Three new compounds from Arnebia euchroma

A new naphthoquinone dimer, arnebiabinone (1), a new phenolic compound, ethyl 9-(2′,5′-dihydroxyphenyl) nonanoate (2), and a new natural product, octyl ferulate (3), were isolated from the EtOH extract of dried roots of Arnebia euchroma (Royle) Johnst. Their structures were elucidated on the basis of chemical reaction and spectral analysis.     

新氟喹诺酮类抗菌药普利沙星

普利沙星是新口服的氟喹诺酮类抗菌药.本品为前体药,其活性代谢产物通过阻碍DNA拓扑异构酶使细菌DNA无法形成超螺旋,导致细菌细胞无法分裂繁殖.临床上用于治疗各种敏感致病菌引起的感染.本品不良反应较少,尤其是光敏性在同类药中是最小的.综述普利沙星的药理作用、药动学及临床评价.     

杀精剂硝苯柳胺合成及药效学研究

目的:合成杀精剂硝苯柳胺,并研究其体内外杀精作用.方法:对杀精剂硝苯柳胺的合成路线和工艺条件进行优化,对产品结构进行分析、检测和成本估算.研究其体内外杀精作用和抗妇科感染作用并观察其毒理学.结果:本品合成路线短,工艺简单,收率高,提纯方便,能耗小,成本低,杀精作用强,无不良反应,遗传毒理试验显示其无"三致"作用.结论:本品有望成为一种安全、高效、廉价、方便的新型避孕药和抗妇科感染剂.     

Thiadiazolidinones: a new class of alanine racemase inhibitors with antimicrobial activity against methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a human pathogen and a major cause of hospital-acquired infections. New antibacterial agents that have not been compromised by bacterial resistance are needed to treat MRSA-related infections. We chose the S. aureus cell wall synthesis enzyme, alanine racemase (Alr) as the target for a high-throughput screening effort to obtain novel enzyme inhibitors, which inhibit bacterial growth. Among the ‘hits’ identified was a thiadiazolidinone with chemical properties attractive for lead development. This study evaluated the mode of action, antimicrobial activities, and mammalian cell cytotoxicity of the thiadiazolidinone family in order to assess its potential for development as a therapeutic agent against MRSA. The thiadiazolidones inhibited Alr activity with 50% inhibitory concentrations (IC₅₀) ranging from 0.36 to 6.4 μM, and they appear to inhibit the enzyme irreversibly. The series inhibited the growth of S. aureus, including MRSA strains, with minimal inhibitory concentrations (MICs) ranging from 6.25 to 100 μg/ml. The antimicrobial activity showed selectivity against Gram-positive bacteria and fungi, but not Gram-negative bacteria. The series inhibited human HeLa cell proliferation. Lead development centering on the thiadiazolidinone series would require additional medicinal chemistry efforts to enhance the antibacterial activity and minimize mammalian cell toxicity.     

耐甲氧西林金黄色葡萄球菌多重耐药研究

目的了解本地区耐甲氧西林金黄色葡萄球菌（MRSA）的多重耐药情况。方法收集经头孢西丁纸片扩散试验和青霉素结合蛋白2a胶乳凝集实验分离出的51株MRSA,用β-内酰胺酶实验、D试验、Kirby-Bauer法检测MRSA产β-内酰胺酶以及对红霉素、克林霉素、4种氟喹诺酮类药物（氧氟沙星、诺氟沙星、左旋氧氟沙星、加替沙星）和万古霉素耐药性。结果51株MRSA头孢西丁纸片抑菌圈直径介于6～20mm,产β-内酰胺酶率为84.3%,对红霉素、克林霉素、氟喹诺酮类、万古霉素耐药率分别为98.0%、86.3%、88.2%、0,红霉素诱导克林霉素耐药率为50.0%（3/6）。结论MRSA呈多重耐药,轻度感染可根据药敏结果选万古霉素与氟喹诺酮类？生素联合用药。     

不同个性甲亢患者心理状态调查分析

对比国内常模，甲亢患者的心理状态为心理正常但心理不健康，通过90项症状评分分析，甲亢患者在总分、阳性项目数、阳性项目均分方面都高于常模，在因子分方面，焦虑、抑郁、敌对、人际关系敏感方面都高于国内常模。因此，甲亢患者在进行服药以控制躯体症状的同时，需要介入专业的心理干预，尤其是艾森克人格理论为N分较高的胆汁质、抑郁质的个体应得到更加特别的关注。     

四川省细菌耐药监测网2016—2020年耐甲氧西林金黄色葡萄球菌分布及耐药性分析

摘要：目的 统计分析2016—2020年四川省细菌耐药监测网成员单位耐甲氧西林金黄色葡萄球菌(MRSA)的分布及耐药情况,为抗菌药物的合理应用及细菌耐药变迁提供依据。方法 收集2016—2020年四川省92家成员单位医院门诊及住院患者临床标本中分离的去重金黄色葡萄球菌,按照CARSS的统一技术方案,并参照美国临床和实验室标准协会(CLSI)2019年标准,使用WHONET 5.6软件和SPSS 22.0软件进行数据统计分析。结果 检出的28366株MRSA以痰液(49.4%) 、脓液(39.2%)、血液(5.3%)、尿液 (1.4%)、咽拭子(1.4%)为主要来源。人群分布以成年人为主(43.9%),其次为儿童(27.6%)和老年人(22.9%)。庆大霉素、利福平、左氧氟沙星及复方磺胺甲恶唑呈逐年下降趋势;克林霉素、红霉素一直保持较高耐药水平;未发现对万古霉素、利奈唑胺、替考拉宁耐药的菌株。结论 我省MRSA的检出率及耐药率形势仍然严峻,临床应根据药敏结果合理使用抗菌药物,积极采取有效措施预防和控制感染。     

新疆紫草的HPLC指纹图谱建立、化学模式识别分析及其含量测定

目的:建立新疆紫草的高效液相色谱(HPLC)指纹图谱,进行化学模式识别分析,并测定其中3种成分的含量。方法:采用HPLC法。以乙酰紫草素为参照,绘制34批不同来源新疆紫草药材样品的HPLC指纹图谱,采用《中药色谱指纹图谱相似度评价系统(2012A版)》进行相似度评价,确定共有峰;采用SPSS 19.0、SIMCA 14.1统计软件进行聚类分析、主成分分析和正交偏最小二乘法-判别分析,以变量投影重要性值大于1为标准,筛选影响新疆紫草药材质量的差异标志物,并以相同HPLC法测定其中3种成分的含量。结果:34批新疆紫草药材共有12个共有峰;除市售样品中的3批药材相似度低于0.72外,其余药材的相似度均高于0.86;共指认出左旋紫草素、乙酰紫草素、β,β′-二甲基丙烯酰阿卡宁等3个共有峰。34批新疆紫草药材可聚为2类,其中S1、S4～S6、S13、S15～S20、S22、S26～S34聚为一类,其余聚为一类。前3个主成分因子的方差贡献率分别为52.834%、18.600%、8.387%,累积方差贡献率为79.821%。左旋紫草素、乙酰紫草素、β,β′-二甲基丙烯酰阿卡宁等6个成分为影响其质量的...     

Inhibition of bacterial efflux pumps: a new strategy to combat increasing antimicrobial agent resistance

Resistance to multiple drugs in medically important bacteria results in therapeutic challenges for the clinician. The mechanisms by which bacteria evade the effects of antimicrobial agents are many, but in recent years it has become apparent that efflux is a significant means of resistance and probably explains the intrinsic resistance to numerous drugs observed in species such as Pseudomonas aeruginosa. Drug efflux is mediated by membrane-based hydrophobic proteins belonging to several distinct families, the members of which are related by structural characteristics, mechanism of action and energy source for the transport process. The multi-drug efflux transporters are particularly problematic as they are capable of extruding numerous structurally dissimilar drugs. Inhibition of these pumps, and even those with more limited substrate specificity, has been shown to decrease intrinsic resistance, reverse acquired resistance and reduce the emergence of mutants with higher-level target-based mutational resistance. Combining broad spectrum efflux pump inhibitors with current drugs that are pump substrates can recover clinically relevant activity of those compounds and thus may reduce the need for the discovery and development of new antimicrobial agents that are not pump substrates. Additional effort toward the identification, characterisation and determination of the clinical utility of efflux pump inhibitors is warranted.     

Inhibition of bacterial efflux pumps: a new strategy to combat increasing antimicrobial agent resistance

Resistance to multiple drugs in medically important bacteria results in therapeutic challenges for the clinician. The mechanisms by which bacteria evade the effects of antimicrobial agents are many, but in recent years it has become apparent that efflux is a significant means of resistance and probably explains the intrinsic resistance to numerous drugs observed in species such as Pseudomonas aeruginosa. Drug efflux is mediated by membrane-based hydrophobic proteins belonging to several distinct families, the members of which are related by structural characteristics, mechanism of action and energy source for the transport process. The multi-drug efflux transporters are particularly problematic as they are capable of extruding numerous structurally dissimilar drugs. Inhibition of these pumps, and even those with more limited substrate specificity, has been shown to decrease intrinsic resistance, reverse acquired resistance and reduce the emergence of mutants with higher-level target-based mutational resistance. Combining broad spectrum efflux pump inhibitors with current drugs that are pump substrates can recover clinically relevant activity of those compounds and thus may reduce the need for the discovery and development of new antimicrobial agents that are not pump substrates. Additional effort toward the identification, characterisation and determination of the clinical utility of efflux pump inhibitors is warranted.     

Clonal expansion accounts for an excess of antimicrobial resistance in Staphylococcus aureus colonising HIV-positive individuals in Lagos, Nigeria

Nasal colonisation with Staphylococcus aureus is a risk factor for invasive infection in human immunodeficiency virus (HIV)-positive individuals. This study aimed to characterise colonising S. aureus from regions with a high HIV prevalence. Single nasal swabs were taken from a total of 374 HIV-positive and 370 healthy individuals. Overall, 202 S. aureus carriers were detected. Compared with healthy individuals, HIV-positive subjects were more likely to be S. aureus nasal carriers (33% vs. 21%; P=0.0001). Isolates from HIV-positive individuals were more often resistant to meticillin (16% vs. 8%; P=0.13), chloramphenicol (47% vs. 16%; P<0.0001), sulfamethoxazole/trimethoprim (SXT) (90% vs. 55%; P<0.0001) and ciprofloxacin (18% vs. 0%; P<0.0001). Strains belonging to the spa clonal complexes 3772/ST25 and 064/ST8 were significantly more often isolated from HIV-positive individuals and exhibited greater resistance to ciprofloxacin, SXT and chloramphenicol (spa-CC 3772) or to meticillin (spa-CC 064), respectively. Panton-Valentine leukocidin gene content was high overall and was equally distributed between isolates from HIV-positive and healthy individuals (33% vs. 30%). Genotypic characteristics of colonising isolates were similar to those reported to cause invasive infection in Nigeria. The HIV pandemic contributes to the evolution of antimicrobial resistance in S. aureus. Measures to contain antimicrobial resistance of S. aureus in Nigeria must target risk groups such as HIV-positive individuals.     

High-performance liquid chromatographic analysis of chlorhexidine phosphanilate, a new antimicrobial agent

Chlorhexidine phosphanilate (CHP) is analysed by two separate reversed-phase HPLC methods. CHP was found to be a non-stoichiometric compound with a phosphanilic acid to chlorhexidine ratio of 1.83. By careful choice of solvents, solution pH and HPLC columns, loss of sample due to incomplete dissolution and adsorption to surfaces is avoided. Both methods are shown to be stability-indicating and accurate.     

Human pharmacokinetics of tolfenamic acid,a new anti-inflammatory agent

Summary The pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent was studied in six healthy volunteers after an intravenous dose of 100 mg and oral doses of 100, 200, 400 and 800 mg. The disposition of intravenous tolfenamic acid could be described by two-compartment open model, with a central compartment volume (V_dc) of 5.6±0.31 (mean±SE), volume during -phase (V_d) of 31±21, and a total elimination rate constant (k₁₀) 1.6±0.1 h^–1. The terminal elimination half-life was 2.5±0.6 h and the total plasma clearance 155±15 ml/min. The elimination occured principally by extrarenal mechanisms, the recovery of unchanged drug together with is glucuronide in urine averaging only 8.8% of the intravenous dose. The binding of tolfenamic acid to plasma proteins averaged 99.7%. The gastrointestinal absorption had a mean half-life of 1.7±0.1 h. Based on comparison of areas under the plasma concentration time-curves after intravenous and oral administration, the biovailability of tolfenamic acid capsules averaged 60%. The rate and extent of absorption and the rate of elimination of tolfenamic acid were independent of dose.     

Pharmacokinetics of SUN 1165, a new antiarrhythmic agent,in renal dysfunction

Summary The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg.The apparent volume of distribution at steady state was 1.48 1 · kg^–1, the absorption rate constant was 2.2 h^–1, and plasma protein binding was 26.8% in subjects with normal renal function.These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration.The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml · min^–1 · 1.48 m^–2).Dosage adjustment of SUN 1165 is necessary in renal failure.     

Antibacterial activities of arbekacin, a new aminoglycoside antibiotic, against methicillin-cephem-resistant Staphylococcus aureus

The in vitro and in vivo antibacterial activities of a new aminoglycoside antibiotic, arbekacin (HBK), against methicillin-cephem-resistant Staphylococcus aureus (MRSA) were compared with those of gentamicin (GM), netilmicin (NTL) and amikacin (AMK). The results obtained were summarized as follows: Compared to other aminoglycoside antibiotics, HBK had the highest antibacterial activities against clinically isolated MRSA (46 strains). Therapeutic effects of HBK against experimental systemic infections with MRSA in mice, were superior to those of GM, NTL and AMK. The ED50's of GM, NTL and AMK were more than 2 mg/mouse. Therapeutic effects of HBK against experimental subcutaneous infections with MRSA in mice were also superior to those of GM, NTL and AMK.     

脓液中金黄色葡萄球菌的耐药性监测

目的分析脓液中金黄色葡萄球菌（SA）的耐药性。方法对内蒙古自治区人民医院2009年1月至2013年3月临床分离的227株金黄色葡萄球菌进行分析,细菌鉴定和药敏试验采用法国梅里埃威泰科VITEK2Compact全自动细菌培养鉴定仪。结果脓液中SA的病区来源主要为外科系统,骨科和普外科占52．0％（118／227）,脓液中耐甲氧西林金黄色葡萄球菌（MRSA）的分离为34．4％（78／227）,低于本院文献报道各种标本MRSA的分离率66．0％（194／294）（P〈0．05）。脓液中SA对利奈唑胺、万古霉素、替考拉宁、奎奴普丁／达福普汀和呋喃妥因的耐药率均为0,MRSA对复方新诺明的耐药率低于对甲氧西林敏感的SA（MSSA）（P〈0．05）,对其他抗菌药物MRSA的耐药性高于MSSA（P〈0．05）。β-内酰胺酶阳性和阴性的SA对呋喃类药物和糖肽类药物的耐药率均为0,对青霉素G耐药率前者98．0％（198／202）高于后者68．0％（17／25）,差异有统计学意义（P〈0．05）,对其他抗菌药物的耐药率,前者略高于后者,但差异无统计学意义（P〉0．05）。结论脓液中MRSA的检出率和耐药性较高,临床应继续加强无菌区MRSA的感染控制。     

Studies on phage type, beta-lactamase activity and sensitivity of multiple drug-resistant Staphylococcus aureus isolated from clinical specimens to cefmetazole

The 868 strains of S. aureus were isolated at the Department of Pediatrics, Third Hospital and Aoto Hospital, The Jikei University, School of Medicine and the Kanagawa Prefectural Nursing and Hygienic School Hospital during 6 months from May to October in 1981. From them 66 strains not sensitive to CEZ were selected by a 3-concentration disk method. A total number of 54 strains except for 12 isolated from the same infant patient was examined for their MIC's for 6 drugs, CMZ, CEZ, CTM, CXM, MCIPC and GM. Moreover, phage typing and beta-lactamase activity determination were carried out in them. 1. Antibacterial activity Sixty-six (7.6) of 868 strains were not sensitive to CEZ. The MIC's of CMZ against these resistant strains were between 1.56 and 50 micrograms/ml with a peak between 3.13 and 6.25 micrograms/ml when the 10(5) cells/ml bacterial suspension were inoculated. CMZ was superior in antibacterial activity to CEZ and CXM by about 4 degrees and to CTM by about 3 degrees. MCIPC and GM has higher antibacterial activity against a few strains than CMZ. However, the number of strains with MIC higher than or equal to 50 micrograms/ml was 17 for MCIPC and 40 for GM, but only 2 for CMZ. Thus, the former 2 drugs were far inferior to the latter one. 2. Phage type (1) Nineteen strains (35.2%) had MIC's for CEZ greater than 50 micrograms/ml and CMZ less than 6.25 micrograms/ml. Seventeen of them belonged to the nontypable. (2) Fourteen (25.9%) had MIC's for CEZ greater than 100 micrograms/ml. Of them 9 were allocated to the group III, 3 to the mixed (I + II + III, I + III) group and 2 to the nontypable. (3) Of 20 strains (37.0%) which had MIC's for CEZ greater than 100 micrograms/ml and CMZ less than 6.25 micrograms/ml 5 belonged to the group I, 3 to the group III and 12 to the nontypable. (4) Five strains classified into the group I were all isolated at the Kanagawa Perfectural Nursing and Hygienic School Hospital. (5) Eleven of 15 strains belonging to the group III were isolated at the Third Hospital, The Jikei University, School of Medicine. (6) Seventeen of 21 strains isolated at the Aoto Hospital, The Jikei University, School of Medicine belonged to the nontypable. (7) Phage type was considered to be influenced by difference in areas, infection within hospitals, etc., 3. beta-Lactamase activity beta-Lactamase activity was demonstrated at levels between 0.07 and 3.26 mumol/min/mg in all 54 strains. There was no correlation between MIC for CEZ or CEZ and beta-lactamase activity. It was suggested that beta-lactamase might not contribute to mechanism of resistance of S. aureus to each drug examined.     

新药述评棘白菌素类抗真菌药米卡芬净的药理与临床评价

采卡芬净（FK463）是第2个棘白菌素类抗真菌药物，在体内、外对曲霉菌、念珠菌均有抗新活性。现对其药理作用、药动学、临床评价以及不良反应等做一综述。     

2014-2016年邯郸市中心医院细菌耐药性监测结果分析

目的 了解2014-2016年邯郸市中心医院临床所分离细菌对抗菌药物的耐药性。方法 收集2014年1月1日-2016年12月31日邯郸市中心医院临床所分离的细菌,只分析同一患者同一部位的第一株菌。采用Vitek2-Compact和珠海美华MA120进行鉴定,药敏试验方法采用MIC和KB法,并采用WHONET 5.6软件进行统计分析。结果 邯郸市中心医院2014-2016年分离的菌株分别为3237、4484和4778株,共12499株细菌,其中革兰阴性菌8780株,占70.2%,革兰阳性菌3719株占29.8%。耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的检出率分别为38.38%和65.07%。屎肠球菌对绝大多数所测抗菌药物的耐药率明显高于粪肠球菌,葡萄球菌属和肠球菌属中均未发现万古霉素、替考拉宁和利奈唑胺耐药的菌株。肺炎链球菌以非脑脊液来源为主,成人多于儿童,且儿童分离株对青霉素均敏感,成人分离株青霉素耐药率为1.2%。大肠埃希菌和肺炎克雷伯菌超广谱β-内酰胺酶(ESBL)的检出率分别为49.4%和28.3%,对碳青霉烯类药物耐药率分别为1.8%和4.4%。铜绿假单胞菌对亚胺培南和美罗培南的耐药率分别为20.3%和13.6%,鲍曼不动杆菌对亚胺培南和美罗培南的耐药率分别为63.8%和63.7%。结论 3年间细菌耐药性发生了变化,医生应该依据药敏监测结果合理选择抗菌药物。