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https://www.readbyqxmd.com/read/28747646/metabolic-biomarkers-for-prognostic-prediction-of-pre-diabetes-results-from-a-longitudinal-cohort-study
#1
Hailuan Zeng, Renchao Tong, Wenxin Tong, Qiaoling Yang, Miaoyan Qiu, Aizhen Xiong, Siming Sun, Lili Ding, Hongli Zhang, Li Yang, Jingyan Tian
To investigate the metabolic biomarkers of predicting the transition from pre-diabetes (pre-DM) to normal glucose regulation (NGR) and diabetes (DM) in a longitudinal cohort study. 108 participants with pre-DM were followed up for ten years and divided into 3 groups according to different glycemic outcomes. 20 participants progressed to DM, 20 regressed to NGR, and 68 remained at pre-DM. Alterations in plasma metabolites in these groups were evaluated by untargeted ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS)...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747177/acute-coronary-syndrome-and-acute-kidney-injury-role-of-inflammation-in-worsening-renal-function
#2
Jorge Ortega-Hernández, Rashidi Springall, Fausto Sánchez-Muñoz, Julio-C Arana-Martinez, Héctor González-Pacheco, Rafael Bojalil
BACKGROUND: Acute Kidney Injury (AKI), a common complication of acute coronary syndromes (ACS), is associated with higher mortality and longer hospital stays. The role of cytokines and other mediators is unknown in AKI induced by an ACS (ACS-AKI), leading to several unanswered questions. The worsening of renal function is usually seen as a dichotomous phenomenon instead of a dynamic change, so evaluating changes of the renal function in time may provide valuable information in the ACS-AKI setting...
July 26, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28743859/let-7-microrna-dependent-control-of-leukotriene-signaling-regulates-the-transition-of-hematopoietic-niche-in-mice
#3
Xuan Jiang, John S Hawkins, Jerry Lee, Carlos O Lizama, Frank L Bos, Joan P Zape, Prajakta Ghatpande, Yongbo Peng, Justin Louie, Giorgio Lagna, Ann C Zovein, Akiko Hata
Hematopoietic stem and progenitor cells arise from the vascular endothelium of the dorsal aorta and subsequently switch niche to the fetal liver through unknown mechanisms. Here we report that vascular endothelium-specific deletion of mouse Drosha (Drosha (cKO)), an enzyme essential for microRNA biogenesis, leads to anemia and death. A similar number of hematopoietic stem and progenitor cells emerge from Drosha-deficient and control vascular endothelium, but Drosha (cKO)-derived hematopoietic stem and progenitor cells accumulate in the dorsal aorta and fail to colonize the fetal liver...
July 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28737507/leukotrienes-and-sex-strange-bedfellows
#4
Lewis J Smith
Leukotrienes are proinflammatory lipid mediators that have been shown to be upregulated in several diseases, including asthma, aspirin-exacerbated respiratory disease (AERD), inflammatory bowel disease, and acute respiratory distress syndrome. Leukotrienes have been explored as therapeutic targets for these diseases and others; however, leukotriene inhibitors have had limited success in the clinic. There are noted differences in the incidence of leukotriene-mediated diseases in males and females, but sex as a factor in the response to leukotriene inhibitors has not been fully explored...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28737505/androgen-mediated-sex-bias-impairs-efficiency-of-leukotriene-biosynthesis-inhibitors-in-males
#5
Simona Pace, Carlo Pergola, Friederike Dehm, Antonietta Rossi, Jana Gerstmeier, Fabiana Troisi, Helmut Pein, Anja M Schaible, Christina Weinigel, Silke Rummler, Hinnak Northoff, Stefan Laufer, Thorsten J Maier, Olof Rådmark, Bengt Samuelsson, Andreas Koeberle, Lidia Sautebin, Oliver Werz
Proinflammatory leukotrienes (LTs) are produced by 5-lipoxygenase (5-LO) aided by 5-LO-activating protein (FLAP). LT biosynthesis inhibitors are currently under clinical investigation as treatments for respiratory and cardiovascular diseases. Here, we have revealed a sex bias in the efficiency of clinically relevant LT biosynthesis inhibitors, showing that their effects are superior in females. We found that androgens cause these sex differences by impeding the LT-biosynthetic 5-LO/FLAP complex assembly. Lower doses of the FLAP inhibitor MK886 were required to reduce LTB4 levels in exudates of female versus male mice and rats...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28736941/in-vivo-neutralization-of-%C3%AE-4-and-%C3%AE-7-integrins-inhibits-eosinophil-trafficking-and-prevents-lung-injury-during-tropical-pulmonary-eosinophilia-in-mice
#6
Pankaj Sharma, Aditi Sharma, Mrigank Srivastava
Integrins regulate leukocyte trafficking during homeostasis and inflammatory conditions. However, the role of α4 and β7 integrins in guiding eosinophil transmigration into the lungs during filarial manifestation of Tropical Pulmonary Eosinophilia (TPE) has not been explored. In this study, mice exhibiting TPE manifestations were administered with in vivo neutralizing antibodies against integrins α4 and β7 or their combination and immuno-pathological parameters were evaluated. Results show an intact lung barrier, significantly lower lung inflammation and reduced eosinophil counts in the Bronchoalveolar lavage fluid and lungs of mice receiving anti-α4(+) β7 treatment...
July 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28735623/genes-involved-in-leukotriene-synthesis-pathway-are-dynamically-regulated-during-lung-development-in-rhesus-monkeys
#7
Wanmin Xia, Liang Xie, Bangrong Cao, Shujun Cheng, Huajing Wan, Hanmin Liu
BACKGROUND: Leukotrienes play critical roles in many inflammatory lung diseases and several antagonists of their receptors have been used in the clinical settings. However, the physiological functions of leukotrienes in lung development are still unclear. METHOD: The expression levels of 34 genes involved in leukotriene synthesis and function pathway in the lungs of Rhesus monkey during different developmental time points were determined on a MiSeq platform and analyzed by the reads per kilobase of transcript per million mapped reads (RPKM) method...
July 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28721160/genetic-disruption-of-multidrug-resistance-associated-protein-1-improves-endothelial-function-and-attenuates-atherosclerosis-in-mrp1-ldlr-double-knockout-mice
#8
Julian Jehle, Cornelius F H Müller, Adem Aksoy, Sebastian Zimmer, Georg Nickenig, Vedat Tiyerili
INTRODUCTION: Multidrug resistance-associated protein 1 (MRP1) is an anion transporter which is implicated in the efflux of the intracellular antioxidant anion glutathione as well as leukotrienes. Pharmacological inhibition of MRP1 exhibits antioxidative and anti-atherosclerotic effects both in vitro and in vivo. However, pharmacological inhibitors of MRP1 lack selectivity, which prompted us to study the in vivo impact of a genetic disruption of MRP1 on endothelial dysfunction, reactive oxygen species formation and atherogenesis in an atherosclerotic mouse model...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28718891/mk-reduces-inhaled-chlorine-triggered-ahr-and-airway-inflammation-in-the-mouse
#9
Yoichiro Hamamoto, Satoshi Ano, Benoit Allard, Michael O'Sullivan, Toby K McGovern, James G Martin
BACKGROUND AND PURPOSE: Cysteinyl leukotrienes (CysLTs) are pro-inflammatory lipid mediators that exacerbate disease state in several asthma phenotypes including asthma induced by allergen, virus and exercise. However, the role of CysLTs in irritant-induced airway disease is not well characterized. The purpose of the current study was to investigate the effect of montelukast (MK), a CysLT1R antagonist, on parameters of irritant-induced asthma (IIA) induced by inhalation of chlorine (Cl2 ) in the mouse...
July 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28710425/naja-sputatrix-venom-preconditioning-attenuates-neuroinflammation-in-a-rat-model-of-surgical-brain-injury-via-pla2-5-lox-ltb4-cascade-activation
#10
Yuechun Wang, Prativa Sherchan, Lei Huang, Onat Akyol, Devin W McBride, John H Zhang
Inflammatory preconditioning is a mechanism in which exposure to small doses of inflammatory stimuli prepares the body against future massive insult by activating endogenous protective responses. Phospholipase A2/5-lipoxygenase/leukotriene-B4 (PLA2/5-LOX/LTB4) axis is an important inflammatory signaling pathway. Naja sputatrix (Malayan spitting cobra) venom contains 15% secretory PLA2 of its dry weight. We investigated if Naja sputatrix venom preconditioning (VPC) reduces surgical brain injury (SBI)-induced neuroinflammation via activating PLA2/5-LOX/LTB4 cascade using a partial frontal lobe resection SBI rat model...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28704107/asthma-medication-use-among-adults-with-current-asthma-by-work-related-asthma-status-asthma-call-back-survey-29-states-2012-2013
#11
Katelynn E Dodd, Jacek M Mazurek
OBJECTIVE: Asthma severity is defined as the intensity of treatment required to achieve good control of asthma symptoms. Studies have shown that work-related asthma (WRA) can be associated with poorer asthma control and more severe symptoms than non-WRA. Associations between asthma medications and WRA status were assessed using data from the 2012-2013 Asthma Call-back Survey among ever-employed adults (≥18 years) with current asthma from 29 states. METHODS: Persons with WRA had been told by a physician that their asthma was work-related...
July 13, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28699354/drug-mediated-intracellular-donation-of-nitric-oxide-potently-inhibits-5-lipoxygenase-a-possible-key-to-future-anti-leukotriene-therapy
#12
Jessica Roos, Marcus Peters, Isabelle V Maucher, Benjamin Kühn, Jasmin Fettel, Nadine Hellmuth, Camilla Brat, Benita Sommer, Anja Urbschat, Matthias Piesche, Anja Vogel, Ewgenij Proschak, René Blöcher, Estel la Buscato, Ann-Kathrin Häfner, Carmela Matrone, Oliver Werz, Juliana Heidler, Ilka Wittig, Carlo Angioni, Gerd Geisslinger, Michael J Parnham, Kai Zacharowski, Dieter Steinhilber, Thorsten Jürgen Maier
AIMS: 5-lipoxygenase (5-LO) is the key enzyme of leukotriene biosynthesis and is critically involved in a number of inflammatory diseases such as arthritis, gout, bronchial asthma, atherosclerosis and cancer. Because 5-LO contains critical nucleophilic amino acids, which are sensitive to electrophilic modifications, we determined the consequences of a drug-mediated intracellular release of nitric oxide (NO) on 5-LO product formation by human granulocytes and on 5-LO-dependent pulmonary inflammation in vivo...
July 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28696803/thai-pediatricians-current-practice-toward-childhood-asthma
#13
Harutai Kamalaporn, Pongpan Chawalitdamrong, Aroonwan Preutthipan
BACKGROUND: Childhood asthma is a substantial health burden in Thailand. Due to a lack of pediatric respiratory specialists (pediatric pulmonologists and allergists; RS), most Thai children are cared for by general pediatricians (pediatric primary care providers (PCP)). OBJECTIVES: We investigated whether current practices of Thai pediatricians complied with asthma guidelines and compared practices (diagnosis and treatments) provided by PCP and RS. METHODS: A cross-sectional study was conducted using electronic surveys including four case scenarios of different asthma phenotypes distributed to Thai pediatricians...
July 11, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28696794/the-effects-of-asthma-medications-on-reactive-oxygen-species-production-in-human-monocytes
#14
Ming-Kai Tsai, Yi-Ching Lin, Ming-Yii Huang, Min-Sheng Lee, Chang-Hung Kuo, Po-Lin Kuo, Ching-Hsiung Lin, Chih-Hsing Hung
OBJECTIVE: Asthma is a chronic inflammatory airway disease induced by many environmental factors. The inhalation of allergens and pollutants promote the reactive oxygen species (ROS) production leading to airway inflammation, hyper-responsiveness and remodeling in allergic asthma. The effects of asthma medications on ROS production are unclear. The present study investigated the anti-ROS effects of current asthma medications including inhaled corticosteroid (ICS; budesonide and fluticasone), leukotriene receptor antagonist (LTRA; montelukast), long acting β2 agonists (LABAs; salmeterol and formoterol) and a new extra-LABA (indacaterol)...
July 11, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28694473/5-lo-inhibition-ameliorates-palmitic-acid-induced-er-stress-oxidative-stress-and-insulin-resistance-via-ampk-activation-in-murine-myotubes
#15
Hyun Jeong Kwak, Hye-Eun Choi, Hyae Gyeong Cheon
Leukotriene B4 (LTB4) production via the 5-lipoxygenase (5-LO) pathway contributes to the development of insulin resistance in adipose and hepatic tissues, but the role of LTB4 in skeletal muscle is relatively unknown. Here, the authors investigated the role of LTB4 in C2C12 myotubes in palmitic acid (PA)-induced ER stress, inflammation and insulin resistance. PA (750 μM) evoked lipotoxicity (ER stress, oxidative stress, inflammation and insulin resistance) in association with LTB4 production. 5-LO inhibition reduced all the lipotoxic effects induced by PA...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687195/%C3%AE-2-microglobulin-elicits-itch-related-responses-in-mice-through-the-direct-activation-of-primary-afferent-neurons-expressing-transient-receptor-potential-vanilloid-1
#16
Tsugunobu Andoh, Takahito Maki, Sikai Li, Daisuke Uta
Uremic pruritus is an unpleasant symptom in patients undergoing hemodialysis, and the underlying mechanisms remain unclear. β2-Microglobulin (β2-MG) is well-known as an MHC class I molecule and its level is increased in the plasma of patients undergoing hemodialysis. In this study, we investigated whether β2-MG was a pruritogen in mice. Intradermal injections of β2-MG into the rostral back induced scratching in a dose-dependent manner. Intradermal injection of β2-MG into the cheek also elicited scratching, but not wiping...
July 4, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28687104/angiotensin-converting-enzyme-inhibitor-and-other-drug-associated-angioedema
#17
REVIEW
Cosby Stone, Nancy J Brown
Nonsteroidal antiinflammatory agents, β-lactam antibiotics, non-β lactam antibiotics, and angiotensin-converting enzyme inhibitors are the most common classes of drugs that cause angioedema. Drug-induced angioedema is known to occur via mechanisms mediated by histamine, bradykinin, or leukotriene, and an understanding of these mechanisms is crucial in guiding therapeutic decisions. Nonallergic angioedema occurs in patients with genetic variants that affect metabolism or synthesis of bradykinin, substance P, prostaglandins, or leukotrienes, or when patients are taking drugs that have synergistic mechanisms...
August 2017: Immunology and Allergy Clinics of North America
https://www.readbyqxmd.com/read/28684707/substituted-caffeic-and-ferulic-acid-phenethyl-esters-synthesis-leukotrienes-biosynthesis-inhibition-and-cytotoxic-activity
#18
Pier Morin, Patrick-Denis St-Coeur, Jérémie A Doiron, Marc Cormier, Julie J Poitras, Marc E Surette, Mohamed Touaibia
Glioblastoma multiforme (GBM) is an aggressive brain tumor that correlates with short patient survival and for which therapeutic options are limited. Polyphenolic compounds, including caffeic acid phenethyl ester (CAPE, 1a), have been investigated for their anticancer properties in several types of cancer. To further explore these properties in brain cancer cells, a series of caffeic and ferulic acid esters bearing additional oxygens moieties (OH or OCH₃) were designed and synthesized. (CAPE, 1a), but not ferulic acid phenethyl ester (FAPE, 1b), displayed substantial cytotoxicity against two glioma cell lines...
July 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28684647/hypersensitivity-to-antipyretics-pathogenesis-diagnosis-and-management
#19
REVIEW
Q U Lee
Antipyretics are commonly prescribed drugs and hypersensitivity occurs at rates of 0.01% to 0.3%. Hypersensitivity can be due to immune mechanisms that include type I to IV hypersensitivity. Type I hypersensitivity results from specific immunoglobulin E production following sensitisation on first exposure. Subsequent exposures elicit degranulation of mast cells, culminating an immediate reaction. Non-type I hypersensitivity is a delayed reaction that involves various effector cells, resulting in maculopapular rash, fixed drug eruptions, drug reaction with eosinophilia and systemic symptoms, and Stevens-Johnson syndrome/toxic epidermal necrolysis...
July 7, 2017: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
https://www.readbyqxmd.com/read/28683445/lysophosphatidylcholine-acyltransferase-3-expression-is-associated-with-atherosclerosis-progression
#20
Hiroki Tanaka, Nobuhiro Zaima, Takeshi Sasaki, Naoto Yamamoto, Kazunori Inuzuka, Tatsuro Yata, Takayuki Iwaki, Kazuo Umemura, Hideto Sano, Yuko Suzuki, Tetsumei Urano, Mitsutoshi Setou, Naoki Unno
Free arachidonic acid (AA) is an important precursor of lipid mediators such as leukotrienes and prostaglandins that induces inflammation and is associated with atherosclerosis progression. Recent studies have shown that lysophosphatidylcholine acyltransferase-3 (LPCAT3) converts lysophosphatidylcholine (LPC) and free AA into phosphatidylcholine (PC)-containing AA (arachidonyl-PC) and thereby can regulate intracellular free-AA levels. However, the association between LPCAT3 and atherosclerosis remains to be established...
July 6, 2017: Journal of Vascular Research
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