柱切换HPLC法研究米托蒽醌毫微粒冻干静脉注射剂的药代动力学

建立了血浆中米托蒽醌的柱切换高效液相色谱测定法,测定和比较了米托蒽醌溶液型注射剂和毫微粒冻干静脉注射剂在家兔体内的血药曲线,并研究比较了二者的药代动力学参数。米托恩醌毫微粒冻干注射剂使米托蒽醌在血中浓度大为降低,血中分布容积增大了近5倍,体内平均驻留时间延长了2倍多。表明米托蒽醌毫微粒有明显的体内长效作用,结合其体内分布试验研究结果,表明其具有明显肝靶向分布作用。     

人工牛黄的光解

人工牛黄是广泛用于中成药配方的中药代用品。本文用漫反射光谱法研究了人工牛黄样品在人工光源照射下发生颜色变化的光解规律:在三种光源下,其光解均属二步表观一级反应动力学,即光解曲线是由两段斜率不同的直线组成,初期的光解速度较其后的快2倍左右;不同光源下,紫外灯光解速度最快,荧光高压汞灯次之,碘钨灯最慢;表观光解常数与光波长有关,但基本不随光强度和照射时间乘积改变。而光解时间则与光强度成反比。从得到的动力学方程可预测不同条件下的褪色时间。研究表明,人工牛黄复方中,发生光解的主要成分是胆红素,其余成分不发生引起颜色变化的光解,但在第二步反应中对胆红素的光解有明显影响。     

The fathead minnow in aquatic toxicology: past, present and future

This paper reviews the roles of the fathead minnow (Pimephales promelas) as a small fish model in the field of aquatic toxicology. The species has been (and is) extensively used both for regulatory testing and research, especially in North America. For example, tests with the fathead minnow, ranging from 48-h lethality through partial and full life-cycle assays, are routinely used for regulatory programs aimed at assessing potential risks of new chemicals such as high-production volume materials and pesticides, as well as impacts of complex mixtures like effluents. The species also has been used for a wide variety of research applications focused on topics like the development of quantitative structure-activity relationship models, mixture toxicity, extrapolation of the effects of chemicals across species, and understanding the results of laboratory assays relative to impacts in the field. Attributes of the fathead minnow also make it an excellent model for addressing new challenges in aquatic toxicology, including identification of sensitive life-stages/endpoints for chemicals with differing modes/mechanisms of action, predicting population-level effects based on data collected from lower levels of biological organization, and exploring/understanding the emerging role of genomics in research and regulation.     

Pathogenesis of shigella diarrhea. VII. Evidence for a cell membrane toxin receptor involving β1 {arrow} 4-linked N-acetyl-D-glucosamine oligomers

The binding of ShigeUa dysenteriae 1 cytotoxin to HeLa cells in culture and to isolated rat liver cell membranes was studied by means of an indirect consumption assay of toxicity from the medium, or by determination of cytotoxicity to the HeLa cell monolayer. Both liver cell membranes and HeLa cells removed toxicity from the medium during incubation, in contrast to WI-38 and Y-1 mouse adrenal tumor cells, both of which neither bound nor were affected by the toxin. Uptake of toxin was directly related to concentration of membranes added, time,and temperature, and indirectly related to the ionic strength of the buffer used. The chemical nature of the membrane receptor was characterized by using three principal approaches: (a) enzymatic sensitivity; (b) competitive inhibition and (c) receptor blockade studies. The receptor was destroyed by proteolytic enzymes, phospholipases (which markedly altered the gross appearance of the membrane preparation) and by lysozyme, but not by a variety of other enzymes. Of 28 carbohydrate and glycoprotein haptens studied, including cholera toxin and ganglioside, only the chitin oligosaccharide lysozyme substrates, per N-acetylated chitotriose, chitotetraose, and chitopentaose were effective competitive inhibitors. Greatest inhibition was found with the trimer, N, N’, N” triacetyl chitotriose. Of three lectins studied as possible receptor blockers, including phytohemagglutinin, concanavalin A, and wheat germ agglutinin, only the latter, which is known to possess specific binding affinity for N, N’, N” triacetyl chitotriose, was able to block toxin uptake. Evidence from all three approaches indicate, therefore, existence of a glycoprotein toxin receptor on mammalian cells, with involvement of oligomeric β1{arrow}4-1inked N-acetyl glucosamine in the receptor. This receptor is clearly distinct from the G(M1) ganglioside thought to be involved in the binding of cholera toxin to the cell membrane of a variety of cell types susceptible to its action.     

Evaluation of a commercial kit for measuring vitellogenin in the fathead minnow (Pimephales promelas)

Vitellogenin (vtg) concentrations in oviparous animals such as fish represent an integrated indicator of the status of the reproductive endocrine system. As such, vtg is a common measurement endpoint in tests designed to detect certain classes of endocrine-disrupting chemicals (EDCs). The most common approach to measuring vtg is via enzyme-linked immunosorbent assays (ELISAs). However, because labs testing EDCs in fish often use slightly different ELISAs (e.g., in terms of antibodies, binding antigens, standards), results among studies are not always comparable. One approach to obviating this would be for researchers to use standardized ELISA kits from a common source(s). The fathead minnow (Pimephales promelas) is a small fish model commonly used for EDC testing. The purpose of this study was to evaluate a recently developed commercial ELISA kit for measuring vtg in the fathead minnow. The commercial ELISA, based on a monoclonal antibody to fathead minnow vtg, was compared to an ELISA that utilizes a fathead minnow polyclonal antibody, which has been used extensively in our lab and others for several years. Plasma samples for this comparison came from three studies in which fathead minnows had been exposed to different model EDCs, including an androgen (17beta-trenbolone), an anti-androgen (flutamide), and two CYP19 (aromatase) inhibitors (prochloraz, fadrozole). Results obtained using the two different ELISA methods were consistently similar.     

Screening and testing for endocrine disruption in fish-biomarkers as "signposts," not "traffic lights," in risk assessment

Biomarkers are currently best used as mechanistic "signposts" rather than as "traffic lights" in the environmental risk assessment of endocrine-disrupting chemicals (EDCs). In field studies, biomarkers of exposure [e.g., vitellogenin (VTG) induction in male fish] are powerful tools for tracking single substances and mixtures of concern. Biomarkers also provide linkage between field and laboratory data, thereby playing an important role in directing the need for and design of fish chronic tests for EDCs. It is the adverse effect end points (e.g., altered development, growth, and/or reproduction) from such tests that are most valuable for calculating adverseNOEC (no observed effect concentration) or adverseEC10 (effective concentration for a 10% response) and subsequently deriving predicted no effect concentrations (PNECs). With current uncertainties, biomarkerNOEC or biomarkerEC10 data should not be used in isolation to derive PNECs. In the future, however, there may be scope to increasingly use biomarker data in environmental decision making, if plausible linkages can be made across levels of organization such that adverse outcomes might be envisaged relative to biomarker responses. For biomarkers to fulfil their potential, they should be mechanistically relevant and reproducible (as measured by interlaboratory comparisons of the same protocol). VTG is a good example of such a biomarker in that it provides an insight to the mode of action (estrogenicity) that is vital to fish reproductive health. Interlaboratory reproducibility data for VTG are also encouraging; recent comparisons (using the same immunoassay protocol) have provided coefficients of variation (CVs) of 38-55% (comparable to published CVs of 19-58% for fish survival and growth end points used in regulatory test guidelines). While concern over environmental xenoestrogens has led to the evaluation of reproductive biomarkers in fish, it must be remembered that many substances act via diverse mechanisms of action such that the environmental risk assessment for EDCs is a broad and complex issue. Also, biomarkers such as secondary sexual characteristics, gonadosomatic indices, plasma steroids, and gonadal histology have significant potential for guiding interspecies assessments of EDCs and designing fish chronic tests. To strengthen the utility of EDC biomarkers in fish, we need to establish a historical control database (also considering natural variability) to help differentiate between statistically detectable versus biologically significant responses. In conclusion, as research continues to develop a range of useful EDC biomarkers, environmental decision-making needs to move forward, and it is proposed that the "biomarkers as signposts" approach is a pragmatic way forward in the current risk assessment of EDCs.     

Mammography phototimer technique chart

A phototimer technique chart for mammography is presented along with the methodology used to design it. The chart is based on accurate measurement of breast thickness and helps overcome the inability of the phototimer to track as breast thickness varies. In clinical practice, the chart results in the consistent attainment of optimally exposed films and decreased number of retakes.     

Ecotoxicogenomics: linkages between exposure and effects in assessing risks of aquatic contaminants to fish

Understanding the biological effects of exposures to chemicals in the environment relies on classical methods and emerging technologies in the areas of genomics, proteomics, and metabonomics. Linkages between the historical and newer toxicological tools are currently being developed in order to predict and assess risk. Being able to classify chemicals and other stressors based on effects they have at the molecular, tissue, and organismal levels helps define a systems biology approach to development of streamlined, cost-effective, and comprehensive testing approaches for evaluating environmental hazards. The challenges of the individual technologies and the combinations of tools for ecotoxicogenomics are discussed in application to aquatic toxicology with a particular emphasis on fish testing.