Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

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European Position Paper on Rhinosinusitis and Nasal Polyps 2020

From a Novel

Experimental work during the past 15 years has demonstrated that endothelial cells in the heart play an obligatory role in regulating and maintaining cardiac function, in particular, at the endocardium and in the myocardial capillaries where endothelial cells directly interact with adjacent cardiomyocytes. The emerging field of targeted gene manipulation has led to the contention that cardiac endothelial-cardiomyocytal interaction is a prerequisite for normal cardiac development and growth. Some of the molecular mechanisms and cellular signals governing this interaction, such as neuregulin, vascular endothelial growth factor, and angiopoietin, continue to maintain phenotype and survival of cardiomyocytes in the adult heart. Cardiac endothelial cells, like vascular endothelial cells, also express and release a variety of auto- and paracrine agents, such as nitric oxide, endothelin, prostaglandin I(2), and angiotensin II, which directly influence cardiac metabolism, growth, contractile performance, and rhythmicity of the adult heart. The synthesis, secretion, and, most importantly, the activities of these endothelium-derived substances in the heart are closely linked, interrelated, and interactive. It may therefore be simplistic to try and define their properties independently from one another. Moreover, in relation specifically to the endocardial endothelium, an active transendothelial physicochemical gradient for various ions, or blood-heart barrier, has been demonstrated. Linkage of this blood-heart barrier to the various other endothelium-mediated signaling pathways or to the putative vascular endothelium-derived hyperpolarizing factors remains to be determined. At the early stages of cardiac failure, all major cardiovascular risk factors may cause cardiac endothelial activation as an adaptive response often followed by cardiac endothelial dysfunction. Because of the interdependency of all endothelial signaling pathways, activation or disturbance of any will necessarily affect the others leading to a disturbance of their normal balance, leading to further progression of cardiac failure.

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Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity

Evaluation of the probes 2',7'-dichlorofluorescin diacetate, luminol, and lucigenin as indicators of reactive species formation.

P eroxynitrite is a potent oxidant formed by the rapid reaction between nitric oxide and superoxide radical (1). The peroxynitrite anion is relatively stable, but it can rapidly protonate to peroxynitrous acid, an unstable species, which decomposes with a half-life of about one second at pH 7.4 (1,2). Peroxynitrite can serve as a precursor for other potent reactive species, including nitrogen dioxide, nitronium ion, and an intermediate with hydroxyl radicallike reactivity toward a variety of biological molecules (2). Propofol(2,6-diisopropylphenol) has been used extensively as a rapidly acting intravenous anesthetic with a high therapeutic index for both inducing and maintaining general anesthesia (3). Recent in vitro studies have demonstrated that propofol has potent antioxidant properties very similar to those of a-tocopherol (4-6). Propofol inhibits lipid peroxidation induced by oxidative stress in the rat liver microsomes (5, 6), mitochondria, and brain synaptosomes (6). Although propofol reacts primarily with organic or organoperoxyl radical species (7), its effect on peroxynitrite is not known. Chemiluminescence has been widely used for measuring the production of free radicals and reactive oxygen metabolites from enzyme, cell, or organ systems (8, 9). In the present study, we used the chemiluminescence method for the assessment of the scavenging activity of propofol against peroxynitrite.

Propofol is a peroxynitrite scavenger

The aim of the study was to elucidate the mechanism of the contraction produced by hypoxia in human intrapulmonary artery rings. Hypoxia (5 mm Hg) produced a contraction that was greater when the artery rings were precontracted (with endothelin-1) than when recorded under optimal resting force. The contraction was similar in small-diameter (0.38 to 0.68 mm) and in large-diameter (2.2 to 4.5 mm) artery rings under resting force. Removal of the endothelium markedly reduced or abolished the hypoxic contraction in precontracted artery rings (large diameter, 26 ± 9 to −7 ± 4 g cm−2) or under optimal resting force. Hypoxia markedly reduced or abolished the acetylcholine-induced relaxation in precontracted artery rings without affecting relaxation produced by sodium nitroprusside. Flurbiprofen caused a slight contraction itself (large diameter, 10 ± 3 g cm−2) and significantly inhibited the contraction produced by hypoxia both under resting force (8 ± 2 to 2 ± 1 g cm−2) and in precontracted artery rings (18 ± 2 ...

The role of endothelium in hypoxic constriction of human pulmonary artery rings

Glioblastoma multiforme (GBM) is one of the most lethal forms of cancer in humans, with a median survival of 10 to 12 months. Glioblastoma is highly malignant since the cells are supported by a great number of blood vessels. Although new treatments have been developed by increasing knowledge of molecular nature of the disease, surgical operation remains the standard of care. The TRP (transient receptor potential) superfamily consists of cation-selective channels that have roles in sensory physiology such as thermo- and osmosensation and in several complex diseases such as cancer, cardiovascular, and neuronal diseases. The aim of this study was to investigate the expression levels of TRP channel genes in patients with glioblastoma multiforme and to evaluate the relationship between TRP gene expressions and survival of the patients. Thirty-three patients diagnosed with glioblastoma were enrolled to the study. The expression levels of 21 TRP genes were quantified by using qRT-PCR with dynamic array 48 × 48 chip (BioMark HD System, Fluidigm, South San Francisco, CA, USA). TRPC1, TRPC6, TRPM2, TRPM3, TRPM7, TRPM8, TRPV1, and TRPV2 were found significantly higher in glioblastoma patients. Moreover, there was a significant relationship between the overexpression of TRP genes and the survival of the patients. These results demonstrate for the first time that TRP channels contribute to the progression and survival of the glioblastoma patients.

Gene expressions of TRP channels in glioblastoma multiforme and relation with survival.

BACKGROUND AND OBJECTIVES: Functional endoscopic sinus surgery can be performed under either local or general anaesthesia. The objective of this study was to investigate the haemodynamic effects of perioperatively administered dexmedetomidine, a new generation alpha-2-agonist, in patients for functional endoscopic sinus surgery. METHODS: Sixty-two patients who were planned to undergo functional endoscopic sinus surgery under local anaesthesia were included in the study. Following meperidine premedication, both groups were monitored in a standard manner with electrocardiogram, non-invasive blood pressure and percentages of peripheral saturation of oxygen. Saline intravenous infusion was started in the placebo group, and dexmedetomidine bolus intravenous infusion (an initial loading dose of 1 microg kg-1 given for a 10-min period followed by 0.7 microg kg-1 h-1) was administered to the treatment group. Maintenance dose infusion was stopped 15 min before the end of the surgical procedure. RESULTS: Systolic, diastolic and mean arterial pressures, and heart rate markedly decreased in the dexmedetomidine group. However, dexmedetomidine had no effect on serum nitric oxide levels, measured by a nitric oxide/ozone chemiluminescence method. No significant difference was found in oxygen saturation levels of the two groups. Postoperative nausea and vomiting rates were significantly lower in the dexmedetomidine group. No adverse effects were observed with this alpha-2-agonist. Dexmedetomidine provided appropriate levels of sedation. CONCLUSION: These results suggest that dexmedetomidine provides analgesia, adequate sedation and surgical comfort without adverse effects for patients undergoing functional endoscopic sinus surgery under local anaesthesia.

Effects of dexmedetomidine infusion in patients undergoing functional endoscopic sinus surgery under local anaesthesia.

We have studied the ability of propofol and Intralipid to inhibit reactive oxygen species generated either by stimulated human leucocytes or cell-free systems using luminol chemiluminescence. Human leucocytes were stimulated by a chemotactic peptide, FMLP 1 mumol litre-1, or by a phorbol ester, PMA (protein kinase C activator) 0.1 mumol litre-1. In cell-free experiments, superoxide-hydrogen peroxide, hypochlorous acid or hydroxyl radical-induced chemiluminescence responses were initiated by xanthine 0.1 mmol litre-1 with xanthine oxidase 10 mu. ml-1, NaOCl 70 mumol litre-1 and FeSO4 3 mumol litre-1, respectively. Propofol with Intralipid, and to a lesser degree Intralipid alone, produced a concentration-dependent reduction in chemiluminescence from stimulated leucocytes. Similar attenuations were also observed using propofol with Intralipid on xanthine with xanthine oxidase-, HOCl- and ferrous iron-induced chemiluminescence. However, Intralipid produced a reduction only at high concentrations. Intralipid produced marked decreases in ferrous iron-induced chemiluminescence. This study suggests that propofol had a direct scavenging activity against HOCl, superoxide-hydrogen peroxide and hydroxyl radical in the concentrations used. These direct scavenging effects may contribute to the effect of propofol on human leucocyte chemiluminescence.

Abdullah T. Demiryürek

Papers

Propofol is a peroxynitrite scavenger

The role of endothelium in hypoxic constriction of human pulmonary artery rings

Gene expressions of TRP channels in glioblastoma multiforme and relation with survival.

Effects of dexmedetomidine infusion in patients undergoing functional endoscopic sinus surgery under local anaesthesia.

Propofol and intralipid interact with reactive oxygen species: a chemiluminescence study.