Sepsis-induced Acute Lung Injury [microform] : the Role of Endogenous and Exogenous Nitric Oxide Book For Free Read Now

Sepsis-induced Acute Lung Injury [microform] : the Role of Endogenous and Exogenous Nitric Oxide a well written book and official by Thesis (Ph.D.)--University of Western Ontario at 2003 is very recommended for you if you find book about . a well written book and made by Habib Moshref Razavi, with page thickness 224 Pages. you can found book review at here

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ISBN: 9780612968592


Sepsis-induced acute lung injury (ALI) remains a major clinical problem with significant morbidity and mortality. In sepsis and ALI, a number of cells including inflammatory cells (e.g. neutrophils and macrophages) as well as parenchymal cells (e.g. endothelial and epithelial cells) are activated. Importantly, inducible nitric oxide synthase (iNOS) activation and increased production of NO is a major pathophysiological development in sepsis and ALI. The biology of NO function is multifaceted and complex. The dichotomy of NO function is apparent by its physiological (e.g. bactericidal) as well as injurious effects. This body of work has examined the dual nature of NO function as it relates to its effects in sepsis-induced ALI. The data contained in this thesis shows that inflammatory cell source of iNOS was responsible for enhanced sepsis-induced pulmonary oxidative and nitrosative stress. It was shown that neutrophil iNOS was absolutely essential for impairment of sepsis-induced pulmonary neutrophil infiltration, and was sufficient to increase pulmonary microvascular aveolo-capillary dysfunction and microvascular protein leak. It was also shown that in sepsis, activated alveolar macrophages had a role, albeit an indirect one, in ALI. Accordingly, here macrophages were directly responsible for pulmonary recruitment of neutrophils. Furthermore and in contrast to endogenous NO effects, the administration of excess exogenous NO was associated with a decrease in sepsis-induced pulmonary neutrophil infiltration, iNOS activity and oxidant stress. In summary, our findings suggested an essential role in ALI for sepsis-induced "migratorially" depressed but otherwise "activated" neutrophils. This role was absolutely dependent on neutrophil iNOS activity. Our findings also highlighted the beneficial effects of exogenous NO administration in sepsis-induced ALI. It was shown that in sepsis-induced ALI, inhaled NO imparted some beneficial physiological effects due to its anti-leukocyte activity, which nonetheless did not improve clinically relevant outcomes such as survival. This lack of survival benefit in ALI, might have been due to deleterious effects of inhaled NO in the non-diseased parts of the lung vs. its beneficial effects in the diseased parts.


Sepsis-induced Acute Lung Injury [microform] : the Role of Endogenous and Exogenous Nitric Oxide



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