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R T Zamanian, D J Levine, R C Bourge, S A De Souza, E B Rosenzweig, H Alnuaimat, C Burger, S C Mathai, N Leedom, K DeAngelis, A Lim, T De Marco
Inhaled treprostinil (Tyvaso) has been shown to be a safe and effective addition to pulmonary arterial hypertension (PAH) oral therapies; however, the respiratory-related safety profile of inhaled treprostinil required further elucidation in the setting of routine clinical care. The objectives of this study were to characterize respiratory-related adverse events (AEs) associated with current or recent treatment with inhaled treprostinil and to compare the incidence of respiratory-related AEs in PAH patients treated with inhaled treprostinil with that in patients treated with other Food and Drug Administration (FDA)-approved PAH therapies...
September 2016: Pulmonary Circulation
Manuel J Richter, Ralf Ewert, Christian Warnke, Henning Gall, Simon Classen, Friedrich Grimminger, Eckhard Mayer, Werner Seeger, Hossein-Ardeschir Ghofrani
BACKGROUND: In patients with severe pulmonary arterial hypertension, subcutaneous or catheter-based intravenous application of prostanoids carries a risk of local side effects or systemic infections, which limits their use and acceptance. Recently, a fully implantable pump for continuous application of intravenous treprostinil was approved in Germany. However, surgery is a major risk for patients with severe pulmonary arterial hypertension. The purpose of this study was to investigate the safety of a fully implantable pump inserted under local or general anesthesia in patients with severe pulmonary hypertension...
September 26, 2016: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
Karim El-Kersh, J Shaun Smith
No abstract text is available yet for this article.
August 17, 2016: American Journal of Therapeutics
Ali Ataya, Angelina Somoracki, Jessica Cope, Hassan Alnuaimat
BACKGROUND: Parenteral prostacyclin therapy for PAH has allowed for improvements in functional status, quality of life and mortality. Parenteral therapies however carry an increased risk of line-associated complications. Inhaled prostacyclins are an attractive alternative therapy; however, limited data exists supporting the safety and outcomes after transition. METHODS: We describe a retrospective observational analysis of adults with PAH who were transitioned from a parenteral prostacyclin to inhaled treprostinil at our institution...
October 2016: Pulmonary Pharmacology & Therapeutics
Murali M Chakinala, Jeremy P Feldman, Franz Rischard, Michael Mathier, Meredith Broderick, Nicole Leedom, Kevin Laliberte, R James White
BACKGROUND: Parenteral prostanoids are effective treatment for pulmonary arterial hypertension, but long-term pump infusion systems have significant delivery-related safety and convenience limitations. METHODS: Subjects with a favorable risk profile transitioned from parenteral to oral treprostinil using a protocol-driven titration during 5 days of inpatient observation. Baseline and Week 24 assessments included 6-minute walk distance, echocardiogram, right heart catheterization, pharmacokinetics, treatment satisfaction and quality of life...
June 24, 2016: Journal of Heart and Lung Transplantation
Martin Hennenberg, Melanie Schott, Aysenur Kan, Patrick Keller, Alexander Tamalunas, Anna Ciotkowska, Beata Rutz, Yiming Wang, Frank Strittmatter, Annika Herlemann, Qingfeng Yu, Christian G Stief, Christian Gratzke
BACKGROUND: The phosphodiesterase (PDE) 5 inhibitor tadalafil is available for treatment of male lower urinary tract symptoms (LUTS), while the role of other PDE isoforms for prostate smooth muscle tone is still unknown. Here, we examined effects of the PDE10-selective inhibitor TC-E 5005 on smooth muscle contraction in human prostate tissue. METHODS: Prostate samples were obtained from patients undergoing radical prostatectomy. Expression of PDE10 was addressed by RT-PCR, Western blot, and fluorescence staining with different markers...
November 2016: Prostate
Robert C Bourge, Aaron B Waxman, Mardi Gomberg-Maitland, Shelley M Shapiro, James H Tarver, Dianne L Zwicke, Jeremy P Feldman, Murali M Chakinala, Robert P Frantz, Fernando Torres, Jeffrey Cerkvenik, Marty Morris, Melissa Thalin, Leigh Peterson, Lewis J Rubin
BACKGROUND: The use of systemic prostanoids in severe pulmonary arterial hypertension (PAH) is often limited by patient/physician dissatisfaction with the delivery methods. Complications associated with external pump-delivered continuous therapy include IV catheter-related bloodstream infections and subcutaneous infusion site pain. We therefore investigated a fully implantable intravascular delivery system for treprostinil infusion. METHODS: A multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) was conducted by using an implantable intravascular delivery system...
July 2016: Chest
Ami A Shah, Elena Schiopu, Soumya Chatterjee, Mary Ellen Csuka, Tracy Frech, Avram Goldberg, Robert Spiera, Stanford L Peng, Ryan J McBride, Jody M Cleveland, Virginia Steen
OBJECTIVE: Prior studies investigating the efficacy of oral treprostinil to treat digital ulcers (DU) in systemic sclerosis (SSc)-associated Raynaud phenomenon have yielded conflicting results. In this investigation, we examined whether DU burden increased after patients withdrew from oral treprostinil that was administered during an open-label extension study. METHODS: A multicenter, retrospective study was conducted to determine DU burden in the year after withdrawal from oral treprostinil...
September 2016: Journal of Rheumatology
Wassim H Fares
No abstract text is available yet for this article.
June 15, 2016: American Journal of Respiratory and Critical Care Medicine
R James White, Youlan Rao
No abstract text is available yet for this article.
June 15, 2016: American Journal of Respiratory and Critical Care Medicine
James C Coons, Taylor Miller, Marc A Simon, David C Ishizawar, Michael A Mathier
Oral treprostinil (TRE) is a prostacylin approved for the management of pulmonary arterial hypertension (PAH). Few data exist to guide the use of oral TRE as a replacement for parenteral or inhaled prostacyclins. Therefore, the purpose of this report was to describe our experience with oral TRE to transition patients from parenteral or inhaled TRE. We describe a case series of patients admitted for a 4-day hospital stay to transition from parenteral or inhaled TRE. Appropriate criteria for transition included stable patients with improved symptoms/functional capacity, patients who could not tolerate intravenous prostacyclin due to infection or subcutaneous prostacyclin due to pain, and patient preference for transition...
March 2016: Pulmonary Circulation
Sofie Axelgaard, Sarah Holmboe, Steffen Ringgaard, Thomas K Hillgaard, Stine Andersen, Mona S Hansen, Asger Andersen, Jens E Nielsen-Kudsk
BACKGROUND: Right heart function is an important predictor of morbidity and mortality in pulmonary arterial hypertension and many CHD. We investigated whether treatment with the prostacyclin analogue treprostinil could prevent pressure overload-induced right ventricular hypertrophy and failure. METHODS: Male Wistar rats were randomised to severe pulmonary trunk banding with a 0.5-mm banding clip (n=41), moderate pulmonary trunk banding with a 0.6-mm banding clip (n=36), or sham procedure (n=10)...
April 18, 2016: Cardiology in the Young
Karim El-Kersh, Kathryn M Ruf, J Shaun Smith
There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil...
March 18, 2016: American Journal of Therapeutics
Zahra Kazemi, Christian Bergmayr, Michaela Prchal-Murphy, Tahereh Javaheri, Madeleine Themanns, Ha T T Pham, Wolfgang Strohmaier, Veronika Sexl, Michael Freissmuth, Eva Zebedin-Brandl
Activation of Gs-coupled receptors enhances engraftment of hematopoietic stem and progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a prostacyclin analog approved for the treatment of pulmonary hypertension, can be repurposed to improve hematopoietic stem cell transplantation. Murine and human HSPCs were isolated from bone marrow and umbilical cord blood, respectively. Prostanoid receptor agonists and the combination thereof with forskolin were tested for their capacity to stimulate [(3)H]cAMP accumulation in HSPCs...
June 2016: Molecular Pharmacology
Ferdous Khan, Pinky Karim Syeda, Michael Nii N Nartey, Mohammad Shahidur Rahman, Mohammad Safiqul Islam, Kohji Nishimura, Mitsuo Jisaka, Fumiaki Shono, Kazushige Yokota
We have previously shown that cultured adipocytes have the ability to biosynthesize prostaglandin (PG) I2 called alternatively as prostacyclin during the maturation phase by the positive regulation of gene expression of PGI synthase and the prostanoid IP receptor. To clarify how prostacyclin regulates adipogenesis, we investigated the effects of prostacyclin and the specific agonists or antagonists for the IP receptor on the storage of fats during the maturation phase of cultured adipocytes. Exogenous PGI2 and the related selective agonists for the IP receptor including MRE-269 and treprostinil rescued the storage of fats attenuated by aspirin, a cyclooxygenase inhibitor...
March 5, 2016: Cytotechnology
Steven C Pugliese, Todd M Bull
The development of parenteral prostacyclin therapy marked a dramatic breakthrough in the treatment of pulmonary arterial hypertension (PAH). Intravenous (IV) epoprostenol was the first PAH specific therapy and to date, remains the only treatment to demonstrate a mortality benefit. Because of the inherent complexities and risks of treating patients with continuous infusion IV therapy, there is great interest in the development of an oral prostacyclin analog that could mimic the benefits of IV therapy. Herein, we highlight the development of oral prostacyclin therapy, focusing on oral treprostinil, the only US Food and Drug Administration approved oral prostacyclin...
2016: Integrated Blood Pressure Control
Florence Gaillard-Bigot, Matthieu Roustit, Sophie Blaise, Claire Cracowski, Christophe Seinturier, Bernard Imbert, Patrick Carpentier, Jean-Luc Cracowski
INTRODUCTION: Severe Raynaud's syndrome and DUs are the most prevalent manifestations of SSc peripheral microvascular disease. We tested whether treprostinil iontophoresis on the finger pad of patients with SSc would improve digital blood flow during hand cooling. METHODS: Eleven patients with limited cutaneous SSc underwent a double-blinded iontophoresis of treprostinil (2.56 × 10(-4) M during two hours) and placebo (NaCl 0.9%) on two finger pads. Then, the hand was inserted for 30 minutes in a fenestrated cooling box at 8 °C, and skin blood flow was recorded continuously using LSCI...
April 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Kishan S Parikh, Sudarshan Rajagopal, Terry Fortin, Victor F Tapson, Abby D Poms
Pulmonary arterial hypertension (PAH) has emerging therapeutic options including prostacyclin analogs. Inhaled therapy offers advantages compared with alternative routes of administration. We aimed to determine the safety and tolerability of inhaled treprostinil (iTRE) titrated to target maintenance dose higher than the labeled dose for PAH. Our study included 80 consecutive patients (69% female, 70% White) followed at the Duke University Medical Center prescribed iTRE at dose >9 breaths (54 μg). Etiology of pulmonary hypertension was most frequently PAH (51%) or secondary to lung disease (35%)...
April 2016: Journal of Cardiovascular Pharmacology
Guoliang Wang, Rui Fan, Ruirui Ji, Wenxin Zou, Daniel J Penny, Nidhy P Varghese, Yuxin Fan
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, progressive, fatal vascular disorder. Genetic predisposition plays vital roles in the development of PAH, with most mutations being identified in genes involved in the transforming growth factor beta (TGF-β) signaling pathways. Defects in the BMP9 gene have been documented in hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, which is occasionally associated with PAH. Selective enhancement of endothelial BMPR2 with BMP9 reverses pulmonary arterial hypertension...
2016: BMC Pulmonary Medicine
Elena K Grant, John T Berger
Tetralogy of Fallot (TOF) with pulmonary atresia (PA) and multiple aortopulmonary collaterals (MAPCAs) is a rare and severe form of congenital heart disease with poor prognosis. Aortopulmonary collaterals expose pulmonary arterioles to systemic pressure resulting in pulmonary hypertension (PH). To date, reports regarding the role of PH medications in this population are sparse. The objective of this study was to assess the effect of PH medications in patients with TOF, PA and MAPCAs or similar anatomy, with emphasis on symptoms, echocardiography and invasive hemodynamics...
February 2016: Pediatric Cardiology
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