应用正交试验减少静脉用药集中调配中心难溶性抗菌药物残留量

[摘要]目的：利用正交试验降低静脉用药调配中心难溶抗菌药物的残留量。方法：选定溶媒类型、溶媒体积和溶药针类型三个因素,每个因素确定两个水平,即溶媒类型为0.9%氯化钠注射液和灭菌注射用水,溶媒体积为5 mL和8 mL,溶药针类型为直孔溶药针和侧孔溶药针,进行三因素两水平的正交试验,考察各个因素对静脉用药调配中心难溶抗菌药物残留体积和残留量的影响。结果：影响静脉用药调配中心难溶抗菌药物残留体积的主次因素为溶药针类型最大,溶媒体积次之,溶媒类型最小;影响残留量的主次因素为溶媒体积最大,溶药针类型次之,溶媒类型最小。结论：选择适宜溶媒类型、溶媒体积和溶药针类型调配难溶性抗菌药物,可降低西林瓶内的残留量,提高成品输液质量。     

Peripheral nervous system function and organophosphate pesticide use among licensed pesticide applicators in the Agricultural Health Study

Background: Evidence is limited that long-term human exposure to organophosphate (OP) pesticides, without poisoning, is associated with adverse peripheral nervous system (PNS) function.Objective: We investigated associations between OP pesticide use and PNS function by administering PNS tests to 701 male pesticide applicators in the Agricultural Health Study (AHS).Methods: Participants completed a neurological physical examination (NPx) and electrophysiological tests as well as tests of hand strength, sway speed, and vibrotactile threshold. Self-reported information on lifetime use of 16 OP pesticides was obtained from AHS interviews and a study questionnaire. Associations between pesticide use and measures of PNS function were estimated with linear and logistic regression controlling for age and outcome-specific covariates.Results: Significantly increased odds ratios (ORs) were observed for associations between ever use of 10 of the 16 OP pesticides and one or more of six NPx outcomes. Most notably, abnormal toe proprioception was significantly associated with ever use of 6 OP pesticides, with ORs ranging from 2.03 to 3.06; monotonic increases in strength of association with increasing use was observed for 3 of the 6 pesticides. Mostly null associations were observed between OP pesticide use and electrophysiological tests, hand strength, sway speed, and vibrotactile threshold.Conclusions: This study provides some evidence that long-term exposure to OP pesticides is associated with signs of impaired PNS function among pesticide applicators.     

血液灌流联合血液滤过救治急性重度农药中毒的体会

目的:探讨血液灌流(HP)联合连续性静-静脉血液滤过(CVVH)在急性重度农药中毒治疗中的作用和价值。方法:选取2010年8月22例急性重度农药中毒患者在传统综合治疗措施的基础上进行HP+CVVH治疗的病例,严密观察患者在抢救过程中生命体征、内环境变化和治疗效果。结果:22例急性重症农药中毒患者20例抢救成功,2例死亡,取得满意疗效。结论:HP+CVVH在急性重度农药中毒患者救治中具有较好作用,能大大提高其抢救成功率。     

HP联合CVVH治疗急性重度农药中毒11例的体会

目的:探讨血液灌流(HP)联合连续性静-静脉血液滤过(CVVH)在急性重度农药中毒治疗中的护理。方法:选取2010年9月~2011年11月急性重度农药中毒11例患者在传统对症解毒抢救治疗措施的同时,进行HP加CVVH治疗,严密观察患者在抢救过程中生命体征及血液内环境变化和抢救治疗效果。结果:11例急性重症农药中毒患者均抢救成功,取得满意疗效。结论:HP加CVVH在急性重度农药中毒患者治疗中具有较好作用,能提高其抢救成功率。     

毒死蜱在韭菜和土壤中最终残留的研究

为了全面准确地评价毒死蜱及其制剂在韭菜园中使用后的生态环境安全性,指导毒死蜱及其制剂的科学合理使用,有效地保护农业生态环境,确保农产品质量安全;本文借助气相色谱检测技术,通过田间试验研究毒死蜱在韭菜和土壤中的最终残留。实验结果表明,在韭菜生长期按常规用药剂量和高剂量喷施毒死蜱,毒死蜱最终残留表现为：韭菜〈土壤,施药后3d、7d、14d后韭菜中的毒死蜱最终残留量均小于0.1mg/kg,符合GB18406.1-2001《农产品安全质量无公害蔬菜安全要求》（Safety qualification for agricultural product-Safety requirements for non-environmental pollution vegetable）规定的最大残留量1.0mg/kg和GB2763-2005《食品中农药最大残留限量》规定的0.1mg/kg。     

Intramolecular allosteric communication in dopamine D2 receptor revealed by evolutionary amino acid covariation

The structural basis of allosteric signaling in G protein-coupled receptors (GPCRs) is important in guiding design of therapeutics and understanding phenotypic consequences of genetic variation. The Evolutionary Trace (ET) algorithm previously proved effective in redesigning receptors to mimic the ligand specificities of functionally distinct homologs. We now expand ET to consider mutual information, with validation in GPCR structure and dopamine D2 receptor (D2R) function. The new algorithm, called ET-MIp, identifies evolutionarily relevant patterns of amino acid covariations. The improved predictions of structural proximity and D2R mutagenesis demonstrate that ET-MIp predicts functional interactions between residue pairs, particularly potency and efficacy of activation by dopamine. Remarkably, although most of the residue pairs chosen for mutagenesis are neither in the binding pocket nor in contact with each other, many exhibited functional interactions, implying at-a-distance coupling. The functional interaction between the coupled pairs correlated best with the evolutionary coupling potential derived from dopamine receptor sequences rather than with broader sets of GPCR sequences. These data suggest that the allosteric communication responsible for dopamine responses is resolved by ET-MIp and best discerned within a short evolutionary distance. Most double mutants restored dopamine response to wild-type levels, also suggesting that tight regulation of the response to dopamine drove the coevolution and intramolecular communications between coupled residues. Our approach provides a general tool to identify evolutionary covariation patterns in small sets of close sequence homologs and to translate them into functional linkages between residues.Identifying residues that coevolved to maintain or acquire fitness properties is critical for understanding protein structure, function, and evolution (1). Previous studies have shown that covarying residue pairs, those that exhibit correlated amino acid changes in large multiple sequence alignments, tend to form structural contacts (2–7), enhancing predictions of protein 3D structures (8–11). Covariation can also involve distal residues, but the function of these at-a-distance couplings is elusive and has been attributed to background noise, alternative protein conformations, or subunit interactions of protein homooligomers (5, 7, 12). Alternately, distal covarying residue pairs could indicate allosteric couplings (6, 13–18).The possibility of capturing intramolecular allosteric communication by amino acid covariation analysis of protein family sequences has not been extensively explored. Nonproximal thermodynamic coupling between correlated residue pairs was noted in 274 PDZ domains (14), but the relationship to allostery is still debated (19, 20). It may be that distinctive allosteric mechanisms, even among close homologs, limit the extraction of allosteric couplings from sequences (13). Our previous identification of residues important for allosteric signaling within G protein-coupled receptors (GPCRs) using Evolutionary Trace (ET) (21–24) and strong conservation of some of the residues implicated led us to ask whether ET could also uncover couplings among protein sequence positions not in direct contact.ET estimates the relative functional sensitivity of a protein to variations at each residue position using phylogenetic distances to account for the functional divergence among sequence homologs (25, 26). Similar ideas can be applied to pairs of sequence positions to recompute ET as the average importance of the couplings between a residue and its direct structural neighbors (27). To measure the evolutionary coupling information between residue pairs, we present a new algorithm, ET-MIp, that integrates the mutual information metric (MIp) (5) to the ET framework. We used dopamine D2 receptor (D2R), a target of drugs for neurological and psychiatric diseases (28), to test whether ET-MIp could elucidate the allosteric functional communications from amino acid covariation patterns and resolve the evolutionary distance at which the allosteric pathways of D2R homologs are sufficiently conserved to detect residue−residue coupling signatures. D2R is expressed in the central nervous system and responds to dopamine, the major catecholamine neurotransmitter. Canonical D2R signaling is effected by G_i/o class G proteins, which regulate ion channels (29, 30), MAPK kinases (31), phospholipase C (32), and inhibition of adenylyl cyclase (33). D1 class receptors (D1R and D5R) have lower affinities for dopamine (34–36) and activate adenylyl cyclase through G_s class G proteins. To characterize allosteric communication between covarying pairs of residues ranked as important by ET (ET residue pairs), we examined functional coupling for ligand binding affinities and downstream G_i activation induced by agonist-stimulated D2R.     

Role of penehyclidine in acute organophosphorus pesticide poisoning

BACKGROUND:Penehyclidine is a newly developed anticholinergic agent.We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning(OP)patients.METHODS:We searched the Pubmed,Cochrane library,EMBASE,Chinese National Knowledge Infrastructure(CNKI),Chinese Biomedical literature(CBM)and Wanfang databases.Randomized controlled trials(RCTs)recruiting acute OP patients were identifi ed for meta-analysis.Main outcomes included cure rate,mortality rate,time to atropinization,time to 60%normal acetylcholinesterase(AchE)level,rate of intermediate syndrome(IMS)and rate of adverse drug reactions(ADR).RESULTS:Sixteen RCTs involving 1,334 patients were identifi ed.Compared with the atropineor penehyclidine-alone groups,atropine combined with penehyclidine significantly increased the cure rate(penehyclidine+atropine vs.atropine,0.97 vs.0.86,RR 1.13,95%CI[1.07–1.19];penehyclidine+atropine vs.penehyclidine,0.93 vs.0.80,RR 1.08,95%CI[1.01–1.15])and reduced the mortality rate(penehyclidine+atropine vs.atropine,0.015 vs.0.11,RR 0.17,95%CI[0.06–0.49];penehyclidine+atropine vs.penehyclidine,0.13 vs.0.08,RR 0.23,95%CI[0.04–1.28]).Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery,the rate of IMS and the rate of ADR.Compared with a single dose of atropine,a single dose of penehyclidine also signifi cantly elevated the cure rate,reduced times to atropinization,AchE recovery,and rate of IMS.CONCLUSION:Atropine combined with penehyclidine benefi ts OP patients by enhancing the cure rate,mortality rate,time to atropinization,AchE recovery,IMS rate,total ADR and duration of hospitalization.Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.     

饮用水中多种有机磷农药残留的气相色谱-三重四极杆质谱测定法

目的建立一种同时测定饮用水中7种有机磷农药残留量的气相色谱-三重四极杆质谱（GC-MS/MS）方法。方法采用液-液萃取方法,用二氯甲烷对水样中7种有机磷农药进行提取,无水硫酸钠脱水,滤液在40℃水浴中旋转蒸发近干,用二氯甲烷定容,GC-MS/MS测定,外标法定量。结果 7种有机磷农药在21 min内分离,在0.01-10 mg/L范围内相关系数r2均在0.99以上,在0.05、0.25和0.45 mg/L 3个水平加标回收率在78.9%-99.3%之间,相对标准偏差均小于10%,检出限为0.02-0.06μg/L。结论该方法操作简单,准确度和精密度高,消除了其他有机磷农药的干扰,避免假阳性的出现,适用于饮用水中7种有机磷农药残留量的检测和确证。     

血液灌流对急性重度有机磷农药中毒的疗效探讨

目的探讨血液灌流对急性重度有机磷农药中毒治疗方面的临床效果。方法将急诊收治的急性重度有机磷农药中毒病例40例分为观察组11例,对照组29例。对照组采取常规治疗方式,观察组在此基础上予以血液灌流治疗,对比两组病例的治愈率、昏迷到清醒的时间长短、阿托品的用量及灌流前后胆碱酯酶水平的变化。结果两组病例在治愈率、阿托品总用量方面差异无统计学意义（P〉0．05）,而昏迷至清醒的时间差异有统计学意义（P〈0．05）,观察组病例治疗前后,血液胆碱酯酶的水平差异有统计学意义（P〈0．05）。结论采用血液灌流治疗急性重度有机磷农药中毒效果较为满意,应大力推广使用。