• 【与史蒂文斯-约翰逊综合症相比,具有嗜酸性粒细胞增多和全身症状的皮疹-该病例表明当前分类中的绊脚石。】 复制标题 收藏 收藏
    DOI:10.1159/000095437 复制DOI
    作者列表:Wolf R,Davidovici B,Matz H,Mahlab K,Orion E,Sthoeger ZM
    BACKGROUND & AIMS: :A 43-year-old man developed a skin eruption characterized by 'macules with blisters' typical to Stevens-Johnson syndrome, as well as erosions of the lips and buccal mucosa, 2 weeks after he had started treatment with lamotrigine. He had a fever (39.6 degrees C), elevated liver enzymes and atypical lymphocytes in the peripheral blood. This undoubtedly reflects a case of Stevens-Johnson syndrome induced by lamotrigine, but it can also fulfill the criteria of anticonvulsant hypersensitivity syndrome or drug rash with eosinophilia and systemic signs. A case that precisely fits the definition of two syndromes that have different characteristics, different treatments and different prognoses indicates that there is a flaw in the classification.
    背景与目标: :开始使用拉莫三嗪治疗2周后,一名43岁的男子出现了以史蒂文斯-约翰逊综合症为特征的“具有水泡的斑疹”以及嘴唇和颊粘膜糜烂的皮肤疹。他发烧(39.6摄氏度),外周血肝酶和非典型淋巴细胞增多。这无疑反映了拉莫三嗪诱发的史蒂文斯-约翰逊综合症,但它也可以满足抗惊厥超敏反应综合症或嗜酸性粒细胞增多和全身性症状的皮疹的标准。一个病例恰好符合两种具有不同特征,不同治疗方法和不同预后的综合症的定义,表明该分类存在缺陷。
  • 【[干燥综合征。从风湿病学的角度看当前方面]。】 复制标题 收藏 收藏
    DOI:10.1007/s00393-006-0101-0 复制DOI
    作者列表:Tomiak C,Dörner T
    BACKGROUND & AIMS: :Sjögren's syndrome is an autoimmune disease of the exocrine glands characterized by the leading symptoms of keratoconjunctivitis and stomatitis sicca based on a complex pathogenesis. The prevalence is about 0.5-1%; primary Sjögren's syndrome is differentiated from secondary Sjögren's syndrome associated with other autoimmune disorders. The diagnosis is established by the presence of subjective complaints and objective evidence of sicca symptoms, anti-Ro(SSA)/La(SSB) antibodies, and/or focal lymphocytic infiltration of the glandular tissue. In addition to the typical sicca symptomatology, which is managed symptomatically by substitution and stimulation therapy, some patients exhibit extraglandular manifestations. Complaints involving the musculoskeletal system and inner ear dominate and are treated by the rheumatologist. The indication for base therapy is tailored to individual needs, but the efficacy of this approach has not been established in studies. About 5-10% of the patients with primary Sjögren's syndrome develop a B-cell non-Hodgkin's lymphoma. The disease requires interdisciplinary management including, among others, ophthalmologists, dentists, and otorhinolaryngologists, depending on the clinical picture.
    背景与目标: :Sjögren综合征是外分泌腺的一种自身免疫性疾病,其特征是基于复杂的发病机制,导致角膜结膜炎和干燥性口腔炎的主要症状。患病率约为0.5-1%;原发性干燥综合征与其他自身免疫性疾病相关的继发性干燥综合征有所区别。通过主观主诉和干燥症状的客观证据,抗Ro(SSA)/ La(SSB)抗体和/或腺组织的局灶性淋巴细胞浸润来建立诊断。除了典型的干燥症状外,通过替代疗法和刺激疗法对症治疗,一些患者还表现出腺外表现。涉及骨骼肌肉系统和内耳的投诉占主导地位,风湿病学家对此进行了治疗。基础治疗的适应症是根据个人需要量身定制的,但是这种方法的功效尚未在研究中得到证实。约有5-10%的原发性干燥综合征患者会发展为B细胞非霍奇金淋巴瘤。该疾病需要跨学科管理,具体取决于临床情况,其中包括眼科医生,牙医和耳鼻喉科医生。
  • 【抗生素浸渍的PMMA髋关节垫片:当前状态。】 复制标题 收藏 收藏
    DOI:10.1080/17453670610012719 复制DOI
    作者列表:Anagnostakos K,Fürst O,Kelm J
    BACKGROUND & AIMS: :The infection rate after primary hip arthroplasty lies at 1-2%. In the past few years, a two-stage protocol with the implantation of an antibiotic-loaded spacer has become a popular procedure in the treatment of infected hip joint arthroplasties. In this review, we pay special attention to the elution characteristics of the spacers, their mechanical stability and the clinical response. We conclude that hip spacers are an effective method in the treatment of hip joint infections, with success rates of over 90%.
    背景与目标: :原发性髋关节置换术后的感染率为1-2%。在过去的几年中,采用两阶段方案植入载有抗生素的间隔物已成为治疗感染性髋关节置换术的流行方法。在这篇综述中,我们特别注意间隔物的洗脱特性,它们的机械稳定性和临床反应。我们得出的结论是,间隔垫片是一种治疗髋关节感染的有效方法,成功率超过90%。
  • 【缓慢失活的钙电流在分泌降钙素的细胞中充当钙传感器。】 复制标题 收藏 收藏
    DOI:10.1016/0014-5793(90)81048-s 复制DOI
    作者列表:Scherübl H,Schultz G,Hescheler J
    BACKGROUND & AIMS: :Calcitonin (CT)-secreting cells (C-cells) are remarkably sensitive to changes in the extracellular Ca2+ concentration. In order to detect the mechanism by which C-cells monitor Ca2+, we compared a C-cell line responding to Ca2+ (rMTC cells) with another one known to have a defect in this Ca2+ signal transduction (TT cells). Rises of the Ca2+ concentration caused rMTC cells to depolarize and/or elicited spontaneous action potentials. Under voltage-clamp conditions, rMTC cells showed a slowly decaying Ca2+ inward current which was sensitive to dihydropyridines but not to Ni2+ at a low concentration. In contrast, the 'defective' TT cells neither depolarized nor fired action potentials with high Ca2+; they only exhibited an Ni2(+)-sensitive, transient Ca2+ current. The data strongly suggest that the slowly inactivating Ca2+ current is a prerequisite for Ca2(+)-sensitivity of C-cells and that fast inactivating channels are not sufficient to act as sensors of the extracellular Ca2+ concentration.
    背景与目标: :分泌降钙素(CT)的细胞(C细胞)对细胞外Ca2浓度的变化非常敏感。为了检测C细胞监测Ca2的机制,我们将响应Ca2的C细胞系(rMTC细胞)与已知在Ca2信号转导中存在缺陷的另一种细胞(TT细胞)进行了比较。 Ca 2浓度的升高引起rMTC细胞去极化和/或引起自发动作电位。在电压钳制条件下,rMTC细胞显示出缓慢衰减的Ca2内向电流,该电流对二氢吡啶敏感,但对低浓度的Ni2不敏感。相反,“缺陷”的TT细胞既没有去极化也没有激发具有高Ca2的动作电位。它们仅表现出对Ni2()敏感的瞬态Ca2电流。数据强烈表明,缓慢失活的Ca2电流是C细胞对Ca2()敏感性的先决条件,而快速失活的通道不足以充当细胞外Ca2浓度的传感器。
  • 【常染色体显性遗传性多囊肾患者的囊肿感染诊断:当前模式的属性和局限性。】 复制标题 收藏 收藏
    DOI:10.1093/ndt/gfs352 复制DOI
    作者列表:Jouret F,Lhommel R,Devuyst O,Annet L,Pirson Y,Hassoun Z,Kanaan N
    BACKGROUND & AIMS: :Cyst infection is a diagnostic challenge in patients with autosomal dominant polycystic kidney disease (ADPKD) because of the lack of specific manifestations and limitations of conventional imaging procedures. Still, recent clinical observations and series have highlighted common criteria for this condition. Cyst infection is diagnosed if confirmed by cyst fluid analysis showing bacteria and neutrophils, and as a probable diagnosis if all four of the following criteria are concomitantly met: temperature of >38°C for >3 days, loin or liver tenderness, C-reactive protein plasma level of >5 mg/dL and no evidence for intracystic bleeding on computed tomography (CT). In addition, the elevation of serum carbohydrate antigen 19-9 (CA19-9) has been proposed as a biomarker for hepatic cyst infection. Positron-emission tomography after intravenous injection of 18-fluorodeoxyglucose, combined with CT, proved superior to radiological imaging techniques for the identification and localization of kidney and liver pyocyst. This review summarizes the attributes and limitations of these recent clinical, biological and imaging advances in the diagnosis of cyst infection in patients with ADPKD.
    背景与目标: :由于常染色体显性多囊肾病(ADPKD)患者缺乏特异​​性表现和常规成像程序的局限性,因此对囊性感染的诊断是一项挑战。尽管如此,最近的临床观察和系列研究突显了这种情况的共同标准。如果囊肿液分析证实存在细菌和中性粒细胞,则可以诊断为囊肿感染,并且同时满足以下四个条件都可以诊断为囊肿:温度> 38°C持续3天以上,腰部或肝脏压痛,C反应性血浆血浆蛋白水平> 5 mg / dL,计算机断层扫描(CT)尚无囊内出血的证据。另外,已经提出血清碳水化合物抗原19-9(CA19-9)的升高作为肝囊肿感染的生物标志物。静脉注射18-氟脱氧葡萄糖后与CT结合进行正电子发射断层扫描,证明其优于放射成像技术可用于肾脏和肝囊肿的鉴定和定位。这篇综述总结了ADPKD患者囊肿感染诊断中这些最新的临床,生物学和影像学进展的属性和局限性。
  • 【唾液蛋白质组学的十年:当前的方法和突出的挑战。】 复制标题 收藏 收藏
    DOI:10.1016/j.clinbiochem.2012.10.024 复制DOI
    作者列表:Amado FM,Ferreira RP,Vitorino R
    BACKGROUND & AIMS: :Efforts have been made in the last decade towards the complete characterization of saliva proteome using gel-based and gel-free approaches. The combination of these strategies resulted in the increment of the dynamic range of saliva proteome, which yield in the identification of more than 3,000 different protein species. Comparative protein profiling using isotope labeling and label free approaches has been used for the identification of novel biomarkers for oral and related diseases. Although progresses have been made in saliva proteome characterization, the comparative profiling in different pathophysiological conditions is still at the beginning if compared to other bodily fluids. The potential biomarkers identified so far lack specificity once common differentially expressed proteins were detected in the saliva of patients with distinct diseases. In addition, recent research works focused on saliva peptidome profiling already allowed a better understanding of peptides' physiological role in oral cavity. This review provides an overview of the major achievements in saliva proteomics giving emphasis to methodological concerns related with saliva collection, treatment and analysis, as well as the main advantages and pitfalls underlying salivary proteomic strategies and potential clinical outcomes.
    背景与目标: :在过去的十年中,人们已经在努力使用基于凝胶和无凝胶的方法来完全表征唾液蛋白质组。这些策略的组合导致唾液蛋白质组动态范围的增加,从而可以鉴定出3,000多种不同的蛋白质。使用同位素标记和无标记方法的比较蛋白质谱分析已用于鉴定口腔和相关疾病的新型生物标志物。尽管唾液蛋白质组表征已取得进展,但与其他体液相比,在不同病理生理条件下的比较分析仍处于起步阶段。一旦在患有不同疾病的患者的唾液中检测到常见的差异表达蛋白,迄今鉴定出的潜在生物标志物将缺乏特异性。此外,针对唾液肽组图谱的最新研究工作已经使人们对肽在口腔中的生理作用有了更好的了解。这篇综述概述了唾液蛋白质组学的主要成就,重点是与唾液收集,治疗和分析有关的方法论问题,以及唾液蛋白质组学策略和潜在临床结果的主要优势和陷阱。
  • 【基于G四链体的FRET探针,具有凝血酶结合适体(TBA)序列,设计用于高效荧光检测钾离子。】 复制标题 收藏 收藏
    DOI:10.1002/cbic.200600179 复制DOI
    作者列表:Nagatoishi S,Nojima T,Galezowska E,Juskowiak B,Takenaka S
    BACKGROUND & AIMS: :The dual-labeled oligonucleotide derivative, FAT-0, carrying 6- carboxyfluorescein (FAM) and 6-carboxytetramethylrhodamine (TAMRA) labels at the 5' and 3' termini of the thrombin-binding aptamer (TBA) sequence 5'-GGT TGG TGT GGT TGG-3', and its derivatives, FAT-n (n=3, 5, and 7) with a spacer at the 5'-end of a TBA sequence of T(m)A (m=2, 4, and 6) have been designed and synthesized. These fluorescent probes were developed for monitoring K(+) concentrations in living organisms. Circular dichroism, UV-visible absorption, and fluorescence studies revealed that all FAT-n probes could form intramolecular tetraplex structures after binding K(+). Fluorescence resonance energy transfer and quenching results are discussed taking into account dye-dye contact interactions. The relationship between the fluorescence behavior of the probes and the spacer length in FAT-n was studied in detail and is discussed.
    背景与目标: :双标记的寡核苷酸衍生物FAT-0,在凝血酶结合适体(TBA)序列5'-GGT TGG的5'和3'末端带有6-羧基荧光素(FAM)和6-羧基四甲基罗丹明(TAMRA)标签TGT GGT TGG-3'及其衍生物FAT-n(n = 3、5和7),在T(m)A的TBA序列的5'端带有一个间隔区(m = 2、4、4和6)已经被设计和合成。这些荧光探针用于监测活生物体中的K()浓度。圆二色性,紫外可见吸收和荧光研究表明,所有FAT-n探针在结合K()后均可形成分子内四链体结构。考虑到染料与染料的相互作用,讨论了荧光共振能量转移和猝灭的结果。详细研究了探针的荧光行为与FAT-n中间隔子长度之间的关系。
  • 【重组人TSH刺激在碘治疗弥漫性分化型甲状腺癌中的作用-当前和我们的经验的更新]。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Hasse-Lazar K,Handkiewicz-Junak D,Roskosz J,Szpak-Ulczok S,Krajewska J,Jurecka-Lubieniecka B,Jarzab B
    BACKGROUND & AIMS: :Traditionally, for diagnostic and therapeutic application of radioiodine in patients with differentiated thyroid cancer (DTC), a 4 to 6 week withdrawal of thyroid hormone was applied. Recombinant human TSH (rhTSH) was developed to provide TSH stimulation without withdrawal of thyroid hormone and associated morbidity. The results of rhTSH administration and endogenous TSH stimulation are equivalent in detecting recurrent DTC. At the present time rhTSH is approved as an adjunct for diagnostic procedures and thyroid ablation in patients with DTC. In addition, rhTSH has potential for use in facilitating the treatment of metastases in patients with DTC. In this review we have summarized our own experiences with rhTSH aided radioiodine therapy in patients with disseminated thyroid cancer. Generally, rhTSH was very well tolerated and treatment results were comparable to those achieved with thyroid hormone withdrawal.
    背景与目标: 传统上,对于放射性碘在分化型甲状腺癌(DTC)患者中的诊断和治疗应用,应用了4至6周的甲状腺激素戒断。开发了重组人TSH(rhTSH),可提供TSH刺激,而无需撤回甲状腺激素和相关的发病率。 rhTSH给药和内源性TSH刺激的结果在检测复发性DTC方面是等效的。目前,rhTSH被批准作为DTC患者诊断程序和甲状腺消融的辅助手段。此外,rhTSH具有促进DTC患者转移治疗的潜力。在这篇综述中,我们总结了我们在散播性甲状腺癌患者中使用rhTSH辅助放射碘疗法的经验。通常,rhTSH耐受性非常好,治疗结果与甲状腺激素戒断所获得的结果相当。
  • 【围产期护理的状态:围产期护理服务主管描述的当前和将来的概况。】 复制标题 收藏 收藏
    DOI:10.1097/00005237-199703000-00011 复制DOI
    作者列表:Arnold LS,Angelini DJ,Possinger T
    BACKGROUND & AIMS: The health care industry is in the throes of remarkably penetrating and destabilizing change, the effects of which have been felt earliest by perinatal service directors. In anticipation of future trends marked by rampant change, a survey of perinatal service directors and vice presidents was conducted to elicit their opinions about the current and future states of perinatal health care. Findings supported the notions that change is a constant, that clinical and service excellence is a mandate, and that collaboration is key. Future success will require many old behaviors and systems to be replaced. Leadership to guide us to the future has never been more important.

    背景与目标: 卫生保健行业正处在深刻渗透和破坏稳定的变革的阵痛之中,围产期服务主管最早感受到了这种变革的影响。为了预见未来变化趋势明显的趋势,对围产期服务主管和副总裁进行了一项调查,以征询他们对围产期保健的当前和未来状态的意见。研究结果支持以下观念:变革是永恒的,临床和服务卓越是使命,协作是关键。未来的成功将需要替换许多旧的行为和系统。引领我们走向未来的领导力从未如此重要。

  • 【通过簇离子TOF-SIMS对人脂肪组织中的脂质进行成像。】 复制标题 收藏 收藏
    DOI:10.1002/jemt.20481 复制DOI
    作者列表:Malmberg P,Nygren H,Richter K,Chen Y,Dangardt F,Friberg P,Magnusson Y
    BACKGROUND & AIMS: :Biopsies of human subcutaneous adipose tissue were taken from healthy donors. Samples were high-pressure frozen, freeze-fractured, and freeze dried. Imaging mass spectrometry of samples was performed in a TOF-SIMS mass spectrometer equipped with a bismuth cluster ion source. Blood vessels, the connective tissue, and adipocytes can be seen in TOF-SIMS images. Blood vessels were found labeled by a high content of sodium ions and potassium ions in their lumen and phosphocholine signal in smooth muscle cells of the vessel wall. The connective tissue showed high signal levels of CN(-) fragments, derived from proteins and nucleic acids. Adipocytes showed high signal levels of phosphocholine and cholesterol ubiquitously in their membranes and diacylglycerols in some membrane sites. The central part of adipocytes showed high levels of triacylglycerols and fatty acids. These results are in accordance to those of biochemical studies; however, a precise spatial localization of lipids in adipocytes is demonstrated with MS imaging.
    背景与目标: :人皮下脂肪组织的活检取自健康供体。将样品高压冷冻,冷冻断裂并冷冻干燥。在配备有铋簇离子源的TOF-SIMS质谱仪中进行样品的成像质谱。在TOF-SIMS图像中可以看到血管,结缔组织和脂肪细胞。发现在血管壁的平滑肌细胞中,内腔中的钠离子和钾离子含量较高,并且磷酸胆碱信号标记了高含量的血管。结缔组织显示高信号水平的CN(-)片段,来源于蛋白质和核酸。脂肪细胞的膜中普遍存在高水平的磷酸胆碱和胆固醇信号,某些膜部位普遍存在二酰基甘油。脂肪细胞的中央部分显示出高水平的三酰基甘油和脂肪酸。这些结果与生化研究结果一致;然而,通过MS成像证实了脂肪细胞中脂质的精确空间定位。
  • 【垂体促性腺激素中一种新型的钙激活的对罂粟碱不敏感的钾电流。】 复制标题 收藏 收藏
    DOI:10.1210/endo.138.7.5220 复制DOI
    作者列表:Vergara L,Rojas E,Stojilkovic SS
    BACKGROUND & AIMS: In cultured rat pituitary gonadotrophs, GnRH-induced oscillations in cytosolic calcium concentration ([Ca2+]i) are associated with periodic membrane hyperpolarization. The hyperpolarizing waves are secondary to the activation of apamin-sensitive Ca2+-activated K+ channels that account for a single class of 125I-apamin binding sites present in these cells. In a substantial fraction of gonadotrophs, however, we observed a Ca2+-controlled oscillatory current that was resistant to apamin, even at concentrations five orders of magnitude higher than the dissociation constant (Kd) observed in the binding experiments. With the K+ in the pipette, the apamin-resistant current showed a reversal potential of -42 mV, nearly 40 mV more positive than that of the apamin-sensitive current. With Cs+ in place of K+ in the pipette solution, both the size of the apamin-insensitive current and its reversal potential remained unchanged. Ion substitution studies further revealed that the reversal potential was independent of Cl-. In contrast, an 11 mV hyperpolarizing shift in the reversal potential occurred when extracellular Na+ was reduced to 80 mM. In cells expressing apamin-resistant conductances, addition of apamin evoked a marked increase in the duration of the action potentials and reduction in the frequency of spontaneous spiking. In the presence of GnRH, gonadotrophs exhibit the typical burst pattern of electrical activity. Further exposure of the cells to apamin depolarized the membrane from a silent phase bursting level of about -80 mV to a new level of about -40 mV. These observations indicate that, in addition to apamin-sensitive current, a subpopulation of pituitary gonadotrophs also expresses a cationic component of the Ca2+-activated membrane conductance that has the potential to remodulate spontaneous and agonist-induced electrical activity.

    背景与目标: 在培养的大鼠垂体促性腺激素中,GnRH诱导的胞浆钙浓度([Ca2] i)振荡与周期性膜超极化有关。超极化波是对罂粟碱敏感的Ca2激活的K通道的激活的继发子,这些通道解释了这些细胞中存在的一类125I-apapamin结合位点。然而,在相当一部分的促性腺激素中,即使在比结合实验中观察到的解离常数(Kd)高5个数量级的浓度下,我们也观察到了对apamin有抗性的Ca2控制的振荡电流。当移液器中的K值时,抗木瓜蛋白酶的电流显示出-42 mV的反向电势,比对木瓜蛋白酶敏感的电流的正电势高近40 mV。在移液器中用Cs代替K时,对罂粟碱不敏感电流的大小及其逆转电位均保持不变。离子取代研究进一步表明,逆转电位独立于Cl-。相反,当细胞外Na降至80 mM时,逆转电位发生11 mV超极化变化。在表达抗谷氨酰胺的电导的细胞中,添加谷氨酰胺可引起动作电位持续时间的显着增加和自发加标频率的降低。在存在GnRH的情况下,促性腺激素表现出典型的电活动猝发模式。将细胞进一步暴露于罂粟碱可使膜从约-80 mV的无声相爆发水平去极化至约-40 mV的新水平。这些观察结果表明,除了对罂粟碱敏感的电流外,垂体促性腺激素亚群还表达了Ca2激活的膜电导的阳离子成分,该成分可能会重新调节自发和激动剂诱导的电活动。

  • 【H离子通过细菌光合作用反应中心的P QA状态结合的动力学:蛋白质内的速率限制。】 复制标题 收藏 收藏
    DOI:10.1016/S0006-3495(97)78077-9 复制DOI
    作者列表:Maróti P,Wraight CA
    BACKGROUND & AIMS: The kinetics of flash-induced H+ ion binding by isolated reaction centers (RCs) of Rhodobacter sphaeroides, strain R-26, were measured, using pH indicators and conductimetry, in the presence of terbutryn to block electron transfer between the primary and secondary quinones (QA and QB), and in the absence of exogenous electron donors to the oxidized primary donor, P+, i.e., the P+QA-state. Under these conditions, proton binding by RCs is to the protein rather than to any of the cofactors. After light activation to form P+QA-, the kinetics of proton binding were monoexponential at all pH values studied. At neutral pH, the apparent bimolecular rate constant was close to the diffusional limit for proton transfer in aqueous solution (approximately 10(11) M-1 s-1), but increased significantly in the alkaline pH range (e.g., 2 x 10(13) M-1 s-1 at pH 10). The average slope of the pH dependence was -0.4 instead of -1.0, as might be expected for a H+ diffusion-controlled process. High activation energy (0.54 eV at pH 8.0) and weak viscosity dependence showed that H+ ion uptake by RCs is not limited by diffusion. The salt dependence of the H+ ion binding rate and the pK values of the protonatable amino acid residues of the reaction center implicated surface charge influences, and Gouy-Chapman theory provided a workable description of the ionic effects as arising from modulation of the pH at the surface of the RC. Incubation in D2O caused small increases in the pKs of the protonatable groups and a small, pH (pD)-dependent slowing of the binding rate. The salt, pH, temperature, viscosity, and D2O dependences of the proton uptake by RCs in the P+QA- state were accounted for by three considerations1) parallel pathways of H+ delivery to the RC, contributing to the observed (net) H+ disappearance; 2) rate limitation of the protonation of target groups within the protein by conformational dynamics; and 3) electrostatic influences of charged groups in the protein, via the surface pH.

    背景与目标: 在特布瑞林存在下,通过阻断pH值和电导测定了球形球形红球菌R-26的分离反应中心(RC)的闪光诱导的H离子结合的动力学,并测定了叔丁烯的存在以阻止电子在伯醌和仲醌之间的转移( QA和QB),并且在没有外源电子给体到氧化的初级给体P的情况下,即P QA状态。在这些条件下,RC的质子结合是蛋白质而不是任何辅因子。光活化形成P QA-后,质子结合的动力学在所有研究的pH值下都是单指数的。在中性pH下,表观双分子速率常数接近质子在水溶液中的扩散极限(约10(11)M-1 s-1),但在碱性pH范围内显着增加(例如2 x 10( 13)pH值为10的M-1 s-1。 pH依赖性的平均斜率是-0.4而不是-1.0,这可能是H扩散控制过程所期望的。高活化能(pH 8.0时为0.54 eV)和较弱的粘度依赖性表明RC吸收H离子不受扩散的限制。 H离子结合率与盐的依赖性以及反应中心质子化氨基酸残基的pK值都牵涉表面电荷影响,Gouy-Chapman理论提供了对由于在pH值下pH值的调节而产生的离子效应的可行描述。 RC的表面。在D2O中孵育会导致可质子化基团的pK小幅增加,并导致pH(pD)依赖性的结合速率减慢。 P QA状态下RC吸收质子的盐,pH,温度,粘度和D2O依赖性是由以下三个因素造成的:1)H传递至RC的平行途径,导致观测到的(净)H消失; 2)通过构象动力学限制蛋白质内目标基的质子化速率;和3)通过表面pH值对蛋白质中带电基团的静电影响。

  • 【鼻窦区域肿瘤的动态IMRT治疗:蒙特卡洛计算与治疗计划系统计算和离子室测量的比较。】 复制标题 收藏 收藏
    DOI:10.1177/153303460600500505 复制DOI
    作者列表:Court LE,Jahnke L,Chin D,Song J,Cormack R,Zygmanski P,Tishler RB,Chin L
    BACKGROUND & AIMS: :Results are presented comparing Monte Carlo (MC) calculations for dynamic IMRT treatments of tumors in the sinus region with Eclipse treatment planning system dose calculations, and ion chamber measurements. The EGS4nrc MC code, BEAMnrc, was commissioned to simulate a Varian 21Ex Linac for both open and IMRT fields. The accuracy of the simulation for IMRT plans was evaluated using a head phantom by comparing MC, Eclipse, TLD results, and ion chamber in solid water phantom measurements. The MC code was then used to simulate dose distributions for five patients who were treated using dynamic IMRT for tumors in the sinus region. The results were compared with absolute and relative dose distributions calculated using Eclipse (pencil beam, modified-Batho inhomogeneity correction). Absolute dose differences were also compared with ion chamber results. Comparison of the doses calculated on the head phantom using MC, compared with Eclipse, ion chamber, and TLD measurements showed differences of -3.9%, -1.4%, and -2.0%, respectively (MC is colder). Relative dose distributions for the patient plans calculated using MC agreed well with those calculated using Eclipse with respect to targets and critical organs, indicating the modified-Batho correction is adequate. Average agreement for mean absolute target doses between MC and Eclipse was -3.0 +/-; 2.3% (1 s.d.). Agreement between ion chamber and Eclipse for these patients was -2.2 +/- 1.9%, compared with 0.2 +/- 2.0% for all head and neck IMRT patients. When Eclipse doses were corrected based on ion chamber results, agreement between MC and Eclipse was -0.7 +/- 2.0%, indicating a small systematic uncertainty in the doses calculated using the treatment planning system for this subset of patients.
    背景与目标: :结果比较了用蒙特卡洛(MC)计算窦道区域肿瘤的动态IMRT治疗与Eclipse治疗计划系统剂量计算和离子室测量值的比较结果。调试了EGS4nrc MC代码BEAMnrc,以针对开放领域和IMRT领域模拟Varian 21Ex Linac。通过比较MC,Eclipse,TLD结果和固体水体模测量中的离子室,使用头部体模评估了IMRT计划仿真的准确性。然后,将MC代码用于模拟五名使用动态IMRT进行鼻窦区域肿瘤治疗的患者的剂量分布。将结果与使用Eclipse计算出的绝对和相对剂量分布(铅笔束,改良的Batho不均匀性校正)进行比较。还将绝对剂量差异与离子室结果进行了比较。与使用Eclipse,离子室和TLD进行的测量相比,使用MC在头部模型上计算的剂量进行了比较,分别显示出-3.9%,-1.4%和-2.0%的差异(MC更冷)。对于目标和关键器官,使用MC计算的患者计划的相对剂量分布与使用Eclipse计算的相对剂量分布非常吻合,表明改良的Batho校正是足够的。 MC和Eclipse之间的平均绝对目标剂量的平均一致性为-3.0 /-; 2.3%(1 s.d.)。对于这些患者,离子室和Eclipse之间的一致性为-2.2 /-1.9%,而所有头颈部IMRT患者的一致性为0.2 /-2.0%。根据离子室结果校正Eclipse剂量后,MC和Eclipse之间的一致性为-0.7 /-2.0%,这表明使用治疗计划系统为该患者子集计算的剂量存在很小的系统不确定性。
  • 【神经激肽A抑制来自大鼠输精管的平滑肌细胞中的电压门控K电流。】 复制标题 收藏 收藏
    DOI:10.1016/0014-2999(90)90512-5 复制DOI
    作者列表:Nakazawa K,Inoue K,Fujimori K,Takanaka A
    BACKGROUND & AIMS: :The effects of neurokinin A (NKA) on freshly isolated smooth muscle cells from the rat vas deferens were investigated electrophysiologically. NKA (10(-7) M) prolonged the duration of action potentials without affecting resting potentials. Under voltage-clamp conditions, NKA (10(-7) M) suppressed an outward K+ current activated by depolarizing voltage steps. Substance P (SP, 10(-7) M) did not affect the K+ current, suggesting that NKA is more potent in suppressing the K+ current than SP is, as is also true for the contractions of smooth muscles of the rat vas deferens. The suppression of the K+ conductance now reported may contribute to NKA-induced smooth muscle contraction.
    背景与目标: :电生理学研究了神经激肽A(NKA)对新鲜分离自大鼠输精管的平滑肌细胞的作用。 NKA(10(-7)M)延长了动作电位的持续时间,而不会影响静息电位。在电压钳位条件下,NKA(10(-7)M)抑制了因去极化电压阶跃而激活的向外的K电流。 P物质(SP,10(-7)M)不影响K电流,这表明NKA比SP抑制K电流更有效,大鼠输精管平滑肌的收缩也是如此。现在报道的钾电导的抑制可能有助于NKA诱导的平滑肌收缩。
  • 【直流电疗法与依西酞普兰治疗抑郁症的试验。】 复制标题 收藏 收藏
    DOI:10.1056/NEJMoa1612999 复制DOI
    作者列表:Brunoni AR,Moffa AH,Sampaio-Junior B,Borrione L,Moreno ML,Fernandes RA,Veronezi BP,Nogueira BS,Aparicio LVM,Razza LB,Chamorro R,Tort LC,Fraguas R,Lotufo PA,Gattaz WF,Fregni F,Benseñor IM,ELECT-TDCS Investigators.
    BACKGROUND & AIMS: BACKGROUND:We compared transcranial direct-current stimulation (tDCS) with a selective serotonin-reuptake inhibitor for the treatment of depression. METHODS:In a single-center, double-blind, noninferiority trial involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30-minute, 2-mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS-17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram. RESULTS:A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention-to-treat analysis, the mean (±SD) decrease in the score from baseline was 11.3±6.5 points in the escitalopram group, 9.0±7.1 points in the tDCS group, and 5.8±7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, -2.3 points; 95% confidence interval [CI], -4.3 to -0.4; P=0.69) was lower than the noninferiority margin of -2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points [95% CI, 3.1 to 7.8; P<0.001] and 3.2 points [95% CI, 0.7 to 5.5; P=0.01], respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new-onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups. CONCLUSIONS:In a single-center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10-week period and was associated with more adverse events. (Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo and others; ELECT-TDCS ClinicalTrials.gov number, NCT01894815 .).
    背景与目标: 背景:我们比较了经颅直流电刺激(tDCS)和选择性5-羟色胺再摄取抑制剂治疗抑郁症的效果。
    方法:在一项涉及成人单相抑郁症的单中心,双盲,非自卑性试验中,我们随机分配患者接受tDCS联合口服安慰剂,假tDCS联合依西酞普兰或假tDCS联合口服安慰剂。 tDCS在30分钟,2 mA的额前刺激中连续15个工作日进行给药,然后每周进行7次治疗。依西酞普兰的剂量为每天10 mg,持续3周,之后每天20 mg。主要结局指标是17个项目的汉密尔顿抑郁量表(HDRS-17)得分的变化(范围从0到52,得分越高表示抑郁越多)。 tDCS与依西酞普兰的非劣效性是由置信区间的下限定义的,即降低分数的差异至少是安慰剂与依西酞普兰分数差异的50%。
    结果:共有245例患者接受了随机分组,其中91例患者被分配为依他普仑,94例被分配给tDCS,60例被分配给安慰剂。在意向性治疗分析中,依他普仑组的基线平均得分下降(±SD)为11.3±6.5分,tDCS组为9.0±7.1分,而安慰剂组为5.8±7.9分。 tDCS与依西酞普兰的降幅差异的置信区间的下限(差异-2.3点; 95%的置信区间[CI],-4.3至-0.4; P = 0.69)低于- 2.75(安慰剂减去艾司西酞普兰的50%),因此不能主张非自卑。 Escitalopram和tDCS均优于安慰剂(差异与安慰剂相比,分别为5.5分[95%CI,3.1至7.8; P <0.001]和3.2分[95%CI,0.7至5.5; P = 0.01]。接受tDCS的患者的皮肤发红,耳鸣和神经质发生率高于其他两组,并且tDCS组中的2例患者出现了新发躁狂症。接受艾司西酞普兰治疗的患者比其他两组患者更容易出现困倦和便秘。
    结论:在一项单中心试验中,tDCS治疗抑郁症在10周内并未显示出依他普仑的非劣效性,并伴有更多不良事件。 (由圣保罗埃斯帕多萨基金会和圣保罗基金会资助; ELECT-TDCS ClinicalTrials.gov编号,NCT01894815。)。

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