Agonistic activity of tamoxifen, a selective estrogen-receptor modulator (SERM), on arthritic ovariectomized mice

Arthritis is positively associated with the decline of sex hormones, especially estrogen. Tamoxifen (TMX) is a selective estrogen receptor modulator, possessing agonist or antagonistic activity in different tissues. Thus, the objective of this study was to investigate the effect of TMX on the zymosan-induced arthritis model. Female Swiss normal and ovariectomized (OVX) mice were divided into groups and treated for five days with TMX (0.3, 0.9 or 2.7 mg/kg) or 17-β-estradiol (E2, 50 µg/kg). On the fifth day, arthritis was induced and 4 h later, leukocyte migration into joint cavities was evaluated. The neutrophil migration in OVX animals, but not in normal mice, treated with TMX (all tested doses) was significantly decreased compared with mice that received the vehicle (P≤0.05). Similarly, this effect was also demonstrated in the E2-treated group. Therefore, the present study demonstrates that TMX presented agonist effects in inhibiting neutrophil migration and preventing arthritis progression in OVX mice.

Agonistic activity of tamoxifen, a selective estrogen-receptor modulator (SERM), on arthritic ovariectomized mice.

Arthritis is positively associated with the decline of sex hormones, especially estrogen. Tamoxifen (TMX) is a selective estrogen receptor modulator, possessing agonist or antagonistic activity in different tissues. Thus, the objective of this study was to investigate the effect of TMX on the zymosan-induced arthritis model. Female Swiss normal and ovariectomized (OVX) mice were divided into groups and treated for five days with TMX (0.3, 0.9 or 2.7 mg/kg) or 17-ß-estradiol (E2, 50 µg/kg). On the fifth day, arthritis was induced and 4 h later, leukocyte migration into joint cavities was evaluated. The neutrophil migration in OVX animals, but not in normal mice, treated with TMX (all tested doses) was significantly decreased compared with mice that received the vehicle (P≤0.05). Similarly, this effect was also demonstrated in the E2-treated group. Therefore, the present study demonstrates that TMX presented agonist effects in inhibiting neutrophil migration and preventing arthritis progression in OVX mice.

Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.

Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial.

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.

PP176. SFLT-1: A possibility of precocious diagnosis of preeclampsia.

INTRODUCTION: Preeclampsia (PE) affects 5-8% of all pregnant women and can trigger a severe gestational hypertension framework and eventually develop into eclampsia and HELLP syndrome. Anticipating the damage would be important in order to establish procedures that can reduce adverse outcomes. For this reason, many researches are undertaken to identify ways to make a diagnosis of preeclampsia as early as possible. It has been highlighted in literature the study: the sFlt1 (soluble fms-like tyrosine kinase-1) has been implicated in the precocious diagnosis of pre eclampsia. The sFlt1 is an anti-angiogenic factor produced in response to oxidative stress derived from the deleterious effects of pre-eclampsia. OBJECTIVES: The objective of the study was to evaluate the role of Soluble fms-like tyrosine kinase-1 in the diagnosis of preeclampsia. METHODS: This is a review conducted in the database PubMed and Lilacs. For this purpose, we used the following MeSH, "Vascular Endothelial Growth Factor Receptor-1" OR "FLT1 protein, human" AND "Pre-Eclampsia/diagnosis" in PubMed and "Pre-eclampsia" AND "SFLT1A" in Lilacs, resulting in 84 papers. After reading the abstracts of these studies, we selected the articles analyzed taking into consideration the criteria for inclusion and exclusion. We excluded publications that were not in the period under study (2008 to July 2011) and by study design. Including only case-control, cohort and prospective observational. For a critical analysis of the material, we used the following indicators: researcher, years, central theme, participants, study design and primary outcome. RESULTS: The final results of this study were composed of seven articles and are shown for each target outcome. These vary according to gestational age at which PE is installed and the marker studied (sFlt1 alone or its relation to PlGF - sFlt1/PIGF). Six studies showed greater levels of sFlt1 for the preeclampsia groups when compared to the control group. Significantly differences in antiangiogenic factors seric levels were not found among preeclamptic and eclamptic patients. When associated with another factor, like PIGF, a greater efficacy in the diagnosis of early preeclampsia is shown. Of the studies analyzed, only one (Lynch et al) showed no significant difference between the values of sFlt-1 in groups of early PE, late PE and control for gestational ages between 10 and 15 weeks. As for the relation sFlt-1/PIGF, five studies have considered it even better for PE diagnosis when compared to sFlt-1 isolated. CONCLUSION: The dosage of sFlt1 may be a relevant resource for the early diagnosis of preeclampsia before the installation of target organ damage, especially if measured in the period between 12 and 28 weeks of gestational age. Whereas sFlt-1 manifests itself before the 20th week, that may be interesting clinical point of view since it is this phase that settles the most severe cases, when the adoption of care could prevent further risks. The relationship sFlt1/PIGF, was more appropriate than the measurement of sFlt1 alone. Additional studies are needed to: amplification of the number of women evaluated, establishing gestational age appropriate for study, serum standard and need to consider the relationship between sFlt1 and other factors pro and/or anti-angiogenic.