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https://www.readbyqxmd.com/read/28526762/exacerbation-of-thromboinflammation-by-hyperglycemia-precipitates-cerebral-infarct-growth-and-hemorrhagic-transformation
#1
Jean-Philippe Desilles, Varouna Syvannarath, Véronique Ollivier, Clément Journé, Sandrine Delbosc, Célina Ducroux, William Boisseau, Liliane Louedec, Lucas Di Meglio, Stéphane Loyau, Martine Jandrot-Perrus, Louis Potier, Jean-Baptiste Michel, Mikael Mazighi, Benoit Ho-Tin-Noé
BACKGROUND AND PURPOSE: Admission hyperglycemia is associated with a poor outcome in acute ischemic stroke. How hyperglycemia impacts the pathophysiology of acute ischemic stroke remains largely unknown. We investigated how preexisting hyperglycemia increases ischemia/reperfusion cerebral injury. METHODS: Normoglycemic and streptozotocin-treated hyperglycemic rats were subjected to transient middle cerebral artery occlusion. Infarct growth and brain perfusion were assessed by magnetic resonance imaging...
May 19, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28515093/circulating-soluble-p-selectin-must-dimerize-to-promote-inflammation-and-coagulation-in-mice
#2
Sumith R Panicker, Padmaja Mehta-D'souza, Nan Zhang, Arkadiusz G Klopocki, Bojing Shao, Rodger P McEver
Leukocyte adhesion to P-selectin on activated platelets and endothelial cells induces shedding of the P-selectin ectodomain into the circulation. Plasma soluble P-selectin (sP-selectin) is elevated 3-4-fold in patients with cardiovascular disease. Circulating sP-selectin is thought to trigger signaling in leukocytes that directly contributes to inflammation and thrombosis. However, sP-selectin likely circulates as a monomer, and in vitro studies suggest that sP-selectin must dimerize to induce signaling in leukocytes...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28509684/histone-complexed-dna-fragments-levels-are-associated-with-coagulopathy-endothelial-cell-damage-and-increased-mortality-after-severe-pediatric-trauma
#3
Robert T Russell, Sarah C Christiaans, Tate Nice, Morgan Banks, Vincent Mortellaro, Charity Morgan, Amy Duhachek-Stapelman, Steven J Lisco, Jeffrey D Kerby, Brant M Wagener, Mike K Chen, Jean-François Pittet
BACKGROUND: The release of damage-associated molecular pattern molecules (DAMPs) in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that would be associated with poor outcomes. METHODS: We conducted a prospective observational study of 149 pediatric trauma patients and 62 control patients at two level 1 pediatric trauma centers from 2013-2016...
May 15, 2017: Shock
https://www.readbyqxmd.com/read/28498471/sodium-tanshinone-iia-sulfonate-improves-inflammation-aortic-endothelial-cell-apoptosis-disseminated-intravascular-coagulation-and-multiple-organ-damage-in-a-rat-heat-stroke-model
#4
Fang Chen, Huimin Li, Guoguo Zhu, Xiaojuan Chen, Zhongzhi Tang
The aim of the present study was to investigate the effects of sodium tanshinone IIA sulfonate (STS) on inflammatory responses, aortic endothelial cell apoptosis, disseminated intravascular coagulation (DIC) and multiple organ damage in an animal model of classic heat stroke (CHS). The rats in the heat stroke (HS) and STS‑treated heat stroke (STS‑HS) groups were placed into a pre‑warmed animal temperature controller (ATC) at 35˚C. The moment at which the rectal temperature reached 43.5˚C was considered as the time of onset of HS...
May 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28459353/role-of-coagulopathy-in-glucocorticoid-induced-osteonecrosis-of-the-femoral-head
#5
Qiankun Zhang, Jin L V, Lie Jin
The two major theories of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) are apoptosis and ischaemia. The traditional theory implicates ischaemia as the main aetiological factor because the final common pathway of ONFH is interruption of blood supply to the bone. The most common causes of interruption of blood supply include fat embolism and coagulation disorders. GCs can directly or indirectly lead to coagulation disorders, producing a hypercoagulable state, followed by poor blood flow, ischaemia, and eventually ONFH...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28458284/cancer-stromal-targeting-therapy
#6
Yasuhiro Matsumura
 Recent advances in antibody-drug conjugate (ADC) technology have shown considerable promise in targeted cancer therapy. The ADC strategy should be confined to highly toxic anticancer agents and not to ordinary anti-cancer agents (ACAs) because the affinity of monoclonal antibodies (mAbs) diminishes if more than three ACA molecules are conjugated. According to this principle, higher amounts of ADC should be administered so that each of the ACAs is conjugated to the mAbs. Therefore for an ordinary ACA, nanoparticles should be the preferred drug delivery system (DDS)...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28450451/a-novel-munc13-4-s100a10-annexin-a2-complex-promotes-weibel-palade-body-exocytosis-in-endothelial-cells
#7
Tarek Chehab, Nina Criado Santos, Anna Holthenrich, Sophia N Koerdt, Jennifer Disse, Christian Schuberth, Ali Reza Nazmi, Maaike Neeft, Henriette Koch, Kwun Nok M Man, Sonja M Wojcik, Thomas F J Martin, Peter van der Sluijs, Nils Brose, Volker Gerke
Endothelial cells respond to blood vessel injury by the acute release of pro-coagulant von-Willebrand factor (VWF) that is stored in unique secretory granules called Weibel-Palade bodies (WPBs). Stimulated WPB exocytosis critically depends on the proper recruitment of WPBs to the plasma membrane but factors involved in WPB-plasma membrane tethering are not known. Here we identify Munc13-4, a protein mutated in familial hemophagocytic lymphohistiocytosis 3 (FHL3), as a WPB tethering factor. Munc13-4 promotes histamine-evoked WPB exocytosis, it is present on WPBs, and secretagogue stimulation triggers an increased recruitment of Munc13-4 to WPBs and a clustering of Munc13-4 at sites of WPB-plasma membrane contact...
April 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28450294/gas6-growth-arrest-specific-6-promotes-inflammatory-ccr2-hi-cx3cr1-lo-monocyte-recruitment-in-venous-thrombosis
#8
Sandrine Laurance, François-René Bertin, Talin Ebrahimian, Yusra Kassim, Ryan N Rys, Stéphanie Lehoux, Catherine A Lemarié, Mark D Blostein
OBJECTIVES: Coagulation and inflammation are inter-related. Gas6 (growth arrest-specific 6) promotes venous thrombosis and participates to inflammation through endothelial-innate immune cell interactions. Innate immune cells can provide the initiating stimulus for venous thrombus development. We hypothesize that Gas6 promotes monocyte recruitment during venous thrombosis. APPROACH AND RESULTS: Deep venous thrombosis was induced in wild-type and Gas6-deficient (-/-) mice using 5% FeCl3 and flow reduction in the inferior vena cava...
April 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28431948/serum-peptides-as-putative-modulators-of-inflammation-in-psoriasis
#9
Tetsuhiko Matsuura, Masaaki Sato, Kouhei Nagai, Toshiyuki Sato, Mitsumi Arito, Kazuki Omoteyama, Naoya Suematsu, Kazuki Okamoto, Tomohiro Kato, Yoshinao Soma, Manae S Kurokawa
BACKGROUND: Psoriasis is a refractory inflammatory disease, however, its pathophysiology is still not fully understood. OBJECTIVE: We tried to identify novel serum peptides associated with the pathophysiology of psoriasis. METHODS: Serum peptides from 24 patients with psoriasis vulgaris (PV), 10 patients with psoriatic arthritis (PsA), 14 patients with atopic dermatitis (AD), and 23 healthy control (HC) subjects were analyzed by mass spectrometry...
March 27, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28428724/hepatic-angiosarcoma-with-clinical-and-histological-features-of-kasabach-merritt-syndrome
#10
Sanya Wadhwa, Tae Hun Kim, Leah Lin, Gary Kanel, Takeshi Saito
Hepatic angiosarcoma is a mesenchymal tumor originating from liver sinusoidal endothelial cells. It is an extremely rare malignant neoplasm accounting for less than 1% of primary malignant liver tumors. The deregulated coagulopathy that can be seen in hepatic angiosarcoma fulfills the clinical diagnostic criteria of disseminated intravascular coagulation. However, the mechanism that governs this coagulopathy has been poorly understood. This case report provides histological evidence of the consumption of coagulation factors along with trapped platelets occurring within the tumor, which is the foundation for the concept of Kasabach-Merritt syndrome (KMS)...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28412252/replicative-senescence-promotes-prothrombotic-responses-in-endothelial-cells-role-of-nadph-oxidase-and-cyclooxygenase-derived-oxidative-stress
#11
Grazielle Caroline Silva, Malak Abbas, Sonia Khemais-Benkhiat, Melanie Burban, Thais Porto Ribeiro, Florence Toti, Noureddine Idris-Khodja, Steyner F Côrtes, Valérie B Schini-Kerth
Endothelial senescence has been suggested to promote endothelial dysfunction in age-related vascular disorders. This study evaluated the prothrombotic properties of senescent endothelial cells (ECs) and the underlying mechanism. Serial passaging from passage (P)1 to P4 (replicative senescence) of porcine coronary artery ECs, or treatment of P1 ECs with the endothelial nitric oxide synthase (eNOS) inhibitor L-NAME (premature senescence) induced acquisition of markers of senescence including increased senescence-associated-β-galactosidase (SA-β-gal) activity and p53, p21, p16 expression...
July 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28406995/cell-based-evaluation-of-changes-in-coagulation-activity-induced-by-antineoplastic-drugs-for-the-treatment-of-acute-myeloid-leukemia
#12
Misae Tsunaka, Haruka Shinki, Takatoshi Koyama
Idarubicin (IDR), cytarabine (AraC), and tamibarotene (Am80) are effective for treatment of acute myeloid leukemia (AML). In acute leukemia, the incidence of venous thromboembolism or disseminated intravascular coagulation is associated with induction chemotherapy. Procoagulant effects of IDR, AraC, and Am80 were investigated in a vascular endothelial cell line EAhy926 and AML cell lines HL60 (AML M2), NB4 (AML M3, APL), and U937 (AML M5), focusing on tissue factor (TF), phosphatidylserine (PS), and thrombomodulin (TM)...
2017: PloS One
https://www.readbyqxmd.com/read/28405192/induction-of-osteopontin-by-dengue-virus-3-infection-in-thp-1-cells-inhibition-of-the-synthesis-by-brefelamide-and-its-derivative
#13
Dyshelly N Pascapurnama, Hannah K M Labayo, Isolde Dapat, Divya D Nagarajegowda, Jingge Zhao, Jing Zhang, Osamu Yamada, Haruhisa Kikuchi, Shinichi Egawa, Yoshiteru Oshima, Haorile Chagan-Yasutan, Toshio Hattori
Osteopontin (OPN) is a multifunctional matricellular protein produced by a broad range of cells including osteoclasts, macrophages, T cells, endothelial cells, and vascular smooth muscle cells. OPN modulates various physiological and pathological events such as inflammation, wound healing, and bone formation and remodeling. Dengue virus (DENV) infection causes an increase in plasma OPN levels, which is correlated with the severity of symptoms and coagulation abnormalities. DENV infection also induces OPN gene expression in human macrophages...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28367652/astragaloside-iv-inhibits-pma-induced-epcr-shedding-through-mapks-and-pkc-pathway
#14
Yu Ma, Yi Zhao, Ran Zhang, Xiaoxia Liang, Zhongqiong Yin, Yi Geng, Gang Shu, Xu Song, Yuanfeng Zou, Lixia Li, Lizi Yin, Guizhou Yue, Yinglun Li, Gang Ye, Changliang He
Astragaloside IV (AS-IV), a main active substance isolated from Astragalus membranaceus Bunge, has been shown to have multiple pharmacological effects. Endothelial cell protein C receptor (EPCR) is a marker of inflammation, and is also a major member of protein C (PC) anti-coagulation system. EPCR can be cut off from the cell surface by tumor necrosis factor-α converting enzyme (TACE), which is controlled through mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways. To develop novel therapeutic drug for EPCR shedding, the effect of AS-IV was studied in phorbol-12-myristate 13-acetate (PMA)-induced human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism of AS-IV action was investigated...
April 3, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28364860/regulatory-effects-of-estetrol-on-the-endothelial-plasminogen-pathway-and-endothelial-cell-migration
#15
Maria Magdalena Montt-Guevara, Giulia Palla, Stefania Spina, Guja Bernacchi, Elena Cecchi, Adrian Esteban Campelo, Jorge Eduardo Shortrede, Alessio Canu, Tommaso Simoncini
BACKGROUND: Estetrol (E4) is a natural estrogen produced solely during human pregnancy. E4 is suitable for clinical use since it acts as a selective estrogen receptor modulator. In clinical trials E4 has been seen to have little or no effect on coagulation. Hence, it is interesting to investigate whether E4 alters endothelial-dependent fibrinolysis. OBJECTIVES: We studied the effects of E4 on the fibrinolytic system and whether this could influence the ability of endothelial cells to migrate...
May 2017: Maturitas
https://www.readbyqxmd.com/read/28363198/hemostatic-changes-associated-with-increased-mortality-rates-in-hospitalized-patients-with-hiv-associated-tuberculosis-a-prospective-cohort-study
#16
Saskia Janssen, Charlotte Schutz, Amy M Ward, Mischa A M Huson, Robert J Wilkinson, Rosie Burton, Gary Maartens, Katalin A Wilkinson, Joost C M Meijers, René Lutter, Martin P Grobusch, Graeme Meintjes, Tom van der Poll
Background: Mortality rates remain high for human immunodeficiency virus (HIV)-associated tuberculosis, and our knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-tuberculosis were associated with mortality or decreased survival time and the contribution of mycobacteremia to these effects. Methods: We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 cell counts <350/µL and microbiologically proved tuberculosis...
January 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28353616/associations-between-polymorphisms-in-coagulation-related-genes-and-venous-thromboembolism-a-meta-analysis-with-trial-sequential-analysis
#17
REVIEW
Jun Jiang, Kang Liu, Junjie Zou, Hao Ma, Hongyu Yang, Xiwei Zhang, Yuanyong Jiao
BACKGROUND: Recently, several studies showed that the polymorphisms in the coagulation-related genes might be associated with venous thromboembolism (VTE); however, the results were still controversial. We performed a meta-analysis with trial sequential analysis to investigate the associations between the endothelial cell-activated protein C receptor (EPCR) rs9574, F11 rs2289252, F11 rs2036914, FGG rs2066865, FGG rs1049636, CYP4V2 rs13146272, SERPINC1 rs2227589, and GP6 rs1613662 polymorphisms with the risk of VTE...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28341374/cardiorenal-disease-connection-during-post-menopause-the-protective-role-of-estrogen-in-uremic-toxins-induced-microvascular-dysfunction
#18
REVIEW
Jiayi Pei, Magdalena Harakalova, Hester den Ruijter, Gerard Pasterkamp, Dirk J Duncker, Marianne C Verhaar, Folkert W Asselbergs, Caroline Cheng
Female gender, post-menopause, chronic kidney disease (CKD) and (CKD linked) microvascular disease are important risk factors for developing heart failure with preserved ejection fraction (HFpEF). Enhancing our understanding of the interrelation between these risk factors could greatly benefit the identification of new drug targets for future therapy. This review discusses the evidence for the protective role of estradiol (E2) in CKD-associated microvascular disease and related HFpEF. Elevated circulating levels of uremic toxins (UTs) during CKD may act in synergy with hormonal changes during post-menopause and could lead to coronary microvascular endothelial dysfunction in HFpEF...
March 14, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28328682/early-tranexamic-acid-administration-ameliorates-the-endotheliopathy-of-trauma-and-shock-in-an-in-vitro-model
#19
Lawrence N Diebel, Jonathan V Martin, David M Liberati
BACKGROUND: Systemic vascular endothelial injury is a consequence of trauma (T)/hemorrhagic shock (HS) which results in disturbances of coagulation, inflammation, and endothelial barrier integrity. The effect of T/HS on the endothelium (endotheliopathy of trauma [EoT]) is of intense research interest and may lead to EoT-directed therapies. Administration of tranexamic acid (TXA) in trauma patients is associated with a survival benefit and fewer complications if given early after injury...
June 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28322834/anti-human-cd14-monoclonal-antibody-improves-survival-following-sepsis-induced-by-endotoxin-but-not-following-polymicrobial-infection
#20
Masaki Nakamura, Takashi Takeuchi, Kamon Shirakawa, Shoji Furusako
Cluster of differentiation 14 (CD14), a pattern recognition receptor expressed on myeloid cells and a critical component of the innate immune system, mediates local and systemic host responses to gram-negative bacterial products, including lipopolysaccharide (LPS). Therefore, CD14 is an attractive target for development of sepsis therapies, and several monoclonal anti-CD14 antibodies have been reported. In this study, we prepared an anti-human CD14 monoclonal antibody, F1024-1-3, which suppressed LPS-induced upregulation of pro-inflammatory cytokines and an adhesion molecule in human peripheral mononuclear cells and human vascular endothelial cells...
March 16, 2017: European Journal of Pharmacology
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