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https://www.readbyqxmd.com/read/28341178/mechanisms-underlying-sodium-nitroprusside-induced-tolerance-in-the-mouse-aorta-role-of-ros-and-cyclooxygenase-derived-prostanoids
#1
Mariana C Diniz, Vania C Olivon, Lívia D Tavares, Janaina A Simplicio, Natália A Gonzaga, Daniele G de Souza, Lusiane M Bendhack, Carlos R Tirapelli, Daniella Bonaventura
AIMS: To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-κB activation and pro-inflammatory cytokines production during SNP-induced tolerance. MAIN METHODS: To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60min with SNP (10nmol/L). KEY FINDINGS: Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium-intact aortas for 60min with this inorganic nitrate...
March 21, 2017: Life Sciences
https://www.readbyqxmd.com/read/28337385/comparison-of-ticagrelor-and-high-dose-clopidogrel-on-the-platelet-functions-in-patients-with-inadequate-response-to-clopidogrel
#2
Xinshun Gu, Xianghua Fu, Yanbo Wang, Wenhui Zhang, Weize Fan, Yunfa Jiang, Guozhen Hao, Qing Miao, Yi Li, Wei Zhi
OBJECTIVE: To evaluate the effects of ticagrelor and high-dose clopidogrel on the platelet functions in patients with inadequate response to clopidogrel. METHODS: In this prospective, randomized and controlled study, patients who had been diagnosed as acute coronary syndrome (ACS) with inadequate response to clopidogrel in the Second Hospital of Hebei Medical University from July 2015 to June 2016 were enrolled. Inadequate response to clopidogrel was defined as absolute reduction of platelet aggregation rate (PAR) <30% or PAR >70%...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28315871/effects-of-glycyrrhizin-in-a-mouse-model-of-lung-adenocarcinoma
#3
Qing-Ping Deng, Mao-Jie Wang, Xing Zeng, George Gong Chen, Run-Yue Huang
BACKGROUND: Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2) in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer. METHODS: Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TPα)...
March 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28315343/inhibition-of-agonist-induced-smooth-muscle-contraction-by-picotamide-in-the-male-human-lower-urinary-tract-outflow-region
#4
Martin Hennenberg, Alexander Tamalunas, Yiming Wang, Patrick Keller, Melanie Schott, Frank Strittmatter, Annika Herlemann, Qingfeng Yu, Beata Rutz, Anna Ciotkowska, Christian G Stief, Christian Gratzke
Male lower urinary tract symptoms (LUTS) due to bladder outlet obstruction are characterized by abnormal smooth muscle contractions in the lower urinary tract. Alpha1-adrenoceptor antagonists may induce smooth muscle relaxation in the outflow region and represent the current goldstandard of medical treatment. However, results may be unsatisfactory or inadequate. Apart from α1-adrenoceptor agonists, smooth muscle contraction in the outflow region may be induced by thromboxane A2 (TXA2), endothelins, or muscarinic receptor agonists...
March 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28286123/the-enhancement-of-txa2-receptors-mediated-contractile-response-in-intrarenal-artery-dysfunction-in-type-2-diabetic-mice
#5
Su-Juan Kuang, Jie-Sheng Qian, Hui Yang, Fang Rao, Xiao-Yan Chen, Meng-Zhen Zhang, Zhi-Xin Shan, Qiu-Xiong Lin, Yu-Mei Xue, Shu-Lin Wu, Li Jiang, Chun-Bo Chen, Chun-Yu Deng
Thromboxane A2 (TXA2) has been implicated in the pathogenesis of diabetic vascular complications, although the underlying mechanism remains unclear. The present study investigated the alterations in TXA2 receptor signal transduction in type 2 diabetic renal arteries. The contraction of renal arterial rings in control (db/m+) mice and type 2 diabetic (db/db) mice was measured by a Multi Myograph System. Intracellular calcium concentration ([Ca(2+)]i) in vascular smooth muscle cells was measured by Fluo-4/AM dye and confocal laser scanning microscopy...
March 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28267572/pneumolysin-mediates-heterotypic-aggregation-of-neutrophils-and-platelets-in%C3%A2-vitro
#6
Jan G Nel, Chrisna Durandt, Annette J Theron, Gregory R Tintinger, Roger Pool, Guy A Richards, Timothy J Mitchell, Charles Feldman, Ronald Anderson
OBJECTIVES: Platelets orchestrate the inflammatory activities of neutrophils, possibly contributing to pulmonary and myocardial damage during severe pneumococcal infection. This study tested the hypothesis that the pneumococcal toxin, pneumolysin (Ply), activates production of platelet-activating factor (PAF) and thromboxane A2 (TxA2) by neutrophils, these bioactive lipids being potential mediators of neutrophil:platelet (NP) networking. METHODS: The effects of recombinant Ply (10-80 ng mL(-1)) on the production of PAF and TxA2 by isolated neutrophils were measured using ELISA procedures, and NP aggregation by flow cytometry...
March 4, 2017: Journal of Infection
https://www.readbyqxmd.com/read/28244682/extracellular-histones-disarrange-vasoactive-mediators-release-through-a-cox-nos-interaction-in-human-endothelial-cells
#7
Daniel Pérez-Cremades, Carlos Bueno-Betí, José Luis García-Giménez, José Santiago Ibañez-Cabellos, Carlos Hermenegildo, Federico V Pallardó, Susana Novella
Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone-mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose-dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml...
February 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28139223/urinary-11-dehydro-thromboxane-b2-and-mortality-in-patients-with-stable-coronary-artery-disease
#8
Peter A McCullough, Anupama Vasudevan, Mohanakrishnan Sathyamoorthy, Jeffrey M Schussler, Carlos E Velasco, Luis R Lopez, Caren Swift, Margarita Peterson, Jenna Bennett-Firmin, Raphael Schiffmann, Teodoro Bottiglieri
Antiplatelet therapy with aspirin has been shown to reduce adverse outcomes in patients with coronary artery disease (CAD). Aspirin irreversibly inhibits platelet cyclooxygenase-1 and attenuates thromboxane A2 (TXA2)-mediated platelet aggregation, but there is variable suppression of cyclooxygenase-1. From a cohort of patients with stable CAD, we performed blinded, detailed chart abstraction, and measured urinary 11-dehydro-thromboxane B2 (11dhTxB2), an inactive metabolite of TxA2 from frozen samples. There were 327 men (73%) and 122 women (27%) with a mean age (±SD) of 67 ± 10 and 65 ± 10 years, respectively...
April 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28123708/synthetic-polyphosphate-inhibits-endogenous-coagulation-and-platelet-aggregation-in-vitro
#9
Xiaoyang Yang, Mengjie Wan, Ting Liang, Minyuan Peng, Fangping Chen
Platelet-derived polyphosphate has previously been indicated to induce coagulation. However, industrially synthesized polyphosphate has been found to have different effects from those of the platelet-derived form. The present study investigated whether synthetic sodium polyphosphate inhibits coagulation using routine coagulation tests and thromboelastography. Synthetic polyphosphate was found to inhibit adenosine diphosphate-, epinephrine-, arachidonic acid-, ristocetin-, thrombin-, oxytocin- and pituitrin-induced platelet aggregation...
January 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28115138/endocannabinoid-2-arachidonoylglycerol-protects-inflammatory-insults-from-sulfur-dioxide-inhalation-via-cannabinoid-receptors-in-the-brain
#10
Ben Li, Minjun Chen, Lin Guo, Yang Yun, Guangke Li, Nan Sang
Sulfur dioxide (SO2) pollution in the atmospheric environment causes brain inflammatory insult and inflammatory-related microvasculature dysfunction. However, there are currently no effective medications targeting the harmful outcomes from chemical inhalation. Endocannabinoids (eCBs) are involved in neuronal protection against inflammation-induced neuronal injury. The 2-arachidonoylglycerol (2-AG), the most abundant eCBs and a full agonist for cannabinoid receptors (CB1 and CB2), is also capable of suppressing proinflammatory stimuli and improving microvasculature dysfunction...
January 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28108419/regulation-of-protein-kinase-c-related-kinase-prk-signalling-by-the-tp%C3%AE-and-tp%C3%AE-isoforms-of-the-human-thromboxane-a2-receptor-implications-for-thromboxane-and-androgen-dependent-neoplastic-and-epigenetic-responses-in-prostate-cancer
#11
Aine G O'Sullivan, Eamon P Mulvaney, B Therese Kinsella
The prostanoid thromboxane (TX) A2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA2/TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA2-TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28069828/lpa1-receptor-mediated-thromboxane-a2-release-is-responsible-for-lysophosphatidic-acid-induced-vascular-smooth-muscle-contraction
#12
Péter Tibor Dancs, Éva Ruisanchez, Andrea Balogh, Cecília Rita Panta, Zsuzsanna Miklós, Rolf M Nüsing, Junken Aoki, Jerold Chun, Stefan Offermanns, Gábor Tigyi, Zoltán Benyó
Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6 In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA1-3 agonist VPC31143 induced dose-dependent vasoconstriction...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28031017/nitric-oxide-signaling-and-the-cross-talk-with-prostanoids-pathways-in-vascular-system
#13
Bruno R Silva, Tiago D Paula, Michele Paulo, Lusiane M Bendhack
BACKGROUND: This review provides an overview of the cellular signaling of nitric oxide (NO) and prostanoids in vascular cells and the possible cross talk between their pathways, mainly in hypertension, since the imbalance of these two systems has been attributed to development of some cardiovascular diseases. It also deals with the modulation of vasodilation induced by NO donors. NO is a well-known second messenger involved in many cellular functions. CONCLUSION: In the vascular system, the NO produced by endothelial NO-synthase (eNOS) or released by NO donors acts in vascular smooth muscle cells, the binding of NO to Fe2+-heme of soluble guanylyl-cyclase (sGC) activates sGC and the production of cyclic guanosine-3-5-monophosphate (cGMP)...
December 28, 2016: Medicinal Chemistry
https://www.readbyqxmd.com/read/28028021/ask1-regulates-platelet-granule-secretion-thromboxane-a2-generation-and-thrombus-formation-in-mice
#14
Meghna U Naik, Pravin Patel, Randall Derstine, Ramya Turaga, Xi Chen, Kalyan Golla, Keith B Neeves, Hidenori Ichijo, Ulhas P Naik
Mitogen activated protein kinases (MAPKs) are expressed in platelets and are activated downstream of physiological agonists. Pharmacological and genetic evidence indicate that MAPKs play a significant role in hemostasis and thrombosis, but it is not well understood how MAPKs are activated upon platelet stimulation. Here, we show that Apoptosis Signal-regulating Kinase 1 (ASK1), a member of the MAP3K family, is expressed in both human and murine platelets. ASK1 is rapidly and robustly activated upon platelet stimulation by physiological agonists...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/27951728/effects-of-astaxanthin-on-blood-coagulation-fibrinolysis-and-platelet-aggregation-in-hyperlipidemic-rats
#15
Zu-Yue Deng, Wei-Guang Shan, Shen-Feng Wang, Meng-Mei Hu, Yan Chen
CONTEXT: Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear. OBJECTIVE: The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats. MATERIALS AND METHODS: Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27934923/timosaponin-aiii-induces-antiplatelet-and-antithrombotic-activity-via-gq-mediated-signaling-by-the-thromboxane-a2-receptor
#16
Yue Cong, Limei Wang, Renjun Peng, Yang Zhao, Fan Bai, Chao Yang, Xiaolan Liu, Daqian Wang, Baiping Ma, Yuwen Cong
The thromboxane (Tx) A2 pathway is a major contributor to the amplification of initial platelet activation and is therefore a key drug target. To identify potent small-molecule inhibitors of the thromboxane prostaglandin (TP) receptor, we screened a small steroidal saponin library using U46619-induced rat platelet aggregation assays. Timosaponin AIII (TAIII) was identified as a potent inhibitor of U46619-induced rat platelet aggregation and exhibited superior selectivity for the TP receptor versus other G protein-coupled receptors and a PKC activator...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27927214/antiplatelet-and-antithrombotic-effects-of-cordycepin-enriched-wib-801ce-from-cordyceps-militaris-ex-vivo-in-vivo-and-in-vitro
#17
Hyuk-Woo Kwon, Jung-Hae Shin, Deok Hwi Lim, Woo Jeong Ok, Gi Suk Nam, Min Ji Kim, Ho-Kyun Kwon, Jun-Hee Noh, Je-Young Lee, Hyun-Hong Kim, Jong-Lae Kim, Hwa-Jin Park
BACKGROUND: A species of the fungal genus Cordyceps has been used as a complementary and alternative medicine of traditional Chinese medicine, and its major component cordycepin and cordycepin-enriched WIB-801CE are known to have antiplatelet effects in vitro. However, it is unknown whether they have also endogenous antiplatelet and antithrombotic effects. In this study, to resolve these doubts, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from Cordyceps militaris-hypha, then evaluated its ex vivo, in vivo, and in vitro antiplatelet and antithrombotic effects...
December 7, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27893755/quantification-of-arachidonic-acid-and-its-metabolites-in-rat-tissues-by-uhplc-ms-ms-application-for-the-identification-of-potential-biomarkers-of-benign-prostatic-hyperplasia
#18
Qiaoxia Bian, Weihui Wang, Nannan Wang, Yan Peng, Wen Ma, Ronghua Dai
To evaluate the potential relationship between benign prostatic hyperplasia (BPH) and the arachidonic acid (AA) metabolome, a UHPLC-MS/MS method has been developed and validated for simultaneous determination of AA and its cyclooxygenase(COX) and lipoxygenase(LOX) pathway metabolites (15-HETE, 12-HETE, TXA2, 5-HETE, AA, PGI2, PGF2α, 8-HETE, PGD2, PGE2 and LTB4) in rat tissues. The analytes were extracted from tissue samples with a protein precipitation procedure and then separated on a Shim-pack XR-ODSC18 column with 0...
2016: PloS One
https://www.readbyqxmd.com/read/27852128/antagonistic-effects-of-gingko-biloba-and-sophora-japonica-on-cerebral-vasoconstriction-in-response-to-histamine-5-hydroxytryptamine-u46619-and-bradykinin
#19
Ha Thi Thanh Nguyen, Hai Thanh Nguyen, Md Zahorul Islam, Takeshi Obi, Pitchaya Pothinuch, Thanh Van Nguyen, Tuong Manh Nguyen, Cuong Van Dao, Mitsuya Shiraishi, Atsushi Miyamoto
The aim of this study was to evaluate, for the first time, the antagonistic effects of Gingko biloba leaf (GB) and Sophora japonica L. flower bud (SJ) extracts on cerebral vasoconstriction in response to KCl, extracellular Ca[Formula: see text], histamine, 5-hydroxytryptamine (5-HT), 9,11-dideoxy-9[Formula: see text],11[Formula: see text]-methanoepoxy prostaglandin (PG) F[Formula: see text](U46619) and bradykinin (BK), in order to explain their traditional application for diseases associated with cerebral vasospasm...
2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27845343/directed-transport-of-neutrophil-derived-extracellular-vesicles-enables-platelet-mediated-innate-immune-response
#20
Jan Rossaint, Katharina Kühne, Jennifer Skupski, Hugo Van Aken, Mark R Looney, Andres Hidalgo, Alexander Zarbock
The innate immune response to bacterial infections requires the interaction of neutrophils and platelets. Here, we show that a multistep reciprocal crosstalk exists between these two cell types, ultimately facilitating neutrophil influx into the lung to eliminate infections. Activated platelets adhere to intravascular neutrophils through P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1)-mediated binding, a primary interaction that allows platelets glycoprotein Ibα (GPIbα)-induced generation of neutrophil-derived extracellular vesicles (EV)...
November 15, 2016: Nature Communications
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