Conductometric Soot Sensors : Internally Caused Thermophoresis as an Important Undesired Side Effect

Particulate matter sensors are of interest for application in the exhaust of any combustion processes, especially for automotive aftertreatment systems. Conductometric soot sensors have been serialized recently. They comprise planar interdigital electrodes (IDE) on an insulating substrate. Between the IDEs, a voltage is applied. Soot deposition is accelerated by the resulting electric field due to electrophoresis. With increasing soot deposition, the conductance between the IDE increases. The timely derivative of the conductance can serve as a sensor signal, being a function of the deposition rate. An increasing voltage between the IDE would be useful for detecting low particle exhausts. In the present study, the influence of the applied voltage and the sensor temperature on the soot deposition is investigated. It turned out that the maximum voltage is limited, since the soot film is heated by the resulting current. An internally caused thermophoresis that reduces the rate of soot deposition on the substrate follows. It reduces both the linearity of the response and the sensitivity. These findings may be helpful for the further development of conductometric soot sensors for automotive exhausts, probably also to determine real driving emissions of particulate matter

Pacing with restoration of respiratory sinus arrhythmia improved cardiac contractility and the left ventricular output: a translational study

Introduction: Respiratory sinus arrhythmia (RSA) is a prognostic value for patients with heart failure and is defined as a beat-to-beat variation of the timing between the heart beats. Patients with heart failure or patients with permanent cardiac pacing might benefit from restoration of RSA. The aim of this translational, proof-of-principle study was to evaluate the effect of pacing with or without restored RSAon parameters of LV cardiac contractility and the cardiac output

Effect of Ischemic Preconditioning and Postconditioning on Exosome-Rich Fraction microRNA Levels, in Relation with Electrophysiological Parameters and Ventricular Arrhythmia in Experimental Closed-Chest Reperfused Myocardial Infarction

We investigated the antiarrhythmic effects of ischemic preconditioning (IPC) and postconditioning (PostC) by intracardiac electrocardiogram (ECG) and measured circulating microRNAs (miRs) that are related to cardiac conduction. Domestic pigs underwent 90-min. percutaneous occlusion of the mid left anterior coronary artery, followed by reperfusion. The animals were divided into three groups: acute myocardial infarction (AMI, n = 7), ischemic preconditioning-acute myocardial infarction (IPC-AMI) (n = 9), or AMI-PostC (n = 5). IPC was induced by three 5-min. episodes of repetitive ischemia/reperfusion cycles (rI/R) before AMI. PostC was induced by six 30-s rI/R immediately after induction of reperfusion 90 min after occlusion. Before the angiographic procedure, a NOGA endocardial mapping catheter was placed again the distal anterior ventricular endocardium to record the intracardiac electrogram (R-amplitude, ST-Elevation, ST-area under the curve (AUC), QRS width, and corrected QT time (QTc)) during the entire procedure. An arrhythmia score was calculated. Cardiac MRI was performed after one-month. IPC led to significantly lower ST-elevation, heart rate, and arrhythmia score during ischemia. PostC induced a rapid recovery of R-amplitude, decrease in QTc, and lower arrhythmia score during reperfusion. Slightly higher levels of miR-26 and miR-133 were observed in AMI compared to groups IPC-AMI and AMI-PostC. Significantly lower levels of miR-1, miR-208, and miR-328 were measured in the AMI-PostC group as compared to animals in group AMI and IPC-AMI. The arrhythmia score was not significantly associated with miRNA plasma levels. Cardiac MRI showed significantly smaller infarct size in the IPC-AMI group when compared to the AMI and AMI-PostC groups. Thus, IPC led to better left ventricular ejection fraction at one-month and it exerted antiarrhythmic effects during ischemia, whereas PostC exhibited antiarrhythmic properties after reperfusion, with significant downregulaton of ischemia-related miRNAs

Transcriptional Alterations by Ischaemic Postconditioning in a Pig Infarction Model: Impact on Microvascular Protection

Although the application of cardioprotective ischaemia/reperfusion (I/R) stimuli after myocardial infarction (MI) is a promising concept for salvaging the myocardium, translation to a clinical scenario has not fulfilled expectations. We have previously shown that in pigs, ischaemic postconditioning (IPostC) reduces myocardial oedema and microvascular obstruction (MVO), without influencing myocardial infarct size. In the present study, we analyzed the mechanisms underlying the IPostC-induced microvascular protection by transcriptomic analysis, followed by pathway analysis. Closed-chest reperfused MI was induced by 90 min percutaneous balloon occlusion of the left anterior descending coronary artery, followed by balloon deflation in anaesthetised pigs. Animals were randomised to IPostC (n = 8), MI (non-conditioned, n = 8), or Control (sham-operated, n = 4) groups. After three hours or three days follow-up, myocardial tissue samples were harvested and subjected to RNA-seq analysis. Although the transcriptome analysis revealed similar expression between IPostC and MI in transcripts involved in cardioprotective pathways, we identified gene expression changes responding to IPostC at the three days follow-up. Focal adhesion signaling, downregulated genes participating in cardiomyopathy and activation of blood cells may have critical consequences for microvascular protection. Specific analyses of the gene subsets enriched in the endothelium of the infarcted area, revealed strong deregulation of transcriptional functional clusters, DNA processing, replication and repair, cell proliferation, and focal adhesion, suggesting sustentative function in the endothelial cell layer protection and integrity. The spatial and time-dependent transcriptome analysis of porcine myocardium supports a protective effect of IPostC on coronary microvasculature post-MI

Non-Coding RNAs in Stem Cell Regulation and Cardiac Regeneration: Current Problems and Future Perspectives

Although advances in rapid revascularization strategies following acute myocardial infarction (AMI) have led to improved short and long-term outcomes, the associated loss of cardiomyocytes and the subsequent remodeling result in an impaired ventricular function that can lead to heart failure or death. The poor regenerative capacity of the myocardium and the current lack of effective regenerative therapies have driven stem cell research in search of a possible solution. One approach involves the delivery of stem cells to the site of injury in order to stimulate repair response. Although animal studies initially delivered promising results, the application of similar techniques in humans has been hampered by poor target site retention and oncogenic considerations. In response, several alternative strategies, including the use of non-coding RNAs (ncRNAs), have been introduced with the aim of activating and regulating stem cells or inducing stem cell status in resident cells. Circular RNAs (circRNAs) and microRNAs (miRNAs) are ncRNAs with pivotal functions in cell proliferation and differentiation, whose role in stem cell regulation and potential significance for the field of cardiac regeneration is the primary focus of this review. We also address the general advantages of ncRNAs as promising drivers of cardiac regeneration and potent stem cell regulators

MiR-21, MiR-29a, GATA4, and MEF2c Expression Changes in Endothelin-1 and Angiotensin II Cardiac Hypertrophy Stimulated Isl-1+Sca-1+c-kit+ Porcine Cardiac Progenitor Cells In Vitro

Cost- and time-intensive porcine translational disease models offer great opportunities to test drugs and therapies for pathological cardiac hypertrophy and can be supported by porcine cell culture models that provide further insights into basic disease mechanisms. Cardiac progenitor cells (CPCs) residing in the adult heart have been shown to differentiate in vitro into cardiomyocytes and could contribute to cardiac regeneration. Therefore, it is important to evaluate their changes on the cellular level caused by disease. We successfully isolated Isl1+Sca1+cKit+ porcine CPCs (pCPCs) from pig hearts and stimulated them with endothelin-1 (ET-1) and angiotensin II (Ang II) in vitro. We also performed a cardiac reprogramming transfection and tested the same conditions. Our results show that undifferentiated Isl1+Sca1+cKit+ pCPCs were significantly upregulated in GATA4, MEF2c, and miR-29a gene expressions and in BNP and MCP-1 protein expressions with Ang II stimulation, but they showed no significant changes in miR-29a and MCP-1 when stimulated with ET-1. Differentiated Isl1+Sca1+cKit+ pCPCs exhibited significantly higher levels of MEF2c, GATA4, miR-29a, and miR-21 as well as Cx43 and BNP with Ang II stimulation. pMx-MGT-transfected Isl1+Sca1+cKit+ pCPCs showed significant elevations in MEF2c, GATA4, and BNP expressions when stimulated with ET-1. Our model demonstrates that in vitro stimulation leads to successful Isl1+Sca1+cKit+ pCPC hypertrophy with upregulation of cardiac remodeling associated genes and profibrotic miRNAs and offers great possibilities for further investigations of disease mechanisms and treatment

Alternative Splicing in Cardiovascular Disease—A Survey of Recent Findings

Alternative splicing, a driver of posttranscriptional variance, differs from canonical splicing by arranging the introns and exons of an immature pre-mRNA transcript in a multitude of different ways. Although alternative splicing was discovered almost half a century ago, estimates of the proportion of genes that undergo alternative splicing have risen drastically over the last two decades. Deep sequencing methods and novel bioinformatic algorithms have led to new insights into the prevalence of spliced variants, tissue-specific splicing patterns and the significance of alternative splicing in development and disease. Thus far, the role of alternative splicing has been uncovered in areas ranging from heart development, the response to myocardial infarction to cardiac structural disease. Circular RNAs, a product of alternative back-splicing, were initially discovered in 1976, but landmark publications have only recently identified their regulatory role, tissue-specific expression, and transcriptomic abundance, spurring a renewed interest in the topic. The aim of this review is to provide a brief insight into some of the available findings on the role of alternative splicing in cardiovascular disease, with a focus on atherosclerosis, myocardial infarction, heart failure, dilated cardiomyopathy and circular RNAs in myocardial infarction

Long-term survival of a HCC-patient with severe liver dysfunction treated with sorafenib

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. Prognosis and treatment options are stage dependent. In general, prognosis of patients with unresectable HCC is poor, especially for those patients with impaired liver function. Whereas treatment with the novel molecular tyrosine kinase inhibitor sorafenib (Nexavar) was shown to result in prolonged survival in patients with preserved liver function, its’ possible application in HCC-patients with strongly impaired liver function has not been clearly assessed. Here, we report on a 47-year-old male patient who presented with Child-Pugh class C liver cirrhosis and multifocal, non-resectable HCC. The patient was treated for 27 mo with Sorafenib, which was not associated with major drug-related side effects. During treatment, a reduction in tumour size of 24% was achieved, as assessed by regular CT scan. Moreover, within the 27 mo interval of stable tumour disease, liver function improved from Child-Pugh class C to class A

Reduced histologic neo in-stent restenosis after use of a paclitaxel-coated cutting balloon in porcine coronary arteries

The incidence of in-stent restenosis (ISR) has declined dramatically, but once it develops, no current treatment option, such as drug-eluting stents, drug-coated balloons, or cutting balloons (CBs), prevents re-narrowing of the stented atherosclerotic artery. In this preclinical study, we aimed to improve the efficacy of ISR treatment by coating CBs with paclitaxel (paclitaxel-eluting cutting balloon; PECB) and to characterize the histological features of neo-ISRs that arise after ISR treatment. ISR was induced by bare metal stent (BMS) implantation in coronary arteries in pigs. After one month of follow-up, BMS-induced ISR was treated with either CB or PECB. After another month, we performed quantitative coronary angiography, explanted the treated arteries and assessed histopathological and histomorphometric parameters. In addition, we compared histological features of neo-ISRs with pre-treatment ISRs. Injury, inflammation, fibrin deposition, and endothelialization scores were similar between the CB and PECB groups at one month after ISR treatment. Neointimal area (0.87±0.61 vs. 1.95±1.14 mm 2, p=0.02), mean neointimal thickness (0.40±0.39 vs. 0.99±0.56 mm, p=0.01), and percent area stenosis (27.3±20.4 vs. 48.3±22.9%, p=0.04) were decreased in PECB-treated coronary arteries compared to CB-treated arteries, respectively. Density of cells (predominantly smooth muscle cells; SMCs) was increased in neo-ISRs (3.51±3.05×10 3 vs. 6.35±2.57×10 3 cells/mm 2 , p<0.01),but significantly more CD68 + and CD20 + cells were found in pre-treatment ISRs. In conclusion, PECB treatment of ISRs led to better results in terms of smaller neointimal area and %area stenosis of neo-ISR. SMC density was increased in neo-ISRs in contrast with higher percentage of CD68 + and CD20 + cells in pre- treatment ISRs