℃下,静注给药后的消除相半衰期(t1/2β)分别为18.20和12.46h,表观分布容积(Vd)分别为0.03和0.11L/kg,清除率(CL)均为0.02L/(h·kg)。口灌给药后血药浓度均在12h达到峰值,分布相半衰期(t1/2α)分别为2.84和4.08h,消除相半衰期分别为14.48和12.45h,生物利用度(F)分别为17.02%和18.24%。研究结果表明,温度升高会加快大菱鲆对氟苯尼考的吸收、体内分布和消除,提高口灌方式氟苯尼考利用效率。结合氟苯尼考药效学研究结果,提出给药方案:14℃时,大菱鲆口灌给药剂量25mg/kg BW,每日一次;17℃时,大菱鲆口灌给药剂量22mg/kg BW,每日一次。     

凡纳滨对虾摄食诺氟沙星强化卤虫的药代动力学研究

应用高效液相色谱法研究了凡纳滨对虾(Litopenaeus vannamei)摄食诺氟沙星强化卤虫(Artemia)的药物代谢动力学。结果表明:强化4~8 h,卤虫体内的药物质量浓度达到最高,此后卤虫体内药物摄入和排除达到一个动态平衡;温度影响诺氟沙星在卤虫体内半衰期:体长3mm和6 mm的卤虫,在4,16,28℃时的半衰期分别为51.33,19.29,18.64 h和39.67,13.26,12.6 h。对虾摄食诺氟沙星强化的卤虫后,对虾组织中药物质量浓度经时过程符合一级吸收二室开放模型;投喂剂量对Tmax和Cmax影响较大,当对虾给药质量分数分别为800,400,200mg/kg时,肌肉中给药后出现最高血药的时间或达峰时间分别为0.403,0.540,0.481 h;肝胰脏中给药后出现最高血药的时间或达峰时间分别为0.826,1.839,1.469 h;肌肉中给药后的最高血药质量浓度分别为98.943,46.752,10.887 mg/L;肝胰脏中给药后的最高血药质量浓度分别为738.267,597.352,415.268 mg/L。药物在对虾肌肉的消除半衰期(约26.688 h)明显长于肝胰脏中消除半衰期(约13.988 h)。     

甲基睾丸酮在尼罗罗非鱼(Oreochromis niloticus)肌肉中的代谢和消除规律研究

在实验水温(28±2)℃条件下,以60mg/kg单剂量甲基睾丸酮对尼罗罗非鱼混饲口灌给药后,采用超高效液相色谱-串联质谱联用(UPLC-MS/MS)法测定尼罗罗非鱼肌肉中的药物水平,研究甲基睾丸酮在尼罗罗非鱼肌肉中的代谢及消除规律。结果表明,肌肉中药物浓度时间数据符合一级吸收二室开放模型,主要药代动力学参数达峰时间T(peak)为3.04h,质量浓度C(max)为33.331ng/g,消除半衰期T(1/2)β为23.073h。肌肉中甲基睾丸酮浓度24h内呈指数型下降,具有较高的消除速率,其后消除得较缓慢,消除方程符合C=46.18e0.101t。29d后罗非鱼肌肉中甲基睾丸酮水平在美国FDA的检测限0.8ng/g以下,给药120d后肌肉中检测不到甲基睾丸酮残留。     

土霉素在牙鲆体内的药代动力学研究

采用高效液相色谱法为定性、定量手段,研究土霉素在牙鲆(Paralichthys olivaceus)体内的药代动力学过程,采用DAS(Drug and Statistics)药代动力学程序对数据进行分析.结果表明,牙鲆单剂量口服土霉素后(200 mg/kg),血药经时过程符合二室模型,主要动力学参数如下:吸收半衰期(T(1/2)a)为10.043 h,单剂量给药后牙鲆体内出现最高质量分数的时间(Tmax)为4.000 h,单剂量给药后牙鲆体内最高血药质量分数(Cmax)为0.54 mg/L,药时曲线下总面积(CAU0-72)为17.15 (mg*h)/L,吸收速率常数(Ka)为0.223,消除速率常数(k)为0.476 h-1.牙鲆肌肉中土霉素的经时过程符合一级吸收一室模型,主要动力学参数:T(1/2)a为74.893 h,Tmax为4.000 h,Cmax为3.58 mg/L,CAU0-72为148.56 (mg*h)/L,Ka为0.731,k为2.991 h-1.牙鲆肝脏中土霉素的经时过程符合一级吸收一室模型,主要动力学参数:T(1/2)a为31.376 h,Tmax为4.000 h,Cmax为13.78 mg/L,CAU0-72为494.14 (mg*h)/L,Ka为0.876,k为4.940 h-1.     

Microbial Biomass and Organic Nutrients in the Deep-Sea Sediments of the Central Indian Ocean Basin

In order to assess the impact of deep-sea mining on the in situ benthic life, we measured the microbial standing stock and concentration of organic nutrients in the deep-sea sediments of the Central Indian Ocean Basin in the Indian pioneer area. Sediments were collected using box core and grab samples during September 1996. The total bacterial numbers ranged from 10 10 -10 11 cells per g -1 dry weight sediment. There was a marginal decrease in the number of bacteria from surface to 30 cm depth, though the subsurface section registered a higher number than did the surface. The highest numbers were encountered at depths of 4-8 cm. The retrievable number of bacteria were two orders less in comparison with the direct total counts of bacteria. An almost homogeneous distribution of bacteria, total organic carbon, living biomass, and lipids throughout the depth of cores indicates active microbial and benthic processes in the deep sea sediments. On the other hand, a uniform distribution of total counts of bacteria, carbohydrates, and total organic carbon in all the cores indicates their stable nature and suggests that they can serve as useful parameters for long-term monitoring of the area after the benthic disturbance. Further studies on temporal variability in this region would not only verify the observed norms of distribution of these variables but would also help to understand restabilization processes after the simulated benthic disturbance.     

Assessing the Validity of Seismo-Acoustic Predictor Equations for Obtaining Seabed and Sub-Surface Sediment Physical Properties

The interdependence between the seismo-acoustic properties of a marine sediment and its geotechnical/physical parameters has been known for many years, and it has been postulated that this should allow the extraction of geotechnical information from seismic data. Though in the literature many correlations have been published for the surficial layer, there is a lack of information for greater sediment depths. In this article, a desktop study on a synthetic seafloor model illustrates how the application of published near-surface prediction equations to subsurface sediments (up to several tens of meters burial depth) can lead to spurious predictions. To test this further, acoustic and geotechnical properties were measured on a number of sediment core samples, some of which were subjected to loading in acoustically-equipped consolidation cells (oedometers) to simulate greater burial depth conditions. For low effective pressures (representing small burial depths extending to around 10 meters subsurface), the general applicability of established relationships was confirmed: the prediction of porosity, bulk density, and mean grain size from acoustic velocity and impedance appears generally possible for the investigated sedimentary environments. As effective pressure increases through, the observed relationships deviate more and more from the established ones for the near-surface area. For the samples tested in this study, in some instances increasing pressure even resulted in decreasing velocities. There are several possible explanations for this abnormal behavior, including the presence of gas, overconsolidation, or bimodal grain size distribution. The results indicate that an appropriate depth correction must be introduced into the published prediction equations in order to obtain reliable estimates of physical sediment properties for greater subsurface depths.     

A Review of Some Environmental Issues Affecting Marine Mining

This article reviews information recently available from existing marine and coastal mining for responses to environmental issues affecting marine mining at different depths. It is particularly but not exclusively concerned with those issues affecting seabed biodiversity impact and recovery. Much information has been gathered in the past 10 years from shallow mining operations for construction aggregate, diamonds, and gold, from coastal mines discharging tailings to shallow and deep water, and from experimental deep mining tests. The responses to issues identified are summarized in a series of eight tables intended to facilitate site-specific consideration. Since impacts can spread widely in the surface mixing layer SML, and can affect the biologically productive euphotic zone, the main issues considered arise from the depth of mining relative to the SML of the sea. Where mining is below the SML, the issue is whether it is environmentally better to bring the extraction products to the surface vessel for processing (and waste discharge), or to process the extraction products as much as possible on the seabed. Responses to the issues need to be sitespecific, and dependent on adequate preoperational environmental impact and recovery prediction. For deep tailings disposal from a surface vessel, there are four important environmental unknowns: (1) the possible growth of "marine snow" (bacterial flocs) utilizing the enormous quantities of fine tailings particles (hundreds or thousands of metric tons per day) as nuclei for growth, (2) the possibility that local keystone plankton and nekton species may migrate diurnally down to and beyond the depth of deep discharge and hence be subjected to tailings impact at depth, (3) the burrow-up capability of deep benthos and their ability to survive high rates of tailings deposition, and (4) the pattern and rate of dispersion of a tailings density current through the deep water column from discharge point to seabed. Actions to obtain relevant information in general and site-specifically are suggested.     

Increased Particle Fluxes at the INDEX Site Attributable to Simulated Benthic Disturbance

Particle fluxes were measured 7 m above the sea bottom during the predisturbance, disturbance, and postdisturbance periods by using time series sediment traps attached to seven deep-sea moorings deployed in the INDEX experiment site in the Central Indian Basin. The predisturbance particle fluxes varied between 22.3 to 55.1 mg m -2 day -1 . Increased and variable particle fluxes were recorded by the sediment traps during the disturbance period. The increase observed was 0.5 to 4 times more than the background predisturbance fluxes. The increases in particle fluxes (~4 times) recorded by the sediment trap located in the southwestern direction (DMS-1) were the greatest, which could be the result of preferential movement of resuspended particles generated during the deep-sea benthic disturbance along the general current direction prevailing in this area during the experimental period. Also, the traps located closer to the disturbance area recorded greater fluxes than did the traps far away, across the Deep Sea Sediment Resuspension System path. This variability in recorded particle fluxes by the traps around the disturbance area clearly indicates that physical characteristics such as grain size and density of the resuspended particles produced during the disturbance had an important effect on particle movement. The postdisturbance measurements during ~5 days showed a reduction in particle fluxes of ~50%, indicating rapid particle settlement.     

Geoacoustic Inversion via Genetic Algorithm and Its Application to Manganese Sediment Identification

An acoustic inversion method using a wide-band signal and two near field receivers is proposed and applied to multiple layered seabed models including a manganese sediment. The inversion problem can be formulated into a probabilistic model comprised of signals, a forward model, and additive noise. The forward model simulates wide-band signals, such as chirp signals, and is chosen to be the source-waveletconvolution plane wave modeling method. The wavelet matching technique, using weighted least-squares fitting, estimates the sediment sound-speed and thickness on which determination of the possible numerical ranges for a priori uniform distribution is based. The genetic algorithm is applied to a global optimization problem to find a maximum a posteriori solution for determined a priori search space. Here the object function is defined by an L 2 norm of the difference between measured and modeled signals. Not only the marginal pdf but also its statistics are calculated by numerical evaluation of integrals using the samples selected during importance sampling process of the genetic algorithm.     

海上大直径钢管桩打桩过程中桩周土强度弱化研究

海上大直径钢管桩打桩过程中,桩周土体受到强烈扰动而发生强度弱化,掌握桩周土体强度弱化规律对于准确预测打桩过程、保证工程安全具有重要意义。为研究土体强度弱化规律,开展了环剪试验模拟打桩对桩周土体的扰动,测试土体强度随剪切速率的变化规律,建立了描述土体强度弱化规律的拟合公式,引入到打桩分析软件中。研究结果表明：土体的强度折减程度不仅与土体本身的性质有关还受到土体的埋深和剪切速率的影响,埋深越深土体强度折减程度越低,剪切速率越高土体强度折减越高,在打桩分析中可采用这里推荐的线性折减方法来模拟不同深度处土体强度的折减规律。     

Determination of In Situ Sediment Shear Strength from Advanced Piston Corer Pullout Forces

The advanced piston corer (APC) has been used by the Ocean Drilling Program since 1985 for recovering soft sediments from the ocean floor. The pullout force measured on extracting the core barrel from the sediment is shown to correlate with the average shear strength of the sediment core measured in the ship's laboratory. A simple rule of thumb is derived relating the shear strength of the sediment to the pullout force. Multiple APC holes at individual sites allow the consistency of the pullout measurements to be assessed. The effects of different operational procedures during APC coring are also explored. Although generally applicable, the correlation between pullout force and laboratory measurements of shear strength breaks down for some APC holes, possibly because of the disturbance of some sediment types during the APC coring process. A better understanding of the physical process of APC coring, and its effect on the properties of the sediment both inside and immediately outside the core barrel, would indicate what confidence can be put on the measurement of pullout force as a way of evaluating the in situ shear strength of deep sea sediments.     

Interannual Sea Level Variations and Annual Tides in the Northwestern Pacific

Specific properties of the interannual sea level variations and annual tides in the Northwestern Pacific were studied. Several tide stations were monitored. The monthly mean sea level for the year of 1995 was analyzed at each tide station. A seismic event in 1995, some tectonic activity around the subject area, and the Kuroshio (the oceanic western boundary current) may possibly contaminate results which would have occurred from the astronomical annual tide alone.     

Flow Cytometric Analysis of Coastal Lagoon Bacterioplankton and Picophytoplankton: Fixation and Storage Effects

The effect of different fixation and storage protocols on the flow cytometric (FCM) simultaneous analysis of bacterioplankton and phytoplankton in coastal seawater samples (Mediterranean coastal lagoons) was investigated. FCM measurements (cell number, fluorescence and scatter characteristics) were obtained through DAPI staining. Three fixatives [glutaraldehyde (GA), formaldehyde (FA) and paraformaldehyde (PFA)] and two storage (3 months duration) methods (5 °C and −196 °C) were tested. Two dominant populations were detected in studied samples: bacteria and eukaryotic picophytoplankton. Adding fixatives (2% final concentration) appears necessary to obtain FCM exhaustive counts of all the bacteria and phytoplanktonic cells. This was related to the permeation effect of fixatives which allowed a better DAPI staining of the cells. Maximum fluorescence, i.e. optimal staining of the cells was obtained with FA or PFA, and significant lower fluorescences with GA. Fixed samples stored at 5 °C induced rapid cell loss. Only storage in liquid nitrogen of samples fixed with FA or PFA, allows mid-term (≥4 months) preservation of bacteria or picophytoplankton cell numbers, and limited evolution of DAPI-induced fluorescence and scatter characteristics.