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Coagulation pathways

Cristina Puy, Erik I Tucker, Ivan S Ivanov, David Gailani, Stephanie A Smith, James H Morrissey, András Gruber, Owen J T McCarty
INTRODUCTION: Factor (F) XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa) promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα), in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP) derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively...
2016: PloS One
Juquan Song, Melody R Saeman, Lisa A Baer, Anthony R Cai, Charles E Wade, Steven E Wolf
This study investigated microRNA and target gene profiles under different conditions of burn, bed rest, and exercise training. Male Sprague-Dawley rats (n = 48) were assigned to sham ambulatory, sham hindlimb unloading, burn ambulatory, or burn plus hindlimb unloading groups. Rats received a 40% TBSA scald burn or sham treatments and were ambulatory or hindlimb unloaded. Rats were further assigned to exercise or no exercise. Plantaris tissues were harvested on day 14 and pooled to analyze for microRNA and gene expression profiles...
September 28, 2016: Journal of Burn Care & Research: Official Publication of the American Burn Association
Dmitri Bezinover, Shigekazu Sugino, Yuka Imamura-Kawasawa, Matthew S Bell, Zakiyah Kadry, Piotr K Janicki
We describe a case of fulminant intraoperative thrombosis during deceased donor liver transplantation. Despite significant medical bleeding, the patient suddenly developed diffuse thrombosis in all chambers of the heart and pulmonary vasculature resulting in intraoperative death. The patient's postmortem genetic analysis demonstrated a deleterious missense mutation in a coagulation pathway gene, SERPINC1, which codes for antithrombin III. The level of antithrombin III was not available to directly prove the causality of thrombosis, but our findings suggest that this mutation, in combination with antifibrinolytic administration in a hypercoagulable cirrhotic patient, might have contributed to the development of this catastrophic thrombotic event...
October 5, 2016: A & A Case Reports
Yuejuan Cao, Rongqing Li, Yangchun Li, Tao Zhang, Nan Wu, Jianyan Zhang, Zhaozeng Guo
BACKGROUND: Acute myocardial infarction (AMI) is a common disease with serious mortality and morbidity, worldwide. The present study aimed to identify differentially expressed genes (DEGs) and construct a transcription factor-gene regulatory network to further study the early diagnosis of AMI. METHODS: The integrated analysis of publicly available Gene Expression Omnibus datasets of AMI was performed. Differentially expressed genes were identified between AMI and normal blood samples...
July 26, 2016: Heart, Lung & Circulation
Gayatri Padhy, Anamika Gangwar, Manish Sharma, Kalpana Bhargava, Niroj Kumar Sethy
Padhy Gayatri, Anamika Gangwar, Manish Sharma, Kalpana Bhargava, and Niroj Kumar Sethy. Plasma proteomics of Ladakhi natives reveal functional regulation between renin-angiotensin system and eNOS-cGMP pathway. High Alt Med Biol. 16:000-000, 2016.-Humans have been living in high altitudes for more than 25,000 years but the molecular pathways promoting survival and performance in these extreme environments are not well elucidated. In an attempt to understand human adaptation to high altitudes, we used two-dimensional gel electrophoresis combined with MALDI-TOF/TOF to identify plasma proteins and associated pathways of ethnic Ladakhi natives residing at 3520 m...
October 14, 2016: High Altitude Medicine & Biology
Irene Zolotukhin, David M Markusic, Brett Palaschak, Brad E Hoffman, Meera A Srikanthan, Roland W Herzog
Hemophilia A and B are coagulation disorders resulting from the loss of functional coagulation factor VIII (FVIII) or factor IX proteins, respectively. Gene therapy for hemophilia with adeno-associated virus vectors has shown efficacy in hemophilia B patients. Although hemophilia A patients are more prevalent, the development of therapeutic adeno-associated virus vectors has been impeded by the size of the F8 cDNA and impaired secretion of FVIII protein. Further, it has been reported that over-expression of the FVIII protein induces endoplasmic reticulum stress and activates the unfolded protein response pathway both in vitro and in hepatocytes in vivo, presumably due to retention of misfolded FVIII protein within the endoplasmic reticulum...
2016: Molecular Therapy. Methods & Clinical Development
Sophie Braga-Lagache, Natasha Buchs, Mircea-Ioan Iacovache, Benoit Zuber, Christopher Benjamin Jackson, Manfred Heller
BACKGROUND: Cells of the vascular system release spherical vesicles, called microparticles, in the size range of 0.1-1μm induced by a variety of stress factors resulting in variable concentrations between health and disease. Furthermore, microparticles have intercellular communication/signaling properties and interfere with inflammation and coagulation pathways. Today's most used analytical technology for mecroparticle characterization, flow cytometry, is lacking sensitivity and specificity, which might have led to the publication of contradicting results in the past...
October 12, 2016: Molecular & Cellular Proteomics: MCP
M Adamiak, A Abdelbaset-Ismail, M Suszynska, A Abdel-Latif, J Ratajczak, M Z Ratajczak
Leukemia accepted article preview online, 13 October 2016. doi:10.1038/leu.2016.278.
October 13, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Nasser M Al-Daghri, Majed S Alokail, Antigoni Manousopoulou, Ashley Heinson, Omar Al-Attas, Yousef Al-Saleh, Shaun Sabico, Sobhy Yakout, Christopher H Woelk, George P Chrousos, Spiros D Garbis
BACKGROUND: Overweight adults are at increased risk for cardiovascular disease and vitamin D deficiency, whereas an important feature to vitamin D physiology is its sex dependence. The aim of this study was to examine whether vitamin D status improvement exerts a sexually dimorphic effect on serum proteins associated with cardiovascular risk among overweight adults. METHODS: Unprocessed serum from age- and BMI-matched men (n=26) and pre-menopausal women (n=24) with vitamin D deficiency and after they achieved sufficiency through a 12-month nutritional intervention was analyzed using our previously published depletion-free, quantitative proteomics method...
October 11, 2016: European Journal of Clinical Investigation
C Raspé, L Flöther, R Schneider, M Bucher, P Piso
Due to the significantly improved outcome and quality of life of patients with different tumor entities after cytoreductive surgery (CRS) and HIPEC, there is an increasing number of centers performing CRS and HIPEC procedures. As this procedure is technically challenging with potential high morbidity and mortality, respectively, institutional experience also in the anesthetic and intensive care departments is essential for optimal treatment and prevention of adverse events. Clinical pathways have to be developed to achieve also good results in more comorbid patients with border line indications and extensive surgical procedures...
September 28, 2016: European Journal of Surgical Oncology
Amy Geard, Gift D Pule, David Chelo, Valentina Josiane Ngo Bitoungui, Ambroise Wonkam
Sickle cell disease (SCD) vastly impacts the African continent and is associated with cardiovascular diseases. Stroke, kidney disease, and pulmonary hypertension are considered as proxies of severity in SCD with several genomic loci implicated in their heritability. The present expert review examined the current data on epidemiology and genetic risk factors of stroke, pulmonary hypertension, and kidney disease associated with SCD, as indexed in PubMed(®) and Google Scholar(®). Studies collectively show that stroke and kidney disease each affect ∼10% of SCD patients, with pulmonary hypertension displaying a higher prevalence of 30% among adults with SCD...
October 2016: Omics: a Journal of Integrative Biology
Aihua Hou, Kai Pong Law, Min Qi Tin, Yoon Pin Lim, Louis Tong
Pterygium is a triangular shaped ocular fibrous surface lesion growing from conjunctiva towards central cornea, causing ocular irritation, astigmatism, and visual disturbance. The condition is characterized by epithelial proliferation, fibrovascular growth, chronic inflammation, and prominent extracellular matrix remodeling. Studies have suggested that aberrant extracellular proteins secreted by fibroblasts lead to abnormal matrix production and tissue invasion contributing to the development of the disease...
October 7, 2016: Experimental Eye Research
Divya Ramchandani, Dusten Unruh, Clayton S Lewis, Vladimir Y Bogdanov, Georg F Weber
Molecules of the coagulation pathway predispose patients to cancer-associated thrombosis and also trigger intracellular signaling pathways that promote cancer progression. The primary transcript of tissue factor, the main physiologic trigger of blood clotting, can undergo alternative splicing yielding a secreted variant, termed asTF (alternatively spliced tissue factor). asTF is not required for normal hemostasis, but its expression levels positively correlate with advanced tumor stages in several cancers, including pancreatic adenocarcinoma...
October 10, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Omkar Byadgi, Yao-Chung Chen, Andrew C Barnes, Ming-An Tsai, Pei-Chyi Wang, Shih-Chu Chen
Grey mullet (Mugil cephalus) is an economically important fish species in Taiwan mariculture industry. Moreover, grey mullet are common hosts of a bacterial infection by Lactococcus garvieae. However, until now the information related to the immune system of grey mullet is unclear. Therefore, to understand the molecular basis underlying the host immune response to L. garvieae infection, Illumina HiSeq™ 2000 was used to analyse the head kidney and spleen transcriptome of infected grey mullet. De novo assembly of paired-end reads yielded 55,203 unigenes...
October 5, 2016: Fish & Shellfish Immunology
Xin-Peng Zhao, Shu-Wen He, Bin Yue, Guang-Hua Wang, Min Zhang
Tissue factor pathway inhibitors (TFPIs) are Kunitz-type serine protease inhibitors that reversibly regulate the blood coagulation induced by tissue factor. TFPI family contain two members, TFPI-1 and TFPI-2. Recent studies have shown TFPI-1 and TFPI-2 also play important roles in innate immunity, however, the potential function of teleost TFPI are very limited. In this study, we characterized two TFPI (CsTFPI-1 and CsTFPI-2) molecules from half-smooth tongue sole (Cynoglossus semilaevis), examined their tissue distributions and expression patterns under pathogens stimulation as well as investigated the antibacterial activity of the C-terminal peptides...
October 4, 2016: Fish & Shellfish Immunology
Larissa M Williams, Briony A Lago, Andrew G McArthur, Amogelang R Raphenya, Nicholas Pray, Nabil Saleem, Sophia Salas, Katherine Paulson, Roshni S Mangar, Yang Liu, Andy H Vo, Jordan A Shavit
Development is a complex and well-defined process characterized by rapid cell proliferation and apoptosis. At this stage in life, a developmentally young organism is more sensitive to toxicants as compared to an adult. In response to pro-oxidant exposure, members of the Cap'n'Collar (CNC) basic leucine zipper (b-ZIP) transcription factor family (including Nfe2 and Nfe2-related factors, Nrfs) activate the expression of genes whose protein products contribute to reduced toxicity. Here, we studied the role of the CNC protein, Nfe2, in the developmental response to pro-oxidant exposure in the zebrafish (Danio rerio)...
October 1, 2016: Aquatic Toxicology
Laura Mourino-Alvarez, Montserrat Baldan-Martin, Laura Gonzalez-Calero, Carlos Martinez-Laborde, Tamara Sastre-Oliva, Rafael Moreno-Luna, Luis F Lopez-Almodovar, Pedro L Sanchez, Francisco Fernandez-Aviles, Fernando Vivanco, Luis R Padial, Finn Akerstrom, Gloria Alvarez-Llamas, Fernando de la Cuesta, María G Barderas
BACKGROUND: The most common valve diseases are calcific aortic stenosis (AS) and aortic regurgitation (AR). The former is characterized by thickening of valve leaflets followed by progressive calcification, which produces progressive aortic valve (AV) narrowing, increased pressure afterload on the left ventricle (LV) and subsequent LV hypertrophy. On the other hand, AR is due to malcoaptation of the valve leaflets with resultant diastolic reflux of blood from aorta back to the LV producing volume and pressure overload and progressive LV dilatation...
September 26, 2016: International Journal of Cardiology
Oskar Hällgren, Staffan Svenmarker, Micael Appelblad
OBJECTIVES: To implement a statistical model for protamine titration. DESIGN: Prospective randomized trial. SETTING: University hospital. PARTICIPANTS: Sixty (n = 30+30) patients scheduled for elective coronary artery bypass surgery were randomly assigned to 2 groups. INTERVENTIONS: Protamine dose calculated according to an algorithm established from a statistical model or to a fixed protamine-heparin dose ratio (1:1)...
July 17, 2016: Journal of Cardiothoracic and Vascular Anesthesia
Muktanand Tripathi, Akhand Pratap Singh, Gopal Gupta, Singh Rajender
This study aimed at investigating the expression and localization of the polyol pathway enzymes; aldose reductase (AR) and sorbitol dehydrogenase (SDH), in the male reproductive tract of rat. Gene expression analysis showed maximum expression of AR and SDH in the coagulating glands. Western blot analysis showed a coordinated presence of the two enzymes in the coagulating glands, seminal vesicle and epididymis. Immunohistochemistry showed a concordant expression of the two enzymes in the coagulating gland, which goes well with its function of fructose production in rats...
September 29, 2016: Acta Histochemica
Valery Golderman, Efrat Shavit-Stein, Ilia Tamarin, Yossi Rosman, Shai Shrot, Nurit Rosenberg, Nicola Maggio, Joab Chapman, Arik Eisenkraft
Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests...
2016: PloS One
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