A neuraminidase from Trypanosoma cruzi removes sialic acid from the surface of mammalian myocardial and endothelial cells

Trypanosoma cruzi causes Chagasic heart disease, a major public health problem in Latin America. The mechanism of interaction of this protozooan parasite with host cells is poorly understood. We recently found that the infective trypomastigote form a T. cruzi exhibits neuraminidase activity and can desialylate mammalian erythrocytes. However, it is not known if T. cruzi can also modify the surfaces of cardiovascular cells that are directly involved in the most important clinical manifestations of this disease. Accordingly, this study determined whether T. cruzi can remove sialic acid from cultured rat myocardial or human vascular endothelial cells. Sialic acid was labeled metabolically with the precursor 3H-N-acetyl-D-mannosamine. Soluble neuraminidase, isolated from intact T. cruzi trypomastigotes, caused significant release of labeled material from myocardial cells (e.g., 2,174 +/- 27 dpm/h vs. spontaneous release of 306 +/- 30 dpm/h, n = 4, P less than 0.001). Chromatographic analysis showed that the bulk of the radioactivity released by T. cruzi neuraminidase was sialic acid. Intact T. cruzi trypomastigotes also released sialic acid from metabolically labeled myocardial cells in a concentration-dependent manner. In contrast, a noninfective form of T. cruzi, the amastigote, did not desialylate these cells. Galactose oxidase labeling demonstrated newly desialylated glycoproteins on the surface of myocardial cells treated with T. cruzi neuraminidase. Desialylation of myocardial cells was confirmed histochemically by the appearance of binding sites for peanut agglutinin, a lectin that binds to complex oligosaccharide moieties after removal of the terminal sialyl residue. T. cruzi neuraminidase also removed sialic acid from adult human saphenous vein endothelial cells, as determined by both histochemical and metabolic labeling studies. Thus, infective forms of T. cruzi can chemically modify the surfaces of myocardial and vascular endothelial cells by desialylation. This alteration may play a role in the initial interaction of this parasite with these important target cells of the host cardiovascular system

Coronary Artery Reperfusion

The effects of coronary artery reperfusion 3 hr after coronary occlusion on contractile function and the development of myocardial damage at 24 hr was studied experimentally. In 14 control and 6 reperfused dogs, relationships between epicardial ST segment elevation 15 min after coronary occlusion and myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 hr later were examined. The electrocardiograms were recorded from 10 to 15 sites on the left ventricular epicardium and transmural samples for CPK and histology were obtained from the same sites where epicardial electrocardiograms had been recorded. An inverse relation existed between ST segment elevation (mv) 15 min after occlusion and log CPK activity (IU/ mg of protein) 24 hr later, log CPK = - 0.06ST + 1.26. In dogs subjected to coronary artery reperfusion, there was significantly less CPK depression (log CPK = - 0.01ST + 1.31, [P < 0.01]) than that expected from the control group. In the control group 97% of specimens showing ST segment elevations over 2 mv at 15 min showed abnormal histology 24 hr later. In contrast, in the reperfused group 43% of sites exhibiting elevated ST segment at 15 min showed abnormal histology 24 hr later. In six additional dogs it was shown that the paradoxical movement of the left ventricular wall could be reversed within 1 hr of perfusion. Therefore, by enzymatic and histologic criteria, as well as by functional assessment, coronary artery reperfusion 3 hr after occlusion resulted in salvage of myocardial tissue

Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

The influence of the administration of pharmacologic doses of hydrocortisone on the extent and severity of acute myocardial ischemic injury and on subsequent necrosis after acute coronary occlusion was investigated in 28 dogs. In order to study acute myocardial injury, repeated epicardial electrocardiograms were recorded from 10 to 15 sites on the anterior surface of the left ventricle. Average ST segment elevation (ST) and the number of sites in which ST segment elevation exceeded 2 mV (NST), indices of the magnitude and extent of myocardial injury, respectively, were analyzed at 30 and 60 min after coronary occlusion. In the control group ST and NST did not change significantly in this time interval while in the treated group, which received 50 mg/kg hydrocortisone just after the 30 min recording, ST fell from 3.5+/-0.8 to 1.1+/-0.4 mV (P 2 mV) in the control group showed histologic changes compatible with early myocardial infarction in 96% of specimens, while this occurred only in 61% and 63% of specimens, respectively, in the treated groups, showing that over one third of the sites were protected from undergoing necrosis due to the intervening hydrocortisone treatment. Thus pharmacological doses of hydrocortisone prevent myocardial cells from progressing to ischemic necrosis even when administration is initiated 6 h after coronary occlusion

Three-dimensional flux states as a model for the pseudogap phase of transition metal oxides

We propose that the pseudogap state observed in the transition metal oxides can be explained by a three-dimensional flux state, which exhibits spontaneously generated currents in its ground state due to electron-electron correlations. We compare the energy of the flux state to other classes of mean field states, and find that it is stabilized over a wide range of $t$ and $\delta$. The signature of the state will be peaks in the neutron diffraction spectra, the location and intensity of which are presented. The dependence of the pseudogap in the optical conductivity is calculated based on the parameters in the model.Comment: submitted to Phys. Rev. B on January 8, 200

Benign Conduction Abnormalities in Response to Acute, Moderately-High, Simulated Altitude Exposure

Acclimatization to altitude can improve endurance performance above levels achieved solely by training at sea level. There is natural limitation in the applicability of employing terrestrial altitude training – namely proximity. A simple, non-cumbersome method of simulating altitude is desirable to many types of endurance athletes. The Alto2Lab (Pharma Pacific Inc.), consisting of primarily a breathing tube and silo stack, has shown some potential in this role. There is a lack of evidence regarding whether simulated altitude exposure triggers abnormal cardiovascular responses. The aim of this study was to provide initial evidence of cardiac changes associated with usage patterns that follow distributor guidelines. Twenty-five participants (mean age 29 ± 10.7; 16 males; 9 females) volunteered for the study. Subjects underwent a baseline ECG recording followed by ECG recording during sham (4-5 mins), hypoxia (~6 mins), and recovery (3-4 mins) phases. The sham phase consisted of subjects breathing normoxive air through a foam-filled silo system. The sham stack mimicked the look and feel of the silo system used to produce hypoxia with the difference being a single, soda lime-filled silo. A recovery phase followed hypoxia. Pulse oximetry (SpO2) was used to assess oxygen saturation. Cochran’s Q was employed to test the frequencies of responses across the phases. An independent, blinded, experienced clinician (DK) analyzed the recordings. Two subjects were removed from the final analysis (inability to finish the protocol, baseline right bundle branch block). All subjects demonstrated an increase in heart rate (mean = +16.8 ± 8.0) during the hypoxia (mean oxygen saturation = 82 ± 4.1%) phase. No ECG ischemic changes were seen across any of the phases. Benign conduction abnormalities (sinus arrhythmia = 9; junctional rhythms = 4) occurred with some regularity during hypoxia. These abnormalities occurred with less frequency during the sham and recovery phases. It is possible that an altered breathing pattern or an inadequate washout period between phases might account for these findings. Overall, there was no significant relationship between the heart response and phase (p = .375). While the Alto2Lab did not produce any ECG changes indicative of an ischemic response, the present study used a small sample of healthy, recreationally-active participants. A larger study employing patients among higher risk categories would provide data that is not currently present in the literature and to which this trial cannot speak

Micro-Hall Magnetometry Studies of Thermally Assisted and Pure Quantum Tunneling in Single Molecule Magnet Mn12-Acetate

We have studied the crossover between thermally assisted and pure quantum tunneling in single crystals of high spin (S=10) uniaxial single molecule magnet Mn12-acetate using micro-Hall effect magnetometry. Magnetic hysteresis experiments have been used toinvestigate the energy levels that determine the magnetization reversal as a function of magnetic field and temperature. These experiments demonstrate that the crossover occurs in a narrow (~0.1 K) or broad (~1 K) temperature interval depending on the magnitude and direction of the applied field. For low external fields applied parallel to the easy axis, the energy levels that dominate the tunneling shift abruptly with temperature. In the presence of a transverse field and/or large longitudinal field these energy levels change with temperature more gradually. A comparison of our experimental results with model calculations of this crossover suggest that there are additional mechanisms that enhance the tunneling rate of low lying energy levels and broaden the crossover for small transverse fields.Comment: 5 pages, 5 figure

Coefficient Functions and Open Charm Production in Deep Inelastic Scattering

It is shown that the problem of double counting in open charm production in DIS can be solved by using the expression for DIS coefficient functions in terms of 2PI diagramsComment: 11 pages, REVTeX, no figure

Utility of Two iPhone Device Apps in Assessing Heart Rate at Rest and During Activity

Heart rate (HR) is a critical physiological variable used for prescribing exercise, assessing fitness level and tracking fitness improvements. Electrocardiography (ECG) stands as the criterion measure of HR. While recent development of HR-detecting mobile device applications (apps) has made evaluating HR more convenient; their degree of accuracy is unknown. Therefore, the purpose of this current study was to examine the accuracy and reliability of two-iPhone applications to detect HR at rest and during low-intensity exercise conditions. Eighteen female and 22 male subjects (26 + 9.5 yrs) were prepped for simultaneous detection of HR via three methods: ECG and two HR-detecting apps. App 1, a camera-based app called Azumio Instant Heart Rate (CAM), was used by placement of a finger over the camera lens of the mobile device. App 2, a microphone-based app called Heart Monitor by Bluespark, was employed via placement of an external microphone over the radial pulse. The participants underwent a series of 5-minute stages: seated rest followed by cycle then treadmill walking at low intensities. HR was recorded concurrently, at several time intervals from the three methods once a steady-state HR was reached. The means of the three devices were compared via ANOVA with the significance level set, a priori, at 0.05. Correlation analysis was employed to investigate relationships between the apps and ECG. No statistical difference was found between the CAM and ECG HR (p \u3e 0.05) during the resting and cycle stages. However, during the treadmill phase, there was a significant difference (p = 0.018) between CAM and ECG. Nevertheless, there was a significant (p \u3c 0.05), positive correlation between CAM and ECG under the resting, cycle and treadmill conditions (r = .966, r = .984, r = .877, respectively). Significant differences (p \u3c 0.05) were found for each condition when comparing ECG and MIC HR. Data also revealed poor correlations (p \u3e 0.05; r between -.004 and -.136) between MIC and ECG. The utility of CAM and MIC-based apps to detect HR remains in question as evidence appears to indicate exercise mode and app specificity. Caution should be shown when using these devices. The CAM-based app may accurately detect HR during resting and seated cycling but not during treadmill activity. The MIC-based app is not recommended for use in any condition. Of note, statistical significance may not mitigate usefulness when considering the accuracy of palpation. Additional research is necessary

The Antioxidant Potential of the Mediterranean Diet in Patients at High Cardiovascular Risk: An In-Depth Review of the PREDIMED

Cardiovascular disease (CVD) is the leading global cause of death. Diet is known to be important in the prevention of CVD. The PREDIMED trial tested a relatively low-fat diet versus a high-fat Mediterranean diet (MedDiet) for the primary prevention of CVD. The resulting reduction of the CV composite outcome resulted in a paradigm shift in CV nutrition. Though many dietary factors likely contributed to this effect, this review focuses on the influence of the MedDiet on endogenous antioxidant systems and the effect of dietary polyphenols. Subgroup analysis of the PREDIMED trial revealed increased endogenous antioxidant and decreased pro-oxidant activity in the MedDiet groups. Moreover, higher polyphenol intake was associated with lower incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. This suggests that polyphenols likely contributed to the lower incidence of the primary event in the MedDiet groups. In this article, we summarize the potential benefits of polyphenols found in the MedDiet, specifically the PREDIMED cohort. We also discuss the need for further research to confirm and expand the findings of the PREDIMED in a non-Mediterranean population and to determine the exact mechanisms of action of polyphenols