ABSTRACT
Spinal cord injury (SCI) substantially increases the risk of neurogenic obesity, diabetes, and metabolic syndrome. Much like in the general population, a discussion of these syndromes in SCI would be incomplete without acknowledging the association of SCI with sleep-disordered breathing (SDB). This article will outline the interplay between obesity and obstructive sleep apnea (OSA), discussing the pathophysiology of obesity in OSA both for the general population and SCI population. The role of insulin resistance in SDB and SCI will also be examined. The epidemiology and pathophysiology of OSA and central sleep apnea in SCI are discussed through an examination of current evidence, followed by a review of central sleep apnea in SCI. Principles of diagnosis and management of SDB will also be discussed. Because sleep deprivation in itself can be a risk factor for developing obesity, the significance of comorbid insomnia in SCI is explored. Ultimately, a thorough sleep history, testing, and treatment are key to improving the sleep of individuals with SCI and to potentially reducing the impact of neurogenic obesity and metabolic syndrome.
Subject(s)
Obesity/complications , Sleep Apnea Syndromes/etiology , Spinal Cord Injuries/complications , Adult , Humans , Insulin Resistance , Metabolic Syndrome/etiology , Sleep Apnea Syndromes/metabolism , Sleep Apnea Syndromes/physiopathologyABSTRACT
As a result of their characteristic physical and optical properties, including their size, intense fluorescence, broad excitation, narrow emission and resistance to photobleaching, semiconductor nanocrystals are potentially useful for a variety of biological applications including molecular imaging, live-cell labeling, photodynamic therapy and targeted drug delivery. In this study, zinc sulfide (ZnS) semiconductor nanocrystals were synthesized in the 3 to 4 nm size range with selected capping agents intended to protect the nanocrystal core and increase its biological compatibility. We show that the biocompatibility of ZnS nanocrystals with primary murine splenocytes is influenced by the chemical structure of the outer capping agent on the nanocrystal. Additionally, the cytotoxicity of ZnS nanocrystals increases markedly as a function of time spent in suspension in phosphate-buffered saline (PBS). These data suggest that the potential therapeutic and/or biological use of ZnS nanocrystals is inherently dependent upon the proper choice of capping agent, as well as the conditions of nanocrystal preparation and storage.
Subject(s)
Cell Survival/drug effects , Metal Nanoparticles/toxicity , Spleen/drug effects , Sulfides/toxicity , Zinc Compounds/toxicity , Animals , Biomarkers/metabolism , Cells, Cultured , Female , Metal Nanoparticles/chemistry , Mice , Mice, Inbred C57BL , Pulp Capping and Pulpectomy Agents/chemistry , Spleen/metabolism , Spleen/pathology , Sulfides/chemistry , Suspensions , Time Factors , Zinc Compounds/chemistryABSTRACT
Chronic granulomatous disease (CGD) is caused by defects in the NADPH oxidase complex and is characterized by an increased susceptibility to infection. Other significant complications of CGD include autoimmunity and non-infectious hyperinflammatory disorders. We show that a gp91(phox) deficiency leads to the development of phenotypically altered T lymphocytes in mice and that this abnormal, hyperactive phenotype can be modulated by activation of the adenosine A(2A) receptor. T cells isolated from CGD mice produce significantly higher levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF-α, IL-4 and IL-13 than do WT cells after TCR-mediated activation; treatment with the selective adenosine A(2A) receptor agonist, CGS21680, potently inhibits this response. Additionally, the over exuberant inflammatory response elicited by thioglycollate challenge in gp91(phox) deficient mice is attenuated by CGS21680. These data suggest that treatment with A(2A)R agonists may be an effective therapy by which to regulate the immune system hyperactivity that results from a gp91(phox) deficiency.
