dinoprost and Lupus-Erythematosus--Systemic

Drugs can interfere with the immune system in two basically different ways: (1) they may interact with the specific recognition mechanisms of the immune system and thus induce an allergic response that is specific for the offending agent; (2) drugs may exert pharmacological effects on the immune systems which result in a response that is independent of its recognition structures or they may activate effector and amplification mechanisms that are normally triggered by specific immune processes. Allergic reactions to drugs are different from reactions that exhibit the same clinical symptoms but lack the specificity of an allergic reaction to the offending agent. It has been suggested that those non-specific reactions which mimic the signs and symptoms of allergic reactions should be classified as pseudo-allergic reactions (PAR). PAR are characterized by the following properties which differentiate them from allergic reactions. (1) The symptoms of PAR are qualitatively different from the pharmacological response of a drug and are not related to adverse reactions connected with its pharmacological and toxicological profile. (2) PAR are not specific with regard to the chemical structure of the triggering agent. (3) PAR lack transferability to other subjects of the same species. (4) In contrast to the allergic reactivity, the pseudo-allergic reactivity is not acquired but genetically predetermined. (5) Pseudo-allergic reactivity is often expressed upon the first contact with an eliciting agent. PAR are thus an expression of a pharmacological interaction of drugs or their metabolites in genetically predisposed individuals.

Topics: Anaphylaxis; Aspirin; Complement Activation; Complement System Proteins; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Drug Hypersensitivity; Epitopes; Female; Histamine; Histamine Release; Humans; Immunosuppression Therapy; Lupus Erythematosus, Systemic; Prostaglandins E; Prostaglandins F

To determine the clinical effect of dietary supplementation with low-dose omega-3-polyunsaturated fatty acids on disease activity and endothelial function in patients with systemic lupus erythematosus.. A 24-week randomised double-blind placebo-controlled parallel trial of the effect of 3 g of omega-3-polyunsaturated fatty acids on 60 patients with systemic lupus erythematosus was performed. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and British Isles Lupus Assessment Group index of disease activity for systemic lupus erythematosus (BILAG), endothelial function using flow-mediated dilation (FMD) of the brachial artery, oxidative stress using platelet 8-isoprostanes and analysis of platelet membrane fatty acids were taken at baseline, 12 and 24 weeks.. In the fish oil group there was a significant improvement at 24 weeks in SLAM-R (from 9.4 (SD 3.0) to 6.3 (2.5), p<0.001); in BILAG (from 13.6 (6.0) to 6.7 (3.8), p<0.001); in FMD (from 3.0% (-0.5 to 8.2) to 8.9% (1.3 to 16.9), p<0.001) and in platelet 8-isoprostanes (from 177 pg/mg protein (23-387) to 90 pg/mg protein (32-182), p = 0.007).. Low-dose dietary supplementation with omega-3 fish oils in systemic lupus erythematosus not only has a therapeutic effect on disease activity but also improves endothelial function and reduces oxidative stress and may therefore confer cardiovascular benefits.

Topics: Adult; Biomarkers; Brachial Artery; Cell Membrane; Dietary Supplements; Dinoprost; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Endothelium, Vascular; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Nitroglycerin; Regional Blood Flow; Statistics, Nonparametric; Treatment Outcome; Ultrasonography, Doppler, Pulsed; Vasodilation; Vasodilator Agents

The aim of the present study was to assess oxidative stress and iron metabolism in systemic lupus erythematosus (SLE) patients with and without insulin resistance (IR).. This study included 236 subjects (125 controls and 111 SLE patients). Patients with SLE were divided in two groups: with (n = 72) or without (n = 39) IR.. SLE patients with IR showed higher advanced oxidation protein product (AOPP) levels (p = 0.030) and gamma-glutamyltransferase (GGT) levels (p = 0.001) and lower sulfhydryl groups of proteins (p = 0.0002) and total radical-trapping antioxidant parameter (TRAP) corrected by uric acid (UA) levels (p = 0.04) when compared to SLE patients without IR. However, SLE patients with IR presented lower serum 8-isoprostane (p = 0.05) and carbonyl protein levels (p = 0.04) when compared to SLE patients without IR. Serum ferritin levels were significantly higher in SLE patients (p = 0.0006) than in controls, and SLE patients with IR presented higher serum ferritin levels (p = 0.01) than SLE patients without IR. Patients with SLE showed that IR was inversely correlated to TRAP/UA (r = -0.2724, p = 0.0008) and serum ferritin was positively correlated to AOPP (r = 0.2870, p = 0.004).. This study found that oxidative stress was higher in the group of SLE patients with IR, and increased ferritin, whether caused by the inflammatory process per se or hyperinsulinaemia, can favour the redox process. In addition, the preset data reinforce the need to measure oxidative stress with several methodologies with different assumptions.

Topics: Adult; Age Factors; Anthropometry; Biomarkers; Case-Control Studies; Dinoprost; Disease Progression; Female; Ferritins; Follow-Up Studies; gamma-Glutamyltransferase; Humans; Insulin Resistance; Lupus Erythematosus, Systemic; Male; Middle Aged; Oxidative Stress; Sex Factors; Statistics, Nonparametric

Topics: Arteriosclerosis; Carotid Artery Diseases; Coronary Artery Disease; Dinoprost; Humans; Lipid Peroxidation; Logistic Models; Lupus Erythematosus, Systemic; Oxidative Stress; Tumor Necrosis Factor-alpha

Serum levels of autoantibodies to endogenous bioregulators (prostaglandin F2 alpha, angiotensin II, epinephrine, bovine serum albumin, dinitrophenol) were measured in patients with systemic and integumental lupus erythematosus and donors and the diagnostic significance of deviations of these levels from the norm was evaluated. A total of 75 patients with lupus erythematosus aged 19-54 years with disease lasting for 0.5 to 18 months were examined. Significant differences between patients and donors were observed as regards virtually all parameters except IgG to angiotensin II.

Topics: Adult; Angiotensin II; Autoantibodies; Dinitrophenols; Dinoprost; DNA; Epinephrine; Humans; Immunoenzyme Techniques; Immunoglobulin G; Immunoglobulin M; Lupus Erythematosus, Systemic; Middle Aged; Serum Albumin, Bovine

We measured the urinary excretion of Isoprostane F2alpha-III and Isoprostane-F2alpha-VI, two markers of in vivo lipid peroxidation, and the circulating levels of the prothrombin fragment F1+2, a marker of thrombin generation, in 18 antiphospholipid antibodies-positive patients, in 18 antiphospholipid antibodies-negative patients with systemic lupus erythematosus, and in 20 healthy subjects. Furthermore, 12 patients positive for antiphospholipid antibodies were treated with (n = 7) or without (n = 5) antioxidant vitamins (vitamin E at 900 IU/d and vitamin C at 2, 000 mg/d) for 4 weeks. Compared with antiphospholipid antibodies-negative patients, antiphospholipid antibodies-positive patients had higher urinary values of Isoprostane-F2alpha-III (P =. 0001), Isoprostane-F2alpha-VI (P =.006), and plasma levels of the prothrombin fragment F1+2 (P =.0001). In antiphospholipid-positive patients, F1+2 significantly correlated with Isoprostane-F2alpha-III (Rho =.56, P =.017) and Isoprostane-F2alpha-VI (Rho =.61, P =.008). After 4 weeks of supplementation with antioxidant vitamins, we found a significant decrease in F1+2 levels (P <.005) concomitantly with a significant reduction of both Isoprostane-F2alpha-III (P =.007) and Isoprostane-F2alpha-VI (P <.005). No change of these variables was observed in patients not receiving antioxidant treatment. This study suggests that lipid peroxidation might contribute to the activation of clotting system in patients positive for antiphospholipid antibodies.

Topics: Adolescent; Adult; Antibodies, Antiphospholipid; Ascorbic Acid; Biomarkers; Dinoprost; Female; Fibrinogen; Humans; Lipid Peroxidation; Lupus Erythematosus, Systemic; Male; Middle Aged; Peptide Fragments; Protein Precursors; Prothrombin; Reference Values; Time Factors; Vitamin E

To evaluate the occurrence and clinical significance of lipid peroxidation (oxidative stress) in rheumatic diseases characterized by vascular involvement.. Plasma 8-epi-PGF2alpha (oxidative stress marker) was measured by gas chromatography-mass spectrometry in 36 patients with systemic lupus erythematosus (SLE), 13 with systemic sclerosis (SSc), 13 with systemic vasculitis [Wegener's granulomatosis (WG), n = 4; Churg Strauss syndrome (CSS), n = 3; Behcet syndrome, n = 6], 12 with rheumatoid arthritis (RA) and in 23 healthy controls (n = 23).. 8-epi-PGF2alpha levels were higher in patients with SLE (P = 0.007), SSc (P < 0.001) and vasculitis (P = 0.001) than in controls. In SLE, a positive Coombs' test and arterial hypertension independently predicted 8-epi-PGF2alpha concentrations (P = 0.004 and P = 0.001, respectively). SLE patients not taking prednisolone showed higher 8-epi-PGF2alpha concentrations than SLE patients on prednisolone (P = 0.02). In the latter group, a dose response relationship was noted between 8-epi-PGF2alpha and steroid dosage (r = 0.6, P = 0.0003). In WG and CSS, 8-epi-PGF2alpha concentrations correlated with disease activity (r = 0.8, P = 0.01) and were higher than in patients with Behcet disease (P = 0.003).. Oxidative stress may be pathogenetically relevant in some autoimmune rheumatic diseases with vascular involvement. Amelioration of some clinical manifestations of these diseases may be envisaged by targeting lipid peroxidation with dietary or pharmacological antioxidants.

Topics: Adult; Aged; Autoimmune Diseases; Dinoprost; Female; Humans; Lipid Peroxidation; Lupus Erythematosus, Systemic; Male; Middle Aged; Oxidative Stress; Vascular Diseases; Vasoconstrictor Agents

We have examined the urinary excretion of stable immunoreactive eicosanoids in 23 female patients with systemic lupus erythematosus (SLE), 16 patients with chronic glomerular disease (CGD), and 20 healthy women. SLE patients had significantly higher urinary thromboxane B2 (TXB2) and prostaglandin (PG) E2 excretion and significantly lower 6-keto-PGF1 alpha than did healthy women. In contrast, CGD patients only differed from controls for having reduced 6-keto-PGF1 alpha excretion. The group of SLE patients with active renal lesions differed significantly from the group with inactive lesions for having a lower creatinine clearance and urinary 6-keto-PGF1 alpha and higher urinary TXB2. Higher urinary TXB2 excretion was associated with comparable platelet TXB2 production in whole blood, undetectable TXB2 in peripheral venous blood, and unchanged urinary excretion of 2,3-dinor-TXB2. A significant inverse correlation was found between urinary TXB2 and creatinine clearance rate (CCr). In contrast, the urinary excretion of 6-keto-PGF1 alpha showed a significant linear correlation with both CCr and para-aminohippurate clearance rate (CPAH). In four SLE and seven CGD patients, inhibition of renal cyclooxygenase activity by ibuprofen was associated with a significant reduction in urinary 6-keto-PGF1 alpha and TXB2 and in both CCr and CPAH. However, the average decrease in both clearances was 50% lower in SLE patients than in CGD patients, when fractionated by the reduction in urinary 6-keto-PGF1 alpha or PGE2 excretion. We conclude that the intrarenal synthesis of PGI2 and TXA2 is specifically altered in SLE. Such biochemical alterations are associated with changes in glomerular hemodynamics and may play a role in the progression of SLE nephropathy.

Topics: Adolescent; Adult; Aged; Blood Platelets; Chronic Disease; Dinoprost; Dinoprostone; Epoprostenol; Female; Gas Chromatography-Mass Spectrometry; Glomerulonephritis; Humans; Ibuprofen; Kidney; Kidney Function Tests; Lupus Erythematosus, Systemic; Middle Aged; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Thromboxane A2; Thromboxane B2