Metabolic changes in flatfish hepatic tumours revealed by NMR-based metabolomics and metabolic correlation networks.

Histopathologically well-characterized fish liver was analyzed by 800 MHz 1H NMR metabolomics to identify metabolic changes between healthy and tumor tissue. Data were analyzed by multivariate statistics and metabolic correlation networks, and results revealed elevated anaerobic metabolism and reduced choline metabolism in tumor tissue. Significant negative correlations were observed between alanine-acetate (p = 3.

Ethnic variation in adverse cardiovascular outcomes and bleeding complications in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study.

Background: Atherothrombosis is a common condition affecting individuals worldwide. Its impact on different ethnic groups receiving evidence-based therapy is unclear. We aimed to determine if ethnicity is an independent predictor for cardiovascular events and bleeding complications in a contemporary clinical trial on antiplatelet therapy.

The anti-arrhythmic peptide AAP10 remodels Cx43 and Cx40 expression and function.

The anti-arrhythmic peptide AAP10 has previously been shown to acutely upregulate electrical cell-to-cell coupling mediated via connexin 43 gap junctions. In the present work, we have further examined the connexin (Cx) specificity and mechanism of action of this peptide in HeLa cells expressing Cx43, Cx40 or Cx26. The ability of cells to transfer the small fluorescent dyes Alexa 488 (MW 570) or Alexa 594 (MW 759), as markers for metabolic coupling mediated via gap junctions, before and after exposure to AAP10 and/or the protein kinase C inhibitor chelerythrine for 5 h was determined by microinjection analysis.

Relation between aspirin dose, all-cause mortality, and bleeding in patients with recent cerebrovascular or coronary ischemic events (from the BRAVO Trial).

Despite aspirin's established role in the treatment of atherosclerotic vascular disease, considerable controversy exists regarding its most effective dosing strategy. In a retrospective observational study, we examined the relation between prescribed aspirin dose (<162 mg vs > or =162 mg/day aspirin) and clinical outcome in 4,589 placebo-treated patients enrolled in the Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial over a median follow-up of 366 days. Standard Cox regression analysis was employed because propensity analysis was not feasible.

Formocresol blood levels in children receiving dental treatment under general anesthesia.

Purpose: The purpose of this study was to determine the presence of formocresol in the plasma of children undergoing oral rehabilitation involving pulp therapy under general anesthesia.

Methods: Thirty 2- to 6-year-old preschool children were enrolled in the study. Preoperative, intra-operative, and postoperative peripheral venous samples were collected from each child.

Incomplete inhibition of thromboxane biosynthesis by acetylsalicylic acid: determinants and effect on cardiovascular risk.

Background: Incomplete inhibition of platelet thromboxane generation, as measured by elevated urinary 11-dehydro thromboxane B(2) concentrations, has been associated with an increased risk of cardiovascular events. We aimed to determine the external validity of this association in aspirin-treated patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial and to determine whether there are any modifiable factors or interventions that lower urinary 11-dehydro thromboxane B(2) concentrations that could thereby reduce cardiovascular risk.

Methods And Results: Urinary 11-dehydro thromboxane B(2) concentrations were measured in 3261 aspirin-treated patients at least 1 month after they had been randomly assigned to placebo or clopidogrel.

Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

This article about treatment and prevention of stroke is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading, see the "Grades of Recommendations" chapter by Guyatt et al, CHEST 2008; 133:123S-131S).

Evaluation of a generic quality of life instrument for early childhood caries-related pain.

Objective: This prospective study evaluated the reliability and validity of the Infant and Toddler Child Quality of Life Questionnaire (ITQOL) by comparing quality of life (QOL) of two groups of children afflicted with early childhood dental caries with a caries-free group.

Methods: A convenience sample of 150 children divided into three groups (mean age [months] 51 +/- 15) was studied. Group I (OR) had extensive dental caries and were waiting for several months for treatment under general anesthesia.

Delusional disorder-jealous type: how inclusive are the DSM-IV diagnostic criteria?

Delusional disorder-jealous type is a new diagnostic category in the Diagnostic and Statistical Manual for Disorders, Fourth Edition, Text Revision (DSM-IV-TR; American Psychiatric Association, 2000) in which delusions concerning a partner's infidelity must be present. Therefore, patients who experience a jealousy disorder, but do not experience delusions will not fit the diagnostic criteria. Using a database of 398 case histories of jealousy disorders reported in the literature from 1940-2002, we examined the percentage of these cases that met the diagnostic criteria for delusional disorder-jealous type.

Structure and metal binding properties of ZnuA, a periplasmic zinc transporter from Escherichia coli.

ZnuA is the periplasmic Zn(2+)-binding protein associated with the high-affinity ATP-binding cassette ZnuABC transporter from Escherichia coli. Although several structures of ZnuA and its homologs have been determined, details regarding metal ion stoichiometry, affinity, and specificity as well as the mechanism of metal uptake and transfer remain unclear. The crystal structures of E.

Mortality, kidney disease and cardiac procedures following acute coronary syndrome.

Background: Cardiac interventions are underutilized in patients with chronic kidney disease (CKD) following acute coronary syndrome (ACS) partly due to nephrotoxicity concerns.

Methods: We analyzed outcomes of 4631 subjects with ACS enrolled in the Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion trial, including time to death, time to reduced renal function (50% reduction in estimated glomerular filtration rate (eGFR) or development of end-stage renal disease (ESRD)) and percent change in eGFR from baseline.

Results: Subjects with a lower baseline eGFR were more likely to be older, female and have diabetes, hypertension, congestive heart failure or peripheral vascular disease (all P < 0.

Risk for cardiovascular outcomes among subjects with atherosclerotic cardiovascular disease and greater-than-normal estimated glomerular filtration rate.

Background And Objectives: Estimating equations for calculating glomerular filtration rate (eGFR) occasionally identify patients with elevated eGFR, yet the prognostic significance remains to be determined. This study sought to define the association of an elevated eGFR on the risk for death and cardiovascular outcomes among subjects with atherosclerotic cardiovascular disease.

Design, Setting, Participants, & Measurements: Data from 8941 subjects who had a history of atherosclerotic vascular disease and were enrolled in the Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion trial were analyzed.

Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial.

Objectives: The purpose of this study was to determine the possible benefit of dual antiplatelet therapy in patients with prior myocardial infarction (MI), ischemic stroke, or symptomatic peripheral arterial disease (PAD).

Background: Dual antiplatelet therapy with clopidogrel plus aspirin has been validated in the settings of acute coronary syndromes and coronary stenting. The value of this combination was recently evaluated in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial, where no statistically significant benefit was found in the overall broad population of stable patients studied.

Negative regulation of ASK1 by p21Cip1 involves a small domain that includes Serine 98 that is phosphorylated by ASK1 in vivo.

The cyclin-dependent kinase inhibitor p21(Cip1) regulates multiple cellular functions and protects cells from genotoxic and other cellular stresses. Activation of apoptosis signal-regulating kinase 1 (ASK1) induced by inhibition of mTOR signaling leads to sustained phospho-c-Jun that is suppressed in cells with functional p53 or by forced expression of p21(Cip1). Here we show that small deletions of p21(Cip1) around S98 abrogate its association with ASK1 but do not affect binding to Cdk1, hence distinguishing between the cell cycle-regulating functions of p21(Cip1) and its ability to suppress activation of the ASK1/Jun N-terminal protein kinase (JNK) pathway.

Time-dependent translational response of E. coli to excess Zn(II).

Zinc homeostasis is not well understood beyond methods of import and export. In order to better understand zinc homeostasis in Escherichia coli by identifying Zn(II)-responsive proteins, a proteomic approach was taken. Through the use of two-dimensional gel electrophoresis, we were able to show that the levels of OmpF, AspC, YcdO, Eno, and CysE increased after 30 min of Zn(II) stress, while the levels of Tig, TufA, SelA, and LeuC decreased relative to non-stressed controls.

mTOR and cancer therapy.

Proteins regulating the mammalian target of rapamycin (mTOR), as well as some of the targets of the mTOR kinase, are overexpressed or mutated in cancer. Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of recently developed rapamycin analogs (rapalogs) consisting of synthetically derived compounds containing minor chemical modifications to the parent structure, inhibit the growth of cell lines derived from multiple tumor types in vitro, and tumor models in vivo. Results from clinical trials indicate that the rapalogs may be useful for the treatment of subsets of certain types of cancer.

Transcriptional response of Escherichia coli to TPEN.

DNA microarrays were used to probe the transcriptional response of Escherichia coli to N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). Fifty-five transcripts were significantly up-regulated, including all of the genes that are regulated by Zur and many that are regulated by Fur. In the same TPEN-treated cells, 46 transcripts were significantly down-regulated.

Probing the adaptive response of Escherichia coli to extracellular Zn(II).

The adaptive response of Escherichia coli cells to differing intracellular and extracellular Zn(II) concentrations was evaluated by two-dimensional gel electrophoresis and peptide identifications. Twenty-one Zn(II)-responsive proteins, which were previously not known to be associated with Zn(II), were identified. Most of the proteins were related to cellular metabolism and include membrane transporters and glycolytic and TCA-associated enzymes.

Statin use and sex-specific stroke outcomes in patients with vascular disease.

Background And Purpose: Although statins reduce the risk of stroke in patients with coronary heart disease, possible differing effects of statins on stroke outcomes based on sex remain uncertain. We investigated the relationships between statin use and sex-specific stroke incidence, severity, and mortality.

Methods: Data from 3 trials of oral glycoprotein IIb/IIIa inhibitors (first and second Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes [SYMPHONY] and Blockade of the glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion [BRAVO]) were pooled and stroke outcomes compared among 8191 baseline statin users versus 14,752 nonusers.

The protein tyrosine phosphatase, Shp2, is required for the complete activation of the RAS/MAPK pathway by brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) and other neurotrophins induce a unique prolonged activation of mitogen-activated protein kinase (MAPK) compared with growth factors. Characterization and kinetic and spatial modeling of the signaling pathways underlying this prolonged MAPK activation by BDNF will be important in understanding the physiological role of BDNF in many complex systems in the nervous system. In addition to Shc, fibroblast growth factor receptor substrate 2 (FRS2) is required for the BDNF-induced activation of MAPK.

Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.

Background: Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events.

Methods: We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes.

IRS-1: auditing the effectiveness of mTOR inhibitors.

Rapamycin analogs that inhibit mTOR signaling have antitumor activity against certain lymphomas, but treatment of solid tumors has been less encouraging despite inhibition of mTOR function. Two recent papers give insight into the potential use of mTOR inhibitors. O'Reilly et al.

A global view of atherothrombosis: baseline characteristics in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial.

Background: The manifestations of atherothrombosis such as myocardial infarction, ischemic stroke, limb ischemia, or cardiovascular death pose a global health care burden. Additional therapies to decrease ischemic events in patients with established vascular disease or at risk for developing vascular disease are necessary. We sought to characterize the risk factors and treatments of a diverse contemporary population of patients with atherothrombosis.