米诺环素与夫西地酸对98株耐甲氧西林金黄色葡萄球菌的联合药敏研究

目的评价米诺环素与夫西地酸对临床分离到的98株耐甲氧西林金黄色葡萄球菌(MRSA)的联合体外抗菌活性,及两药联用的抗MRSA效应。方法用棋盘法设计,用微量肉汤稀释法,测定不同浓度组合的抗菌药物对98株临床分离MRSA的最低抑菌浓度,并计算部分抑菌浓度指数(FICI),判定联用效应。结果米诺环素与夫西地酸联用后,2种抗菌药物对临床分离得到的98株MR-SA的MIC50显著降低。FICI分布:FICI≤0.5(协同作用)占57.14%;0.54(拮抗作用)为0。结论米诺环素与夫西地酸体外联用对98株临床分离的MRSA体外抗菌效应以协同作用为主;无关作用较少;无拮抗作用。     

左氧氟沙星与磷霉素联用对30株金黄色葡萄球菌的抗菌活性

目的 评价左氧氟沙星(喹诺酮类抗菌药)与磷霉素(合成抗菌药)联用对30株金黄色葡萄球菌的体外抗菌效应.方法 用棋盘法设计,微量肉汤稀释法测定不同浓度组合的抗菌药物对15株甲氧西林敏感的金黄色葡萄球菌(MSSA)和15株甲氧西林耐药的金黄色葡萄球菌(MRSA)的最低抑菌浓度,并计算部分抑菌浓度指数(FICI)判定联合效应.结果 左氧氟沙星与磷霉素联用后,其对金黄色葡萄球菌的MIC50显著降低,15株MSSA:HCI≤0.5占36.4%;0.52为0.15株MRSA:HCI≤0.5占81.8%;0.52为0.结论 体外左氧氟沙星与磷霉素联用对30株金黄色葡萄球菌主要为协同和相加作用.     

头孢哌酮/舒巴坦(2:1,1:1)联合米诺环素对亚胺培南耐药鲍曼不动杆菌的体外抗菌作用

目的 评价头孢哌酮/舒巴坦(2:1,1:1)与米诺环素(四环素类抗生素)联合用药,对39株临床分离的亚胺培南耐药的鲍曼不动杆菌的体外抗菌效应.方法 将不同浓度2种抗菌药用棋盘法设计,用琼脂稀释法测定不同浓度组合的抗菌药对菌株的最低抑菌浓度(MIC),并计算部分抑菌浓度指数(FICI),判定标准:HCI≤0.5为协同作用;0.54为拮抗作用.结果 2种不同配比的头孢哌酮/舒巴坦同米诺环素联用后,HCI均于0.5～4.0,未观察到协同作用,亦无拮抗作用;2种组合的HCI分布情况相当.结论 2种不同配比的头孢哌酮/舒巴坦同米诺环素联合对本组亚南培南耐药的鲍曼不动杆菌表现为无相关作用.     

磷霉素与头孢哌酮/舒巴坦联用及分别联合其他抗生素对多重耐药鲍曼不动杆菌体外抗菌活性对比研究

目的 评价磷霉素与头孢哌酮/舒巴坦作为基础药物,二者联用及分别与亚胺培南、米诺环素的联合用药方案,用于多重耐药鲍曼不动杆菌的体外联合抗菌效应对比。方法 分离多重耐药鲍曼不动杆菌临床株30株,采用微量肉汤稀释棋盘法,测定不同浓度组合的抗生素联用最低抑菌浓度,并计算部分抑菌浓度指数(fractiona inhibitory concentration index, FICI)判定联合效应。将不同联合用药配伍方案进行对比,评价优劣。结果 磷霉素联合亚胺培南、头孢哌酮/舒巴坦联合亚胺培南、磷霉素联合米诺环素、头孢哌酮/舒巴坦联合米诺环素、头孢哌酮/舒巴坦联合磷霉素,FIC指数分布分别为：FICI≤0.5占56.7%(17/30)、10%(3/30)、36.7%(11/30)、50%(15/30)、6.7%(2/30);0. 5＜FICI≤1占43.3%(13/30)、83.3%(25/30)、63.3%(19/30)、40%(12/30)、50%(15/30);1＜FIC＜4占0、6.7%(2/30)、0、10%(3/30)、43.3%(13/30);FIC≥4均为0。磷霉素和头孢哌酮/舒巴坦分别使联用后的亚胺培南MIC50降为单用时的1/16、1/2,MIC90降为单用时的1/8、1/2;均使联用后的米诺环素MIC50、MIC90降为单用时的1/8和1/4。结论 联合用药方案对比,头孢哌酮/舒巴坦联合米诺环素最具优势,协同作用最强,优于磷霉素联合米诺环素,但提高米诺环素抗菌活性的能力相当。头孢哌酮/舒巴坦联合亚胺培南以相加、无关效应为主,试验结果可见联用后效果逊于磷霉素联合亚胺培南,且磷霉素提高亚胺培南抗菌活性的能力更强。     

嗜麦芽寡养单胞菌对黏菌素的耐药特征及体外联合抗菌活性研究

目的 研究黏菌素分别与氯霉素、左氧氟沙星、头孢他啶、米诺环素及复方磺胺甲噁唑联用对多重耐药嗜麦芽寡养单胞菌的体外抗菌活性。方法 收集2015—2018年分离自温州医科大学附属第一医院的431株嗜麦芽寡养单胞菌;采用微量肉汤稀释法检测黏菌素对嗜麦芽寡养单胞菌的最低抑菌浓度(minimal inhibitory concentration, MIC),计算逐年耐药率;通过棋盘法和微量肉汤稀释法检测黏菌素分别与氯霉素、左氧氟沙星、头孢他啶、米诺环素与复方磺胺甲噁唑联用及各自单用时对多重耐药嗜麦芽寡养单胞菌的MIC值,并通过计算部分抑菌浓度指数(FICI)评价联合抑菌效果。结果 2015—2018年间,我院嗜麦芽寡养单胞菌对黏菌素的耐药率呈现逐年上升趋势;黏菌素与氯霉素、左氧氟沙星及米诺环素联用后均表现为协同或相加作用;与头孢他啶及复方磺胺甲噁唑联用都存在无关作用,未发现拮抗作用。结论 黏菌素与氯霉素、左氧氟沙星、米诺环素联合对多重耐药嗜麦芽寡养单胞菌具有较好的体外抗菌活性,将对临床联合用药治疗多重耐药嗜麦芽寡养单胞菌的选择更具指导意义。     

替加环素联合5种抗菌药物对多重耐药鲍曼不动杆菌的体外活性

目的 评价替加环素分别联合5种临床常用抗不动杆菌属抗菌药物对57株多重耐药鲍曼不动杆菌的体外抗菌作用.方法 琼脂棋盘稀释法测定替加环素分别联合美罗培南、阿米卡星、环丙沙星、粘菌素、舒巴坦对57株对美罗培南、阿米卡星、环丙沙星、米诺环素均耐药的多重耐药鲍曼不动杆菌的最低抑菌浓度(MIC),并计算部分抑菌浓度指数(FICI).结果 替加环素与5种抗菌药物联合后表现为协同或不相关作用,其中协同率较高的组合为替加环素+阿米卡星组,50.9％;其次为替加环素+美罗培南组,29.8％,未发现拮抗现象.结论 替加环素与5种抗菌药物联合对本组多重耐药鲍曼不动杆菌主要表现为不相关作用,但与阿米卡星联合具有相对较高的协同率.     

嗜麦芽寡养单胞菌对黏菌素的耐药特征及体外联合抗菌活性研究

目的 研究黏菌素分别与氯霉素、左氧氟沙星、头孢他啶、米诺环素及复方磺胺甲噁唑联用对多重耐药嗜麦芽寡养单胞菌的体外抗菌活性。方法 收集2015—2018年分离自温州医科大学附属第一医院的431株嗜麦芽寡养单胞菌;采用微量肉汤稀释法检测黏菌素对嗜麦芽寡养单胞菌的最低抑菌浓度(minimal inhibitory concentration, MIC),计算逐年耐药率;通过棋盘法和微量肉汤稀释法检测黏菌素分别与氯霉素、左氧氟沙星、头孢他啶、米诺环素与复方磺胺甲噁唑联用及各自单用时对多重耐药嗜麦芽寡养单胞菌的MIC值,并通过计算部分抑菌浓度指数(FICI)评价联合抑菌效果。结果 2015—2018年间,我院嗜麦芽寡养单胞菌对黏菌素的耐药率呈现逐年上升趋势;黏菌素与氯霉素、左氧氟沙星及米诺环素联用后均表现为协同或相加作用;与头孢他啶及复方磺胺甲噁唑联用都存在无关作用,未发现拮抗作用。结论     

耐碳青霉烯鲍曼不动杆菌的体外联合药敏试验研究

目的：对耐碳青霉烯鲍曼不动杆菌进行体外联合药敏试验,寻找有效的抗菌药物组合。方法：选取临床分离的耐碳青霉烯鲍曼不动杆菌株72株,采取棋盘法设计微量肉汤稀释法进行抗菌药联合体外抑菌试验,判断抗菌药联合应用效应。结果：头孢哌酮/舒巴坦与利福平、米诺环素、美罗培南联合应用及米诺环素与美罗培南联合应用对耐青霉烯鲍曼不动杆菌的抗菌效应主要表现为协同和相加作用;头孢哌酮/舒巴坦与左氧氟沙星联合应用主要表现为无关作用,小部分表现为协同和相加作用。结论：建议对耐碳青霉烯鲍曼不动杆菌引起的院内感染,可联合应用头孢哌酮/舒巴坦和米诺环素、利福平、美罗培南或者联合应用米诺环素和美罗培南进行治疗。     

替加环素单药及与5种抗菌药物联用对耐碳青霉烯类鲍曼不动杆菌的体外抑菌及生物膜清除作用研究#br#

目的 评价替加环素单用及与其他5种临床常用抗菌药物分别联合使用，对耐碳青霉烯类鲍曼不动杆菌(carbapenems-resistant Acinetobacter baumannii, CRAB)的体外抑菌及生物膜清除作用。方法 微量肉汤稀释法测定替加环素、阿米卡星、美罗培南、环丙沙星、黏菌素和舒巴坦对42株CRAB的最低抑菌浓度(minimal inhibititory concentration, MIC)和最低生物被膜清除浓度(minimal biofilm eradication concentration, MBEC)。棋盘稀释法测定替加环素分别联用阿米卡星、美罗培南、环丙沙星、黏菌素和舒巴坦对42株CRAB的MIC值和MBEC值，并计算分级抑菌浓度指数(fractional inhibitory concentration index, FICI)和分级生物膜清除浓度指数(fractional eradication concentration index, FECI)。结果 替加环素与5种抗菌药物分别联用后，对CRAB的抑菌作用和生物被膜清除作用表现为协同或无关，均未发现拮抗现象。其中替加环素与阿米卡星联用后具有较高的协同抑菌率(47.6%, 20/42)，而替加环素与环丙沙星联用后则具有较高的生物膜协同清除率(30.9%, 13/42)。结论 与单药相比，替加环素与5种药物分别联用，对CRAB的体外抑菌及生物膜清除作用具有一定的增强效果。     

米诺环素对白念珠菌抗菌活性的实验室研究

目的 探究米诺环素在白念珠菌感染中的体外抗菌活性.方法 用K-B纸片扩散法对临床标本分离出的白念珠菌进行抗菌药物包括米诺环素的药敏试验,观察并记录所有药敏试验中,米诺环素的敏感程度及敏感率.结果 发现32种抗菌药物中只有米诺环素对自念珠菌有抑菌环,有抑菌环并且直径14mm以上的占41%.结论 米诺环素在体外具有抗真菌药的活性.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Deoxynivalenol in cereals in Russia

A survey of the occurrence of deoxynivalenol (DON) and zearalenone (ZEN) in wheat, rye, barley and maize harvested in 1989-2001 in several regions of Russia has been conducted. A total of 5652 samples of cereals were analysed for DON and ZEN by using TLC and normal-phase HPLC with UV-detector. DON was detected in 69% of 2166 samples from Krasnodar region which is considered to be the major Fusarium endemic region of Russia. The contamination levels ranged from 0.1 till 8.6 ppm, MTEL was exceeded in 37% of these samples. The positive correlation between DON concentration and a percentage of Fusaria-damaged wheat kernels has been shown. DON occurrence and contamination levels were much lower that for wheat. Based on the results of monitoring and the data of average actual consumption of wheat products in Russia, the estimated daily intake of DON per 1 kg of body weight (EDI)was calculated. EDI varied from 0.07 ug in 1990-1991 till 1.40 ug in 1992. Although average EDI were lower than adopted tolerable daily intake (TDI, 3 ug/kg body weight) EDIs for the North-Caucasian region in some cases exceeded TDI.