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Phospholipase A2

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https://www.readbyqxmd.com/read/28334001/effects-of-overweight-and-the-pla2g7-v279f-polymorphism-on-the-association-of-age-with-systolic-blood-pressure
#1
Minjoo Kim, Minkyung Kim, Hye Jin Yoo, Hye Young Jang, Sang-Hyun Lee, Jong Ho Lee
This prospective study aimed to determine the effects of the persistence of overweight for three years and the PLA2G7 V279F polymorphism, as well as the interaction between these factors, on the association of age with blood pressure (BP). Healthy middle-aged subjects with normotensive BP were divided into the normal-weight and overweight groups. The PLA2G7 V279F genotype, BP, lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, and oxidized low-density lipoprotein (ox-LDL) were determined. Lp-PLA2 activity was lower in the F allele subjects (n = 111) than in those with the VV genotype (n = 389)...
2017: PloS One
https://www.readbyqxmd.com/read/28332853/correlations-between-lp-pla2-gene-polymorphisms-and-susceptibility-and-severity-of-acute-pancreatitis-in-a-chinese-population
#2
Min Ma, Chun-Xia Zhai, Cai-Xia Sun
OBJECTIVE: This case-control study explored correlations between LP-PLA2 gene polymorphisms (A379V, V279F, and R92H) and susceptibility and severity of acute pancreatitis (AP) in a Chinese population. MATERIALS AND METHODS: From October 2013 to October 2015, 94 AP patients were chosen as the case group. According to the Acute Physiology and Chronic Health Evaluation (APACHE) II score standard, AP patients were divided into a mild AP (MAP) group (n = 46) and severe AP (SAP) group (n = 48)...
March 23, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28331487/a-clinical-trial-protocol-to-treat-massive-africanized-honeybee-apis-mellifera-attack-with-a-new-apilic-antivenom
#3
Alexandre Naime Barbosa, Leslie Boyer, Jean-Philippe Chippaux, Natalia Bronzatto Medolago, Carlos Antonio Caramori, Ariane Gomes Paixão, João Paulo Vasconcelos Poli, Mônica Bannwart Mendes, Lucilene Delazari Dos Santos, Rui Seabra Ferreira, Benedito Barraviera
BACKGROUND: Envenomation caused by multiple stings from Africanized honeybees Apis mellifera constitutes a public health problem in the Americas. In 2015, the Brazilian Ministry of Health reported 13,597 accidents (incidence of seven cases per 100,000 inhabitants) with 39 deaths (lethality of 0.25%). The toxins present in the venom, which include melittin and phospholipase A2, cause lesions in diverse organs and systems that may be fatal. As there has been no specific treatment to date, management has been symptomatic and supportive only...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28327442/immune-cells-and-mediators-involved-in-the-inflammatory-responses-induced-by-a-p-i-metalloprotease-and-a-phospholipase-a2-from-bothrops-atrox-venom
#4
Danilo L Menaldo, Carolina P Bernardes, Karina F Zoccal, Anna L Jacob-Ferreira, Tássia R Costa, Maria P F M Del Lama, Rose M Z G Naal, Fabiani G Frantz, Lúcia H Faccioli, Suely V Sampaio
Bothrops envenomations can promote severe inflammatory responses by inducing edema, pain, leukocyte recruitment and release of chemical mediators by local cells. In the present study, two toxins from Bothrops atrox venom (the P-I metalloprotease Batroxase and the acidic phospholipase A2 BatroxPLA2) were evaluated in relation to their inflammatory effects induced in vivo and in vitro, mainly focusing on the participation of different immune cells and inflammatory mediators. Both toxins mainly promoted acute inflammatory responses with significant recruitment of neutrophils in the early hours (1-4h) after administration into the peritoneal cavity of C57BL/6 mice, and increased infiltration of mononuclear cells especially after 24h...
March 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28327300/rbaltmip-a-recombinant-alpha-type-myotoxin-inhibitor-from-bothrops-alternatus-rhinocerophis-alternatus-snake-as-a-potential-candidate-to-complement-the-antivenom-therapy
#5
Norival A Santos-Filho, Tiago S Sousa, Johara Boldrini-França, Ludier K Santos-Silva, Danilo L Menaldo, Flávio Henrique-Silva, Adélia C O Cintra, Helen J Laure, Carla C N Mamede, Fábio Oliveira, Thalita B Riul, Marcelo Dias-Baruffi, José C Rosa, Suely V Sampaio
Phospholipase A2 inhibitors (PLIs) are important targets in the search and development of new drugs. This study aimed at evaluating the potential of an alpha-type phospholipase A2 inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake in its recombinant form (rBaltMIP) to complement the conventional antivenom therapy. Biochemical experiments showed that rBaltMIP presented pI 5.8 and molecular masses of ∼21 kDa by SDS-PAGE and 19.57 kDa by MALDI/TOF MS. After tryptic peptides sequencing, the results were compared with other PLIs available in databases, showing 100% identity between rBaltMIP and its native inhibitor BaltMIP and from 92% to 96% identity with other inhibitors...
December 15, 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28326559/a-phase-1-study-to-evaluate-the-safety-and-ldl-cholesterol-lowering-effects-of-rg7652-a-fully-human-monoclonal-antibody-against-proprotein-convertase-subtilisin-kexin-type-9
#6
Amos Baruch, Diana Luca, Robert S Kahn, Kyra J Cowan, Maya Leabman, Nageshwar R Budha, Cecilia P C Chiu, Yan Wu, Daniel Kirchhofer, Andrew Peterson, John C Davis, Whittemore G Tingley
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) downregulates low-density lipoprotein (LDL) receptors, thereby leading to a rise in circulating LDL cholesterol (LDL-C). RG7652 is a fully human monoclonal antibody against PCSK9. This placebo-controlled, phase 1 ascending-dose study in healthy subjects evaluated the safety of RG7652 and its efficacy as a potential LDL-C-lowering drug. HYPOTHESIS: Anti-PCSK9 antibody therapy safely and effectively reduces LDL-C...
March 22, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28323197/postprandial-effects-of-wine-consumption-on-platelet-activating-factor-metabolic-enzymes
#7
Chrysa Argyrou, Ioanna Vlachogianni, George Stamatakis, Constantinos A Demopoulos, Smaragdi Antonopoulou, Elizabeth Fragopoulou
Platelet Activating factor (PAF) is a potent inflammatory mediator that is involved in the initiation and the prolongation of atherosclerosis. The purpose of the study was to investigate the effect of wine consumption on the activity of PAF metabolic enzymes and on IL-6 levels as a cytokine inflammatory marker. Healthy men participated in 4 daily trials and consumed a standardized meal along with Robola wine (trial R), or Cabernet Sauvignon (trial CS), or ethanol solution (trial E), or water (trialW). A significant trial effect was found in the activity of lyso-PAF acetyltransferase (Lyso-PAF AT) (ptrial=0...
March 16, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28321088/drug-induced-interstitial-pneumonitis-in-essential-thrombocythemia-treated-with-anagrelide
#8
Tomohiro Kajiguchi, Sonoko Kamoshita, Takayasu Ito, Mitsuaki Yagi, Tomoki Kimura
Anagrelide, a phospholipase A2 inhibitor, is widely used in the management of essential thrombocythemia. To date, anagrelide has only rarely been reported to be associated with the development of drug-induced interstitial pneumonitis. We herein report two cases of anagrelide-associated interstitial pneumonitis. The patients were a 67-year-old woman and a 75-year-old man, both with essential thrombocythemia. Both cases developed interstitial pneumonitis at 8 weeks after administration of anagrelide. Because anagrelide-induced interstitial pneumonitis was suspected from CT scan and bronchoalveolar lavage fluid findings, anagrelide-therapy was discontinued and corticosteroid administration was initiated...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28315380/primary-structures-and-partial-toxicological-characterization-of-two-phospholipases-a2-from-micrurus-mipartitus-and-micrurus-dumerilii-coral-snake-venoms
#9
Paola Rey-Suárez, Vitelbina Núñez, Mónica Saldarriaga-Córdoba, Bruno Lomonte
Snake venom phospholipases A2 (PLA2) share high sequence identities and a conserved structural scaffold, but show important functional differences. Only a few PLA2s have been purified and characterized from coral snake (Micrurus spp.) venoms, and their role in envenomation remains largely unknown. In this report, we describe the isolation, sequencing and partial functional characterization of two Micrurus PLA2s: MmipPLA2 from Micrurus mipartitus and MdumPLA2 from Micrurus dumerilii, two species of clinical importance in Colombia...
March 14, 2017: Biochimie
https://www.readbyqxmd.com/read/28315303/neuroprotective-effect-of-2-hydroxy-arachidonic-acid-in-a-rat-model-of-transient-middle-cerebral-artery-occlusion
#10
I F Ugidos, M Santos-Galdiano, D Pérez-Rodríguez, B Anuncibay-Soto, E Font-Belmonte, D J López, M Ibarguren, X Busquets, A Fernández López
Stroke modifies the composition of cell membranes by eliciting the breakdown of membrane phospholipids whose products, such as arachidonic acid (AA), are released in the cytosol. The action of enzymes such as cyclooxygenases on AA leads to inflammatory stimuli and increases the cell oxidative stress. We report here the neuroprotective effect of 2-hydroxyarachidonic acid (2OAA), a cyclooxygenase inhibitor derived from AA, as a promising neuroprotective therapy against stroke. The effect of a single dose of 2OAA, administered intragastrically 1 hour after the ischaemic insult, in a rat model of transient middle cerebral artery occlusion (tMCAO) was tested after 24 hours of reperfusion...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28314621/docosahexaenoic-acid-dha-an-essential-nutrient-and-a-nutraceutical-for-brain-health-and-diseases
#11
REVIEW
Grace Y Sun, Agnes Simonyi, Kevin L Fritsche, Dennis Y Chuang, Mark Hannink, Zezong Gu, C Michael Greenlief, Jeffrey K Yao, James C Lee, David Q Beversdorf
Docosahexaenoic acid (DHA), a polyunsaturated fatty acid (PUFA) enriched in phospholipids in the brain and retina, is known to play multi-functional roles in brain health and diseases. While arachidonic acid (AA) is released from membrane phospholipids by cytosolic phospholipase A2 (cPLA2), DHA is linked to action of the Ca(2+)-independent iPLA2. DHA undergoes enzymatic conversion by 15-lipoxygenase (Alox 15) to form oxylipins including resolvins and neuroprotectins, which are powerful lipid mediators. DHA can also undergo non-enzymatic conversion by reacting with oxygen free radicals (ROS), which cause the production of 4-hydoxyhexenal (4-HHE), an aldehyde derivative which can form adducts with DNA, proteins and lipids...
March 10, 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28314136/platelet-microparticle-inspired-clot-responsive-nanomedicine-for-targeted-fibrinolysis
#12
Christa L Pawlowski, Wei Li, Michael Sun, Kavya Ravichandran, DaShawn Hickman, Clarissa Kos, Gurbani Kaur, Anirban Sen Gupta
Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger...
March 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28302413/characterization-of-daboia-russelii-and-naja-naja-venom-neutralizing-ability-of-an-undocumented-indigenous-medication-in-sri-lanka
#13
Madhushika M Silva, Sampath S Seneviratne, Devaka K Weerakoon, Charitha L Goonasekara
BACKGROUND: Indigenous medicinal practice in Sri Lanka talks about powerful compounds extracted from native plants for treating venomous snake bites which are hardly documented in literature but are used by the indigenous doctors for thousand years. OBJECTIVE: We screened the neutralizing ability of a herbal preparation practiced in indigenous medicine of Sri Lanka, consisting of Sansevieria cylindrica, Jatropha podagrica and Citrus aurantiifolia, for its ability to neutralize venom toxins of Naja naja (Common Cobra) and Daboia russelii (Russell's viper)...
March 13, 2017: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/28302166/secreted-phospholipase-a2-of-clonorchis-sinensis-activates-hepatic-stellate-cells-through-a-pathway-involving-jnk-signalling
#14
Yinjuan Wu, Ye Li, Mei Shang, Yu Jian, Caiqin Wang, Adham Sameer A Bardeesi, Zhaolei Li, Tingjin Chen, Lu Zhao, Lina Zhou, Ai He, Yan Huang, Zhiyue Lv, Xinbing Yu, Xuerong Li
BACKGROUND: Secreted phospholipase A2 (sPLA2) is a protein secreted by Clonorchis sinensis and is a component of excretory and secretory products (CsESPs). Phospholipase A2 is well known for its role in liver fibrosis and inhibition of tumour cells. The JNK signalling pathway is involved in hepatic stellate cells (HSCs) activation. Blocking JNK activity with SP600125 inhibits HSCs activation. In a previous study, the protein CssPLA2 was expressed in insoluble inclusion bodies. Therefore, it's necessary to express CssPLA2 in water-soluble form and determine whether the enzymatic activity of CssPLA2 or cell signalling pathways is involved in liver fibrosis caused by clonorchiasis...
March 16, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28301218/retinal-pathology-is-associated-with-increased-blood-retina-barrier-permeability-in-a-diabetic-and-hypercholesterolaemic-pig-model-beneficial-effects-of-the-lppla2-inhibitor-darapladib
#15
Nimish K Acharya, Xin Qi, Eric L Goldwaser, George A Godsey, Hao Wu, Mary C Kosciuk, Theresa A Freeman, Colin H Macphee, Robert L Wilensky, Venkat Venkataraman, Robert G Nagele
Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood-brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta1-42 peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood-retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib...
March 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28300679/px-18-protects-human-saphenous-vein-endothelial-cells-under-arterial-blood-pressure
#16
Koba Kupreishvili, Wim Stooker, Reindert W Emmens, Alexander B A Vonk, Jessica A Sipkens, Annemieke van Dijk, Leon Eijsman, Paul H Quax, Victor W M van Hinsbergh, Paul A J Krijnen, Hans W M Niessen
BACKGROUND: Arterial blood pressure-induced shear stress causes endothelial cell apoptosis and inflammation in vein grafts after coronary artery bypass grafting. As the inflammatory protein type IIA secretory Phospholipase A2 (sPLA2-IIA) has been shown to progress atherosclerosis, we hypothesized a role for sPLA2-IIA herein. MATERIALS AND METHODS: The effects of PX-18, an inhibitor of both sPLA2-IIA and apoptosis, on residual endothelium and the presence of sPLA2-IIA were studied in human saphenous vein segments (n=6) perfused at arterial blood pressure with autologous blood for 6 hours...
March 11, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28294428/probiotics-and-antimicrobial-protein-and-peptide-levels-in-preterm-infants
#17
Tobias Strunk, Julie Hibbert, Dorota Doherty, Caitlyn Granland, Stephanie Trend, Karen Simmer, David Burgner, Sanjay Patole, Andrew Currie
AIM: To characterise the secreted and inducible antimicrobial protein and peptide (APP) levels in a prospective cohort of preterm infants (<30 weeks gestational age) with or without Bifidobacterium breve M16V supplementation during the first month of life. METHODS: We analysed serial biosamples of infants who did (n=13) or did not receive (n=62) B. breve (3×10(9) cfu/day). Peripheral blood was obtained on days 1, 14 and 28, and infant stool prior to commencement of probiotic supplementation and on day 21...
March 12, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28289073/sympathetic-nervous-activity-in-patients-with-acute-coronary-syndrome-a-comparative-study-of-inflammatory-biomarkers
#18
Humberto Graner Moreira, Rony Lopes Lage, Daniel G Martinez, Larissa Ferreira-Santos, Maria U P B Rondon, Carlos Eduardo Negrão, Jose C Nicolau
Previous studies have shown that both sympathetic hyperactivity and enhanced inflammatory responses are associated with poor outcomes in patients with acute coronary syndrome (ACS). Whether there is a correlation between these two characteristics remains unclear. Thirty-four patients with uncomplicated ACS were evaluated; their mean age was 51.7 ± 7.0 years, 79.4% were male, and 94.1% had myocardial infarction. On the fourth day of hospitalization, they underwent muscle sympathetic nerve activity (MSNA) analysis (microneurography), as well as ultrasensitive C-reactive protein (usCRP), interleukin-6 (IL-6) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity measurements...
March 13, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28287729/functional-and-structural-characterization-of-a-thermostable-phospholipase-a2-from-a-sparidae-fish-diplodus-annularis
#19
Nabil Smichi, Houcemeddine Othman, Neila Achouri, Alexandre Noiriel, Vincent Arondel, Najet Srairi-Abid, Abdelkarim Abousalham, Youssef Gargouri, Nabil Miled, Ahmed Fendri
Novel phospholipase (PLA2) genes from the Sparidae family were cloned. The sequenced PLA2 revealed an identity with pancreatic PLA2 group IB. To better understand the structure/function relationships of these enzymes and their evolution, the Diplodus annularis PLA2 (DaPLA2) was overexpressed in E. coli. The refolded enzyme was purified by Ni-affinity chromatography and has a molecular mass of 15 kDa as determined by MALDI-TOF spectrometry. Interestingly, unlike the pancreatic type, the DaPLA2 was active and stable at higher temperatures, which suggests its great potential in biotechnological applications...
March 13, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28286182/crotalus-helleri-venom-preconditioning-reduces-postoperative-cerebral-edema-and-improves-neurological-outcomes-after-surgical-brain-injury
#20
Cherine H Kim, Devin W McBride, Prativa Sherchan, Carl E Person, Eric C K Gren, Wayne Kelln, Tim Lekic, William K Hayes, Jiping Tang, John H Zhang
INTRODUCTION: Postoperative cerebral edema is a devastating complication in neurosurgical patients. Loss of blood-brain barrier integrity has been shown to lead to the development of brain edema following neurosurgical procedures. The aim of this study was to evaluate preconditioning with Crotalus helleri venom (Cv-PC) as a potential preventive therapy for reducing postoperative brain edema in the rodent SBI model. C. helleri venom is known to contain phospholipase A2 (PLA2), an enzyme upstream to cyclooxygenase-2 (COX-2) in the inflammatory cascade, acts to increase the production of inflammatory mediators, such as prostaglandins...
March 9, 2017: Neurobiology of Disease
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