ABSTRACT
The progression and exacerbations of chronic obstructive pulmonary disease (COPD) are intimately associated with tobacco smoke/biomass fuel-induced oxidative and aldehyde/carbonyl stress. Alterations in redox signaling proinflammatory kinases and transcription factors, steroid resistance, unfolded protein response, mucus hypersecretion, extracellular matrix remodeling, autophagy/apoptosis, epigenetic changes, cellular senescence/aging, endothelial dysfunction, autoimmunity, and skeletal muscle dysfunction are some of the pathological hallmarks of COPD. In light of the above it would be prudent to target systemic and local oxidative stress with agents that can modulate the antioxidants/ redox system or by boosting the endogenous levels of antioxidants for the treatment and management of COPD. Identification of various antioxidant agents, such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine, ergothioneine, and carbocysteine lysine salt), dietary natural product-derived polyphenols and other compounds (curcumin, resveratrol, green tea catechins, quercetin sulforaphane, lycopene, acai, alpha-lipoic acid, tocotrienols, and apocynin) have made it possible to modulate various biochemical aspects of COPD. Various researches and clinical trials have revealed that these antioxidants can detoxify free radicals and oxidants, control expression of redox and glutathione biosynthesis genes, chromatin remodeling, and ultimately inflammatory gene expression. In addition, modulation of cigarette smoke-induced oxidative stress and related cellular changes have also been reported to be effected by synthetic molecules. This includes specific spin traps like α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419, lipid peroxidation and protein carbonylation blockers/inhibitors, such as edaravone and lazaroids/tirilazad, myeloperoxidase inhibitors, as well as specialized pro-resolving mediators/inflammatory resolving lipid mediators, omega-3 fatty acids, vitamin D, and hydrogen sulfide. According to various studies it appears that the administration of multiple antioxidants could be a more effective mode used in the treatment of COPD. In this review, various pharmacological and dietary approaches to enhance lung antioxidant levels and beneficial effects of antioxidant therapeutics in treating or intervening the progression of COPD have been discussed.
Subject(s)
Antioxidants/therapeutic use , Lung/drug effects , Lung/metabolism , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/metabolism , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Free Radicals/metabolism , Humans , Lipid Peroxidation/drug effects , Lung/physiopathology , Oxidative Stress/drug effects , Protein Carbonylation/drug effects , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Smoke/adverse effects , Nicotiana/adverse effectsABSTRACT
BACKGROUND: Many anti-epileptics cause resistance to non-depolarizing neuromuscular blocking agents, but this has not been reported for valproic acid (VPA). We hypothesized that VPA would increase the rocuronium requirement and that magnesium sulphate (MgSO(4)) may reduce this increase. METHODS: Fifty-five patients undergoing cerebrovascular surgeries were studied. Subjects were allocated into three groups at a 1:1:1 ratio: Groups VM, VC, and C. Groups VM and VC were given VPA premedication; Group C was not. A rocuronium injection (0.6 mg kg(-1) i.v.) was administered to Group VM, followed by MgSO(4) as a 50 mg kg(-1) i.v. bolus and 15 mg kg(-1) h(-1) infusion. The same volume of 0.9% saline was administered to the other groups. Supplementary rocuronium (0.15 mg kg(-1)) was given whenever the train-of-four count reached 2. Rocuronium requirements (primary outcome), mean arterial pressure (MAP), heart rate (HR), nausea, vomiting, shivering, and use of anti-emetics and nicardipine were compared. RESULTS: Group VC showed the highest rocuronium requirement [mg kg(-1) h(-1): 0.47 (0.08) vs 0.33 (0.12) (Group C), 0.31 (0.07) (Group VM); P<0.001]. MAP, intraoperative HR, nausea, vomiting, shivering, and use of anti-emetics and nicardipine were not significantly different among the groups. Postoperative HR was lower in Group VM than in Group VC. CONCLUSIONS: VPA increased the rocuronium requirement, and MgSO(4) infusion attenuated this increase.
Subject(s)
Androstanols/administration & dosage , Anticonvulsants/pharmacology , Cerebrovascular Disorders/surgery , Magnesium Sulfate/pharmacology , Neuromuscular Nondepolarizing Agents/administration & dosage , Valproic Acid/pharmacology , Adolescent , Adult , Aged , Blood Pressure/drug effects , Craniotomy , Double-Blind Method , Drug Interactions , Female , Heart Rate/drug effects , Humans , Male , Middle Aged , RocuroniumABSTRACT
The purpose of this study was to compare the fracture resistance of copy-milled and conventional In-Ceram crowns. Four groups of 10 uniform sized all-ceramic anterior crowns were fabricated for this test: (1) In-Ceram Spinell (2) In-Ceram Alumina (3) Celay In-Ceram Spinell, and (4) Celay In-Ceram Alumina crowns. All specimens were cemented on stainless steel master die with resin cement and stored in 37 degrees C water for one day prior to loading into a universal testing machine. Using a steel ball at a crosshead speed of 0.5 mm min-1, the crowns were loaded at 30 degrees C angle until catastrophic failure occurred. Mean fracture strength was analysed and compared. Under the conditions of this study and the materials used, the following conclusions were drawn: 1. The strength of Celay In-Ceram anterior crowns had a slightly higher fracture strength than conventional In-Ceram crowns. 2. In-Ceram Alumina crowns had a significantly higher fracture strength than In-Ceram Spinell crowns in both conventional and copy milling methods.