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Pathobiology of acute pancreatitis: focus on intracellular calcium and calmodulin. 急性胰腺炎的病理生物学:聚焦于细胞内钙和钙调蛋白。
Pub Date : 2011-01-01 Epub Date: 2011-08-01 DOI: 10.3410/M3-15
Ole H Petersen, Oleg V Gerasimenko, Julia V Gerasimenko

The exocrine pancreas synthesizes all the enzymes needed for intestinal breakdown of proteins, fats, and carbohydrates in our diet. Unfortunately, the proteases needed for the digestion of the meat we eat can, if inappropriately activated inside the acinar cells, also digest the pancreas itself as well as the surrounding tissues, which is what happens in the sometimes fatal human disease acute pancreatitis. The disease is currently untreatable, but significant progress has recently been made in understanding the fundamental processes initiating the pathological changes underlying pancreatic autodigestion. It is now clear that intracellular trypsin activation-a crucial step in pathogenesis-is due to excessive release of Ca(2+) from intracellular stores, principally via two types of inositol trisphosphate receptor. The unexpected recent discovery of an intrinsic protective mechanism caused by intracellular calmodulin and, specifically, the finding that this protective effect can be boosted by a membrane-permeable Ca(2+)-like peptide are promising.

外分泌胰腺合成肠道分解我们饮食中的蛋白质、脂肪和碳水化合物所需的所有酶。不幸的是,消化肉类所需的蛋白酶,如果在腺泡细胞内被不恰当地激活,也会消化胰腺本身以及周围的组织,这就是有时致命的人类疾病急性胰腺炎所发生的情况。这种疾病目前无法治疗,但最近在了解引发胰腺自身消化的病理变化的基本过程方面取得了重大进展。现在清楚的是,细胞内胰蛋白酶激活——发病的关键步骤——是由于Ca(2+)从细胞内储存过度释放,主要通过两种类型的肌醇三磷酸受体。最近意外发现了细胞内钙调素引起的内在保护机制,特别是发现这种保护作用可以通过膜渗透性Ca(2+)样肽来增强,这是有希望的。
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引用次数: 0
Cancer, stem cells and cancer stem cells: old ideas, new developments. 癌症,干细胞和癌症干细胞:旧思想,新发展。
Pub Date : 2011-01-01 Epub Date: 2011-12-01 DOI: 10.3410/M3-23
Saghi Ghaffari

It has been suggested that, at least in some forms of cancer, a sub-population of slow-cycling, therapy-resistant cancer stem cells exists that has the ability to reconstitute the tumor in its entirety. If true, this model implies that conventional therapies based on targeting highly cycling cells within the tumor will leave the slow-cycling stem cell population intact, giving them the opportunity to reinitiate the tumor at a later date. This review discusses the evidence for this model and the likely implications for cancer treatment.

研究表明,至少在某些形式的癌症中,存在一种慢循环、抗治疗的癌症干细胞亚群,它们具有完整重建肿瘤的能力。如果这是真的,该模型意味着基于靶向肿瘤内高循环细胞的传统疗法将使缓慢循环的干细胞群保持完整,使它们有机会在以后重新启动肿瘤。这篇综述讨论了该模型的证据以及可能对癌症治疗的影响。
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引用次数: 23
Clostridium difficile--a moving target. 艰难梭菌——一个移动的目标。
Pub Date : 2011-01-01 Epub Date: 2011-03-01 DOI: 10.3410/M3-6
Glenn S Tillotson, Joni Tillotson

Clostridium difficile has been recognized as a pathogen in humans for over 40 years, but in the past decade the incidence has increased and, more importantly, the clinical presentation and consequences have become more serious, with increased morbidity and mortality. The emergence of a new, more pathogenic strain, BI/NAP1/027, has driven these shifts. Treatment of this disease has been with two antibiotics, metronidazole and vancomycin, but increasing recurrence, not uncommon with C. difficile infections, has prompted research into several alternative therapies. These include a new class of antibiotic (fidaxomicin), a monoclonal antibody, a vaccine, and most recently a biotherapeutic (which, in this case, is a nontoxin-producing strain of C. difficile). The future management of C. difficile infection will probably require a combination of these approaches once we have the data from ongoing studies.

艰难梭菌被认为是一种人类病原体已有40多年的历史,但在过去的十年中,其发病率有所增加,更重要的是,其临床表现和后果变得更加严重,发病率和死亡率都有所增加。一种新的、致病性更强的菌株BI/NAP1/027的出现推动了这些变化。这种疾病的治疗一直使用甲硝唑和万古霉素两种抗生素,但难辨梭菌感染的复发率越来越高,这促使人们研究几种替代疗法。其中包括一类新的抗生素(非达霉素),一种单克隆抗体,一种疫苗,以及最近的一种生物治疗药物(在这种情况下,是一种不产生毒素的艰难梭菌菌株)。一旦我们从正在进行的研究中获得数据,未来艰难梭菌感染的管理可能需要这些方法的组合。
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引用次数: 18
Inflammation as a target for improving health in chronic kidney disease. 炎症作为改善慢性肾脏疾病健康的目标。
Pub Date : 2010-12-17 DOI: 10.3410/M2-88
Peter Stenvinkel

Since the first reports in the late 1990s connecting elevated circulating levels of C-reactive protein in patients with end-stage renal disease with an atherogenic, wasted phenotype and poor outcome, more than 3600 publications related to the subject have appeared on the Medline bibliographic database. This reflects the exponential interest that this topic has evoked in the field of nephrology, and the possibility of treating this common uremic complication has been much discussed. Several small studies have implied that various nutritional and pharmacological treatment strategies have beneficial effects on surrogate markers of inflammation. However, no randomized controlled trials on anti-inflammatory treatment have yet been performed to test the hypothesis that persistent low-grade inflammation contributes to uremic morbidity and mortality.

自20世纪90年代末首次报道将终末期肾病患者循环c反应蛋白水平升高与动脉粥样硬化、表型浪费和预后不良联系起来以来,Medline书目数据库上已经出现了3600多篇与该主题相关的出版物。这反映了这个话题在肾脏病学领域引起的指数兴趣,并且治疗这种常见尿毒症并发症的可能性已经得到了很多讨论。几项小型研究表明,各种营养和药物治疗策略对炎症的替代标志物有有益的影响。然而,目前还没有关于抗炎治疗的随机对照试验来验证持续性低度炎症导致尿毒症发病率和死亡率的假设。
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引用次数: 6
Serrated polyps of the colon. 结肠的锯齿状息肉
Pub Date : 2010-12-17 DOI: 10.3410/M2-89
Aravind Sugumar, Frank A Sinicrope

Until recently, colonic polyps were traditionally classified as either hyperplastic or adenomatous, and only the latter were believed to have the potential to progress to carcinoma. However, it is now appreciated that a subset of serrated polyps also appear to have malignant potential. Serrated polyps are a heterogeneous group of colon polyps that include hyperplastic polyps, sessile serrated adenomas (SSAs), traditional serrated adenomas, and mixed polyps. Insights into these polyps were derived, in part, from studies of patients with the hyperplastic polyposis syndrome. SSAs show a predilection for the right colon, have a distinct histology, and their molecular genetic profile has recently been linked to a pathway for colon tumorigenesis that is characterized by microsatellite instability. Based upon available evidence, it is recommended that patients with serrated adenomas undergo colonoscopic follow-up at the same frequency as for conventional adenomas. It is important that physicians are aware of serrated polyps, particularly serrated adenomas and their relationship to colon cancer, and their proper clinical management.

直到最近,结肠息肉传统上被分为增生性或腺瘤性,只有后者被认为有可能发展为癌。然而,现在认识到,一个子集的锯齿状息肉也似乎有恶性潜能。锯齿状息肉是一种异质性的结肠息肉,包括增生性息肉、无柄锯齿状腺瘤(SSAs)、传统锯齿状腺瘤和混合型息肉。对这些息肉的了解部分来自对增生性息肉综合征患者的研究。SSAs表现出对右结肠的偏爱,具有独特的组织学,其分子遗传谱最近与以微卫星不稳定性为特征的结肠肿瘤发生途径有关。根据现有证据,建议锯齿状腺瘤患者接受结肠镜随访,随访频率与常规腺瘤相同。重要的是,医生要意识到锯齿状息肉,特别是锯齿状腺瘤及其与结肠癌的关系,以及正确的临床治疗。
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引用次数: 20
An updated review of current concepts in the management of carotid stenosis. 颈动脉狭窄管理的最新概念综述。
Pub Date : 2010-12-17 DOI: 10.3410/M2-91
Norman R Hertzer

Several large randomized clinical trials in North America and Europe concluded over a decade ago that carotid endarterectomy plus medical management was significantly better than medical management alone for stroke prevention in either symptomatic or asymptomatic patients with severe carotid stenosis. Percutaneous carotid angioplasty now represents yet another treatment option that currently appears to have a higher risk than endarterectomy in symptomatic patients as well as in those who are 70 years of age or older. For these reasons, there is a consensus that angioplasty should be used cautiously in such patients and probably remains most appropriate either in the context of ongoing randomized trials or for patients who are at a higher-than-average risk for conventional surgical treatment.

十多年前,北美和欧洲的几项大型随机临床试验得出结论,对于有症状或无症状的严重颈动脉狭窄患者,颈动脉内膜切除术加药物治疗明显优于单独药物治疗预防卒中。经皮颈动脉成形术现在是另一种治疗选择,目前在有症状的患者以及70岁或以上的患者中,其风险似乎高于动脉内膜切除术。由于这些原因,人们一致认为血管成形术在此类患者中应谨慎使用,并且可能在正在进行的随机试验背景下或在常规手术治疗风险高于平均水平的患者中仍然是最合适的。
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引用次数: 4
Use of dexmedetomidine for pain control. 右美托咪定用于疼痛控制。
Pub Date : 2010-12-17 DOI: 10.3410/M2-90
Irina Grosu, Patricia Lavand'homme

For many years, clonidine, an α2-adrenergic receptor (α2-AR) agonist, has been widely used as an analgesic adjuvant in perioperative conditions and pain therapy. Dexmedetomidine (DMET) is currently the most potent α2-AR agonist available and was first approved as a sedative agent for use in the intensive care unit. However, DMET has recently been investigated for its analgesic effects and has the potential to become an alternative to clonidine.

多年来,可乐定作为α2-肾上腺素能受体(α2-AR)激动剂被广泛用作围手术期和疼痛治疗的镇痛辅助剂。右美托咪定(DMET)是目前可用的最有效的α2-AR激动剂,首次被批准用作重症监护病房的镇静剂。然而,DMET最近被研究其镇痛作用,并有可能成为可乐定的替代品。
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引用次数: 82
HIV-associated anal cancer. 与艾滋病毒相关的肛门癌
Pub Date : 2010-12-08 DOI: 10.3410/M2-85
Thomas Newsom-Davis, Mark Bower

HIV-associated anal carcinoma, a non-AIDS-defining cancer, is a human papillomavirus-associated malignancy with a spectrum of preinvasive changes. The standardized incidence ratio for anal cancer in patients with HIV/AIDS is 20-50. Algorithms for anal cancer screening include anal cytology followed by high-resolution anoscopy for those with abnormal findings. Outpatient topical treatments for anal intraepithelial neoplasia include infrared coagulation therapy, trichloroacetic acid, and imiquimod. The development of cost-effective national screening programs for HIV-associated anal cancer remains a challenge.

艾滋病毒相关性肛门癌是一种非艾滋病定义的癌症,是一种与人类乳头瘤病毒相关的恶性肿瘤,具有一系列浸润前病变。艾滋病毒/艾滋病患者的肛门癌标准化发病率为 20-50。肛门癌筛查方案包括肛门细胞学检查,然后对检查结果异常者进行高分辨率肛门镜检查。肛门上皮内瘤变的门诊局部治疗包括红外线凝固疗法、三氯乙酸和咪喹莫特。针对艾滋病毒相关肛门癌制定具有成本效益的国家筛查计划仍然是一项挑战。
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引用次数: 0
Proteomics in rheumatology: the dawn of a new era. 风湿病学中的蛋白质组学:新时代的曙光。
Pub Date : 2010-12-08 DOI: 10.3410/M2-87
Kamala Vanarsa, Chandra Mohan

Most rheumatic autoimmune diseases are complex in terms of their genetic origins and underlying pathogenic processes. Non-hypothesis-driven scanning platforms are adding novel insights to our understanding of these multifactorial diseases. This review summarizes the handful of recent proteomic studies that have been executed using samples from patients with rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, osteoarthritis, or Sjogren's syndrome. The candidate biomarkers that have been uncovered in the reviewed studies have potential applications in diagnosis, prognosis, and theranostics. Though we are at the infancy of the proteomics era in rheumatology, the limited number of molecules uncovered thus far already hold promise. Ongoing research in proteomics holds tremendous potential for shaping how rheumatic diseases are diagnosed, prognosticated, and managed clinically over the coming years.

大多数风湿性自身免疫性疾病在其遗传起源和潜在致病过程方面是复杂的。非假设驱动的扫描平台为我们对这些多因素疾病的理解增加了新的见解。本综述总结了最近对类风湿关节炎、系统性红斑狼疮、强直性脊柱炎、骨关节炎或干燥综合征患者样本进行的少量蛋白质组学研究。在回顾的研究中发现的候选生物标志物在诊断、预后和治疗方面具有潜在的应用前景。虽然我们还处于风湿病学蛋白质组学时代的初级阶段,但迄今为止发现的有限数量的分子已经带来了希望。正在进行的蛋白质组学研究在未来几年对风湿性疾病的诊断、预测和临床管理具有巨大的潜力。
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引用次数: 24
Recent advances in magnetic resonance imaging of prostate cancer. 前列腺癌磁共振成像研究进展。
Pub Date : 2010-12-08 DOI: 10.3410/M2-86
Nathan Lawrentschuk, Uri Lindner

This concise review attempts to highlight the recent advances in magnetic resonance imaging (MRI) in relation to all the different aspects of prostate cancer (PCa), and outlines future implications of MRI in the diagnosis, treatment, and surveillance of PCa.

这篇简明的综述试图强调磁共振成像(MRI)在前列腺癌(PCa)的所有不同方面的最新进展,并概述MRI在前列腺癌的诊断、治疗和监测方面的未来意义。
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引用次数: 4
期刊
F1000 medicine reports
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