Supplement to the Carcinogenic Potency Database (CPDB): results of animal bioassays published in the general literature through 1997 and by the National Toxicology Program in 1997-1998.

The Carcinogenic Potency Database (CPDB) is a systematic and unifying resource that standardizes the results of chronic, long-term animal cancer tests which have been conducted since the 1950s. The analyses include sufficient information on each experiment to permit research into many areas of carcinogenesis. Both qualitative and quantitative information is reported on positive and negative experiments that meet a set of inclusion criteria. A measure of carcinogenic potency, TD(50) (daily dose rate in mg/kg body weight/day to induce tumors in half of test animals that would have remained tumor-free at zero dose), is estimated for each tissue-tumor combination reported. This article is the ninth publication of a chronological plot of the CPDB; it presents results on 560 experiments of 188 chemicals in mice, rats, and hamsters from 185 publications in the general literature updated through 1997, and from 15 Reports of the National Toxicology Program in 1997-1998. The test agents cover a wide variety of uses and chemical classes. The CPDB Web Site (http://potency.berkeley.edu/) presents the combined database of all published plots in a variety of formats as well as summary tables by chemical and by target organ, supplemental materials on dosing and survival, a detailed guide to using the plot formats, and documentation of methods and publications. The overall CPDB, including the results in this article, presents easily accessible results of 6153 experiments on 1485 chemicals from 1426 papers and 429 NCI/NTP (National Cancer Institute/National Toxicology program) Technical Reports. A tab-separated format of the full CPDB for reading the data into spreadsheets or database applications is available on the Web Site.     

Biological Markers of Environmental Contamination in Marine Ecosystems: Biomar Project Coordinating Group

Biochemical markers measured in marine animals can be investigated to improve their detection, quantification and to understand the significance of their exposure to contaminants in the marine environment. The main objectives of the BIOMAR project are the following: (i) Getting a better knowledge about biological mechanisms developed by marine organisms (mussel, fish, sea star, sea urchin) in coastal environments under the effects of contaminants, by in virro and in vivo experiments; (ii) Investigation of the relationship between biochemical markers measured in marine organisms and chemical pollutants (aromatic compounds, PCB, heavy metals) determined in the marine environment (sediment, water and biota); (iii) Characterization of the criteria and physiological/biochemical/cellular parameters for an efficient coastal contamination biomonitoring program based on biomarkers; and (iv) Automation of biomarker measurements for routine and onboard analysis. An overview of the results is presented from laboratory and field experiments with multimarker and multispecies approaches as the main objective.     

统计模拟分光光度法测定氨基酸注射液诸组分含量

应用统计模拟分光光度法同时测定复方制剂组分含量．在复方制剂合格限的（８７±１７）％范围内，以２％浓度单位递增，利用均匀设计法设计实验方案配制１７水平的合成样品液，绘制其溶液的紫外吸收光谱，选择组分含量随吸光度变化大的灵敏波长，并测出对应的吸光度，用逐步回归法构造反映该复方制剂在灵敏波长下吸光度与组分含量关系的数学模型；根据构造的数学模型，在计算机上算出诸组分含量在含量合格限范围内的详尽组合．在测定未知样品时，只须在灵敏波长下测得其溶液的吸光度，采用全组合法寻优，求出未知样品诸组分含量．     

中药大黄质量的化学模式识别

本文用PRIMA法对大黄属(Rheum)6种植物的29个样品的质量进行了化学模式识别研究。以泻下药理实验的结果佐证、核对。根据35维HPLC数据或16维UV数据,与SIMCA法、Bayes判别法、非线性映照法(NLM)等模式识别法比较,PRIMA法具有计算速度快、适用范围广的特点,比植物形态学方法的正确率高。本文还根据一阶导数紫外光谱提供的数据,简化了化学模式识別法鉴定中药大黄的操作步骤。     

蝮蛇抗栓酶化学稳定性的研究

本实验在广泛pH范围内对蝮蛇抗栓酶的化学稳定性进行了研究,测定不同温度下不同pH时的速率常数,得到不同pH时的分解活化能及不同温度下的稳定pH值。活化能数值在pH为6.00及7.60时出现极大值,而不同温度下的两个最稳定(pH)m恰恰落在这两个pH范围内。     

双(β-二酮络)钛(Ⅳ)螯合物的合成及抗肿瘤活性

Nine cis-β-diketonato titanium (Ⅳ) complexes were synthesized and their chemical structures were confirmed by IR,UV spectra and elemental analyses. Among them 6 complexes have not been reported before.Preliminary pharmacological experiments showed that this kind of complexes were active against tumors.     

Mechanisms of star fruit-induced acute renal failure

We have previously discovered that star fruit can induce oliguric acute renal failure. To investigate the mechanisms of star fruit-associated acute oxalate nephropathy, the nephrotoxic effect of star fruit was examined in both cellular experiments and animal models. We evaluated renal function, pathological changes in kidney tissues and apoptotic effects using terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay in four groups of rats -- a control group (CG), fed with tap water (1); a star fruit group (SG), fed with star fruit juice naturally containing 0.2M oxalate (2); and oxalate groups (OxG), fed with 0.2M (3) or 0.4M (4) oxalate solution. The effects of both star fruit juice and oxalate on MDCK cells were also analyzed by flow cytometry. We found that the mean creatinine clearance was significantly lower in the SG, 0.2M OxG and 0.4M OxG. Dose-dependent apoptotic effects were evident from the TUNEL assay, and flow cytometry analysis of treated MDCK cells showed dose- and time-dependent effects. Our findings suggest that star fruit juice produces acute renal injury, not only through the obstructive effect of calcium oxalate crystals, but also by inducing apoptosis of renal epithelial cells, which may be caused by the levels of oxalate in the fruit.     

Treatment of microarray experiments as split-plot designs

This paper shows that microarray experiments are split-plot, or split-unit, designs. The larger size experimental unit (the whole plot) is the array, and the treatment applied to this unit is the treatment given to the cells which produce the cDNA that is hybridized to the array. The smaller size experimental unit (the subplot) is the spot on the array, and the treatment applied to this unit is the gene giving rise to the DNA or oligonucleotide attached at that spot. Various treatment and design structures can be applied to the whole plot and the subplot; we consider the model equations appropriate to different designs. Preliminary normalization of the data can be avoided by including appropriate blocking terms in the model equation. We show how conventional analysis of variance can be used to test for significant differences in expression, and consider multiplicity corrections and graphical methods for identifying important expression differences.     

Studies of pilocarpine:carbomer intermolecular interactions

The interactions between pilocarpine (PIL) and the anionic polyelectrolyte carbomer (CBR) were investigated. The effects of the chemical interactions on the chemical stability of the drug also were evaluated. The binary system was characterized by nuclear magnetic resonance techniques, Fourier-transform infrared spectroscopy (FT-IR), X-ray powder diffraction, scanning electron microscopy (SEM) and thermal analysis. The experiments showed that the complex, prepared by freeze-drying, is a solid amorphous form different from its precursors, thereby offering an interesting alternative for the preparation of extended release matrices. The solution stability of PIL was studied at pH 7 and 8, at 70 °C. The PIL solution stability was evaluated alone and in the presence of CBR. Results indicated that the drug in the presence of the polymer is 3.3 and 3.5 times more stable, at pH 7 and pH 8, respectively, than the drug without CBR. The activation energy and the frequency factor, according to Arrhenius plot, were estimated to be 13.9 ± 0.4 and 14.8 ± 0.5 kcalmol(-1), and 6.1 ± 0.3 and 7.6 ± 0.3, with and without the polymer, respectively.     

人参质量的化学模糊模式识别

模拟中医用药习惯制备25个生态环境和生长年数不同的人参样品的水、酒提取液,用紫外—可见分光光度法、高效液相色谱法和电感偶合等离子体发射光谱法获取反映提取液内化学成分整体的数据。再用抗疲劳作用、抗利尿作用和巨噬细胞吞噬功能测定提取液的生物活性。然后以药理实验的结果为依据对上述化学数据进行特征抽取,求解模糊关系方程,以探明人参疗效权重不同的有效成分和它们的配伍关系。最后通过成分的相关分析,制定出一个评价人参质量的新方案。所提出的方法学对中药质量的评价和中药有效成分的确定具有普遍意义。     

Development and evaluation of an in vitro method for prediction of human drug absorption I. Assessment of artificial membrane composition.

A study was undertaken aimed at developing a dynamic in vitro method based on the use of artificial membranes for screening and prediction of the absorption properties of drugs. The development of a suitable artificial membrane simulating the behaviour of the natural gastrointestinal one is the critical step for the fulfillment of this research and it has been the aim of the present work. A series of filters of different chemical nature and different characteristics (pore size, percent of porosity, thickness) were evaluated and compared in order to select the most suitable one to use as support for the artificial lipid membrane preparation. Permeation experiments were performed by using naproxen as reference model drug. The target was to achieve a naproxen apparent permeability (P(app)) value close to that previously obtained using a Caco-2 cell dynamic methodology (4.88 x 10(-5)cms(-1)), which related well to the fraction of dose absorbed in vivo in human. Filters of cellulose nitrate-acetate mixture with a porosity of 70% and 0.025 microm pore size were selected on the basis of the highest reproducibility of results and suitable drug P(app) value obtained. Mixture design experiments were then carried out in order to optimize the composition of the lipid mixture to use for porous support impregnation to obtain the desired P(app) value. Sixteen different lipid mixtures were prepared according to mixture experimental plan and evaluated by diffusion experiments. The contour plot obtained was used to select an optimum lipidic mixture (cholesterol 2.10%; Lipoid((R)) E 80 1.70%; n-octanol 96.2%) for the cellulose nitrate-acetate membrane impregnation. The experimental response obtained from diffusion experiments performed by utilising the optimised lipidic impregnation mixture, was 4.88 x 10(-5)cms(-1), matching exactly the prefixed target.     

Computer modelling of the binding of non-selective ligands to biological receptors

The application of common linearization methods (logprobit analysis or Hill plot transformation) to the evaluation of receptor binding experiments leads to serious errors, if the ligands used possess insufficient receptor selectivity. The use of simultaneous non-linear curvefitting procedures in this case is recommended and illustrated.     

An expression of within-plate uncertainty in sandwich ELISA

This paper puts forward a method to describe an equation of the within-plate uncertainty (relative standard deviation (R.S.D.) of measurements) as a function of analyte concentration in sandwich enzyme-linked immunosorbent assay (ELISA). A kit for thyroid stimulating hormone is taken as an example. The pipetting procedures of analyte solution and chromogen-substrate solution and absorbance inherent to the wells of a microplate are identified as major error sources and their variability is included as parameters in the uncertainty equation. These parameters can be determined by the experiments with distilled water. The theoretical R.S.D. is shown to be in good agreement with the results of the repeated experiments using the real samples. Since the theory gives a continuous plot of R.S.D. against concentration, the uncertainty structure of the ELISA kit can be recognized over a wide concentration range and the detection limit and quantitation range can easily be determined on the plot.     

Transient inhibition of cyp3a in rats by star fruit juice.

Star fruit juice is a potent in vitro inhibitor of CYP3A; however, few reports are available on the inhibition of CYP3A activities by star fruit juice in vivo. Therefore, in this study, we investigated the CYP3A-mediated star fruit-drug interaction in vivo. The effect of star fruit juice on carbamazepine pharmacokinetics was examined in rats. In comparison with water, the area under the concentration-time curve (AUC) of carbamazepine was approximately 1.3-fold greater when star fruit juice (2 ml) was orally administered 1 h before the oral administration of carbamazepine (50 mg/kg). In contrast, the elimination half-life of carbamazepine and the AUC ratio of carbamazepine 10,11-epoxide to carbamazepine were not altered by the administration of star fruit juice. These results suggest that star fruit juice impairs the function of enteric CYP3A, but not of hepatic CYP3A. In addition, we evaluated the time course of recovery of CYP3A activity that was reduced after the treatment with star fruit juice. The inhibition by star fruit juice was recovered within approximately 24 h. These data suggest that the effect of star fruit juice is mainly reversible and transient. Thus, we discovered that star fruit juice alters the carbamazepine pharmacokinetics in rats.     

壳聚糖与一些化学试剂反应

目的：为壳聚糖寻找适当质量控制方法。方法：通过化学试验,筛选出最佳方法。结果：为壳聚糖检测得到了一些灵敏和明显特征的方法。结论：为壳聚糖进行质量控制提供了一些良好方法。     

MUSCARINIC RECEPTOR INHIBITION AND OTHER EFFECTS OF PANCURONIUM IN THE RABBIT EAR ARTERY PREPARATION

The effect of pancuronium in the rabbit ear artery was investigated in order to measure the inhibition it produces at the prejunctional muscarinic receptor on sympathetic nerve endings in this tissue. Pancuronium (0.1-0.2 mmol/l) produced an enhancement of responses to transmural electrical stimulation but this effect was absent in experiments conducted in the presence of cocaine (10 mumol/l) suggesting that an inhibition of the uptake1 mechanism occurs with pancuronium in this tissue. Pancuronium (10 mumol/l) in the presence of cocaine (10 mumol/l) and yohimbine (1 mumol/l) caused a small transient increase in resting output of tritium from arteries preincubated with 3H-noradrenaline but did not affect stimulated output of tritium nor the perfusion pressure in perfused preparations. Pancuronium in the presence of cocaine or cocaine plus yohimbine caused a parallel shift of the concentration-response curve for the inhibitory effect of carbachol (CCh) on the increase in perfusion pressure induced by nervous stimulation. An Arunlakshana-Schild plot of the data was linear but the slopes of 0.92 and 0.95 respectively, were significantly different from unity (P less than 0.05). The calculated pKB value suggests that pancuronium has a different affinity for prejunctional muscarinic receptors on sympathetic nerve endings in this tissue compared to that previously reported in cardiac or ileal smooth muscle.     

22株星形奴卡菌的临床分布及其耐药性分析

目的：分析星形奴卡菌的临床感染和对抗生素的耐药性,指导临床治疗。方法：对2000年7月～2010年5月从临床分离的星形奴卡菌的临床分布特点,伴随的原发疾病及耐药情况进行回顾分析。结果：星形奴卡菌主要引起呼吸道感染,这种感染常伴随多种原发的基础性疾病,磺胺类药物是治疗星形奴卡菌感染的首选用药。结论：监测本地区星形奴卡菌对药物,特别对磺胺类药物的耐药性,根据药敏试验针对性选用抗菌药物,为临床治疗提供指导意见。     

Thermodynamic basis for expressing dose logarithmically

The current explanations for using a logarithmic scale for the dose of a chemical, administered to a biological system, have all been empirical. There is a fundamental, thermodynamic reason why a logarithmic scale must be used. The chemical potential is the effect that a chemical exerts on any system, including biological systems. The chemical potential of a chemical in any system is directly proportional to the logarithm of its activity or concentration. Lack of understanding of this concept and the consequent use of a linear scale for dose has led to misinterpretation of many biological experiments.     

化学物质成瘾的管理:美沙酮门诊的职责

对化学物质成瘾的管理是一个非常复杂的问题,并且还没有一种简单的方法可以解决这个问题。对每个人的帮助都必须结合各自的生活环境。然而,一般说来还是有一些一般性的准则可以遵循。例如,公共卫生学者们认为疾病的预防非常重要。一级预防、二级预防、三级预防措施成为主要的准则。在这个并不完美的世界里,社会科学家们则热衷于降低危险度。这非常有用,尤其在化学物质成瘾方面以减少供应、减少需求和降低危害为目标时非常有用。临床医生是比较注重实效的人,他们喜欢根据病人的症状和体征治疗疾病,尤其当疾病的病因是多因素的并非常复杂之时。然而,反复复吸这一长期存在的过程是最让人头疼的难题,对于化学物质成瘾者也一样。这样他们就必须向公共卫生学者们或社会科学家们求助。从公共卫生的角度看,化学物质成瘾的初级预防是建立在识别出主要原因的基础之上。通常认为比较突出的两个因素是:第一,某种化学物质的存在;第二,服用这种物质后机体出现渴求效应。我们认为第二个因素引导着第一个因素。可以假设,如果一个人没有任何渴求就不会再使用它了;另一方面,如果出现反复强烈的渴求就会持续不断地去寻求这种物质。这大概就是当一个人成瘾后的情形了。但是,实际上,我们更注重铲除非法物质的存在,而不太注重控制个体对这些物质的渴求。最简单的一种解释就是前一种工作更为简单易行。那么,如果一个人不再受化学物质所约束呢?另外,护理人员往往会采用简单的方法,他们帮助吸毒成瘾者脱毒,并天真地认为这样就可以摆脱毒瘾。但经验告诉我们事实并非如此,脱毒只是对成瘾者管理过程的第一步,许多预防措施(包括预防的复吸、个体和家庭的心理治疗、后期护理等等)以及社会-家庭的支持都是为保持完全戒断的必要步骤。这些都是二级预防和三级预防的措施,这方面医生和非政府组织人员都是专家,但他们需要有足够的财政支持。美沙酮是一种合成的阿片类物质,可用于脱毒,也可用于替代海洛因及其他阿片类药物的成瘾。作为替代药物,它对成瘾者产生的伤害较小,但能保持药物使用者更为稳定的生活功能状态。据了解,吸毒成瘾者更倾向于采取美沙酮维持治疗而不愿意采用脱毒治疗。从社会科学的角度看,通过铲除社会中的非法物质以减少其供应和控制个体渴求以降低对物质的需求是第一步中非常重要的两项措施。医院和社区治疗对消除副作用,并对进一步降低个体对非法药物的需求和保持操守是必要的。用美沙酮、丁丙诺啡或LAAM的替代治疗,以及后来采取的清洁针具交换方案都是用于降低危害的。在所有降低危害的措施中,美沙酮维持治疗(MMT)是国际上较为广泛接受并在2003年后被亚洲国家开始接受的方法。在2003年之前,香港也许是唯一允许开展MMT的亚洲国家。最近几年在亚洲国家MMT的激增表明MMT是受欢迎的。实际上,由于人类免疫缺陷病毒(HIV)的感染传播,MMT已成为人们关注的焦点。现在人们普遍认为MMT通过减少或停止非法物质的口服外给药而防止感染艾滋病是一种有效的措施,这是和化学物质成瘾进一步斗争的砝码,但是否足够呢?MMT对艾滋病的作用是初级预防,但它仅仅是化学物质成瘾的三级预防措施。因此,MMT在防止HIV的传播感染上可能可以带来重大的收获,但在成瘾的预防中则只是一项被动的举措。在后者中,更重要的是要加强初级预防和二级预防,或者,在社会科学家看来,应该减少非法物质的供应和需求。在这些任务中,政府无疑该加强阻止非法药物供应的措施。如何控制个体对非法物质的需求,并对成瘾者加强临床、社会家庭的管理?这些任务需要成瘾这一特殊领域中的临床医师(精神科医生,护士),社会工作者以及临床心理学家的共同努力。换言之,对于政府而言,重要的是控制非法药物的需求并停止非法物质的供应,而且MMT也有助于以降低危害,保持社会功能以及阻止HIV通过血液传播蔓延。但是,还必须有足够的专家和适当的处理设施对成瘾的个体进行管理,并帮助预防其复吸。否则,可能在遏制成瘾蔓延上就没有效果。这可能间接地增加作为艾滋病病毒感染初级预防机构的MMT门诊的负担并致使其难以有效运作。     

Medicare star ratings: Stakeholder proceedings on community pharmacy and managed care partnerships in quality: American Pharmacists Association and Academy of Managed Care Pharmacy

ObjectivesTo describe the Medicare star rating system, created by the Centers for Medicare & Medicaid Services (CMS) in 2007; identify quality measures that can potentially be improved through collaboration between health plans and community pharmacy; provide examples of current collaboration between health plans and community pharmacy; and identify collaboration goals, challenges, components, and strategies.Data sourcesNational thought leaders at a conference titled CMS Star Ratings: A Stakeholder Discussion, held on March 21, 2013, supplemented with related information from the literature.SummaryThe Medicare star rating system is part of CMS's efforts to define, measure, and reward quality health care. Approximately one-half of the star rating performance measures can be influenced directly by community pharmacists working in conjunction with payers that must meet the quality measures. In 2012, a weighting system for star ratings was implemented. Of 10 triple-weighted ratings, 8 are related directly and indirectly to medication therapy and thus have the potential to be improved by pharmacist intervention. Plan ratings can have a substantial impact on beneficiary enrollment. Since very small improvements in performance measures can translate into large effects on star ratings, concerted efforts to improve pharmacy-related measures could move a plan to a higher star rating; conversely, inattention to areas such as high-risk medications, antidiabetic pharmacotherapy, and medication adherence could lower a plan's star rating. Topics discussed in this article include the Electronic Quality Improvement Platform for Plans and Pharmacies, or EQUIPP, the payer perspective on pharmacies, programs currently under way in community pharmacies, and ways plans and pharmacies can better collaborate with each other.ConclusionThe pharmacist's ability to work directly with patients to improve medication use is a critical factor in improving health plan Medicare star ratings. Health plans and community pharmacies must forge partnerships based on well-defined goals and innovative tactics to ensure care quality consistent with evolving public and private payment models.