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Showing 981–1000 of 2058 publications.
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Bhandare, Amol M.; Mohammed, Suja; Pilowsky, Paul M.; Farnham, M. M. J.Seizures are accompanied by cardiovascular changes that are a major cause of sudden unexpected death in epilepsy (SUDEP). Seizures activate inflammatory responses in the cardiovascular nuclei of the medulla oblongata and increase neuronal excitability. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with autocrine and paracrine neuroprotective properties. Microglia are key players in inflammatory responses in the CNS.Wesought to determine whether PACAP and microglia mitigate the adverse effects of seizure on cardiovascular function in a rat model of temporal lobe epilepsy. Kainic acid (KA)-induced seizures increased splanchnic sympathetic nerve activity by 97%, accompanied by increase in heart rate (HR) but not blood pressure (BP). Intrathecal infusion of the PACAP antagonist PACAP(6-38) or the microglia antagonists minocycline and doxycycline augmented sympathetic responses to KAinduced seizures. PACAP(6-38) caused a 161% increase, whereas minocycline and doxycycline caused a 225% and 215% increase, respectively. In intrathecal PACAP-antagonist-treated rats, both BP and HR increased, whereas after treatment with microglial antagonists, only BP was significantly increased compared with control. Our findings support the idea that PACAP and its action on microglia at the level of the spinal cord elicit cardioprotective effects during seizure. However, intrathecal PACAP did not show additive effects, suggesting that the agonist effect was at maximum. The protective effect of microglia may occur by adoption of an M2 phenotype and expression of factors such as TGF-? and IL-10 that promote neuronal quiescence. In summary, therapeutic interventions targeting PACAP and microglia could be a promising strategy for preventing SUDEP. 2015 the authors.
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Pilowsky, Paul M.[No abstract available]
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Machaalani, Rita; Ghazavi, Emma; Hinton, Tina; Waters, Karen Ann; Hennessy, AnnemarieSmoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 ?, 4 ?, and 1 ?, ? and ? subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n. =. 8) to controls (n. =. 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of ?2, ?3, ?4, ?9, ?2 and ?4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the ?9 subunit, and decreased expression of the ? subunit. At the protein level, expression of both ?9 and ? was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically ?9 and ? subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (?9), and increased calcification and apoptosis (?), seen in the placentas of smoking women. 2014 Elsevier Inc.
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Lambert, Gilles; Petrides, Francine; Chatelais, Mathias; Blom, Dirk J.; Choque, Benjamin; Tabet, Fatiha; Wong, Gida; Rye, Kerry Anne; Hooper, Amanda J.; Burnett, John R.; Barter, Philip J.; Marais, Adrian DavidObjectives Do elevated proprotein convertase subtilisin/kexin type 9 (PCSK9) levels constitute an even greater risk for patients who already have reduced low-density lipoprotein receptor (LDLR) levels, such as those with heterozygous familial hypercholesterolemia (HeFH)? Background As a circulating inhibitor of LDLR, PCSK9 is an attractive target for lowering LDL-cholesterol (LDL-C) levels. Methods Circulating PCSK9 levels were measured by enzyme-linked immunosorbent assay in nontreated patients with HeFH carrying a D206E (n = 237), V408M (n = 117), or D154N (n = 38) LDLR missense mutation and in normolipidemic controls (n = 152). Skin fibroblasts and lymphocytes were isolated from a subset of patients and grown in 0.5% serum and mevastatin with increasing amounts of recombinant PCSK9. LDLR abundance at the cell surface was determined by flow cytometry. Results PCSK9 reduced LDLR expression in a dose-dependent manner in control and FH fibroblasts to similar extents, by up to 77 8% and 82 7%, respectively. Likewise, PCSK9 reduced LDLR abundance by 39 8% in nonfamilial hypercholesterolemia (non-FH) and by 45 10% in HeFH lymphocytes, irrespective of their LDLR mutation status. We found positive correlations of the same magnitude between PCSK9 and LDL-C levels in controls (beta = 0.22; p = 0.0003), D206E (beta = 0.20; p = 0.0002), V408M (beta = 0.24; p = 0.0002), and D154N (beta = 0.25; p = 0.048) patients with HeFH. The strengths of these associations were all similar. Conclusions Elevated PCSK9 levels are equally detrimental for patients with HeFH or non-FH: a 100-ng/ml increase in PCSK9 will lead to an increase in LDL-C of 0.20 to 0.25 mmol/l in controls and HeFH alike, irrespective of their LDLR mutation. This explains why patients with non-FH or HeFH respond equally well to monoclonal antibodies targeting PCSK9. 2014 by the American College of Cardiology Foundation Published by Elsevier Inc.
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Luo, Lin; Wall, A. A.; Yeo, Jeremy Changyu; Condon, Nicholas D.; Norwood, Suzanne J.; Schoenwaelder, Simone M.; Chen, Kaiwen W.; Jackson, Shaun P.; Jenkins, Brendan J.; Hartland, Elizabeth Louise; Schroder, Kate; Collins, Brett M.; Sweet, Matthew J.; Stow, Jennifer L.Toll-like receptor 4 (TLR4) is activated by bacterial lipopolysaccharide (LPS) to mount innate immune responses. The TLR4-induced release of pro- and anti-inflammatory cytokines generates robust inflammatory responses, which must then be restrained to avoid disease. New mechanisms for the critical regulation of TLR-induced cytokine responses are still emerging. Here we find TLR4 complexes localized in LPS-induced dorsal ruffles on the surface of macrophages. We discover that the small GTPase Rab8a is enriched in these ruffles and recruits phosphatidylinositol 3-kinase (PI3K 3) as an effector by interacting directly through its Ras-binding domain. Rab8a and PI3K 3 function to regulate Akt signalling generated by surface TLR4. Rab8a and PI3K 3 do not affect TLR4 endocytosis, but instead regulate mammalian target of rapamycin signalling as a mechanism for biasing the cytokine profile to constrain inflammation in innate immunity. 2014 Macmillan Publishers Limited. All rights reserved.
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Managing antithrombotic therapy in patients with both atrial fibrillation and coronary heart diseaseThompson, Peter Lindsay; Verheugt, Freek W.AaPurpose: Atrial fibrillation (AF) and coronary heart disease (CHD) commonly occur together. Previous consensus guidelines were published before the wide availability of novel oral anticoagulants (NOACs) and newer P2Y<inf>12</inf> antiplatelet agents. We examine recent evidence to guide management in 3 categories of patients with AF and CHD: patients with stable CHD, nonstented patients with recent acute coronary syndrome, and patients with a coronary stent requiring dual-antiplatelet therapy. Methods: We conducted a literature search by evaluation of PubMed and other data sources including international meeting reports. We critically reviewed recent clinical trial and relevant registry evidence to update European and US consensus documents. Findings: Oral anticoagulation with warfarin or NOACs is required to prevent embolic stroke in AF, and antiplatelet therapy is insufficient for this purpose. Antiplatelet therapy using monotherapy with aspirin is the standard of care in stable CHD. Dualantiplatelet therapy with aspirin and clopidogrel or a new P2Y<inf>12</inf> inhibitor (dual-antiplatelet therapy) is needed to reduce coronary events after an acute coronary syndrome or after percutaneous coronary intervention. Combinations of these agents increase the risk of bleeding, and limited clinical trial evidence suggests that withdrawal of aspirin may reduce bleeding without increasing coronary events. Implications: Available clinical trials and registries provide remarkably little evidence to guide difficult clinical decision making in patients with combined AF and CHD. In patients on triple antithrombotic therapy with vitamin K antagonists, aspirin, and clopidogrel, a single clinical trial indicates that withdrawal of aspirin may reduce bleeding risk without increasing the risk of coronary thrombosis. It is unclear whether this evidence applies to combinations of NOACs and newer P2Y<inf>12</inf> inhibitors. Clinical trials of combinations of the newer antithrombotic agents are urgently needed to guide clinical care. 2014, Elsevier HS Journals, Inc. All rights reserved.
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Lecce, Laura; Lam, Yuen Ting; Lindsay, Laura A.; Yuen, Sui Ching G.; Simpson, Philippa J.L.; Handelsman, David J.; Ng, Martin K.C.There is a progressive impairment of vascular repair mechanisms with advancing age concomitant with a steady decline in circulating androgen levels in men. Emerging evidence indicates androgens regulate angiogenesis; however, little research has focused on the impact of age upon androgen-mediated regulation of angiogenic mechanisms. Human dermal fibroblasts from young (<30 years) and older (>65 years) men were incubated with DHT, with or without androgen receptor antagonist hydroxyflutamide, or phosphoinositide 3-kinase inhibitor. Fibroblast-conditioned medium was used to stimulate angiogenic functions in human umbilical vein endothelial cells. Nuclear fractionation and fluorescence microscopy were used to study androgen receptor (AR) distribution. Conditioned medium from fibroblasts of young men, but not old men, treated with DHT produced a 3-fold increase in human umbilical vein endothelial cell tubulogenesis and 2-fold increase in migration via increased vascular endothelial growth factor (VEGF) expression and secretion, predominantly of VEGF145. DHT-induced VEGF secretion from fibroblasts of young men was AR-dependent and increased AKT phosphorylation, which was abrogated by phosphoinositide 3-kinase inhibition. By contrast, fibroblasts from older men were unresponsive to DHT and lacked androgen-mediated enhancement in VEGF production. These findings were associated with reduced AR nuclear translocation in old fibroblasts. The failure of DHT-induced paracrine stimulation of angiogenesis in fibroblasts from older men is likely due to defective nuclear translocation of AR. This first demonstration of androgen resistance (or insensitivity) acquired by human fibroblasts with aging suggests that pharmacological testosterone therapy for old men may be less effective in enhancing angiogenesis and facilitating tissue regeneration mechanisms reliant on paracrine release of VEGF.
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Islam, Shahidul M.; Esselle, Karu P.; Bull, David; Pilowsky, Paul M.The main aim of our research is to convert an existing ultra-high frequency (UHF) telemetry system, operating in free space, to an implantable telemetry system. This system, based on active radio-frequency identification (RFID) technology, will be initially implanted in rats for transmission of physiological signals to a monitoring station outside the cage. Designing an implantable compact antenna to suit the space available in the active RFID tag is the most important step in this conversion. In this paper, two placements options are considered - on the ground-plane side and on the component-side of the tag. Novel implantable planar inverted-F antennas (PIFAs) with biocompatible material coatings were designed for each case. The ground plane of the antenna, together with the tag circuit ground, helped to reduce radiation into the rat's body. A rat tissue model is considered and the critical design parameters such as biocompatible coating permittivity, that have a profound effect on antenna performance, are identified. The input reflection coefficient, radiation pattern and efficiency are presented. 2014 IEEE.
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Cao, Lei; Pilowsky, Paul M.Objective: To investigate the role of the sympathetic nervous system in the cardiovascular response to quiet standing in the postprandial state. Method: Following a 30. min pre-ingestion phase, 14 healthy young male subjects consumed a 600. kcal carbohydrate-rich meal. Arterial blood pressure (BP) and heart rate (HR) were recorded for a further 120. min. Measurements were obtained (Finometer) in both the supine (5. min) and standing (5. min) condition every 30. min. Power spectral analysis of RR-interval and BP variability was calculated, and heart rate responses to the baroreceptor reflex were calculated to estimate spontaneous baroreflex sensitivity (sBRS). Derived stroke volume (SV) was measured to track changes to postural stress postprandially. Results: Quiet standing increased RR-interval low frequency power, ratio of RR-interval low frequency power/high frequency power (ratio of RR LF/HF), and systolic BP low frequency power (SBP LF power), and decreased RR HF power and sBRS before, and after eating. After meal ingestion, SBP LF power increased and sBRS decreased in lying and standing conditions. During quiet standing postprandially, DBP and the mean arterial pressure increased (P<0.01). The increased BP is associated with increased SV (P<0.05) early postprandially, and increased SBP LF power (P<0.01) in the later postprandial phase. SBP LF power is inversely correlated with SV postprandially (P<0.001, R2=0.96). Conclusion: The findings suggest a sympathetic activation mediated by baroreflex resetting. Quiet standing in the postprandial state enhances sympathetic outflow to the vasculature, increasing BP. SV may be a compensatory factor stabilising BP during quiet standing early postprandially. 2014.
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Vickers, Kasey C.; Landstreet, Stuart R.; Levin, Michael G.; Shoucri, Bassem M.; Toth, Cynthia L.; Taylor, Robert C.; Palmisano, Brian T.; Tabet, Fatiha; Cui, Huanhuan L.; Rye, Kerry Anne; Sethupathy, Praveen; Remaley, Alan ThomasMicroRNAs (miRNAs) regulate a wide variety of biological processes and contribute to metabolic homeostasis. Here, we demonstrate that microRNA-223 (miR-223), an miRNA previously associated with inflammation, also controls multiple mechanisms associated with cholesterol metabolism. miR-223 promoter activity and mature levels were found to be linked to cellular cholesterol states in hepatoma cells. Moreover, hypercholesterolemia was associated with increased hepatic miR-223 levels in athero-prone mice. miR-223 was found to regulate high-density lipoprotein-cholesterol (HDL-C) uptake, through direct targeting and repression of scavenger receptor BI, and to inhibit cholesterol biosynthesis through the direct repression of sterol enzymes 3-hydroxy-3-methylglutaryl-CoA synthase 1 and methylsterol monooxygenase 1 in humans. Additionally, miR-223 was found to indirectly promote ATP-binding cassette transporter A1 expression (mRNA and protein) through Sp3, thereby enhancing cellular cholesterol efflux. Finally, genetic ablation of miR-223 in mice resulted in increased HDL-C levels and particle size, as well as increased hepatic and plasma total cholesterol levels. In summary, we identified a critical role for miR-223 in systemic cholesterol regulation by coordinated posttranscriptional control of multiple genes in lipoprotein and cholesterol metabolism.
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Xia, Qiong; Kahramanian, Andranik; Arnott, Clare; Bao, Shishan San; Patel, Sanjay[No abstract available]
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Hawkins, Clare L.Cyanate is a uremic toxin responsible for the carbamylation of proteins, which has been implicated as playing a key role in accelerating the progression of atherosclerosis in patients with chronic kidney disease. El-Gamal et al. report that while cyanate promotes protein carbamylation in vivo, the resulting endothelial dysfunction observed is consistent with reactions mediated by cyanate itself, rather than by carbamylated proteins. This provides new insight into the relationship between uremia and cardiovascular disease. 2014 International Society of Nephrology.
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Young, Jennifer A.; Ting, Kaka; Li, Jia; Mler, Thorleif; Dunn, Louise L.; Lu, Ying; Lay, Angelina J.; Moses, Joshua; Prado-Louren, Leonel; Khachigian, Levon M.; Ng, Martin; Gregory, Philip A.; Goodall, Gregory J.; Tsykin, Anna; Lichtenstein, Ilana; Hahn, Christopher N.; Tran, Nham T.; Shackel, Nicholas Adam; Kench, J. G.; McCAUGHAN, G. W.; Vadas, Mathew A.; Gamble, Jennifer R.[No abstract available]
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Islam, Shahidul M.; Esselle, Karu P.; Bull, David; Pilowsky, Paul M.This paper compares the performance of two compact implantable planar inverted-F antennas (I-PIFAs) designed to operate in the UHF ISM band around 900MHz. The total dimensions of Antenna 1 (Hilbert I-PIFA) and Antenna 2 (planar strip I-PIFA) are 253.6mm3 and 13.5114.25mm3, respectively. A trade-off between the size, bandwidth and radiation efficiency is demonstrated. The larger antenna has a wider bandwidth as expected but both antennas operate well over the Australian ISM band. The radiation efficiencies of the two antennas, when implanted inside a rat, are 1.3% and 0.38%, respectively. 2014 IEEE.
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Jongberg, Sisse; Lund, Marianne Nissen; Skibsted And, Leif H.; Davies, Michael J.Radical transfer from perferrylmyoglobin to other target species (myofibrillar proteins, MPI) and bovine serum albumin (BSA), extracts from green tea (GTE), mat(ME), and rosemary (RE), and three phenolic compounds, catechin, caffeic acid, and carnosic acid) was investigated by electron paramagnetic resonance (EPR) spectroscopy to determine the concentrations of plant extracts required to protect against protein oxidation. Blocking of MPI thiol groups by N-ethylmaleimide was found to reduce the rate of reaction of MPI with perferrylmyoglobin radicals, signifying the importance of protein thiols as radical scavengers. GTE had the highest phenolic content of the three extracts and was most effective as a radical scavenger. IC<inf>50</inf> values indicated that the molar ratio between phenols in plant extract and MPI thiols needs to be >15 in order to obtain efficient protection against protein-to-protein radical transfer in meat. Caffeic acid was found most effective among the plant phenols. 2014 American Chemical Society.
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Deng, Wei; Goldys, Ewa M.; Farnham, M. M. J.; Pilowsky, Paul M.Neuronal stimulation by light is a novel approach in the emerging field of optogenetics, where genetic engineering is used to introduce light-activated channels. However, light is also capable of stimulating neurons even in the absence of genetic modifications through a range of physical and biological mechanisms. As a result, rigorous design of optogenetic experiments needs to take note of alternative and parallel effects of light illumination of neuronal tissues. Thus all matters relating to light penetration are critical to the development of studies using light-activated proteins. This paper discusses ways to quantify light, light penetration in tissue, as well as light stimulation of neurons in physiological conditions. We also describe the direct effect of light on neurons investigated at different sites. 2014 the American Physiological Society.
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Samaras, Katherine; Morris, Margaret J.; Lord, Reginald V.; Kavurma, Mary M.Background and aims: Bariatric surgery improves health outcomes in the obese and reduces some aspects of obesity-associated systemic inflammation. Little is known however about its effects on circulating TNF-related apoptosis-inducing ligand (TRAIL) and osteoprotegerin level, which regulate apoptosis and are implicated in atherogenesis. Our objective was to identify whether circulating TRAIL and osteoprotegerin levels are influenced by the energy restriction and weight loss that follows bariatric surgery in obese patients with glucose disorders. Methods: 15 morbidly obese individuals with type 2 diabetes mellitus (T2D) or glucose intolerance were recruited for bariatric surgery. Participants were assessed for weight, waist circumference and BMI at baseline, then 2 and 12 weeks following energy restriction with bariatric surgery. Laparoscopic adjustable gastric band placement was performed. Fasted blood samples were collected and an oral glucose tolerance test was performed at each visit. Metabolic parameters and plasma chemistries were assessed. Circulating TRAIL, osteoprotegerin and leptin levels were measured. Results: A significant increase in circulating TRAIL levels was observed at 12 weeks relative to baseline in participants who suppressed leptin levels. The percentage change in TRAIL was inversely related to the percentage change in fasting insulin and HOMA-?. In contrast, osteoprotegerin levels and the osteoprotegerin:TRAIL ratio were significantly reduced following bariatric surgery. The change in osteoprotegerin:TRAIL ratio positively related to the percentage change in fasting glucose. Conclusions: Energy restriction after bariatric surgery is associated with increased circulating TRAIL levels and reduced osteoprotegerin levels and osteoprotegerin:TRAIL ratio in obese humans with dysglycaemia. Changes in the TRAIL and osteoprotegerin:TRAIL ratio related to changes in fasting insulin, suggesting a possible role in glucose improvements after bariatric surgery. Mechanistic studies will clarify the role of TRAIL and osteoprotegerin in health and disease. 2014 .
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Yeo, Giselle C.; Baldock, Clair; Wise, Steven G.; Weiss, Anthony StevenTropoelastin is an extracellular matrix protein that assembles into elastic fibers that provide elasticity and strength to vertebrate tissues. Although the contributions of specific tropoelastin regions during each stage of elastogenesis are still not fully understood, studies predominantly recognize the central hinge/bridge and C-terminal foot as the major participants in tropoelastin assembly, with a number of interactions mediated by the abundant positively charged residues within these regions. However, much less is known about the importance of the rarely occurring negatively charged residues and the N-terminal coil region in tropoelastin assembly. The sole negatively charged residue in the first half of human tropoelastin is aspartate 72. In contrast, the same region comprises 17 positively charged residues. We mutated this aspartate residue to alanine and assessed the elastogenic capacity of this novel construct. We found that D72A tropoelastin has a decreased propensity for initial self-association, and it cross-links aberrantly into denser, less porous hydrogels with reduced swelling properties. Although the mutant can bind cells normally, it does not form elastic fibers with human dermal fibroblasts and forms fewer atypical fibers with human retinal pigmented epithelial cells. This impaired functionality is associated with conformational changes in the N-terminal region. Our results strongly point to the role of the Asp-72 site in stabilizing the N-terminal segment of human tropoelastin and the importance of this region in facilitating elastic fiber assembly. 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
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Bonifay, Vincent; Barrett, Tessa J.; Pattison, David I.; Davies, Michael J.; Hawkins, Clare L.; Ashby, Michael T.Human defensive peroxidases, including lactoperoxidase (LPO) and myeloperoxidase (MPO), are capable of catalyzing the oxidation of halides (X-) by H<inf>2</inf>O<inf>2</inf> to give hypohalous acids (HOX) for the purpose of cellular defense. Substrate selectivity depends upon the relative abundance of the halides, but the pseudo-halide thiocyanate (SCN-) is a major substrate, and sometimes the exclusive substrate, of all defensive peroxidases in most physiologic fluids. The resulting hypothiocyanous acid (HOSCN) has been implicated in cellular damage via thiol oxidation. While thiols are believed to be the primary target of HOSCN in vivo, Trp residues have also been implicated as targets for HOSCN. However, the mechanism involved in HOSCN-mediated Trp oxidation was not established. Trp residues in proteins appeared to be susceptible to oxidation by HOSCN, whereas free Trp and Trp residues in small peptides were found to be unreactive. We show that HOSCN-induced Trp oxidation is dependent on pH, with oxidation of free Trp, and Trp-containing peptides observed when the pH is below 2. These conditions mimic those employed previously to precipitate proteins after treatment with HOSCN, which accounts for the discrepancy in the results reported for proteins versus free Trp and small peptides. The reactant in these cases may be thiocyanogen ((SCN)<inf>2</inf>), which is produced by comproportionation of HOSCN and SCN- at low pH. Reaction of thiocyanate-derived oxidants with protein Trp residues at low pH results in the formation of a number of oxidation products, including mono- and di-oxygenated derivatives, which are also formed with other hypohalous acids. Our data suggest that significant modification of Trp by HOSCN in vivo is likely to have limited biological relevance. 2014 Elsevier Inc.
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Arsenault, Beno J.; Barter, Philip J.; DeMicco, David A.; Bao, Weihang; Preston, Gregory M.; LaRosa, John C.; Grundy, Scott M.; Deedwania, Prakash ?.; Greten, Heiner; Wenger, Nanette Kass; Shepherd, James; Waters, David D.; Kastelein, Johannes Jacob PieterSeveral plasma non-lipid biomarkers have been shown to predict major cardiovascular events (MCVEs) in population studies. Our objective was to investigate the relationship between lipid and non-lipid biomarkers levels achieved during statin therapy and the incidence of MCVEs in patients with stable coronary heart disease (CHD). We conducted a substudy of the TNT (Treating to New Targets) study, which was a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of CHD. Fasting plasma levels of standard lipids and of 18 non-lipid biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in 157 patients who experienced MCVEs during the 4.9 years of study follow-up and in 1349 controls. MCVE was defined as CHD death, nonfatal, non-procedure-related myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke. After adjusting for age, sex and treatment arm, plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), insulin, neopterin, N-terminal pro-brain natriuretic peptide (BNP), lipoprotein(a) [Lp(a)], and the soluble receptor for advanced glycation end products (sRAGE) were predictive - 2014 Arsenault et al. This Funding: This study was funded by Pfizer Inc. Benoit J. Arsenault is supported by a post-doctoral fellowship from the Fonds de la recherche en santdu Quec and the Fondation de l9Institut universitaire de cardiologie et de pneumologie de Quec. Two authors are Pfizer employees and may hold stock in the company. As sponsor, Pfizer in cooperation with the steering committee had a role in all aspects of the study. The secondary biomarker analysis was funded by Pfizer. However, the decision to publish and preparation of the manuscript was driven solely by the authors. of recurrent MCVEs (P#0.02 for each doubling of plasma concentration). However, no significant association was observed between the risk of recurrent MCVEs and plasma levels of low-density lipoprotein cholesterol, adiponectin, cystatin C, lipoprotein-associated phospholipase A2, monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, osteopontin, soluble CD40 ligand, soluble intercellular adhesion molecule-1, or soluble vascular cell adhesion molecule-1. After further adjustment for diabetes, hypertension, smoking, and BMI, the relationship between hsCRP, insulin and MCVE were no longer significant, while the relationship between Lp(a), neopterin, NT-proBNP and sRAGE and MCVE remained statistically significant. In conclusion, in patients with CHD treated with atorvastatin, plasma levels of Lp(a), neopterin, NT-proBNP, and sRAGE are associated with the risk of recurrent MCVEs.
