盐酸左氧氟沙星氯化钠注射液无菌检查法Mg~(2+)加入方法验证

目的研究Mg2+在盐酸左氧氟沙星氯化钠注射液无菌检查法中的应用。方法在培养基及冲洗液中加入不同浓度的Mg2+,观察不同方法中6种阳性对照菌的生长情况。结果 Mg2+浓度和加入方式对去除盐酸左氧氟沙星氯化钠注射液的抑菌性有不同的影响。结论含Mg2+浓度为0.2 mol.L-1的培养基能够有效去除盐酸左氧氟沙星氯化钠注射液药物的抑菌性。     

无菌检查中消除喹诺酮类药物抗菌活性的方法研究

目的考察Mg2+、β-环糊精、组氨酸-卵磷脂-聚山梨酯80对不同浓度莫西沙星的中和效果,完善喹诺酮类药物的无菌检验方法。方法将试验菌直接接种至含一定浓度的莫西沙星培养基中,同时更换冲洗液和冲洗量,结合中和法,用薄膜过滤法对6个品种进行方法学验证。结果Mg2+的中和效果最好,采用薄膜过滤法和中和法能有效消除其抗菌活性。结论建议将验证方法收载入《中国药典》。     

降低喹诺酮类药物抗菌活性的金属离子筛选

目的对金属离子是否可作为中和剂用于喹诺酮类药物微生物限度检查进行初步筛选。方法在不同平皿中加入不同体积的同浓度金属离子,然后均加入实验菌株(50～100cfu.mL-1),进行菌落计数。结果 Al 3+、Fe3+、Mn2+本身对实验菌株生长有明显的抑制作用,而Ca2+和Mg2+对实验菌株的生长没有干扰,但Mg2+的中和效果更好。结论 Mg2+可作为中和剂应用于喹诺酮类药物微生物限度检查。     

硝基咪唑类药物无菌检查中吐温80应用的研究

目的研究吐温80在硝唑类药物无菌检查法中的应用。方法在培养基及冲洗液中加入不同浓度的吐温80,观察不同方法中6种阳性对照菌的生长情况。结果吐温80浓度和加入方式对去除硝基咪唑类药物的抑菌性有不同的影响。结论含吐温80浓度为0.5%的培养基能够有效去除硝基咪唑类药物的抑菌性。     

喹诺酮类药物的不良反应

喹诺酮类是人工合成的含 4-喹诺酮基本结构 ,对细菌 DNA螺旋酶 (DNAgyrase)具有选择性抑制的抗菌药物 ,目前发展迅速 ,临床应用极广。本文主要阐述氟喹诺酮类药物的毒性 ,特别关注抗革兰氏阳性菌活性增强的新氟喹诺酮类药物如 :左氧氟沙星、司帕沙星、格帕沙星、曲伐沙星和莫西沙星。所以喹诺酮类药物一个共同特征是与二价阳离子形成螯合物 ,水溶液中 ,氟喹诺酮类药物与二价金属阳离子稳定常数顺序为 :Cu2 + >Fe2 + >Zn2 + >Mg2 + >Ca2 + 。喹诺酮类药物与金属离子的密切关系似乎是抗菌治疗的先决条件 ,可能喹诺酮类药物通过一个 Mg2 +…     

喹诺酮类药物治疗下呼吸道感染性疾病的合理应用

目的：对使用喹诺酮类药物治疗下呼吸道感染性疾病的情况进行统计,采用细菌耐药突变选择窗理论,通过最低抑菌浓度和防突变选择浓度为临床治疗中合理使用喹诺酮类药物提供科学依据。方法：随机抽取下呼吸道感染病例108例,统计用药种类、喹诺酮类药物所占比例以及喹诺酮类药物与其他药物联合使用情况,采用MSW对患者的治疗结果进行分析。结果：使用喹诺酮类药物69例（占总病例的63.9%）,其中喹诺酮类药物与其他药物联合使用的28例（占40.6%）。结论：采用喹诺酮类药物治疗下呼吸道感染性疾病符合MSW,用药合理,但该类药物与β-内酰胺类药物联合使用易导致细菌多重耐药性的突变。     

喹诺酮类药物在下呼吸道感染性疾病中的合理应用

目的采用细菌耐药突变选择窗（MSW）理论对下呼吸道感染性疾病患者氟喹诺酮类药物使用情况进行分析,以最低抑菌浓度（MIC）和防突变选择浓度（MPC）指导临床合理使用氟喹诺酮类药物,减少耐药菌产生。方法抽取呼吸内科病历100份,统计用药情况和氟喹诺酮类药物使用种类,以及氟喹诺酮类药物在抗菌药物中所占比例、氟喹诺酮类药物与其他药物联合应用情况,采用MSW理论对结果进行分析。结果100份住院病历中抗菌药物使用率100.0%,使用喹诺酮类药物61例（占61.0%）,其中氟喹诺酮类药物与β内酰胺类抗生素联合应用26例（占42.6%）。结论氟喹诺酮类抗菌药物治疗下呼吸道感染性疾病符合MSW理论,使用合理。但氟喹诺酮类药物与β内酰胺类药物联用不能关闭MSW,且更易导致细菌产生多重耐药性。     

氟嗪酸的后效应与Mg~(2+)的影响

曾有报道尿中喹诺酮类药物的活性与Mg~(2+)浓度和pH有关。本文测定了Mg~(2+)对金葡菌的生长,对氟嗪酸活性和抗菌后效应(PAE)的影响。作者采用MHB和MHB+MgCl_2的培养方法测定氟嗪酸的PAE和MIC,并按以下条件分别进行菌落计数。1.用1.4mg/L氟嗪酸培养2小时;2.用清洗离心方法除去药物;3.在无药物的培养基中进一步培养。每次实验重复3～4次,从第一个与对照有显著不同的数据开始记录,数据进行t湿著性测验。     

替硝唑氯化钠注射液无菌检查中吐温80应用的研究

目的研究吐温80在替硝唑氯化钠注射液无菌检查法中的应用。方法在培养基及冲洗液中加入不同浓度的吐温80,观察不同浓度中6种阳性对照菌的生长情况。结果吐温80浓度和加入方式对去除替硝唑氯化钠注射液的抑菌性有不同的影响。结论含吐温80 5mL.L-1的培养基能够有效去除替硝唑氯化钠注射液的抑菌性。     

喹诺酮类药物用于结核病治疗的探讨

喹诺酮类是人工合成的含有4-喹酮母核的一类抗菌药,具有广谱、高效、给药方便的特点,与其他常用抗菌药无交叉耐药性,另外,这类药物对结核分枝杆菌抗菌作用强,并且在肺组织、呼吸道粘膜组织中的浓度均超过对结核分枝杆菌的最低抑菌浓度（MIC）,并且在感染部位的组织浓度对血药浓度的比值较正常组织中高,尤其是在痰、支气管粘膜、肺等组织的药浓度／血清浓度为2倍或更高,显示了喹诺酮类对肺结核的强大治疗作用。随着近年来在结核病治疗中的应用,喹诺酮类药物为临床治疗结核病开拓了更为广阔的前景。然而,同样由于其广泛应用,在治疗结核病的过程中开始出现喹诺酮类药物的滥用,     

Ciprofloxacin causes cytoskeletal changes and detachment of human and rat chondrocytes in vitro

Quinolones cause damage of articular cartilage in different species by forming chelate complexes with divalent cations and inducing magnesium deficiency. Cations are important for regular function of integrins, a group of transmembrane proteins which connect extracellular matrix proteins with the intracellular cytoskeleton. We have shown that cultivation of rat chondrocytes in ciprofloxacin (CFX)-supplemented and Mg(2+)-free medium led to pronounced changes in the cytoskeleton and decreased adhesion of cells to the culture dish. In order to test whether or not these effects are species-specific, we extended our studies on human chondrocytes. Human chondrocytes cultivated in CFX-supplemented medium (10, 40, 80 and 160 microg/ml) or Mg(2+)-free medium showed decreased ability to adhere to growth support, cell shape changes, and alterations in actin and vimentin cytoskeleton in a concentration dependent manner. Attachment of human chondrocytes to collagen type II coated cover slips was reduced to 90% in CFX group and 75% in Mg(2+)-free group on day 1. This effect even increased after 4 days of culture in the respective medium (32% in CFX and 58% in Mg(2+)-free group). We concluded that Mg(2+) deficiency is exerted via integrins, resulting in decreased ability to attach to extracellular matrix proteins and cytoskeletal changes. These effects are not species-specific. The attachment assay proves to be an easy to use experimental set-up to test ciprofloxacin and other quinolones for their chondrotoxic effects.     

Removal of extracellular Mg2+ suppresses sulfation of glycoconjugates secreted from rabbit trachea in culture.

The influences of extracellular Ca2+ and Mg2+ concentrations on the basal secretion of glycoconjugates from rabbit trachea in organ culture were examined. Over 80% of the 35S-labeled and [3H]glucosamine-labeled glycoconjugates secreted by the trachea were digested upon incubation with chondroitinase ABC. The basal secretion did not occur in the medium at 4 degrees C, indicating an energy-dependent process. The basal secretion at 37 degrees C of 35S-labeled glycoconjugates was prominently suppressed in Mg(2+)-free Tyrode solution but not in Ca(2+)-free Tyrode solution containing ethyleneglycol bis(2-aminoethylether)tetraacetic acid (EGTA). In contrast, the basal secretion of [3H]glucosamine-labeled glycoconjugates was not affected by the Mg2+ concentration in the medium. The results suggest that extracellular Mg2+ largely contributes to sulfation of glycoconjugates basally secreted from rabbit trachea.     

Ultrastructural characterization of murine limb buds after in vitro exposure to grepafloxacin and other fluoroquinolones

The effects of selected quinolones (levofloxacin, lomefloxacin, temafloxacin and grepafloxacin) on growth and differentiation of murine limb buds were studied in vitro. Ciprofloxacin and ofloxacin served as controls. We used limb buds from 12-day-old mouse embryos that were grown for 6 days in a serum-free, standard or magnesium-deficient medium. Besides evaluation under a dissecting microscope, we used electron microscopy to characterize the effects in detail. The following results are noteworthy. (1) Comparing the effects of standard and magnesium-deficient medium after 3 and 6 days in culture, we found ultrastructural changes after 6 days only. (2) Direct comparison of ofloxacin (racemate) and levofloxacin (L-enantiomer) showed that they had a similar, rather low, potential for affecting cartilage development. (3) The effects of temafloxacin and ciprofloxacin were more pronounced in magnesium-deficient medium, but those of the other drugs were not. (4) Grepafloxacin was the most active quinolone in this assay. It impaired growth and differentiation of limb buds at 30 mg/l; at higher concentrations the explants did not grow. With lower concentrations of 10 mg grepafloxacin/l, no effects were detectable under a dissecting microscope but characteristic changes were seen by electron microscopy. We observed electron-dense aggregates on and within chondrocytes, detachment of the cell membrane from the matrix with matrix-free pericellular areas around chondrocytes, and swelling of cell organelles such as mitochondria and rough endoplasmic reticulum. (5) The affinity of grepafloxacin for divalent cations (Mg2+, Ca2+) was studied by measuring the fluorescence of grepafloxacin solution at various concentrations of Mg2+ and Ca2+. Grepafloxacin showed a relatively high affinity for Ca2+ in the fluorescence assay, which was more pronounced than the affinities of six other fluoroquinolones tested before.     

Effects of secretagogues on intracellular free calcium and magnesium concentrations in rat pancreatic acinar cells.

1. Rat pancreatic acinar cells were loaded with Fura 2 AM or Magfura AM and levels of cytosolic Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were observed. 2. Addition of acetylcholine (ACh) evoked a transient rise in [Ca2+]i. The component of the rise dependent on extracellular Ca2+ sources, but not intracellular sources, was seen to be enhanced when both ACh and 5 mM Ca2+ were present in the medium. In the presence of elevated extracellular Mg2+ (10 mM) and ACh both components of the Ca2+ transient were inhibited. 3. Both GTP gamma S and fluoroaluminate, which can directly stimulate G-proteins, evoked a transient rise in [Ca2+]i in acinar cells. These responses were inhibited in the presence of elevated Mg2+. 4. Resting [Mg2+]i was seen to be 1.36 mM +/- 0.08 (n = 29) for cells in normal medium, 1.8 mM +/- 0.08 (n = 6) in elevated Mg2+ medium and 0.93 mM +/- 0.02 (n = 5) in cells bathed and Mg(2+)-free medium. Addition of ACh led to reductions in [Mg2+]i in cells bathed in normal medium and Mg(2+)-free medium but not elevated Mg2+ medium. 5. It is concluded that levels of extracellular Mg2+ strongly influence [Mg2+]i and [Ca2+]i mobilization during ACh-evoked responses. Mg2+ does not appear to be exerting its effects by influencing receptor-agonist interactions or by competing with Ca2+ at extracellular sites of Ca2+ uptake.     

Mg2+在药物无菌检查中的应用

为了适应新时期科技期刊数字化发展的需要,本刊已完成过刊的数字化制作工作。在创刊25周年之际,特在本刊网站www.chinjmap.com推出。各位读者可以通过网络随时随地查阅本刊所有已刊出文献的全文。     

腹腔感染的抗菌药联用分析

目的:调查我院腹腔感染中抗菌药联合使用情况.方法:利用我院HIS系统,对抗菌药联用进行统计分析.结果:抗菌药使用高于卫生部规定.抗菌药联用以两联用药为主共152例,联用类别:β-内酰胺类+喹诺酮类,碳青霉烯类+糖肽类,β-内酰胺类+糖肽类,占据药物联用品种的前三位.三联用药为14例.存在抗菌药联用不合理现象及喹诺酮类药物使用过度的问题.结论:抗菌药使用要依据药敏试验及细菌培养结果进行调整,存在联合应用指征方可联用.     

Effect of magnesium deficiency on intracellular ATP levels in human lens epithelial cells

Cataractous lenses have an altered distribution of the intracellular ionic environment, and the lens ionic imbalance with increased levels of calcium (Ca2+) and sodium (Na+), coupled with decreased levels of magnesium (Mg2+) and potassium (K+), is related to cataract development in human senile cataracts. We previously found that the decrease of ATP in lenses caused lens ionic imbalance, and probably decrease in ATPase function. In this study, we investigated the effect of Mg2+ deficiency on cataract progression using human lens epithelial (HLE) cells. Expression levels of inducible nitric oxide synthase (iNOS) mRNA in HLE cells were significantly greater in Mg2+-deficient medium (Mg2+ 0.021 mM) than in normal Mg2+ medium (Mg2+ 0.77 mM). The NO release from the HLE cells cultured with Mg2+-deficient medium also increased. On the other hand, the ATP levels in HLE cells 24 h after incubation with Mg2+-deficient medium were lower than that with normal Mg2+ medium. The Ca2+- and Na+/K+-ATPase activities in HLE cells until 24 h incubation with normal Mg2+ or Mg2+-deficient medium did not change. Both diethyldithiocarbamate 10 microM and aminoguanidine 250 microM attenuated the increase of NO release, and caused an increase in ATP levels in HLE cells 24 h after incubation with Mg2+-deficient medium. These results suggest that Mg2+ deficiency enhances NO production via iNOS in the lens. It is possible that the excessive production of NO cause the decrease of ATP levels. These results show that Mg2+ deficiency in the lens may cause an acceleration of the progression of lens opacification.     

Development of measurement of new quinolones in body fluids by HPLC using column switching and their application to drug interaction

A high-performance liquid chromatography (HPLC) assay was developed for the determination of 6 new quinolones in the plasma. The plasma samples were directly introduced onto a HPLC column after filtering through a Molcut II membrane filter, which removes high molecular weight proteins. New quinolone in filtrate was separated from interfering substances and retained on a pre-column using an ODS stationary phase and then was introduced onto an analytical column with an ODS stationary phase by column switching. New quinolones were detected by ultraviolet absorbance in the range of 269-300 nm. Determinations of new quinolones were possible over the concentration range of 50-4000 ng/ml; the limits of detection were 20 ng/ml. The recoveries of the new quinolones added to the plasma were 96.1-101.4% with a coefficient of variation of less than 5.0%. These methods were applied to drug level monitoring in the plasma of patients treated with new quinolones and in that of healthy volunteers participating in pharmacokinetic studies. In addition, these methods were applied to a drug interaction between new quinolones and metal cation (e.g.; Mg2+, Al3+ or Fe2+) containing agents. Furthermore, this method was applied to the determination of skin tissue level of ofloxacin in patients after treatment with ofloxacin. A correlation between serum levels and skin tissue levels of ofloxacin was determined for 30 patients after oral administration of ofloxacin. A good correlation was obtained and the coefficient of the correlation was 0.84.     

我院2005年-2006年氟喹诺酮类抗菌药物应用分析

目的：了解我院氟喹诺酮类抗菌药物的应用情况。方法：对2005年～2006年我院氟喹诺酮类抗菌药物使用数量、消耗金额、用药频度（DDDs）和日均费用（DDDc）进行统计分析。结果：2005年～2006年均是氟喹诺酮类抗菌药物片剂的用药频度最高，注射液中用药频度最高为加替沙星。2006年氟喹诺酮类抗菌药物日均费用均低于2005年。结论：近2年内氟喹诺酮类抗菌药物的使用情况基本一致，随着氟喹诺酮类抗菌药耐药问题的日益严重，在医院内部有计划地更替使用抗菌药物、减缓抗菌药物耐药性发展的任务已迫在眉睫。