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https://www.readbyqxmd.com/read/28926093/pulmonary-hypertension-molecular-aspects-of-current-therapeutic-intervention-and-future-direction
#1
Taruna Katyal Arora, Amit KumarArora, Monika Katyal Sachdeva, Satyendra Kumar Rajput, Arun Kumar Sharma
Pulmonary hypertension (PH) is a life-threatening lung disorder with towering prevalence and risk for future has been gradually rising worldwide. Even, no specific medications are available for pulmonary hypertension; various classes of treatment based upon the origin and magnitude of hypertension are still used for the treatment of PH. Consideration of molecular or signaling modulation is the imperative approach that can offer a new notion for prevalent pharmacotherapeutic agents. Instead of concurrent targets, including endothelin receptor antagonists (ETA/ETB), phosphodiesterase 5 inhibitor (PDF-5), calcium channel blockers, anticoagulants, diuretics and long acting prostacyclin analogue, recent scientific reports revealed the numerous potential alternative therapeutic approaches that can significantly target the pathological signaling alteration associated with PH...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28912617/pulmonary-hypertension-clinical-parameters-of-a-difficult-case-in-pregnancy
#2
Byron C Calhoun
Treatment of pulmonary hypertension in pregnancy with a prostacyclin analogue-iloprost and/or calcium channel antagonists appears to improve outcomes and survival. These medications could have been administered to the patient and the response monitored. If the patient did not respond to therapy, this patient may have had either a referral to or transfer to another high risk center with more experience in this type of pregnant patient. There is no literature to support termination of pregnancy improving maternal survival outcomes in these patients, even though termination is recommended by all obstetrical textbooks...
August 2017: Linacre Quarterly
https://www.readbyqxmd.com/read/28893866/randomised-placebo-controlled-safety-and-tolerability-trial-of-fk506-tacrolimus-for-pulmonary-arterial-hypertension
#3
Edda Spiekerkoetter, Yon K Sung, Deepti Sudheendra, Valerie Scott, Patricia Del Rosario, Matthew Bill, Francois Haddad, Janel Long-Boyle, Haley Hedlin, Roham T Zamanian
Pulmonary arterial hypertension (PAH) is a devastating disease characterised by occlusive pulmonary vasculopathy. Activation of bone morphogenetic protein receptor 2 (BMPR2) signalling by FK506 (tacrolimus) reverses occlusive vasculopathy in rodent PAH models. Here, we determined the safety and tolerability of low-level FK506 therapy in stable PAH patients.We performed a randomised, double-blind, placebo-controlled, 16-week, single-centre, phase IIa trial in PAH patients with New York Heart Association functional class II/III symptoms using three FK506 target levels (<2, 2-3 and 3-5 ng·mL(-1))...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28891448/a-special-focus-on-selexipag-treatment-of-pulmonary-arterial-hypertension
#4
Louise Marqvard Sørensen, Markus Wehland, Marcus Krüger, Ulf Simonsen, Mohamed Zakaria Nassef, Manfred Infanger, Daniela Grimm
BACKGROUND: This review focuses on the treatment of pulmonary arterial hypertension (PAH) with selexipag and compares its drug-related therapeutic effects with those of prostacyclin analogues. METHODS: We searched the relevant literature and summarized the current clinical trials concerning selexipag and PAH. RESULTS: With only few cases per million, PAH is a rare disease, but when untreated it can be life threatening. PAH is linked to elevated levels of endothelin (ET-1) and decreased levels of nitric oxide (NO) and prostacyclin (PGI2)...
September 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28887131/prostacyclin-mimetics-afford-protection-against-lipopolysaccharide-d-galactosamine-induced-acute-liver-injury-in-mice
#5
Hiroki Misawa, Wakana Ohashi, Kengo Tomita, Kohshi Hattori, Yutaka Shimada, Yuichi Hattori
Prostacyclin (PGI2) serves as a protective, anti-inflammatory mediator and PGI2 mimetics may be useful as a hepatoprotective agent. We examined whether two PGI2 mimetics, ONO-1301 and beraprost, are beneficial in acute liver injury and attempted to delineate the possible mechanism underlying the hepatoprotective effect. Acute liver injury was induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice. Mice were given an intraperitoneal injection of PGI2 mimetics 1h before LPS/GalN challenge. Both ONO-1301 and beraprost significantly declined the LPS/GalN-induced increase in serum aminotransferase activity...
September 5, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28880908/prostacyclin-thromboxane-and-glomerular-filtration-rate-are-abnormal-in-sickle-cell-pregnancy
#6
Opeyemi Abayomi Obilade, Alani Suleimon Akanmu, Fiona Broughton Pipkin, Bosede Bukola Afolabi
BACKGROUND: Pregnancy increases the risk of morbidity and mortality in sickle cell disease. We previously showed pregnant women with sickle cell disease to have a relatively low plasma renin concentration in late pregnancy, associated with a lack of the expected plasma volume expansion. We hypothesized this to be due to increased systemic vascular resistance through an imbalance between the vasodilator prostacyclin and vasoconstrictor thromboxane, associated with decreased glomerular filtration rate (GFR)...
2017: PloS One
https://www.readbyqxmd.com/read/28857461/ly3127760-a-selective-prostaglandin-e4-ep4-receptor-antagonist-and-celecoxib-a-comparison-of-pharmacological-profiles
#7
Yan Jin, Claire Smith, Leijun Hu, David E Coutant, Kelly Whitehurst, Krista Phipps, Terry Ann McNearney, Xiao Yang, Bradley Ackermann, Thomas Pottanat, William Landschulz
Safety, tolerability, and pharmacology profiles of LY3127760, an EP4 antagonist, were explored in healthy subjects in a subject/investigator-blind, parallel-group, multiple-ascending dose study. Cohorts consisted of 13 patients randomized to LY3127760, celecoxib (400 mg), or placebo (9:2:2 ratio) for 28 days. LY3127760 was well tolerated; the most commonly observed adverse events were gastrointestinal, similar to celecoxib. LY3127760 increased release of ex vivo tumor necrosis factor alpha after lipopolysaccharide/prostaglandin E2 stimulation when compared with placebo, suggesting a dose-dependent blockade of the EP4 receptor...
August 30, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28857417/increased-myoendothelial-feedback-is-associated-with-increased-connexin37-and-ik1-channel-expression-in-mesenteric-arteries-of-diet-induced-hyperhomocysteinemic-mice
#8
Robin C Looft-Wilson, Cara R Goodell, Christina A Mutch, Stephanie M Mutchler, Kayla L Miller, Monique Guraya
OBJECTIVE: Previously, we found that diet-induced HHcy in mice caused decreased eNOS expression and signaling in mesenteric arteries, but greatly enhanced non-NOS, non-prostacyclin-dependent vasodilation, which involves myoendothelial gap junction (MEJ) communication. To further assess whether HHcy enhances MEJ communication, this study examined endothelium-dependent attenuation of phenylephrine-induced vasoconstriction (myoendothelial feedback) and key molecules involved. METHODS: Myoendothelial feedback was examined in isolated mouse mesenteric arteries, after 6-wk diet-induced HHcy, using pressure myography...
August 31, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28852049/nonsteroidal-anti-inflammatory-drug-interaction-with-prostacyclin-synthase-protects-from-miscarriage
#9
Digna R Velez Edwards, Todd L Edwards, Michael J Bray, Eric Torstenson, Sarah Jones, Martha J Shrubsole, Harvey J Muff, Katherine E Hartmann
This study evaluates the relationship between single nucleotide polymorphisms (SNPs) in nonsteroidal anti-inflammatory drug (NSAID) metabolism and related pathways and spontaneous abortion (SAB, gestation < 20 weeks) risk. Women were enrolled in Right from the Start (2004-2010) prospective cohort. Periconceptional NSAIDs reported through the sixth week of pregnancy were obtained from study interviews. We evaluated 201 SNPs in 600 European American women. Interaction analyses between NSAID use and SNPs were conducted using logistic regression, adjusted for confounders...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851689/the-second-generation-pgi2-analogue-treprostinil-fails-to-chemoprevent-tumors-in-a-murine-lung-adenocarcinoma-model
#10
Lori D Dwyer-Nield, Gregory A Hickey, Micah Friedman, Kevin Choo, Debbie G McArthur, Meredith A Tennis, Melissa L New, Mark Geraci, Robert L Keith
Prostacyclin (prostaglandin I2, PGI2) over-production in FVB/N mice prevents the formation of carcinogen and tobacco smoke induced adenomas, and administration of the oral prostacyclin analog iloprost to wild type mice also prevented carcinogen-induced mouse lung adenoma formation. Former smokers taking oral iloprost showed improved bronchial dysplasia histology compared to placebo. Next generation oral prostacyclin analogues, like treprostinil, were developed for treatment of pulmonary arterial hypertension (PAH)...
August 29, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28840065/management-of-acute-subdural-hematoma-in-a-patient-with-portopulmonary-hypertension-on-prostanoid-therapy
#11
Richard Rammo, Adam Robin, Jessin John, Aqueel Pabaney, Panayiotis Varelas, Max Kole
BACKGROUND: Treprostinil is a prostacyclin analog used to treat portopulmonary hypertension (PPHTN) and is one of several drugs shown to increase survival, but results in platelet dysfunction. Little is known about the management of patients on treprostinil who present with an acute subdural hematoma (aSDH). We describe such a case and offer our recommendations on management based on our experience and review of the literature. CASE DESCRIPTION: A 63-year-old, right-handed female with a history of PPHTN presented with severe headache and was found to have a large left aSDH with midline shift on imaging...
2017: Surgical Neurology International
https://www.readbyqxmd.com/read/28834088/vegf-synthesis-is-induced-by-prostacyclin-and-tgf-%C3%AE-in-distal-lung-fibroblasts-from-copd-patients-and-control-subjects-implications-for-pulmonary-vascular-remodelling
#12
Gunilla Westergren-Thorsson, Mariam Bagher, Annika Andersson-Sjöland, Lena Thiman, Claes-Göran Löfdahl, Oskar Hallgren, Leif Bjermer, Anna-Karin Larsson-Callerfelt
BACKGROUND AND OBJECTIVE: Involvement of pulmonary vascular remodelling is a characteristic sign in COPD. Vascular mediators such as vascular endothelial growth factor (VEGF) and prostacyclin may regulate fibroblast activity. The objective was to study the synthesis of VEGF and interactions with prostacyclin and transforming growth factor (TGF)-β1 in lung fibroblasts from patients with COPD and healthy control subjects. To further explore the autocrine role of synthesized VEGF on fibroblast activity, studies were performed in human lung fibroblasts (HFL-1)...
August 22, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28827689/increased-role-of-e-prostanoid-receptor-3-in-prostacyclin-evoked-contractile-activity-of-spontaneously-hypertensive-rat-mesenteric-resistance-arteries
#13
Bin Liu, Mengyi Zhan, Yingzhan Zhang, Hui Li, Xiangzhong Wu, Fengfeng Zhuang, Wenhong Luo, Yingbi Zhou
This study aimed to determine whether E prostanoid receptor-3 (EP3) is involved in prostacyclin (PGI2)-evoked vasoconstrictor activity of resistance arteries and if so, how it changes under hypertensive conditions. Mesenteric resistance arteries from Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were isolated for functional and biochemical studies. Here we show that in vessels from WKYs, PGI2 or the endothelial muscarinic agonist ACh (which stimulates in vitro PGI2 synthesis) evoked vasoconstrictor activity, which increased in SHRs...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819824/-update-pulmonary-arterial-hypertension-definitions-diagnosis-therapy
#14
N Sommer, M J Richter, K Tello, F Grimminger, W Seeger, H A Ghofrani, H Gall
The term pulmonary arterial hypertension comprises a group of pulmonary vascular diseases of different etiologies that are characterized by similar precapillary vascular remodeling processes and result in exertional dyspnea and right heart insufficiency. The specific pharmacological treatment approach considers the risk of mortality and phenotypical properties and includes treatment with phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostanoids, as well as with more novel substances, such as a soluble guanylyl cyclase stimulator and an oral prostacyclin receptor agonist...
August 17, 2017: Der Internist
https://www.readbyqxmd.com/read/28818881/selexipag-for-the-treatment-of-connective-tissue-disease-associated-pulmonary-arterial-hypertension
#15
Sean Gaine, Kelly Chin, Gerry Coghlan, Richard Channick, Lilla Di Scala, Nazzareno Galiè, Hossein-Ardeschir Ghofrani, Irene M Lang, Vallerie McLaughlin, Ralph Preiss, Lewis J Rubin, Gérald Simonneau, Olivier Sitbon, Victor F Tapson, Marius M Hoeper
Patients with connective tissue disease-associated pulmonary arterial hypertension (PAH-CTD) have a poor prognosis compared with other aetiologies. The underlying CTD can influence treatment response and outcomes. We characterised the GRIPHON study PAH-CTD subgroup and evaluated response to selexipag.Of 334 patients with PAH-CTD, PAH was associated with systemic sclerosis (PAH-SSc) in 170, systemic lupus erythematosus (PAH-SLE) in 82 and mixed CTD/CTD-other in 82. For the primary composite endpoint of morbidity/mortality, hazard ratios (HR) and 95% CI were calculated using Cox proportional hazard models...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28811905/surgical-sympathectomy-for-buerger-s-disease
#16
REVIEW
Daniel G Cacione, Daniel H Moreno, Luis Cu Nakano, José Cc Baptista-Silva
Buerger's disease is characterized by recurring progressive inflammation and occlusions in small and medium arteries and veins of the limbs. Its cause is unknown, but it is most common in young men with a history of tobacco use. It is responsible for ischemic ulcers and extreme pain in the hands and feet. In many cases, notably in patients with the most severe presentations, there is no possibility of improving the condition with surgery (limb revascularisation), and therefore, alternative therapies (e.g. sympathectomy) is used...
August 2017: JRSM Open
https://www.readbyqxmd.com/read/28806480/aerosolized-prostacyclins-for-acute-respiratory-distress-syndrome-ards
#17
REVIEW
Arash Afshari, Anders Bastholm Bille, Mikkel Allingstrup
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a critical condition that is associated with high mortality and morbidity. Aerosolized prostacyclin has been used to improve oxygenation despite the limited evidence available so far.This review was originally published in 2010 and updated in 2017. OBJECTIVES: To assess the benefits and harms of aerosolized prostacyclin in adults and children with ARDS. SEARCH METHODS: In this update, we searched CENTRAL (2017, Issue 4); MEDLINE (OvidSP), Embase (OvidSP), ISI BIOSIS Previews, ISI Web of Science, LILACS, CINAHL (EBSCOhost), and three trials registers...
July 24, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28800765/therapeutic-effects-of-flurbiprofen-axetil-on-mesenteric-traction-syndrome-randomized-clinical-trial
#18
Hidemasa Takahashi, Dai Shida, Kyoko Tagawa, Ryo Iwamoto, Makoto Arita, Hiroyuki Arai, Takeo Suzuki
BACKGROUND: This study aimed to reveal the appropriate timing for the intravenous administration of flurbiprofen axetil for preventing mesenteric traction syndrome (MTS), caused by prostacyclin release. METHODS: In this prospective, randomized, clinical study, forty-five patients who were undergoing elective surgery for colorectal cancer via laparotomy were enrolled. Patients were randomly divided into 3 groups: a preoperative group (n = 16) receiving flurbiprofen axetil directly before surgery; a post-MTS group (n = 14) receiving following MTS onset; and a control group (n = 15) who were not administered flurbiprofen axetil...
August 11, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28800645/analysis-of-endogenous-lipids-during-intestinal-wound-healing
#19
Yunna Lee, Jieun Choo, Su Jin Kim, Gwangbeom Heo, Charalabos Pothoulakis, Yong-Hak Kim, Eunok Im
Intestinal wound healing is a new therapeutic goal for inflammatory bowel disease (IBD) as complete healing of the mucosa is the key element of clinical remission in IBD. Previous studies showed that termination of inflammation can be achieved by adding pro-resolving lipids like DHA and EPA exogenously. However, the roles of these lipids in mucosal healing have not been investigated. To recapitulate intestinal healing process, mice were received dextran sodium sulfate (DSS) for 7 days in the drinking water followed by regular tap water for 5 additional days...
2017: PloS One
https://www.readbyqxmd.com/read/28791952/novel-strategies-for-treatment-of-pulmonary-arterial-hypertension
#20
REVIEW
Magdalena Jasińska-Stroschein, Daria Orszulak-Michalak
Pulmonary hypertension (PH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. Special population include patents with pulmonary arterial hypertension (PAH). A greater understanding of the epidemiology, pathogenesis, and pathophysiology of PAH has led to significant advances over the past few years. Modern drug therapy provides a significant improvement in patient symptomatic status and a slower rate of clinical deterioration...
July 11, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
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