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https://www.readbyqxmd.com/read/28932114/spermidine-mediated-poly-lactic-co-glycolic-acid-nanoparticles-containing-fluorofenidone-for-the-treatment-of-idiopathic-pulmonary-fibrosis
#1
Jing Tang, Jianming Li, Guo Li, Haitao Zhang, Ling Wang, Dai Li, Jinsong Ding
Idiopathic pulmonary fibrosis is a progressive, fatal lung disease with poor survival. The advances made in deciphering this disease have led to the approval of different antifibrotic molecules, such as pirfenidone and nintedanib. An increasing number of studies with particles (liposomes, nanoparticles [NPs], microspheres, nanopolymersomes, and nanoliposomes) modified with different functional groups have demonstrated improvement in lung-targeted drug delivery. In the present study, we prepared, characterized, and evaluated spermidine (Spd)-modified poly(lactic-co-glycolic acid) (PLGA) NPs as carriers for fluorofenidone (AKF) to improve the antifibrotic efficacy of this drug in the lung...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28915874/unmet-needs-in-the-treatment-of-idiopathic-pulmonary-fibrosis-insights-from-patient-chart-review-in-five-european-countries
#2
Toby M Maher, Maria Molina-Molina, Anne-Marie Russell, Francesco Bonella, Stéphane Jouneau, Elena Ripamonti, Judit Axmann, Carlo Vancheri
BACKGROUND: Two antifibrotic drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF). In this analysis, treatment patterns of European patients with IPF were investigated to understand antifibrotic prescribing and identify unmet needs in IPF treatment practice. METHODS: Between February and March 2016, respiratory physicians from France, Germany, Italy, Spain, and the UK participated in an online questionnaire designed to collect information on IPF treatment patterns in patients under their care...
September 15, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28912805/antifibrotic-effect-of-lactulose-on-a-methotrexate-induced-liver-injury-model
#3
Banu Taskin, Mümin Alper Erdoğan, Gürkan Yiğittürk, Damla Günenç, Oytun Erbaş
The most severe side effect of prolonged MTX treatment is hepatotoxicity. The aim of this study is to investigate the effect of lactulose treatment on MTX-induced hepatotoxicity in a rat model. Twenty-four male rats were included in the study. Sixteen rats were given a single dose of 20 mg/kg MTX to induce liver injury. Eight rats were given no drugs. 16 MTX-given rats were divided into two equal groups. Group 1 subjects were given lactulose 5 g/kg/day, and group 2 subjects were given saline 1 ml/kg/day for 10 days...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28911022/hypertensive-cardiovascular-risk-pulsatile-hemodynamics-gender-and-therapeutic-implications
#4
Michel E Safar, Harold Smulyan
PURPOSE: In recent years, the predictive value of 2 pulsatile parameters has been extensively studied in hypertension: aortic stiffness and pulse pressure (PP) amplification. Aortic stiffness is an index of aortic rigidity and PP-amplification is the ratio between central and brachial PP, an indirect evaluation of wave reflections. Both are safe, independent, noninvasive predictors of overall and cardiovascular risk. Our purpose is to determine the validity of these parameters in 2 different circumstances: gender and therapeutic implications...
October 1, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28898237/nintedanib-selectively-inhibits-the-activation-and-tumour-promoting-effects-of-fibroblasts-from-lung-adenocarcinoma-patients
#5
M Gabasa, R Ikemori, F Hilberg, N Reguart, J Alcaraz
BACKGROUND: Nintedanib is a clinically approved multikinase receptor inhibitor to treat non-small cell lung cancer with adenocarcinoma (ADC) histology in combination with docetaxel, based on the clinical benefits reported on ADC but not on squamous cell carcinoma (SCC), which are the two most common histologic lung cancer subtypes. METHODS: We examined the potential role of tumour-associated fibroblasts (TAFs) in the differential effects of nintedanib in ADC and SCC...
September 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28893365/coffee-consumption-and-prevention-of-cirrhosis-in-support-of-the-caffeine-hypothesis
#6
Jonathan Dranoff
It is widely acknowledged that coffee is the most widely used drug on Earth. While this is true, coffee is also a foodstuff with wide variation, so its use is often directed at satisfying dietary urges. When used as a drug, coffee is almost invariably used as a stimulant rather than to treat or prevent particular diseases. Thus, it has been an exciting revelation in recent years that coffee consumption is inversely related to progression of liver fibrosis to cirrhosis and even hepatocellular carcinoma.As is often the case, epidemiological observations have preceded pathophysiological explanations for this effect...
September 11, 2017: Gene Expression
https://www.readbyqxmd.com/read/28890106/development-of-a-peptide-modified-sirna-nanocomplex-for-hepatic-stellate-cells
#7
Zhen Zhao, Yuanke Li, Akshay Jain, Zhijin Chen, Hao Liu, Wei Jin, Kun Cheng
Insulin-like growth factor 2 receptor (IGF2R) is overexpressed in activated hepatic stellate cells (HSCs) and therefore can be utilized for HSC-specific drug delivery. We recently discovered an IGF2R-specific peptide using a novel biopanning. Here, we adopted biotin-conjugated IGF2R-specific peptide, cholesterol, and vitamin A as the targeting ligands for the neutravidin-based siRNA nanocomplex to deliver PCBP2 siRNA, a potentially antifibrotic agent, to HSCs. Compared to vitamin A and cholesterol, the IGF2R-specific peptide exhibited the highest targeting effect to human LX-2 HSC, rat HSC-T6 cell line, and activated primary rat HSCs...
September 7, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28880053/liver-fibrosis-the-2017-state-of-art
#8
Gian P Caviglia, Chiara Rosso, Sharmila Fagoonee, Giorgio M Saracco, Rinaldo Pellicano
Liver fibrosis is a wound-healing response to a wide spectrum of chronic liver injuries. It is characterized by loss of hepatocytes and alteration in hepatic architecture following an imbalance between extracellular matrix synthesis and degradation. Irrespectively of underlying etiology, fibrosis may progress to cirrhosis and specific pathogenetic mechanisms as well as different disease patterns may be identified according to etiology. Liver biopsy is still considered the gold standard for fibrosis assessment, despite the fact that it is invasive, has poor patient compliance and is not exempt of complications...
September 5, 2017: Panminerva Medica
https://www.readbyqxmd.com/read/28873458/anti-fibrotic-effects-of-valproic-acid-in-experimental-peritoneal-fibrosis
#9
Elerson C Costalonga, Luiza J de Freitas, Deise da S P Aragone, Filipe M O Silva, Irene L Noronha
BACKGROUND: Progressive fibrous thickening of the peritoneal membrane is a complication of long-term peritoneal dialysis (PD). TGF-β/Smad pathway activation, inflammation, and neoangiogenesis play important roles in peritoneal membrane (PM) changes induced by PD. Recently, histone deacetilase inhibitors (HDACi) have shown anti-fibrotic and anti-inflammatory effects in different experimental models. These drugs prevent deacetylation of histones causing a loosen chromatin, which in turn induce the expression of some anti-fibrotic genes...
2017: PloS One
https://www.readbyqxmd.com/read/28871791/real-time-bioimpedance-sensing-of-antifibrotic-drug-action-in-primary-human-cells
#10
Maryam Parviz, Priyanka Toshniwal, Helena Viola, Livia C Hool, P Mark W Fear, Fiona Wood, Katharina Gaus, K Swaminathan Iyer, John Justin Gooding
Fibrotic diseases are among the most serious health issues with severe burdens due to their chronic nature and a large number of patients suffering from the debilitating effects and long-term sequelae. Collagenase treatment is a non-surgical option but has limited results. To date, there is no potent non-invasive solution for fibrosis. Part of the reason for this is the lack of appropriate in vitro live cell screening tools to assess the efficacy of new therapeutical agents. Here, we demonstrate the utility of a cell-based electrochemical impedance biosensor platform to screen the efficacy of potential antifibrotic compounds...
September 5, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28864467/upregulation-of-epac-1-in-hepatic-stellate-cells-by-prostaglandin-e2-in-liver-fibrosis-is-associated-with-reduced-fibrogenesis
#11
Marlies Schippers, Leonie Beljaars, Eduard Post, Sophie Lotersztajn, Catharina Reker-Smit, Bing Han, Pablo A Llancao, Martina Schmidt, Klaas Poelstra
Exchange protein activated by cAMP (Epac-1) is an important signaling mechanism for cAMP-mediated effects but factors that change Epac-1 levels are unknown. Such factors are relevant because it has been postulated that Epac-1 directly affects fibrogenesis. Prostaglandin E2 (PGE2) is a well-known cAMP-activator and we therefore studied the effects of this cyclo-oxygenase product on Epac-1 expression and on fibrogenesis within the liver. Liver fibrosis was induced by 8 weeks CCL4 administration to mice. In the last 2 weeks, mice received vehicle, PGE2, COX-2 inhibitor Niflumic acid (NFA), or PGE2 coupled to cell-specific carriers to hepatocytes, Kupffer cells or hepatic stellate cells (HSC)...
September 1, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28861727/managing-idiopathic-pulmonary-fibrosis-which-drug-for-which-patient
#12
Conal Hayton, Nazia Chaudhuri
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with high mortality. Two novel antifibrotic agents, pirfenidone and nintedanib, have received licences for use in IPF in recent years. Phase III, multinational, randomised control trials have provided evidence that both drugs reduce decline in forced vital capacity (FVC) over time, while further post hoc studies have suggested that both pirfenidone and nintedanib can be efficacious, regardless of age and severity of baseline lung function...
August 31, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28860912/causes-of-unsatisfactory-results-of-the-use-of-mitomycin-c-in-endoscopic-endonasal-dacryocystorhinostomy
#13
E L Atkova, A A Fedorov, A O Root, S D Iartsev, N N Krakhovetsky, V D Yartsev
PURPOSE: To study the antifibrotic effectiveness of mitomycin-C in the tissues of the ostium site after it application for endonasal endoscopic dacryocystorhinostomy. MATERIAL AND METHODS: The study included 45 patients (48 cases) with primary obstruction of the nasolacrimal duct. All patients underwent endoscopic endonasal dacryocystorhinostomy (EEDCR). At the final stage of the operation, a swab with MMC was placed in the region of the formed ostium at a concentration of 0...
July 2017: Saudi Journal of Ophthalmology: Official Journal of the Saudi Ophthalmological Society
https://www.readbyqxmd.com/read/28770223/plumbagin-alleviates-capillarization-of-hepatic-sinusoids-in-vitro-by-downregulating-et-1-vegf-ln-and-type-iv-collagen
#14
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
#15
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%C3%A2-vivo
#16
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
#17
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
#18
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 and, so far, 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...
September 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
#19
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
#20
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
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