ABSTRACT
Mental stress is an important factor contributing to recognized mechanisms underlying cardiovascular events. Among these, stress-related endothelial dysfunction is an early risk factor that predicts future development of severe cardiovascular disorders. Acute mental stress by a variety of tests impairs endothelial function in humans, although the opposite results have been reported by some investigators. Chronic stress always deteriorates endothelial function in humans and experimental animals. Stress hormones, such as glucocorticoids and pro-inflammatory cytokines, and endothelin-1 liberated in response to mental stress participate in endothelial dysfunction possibly via downregulation of endothelial nitric oxide synthase (eNOS) expression, eNOS inactivation, decreased nitric oxide (NO) actions, and increased NO degradation, together with vasoconstriction counteracting against NO-induced vasodilatation. Catecholamines do not directly affect endothelial function but impair its function when blood pressure elevation by the amines is sustained. Endogenous opioids favorably affect endothelial function, which counteract deteriorating effects of other stress hormones and mediators. Inhibition of cortisol and endothelin-1 production, prevention of pro-inflammatory mediator accumulation, hypnotics, mirthful laughter, humor orientation, and lifestyle modification would contribute to the prevention and treatment for stress-related endothelial dysfunction and future serious cardiovascular disease.
Subject(s)
Cardiovascular Diseases/etiology , Cardiovascular Diseases/physiopathology , Endothelium, Vascular/physiology , Stress, Psychological/complications , Animals , Catecholamines/metabolism , Cytokines/metabolism , Endothelin-1/metabolism , Humans , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/metabolism , Opioid Peptides/metabolism , Risk FactorsABSTRACT
Nitric oxide (NO) is widely recognized to be quite an important intercellular messenger in the cardiovascular and nervous systems or immunological reactions, including that in the eye. This molecule formed by constitutive NO synthase (NOS), endothelial (eNOS) and neuronal (nNOS), contributes to physiologically regulate ocular hemodynamics and cell viability and protects vascular endothelial cells and nerve cells or fibers against pathogenic factors associated with glaucoma, ischemia, and diabetes mellitus. Ocular blood flow is regulated by NO derived from the endothelium and efferent nitrergic neurons. Endothelial dysfunction impairs ocular hemodynamics by reducing the bioavailability of NO and increasing the production of reactive oxygen species (ROS). On the other hand, NO formed by inducible NOS (iNOS) expressed under influences of inflammatory mediators evokes neurodegeneration and cell apoptosis, leading to serious ocular diseases. NO over-produced by nNOS in the retina stimulated by excitotoxic amino acids or exposed to ischemia also mediates retinal injury. Because of these dichotomous roles of NO, which has both beneficial and pathogenic actions, one may face difficulties in constructing therapeutic strategies with NO supplementation or NOS inhibition. Up-to-date information concerning physiological roles of NO produced by the different NOS isoforms in the eye and interactions between NO and glaucoma, retinal ischemia, or diabetic retinopathy would help clinicians to select a valid pharmacological therapy that would be appropriate for a specific ocular disease.
Subject(s)
Diabetic Retinopathy/physiopathology , Eye/blood supply , Glaucoma/physiopathology , Nitric Oxide/physiology , Animals , Blood Flow Velocity/physiology , Endothelium, Vascular/enzymology , Humans , Nitric Oxide Synthase Type I/metabolism , Nitric Oxide Synthase Type II/metabolism , Oxidative Stress , Reactive Oxygen SpeciesABSTRACT
BACKGROUND: This study was designed to evaluate the concomitant use of weekly docetaxel and hyperfractionated radiotherapy for the treatment of head and neck cancer (HNC). PATIENTS AND METHODS: Twenty-five patients with advanced squamous cell HNC were treated with hyperfractionated radiotherapy (72 Gy at 1.2 Gy twice per day) and weekly chemotherapy with docetaxel (10 mg/m2). RESULTS: Toxicity was significant, with grade 2 to 4 mucositis observed in 100% and lymphopenia in 84%. Seventeen patients (68%) received the full chemotherapy regimen as planned. The initial overall response rate was 88.0%, while the complete response rate was 68.0%. At a median follow-up period of 10 months, the 2-year Kaplan-Meier projected overall survival was 47.3%, and the cause-specific survival was 81.8%. CONCLUSIONS: This study demonstrated that hyperfractionated radiotherapy with weekly docetaxel achieved better initial response than conventional radiotherapy. In addition, the acute toxicity of this regimen was within the acceptable limits of severity.
