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Showing 1021–1040 of 2058 publications.
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Comparison of indirect and direct blood pressure measurements in baboons during ketamine anaesthesiaYeung, Kristen R.; Lind, Joanne Maree; Heffernan, Scott J.; Sunderland, Neroli; Hennessy, Annemarie; Makris, AngelaBackground: The aim of this study was to assess agreement between different methods of blood pressure measurement in anaesthetised baboons. Methods: Systolic and diastolic blood pressure (SBP and DBP) were measured in anaesthetised baboons using intra-arterial radiotelemetry, automated oscillometry and mercury sphygmomanometry. Correlation between the different methods was assessed. Results: The correlation between intra-arterial radiotelemetry and automated oscillometry was 0.9 (P < 0.001) for SBP and 0.9 (P < 0.001) for DBP. Between-method differences were -4.4 7.2 mm Hg for SBP and -3.4 7.1 mm Hg for DBP. For automated oscillometry vs. mercury sphygmomanometry, correlation was 0.4 for both SBP (P < 0.001) and DBP (P < 0.001). Between-method differences were 7.9 12.7 mm Hg for SBP and 7.3 12.6 mm Hg for DBP. Conclusions: Our study demonstrates that automated oscillometry may be an appropriate alternative to telemetry for measuring blood pressure in anaesthetised baboons. 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Liu, Hongjuan; Wise, Steven G.; Rnjak-Kovacina, Jelena; Kaplan, David L.; Bilek, Marcela M.M.; Weiss, Anthony Steven; Fei, Jian; Bao, Shishan SanBlended polymers are used extensively in many critical medical conditions as components of permanently implanted devices. Hybrid protein polymers containing recombinant human tropoelastin and silk fibroin have favorable characteristics as implantable scaffolds in terms of mechanical and biological properties. A firefly luciferase transgenic mouse model was used to monitor real-time IL-1? production localized to the site of biomaterial implantation, to observe the acute immune response (up to 5 days) to these materials. Significantly reduced levels of IL-1? were observed in silk/tropoelastin implants compared to control silk only implants at 1, 2 and 3 days post-surgery. Subsequently, mice (n = 9) were euthanized at 10 days (10D) and 3 weeks (3W) post-surgery to assess inflammatory cell infiltration and collagen deposition, using histopathology and immunohistochemistry. Compared to control silk only implants, fewer total inflammatory cells were found in silk/tropoelastin (~29% at 10D and ~47% at 3W). Also fewer ingrowth cells (~42% at 10D and ~63% at 3W) were observed within the silk/tropoelastin implants compared to silk only. Lower IL-6 (~52%) and MMP-2 (~84%) (pro-inflammatory) were also detected for silk/tropoelastin at 10 days. After 3 weeks implantation, reduced neovascularization (vWF ~43%), fewer proliferating cells (Ki67 ~58% and PCNA ~41%), macrophages (F4/80 ~64%), lower IL-10 (~47%) and MMP-9 (~55%) were also observed in silk/tropoelastin materials compared to silk only. Together, these results suggest that incorporation of tropoelastin improves on the established biocompatibility of silk fibroin, uniquely measured here as a reduced foreign body inflammatory response. 2014.
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Rayner, Benjamin Saul; Love, Dominic T.; Hawkins, Clare L.Myeloperoxidase is an important heme enzyme released by activated leukocytes that catalyzes the reaction of hydrogen peroxide with halide and pseudo-halide ions to form various hypohalous acids. Hypohalous acids are chemical oxidants that have potent antibacterial, antiviral, and antifungal properties and, as such, play key roles in the human immune system. However, increasing evidence supports an alternative role for myeloperoxidase-derived oxidants in the development of disease. Excessive production of hypohalous acids, particularly during chronic inflammation, leads to the initiation and accumulation of cellular damage that has been implicated in many human pathologies including atherosclerosis, neurodegenerative disease, lung disease, arthritis, inflammatory cancers, and kidney disease. This has sparked a significant interest in developing a greater understanding of the mechanisms involved in myeloperoxidase-derived oxidant-induced mammalian cell damage. This article reviews recent developments in our understanding of the cellular reactivity of hypochlorous acid, hypobromous acid, and hypothiocyanous acid, the major oxidants produced by myeloperoxidase under physiological conditions. 2014 Elsevier Inc.
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Thompson, Peter Lindsay; Judkins, Christopher; Thompson, Angus G.After recovery from myocardial infarction, patients should receive aspirin and statin therapy and be evaluated regarding their need for coronary revascularisation, additional pharmacological treatment and possible device therapy.
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Xu, Bei; Charlton, Francesca; Makris, Angela; Hennessy, AnnemarieIntroduction The interaction between trophoblast cells and maternal uterine endothelium is important for placental vascular modelling. Nitric oxide (NO) is a potent vasorelaxant that regulates systemic blood pressure and is reduced in preeclampsia. NO may affect placental cell interaction. Objectives This study was to examine whether NO plays a role in regulating TNF-? induced inhibition of trophoblast cell integration into endothelial cellular networks in-vitro. Methods Red fluorescent-labelled human uterine myometrial microvascular endothelial cells (UtMVECs) were seeded on Matrigel. After endothelial cellular networks formed, green fluorescent-labelled HTR-8/SVneo trophoblast cells were co-cultured with endothelial cells, together with/without TNF-? (0.5 ng/ml) and/or NO donor, sodium nitroprusside dihydrate (SNP) (100 ?M). Images were captured after 24 h. The effects on HTR-8/SVneo cell integration were quantified by Image Analysis software. The cells were then recovered from Matrigel to extract mRNA. Quantitative PCR was performed to evaluate the expression of eNOS, VCAM-1 and E-selectin. The concentrations of sVCAM-1 and sE-selectin in the conditioned medium were measured by ELISA. Results TNF-? inhibited HTR-8/SVneo trophoblast cell integration into endothelial cellular networks, as well as decreased eNOS mRNA expression. Increases in VCAM-1 and E-selectin in cellular mRNA and protein concentrations in the conditioned medium were also seen. The NO donor reversed the inhibitory effect of TNF-? on trophoblast integration and increased eNOS mRNA expression. SNP also reduced sE-selectin and sVCAM-1 expressions which were increased by TNF-? in the conditioned medium. Conclusion Our data suggest the inhibitory effect of TNF-? on trophoblast integration may be mediated by NO, via reducing endothelial cell activation. 2014 Elsevier Ltd. All rights reserved.
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Lord, Megan S.; Chuang, Christine Y.; Melrose, James; Davies, Michael J.; Iozzo, Renato V.; Whitelock, JohnSmooth muscle cell proliferation can be inhibited by heparan sulfate proteoglycans whereas the removal or digestion of heparan sulfate from perlecan promotes their proliferation. In this study we characterized the glycosaminoglycan side chains of perlecan isolated from either primary human coronary artery smooth muscle or endothelial cells and determined their roles in mediating cell adhesion and proliferation, and in fibroblast growth factor (FGF) binding and signaling. Smooth muscle cell perlecan was decorated with both heparan sulfate and chondroitin sulfate, whereas endothelial perlecan contained exclusively heparan sulfate chains. Smooth muscle cells bound to the protein core of perlecan only when the glycosaminoglycans were removed, and this binding involved a novel site in domain III as well as domain V/endorepellin and the ?<inf>2</inf>?<inf>1</inf> integrin. In contrast, endothelial cells adhered to the protein core of perlecan in the presence of glycosaminoglycans. Smooth muscle cell perlecan bound both FGF1 and FGF2 via its heparan sulfate chains and promoted the signaling of FGF2 but not FGF1. Also endothelial cell perlecan bound both FGF1 and FGF2 via its heparan sulfate chains, but in contrast, promoted the signaling of both growth factors. Based on this differential bioactivity, we propose that perlecan synthesized by smooth muscle cells differs from that synthesized by endothelial cells by possessing different signaling capabilities, primarily, but not exclusively, due to a differential glycanation. The end result is a differential modulation of cell adhesion, proliferation and growth factor signaling in these two key cellular constituents of blood vessels. 2014 International Society of Matrix Biology.
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Storkey, Corin M.; Davies, Michael J.; Pattison, David I.Activated white cells use oxidants generated by the heme enzyme myeloperoxidase to kill invading pathogens. This enzyme utilizes H <inf>2</inf>O<inf>2</inf> and Cl-, Br-, or SCN- to generate the oxidants HOCl, HOBr, and HOSCN, respectively. Whereas controlled production of these species is vital in maintaining good health, their uncontrolled or inappropriate formation (as occurs at sites of inflammation) can cause host tissue damage that has been associated with multiple inflammatory pathologies including cardiovascular diseases and cancer. Previous studies have reported that sulfur-containing species are major targets for HOCl but as the reactions are fast the only physiologically relevant kinetic data available have been extrapolated from data measured at high pH (>10). In this study these values have been determined at pH 7.4 using a newly developed competition kinetic approach that employs a fluorescently tagged methionine derivative as the competitive substrate (k(HOCl + Fmoc-Met), 1.508 M-1 s-1). This assay was validated using the known k(HOCl + NADH) value and has allowed revised k values for the reactions of HOCl with Cys, N-acetylcysteine, and glutathione to be determined as 3.608, 2.907, and 1.2408 M-1 s-1, respectively. Similar experiments with methionine derivatives yielded k values of 3.40 7 M-1 s-1 for Met and 1.708 M-1 s-1 for N-acetylmethionine. The k values determined here for the reaction of HOCl with thiols are up to 10-fold higher than those previously determined and further emphasize the critical importance of reactions of HOCl with thiol targets in biological systems. 2014 Elsevier Inc.
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Bautista, Tara G.; Pitts, Teresa E.; Pilowsky, Paul M.; Morris, Kendall F.The respiratory system works with the cardiovascular system to supply tissues with oxygen, to remove carbon dioxide, and to maintain a normal acid-base balance (i.e. blood gas homeostasis). The basic breathing rhythm is generated in the ventrolateral medulla in a column of cells that extends in the caudal direction from the caudal pole of the facial motor nucleus (VIIn) to the spino-medullary junction. The breathing networks are also vitally important in a host of other behaviors, such as swallow, cough, emesis, expiration reflex, micturition, defecation, parturition, suckling, locomotion, and vocalization. These networks control the primary muscle of inspiration, the diaphragm, as well as a host of upper airway and abdominal muscles, to accomplish these tasks without compromising blood gas homeostasis. The core respiratory networks are also modulated by many sensory inputs from the periphery as well as modulatory inputs from other brain regions, notably the dorsolateral-pontine and midline-raphnuclei. 2014 Elsevier Inc. All rights reserved.
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Baljinnyam, Erdene; Umemura, Masanari; Chuang, Christine Y.; de Lorenzo, Mariana S.; Iwatsubo, Mizuka; Chen, Suzie; Goydos, James S.; Ishikawa, Yoshihioro; Whitelock, John; Iwatsubo, KousakuSummary: Fibroblast growth factor (FGF2) regulates endothelial and melanoma cell migration. The binding of FGF2 to its receptor requires N-sulfated heparan sulfate (HS) glycosamine. We have previously reported that Epac1, an exchange protein activated by cAMP, increases N-sulfation of HS in melanoma. Therefore, we examined whether Epac1 regulates FGF2-mediated cell-cell communication. Conditioned medium (CM) of melanoma cells with abundant expression of Epac1 increased migration of human umbilical endothelial cells (HUVEC) and melanoma cells with poor expression of Epac1. CM-induced increase in migration was inhibited by antagonizing FGF2, by the removal of HS and by the knockdown of Epac1. In addition, knockdown of Epac1 suppressed the binding of FGF2 to FGF receptor in HUVEC, and in vivo angiogenesis in melanoma. Furthermore, knockdown of Epac1 reduced N-sulfation of HS chains attached to perlecan, a major secreted type of HS proteoglycan that mediates the binding of FGF2 to FGF receptor. These data suggested that Epac1 in melanoma cells regulates melanoma progression via the HS-FGF2-mediated cell-cell communication. 2014 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons Ltd.
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Surmon, Laura; Bobek, Gabriele; Chiu, Christine L.; Young, S.; Makris, Angela; Lind, Joanne Maree; Hennessy, AnnemarieObjective: Gene expression studies often pool tissues from multiple placentas when using animal models of preeclampsia without accounting for the potential confounders of litter origin or pup sex. We aimed to determine whether placental gene expression differs based on sex or litter. Methods: We examined the differential expression of soluble fms-like tyrosine kinase 1 (Flt-1) using 35 pups from six normal pregnant mice. Results: Expression of sFlt-1 (p = 0.003) was significantly different between litters but not between sexes (p = 0.17). Conclusions: These findings highlight the importance of adequate sampling from multiple litters in expression studies when using animal models in clinical research. 2014 Informa Healthcare USA, Inc.
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Morgan, Philip E.; Sheahan, Pamela J.; Davies, Michael J.Diabetes is associated with elevated plasma glucose, increased reactive aldehyde formation, oxidative damage, and glycation/glycoxidation of biomolecules. Cellular detoxification of, or protection against, such modifications commonly requires NADPH-dependent reducing equivalents (e.g. GSH). We hypothesised that reactive aldehydes may modulate cellular redox status via the inhibition of NADPH-generating enzymes, resulting in decreased thiol and NADPH levels. Primary human coronary artery endothelial cells (HCAEC) were incubated with high glucose (25 mM, 24 h, 37C), or methylglyoxal (MGO), glyoxal, or glycolaldehyde (100-500 ?M, 1 h, 37C), before quantification of intracellular thiols and NADPH-generating enzyme activities. Exposure to MGO, but not the other species examined, significantly (P<0.05) decreased total thiols (?35%), further experiments with MGO showed significant losses of GSH (?40%) and NADPH (?10%); these changes did not result in an immediate loss of cell viability. Significantly decreased (?10%) NADPH-producing enzyme activity was observed for HCAEC when glucose-6-phosphate or 2-deoxyglucose-6-phosphate were used as substrates. Cell lysate experiments showed significant MGO-dose dependent inhibition of glucose-6-phosphate- dependent enzymes and isocitrate dehydrogenase, but not malic enzyme. Analysis of intact cell or lysate proteins showed that arginine-derived hydroimidazolones were the predominant advanced glycation end-product (AGE) formed; lower levels of N?-(carboxyethyl)lysine (CEL) and N?- (carboxymethyl)lysine (CML) were also detected. These data support a novel mechanism by which MGO exposure results in changes in redox status in human coronary artery endothelial cells, via inhibition of NADPH-generating enzymes, with resultant changes in reduced protein thiol and GSH levels. These changes may contribute to the endothelial cell dysfunction observed in diabetes-associated atherosclerosis. 2014 Morgan et al.
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Chuang, Christine Y.; Degendorfer, Georg; Davies, Michael J.There is accumulating evidence that damage to extracellular materials and particularly the extracellular matrix, can play a major role in multiple human pathologies. In contrast to cells, the extracellular compartment of most biological tissues is relatively poorly equipped to prevent or repair damage caused by oxidation due to lower levels of antioxidant defenses (low molecular mass and enzymatic) and repair systems (both catabolic and enzymatic). The extracellular compartment is therefore likely to be subject to both an increased extent of damage and an overall accumulation of damage due to slow turnover and/or poor repair. The nature and consequences of damage to the extracellular matrix is poorly understood, despite evidence that changes in matrix structure influences not only structural integrity, but also cell adhesion, proliferation, migration and signaling, and cytokine and growth factor binding. In this article the nature of the extracellular matrix is briefly reviewed, together with evidence for the presence of matrix modifications in cardiovascular disease. The oxidants and mechanisms that are known to damage extracellular matrix are reviewed, together with the limited data available to date on how such changes affect structural properties and cellular behavior. 2014 Informa UK, Ltd.
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Nedoboy, Polina E.; Morgan, Philip E.; Mocatta, Tessa J.; Richards, Arthur Mark; Winterbourn, Christine C.; Davies, Michael J.Elevated levels of myeloperoxidase (MPO) are associated with poor cardiovascular outcomes. MPO uses H2O2 to generate oxidants including HOCl and HOSCN, from chloride and thiocyanate (SCN-) ions, respectively. SCN- is the preferred substrate. Elevation of this anion decreases HOCl generation and increases HOSCN formation, a thiol-specific oxidant. Such changes are of potential relevance to people with elevated SCN- levels, such as smokers. In this retrospective study, we examined whether elevated plasma MPO and SCN- levels increased thiol oxidation as a result of increased HOSCN formation, and impacted on long-term survival in 176 subjects (74 non-smokers, 46 smokers, and 56 previous smokers) hospitalized after a first myocardial infarction. Plasma thiols were not significantly altered in smokers compared to non-smokers or past smokers. However, significant positive correlations were detected between SCN- levels and MPO-induced thiol loss in the total population (r = 0.19, P = 0.020) and smokers alone (r = 0.58, P < 0.0001). Twelve-year all-cause mortality data indicate that above median MPO is significantly associated with higher mortality, but below-median MPO and above-median SCN- results in increased survival, compared to below-median SCN-. Cox proportional hazard analysis showed a significant decrease in mortality for each 1 ?M increase in SCN - (0.991; P = 0.040). Subject age was, as expected, a strong predictor of subject survival. Overall these data suggest that subjects with below-median MPO and above-median SCN- have better long-term survival, and that elevated plasma levels of SCN- might be protective in at least some populations. 2014 Informa UK, Ltd.
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Islam, Shahidul M.; Esselle, Karu P.; Bull, David; Pilowsky, Paul M.The two major challenges associated with the conversion of a wireless system operating in air to an implantable version, antenna detuning and biocompatibility, are addressed in a coherent way. An RF identification (RFID)-based biomedical telemetry system designed for free-space operation was chosen as the starting reference. A new pin-compatible space-saving antenna with a ground plane was designed, fabricated, and tested to replace the original 'free-space' antenna in the active RFID tag without making any other changes to the tag circuit, such that the tag would function well when it is placed under rat skin and fat. Biocompatibility and potential antenna detuning due to rat tissue variations were addressed in the design process, without significantly increasing the tag physical height, by applying a thin coating of biocompatible material directly over the antenna. The operation of the medical telemetry system was successfully demonstrated, with the tag placed under rat skin and fat, and its range of 60-72 cm was found to be sufficient to support medical research experiments conducted with rats in cages. Due to the biocompatible coating over the antenna, antenna matching is very insensitive to changes in tissue dielectric constants and thickness. The footprint of the new antenna is 33% less than that of the original antenna, its measured 10-dB return-loss bandwidth is 100 MHz or 11%, and overall efficiency is 0.82% at 920 MHz. 2014 IEEE.
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Xing, Tao; Pilowsky, Paul M.; Fong, Angelina Y.Sleep apnea is associated with repeated episodes of hypoxemia, causing marked increase in sympathetic nerve activity and blood pressure. Considerable evidence suggests that intermittent hypoxia (IH) resulting from apnea is the primary stimulus for sympathetic overactivity in sleep apnea patients. Several IH protocols have been developed either in animals or in humans to investigate mechanisms underlying the altered autonomic regulation of the circulation. Most of these protocols involve several days (10-40 days) of IH exposure, that is, chronic intermittent hypoxia (CIH). Recent data suggest that a single session of IH exposure, that is, acute intermittent hypoxia (AIH), is already capable of increasing tonic sympathetic nerve output (sympathetic long-term facilitation, LTF) and altering chemo- and baroreflexes with or without elevation of blood pressure. This indicates that IH alters the autonomic neurocirculatory at a very early time point, although the mechanisms underlying this neuroplasticity have not been explored in detail. The purpose of this chapter is to briefly review the effects of AIH on sympathetic LTF and alteration of autonomic reflexes in comparison with the studies from CIH studies. We will also discuss the potential central and peripheral mechanism underlying sympathetic LTF. 2014 Elsevier B.V.
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Cochran, Blake J.; Bisoendial, Radjesh J.; Hou, Liming; Glaros, Elias N.; Rossy, Jie; Thomas, Shane R.; Barter, Philip J.; Rye, Kerry AnneObjective - Therapeutic interventions that increase plasma levels of high-density lipoproteins and apolipoprotein A-I (apoA-I) A-I, the major high-density lipoprotein apolipoprotein, improve glycemic control in people with type 2 diabetes mellitus. High-density lipoproteins and apoA-I also enhance insulin synthesis and secretion in isolated pancreatic islets and clonal ?-cell lines. This study identifies the signaling pathways that mediate these effects.Approach and Results - Incubation with apoA-I increased cAMP accumulation in Ins-1E cells in a concentration-dependent manner. The increase in cAMP levels was inhibited by preincubating the cells with the cell-permeable, transmembrane adenylate cyclase inhibitor, 2'5' dideoxyadenosine, but not with KH7, which inhibits soluble adenylyl cyclases. Incubation of Ins-1E cells with apoA-I resulted in colocalization of ATP-binding cassette transporter A1 with the G?s subunit of a heterotrimeric G-protein and a G?s subunit-dependent increase in insulin secretion. Incubation of Ins-1E cells with apoA-I also increased protein kinase A phosphorylation and reduced the nuclear localization of forkhead box protein O1 (FoxO1). Preincubation of Ins-1E cells with the protein kinase A-specific inhibitors, H89 and PKI amide, prevented apoA-I from increasing insulin secretion and mediating the nuclear exclusion of FoxO1. Transfection of Ins-1E cells with a mutated FoxO1 that is restricted to the nucleus confirmed the requirement for FoxO1 nuclear exclusion by blocking insulin secretion in apoA-I-treated Ins-1E cells. ApoA-I also increased Irs1, Irs2, Ins1, Ins2, and Pdx1 mRNA levels.Conclusions - ApoA-I increases insulin synthesis and secretion via a heterotrimeric G-protein-cAMP-protein kinase A-FoxO1-dependent mechanism that involves transmembrane adenylyl cyclases and increased transcription of key insulin response and ?-cell survival genes. 2014 American Heart Association, Inc.
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Bautista, Tara G.; Sun, Qijian; Pilowsky, Paul M.Swallowing and breathing utilize common muscles and an anatomical passage: the pharynx. The risk of aspiration of ingested material is minimized not only by the laryngeal adduction of the vocal folds and laryngeal elevation but also by the precise coordination of swallows with breathing. Namely, swallows: (1) are preferentially initiated in the postinspiratory/expiratory phase, (2) are accompanied by a brief apnea, and (3) are often followed by an expiration and delay of the next breath. This review summarizes the expiratory evidence on the brainstem regions comprising the central pattern generator (CPG) that produces the pharyngeal stage of swallow, how the motor acts of swallowing and breathing are coordinated, and lastly, brainstem regions where the swallowing and respiratory CPGs may interact in order to ensure "safe" swallows. 2014 Elsevier B.V.
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Pilowsky, Paul M.Over the last 20 years, it has become clear that many functionally defined autonomic neurons in the brainstem contain many more than one neurotransmitter. Here, the possible role and functions of colocalized neuropeptides in the caudal raphe nuclei of the medulla oblongata are discussed. Caudal raphe neurons provide an extensive input to neurons throughout the brainstem and spinal cord, including respiratory and cardiovascular neurons. It is concluded that one plausible function of colocalized neuropeptides is to maintain the membrane potential of target neurons within a defined window so that they remain able to function at extremes of activity. 2014 Elsevier B.V.
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Lopez, Derrick G.; Katzenellenbogen, Judith Masha; Sanfilippo, Frank Mario; Woods, John A.; T Hobbs, Michael S.; Knuiman, Matthew William; Briffa, Tom G.; Thompson, Peter Lindsay; Thompson, Sandra ClaireIntroduction: Aboriginal Australians have a substantially higher frequency of ischaemic heart disease (IHD) event than their non-Aboriginal counterparts, together with a higher prevalence of comorbidities. The pattern of healt service provision for IHD suggests inequitable delivery of important diagnostic procedures. Published data o disparities in IHD management among Aboriginal Australians are conflicting, and the role of comorbidities ha not been adequately delineated. We compared the profiles of Aboriginal and non-Aboriginal patients in th metropolitan area undergoing emergency IHD admissions at Western Australian metropolitan hospitals, an investigated the determinants of receiving coronary angiography Methods: Person-linked administrative hospital and mortality records were used to identify 28-day survivors of IH emergency admission events (n =20,816) commencing at metropolitan hospitals in 2005-09. The outcome measur was receipt of angiography. The Aboriginal to non-Aboriginal risk ratio (RR) was estimated from a multivariabl Poisson log-linear regression model with allowance for multiple IHD events in individuals. The subgroup o myocardial infarction (MI) events was modelled separately Results: Compared with their non-Aboriginal counterparts, Aboriginal IHD patients were younger and more likel to have comorbidities. In the age-and sex-Adjusted model, Aboriginal patients were less likely than others t receive angiography (RRIHD 0.77, 95% CI 0.72-0.83; RRMI 0.81, 95% CI 0.75-0.87) but in the full multivariable model thi disparity was accounted for by comorbidities as well as IHD category and MI subtype, and private health insuranc (RRIHD 0.95, 95% CI 0.89-1.01; RRMI 0.94, 95% CI 0.88-1.01). When stratified by age groups, this disparity was no significant in the 25-54 year age group (RRMI 0.95, 95% CI 0.88-1.02) but was significant in the 55-84 year age grou (RRMI 0.88, 95% CI 0.77-0.99). 2014 Lopez et al.
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Gad, Nicholas A.; Mizdrak, Jasminka; Pattison, David I.; Davies, Michael J.; Truscott, Roger John Willis; Jamie, Joanne F.Purpose. 3-Hydroxykynurenine O-?-D-glucoside (3OHKG) protects the lens from UV damage, and novel related species may act analogously. The aim of this study was to detect, quantify, and elucidate the structures of novel 3-hydroxykynurenine glucoside-derived metabolites present in the human lens. Methods. Compounds were detected and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 24 human lenses of different ages, of which 22 were normal and two had cataract. Structures of these were confirmed through total synthesis. Results. 3OHKG concentrations decreased with age in the lens nuclei, whereas the levels of three novel species, 4-(2-amino-3-hydroxyphenyl)-2-hydroxy-4-oxobutanoic acid O-?-D-glucoside (3OHKG-W), 3-hydroxykynurenine O-?-D-glucoside yellow (3OHKG-Y), and 2-amino-3-hydroxyacetophenone O-?-D-glucoside (AHAG), increased, though to different extents. In contrast, the concentrations present in the cortex of the lens remained constant with age. Conclusions. Three novel 3OHKG-derived metabolites have been detected in extracts from human lenses. 2014 The Association for Research in Vision and Ophthalmology, Inc.
