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https://www.readbyqxmd.com/read/28770223/plumbagin-alleviates-capillarization-of-hepatic-sinusoids-in-vitro-by-downregulating-et-1-vegf-ln-and-type-iv-collagen
#1
Guiyu Li, Yue Peng, Tiejian Zhao, Jiyong Lin, Xuelin Duan, Yanfei Wei, Jing Ma
Critical roles for liver sinusoidal endothelial cells (LSECs) in liver fibrosis have been demonstrated, while little is known regarding the underlying molecular mechanisms of drugs delivered to the LSECs. Our previous study revealed that plumbagin plays an antifibrotic role in liver fibrosis. In this study, we investigated whether plumbagin alleviates capillarization of hepatic sinusoids by downregulating endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), laminin (LN), and type IV collagen on leptin-stimulated LSECs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28760302/developmental-therapeutics-in-myeloproliferative-neoplasms
#2
REVIEW
Prithviraj Bose, Srdan Verstovsek
The unprecedented success of the Janus kinase (JAK) 1/2 inhibitor ruxolitinib in myelofibrosis (MF) provided much-needed impetus for clinical drug development for the Philadelphia chromosome-negative myeloproliferative neoplasms. The survival benefit conferred by this agent, along with its marked efficacy with regard to spleen volume and symptom reduction, have made ruxolitinib the cornerstone of drug therapy in MF. However, there remain significant unmet needs in the treatment of patients with MF, and many novel classes of agents continue to be investigated in efforts to build on the progress made with ruxolitinib...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28757441/exogenous-nitric-oxide-enhances-the-prophylactic-effect-of-aminoguanidine-a-preferred-inos-inhibitor-on-bleomycin-induced-fibrosis-in-the-lung-implications-for-the-direct-roles-of-the-no-molecule-in-vivo
#3
Chao Chen, Xiao-Jing Yun, Li-Ze Liu, Hong Guo, Lian-Feng Liu, Xiao-Ling Chen
OBJECTIVE: Inducible nitric oxide synthase (iNOS) aggravates and endothelial nitric oxide synthase (eNOS) ameliorates fibrosis in the lung. Our previous study demonstrated that aminoguanidine (AG), a preferred iNOS inhibitor, prevents bleomycin-induced injury and fibrosis in the lung. The diethylenetriamine nitric oxide adduct (DETA/NO) is a slow-release NO donor. Here, to clarify the exact role of the nitric oxide (NO) molecule in the pathogenesis of pulmonary fibrosis in vivo, we observed the effects of inhalation of aerosolized DETA/NO on fibrosis in the lungs of bleomycin-exposed rats with AG treatment, including the effects on the myofibroblast number, collagen deposition, peroxynitrite anion (ONOO(-)) formation, and injury in the lung...
July 27, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28696894/preference-of-aerosolized-pirfenidone-to-oral-intake-an-experimental-model-of-pulmonary-fibrosis-by-paraquat
#4
Rokhsana Rasooli, Hamid Rajaian, Abbas Pardakhty, Ali Mandegary
BACKGROUND: Inhalation drug delivery is a fast, effective, and safe route of delivering medication directly to the lungs. Thanks to the large surface area and highly vascularized epithelium in lung, pulmonary drug delivery has been considered as an effective route to deliver drugs to the systemic circulation. Pirfenidone (PF), an oral antifibrotic agent, has been shown to slow down the progression of the lung fibrosis. Inhalation or intrapulmonary delivery of PF appears to be a good alternative to optimize drug delivery and minimize the dosage, adverse and nonspecific effects...
July 11, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28691737/evaluating-the-antifibrotic-potency-of-galunisertib-in-a-human-ex-vivo-model-of-liver-fibrosis
#5
Theerut Luangmonkong, Su Suriguga, Emilia Bigaeva, Miriam Boersema, Dorenda Oosterhuis, Koert P de Jong, Detlef Schuppan, Henricus A M Mutsaers, Peter Olinga
BACKGROUND AND PURPOSE: Liver fibrosis is a major cause of liver-related mortality. Yet, to date, no effective antifibrotic drug is available. Galunisertib, a TGF-β receptor type I kinase inhibitor, is a potential candidate for the treatment of liver fibrosis. Here, we evaluated the potency of galunisertib in a human ex vivo model of liver fibrosis. EXPERIMENTAL APPROACH: Antifibrotic potency and associated mechanisms were studied ex vivo, using both healthy and cirrhotic human precision-cut liver slices...
July 10, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28668400/idiopathic-pulmonary-fibrosis-in-the-era-of-antifibrotic-therapy-searching-for-new-opportunities-grounded-in-evidence
#6
C Robalo-Cordeiro, P Campos, L Carvalho, A Borba, S Clemente, S Freitas, S Furtado, J M Jesus, C Leal, A Marques, N Melo, C Souto-Moura, S Neves, V Sousa, A Santos, A Morais
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease that up to now has been associated with a poor prognosis. However, the results of the INPULSIS and ASCEND trials and the approval of nintedanib and pirfenidone have marked the beginning of a new era for IPF patients. Questions remain, however. Should these drugs be used earlier? What effect will they have on more severe disease? Will their effects last beyond the trial period? This manuscript is the outcome of a multidisciplinary meeting between pulmonology, radiology, and pathology clinicians on the use of antifibrotic agents in IPF...
June 28, 2017: Revista Portuguesa de Pneumologia
https://www.readbyqxmd.com/read/28667654/idiopathic-pulmonary-fibrosis-ipf-common-practice-in-poland-before-the-antifibrotic-drugs-era
#7
Wojciech Jerzy Piotrowski, Magdalena M Martusewicz-Boros, Adam J Białas, Katarzyna Lewandowska
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and debilitating lung disease with a median survival time of 3-5 years. For now, pirfenidone (PIR) and nintedanib (NTB) are the only drugs that can slow down the disease's progression. In Poland, these drugs, although registered for legal use, had not been reimbursed for IPF patients until the end of the year 2016. Aim of the study was to assess what was common practice in terms of diagnosis and treatment in the period before antifibrotic drugs became available for IPF patients in Poland...
2017: Advances in Respiratory Medicine
https://www.readbyqxmd.com/read/28636088/multicompartment-drug-release-system-for-dynamic-modulation-of-tissue-responses
#8
Aaron H Morris, Rajwant S Mahal, Jillian Udell, Michelle Wu, Themis R Kyriakides
Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure...
June 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28629920/pulmonary-hypertension-in-parenchymal-lung-diseases-any-future-for-new-therapies
#9
REVIEW
Sergio Harari, Davide Elia, Marc Humbert
Pulmonary hypertension (PH) due to chronic lung diseases is associated with a poor prognosis, regardless of the underlying respiratory condition. Updated PH guidelines recommend optimal treatment of the underlying lung disease, including long-term oxygen therapy, in patients with chronic hypoxaemia despite the lack of randomized controlled clinical trials supporting this statement. So far, randomized controlled trials on drugs approved for pulmonary arterial hypertension (PAH) have yielded discouraging results in both interstitial lung diseases (ILD) and chronic obstructive pulmonary diseases (COPD) with PH...
June 16, 2017: Chest
https://www.readbyqxmd.com/read/28622199/antifibrotic-drugs-as-treatment-of-nonidiopathic-pulmonary-fibrosis-interstitial-pneumonias-the-time-is-now
#10
Michael Kreuter, Julia Wälscher, Jürgen Behr
PURPOSE OF REVIEW: Therapeutic advances in the management of idiopathic pulmonary fibrosis (IPF) has led to improved outcomes with the use of the antifibrotic agents pirfenidone and nintedanib, with a number of randomized studies demonstrating benefits in slowing disease progression in IPF. However, treatment of other fibrosing interstitial lung diseases (ILD) remains challenging. RECENT FINDINGS: Observational and uncontrolled studies investigating pirfenidone and nintedanib in non-IPF ILDs suggest potential benefits, although the data is weak...
September 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28609115/molecular-targets-of-dietary-phytochemicals-for-possible-prevention-and-therapy-of-uterine-fibroids-focus-on-fibrosis
#11
Md Soriful Islam, Most Mauluda Akhtar, James H Segars, Mario Castellucci, Pasquapina Ciarmela
Uterine fibroids (myomas or leiomyomas) are common benign tumors of reproductive aged women. Fibroids are clinically apparent in 20-50% of women, and cause abnormal uterine bleeding, abdominal pain and discomfort, pregnancy complications and infertility. Unfortunately, limited numbers of medical treatment are available but no effective preventive strategies exist. Moreover, the benefits of medical treatments are tempered by lack of efficacy or serious adverse side effects. Fibrosis has recently been recognized as a key pathological event in leiomyoma development and growth...
November 22, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28598197/hypersensitivity-pneumonitis-perspectives-in-diagnosis-and-management
#12
Martina Vasakova, Ferran Morell, Simon Walsh, Kevin Leslie, Ganesh Raghu
Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease caused by recurrent exposure to one or more offending inducers in genetically susceptible individuals. It mimics other acute and chronic pulmonary diseases and is often misdiagnosed as idiopathic pulmonary fibrosis (IPF) or another idiopathic interstitial pneumonia if the history of exposure to the inducer is not elicited. We propose a new classification of HP based not only on clinical data but also radiologic and histopathologic findings which might have potential to serve as predictors of disease behaviour and therefore guide management...
June 9, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28576410/phenylpyrrolidine-structural-mimics-of-pirfenidone-lacking-antifibrotic-activity-a-new-tool-for-mechanism-of-action-studies
#13
Andrew J Haak, Megan A Girtman, Mohamed F Ali, Eva M Carmona, Andrew H Limper, Daniel J Tschumperlin
Pirfenidone recently received FDA approval as one of the first two drugs designed to treat idiopathic pulmonary fibrosis. While the clinical data continues to support the efficacy of pirfenidone, the specific molecular mechanism of action of this drug has not been fully defined. From a chemical perspective the comparatively simple and lipophilic structure of pirfenidone combined with its administration at high doses, both experimentally and clinically, complicates some of the basic tenants of drug action and drug design...
May 30, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28575896/pirfenidone-and-nintedanib-for-treatment-of-idiopathic-pulmonary-fibrosis
#14
REVIEW
Gayathri Sathiyamoorthy, Sameep Sehgal, Rendell W Ashton
Idiopathic pulmonary fibrosis is one of the most common entities of the family of disorders known as the interstitial lung diseases. It is a chronic, progressive, and often-fatal disease with a median survival time of 3 to 5 years. In 2014 the US Food and Drug Administration approved pirfenidone and nintedanib, two antifibrotic agents for the treatment of idiopathic pulmonary fibrosis. Because these are the only drugs approved that can alter the course of this rare but fatal disease, this article reviews the major studies that led to the approval of these drugs and examines the indications for treatment and the expected outcomes of therapy...
June 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28562527/successful-treatment-of-infliximab-in-a-patient-with-scleroderma-a-case-report
#15
Ting Li, Yaoyang Liu, Huji Xu
RATIONALE: Systemic Scleroderma (SSc) is a rare connective tissue disease clinically characterized by cutaneous sclerosis and variable systemic involvement. No drug is currently available to effectively reverse the fibrotic process in SSc. Previous reports have suggested that the tumor necrosis factor (TNF) antagonists could be useful for the treatment of fibrotic disorders. However, TNFα has long been considered as an antifibrotic cytokine. Whether TNF antagonist is effective for SSc patients needs to be tested...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28559525/reactivation-pulmonary-tuberculosis-in-two-patients-treated-with-pirfenidone
#16
Mohammad Khan, Majed Alghamdi, Hamdan Al-Jahdali
We report two cases of patients with biopsy-proven idiopathic pulmonary fibrosis (IPF) who were treated with new antifibrotic agent for pirfenidone for more than 12 months. Both cases developed cavitary pulmonary tuberculosis (TB) proven by positive sputum TB culture. Both cases were treated with standard anti-TB drugs for 9 months and had complete clinical and radiological resolution. To our knowledge, these are the first reported human cases of patients with IPF who have been on pirfenidone and developed cavitary pulmonary TB...
April 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28558396/-german-guideline-for-idiopathic-pulmonary-fibrosis-update-on-pharmacological-therapies-2017
#17
Jürgen Behr, Andreas Günther, Francesco Bonella, Klaus Geißler, Dirk Koschel, Michael Kreuter, Antje Prasse, Nicolas Schönfeld, Helmut Sitter, Joachim Müller-Quernheim, Ulrich Costabel
Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a median survival of 2 - 4 years after diagnosis. Since the publication of the German IPF guideline in 2013 new treatment trials have been published, necessitating an update of the pharmacological therapy of IPF. Different from the previous guideline, the GRADE system was discarded and replaced by the Oxford evidence classification system which allows a more differentiated judgement. The following pharmacological therapies were rated not suitable for the treatment of IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone, azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan...
July 2017: Pneumologie
https://www.readbyqxmd.com/read/28546962/recent-advances-of-curcumin-in-the-prevention-and-treatment-of-renal-fibrosis
#18
REVIEW
Xuejiao Sun, Yi Liu, Cheng Li, Xiting Wang, Ruyuan Zhu, Chenyue Liu, Haixia Liu, Lili Wang, Rufeng Ma, Min Fu, Dongwei Zhang, Yu Li
Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one(B06)) in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28496142/src-homology-protein-tyrosine-phosphatase-1-agonist-sc-43-reduces-liver-fibrosis
#19
Tung-Hung Su, Chung-Wai Shiau, Ping Jao, Nian-Jie Yang, Wei-Tien Tai, Chun-Jen Liu, Tai-Chung Tseng, Hung-Chih Yang, Chen-Hua Liu, Kai-Wen Huang, Ting-Chen Hu, Yu-Jen Huang, Yao-Ming Wu, Li-Ju Chen, Pei-Jer Chen, Ding-Shinn Chen, Kuen-Feng Chen, Jia-Horng Kao
This study aimed to investigate the role of src-homology protein tyrosine phosphatase-1 (SHP-1)-signal transducer and activator of transcription 3 (STAT3) pathway in liver fibrogenesis and the anti-fibrotic effect of SHP-1 agonist. The antifibrotic activity of SC-43, a sorafenib derivative with an enhanced SHP-1 activity, was evaluated in two fibrosis mouse models by carbon tetrachloride induction and bile duct ligation. Rat, human, and primary mouse hepatic stellate cells (HSCs) were used for mechanistic investigations...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28484954/repurposing-pentoxifylline-for-the-treatment-of-fibrosis-an-overview
#20
REVIEW
Wei Xiong Wen, Siang Yin Lee, Rafaella Siang, Rhun Yian Koh
Fibrosis is a potentially debilitating disease with high morbidity rates. It is estimated that half of all deaths that occur in the USA are attributed to fibrotic disorders. Fibrotic disorders are characterized primarily by disruption in the extracellular matrix deposition and breakdown equilibrium, leading to the accumulation of excessive amounts of extracellular matrix. Given the potentially high prevalence of fibrosis and the paucity of agents currently available for the treatment of this disease, there is an urgent need for the identification of drugs that can be utilized to treat the disease...
May 8, 2017: Advances in Therapy
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