Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species (ROS) are cytotoxic, causing inflammatory disease, including tissue necrosis, organ failure, atherosclerosis, infertility, birth defects, premature aging, mutations and malignancy. ROS are produced in the metabolism of drugs and industrial chemicals by (i) one-electron peroxidase oxidations to form cation radicals, (ii) cytochrome P450 metabolism to free radical products, (iii) stabilisation of the ROS-generator, CYP2E1, and (iv) futile cycling of other cytochromes P450. ROS production initiates inflammation which unless quenched may result in chronic inflammatory disease states, e.g. hepatitis, nephritis, myositis, scleroderma, lupus erythematosus, multiple system organ failure. Quenching of ROS is affected by the redox buffer, glutathione (GSH), and the antioxidants, ascorbic acid, tocopherols, retinoids, in conjunction with the redox enzymes, GSH reductase, GSH peroxidase, catalase and superoxide dismutase. Many industrial workers with symptoms of systemic inflammation, resulting from exposure to toxic chemicals, are diagnosed as having rheumatoid arthritis, virus infections, or other microbial lesions, largely because many physicians are unaware that exposure to certain chemicals can initiate inflammatory disease states.
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PMID:Chemical toxicity and reactive oxygen species. 911 92

Understanding the development of autoimmunity is a crucial step toward improving the management, not only of autoimmune diseases, but also of tumors and primary immunodeficiency syndromes. The rapid expansion of knowledge on autoimmunity is fueling the development of a novel approach known as targeted immunotherapy. The present review will concentrate on ten areas where major advances have been achieved: 1) early regulation of B-cell mediated autoimmunity; 2) thymic regulation of tolerance to tissue-restricted antigens via the transcription factor AIRE; 3) role for a population of regulatory T cells (CD4+ CD25+ Tregs) with unique effects; 4) major role for dendritic cells in the development of autoimmunity in conditions such as lupus; 5) role for T cells in autoimmune diseases; 6) role for T cells in rheumatoid arthritis, with new data from a murine model of spontaneous arthritis related to a ZAP-70 mutation; 7) role for the environment via innate immunity, in particular mediated by the toll-like receptors (TLR); identification of new autoantigens with the description of sense-antisense peptides (e.g., proteinase 3-complementary proteinase 3); the immunosenescence concept, which suggests that some autoimmune diseases may be related to premature aging of the immune system; 10) identification of new immunotherapy targets, including costimulation pathway molecules (CD28, CTLA4), original activation systems (BAFF/BLyS), and receptors such as TLRs. These exciting insights into the pathogenic mechanisms underlying immune dysfunction will play a key role in advancing the field of immunorheumatology.
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PMID:Novel concepts and treatments for autoimmune disease: ten focal points. 1558 31

Carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and endothelium-dependent flow-mediated dilatation (FMD) have been repeatedly showed to be related to premature atherosclerosis and cardiovascular diseases in different settings of population. The increased arterial stiffness and endothelium dysfunction may add to premature aging of the arteries in systemic lupus erythematosus (SLE) patients. Still data about arterial stiffness and endothelium function in inflammatory rheumatic diseases are not well described. The aim of this study was to determine the PWV, its derivate marker AIx and FMD and factors possibly influencing them in young SLE women without significant organ damage. Thirty women between 23 and 55 years with an established SLE diagnosis and 66 healthy women were consequently included in the study and both groups were comparable according to age, body mass index (BMI), serum lipid profile and creatinine. PWV was determined by measuring carotid-radial pulse wave transit time with the help of applanation tonometry and AIx, its derivate marker, was calculated as a difference between two waveform peaks expressed as a percentage of the pulse pressure. The FMD was performed by obtaining the repeated scans of the brachial artery at rest and during reactive hyperemia. In SLE women, PWV and AIx were significantly higher and FMD was not different from controls. In linear multiple stepwise regression analysis if patients and controls were both considered, PWV was weakly related to mean blood pressure (MBP), AIx was mostly predicted by age and MBP and FMD was predicted by the diameter of blood vessel, BMI, high density lipoproteins. If the sole SLE setting was analyzed, PWV was not related to any of the pending parameters, AIx turned out to be related to organ damage measured by Systemic Lupus International collaborative Clinics (SLICC) index and age, and FMD obtained strong and significant relation with vessel diameter, and BMI, and disease duration. Regardless of the small number of study group patients, we can state that controlling for MBP and taking measures towards organ damage prevention can partially slow down the process of early atherosclerosis in SLE patients.
Lupus 2009 May
PMID:Arterial wall dysfunction in systemic lupus erythematosus. 1939 54

Face vascularized composite allografts (FVCAs) have helped patients with severe facial disfigurement, with acute rejection now largely controlled through iatrogenic immunosuppression. However, little is known regarding the incidence and mechanism(s) of more long-term pathologic alterations in FVCAs that may affect function and graft durability. Protocol surveillance biopsy specimens for up to an 8-year interval in 7 patients who received FVCAs at our institution revealed histopathologic evidence of chronic rejection. Clinical manifestations included features of premature aging, mottled leukoderma accentuating suture lines, telangiectasia, and dryness of nasal mucosa. Pathologic changes consisted of epidermal thinning accompanied by discrete foci of lymphocyte-mediated cytotoxicity, hyperkeratosis, follicular plugging, vascular ectasia, and sclerosis beneath the epidermal layer associated with collagen type I deposition. Genomic interrogation and immunohistochemistry of sclerotic zones revealed upregulation of the AP-1 pathway components, JunB and c-Fos, previously implicated in overproduction of type I dermal collagen in the setting of systemic sclerosis. We conclude that some patients develop chronic rejection in FVCAs with striking similarities to alterations seen in certain autoimmune cutaneous disorders (lupus erythematosus and scleroderma/chronic sclerodermoid graft-versus-host disease). Identification of relevant pathways and genes, such as JunB and c-Fos, may provide new targets for preventative therapies for chronic immune-mediated changes in vascularized composite allografts.
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PMID:Chronic rejection of human face allografts. 3031 35