微粒体与冠状动脉粥样硬化的相关性研究进展

微粒体是细胞活化、凋亡过程中形成的微小颗粒。微粒体目前被认为是炎症反应的主要介质,可能在动脉粥样硬化斑块形成和随后导致急性冠脉综合征的发生、发展、形成中起作用。微粒体参与了动脉粥样硬化斑块的形成及破裂、凝血的启动以及血栓的形成,通过对微粒体的研究,可以增加对冠状动脉粥样硬化性心脏病发病机制的认识。     

血浆B型利钠肽预测肺动脉高压的价值

目的:探讨血浆B型利钠肽(BNP)浓度预测肺动脉高压的价值。方法:采用化学发光微粒子免疫分析(CMIA)测定48例肺动脉高压患者和46例健康体检正常者外周血浆BNP浓度。超声心动图根据三尖瓣返流估测肺动脉收缩压(SPAP)。比较正常对照组和肺动脉高压组血浆BNP浓度以及统计分析血浆BNP浓度与肺动脉高压之间相关性。结果:正常对照组血浆BNP浓度与肺动脉高压组有显著性差异(P<0.05),轻、中度肺动脉高压组与重度肺动脉高压组血浆BNP浓度无统计学差异(P>0.05),血浆BNP浓度与肺动脉高压有相关性(r=0.394,P<0.01)。结论:血浆BNP浓度与肺动脉高压存在相关性,但血浆BNP浓度并不代表肺动脉高压严重程度。     

Characterizing the kinetics of presepsin and associated inflammatory biomarkers in human endotoxemia

In this study, we describe the kinetics of a new potential inflammatory biomarker, presepsin, together with a panel of well-established biomarkers in a human endotoxemia study. We evaluated biomarker correlations and identified combinations that could hold valuable insights regarding the state of infection.

     

Novel polymer-grafted starch microparticles for mucosal delivery of vaccines.

Recent studies have demonstrated that systemic and mucosal administration of soluble antigens in biodegradable microparticles can potentiate antigen-specific humoral and cellular immune responses. However, current microparticle formulations are not adequate for all vaccine antigens, necessitating the further development of microparticle carrier systems. In this study, we developed a novel microparticle fabrication technique in which human serum albumin (HSA) was entrapped in starch microparticles grafted with 3-(triethoxysilyl)-propyl-terminated polydimethylsiloxane (TS-PDMS), a biocompatible silicone polymer. The immunogenicity of HSA was preserved during the microparticle fabrication process. Following intraperitoneal immunization of mice, TS-PDMS-grafted microparticles (MP) dramatically enhanced serum IgG responses compared with ungrafted MP and soluble HSA alone (P < 0.001). When delivered orally, both TS-PDMS-grafted and ungrafted microparticles elicited HSA-specific IgA responses in gut secretions, in contrast to orally administered soluble antigen. Indeed, TS-PDMS-grafted microparticles stimulated significantly stronger serum IgG (P < 0.005) and IgA (P < 0.001) responses compared with those elicited by ungrafted microparticles. These findings indicate that TS-PDMS-grafted starch microparticles have potential as systemic and mucosal vaccine delivery vehicles.     

Suppression of atopic dermatitis in mice model by reducing inflammation utilizing phosphatidylserine-coated biodegradable microparticles

Controlling inflammatory response is important to avoid chronic inflammation in many diseases including atopic dermatitis (AD). In this research, we tried using a phosphatidylserine (PS)-coated microparticles in the AD mouse model for achieving the modulation of the macrophage phenotype to an anti-inflammatory state. Here, we prepared poly (D,L-lactic acid) microparticle coated with PS on the outside shell. We confirmed the cellular uptake of the PS-coated microparticle, which leads to the significant downregulation of the inflammatory cytokine production. In the mouse model of AD, the PS-coated microparticle was injected subcutaneously for a period of 12 days. The mice showed significant reduction in the development of AD symptoms comparing with the mice treated with the PC-coated microparticle.     

Role of biomarkers in toxicity treatment "metabonomics" as a new biomarker discovery method

For the treatment of clinical toxicity, investigations to determine the offending substance and rapid treatment are required. Particularly in the case of drug development, the side-effect biomarkers anticipated in a clinical study are based on various toxicological information gleaned from non-clinical studies. In fact, drug development may be discontinued if no biomarkers can be detected using conventional clinical laboratory methodology; therefore, new approaches for finding biomarkers are needed. The use of molecular toxicological methods using omics technology is expected to be an effective future approach. Metabonomics is the omics approach that inspects the movement of endogenous metabolites comprehensively and searches for a toxicological mechanism or biomarker. It is expected to become a useful biomarker discovery tool; in fact, reports about new biomarker discoveries made using metabonomics have already been published; however, the rate of metabolite identification and metabolism map development are not yet sufficient. Therefore, the development of a database containing this type of information as well as clinical information is necessary to be able to apply this technology to toxicological biomarker discovery. Further, studies for translation from the non-clinical to the clinical setting are very important for discovering useful metabonomic side-effect biomarkers. Therefore, building new collaborative relationships between pharmaceutical companies, doctors, medical technologists, and diagnostic agent companies is considered to be important.     

肾素-血管紧张素系统中的肾素对高血压诊断分型的意义

肾素-血管紧张素系统是体内血压调节的重要机制.本文总结了经典的RAS系统与近年来发展形成的非经典RAS系统.同时概述了RAS系统中重要的限速酶肾素;并对肾素在高血压分型诊断中的两种不同的表征:肾素活性与直接肾素做了比较,为肾素在临床诊断上的应用提供了选择依据.     

Salivary uric acid and C‐reactive protein associations with hypertension in Midwestern Latino preadolescents and their parents

Latino families face increased risk for hypertension. Serum‐based uric acid and C‐reactive protein have been linked to hypertension. However, a paucity of salivary biomarker data exists in this area for Latino families. Using salivary biomarkers enables less invasive options for biomedical and biosocial research, which is especially important among vulnerable populations facing increased health disparities. This study examined the associations between salivary uric (sUA) acid, salivary C‐reactive protein (sCRP), and hypertension among 151 participants (57 children, 57 mothers, 37 fathers) from 57 Midwestern Latino families. Participants self‐administered the salivary samples, and blood pressure was measured by researchers. Results showed sUA was associated across family members, and child hypertension was related to parents′ hypertension. sCRP was only related to sUA in fathers. Findings highlight the family‐level health connections, along with the importance for further investigations using salivary biomarkers with Latinos, and the need for a robust sUA cut‐off for hyperuricemia.     

Prevalent Hypertension and Stroke in the Sleep Heart Health Study: Association with an ECG-derived Spectrographic Marker of Cardiopulmonary Coupling

Study Objectives:

The electrocardiogram (ECG)-based sleep spectrogram generates a map of cardiopulmonary coupling based on heart rate variability and respiration derived from QRS amplitude variations. A distinct spectrographic phenotype, designated as narrow-band elevated low frequency coupling (e-LFC_NB), has been associated with central apneas and periodic breathing and predicts sleep laboratory failure of continuous positive airway pressure therapy. This study assesses, at a population level, the associations of this spectrographic biomarker with prevalent cardiovascular disease using the Sleep Heart Health Study (SHHS)-I dataset.

Design:

Retrospective analysis of the Sleep Heart Health Study-I dataset.

Setting:

Laboratory for complex physiologic signals analysis.

Measurements and Results:

The fully-automated ECG-derived sleep spectrogram technique was applied to 5247 (of the original 6441) polysomnograms from the SHHS-I. Associations were estimated with use of various drugs and pathologies including prevalent hypertension and cardiovascular and cerebrovascular disease. Increasing with age and more common in males, e-LFC_NB is also associated with greater severity of sleep apnea and fragmented sleep. After adjustment for potential confounders, an independent association with prevalent hypertension and stroke was found.

Conclusions:

An ECG-derived spectrographic marker related to low frequency cardiopulmonary coupling is associated with greater sleep apnea severity. Whether this biomarker is solely a sign of more severe disease or whether it reflects primary alterations in sleep apnea pathophysiology (which may either cause or result from sleep apnea) is unknown. This ECG-based spectral marker is associated with a higher prevalence of hypertension and stroke.

Citation:

Thomas RJ; Weiss MD; Mietus JE; Peng CK; Goldberger AL; Gottlieb DJ. Prevalent hypertension and stroke in the sleep heart health study: association with an ECG-derived spectrographic marker of cardiopulmonary coupling. SLEEP 2009;32(7):897-904.     

Microparticle‐enhanced nephelometric immunoassay of plasminogen in bovine milk

A sensitive microparticle‐enhanced nephelometric immunoassay of bovine plasminogen (detection limit in reaction mixture, 4 fig l^‐1) is described. It is based on nephelometric measurement of the light scattered by microparticle clusters formed during a sandwich assay that uses microparticle‐anti‐plasminogen conjugate and free antibodies from antiplasminogen rabbit antiserum. This immunoassay was performed in 200‐fold diluted bovine milk, after release of plasminogen from caseins by ε‐amino‐n‐caproic acid treatment and elimination of the caseins. It allowed the quantification of plasminogen in milk for a wide range of concentrations (0.9–14.4 mg l^‐1), with accuracy (linear recovery in overloading assays) and precision (within‐ and between‐run coefficients of variation lower than 5%). When it was applied to 106 herd milk samples, this microparticle‐enhanced nephelometric immunoassay yielded milk plasminogen concentrations ranging between 1.1 and 4.9 mg l^‐1, with a mean of 2.0 mg l^‐1, and disclosed possible seasonal variations.     

Microparticle agglutination versus antibody-capture enzyme immunoassay for diagnosis of community-acquiredMycoplasma pneumoniae pneumonia

Community-acquiredMycoplasma pneumoniae pneumonia is a common disease which is usually diagnosed by serological methods. The objective of the present study was to understand the diagnostic significance and test characteristics of two different serological tests used to identify currentMycoplasma pneumoniae infection. Three hundred sixty-six patients who suffered from community-acquired pneumonia served as the study population. Six hundred ninety-four (328 paired and 38 unpaired) sera were examined for the presence of antibodies toMycoplasma pneumoniae with commercial kits based on two serological methods, microparticle agglutination and antibody-capture EIA. Agreement between the two kits was 85.2 % when individual sera were compared (Kappa=0.62) and 88.5 % when patients were compared (Kappa=0.69). The positive predictive value and the specificity for the identification of currentMycoplasma pneumoniae infection using a single acute-phase serum were 49.3 % and 86.9 %, respectively, for the microparticle agglutination method, compared to 91.3 % and 97.7 % for the antibody-capture EIA method (p<0.001). The negative predictive value and the sensitivity were 86.3 % and 48.1 % for the microparticle agglutination, not significantly different from the corresponding values of 86.5 % and 61.2 % for the antibody-capture EIA. It is concluded that the overall agreement between the two methods tested is good, but not perfect. The methods complement each other in the identification ofMycoplasma pneumoniae as the causative agent in patients with community-acquired pneumonia.     

Could Pin1 help us conquer essential hypertension at an earlier stage? A promising early-diagnostic biomarker and its therapeutic implications for the disease

Essential hypertension is a major risk factor for cardiovascular morbidity and mortality, and the early-diagnosis is very important for the prevention of essential hypertension. Previously, we found that Pin1, the only known enzyme isomerizing pSer/pThr-Pro motifs in proteins, may gradually become inactive under conditions of stress such as intracellular acidification and fever. Interestingly, essential hypertension and the dysfunction of Pin1 often synchronously occur with the increasing age. Recent evidence indicates that Pin1 primarily increases the activity of endothelial nitric oxide synthase (eNOS) and the production of nitric oxide (NO) in multiple ways, significantly promoting the relaxation response of blood vessels and preventing the elevation of blood pressure. Further, the inhibition of Pin1 results in significantly increased blood pressure in rats. So, we hypothesized and evaluated the potential of Pin1 to be a new early-diagnostic biomarker as well as a therapeutic drug for essential hypertension. The unique activity of Pin1 and some epidemiological and experimental data evidence that the decreased activity of Pin1 may be closely associated with the development of essential hypertension. The factors that may impact the activity of Pin1 and correlate with the risk of essential hypertension were also discussed. These findings indicate that Pin1 plays a key and permanent role in efficiently preventing the development of essential hypertension, and that Pin1 may be a promising early-diagnostic biomarker as well as an effective therapeutic drug for the early-diagnosis, prevention, and treatment of essential hypertension, potentially decreasing the risk of cardiovascular morbidity and mortality.     

Spontaneous short-term variations of circulating endothelin-1 in pulmonary hypertension

Endothelin-1 (ET-1) is overexpressed in pulmonary arteries of pulmonary hypertension (PH) patients and contributes to the sustained vasoconstriction, remodeling process, and thrombosis of vessels that underlie development and progression of this disease. Increased circulating ET-1 correlates with markers of PH severity, and ET-1 is regarded as a potential diagnostic and prognostic biomarker in PH. Because the within-individual variability measured in PH patients and in healthy subjects contributes to determine the biomarker predictive value and must be taken into account to establish cutoff values, we determined the short-term variability of circulating ET-1 in controls and in PH patients.     

不同离心条件对HBsAg检测结果的影响

目的通过全自动微粒子化学发光法检测乙肝表面抗原(HBsAg)的反应结果,探讨不同离心条件对HBsAg检测结果的影响。方法取本院临床患者静脉血3 ml于分离胶促凝采血管中,均分为2管,分别用3 600 r/min(2 898 g)10 min和8 819 r/min(10 000 g)10 min分离血清,分别检测上清液中HBsAg含量。共收集临床标本324份,对测定结果通过卡方检验分析不同离心速度组间检测结果是否有差异。检测仪器为美国雅培公司I2000全自动微粒子化学发光免疫分析仪,检测试剂为雅培公司的仪器配套试剂。并将乙肝表面抗原浓度在0.05～10 IU/ml的224份弱阳性血清标本进行确认试验,对比两种离心条件下的乙肝表面抗原检测假阳性率。结果卡方检验分析结果表明,两种离心条件下的乙肝表面抗原检测结果有统计学差异(P<0.001)。HBsAg浓度处于0.05～0.44 IU/ml范围内的弱阳性标本在不同离心条件后的检测结果有统计学差异(P<0.05),其他范围内的标本结果无统计学差异(P>0.05)。抗体中和确认试验阳性202例,则2 898 g 10 min分离血清,检测上清液中HBsAg含量的假阳性率为9.82%。10 000 g 10 min分离血清检测不会导致假阴性标本出现。结论获得准确、快速的检验结果,标本的质量更关键。严格按照试剂说明书规定的标本采集要求,离心操作,就可得到准确的实验结果。这说明,标本的离心处理好坏直接影响实验结果的准确性。对HBsAg低值弱阳性标本,应进行高速离心复核,抗体中和确认试验可作为HBsAg弱阳性标本进一步确认的手段。     

单微颗粒在血管内运动状态的力学分析

目的分析单个微颗粒在血管内的受力情况及影响其运动状态的因素。方法以靶向给药中血管流体中的微颗粒为研究对象,将血管模型简化成平行平板流动腔内的泊肃叶流动,依次分析单个微颗粒在流场中所受各个力的具体计算方法,通过力与力矩平衡条件列出微颗粒运动状态的方程,利用数值计算方法得到微颗粒所受力与颗粒粒径、流体流量之间的关系以及临界运动状态时粒径与流量的关系。结果流量增加和微颗粒粒径越大,微颗粒越容易滚动、滑移和上升;在流量和粒径关系图上,上升运动的临界线要高于滑移运动的临界线,而滚动运动临界线处于最下方。结论对于人体血液流量,微颗粒不会做上升运动。随着流量减少,一定粒径的颗粒可以从滑移运动过渡到纯滚动运动,在有弹性变形的情形下会出现完全静止。恰当选择颗粒的粒径及颗粒的表面黏附度对药物颗粒通过血液输送到达标靶位置至关重要。     

Diagnosis ofMycoplasma pneumoniae infection by microparticle aggluination and antibody-capture enzyme-immunoassay

The performance of two new commercial assays for the serological diagnosis ofMycoplasma pneumoniae infection (microparticle agglutination and antibody-capture enzyme-immunoassay) was studied using a panel of 169 serum samples from patients withMycoplasma pneumoniae pneumonia and a control group. Both assays were shown to be sensitive and specific for diagnosis. The performance of the capture immunoassay, however, decreased in older patients, probably due to its inability to detect cases of reinfection without IgM antibody response.     

Student award for outstanding research winner in the Ph.D. category for the 9th World Biomaterials Congress, Chengdu, China, June 1-5, 2012: synthesis and application of photodegradable microspheres for spatiotemporal control of protein delivery

In this study, the authors present a photodegradable microparticle system that can be used to entrap and deliver bioactive proteins to cells during culture. By using a photosensitive delivery system, experimenters can achieve a wide variety of spatiotemporally regulated release profiles with a single microparticle formulation, thereby, enabling one to probe many questions as to how protein presentation can be manipulated to regulate cell function. Photodegradable microparticles were synthesized via inverse suspension polymerization with a mean diameter of 22 μm, and degradation was demonstrated upon exposure to several irradiation conditions. The protein-loaded depots were incorporated into cell cultures and release of bioactive protein was quantified during the photodegradation process. This phototriggered release allowed for the delivery of TGF-β1 to stimulate PE25 cells and for the delivery of fluorescently labeled Annexin V to assay apoptotic 3T3 fibroblasts during culture. By incorporating these photoresponsive protein delivery depots into cell culture, new types of experiments are now possible to test hypotheses about how individual or multiple soluble factors might affect cell function when presented in a uniform, temporally varying, or gradient manner.     

QUANTITATION OF HYALURONIC ACID IN SERUM WITH AUTOMATED MICROPARTICLE PHOTOMETRIC AGGLUTINATION ASSAY

ABSTRACT

A microparticle photometric agglutination assay to quantitate hyaluronic acid (HA) in serum has been developed. The principle of the method is that hyaluronic acid binding protein covalently sensitized on microparticle surface initiates the particles to agglutinate in the presence of HA. By measuring the time-course of transmittance changes at 800 nm, due to the particles’ agglutination, HA concentration is estimated as a function of the magnitude of agglutination in a fully automated immunochemistry analyzer. The analytical range for HA was found to be between 10 and 1200 ng/mL. The precision (CV) was between 3.0 and 8.4% in the intra-assay (n = 10), and 4.8 and 8.9% in the inter-assay (n = 3). The lower limit of detection was 10 ng/mL. The deviation of the linearity study indicated within 8% of expected values, and the analytical recovery was between 96.5 and 106.3%. The correlation coefficient against HA plate ELISA was 0.989 with a slope of 1.01 (n = 31).     

Recommendations for the evaluation of pathology data in nonclinical safety biomarker qualification studies

A set of best practices for the conduct of histopathology evaluation in nonclinical safety studies was endorsed by the Society of Toxicologic Pathology (STP) in 2004. These best practices indicate that the study pathologist should have knowledge of the treatment group and access to all available study-related data for the animal from which the tissue was obtained. A new set of best practices for the conduct of histopathology review for safety biomarker qualification for nonclinical studies has been endorsed by the STP and is summarized in this document. These best practices are generally similar to those for nonclinical safety studies, specifically that the pathologist be "unblinded" or have access to study data. Although histopathology evaluation in biomarker qualification studies must be performed without knowledge of novel biomarker data, the study pathologist(s) should be involved in the attendant meta-analyses of these data. Blinded evaluation is an experimental tool in biomarker qualification studies that is appropriate only when well-defined criteria for specific histopathologic findings are identified prior to blinded review. Additionally, this paper also considers the management of bias, the use of a tiered evaluation approach, the importance of using qualified pathologists and standard reporting, and the management of spontaneous findings.     

Effect of nondipper hypertension on coronary artery disease progression in patients with chronic coronary syndrome

Background/aimIt has been suggested that there is a significant progress in coronary artery disease (CAD) by many pathophysiological mechanisms. Nondipper hypertension (NDH) has been shown to have higher target organ damage and have a higher rate of cardiovascular mortality and morbidity. In this study, we investigated the effect of nondipper hypertension on the progression of coronary atherosclerosis.Materials and methodsA total of 186 patients who underwent coronary angiography twice between 6 months and 3 years were included in the study. Coronary angiography was repeated on the admission day due to angina or positive exercise test and the patients were divided into groups.ResultsProgression of coronary artery disease was detected in 58 of 186 patients. Seventy-one of the total patients were found to be nondipper hypertensive. Nondipper hypertension, hypertension, diabetes mellitus, low-density lipoprotein, and total cholesterol were found to be effective in the progression of CAD. Among these parameters, it was seen that nondipper hypertension and hyperlipidemia were the most important independent risk factors.Conclusion Coronary artery disease is a progressive disease, and this progression depends on many reasons. In our study, we showed that nondipper hypertension is a new parameter that is effective in CAD progression.