Search results for "FIBROSIS"

SiRNA-mediated in vivo gene knockdown by acid-degradable cationic nanohydrogel particles

2017

Cationic nanohydrogel particles have become an attractive tool for systemic siRNA delivery, but improvement of their in vivo tolerance is desirable, especially to prevent potential long term side effects by tissue and cellular accumulation. Here, we designed novel ketal cross-linked cationic nanohydrogel particles that were assessed for reduced tissue accumulation and robust siRNA delivery in vitro and in vivo. An oligo-amine cross-linker equipped with a ketal moiety in its core was synthesized and applied to nanohydrogel cross-linking of self-assembled reactive ester block copolymers in DMSO. The resulting acid-sensitive cationic nanoparticles spontaneously disassembled over time in acidic…

Reply: Fibrosis in liver as a predictive marker for hepatitis C virus therapy

2010

P80Cannabinoid receptor CB2 prevents development of heart failure in a murine model of pressure overload

2014

Purpose: Cardiac adaptation to pressure overload is associated with inflammatory reaction, which untreated leads to myocardial fibrosis and heart failure. We have recently demonstrated that endogenous cannabinoids and the cannabinoid receptor 2 (CB2) are activated and associated with persistent inflammation in hypertrophic myocardium of patients with aortic valve stenosis. Therefore, we investigated the role of the CB2 in a mouse model of pressure overload. Methods: Transverse aortic constriction was performed in CB2-/--mice and their wildtype littermates (CB2+/+; n=8-12/group). Taqman® RT-qPCR analysis was performed after 3 and 7 days. After M-mode echocardiography and Millar® pressure-vol…

PWE-140 Comparison Of 4 Serum Markers Panels of Fibrosis in Chc: Variants of the Hyaluronic Acid (HA) Assay Significantly Affect Their Diagnostic Per…

2013

Introduction The detection of advancing fibrosis in patients with CHC and prior treatment failure is important for ascertaining prognosis. HA has been used alone and as a constituent component of fibrosis marker panels. The aim of this study was to compare the performance of 4 marker panels in the detection of moderate-to-severe fibrosis (Metavir F2–4) and to assess the influence on diagnostic performance of using 2 different validated assays for HA. Methods 80 patients with CHC, all non-responders or relapsers to IFN-based treatment, were included in this study. Sera obtained within 6 months of liver biopsy were used to measure 4 biomarker panels incorporating HA (ELF, Fibrospect-II, Hepas…

Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo.

2009

Abstract Background and purpose HMG-CoA-reductase inhibitors (statins) are widely used lipid-lowering drugs. Moreover, they have pleiotropic effects on cellular stress responses, proliferation and apoptosis in vitro . Here, we investigated whether lovastatin attenuates acute and subchronic ionizing radiation-induced normal tissue toxicity in vivo . Materials and methods Four hours to 24h after total body irradiation (6Gy) of Balb/c mice, acute pro-inflammatory and pro-fibrotic responses were analyzed. To comprise subchronic radiation toxicity, mice were irradiated twice with 2.5Gy and analyses were performed 3weeks after the first radiation treatment. Molecular markers of inflammation and f…

Bortezomib Partially Improves Laminin α2 Chain–Deficient Muscular Dystrophy

2014

Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measu…

An overview on chemical structures as ΔF508-CFTR correctors

2019

Deletion of phenylalanine at position 508 (F508del) in the CFTR protein, is the most common mutation causing cystic fibrosis (CF). F508del causes misfolding and rapid degradation of CFTR protein a defect that can be targeted with pharmacological agents termed “correctors”. Correctors belong to various chemical classes but are generally small molecules based on nitrogen sulfur or oxygen heterocycles. The mechanism of action of correctors is generally unknown but there is experimental evidence that some of them can directly act on mutant CFTR improving folding and stability. Here we overview the characteristics of the various F508del correctors described so far to obtain indications on key ch…

Reply to ‘Genetic and clinical data reinforce the role of GAS6 and TAM receptors in liver fibrosis’

2016

Polyanion–tobramycin nanocomplexes into functional microparticles for the treatment of Pseudomonas aeruginosa infections in cystic fibrosis

2016

Aim: Efficacy of antibiotics in cystic fibrosis (CF) is compromised by the poor penetration through mucus barrier. This work proposes a new ‘nano-into-micro’ approach, used to obtain a combinatorial effect: achieve a sustained delivery of tobramycin and overcome mucus barrier. Methods: Mannitol microparticles (MPs) were loaded with a tobramycin polymeric nanocomplex and characterized in presence of CF artificial mucus. Results & discussion: MPs are able to alter the rheological properties of CF artificial mucus, enhancing drug penetration into it and allowing a prolonged drug release. MPs resulted to be effective in Pseudomonas aeruginosa infections if compared with free tobramycin. Co…

Nanometric ion pair complexes of tobramycin forming microparticles for the treatment of Pseudomonas aeruginosa infections in cystic fibrosis

2019

Abstract Sustained pulmonary delivery of tobramycin from microparticles composed of drug/polymer nanocomplexes offers several advantages against traditional delivery methods. Namely, in patients with cystic fibrosis, microparticle delivery can protect the tobramycin being delivered from strong mucoadhesive interactions, thus avoiding effects on its diffusion toward the infection site. Polymeric ion-pair complexes were obtained starting from two synthetic polyanions, through impregnation of their solid dissociated forms with tobramycin in aqueous solution. The structure of these polymeric systems was characterized, and their activities were examined against various biofilm-forming Pseudomona…