bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluoxetine protects against monocrotaline-induced pulmonary arterial remodeling by inhibition of hypoxia-inducible factor-1α and vascular endothelial growth factor
Authors: Han Dan-Dan , Wang Yun , Zhang Xin-Hua , Liu Jin-Rong , Wang Huai-Liang 
Published: March 2012

The selective serotonin re-uptake inhibitor fluoxetine has been shown to protect against monocrotaline (MCT)-induced pulmonary hypertension in rats. To investigate the possible role of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in mediating this protective effect, MCT-treated rats were administered fluoxetine by gavage, at doses of 2 mg/kg body mass or 10 mg/kg once daily for 3 weeks. Changes in pulmonary hemodynamic parameters, pulmonary artery morphologies, and expressions of HIF-1α and VEGF were assessed. Fluoxetine at the 10 mg/kg dose, but not at the 2 mg/kg dose, attenuated the effects of MCT on pulmonary artery pressure, right ventricle index, and medial wall thickness. In addition, 10 mg/kg fluoxetine mitigated the MCT-induced up-regulation of HIF-1α and VEGF protein and reactive oxygen species (ROS) in the lungs. This dosage also decreased pERK1/2 levels and inhibited proliferation of pulmonary arterial smooth muscle cells in MCT-treated rats. In conclusion, fluoxetine can protect against MCT-induced pulmonary arterial remodeling, which linked to reduced ROS generation and decreased HIF-1α and VEGF protein levels via the ERK1/2 phosphorylation pathway.
Enhanced expression of salusin-β contributes to progression of atherosclerosis in LDL receptor deficient mice
Authors: Zhou Cheng-Hua , Liu Lan-Lan , Wu Yu-Qing , Song Zheng , Xing Shu-Hua 
Published: March 2012

Atherosclerosis is an important underlying pathology of cardiovascular diseases. The aim of this study was to observe the expression of salusin-β, a new vasoactive peptide, in vascular tissues of low-density lipoprotein receptor deficient (LDLR–/–) mice, and to evaluate the effect of salusin-β on the development of atherosclerosis in LDLR–/– mice. Six-week-old, male LDLR–/– mice were subcutaneously injected with salusin-β or the vehicle, once a day for 12 weeks. The expressions of salusin-β in both mRNA and peptide levels were determined by reverse transcription – polymerase chain reaction, Western blot, and immunohistochemistry. Atherosclerotic lesions were analyzed by staining with hematoxylin and eosin or oil red O. Our results showed that expression of salusin-β in mRNA and salusin-β peptide levels were enhanced in LDLR–/– mice. Subcutaneous injection of salusin-β significantly aggravated the atherosclerotic lesions, and increased lipid deposits in the arteries of LDLR–/– mice. Moreover, salusin-β significantly increased the serum level of low-density lipoprotein cholesterol, but not total cholesterol, triglycerides, or high-density lipoprotein cholesterol. These results suggest that the enhanced expression of salusin-β contributes to progression of atherosclerosis in LDLR–/– mice by up-regulating the serum low-density lipoprotein cholesterol level. This study provides a potential therapeutic target for the prevention and treatment of atherosclerosis.
Activation of Ras/PI3K/ERK Pathway Induces c-Myc Stabilization to Upregulate Argininosuccinate Synthetase, Leading to Arginine Deiminase Resistance in Melanoma Cells
Authors: Tsai Wen-Bin , Aiba Isamu , Long Yan , Lin Hui-Kuan , Feun Lynn , Savaraj Niramol , Kuo Macus Tien 
Published: March 2012

Abstract
Melanomas and other cancers that do not express argininosuccinate synthetase (AS), the rate-limiting enzyme for arginine biosynthesis, are sensitive to arginine depletion with pegylated arginine deiminase (ADI-PEG20). However, ADI resistance eventually develops in tumors because of AS upregulation. Although it has been shown that AS upregulation involves c-Myc, the underlying mechanisms remain unknown. Here we show that ADI-PEG20 activates Ras signaling and the effector extracellular signal–regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/AKT/GSK-3β kinase cascades, resulting in phosphorylation and stabilization of c-Myc by attenuation of its ubiquitin-mediated protein degradation mechanism. Inhibition of the induced cell signaling pathways using PI3K/AKT inhibitors suppressed c-Myc induction and enhanced ADI-mediated cell killing. Notably, in an animal model of AS-negative melanoma, combination therapy using a PI3K inhibitor plus ADI-PEG20 yielded additive antitumor effects as compared with either agent alone. Taken together, our findings offer mechanistic insight into arginine deprivation metabolism and ADI resistance, and they illustrate how combining inhibitors of the Ras/ERK and PI3K/AKT signaling pathways may improve ADI-PEG20 anticancer responses. Cancer Res; 72(10); 2622–33. ©2012 AACR.
Molecular Profiling of Pancreatic Neuroendocrine Tumors in Sporadic and Von Hippel-Lindau Patients
Authors: Speisky Daniela , Duces Aurélie , Bièche Ivan , Rebours Vinciane , Hammel Pascal , Sauvanet Alain , Richard Stéphane , Bedossa Pierre , Vidaud Michel , Murat Arnaud , Niccoli Patricia , Scoazec Jean-Yves , Ruszniewski Philippe , Couvelard Anne 
Published: March 2012

Abstract
Purpose: Von Hippel-Lindau (VHL) disease is an inherited syndrome caused by germline mutations in the VHL tumor suppressor gene, predisposing to a variety of neoplasms including pancreatic neuroendocrine tumors (PanNET). In VHL disease, PanNET probably progress according to a specific pathway of carcinogenesis. Our aim was to characterize by molecular quantitative analysis a panel of molecules implicated in the VHL pathway and in tumor progression in the PanNET of patients with VHL.
Experimental Design: The expression of 52 genes was studied by quantitative reverse transcriptase PCR in 18 patients with VHL operated on for PanNET and compared with 16 non-VHL PanNET. The VHL and non-VHL tumors were matched according to their size and cell proliferation. For some genes, we looked for differences in the protein expression in VHL PanNET (n = 31), microadenomas (n = 22), and non-VHL PanNET (n = 16), included in tissue microarray blocks.
Results: Nineteen (36%) genes were significantly upregulated and three (6%) downregulated in VHL PanNET. The upregulated genes were related to (i) hypoxia-inducible factor (HIF) molecules (CA9, HIF2A, and GLUT1), (ii) angiogenesis (CDH5, VEGFR1, EDNRA, ANGPT2, CD34, VEGFR2, VEGFA, and ANGPT1), (iii) the processes of epithelial–mesenchymal transition (VIM) and/or metastasis (LAMA4 and CXCR4), (iv) growth factors and receptors (PDGFB, IRS1, and ERBB1), or (v) cell cycle (CCND1 and CDKN2A). The downregulated genes were related to (i) EMT (OCLN) and (ii) signaling pathways (RPS6KB1 and GADD45B).
Conclusion: This study shows that the progression of PanNET in patients with VHL tumors follows a specific pathway and supports that targeting molecules specifically involved may be of therapeutic importance. Clin Cancer Res; 18(10); 2838–49. ©2012 AACR.
Determinants of Residual Risk in Secondary Prevention Patients Treated With High- Versus Low-Dose Statin Therapy
Authors: Mora Samia , Wenger Nanette K. , DeMicco David A. , Breazna Andrei , Boekholdt S. Matthijs , Arsenault Benoit J. , Deedwania Prakash , Kastelein John J.P. , Waters David D. 
Published: March 2012

Background—
Cardiovascular events occur among statin-treated patients, albeit at lower rates. Risk factors for this “residual risk” have not been studied comprehensively. We aimed to identify determinants of this risk above and beyond lipid-related risk factors.

Methods and Results—

A total of 9251 coronary patients with low-density lipoprotein cholesterol <130 mg/dL randomized to double-blind atorvastatin 10 or 80 mg/d in the Treating to New Targets (TNT) study had complete on-treatment 1-year lipid data. Median follow-up was 4.9 years. The primary end point was major cardiovascular events (n=729): coronary death, nonfatal myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. Multivariable determinants of increased risk were older age (adjusted hazard ratio [aHR], 1.13 per 1 SD [8.8 years]; 95% confidence interval [CI], 1.04–1.23), increased body mass index (aHR, 1.09; 95% CI, 1.02–1.17 per 4.5 kg/m
2
), male sex (aHR, 1.33; 95% CI, 1.07–1.65), hypertension (aHR, 1.38; 95% CI, 1.17–1.63), diabetes mellitus (aHR, 1.33; 95% CI, 1.11–1.60), baseline apolipoprotein B (aHR, 1.19; 95% CI, 1.11–1.28 per 19 mg/dL), and blood urea nitrogen (aHR, 1.10; 95% CI, 1.03–1.17 per 4.9 mg/dL), in addition to current smoking, prior cardiovascular disease, and calcium channel blocker use. Determinants of decreased risk were high-dose statin (aHR, 0.82; 95% CI, 0.70–0.94), aspirin use (aHR, 0.67; 95% CI, 0.56–0.81), and baseline apolipoprotein A-I (aHR, 0.91; 95% CI, 0.84–0.99 per 25 mg/dL). On-treatment 1-year lipids or apolipoproteins were not additionally associated with risk in multivariable models. Known baseline variables performed moderately well in discriminating future cases from noncases (Harrell c index=0.679).

Conclusions—
Determinants of residual risk in statin-treated secondary prevention patients included lipid-related and nonlipid factors such as baseline apolipoproteins, increased body mass index, smoking, hypertension, and diabetes mellitus. A multifaceted prevention approach should be underscored to address this risk.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00327691.
Pharmacological Induction of Heme Oxygenase-1 by a Triterpenoid Protects Neurons Against Ischemic Injury
Authors: Zhang Feng , Wang Suping , Zhang Meijuan , Weng Zhongfang , Li Peiying , Gan Yu , Zhang Lili , Cao Guodong , Gao Yanqin , Leak Rehana K. , Sporn Michael B. , Chen Jun 
Published: March 2012

Background and Purpose—
Heme oxygenase-1 (HO-1) is an inducible Phase 2 enzyme that degrades toxic heme; its role in cerebral ischemia is not fully understood. We hypothesize that chemically induced HO-1 upregulation with the novel triterpenoid CDDO-Im (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a robust inducer of Phase 2 genes, protects neurons against ischemic injury.

Methods—
Using 3 different models of ischemia, including oxygen–glucose deprivation in neuronal cultures, global ischemia in rats, and focal ischemia in mice, we determined (1) whether CDDO-Im induces HO-1 expression and protects against ischemic injury; and (2) whether HO-1 inhibition disrupts the neuroprotective effect of CDDO-Im.

Results—
CDDO-Im treatment (50–300 nmol/L) resulted in 8-fold HO-1 upregulation in cultured neurons and protected against oxygen–glucose deprivation. The protection was abolished when the cultures were transfected with nuclear factor (erythroid-derived 2) like-2–shRNA or coincubated with tin protoporphyrin IX, a specific HO-1 inhibitor. In the rat model of global ischemia, intracerebroventricular infusion of CDDO-Im (0.5–1.5 μg) augmented HO-1 expression in hippocampal neurons and resulted in significant increases in CA1 neuronal survival after global ischemia. To further strengthen the clinical relevance of the CDDO-Im treatment, we tested its effects in the mouse model of temporary focal ischemia (60 minutes). Postischemic intraperitoneal injection of CDDO-Im (10–100 μg) enhanced HO-1 expression and significantly reduced neurological dysfunction and infarct volume. Intracerebroventricular infusion of tin protoporphyrin IX reduced the neuroprotective effect of CDDO-Im against global and focal ischemia.

Conclusions—
CDDO-Im confers neuroprotection against ischemic injury by upregulating HO-1, suggesting that enhance of HO-1 expression may be a legitimate strategy for therapeutic intervention of stroke.
A Nonoscillatory Discontinuous Galerkin Transport Scheme on the Cubed Sphere
Authors: Zhang Yifan , Nair Ramachandran D. 
Published: March 2012

Abstract
The discontinuous Galerkin (DG) method is high order, conservative, and offers excellent parallel efficiency. However, when there are discontinuities in the solution, the DG transport scheme generates spurious oscillations that reduce the quality of the numerical solution. For applications such as the atmospheric tracer transport modeling, a nonoscillatory, positivity-preserving solution is a basic requirement. To suppress the oscillations in the DG solution, a limiter based on the Hermite-Weighted Essentially Nonoscillatory (H-WENO) method has been implemented for a third-order DG transport scheme. However, the H-WENO limiter can still produce wiggles with small amplitudes in the solutions, but this issue has been addressed by combining the limiter with a bound-preserving (BP) filter. The BP filter is local and easy to implement and can be used for making the solution strictly positivity preserving. The DG scheme combined with the limiter and filter preserves the accuracy of the numerical solution in the smooth regions while effectively eliminating overshoots and undershoots. The resulting nonoscillatory DG scheme is third-order accurate (P2-DG) and based on the modal discretization. The 2D Cartesian scheme is further extended to the cubed-sphere geometry, which employs nonorthogonal, curvilinear coordinates. The accuracy and effectiveness of the limiter and filter are demonstrated with several benchmark tests on both the Cartesian and spherical geometries.
Medial Patellofemoral Ligament Reconstruction Using Semitendinosus Tendons
Authors: Xie Guoming , Zhao Jinzhong , Huangfu Xiaoqiao , He Yaohua 
Published: March 2012

Background: The comparative clinical outcome of medial patellofemoral ligament reconstruction (MPFLR) using semitendinosus tendons with and without polyester suture augmentation for recurrent patellar instability is unknown. Hypothesis: Medial patellofemoral ligament reconstruction with polyester suture augmentation will yield better results than MPFLR without augmentation for recurrent patellar instability in adults. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: One hundred patients with recurrent patellar instability receiving MPFLR using semitendinosus tendons were randomly divided into 2 groups either with or without polyester suture augmentation. Tibial tubercle transfer was performed in most cases. Follow-ups were performed at 12, 24, and 60 months postoperatively, and computed tomography (CT) was performed immediately after the operation and at follow-up. The passive patellar glide test was performed before surgery, immediately after MPFLR during the operation, and at each follow-up point. The degree of knee function was evaluated preoperatively and at 2 and 5 years postoperatively using the International Knee Documentation Committee, Lysholm, and Kujala rating scales. Redislocation or multiple episodes of patellar instability were considered failures. Results: Forty-two patients in the augmentation group and 43 patients in the nonaugmentation group were followed for 5 years and received complete serial CT examinations and functional evaluations. The correction of the static patellar position deteriorated over time in the nonaugmentation group but not in the augmentation group. The results of the passive patellar glide test indicated stable patellae in all patients immediately after MPFLR and more stable patellae in the augmentation group at each follow-up point. Functional evaluations at 2 and 5 years revealed statistically significant superior results in the augmentation group. Finally, no patient in the augmentation group and 2 (4.7%) in the nonaugmentation group experienced episodes of redislocation, and 1 patient (2.4%) in the augmentation group and 8 (18.6%) in the nonaugmentation group experienced multiple episodes of patellar instability, resulting in failure rates of 2.4% and 23.3% in the augmentation group and nonaugmentation group, respectively ( P = .004). Conclusion: Medial patellofemoral ligament reconstruction with polyester suture augmentation results in better static patellar position, dynamic stability, and functional outcome than without augmentation in the treatment of recurrent patellar dislocation in adults.
Impact of a psychiatric unit’s daily discharge rates on emergency department flow
Authors: Bastiampillai Tarun , Schrader Geoffrey , Dhillon Rohan , Strobel Jörg , Bidargaddi Niranjan 
Published: March 2012

Objective: To investigate relationships between time spent in the emergency department (ED) in patients requiring admission to the psychiatric ward, the day of the week of presentation and the daily number of discharges from the psychiatric ward. Method: Retrospective analysis of patient flow as a function of day of week, time of day (a.m., p.m.), number of patients requiring admission and number of ward discharges over a one-year period, for all mental health related presentations to the ED of the Queen Elizabeth Hospital in Adelaide, South Australia, before their admission to the psychiatric inpatient facility. Results: The time spent by patients in the ED waiting for admission to the psychiatric ward was significantly greater on weekends. There were significantly fewer discharges from the psychiatric ward during weekends compared with weekdays. The average time spent by patients in the ED requiring admission to the psychiatric ward for those days when there were vacant beds was 17.9 hours (SD=14.5). More people presented to the ED with a psychiatric diagnosis in the afternoons. There was a significant inverse correlation between the time spent by patients in the ED requiring admission to the psychiatric ward per day and the number of discharges from the psychiatric ward per day. Conclusion: These findings demonstrate that patient flow is significantly slower on weekends because of fewer discharges from the ward, leading to longer times spent in the ED before ward transfer. Waiting times in the ED were very substantially greater than the proposed 4-hour target even when vacant beds were available, raising considerable doubt about that target being realistic for psychiatric patients.
Comprehension and companionship in the emergency department as predictors of treatment adherence
Authors: Nitzan Uri , Hirsch Efrat , Walter Garry , Lurie Ido , Aviram Shai , Bloch Yuval 
Published: March 2012

Objective: Lack of adherence to recommended treatment poses major clinical and economic challenges for psychiatry, and requires further examination. In this pilot study, we aimed to prospectively investigate the association between the level of understanding of psychiatric emergency department (ED) discharge recommendations and the presence of a companion with short-term treatment adherence. Method: Sixty subjects were evaluated twice: upon ED discharge and a month later. Instruments included a structured questionnaire based on the MacArthur Competence Assessment Tool for Treatment, Mini Mental State Examination, and corroboration of data with the computerized hospital medical file. In order to control for the possibility that evaluation of the understanding of recommendations might positively influence adherence, the 60 subjects were randomly assigned into 50 who were interviewed with the full survey tool and 10 who were not asked questions about their understanding of treatment and/or follow-up recommendations. Results: Understanding of discharge recommendations and the presence of a companion enhanced adherence. Conclusions: This preliminary study suggests that ensuring patients’ understanding of treatment recommendations and encouraging the company of patients are achievable, practical strategies that may improve adherence and thereby promote better outcomes.
Castoriadis as a civilizational analyst
Authors: Arnason Johann P. 
Published: March 2012

This article argues that a civilizational perspective is central to Castoriadis’s interpretation of ancient Greece, even if he does not use the language of civilizational analysis. More specifically, his line of argument has clear affinities with Eisenstadt’s definition of the ‘civilizational dimension’ in terms of connections between cultural interpretations of the world and institutional forms of social life. Castoriadis has less to say about geocultural and geopolitical structures of the Greek world, which would also be important topics for a balanced civilizational approach. His distinctive variation on the civilizational theme rests on the idea of social imaginary significations; in the ancient Greek case, this starting point leads to the reconstruction of a ‘primary grasp of the world’, an imaginary core that conditions further developments and innovations. This core component of Greek culture centres on the human condition as the existence of mortals in a world characterized by imperfect order and underlying chaos. The Homeric poems are Castoriadis’s main source for the contents and directions of this original Greek imaginary. He understands the Homeric world as a framework within which the transformation of the polis towards autonomy could be initiated. Thus, the result is a strong emphasis on the archaic period as a formative phase of the whole Greek civilizational trajectory.
A generalization and improvement of Chidume theorems for total asymptotically nonexpansive mappings in Banach spaces
Authors: Chang Shih-sen , Kim Jong Kyu , Lee H W Joseph , Chan Chi Kin 
Published: March 2012

Abstract
The purpose of this article is to establish some new approximation theorems of common fixed points for a countable family of total asymptotically quasi-nonexpansive mappings in Banach spaces which generalize and improve the corresponding theorems of Chidume et al. and others.

2000 AMS Subject Classification: 47J05; 47H09; 49J25.