Search results for "Fibrosis"

Furocoumarins as multi-target agents in the treatment of cystic fibrosis.

2019

Multi-target molecular entities, offer a path to progress both in understanding causes of disease and in defining effective small molecule treatments. Coumarin and its derivatives belong to an important group of natural compounds with diverse biological properties. They are found in vegetables and plants for which literature reports thousands of publications for the great variety of biological applications among which the photoprotective effects, thus being considered multi-targeting agents. Their furan condensed analogues constitute the family of furocoumarins, less represented in the literature, endowed with photosensitizing properties and often used for the treatment of skin diseases suc…

Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives.

2015

Abstract Premature stop codons are the result of nonsense mutations occurring within the coding sequence of a gene. These mutations lead to the synthesis of a truncated protein and are responsible for several genetic diseases. A potential pharmacological approach to treat these diseases is to promote the translational readthrough of premature stop codons by small molecules aiming to restore the full-length protein. The compound PTC124 (Ataluren) was reported to promote the readthrough of the premature UGA stop codon, although its activity was questioned. The potential interaction of PTC124 with mutated mRNA was recently suggested by molecular dynamics (MD) studies highlighting the importanc…

Inhalable nano into micro dry powders for ivacaftor delivery: The role of mannitol and cysteamine as mucus-active agents.

2020

In this paper the innovative approach of Nano into micro (NiM9 was developed to produce Nanoparticles loaded Ivacaftor to incorporate into mannitol or mannitol/cysteamine micromatrices for drug pulmonary administration in CF. Nanoparticles composed by a mixture of two polyhydrohydroxyethtylaspartamide copolymers containing a loading of Ivacaftor of 15.5 % w/w were produced. These Nanoparticles were incorporated into microparticles to obtain NiM that were characterized in terms of size and size distribution, interaction with CF-AM by rheological and turbidimetric studies as well as by aerodynamic diameter measurements. Finally the activity of Ivacaftor into these NiM was evaluated by in vitr…

HETEROCYCLIC COMPOUNDS AND MEDICAL USE THEREOF

2019

The present invention relates to heterocyclic nitrogen compounds, use thereof as a medicament and pharmaceutical compositions thereof. Furthermore, the invention provides combinations of compounds of general formula (I) with therapeutic agents, such as correctors, potentiators and amplifiers of dysfunctional proteins.

Identification of a new molecule with readthrough activity to rescue CFTR protein function

In Cystic fibrosis (CF) disease nonsense mutations in the CFTR gene cause absence of the CFTR protein expression and a more severe form of the disease. About 10% of patient affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by translational readthrough inducing drugs such as Ataluren. In this context we aimed to compare the 1,2,4-oxadiazole core of Ataluren with a slightly different scaffold, the 1,3,4oxadiazole core. By a validated protocol consisting of computational screening, synthesis and biological tests we identified, a new small molecule with 1,3,4-oxadiazole core (2a/NV2445…

Valutazione quantitativa tridimensionale del parenchima polmonare affetto da fibrosi cistica : risultati preliminari

2007

Purpose. The aim of this study was to assess the feasibility of three-dimensional (3D) reconstructions and quantitative analysis of the volume of each component of the lung with cystic fibrosis (CF). Materials and methods. Twenty-two patients with CF (mean age 17±8 yeas) were included in the study. The patients underwent an unenhanced single-slice spiral computed tomography (CT) chest scan with the following parameters: collimation 3 mm, table feed 6 mm×rot-1, reconstruction interval 1 mm, soft tissue reconstruction kernel. Four image data sets were obtained: native axial slices, cine-mode display, virtual bronchographic volumerendered images with algorithm for tissue transition display and…

[Anti-Pseudomonas aeruginosa antibodies and lung disease in cystic fibrosis]

2003

The aim of our study was to diagnose and to control three aspects of the evolution of lung disease in CF: the absence of infection, the intermittent colonization and chronic infection by Pseudomonas aeruginosa. Therefore a study of anti-pseudomonas antibodies (Ab) (anti-protease, anti-elastin and antihexo-toxin A) for diagnosis and follow-up of CF patients was considered. Moreover, we related the presence of Ab to the sputum culture, to FEV1, to patient age and to genotype. Tbe Ab were dosed in 121 patients by quantitative ELISA method. Values < 1: 500 were considered negative, values> 1: 500 and < 1:1250 borderline, and > 1:1250 positive. 16.5% of patients did not have Ab, 17% …

Cellular cytotoxicity against autologous hepatocytes in alcoholic liver disease.

2008

We tested lymphocyte cytotoxicity against autologous hepatocytes in patients with alcoholic liver disease (ALD). The following cytotoxicity values were found (mean +/- SEM): alcohol-induced steatosis with or without fibrosis 16.5 +/- 2% (n = 29), alcoholic cirrhosis 28 +/- 4% (n = 13), controls with normal liver histology or minimal changes 6 +/- 2% (n = 11). The differences were statistically significant (both forms of ALD versus controls p less than 0.005). T-cell as well as non-T-cell-enriched lymphocyte fractions showed increased cytotoxicity in ALD. We did not observe a correlation between cellular cytotoxicity and the degree of biochemical or histological alterations within the groups…

Impaired Transporter Associated with Antigen Processing (TAP) Function Attributable to a Single Amino Acid Alteration in the Peptide TAP Subunit TAP1

2003

Abstract The heterodimeric peptide transporter TAP belongs to the ABC transporter family. Sequence comparisons with the P-glycoprotein and cystic fibrosis transmembrane conductance regulator and the functional properties of selective amino acids in these ABC transporters postulated that the glutamic acid at position 263 and the phenylalanine at position 265 of the TAP1 subunit could affect peptide transporter function. To define the role of both amino acids, TAP1 mutants containing a deletion or a substitution to alanine at position 263 or 265 were generated and stably expressed in murine and human TAP1−/− cells. The different TAP1 mutants were characterized in terms of expression and funct…

Comparison of Physical Activity and Sedentary Behaviour between Schoolchildren with Cystic Fibrosis and Healthy Controls: A Gender Analysis

2021

The purpose of this study was to examine differences in sports participation and the levels of physical activity (PA) and sedentary behaviour (SB) between schoolchildren with cystic fibrosis (CF) and a healthy control group (CG) taking into account the gender variable. PA and SB were measured with an accelerometer for 7 consecutive days in 44 children (24 girls