生长因子诱导视网膜色素上皮细胞增殖的协同作用研究

目的从细胞水平探讨生长因子:肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)和碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)对视网膜色素上皮(retinal pigment epithelium,RPE)细胞增殖的协同调控作用。方法通过PPE细胞培养，采用氚标胸腺嘧啶核苷(3 H-thymidine,3 H-TdR)掺入测定三种生长因子单用和分别联用诱导RPE细胞DNA合成改变，细胞计数观察RPE细胞生长变化。结果三种生长因子单用均可明显促进RPE细胞DNA合成及细胞数目增加,TNF-α、IL-β和bFGF的3 H-TdR掺入每分钟计数值(counts per minute,cpm)分别是对照组的2.74、2.66和1.69倍(P<0.05)。两种生长因子联用较单用cpm明显提高,其中TNF-α+IL-βcpm是对照组的3.14倍(P<0.05)。三种生长因子联用时cpm是对照组的3.74倍(P<0.05)。结论三种生长因子间存在促RPE细胞增殖的协同作用,这可能是生长因子对RPE细胞增殖的重要调控机制之一。(中华眼底病杂志,1998,14:95-97)     

Pan-drug-resistant Pseudomonas aeruginosa causing nosocomial infection at a university hospital in Taiwan

This study evaluated the clinical and microbiological characteristics of 16 patients who were colonised or infected with 26 isolates of pan-drug-resistant Pseudomonas aeruginosa (PDRPA; intermediately-resistant or resistant to all cephalosporins, piperacillin-tazobactam, aztreonam, carbapenems, ciprofloxacin and aminoglycosides) in a university hospital during 1999-2002. All the isolates had colistin MICs < or = 4 mg/L, 19 (73%) isolates had bla(VIM-3), and 25 (96%) isolates had class I integrons (intI). Time-kill studies for two PDRPA blood isolates demonstrated synergism for cefepime-amikacin after 24 h. Pulsed-field gel electrophoresis analysis of the isolates revealed a polyclonal nature (12 pulsotypes), although clonal dissemination of PDRPA isolates among these patients was also present.     

吗丙嗪增强阿霉素的体外抗肿瘤细胞毒作用(英文)

吗丙嗪(Pro)0.313,0.625和1.25μg·ml~(-1)可增强阿霉素(Dox)体外对艾氏腹水癌(EAC)的细胞毒作用;Pro 116.5,233和466 μg·ml~(-1)也可明显增加EAC细胞中的Dox含量,在S_(37)荷瘤小鼠中Pro可降低肝细胞线粒体而增加肿瘤细胞线粒体中Dox诱发的MDA含量。提示Pro的增效作用可能与其增加肿瘤细胞中Dox积聚有关,或许与MDA含量亦有关。     

Potential synergism between hypnosis and acupuncture—is the whole more than the sum of its parts?

Both hypnosis and acupuncture have gained credibility over theyears in their effectiveness for treating various health conditions.Currently, each of these treatments is administered in distinctsettings and separate times. That is, even if patients receiveboth treatments as part of a multidimensional therapeutic program,they would typically receive them separately rather than simultaneouslyat the same session. This separation however might be undesirablesince, at least theoretically, hypnosis and acupuncture couldpotentially augment each other if administered concomitantly.In this article we outline the rationale for this hypothesisand discuss the potential ramifications of its implementation.     

An analysis for a cross-over cohort study with an application to the study of triggers of Menière's disease

When studying the effect of a transient exposure on the risk of a rare illness, for time and cost effectiveness it is desirable to follow a cohort of individuals who are 'prone' to the illness over an observation period. In this paper, we present a method of analysis for data arising from such a study. The proposed method can be used to estimate the relative risk of an exposure triggering the illness and the distribution of the time delay from exposure to the onset of illness. The model is extended to include covariate effects and to the situation where there are two types of exposure. For the two types of exposures situation, a model to handle a possible synergism of the exposures is proposed. Finally, the method is applied to study the potential triggers of attacks of Menière's disease.     

Sinus arrest caused by atenolol-verapamil combination

A case on concomitant atenolol-verapamil therapy for hypertension and angina pectoris, developing sinus arrest and life-threatening bradycardia is described. The complication occurred with low doses of both the agents and normal electrophysiologic status of the heart. The example suggests that pharmacodynamic synergism contributes more than pharmacokinetic interaction causing adverse reactions during beta blocker-verapamil therapy.     

Anti-vWf Antibodies Induce GPIbα and FcγRII Mediated Platelet Aggregation Only at Low Shear Forces

Background/Methods: Anti-von Willebrand factor (vWf) antibody mediated platelet activation was studied using 2 monoclonal anti-vWf antibodies promoting the binding of vWf to GPIb: 1C1E7 (IgG2a) reacting with the vWf N-terminus and 75H4B12 (IgM), characterized in this paper and studied in association with 1C1E7. Results: 75H4B12 binds to an N-terminal epitope in vWf, different from that reacting with 1C1E7. When com-bined, 1C1E7 and 75H4B12 promoted vWf binding to isolated GPIb under static conditions, even in the absence of ristocetin or botrocetin, and induced platelet aggregation synergistically in the presence of zero to subthreshold ristocetin concentrations. Specific inhibitors of GPIb-vWf interactions prevented vWf binding to GPIb in ELISA and during platelet aggregation. In addition, the 1C1E7 dependent platelet aggregation involved Fc receptor mediated platelet activation, a phenomenon even more pronounced when 1C1E7 and 75H4B12 were combined. A 75H4B12 binding phage expressing a peptide homologous with vWf sequence 88–95 neutralized the antibody induced platelet activation. However, at arterial shear rates, both 1C1E7 and 75H4B12 potently prolonged cartridge closure times in the PFA-100, compatible with inhibition of platelets by vWf, unfolded by the combined action of shear stress and antibodies. Conclusions: We conclude that antibodies directed against different epitopes in the N-terminus of vWf modify the folded vWf structure synergistically and enhance A1 domain mediated vWf binding to platelet GPIb at low shear forces. In addition, once platelet-bound, IgG antibodies potently activate platelets via the FcII receptor. Thus, such antibodies may promote immune mediated thrombosis at low shear rates, typical of the venous circulation. In contrast, at arterial shear rates, anti-vWf antibodies may rather compromise platelet function following enhanced binding of the unfolded vWf multimers to platelets, shielding platelets from interacting with subendothelial and soluble ligands.     

Mechanism of action and initial evaluation of a membrane active all-D-enantiomer antimicrobial peptidomimetic

Development of therapy against infections caused by antibiotic-resistant pathogens is a major unmet need in contemporary medicine. In previous work, our group chemically modified an antimicrobial peptidomimetic motif for targeted applications against cancer and obesity. Here, we show that the modified motif per se is resistant to proteolytic degradation and is a candidate antiinfective agent. We also show that the susceptibility of microorganisms to the drug is independent of bacterial growth phase. Moreover, this peptidomimetic selectively interferes with the integrity and function of the microbial surface lipid bilayer, data indicative that bacterial death results from membrane disruption followed by dissipation of membrane potential. Finally, we demonstrate two potential translational applications: use against biofilms and synergy with antibiotics in use. In summary, we introduce the mechanism of action and the initial evaluation of a prototype drug and a platform for the development of D-enantiomer antimicrobial peptidomimetics that target bacterial membranes of certain Gram-negative problem pathogens with promising translational applications.     

氯丙嗪对紫杉醇协同作用的实验研究

目的 观察氯丙嗪与紫杉醇联合应用对人肺巨细胞癌株（PLA801D）增殖抑制及对其细胞周期的影响。方法 采用MTT法检测不同浓度紫杉醇单独及与氯丙嗪联合使用时对PLA801D细胞的生长抑制率；应用流式细胞术分析单独及联合用药后，PLA801D细胞周期的变化和凋亡率。结果 单药组诱导的凋亡率随紫杉醇剂量增加而升高，当紫杉醇浓度为24μg／ml时，诱导的凋亡率最高为13．2％；而两药联用（紫杉醇剂量不变，氯丙嗪剂量为4μg/ml），诱导的凋亡率明显高于紫杉醇单用组为55．8％，两组比较差异显著（P〈0．01）。同时，两药联用比单用抑瘤率亦有不同程度的提高（P〈0．05），且呈时间、剂量依赖性。结论 在一定浓度范围内，氯丙嗪在增强紫杉醇诱导PLA801D细胞凋亡及增殖抑制作用上具有明显的协同效应。