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Edmund Burke, Sanjeev A Datar
PURPOSE OF REVIEW: The essential role of the lymphatic system in fluid homeostasis, nutrient transport, and immune trafficking is well recognized; however, there is limited understanding of the mechanisms that regulate lymphatic function, particularly in the setting of critical illness. The lymphatics likely affect disease severity and progression in every condition, from severe systemic inflammatory states to respiratory failure. Here, we review structural and functional disorders of the lymphatic system, both congenital and acquired, as they relate to care of the pediatric patient in the intensive care setting, including novel areas of research into medical and procedural therapeutic interventions...
March 13, 2018: Current Opinion in Pediatrics
Kyung-Ah Cho, Minhwa Park, Yu-Hee Kim, Hea-Young Park Choo, Kyung Ho Lee
Mast cells are central regulators of allergic inflammation that function by releasing various proallergic inflammatory mediators, including histamine, eicosanoids and proinflammatory cytokines. Occasionally, bacterial infections may initiate or worsen allergic inflammation. A number of studies have indicated that activation of lipoxygenase in mast cells positive regulates allergic inflammatory responses by generating leukotrienes and proinflammatory cytokines. In the present study, the effects of benzoxazole derivatives on the lipopolysaccharide (LPS)‑induced expression of proinflammatory cytokines, production of histamine and surface expression of co‑stimulatory molecules on bone marrow-derived mast cells (BMMCs) were studied...
March 9, 2018: Molecular Medicine Reports
Paul C Norris, Charles N Serhan
Metabolomics enables a systems approach to interrogate the bioactive mediators, their pathways and further metabolites involved in the physiology and pathophysiology of human and animal tissues. New metabololipidomic approaches with mass spectrometry presented in this brief review can now be utilized for the identification and profiling of lipid mediator networks that control inflammation-resolution in human blood and healthy and diseased solid tissues. Coagulation of blood is a protective response that prevents excessive bleeding on injury of blood vessels...
March 7, 2018: Biochemical and Biophysical Research Communications
Miku Maruyama, Miki Kobayashi, Takeshi Uchida, Eisaku Shimizu, Hironori Higashio, Misa Ohno, Shota Uesugi, Ken-Ichi Kimura
Amber is fossilized tree resin and several biologically active compounds were isolated from ambers using the growth-restoring activity of the mutant yeast [Saccharomyces cerevisiae (zds1∆ erg3∆ pdr1∆ pdr3∆)] involving Ca2+ -signal transduction. The aim of this study is to investigate the anti-allergic effect of both the methanol extract of Kuji amber (MEKA) and its main biologically active constituent, kujigamberol (15,20-dinor-5,7,9-labdatrien-18-ol) having activity against the mutant yeast. Both MEKA and kujigamberol inhibited the degranulation of RBL-2H3 cells by stimulation of thapsigargin (Tg) (IC50  = 15...
March 5, 2018: Fitoterapia
Nikolaos Lazarinis, Johan Bood, Cristina Gomez, Johan Kolmert, Ann-Sofie Lantz, Pär Gyllfors, Andy Davis, Craig E Wheelock, Sven-Erik Dahlén, Barbro Dahlén
BACKGROUND: Leukotriene E4 (LTE4 ) is the final active metabolite among the cysteinyl leukotrienes (CysLTs). Animal studies have identified a distinct LTE4 receptor, suggesting that current CysLT1 receptor antagonists may provide incomplete inhibition of CysLT responses. OBJECTIVE: We tested this hypothesis by assessing the influence of the CysLT1 antagonist montelukast on responses induced by inhalation of LTE4 in asthmatic subjects. METHODS: Fourteen subjects with mild intermittent asthma and two subjects with aspirin exacerbated respiratory disease (AERD) received montelukast 20 mg bid and placebo for 5-7 days in a randomized, double blind, crossover study (NCT01841164)...
March 5, 2018: Journal of Allergy and Clinical Immunology
Katharine C Pike, Melika Akhbari, Dylan Kneale, Katherine M Harris
BACKGROUND: Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of risk factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. Since this peak is predictable, interventions targeting modifiable risk factors might reduce exacerbation-associated morbidity and strain upon health resources. The peak occurs in September in the Northern Hemisphere and in February in the Southern Hemisphere...
March 8, 2018: Cochrane Database of Systematic Reviews
Hans Ericsson, Karin Nelander, Maria Lagerstrom-Fermer, Clare Balendran, Maria Bhat, Ligia Chialda, Li-Ming Gan, Maria Heijer, Magnus Kjaer, John Lambert, Eva-Lotte Lindstedt, Gun-Britt Forsberg, Carl Whatling, Stanko Skrtic
We evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD5718, a novel 5-lipooxygenase activating protein (FLAP) inhibitor, in a randomized, single-blind, placebo-controlled, first-in-human (FIH) study consisting of single and multiple ascending dosing (SAD and MAD) for 10 days in healthy subjects. Target engagement was measured by ex vivo calcium ionophore stimulated leukotriene B (LTB4 ) production in whole blood and endogenous leukotriene E (LTE4 ) in urine. No clinically relevant safety and tolerability findings were observed...
March 8, 2018: Clinical and Translational Science
M A W Hermans, R Otten, A F Karim, M S van Maaren
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of hypersensitivity reactions. Several distinct clinical syndromes are described regarding NSAID hypersensitivity. Such a reaction is generally caused by a non-immunological mechanism. In susceptible patients, COX-1 inhibition leads to an imbalance in lipid mediators such as leukotrienes and prostaglandins. It is essential to distinguish multiple nonspecific NSAID hypersensitivity from single NSAID hypersensitivity, since the management of these respective syndromes is essentially different...
March 2018: Netherlands Journal of Medicine
A A Szczepańska, M Łupicka, B M Socha, A J Korzekwa
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the superfamily of nuclear receptors. Three isoforms have been described: alpha (PPARα), delta (PPARδ), and gamma (PPARγ). PPARs heterodimerize with retinoid X receptors (RXRs: RXRα, RXRβ and RXRγ). PPAR activity can be modulated by several ligands, including arachidonic acid (AA) metabolites. The aims of the study were to determine the effect of AA metabolites (prostaglandin [PG]E2 , PGF2α , leukotriene [LT]B4 , and LTC4 ) on mRNA (real-time PCR) and protein expression (Western blotting) of PPARα, PPARδ, and PPARγ, and on mRNA expression of RXRα, RXRβ, and RXRγ, in bovine epithelial, stromal, and myometrial primary uterine cells and in bovine stromal cells with silenced PPAR genes (N=10)...
March 3, 2018: General and Comparative Endocrinology
Mahboobeh Haji Sadeghi, Caroline E Wright, Simon Hart, Michael Crooks, Alyn Morice
BACKGROUND: Whether the fraction of exhaled nitric oxide (FeNO) measurement can predict the response to anti-inflammatory treatment in chronic cough is unknown. OBJECTIVE: To explore whether the effectiveness of treatment with 10 mg of montelukast or 20 mg of prednisolone in patients with chronic cough is predicted by FeNO level. METHODS: In this randomized, open-label, controlled pilot study conducted in the Clinical Trial Unit in Castle Hospital in the United Kingdom, 50 nonsmoking patients with a cough that lasted more than 8 weeks were sequentially enrolled in the study...
March 2018: Annals of Allergy, Asthma & Immunology
Eneida S Oliveira, Stella G Colombarolli, Camila S Nascimento, Izabella C A Batista, Jorge G G Ferreira, Daniele L R Alvarenga, Laís O B de Sousa, Rafael R Assis, Marcele N Rocha, Érica A R Alves, Carlos E Calzavara-Silva
The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus -induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated...
February 28, 2018: Viruses
Kurt Appel, Eduardo Munoz, Carmen Navarrete, Cristina Cruz-Teno, Andreas Biller, Eva Thiemann
Immulina® , a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis ( Spirulina ) is a potent activator of innate immune cells. On the other hand, it is well documented that Spirulina exerts anti-inflammatory effects and showed promising effects with respect to the relief of allergic rhinitis symptoms. Taking into account these findings, we decided to elucidate whether Immulina® , and immunLoges® (a commercial available multicomponent nutraceutical with Immulina® as a main ingredient) beyond immune-enhancing effects, might also exert inhibitory effects in the induced allergic inflammatory response and on histamine release from RBL-2H3 mast cells...
February 26, 2018: Plants (Basel, Switzerland)
Andreas Koeberle, Arne Henkel, Moritz Verhoff, Lars Tausch, Stefanie König, Dagmar Fischer, Nicole Kather, Stefanie Seitz, Michael Paul, Johann Jauch, Oliver Werz
Age-related diseases, such as osteoarthritis, Alzheimer's disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component...
February 24, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Soo-Yeon Jeong, Yoo Na Im, Ji Young Youm, Hern-Ku Lee, Suhn-Young Im
Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a multifactorial inflammatory disease of the small intestine and colon. Many investigators have reported that l-glutamine (Gln) therapy improves outcomes of experimental colitis models, although the mechanism is not fully understood. Regarding the anti-inflammatory properties of Gln, we have shown that Gln can effectively deactivate cytosolic phospholipase A₂ (cPLA₂) by rapid induction of MAPK phosphatase (MKP)-1. In this study, we explore the possibility that Gln ameliorates dextran sulfate sodium (DSS)-induced colitis via MKP-1 induction, resulting in inhibition of cPLA₂, which has been reported to play a key role in the pathogenesis of IBD...
March 1, 2018: Nutrients
Nan Chiang, Ian R Riley, Jesmond Dalli, Ana R Rodriguez, Bernd W Spur, Charles N Serhan
Resolution of acute inflammation is governed, in part, by lipid mediator class switching from proinflammatory eicosanoids to specialized proresolving mediators, including a recently identified new pathway of mediators, termed maresin conjugates in tissue regeneration (MCTR), which includes MCTR1, MCTR2, and MCTR3. Here, we addressed whether each MCTR can impact the known vascular actions of cysteinyl leukotrienes. Leukotriene D4 (LTD4 ; 1.5 nmol/mouse) initiated vascular leakage in mouse cremaster vessels, which was reduced (>75%) by MCTR1 and MCTR2 (0...
February 28, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Bruce A Rosa, Taniawati Supali, Lincoln Gankpala, Yenny Djuardi, Erliyani Sartono, Yanjiao Zhou, Kerstin Fischer, John Martin, Rahul Tyagi, Fatorma K Bolay, Peter U Fischer, Maria Yazdanbakhsh, Makedonka Mitreva
BACKGROUND: The human intestine and its microbiota is the most common infection site for soil-transmitted helminths (STHs), which affect the well-being of ~ 1.5 billion people worldwide. The complex cross-kingdom interactions are not well understood. RESULTS: A cross-sectional analysis identified conserved microbial signatures positively or negatively associated with STH infections across Liberia and Indonesia, and longitudinal samples analysis from a double-blind randomized trial showed that the gut microbiota responds to deworming but does not transition closer to the uninfected state...
February 28, 2018: Microbiome
John L Wallace
Eicosanoids play important roles in modulating inflammation throughout the body. The gastrointestinal tract, in part because of its intimate relationship with the gut microbiota, is in a constant state of low-grade inflammation. Eicosanoids like prostaglandins, lipoxins and leukotrienes play essential roles in maintenance of mucosal integrity. On the other hand, in some circumstances these mediators can become major drivers of inflammatory processes when the lining of the GI tract is breached. Drugs such as nonsteroidal anti-inflammatories, by altering the production of various eicosanoids, can dramatically impact the ability of the GI tract to respond appropriately to injury...
February 27, 2018: British Journal of Pharmacology
Sneh Biyani, M Jedorah Benson, Sarah C DeShields, Tina D Cunningham, Cristina M Baldassari
Objective Due to limitations of polysomnography (PSG), novel ways to evaluate pediatric obstructive sleep apnea (OSA) are needed. Urinary leukotriene E4 (LTE4), an inflammatory marker, has been identified as a potential biomarker for pediatric OSA. The objective of the study was to assess whether urinary LTE4 levels correlate with OSA severity, as determined by obstructive apnea-hypopnea index (AHI) and nadir oxygen saturation. Study Design Prospective trial. Setting Tertiary care children's hospital. Subjects and Methods Children (age, 3-16 years) with sleep-disordered breathing (SDB) who were referred for PSG were included...
February 1, 2018: Otolaryngology—Head and Neck Surgery
Huijun Wu, Hui Liu, Fengtong Zuo, Lihua Zhang
Cerebral ischemia injury is a clinical, frequently occurring disease, which causes a heavy burden on society and families. It has been demonstrated that cytosolic phospholipase A2α (cPLA2α) is significant in neurological injury caused by ischemic brain injury, and inhibition of cPLA2α may reduce stroke injury. In the present study, the role of cPLA2α was investigated in a mouse model of middle cerebral artery occlusion and/or reperfusion (MCAO/R) using an effective cPLA2α inhibitor and adenoviruses‑mediated RNA interference...
February 15, 2018: Molecular Medicine Reports
Bin Li, Xiao Han, Xin Ye, Jianbo Ni, Jianghong Wu, Juanjuan Dai, Zengkai Wu, Congying Chen, Rong Wan, Xingpeng Wang, Guoyong Hu
Leukotriene B4 (LTB4) is a potent chemoattractant and inflammatory mediator involved in multiple inflammatory diseases. Substance P (SP) has been reported to promote production of LTB4 in itch-associated response in vivo and in some immune cells in vitro. Here, we investigated the role of LTB4 in acute pancreatitis (AP), AP-associated acute lung injury (ALI) and the related mechanisms of LTB4 production in AP. In vivo, murine AP model was induced by caerulein and lipopolysaccharide or L-arginine. The levels of LTB4 and its specific receptor BLT1 were markedly upregulated in both AP models...
February 23, 2018: International Immunopharmacology
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