Recent advances in the syntheses of anthracene derivatives.

Anthracene and anthracene derivatives have been extensively studied over the years because of their interesting photophysical, photochemical, and biological properties. They are currently the subject of research in several areas, which investigate their use in the biological field and their application in OLEDs, OFETs, polymeric materials, solar cells, and many other organic materials. Their synthesis remains challenging, but some important preparative methods have been reported, especially in the last decade. This review presents an update of the recent strategies that have been employed to prepare anthracene derivatives. It encompasses papers published over the last twelve years (2008-2020) and focuses on direct and indirect methods to construct anthracene and anthraquinone frameworks.

Maternal serum PAPP-A as an early marker of obstetric complications?

OBJECTIVE: The aim of this study was to investigate whether low first-trimester PAPP-A levels are associated with an adverse pregnancy outcome. MATERIALS AND METHODS: A retrospective case-control study was carried out using a Down's syndrome assays database over a 6-year period, between the 8th and 11th week of pregnancy. There were 164 women with PAPP-A multiples of median (MoM) levels <0.3 and 1,640 women with PAPP-A MoM levels ≥0.3 who served as a control group. Outcome measures were the prevalence of miscarriages, gestational hypertension, preeclampsia, pre-term delivery, gestational diabetes and intrauterine growth retardation in both groups. RESULTS: The two groups significantly differed only for miscarriages: 29 (17.7%) vs. 159 (9.7%), p = 0.04, OR 1.7; gestational hypertension: 15 (9.1%) vs. 74 (4.5%), p = 0.02, OR 2.1, and preeclampsia: 9 (5.5%) vs. 29 (1.8%), p = 0.02, OR 2.5. DISCUSSION: Even if in this study the PAPP-A cutoff considered was lower and was assayed in an earlier period compared with other studies, the detection rate for adverse pregnancy outcomes did not improve.

Neutrophil gelatinase-associated lipocalin serum evaluation through normal pregnancy and in pregnancies complicated by preeclampsia.

Neutrophil gelatinase-associated lipocalin (NGAL) was evaluated prospectively through normal pregnancy and pregnancies complicated by preeclampsia syndrome. Sixty women enrolled in the study were evaluated for serum NGAL levels at 9-11 weeks gestation, at 24-26 weeks gestation and at delivery. Thirty women were affected by preeclampsia and 30 women with uncomplicated pregnancies formed the control group. NGAL serum concentrations in the preeclampsia group were higher compared to the control group, with significant differences in each trimester. In the first trimester, the median values were: 29.9 ng/mL [interquartile range (IQR) 24.1-50.1] versus 13.6 ng/mL (IQR 9.1-19.9; p < 0.001); in the second trimester: 59.6 ng/mL (IQR 25.3-82.6) versus 16.3 ng/mL (IQR 11.3-23.3; p < 0.001); and in the third trimester: 57.2 ng/mL (IQR 18.7-70.9) versus 15.8 ng/mL (IQR 9.1-22.5; p < 0.001). NGAL serum values were positively correlated with systolic and diastolic blood pressure and with proteinuria.

Second trimester neutrophil gelatinase-associated lipocalin as a potential prediagnostic marker of preeclampsia.

Neutrophil gelatinase-associated lipocalin (NGAL) concentrations, a product of neutrophils, were investigated in normal and preeclamptic pregnancies. Prospectively collected data and late second trimester (24-26 weeks) serum samples from 48 women who subsequently developed preeclampsia (PE) and 96 control women with uncomplicated pregnancies were compared. Serum NGAL values, as determined by quantitative sandwich enzyme immunoassay, were significantly increased in the preeclamptic compared to the control women: 76.9 ng/ml (interquartile range 39.7-96.5) versus 16.0 ng/ml (interquartile range 11.2-24.4) (p<0.001), and were positively correlated to blood pressure and proteinuria, showing a high sensitivity (75%) and specificity (94.5%). The results suggest that serum NGAL might be involved in the pathophysiology of PE and could be a marker for this syndrome.

Endoglin, PlGF and sFlt-1 as markers for predicting pre-eclampsia.

OBJECTIVE: To evaluate the ability of endoglin, placental growth factor (PlGF) and the soluble form of vascular endothelial growth factor receptor (sFlt-1) measurements in gestational weeks 24-28 were used to predict pre-eclampsia. DESIGN: Observational, prospective study. Setting. Department of Gynecological, Obstetrical Sciences and Reproductive Medicine, University of Messina. Sample. Fifty-two pre-eclamptic and 52 healthy pregnant women. METHODS: A maternal serum sample was frozen and stored at 1-h 50-g glucose challenge test between 24 and 28 weeks' gestation. A second maternal serum sample was collected at admission for the onset of the disease in the pre-eclamptic group and at admission for delivery in the control group. Levels of endoglin, sFlt-1 and the PlGF were measured in the stored serum. Pre-eclamptic subjects were also divided into women with early-onset (<37 weeks) and women with late-onset pre-eclampsia (> or =37 weeks). RESULTS: Levels of endoglin, sFlt-1, and sFlt-1:PlGF ratio were found to be higher in the pre-eclamptic group in both trimesters. No differences were found between early- and late-onset pre-eclamptic. The Receiver Operating Characteristics curve, applied to the second trimester marker values, showed the best diagnostic profile for sFlt-1:PlGF (area under the curve, AUC=0.92) followed by endoglin (AUC=0.88), sFlt-1 (AUC=0.87) and PlGF (AUC=0.83). This finding was confirmed by Bayesian analysis which highlighted a specificity, a sensitivity, a diagnostic accuracy, a positive predictive value and a negative predictive value of 88.5% for sFlt-1:PlGF using a cut-off of 38.47. CONCLUSIONS: Endoglin, PlGF and sFlt-1 might be used as markers for predicting pre-eclampsia, but sFlt-1:PlGF seems to be more accurate.

Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate in a 12-month, prospective, randomized, double-blind, placebo-controlled study whether pure administration of the phytoestrogen genistein (54 mg/d) might reduce the number and severity of hot flushes in postmenopausal women with no adverse effect on the endometrium. DESIGN: A total of 389 participants met the main study criteria and were randomly assigned to receive the phytoestrogen genistein (n=198) or placebo (n=191). About 40% of participants in both groups did not suffer from hot flushes, and the evaluation was performed in a subgroup of 247 participants (genistein, n=125; placebo, n=122). Reductions from baseline in the frequency and severity of hot flushes were the principal criteria of efficacy. Endometrial thickness was evaluated by ultrasonography. The maturation value was also used to determine hormonal action on the vaginal cells. RESULTS: There were no significant differences in age, time since menopause, body mass index, and vasomotor symptoms between groups at baseline (4.4 +/- 0.33 hot flushes per day in the genistein group and 4.2 +/- 0.35 hot flushes per day in the control group). The effect was already evident in the first month and reached its peak after 12 months of genistein therapy (-56.4% reduction in the mean number of hot flushes). Furthermore, there was a significant difference between the two groups at each evaluation time (1, 3, 6, and 12 months). No significant difference was found in mean endometrial thickness and maturation value score between the two groups, either at baseline or after 12 months. CONCLUSIONS: The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on endometrium.

Midtrimester amniotic fluid leptin and insulin levels and subsequent gestational diabetes.

AIMS: To evaluate midtrimester amniotic fluid leptin levels in pregnancies subsequently complicated by gestational diabetes. METHODS: We studied 32 pregnant women with gestational diabetes and a control group of 43 normal pregnancies with an adequate gestational age fetus. All underwent a midtrimester amniocentesis: leptin and insulin were measured in the amniotic fluid. Data were compared with the Mann-Whitney U-test. RESULTS: Median leptin concentrations in the amniotic fluid of the gestational diabetes mellitus patients were significantly higher than in the control group (15.1 vs. 7.9 ng/ml) (p = 0.001); amniotic insulin concentrations were also higher in the gestational diabetes mellitus than in the control group (0.67 vs. 0.38 microU/ml) (p = 0.02). Furthermore, amniotic fluid leptin levels were directly correlated with amniotic insulin concentrations; instead, there was no correlation with maternal BMI and birth weight. CONCLUSION: Our data suggest that in pregnancies subsequently complicated by gestational diabetes, amniotic fluid leptin and insulin levels are higher in the early fetal period.

C-reactive protein as an early predictor of gestational diabetes mellitus.

OBJECTIVE: To assess whether C-reactive protein at the beginning of the midtrimester is significantly increased in patients who subsequently develop gestational diabetes mellitus (GDM). STUDY DESIGN: A total of 72 subjects who underwent a Down screening program between the 14th and 16th weeks of gestation were studied: 32 developed GDM, and 40 were controls. The C-reactive protein serum levels were evaluated in all patients. RESULTS: There was a significant difference in body mass index (BMI) mean values between the GDM group (30.8 +/- 8.5) and control group (24.7 +/- 2.8), but in spite of this, no significant difference in C-reactive protein was found in the 2 groups. The median serum C-reactive protein values were 9.0 mg/dL (2.4-17, 5-95% CI) in the GDM group and 8.7 mg/dL (3.8-11.2, 5-95% CI) in the control group (p = 0.3). There was no correlation between C-reactive protein serum levels and BMI, birth weight or fasting insulin. CONCLUSION: C-reactive protein has no predictive value in GDM, and no positive correlation is found between BMI and this inflammation marker.

Second trimester amniotic fluid myo-inositol concentrations in women later developing gestational diabetes mellitus or pregnancy-induced hypertension.

OBJECTIVE: To evaluate myo-inositol concentrations in amniotic fluid in women later developing gestational diabetes and hypertension. METHODS: A retrospective study was carried out with three groups of amniotic fluid samples (15-18 gestational weeks): 30 gestational hypertension pregnancies, 30 gestational diabetes pregnancies, and 30 normal pregnancy. RESULTS: A significant difference was observed in myo-inositol concentrations between the median gestational diabetes values (124.0 µmol/L, IQR 90.0-162.5) and the control group values (79.0 µmol/L, IQR 62.0-107.5), but also with gestational hypertension median values (79.0 µmol/L, IQR 67.75-92.0) (p < 0.001). CONCLUSIONS: This study has shown that myo-inositol concentrations in amniotic fluid increased significantly in women later developing gestational diabetes compared to the control group.

Plasma adiponectin concentration in early pregnancy and subsequent risk of hypertensive disorders.

OBJECTIVE: Adiponectin is an exclusively adipose tissue-derived protein. Low plasma adiponectin levels have been found in hypertensive men. Our objective was to evaluate whether low first-trimester plasma adiponectin values were predictive of hypertensive disorders later in pregnancy. METHODS: A nested case-control study was carried out on a cohort of 1,842 pregnant women who participated in the first-trimester Down syndrome screening program; 34 developed preeclampsia and 48 gestational hypertension. A control group of 82 nonhypertensive uneventful pregnancies was selected. Plasma adiponectin was determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Adiponectin median concentrations in the group which subsequently became hypertensive were significantly lower than those in the control group (7.6 versus 13.0 microg/mL) (P < .001). When the 2 hypertensive subgroups were considered, the plasma adiponectin median value in the preeclampsia group was significantly lower than that in the gestational hypertension group (6.6 versus 9.3 microg/mL) (P = .01). Regression analysis showed an inverse correlation between plasma adiponectin concentrations and maternal age, gestational age, body mass index, systolic blood pressure, and proteinuria. Approximately 34% of hypertensive pregnancies, compared with 7% of controls (P < .001), had plasma adiponectin concentrations less than 6.4 microg/mL (mean value of lower quartile of distribution among control patients). After adjusting for maternal age, all these women experienced a 6.6-fold (95% confidence interval 2.5-17.8) increased risk of pregnancy hypertension, compared with those women who had higher concentrations. CONCLUSION: Our findings suggest a strong association between hypoadiponectinemia and the risk of hypertensive disorders in pregnancy, especially with preeclampsia.

ICAM-1 in maternal serum and amniotic fluid as an early marker of preeclampsia and IUGR.

OBJECTIVE: To determine if plasma and amniotic fluid levels of intercellular adhesion molecule-1 (ICAM-1) at 16 weeks' gestation could be predictive of preeclampsia or intrauterine growth retardation (IUGR). STUDY DESIGN: A retrospective analysis was undertaken in 44 serum samples stored for Down's syndrome screening at 16 weeks' gestation and 44 amniotic fluid samples obtained by midtrimester amniocentesis. RESULTS: No significant difference was found between women who subsequently developed preeclampsia or IUGR and the control group. CONCLUSION: This study failed to demonstrate that ICAM-1 may be an early serum marker of preeclampsia or an amniotic fluid marker of IUGR.

The effect of the phytoestrogen genistein and hormone replacement therapy on homocysteine and C-reactive protein level in postmenopausal women.

BACKGROUND: The aim of the study was to evaluate the effect, in postmenopausal women, of the phytoestrogen genistein and hormone replacement therapy (HRT) on circulating two independent factors of cardiovascular risk: homocysteine and C-reactive protein (CRP). METHODS: Ninety healthy postmenopausal women, from 50 to 60 years of age, were randomly assigned to receive genistein (n = 30; 54 mg/die) or continuous combined estrogen/progestin therapy (17-beta-estradiol 1 mg plus norethisterone acetate 0.5 mg) or placebo. Plasma homocysteine and serum CRP were measured at baseline and after 6 months of treatment. RESULTS: In the genistein group, plasma homocysteine and serum CRP showed no statistically significant difference from baseline (homocysteine: 11.36 +/- 0.39 micromol/l; CRP: 1.73 +/- 0.31 mg/l) to 6 months treatment (homocysteine: 10.72 +/- 0.46 micromol/l; CRP: 2.13 +/- 0.45 mg/l), without any significant difference versus the placebo group (homocysteine: 11.25 +/- 0.43 micromol/l; CRP: 1.74 +/- 0.22 mg/l). In the HRT group there was a slight, but not significant reduction, of plasma homocysteine mean value from baseline (11.21 +/- 0.44 micromol/l) to 6 months treatment (10.45 +/- 0.38 micromol/l); whereas CRP mean value at the end of treatment (3.30 +/- 0.55 mg/l) was significantly higher from baseline (1.61 +/- 0.25 mg/l) (P < 0.01). However, after 6 months, no significant difference existed with the other two groups. CONCLUSIONS: The phytoestrogen genistein, after 6 months treatment, does not modify the independent cardiovascular risk linked to circulating homocysteine or CRP level. Our experience confirms critical increase of CRP serum level after HRT treatment, but not plasma homocysteine significant variation.

Is mid-trimester maternal serum inhibin-A a marker of preeclampsia or intrauterine growth restriction?

BACKGROUND: To evaluate maternal serum Multiple of Median inhibin-A in mid-trimester blood samples of women who subsequently developed preeclampsia, gestational hypertension and intrauterine growth restriction and controls. Also, to verify whether this marker is related to these pathological conditions. METHODS: Retrospective analysis of serum samples from a bank of stored serum, originally taken for Down's syndrome screening over 15-18 weeks, was performed. The sample consisted of 20 patients with gestational hypertension, 20 patients with preeclampsia, 10 patients with intrauterine growth restriction and 40 controls. RESULTS: No statistically significant difference of inhibin-A Multiple of Median values between the control group and the preeclamptic or gestational hypertension groups was found. There was a statistically significant elevation in the intrauterine growth restriction group in comparison with the control group, and the same was true for each subgroup of gestational hypertension and preeclampsia complicated by intrauterine growth restriction. CONCLUSION: Elevated maternal inhibin-A concentrations in the second trimester are strongly associated with intrauterine growth restriction and not with preeclampsia, as previously stated.

Plasma homocysteine in early and late pregnancies complicated with preeclampsia and isolated intrauterine growth restriction.

BACKGROUND: Elevated circulating homocysteine is an independent risk factor for cardiovascular disease. Increased homocysteine plasma levels have been reported to occur in approximately 20-30% of women with preeclampsia and it has been suggested that they may predict the subsequent development of preeclampsia. METHODS: In a cohort of 1874 pregnant women followed longitudinally, who participated in the Down screening program, 27 developed preeclampsia and 36 intrauterine growth restriction (IUGR). A control group of 63 uneventful pregnancies was selected. Plasma homocysteine was assayed in the early second trimester and at delivery in all groups. Data were compared with Wilcoxon's matched-pair test. RESULTS: No statistically significant difference of plasma homocysteine between controls and preeclamptic or IUGR pregnancies in the early second trimester were found. There was a significant difference, only at delivery, between the preeclamptic subjects and the controls. CONCLUSIONS: We failed to demonstrate a plasma homocysteine predictive value in pregnancies subsequently complicated by preeclampsia and IUGR. As previously stated, we found that an elevated homocysteine plasma level is associated with overt preeclampsia.

Neurokinin B and nitric oxide plasma levels in pre-eclampsia and isolated intrauterine growth restriction.

OBJECTIVE: To verify if neurokinin B plasma level is increased in pre-eclampsia and IUGR. Also, to ascertain if there is a correlation between neurokinin B plasma level and nitric oxide production. DESIGN: A total of 90 pregnant women were studied. Thirty had a gestation complicated by pre-eclampsia and 30 by isolated IUGR; the other 30 were controls. In all patients, neurokinin B plasma level and nitric oxide metabolites (nitrites/nitrates) level were measured. SETTING: University, General Hospital, Messina, Italy. METHODS: Neurokinin B blood samples were taken at 33.5 weeks of gestation and at term. Samples for nitric oxide breakdown products were taken at delivery from the antecubital vein and then from the umbilical vein. RESULTS: Neurokinin B plasma levels in the pre-eclamptic and IUGR groups were significantly higher than controls. Nitric oxide metabolites levels in pre-eclamptic and IUGR patients were also higher than controls. Regression analysis showed a significant correlation among neurokinin B plasma values and nitric oxide metabolite levels either in pre-eclampsia, in IUGR or in the control group. CONCLUSION: Neurokinin B could be involved in pregnancy haemodynamic adaptation via nitric oxide production. In pregnancies complicated with pre-eclampsia and IUGR, increased neurokinin B plasma level, correlated well with increased nitric oxide metabolite level, which may be a compensatory mechanism to improve blood flow to the uteroplacental unit.