Search results for " INFLAMMATION"

Development of polymer-based nanoparticles for Zileuton delivery to the lung : PMeOx and PMeOzi surface chemistry reduces interactions with mucins

2021

In this paper, two amphiphilic graft copolymers were synthesized by grafting polylactic acid (PLA) as hydrophobic chain and poly(2-methyl-2-oxazoline) (PMeOx) or poly(2-methyl-2-oxazine) (PMeOzi) as hydrophilic chain, respectively, to a backbone of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA). These original graft copolymers were used to prepare nanoparticles delivering Zileuton in inhalation therapy. Among various tested methods, direct nanoprecipitation proved to be the best technique to prepare nanoparticles with the smallest dimensions, the narrowest dimensional distribution and a spherical shape. To overcome the size limitations for administration by inhalation, the nano-into-micr…

Systemic inflammation in primary hypercholesterolemia results in platelet and leukocyte activation and their enhanced endothelial adhesiveness

2018

Incretin-Based Therapies Role in COVID-19 Era: Evolving Insights

2020

The current coronavirus disease 2019 (COVID-19) pandemic has led the scientific community to breach new frontiers in the understanding of human physiology and disease pathogenesis. It has been hypothesized that the human dipeptidyl peptidase 4 (DPP4) enzyme receptor may be a functional target for the spike proteins of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Since DPP4-inhibitors are currently used for the treatment of patients with type-2 diabetes (T2DM), there is currently high interest in the possibility that these agents, or incretin-based therapies (IBTs) in general, may be of benefit against the new coronavirus infection. Diabetes is associated with increased COV…

Pro-inflammatory T helper 17 directly harms oligodendrocytes in neuroinflammation.

2021

Significance Multiple sclerosis (MS) is a neuroinflammatory, demyelinating disease that represents one of the most frequent causes of irreversible disability in young adults. Treatment options to halt disability are limited. We discovered that T helper (Th)17 cells in contact with oligodendrocytes produce higher levels of glutamate and induce significantly greater oligodendrocyte damage than their Th2 counterpart. Blockade of CD29, which is linked to glutamate release pathways and expressed in high levels on Th17 cells, preserved human oligodendrocyte processes from Th17-mediated injury. Our data thus provide evidence for the direct and deleterious attack of Th17 cells on the myelin compart…

C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function.

2009

AbstractWe describe a novel localization of C7 as a membrane-bound molecule on endothelial cells (ECs). Data obtained by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis, Northern blot analysis, and mass spectrometry revealed that membrane-associated C7 (mC7) was indistinguishable from soluble C7 and was associated with vimentin on the cell surface. mC7 interacted with the other late complement components to form membrane-bound TCC (mTCC). Unlike the soluble SC5b-9, mTCC failed to stimulate ECs to express adhesion molecules, to secrete IL-8, and to induce albumin leakage through a monolayer of ECs, and more importantly protected ECs from the proinf…

Cellular network in airways inflammation and remodelling

2002

Chronic inflammation and airway remodelling are two key steps in asthma pathophysiology. The development of chronic airway inflammation depends upon the continuous recruitment of inflammatory cells from the bloodstream towards the bronchial mucosa and by their subsequent functional activation. The release of inflammatory mediators by activated cells contributes to the generation of a complex network which involves mobile inflammatory cells and structural cells such as epithelial cells, fibroblasts and myofibroblasts. This network is responsible for the amplification and persistence of the inflammatory process as well as for the development of a peculiar microenvironment which can directly m…

The effect of different periods of argon deaeration on exhaled breath condensate pH.

2011

Exhaled breath condensate (EBC) pH has been considered as a biomarker of airway inflammation in asthma. However, little information is available on the duration of argon deaeration required to achieve a stable pH in EBC samples.To identify differences in EBC pH after argon deaeration for 2, 4, and 8 min.EBC pH was determined in EBC samples from 48 subjects with allergic rhinitis (11 asthmatics) and 14 healthy volunteers without deaeration and after argon deaeration for 2, 4, and 8 min.The mean (95% CI) pH values obtained from samples analyzed after 4 min [7.66 (7.52-7.80)] and 8 min [7.70 (7.55-7.85)] of argon deaeration were significantly less acidic (p.001) than those identified after 2 m…

Hypoxia-induced dysfunction of rat diaphragm

2004

Contains fulltext : 47331.pdf (Publisher’s version ) (Closed access) Oxidants may play a role in hypoxia-induced respiratory muscle dysfunction. In the present study we hypothesized that hypoxia-induced impairment in diaphragm contractility is associated with elevated peroxynitrite generation. In addition, we hypothesized that strenuous contractility of the diaphragm increases peroxynitrite formation. In vitro force-frequency relationship, isotonic fatigability, and nitrotyrosine levels were assessed under hypoxic (Po(2) approximately 6.5 kPa) and hyperoxic (Po(2) approximately 88.2 kPa) control conditions and also in the presence of authentic peroxynitrite (60 min), ebselen (60 min), and t…

Epithelial-mesenchymal communication in the pathogenesis of chronic asthma.

2005

Although Th-2-mediated inflammation is a key therapeutic target in asthma, its relationship to altered structure and functions of the airways is largely unknown. In addition to inflammation, asthma is a disorder involving the airway epithelium that is more vulnerable to environmental injury and responds to this by impaired healing. This establishes a chronic wound scenario that is capable of sustaining chronic inflammation as well as remodeling. This response occurs as a consequence of activation of the epithelial-mesenchymal unit, involving reciprocal activities of growth factors belonging to the fibroblast growth factor, epidermal growth factor, and transforming growth factor-beta familie…

Future Directions in the Pharmacologic Therapy of Chronic Obstructive Pulmonary Disease

2005

Current therapy for chronic obstructive pulmonary disease (COPD) fails to alter its relentless progression. This remains a significant challenge and unmet need. A recent advance is the demonstration that treatment with a fixed dose of an inhaled corticosteroid and a long-acting beta2-agonist in COPD improves lung function and quality of life, and reduces exacerbation more effectively than either drug alone. Other improvements include the introduction of tiotropium, a once-daily anticholinergic. In advanced clinical development are other once-daily bronchodilators and combinations of anticholinergic drugs and beta2-agonists. Increased understanding of the pathogenesis of COPD has led to nove…