From bench to bedside

ABSTRACT: Because the microcirculation has emerged as an important reanimation target, appropriate methods to monitor the microcirculatory function are crucial. Several teams have now succeeded in crossing this bridge from bench to bedside, but the choice of the tissues of interest remains a debate. The potential accessible vascular beds that doctors could use in reanimation strategies and the relationship of these beds to more relevant microcirculatory ones are important issues to address.     

From bench to bedside

Ohne Zusammenfassung     

Targeting the oncogene eIF4E in cancer: From the bench to clinical trials

Identifying and targeting specific oncogenes, with the hope that the resultant therapies may eventually prove to exert positive clinical effects, is a major effort in the area of cancer therapeutics. The eukaryotic translation initiation factor, eIF4E, is overexpressed in many cancers, including acute myeloid leukemia. The role of eIF4E in oncogenic transformation and the development of a means to directly target its activity with ribavirin are discussed here. Results from early stage clinical trials and factors contributing to the development of clinical resistance to ribavirin are also described.     

Modern blepharoplasty: From bench to bedside

The demand for procedures aiming to rejuvenate the upper third part of the face and the periocular region has increased in the past several years. Blepharoplasty is one of the most frequently performed procedures worldwide to date. Surgery is currently the first choice in order to achieve permanent and effective results; however, it is burdened by potential surgical complications feared by patients. There is an increasing trend in individuals to request less invasive, non-surgical, effective, and safe procedures for eyelid treatment. The aim of this minireview is to present a brief overview of non-surgical blepharoplasty techniques that have been reported in the literature in the past 10 years. Numerous modern techniques that provide a rejuvenation of the entire area have been described. Numerous less invasive methods have been proposed in the current literature and in modern-day routine clinical settings. Dermal fillers are a commonly chosen option for providing enhanced aesthetic results, especially considering that volume loss can be one of the main underlying causes of facial and periorbital aging. Deoxycholic acid use may be considered when the problem is represented by periorbital excess fat deposits. The simultaneous excess and loss of elasticity of the skin can be assessed with techniques such as lasers and plasma exeresis. Furthermore, techniques such as platelet-rich plasma injections and the insertion of twisted polydioxanone threads are emerging as viable methods to rejuvenate the periorbital region.     

临床医学实验室生物参考区间的建立

目的以血清总胆固醇（TC）、高密度脂蛋白胆固醇（HDL—C）2个生化项目为例,探讨适合本实验室建立生物参考区间的方法。方法结合ISO15189：2003（E）《医学实验室——质量和能力的专用要求》条款要求和美国临床实验室标准化委员会（NCCLS）C28-A2文件推荐方法,先引用权威书刊、厂家试剂说明书或转移其他医院实验室的生物参考区间,然后进行实验验证,验证不通过的项目,收集120例健康参考个体自建适用于本实验室的生物参考区间,定期进行临床评审。结果TC现用生物参考区间验证通过,可以继续使用;HDL—C验证不通过,不适用,须自建生物参考区间,自建区间为男性0．82～1．82mmol／L、女性0．89～1．97mmol／L。结论采用本研究方法确立临床医学实验室生物参考区间从多途径保证检验指标的生物参考区间可靠、准确、科学、实用,能确保生物参考区间符合临床要求,值得推广应用。     

Development and therapeutic potential of autotaxin small molecule inhibitors: From bench to advanced clinical trials

Several years after its isolation from melanoma cells, an increasing body of experimental evidence has established the involvement of Autotaxin (ATX) in the pathogenesis of several diseases. ATX, an extracellular enzyme responsible for the hydrolysis of lysophosphatidylcholine (LPC) into the bioactive lipid lysophosphatidic acid (LPA), is overexpressed in a variety of human metastatic cancers and is strongly implicated in chronic inflammation and liver toxicity, fibrotic diseases, and thrombosis. Accordingly, the ATX-LPA signaling pathway is considered a tractable target for therapeutic intervention substantiated by the multitude of research campaigns that have been successful in identifying ATX inhibitors by both academia and industry. Furthermore, from a therapeutic standpoint, the entry and the so far promising results of the first ATX inhibitor in advanced clinical trials against idiopathic pulmonary fibrosis (IPF) lends support to the viability of this approach, bringing it to the forefront of drug discovery efforts. The present review article aims to provide a comprehensive overview of the most important series of ATX inhibitors developed so far. Special weight is lent to the design, structure activity relationship and mode of binding studies carried out, leading to the identification of advanced leads. The most significant in vitro and in vivo pharmacological results of these advanced leads are also summarized. Lastly, the development of the first ATX inhibitor entered in clinical trials accompanied by its phase 1 and 2a clinical trial data is disclosed.     

From bench to bedside: bacterial growth and cytokines

The recognition that neutrophils, macrophages, and other components of the inflammatory cascade participate in the generation and progression of acute lung injury/acute respiratory distress syndrome has resulted in the use of anti-inflammatory agents in an attempt to attenuate this inflammatory response and to prevent further progression of the acute lung injury. The recent finding that cytokines, in part mediators of this ''overwhelming'' inflammatory reaction, may also stimulate bacterial growth, impair bacterial clearance, and promote the subsequent development of nosocomial infections may have important implications to the management of the acute lung injury/acute respiratory distress syndrome patient.     

From bench to bedside: bacterial growth and cytokines

The recognition that neutrophils, macrophages, and other components of the inflammatory cascade participate in the generation and progression of acute lung injury/acute respiratory distress syndrome has resulted in the use of anti-inflammatory agents in an attempt to attenuate this inflammatory response and to prevent further progression of the acute lung injury. The recent finding that cytokines, in part mediators of this 'overwhelming' inflammatory reaction, may also stimulate bacterial growth, impair bacterial clearance, and promote the subsequent development of nosocomial infections may have important implications to the management of the acute lung injury/acute respiratory distress syndrome patient.     

Anti-angiogenic drugs: from bench to clinical trials

Angiogenesis, the generation of new capillaries through a process of pre-existing microvessel sprouting, is under stringent control and normally occurs only during embryonic and post-embryonic development, reproductive cycle, and wound repair. However, in many pathological conditions (solid tumor progression, metastasis, diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among others), the disease appears to be associated with persistent upregulated angiogenesis. The development of specific anti-angiogenic agents arises as an attractive therapeutic approach for the treatment of cancer and other angiogenesis-dependent diseases. The formation of new blood vessels is a complex multi-step process. Endothelial cells resting in the parent vessels are activated by an angiogenic signal and stimulated to synthesize and release degradative enzymes allowing endothelial cells to migrate, proliferate and finally differentiate to give rise to capillary tubules. Any of these steps may be a potential target for pharmacological intervention. In spite of the disappointing results obtained initially in clinical trials with anti-angiogenic drugs, recent reports with positive results in phases II and III trials encourage expectations in their therapeutic potential. This review discusses the current approaches for the discovery of new compounds that inhibit angiogenesis, with emphasis on the clinical developmental status of anti-angiogenic drugs.     

Antimicrobial resistance in Acinetobacter baumannii: From bench to bedside

Acinetobacter baumannii (A. baumannii) is undoubtedly one of the most successful pathogens in the modern healthcare system. With invasive procedures, antibiotic use and immunocompromised hosts increasing in recent years, A. baumannii has become endemic in hospitals due to its versatile genetic machinery, which allows it to quickly evolve resistance factors, and to its remarkable ability to tolerate harsh environments. Infections and outbreaks caused by multidrug-resistant A. baumannii (MDRAB) are prevalent and have been reported worldwide over the past twenty or more years. To address this problem effectively, knowledge of species identification, typing methods, clinical manifestations, risk factors, and virulence factors is essential. The global epidemiology of MDRAB is monitored by persistent surveillance programs. Because few effective antibiotics are available, clinicians often face serious challenges when treating patients with MDRAB. Therefore, a deep understanding of the resistance mechanisms used by MDRAB can shed light on two possible strategies to combat the dissemination of antimicrobial resistance: stringent infection control and antibiotic treatments, of which colistin-based combination therapy is the mainstream strategy. However, due to the current unsatisfying therapeutic outcomes, there is a great need to develop and evaluate the efficacy of new antibiotics and to understand the role of other potential alternatives, such as antimicrobial peptides, in the treatment of MDRAB infections.