国产司帕沙星体内外抗菌作用

采用琼脂二倍稀释法测定了国产司帕沙星(SPFLX)对537株临床分离革兰氏阳性、阴性需氧菌和厌氧菌的体外抗菌活力,并与同类产品中的环丙沙星、氧氟沙星、诺氟沙星进行比较。结果表明SPFLX具有广谱高效的体外抗菌作用,该品对革兰氏阳性球菌具有很强抑菌活力,对金黄色葡萄球菌(包括喹诺酮类耐药株及甲氧西林耐药株MRSA)具较强的抑菌活力,MIC范围在<0.004～16mg/L,表葡菌、化脓性链球菌、粪链球菌、肺炎链球菌的MIC在0.015～8mg/L。SPFLX对革兰氏阴性细菌中的大肠杆菌、克氏肺炎杆菌亦具有强抑菌作用,MIC_(50)在0.03～0.06mg/L,对变形杆菌属、粘质沙雷氏菌的MIC_(50)在0.125～0.5mg/L,对绿脓杆菌的MIC_(50)、     

司帕沙星的药效学研究

司帕沙星(sparfloxacin-SFIX)对G~+菌有较强的抗菌活性,MIC范围为0.03～1μg/ml,对G~-菌的抗菌活性也较强,MIC为0.005～1μg/ml。司帕沙星对38株肺炎链球菌的MIC_(50)比CP-FIX,OFIX,NFIX,ENX,EM,强4～32倍,对其它G~+菌抗菌作用也强于CPFIX,OFIX,NFIX。对绿脓杆菌的MIC_(50)和MIC_(90)稍低于CPFIX。对大肠杆菌,变形杆菌,肺炎杆菌的MIC_(50)和MIC_(90)与CPFIX,NFIX接近,但小于OFIX,ENX,GM。对流感杆菌、不动杆菌,淋球菌的抗菌作用明显优于对照药。SFIX对厌氧菌也有明显的抗菌作用其MIC_(50)和MIC_(90)同灭滴灵接近,但明显强于CPFIX,OFIX,EM。SFIX有良好的杀菌作用,G~+菌杀菌作用较强,对G~-菌杀菌作用稍逊于CPFIX,强于OFIX,NFIX。SFIX对金葡菌的杀菌曲线,与OFIX,CPFIX相类似,杀菌作用     

甲磺酸司帕沙星的药效学研究

甲磺酸司帕沙星(MSASFLX),是我所新研制和开发的一种新型的氟喹诺酮类抗菌药。为了考察其体内外抗菌作用,我们对MSASFLX的体内外抗菌活性与同类药进行药效学比较。MSASFLX对G^ 菌的抗菌作用与口服司帕沙星(SFLX)接近,比乳酸环丙沙星(Lac-CPFLX)及氧氟沙星(OFLX)强,对G^-菌的抗菌作用与SFLX和Lac-CPFLX近似,     

成都地区几种常用氟喹诺酮类药体外及体内抗菌活性比较

六种氟喹诺酮类药 (司帕沙星、妥舒沙星、环丙沙星、氧氟沙星、氟罗沙星及诺氟沙星 )对成都地区 780株临床分离的致病菌 ,其中革兰阳性菌 3 45株 ,革兰阴性菌 40 0株 ,厌氧菌 3 5株 ,进行体外抑菌试验 ,对其中体外抗菌作用强的三种药物进行感染小鼠败血症体内保护试验。体外MICs测定结果表明对MSSA与MSSE及MRSA与MRSE均以司帕沙星与妥舒沙星为最强 ,他们的MICs范围分别为 0 .0 0 4～ 2mg/L及 0 .0 1 5～ 1 6mg/kg ,大多敏感。对化脓性链球菌、粪肠球菌、乙型溶血性链球菌及肺链球菌亦呈现强抗菌活性MICs为 0 .0 0 88mg/L ,抗菌活…     

可利霉素对临床分离菌的体内外研究

目的:评价可利霉素对临床分离菌的体内外的抗菌作用.方法:应用最低有效浓度(Minimum inhibitory concentration,MIC)评价临床分离菌体外抗菌活性;通过小鼠生存率计算半数有效量(Median effective dose,ED50)了解可利霉素体内抗菌活性.结果:可利霉素对临床分离的200株鲍曼不动杆菌的MIC值在64-128μg?mL-1之间,对耐碳青霉烯的临床分离鲍曼不动杆菌的MIC值在128μg?mL-1,体外实验表明其抗菌活性不佳,但对耐碳青霉烯的临床分离鲍曼不动杆菌的半数有效量(ED50)153.2 mg?kg-1;耐碳青霉烯肺炎克雷伯菌ED50为112.2 mg?kg-1.结论:可利霉素对临床分离的鲍曼不动杆菌和耐碳青霉烯的细菌体外抗菌活性较弱,而在体内对耐碳青霉烯的临床分离鲍曼不动杆菌和肺炎克雷伯菌有一定的抗菌作用.     

国产司帕沙星两种制剂的生物等效性研究

12例健康男性志愿受试者采用随机交叉给药方案,分别单剂口服国产司帕沙星颗粒剂和胶囊剂400mg,进行生物等效性研究。用RP-HPLC法测定血清中司帕沙星浓度,试验结果表明:血药浓度—时间数据经3p97程序自动拟合,符合一室模型。颗粒剂和胶囊剂的达峰时间分别为4.79±0.40和4.79±0.     

司帕沙星对小鼠围产期毒性试验

国产司帕沙星为氟喹诺类新抗菌药物,从妊娠第15天至分娩后哺乳期的第21天每日经口灌服司帕沙星20和100mg/kg,对昆明种小鼠妊娠后期及产后整个哺乳期,对F_1和F_2代动物的生长发育,交配率和繁殖率均无影响。     

西咪替丁对小鼠中孕妊娠影响的实验研究

目的 :初步研究西咪替丁对中孕妊娠的影响。方法 :用昆明种小鼠 ,在妊娠第 9～ 1 2天分别连续灌胃给予西咪替丁 80mg·kg 1,1 60mg·kg 1,3 2 0mg·kg 1,640mg·kg 1,于妊娠第 1 6天解剖记录活胎数 ,吸收胎死胎数。结果 :西咪替丁 1 60mg·kg 1,3 2 0mg·kg 1,640mg·kg 1剂量对小鼠的妊娠抑制率分别为 1 0 % ,45 % ( p <0 .0 0 5 ) ,65 % ( p <0 .0 0 5 )。 结论 :西咪替丁具有一定的终止中孕妊娠作用。     

阿莫西林与舒巴坦合用的抗菌活性增效作用

1．临床分离产酶菌(200株)体外抗菌活性实验。结果表明，舒巴坦(SBT)单用抗菌作用甚弱，阿莫西林(AMOX)与SBT以2：1合用对产酶金葡菌、表葡菌及G杆菌大肠、克肺、阴沟、产气、痢疾、变形、伤寒、绿脓等杆菌的MIC50分别是阿莫西林单用的1／64、1／16、1／8、1／64、1／16、1／16、1／8、1／8、1／4、1／2。其抗菌活性增强2～64倍。     

洛美沙星体外抗菌活性研究

洛美沙星是由日本北陆公司于1985年开始研制的新喹诺酮类抗菌药物,上海医药工业研究院于1990年研制成功,本文测定了国产洛美沙星对临床分离的966株需氧菌与93株厌氧菌的抗菌作用,并与进口品及8种有关抗菌药物进行比较。对非产酶金葡菌和产酶组对甲氧西林敏感金葡菌(MSSA)的MIC_(50)为0.5～1ms/L时β—溶血性链球菌的MIC_(50)为2mg/L;对肠杆菌科细菌的MIC_(50)除雷极氏杆菌为64mg     

司帕沙星对啮齿动物微核试验

NIH系小鼠灌服司帕沙星,口服剂量分别为250、1000和2500mg/kg时微核发生率在5‰以下,试验结果与空白对照相似判为阴性。     

左氧氟沙星延长离体豚鼠乳头肌的动作电位时程

目的观察左氧氟沙星(LVFX)对豚鼠心肌动作电位的影响,并以司帕沙星(SPX)为阳性对照物比较二者对心肌的毒性作用。方法微电极记录豚鼠右心室乳头肌动作电位。结果刺激频率为1 Hz时,各浓度的SPX均显著性延长APD50和APD90,而LVFX浓度超过10μmol/L时明显延长APD50和APD90。结论LVFX和SPX均引起APD延长,前者效应较后者弱,仅在大剂量时有导致QT间期延长的潜在毒性。     

安妥沙星延长离体豚鼠心肌动作电位

目的 观察氟喹诺酮类抗菌药安妥沙星(ATFX)对豚鼠心肌动作电位的影响.方法 微电极记录豚鼠右心室乳头肌动作电位.结果 (1)当刺激周长为1000 ms时,各浓度的司帕沙星(SPX)均显著性延长APD50和APD90(P<0.05),而左氧氟沙星(LVFX)和ATFX在浓度超过10μmol/L时明显延长APD90(P<0.05),且ATFX延长APD90的效应明显弱于LVFX和SPX.(2)用E-4031阻断IKr电流,ATFX延长APD90的效应部分被逆转;而用Chro-manol 293B阻断IKr电流,ATFX延长APD90的效应仍存在(P<0.05);但E-4031和Chromanol 293B共同作用阻断IK电流后,ATFX延长APD90的效应可明显被逆转.(3)在药物浓度为10μmol/L时,随着刺激周长的延长,3种药物虽呈不同程度延长APD90,但相差无显著性,提示药物引起的APD延长无明显的频率依赖性.结论 ATFX可能通过抑制IKr,电流而延长APD,但其效应明显弱于LVFX和SPX.     

Enzyme-linked immunosorbent assays of fluoroquinolones with selective and group specificities

Two ciprofloxacin (CF)–bovine serum albumin conjugates with oppositely orientated hapten and gemifloxacin (GF)–glucose oxidase synthesised by activated esters method, carbodiimide condensation and glutaraldehyde linking, respectively, were used as immunogens. A wide spectrum of immobilised antigens different in carrier, type of hapten (CF, GF, sparfloxacin), hapten load and conjugating method were prepared. Thirteen variants of competitive indirect enzyme-linked immunosorbent assay (ELISA) using three rabbit antisera and solid-phase conjugates were developed to detect fluoroquinolones (FQs). The immunoreagent combinations allowed to determine CF and GF selectively, to carry out the quantification of CF, enrofloxacin, norfloxacin, pefloxacin and lomefloxacin practically with equal efficacy. Under the conditions of group-specific ELISAs the immunochemical activity of 9–10 FQ representatives differed only 10–20 times. The possibility of efficient influence on ELISA specificity and sensitivity with especially selected immobilised antigens was demonstrated.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.