Antiphospholipid antibodies and the risk of severe and non-severe pre-eclampsia: the NOHA case-control study.

BACKGROUND: pre-eclampsia (PEecl) can be defined as non-severe (NS-PEecl) or severe (S-PEecl). Our study aimed to determine the incidence of antiphospholipid antibodies (aPLs) in women with a past history of NS-PEecl or S-PEecl. PATIENTS AND METHODS: This case-control study includes 195 control women, 199 NS-PEecl patients and 143 S-PEecl patients whose plasma samples were collected 6 months after their first delivery. Each plasma was tested for lupus anticoagulant (LA), anticardiolipin (aCL) and antiß2GP1 antibodies, as well as antibodies against phosphatidylserine/prothrombin complex (aPS/PT) and domain I of the ß2GP1. RESULTS: When compared with the control group no significant associations were found for the NS-PEecl group after adjustment of confounding variables. For the S-PEecl group, there was an association with antiß2GP1 immunoglobulin G (IgG) (OR 16.91, 95% CI 3.71-77.06), as well as age, obesity, smoking and multiparity. Antiß2GP1-domain I IgG was associated with aCL, antiß2GP1 and aPS/PT IgG in the three groups. aPS/PT IgG was associated with aCL IgG, and aPS/PT IgM was associated with aCL and antiß2GP1 IgM in the three groups. CONCLUSION: S-PEecl is a distinct entity from NS-PEecl and is mainly associated with the presence of antiß2GP1 IgG. Antiß2GP1 domain I correlates with other aPL IgG tests, and aPS/PT may be promising in patients for whom LA tests cannot be interpreted.

Hydroxychloroquine restores trophoblast fusion affected by antiphospholipid antibodies.

BACKGROUND: Obstetric antiphospholipid syndrome (APS) is defined by pregnancy complications associated with antiphospholipid antibodies (aPL). The mechanisms of the pathogenic effects of aPL in pregnancy are poorly understood. Toll-like receptors (TLR) have been implicated previously in APS. OBJECTIVES: The aims of our study were (1) to determine aPL effects on trophoblastic cell fusion and differentiation, (2) to identify which TLR is involved in this process, and (3) to evaluate the efficacy of hydroxychloroquine (HCQ) to counteract the effects of aPL. METHODS: BeWo cells are a model for trophoblast fusion and differentiation. Fusion index was assessed by immunocytochemical examination, and biochemical differentiation by using ELISA-measured ß-human choronic gonadotropin hormone (ß-hCG) secretion. We used three types of aPL to study their effect on cell fusion and differentiation: aPL derived from obstetric APS patients and affinity purified and polyclonal rabbit anti-ß2-glycoprotein-1 (anti-ß2GP1) antibodies. Experiments on fusion were confirmed using primary cytotrophoblastic cells. RESULTS: All of the types of aPL used decreased the fusion index in BeWo and primary trophoblastic cells (64%, 52%, and 41% for BeWo cells and 67% and 62% for primary cells, respectively), and anti-ß2GP1 antibodies decreased hCG secretion in BeWo cells (41%). To block TLR4 antibodies or to abolish TLR4 cell surface expression restored fusion index in both cell types and ß-human choronic gonadotropin hormone excretion in BeWo cells. HCQ treatment induced the same effect and decreased TLR4 mRNA (40% and 35%, respectively) and protein expressions (62% and 42%, respectively) in BeWo cells. CONCLUSION: Anti-ß2GP1 antibodies decrease trophoblastic differentiation via TLR4. This effect is restored by HCQ, suggesting its therapeutic interest in APS pregnancies.

Obstetrical antiphospholipid syndrome: from the pathogenesis to the clinical and therapeutic implications.

Antiphospholipid syndrome (APS) is an acquired thrombophilia with clinical manifestations associated with the presence of antiphospholipid antibodies (aPL) in patient plasma. Obstetrical APS is a complex entity that may affect both mother and fetus throughout the entire pregnancy with high morbidity. Clinical complications are as various as recurrent fetal losses, stillbirth, intrauterine growth restriction (IUGR), and preeclampsia. Pathogenesis of aPL targets trophoblastic cells directly, mainly via proapoptotic, proinflammatory mechanisms, and uncontrolled immunomodulatory responses. Actual first-line treatment is limited to low-dose aspirin (LDA) and low-molecular weight heparin (LMWH) and still failed in 30% of the cases. APS pregnancies should be a major field in obstetrical research, and new therapeutics are still in progress.

Efficacy and safety of topical hirudin (Hirudex): a double-blind, placebo-controlled study.

Hirudin, a thrombin inhibitor isolated from the leech Hirudo medicinalis, has been long known for its anticoagulant effects. In 1990, the former German BGA has published a monograph on Hirudo medicinalis extract (containing Hirudin and Eglin), stating that its local use is indicated in bruises with or without hematoma. The aim of this double-blind, placebo-controlled clinical trial was to evaluate the efficacy and safety of a Hirudin-containing cream (Hirudex cream; Hirudo medicinalis extract 280 UI/100 g) in patients affected with bruises with or without hematoma. 60 men and women between the ages of 18 and 65 years with a unilateral acute musculoskeletal injury (bruise) with or without hematoma were included. Dosage schedule and application route for both treatments were the following: 3-4 daily applications for 5 days for a total of 15-20 administrations during the whole study period. In the Hirudin group, a highly statistically and clinically significant improvement were noted. Although a statistical improvement was also seen in patients treated with placebo, this was less pronounced, and a highly significant between-group difference was noted for all three major efficacy parameters at each follow-up visit in favour of Hirudin. Both the patients and the investigator considered the overall assessment of efficacy at the end of the study to be significantly better (p < 0.001) in the Hirudin group than in the placebo group. Results of this study suggest that Hirudin is an effective local treatment in patients with mild to moderate bruises.

Sustainable forest management and gender equality. Women and forests.

PIP: This article focuses on deforestation and women's participation in environmental development. Deforestation substantially contributes to accelerated changes in global climates and robs the world of irreplaceable biodiversity. Approximately 100 million hectares of forests have been lost throughout the world since 1950, with the world losing up to 20.4 million hectares of tropical forests annually. Moreover, women's participation in environmental development is currently impeded by many factors such as problems of land tenure and ownership. In order to have a balance between greater productivity and environmental protection, policymakers should ensure that agricultural and forestry extension services are designed incorporating a balanced gender perspective, including women's full participation in decision-making fora, and building upon their knowledge of community concerns. This article further cited examples of women's participation in several countries and identified eight steps to incorporate women in project design.^ieng