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https://www.readbyqxmd.com/read/29909495/the-neuro-immune-regulators-niregs-promote-tissue-resilience-a-vital-component-of-the-host-s-defense-strategy-against-neuroinflammation
#1
REVIEW
Yosra Bedoui, Jim W Neal, Philippe Gasque
An effective protective inflammatory response in the brain is crucial for the clearance of pathogens (e.g. microbes, amyloid fibrils, prionSC ) and should be closely regulated. However, the CNS seems to have limited tissue resilience to withstand the detrimental effects of uncontrolled inflammation compromising functional recovery and tissue repair. Newly described neuro-immune-regulators (NIREGs) are functionally related proteins regulating the severity and duration of the host inflammatory response. NIREGs such as CD200, CD47 and CX3CL1 are vital for increasing tissue resilience and are constitutively expressed by neurons...
June 16, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29908043/a-first-in-human-study-of-the-safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-pf-06741086-an-anti-tfpi-monoclonal-antibody-in-healthy-volunteers
#2
Matthew Cardinal, Constantino Kantaridis, Tong Zhu, Pengling Sun, Debra D Pittman, John E Murphy, Steven Arkin
BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a protease inhibitor of tissue factor-activated coagulation factor VII (TF-FVIIa) complex and activated factor X (FXa). PF-06741086 is a monoclonal antibody that targets TFPI to increase clotting activity. OBJECTIVES: This study was a randomized, double-blind, sponsor-open, placebo-controlled, single intravenous (IV) or subcutaneous (SC) dose escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-06741086...
June 16, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29903766/cytoprotective-and-pro-angiogenic-functions-of-thrombomodulin-are-preserved-in-the-c-loop-of-the-fifth-epidermal-growth-factor-like-domain
#3
Xiangmin Wang, Bin Pan, Goichi Honda, Xintao Wang, Yuko Hashimoto, Hiroshi Ohkawara, Kailin Xu, Lingyu Zeng, Takayuki Ikezoe
We previously found that the fifth epidermal growth factor-like domain of thrombomodulin (TME5) exerts cytoprotective and pro-angiogenic functions via G-protein coupled receptor 15 (GPR15). TME5 is comprised of three S-S bonds that divide it into three loops: A (TME5A), B (TME5B), and C (TME5C). Here, we identified the minimum structure of TME5 that produces favorable effects in vascular endothelial cells (ECs). We found that TME5C, composed of 19 amino acids, but not TME5A or TME5B, stimulated the proliferation of human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs)...
June 14, 2018: Haematologica
https://www.readbyqxmd.com/read/29898868/optimal-tr-band-weaning-strategy-while-minimizing-vascular-access-site-complications
#4
Sunay Shah, Ryan Gindi, Mir B Basir, Akshay Khandelwal, Mohammad Alqarqaz, Mohammad Zaidan, Michele Voeltz, Gerald Koenig, Henry E Kim, William W O'Neill, Khaldoon Alaswad
INTRODUCTION: The purpose of the study is to develop an optimal TR-Band weaning strategy while minimizing vascular access site complications of hematoma or radial artery occlusion (RAO). METHODS: The trial was a randomized, prospective, single center study of 129 patients who underwent cardiac catheterization via the radial artery. Group A was an accelerated protocol in which weaning was initiated 20 min after sheath removal. Group B was an adjusted protocol, in which weaning was dependent on the amount of anti-platelet or anti-coagulation used...
April 14, 2018: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/29897553/the-bile-sequestrant-cholestyramine-increases-survival-in-a-rabbit-model-of-brodifacoum-poisoning
#5
Matthew Lindeblad, Alexander Lyubimov, Richard van Breemen, Kamil Gierszal, Guy Weinberg, Israel Rubinstein, Douglas L Feinstein
Patients exposed to long acting anticoagulant rodenticides (LAARs) are typically administered large amounts of oral vitamin K1 (VK1) to counteract life-threatening anti-coagulant effects. While VK1 treatment effectively prevents mortality, additional methods are needed to reduce the long duration of VK1 treatment which can last for months at high expense. We developed a model of brodifacoum (BDF) poisoning, one of the most potent LAARs, in adult male New Zealand White (NZW) rabbits. The LD50 for oral BDF was determined to be 192 μg/kg, similar to that calculated for adult rats...
June 12, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29891376/investigation-of-hepatic-warfarin-metabolism-activity-in-rodenticide-resistant-black-rats-rattus-rattus-in-tokyo-by-in-situ-liver-perfusion
#6
Kazuki Takeda, Yoshinori Ikenaka, Kazuyuki D Tanaka, Shouta M M Nakayama, Tsutomu Tanikawa, Hazuki Mizukawa, Mayumi Ishizuka
Anti-blood coagulation rodenticides, such as warfarin, have been used all over the world. They inhibit vitamin K epoxide reductase (VKOR), which is necessary for producing several blood clotting factors. This inhibition by rodenticides results in lethal hemorrhage in rodents. However, heavy usage of these agents has led to the appearance of rodenticide-resistant rats. There are two major mechanisms underlying this resistance, i.e., mutation of the target enzyme of warfarin, VKOR, and enhanced metabolism of warfarin...
June 2018: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29890905/optimized-adeno-associated-virus-mediated-human-factor-viii-gene-therapy-in-cynomolgus-macaques
#7
Jenny Greig, Jayme Nordin, John White, Qiang Wang, Erin Bote, Tamara Goode, Roberto Calcedo, Samuel Wadsworth, Lili Wang, James M Wilson
Hemophilia A is a common hereditary bleeding disorder that is characterized by a deficiency of human blood coagulation factor VIII (hFVIII). Previous studies with adeno-associated viral (AAV) vectors identified two liver-specific promoter and enhancer combinations (E03.TTR and E12.A1AT) that drove high level expression of a codon-optimized, B-domain-deleted hFVIII transgene in a mouse model of the disease. Here, we further evaluated these enhancer/promoter combinations in cynomolgus macaques using two different AAV capsids (AAVrh10 and AAVhu37)...
June 11, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29890519/betrixaban-impact-on-routine-and-specific-coagulation-assays-a-practical-laboratory-guide
#8
Romain Siriez, Jonathan Evrard, Jean-Michel Dogné, Lionel Pochet, Damien Gheldof, Bernard Chatelain, François Mullier, Jonathan Douxfils
INTRODUCTION:  Betrixaban is a novel direct oral factor Xa inhibitor approved by the Food and Drug Administration for prophylaxis of venous thromboembolism in adult patients hospitalized for an acute illness at risk for thromboembolic complications. Assessment of the anti-coagulant effect of betrixaban may be useful in some situations. Also, clinicians need to know how routine coagulation assays are influenced. OBJECTIVE:  The aim of this study is to determine which coagulation assay(s) should be used to assess the impact of betrixaban on haemostasis and provide laboratory guidance for their interpretation...
June 11, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29886333/fate-and-wetting-potential-of-bio-refractory-organics-in-membrane-distillation-for-coke-wastewater-treatment
#9
Jing Ren, Jianfeng Li, Zuliang Chen, Fangqin Cheng
Membrane distillation (MD) has been hindered in industrial applications due to the potential wetting or fouling caused by complicated organic compositions. This study investigated the correlations between the fate and wetting potential of bio-refractory organics in the MD process, where three coke wastewater samples pre-treated with bio-degradation and coagulation served as feed solutions. Results showed that although most of the bio-refractory organics in coke wastewater were rejected by the hydrophobic membrane, some volatile aromatic organics including benzenes, phenols, quinolines and naphthalenes passed through the membrane during the MD process...
June 2, 2018: Chemosphere
https://www.readbyqxmd.com/read/29886066/the-evolution-of-activated-protein-c-plasma-levels-in-septic-shock-and-its-association-with-mortality-a-prospective-observational-study
#10
Tobias Becher, Jens Müller, Ibrahim Akin, Stefan Baumann, Katharina Bosch, Ksenija Stach, Martin Borggrefe, Bernd Pötzsch, Dirk Loßnitzer
PURPOSE: Septic shock is commonly associated with hemostatic abnormalities. The endothelium-activated serine protease activated protein C (APC) plays a pivotal role in limiting coagulation and possesses anti-apoptotic and anti-inflammatory properties. We hypothesized that APC levels correlate with established coagulation parameters and provide prognostic information in patients with septic shock. METHODS: We conducted a prospective, observational cohort study in patients with septic shock...
June 2, 2018: Journal of Critical Care
https://www.readbyqxmd.com/read/29885183/experience-of-hundred-cases-of-transurethral-resection-of-prostate-at-tertiary-care-hospital-in-karachi
#11
Shahnawaz Rajpar, Bilal Surya, Khalil Mobin, Santosh Kumar
To share the experience of 100 cases of Transurethral Resection of Prostate (TURP), This cross-sectional study was conducted in the Department of Urology, SMBBMC and Lyari General Hospital, Karachi from 1.1.13 to 30.4.15. One hundred cases were selected through purposive sampling. Patients who underwent TURP were included. Those with two life threatening co-morbidities, positive urine culture and patients on anti coagulant medications were excluded from the study. Mean age of the patients was 66±6.2 years with minimum 60 years and maximum 85 years...
May 2018: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/29877044/modified-clot-waveform-analysis-to-measure-plasma-coagulation-potential-in-the-presence-of-the-anti-factor-ixa-factor-x-bispecific-antibody-emicizumab-comment
#12
Takeshi Matsumoto, Hideo Wada, Hidemi Toyoda, Masahiro Hirayama, Yoshiki Yamashita, Naoyuki Katayama
A patient with hemophilia A had severe coagulation factor VIII (FVIII) deficiency and required injection with FVIII concentrates two or three times a week. Although the extended-half-life (EHL) [1] FVIII products and emicizumab [2, 3], a bispecific antibody for FX and FIX can reduce the injection frequency for FVIII products, monitoring the FVIII activity is difficult using the activated partial thromboplastin time (APTT) assay. The development of an APTT waveform including first and second derivatives can provide new information on hemostatic abnormalities [4]...
June 7, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29876506/-will-she-live-a-long-happy-life-parents-concerns-for-their-children-with-fontan-circulation
#13
Karin du Plessis, Rebecca Peters, Ingrid King, Kirsty Robertson, Jonathan Mackley, Rachel Maree, Tracy Stanley, Louise Pickford, Brian Rose, Matthew Orchard, Helen Stewart, Yves d'Udekem
Background: Families of children at the worst end of the congenital heart disease endure a significant burden which is often not clearly delineated in the clinical literature. We examined the greatest concerns of parents whose children have a Fontan circulation. Methods: Parents ( N  = 107) of children in the Australian and New Zealand Fontan Registry completed online surveys with open-ended and closed questions. A qualitative method approach incorporating thematic analyses was used...
March 2018: IJC Heart & Vasculature
https://www.readbyqxmd.com/read/29876337/the-role-of-inflammation-in-venous-thromboembolism
#14
REVIEW
Brian R Branchford, Shannon L Carpenter
Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT), and pulmonary embolism (PE), is becoming increasingly recognized as a cause of morbidity and mortality in pediatrics, particularly among hospitalized children. Furthermore, evidence is accumulating that suggests the inflammatory response may be a cause, as well as consequence, of VTE, but current anticoagulation treatment regimens are not designed to inhibit inflammation. In fact, many established clinical VTE risk factors such as surgery, obesity, cystic fibrosis, sepsis, systemic infection, cancer, inflammatory bowel disease, and lupus likely modulate thrombosis through inflammatory mediators...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29874689/pharmacodynamic-effects-of-a-6-hour-regimen-of-enoxaparin-in-patients-undergoing-primary-percutaneous-coronary-intervention-penny-pci-study
#15
Wael Sumaya, William A E Parker, Rebekah Fretwell, Ian R Hall, David S Barmby, James D Richardson, Javaid Iqbal, Zulfiquar Adam, Kenneth P Morgan, Julian P Gunn, Annah E Mason, Heather M Judge, Christopher P Gale, Ramzi A Ajjan, Robert F Storey
Delayed onset of action of oral P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0...
June 6, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29872658/cytokines-adhesion-molecules-and-matrix-metalloproteases-as-predisposing-diagnostic-and-prognostic-factors-in-venous-thrombosis
#16
REVIEW
Knut A Mosevoll, Silje Johansen, Øystein Wendelbo, Ina Nepstad, Øystein Bruserud, Håkon Reikvam
The inflammatory response is a well-established part of, and a prerequisite for, venous thrombosis. To better understand the pathophysiology of venous thrombosis and to identify improved diagnostic biomarkers, further studies of the relationship between inflammation and coagulation are needed. We review previous studies concerning inflammatory biomarkers in venous thromboembolism, in particular cytokines, soluble adhesion molecules and matrix metalloproteases as predisposing, diagnostic and prognostic factors in venous thrombosis...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29870459/novel-approaches-to-block-complement
#17
Georg A Böhmig, Markus Wahrmann, Farsad Eskandary, Lionel Rostaing
The complement system may contribute in many ways to transplant injury, being a promising target for specific therapeutic interventions. There is evidence that the monoclonal anti-C5 antibody eculizumab is effective in the prevention and treatment of early antibody-mediated rejection (ABMR), but terminal complement blockade might be of limited efficiency in chronic rejection. Given the diversity of immunological events triggered by activation steps upstream to C5, in particular, opsonin and anaphylatoxin formation through C3 cleavage, one may argue that, in the specific context of ABMR, inhibition of antibody-triggered classical pathway (CP) activation might be beneficial...
June 4, 2018: Transplantation
https://www.readbyqxmd.com/read/29869801/figure-of-eight-sutures-for-hemostasis-result-in-shorter-lab-recovery-time-after-ablation-for-atrial-fibrillation
#18
Joshua Payne, Trent Bickel, Sandeep Gautam
BACKGROUND: Ablation for atrial fibrillation (AF) requires multiple venous sheaths and anticoagulation with heparin, both risk factors for bleeding complications. Manual compression (MC) with heparin reversal is the standard method to achieve venous hemostasis post ablation, however temporary figure-of-eight sutures (F8S) are an alternative. While this technique has been shown to be safe and effective, little is known about its effect on post-procedural recovery time. METHODS: In this retrospective cohort study, consecutive patients who underwent AF radiofrequency ablation over a 23 month period were reviewed for type of hemostasis (manual compression or figure-of-eight suture), demographics, peri-procedural anticoagulation, groin complications, and procedural duration...
June 5, 2018: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/29867951/cellular-and-molecular-mechanisms-of-anti-phospholipid-syndrome
#19
REVIEW
Marko Radic, Debendra Pattanaik
The primary anti-phospholipid syndrome (APS) is characterized by the production of antibodies that bind the phospholipid-binding protein β2 glycoprotein I (β2GPI) or that directly recognize negatively charged membrane phospholipids in a manner that may contribute to arterial or venous thrombosis. Clinically, the binding of antibodies to β2GPI could contribute to pathogenesis by formation of immune complexes or modification of coagulation steps that operate along cell surfaces. However, additional events are likely to play a role in pathogenesis, including platelet and endothelial cell activation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29866521/a-study-on-indices-of-apixaban-anticoagulation-a-single-center-prospective-study
#20
Maki Komiyama, Yusuke Miyazaki, Hiromichi Wada, Moritake Iguchi, Mitsuru Abe, Hisashi Ogawa, Masaharu Akao, Hajime Yamakage, Noriko Satoh-Asahara, Yoichi Sunagawa, Tatsuya Morimoto, Koji Hasegawa
BACKGROUND: Depending on the characteristics of patients, the blood concentration of apixaban can unexpectedly increase, possibly leading to bleeding events. Anti-FXa activity reflects the apixaban blood concentration; however, measurement of this activity is both time-consuming and expensive. The current study aimed to evaluate the usefulness of routinely measured coagulation indices as future indicators of the efficacy and safety of apixaban. METHODS: Eighteen nonvalvular atrial fibrillation patients administered apixaban (average, 52...
May 16, 2018: Journal of Pharmacological Sciences
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