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antifibrotic drug

Vu Huy Luong, Takenao Chino, Noritaka Oyama, Takashi Matsushita, Yoko Sasaki, Dai Ogura, Shin-Ichiro Niwa, Tanima Biswas, Akiyuki Hamasaki, Mikako Fujita, Yoshinari Okamoto, Masami Otsuka, Hironobu Ihn, Minoru Hasegawa
BACKGROUND: Transforming growth factor-β (TGF-β)/Smad signaling is well known to play a critical role in the pathogenesis of systemic sclerosis (SSc). We previously developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect. The purpose of the present study was to clarify the effects of this drug in human skin fibroblasts and in a preclinical model of SSc. METHODS: The effects of HPH-15 on expression of extracellular matrix components and TGF-β signaling in human dermal fibroblasts were analyzed...
March 15, 2018: Arthritis Research & Therapy
Jean-Eric Tarride, Robert B Hopkins, Natasha Burke, Jason R Guertin, Daria O'Reilly, Charlene D Fell, Genevieve Dion, Martin Kolb
Background: Idiopathic pulmonary fibrosis (IPF), although rare, is a severe and costly disease. Objective: To estimate the clinical and economic burden of IPF over multiple years before and after diagnosis using comprehensive administrative databases for the province of Quebec, Canada. Methods: Several administrative databases from Quebec, providing information on hospital care, community care, and pharmaceuticals, were linked over a 5-year period ending March 31, 2011, which was before approval of antifibrotic drugs in Canada...
2018: ClinicoEconomics and Outcomes Research: CEOR
Xi Li, Qianwen Jin, Qunyan Yao, Beili Xu, Lixin Li, Shuncai Zhang, Chuantao Tu
At present, there are no effective antifibrotic drugs for patients with chronic liver disease; hence, the development of antifibrotic therapies is urgently needed. Here, we performed an experimental and translational study to investigate the potential and underlying mechanism of quercetin treatment in liver fibrosis, mainly focusing on the impact of quercetin on macrophages activation and polarization. BALB/c mice were induced liver fibrosis by carbon tetrachloride (CCl4 ) for 8 weeks and concomitantly treated with quercetin (50 mg/kg) or vehicle by daily gavage...
2018: Frontiers in Pharmacology
Caroline L Hall, Adrienne R Wells, Kai P Leung
Pirfenidone (PFD) is a synthetic small molecule inhibitor with demonstrated anti-inflammatory and antifibrotic properties in vitro and in vivo. The exact mechanism(s) of PFD action remain unclear, due in part to the broad effects of this drug on the complex processes involved in inflammation and fibrosis. While PFD is FDA-approved for the treatment of idiopathic pulmonary fibrosis, the efficacy of this compound for the treatment of dermal fibrosis has not yet been fully characterized. Dermal fibrosis is the pathological formation of excess fibrous connective tissue of the skin, usually the result of traumatic cutaneous injury...
March 1, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Bjørn Stæhr Madsen, Jonel Trebicka, Maja Thiele, Mads Israelsen, Manimozhiyan Arumugan, Troels Havelund, Aleksander Krag
BACKGROUND: Alcoholic liver disease is the leading cause of cirrhosis worldwide. Due to an increase in alcohol overuse, alcoholic liver disease has become an increased burden on health care systems. Abstinence from alcohol remains the cornerstone of alcoholic liver disease treatment; however, this approach is hampered by frequent relapse and lack of specific therapy for treating advanced cases of liver disease. In the present study, we hypothesized that gut microbiota drive the development of liver fibrosis and that modulation of gut microbiota with the gut-selective, nonabsorbable antibiotic rifaximin attenuates alcoholic liver fibrosis...
February 26, 2018: Trials
Jennifer Y Chen, Yanjie Ren, Peng Yan, Morgan E Belina, Raymond T Chung, Adeel A Butt
Recent preclinical studies have suggested an antifibrotic role for tricyclic antidepressants. Using the Electronically Retrieved Cohort of HCV Infected Veterans, we aimed to evaluate the impact of TCA use on fibrosis progression and development of hepatocellular carcinoma (HCC) among HCV-infected persons. Subjects were categorized according to use of tricyclic antidepressants, selective serotonin reuptake inhibitors, or no antidepressants. tricyclic antidepressants or selective serotonin uptake inhibitors use was defined according to cumulative defined daily dose, and categories were mutually exclusive...
February 25, 2018: Journal of Viral Hepatitis
Michelle Vega-Olivo, Gerard J Criner
Idiopathic pulmonary fibrosis (IPF) is a rare disease characterized by decline in lung function, dyspnea, and cough. The clinical course of IPF is variable and unpredictable. Early referral to specialists is key to ensure timely and accurate diagnosis. Two antifibrotic drugs (nintedanib and pirfenidone) have been approved for the treatment of IPF.
February 19, 2018: Nurse Practitioner
Nikolaos A Afratis, Moises Selman, Annie Pardo, Irit Sagi
Fibrosis is the extensive accumulation and buildup of extracellular matrix components, especially fibrillar collagens, during wound healing in response to tissue injury. During all individual stages of fibrosis ECM proteases, mainly matrix metalloproteinases, have diverse roles. The functional role of MMPs and their endogenous inhibitors are differentiated among their family members, and according to the different stages of fibrosis. MMPs levels are elevated in several inflammatory and non-inflammatory fibrotic tissues contributing to the development, progression or resolution of the disease, whereas in other tissues their expression levels can be diminished or be stable to the baseline...
February 8, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Caressa Lietman, Brian Wu, Sarah Lechner, Andrew Shinar, Madhur Sehgal, Evgeny Rossomacha, Poulami Datta, Anirudh Sharma, Rajiv Gandhi, Mohit Kapoor, Pampee P Young
Osteoarthritis (OA) is a degenerative joint disease involving both cartilage and synovium. The canonical Wnt/β-catenin pathway, which is activated in OA, is emerging as an important regulator of tissue repair and fibrosis. This study seeks to examine Wnt pathway effects on synovial fibroblasts and articular chondrocytes as well as the therapeutic effects of Wnt inhibition on OA disease severity. Mice underwent destabilization of the medial meniscus surgery and were treated by intra-articular injection with XAV-939, a small-molecule inhibitor of Wnt/β-catenin signaling...
February 8, 2018: JCI Insight
Tobias Kuehl, David Lagares
Organs and tissues in mammals can undergo self-repair following injury. However, chronic or severe tissue injury leads to the development of dense scar tissue or fibrosis at the expense of regeneration. The identification of novel therapeutic strategies aiming at reversing fibrosis is therefore a major clinical unmet need in regenerative medicine. Persistent activation of scar-forming myofibroblasts distinguishes non-resolving pathological fibrosis from self-limited physiological wound healing. Thus, therapeutic strategies selectively inducing myofibroblast apoptosis could prevent progression and potentially reverse established fibrosis in fibrotic diseases...
January 30, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Nipun Verma, Pramod Kumar, Suvradeep Mitra, Sunil Taneja, Sahajal Dhooria, Ashim Das, Ajay Duseja, Radha Krishan Dhiman, Yogesh Chawla
Idiosyncratic drug-induced liver injury (DILI) is ranked among the top most common etiologies of acute liver failure (ALF). It carries poor transplant-free survival. Pirfenidone is an anti-inflammatory and antifibrotic drug that is commonly used for the treatment of idiopathic pulmonary fibrosis (IPF). Hepatotoxicity due to pirfenidone is rare and generally manifests as a mild rise in serum aminotransferases. In this mini-review, we report an unusual case of idiosyncratic DILI due to pirfenidone presenting as ALF, with emphasis on the definition, classification, diagnostic criteria, histopathology, molecular markers, and treatment options for DILI and related ALF...
February 2018: Hepatology communications
Guillaume Wettstein, Jean-Michel Luccarini, Laurence Poekes, Patrick Faye, Francine Kupkowski, Vanessa Adarbes, Evelyne Defrêne, Céline Estivalet, Xavier Gawronski, Ingrid Jantzen, Alain Philippot, Julien Tessier, Pascale Tuyaa-Boustugue, Fiona Oakley, Derek A Mann, Isabelle Leclercq, Sven Francque, Irena Konstantinova, Pierre Broqua, Jean-Louis Junien
IVA337 is a pan-peroxisome proliferator-activated receptor (PPAR) agonist with moderate and well-balanced activity on the three PPAR isoforms (α, γ, δ). PPARs are regulators of lipid metabolism, inflammation, insulin resistance, and fibrogenesis. Different single or dual PPAR agonists have been investigated for their therapeutic potential in nonalcoholic steatohepatitis (NASH), a chronic liver condition in which steatosis coexists with necroinflammation, potentially leading to liver fibrosis and cirrhosis...
August 2017: Hepatology communications
Argyrios Tzouvelekis, Theodoros Karampitsakos, Maria Kontou, Andreas Granitsas, Ioanna Malliou, Aris Anagnostopoulos, Paschalis Ntolios, Vasilios Tzilas, Evangelos Bouros, Paschalis Steiropoulos, Serafeim Chrysikos, Katerina Dimakou, Nikolaos Koulouris, Demosthenes Bouros
BACKGROUND: Nintedanib represents an antifibrotic compound able to slow down disease progression of patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To investigate the safety and efficacy of nintedanib in patients with IPF in a real-life setting. METHODS: This was a multicentre, retrospective, observational, real-life study for patients with IPF receiving nintedanib between October 2014 and October 2016. RESULTS: We identified 94 patients with IPF receiving nintedanib (72 males, mean age±SD: 73...
January 20, 2018: Pulmonary Pharmacology & Therapeutics
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...
January 16, 2018: Pneumologie
Maysa Mohamed Kamel Sobhy, Soheir Sayed Mahmoud, Shaimaa Helmy El-Sayed, Enas Mohamed Ali Rizk, Amira Raafat, Mohamed Sherif Ismail Negm
Schistosomiasis mansoni is considered one of the most common fibrotic diseases resulting from inflammation and deposition of fibrous tissue around parasitic eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge administration of it in endemic areas and its incompetence towards the immature stages have raised serious alarms against the development of drug resistance. Few drugs are directed to reverse schistosomal liver fibrosis, particularly at the chronic and advanced stages of the disease...
January 10, 2018: Experimental Parasitology
Bart de Brouwer, Ianthe Piscaer, Jan H von der Thusen, Jan C Grutters, Roger Eg Schutgens, Emiel Fm Wouters, Rob Janssen
There is an ongoing need for additional interventions in idiopathic pulmonary fibrosis (IPF) as antifibrotic drugs currently available only inhibit and do not stall disease progression. Vitamin K is a co-factor for the activation of coagulation factors. However, it is also required to activate proteins with functions outside of the coagulation cascade, such as matrix Gla protein (MGP), a defender against soft tissue calcification. Vitamin K antagonists are anticoagulants that are, for unknown reasons, associated with increased mortality in IPF...
January 5, 2018: Expert Review of Respiratory Medicine
Madalina V Nastase, Jinyang Zeng-Brouwers, Malgorzata Wygrecka, Liliana Schaefer
Renal fibrosis is the common outcome of many chronic kidney diseases (CKD) independent of the underlying etiology. Despite a host of promising experimental data, currently available strategies only ameliorate or delay the progression of CKD but do not reverse fibrosis. One of the major impediments of translating novel antifibrotic strategies from bench to bedside is due to the intricacies of the drug delivery process. In this review, we briefly describe mechanisms of renal fibrosis and methods of drug transfer into the kidney...
December 26, 2017: Advanced Drug Delivery Reviews
Yoshio Sumida, Masashi Yoneda
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy. The efficacy of vitamin E and pioglitazone has been established in nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD. GLP-1RA and SGLT2 inhibitors, which are currently approved for use in diabetes, have shown early efficacy in NASH, and also have beneficial cardiovascular or renal effects. Innovative NASH therapies include four main pathways. The first approach is targeting hepatic fat accumulation...
December 16, 2017: Journal of Gastroenterology
Argyrios Tzouvelekis, Theodoros Karampitsakos, Paschalis Ntolios, Vasilios Tzilas, Evangelos Bouros, Evangelos Markozannes, Ioanna Malliou, Aris Anagnostopoulos, Andreas Granitsas, Paschalis Steiropoulos, Katerina Dimakou, Serafeim Chrysikos, Nikolaos Koulouris, Demosthenes Bouros
Background: Pirfenidone is an antifibrotic compound able to slow down disease progression in patients with idiopathic pulmonary fibrosis (IPF). Objective: To investigate the safety and efficacy of pirfenidone in patients with IPF in a real-life setting. Methods: This was a multicenter, retrospective, real-life, observational study for patients with IPF receiving pirfenidone. Results: We identified 92 patients with IPF receiving pirfenidone...
2017: Frontiers in Medicine
Chiara Scelfo, Antonella Caminati, Sergio Harari
Idiopathic pulmonary fibrosis (IPF) is a rare pulmonary disease with a poor prognosis and severe impact on quality of life. Early diagnosis is still challenging and important delays are registered before final diagnosis can be reached. Available tools fail to predict the variable course of the disease and to evaluate response to antifibrotic drugs. Despite the recent approval of pirfenidone and nintedanib, significant challenges remain to improve prognosis and quality of life. It is hoped that the new insights gained in pathobiology in the last few years will lead to further advances in the diagnosis and management of IPF...
2017: F1000Research
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