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The New Oral Anticoagulants For The Treatment Of Venous Thromboembolism: A New Paradigm Shift In Antithrombotic Therapy., Taki Galanis, Gina Keiffer, Geno J Merli

Department of Medicine Faculty Papers

BACKGROUND: Several novel oral anticoagulants have been studied for the prevention and treatment of venous thromboembolism (VTE) in different patient populations. Clinicians will increasingly encounter scenarios in which they must choose among these and conventional anticoagulants for the treatment of this potentially fatal condition.

OBJECTIVE: To review the results of Phase III clinical trials that investigated the novel oral anticoagulants for the treatment of deep vein thrombosis and pulmonary embolism. Potential advantages and disadvantages of these anticoagulant agents with respect to each other and conventional therapy will also be explored through a case-based approach.

METHODS: A literature search in PubMed …

Adrenergic Signaling Regulates Mitochondrial Ca2+ Uptake Through Pyk2-Dependent Tyrosine Phosphorylation Of The Mitochondrial Ca2+ Uniporter., Jin O-Uchi, Bong Sook Jhun, Shangcheng Xu, Stephen Hurst, Anna Raffaello, Xiaoyun Liu, Bing Yi, Huiliang Zhang, Polina Gross, Jyotsna Mishra, Alina Ainbinder, Sarah Kettlewell, Godfrey L Smith, Robert T Dirksen, Wang Wang, Rosario Rizzuto, Shey-Shing Sheu

Department of Medicine Faculty Papers

AIMS: Mitochondrial Ca2+ homeostasis is crucial for balancing cell survival and death. The recent discovery of the molecular identity of the mitochondrial Ca2+ uniporter pore (MCU) opens new possibilities for applying genetic approaches to study mitochondrial Ca2+ regulation in various cell types, including cardiac myocytes. Basal tyrosine phosphorylation of MCU was reported from mass spectroscopy of human and mouse tissues, but the signaling pathways that regulate mitochondrial Ca2+ entry through posttranslational modifications of MCU are completely unknown. Therefore, we investigated α1-adrenergic-mediated signal transduction of MCU posttranslational modification and function in cardiac cells.

RESULTS: α1-adrenoceptor (α1-AR) signaling translocated activated proline-rich tyrosine …

Mitochondrial Ion Channels/Transporters As Sensors And Regulators Of Cellular Redox Signaling., Jin O-Uchi, Shin-Young Ryu, Bong Sook Jhun, Stephen Hurst, Shey-Shing Sheu

Department of Medicine Faculty Papers

SIGNIFICANCE: Mitochondrial ion channels/transporters and the electron transport chain (ETC) serve as key sensors and regulators for cellular redox signaling, the production of reactive oxygen species (ROS) and nitrogen species (RNS) in mitochondria, and balancing cell survival and death. Although the functional and pharmacological characteristics of mitochondrial ion transport mechanisms have been extensively studied for several decades, the majority of the molecular identities that are responsible for these channels/transporters have remained a mystery until very recently.

RECENT ADVANCES: Recent breakthrough studies uncovered the molecular identities of the diverse array of major mitochondrial ion channels/transporters, including the mitochondrial Ca2+ uniporter pore, …

Isprm Discussion Paper: Proposing A Conceptual Description Of Health-Related Rehabilitation Services., Thorsten Meyer, Christoph Gutenbrunner, Carlotte Kiekens, Dimitrios Skempes, John L Melvin, Kuno Schedler, Marta Imamura, Gerold Stucki

Department of Rehabilitation Medicine Faculty Papers

There is a need for a comprehensive classification system of health-related rehabilitation services. For conceptual clarity our aim is to provide a health-related conceptual description of the term "rehabilitation service". First, we introduce a common understanding of the term "rehabilitation", based on the current definition in the World Health Organization's World Report on Disability, and a conceptual description of rehabilitation agreed upon by international Physical and Rehabilitation Medicine organizations. From a health perspective, rehabilitation can be regarded as a general health strategy with the aim of enabling persons with health conditions experiencing or likely to experience disability to achieve and …

Microrna-138 Regulates Hypoxia-Induced Endothelial Cell Dysfunction By Targeting S100a1., Anagha Sen, Shumei Ren, Carolin Lerchenmüller, Jianxin Sun, Norbert Weiss, Patrick Most, Karsten Peppel

Center for Translational Medicine Faculty Papers

The Ca(2+) sensor S100A1 is essential for proper endothelial cell (EC) nitric oxide (NO) synthase (eNOS) activation. S100A1 levels are greatly reduced in primary human microvascular ECs subjected to hypoxia, rendering them dysfunctional. However mechanisms that regulate S100A1 levels in ECs are unknown. Here we show that ECs transfected with a S100A1-3' untranslated region (UTR) luciferase reporter construct display significantly reduced gene expression when subjected to low oxygen levels or chemical hypoxia. Bioinformatic analysis suggested that microRNA -138 (MiR-138) could target the 3'UTR of S100A1. Patients with critical limb ischemia (CLI) or mice subjected to femoral artery resection (FAR) displayed …

Biosynthetic Pathways And The Role Of The Mas Receptor In The Effects Of Angiotensin-(1-7) In Smooth Muscles., Marcio Augusto Fressatto De Godoy, Larissa Pernomian, Ana Maria De Oliveira, Satish Rattan

Department of Medicine Faculty Papers

Ang-(1-7) is produced via degradation of Ang II by the human angiotensin converting enzyme, also known as ACE2. In the cardiovascular system, Ang-(1-7) has been shown to produce effects that are opposite to those of Ang II. These include smooth muscle relaxation and cardioprotection. While the roles of Ang-(1-7) in other systems are currently topic of intense research, functional data suggest a relaxation action in gastrointestinal smooth muscles in a way that corroborates the results obtained from vascular tissues. However, more studies are necessary to determine a relevant role for Ang-(1-7) in the gastrointestinal system. The Ang-(1-7) actions are mediated …

Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Mitochondria Take Center Stage., Shey-Shing Sheu, Robert T Dirksen, Edward N Pugh

Center for Translational Medicine Faculty Papers

No abstract provided.