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https://www.readbyqxmd.com/read/28547570/the-effect-of-iloprost-on-cell-proliferation-and-angiogenesis-related-gene-expression-in-human-periodontal-ligament-cells
#1
Thanomsuk Jearanaiphaisarn, Teeranuch Sanharati, Prasit Pavasant, Chalida Nakalekha Limjeerajarus
Periodontal ligament is considered a rich source of mesenchymal stem cells for pulp regeneration. This study investigated the effect of iloprost, a prostacyclin analog, on cell proliferation and the expression of angiogenesis-related genes in human periodontal ligament cells (hPDLs) in vitro. The hPDLs were treated with 10(-9)-10(-6) M iloprost for 1, 6 and 24 h. Cell proliferation was determined by an MTT assay. Vascular endothelial growth factor (VEGF), alpha-1 type I collagen (COL1), and basic fibroblast growth factor (bFGF) mRNA expression were determined by semi-quantitative and qPCR...
May 25, 2017: Odontology
https://www.readbyqxmd.com/read/28546372/inhaled-pulmonary-vasodilators-are-there-indications-within-the-pediatric-icu
#2
Bradley A Kuch, Alvin L Saville, Joan Sanchez De Toledo, Shekhar T Venkataraman
Inhaled nitric oxide (INO) is only FDA-cleared for neonates (> 34 weeks gestation) with hypoxic respiratory failure-associated pulmonary hypertension. Off-label use of INO is common in the pediatric population despite a lack of evidence regarding survival benefit, questioning whether the therapy should be considered outside the neonatal period. A lack of definitive evidence combined with increasing health-care costs has led to the use of less costly inhaled prostacyclin as an alternative to INO, presenting unique patient safety concerns...
June 2017: Respiratory Care
https://www.readbyqxmd.com/read/28545516/improving-the-regenerative-potential-of-olfactory-ensheathing-cells-by-overexpressing-prostacyclin-synthetase-and-its-application-in-spinal-cord-repair
#3
May-Jywan Tsai, Chi-Ting Huang, Yong-San Huang, Ching-Feng Weng, Song-Kun Shyue, Ming-Chao Huang, Dann-Ying Liou, Yan-Ru Lin, Chu-Hsun Cheng, Huai-Sheng Kuo, Yilo Lin, Meng-Jen Lee, Wen-Hung Huang, Wen-Cheng Huang, Henrich Cheng
BACKGROUND: Olfactory ensheathing cells (OEC), specialized glia that ensheathe bundles of olfactory nerves, have been reported as a favorable substrate for axonal regeneration. Grafting OEC to injured spinal cord appears to facilitate axonal regeneration although the functional recovery is limited. In an attempt to improve the growth-promoting properties of OEC, we transduced prostacyclin synthase (PGIS) to OEC via adenoviral (Ad) gene transfer and examined the effect of OEC with enhanced prostacyclin synthesis in co-culture and in vivo...
May 25, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28533260/relationship-between-monocyte-platelet-aggregation-and-endothelial-function-in-middle-aged-and-elderly-adults
#4
Andrew Haynes, Matthew D Linden, Elisa Robey, Louise H Naylor, Kay L Cox, Nicola T Lautenschlager, Daniel J Green
Low-grade inflammation, endothelial dysfunction, and platelet hyper-reactivity to agonists are associated with an increased risk of cardiovascular events. In vitro and animal studies infer an inverse mechanistic relationship between platelet activation and the production of endothelium-derived nitric oxide and prostacyclin. This concept is supported by evidence of an inverse relationship between endothelial function and platelet activation in high-risk cardiac patients. The aim of this study was to investigate what relationship, if any, exists between platelet and endothelial function in healthy, middle-aged, and elderly adults...
May 2017: Physiological Reports
https://www.readbyqxmd.com/read/28533253/selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#5
Zachary R Noel, Kazuhiko Kido, Tracy E Macaulay
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosing and administration, and place in therapy of selexipag, an orally administered selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension (PAH), are reviewed. SUMMARY: The first-in-class oral prostacyclin IP receptor agonist selexipag (Uptravi, Actelion Pharmaceuticals) was approved by the Food and Drug Administration in December 2015...
May 22, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28530128/in-vivo-endocrine-secretion-of-prostacyclin-following-expression-of-a-cox-1-pgis-fusion-protein-in-the-salivary-glands-of-rats-via-non-viral-gene-therapy
#6
Zhimin Wang, Raymond L Benza, Lee Zourelias, Angela Sanguino, Ramaz Geguchadze, Kelly J Shields, Changgong Wu, Kristin B Highland, Michael J Passineau
Pulmonary arterial hypertension is a progressive disease that culminates in right heart failure and death. Prostacyclin(PGI2) and its derivatives are effective treatments for PAH when administered as continuous parenteral infusions. This treatment paradigm requires medical sophistication, and patients are at risk for complications from an indewelling catheter; drug interruptions may result in rebound pulmonary hypertension and death. We hypothesized that the salivary gland can be repurposed into an endogenous production site for circulating PGI2 through the expression of a fusion protein embodying cyclooxygenase-1(Cox1) and prostacyclin synthase(PGIS) domains...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28527831/different-efficacy-of-inhaled-and-oral-medications-in-pulmonary-hypertension
#7
Batool J AbuHalimeh, Joseph G Parambil, Adriano R Tonelli
Pulmonary arterial hypertension (PAH) is progressive disorder characterized by elevated pulmonary vascular resistance that can lead to right heart failure and death. One of the main therapeutic options for PAH are medications targeting the prostacyclin pathway. Treprostinil is a prostacyclin analogue and selexipag is a selective IP receptor agonist. Treprostinil can be delivered by a variety of routes including oral, inhaled, subcutaneous and intravenous. Selexipag is currently approved as an oral formulation...
May 17, 2017: Heart & Lung: the Journal of Critical Care
https://www.readbyqxmd.com/read/28524738/selexipag-a-selective-prostacyclin-receptor-agonist-in-pulmonary-arterial-hypertension-a-pharmacology-review
#8
Jesús Honorato Pérez
Pulmonary hypertension is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest. Management of pulmonary arterial hypertension (PAH) includes specific drug therapy with calcium channel blockers in vasoreactive patients, or drugs approved for PAH in non-reactive patients that target the endothelin, nitric-oxide and prostacyclin pathways. Areas covered: The review covers receptor selectivity, pharmacokinetics, pharmacodynamics and adverse effects (AEs) of intravenous (IV) epoprostenol (synthetic prostacyclin); the prostacyclin analogs iloprost, beraprost, and treprostinil administered by IV, subcutaneous, inhaled or oral routes; and the oral selective prostacyclin receptor agonist selexipag...
May 19, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28524176/lentivirus-mediated-microrna-124-gene-modified-bone-marrow-mesenchymal-stem-cell-transplantation-promotes-the-repair-of-spinal-cord-injury-in-rats
#9
Jia-Lin Song, Wei Zheng, Wei Chen, Yun Qian, Yuan-Ming Ouyang, Cun-Yi Fan
Our study aims to explore the effects of lentivirus-mediated microRNA-124 (miR-124) gene-modified bone marrow mesenchymal stem cell (BMSC) transplantation on the repair of spinal cord injury (SCI) in rats. BMSCs were isolated from the bone marrow of rats. The target gene miR-124 was identified using a luciferase-reporter gene assay. Seventy-two rats were selected for construction of the SCI model, and the rats were randomly divided into the blank group, sham group, SCI group, negative control (NC) group, overexpressed miR-124 group and si-PDXK group...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28520567/persistent-hypotension-and-cerebral-swelling-resulting-from-mesenteric-traction-syndrome-after-omental-to-pial-pedicle-flap-transfer-in-a-young-woman-with-refractory-moyamoya-disease-a-case-report
#10
Harvey J Woehlck, Suneeta Gollapudy, Christopher J Roberts, Akinwunmi Oni-Orisan, Raphael H Sacho, Paul S Pagel
Superficial temporal arterial to middle cerebral arterial anastomosis is often the initial surgical treatment of Moyamoya disease. In refractory cases, placing a pedicle flap of omentum over the ischemic brain has resulted in clinical improvement or stabilization of symptoms. We present a case of persistent mesenteric traction syndrome manifested by hypotension unresponsive to conventional doses of vasopressors during and after pulling the omentum to the brain. As prostacyclin is a major mediator of hypotension from mesenteric traction syndrome and also a cerebral vasodilator, we discuss the possibility that brain swelling may be a manifestation of mesenteric traction syndrome...
May 17, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28513869/transition-of-intravenous-treprostinil-to-oral-therapy-in-a-patient-with-functional-class-iv-chronic-thromboembolic-pulmonary-hypertension
#11
Kristina M Thurber, Breann M Williams, Ruth E Bates, Robert P Frantz
Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when pulmonary emboli fail to resolve with anticoagulation. For patients with inoperable or residual CTEPH, riociguat is currently the only therapy approved by the United States Food and Drug Administration. However, some patients with CTEPH may require therapy beyond riociguat, such as intravenous prostacyclins, which can present significant administration challenges in patients with complex comorbid conditions. We describe a 42-year-old man with T12 paraplegia complicated by CTEPH (functional class IV with substantial right ventricular dysfunction) and severe pressure ulcers...
May 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28506876/role-of-prostacyclin-synthase-in-carcinogenesis
#12
REVIEW
Yuka Sasaki, Tsubasa Ochiai, Masaya Takamura, Yukihiro Kondo, Chieko Yokoyama, Shuntaro Hara
Prostacyclin (PGI2) synthase (PGIS) and microsomal prostaglandin (PG) E synthase-1 (PGES-1) functionally couple with inducible cyclooxygenase-2 (COX-2) as their upstream enzymes to produce PGI2 and PGE2, respectively. Non-steroidal anti-inflammatory drugs exert their pharmacological effects including antitumor effects by the inhibition of COX-2 and thereby suppress this PG biosynthesis. PGIS is abundantly expressed in vascular endothelial and smooth muscle cells and was shown to be critical for the regulation of platelet aggregation and vascular tone...
May 12, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28499411/paraneoplastic-acral-vascular-syndrome-in-a-patient-with-metastatic-melanoma-under-immune-checkpoint-blockade
#13
Thilo Gambichler, Stefanie Strutzmann, Andrea Tannapfel, Laura Susok
BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon which is observed in patients with adenocarcinomas and other malignancies. Various potential pathogenic mechanisms such as tumour invasion of sympathetic nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted substances, and immunological mechanisms have been suggested. CASE PRESENTATION: We report a 60-year-old Caucasian male attended our hospital with a bulky lymph node mass in the right axilla...
May 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28494686/clinical-pharmacology-efficacy-and-safety-of-selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#14
Shirin Bruderer, Noémie Hurst, Tatiana Remenova, Jasper Dingemanse
Selexipag is the first oral, non-prostanoid, selective prostacyclin receptor (IP receptor) agonist, approved for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients. Areas covered: This article reviews the clinical pharmacology, efficacy, and safety of selexipag in the treatment of PAH. Expert opinion: Selexipag is the first oral drug that selectively targets the prostacyclin pathway, and has evidence of long-term efficacy and safety. In the global phase 3 study GRIPHON (NCT01106014) in PAH patients, selexipag significantly reduced the risk of the primary composite outcome of morbidity/mortality (M/M)...
June 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28478978/interactions-among-variants-in-eicosanoid-genes-increase-risk-of-atherothrombotic-stroke-in-chinese-populations
#15
Xingyang Yi, Jing Lin, Chun Wang, Ruyue Huang, Yingying Liu
BACKGROUND: Eicosanoids are lipid mediators that may play a role in ischemic stroke (IS). However, the association of variants in eicosanoid genes and these interactions with IS risk has not been investigated. The aim of the present study was to investigate the association of 11 variants in eicosanoid genes with IS and to determine whether these gene-gene interactions increase the risk of IS. METHODS: Eleven variants in prostaglandin H synthase-1 (PTGS1), PTGS2, thromboxane A2 synthase (TBXAS1), prostacyclin synthase (PTGIS), and prostaglandin E synthase (PTGES) genes were examined using mass spectrometry method in 297 patients with atherothrombotic stroke and 291 controls...
May 3, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28478717/selexipag-an-oral-prostacyclin-receptor-agonist-for-pulmonary-arterial-hypertension
#16
William L Baker, Konstadina Darsaklis, Aditi Singhvi, Edward L Salerno
OBJECTIVE: To evaluate the data supporting the approval of selexipag and discuss its potential place in therapy for managing pulmonary arterial hypertension (PAH). DATA SOURCES: A systematic review of the literature for all relevant articles was performed through January 16, 2017, using MEDLINE and SCOPUS. A manual search of references from reports of clinical trials, review articles, and recent conference abstracts was performed to identify additional relevant studies...
June 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28476928/the-selexipag-active-metabolite-act-333679-displays-strong-anti-contractile-and-anti-remodeling-effects-but-low-%C3%AE-arrestin-recruitment-and-desensitization-potential
#17
John Gatfield, Katalin Menyhart, Daniel Wanner, Carmela Gnerre, Lucile Monnier, Keith Morrison, Patrick Hess, Marc Iglarz, Martine Clozel, Oliver Nayler
Prostacyclin (PGI2) receptor (IP receptor) agonists, which are indicated for the treatment of pulmonary arterial hypertension (PAH), increase cytosolic cAMP levels and thereby inhibit pulmonary vasoconstriction, pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular matrix synthesis. Selexipag (Uptravi(®)) is the first non-prostanoid IP receptor agonist, it is available orally and was recently approved for the treatment of PAH. In this study we show that the active metabolite of selexipag and the main contributor to clinical efficacy, ACT-333679 (previously known as MRE-269), behaved as full agonist in multiple PAH-relevant receptor-distal - or downstream - cellular readouts with a maximal efficacy comparable to that of the prototypic PGI2 analog iloprost: In PASMC, ACT-333679 potently induced cellular relaxation (EC50=4...
May 5, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28468233/nanoparticle-mediated-drug-delivery-system-for-pulmonary-arterial-hypertension
#18
REVIEW
Kazufumi Nakamura, Hiromi Matsubara, Satoshi Akagi, Toshihiro Sarashina, Kentaro Ejiri, Norifumi Kawakita, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Nobuhiro Nishii, Hiroshi Ito
Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost) -incorporated nanoparticles and imatinib (a PDGF-receptor tyrosine kinase inhibitor) -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of pulmonary arterial hypertension (PAH) and in human PAH-pulmonary arterial smooth muscle cells have been reported...
April 29, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28464760/transition-from-subcutaneous-or-inhaled-treprostinil-to-oral-treprostinil-at-home-in-patients-with-pulmonary-arterial-hypertension-a-retrospective-case-series
#19
Kimberly A Ackerbauer, Rajive Tandon
Pulmonary arterial hypertension (PAH) is a progressive condition that can lead to right ventricular failure and death. Treprostinil is a prostacyclin analogue that has proven clinical efficacy in patients with PAH. Difficulties in the administration of inhaled and parenteral prostacyclins led to the development of extended-release treprostinil diolamine for oral use. Limited data exist on the transition to oral treprostinil. The purpose of this case series is to describe the transition from subcutaneous or inhaled treprostinil to oral treprostinil in the outpatient setting...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28462839/synthesis-of-both-enantiomers-of-1-2-3-4-tetrahydroisoquinoline-derivative-ippam-1-and-enantio-dependency-of-its-positive-allosteric-modulation-of-prostacyclin-receptor
#20
Kohki Yamamoto, Toshifumi Suzuki, Riyo Imamura, Tetsuo Nagano, Takayoshi Okabe, Hiroyuki Miyachi
We present a practical synthesis of both enantiomers of 1,2,3,4-tetrahydroisoquinoline derivative IPPAM-1 (1), which is a positive allosteric modulator (PAM) of prostacyclin receptor (IP) and a candidate for treatment of pulmonary arterial hypertension without the side effects caused by IP agonists. Assay of cAMP production by CHO-K1 cells stably expressing human IP clearly demonstrated that the IPPAM activity resides exclusively on the R-form of 1.
March 29, 2017: Bioorganic & Medicinal Chemistry Letters
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