ABSTRACT
BACKGROUND: Idiopathic inflammatory demyelinating disorders (IIDD) affect the central nervous system. In classical multiple sclerosis (CMS), brain, optic nerves [optic neuritis (ON)] and spinal cord [acute transverse myelitis (ATM)] are affected. In neuromyelitis optica (NMO), optic nerves and spinal cord are predominantly affected. NMO-IgG, an autoantibody targeting aquaporin-4, is a marker for NMO. We studied the frequency and clinical relevance of NMO-IgG seropositivity in IIDD patients. METHODS: Neuromyelitis optica-IgG was detected by indirect immunofluorescence using primate cerebellum. RESULTS: Neuromyelitis optica-IgG was detected in six of 10 NMO patients (60%), six of 10 idiopathic relapsing transverse myelitis (IRTM) patients (60%), two of nine idiopathic relapsing ON patients (22%), one of 11 patients (9%) having single ON attack, one of 30 CMS patients (3%), and none of patients having single ATM attack or controls. Comparing NMO-IgG seropositive (n = 12) with NMO-IgG seronegative (n = 8) patients having NMO or IRTM, NMO-IgG seropositivity was associated with a higher relapse rate in first 2 years, 1.5 and 0.6 attacks/year for seropositive and seronegative groups respectively (P = 0.006), and non-significant trend towards more severe ON and myelitis with poorer clinical outcome. CONCLUSION: Neuromyelitis optica -IgG facilitates diagnosis of NMO spectrum disorders. NMO-IgG seropositivity is associated with higher relapse rate in first 2 years.
Subject(s)
Autoantibodies/blood , Autoimmune Diseases of the Nervous System/immunology , Demyelinating Diseases/immunology , Immunoglobulin G/blood , Neuromyelitis Optica/immunology , Adult , Aged , Aquaporin 4/immunology , Female , Fluorescent Antibody Technique, Indirect , Humans , Logistic Models , Male , Middle Aged , Multiple Sclerosis/immunology , Myelitis, Transverse/immunology , Optic Neuritis/immunology , Recurrence , Young AdultABSTRACT
Previously we have shown that E2 down regulates S-COMT expression. Here the effects of four phthalate esters and 4-(tert-octyl)phenol on the intra-cellular levels of S-COMT and COMT activity were studied in MCF-7 cells as a measure of estrogenic activity of these compounds. The four phthalate esters caused significant reductions in both S-COMT protein and COMT activity levels. These effects were inhibited by the ERalpha receptor antagonist ICI182780. 4-(tert-octyl)phenol also caused reductions in these parameters, but the effects were not abolished by ICI182780. Assay of S-COMT protein levels represents a simple and convenient method of assessing the estrogenic potential of a compound.
Subject(s)
Catechol O-Methyltransferase/biosynthesis , Environmental Pollutants/toxicity , Plasticizers/toxicity , Blotting, Western , Cell Line, Tumor , Electrophoresis, Polyacrylamide Gel , Estradiol/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Humans , Indicators and Reagents , Phthalic Acids/toxicity , Polychlorinated Biphenyls/pharmacologyABSTRACT
Commercial PCB mixtures have been shown to induce liver tumors in female rats and this effect has been attributed to the effects of PCBs on estrogen metabolism. Catechol metabolites of PCBs are potent inhibitors of COMT activity and are likely to contribute significantly to reduced clearance of genotoxic catechol metabolites of estrogen. The effect of PCB metabolites on COMT expression in cultured cells was investigated to explore potential mechanisms by which PCB exposure alters catechol estrogen clearance. We hypothesize that estrogenic PCB metabolites may contribute to reduction of COMT expression via interaction with the estrogen receptor. To test this hypothesis, human MCF-7 cells were exposed to PCB analogues and the expression of COMT determined. Western blot analysis demonstrated that COMT protein levels were statistically significantly reduced by both the phenolic and the catechol compounds, an effect which was abolished by the anti-estrogen, ICI182780. The above suggests that COMT levels may be reduced by estrogenic PCB metabolites, via interactions between PCB metabolites and the ER. It supports the hypothesis that both phenolic and catechol metabolites of PCBs may contribute to PCB-mediated carcinogenesis through reduction of COMT levels and activities and subsequent reduction in clearance of endogenous and xenobiotic catechols.
Subject(s)
Catechol O-Methyltransferase/biosynthesis , Catechols/toxicity , Environmental Pollutants/toxicity , Estrogens, Non-Steroidal , Neoplasms/chemically induced , Phenols/toxicity , Polychlorinated Biphenyls/toxicity , Receptors, Estrogen/drug effects , Actins/toxicity , Blotting, Western , Catechols/metabolism , Catechols/pharmacology , Cell Line, Tumor , Electrophoresis, Polyacrylamide Gel , Environmental Pollutants/metabolism , Environmental Pollutants/pharmacology , Estradiol/analogs & derivatives , Estradiol/pharmacology , Estrogen Antagonists/pharmacology , Fulvestrant , Humans , Neoplasms/epidemiology , Phenols/metabolism , Phenols/pharmacology , Polychlorinated Biphenyls/metabolism , Polychlorinated Biphenyls/pharmacology , RiskABSTRACT
The roles of uncoupling proteins (UCPs) are discussed. Particular attention has been paid to the roles of UCP2 to UCP5 as agents mediating thermogenesis, and to the concept of limited or "mild" uncoupling as a means of reducing oxidative stress. The role of the endocrine system, thyroid hormones and catecholamines, in regulating expression of UCPs is also discussed.
Subject(s)
Carrier Proteins/physiology , Endocrine Disruptors/pharmacology , Membrane Proteins/physiology , Membrane Transport Proteins/physiology , Oxidative Stress/physiology , Thermogenesis/physiology , Adenosine Triphosphate/metabolism , Animals , Catecholamines/physiology , Humans , Ion Channels , Mitochondrial Proteins/physiology , Thyroid Hormones/physiology , Uncoupling Agents , Uncoupling Protein 1 , Uncoupling Protein 2 , Uncoupling Protein 3ABSTRACT
In this study, we established an embryo model to study the effects of ethanol on fetal development. When embryos of Xenopus laevis (the African clawed frog) were exposed to ethanol, the resultant tadpoles had significantly reduced brain sizes (microencephaly) and retarded growth rates. These effects, similar to those observed in human fetal alcohol syndrome (FAS), were dose- and time-dependent. We further showed that the antioxidant ascorbic acid (vitamin C) could inhibit the ethanol-induced reactive oxygen species (ROS) production and NF-kappaB activation and protect the ethanol-treated embryos against microencephaly and growth retardation. These results suggest the involvement of NF-kappaB and oxidative stress in ethanol-mediated developmental defects, and the potential use of ascorbic acid as a new and effective protective agent for FAS.
