ABSTRACT
OBJECTIVE: To examine the effect of a combination of screening and treatment with low-dose aspirin on the prevalence of early-onset pre-eclampsia (PE). METHODS: This was a retrospective analysis of two consecutive cohorts of women screened for early PE. The first cohort was observed to determine whether algorithms developed to screen for PE at 11 to 13 + 6 weeks' gestation could be applied to our population. High-risk women in the second cohort were advised on their risk and offered aspirin (150 mg at night), with treatment starting immediately after screening. The prevalence of early PE and the proportion of women with PE delivering at 34-37 weeks' gestation were compared between the cohorts. RESULTS: In the observational and interventional cohorts, 3066 and 2717 women, respectively, were screened. There were 12 (0.4%) cases of early PE in the observational cohort and one (0.04%) in the interventional cohort (P < 0.01). Among all women with PE delivering before 37 weeks, 25 (0.83%) were in the observational cohort and 10 (0.37%) in the interventional cohort (P = 0.03). CONCLUSIONS: A strategy of first-trimester screening for early PE coupled with prescription of aspirin to the high-risk group appears to be effective in reducing the prevalence of early PE.
Subject(s)
Aspirin/administration & dosage , Platelet Aggregation Inhibitors/administration & dosage , Pre-Eclampsia/prevention & control , Adult , Australia/epidemiology , Cohort Studies , Female , Gestational Age , Humans , Infant, Newborn , Pre-Eclampsia/diagnosis , Pre-Eclampsia/diagnostic imaging , Pre-Eclampsia/epidemiology , Predictive Value of Tests , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, First , Retrospective Studies , Risk Factors , Ultrasonography, Doppler, Pulsed/methodsABSTRACT
Matrix metalloproteinases (MMPs) have recently been implicated in the pathogenesis of multiple sclerosis. Their suggested role includes the disruption of the blood-brain barrier, immune cell transmigration into the central nervous system, and myelin degradation. The present study characterized the mRNA level of a wide spectrum of MMPs and tissue inhibitors of metalloproteinases (TIMPs) expressed by peripheral blood leukocytes from relapsing-remitting (n = 16) and secondary-progressive (n = 12) multiple sclerosis patients. The expression of the same MMPs and TIMPs was evaluated also in a prospective 12-month follow-up of 6 patients randomly chosen from each of the 2 groups during interferon beta-1a treatment. Reverse transcription-polymerase chain reaction assessment demonstrated elevated levels of MT1-MMP and MMP-7 mRNA levels in both groups of patients, and no significant differences in MMP-9 levels, compared with healthy controls. Divergent expression of MMP-2 between relapsing-remitting and secondary-progressive patients compared with controls was observed. Interferon-beta treatment was associated with significant suppression of MMP-9 and MMP-7 mRNA in relapsing-remitting patients, though no significant changes were observed in the secondary-progressive group. These results contribute to the understanding of the IFN-beta-mediated immunomodulatory and therapeutic effects in multiple sclerosis patients and also support evidence for distinct immune mechanism(s) underlying relapsing-remitting versus secondary-progressive multiple sclerosis. The study also suggests that MMPs may be considered as potential biomarkers for response to treatment as well as targets for immunotherapy in multiple sclerosis.
Subject(s)
Adjuvants, Immunologic/pharmacology , Interferon-beta/pharmacology , Matrix Metalloproteinases/genetics , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-2/genetics , Adolescent , Adult , Female , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Enzymologic/immunology , Humans , Leukocytes/enzymology , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 7/genetics , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinases, Membrane-Associated , Metalloendopeptidases/genetics , Middle Aged , Multiple Sclerosis, Chronic Progressive/enzymology , Multiple Sclerosis, Relapsing-Remitting/enzymology , RNA, Messenger/analysisABSTRACT
The synthetic polypeptide copolymer-1 (Cop-1; Copaxone; Glatiramer Acetate) has been recently approved as an effective treatment in relapsing multiple sclerosis (MS). A large body of evidence demonstrates that Cop-1 induces active suppression of CNS-inflammatory disease in animal models. However, Cop-1-mediated suppressor mechanisms have not yet been elucidated in humans. A 12-month open study following clinical and immunological parameters of ten relapsing MS patients treated with Cop-1 is presented. Relapse rates and disability scores (EDSS) were evaluated prior to and after 12 months of treatment. The immunological parameters assessed prior to and at 3 months' interval during treatment included serum levels of soluble IL-2 receptor (sIL-2R) and IL-10 as well as leukocyte cytokine mRNA expression of TNF alpha, IL-4 and TGF-beta. Copaxone treatment was found to lead to a significant reduction in the mean annual relapse rate (from 1.4 prior to treatment to 0.6 during treatment) and stabilization of disability in 90% of the patients. The treatment was accompanied by an elevation of serum IL-10 levels, suppression of the pro-inflammatory cytokine TNF alpha mRNA, and an elevation of the anti-inflammatory cytokines TGF-beta and IL-4 mRNAs in PBLs. These results suggest that the beneficial clinical effects of Copaxone in MS patients may be attributed to changes in activation of T cell subsets and a shift from Th1 to Th2/Th3 cytokine profile, probably leading to Cop-1-driven mechanisms of bystander suppression.
