用于老年基础医学研究与临床辅助诊断的神经肽Y及其受体Y1-6检测方法的初步设想

神经肽Y（NPY）作为机体内一种主要的神经递质和能量调控因子，广泛参与机体各种生理功能的调节，是维持机体内环境稳态的重要物质之一。随着对其研究的不断深入，人们发现它可通过与特定靶细胞膜上不同NPY受体Y1-6的特异性结合而启动并激活相应细胞信号传导通路，从而参与对机体生理功能和靶细胞增殖分化的调控，且NPY及其受体在体内的表达水平又可影响机体的正常生理功能、细胞代谢活动、以及这种改变所诱导或促进或参与的某些老年性疾病的发生、发展及转归，并对相关药物的防治带来明显影响。因此，对NPY及其受体含量的检测项目已成为相关老年性疾病与合并症的发病机制分析、疾病进程观察、治疗效果评价、疾病痊愈判断及预后跟踪随访的重要辅助诊断指标之一。为此，本文通过对可用于老年基础医学研究与临床辅助诊断的NPY及其受体检测的酶联免疫吸附法、放射免疫测定法、荧光免疫检测法、化学发光免疫分析法、免疫组织化学法、压电石英晶片免疫传感器法、免疫印迹法、斑点免疫层析及胶体金法、受体放射配基结合分析法、放射自显影法、液体芯片技术、微粒子酶免分析法等进行NPY及其受体检测方法的综述，并提出前瞻性设想和设计，希望这些用于检测NPY及其受体指标的方法能为未来老年医学的研究和临床应用奠定基础。     

Migraine and cluster headache – the common link

Although clinically distinguishable, migraine and cluster headache share prominent features such as unilateral pain, common pharmacological triggers such glyceryl trinitrate, histamine, calcitonin gene-related peptide (CGRP) and response to triptans and neuromodulation. Recent data also suggest efficacy of anti CGRP monoclonal antibodies in both migraine and cluster headache. While exact mechanisms behind both disorders remain to be fully understood, the trigeminovascular system represents one possible common pathophysiological pathway and network of both disorders. Here, we review past and current literature shedding light on similarities and differences in phenotype, heritability, pathophysiology, imaging findings and treatment options of migraine and cluster headache. A continued focus on their shared pathophysiological pathways may be important in paving future treatment avenues that could benefit both migraine and cluster headache patients.     

Bone morphogenic protein-9 stimulates endothelin-1 release from human pulmonary microvascular endothelial cells: A potential mechanism for elevated ET-1 levels in pulmonary arterial hypertension

Abnormalities of signalling for the transforming growth factor beta (TGFβ) family of peptides, including bone morphogenic proteins (BMP), have been described in heritable pulmonary arterial hypertension (PAH). TGFβ can modulate synthesis of the vasoconstrictor and mitogen, endothelin-1 (ET-1), a mediator that contributes to the pathogenesis of PAH. BMP-9 is a circulating peptide recently recognized to affect endothelial function. The stimuli for increased microvascular endothelial production of ET-1 in PAH are unknown. We therefore studied the effects of BMP-9 on ET-1 production by human lung blood microvascular endothelial cells (HMVEC-LBl) in vitro. In vitro, BMP-9 increased ET-1 production by HMVEC-LBl. The effect was identical to TGFβ-1, but BMP-9 and TGFβ-1 combined further increased ET-1 levels by 29%. As compared to TGFβ-1, BMP-9 induced more potent and rapid phosphorylation of Smad 1/5, the downstream signalling molecules of the activin-like kinase 1 (ALK-1) receptor. Moreover, as has been previously shown for endothelial cells of other origin, BMP-9 also induced Smad 2 phosphorylation in HMVEC-LBl. In conclusion, BMP-9 stimulates ET-1 production by HMVEC-LBl in vitro. BMP-9 signals via several Smad pathways. These studies provide novel mechanisms for the potentiation of PAH.     

Impact of treatment‐related liver toxicity on the outcome of HCV‐positive non‐Hodgkin's lymphomas

We studied 160 Hepatitis C virus (HCV)‐positive patients with NHL (59 indolent NHL, 101 aggressive). Median age was 67 years. HCV‐RNA was present in 146. HBsAg was positive in seven patients. At diagnosis, ALT value was above UNL in 67 patients. One hundred and twenty patients received an anthracycline‐based therapy, alkylators, 28 received chemotherapy plus rituximab. Cytotoxic drugs dose was reduced in 63 patients. Among 93 patients with normal ALT at presentation, 16 patients developed WHO grade II–III liver toxicity. Among 67 patients with abnormal ALT, eight patients had a 3.5 times elevation during treatment. Among 28 patients treated with rituximab and chemotherapy, five patients (18%) developed liver toxicity. Thirty four patients (21%) did not complete treatment (eight for liver toxicity). Median progression‐free survival (PFS) for patients who experienced liver toxicity is significantly shorter than median PFS of patients without toxicity (respectively, 2 years and 3.7 years, P = 0.03). After a median F‐UP of 2 years, 32 patients died (three for hepatic failure). A significant proportion of patients with HCV+ NHL develop liver toxicity often leading to interruption of treatment. This could be a limit to the application of immunochemotherapy programs. HCV+ lymphomas represent a distinct clinical subset of NHL that deserves specific clinical approach to limit liver toxicity and ameliorate survival. Am. J. Hematol., 2010. © 2009 Wiley‐Liss, Inc.     

Advanced computer aided technologies for design automation in footwear industry

In the footwear industry there is growing methodological research linking advanced computer-based technologies to the traditional manufacturing process. This paper deals with the automation of shoe design phases and describes a computer aided design system that brings together theories and tools from geometric modeling, image processing, and reverse engineering. At first, the paper reviews the current technologies used for creating new shoe models. Then the paper presents an approach based on shoe 3D virtual modeling in order to overcome the traditional time-consuming manual operations. The approach is concretized into dedicated tools able to automatically perform design of the last shape model and flattening of the shoe styling curves represented in the virtual prototype. The modeling tool uses 3D geometric rules derived from the analysis of strategies adopted by skilled manual operators, while the styling curves recognition and flattening are based on specific image processing algorithms and geometrical deformation rules. Experimental results show a good compromise between quality results and modeling time.     

Biomechanical Properties of Skin in Massive Weight Loss Patients

Background  

The aim of this study is to assess skin strength in MWL patients relative to control cosmetic abdominoplasty patients biophysically, biochemically, and histologically. Growing success of weight loss programs has brought about an increase in the MWL population. Skin quality is thought to be impaired by MWL, but there are no compelling studies that have fully addressed the structural mechanisms involved.