欧洲药典适用性认证介绍

目的介绍欧洲药典适用性认证程序,为国内药品监管机构和原料药生产企业提供信息,促进我国原料药生产企业的国际化。方法通过查阅调研欧盟相关药品法规和与EDQM同行面对面的交流,详细了解欧洲药典适用性认证的组织机构和具体程序。结果与结论欧洲药典适用性认证程序在对原料药的质量控制有重要作用,加强了药典的监管力度,进一步保证了原料药的质量、安全性和有效性。     

子宫中隔切除术后预防粘连方法探讨

目的 探讨子宫中隔并不孕患者宫腔镜术后不同处理方法预防宫腔粘连的效果.方法 55例子宫中隔并不孕患者行腹腔镜监护下宫腔镜子宫中隔切除术(TCRS),术后针对不同患者采用不同术后处理措施,包括宫腔放置与不放IUD,是否进行人工周期治疗,部分患者术后使用GnRH-a类药物治疗术后第1、3个月行宫腔镜检查随访,宫内放置IUD的患者;于术后第3个月取环.结果 54例患者术后进行宫腔镜检查随访,其中40例分别于术后第1、3个月完成了术后2次宫腔镜检查,另14例只完成一次检查.宫腔术后放环与否对术后宫腔形态影响无差异(P>0.05),术后使用人工周期治疗患者较未使用者子宫内膜厚,此两者术后第3个月宫腔镜检查发现宫底创面均已有内膜覆盖.使用GnRH-a类药物患者术后官腔形态满意.结论 TCRS术后宫腔放置IUD无助于预防术后粘连的发生;术后人工周期治疗应更个体化并有针对性的使用GnRH-a类药物治疗.术后及时进行宫腔镜检查随访可防止术后宫底新粘连的形成.     

Certification of suitability of monographs of the European pharmacopoeia

In April 1994, t he European Pharmacopoeia Commission set up a new procedure for the "Certification of Suitability of Monographs of the European Pharmacopoela" to deal with the changing requirements of the licensing authorities and the growth of international trade, notably as regards raw materials to be used in the manufacture of medicines. This procedure was the result of extensive collaboration between the licensing authorities of the European Union and the other parties to the European Pharmacopoeia Convention, and it enables a manufacturer of a raw material for pharmaceutical use to demonstrate that the purity of their substance is suitably controlled by the monograph of the European Pharmacopoeia; this demonstration is now required by the guideline on "Requirements in Relation to Active Substances" published in Volume 3A of the Rules Governing Medicinal Products in the European Union. Initially set up in response to problems with impurities of synthesis and residual solvents that can vary from one manufacturer to another, the procedure has gradually been extended to a very wide range of products including products of fermentation and, more recently, products with risk of transmitting agents of animal spongiform encephalopathies.     

Simulation of intratumoral release of Etanidazole: effects of the size of surgical opening

The efficacy of radiotherapy can be enhanced by the delivery of radiosensitizer (Etanidazole) to brain tumor from biodegradable polymer implants. This process is investigated by simulation carried out at a cut section of tumor with polymeric wafers of Etanidazole loading implanted in the resected cavity. The coupled mass and momentum equations are solved to obtain the transient solution of the drug distribution in the tumor. The polymeric delivery shows high therapeutic index, indicating the wafers' success in delivering more drugs to the tumor rather than to the tissue. The penetration distance of Etanidazole was found to decrease from 14 mm (at 5th/40th day after implantation) to 6.5 mm (at 30th/75th day), suggesting an initial high burst of drug release which cause nearby tissue toxicity and a low effective drug delivery towards the later stages. The short penetration depth is due to Etanidazole having low interstitial Peclet number and high elimination/diffusion modulus. Edema causes the interstitial pressure, velocity, and concentration to increase in all domains, and leads to enhanced convection and a lowering of therapeutic index. Simulations on the open tumor geometry show significantly lower efficacy of the drug delivery due to the uneven distribution of drug in the tumor zone.     

Concentration-dependence of biomarkers of exposure of methylenediphenyl-diisocyanate following acute inhalation exposure of rats

Rats were nose-only exposed for 6 h to polymeric methylenediphenyl-diisocyanate (pMDI). Concentrations varied from 0.12 to 12.7 mg/m(3) using a highly respirable aerosol. In regard to the concentration of the monomeric fraction of MDI contained in pMDI, the lowest concentration was in the range of the current workplace limit of MDI which is 0.05 mg/m(3). Biomarkers of exposure were determined in hydrolyzed urine (collection started after cessation of exposure for approximately 18 h; acid hydrolysis) and hydrolyzed hemoglobin (collection of blood approximately 20 h after cessation of exposure; alkaline hydrolysis). The determination revealed two-order of magnitudes higher yields of the biomarkers in urine when compared to hemoglobin. The concentration of analytes from the respective biological matrix was highly correlated with the airborne concentration of pMDI whilst their yields exhibited a reciprocal relationship to the airborne concentration of pMDI. A linear relationship could only be demonstrated by using a logarithmic transformation of data. With respect to the amount of 4,4'-methylenediphenyldianiline creatinine (MDA/g creatinine) in hydrolyzed urine of rats at an exposure level similar to the current workplace concentration of MDI, this marker of exposure was approximately 10-times lower in rats than predicted for humans. This suggests that the extrapolation of animal data to man as well as from one exposure regimen to another, without taking into consideration the different deposition/retention patterns of vapors (相似文献   

大肠艾希菌对20种抗生素的耐药性分析

用VITEK微生物自动分析仪对分纯的菌株进行鉴定和药敏试验。结果大肠艾希菌对青霉素类抗生素、喹诺酮类抗生素、复方新诺明的耐药率在69．2％～81．0％之间;氨基糖甙类中庆大霉素的耐药率最高达62．9％,丁胺卡那霉素的耐药率量低为16．7％;第一代头孢菌的耐药率明显高于第三代头孢菌素;而呋喃坦啶、泰能的敏感率分别为89．5％和100％。结果说明该菌对多种抗生素呈高度耐药,选用抗生素应以药敏试验结果为准。丁胺卡那霉素、第三代头孢菌素、呋喃坦啶、泰能都具有较高的抗菌活性。     

原发性十二指肠恶性肿瘤76例临床分析

目的分析原发性十二指肠恶性肿瘤临床表现、病理类型,探讨如何进行辅助检查的选择与减少病例的误诊。方法回顾性分析1997年3月至2008年3月收治的76例确诊为原发性十二指肠恶性肿瘤患者的临床资料。结果临床表现无特异性,可有腹痛、腹胀、黄疸、呕吐以及消化道出血等表现。从起病到入院确诊平均病程6.5个月。肿瘤好发于十二指肠降部,共64例,另外球部6例,水平部6例,升部0例,病理类型以腺癌为主,占90.8%。辅助检查以胃镜加十二指肠镜检出率最高91.2%,造影检查为87.1%,CT83.3%,B超70.4%,CA-19973.6%。结论提高原发性十二指肠恶性肿瘤预后的关键是早期诊断,对上述临床表现不能用常见疾病解释者应提高警惕,结合RECP、Gl、胃镜、CT、B超等多项辅助检查,可望达到早期诊断的目的。     

Mechanism of action of rituximab

The CD20 antigen is strongly and stably expressed on cells of the B-cell lineage, but not on stem cells, and is thus an ideal target antigen for antibody therapy of B-cell malignancies. Rituximab is a human-mouse chimeric monoclonal antibody to the CD20 antigen that kills B-cells by a number of different effector mechanisms. The human IgG component of the antibody is able to bind human complement and also interact with effector cells to kill cells by antibody-dependent cell-mediated cytotoxicity. Some investigators have also shown direct effects of the antibody on human tumor cell lines expressing CD20. These effects include inhibition of proliferation, induction of apoptosis and increased sensitivity to chemotherapeutic agents, although the extent to which each of these mechanisms may contribute to the anti-tumor action of rituximab remains to be determined. Rituximab thus acts by additional mechanisms compared to conventional chemotherapeutic agents. The chimeric nature of the antibody results in minimal immunogenicity and allows repeat use. The antibody may be combined with conventional chemotherapy, with potential for increased efficacy with minimal added toxicity.     

肠球菌感染现状及其耐药性的变迁

目的了解肠球菌感染现状及其耐药性的变迁,为预防和治疗肠球菌感染提供依据。方法收集孙逸仙纪念医院2009～2011年患者标本中分离的肠球菌属,按照CLSI推荐的方法和判断标准,用纸片扩散法进行药敏试验,用WHONET5.3软件和SPSS13软件进行统计分析。结果近3年从各种临床标本中共分离出1016株肠球菌,粪肠球菌587株（57.78%）,屎肠球菌370株（36.42%）。标本主要来源于尿液（21.26%）、痰液（17.42%）、体液及胆汁（17.22%）。粪肠球菌对氨苄西林/舒巴坦、氨苄西林、亚胺培南耐药率较低,分别为0%、7.5%、7.5%左右,对高浓度庆大霉素耐药率为50%左右;屎肠球菌耐药性明显高于粪肠球菌,对氨苄西林/舒巴坦耐药率超过90%,对高浓度庆大霉素耐药率超过70%,但对喹奴普汀/达福普汀仅为0.96%。肠球菌属细菌对利奈唑胺、万古霉素、替考拉宁仍最敏感（耐药率≤5%）,2010及2011年分别分离出耐万古霉素屎肠球菌1株及8株,耐利奈唑胺的粪肠球菌6株及4株,2011年分离出耐替考拉宁的屎肠球菌5株。结论万古霉素、替考拉宁和利奈唑胺是对肠球菌抑菌率最高的药物,万古霉素耐药肠球菌发生率有增加趋势,特别是出现了个别利奈唑胺耐药的肠球菌菌株,因此,监测肠球菌属的耐药状况对指导临床治疗具有重要意义。     

某院万古霉素临床用药合理性分析

目的:了解该院住院患者万古霉素的使用情况,评价其用药合理性。方法:采用回顾性调查方法,提取该院2008年住院患者208份使用万古霉素的病历,记录相关信息,参考《中国药典》(2005年版)和《新编药物学》(第15版)及实际临床经验,采用药物利用指数(DUI)对万古霉素使用合理性进行分析。结果:在208份病历中,合理用药60例(28.85%),基本合理82例(36.54%),不合理72例(34.62%)。结论:该院万古霉素的应用情况基本合理,但对适应证的把握有待提高,应加大力度执行《抗菌药物临床应用指导原则》,严格掌握适应证,减少经验用药,防止和延缓耐药菌株的蔓延,延长其使用寿命,使其在临床的使用更加安全、合理、有效。     

Maturation pathway of hemolysin of Aeromonas sobria and the mechanism of action of the hemolysin

Aeromonas sobria has been recognized as pathogens associated with acute gastroenteritis in both adults and children. The major virulence factor has been proposed to be hemolysin which possesses both hemolytic and enterotoxic activities. Mature (bio-active) hemolysin secreted out of cells binds to the target cells of the host and injure the cells. However, hemolysin remained in bacteria can not express such toxicity. It means that the maturation and secretion pathway of hemolysin is closely related to the pathogenicity of bacteria. Therefore, I examined the pathway and clarified the following events. Hemolysin synthesized in cytoplasm translocates across the inner membrane and appears in a periplasmic space. Hemolysins appeared in the space associates to form dimer in the space. The C-terminal region of hemolysin functions as a trigger in the association. Dimerized hemolysin crosses the outer membrane and emerges in milieu, but monomer can not cross it. Therefore, the C-terminal region of hemolysin attributes not only to the formation of the dimer but also to its secretion into milieu. Hemolysin emerged in milieu is inactive. Inactive hemolysin is converted to bio-Active hemolysin by deleting its carboxyl-terminal 42-amino-acid peptide. Active hemolysin generated binds to the receptor of the target cell and stimulates the production of cyclic AMP by the cell. I assume that this stimulation closely relates to the induction of diarrhea by hemolysin.     

Antimicrobial susceptibilities of clinical isolates of Morganella-proteus-providencia group of bacteria

We examined in vitro susceptibilities of 3,109 isolates belonging to 5 species of Proteeae to 2 penicillins, 5 cephems and 2 aminoglycosides. The isolates were collected from 69 hospital laboratories throughout Japan between 1986 and 1988. Minimal inhibitory concentrations were determined using the agar dilution method with inoculation of 10(8) cells/ml of bacteria. Proteus mirabilis had marked susceptibilities to the penicillins and cephems tested. Proteus vulgaris and Morganella morganii were similar in their susceptibilities to ampicillin (ABPC), piperacillin (PIPC), cefazolin (CEZ), cefotiam (CTM), latamoxef, gentamicin (GM) and netilmicin (NTL), but M. morganii was slightly more resistant to cefmetazole and ceftizoxime (CZX) than P. vulgaris. Providencia rettgeri also had a susceptibility pattern similar to that of P. vulgaris, except that P. rettgeri showed higher resistances to CZX, GM and NTL. Providencia stuartii had a very similar susceptibility pattern to P. rettgeri, but P. stuartii was much more resistant to GM and NTL than the latter. Some major differences on susceptibilities were clearly evident among the 5 species of Proteeae tested. Notable species-specific differences included higher susceptibilities of P. mirabilis to ABPC, PIPC, CEZ and CTM than others and stronger resistances of P. rettgeri and P. stuartii to GM and NTL.     

Mechanism of action of rituximab

Rituximab, the humanized chimeric anti-CD20 monoclonal antibody, represents a powerful tool for treating B-cell malignancies and is licensed for the treatment of relapsed or chemorefractory low-grade or follicular non-Hodgkin's lymphoma (NHL). It has a unique mode of action and can induce killing of CD20+ cells via multiple mechanisms. The direct effects of rituximab include complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity, and the indirect effects include structural changes, apoptosis, and sensitization of cancer cells to chemotherapy. In vitro studies have made a significant contribution to the understanding of these mechanisms of action and have led to the development of innovative and effective treatment strategies to optimize patient response. The most significant of these strategies is the combination of rituximab and CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), which is proving a highly effective combination in the treatment of NHL. However, all patients do not respond equally well to rituximab, and in vitro studies have identified a possible mechanism of resistance involving the anti-complement inhibitors CD55 and CD59. Neutralizing antibodies to CD55 and CD59 can overcome resistance to rituximab-mediated complement-mediated cytotoxicity in vitro. This paper overviews our understanding of the mechanisms of action of rituximab and identifies how this knowledge could be applied in a clinical setting to maximize response in both sensitive and resistant patients.     

Roles of interstitial cells of Cajal in regulation of motility of the mouse intestine

The role of interstitial cells of Cajal (ICC) in contractile activity of the gastrointestinal tract has been intensely studied. Among ICC present within various regions of the gastrointestinal tissue, ICC within the myenteric plexus (ICC-MY) and within the submuscular plexus (ICC-SMP) are regarded as the pacemaker. Action potentials initiated in ICC were suggested to propagate to adjacent smooth muscle cells and to induce the spontaneous activity. It was suggested that ACh-mediated contraction and nitric oxide-mediated relaxation were induced after these neuronal signals were transmitted to ICC and then to smooth muscle via the gap junction. This suggestion was based on the findings mainly in the esophagus, stomach, and small intestine by using ICC-deficient mice (W/W(V) and Sl/Sl(d)). In our studies, ICC-MY were shown to be closely associated with neuron-mediated contractile and relaxant responses and to be associated with neural reflexes for peristalsis, since ascending and descending reflexes were not seen in W/W(V) mice. In the distal colon of W/W(V) mice, in which ICC-MY and -IM were lost, these neural responses remained unchanged. It seems likely that ICC-MY and ICC-IM do not have any role in inducing these responses in the distal colon. It is concluded that the extent of association of ICC with the motility and the manner of the association vary from region to region in the gastrointestinal tract.     

A Criticism of the Practice of Prescribing Subtherapeutic Doses of Antidepressants for the Treatment of Depression

At doses greater than 125–150 mg daily, tricyclic antidepressants (TCAs) have been shown to be effective in patients with depressive illness. There is nevertheless, a pronounced tendency in general practice to prescribe antidepressants at half the dose likely to be prescribed for the same patient by a psychiatrist. The principal motivation for subtherapeutic dosing in primary care is to avoid the side-effects of TCAs which are likely to deter patients from complying with treatment. The misconception also prevails among some general practitioners that patients seen in general practice have less severe disorders and therefore require a reduced dose. Yet there is no clinical evidence to show that at doses of 75 mg daily or lower, TCAs are effective in the treatment of depressive illness. It is against all the principles of therapeutics to prescribe a given drug at a dosage below its therapeutic level. A more rational strategy would be to select a better tolerated antidepressant at the outset, such as one of the second generation antidepressants.     

中药专利保护对中药品种保护的辅助作用分析

为了更好、更有效地保护中药的知识产权,使国内中药产品走向国际市场,本文对中药品种保护和专利保护进行详细分析,比较中药专利保护和中药品种保护之间的优劣势,以便能够结合两者的优势,灵活运用这两种保护制度,达到最佳保护中药知识产权的目的.     

72株志贺菌耐药情况分析

目的 :了解近5年来我院志贺菌耐药情况变化。方法 :采集临床细菌性痢疾可疑病例粪便 ,进行培养及药敏试验检查。结果 :志贺菌对氨苄青霉素、氟喹诺酮的耐药性明显提高 ,对丁胺卡那霉素、头孢哌酮仍高度敏感。结论 :严格掌握抗菌药物用药指征 ,对预防细菌耐药性的产生 ,具有重要临床意义。     

The effects of cocaine and diphenhydramine upon the reactivity of rat vas deferens to supramaximal doses of noradrenaline and of other agonists: the mode of action of cocaine.

The effects of cocaine on responses to supramaximal concentrations of agonists have been studied in preparations of rat vas deferens. Cocaine 10 muM decreased the mean time to peak and increased the mean magnitude of responses to noradrenaline but not to supramaximal field stimulation of sympathetic fibres, to high potassium or to methoxamine. Diphenydramine 10 muM affected responses to noradrenaline similarly. It is proposed that the prejunctional action of cocaine and of diphenhydramine to reduce the rate of neuronal uptake of noradrenaline may provide a sufficient explanation for the enhanced reactivity of the vas deferens to noradrenaline, as this would allow an increased rate of rise of amine concentration at the receptors. Cocaine also enhanced the reactivity of the vas deferens to acetylcholine. The basis of this enhancement by cocaine of the reactivity of the vas deferens to acetylcholine remains to be established, but clearly is not mediated postjunctionally since responses to carbachol were not similarly affected.     

Biochemistry of reduction of nitro heterocycles

Misonidazole is a metabolically active drug. Its addition to cells causes an immediate alteration in cellular electron transfer pathways. Under aerobic conditions the metabolic alterations can result in futile cycling with electron transfer to oxygen and production of peroxide. Thiol levels are extremely important in protecting the cell against the peroxide formation and potentially hazardous conditions for hydroxyl radical production. Nevertheless such electron shunting out of cellular metabolism will result in alterations in pentose cycle, glycolysis and cellular capacity to reduce metabolites to essential intermediates needed in DNA metabolism (i.e. deoxyribonucleotides). Glutathione must be depleted to very low levels before toxic effects of misonidazole and other nitro compounds are manifested in cell death via peroxidative damage. Under hypoxic conditions misonidazole also diverts the pentose cycle via its own reduction; however, unlike the aerobic conditions, there are a number of reductive intermediates produced that react with non-protein thiols such as GSH as well as protein thiols. The reaction with protein thiols results in the inhibition of glycolysis and other as yet undetermined enzyme systems. The consequences of the hypoxic pretreatment of cells with nitro compounds are increased vulnerability to radiation and chemotherapeutic drugs such as L-PAM, cis-platinum and bleomycin. The role that altered enzyme activity has in the cellular response to misonidazole and chemotherapeutic agents remains to be determined. It is also clear that the GSH depleted state not only makes cells more vulnerable to oxidative stress but also to hypoxic intermediates produced by the reduction of misonidazole beyond the one electron stage. The relevancy of the present work to the proposed use of thiol depletion in vivo to enhance the radiation or chemotherapeutic response of tumor tissue lies with the following considerations. Apparently, spontaneous peroxidative damage to normal tissue such as liver can occur with GSH depletion to 10-20% of control and with other normal tissue when GSH reaches 50% of control. This situation can obviously become more critical if peroxide producing drugs are administered. The only advantage to such combined drug treatments would lie in the possibility that tumors vary in their catalase and peroxidase activity and consequently may be more vulnerable to oxidative stress (cf. review by Meister. Our tumor model, the A549 human lung carcinoma cell in vitro, appears to be an exception because it has catalase, peroxidase and a high content of GSH.(ABSTRACT TRUNCATED AT 400 WORDS)