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Pharmaceuticals
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Genes, Mechanisms and Drugs for Asthma
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Genes, Mechanisms and Drugs for Asthma

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 March 2011) | Viewed by 25589

Special Issue Information

Dear Colleagues,

Asthma is a complex, inflammatory disorder characterized by airflow obstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation. Asthma is caused by environmental factors and a combination of genetic and environmental stimuli. Intense genetic studies in the last decade revealed that multiple genetic loci are involved in the etiology of asthma. Recent cellular, molecular, and animal model studies have revealed that several cellular events are involved in the progression of asthma, including: increased T-helper type 2 cytokines leading to the recruitment of inflammatory cells to the airway and, increased production of reactive oxygen species and mitochondrial dysfunction in the activated inflammatory cells, leading to tissue injury in the bronchial epithelium. The purpose of this issue is to assess the current status of research in asthma: 1) recent progress in genetic studies of asthma; 2) advances in cells/tissues from asthmatic humans, and induced animal models of allergic asthma; and 3) recent developments in therapeutics of asthma. This issue also discusses the current status of mitochondrial approaches in induced animal models of allergic asthma, and also in patients with asthma.

Dr. P. Hemachandra Reddy
Guest Editor

Keywords

  • inflammation
  • reactive oxygen species
  • mitochondrial dysfunction
  • oxidative stress
  • antioxidant therapeutics
  • allergic asthma
  • airway inflammation

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Published Papers (2 papers)

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Research

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242 KiB  
Article
L-Arginine Supplementation and Metabolism in Asthma
by Nicholas J. Kenyon, Michael Last, Jennifer M. Bratt, Vivian W. Kwan, Erin O’Roark and Angela Linderholm
Pharmaceuticals 2011, 4(1), 187-201; https://doi.org/10.3390/ph4010187 - 12 Jan 2011
Cited by 19 | Viewed by 10850
Abstract
L-Arginine, the amino acid substrate for nitric oxide synthase, has been tested as a therapeutic intervention in a variety of chronic diseases and is commonly used as a nutritional supplement. In this study, we hypothesized that a subset of moderate to severe persistent [...] Read more.
L-Arginine, the amino acid substrate for nitric oxide synthase, has been tested as a therapeutic intervention in a variety of chronic diseases and is commonly used as a nutritional supplement. In this study, we hypothesized that a subset of moderate to severe persistent asthma patients would benefit from supplementation with L-arginine by transiently increasing nitric oxide levels, resulting in bronchodilation and a reduction in inflammation. The pilot study consisted of a 3 month randomized, double-blind, placebo-controlled trial of L-arginine (0.05 g/kg twice daily) in patients with moderate to severe asthma. We measured spirometry, exhaled breath nitric oxide, serum arginine metabolites, questionnaire scores, daily medication use and PEFR with the primary endpoint being the number of minor exacerbations at three months. Interim analysis of the 20 subjects showed no difference in the number of exacerbations, exhaled nitric oxide levels or lung function between groups, though participants in the L-arginine group had higher serum L-arginine at day 60 (2.0 ± 0.6 × 10−3 vs. 1.1 ± 0.2 × 10−3 µmol/L, p < 0.05), ornithine at day 30 (2.4 ± 0.9 vs. 1.2 ± 0.3 µmol/L serum, p < 0.05) and ADMA at day 30 (6.0 ± 1.5 × 10−1 vs. 2.6 ± 0.6 × 10−1 µmol/L serum, p < 0.05) on average compared to the placebo group. The study was terminated prematurely. Supplementing asthma subjects with L-arginine increases plasma levels; whether subgroups might benefit from such supplementation requires further study. Full article
(This article belongs to the Special Issue Genes, Mechanisms and Drugs for Asthma)
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Review

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Review
Mitochondrial Dysfunction and Oxidative Stress in Asthma: Implications for Mitochondria-Targeted Antioxidant Therapeutics
by P. Hemachandra Reddy
Pharmaceuticals 2011, 4(3), 429-456; https://doi.org/10.3390/ph4030429 - 25 Feb 2011
Cited by 105 | Viewed by 14168
Abstract
Asthma is a complex, inflammatory disorder characterized by airflow obstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation. Asthma is caused by environmental factors and a combination of genetic and environmental stimuli. Genetic studies have revealed that multiple loci are involved in the [...] Read more.
Asthma is a complex, inflammatory disorder characterized by airflow obstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation. Asthma is caused by environmental factors and a combination of genetic and environmental stimuli. Genetic studies have revealed that multiple loci are involved in the etiology of asthma. Recent cellular, molecular, and animal-model studies have revealed several cellular events that are involved in the progression of asthma, including: increased Th2 cytokines leading to the recruitment of inflammatory cells to the airway, and an increase in the production of reactive oxygen species and mitochondrial dysfunction in the activated inflammatory cells, leading to tissue injury in the bronchial epithelium. Further, aging and animal model studies have revealed that mitochondrial dysfunction and oxidative stress are involved and play a large role in asthma. Recent studies using experimental allergic asthmatic mouse models and peripheral cells and tissues from asthmatic humans have revealed antioxidants as promising treatments for people with asthma. This article summarizes the latest research findings on the involvement of inflammatory changes, and mitochondrial dysfunction/oxidative stress in the development and progression of asthma. This article also addresses the relationship between aging and age-related immunity in triggering asthma, the antioxidant therapeutic strategies in treating people with asthma. Full article
(This article belongs to the Special Issue Genes, Mechanisms and Drugs for Asthma)
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