bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics Of Board-Level Drop Impact
Authors: Wong E. H.
Published: September 2005

The dynamic response of the printed circuit board (PCB) in a standard board-level drop impact test has been modeled as a spring-mass system, a beam, and a plate. Analytical solutions for the time-response and amplification of the deflection, bending moment, and acceleration at any point on the PCB have been developed and validated with finite element analysis. The analyses have shown that (i) the response of the PCB was dominated by the fundamental mode and (ii) the response of the PCB depends heavily on the ratio between the frequency of the PCB and the input acceleration pulse. The bending moment on the PCB has been shown beyond doubt to be responsible for the interconnection stress; the maximum moment on the PCB can be most effectively reduced through reducing the PCB thickness. The rapid receding of the higher modes in the moment response suggests that it can be adequately and effectively modeled using the standard implicit time-integration code.
A Micromechanics-Based Vapor Pressure Model in Electronic Packages
Authors: Fan X. J. , Zhou J. , Zhang G. Q. , Ernst L. J.
Published: September 2005

A complete vapor pressure model based on a micromechanics approach is developed in this paper. The model can be extended to calculate the initial vapor pressure as traction loading subjected to the interfaces after the delamination. The impact of the vapor pressure induced expanison on the material’s deformation is discussed.
Prediction of Wire Sweep During the Encapsulation of IC Packaging With Wire Density Effect
Authors: Pei Chien-Chang , Hwang Sheng-Jye
Published: September 2005

More wires in a package and smaller wire gaps are the trend in the integrated circuit (IC) packaging industry. The effect of wire density is becoming increasingly apparent, especially on the flow pattern of the epoxy molding compound during the molding process and, hence, on the amount of wire sweep. In most mold flow simulations, the wire density effect is ignored. In order to consider the wire density effect on the predicted amount of wire sweep in the analysis, several indirect approaches were used by researchers before. But those approaches were not general enough to be applied to all cases. This paper presents a more direct and convenient approach to consider wire density effect by including wires in the mesh model for three-dimensional (3D) mold-filling analysis. A thin small outline package (TSOP) with 53 wires is used as the demonstration example, and all the wires are modeled in the 3D mesh. By comparison with experimental results, it is shown that this approach can accurately describe the wire density effect. When the wires are included in the mesh model, the predicted wire sweep results are better than those without considering the wire density effect.
Effect of Stress on the Dielectric Constant of Alumina
Authors: Wen Sihai , Chung D. D. L.
Published: September 2005

The relative dielectric constant (10 kHz) of alumina was found to increase reversibly (by up to 13%) with compressive stress (up to 18 MPa). The effect of stress on the relative dielectric constant diminishes with increasing stress, such that it is almost absent when the stress exceeds ∼7MPa. The relative dielectric constant is higher during loading than subsequent unloading.
Design of Micro-Temperature Sensor Array With Thin Film Thermocouples
Authors: Park Jong-Jin , Taya Minoru
Published: September 2005

We are in the process of developing a micro-temperature sensor array with T-type (copper–constantan) thin film thermocouples (TFTCs) to measure the chip temperature distribution of electronic packages. A thin aluminum nitride (AlN) layer of 100 nm thickness was deposited on a silicon substrate. AlN acts not only as an electrical insulator but also as a thermal conductor between the silicon substrate and thin film thermocouples. Copper thin film with a thickness of 50 nm and constantan thin film with the same thickness were deposited on the AlN layer. The sensor array has 10×10 junctions within a 9mm×9mm area, and each junction covers a 100μm×100μm area. Electro-thermal forces measured by TFTCs using one-dimensional steady-state heat conduction were compared with the electro-thermal forces measured by standard thermocouples, and the difference between the Seebeck coefficients of the copper material and the constantan thin film was calculated according to these measurements. In order to verify the sensor array, it was placed under two-dimensional steady-state heat conduction, and electro-thermal forces were measured and converted to temperatures. Finite element analysis simulation results were compared with the temperatures, and with experimental measurements were found to be in agreement with the simulated values.
Effects of Two-Dimensional Roughness in Flow in Microchannels
Authors: Wang Xiang-Qi , Yap Christopher , Mujumdar Arun Sadashiv
Published: September 2005

The friction factors of single-phase microchannel with various roughness elements (rectangular, triangular, elliptical) were investigated numerically. The two-dimensional numerical solution shows significant influence of surface roughness including the height, size, and spacing of the roughness elements on the Poiseuille number. The fluid temperature effects are also investigated numerically for the rough channels.
Deep Impact: Excavating Comet Tempel 1
Authors: A'Hearn M. F. , Belton M. J. S. , Delamere W. A. , Kissel J. , Klaasen K. P. , McFadden L. A. , Meech K. J. , Melosh H. J. , Schultz P. H. , Sunshine J. M. , Thomas P. C. , Veverka J. , Yeomans D. K. , Baca M. W. , Busko I. , Crockett C. J. , Collins S. M. , Desnoyer M. , Eberhardy C. A. , Ernst C. M. , Farnham T. L. , Feaga L. , Groussin O. , Hampton D. , Ipatov S. I. , Li J.-Y. , Lindler D. , Lisse C. M. , Mastrodemos N. , Owen W. M. , Richardson J. E. , Wellnitz D. D. , White R. L.
Published: September 2005

Deep Impact collided with comet Tempel 1, excavating a crater controlled by gravity. The comet's outer layer is composed of 1- to 100-micrometer fine particles with negligible strength (<65 pascals). Local gravitational field and average nucleus density (600 kilograms per cubic meter) are estimated from ejecta fallback. Initial ejecta were hot (>1000 kelvins). A large increase in organic material occurred during and after the event, with smaller changes in carbon dioxide relative to water. On approach, the spacecraft observed frequent natural outbursts, a mean radius of 3.0 Â± 0.1 kilometers, smooth and rough terrain, scarps, and impact craters. A thermal map indicates a surface in equilibrium with sunlight.
BIOLOGY OF BACTERIOCYTE-ASSOCIATED ENDOSYMBIONTS OF PLANT SAP-SUCKING INSECTS
Authors: Baumann Paul
Published: September 2005

Psyllids, whiteflies, aphids, and mealybugs are members of the suborder Sternorrhyncha and share a common property, namely the utilization of plant sap as their food source. Each of these insect groups has an obligatory association with a different prokaryotic endosymbiont, and the association is the result of a single infection followed by maternal, vertical transmission of the endosymbionts. The result of this association is the domestication of the free-living bacterium to serve the purposes of the host, namely the synthesis of essential amino acids. This domestication is probably in all cases accompanied by a major reduction in genome size. The different properties of the genomes and fragments of the genomes of these endosymbionts suggest that there are different constraints on the permissible evolutionary changes that are probably a function of the gene repertoire of the endosymbiont ancestor and the gene losses that occurred during the reduction of genome size.

Pel piacer di porle in lista.

Leporello

Because Annushka has already bought the sunflower oil, and not only bought it, but spilled it too.

Master and Margarita
LOOKING BACK
Authors: Cohen Georges N.
Published: September 2005

My encounter with Jacques Monod has shaped my scientific career. After a short incursion in the biochemistry of strict anaerobes, and after elucidating the biosynthetic pathway leading from aspartate to threonine in Escherichia coli, I joined his laboratory. With him and Howard Rickenberg, I discovered the stereospecific permeability of galactosides and amino acids (permeases). After this intermezzo, I returned to the analysis of biosynthetic pathways and of their regulation by allosteric feedback inhibition and repression in E. coli. Among others, my studies led to the discovery of the tryptophan and methionine repressors, to the incorporation of amino acid analogues in proteins, including selenomethionine (which much later led to progress in protein crystallography), to the definition of isofunctional and multifunctional enzymes, and to the elucidation of the primary structure of most of the enzymes leading to threonine and methionine.
Thrombopoietin stimulates migration and activates multiple signaling pathways in hepatoblastoma cells
Authors: Romanelli Roberto G. , Petrai Ilaria , Robino Gaia , Efsen Eva , Novo Erica , Bonacchi Andrea , Pagliai Gabriella , Grossi Alberto , Parola Maurizio , Navari Nadia , Delogu Wanda , Vizzutti Francesco , Rombouts Krista , Gentilini Paolo , Laffi Giacomo , Marra Fabio
Published: September 2005

Thrombopoietin (TPO), a cytokine that participates in the differentiation and maturation of megakaryocytes, is produced in the liver, but only limited information is available on the biological response of liver-derived cells to TPO. In this study, we investigated whether HepG2 cells express c-Mpl, the receptor for TPO, and whether TPO elicits biological responses and intracellular signaling in this cell type. Specific transcripts for c-Mpl were detected in HepG2 cells by RT-PCR, and expression of the protein was demonstrated by Western blot analysis and immunofluorescence. Exposure of HepG2 cells to TPO was associated with a dose-dependent increase in cell migration and chemoinvasion through Matrigel-coated filters. A checkerboard analysis showed that the effects of TPO on cell migration were dependent on both chemotaxis and chemokinesis. Exposure of HepG2 cells to TPO resulted in the activation of different members of the MAPK family, including ERK and JNK, as assessed using phosphorylation-specific antibodies and immune complex kinase assays. TPO also activated phosphatidylinositol 3-kinase (PI3K) and the downstream kinase Akt in a time-dependent manner. Finally, activation of c-Mpl was associated with increased activation of nuclear factor-κB. With the use of specific inhibitors, tyrosine phosphorylation and activation of PI3K were found to be required for the induction of migration in response to TPO. We conclude that TPO exerts biological actions on cultured hepatoblastoma cells via activation of c-Mpl and its downstream signaling.
Coordinated regulation of c-Myc and Max in rat liver development
Authors: Sanders Jennifer A. , Gruppuso Philip A.
Published: September 2005

The processes of liver development and regeneration involve regulation of a key network of transcription factors, the c -myc/ max/ mad network. This network regulates the expression of genes involved in hepatocyte proliferation, growth, metabolism, and differentiation. In previous studies on the expression and localization of c-Myc in the fetal and adult liver, we made the unexpected observation that c-Myc content was similar in the two. However, c-Myc was localized predominantly to the nucleolus in the adult liver. On the basis of this finding, we went on to characterize the expression patterns of the other members of the network, max and mad, comparing their regulation during late fetal development with the proliferation of mature hepatocytes that is seen in liver regeneration. We found that Max content, rather than being constitutive, as predicted by other studies, was elevated in the fetal liver compared with the adult liver. Its content correlated with hepatocyte proliferation during the perinatal transition. In contrast, mad4 expression was decreased in the fetal liver compared with the adult liver. Nucleolar localization of c-Myc coincided with changes in Max content. To explore this relationship, we overexpressed Max in cultured adult hepatocytes. High levels of Max resulted in a shift in c-Myc localization from nucleolar to diffuse nuclear. In contrast, liver regeneration was associated with an increase in c-Myc content but no change in Max content. We conclude that the regulation of Max content during liver development and its potential role in determining c-Myc localization are means by which Max may control the biological activity of the c-Myc/Max/Mad network during liver development.
Prostacyclin agonist with thromboxane synthase inhibitory activity (ONO-1301) attenuates bleomycin-induced pulmonary fibrosis in mice
Authors: Murakami Shinsuke , Nagaya Noritoshi , Itoh Takefumi , Kataoka Masaharu , Iwase Takashi , Horio Takeshi , Miyahara Yoshinori , Sakai Yoshiki , Kangawa Kenji , Kimura Hiroshi
Published: September 2005

The balance between prostacyclin and thromboxane A2 (TXA2) plays an important role in pulmonary homeostasis. However, little information is available regarding the therapeutic potency of these prostanoids for pulmonary fibrosis. We have recently developed ONO-1301, a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. Thus we investigated whether repeated administration of ONO-1301 attenuates bleomycin-induced pulmonary fibrosis in mice. After intratracheal injection of bleomycin or saline, mice were randomized to receive repeated subcutaneous administration of ONO-1301 or vehicle. Bronchoalveolar lavage (BAL) and histological analyses were performed at 3, 7, and 14 days after bleomycin injection. In vitro studies using mouse lung fibroblasts were also performed. ONO-1301 significantly attenuated the development of bleomycin-induced pulmonary fibrosis, as indicated by significant decreases in Ashcroft score and lung hydroxyproline content. ONO-1301 significantly reduced total cell count, neutrophil count, and total protein level in BAL fluid in association with a marked reduction of TXB2. A single administration of ONO-1301 significantly increased plasma cAMP level for >2 h. In vitro, ONO-1301 and a cAMP analog dose-dependently reduced cell proliferation in mouse lung fibroblasts. The reduction in cell proliferation by ONO-1301 was attenuated by a protein kinase A (PKA) inhibitor. Furthermore, bleomycin mice treated with ONO-1301 had a significantly higher survival rate than those given vehicle. These results suggest that repeated administration of ONO-1301 attenuates the development of bleomycin-induced pulmonary fibrosis and improves survival in bleomycin mice, at least in part by inhibition of TXA2 synthesis and activation of the cAMP/PKA pathway.
Biliverdin administration protects against endotoxin-induced acute lung injury in rats
Authors: Sarady-Andrews Judit K. , Liu Fang , Gallo David , Nakao Atsunori , Overhaus Marcus , Öllinger Robert , Choi Augustine M. , Otterbein Leo E.
Published: September 2005

Given the high morbidity and mortality rates associated with pulmonary inflammation in sepsis, there is a pressing need for new therapeutic modalities to prevent acute respiratory distress. The enzyme heme oxygenase-1 (HO-1) provides potent cytoprotection against lung injury; however, the mechanism by which it does so is unclear. HO-1 catabolizes heme into biliverdin (BV), which is rapidly converted to bilirubin by BV reductase. We tested the hypothesis that BV administration could substitute for the effects observed with HO-1. Using the well-described rat model of LPS-induced shock, we demonstrate that exposure to BV imparts a potent defense against lethal endotoxemia systemically, as well as in the lungs, and effectively abrogates the inflammatory response. BV administration before a lethal dose of LPS leads to a significant improvement in long-term survival: 87% vs. 20% in sham-treated controls. BV treatment suppressed LPS-induced increases in lung permeability and lung alveolitis and significantly reduced serum levels of the LPS-induced proinflammatory cytokine IL-6. Moreover, bilirubin administered just after LPS also abrogated lung inflammation. BV treatment also augmented expression of the anti-inflammatory cytokine IL-10. Similar effects on production were observed with BV treatment in vitro in mouse lung endothelial cells and RAW 264.7 macrophages treated with LPS. In conclusion, these data demonstrate that BV can modulate the inflammatory response and suppress pathophysiological changes in the lung and may therefore have therapeutic application in inflammatory disease states of the lung.
Pyrexia, anorexia, adipsia, and depressed motor activity in rats during systemic inflammation induced by the Toll-like receptors-2 and -6 agonists MALP-2 and FSL-1
Authors: Hübschle Thomas , Mütze Jörg , Mühlradt Peter F. , Korte Stefan , Gerstberger Rüdiger , Roth Joachim
Published: September 2005

Macrophage-activating lipopeptide-2 (MALP-2) from Mycoplasma fermentans has been identified as a pathogen-associated molecular pattern of Mycoplasmas that causes activation of the innate immune system through the activation of the heterodimeric Toll-like receptors (TLRs)-2 and -6. The aim of this study was to characterize the ability of MALP-2 and a synthetic analog fibroblast-stimulating lipopeptide-1 (FSL-1; represents the NH2-terminal sequence of a lipoprotein from M. salivarium) to act as exogenous pyrogens, to induce formation of cytokines (endogenous pyrogens), and to cause sickness behavior, such as depressed motor activity, anorexia, and adipsia. For this purpose, body temperature, activity, food intake, and water intake were recorded for 3 days by use of telemetry devices in several groups of rats treated with MALP-2/FSL-1 or the respective control solutions. Intraperitoneal injections of FSL-1 caused fever at doses of 10 or 100 μg/kg, which was preceded by a pronounced phase of hypothermia in response to a dose of 1,000 μg/kg. The maximal fever (a peak of 1.5°C above baseline) was caused by the 100 μg/kg dose with almost identical responses to both MALP-2 and FSL-1. Fever was accompanied by pronounced rises of the proinflammatory cytokines TNF and IL-6 in plasma. Treatment with the TLR-2 and -6 agonists further induced a dose-dependent manifestation of anorexia and adipsia, as well as a reduction of motor activity. We could thus demonstrate that activation of TLR-2 and -6 can induce systemic inflammation in rats accompanied by the classical signs of brain-controlled illness responses.
Measurement of pharyngeal cross-sectional area by finite element analysis
Authors: Mansour Khaled F. , Rowley James A. , Badr M. Safwan
Published: September 2005

A noninvasive measurement of pharyngeal cross-sectional area (CSA) during sleep would be advantageous for research studies. We hypothesized that CSA could be calculated from the measured pharyngeal pressure and flow by finite element analysis (FEA). The retropalatal airway was visualized by using a fiber-optic scope to obtain the measured CSA (mCSA). Flow was measured with a pneumotachometer, and pharyngeal pressure was measured with a pressure catheter at the palatal rim. FEA was performed as follows: by using a three-dimensional image of the upper airway, a mesh of finite elements was created. Specialized software was used to allow the simultaneous calculation of velocity and area for each element by using the measured pressure and flow. In the development phase, 677 simultaneous measurements of CSA, pressure, and flow from one subject during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were entered into the software to determine a series of equations, based on the continuity and momentum equations, that could calculate the CSA (cCSA). In the validation phase, the final equations were used to calculate the CSA from 1,767 simultaneous measurements of pressure and flow obtained during wakefulness, NREM, and REM sleep from 14 subjects. In both phases, mCSA and cCSA were compared by Bland-Altman analysis. For development breaths, the mean difference between mCSA and cCSA was 0.0 mm2 (95% CI, −0.1, 0.1 mm2). For NREM validation breaths, the mean difference between mCSA and cCSA was 1.1 mm2 (95% CI 1.3, 1.5 mm2). Pharyngeal CSA can be accurately calculated from measured pharyngeal pressure and flow by FEA.
Cardiopulmonary baroreflex is reset during dynamic exercise
Authors: Ogoh Shigehiko , Brothers R. Matthew , Barnes Quinton , Eubank Wendy L. , Hawkins Megan N. , Purkayastha Sushmita , O-Yurvati Albert , Raven Peter B.
Published: September 2005

The purpose of this study was to examine the hypothesis that the operating point of the cardiopulmonary baroreflex resets to the higher cardiac filling pressure of exercise associated with the increased cardiac filling volumes. Eight men (age 26 ± 1 yr; height 180 ± 3 cm; weight 86 ± 6 kg; means ± SE) participated in the present study. Lower body negative pressure (LBNP) was applied at 8 and 16 Torr to decrease central venous pressure (CVP) at rest and during steady-state leg cycling at 50% peak oxygen uptake (104 ± 20 W). Subsequently, two discrete infusions of 25% human serum albumin solution were administered until CVP was increased by 1.8 ± 0.6 and 2.4 ± 0.4 mmHg at rest and 2.9 ± 0.9 and 4.6 ± 0.9 mmHg during exercise. During all protocols, heart rate, arterial blood pressure, and CVP were recorded continuously. At each stage of LBNP or albumin infusion, forearm blood flow and cardiac output were measured. During exercise, forearm vascular conductance increased from 7.5 ± 0.5 to 8.7 ± 0.6 U ( P = 0.024) and total systemic vascular conductance from 7.2 ± 0.2 to 13.5 ± 0.9 l·min−1·mmHg−1 ( P < 0.001). However, there was no significant difference in the responses of both forearm vascular conductance and total systemic vascular conductance to LBNP and the infusion of albumin between rest and exercise. These data indicate that the cardiopulmonary baroreflex had been reset during exercise to the new operating point associated with the exercise-induced change in cardiac filling volume.
Sirolimus- versus Paclitaxel-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Stenosis
Authors: Lee Sang Hak , Ko Young-Guk , Jang Yangsoo , Kwon Hyuck Moon , Lee Seung-Hwan , Yoon Jung Han , Park Si Hoon , Kim Byung Ok , Jeon Dong Woon , Yang Joo Young , Ryu Seung-Ki
Published: September 2005

We performed this study in order to compare the immediate and mid-term outcomes of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in lesions of the unprotected left main coronary artery (LMCA). We assessed 54 patients from 5 centers who had undergone unprotected LMCA stenting (35 SES and 19 PES). The procedural success rates were 100 and 95%, respectively, in the SES and PES patients (p = 0.19). At the 6-month clinical follow-up, the event-free probability was 100% in the SES group, and 88% in the PES group (p = 0.07). At the 6-month angiographic follow-up (n = 24), the SES group exhibited a slightly lower late loss than did the PES group (0.24 ± 0.44 vs. 0.65 ± 0.60 mm, p = 0.09), and the restenosis rates were 8 and 9% (p = 0.94) in the SES and PES patients, respectively. In conclusion, both groups exhibited excellent in-hospital and 6-month outcomes with no significant differences between them.
Clinician Underappreciation of Interatrial Block in a General Hospital Population
Authors: Ariyarajah Vignendra , Puri Puneet , Spodick David H.
Published: September 2005

Introduction: Interatrial block (IAB; P wave ≧110 ms), a conduction delay between the right and left atria (LA), is highly prevalent and strongly associated with atrial tachyarrhythmias, LA electromechanical dysfunction as well as a risk of embolism. Nonetheless, clinicians’ underappreciation of its existence and sequelae remains. We appraised this issue in a general hospital population. Methods: From the database of 730 12-lead electrocardiograms (ECGs) of patients aged 17–98 years (mean age 67.80 years; female patients 53.56%) in a tertiary care teaching general hospital, we recorded the computer-generated diagnostic readings of the ECGs and also the official cardiologist and hospitalist ECG interpretations and documentations. For increased sensitivity and specificity, and because the mode P wave duration in IAB is 120 ms, P waves ≧120 ms in any lead were used to diagnose IAB. Results: Six hundred and fifty-three ECGs (89.45%) showed sinus rhythm, and of those, IAB was documented on 309 ECGs (47.32%). LA enlargement was cited 29 times (3.97%), while possible LA enlargement and biatrial enlargement were cited 17 (2.32%) and 6 times (0.82%), respectively. One cardiologist’s ECG interpretation documented IAB (0.32%), but none of the other medical staff diagnosed IAB or abnormal P wave duration. Conclusion: This study demonstrates to extremes how IAB went undiagnosed in a general hospital population. Until more awareness of IAB is cultivated, such ignorance of the existence and sequelae of IAB could continue. Configuring ECG software to include P wave durations in computer-generated ECG readings could be useful in aiding diagnosis.
Broad-Spectrum Chemokine Inhibition Reduces Vascular Macrophage Accumulation and Collagenolysis Consistent with Plaque Stabilization in Mice
Authors: Reckless Jill , Tatalick Laurie , Wilbert Sybille , McKilligin Elaine , Grainger David J.
Published: September 2005

Background: A major determinant of the risk of myocardial infarction is the stability of the atherosclerotic plaque. Macrophage-rich plaques are more vulnerable to rupture, since macrophages excrete an excess of matrix-degrading enzymes over their inhibitors, reducing collagen content and thinning the fibrous cap. Several genetic studies have shown that disruption of signalling by the chemokine monocyte chemoattractant protein 1 reduced the lipid lesion area and macrophage accumulation in the vessel wall. Methods: We have tested whether a similar reduction in macrophage accumulation could be achieved pharmacologically by treating apolipoprotein-E-deficient mice with the chemokine inhibitor NR58-3.14.3. Results: Mice treated for various periods of time (from several days to 6 months) with NR58-3.14.3 (approximately 30 mg/kg/day) consistently had 30–40% fewer macrophages in vascular lesions, compared with mice treated with the inactive control NR58-3.14.4 or PBS vehicle. Similarly, cleaved collagen staining was lower in mice treated for up to 7 days, although this effect was not maintained when treatment time was extended to 12 weeks. The vascular lipid lesion area was unaffected by treatment, but total collagen I staining and smooth muscle cell number were both increased, suggesting that a shift to a more stable plaque phenotype had been achieved. Conclusions: Strategies, such as chemokine inhibition, to attenuate macrophage accumulation may therefore be useful to promote stabilization of atherosclerotic plaques.
Identification of Good Responders to Rhythm Control of Paroxysmal and Persistent Atrial Fibrillation by Transthoracic and Transesophageal Echocardiography
Authors: Wang Yi-Chih , Lin Lung-Chun , Lin Mao-Shin , Lai Ling-Ping , Hwang Juey-Jen , Tseng Yung-Zu , Tseng Chuen-Den , Lin Jiunn-Lee
Published: September 2005

Background: Identification of good responders to rhythm control in the management of atrial fibrillation (AF) is worthwhile in terms of increasing hemodynamic benefit and decreasing the likelihood of unstable anticoagulation even after the Atrial Fibrillation Follow-Up Investigation of Rhythm Management. Methods: We tested the hypothesis that atrial substrate determines the risk of recurrence on rhythm control both in patients with paroxysmal AF (PAF) and in those with persistent or sustained AF (≧1 week, SAF). There were 90 consecutive patients (mean age 63 ± 12 years, 67 males and 23 females) with previous PAF (n = 66) or SAF (n = 24). They were maintained in sinus rhythm successfully for at least 1 month after conversion and then studied by transthoracic and transesophageal echocardiography. All of the patients were followed regularly by determination of symptoms, 12-lead ECG and intermittent Holter recording to determine recurrence of AF after echocardiographic study. Results: After 9.1 ± 3.8 (range 3–12) months of follow-up, 23 of the 90 (26%) patients had documented recurrence of AF (67 without recurrence). Univariate analysis of demographic characteristics, medications, ECG and echocardiographic parameters revealed that, compared with the group of patients without recurrent AF, the group of those with it included more members of the SAF group (11/27 vs. 13/67, p = 0.039), included more male subjects (22/23 vs. 45/67, p = 0.045), had a larger left atrial volume index (LAVI; 27 ± 9 vs. 22 ± 9 ml/m2, p = 0.024) and had lower LA appendage peak emptying velocity (LAAPEV; 42 ± 15 vs. 55 ± 22 cm/s, p = 0.01). Multivariate Cox proportional hazards regression analysis adjusted for age, gender and AF group revealed that patients with LAVI <30 ml/m2 and LAAPEV >46 cm/s had the least recurrence of AF (relative risk 0.18, 95% confidence interval 0.06–0.55, vs. with LAVI >30 ml/m2 or LAAPEV <46 cm/s, p = 0.002). Kaplan-Meier probability of freedom from AF recurrence was significantly better when LAVI <30 ml/m2 (log-rank p = 0.02), LAAPEV > 46 cm/s (p = 0.013) or both (p = 0.004). The superiority to predict the rate of sinus rhythm maintenance was the same in the PAF and SAF groups. Conclusions: Good responders to rhythm control in the PAF and SAF groups share the characteristics of smaller LA volume and better LAA contractile function, emphasizing the critical role of atrial substrate remodeling in recurrence of AF.
Statins, Ventricular Arrhythmias and Heart Rate Variability in Patients with Implantable Cardioverter Defibrillators and Coronary Heart Disease
Authors: Riahi Sam , Schmidt Erik Berg , Christensen Jeppe Hagstrup , Heath Finn , Pedersen Anders Kirstein , Nielsen Jens Cosedis , Mølgaard Henning , Toft Egon
Published: September 2005

The aim of this study was to evaluate whether the incidence of ventricular arrhythmias and heart rate variability were influenced by statin treatment and lipid levels in patients treated with an implantable cardioverter defibrillator (ICD). Heart rate variability measurements were performed in 86 patients with coronary heart disease and an ICD implant. The number of events with ventricular fibrillation and ventricular tachycardia were recorded during a 12-month period. This study lends little support for an antiarrhythmic effect of statins or any relation between plasma lipids and lipoproteins and malignant ventricular arrhythmias in patients with an ICD.
The Severity of Myocardial Ischemia Can Be Predicted by the Exercise Electrocardiogram
Authors: Polizos George , Ghamsary Mark , Ellestad Myrvin H.
Published: September 2005

The aim of the study was to evaluate the utility of exercise-induced ECG changes in predicting the degree of myocardial ischemia as compared to angiographic and nuclear scintigraphic images. Four hundred and seventy one patients in whom exercise nuclear scintigraphy and coronary angiography revealed significant coronary narrowing (≧70% luminal diameter narrowing) were studied. Down-sloping ST depression was found to be the best predictor of a large area of reversible ischemia (RI). Time of resolution of ST depression was the second most powerful predictor and the time of onset of ST depression was the third best predictor. RI on nuclear scintigraphy correlated better than angiographic findings with the ECG changes.
Regional Citrate Anticoagulation in Continuous Hemodialysis – Acid-Base and Electrolyte Balance at an Increased Dose of Dialysis
Authors: Morgera Stanislao , Haase Michael , Rückert Matthias , Krieg Hanno , Kastrup Marc , Krausch Dietmar , Vargas-Hein Ortrud , Zuckermann-Becker Heidrun , Peters Harm , Pohlmeier Robert , Neumayer Hans-H.
Published: September 2005

Background: Citrate anticoagulation is an excellent alternative to heparin anticoagulation for patients at high risk of bleeding requiring continuous renal replacement therapy. However, citrate anticoagulation has some potential adverse effects such as metabolic alkalosis and acidosis, hypernatremia, hypo- and hypercalcemia. Thus, most citrate anticoagulation protocols use specially designed dialysis fluids to compensate for most of these disarrangements. This study aimed at establishing a citrate anticoagulation protocol designed for a dialysate flow rate of about 2 l/h. Methods: Based on theoretical considerations we composed a dialysis fluid suitable for a 2 l/h dialysis flow rate. The dialysate contained 133 mmol/l sodium, 2 mmol/l potassium, 1.1 mmol/l magnesium, 25 mmol/l lactate, and 112.2 mmol/l chloride. Results: Twenty-three patients were included in the study. During the treatments minor flow rate adaptations were needed and the treatments were well tolerated. Filter life was appropriate (51.3 ± 24.6 h). Thirteen patients developed a mild metabolic alkalosis (pH > 7.45 plus BE > +3) which was easily counteracted by increasing the dialysis fluid flow (by increments of 500 ml). Acid-base values returned to normal within 24 h after increasing the dialysate flow. The maximum dialysate flow was 3,000 ml/h. Hypernatremia and hypocalcemia were not observed. The systemic ionized calcium concentration was successfully controlled by adjustments of a continuous calcium infusion made with respect to the results of 6-hourly measurements. Conclusion: The analyzed citrate anticoagulation protocol was well tolerated and filter lifetime was appropriate. Regional anticoagulation with trisodium citrate in combination with a customized calcium-free dialysate is a safe and effective alternative to a heparin-based anticoagulation regimen.
Early Increased Levels of Matrix Metalloproteinase-9 in Neonates Recovering from Respiratory Distress Syndrome
Authors: Dik Willem A. , van Kaam Anton H.L.C. , Dekker Tamara , Naber Brigitta A.E. , Janssen Daphne J. , Kroon A.A. , Zimmermann Luc J.I. , Versnel Marjan A. , Lutter René
Published: September 2005

Aim: Matrix metalloproteinases (MMPs) play an eminent role in airway injury and remodelling. We explored the hypothesis that pulmonary MMP levels would differ early after birth (2–4 days) between infants with resolving respiratory distress syndrome (RDS) and infants developing chronic lung disease of prematurity (CLD). Methods: Thirty-two prematurely born infants (gestational age ≤30 weeks) diagnosed with RDS were included. In 13 infants RDS resolved while 19 developed CLD. MMP-2 and MMP-9 in bronchoalveolar lavage (BAL) fluids collected on postnatal days 2, 4, 7 and 10 were analyzed by zymography and densitometry. Immunochemistry was performed on BAL cells and lung tissue to identify cellular sources of MMP-9 in RDS and CLD. Results: Median MMP-9 levels increased significantly on day 2 in BAL fluid from patients with resolving RDS (median values MMP-9 = 42.0 arbitrary units (AU)) compared to CLD patients (MMP-9 = 5.4 AU). MMP-9 and neutrophil lipocalin-associated MMP-9 (NGAL) were significantly higher on day 4 in BAL fluid from resolving RDS (MMP-9 = 65.8 AU; NGAL = 16.1 AU) compared to CLD (MMP-9 = 25.4 AU; NGAL = 2.0 AU), Levels of MMP-9 and NGAL increased subsequently on days 7 and 10 in CLD. No differences in MMP-2 levels were detected between RDS and CLD. Neutrophils, macrophages and alveolar type-II epithelial cells were identified as potential sources of MMP-9. Conclusion: Our findings indicate differences in early MMP-9 BAL fluid levels between resolving RDS and developing CLD, which may relate to the ability to raise an early and adequate response to the initial injury.
Effect of Decreased Umbilical Blood Flow and Hemorrhage, and Decreased Prostaglandins on the Ductus Venosus Diameter in the Rat
Authors: Takeuchi Daiji , Momma Kazuo
Published: September 2005

Background: The closing mechanisms of the ductus venosus (DV) have not yet been revealed. Objectives: The aims of this study were to document the perinatal closing process of the DV, to study the suppression of prostaglandins by indomethacin, and to determine the effects of umbilical blood flow to the fetal DV. Methods: The proximal and distal DV diameters were studied in near-term fetal and neonatal rats with the rapid whole-body freezing method. Results: The DV diameter changed sensitively at birth, and decreased by 10% immediately after the cessation of the umbilical circulation. Umbilical hemorrhage caused an additional decrease in the DV diameter compared with neonate without the hemorrhage. The neonates showed a DV diameter decreased by 20% at 30 min and 30% at 60 min after birth. The fetal DV was tubular, and the neonatal DV was horn-shaped with a smaller inlet than outlet. A small dose (0.1 mg/kg) of indomethacin administered to the pregnant rats induced a reduction in prostaglandins and decreased the fetal DV diameter to 80% of the control. Indomethacin at a large dose (10 mg/kg), administered to the dams, induced a reduction in prostaglandins, severe constriction of the ductus arteriosus, and decreased blood flow through the descending aorta umbilicus, and caused a further reduction in the DV diameter to 70–80% of the control. A large dose of nifedipine (10 mg/kg), which causes cardiac suppression and heart failure in the fetus, was administered to near-term rats to study the effect of decreased fetal cardiac output and blood flow passing through the DV. Nifedipine induced a 20% decrease in the DV diameter for 2–8 h. In all 1-hour-old neonates with or without pretreatment, the inlet diameter of the DV was reduced more than the outlet diameter, and the DV showed a horn-shaped morphology. Conclusion: In conclusion, perinatal cessation of the umbilical circulation and umbilical hemorrhage are associated with an immediate decrease in DV diameter. The DV diameter is also reduced in other conditions associated with decreased umbilical blood flow, such as induced by nifedipine which leads to heart failure and constricting of the ductus arteriosus induced by indomethacin. The constricting effect of a small dose of indomethacin suggests that prostaglandins dilate the DV physiologically.
Development of the Rhombencephalon: Molecular Evolution and Genetic Regulation
Authors: Wang Chi Chiu
Published: September 2005

The central nervous system develops with incredible precision during embryonic development, controlled by the orchestration of cell fate determination, cell proliferation, and cell growth. The development of the rhombencephalon is the most comprehensively analysed region of the embryonic brain in terms of cell patterning and compartmentalisation. The rhombomeric organisation of the rhombencephalon provides an important cellular and genetic blueprint for establishing many of the characteristic features of the central and peripheral nervous systems. The morphogenesis of the rhombencephalon and the generation of the rhombomeric segments, in an anterior to posterior sequence, coincides with the establishment of precise expression domains of a number of transcription factors (e.g. Hox, kreisler and Krox20), signalling molecules (e.g. Eph/ephrins), membrane and nuclear receptors (such as RAR/RXR) and enzymes involved in the retinoid biosynthetic pathway. In addition, the rhombencephalon is patterned dorsoventrally by key factors such as the BMPs, Fgfs, Wnt and SHH. In this review, the current knowledge of the roles of these signalling factors and the molecular evolutionary evidence for the development of the vertebrate brain in terms of the mechanisms underlying the formation and specification of the rhombencephalon will be discussed.
Different Aging Patterns of the Neuronal and Inducible Isoforms of Nitric Oxide Synthase in Mouse Hippocampus by Immunohistochemistry
Authors: Wong Ho Wai , Mak Ying Tat , Yu Mang Chung , Yew David Tai Wai
Published: September 2005

Background: Nitric oxide synthase (NOS) produces nitric oxide (NO) from arginine, and both NOS and NO play important roles in the normal aging of the hippocampus. Aim: To study the age-related distribution patterns of the neuronal (nNOS) and the inducible (iNOS) isoforms of NOS in the mouse hippocampus, and their roles in the aging mechanism. Result: The nNOS significantly decreased in the aged hippocampus whereas iNOS increased significantly. The nNOS expressed in interneuron-like cells distributed mainly in the dentate gyrus and the pyramidal layer. iNOS was possibly expressed in both old and newly proliferated astrocytes mainly found in the stratum oriens, stratum lacunosum-moleculare and to a lesser extent in the fimbria and dentate gyrus. The astrocyte number also significantly increased in the aged hippocampus. In fact, iNOS was almost absent in the young hippocampus. Those cells expressing the two isoforms were not apoptotic. Conclusion: The results suggested different expression patterns for nNOS and iNOS during aging in terms of the localization, expression levels and cell types involved. These changes were unlikely to involve apoptosis. This might signify an alteration in the normal functions of the hippocampus during aging such as long-term potentiation.
High Serum Bilirubin Concentrations Preserve Coronary Flow Reserve and Coronary Microvascular Functions
Authors: Gullu Hakan , Erdogan Dogan , Tok Derya , Topcu Semra , Caliskan Mustafa , Ulus Taner , Muderrisoglu Haldun
Published: September 2005

Background—

Elevated serum bilirubin concentrations protect against atherosclerotic diseases; however, it is not clear whether higher serum bilirubin concentrations in physiological ranges work in favor of the cardiovascular system in younger persons with no cardiovascular risk factors. Accordingly, we investigated the effects of high, intermediate, and low serum bilirubin concentrations on coronary flow reserve (CFR).

Methods and Results—

Fifty-two healthy subjects with hyperbilirubinemia (total bilirubin 1.43±0.33 mg/dL; mean age 35.9±7.3), 55 subjects with intermediate bilirubin level (total bilirubin: 0.69±0.11 mg/dL; mean age: 36.4±6.8), and 53 healthy subjects with hypobilirubinemia (total bilirubin 0.37±0.08 mg/dL; mean age, 37.6±6.6) were studied. Transthoracic second harmonic Doppler echocardiography examination was performed using an Acuson Sequoia C256 Echocardiography System. Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion (0.84 mg/kg over 6 minutes). CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. Demographic features, coronary risk factors, echocardiographic measurements, and biochemical measurements were similar among the 3 groups, except high-sensitivity C-reactive protein (hsCRP). CFR values were significantly higher in subjects with high bilirubin concentrations than those were in the intermediate and the low bilirubin groups (3.19±0.73; 2.75±0.42; 2.56±0.52, respectively;
P
<0.0001), and hsCRP levels were significantly lower in subjects with high bilirubin concentrations than those in both intermediate and low bilirubin groups (1.4±1.0, 2.0±1.7, 3.0±1.9 mg/L, respectively;
P
<0.001). hsCRP levels correlated with total bilirubin concentration and with CFR.

Conclusion—

Elevated serum bilirubin concentrations protect from CFR impairment, coronary microvascular dysfunction, and possibly coronary atherosclerosis.
Selective Insulin Resistance Affecting Nitric Oxide Release But Not Plasminogen Activator Inhibitor-1 Synthesis in Fibroblasts From Insulin-Resistant Individuals
Authors: Pandolfi Assunta , Solini Anna , Pellegrini Giuliana , Mincione Gabriella , Di Silvestre Sara , Chiozzi Paola , Giardinelli Annalisa , Di Marcantonio Maria Carmela , Piccirelli Alessandro , Capani Fabio , Consoli Agostino
Published: September 2005

Objectives—

Insulin activates several processes potentially dangerous for the arterial wall and hyperinsulinemia might be atherogenic. However, other insulin effects are protective for the vessel wall and thus anti-atherogenic. Aim of this study was to investigate whether insulin effects on potentially pro-atherogenic and anti-atherogenic processes were differently affected in cells from insulin-resistant individuals.

Methods and Results—

We determined insulin effect on nitric oxide (NO) production and plasminogen activator inhibitor (PAI)-1 synthesis in 12 fibroblast strains obtained from skin biopsy samples of 6 insulin-sensitive (IS) (clamp M >7 mg/kg body weight per minute) and 6 insulin-resistant (IR) (clamp M <5 mg/kg body weight per minute) healthy volunteers. Insulin effects on NO release and Akt phosphorylation were significantly impaired in fibroblasts from IR as compared with IS individuals. Conversely, there was not any difference between IR and IS strains in insulin ability to increase PAI-1 antigen levels and, after 24-hour insulin incubation, PAI-1 mRNA increase in IR strains was only slightly less than in IS strains. Insulin ability to induce MAPK activation was also comparable in IR and IS cells.

Conclusions—

We conclude that in cells from IR individuals, insulin action on anti-atherogenic processes, such as NO release, is impaired, whereas the hormone ability to stimulate atherogenic processes, such as PAI-1 release, is preserved.
NADPH Oxidase–Derived Superoxide Anion Mediates Angiotensin II–Induced Pressor Effect via Activation of p38 Mitogen–Activated Protein Kinase in the Rostral Ventrolateral Medulla
Authors: Chan Samuel H.H. , Hsu Kuei-Sen , Huang Chiung-Chun , Wang Ling-Lin , Ou Chen-Chun , Chan Julie Y.H.
Published: September 2005

The rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons are located, is a central site via which angiotensin II (Ang II) elicits its pressor effect. We tested the hypothesis that NADPH oxidase-derived superoxide anion (O
2
·−
) in the RVLM mediates Ang II–induced pressor response via activation of mitogen-activated protein kinase (MAPK) signaling pathways. Bilateral microinjection of Ang II into the RVLM resulted in an angiotensin subtype 1 (AT
1
) receptor-dependent phosphorylation of p38 MAPK and extracellular signal-regulated protein kinase (ERK)1/2, but not stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK), in the ventrolateral medulla. The Ang II–induced p38 MAPK or ERK1/2 phosphorylation was attenuated by application into the RVLM of a NADPH oxidase inhibitor, diphenyleneiodonium chloride (DPI), an antisense oligonucleotide that targets against
p22phox
or
p47phox
subunit of NADPH oxidase mRNA, or the superoxide dismutase mimetic tempol. DPI or antisense
p22phox
or
p47phox
oligonucleotide treatment also attenuated the AT
1
receptor-dependent increase in O
2
·−
production in the ventrolateral medulla elicited by Ang II at the RVLM. Functionally, Ang II–elicited pressor response in the RVLM was attenuated by DPI, tempol, or a p38 MAPK inhibitor, SB203580. The AT
1
receptor-mediated enhancement of the frequency of glutamate-sensitive spontaneous excitatory postsynaptic currents induced by Ang II in RVLM neurons was also abolished by SB203580. These results suggest that NADPH oxidase-derived O
2
·−
underlies the activation of p38 MAPK or ERK1/2 by Ang II in the ventrolateral medulla. Furthermore, the p38 MAPK signaling pathway may mediate Ang II–induced pressor response via enhancement of presynaptic release of glutamate to RVLM neurons.