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      Efficacy of resveratrol to supplement oral nifedipine treatment in pregnancy-induced preeclampsia

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          Abstract

          Objective

          Preeclampsia (PE) is a complication affecting pregnant women worldwide, which usually manifests as severe maternal hypertension. Resveratrol (RESV), a naturally existing polyphenol, is known to exhibit beneficial effects in cardiovascular disease including hypertension. We evaluated the outcome of treatment combining oral nifedipine (NIFE) and RESV against PE.

          Design and methods

          Using a randomized group assignment, 400 PE patients were enrolled and received oral treatments of either NIFE + RESV or NIFE + placebo. Primary endpoints were defined as time to control blood pressure and time before a new hypertensive crisis. Secondary endpoints were defined as the number of doses needed to control blood pressure, maternal and neonatal adverse effects.

          Results

          Compared with the NIFE + placebo group, the time needed to control blood pressure was significantly reduced in NIFE + RESV group, while time before a new hypertensive crisis was greatly delayed in NIFE + RESV group. The number of treatment doses needed to control blood pressure was also categorically lower in NIFE + RESV group. No differences in maternal or neonatal adverse effects were observed between the two treatment groups.

          Conclusion

          Our data support the potential of RESV as a safe and effective adjuvant of oral NIFE to attenuate hypertensive symptoms among PE patients.

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          Most cited references34

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          Resveratrol and Cardiovascular Diseases

          The increased incidence of cardiovascular diseases (CVDs) has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES), a polyphenolic compound notably present in grapes and red wine, has been involved in the “French paradox”. RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS). RES was able to scavenge •OH/O2 •− and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC) under glucose-induced oxidative stress, RES restored the activity of dimethylargininedimethylaminohydrolase (DDAH), an enzyme that degrades an endogenous inhibitor of eNOS named asymmetric dimethylarginine (ADMA). Thus, RES could improve •NO availability and decrease the endothelial dysfunction observed in diabetes. Preclinical studies have made it possible to identify molecular targets (SIRT-1, AMPK, Nrf2, NFκB…); however, there are limited human clinical trials, and difficulties in the interpretation of results arise from the use of high-dose RES supplements in research studies, whereas low RES concentrations are present in red wine. The discussions on potential beneficial effects of RES in CVDs (atherosclerosis, hypertension, stroke, myocardial infarction, heart failure) should compare the results of preclinical studies with those of clinical trials.
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            Matrix metalloproteinase-9 deficiency phenocopies features of preeclampsia and intrauterine growth restriction.

            The pregnancy complication preeclampsia (PE), which occurs in approximately 3% to 8% of human pregnancies, is characterized by placental pathologies that can lead to significant fetal and maternal morbidity and mortality. Currently, the only known cure is delivery of the placenta. As the etiology of PE remains unknown, it is vital to find models to study this common syndrome. Here we show that matrix metalloproteinase-9 (MMP9) deficiency causes physiological and placental abnormalities in mice, which mimic features of PE. As with the severe cases of this syndrome, which commence early in gestation, MMP9-null mouse embryos exhibit deficiencies in trophoblast differentiation and invasion shortly after implantation, along with intrauterine growth restriction or embryonic death. Reciprocal embryo transfer experiments demonstrated that embryonic MMP9 is a major contributor to normal implantation, but maternal MMP9 also plays a role in embryonic trophoblast development. Pregnant MMP9-null mice bearing null embryos exhibited clinical features of PE as VEGF dysregulation and proteinuria accompanied by preexisting elevated blood pressure and kidney pathology. Thus, our data show that fetal and maternal MMP9 play a role in the development of PE and establish the MMP9-null mice as a much-needed model to study the clinical course of this syndrome.
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              Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy.

              This guideline summarizes the quality of the evidence to date and provides a reasonable approach to the diagnosis, evaluation, and treatment of the hypertensive disorders of pregnancy (HDP). The literature reviewed included the original HDP guidelines and their reference lists and an update from 1995. Using key words, Medline was searched for literature published between 1995 and 2007. Articles were restricted to those published in French or English. Recommendations were evaluated using the criteria of the Canadian Task Force on Preventive Health Care (Table 1). This guideline was developed by the Society of Obstetricians and Gynaecologists of Canada and was partly supported by an unrestricted educational grant from the British Columbia Perinatal Health Program (formerly the British Columbia Reproductive Care Program or BCRCP). The Canadian Hypertension Society provided assistance with the literature search and some travel support for one author. Much of the Canadian research cited in this document has been funded by the Canadian Institutes of Health Research. The potential for ongoing support is gratefully acknowledged.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                November 2017
                12 September 2017
                : 6
                : 8
                : 595-600
                Affiliations
                [1 ]Department of Obstetrics and Gynecology Maternal and Child Health Care Hospital of Shandong Province, Jinan, Shandong Province, China
                [2 ]Department of Obstetrics and Gynecology Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China
                [3 ]Department of Obstetrics and Gynecology Zoucheng People’s Hospital, Zoucheng, Shandong Province, China
                Author notes
                Correspondence should be addressed to Q Chen; Email: jnzccq@ 123456126.com
                Article
                EC170130
                10.1530/EC-17-0130
                5633060
                28993436
                5157430e-afc0-4037-99bf-c483525faf45
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 24 August 2017
                : 12 September 2017
                Product
                Categories
                Research

                preeclampsia,resveratrol,nifedipine,hypertension,pregnancy
                preeclampsia, resveratrol, nifedipine, hypertension, pregnancy

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