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Coagulation cascade

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https://www.readbyqxmd.com/read/28448952/sepsis-and-septic-shock-pathogenesis-and-treatment-perspectives
#1
REVIEW
Hayk Minasyan
The majority of bacteremias do not develop to sepsis: bacteria are cleared from the bloodstream. Oxygen released from erythrocytes and humoral immunity kill bacteria in the bloodstream. Sepsis develops if bacteria are resistant to oxidation and proliferate in erythrocytes. Bacteria provoke oxygen release from erythrocytes to arterial blood. Abundant release of oxygen to the plasma triggers a cascade of events that cause: 1. oxygen delivery failure to cells; 2. oxidation of plasma components that impairs humoral regulation and inactivates immune complexes; 3...
April 18, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28445073/plasminogen-activator-inhibitor-1-is-critical-in-alcohol-enhanced-acute-lung-injury-in-mice
#2
Lauren G Poole, Veronica L Massey, Deanna L Siow, Edilson Torres-González, Nikole L Warner, James P Luyendyk, Jeffrey D Ritzenthaler, Jesse Roman, Gavin E Arteel
RATIONALE: Chronic alcohol exposure is a clinically important risk factor for development of acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). However, the mechanisms by which alcohol sensitizes the lung to development of this disease are poorly understood. OBJECTIVES: We determined the role of the anti-fibrinolytic protein plasminogen activator inhibitor-1 (PAI-1) in alcohol enhancement of experimental endotoxin-induced ALI. METHODS: Wild-type (WT), PAI-1(-/-) and Integrin β3(-/-) mice were fed ethanol-containing Lieber-DeCarli liquid or control diet for 6 weeks followed by systemic lipopolysaccharide (LPS) challenge...
April 26, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28439253/secondary-hematoma-expansion-and-perihemorrhagic-edema-after-intracerebral-hemorrhage-from-bench-work-to-practical-aspects
#3
REVIEW
Krista Lim-Hing, Fred Rincon
Intracerebral hemorrhages (ICH) represent about 10-15% of all strokes per year in the United States alone. Key variables influencing the long-term outcome after ICH are hematoma size and growth. Although death may occur at the time of the hemorrhage, delayed neurologic deterioration frequently occurs with hematoma growth and neuronal injury of the surrounding tissue. Perihematoma edema has also been implicated as a contributing factor for delayed neurologic deterioration after ICH. Cerebral edema results from both blood-brain barrier disruption and local generation of osmotically active substances...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28436027/production-and-characterization-of-active-recombinant-human-factor-ii-with-consistent-sialylation
#4
Jeong H Lee, Jason Reier, Kelley M Heffner, Christopher Barton, David Spencer, Albert E Schmelzer, Raghavan Venkat
Coagulation factor II (prothrombin; FII) is the pre-proteolyzed precursor to thrombin in the coagulation cascade. It has ten sites of gamma-carboxylation, which are required for its bioactivity, and is N-glycosylated at three of four putative sites. Production of recombinant human FII (rhFII) using a platform fed-batch process designed for monoclonal antibody production resulted in low levels of gamma-carboxylation and sialylation. There have not been any prior reports of successful process development and clinical manufacture of rhFII with optimal, consistent gamma-carboxylation and sialylation...
April 24, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28432618/the-identification-of-key-genes-and-pathways-in-hepatocellular-carcinoma-by-bioinformatics-analysis-of-high-throughput-data
#5
Chaoyang Zhang, Li Peng, Yaqin Zhang, Zhaoyang Liu, Wenling Li, Shilian Chen, Guancheng Li
Liver cancer is a serious threat to public health and has fairly complicated pathogenesis. Therefore, the identification of key genes and pathways is of much importance for clarifying molecular mechanism of hepatocellular carcinoma (HCC) initiation and progression. HCC-associated gene expression dataset was downloaded from Gene Expression Omnibus database. Statistical software R was used for significance analysis of differentially expressed genes (DEGs) between liver cancer samples and normal samples. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, based on R software, were applied for the identification of pathways in which DEGs significantly enriched...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28430386/peptidome-analysis-of-human-serum-from-normal-and-preeclamptic-pregnancies
#6
Xiaonan Dai, Xuejing Song, Can Rui, Li Meng, Xuan Xue, Hongjuan Ding, Rong Shen, Jun Li, Jingyun Li, Yuanqing Lu, Wei Long
Preeclampsia is a kind of disease that severely harms the health of pregnant women and infants. To better understand the molecular mechanisms involved in preeclampsia, we used liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) to construct a comparative peptidomic profiling of human serum between normal and preeclamptic pregnancies. A total of 201 peptides were confidently identified, with 21 up-regulated and 3 down-regulated. Further analysis indicated that these differentially expressed peptides correlate with enzyme regulator activity, biological regulation, and coagulation cascades occurring during pathological changes of preeclampsia...
April 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28427844/cost-effectiveness-of-influenza-vaccination-in-patients-with-acute-coronary-syndrome-in-korea
#7
Jinuk Suh, Boyeon Kim, Yunseok Yang, Dong-Churl Suh, Eunyoung Kim
BACKGROUND: Influenza can cause cardiovascular abnormalities by inappropriately activating the coagulation cascade. Therefore, influenza vaccination is important because it decreases the risk of hospitalization for and mortality associated with heart disease. In particular, it reduces the occurrence of major adverse cardiovascular events (MACEs) in acute coronary syndrome (ACS) patients. Our study aimed to estimate the disease burden of MACEs and its related direct and indirect costs in ACS patients...
April 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28427159/genome-wide-analysis-of-long-noncoding-rna-and-mrna-co-expression-profile-in-intrahepatic-cholangiocarcinoma-tissue-by-rna-sequencing
#8
Wenhui Yang, Yuan Li, Xia Song, Jun Xu, Jun Xie
Long noncoding RNAs (lncRNAs), which are pervasively transcribed in the genome, are emerging in molecular biology as crucial regulators of cancer. RNA-seq data were downloaded from GEO of NCBI and further analyzed to identify novel targets in intrahepatic cholangiocarcinoma (iCCA).We investigated differences in lncRNA and mRNA profiles between 7 pairs of iCCA and adjacent normal tissues. 230 lncRNAs were differentially expressed more than four-fold change in iCCA tissues. Among these, 97 were upregulated and 133 downregulated relatively to normal tissues...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419850/overpressure-blast-injury-induced-oxidative-stress-and-neuroinflammation-response-in-rat-frontal-cortex-and-cerebellum
#9
Hale Z Toklu, Zhihui Yang, Sehkar Oktay, Yasemin Sakarya, Nataliya Kirichenko, Michael K Matheny, Judy Muller-Delp, Kevin Strang, Philip J Scarpace, Kevin K W Wang, Nihal Tümer
BACKGROUND & AIM: Overpressure blast-wave induced brain injury (OBI) and its long-term neurological outcome pose significant concerns for military personnel. Our aim is to investigate the mechanism of injury due to OBI. METHODS: Rats were divided into 3 groups: 1) Control, 2) OBI (exposed 30psi peak pressure, 2-2.5ms), 3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and brain (cortex and cerebellum) tissues were collected at 24h post injury...
April 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28415603/synthesis-and-evaluation-of-anthranilamide-based-derivatives-as-fxa-inhibitors
#10
Changjiang Huang, Wenzhi Wang, Yao Li, Shijun Zhang, Fancui Meng, Weiren Xu, Jing Yuan, Ligong Chen
Factor Xa (FXa) plays a significant role in the blood coagulation cascade and is a promising target for anticoagulation drugs. Three oral FXa inhibitors have been approved by FDA for treating thrombotic diseases. In this study, 43 novel compounds were synthesized anthranilamide-based FXa inhibitors aiming to ameliorate the toxicity of traditional FXa inhibitors in clinic. The data indicated that the compounds 6a, 6a-b, 6a-e, 6k, 6k-a and 6k-b showed remarkable FXa inhibitory activity and excellent selectivity over thrombin in vitro...
March 21, 2017: Oncotarget
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 da 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...
April 12, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28405673/gly74ser-mutation-in-protein-c-causes-thrombosis-due-to-a-defect-in-protein-s-dependent-anticoagulant-function
#12
Changming Chen, Likui Yang, Bruno O Villoutreix, Xuefeng Wang, Qiulan Ding, Alireza R Rezaie
Protein C is a vitamin K-dependent serine protease zymogen in plasma which upon activation by thrombin in complex with thrombomodulin (TM) down-regulates the clotting cascade by a feedback loop inhibition mechanism. Activated protein C (APC) exerts its anticoagulant function through protein S-dependent degradation of factors Va and VIIIa. We recently identified a venous thrombosis patient whose plasma level of protein C antigen is normal, but its anticoagulant activity is only 34 % of the normal level. Genetic analysis revealed that the proband and her younger brother carry a novel heterozygous mutation c...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28403626/direct-factor-ixa-inhibition-with-the-rna-aptamer-pegnivacogin-reduces-platelet-reactivity-in-vitro-and-residual-platelet-aggregation-in-patients-with-acute-coronary-syndromes
#13
Dawid L Staudacher, Vera Putz, Lukas Heger, Jochen Reinöhl, Marcus Hortmann, Steven L Zelenkofske, Richard C Becker, Christopher P Rusconi, Christoph Bode, Ingo Ahrens
BACKGROUND: Residual platelet reactivity is a predictor of poor prognosis in patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention. Thrombin is a major platelet activator and upon initiation of the coagulation cascade, it is subsequently produced downstream of factor IXa, which itself is known to be increased in ACS. Pegnivacogin is a novel RNA-aptamer based factor IXa inhibitor featuring a reversal agent, anivamersen. We hypothesized that pegnivacogin could reduce platelet reactivity...
April 1, 2017: European Heart Journal. Acute Cardiovascular Care
https://www.readbyqxmd.com/read/28391321/host-genotype-and-microbiota-contribute-asymmetrically-to-transcriptional-variation-in-the-threespine-stickleback-gut
#14
Clayton M Small, Kathryn Milligan-Myhre, Susan Bassham, Karen Guillemin, William A Cresko
Recent studies of interactions between hosts and their resident microbes have revealed important ecological and evolutionary consequences that emerge from these complex interspecies relationships, including diseases that occur when the interactions go awry. Given the preponderance of these interactions, we hypothesized that effects of the microbiota on gene expression in the developing gut-an important aspect of host biology-would be pervasive, and that these effects would be both comparable in magnitude to and contingent on effects of the host genetic background...
March 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28388863/perioperative-coagulation-management-of-a-hemophilia-a-patient-during-cardiac-surgery
#15
Patrick Odonkor, Archana Srinivas, Erik Strauss, Brittney Williams, Michael Mazzeffi, Kenichi A Tanaka
Perioperative management of cardiovascular surgical procedures requiring cardiopulmonary bypass (CPB) in patients with hemophilia A poses a clinical challenge in coagulation management. Use of CPB requires the administration of an anticoagulant, usually unfractionated heparin, and also causes dilutional coagulopathy, platelet dysfunction or platelet consumption coagulopathy. Hypothermia and activation of the inflammatory cascade also affect coagulation. The effects of CPB on circulating levels of factor VIII have not been clearly defined...
April 1, 2017: Seminars in Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28378693/hematoma-expansion-following-intracerebral-hemorrhage-mechanisms-targeting-the-coagulation-cascade-and-platelet-activation
#16
Sherrefa R Burchell, Jiping Tang, John H Zhang
Hematoma expansion (HE), defined as a greater than 33% increase in intracerebral hemorrhage (ICH) volume within the first 24 hours, results in significant neurological deficits, and enhancement of ICH-induced primary and secondary brain injury. An escalation in the use of oral anticoagulants has led to a surge in the incidences of oral anticoagulation-associated ICH (OAT-ICH), which has been associated with a greater risk for HE and worse functional outcomes following ICH. The oral anticoagulants in use include vitamin K antagonists, and direct thrombin and factor Xa inhibitors...
March 29, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28376529/role-of-direct-oral-anticoagulants-in-the-management-of-anticoagulation
#17
Rajiv N Thakkar, Suman W Rathbun, Scott M Wright
For decades, vitamin K antagonists (VKAs) have been the oral treatment of choice for many thromboembolic conditions. The limitations of VKAs include the need for monitoring through blood testing, drug interactions, and narrow therapeutic windows. These shortcomings have led to the development of direct oral anticoagulants. These new oral agents act on specific targets in the coagulation cascade (eg, factor Xa, thrombin) and negate some of the shortcomings of VKAs. This article reviews the roles of dabigatran, rivaroxaban, apixaban, and edoxaban in stroke prevention in nonvalvular atrial fibrillation, for prevention of venous thromboembolism after orthopedic surgery, and in the treatment of venous thromboembolism...
April 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28369997/gene-expression-profile-after-knockdown-of-usp18-in-hepg2-2-15-cells
#18
Lin Li, Qing-Song Lei, Ling-Na Kong, Shu-Jun Zhang, Bo Qin
In our previous work, we found that the expression of ubiquitin-specific protease 18 (USP18), also known as UBP43, is associated with the efficiency of interferon alpha (IFN-α) treatment in patients with chronic hepatitis B (CHB). To elucidate the influence of USP18 on hepatitis B virus (HBV) replication and the mechanism of this activity, we silenced USP18 by introducing short hairpin RNA (shRNA) into Hepg2.2.15 cells. To identify the changed genes and pathways in Hepg2.2.15-shRNA-USP18 cells, we performed a microarray gene expression analysis to compare the Hepg2...
March 31, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28369597/exploring-chronic-drug-effects-on-microengineered-human-liver-cultures-using-global-gene-expression-profiling
#19
Brenton R Ware, Michael McVay, Wendy Y Sunada, Salman R Khetani
Global gene expression profiling is useful for elucidating a drug's mechanism of action (MOA) on the liver; however, such profiling in rats is not very sensitive for predicting human drug-induced liver injury, while de-differentiated monolayers of primary human hepatocytes (PHHs) do not permit chronic drug treatment. In contrast, micropatterned co-cultures (MPCCs) containing PHH colonies and 3T3-J2 fibroblasts maintain a stable liver phenotype for 4-6 weeks. Here, we used MPCCs to test the hypothesis that global gene expression patterns in stable PHHs can be used to distinguish clinical hepatotoxic drugs from their non-liver-toxic analogs and understand the MOA prior to the onset of overt hepatotoxicity...
March 24, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28366787/manduca-sexta-hemolymph-protease-1-activated-by%C3%A2-an%C3%A2-unconventional-non-proteolytic-mechanism-mediates%C3%A2-immune%C3%A2-responses
#20
Yan He, Yang Wang, Fan Yang, Haobo Jiang
Tissue damage or pathogen invasion triggers the auto-proteolysis of an initiating serine protease (SP), rapidly leading to sequential cleavage activation of other cascade members to set off innate immune responses in insects. Recently, we presented evidence that Manduca sexta hemolymph protease-1 zymogen (proHP1) is a member of the SP system in this species, and may activate proHP6. HP6 stimulates melanization and induces antimicrobial peptide synthesis. Here we report that proHP1 adopts an active conformation (*) to carry out its function, without a requirement for proteolytic activation...
March 31, 2017: Insect Biochemistry and Molecular Biology
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