silicon and Myocardial-Infarction

Based on the necessity and urgency of cardiac troponin I (cTnI) detection for the diagnosis of myocardial infarction, a novel unlabeled photoelectrochemical (PEC) immunosensor has been developed to detect cTnI rapidly and sensitively. Silicon nanowire arrays (SiNWs) were prepared

Topics: Biosensing Techniques; Electrochemical Techniques; Humans; Immunoassay; Myocardial Infarction; Nanowires; Reproducibility of Results; Silicon; Troponin I

Early diagnosis of acute myocardial infarction (AMI) significantly reduce the mortality rate and can be achieved via high-sensitive detection of AMI specific cardiac troponin I (cTnI) biomarker. Here, we present normal-incident type solution-immersed silicon (NI-SIS) ellipsometric biosensor, designed for ultra-high sensitive, high-throughput, label-free detection of the target protein. The NI-SIS sensors are equipped with a specially designed prism that maintains the angle of incidence close to the Brewster angle during operation, which significantly reduces SIS noise signals induced by the refractive index fluctuations of the surrounding medium, improves the signal-to-noise ratio, in-results lowers the detection limit. We applied NI-SIS biosensor for ultra-sensitive detection of cTnI biomarkers in human serum. The optimized sensor chip fabrication and detection operation procedures are proposed. The wide linear concentration ranges of fg/mL to ng/mL is achieved with the detection limit of 22.0 fg/mL of cTnI. The analytical correlation was assessed by linear regression analysis with the results of the Pathfast reference system. These impressive biosensing capabilities of NI-SIS technology have huge potentials for accurate detection of target species in different application areas, such as diagnosis, drug discovery, and food contaminations.

Topics: Biomarkers; Biosensing Techniques; Humans; Incidence; Myocardial Infarction; Silicon; Troponin I

Acute myocardial infarction (MI) is the leading cause of high mortality and morbidity rate worldwide, early and accurate diagnosis can increase the chances of survival. In this work, we report a simple, ultrasensitive, label-free, and high-throughput solution immersed silicon (SIS) immunosensor based on non-reflection condition (NRC) for p-polarized wave for early diagnosis of MI. SIS sensor chips are just a thin dielectric polymer layer on the silicon surface, which can be functionalized for specific application. At NRC, SIS sensors are extremely sensitive to the growing thickness of a bio-layer on the sensor surface while independent of refractive index change of the surrounding medium. Therefore, SIS signal is free from thermal noise, unlike surface plasmon resonance based sensor. Also, there is no need of reference signal which facilitates fast and accurate interaction measurement. Here, SIS technology is applied to tackle two issues in MI diagnosis: high sensitivity with the direct assay and the ability to measure in human serum. Myoglobin, creatine kinase-MB, and cardiac troponin I (cTnI) proteins were used as the MI biomarkers. We were able to measure over a broad concentration range with the detection limit of 5 and 10pg/ml for cTnI in PBS and blood serum, respectively. The response time is about 5min. This novel technique is a suitable candidate for cost effective point-of-care application.

Topics: Biosensing Techniques; Creatine Kinase, MB Form; Equipment Design; Humans; Lab-On-A-Chip Devices; Myocardial Infarction; Myoglobin; Point-of-Care Systems; Sensitivity and Specificity; Silicon; Troponin I

Long-term exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity and mortality but little is known about the role of the chemical composition of PM. This study examined the association of residential long-term exposure to PM components with incident coronary events.. Eleven cohorts from Finland, Sweden, Denmark, Germany, and Italy participated in this analysis. 5,157 incident coronary events were identified within 100,166 persons followed on average for 11.5 years. Long-term residential concentrations of PM < 10 μm (PM10), PM < 2.5 μm (PM2.5), and a priori selected constituents (copper, iron, nickel, potassium, silicon, sulfur, vanadium, and zinc) were estimated with land-use regression models. We used Cox proportional hazard models adjusted for a common set of confounders to estimate cohort-specific component effects with and without including PM mass, and random effects meta-analyses to pool cohort-specific results.. A 100 ng/m³ increase in PM10 K and a 50 ng/m³ increase in PM2.5 K were associated with a 6% (hazard ratio and 95% confidence interval: 1.06 [1.01, 1.12]) and 18% (1.18 [1.06, 1.32]) increase in coronary events. Estimates for PM10 Si and PM2.5 Fe were also elevated. All other PM constituents indicated a positive association with coronary events. When additionally adjusting for PM mass, the estimates decreased except for K.. This multicenter study of 11 European cohorts pointed to an association between long-term exposure to PM constituents and coronary events, especially for indicators of road dust.

Topics: Adult; Aged; Air Pollution; Cohort Studies; Copper; Denmark; Environmental Exposure; Female; Finland; Germany; Humans; Incidence; Iron; Italy; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Nickel; Particulate Matter; Potassium; Proportional Hazards Models; Silicon; Sulfur; Sweden; Time Factors; Vanadium; Zinc

Despite the benefits of mesenchymal stromal cell (MSC) transplantation in cardiac tissue, detailed in vivo observations have shown that MSCs only survive for a brief period after transplantation due to harsh microenvironmental conditions, including ischemia, inflammation and anoikis, in the infarcted myocardium. Thus, new strategies are needed to enhance MSC survival and inhibit cardiac remodeling. Studies have now demonstrated that chemokine [C-C motif] ligand 2 (CCL2) and its cognate receptor C-C chemokine receptor 2 (CCR2) promote excessive Ly6C(high) inflammatory monocyte infiltration at the infarct in response to ischemic myocardial injury. Therefore, decreasing the activities of these monocytes immediately after acute myocardial infarction (AMI) could be beneficial for AMI patients.. This study tested the hypothesis that therapeutic siRNA-loaded photoluminescent mesoporous silicon nanoparticles (PMSNs) targeting CCR2 expression in Ly6C(high) inflammatory monocytes decrease the accumulation of these cells in the infarct, improve the efficacy of MSC transplantation and attenuate myocardial remodeling.. PMSNs carrying therapeutic siCCR2 were first synthesized without the inclusion of fluorescent materials or dyes. After AMI BALB/c mice were established, 10(5) 5-ethynyl-2'- deoxyuridine (EdU)-labeled MSCs suspended in 100 µl of phosphate buffered saline (PBS) were injected into the border zone of the infarct of each mouse. PMSNs-siCCR2 (25 µg/g) were also intravenously injected via the tail vein immediately following AMI induction. Control mice were injected with an equal amount of PMSNs without siCCR2. PMSNs-siCCR2 were examined in vivo using near-infrared imaging technology. The therapeutic effects of PMSNs-siCCR2 for MSC transplantation were determined at the mRNA, protein and functional levels.. PMSNs-siCCR2 circulated freely in vivo and were cleared in a relatively short period of time (t(½)=37 min) with no evidence of toxicity. The therapeutic PMSNs-siCCR2 showed higher levels of cellular accumulation in Ly6C(high) monocytes in the spleen and more efficient degradation of CCR2 compared with the control (8.04%±2.17% vs. 20.02%±4.55%, p<0.001). Subsequently, the PMSNs-siCCR2 decreased the accumulation of CD11b-positive monocytes at the infarct (49.3%±17.34% vs. 61.32%±22.43%, p<0.001) on day 1. Increased survival of transplanted MSCs (13±3/mm(2) vs. 4±1/mm(2), p<0.001) and significantly decreased TdT-mediated dUTP nick end labeling (TUNEL)(+) cardiac myocytes (17.44%±6.26% vs. 39.49%±13.28%, p<0.001) were then identified in the infarct zone three days after AMI induction in the PMSNs-siCCR2 group. Three weeks after MSC injection, significant increases were observed in the vascular density (235.5±39.6/mm(2) vs. 147.4±20.3/mm(2), p<0.001) and the cardiac myosin-positive area (21.7%±8.4% vs. 13.2%±4.4%, p<0.001) of the infarct border zone. In addition, significant amelioration of left ventricular (LV) remodeling (thickness of the LV posterior walls) (0.84±0.11 mm vs. 0.61±0.08 mm, p<0.001) was also observed at the same time compared with the control group.. PMSNs-siCCR2-mediated CCR2 gene silencing in Ly6C(high) monocytes improved the effectiveness of MSC transplantation and selectively ameliorated myocardial remodeling after AMI. These results suggest that PMSNs-siCCR2 could potentially be used to develop an anti-inflammatory therapy for post-AMI MSC transplantation.

Topics: Animals; Humans; Luminescence; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Myocardial Infarction; Nanoparticles; Porosity; Receptors, CCR2; RNA Interference; Silicon

Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI. The local injection of THCPSi microparticles into the myocardium led to significant higher activation of inflammatory cytokine and fibrosis promoting genes compared to TOPSi micro and nanoparticles; however, both particles showed no significant effect on myocardial fibrosis at one week post-injection. Our results suggest that THCPSi and TOPSi micro and nanoparticles could be applied for cardiac delivery of therapeutic agents in the future, and the PSi biomaterials might serve as a promising platform for the specific treatment of heart diseases.

Topics: Animals; Biocompatible Materials; Cells, Cultured; Drug Carriers; Drug Delivery Systems; Fibrosis; Gene Expression Regulation; Inflammation; Male; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Porosity; Rats; Rats, Sprague-Dawley; Silicon

Early detection of cardiac biomarkers for diagnosis of heart attack is the key to saving lives. Conventional method of detection like the enzyme-linked immunosorbent assay (ELISA) is time consuming and low in sensitivity. Here, we present a label-free detection system consisting of an array of silicon nanowire sensors and an interface readout application specific integrated circuit (ASIC). This system provides a rapid solution that is highly sensitive and is able to perform direct simultaneous-multiplexed detection of cardiac biomarkers in serum. Nanowire sensor arrays were demonstrated to have the required selectivity and sensitivity to perform multiplexed detection of 100 fg/ml troponin T, creatine kinase MM, and creatine kinase MB in serum. A good correlation between measurements from a probe station and the readout ASIC was obtained. Our detection system is expected to address the existing limitations in cardiac health management that are currently imposed by the conventional testing platform, and opens up possibilities in the development of a miniaturized device for point-of-care diagnostic applications.

Topics: Antibodies, Immobilized; Biomarkers; Biosensing Techniques; Creatine Kinase, MB Form; Creatine Kinase, MM Form; Equipment Design; Heart Diseases; Humans; Limit of Detection; Myocardial Infarction; Nanowires; Point-of-Care Systems; Silicon; Troponin T

A new technique is presented that allows measurement of protein concentrations in the picomolar range with an assay time of only 10-20 min. The method is an enzyme-linked immunosorbent assay (ELISA), but uses in-situ ellipsometric measurement of a precipitating enzyme product instead of the usual colorimetric detection of accumulating enzyme product in solution. Quantitative validation was obtained by use of annexin V, a protein with high binding affinity for phosphatidylserine-containing phospholipid membranes, resulting in a transport-limited adsorption rate. This property was exploited to obtain a range of low surface concentrations of annexin V by timed exposures of phospholipid bilayers to known concentrations of annexin V. Using polyvinylchloride (PVC)-coated and silanized silicon slides, various versions of this technique were used for the rapid assay of fatty acid-binding protein (FABP), a recently introduced early marker for acute myocardial infarction with a normal plasma concentration below 1 nmol/l, interleukin 6 (IL-6), a cytokine with normal plasma concentrations below 1 pmol/l, and again, annexin V. A possible future application of the method in the development of a one-step ELISA is discussed.

Topics: Annexin A5; Biomarkers; Biophysical Phenomena; Biophysics; Carrier Proteins; Chemical Precipitation; Enzyme-Linked Immunosorbent Assay; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Humans; Interleukin-6; Lipid Bilayers; Myelin P2 Protein; Myocardial Infarction; Neoplasm Proteins; Phospholipids; Proteins; Sensitivity and Specificity; Silicon; Tumor Suppressor Proteins

In order to diagnose patients in thrombotic state, it is quite important to detect increased concentration of plasma thromboxane B2 (TXB2), a stable catabolite of TXA2. To determine plasma TXB2 levels with high sensitivity and selectivity, we employed gas chromatography-mass spectrometry (GC/MS). The trimethylsilyl (TMS) ether derivatives conventionally employed in GC/MS analysis of prostanoids are not suitable for quantitation of plasma prostanoids, because the mass spectra are deficient in ions with high intensity in the high mass range and TMS ether derivatives are sensitive to moisture. To solve these problems we employed tert-butyldimethylsilyl (t-BDMS) ether derivatives, based on the observation that t-BDMS ether derivatives afforded abundant ions at [M-57]+ and showed good hydrolytic stability. The reaction conditions of tert-butyldimethylsilylation were also examined to optimize the selected ion monitoring response. The t-BDMS ether derivatives of prostanoids were successfully analyzed with a short capillary column with a relatively large diameter, with maintaining good separation. In conjunction with the use of reversed-phase high performance liquid chromatography as purification procedure, a sensitive and reproducible stable isotope dilution assay of plasma TXB2 was developed. The values obtained by this method correlated well with those obtained by the radioimmunoassay we have developed.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angina Pectoris; Coronary Vasospasm; Dinoprost; Dinoprostone; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Myocardial Infarction; Organosilicon Compounds; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Silicon; Thromboxane B2; Thromboxanes

The content of Si, Fe, S, Ca, Cl in different heart compartments was studied in the autopsy material of human myocardium obtained after sudden cardiac death preceded by emotional stress. Damage of the element content was detected both within the myocardium of one chamber and the whole heart. Zones of high intracellular Ca content were found in the myocardium of the left ventricle and right atrium. Their location coincided with the area of ultrastructural alterations, which were earlier characterized as calcium damage of the myocardium. The same sites were characterized by high Cl content. The size of the areas was determined by roentgenologic mapping. S and Fe content was also different in different heart compartments.

Topics: Calcium; Chlorine; Death, Sudden; Electron Probe Microanalysis; Humans; Iron; Male; Middle Aged; Myocardial Infarction; Myocardium; Silicon; Sulfur

Topics: Alcohols; Animals; Calcium Phosphates; Coronary Disease; Culture Techniques; Dogs; Magnesium; Microscopy, Electron; Mitochondria; Mitochondria, Muscle; Myocardial Infarction; Osmium; Phosphorus; Silicon; Submitochondrial Particles; Sulfur

Topics: Adult; Aged; Aluminum; Calcium; Copper; Female; Humans; Hypocalcemia; Magnesium; Male; Middle Aged; Myocardial Infarction; Silicon; Trace Elements