O13 Trimethylaminuria,diet and a ‘fish‐like’ odour

Trimethylaminuria, also known colloquially as the fish malodour syndrome, is a metabolic disorder characterized by the presence of abnormal amounts of the dietary‐derived tertiary amine, trimethylamine, in the urine, sweat, expired air and other bodily secretions. Trimethylamine usually undergoes metabolism to form the innocuous metabolite, trimethylamine N‐oxide. However, ‘greater‐than‐normal’ amounts of trimethylamine may accumulate within the body owing to a mismatch in the enzyme's capacity to undertake this N‐oxidation reaction and the substrate load it has to process. Trimethylamine itself is a volatile substance and has the powerful aroma of rotting fish, conferring upon the sufferer a highly objectionable body odour, which can be destructive to the personal, social and work life of the affected individual. As more cases of this condition have been uncovered it has become apparent that there are several sub‐types of this disorder, falling into two major categories, and this has allowed a clearer picture to emerge. First, there are those forms that are related to a dysfunction of the normal enzyme (flavin‐containing monooxygenase 3; FMO3) activity owing to genetic, hormonal or inhibitory chemical influences. Secondly, there are those forms arising from substrate overload of enzyme activity (either in a normal or depressed state) such as an excess of dietary precursors or variations of gut microflora resulting in enhanced liberation of trimethylamine. Clearly, certain aspects of these two categories are intimately entwined and several factors may act together to give rise to the disorder. In recent years much progress has been made at all levels in our understanding of this condition. This presentation will summarize this progress, draw attention to the different types of the condition and highlight aspects that require further investigation. S.C. Mitchell, R.L. Smith (2001). Trimethylaminuria: the fish malodour syndrome. Drug Metabolism and Disposition 29 : 517–521. J.R. Cashman, K. Camp, S.S. Fakharzadeh, P.V. Fennessey, R.N. Hines, O.A. Mamer, S.C. Mitchell, G. Preti, D. Schlenk, R.L. Smith, S.S. Tjoa, D.E. Williams, S. Yannicelli (2003). Biochemical and clinical aspects of the human flavin‐containing monooxygenase form 3 (FMO3) related to trimethylaminuria. Current Drug Metabolism 4 : 151–170.     

Immunolocalization of beta 1 integrins in platelets and platelet- derived microvesicles

Human platelets contain several adhesion receptors belonging to the integrin superfamily. At least three beta 1 integrins are present on platelets and have been shown to mediate platelet adhesion to collagen, fibronectin, and laminin. To study the cellular localization of the beta 1 integrins in platelets, we produced a polyclonal antibody by immunization of goat 172 with purified beta 1 subunit from HPB-ALL cells. Antibody 172 (Ab172) specifically immunoblotted a 135-Kd protein in a lysate of whole platelets. The reactivity of Ab172 with platelet membrane proteins was further determined by immunoprecipitation of lysates of surface-radioiodinated platelets. Ab172 immunoprecipitates, resolved by nonreducing/reducing two-dimensional sodium dodecyl sulfate- polyacrylamide gel electrophoresis consisted of three labeled proteins with migrational properties of platelet glycoprotein (GP)Ia, GPIc and GPIIa. Neither GPIIb/IIIa nor the vitronectin receptor were immunoprecipitated by Ab172, confirming a lack of cross-reactivity with the beta 3 integrins in platelets. Immunofluorescence studies using Ab172 were performed to investigate the cellular distribution of beta 1 integrins in platelets. Fluorescent labeling of intact cells demonstrated the presence of beta 1 antigen on the surface of resting cells. Permeabilization of platelets with Triton X-100 showed the presence of an intracellular pool of beta 1 antigen. Double-label experiments using Ab172 and AP-2 (anti-GPIIb/IIIa) showed identical labeling patterns, suggesting a similar subcellular distribution for these integrins. Following thrombin stimulation, permeabilized cells showed a centralized clearing of both beta 1 antigen and GPIIb/IIIa as well as an intensification of surface labeling for beta 1 antigen. These findings suggest the translocation of intracellular beta 1 antigen to the platelet surface as a result of thrombin stimulation. Because platelet-derived microvesicles have been reported to contain GPIIb/IIIa, we investigated the possible distribution of beta 1 integrins in these structures. Microvesicles, produced as a result of platelet activation, were labeled with Ab172, suggesting the distribution of beta 1 integrins in these structures as well as in intact cells.     

The value of biomarker-guided antibiotic therapy

ABSTRACT

Introduction

There is an increasing interest to individualize patient management and decisions regarding antibiotic treatment. Biomarkers may provide relevant information for this purpose.     

基于Linux和通用分组无线业务的心电无线监护设计

①介绍了一种具有实时检测和报警功能的无线心电监护系统。系统采用32位单片机S3C2410X微控制器为核心,采用SIM100E为通用分组无线业务模块,基于Linux进行软件设计。整个程序可分为3大部分:采集显示、心电分析和自动报警。着重介绍了Linux操作系统下心电检测分析和自动报警程序的设计。②整个心电监护系统的硬件设计可分为5个部分:心电采集模块、存储模块、通讯模块、人机接口模块和电源模块。③实验结果表明系统能够实现对患者心电信号的实时监测,并能够检测心动过速、心动过缓、心律不齐、停搏和漏搏等5种心律失常,当出现这些心律失常时,能够通过通用分组无线业务以手机短信形式发送报警。