A theoretical description of blood flow through the mitral orifice

A nonlinear differential equation describing the Doppler velocity profile for blood flow through the mitral valve has been derived. This equation is based on fluid dynamics and a simple, but comprehensive model of atrial and ventricular mechanics. A numerical solution to the equation is described and provides excellent agreement with Doppler velocity curves obtained clinically. One important result of the theory is that in patients with mitral stenosis, the slope of the clinically observed straight-line descent of the velocity profile is proportional to the mitral orifice area and inversely proportional to the atrioventricular compliance.     

Identification and quantification of prosthetic mitral regurgitation by flow convergence method using transthoracic approach

Ultrasound is the preferred imaging modality in diagnosis of vascular complications following cardiac catheterization and intervention. In some cases, however, bleeding surrounding the femoral vessels, may severely distort the color Doppler images, making detection of venous complications especially difficult. This report refers to such a case where post-catheterization haematoma was suspected to cause an obstruction of the femoral vein. Spectral Doppler recordings of blood flow in the common femoral vein, up-stream, distal to the hemorrhagic area, confirmed the diagnosis of obstruction by demonstrating changes in the venous flow pattern in the common femoral vein, consistent with venous hypertension. Due to the poor quality of the ultrasound images, the exact cause of the obstruction had to be established by another imaging modality, not affected by haemorrhages. CT showed that the common femoral vein was compressed at the puncture site by surrounding haemorrhages. Thus, when bleeding due to cardiac catheterization is associated with possible venous obstruction and findings by color Doppler are equivocal due to degradation of the color-Doppler image, detection of venous hypertension by spectral Doppler, performed distal to the bleeding area, strongly supports the presence of venous obstruction where the exact cause may be established by CT.     

A new automated method for the quantification of mitral regurgitant volume and dynamic regurgitant orifice area based on a normalized centerline velocity distribution using color M-mode and continuous wave Doppler imaging

Previous echocardiographic techniques for quantifying valvular regurgitation (PISA) are limited by factors including uncertainties in orifice location and hemispheric convergence assumption. Using computational fluid dynamics simulations, we developed a new model for the estimation of orifice diameter and regurgitant volume without the aforementioned assumptions of the PISA technique. Using experimental data obtained from the in vitro flow model we successfully validated our new model. The model output (y) and reference (x) values were in close agreement (y = 0.95x + 0.38, r = 0.96, error = 1.68 +/- 7.54% for the orifice diameter and y = 1.18x - 4.72, r = 0.93, error = 6.48 +/- 16.81% for the regurgitant volume).     

Probe for production and measurement of acute mitral regurgitant flow in dog.

A probe for production and measurement of acute mitral regurgitation in dogs is described. It consists of a tube that is introduced into the mitral valve through the left atrial appendage. Regurgitant flow through the tube is measured by an electromagnetic device. Variation of flow and zero flow are achieved by narrowing or occluding the tube with a rubber cuff. In animals weighing 30-50 kg, the probe does not produce significant mitral stenosis and the mitral leaflets fit closely around the probe during ventricular systole. The instantaneous relationship between mitral regurgitant flow (MRF) and the gradient between left ventricular and left atrial pressure shows a marked delay of MRF at the beginning and end of regurgitation. This delay can be attributed to some extent to electrical phase lag and to the small movement of the probe relative to the mitral valve during the cardiac cycle. Measurement of regurgitant stroke volume is affected by this movement only to a small extent.     

Fluid mechanics of regurgitant jets and calculation of the effective regurgitant orifice in free or complex configurations

The velocity fields of turbulent jets can be described using a single formula which includes two empirical constants: k(core) determining the length of the central core and k(turb) the jet widening. Flow models simulating jet adhesion, confinement and noncircular orifices were studied using laser Doppler anemometer and the modifications of the constants were derived from series of velocity profiles. In circular free jets, k(core) was found equal to 4.1 with a variability of 1.4%. In complex configurations, its variability was equal to 15.2%. For k(turb), the value for free circular jets was of 45.2 with a variability of 6.0% and this variability in complex configurations was significantly higher (30. 1%, p=0.025). The correlation between the actual orifice size and the jet extension was poor (r=0.52). However, the almost constant value of k(core) allowed to define a new algorithm calculating the regurgitant orifice diameter with the use of outlines of the jet image (r=0.89). In conclusion, the fluid mechanics of regurgitant jets is modified in complex configurations but, due to the relative independency of the central core, velocity fields could be used to evaluate the dimensions of the effective regurgitant orifice.     

A novel insight into the cost–benefit model for the evolution of botanical carnivory

Background The cost–benefit model for the evolution of botanical carnivory provides a conceptual framework for interpreting a wide range of comparative and experimental studies on carnivorous plants. This model assumes that the modified leaves called traps represent a significant cost for the plant, and this cost is outweighed by the benefits from increased nutrient uptake from prey, in terms of enhancing the rate of photosynthesis per unit leaf mass or area (A_N) in the microsites inhabited by carnivorous plants.Scope This review summarizes results from the classical interpretation of the cost–benefit model for evolution of botanical carnivory and highlights the costs and benefits of active trapping mechanisms, including water pumping, electrical signalling and accumulation of jasmonates. Novel alternative sequestration strategies (utilization of leaf litter and faeces) in carnivorous plants are also discussed in the context of the cost–benefit model.Conclusions Traps of carnivorous plants have lower A_N than leaves, and the leaves have higher A_N after feeding. Prey digestion, water pumping and electrical signalling represent a significant carbon cost (as an increased rate of respiration, R_D) for carnivorous plants. On the other hand, jasmonate accumulation during the digestive period and reprogramming of gene expression from growth and photosynthesis to prey digestion optimizes enzyme production in comparison with constitutive secretion. This inducibility may have evolved as a cost-saving strategy beneficial for carnivorous plants. The similarities between plant defence mechanisms and botanical carnivory are highlighted.     

TGF-beta signaling from a three-dimensional perspective: insight into selection of partners

Members of the transforming growth factor beta (TGF-beta) family, which include TGF-beta s, activins and bone morphogenetic proteins (BMPs), are potent regulators of cell proliferation, differentiation, migration and apoptosis. They act through binding to and activating serine/threonine kinase receptors on the cell surface and triggering intracellular signaling pathways in which Smad proteins have essential roles. Here, we discuss recent structure-based studies of TGF-beta s and BMPs, their receptors, and of Smad proteins, which have unravelled insights into ligand specificity, receptor and Smad activation, as well as new features of Smads as phosphoserine-binding entities.     

Effect of systolic flow rate on the prediction of effective prosthetic valve orifice area

The Gorlin equation for the hemodynamic assessment of valve area is commonly used in cardiac catheterization laboratories. A study was performed to test the prediction capabilities of the Gorlin formula as well as the Aaslid and Gabbay formula for the effective orifice area of prosthetic heart valves. Pressure gradient, flow, and valve opening area measurements were performed on four 27 mm valve prostheses (two mechanical bileaflet designs, St. Jude and Edwards-Duromedics, an Edwards pericardial tissue valve, and a trileaflet polyurethane valve) each mounted in the aortic position of an in vitro pulse duplicator. With the known valve orifice area, a different discharge coefficient was computed for each of the four valves and three orifice area formulas. After some theoretical considerations, it was proposed that the discharge coefficient would be a function of the flow rate through the valve. All discharge coefficients were observed to increase with increasing systolic flow rate. An empirical relationship of discharge coefficient as a linear function of systolic flow rate was determined through a regression analysis, with a different relationship for each valve and each orifice area formula. Using this relationship in the orifice area formulas improved the accuracy of the prediction of the effective orifice area with all three formulas performing equally well.     

Nitrates and Angina: an insight into arterialand venular involvement in blood flow regulation

This study tested the hypothesis that venular resistance increases during ischaemia and that a prevalent nitrates-induced venodilationis the cruc a mechanism underlying their ability to relieve ischaemia. Using the model of postreactive hyperaemia we used mercuryin-rubber surain gauges to measure forearm blood flow (FBF) and forearm circumference (FC) before and after 5 mg sublingual isosorbide dinitrate in twelve healthy volunteers. The FC change during reactive hyperaemia was evaluated according to a hydraulic model which assumes that arteriolar resistance (AR) controls the blood inflow and that venular resistance (VR) controls the blood outflow of the vascular capillary reservoir. In this setting FC represents the reservoir volume and any change in this parameter represents the instantaneous difference between input and output flows.In the absence of nitrates and five minutes of arterial closure, the hyperaemic FC curve shows a rapid increase followed by a slow recovery demonstrating a rapid inflow followed by a delayed outflow of the reservoir. This behaviour may be explained by assuming an initial very low arterial resistance and high venular resistance, followed by a slow requilibrium of the two.Repeating the experiment after nitrates intake, the hyperaemic FC curve shows a reduced dimension and a faster recovery to the baseline. Compared with the previous condition, this finding may be explained by assuming a reduced initial venular resistance, which facilitates the blood outflow and hence muscle perfusion. Our findings are coherent with an ischaemia-induced arteriolar dilatation which facilitates filling, and a simultaneous venular constriction which opposes emptying (arteriovenous ischaemic mismatch): the action of the nitrates seems to restore the mismatch by acting on the venous side.     

The three-dimensional structure of the tenth type III module of fibronectin: an insight into RGD-mediated interactions.

The solution structure of the tenth type III module of fibronectin has been determined using nuclear magnetic resonance techniques. The molecule has a fold similar to that of immunoglobulin domains, with seven beta strands forming two antiparallel beta sheets, which pack against each other. Both beta sheets contribute conserved hydrophobic residues to a compact core. The topology is more similar to that of domain 2 of CD4, PapD, and the extracellular domain of the human growth hormone receptor than to that of immunoglobulin C domains. The module contains an Arg-Gly-Asp sequence known to be involved in cell adhesion. This tripeptide is solvent exposed and lies on a conformationally mobile loop between strands F and G, consistent with its cell adhesion function.     

Mechanistic insight into the physiological relevance of helical blood flow in the human aorta: an in vivo study

The hemodynamics within the aorta of five healthy humans were investigated to gain insight into the complex helical flow patterns that arise from the existence of asymmetries in the aortic region. The adopted approach is aimed at (1) overcoming the relative paucity of quantitative data regarding helical blood flow dynamics in the human aorta and (2) identifying common characteristics in physiological aortic flow topology, in terms of its helical content. Four-dimensional phase-contrast magnetic resonance imaging (4D PC MRI) was combined with algorithms for the calculation of advanced fluid dynamics in this study. These algorithms allowed us to obtain a 4D representation of intra-aortic flow fields and to quantify the aortic helical flow. For our purposes, helicity was used as a measure of the alignment of the velocity and the vorticity. There were two key findings of our study: (1) intra-individual analysis revealed a statistically significant difference in the helical content at different phases of systole and (2) group analysis suggested that aortic helical blood flow dynamics is an emerging behavior that is common to normal individuals. Our results also suggest that helical flow might be caused by natural optimization of fluid transport processes in the cardiovascular system, aimed at obtaining efficient perfusion. The approach here applied to assess in vivo helical blood flow could be the starting point to elucidate the role played by helicity in the generation and decay of rotating flows in the thoracic aorta.     

A new insight into the pathogenesis of filarial disease

Filariasis is a major public health problem throughout many regions of the tropics. The disease is caused by several species of filarial nematode including Wuchereria bancrofti and Brugia malayi, the agents of lymphatic filariasis, and Onchocerca volvulus, the cause of 'riverblindness'. Disease caused by these worms varies depending on the tissue location of the parasite, and is associated with episodes of acute and chronic inflammation. These pathologies, including elephantiasis and blindness, rank among the most disabling in the world. Studies aimed at characterizing the molecular nature of the inflammatory stimuli derived from filarial nematodes uncovered a long forgotten secret, their symbiont Wolbachia. LPS-like molecules from these intracellular bacteria are responsible for potent inflammatory responses from macrophages and in animal models of filarial disease. Wolbachia has also been associated with severe inflammatory reactions to filarial chemotherapy, being released into the blood following the death of the parasite. Recent studies in animal models even implicate Wolbachia in the onset of lymphodema and blindness. Taken together these studies suggest a major role for Wolbachia in the pathogenesis of filarial disease. It may be possible, through the use of antibiotic therapy, to clear worms of their bacteria, in the hope that this will prevent the onset and development of filarial pathology.     

二尖瓣关闭不全患者的运动病理生理学特征的临床研究报告

目的:通过心肺运动试验(CPET)进行二尖瓣关闭不全的运动病理生理学特征的相关研究.方法:自2016年以来签署知情同意后,严格质控下完成规范化CPET极限运动的中重度二尖瓣关闭不全患者26例,取同期正常人11例为对照组.将CPET核心指标按照标准方法分析计算,并与正常人比较,进行组间统计学独立样本t检验.同时将患者是否...     

Specific incorporation of L-glutamine into volicitin in the regurgitant of Spodoptera litura

Volicitin, [N-(17-hydroxylinolenoyl)-L-glutamine], was identified as an elicitor of plant volatiles from a Spodoptera exigua regurgitant. It has been proposed that gut microbes synthesize volicitin from glutamine, a predominant amino acid component in the insect gut. However, we found that glutamine was not a major component in the regurgitant of Spodoptera litura, although L-glutamine was exclusively incorporated into volicitin by S. litura fed on diets enriched with various amino acids. This selectivity of glutamine as a substrate was not due to a dominant occurrence in the insect gut.     

Chordal tethering: a unique cause of structural mitral regurgitation in dilated cardiomyopathy

Mitral regurgitation in dilated cardiomyopathy is usually considered "functional," and many such patients are treated medically. Surgery is often offered as a last resort in select patients who have failed medical therapy. We report a patient with dilated cardiomyopathy with ventricular tachycardia and ventricular dyssynchrony and "structural mitral regurgitation" due to chordal tethering, which was managed surgically using a minimally invasive approach.     

A new insight into the gelatinization process of native starches

The gelatinization characteristics of seven different food starches (regular corn, high-amylose corn, waxy corn, wheat, rice, potato, and tapioca) were investigated. Each starch sample type was heated to 35, 40, 45, etc. up to 85 °C at 5 °C intervals, and freeze-dried. The treated samples were analyzed using light microscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and high-performance size exclusion chromatography (HPSEC). When heated, granules underwent structural changes prior to the visible morphological changes that took place during gelatinization. The nature of these structural changes depended on starch type. These results indicate that the starch gelatinization process is more complex than a simple granular order-to-disorder transition.     

A novel insight into the mechanism of mammalian selenoprotein synthesis

The amino acid selenocysteine is encoded by UGA, usually a stop codon, thus requiring a specialized machinery to enable its incorporation into selenoproteins. The machinery comprises the tRNA^Sec, a 3′-UTR mRNA stem–loop termed SElenoCysteine Insertion Sequence (SECIS), which is mandatory for recoding UGA as a Sec codon, the SECIS Binding Protein 2 (SBP2), and other proteins. Little is known about the molecular mechanism and, in particular, when, where, and how the SECIS and SBP2 contact the ribosome. Previous work by others used the isolated SECIS RNA to address this question. Here, we developed a novel approach using instead engineered minimal selenoprotein mRNAs containing SECIS elements derivatized with photoreactive groups. By cross-linking experiments in rabbit reticulocyte lysate, new information could be gained about the SBP2 and SECIS contacts with components of the translation machinery at various translation steps. In particular, we found that SBP2 was bound only to the SECIS in 48S pre-initiation and 80S pretranslocation complexes. In the complex where the Sec-tRNA^Sec was accommodated to the A site but transpeptidation was blocked, SBP2 bound the ribosome and possibly the SECIS element as well, and the SECIS had flexible contacts with the 60S ribosomal subunit involving several ribosomal proteins. Altogether, our findings led to broadening our understanding about the unique mechanism of selenocysteine incorporation in mammals.     

A systems biology-led insight into the role of the proteome in neurodegenerative diseases

Introduction: Multifactorial disorders are the result of nonlinear interactions of several factors; therefore, a reductionist approach does not appear to be appropriate. Proteomics is a global approach that can be efficiently used to investigate pathogenetic mechanisms of neurodegenerative diseases.

Areas covered: Here, we report a general introduction about the systems biology approach and mechanistic insights recently obtained by over-representation analysis of proteomics data of cellular and animal models of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders, as well as of affected human tissues.

Expert commentary: As an inductive method, proteomics is based on unbiased observations that further require validation of generated hypotheses. Pathway databases and over-representation analysis tools allow researchers to assign an expectation value to pathogenetic mechanisms linked to neurodegenerative diseases. The systems biology approach based on omics data may be the key to unravel the complex mechanisms underlying neurodegeneration.