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https://www.readbyqxmd.com/read/29792868/ah6809-decreases-production-of-inflammatory-mediators-by-pge-2-ep2-camp-signaling-pathway-in-an-experimentally-induced-pure-cerebral-concussion-in-rats
#1
Ping Li, Hongyan Jiang, Haiying Wu, Deye Wu, Hengxi Li, Jianyun Yu, Jianghua Lai
Increasing evidence suggests that PGE2 metabolic pathway is involved in pathological changes of the secondary brain injury after traumatic brain injury. However, the underlying mechanisms, in particular, the correlation between various key enzymes and the brain injury, has remained to be fully explored. More specifically, it remains to be ascertained whether AH6809 (an EP2 receptor antagonist) would interfere with the downstream of the PGE2 , regulate the inflammatory mediators and improve neuronal damage in the hippocampus by PGE2 - EP2 - cAMP signaling pathway...
May 21, 2018: Brain Research
https://www.readbyqxmd.com/read/29791923/inhaled-treprostinil-prodrug-lipid-nanoparticle-formulations-provide-long-acting-pulmonary-vasodilation
#2
Franziska G Leifer, Donna M Konicek, Kuan-Ju Chen, Adam J Plaunt, Dany Salvail, Charles E Laurent, Michel R Corboz, Zhili Li, Richard W Chapman, Walter R Perkins, Vladimir S Malinin
Treprostinil (TRE), a prostanoid analogue approved in the USA for the treatment of pulmonary arterial hypertension, requires continuous infusion or multiple dosing sessions per day for inhaled and oral routes of administration due to its short half-life. The inhaled drug is known to induce adverse systemic and local effects including headache, nausea, cough, and throat irritation which may be due at least in part to transiently high drug concentrations in the lungs and plasma immediately following administration [1]...
May 23, 2018: Drug Research
https://www.readbyqxmd.com/read/29781586/treatment-algorithms-for-systemic-sclerosis-according-to-experts
#3
Andreu Fernández-Codina, Kyle M Walker, Janet E Pope
INTRODUCTION: Treatment for many aspects of systemic sclerosis (SSc) lacks agreement. OBJECTIVES: To generate SSc treatment algorithms endorsed by high percentage of SSc experts. METHODS: Experts from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research group (N=170) were asked whether they agreed with SSc algorithms (from 2012). Two consensus rounds refined agreement; 62 (36%), 54 (32%) and 48 (28%) experts completed surveys...
May 21, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29773555/prostaglandin-f-2%C3%AE-facilitates-hepatic-glucose-production-through-camkii%C3%AE-p38-foxo1-signaling-pathway-in-fasting-and-obesity
#4
Yuanyang Wang, Shuai Yan, Bing Xiao, Shengkai Zuo, Qianqian Zhang, Guilin Chen, Yu Yu, Di Chen, Qian Liu, Yi Liu, Yujun Shen, Ying Yu
Gluconeogenesis is drastically increased in patients with type 2 diabetes and accounts for increased fasting plasma glucose concentrations. Circulating prostaglandin (PG) F2α is also markedly elevated in diabetes mellitus; however, whether and how PGF2α regulates hepatic glucose metabolism remain unknown. Here, we demonstrated that PGF2α receptor (F-prostanoid receptor; FP) was upregulated in livers of mice upon fasting- and diabetic stress. Hepatic deletion of the FP receptor suppressed fasting-induced hepatic gluconeogenesis, whereas FP overexpression enhanced hepatic gluconeogenesis in mice...
May 17, 2018: Diabetes
https://www.readbyqxmd.com/read/29746568/the-protective-effect-of-the-ep2-receptor-on-tgf-%C3%AE-1-induced-podocyte-injury-via-the-pi3k-akt-signaling-pathway
#5
Jing Liu, Yi-de Zhang, Xiao-Lan Chen, Xue-Ling Zhu, Xu Chen, Jian-Hua Wu, Nai-Feng Guo
Transforming growth factor β1 (TGF-β1) plays a central role in chronic kidney diseases. TGF-β1 induction causes podocyte injury, which results in proteinuria and renal failure. However, the effect of the prostaglandin E2 /E-prostanoid receptor (EP2) on TGF-β1-induced podocyte injury remains unknown. Previous studies have shown that phosphoinositide 3-OH kinase (PI3K)/Akt is widespread in cells, and is vital for the regulation of cell proliferation, differentiation, apoptosis and metabolism. In this study, we cultured immortalized mouse podocytes in vitro in different groups: control group; TGF-β1 (5ng/ml) group; EP2 agonist Butaprost treatment (10-7, 10-6, or 10-5mol/L) +TGF-β1 group; EP2 antagonist AH6809 treatment (10-7, 10-6, or 10-5mol / L) + TGF-β1 group...
2018: PloS One
https://www.readbyqxmd.com/read/29743918/effect-of-lavender-lavandula-angustifolia-essential-oil-on-acute-inflammatory-response
#6
Gabriel Fernando Esteves Cardia, Saulo Euclides Silva-Filho, Expedito Leite Silva, Nancy Sayuri Uchida, Heitor Augusto Otaviano Cavalcante, Larissa Laila Cassarotti, Valter Eduardo Cocco Salvadego, Ricardo Alexandre Spironello, Ciomar Aparecida Bersani-Amado, Roberto Kenji Nakamura Cuman
Lavandula angustifolia is a plant of Lamiaceae family, with many therapeutic properties and biological activities, such as anticonvulsant, anxiolytic, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of this study was to evaluate the effect of Lavandula angustifolia Mill. essential oil (LEO) on acute inflammatory response. LEO was analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods and showed predominance of 1,8-cineole (39...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29738273/the-antipyretic-effect-of-paracetamol-occurs-independent-of-transient-receptor-potential-ankyrin-1-mediated-hypothermia-and-is-associated-with-prostaglandin-inhibition-in-the-brain
#7
Elahe Mirrasekhian, Johan L Å Nilsson, Kiseko Shionoya, Anders Blomgren, Peter M Zygmunt, David Engblom, Edward D Högestätt, Anders Blomqvist
The mode of action of paracetamol (acetaminophen), which is widely used for treating pain and fever, has remained obscure, but may involve several distinct mechanisms, including cyclooxygenase inhibition and transient receptor potential ankyrin 1 (TRPA1) channel activation, the latter being recently associated with paracetamol's propensity to elicit hypothermia at higher doses. Here, we examined whether the antipyretic effect of paracetamol was due to TRPA1 activation or cyclooxygenase inhibition. Treatment of wild-type and TRPA1 knockout mice rendered febrile by immune challenge with LPS with a dose of paracetamol that did not produce hypothermia (150 mg/kg) but is known to be analgetic, abolished fever in both genotypes...
May 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29733297/role-of-prostanoids-in-gastrointestinal-cancer
#8
Dingzhi Wang, Raymond N DuBois
Chronic inflammation is a risk factor for gastrointestinal cancer and other diseases. Most studies have focused on cytokines and chemokines as mediators connecting chronic inflammation to cancer, whereas the involvement of lipid mediators, including prostanoids, has not been extensively investigated. Prostanoids are among the earliest signaling molecules released in response to inflammation. Multiple lines of evidence suggest that prostanoids are involved in gastrointestinal cancer. In this Review, we discuss how prostanoids impact gastrointestinal cancer development...
May 7, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29709917/knockout-of-ceramide-kinase-aggravates-pathological-and-lethal-responses-in-mice-with-experimental-colitis
#9
Satomi Suzuki, Ai Tanaka, Hiroyuki Nakamura, Toshihiko Murayama
Sphingolipids and their metabolic enzymes are implicated in ulcerative colitis. Ceramide kinase (CerK) catalyzes the phosphorylation of ceramide to ceramide-1-phosphate (C1P). Previous studies showed the activation of CerK by the pro-inflammatory cytokine interleukin-1β, the C1P-induced up-regulation of prostanoids exerting protective effects against colitis, and the C1P-induced down-regulation of the pro-inflammatory cytokine tumor necrosis factor-α. In order to elucidate CerK/C1P functions in colitis, we examined the severity of dextran sodium sulfate (DSS)-induced colitis in wild-type (WT) and CerK deletion (CerK(-/-) ) mice...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29679599/mortality-in-pulmonary-arterial-hypertension-patients-treated-with-continuous-prostanoids
#10
S D Bartolome, N Sood, T S Shah, K Styrvoky, F T Torres, K M Chin
INTRODUCTION: Parenteral prostanoids are considered the treatment of choice for patients with severe pulmonary arterial hypertension (PAH). Prognostic studies for patients treated in the modern era are limited. METHODS: In this retrospective cohort study, patients initiating IV epoprostenol or IV or SC treprostinil therapy for PAH from 2007-2016 at UT Southwestern, Dallas, TX and Ohio State University, Columbus, OH were included. Transplant-free survival was assessed from the time of IV/SC initiation and from the time of first follow-up...
April 18, 2018: Chest
https://www.readbyqxmd.com/read/29679483/prostaglandin-fp-receptor-antagonists-discovery-pharmacological-characterization-and-therapeutic-utility
#11
REVIEW
Najam A Sharif, Peter G Klimko
In contrast to the availability of potent and selective antagonists of several prostaglandin (PG) receptor types (including DP1 , DP2 , EP, and TP receptors), there has been a paucity of well-characterized, selective FP-receptor antagonists. The earliest ones included dimethyl amide and dimethyl amine derivatives of PGF2α , but these have failed to gain prominence. The fluorinated PGF2α analogs, AL-8810 and AL-3138, were subsequently discovered as competitive and non-competitive FP-receptor antagonists, respectively...
April 21, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29676940/differential-compensation-of-two-cyclooxygenases-in-renal-homeostasis-is-independent-of-prostaglandin-synthetic-capacity-under-basal-conditions
#12
Xinzhi Li, Liudmila L Mazaleuskaya, Laurel L Ballantyne, Hu Meng, Garret A FitzGerald, Colin D Funk
The distinct functions of each cyclooxygenase (COX) isoform in renal homeostasis have been the subject of intense investigation for many years. We took the novel approach of using 3 characterized mouse lines, where the prostaglandin (PG)-endoperoxide synthase genes 1 and 2 ( Ptgs1 and Ptgs2) substitute for one another to delineate distinct roles and the potential for COX isoform substitution. Flipped Ptgs genes generate a reversed COX-expression pattern in the kidney, where the knockin COX-2 is highly expressed...
April 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29673264/advances-in-extracellular-ligand-recognition-sites-on-prostanoid-receptors
#13
Yan Li, Anna Xu, Qinglan Ling, Ke-He Ruan
No abstract text is available yet for this article.
April 20, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29669171/prostaglandin-analogues-and-nitric-oxide-contribution-in-the-treatment-of-ocular-hypertension-and-glaucoma
#14
REVIEW
Francesco Impagnatiello, Elena Bastia, Nicoletta Almirante, Stefania Brambilla, Brigitte Duquesroix, Angela C Kothe, Michael V W Bergamini
In patients with ocular hypertension or glaucoma all treatments aim at lowering intraocular pressure (IOP) by modulating aqueous humor (AH) production and/or uveoscleral and trabecular meshwork /Schlemm's canal AH drainage. Prostaglandin (PG) analogues are considered the 'gold standard', and are the most frequently used IOP-lowering agents. Recent data support an important role of nitric oxide (NO) in regulating IOP. Thus novel PG analogues carrying a NO-donating moiety were recently advanced. Latanoprostene bunod (LBN) and NCX 470, respectively a NO-donating derivative of latanoprost and bimatoprost, are examples of such compounds...
April 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29658630/lumbar-sympathectomy-versus-prostanoids-for-critical-limb-ischaemia-due-to-non-reconstructable-peripheral-arterial-disease
#15
REVIEW
Indrani Sen, Sunil Agarwal, Prathap Tharyan, Rachel Forster
BACKGROUND: Peripheral arterial disease (PAD) is a common circulatory problem that can lead to reduced blood flow to the limbs, which may result in critical limb ischaemia (CLI), a painful manifestation that occurs when a person is at rest. The mainstay of treatment for CLI is surgical or endovascular repair. However, when these means of treatment are not suitable, due to anatomical reasons or comorbidities, treatment for pain is limited. Lumbar sympathectomy and prostanoids have both been shown to reduce pain from CLI in people who suffer from non-reconstructable PAD, but there is currently insufficient evidence to determine if one treatment is superior...
April 16, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29626715/targeting-therapeutics-to-bone-by-conjugation-with-bisphosphonates
#16
REVIEW
Robert N Young, Marc D Grynpas
Bisphosphonates target and bind avidly to the mineral (hydroxyapatite) found in bone. This targeting ability has been exploited to design and prepare bisphosphonate conjugate prodrugs to deliver a wide variety of drug molecules selectively to bones. It is important that conjugates be stable in the blood stream and that conjugate that is not taken up by bone is eliminated rapidly. The prodrugs should release active drug at a rate appropriate so as to provide efficacy. Radiolabelling is the best method to quantify and evaluate pharmacokinetics, tissue distribution, bone uptake and release of the active drug(s)...
April 4, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29623045/relaxin-deficiency-leads-to-uterine-artery-dysfunction-during-pregnancy-in-mice
#17
Sarah A Marshall, Sevvandi N Senadheera, Maria Jelinic, Kelly O'Sullivan, Laura J Parry, Marianne Tare
The uterine vasculature undergoes profound adaptations in response to pregnancy. Augmentation of endothelial vasodilator function and reduced smooth muscle reactivity are factors contributing to uterine artery adaptation and are critical for adequate placental perfusion. The peptide hormone relaxin has an important role in mediating the normal maternal renal vascular adaptations during pregnancy through a reduction in myogenic tone and an increase in flow-mediated vasodilation. Little is known however about the influence of endogenous relaxin on the uterine artery during pregnancy...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29608499/diagnosis-treatment-and-management-of-orthotopic-liver-transplant-candidates-with-portopulmonary-hypertension
#18
Anna Koulava, Abdallah Sannani, Avi Levine, Chhaya Aggarwal Gupta, Sarina Khanal, William Frishman, Roxana Bodin, David C Wolf, William Aronow, Gregg M Lanier
Portopulmonary hypertension (POPH) is seen in 5-8% of orthotopic liver transplantation (OLT) candidates and has significant implications for clinical outcomes. POPH is characterized by vasoconstriction and remodeling of the pulmonary vasculature. It is exacerbated by the hyperdynamic circulation that is common in advanced liver disease. Screening all OLT candidates with transthoracic echocardiography to assess pulmonary pressures and right ventricular function is crucial, as clinical symptoms alone are not reliable...
March 30, 2018: Cardiology in Review
https://www.readbyqxmd.com/read/29607536/dp1-receptor-signaling-prevents-the-onset-of-intrinsic-apoptosis-in-eosinophils-and-functions-as-a-transcriptional-modulator
#19
Miriam Peinhaupt, David Roula, Anna Theiler, Miriam Sedej, Rudolf Schicho, Gunther Marsche, Eva M Sturm, Ian Sabroe, Marc E Rothenberg, Akos Heinemann
Prostaglandin (PG) D2 is the ligand for the G-protein coupled receptors DP1 (D-type prostanoid receptor 1) and DP2 (also known as chemoattractant receptor homologous molecule, expressed on Th2 cells; CRTH2). Both, DP1 and DP2 are expressed on the cellular surface of eosinophils; although it has become quite clear that PGD2 induces eosinophil migration mainly via DP2 receptors, the role of DP1 in eosinophil responses has remained elusive. In this study, we addressed how DP1 receptor signaling complements the pro-inflammatory effects of DP2...
April 1, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29599139/protective-role-of-mpges-1-microsomal-prostaglandin-e-synthase-1-derived-pge-2-prostaglandin-e2-and-the-endothelial-ep4-prostaglandin-e-receptor-in-vascular-responses-to-injury
#20
Huifeng Hao, Sheng Hu, Qing Wan, Chuansheng Xu, Hong Chen, Liyuan Zhu, Zhenyu Xu, Jian Meng, Richard M Breyer, Nailin Li, De-Pei Liu, Garret A FitzGerald, Miao Wang
OBJECTIVE: Deletion of mPGES-1 (microsomal prostaglandin E synthase-1)-an anti-inflammatory target alternative to COX (cyclooxygenase)-2-attenuates injury-induced neointima formation in mice. This is attributable to the augmented levels of PGI2 (prostacyclin)-a known restraint of the vascular response to injury, acting via IP (I prostanoid receptor). To examine the role of mPGES-1-derived PGE2 (prostaglandin E2) in vascular remodeling without the IP. APPROACH AND RESULTS: Mice deficient in both IP and mPGES-1 (DKO [double knockout] and littermate controls [IP KO (knockout)]) were subjected to angioplasty wire injury...
March 29, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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