The selectivity of different external binding sites for quaternary ammonium ions in cloned potassium channels

Tetraethylammonium (TEA) is thought to be the most effective quaternary ammonium (QA) ion blocker at the external site of K⁺ channels, and small changes to the TEA ion reduce its potency. To examine the properties of the external QA receptor, we applied a variety of QA ions to excised patches from human embryonic kidney cells or Xenopus oocytes transfected with the delayed rectifying K⁺ channels Kv 2.1 and Kv 3.1. In outside-out patches of Kv 3.1, the relative potencies were TEA > tetrapropylammonium (TPA) > tetrabutylammonium (TBA). In contrast to Kv 3.1, the relative potencies in Kv 2.1 were TBA > TEA > TPA. In Kv 3.1 and Kv 2.1, external tetrapentylammonium (TPeA) blocked K⁺ currents in a fast, reversible and, in contrast to TEA, time-dependent manner. The external binding of TPeA appeared to be voltage independent, unlike the effects of TPeA applied to inside-out patches. External n-alkyl-triethylammonium compounds (C₈, C₁₀ chain length) had a lower affinity than TEA in Kv 3.1, but a higher affinity than TEA in Kv 2.1. In Kv 3.1, the decrease in QA affinity was large when one or two methyl groups were substituted for ethyl groups in TEA, but minor when propyl groups replaced ethyl groups. Changes in the free energy of binding could be correlated to changes in the free energy of hydration of TEA derivatives calculated by continuum methodology. These results reveal a substantial hydrophobic component of external QA ion binding to Kv 2.1, and to a lesser degree to Kv 3.1, in addition to the generally accepted electrostatic interactions. The chain length of hydrophobic TEA derivatives affects the affinity for the hydrophobic binding site, whereas the hydropathy of QA ions determines the electrostatic interaction energy.     

BACTEC 9050自动血培养仪的临床应用

目的 评价BACTEC 9050自动血培养仪的临床应用情况。方法 分析2年来自动血培养仪检测的阳性率、阳性报警时间、菌种鉴定及临床分析。结果 检测2424份血培养标本，分离出328株菌，总阳性率为13．5％（328／2424），其中革兰阴性菌167株（50．91％，167／328），阳性菌112株（34、15％，112／328），真菌49株（14．94％，49／328）。分离率居前三位的细菌是大肠埃希菌（22．86％），金黄色葡萄球菌和肺炎克雷白菌（10．36％），白色念珠菌（7、32％）。在全部328例阳性瓶中，24h阳性报告率为51．36％，48及72h阳性率分别为78．5％、92．3％。结论 BACTEC 9050自动血培养仪对肠杆菌、葡萄球菌及真菌具有较好的检测能力。     

Polo-like kinase 1 inhibitors in mono- and combination therapies: a new strategy for treating malignancies

Polo-like kinase 1 (Plk1) inhibitors belong to a new class of drugs for the treatment of malignant diseases. They selectively act against a target (Plk1) which is involved in different stages of mitosis such as centrosome maturation, spindle formation, chromosome separation and cytokinesis. Because Plk1 is mainly expressed in proliferating tissues and overexpressed in cancers, its inhibition is potentially less prone to toxicities associated with current antimitotic agents, which also act on nondividing cells. Several Plk1 inhibitors are being evaluated as cancer treatment drugs. Based on the essential role of Plk1 during mitosis, Plk1 inhibitors target all rapidly dividing cells irrespective of their tumor suppressor or oncogene mutations. In this article, their mechanisms of action, efficacy and toxicity profile are discussed.     

Use of MALDI-TOF MS (Bruker Daltonics) for identification of Mycobacterium species isolated directly from liquid medium

ObjectivesThe aim of this study was to describe the evaluation of the use of MALDI-TOF MS for the identification of non-tuberculous mycobacteria (NTM) and Mycobacterium tuberculosis directly from liquid MGIT cultures from January 2017 to December 2017.Material/methodsA total of 155 isolates (mainly respiratory) were analyzed by MALDI-TOF MS (Bruker Daltonics) directly from MGIT liquid medium with a previous extraction procedure.ResultsMALDI-TOF MS generated acceptable scores for 152 isolates (98.06%). Fifty isolates were identified as M. tuberculosis complex and the remaining 105 as NTM (M. abscessus subsp. abscessus, M. avium, M. celatum, M chelonae, M. chimaera, M. fortuitum, M. gordonae, M. intracellulare, M. kansasii, M. lentiflavum, M. mageritense, M. mucogenicum and M. xenopi).ConclusionsThese results indicate that MALDI-TOF MS can be useful to identify mycobacteria directly from MGIT cultures and is an accurate, rapid and cost-effective system to be used as a routine method.     

Subclinical Hypothyroidism Is Associated With Adverse Prognosis in Heart Failure Patients

Background

It is widely recognized that overt hyper- as well as hypothyroidism are potential causes of heart failure (HF). Additionally it has been recently reported that subclinical hypothyroidism (sub-hypo) is associated with atherosclerosis, development of HF, and cardiovascular death. We aimed to clarify the effect of sub-hypo on prognosis of HF, and underlying hemodynamics and exercise capacity.

Comparative evaluation of BACTEC 460TB system and Lowenstein-Jensen medium for the isolation of M. tuberculosis from cerebrospinal fluid samples of tuberculous meningitis patients

PURPOSE: To evaluate the role of the radiometric BACTEC 460TB system and the conventional Lowenstein-Jensen (LJ) medium for isolation of M. tuberculosis from cerebrospinal fluid (CSF) samples of tuberculous meningitis (TBM) patients. METHODS: CSF specimens (n=2325) from suspected TBM patients were processed for isolation of mycobacteria by inoculating BACTEC 12B medium and the LJ medium. The isolation of mycobacteria in both media was confirmed by microscopy and biochemical identification. Drug sensitivity testing for the anti-TB drugs was carried out by BACTEC radiometric method. RESULTS: Among the total 2325 CSF specimens processed by both methods, M. tuberculosis was isolated from 256 specimens. The isolation rates were 93% and 39% for the BACTEC system and LJ medium respectively. Both the media supported growth in 32% of the culture-positive specimens. BACTEC system alone yielded growth in 61% and LJ alone in 7%, of the culture-positive specimens. Among 205 isolates tested for drug susceptibility 81% were sensitive to all the drugs tested and 19% were resistant. CONCLUSIONS: The BACTEC 460TB system provides a highly sensitive and rapid tool for the isolation and drug susceptibility testing of M. tuberculosis, from CSF of TBM patients. Use of a solid medium in conjunction with the BACTEC 12B medium is essential for optimal recovery for M. tuberculosis from CSF specimens.     

Experimental Investigation of Integrated Circular Triple-Wire Pulse GMAW of Q960E High-Strength Steel for Construction Machinery

Multi-wire welding has received much attention in the machinery industry due to its high efficiency. The aim of this study was to investigate a novel pulse gas metal arc welding (GMAW) that has circular triple-wire electrodes. The effect of the pulse phage angle on arc stability was particularly studied. Research showed that for typical phase angles the arc stability from low to high is 180°, 0°, and 120°, and the arcs are very stable at 120°. The triple-wire welding was used to weld a 9 mm thick Q960E steel, which is typically used for the arm of construction machinery. When the welding heat input was controlled at 1.26–1.56 kJ/mm, the weld zone was dominated by acicular ferrite, and the coarse-grained zone of the heat-affected zone was a mixed structure of lath martensite and lath bainite. The tensile strength of the welded joint reached 85% of the base metal and the impact toughness was above 62 J, which can meet the requirements of construction machinery. This indicates that the triple-wire welding has great potential to achieve efficient and high-quality welding for the construction machinery.     

不同实验室方法在肺结核辅助诊断中的应用评价

目的评价不同实验室方法在肺结核(PTB)诊断中的应用效能,为PTB的早期诊断提供数据参考。方法 2016年1月至2018年12月在上海市同仁医院肺科门诊诊治的298例疑似PTB患者,依照临床诊断,分为活动性肺结核组138例、非活动性肺结核组43例、非肺结核组117例。对其痰标本分别采用痰涂片快速抗酸染色、MGIT培养、Xpert MTB/RIF分子检测,采用卡方检验比较其敏感性、特异性。结果 3种方法在区分活动性肺结核组与非活动性肺结核合并非肺结核组上具有一定的意义(χ~2值分别为89.08,138.94,137.12,P均0.01),非活动性肺结核组与非肺结核组的阳性率之间差异无统计学意义。痰涂片、MGIT培养、Xpert MTB/RIF和3种方法联合检测诊断活动性肺结核的敏感性分别为45.7%(63/138)、63.8%(88/138)、65.4%(87/133)和78.2%(104/133),MGIT培养和Xpert MTB/RIF敏感性高于痰涂片(χ~2值分别为35.79和11.26,P均0.01),MGIT培养和Xpert MTB/RIF的敏感性差异无统计学意义(χ~2=29.87,P0.05),联合检测敏感性高于3种方法单独检测(χ~2值分别为30.84,64.62,70.14,P均0.01);诊断特异性分别为99.1%(116/117)、98.3%(115/116)、99.1%(113/114)和97.3%(110/113),3种方法的特异性差异无统计学意义。结论 MGIT培养与Xpert MTB/RIF对PTB检测具有较高的敏感性,3种方法联合检测可提高敏感性。     

液体培养基比色法快速检测结核分枝杆菌耐药性

目的探讨液体培养基比色法在结核分枝杆菌（MTB）耐药性快速测定中的应用价值。方法将MTB分别接种于含药和不含药的液体培养基中，37℃培养6d，然后加入NaNO3试剂，37℃培养1d，进行硝酸盐还原检测试验。根据液体培养基颜色变化情况，判断药敏结果。将检测结果与Bactec．960测定结果比较，分析硝酸盐还原酶比色法检测MTB耐药性的敏感性、特异性和准确性。结果以Bactee．960检测结果为判断标准，液体培养基比色法检测链霉素、异烟肼、利福平和乙胺丁醇耐药性结果与Bactec．960的符合率分别为100．0％、96．9％、98．1％和97．5％。结论液体培养基比色法检测MTB耐药性具有很高的敏感性和特异性，且需时较短、操作简便、结果准确、不需特殊仪器设备，可作为MTB耐药性的快速筛选方法。     

Darkfield examination and allied procedures

When Schaudinn and Hoffmann made the initial discovery of T. pallidum in 1905, they did so with an ordinary light microscope. The difficulty of visualizing the pale treponeme under those circumstances will become apparent immediately to anyone who cares to try it, and the virtual transparency of the organism was, of course, the feature that led to Schaudinn's choice of “pallida” (and later “pallidum”) for the species name of his find. Shortly after the discovery, several German optical firms exhibited prototypes of the newly developed darkfield microscopes, and, in 1906, Landsteiner and Mucha¹ were the first to recommend the use of these instruments to demonstrate T. pallidum. Within a year, darkfield microscopy had become almost routine in the investigation of early and congenital syphilis in the European clinics. The procedure was introduced into the United States in 1909 by Udo Wile,² and a survey of the literature of the period shows that by 1914 a recognition of both the strengths and weaknesses of the technique and an understanding of the morphology of the organisms likely to be encountered were remarkably complete.The strongest indications for the use of the darkfield in the current management of venereal disease exist in two special situations: 1) the investigation of lesions in suspected cases of congenital syphilis and 2) the search for organisms in suspected cases of primary syphilis, especially during the initial period of seronegativity. The procedure has lost ground in the latter situation, owing in part to the increasing effectiveness of the newer treponemal and nontreponemal tests in detecting the presence of the disease in its earliest state; but it is premature to conclude, as in the recent statement by one experienced venereologist, that “in the foreseeable future the darkfield examination will be of historical interest, except for those in research.”³The purpose of this section is to summarize the technique and the findings to be expected in the darkfield and other methods employed in the examination of material taken directly from early syphilitic lesions. A step-by-step method for combining the results of these procedures and the results of physical examination and serologic testing to make the diagnosis of infectious syphilis is given in Chapter 11.