bluuebunny/crossref_metadata_2025 huggingface dataset:
Infrared Spectroscopy of Anionic, Cationic, and Zwitterionic Surfactants
Authors: Viana Rommel B. , da Silva Albérico B. F. , Pimentel André S.
Published: June 2012

This paper describes the ordering degree of anionic, cationic, and zwitterionic surfactants with the increase of their packing density on Ge substrate by using Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy. This work shows new insights on the conformational order of sodium dodecyl sulfate (SDS), N-hexadecyl-N-N-dimethyl-3-ammonio-1-propane-sulfonate (HPS), hexadecyl-trimethylammonium bromide (CTAB), and dodecyl trimethylammonium bromide (DTAB). DFT and semiempirical calculations are also performed in order to evaluate the effect of headgroup hydration and counterion. The CH2 asymmetric and symmetric stretching bands for the SDS molecule show a shift of 1.7 and 0.9 cm−1 to higher frequencies as the packing density increases, while it is observed a shift of 2.6 and 2.7 cm−1 for the HPS molecule, respectively. The DTAB molecule shows a shift of 4.5 cm−1 to lower frequencies for both CH2 asymmetric and symmetric stretching bands as the packing density increases, indicating the decrease of gauche conformations and the increase of all-trans conformations over the aliphatic chain.
Robust Multihop Localization for Wireless Sensor Networks with Unreliable Beacons
Authors: Feng Renjian , Guo Xiaolei , Yu Ning , Wan Jiangwen
Published: June 2012

Multihop localization is a popular approach for determining the positions of normal nodes in large-scale wireless sensor networks. However, most existing multihop localization studies assume that the declared positions of beacon nodes are always reliable or even free of errors, which is not a valid assumption in practice. In this paper, we propose a robust multihop localization algorithm (RMLA) based on trust evaluation for diminishing the effect of unreliable beacons on the accuracy of node localization. Firstly, the trust evaluation framework is established on the basis of evidence theory. According to the multihop geometric relationship among nodes, every beacon evaluates the reliability of other beacons' declared positions. Then, the normal nodes integrate the evaluation results to obtain the total trust degrees of their multihop communication beacons, by use of an average method or an enhanced D-S evidence combination rule. Finally, the normal nodes employ the weighted Taylor-series least squares solver to estimate the optimal values of their coordinates. Extensive simulation results in isotropic and anisotropic networks show the robustness and effectiveness of our algorithm.
Neuropathic Bladder Caused by Caudal Regression Syndrome without Any Other Neurogenic Symptoms
Authors: Moritoki Yoshinobu , Kojima Yoshiyuki , Kamisawa Hideyuki , Mizuno Kentaro , Kohri Kenjiro , Hayashi Yutaro
Published: June 2012

Caudal regression syndrome (CRS) is a rare congenital vertebral anomaly, which occurs most often in combination with spinal cord malformations and morphologic dysfunctions of the lower extremities; these signs are useful for both patients and clinicians in the diagnosis of this syndrome. However, in certain cases, clinicians have failed to identify the syndrome due to the lack of apparent anomalies, resulting in the progression of renal dysfunction caused by neuropathic bladder when CRS is eventually identified. Here, we report a case of a 2-year-old girl who was referred to our hospital for vesicoureteral reflux. At examination, she presented no neurological symptoms; however, on cystourethrography and CT scanning we found that the sacral bone was absent, through which CRS was diagnosed. A urodynamic study indicated detrusor-sphincter dyssynergia, and clean intermittent catheterization was initiated. In the present report, we describe a case of CRS with no neurologic symptoms other than a neuropathic bladder. The lack of outward signs can result in delayed diagnosis. Thus, urological examinations, including a urodynamic study, might be the only clue for identifying an underlying neurologic injury involving the lower spinal cord.
Biopsied Oral Soft Tissue Lesions in Kuwait: A Six-Year Retrospective Analysis
Authors: Ali Mohammad , Sundaram Devipriya
Published: June 2012

Objectives: The aim of this study was to determine the relative frequency of biopsied oral soft tissue lesions in Kuwait. Materials and Methods: Biopsy records and microscopic sections of all oral soft tissue biopsies seen in the Department of Histopathology at Al-Amiri Hospital, Kuwait, between January 2004 and December 2009 were reviewed. The biopsies were divided into two major groups; group 1: nonneoplastic lesions, and group 2: neoplastic lesions. Group 1 was subdivided into reactive, inflammatory, cyst/cyst-like, dysplastic, and pigmented lesions. Group 2 was subdivided into epithelial and mesenchymal lesions, and also into benign and malignant lesions. Results: Of the 858 biopsies, 732 (85.3%) were nonneoplastic while the remaining 126 (14.7%) were neoplastic. In group 1, more than half of the lesions were within the reactive subgroup (n = 386; 52.7%) while in group 2, 94 (74.6%) lesions were epithelial in origin and 32 (25.4%) were mesenchymal. In addition, 70 (55.6%) lesions were malignant and 56 (44.4%) were benign. Of the 858 biopsies, the most common lesions were fibrous hyperplasias: 178 (20.7%); mucoceles: 110 (12.8%); pyogenic granulomas: 94 (11.0%); squamous cell carcinomas: 56 (6.5%), and lichenoid mucositis: 49 (5.7%). Conclusions: The majority of the lesions were nonneoplastic and were related to local irritation or trauma. Most neoplastic lesions were epithelial in origin. Oral squamous cell carcinoma was one of the most prevalent oral lesions highlighting the importance of prevention, early detection and diagnosis of oral cancer.
Comparative Evaluation of Therapy with L-Thyroxine versus No Treatment in Children with Idiopathic and Mild Subclinical Hypothyroidism
Authors: Wasniewska Malgorzata , Corrias Andrea , Aversa Tommaso , Valenzise Mariella , Mussa Alessandro , De Martino Lucia , Lombardo Fortunato , De Luca Filippo , Salerno Mariacarolina
Published: June 2012

Background: The question of whether children with subclinical hypothyroidism (SH) should be treated or not is controversial due to the lack of studies on outcomes of SH children treated with L-thyroxine (L-T4) versus those receiving no therapy. Objectives: (a) To evaluate thyroid tests under L-T4 and after therapy withdrawal in 69 SH children (group A) and (b) to compare our results with those recorded in 92 untreated children (group B). Design: Group A children were treated for 24 months and TSH and FT4 levels 3 months after therapy withdrawal were compared with those measured in group B at the end of follow-up in order to investigate treatment effects. Results: The prevalence of children who had normalized TSH at the end of follow-up was higher in group A, but the prevalence of those who had normalized or maintained unchanged TSH was similar in the two groups, as was the prevalence of children who exhibited a TSH increase >10 mU/l. In group A, TSH values at 27 months were associated with baseline values. Conclusions: (a) Two-year treatment in SH children is unable to modify posttherapy outcome of hyperthyrotropinemia; (b) therapy is unable to prevent the risk of further TSH increase after treatment withdrawal, and (c) posttherapy TSH outcome is conditioned by baseline TSH.
Inhibition of Prostaglandin E
2
Synthesis in Abdominal Aortic Aneurysms
Authors: Walton Lesley J. , Franklin Ian J. , Bayston Trevor , Brown Louise C. , Greenhalgh Roger M. , Taylor Graham W. , Powell Janet T.
Published: June 2012

Background
—There is no treatment proven to limit the growth of abdominal aortic aneurysms, in which the histological hallmarks include inflammation and medial atrophy, with apoptosis of smooth muscle cells and destruction of elastin.

Methods and Results
—Aneurysm biopsies were used for explant cultures, the preparation of smooth muscle cell cultures, and isolation of macrophages. Tissue macrophages stained strongly for cyclooxygenase 2. Prostaglandin E
2
(PGE
2
) concentrations in aneurysm tissue homogenates, conditioned medium from explants, and isolated macrophages were 49±22 ng/g, 319±38 ng/mL, and 22±21 ng/mL, respectively. PGE
2
inhibited DNA synthesis and proliferation in normal aortic smooth muscle cells (IC
50
, 23.2±3.8 and 23.6±4.5 ng/mL, respectively). In smooth muscle cells derived from aneurysmal aorta, PGE
2
also caused cell death, with generation of oligonucleosomes. Conditioned medium from the mixed smooth muscle and monocyte cultures derived from explants also had potent growth-inhibitory effects, and fractionation of this medium showed that the growth-inhibitory molecule(s) coeluted with PGE
2
. In explants, indomethacin 10 μmol/L or mefenamic acid 10 μmol/L abolished PGE
2
secretion and significantly reduced IL-1β and IL-6 secretion. In a separate case-control study, the expansion of abdominal aortic aneurysms was compared in 15 patients taking nonsteroidal anti-inflammatory drugs and 63 control subjects; median growth rates were 1.5 and 3.2 mm/y, respectively,
P
=0.001.

Conclusions
—The adverse effects of PGE
2
on aortic smooth muscle cell viability and cytokine secretion in vitro and the apparent effect of anti-inflammatory drugs to lower aneurysm growth rates suggest that selective inhibition of PGE
2
synthesis could be an effective treatment to curtail aneurysm expansion.
Interleukin-6 and RANTES in Takayasu Arteritis
Authors: Noris Marina , Daina Erica , Gamba Sara , Bonazzola Samantha , Remuzzi Giuseppe
Published: June 2012

Background
—In patients with Takayasu arteritis, circulating lymphocytes are activated, and histological findings indicate that cell-mediated immunity plays an important role in the pathogenetic sequence leading to vascular lesions.

Methods and Results
—To delineate the profile of inflammatory and chemoattractant cytokines involved in T-cell activation in Takayasu arteritis, we measured by ELISA serum levels of interleukin (IL)-6, IL-1β, and RANTES in 18 patients. Subsequently, we wanted to establish whether any of these molecules could be used as a marker to monitor the clinical course of the disease and to predict disease exacerbations. We found that all patients with Takayasu arteritis studied during an active phase of the disease have increased serum concentration of IL-6 compared with healthy control subjects (
P
<0.01). Enhanced IL-6 serum levels paralleled disease activity to the extent that its serum concentrations were comparable to those of control subjects when patients were studied in remission. RANTES concentrations were also higher than normal in the serum of all patients with Takayasu arteritis (
P
<0.01) studied during an active phase of the disease. RANTES serum levels tended to normalize in remission, but values remained higher than those of control subjects (
P
<0.05). In contrast, serum concentrations of IL-1β were below the detection limit of ELISA in both healthy subjects and all patients with Takayasu arteritis. A positive correlation was found between either IL-6 (ρ=0.705,
P
<0.01) or RANTES (ρ=0.607,
P
<0.05) serum level and disease activity.

Conclusions
—The close correlation of serum IL-6 and RANTES levels with disease activity suggests that these cytokines contribute to vasculitic lesions in Takayasu arteritis and raises the possibility that their monitoring in serum helps clinicians find adequate treatment adjustments in individual patients.
Prediction of Coronary and Cerebrovascular Morbidity and Mortality by Direct Continuous Ambulatory Blood Pressure Monitoring in Essential Hypertension
Authors: Khattar Rajdeep S. , Swales John D. , Banfield Ann , Dore Caroline , Senior Roxy , Lahiri Avijit
Published: June 2012

Background
—The goal of this study was to assess the prognostic value of ambulatory versus clinic blood pressure measurement and to relate cardiovascular risk to ambulatory systolic and diastolic blood pressure levels.

Methods and Results
—The study population consisted of 688 patients 51±11 years of age who had undergone pretreatment 24-hour intra-arterial ambulatory blood pressure monitoring on the basis of elevated clinic blood pressure. A total of 157 first events were recorded during a 9.2±4.1-year follow-up period. The predictive value of a regression model containing age, sex, race, body mass index, smoking, diabetes mellitus, fasting cholesterol level, and previous history of cardiovascular disease was significantly improved by the addition of any ambulatory systolic or diastolic blood pressure parameter (whether 24-hour, daytime, or nighttime mean) or pulse pressure, whereas inclusion of baseline clinic blood pressure variables did not enhance the prediction of events. The most predictive models contained the ambulatory systolic blood pressure parameters. In the model containing 24-hour mean ambulatory systolic blood pressure (
P
=0.001), age (
P
<0.001), male sex (
P
<0.001), South Asian origin (
P
=0.008), diabetes mellitus (
P
=0.05), and previous cardiovascular disease (
P
<0.001) were additional independent predictors of events. Whereas 24-hour ambulatory systolic blood pressure was linearly related to the incidence of both coronary and cerebrovascular events, 24-hour ambulatory diastolic blood pressure exhibited a positive linear relationship with cerebrovascular events but a curvilinear relationship with coronary events.

Conclusions
—Ambulatory blood pressure is superior to clinic measurement for the assessment of cardiovascular risk; there is no reduction in coronary risk at lower levels of ambulatory diastolic blood pressure.
Involvement of Cardiotrophin-1 in Cardiac Myocyte-Nonmyocyte Interactions During Hypertrophy of Rat Cardiac Myocytes In Vitro
Authors: Kuwahara Koichiro , Saito Yoshihiko , Harada Masaki , Ishikawa Masahiro , Ogawa Emiko , Miyamoto Yoshihiro , Hamanaka Ichiro , Kamitani Shigeki , Kajiyama Noboru , Takahashi Nobuki , Nakagawa Osamu , Masuda Izuru , Nakao Kazuwa
Published: June 2012

Background
—The mechanism responsible for cardiac hypertrophy is currently conceptualized as having 2 components, mediated by cardiac myocytes and nonmyocytes, respectively. The interaction between myocytes and nonmyocytes via growth factors and/or cytokines plays an important role in the development of cardiac hypertrophy. We found that cardiac myocytes showed hypertrophic changes when cocultured with cardiac nonmyocytes. Cardiotrophin-1 (CT-1), a new member of the interleukin-6 family of cytokines, was identified by its ability to induce hypertrophic response in cardiac myocytes. In this study, we used the in vitro coculture system to examine how CT-1 is involved in the interaction between cardiac myocytes and nonmyocytes during the hypertrophy process.

Methods and Results
—RNase protection assay revealed that CT-1 mRNA levels were 3.5 times higher in cultured cardiac nonmyocytes than in cultured cardiac myocytes. We developed anti–CT-1 antibodies and found that they significantly inhibited the increased atrial and brain natriuretic peptide secretion and protein synthesis characteristic of hypertrophic changes of myocytes in the coculture. In addition, non–myocyte-conditioned medium rapidly elicited tyrosine phosphorylation of STAT3 and induced an increase in natriuretic peptide secretion and protein synthesis in cultured cardiac myocytes; these effects were partially suppressed by anti–CT-1 antibodies. Finally, the hypertrophic effects of CT-1 and endothelin-1, which we had previously implicated in the hypertrophic activity in the coculture, were additive in cardiac myocytes.

Conclusions
—These results show that CT-1 secreted from cardiac nonmyocytes is significantly involved in the hypertrophic changes of cardiac myocytes in the coculture and suggest that CT-1 is an important local regulator in the process of cardiac hypertrophy.
Angiotensin II Induces Vascular Cell Adhesion Molecule-1 Expression In Rat Vasculature
Authors: Tummala Pradyumna E. , Chen Xi-Lin , Sundell Cynthia L. , Laursen Jørn Bech , Hammes C. Patricia , Alexander R. Wayne , Harrison David G. , Medford Russell M.
Published: June 2012

Background
—Cardiovascular ischemic events may occur more frequently in hypertensive patients with activated renin-angiotensin systems. We tested the hypothesis that angiotensin II (Ang II) may contribute to atherosclerosis by increasing expression of vascular inflammatory genes such as vascular cell adhesion molecule-1 (VCAM-1).

Methods and Results
—Rats infused with norepinephrine or Ang II for 6 days developed similar hypertensive responses, but only Ang II-treated rats exhibited significant increases in aortic VCAM-1 protein and mRNA expression. Oral losartan treatment (50 mg · kg
−1
· d
−1
) inhibited Ang II-induced hypertension and aortic VCAM-1 mRNA expression. Ang II treatment significantly increased VCAM-1 mRNA expression in cultured rat aortic smooth muscle cells (RASMCs). Ang II also induced nuclear NF-κB-like binding activity and transactivated an NF-κB–driven VCAM-1 promoter. Losartan and proteasome inhibitors blocked Ang II-induced NF-κB activation and VCAM-1 mRNA accumulation. IκB-α overexpression in RASMCs inhibited Ang II-induced VCAM-1 promoter transactivation.

Conclusions
—Ang II may contribute to atherogenesis by activation of VCAM-1 through proteasome dependent, NF-κB-like transcriptional mechanisms.
Pharmacotherapy of Neurally Mediated Syncope
Authors: Benditt David G. , Fahy Gerard J. , Lurie Keith G. , Sakaguchi Scott , Fabian William , Samniah Nemer
Published: June 2012

Abstract
—A wide variety of pharmacological agents are currently used for prevention of recurrent neurally mediated syncope, especially the vasovagal faint. None, however, have unequivocally proven long-term effectiveness based on adequate randomized clinical trials. At the present time, β-adrenergic receptor blockade, along with agents that increase central volume (eg, fludrocortisone, electrolyte-containing beverages), appear to be favored treatment options. The antiarrhythmic agent disopyramide and various serotonin reuptake blockers have also been reported to be beneficial. Finally, vasoconstrictor agents such as midodrine offer promise and remain the subject of clinical study. Ultimately, though, detailed study of the pathophysiology of these syncopal disorders and more aggressive pursuit of carefully designed placebo-controlled treatment studies are essential if pharmacological prevention of recurrent neurally mediated syncope is to be placed on a firm foundation.
Single-Unit Sympathetic Discharge
Authors: Greenwood John P. , Stoker John B. , Mary David A. S. G.
Published: June 2012

Background
—Reports demonstrating sympathetic hyperactivity in hypertension with the use of microneurography have been inconsistent. One possible reason is that previous studies have assessed muscle sympathetic nerve activity (MSNA) from integrated voltage waves (“bursts”) recorded from multiunit discharges. We studied single units with defined vasoconstrictor properties (s-MSNA) to further characterize sympathetic output in hypertensive disease.

Methods and Results
—We examined 74 subjects with a wide range of arterial blood pressure that were considered to be either normal (NT), high normal (HN), or stages 1 to 3 essential hypertension (EHT-1, EHT-2/3). All had their peripheral sympathetic activity measured from both multiunit bursts and single-unit vasoconstrictor impulses. There was a significant correlation between s-MSNA and MSNA, and results of variability studies were similar. The EHT-1 and EHT-2/3 groups had greater s-MSNA and MSNA than did the matched NT group (always
P
<0.01). The HN group also had greater s-MSNA and MSNA than did the NT group (mean±SEM; 43±5 vs 29±2 impulses/100 beats,
P
<0.05; 36±4 vs 24±2 bursts/100 beats,
P
<0.05). In addition, the EHT-1 group had significantly greater s-MSNA than did the EHT-2/3 group (63±6 vs 51±3 impulses/100 beats,
P
<0.05), which could not be demonstrated with MSNA bursts.

Conclusions
—Quantification from single vasoconstrictor units has provided additional evidence in established essential hypertension of increased central sympathetic output. Furthermore, in the mild or early stages of hypertension, this technique has provided new evidence of augmented sympathetic output compared with more severe hypertension.
Reentrant Pathway During Ventricular Echoes Is Confined to the Atrioventricular Node
Authors: Loh Peter , de Bakker Jacques M. T. , Hocini Mélèze , Thibault Bernard , Hauer Richard N. W. , Janse Michiel J.
Published: June 2012

Background
—During ventricular echoes, reentrant excitation is supposed to involve 2 functionally distinct pathways in the atrioventricular (AV) nodal area. The exact pathway of reentrant excitation is unknown. The objectives of this study were to analyze electrical activity in the AV nodal area after ventricular stimulation and during ventricular echoes and to assess the role of perinodal atrial tissue in AV nodal reentry.

Methods and Results
—In 16 isolated, blood-perfused canine hearts, multiterminal electrodes were used to map electrical activity in Koch’s triangle after ventricular stimulation and during ventricular echoes. The subendocardial cell layers were chemically destroyed in 3 hearts. Incisions in the posterior approach to the compact node were made in 6 hearts. The apex of the triangle of Koch was surgically dissociated from the perinodal atrial tissue in 5 hearts. Retrograde atrial activation occurred via 2 distinct endocardial exit sites. Ventricular echoes could be induced in all hearts irrespective of the atrial activation pattern. Simultaneous retrograde activation of both exit sites often preceded reciprocation. Ventricular echoes were demonstrable after chemical destruction of the endocardium and after surgical dissociation of the perinodal atrial tissue from the AV node.

Conclusions
—Our data show that the reentrant pathway during ventricular echoes is confined to the AV node. The tissue that connects the node to the endocardial exit sites has to be excluded from the reentrant circuit responsible for single echoes.
New Insights Regarding the Atrial Flutter Reentrant Circuit
Authors: Uno Kikuya , Kumagai Koichiro , Khrestian Celeen M. , Waldo Albert L.
Published: June 2012

Background
—We studied atrial activation during induced atrial flutter in the canine sterile pericarditis model to test the hypothesis that the atrial flutter reentrant circuit includes a septal component.

Methods and Results
—We studied 10 episodes of induced, sustained (>5 minutes) atrial flutter in 9 dogs. In all episodes, the reentrant circuit included a septal component. In 6 episodes, there were 2 reentrant circuits, one in the right atrial free wall and the second involving the atrial septum, Bachmann’s bundle, and the right atrial free wall; both circuits shared a pathway in the right atrial free wall (figure-of-eight). The direction (superior or inferior) of the septal wave front of the second circuit correlated with the direction (clockwise or counterclockwise, respectively) of the right atrial free-wall circuit. A line of functional block in the right atrial free wall was part of both reentrant circuits. In the other 4 atrial flutter episodes, only 1 reentrant circuit was present, with activation in an inferior-to-superior direction in the septum and a superior-to-inferior direction in the right atrial free wall in 2 episodes and in the opposite direction in the other 2 episodes. In all atrial flutter episodes, the flutter wave polarity in ECG lead II was determined by the direction of activation in the left atrium; polarity was positive when the direction was superior to inferior and negative when the direction was inferior to superior.

Conclusions
—In this model of atrial flutter, the reentrant circuit (1) always included a septal component, (2) did not always require a right atrial free-wall reentrant circuit, (3) demonstrated figure-of-eight reentry when a reentrant circuit was present in the right atrial free wall, and (4) was associated with a line of functional block in the right atrial free wall.
Constrictive Pericarditis in the Modern Era
Authors: Ling Lieng H. , Oh Jae K. , Schaff Hartzell V. , Danielson Gordon K. , Mahoney Douglas W. , Seward James B. , Tajik A. Jamil
Published: June 2012

Background
—The clinical spectrum of constrictive pericarditis (CP) has been affected by a change in incidence of etiological factors. We sought to determine the impact of these changes on the outcome of pericardiectomy.

Methods and Results
—The contemporary spectrum of CP in 135 patients (76% male) evaluated at the Mayo Clinic from 1985 to 1995 was compared with that of a historic cohort. Notable trends were an increasing frequency of CP due to cardiac surgery and mediastinal radiation and presentation in older patients (median age, 61 versus 45 years). Perioperative mortality decreased (6% versus 14%,
P
=0.011), but late survival was inferior to that of an age- and sex-matched US population (57±8% at 10 years). The long-term outcome was predicted independently by 3 variables in stepwise logistic regression analyses: (1) age, (2) NYHA class, and most powerfully, (3) a postradiation cause. Of 90 late survivors in whom functional class could be determined, functional status had improved markedly (2.6±0.7 at baseline versus 1.5±0.8 at latest follow-up [
P
<0.0001]), with 83% being free of clinical symptoms.

Conclusions
—The evolving profile of CP, with increasingly older patients and those with radiation-induced disease in the past decade, significantly affects postoperative prognosis. Long-term results of pericardiectomy are disappointing for some patient groups, especially those with radiation-induced CP. By contrast, surgery alleviates or improves symptoms in the majority of late survivors.
1166 A/C Polymorphism of the Angiotensin II Type 1 Receptor Gene and the Response to Short-Term Infusion of Angiotensin II
Authors: Hilgers Karl F. , Langenfeld Matthias R. W. , Schlaich Markus , Veelken Roland , Schmieder Roland E.
Published: June 2012

Background
—Previous studies reported an association of the 1166 A/C polymorphism of the angiotensin II (Ang II) type 1 receptor gene with high blood pressure and cardiovascular disease. We tested the hypothesis that this polymorphism affects the blood-pressure, renal hemodynamic, and aldosterone response to infused Ang II.

Methods and Results
—Young, male, white volunteers (n=116) with normal (n=65) or mildly elevated (n=51) blood pressure on a high salt intake were genotyped for the 1166 A/C polymorphism. Two doses of Ang II (0.5 and 3 ng · kg
−1
· min
−1
over 30 minutes each) increased blood pressure, plasma aldosterone, glomerular filtration rate, and filtration fraction and decreased renal blood flow. The blood-pressure, renal hemodynamic, and aldosterone responses were not significantly different between subjects homozygous for the A allele (n=56) and heterozygous subjects (n=47) or subjects homozygous for the C allele (n=13). Comparison of A allele homozygotes with all C allele carriers pooled (n=60) or restriction of the analysis to normotensive volunteers also revealed no significant differences between genotypes.

Conclusions
—The 1166 C variant of the Ang II type 1 receptor does not lead to a greater blood-pressure, aldosterone, or renal vascular response to infused Ang II in young, male, white subjects. We conclude that the 1166 A/C polymorphism does not have a major effect on these actions of Ang II.
Mast Cells Cause Apoptosis of Cardiomyocytes and Proliferation of Other Intramyocardial Cells In Vitro
Authors: Hara Masatake , Matsumori Akira , Ono Koh , Kido Hiroshi , Hwang Myung-Woo , Miyamoto Tadashi , Iwasaki Atsushi , Okada Masaharu , Nakatani Kazuki , Sasayama Shigetake
Published: June 2012

Background
—Mast cells are multifunctional cells containing various mediators such as cytokines, proteases, and histamine. They are found in the human heart and have been implicated in ventricular hypertrophy and heart failure. However, their roles in pathogenesis of these diseases are unknown.

Methods and Results
—Cultured cardiomyocytes from neonatal rats were incubated with mast cell granules (MCGs) for 24 hours. The highest concentration of diluted MCGs caused the death of ≈70% of cardiomyocytes. This cell death was proved to be apoptosis, as quantified by electron microscopy and biochemical criteria. MCG-mediated cytotoxicity was prevented by pretreatment of MCGs with protease inhibitors or a neutralizing antibody against rat mast cell chymase 1 (RMCP 1). RMCP 1 by itself was proved to induce cell death of cardiomyocytes. These results suggest that RMCP 1 contained in MCGs causes the death of cardiomyocytes. In contrast, MCGs induced the proliferation of intramyocardial cells other than myocytes. RMCP 1 was also proved to induce their proliferation.

Conclusions
—Mast cells cause apoptosis of cardiomyocytes and proliferation of other intramyocardial cells via the activity of RMCP 1. Our results suggest that mast cell chymase may play a role in the progression of heart failure, because loss of cardiomyocytes and proliferation of nonmyocardial cells exaggerate its pathophysiology.
Role of Papillary Muscle in the Generation and Maintenance of Reentry During Ventricular Tachycardia and Fibrillation in Isolated Swine Right Ventricle
Authors: Kim Young-Hoon , Xie Fagen , Yashima Masaaki , Wu Tsu-Juey , Valderrábano Miguel , Lee Moon-Hyoung , Ohara Toshihiko , Voroshilovsky Olga , Doshi Rahul N. , Fishbein Michael C. , Qu Zhilin , Garfinkel Alan , Weiss James N. , Karagueuzian Hrayr S. , Chen Peng-Sheng
Published: June 2012

Background
—The role of papillary muscle (PM) in the generation and maintenance of reentry is unclear.

Methods and Results
—Computerized mapping (477 bipolar electrodes, 1.6-mm resolution) was performed in fibrillating right ventricles (RVs) of swine in vitro. During ventricular fibrillation (VF), reentrant wave fronts often transiently anchored to the PM. Tissue mass reduction was then performed in 10 RVs until VF converted to ventricular tachycardia (VT). In an additional 6 RVs, procainamide infusion converted VF to VT. Maps showed that 77% (34 of 44) of all VT episodes were associated with a single reentrant wave front anchored to the PM. Purkinje fiber potentials preceded the local myocardial activation, and these potentials were recorded mostly around the PM. When PM was trimmed to the level of endocardium (n=4), sustained VT was no longer inducible. Transmembrane potential recordings (n=5) at the PM revealed full action potential during pacing, without evidence of ischemia. Computer simulation studies confirmed the role of PM as a spiral wave anchoring site that stabilized wave conduction.

Conclusions
—We conclude that PM is important in the generation and maintenance of reentry during VT and VF.
Regulation of Shear Stress in the Canine Coronary Microcirculation
Authors: Stepp David W. , Nishikawa Yasuhiro , Chilian William M.
Published: June 2012

Background
—Physical forces, such as pressure and flow, are well known to affect vascular function in the coronary circulation. Increases in shear stress produce vasodilation in coronary arterioles in vitro, and constant-flow preparations suggest a role for shear stress–induced vasodilation during adjustments to metabolic demand in vivo. Hypothetically, the regulation of shear stress can be viewed as a negative feedback control scheme (increased velocity → increased shear → vasodilation → decreased velocity → shear normalized). Therefore, we hypothesized that shear stress would be at least partially regulated during conditions of elevated flow.

Methods and Results
—We used fluorescence microangiography to measure microvascular diameters and velocities in the coronary circulation in vivo and used these variables to calculate shear stress. Measurements were obtained under basal conditions, during maximal coronary blood flow, and after inhibition of NO synthase. Basal shear stress in the coronary circulation averaged 10 dyn/cm
2
in small arteries and 19 dyn/cm
2
in arterioles. Regulation of shear stress was observed in small arteries during adenosine-induced increases in coronary blood flow, but arterioles showed minimal regulation. NO synthase blockade had no effect on basal shear stress but completely abolished its regulation in small arteries during vasodilation.

Conclusions
—Our data provide the first quantitative estimates of microvascular shear stress in the coronary circulation. Moreover, our results suggest that shear stress in small coronary arteries is regulated by NO release from the endothelium.
Angiotensin II Stimulates Intercellular Adhesion Molecule-1 (ICAM-1) Expression by Human Vascular Endothelial Cells and Increases Soluble ICAM-1 Release In Vivo
Authors: Pastore L. , Tessitore A. , Martinotti S. , Toniato E. , Alesse E. , Bravi M. C. , Ferri C. , Desideri G. , Gulino A. , Santucci A.
Published: June 2012

Background
—We evaluated whether angiotensin II (Ang II) influenced intercellular adhesion molecule (ICAM)-1 expression by human vascular endothelial cells derived from umbilical cord veins (HUVECs) and plasma soluble ICAM-1 levels in vivo.

Methods and Results
—Cultured HUVECs were incubated with Ang II (from 10
−9
to 10
−6
mol/L) with or without candesartan and PD12319 (inhibitors of Ang II AT
1
and AT
2
receptors, respectively) for various times up to 4 hours. Total RNA was then extracted from HUVECs, and Northern blots were probed with a 1.9-kb ICAM-1 cDNA fragment. HUVEC supernatants were used to assess soluble ICAM-1 release by ELISA. Northern blot analysis detected a strong increase of ICAM-1 mRNA after 2-hour incubation with Ang II. The response was inhibited by candesartan. Soluble ICAM-1 release by HUVECs also increased (
P
<0.002) after 2-hour Ang II stimulation. In vivo, Ang II (at an initial rate of 1.0 ng · kg
−1
· min
−1
, to be increased each 30 minutes by 2.0 ng · kg
−1
· min
−1
to the final rate of 7.0 ng · kg
−1
· min
−1
) was infused in 8 normotensive and 12 essential hypertensive individuals. In the latter, Ang II was reinfused after 4 weeks on either placebo (n=3), losartan (50 mg UID, n=5), or atenolol (50 mg UID, n=4) treatment. Plasma soluble ICAM-1 levels increased after Ang II infusion in hypertensives and normotensives (
P
<0.0001 after 90 minutes). Losartan reduced baseline soluble ICAM-1 levels (
P
<0.05) and Ang II–related ICAM-1 increments.

Conclusions
—Ang II upregulates ICAM-1 expression by HUVECs and stimulates in vitro and in vivo soluble ICAM-1 release. AT
1
receptor blockade inhibits such endothelial effects of Ang II.
Vasoconstriction to Endogenous Endothelin-1 Is Increased in the Peripheral Circulation of Patients With Essential Hypertension
Authors: Taddei Stefano , Virdis Agostino , Ghiadoni Lorenzo , Sudano Isabella , Notari Massimo , Salvetti Antonio
Published: June 2012

Background
—In humans, endothelin (ET)-1 could be implicated in the pathophysiology of several cardiovascular diseases, including essential hypertension. We therefore evaluated the role of ET-1 in control of vascular tone in essential hypertension.

Methods and Results
—We used strain-gauge venous plethysmography to test changes in forearm blood flow induced by intrabrachial infusion of TAK-044 (10, 30, and 100 μg · 100 mL
−1
· min
−1
), an ET
A
/ET
B
receptor antagonist, or sodium nitroprusside (1 and 2 μg · 100 mL
−1
· min
−1
), a vasodilator that acts on smooth muscle cells, in hypertensive patients and healthy controls (n=10 in each group). The NO pathway was also evaluated by infusion of
N
G
-monomethyl-
l
-arginine, (L-NMMA; 10, 30, and 100 μg · 100 mL
−1
· min
−1
), an NO synthase inhibitor, and norepinephrine (3, 9, and 30 ng · 100 mL
−1
· min
−1
) as control. Immunoreactive plasma ET-1 was measured by radioimmunoassay. In hypertensive patients, TAK-044 caused a vasodilation that was significantly (
P
<0.01) increased compared with normotensive subjects. Moreover, vasoconstriction to L-NMMA was significantly (
P
<0.01) decreased in hypertensive patients compared with controls. In contrast, the vascular responses to sodium nitroprusside and norepinephrine, as well as levels of immunoreactive plasma ET-1, were similar in hypertensive patients and controls. In the study population, vasodilation to TAK-044 and vasoconstriction to L-NMMA showed an inverse correlation (
r
=−0.56,
P
<0.05).

Conclusions
—These results indicate that TAK-044 caused a greater degree of vasodilation in the forearm vessels of essential hypertensive patients compared with normotensive subjects, an alteration associated with decreased tonic NO release.
Utility of Fast Cine Magnetic Resonance Imaging and Display for the Detection of Myocardial Ischemia in Patients Not Well Suited for Second Harmonic Stress Echocardiography
Authors: Hundley W. Gregory , Hamilton Craig A. , Thomas Mark S. , Herrington David M. , Salido Tiffany B. , Kitzman Dalane W. , Little William C. , Link Kerry M.
Published: June 2012

Background
—Some patients referred for pharmacological stress testing with transthoracic echocardiography (TTE) are unable to undergo testing owing to poor acoustic windows. Fast cine MRI can be used to assess left ventricular contraction, but its utility for detection of myocardial ischemia in patients poorly suited for echocardiography is unknown.

Methods and Results
—One hundred fifty-three patients (86 men and 67 women aged 30 to 88 years) with poor acoustic windows that prevented adequate second harmonic TTE imaging were consecutively referred for MRI to diagnose inducible myocardial ischemia during intravenous dobutamine and atropine. Diagnostic studies were completed in an average of 53 minutes. No patients experienced myocardial infarction, ventricular fibrillation, exacerbation of congestive heart failure, or death. In patients who underwent computer-assisted quantitative coronary angiography, the sensitivity and specificity for detecting a >50% luminal diameter narrowing were 83% and 83%, respectively. In the 103 patients with a negative MRI examination, the cardiovascular occurrence–free survival rate was 97%.

Conclusions
—Fast cine cardiac MRI provides a mechanism to assess left ventricular contraction and diagnose inducible myocardial ischemia in patients not well suited for stress echocardiography.
The Gene Encoding Atrial Natriuretic Peptide and the Risk of Human Stroke
Authors: Rubattu Speranza , Ridker Paul , Stampfer Meir J. , Volpe Massimo , Hennekens Charles H. , Lindpaintner Klaus
Published: June 2012

Background
—Recent evidence from an animal model of stroke, the stroke-prone spontaneously hypertensive rat, implicated the gene encoding atrial natriuretic peptide (
ANP
) as a possible candidate contributing to the likelihood of experiencing a stroke. The purpose of the present study was to investigate the role of
ANP
in the pathogenesis of cerebrovascular accidents in humans.

Methods and Results
—We investigated 2 previously known markers at
ANP
,
G1837A
and
T2238C
, for their possible association with the occurrence of stroke. This was the largest matched case-controlled sample studied thus far; the sample was drawn from a large prospective study (the Physician’s Health Study). When assuming a dominant mode of inheritance, a statistically significant positive association was observed for the
1837A
allele, indicating an odds ratio of 1.64 (95% confidence interval, 1.01 to 2.65) for stroke. This observation led to the discovery of a new molecular variant in exon 1,
G664A,
which was responsible for a valine-to-methionine substitution in the proANP peptide. This mutation, which was in linkage disequilibrium with the
G1837A
marker, was associated with the occurrence of stroke (odds ratio, 2.0; 95% confidence interval, 1.17 to 3.19;
P
=0.01).

Conclusions
—Our findings suggest that molecular variants of the ANP gene may represent an independent risk factor for cerebrovascular accidents in humans. The strong parallelism to the experimental data obtained in the stroke-prone animal model provides assurance for the relevance of our observation.
Circulating Insulin and Insulin Growth Factor-1 Are Independent Determinants of Left Ventricular Mass and Geometry in Essential Hypertension
Authors: Verdecchia Paolo , Reboldi Gianpaolo , Schillaci Giuseppe , Borgioni Claudia , Ciucci Antonella , Telera Maria Pia , Santeusanio Fausto , Porcellati Carlo , Brunetti Paolo
Published: June 2012

Background
—It is unclear whether insulin and insulin-like growth factor-1 (IGF-1) are independent determinants of left ventricular (LV) mass in essential hypertension.

Methods and Results
—We studied 101 never-treated nondiabetic subjects with essential hypertension. All had 24-hour noninvasive ambulatory blood pressure (ABP) monitoring and a 75-g oral glucose tolerance test. We determined fasting glucose, insulin, and IGF-1 and postload glucose and insulin 2 hours after glucose. Insulin resistance was estimated by the homeostasis model assessment (HOMA
IR
) formula. LV mass showed an association with body mass index (BMI) (
r
=0.47;
P
<0.01), postload insulin (
r
=0.54;
P
<0.01), HOMA
IR
(
r
=0.39;
P
<0.01), and IGF-1 (
r
=0.43;
P
<0.01) and a weaker association with average 24-hour systolic and diastolic ABPs (
r
=0.29 and
r
=0.26;
P
<0.05) and basal insulin (
r
=0.31;
P
<0.05). Relative wall thickness was positively related to IGF-1 (
r
=0.39;
P
<0.01) but not to fasting or 2-hour postload insulin, HOMA
IR
, and glucose. In a multiple regression analysis, the final LV mass model (
R
2
=0.64) included IGF-1, postload insulin, average 24-hour systolic ABP, sex, and BMI. IGF-1 and postload insulin accounted for >40% of variability of LV mass. The final model (
R
2
=0.36) for relative wall thickness included IGF-1 (16% total explained variability), average 24-hour systolic ABP, sex, BMI, and age but not insulin and HOMA
IR
.

Conclusions
—These data indicate that insulin and IGF-1 are powerful independent determinants of LV mass and geometry in untreated subjects with essential hypertension and normal glucose tolerance.
Contribution of Endothelin-1 to Myocardial Injury in a Murine Model of Myocarditis
Authors: Ono Koh , Matsumori Akira , Shioi Tetsuo , Furukawa Yutaka , Sasayama Shigetake
Published: June 2012

Background
—Endothelin (ET) is one of the most important contributing factors in the pathophysiology of cardiovascular diseases. However, little is known about its role in myocarditis.

Methods and Results
—Four-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus. Expression levels of ET-converting enzyme-1 (ECE-1) and prepro-ET-1 mRNA were significantly increased at 7 and 14 days after virus inoculation. Plasma and myocardial ET-1 levels were significantly higher in infected than noninfected mice between 5 and 14 days after virus inoculation. Immunohistochemical analyses revealed that not only endothelial cells and myocytes but also infiltrating mononuclear cells produced ET-1 protein at 7 days. Oral bosentan, a mixed ET-1 receptor antagonist, was administered after virus inoculation in doses of 0 (control group), 10, or 100 mg · kg
−1
· d
−1
, and the animals were killed on day 14. Mean heart weight/body weight ratios were 8.3±1.8 versus 11.2±2.4 versus 10.8±2.4 in the bosentan 100 mg · kg
−1
· d
−1
versus 10 mg · kg
−1
· d
−1
versus control groups, respectively (
P
<0.05). Corresponding histological scores for myocardial necrosis were 2.0±0.2 versus 2.9±0.3 versus 3.0±0.4 (
P
<0.05), and cellular infiltration scores were 2.3±0.3 versus 2.9±0.4 versus 3.3±0.4 (
P
<0.05). Animals killed on day 5 had significantly smaller necrotic areas after treatment with bosentan 100 mg · kg
−1
· d
−1
than the group treated with a lower dose or the control group, despite the absence of differences in virus titers.

Conclusions
—This study suggests that ET-1 plays an important pathophysiological role in viral myocarditis. Treatment with bosentan had a cardioprotective effect without modifying viral replication.
Digoxin Delays Recovery From Tachycardia-Induced Electrical Remodeling of the Atria
Authors: Tieleman Robert G. , Blaauw Yuri , Van Gelder Isabelle C. , De Langen Cees D. J. , de Kam Pieter J. , Grandjean Jan G. , Patberg Kornelis W. , Bel Klaas J. , Allessie Maurits A. , Crijns Harry J. G. M.
Published: June 2012

Background
—Atrial fibrillation (AF) induces electrical remodeling, which is thought to be responsible for the low success rate of antiarrhythmic treatment in AF of longer duration. Electrical remodeling seems to be related to tachycardia-induced intracellular calcium overload. Due to its vagomimetic action, digoxin is widely used to control the ventricular rate during AF, but it also increases intracellular calcium. On the basis of these characteristics, we hypothesized that digoxin would aggravate tachycardia-induced electrical remodeling.

Methods and Results
—We analyzed the atrial effective refractory period (AERP) at cycle lengths of 430, 300, and 200 ms during 24 hours of rapid atrio/ventricular (300/150 bpm) pacing in 7 chronically instrumented conscious goats treated with digoxin or saline. Digoxin decreased the spontaneous heart rate but had no other effects on baseline electrophysiological characteristics. In addition to a moderate increase in the rate of electrical remodeling during rapid pacing, digoxin significantly delayed the recovery from electrical remodeling after cessation of pacing (at 430, 300, and 200 ms:
P
=0.001,
P
=0.0015, and
P
=0.007, respectively). This was paralleled by an increased inducibility and duration of AF during digoxin. Multivariate analysis revealed that both a short AERP and treatment with digoxin were independent predictors of inducibility (
P
=0.001 and
P
=0.03, respectively) and duration (
P
=0.001 for both) of AF.

Conclusions
—Digoxin aggravates tachycardia-induced atrial electrical remodeling and delays recovery from electrical remodeling in the goat, which increases the inducibility and duration of AF.
Vascular Effects of Estrogen and Vitamin E Therapies in Postmenopausal Women
Authors: Koh Kwang Kon , Blum Arnon , Hathaway Londa , Mincemoyer Rita , Csako Gyorgy , Waclawiw Myron A. , Panza Julio A. , Cannon Richard O.
Published: June 2012

Background
—Estrogen and vitamin E therapies have been suggested to reduce cardiovascular risk, but comparison of the vascular effects of these therapies to determine mechanisms of potential benefit has not been performed in postmenopausal women.

Methods and Results
—In a double-blind, 3-period crossover study, we randomly assigned 28 healthy postmenopausal women to conjugated equine estrogens (CE) 0.625 mg/d, vitamin E 800 IU/d, and their combination, with measurements made before and after each 6-week treatment period. The ratio of LDL to HDL cholesterol and lipoprotein(a) decreased on therapies including CE but increased on vitamin E alone (
P
<0.001 and
P
=0.002, respectively, by ANOVA). Brachial artery flow–mediated dilation improved on all therapies (all
P
<0.001 versus pretreatment values) and to a similar degree (
P
=0.267 by ANOVA). No therapy improved the dilator response to nitroglycerin. CE lowered serum levels of cell adhesion molecules E-selectin, ICAM-1, and VCAM-1 (all
P
<0.05 versus pretreatment values). Vitamin E had no significant effect on levels of these markers of inflammation (
P
<0.001 by ANOVA for E-selectin). CE alone or combined with vitamin E but not vitamin E alone lowered or showed a trend for lowering plasma levels of plasminogen activator inhibitor type-1 (
P
=0.069 by ANOVA).

Conclusions
—Estrogen and vitamin E therapies similarly improved arterial endothelium-dependent vasodilator responsiveness consistent with increased nitric oxide in healthy postmenopausal women, despite divergent effects on atherogenic lipoproteins. However, only estrogen reduced markers of vascular disease.