scholarly journals Targeted Drug Delivery Technologies Potentiate the Overall Therapeutic Efficacy of an Indole Derivative in a Mouse Cystic Fibrosis Setting

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1601
Author(s):  
Matteo Puccetti ◽  
Marilena Pariano ◽  
Giorgia Renga ◽  
Ilaria Santarelli ◽  
Fiorella D’Onofrio ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Targeted Drug Delivery ◽  
Fungal Infections ◽  
Murine Models ◽  
Multisystem Disease ◽  
Aryl Hydrocarbon ◽  
Target Organs ◽  
Infection And Inflammation ◽  
Anti Inflammatory ◽  
Inflammatory Toxicity

Inflammation plays a major role in the pathophysiology of cystic fibrosis (CF), a multisystem disease. Anti-inflammatory therapies are, therefore, of interest in CF, provided that the inhibition of inflammation does not compromise the ability to fight pathogens. Here, we assess whether indole-3-aldehyde (3-IAld), a ligand of the aryl hydrocarbon receptor (AhR), may encompass such an activity. We resorted to biopharmaceutical technologies in order to deliver 3-IAld directly into the lung, via dry powder inhalation, or into the gut, via enteric microparticles, in murine models of CF infection and inflammation. We found the site-specific delivery of 3-IAld to be an efficient strategy to restore immune and microbial homeostasis in CF organs, and mitigate lung and gut inflammatory pathology in response to fungal infections, in the relative absence of local and systemic inflammatory toxicity. Thus, enhanced delivery to target organs of AhR agonists, such as 3-IAld, may pave the way for the development of safe and effective anti-inflammatory agents in CF.

scholarly journals Enhancing Cystic Fibrosis Immune Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna M. van Heeckeren ◽  
Morgan T. Sutton ◽  
David R. Fletcher ◽  
Craig A. Hodges ◽  
Arnold I. Caplan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Inflammatory Response ◽  
Effective Means ◽  
Treatment Regimens ◽  
Cell Based Therapy ◽  
Inflammatory Status ◽  
Clinical Consequences ◽  
Infection And Inflammation ◽  
Anti Inflammatory ◽  
Improvement In Survival

In cystic fibrosis (CF), sustained infection and exuberant inflammation results in debilitating and often fatal lung disease. Advancement in CF therapeutics has provided successful treatment regimens for a variety of clinical consequences in CF; however effective means to treat the pulmonary infection and inflammation continues to be problematic. Even with the successful development of small molecule cystic fibrosis transmembrane conductance regulator (CFTR) correctors and potentiators, there is only a modest effect on established infection and inflammation in CF patients. In the pursuit of therapeutics to treat inflammation, the conundrum to address is how to overcome the inflammatory response without jeopardizing the required immunity to manage pathogens and prevent infection. The key therapeutic would have the capacity to dull the inflammatory response, while sustaining the ability to manage infections. Advances in cell-based therapy have opened up the avenue for dynamic and versatile immune interventions that may support this requirement. Cell based therapy has the capacity to augment the patient’s own ability to manage their inflammatory status while at the same time sustaining anti-pathogen immunity. The studies highlighted in this manuscript outline the potential use of cell-based therapy for CF. The data demonstrate that 1) total bone marrow aspirates containing Cftr sufficient hematopoietic and mesenchymal stem cells (hMSCs) provide Cftr deficient mice >50% improvement in survival and improved management of infection and inflammation; 2) myeloid cells can provide sufficient Cftr to provide pre-clinical anti-inflammatory and antimicrobial benefit; 3) hMSCs provide significant improvement in survival and management of infection and inflammation in CF; 4) the combined interaction between macrophages and hMSCs can potentially enhance anti-inflammatory and antimicrobial support through manipulating PPARγ. These data support the development of optimized cell-based therapeutics to enhance CF patient’s own immune repertoire and capacity to maintain the balance between inflammation and pathogen management.

scholarly journals Monitoring infection and inflammation in murine models of cystic fibrosis with magnetic resonance imaging

2008 ◽  
Vol 28 (2) ◽  
pp. 527-532 ◽  
Author(s):  
Vipul R. Sheth ◽  
R. Christiaan van Heeckeren ◽  
Alma G. Wilson ◽  
Anna M. van Heeckeren ◽  
Mark D. Pagel
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cystic Fibrosis ◽  
Magnetic Resonance ◽  
Murine Models ◽  
Resonance Imaging ◽  
Infection And Inflammation

scholarly journals Allergic Diseases Caused by Aspergillus Species in Patients with Cystic Fibrosis

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 357
Author(s):  
Aidan K. Curran ◽  
David L. Hava
Keyword(s):  
Cystic Fibrosis ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Hyphal Growth ◽  
Allergic Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Th2 Immune Response ◽  
Difficulty Breathing ◽  
Oral Corticosteroids

Aspergillus spp. are spore forming molds; a subset of which are clinically relevant to humans and can cause significant morbidity and mortality. A. fumigatus causes chronic infection in patients with chronic lung disease such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). In patients with CF, A. fumigatus infection can lead to allergic disease, such as allergic bronchopulmonary aspergillosis (ABPA) which is associated with high rates of hospitalizations for acute exacerbations and lower lung function. ABPA results from TH2 immune response to Aspergillus antigens produced during hyphal growth, marked by high levels of IgE and eosinophil activation. Clinically, patients with ABPA experience difficulty breathing; exacerbations of disease and are at high risk for bronchiectasis and lung fibrosis. Oral corticosteroids are used to manage aspects of the inflammatory response and antifungal agents are used to reduce fungal burden and lower the exposure to fungal antigens. As the appreciation for the severity of fungal infections has grown, new therapies have emerged that aim to improve treatment and outcomes for patients with CF.

scholarly journals Techniques for the Assessment of In Vitro and In Vivo Antifungal Combinations

2021 ◽  
Vol 7 (2) ◽  
pp. 113
Author(s):  
Anne-Laure Bidaud ◽  
Patrick Schwarz ◽  
Guillaume Herbreteau ◽  
Eric Dannaoui
Keyword(s):  
Animal Models ◽  
Fungal Infections ◽  
Acquired Resistance ◽  
Adequate Treatment ◽  
Combination Treatments ◽  
Target Organs ◽  
Fungal Load ◽  
Time Kill

Systemic fungal infections are associated with high mortality rates despite adequate treatment. Moreover, acquired resistance to antifungals is increasing, which further complicates the therapeutic management. One strategy to overcome antifungal resistance is to use antifungal combinations. In vitro, several techniques are used to assess drug interactions, such as the broth microdilution checkerboard, agar-diffusion methods, and time-kill curves. Currently, the most widely used technique is the checkerboard method. The aim of all these techniques is to determine if the interaction between antifungal agents is synergistic, indifferent, or antagonistic. However, the interpretation of the results remains difficult. Several methods of analysis can be used, based on different theories. The most commonly used method is the calculation of the fractional inhibitory concentration index. Determination of the usefulness of combination treatments in patients needs well-conducted clinical trials, which are difficult. It is therefore important to study antifungal combinations in vivo, in experimental animal models of fungal infections. Although mammalian models have mostly been used, new alternative animal models in invertebrates look promising. To evaluate the antifungal efficacy, the most commonly used criteria are the mortality rate and the fungal load in the target organs.

Anti-inflammatory effects of montelukast in mild cystic fibrosis

2002 ◽  
Vol 89 (6) ◽  
pp. 599-605 ◽  
Author(s):  
Sabina Schmitt-Grohé ◽  
Olaf Eickmeier ◽  
Ralf Schubert ◽  
Christina Bez ◽  
Stefan Zielen
Keyword(s):  
Cystic Fibrosis ◽  
Anti Inflammatory

Ketoconazole-p Aminobenzoic Cocrystal Exhibits a Potent Anti-inflammatory Effect on the Skin of BALBc Mice 

2021 ◽  
Author(s):  
Sorina Danescu ◽  
Gabriela Adriana Filip ◽  
Remus Moldovan ◽  
Diana Olteanu ◽  
Andras Nagy ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Parent Drug ◽  
Mouse Ear ◽  
Anti Inflammatory ◽  
Nfκb Pathway ◽  
Cutaneous Mycosis ◽  
Anti Inflammatory Cytokine ◽  
Global Health Problem ◽  
Inflammatory Action ◽  
Inflammatory Effect

Abstract Fungal infections are a growing global health problem. Therefore, our group has designed and characterized a novel cocrystal formulation starting from ketoconazole and para-amino benzoic acid, named KET-PABA aiming to improve the bioavailability, biocompatibility, and efficiency of the parent drug. The cocrystal showed improved physical properties, such as stability in suspension, solubility, as well as antimycotic efficiency as compared to ketoconazole. The current study investigated the local possible side effects induced on BALBc mice skin by the application of KET-PABA cocrystal. KET-PABA proved to be safe, without signs of skin sensitization as shown by the mouse ear sensitization test (MEST), or histopathology. KET-PABA induced a potent anti-inflammatory effect through the inhibition of proinflammatory cytokines such as IL1α, IL1β, IL6 and TNFα, and other inflammation promoters such as NRF2, compared to the vehicle. KET-PABA had no effect on the levels of the anti-inflammatory cytokine IL10, or proinflammatory enzyme COX2 and had minimal effects on the activation of the NFκB pathway. Overall, KET-PABA application induced no sensitization, moreover, it induced an anti-inflammatory response. Based on the improved antimycotic effect versus ketoconazole and the anti-inflammatory action, KET-PABA cocrystal has the potential to be an efficient drug in the treatment of cutaneous mycosis.

Dihydroquercetin as potential immunonutrient in treatment of COVID-19

2021 ◽  
pp. 28-32
Author(s):  
V. V. Tatarinov ◽  
S. V. Orlova ◽  
E. A. Nikitina ◽  
E. V. Prokopenko ◽  
A. N. Vodolazkaya ◽  
...  
Keyword(s):  
Biological Activity ◽  
Recovery Period ◽  
Enzymatic Reactions ◽  
Target Organs ◽  
Wide Range ◽  
Complex Therapy ◽  
Main Target ◽  
Low Toxicity ◽  
Anti Inflammatory

The main aspects of the antiviral, anti-inflammatory, antioxidant and hepatoprotective properties of dihydroquercetin (DHQ), which may affect the course of COVID-19, are considered. Given the low toxicity and a wide range of biological activity, aimed not only at suppressing enzymatic reactions with the participation of coronavirus, but also at eliminating the lesions caused by it in all the main target organs, dihydroquercetin can be recommended for inclusion in the complex therapy of the disease and during the recovery period of COVID-19.

Sign in / Sign up

Export Citation Format

Share Document