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Building a better aspirin: gaseous solutions to a century-old problem.

ABSTRACT: The gastrointestinal adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) have been recognized since shortly after the introduction of aspirin to the marketplace over a century ago. However, the underlying pathogenesis of NSAID-induced gastropathy remains incompletely understood. Advances in understanding some of the factors that contribute to the mucosal injury have provided clues for the development of safer NSAIDs. The inhibitory effects of nitric oxide (NO) on NSAID-induced leukocyte adherence were exploited in the development of NO-releasing NSAIDs. As well as eliciting less gastrointestinal damage than conventional NSAIDs, these drugs do not elevate blood pressure and show anti-inflammatory effects, additional to those of the parent drugs. Modification of other drugs in a similar manner (i.e., NO-releasing derivatives) has similarly resulted in more effective drugs. More recently, hydrogen sulphide-releasing derivatives of NSAIDs and of other drugs, have been developed, based on the observed ability of H(2)S to reduce inflammation and pain in experimental models. H(2)S-releasing NSAIDs produce negligible gastric damage and exhibit enhanced anti-inflammatory potency as compared to the parent drugs. The NO-NSAIDs and H(2)S-releasing NSAIDs represent examples of new anti-inflammatory drugs with greatly reduced toxicity and improved therapeutic activity, both created through the concept of exploiting the beneficial effects of endogenous gaseous mediators.

SUBMITTER: Wallace JL

PROVIDER: S-EPMC2050827 | biostudies-other | 2007 Oct

REPOSITORIES: biostudies-other

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Project description:Clinical Scenario: Even though chronological aging is an inevitable phenomenological consequence occurring in every living organism, it is biological aging that may be the most significant factor challenging our quality of life. Development of functional limitations, resulting from improper maintenance and restoration of various organ systems, ultimately leads to reduced health and independence. Skeletal muscle is an organ system that, when challenged, is often injured in response to varying stimuli. Overt muscle-strain injury can be traumatic, clinically diagnosable, properly managed, and a remarkably common event, yet our contemporary understanding of how age and environmental stressors affect the initial and subsequent induction of injury and how the biological processes resulting from this event are modifiable and, eventually, lead to functional restoration and healing of skeletal muscle and adjacent tissues is presently unclear. Even though the secondary injury response to and recovery from "contraction-induced" skeletal-muscle injury are impaired with aging, there is no scientific consensus as to the exact mechanism responsible for this event. Given the multitude of investigative approaches, particular consideration given to the appropriateness of the muscle-injury model, or research paradigm, is critical so that outcomes may be physiologically relevant and translational. In this case, methods implementing stretch-shortening contractions, the most common form of muscle movements used by all mammals during physical movement, work, and activity, are highlighted. CLINICAL RELEVANCE:Understanding the fundamental evidence regarding how aging influences the responsivity of skeletal muscle to strain injury is vital for informing how clinicians approach and implement preventive strategies, as well as therapeutic interventions. From a practical perspective, maintaining or improving the overall health and tissue quality of skeletal muscle as one ages will positively affect skeletal muscle's safety threshold and responsivity, which may reduce incidence of injury, improve recovery time, and lessen overall fiscal burdens.

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Building a better aspirin: gaseous solutions to a century-old problem.

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