Marina Zonca

Hypertension in pregnancy: Changes in activin a maternal serum concentration

Human placenta is the major source of activin A in maternal circulation. The aim of the present study was to evaluate maternal activin A serum concentration in pregnant women with chronic hypertension (n = 14), pregnancy-induced hypertension (n = 10) or pre-eclampsia (n = 16). In the group of pregnant women with chronic hypertension and of healthy pregnant women (n = 10) activin A was measured in samples collected longitudinally throughout gestation. Using a specific two-site enzyme-linked immunosorbent assay, it has been possible to measure maternal serum activin A concentration. In addition, the effect of recombinant human activin A administration on mean arterial pressure and heart rate in female rats have been also investigated. Mean +/- SEM of maternal serum activin A concentration in pre-eclamptic women (57.4 +/- 28.3 ng/ml), was significantly higher than in women with pregnancy-induced hypertension (14.8 +/- 10.5 ng/ml), chronic hypertension (10.3 +/- 5.4 ng/ml) or healthy control women (9.2 +/- 9.4 ng/ml) (P < 0.01). Serum activin A levels evaluated 2 weeks after anti-hypertensive treatment were not significantly different in pre-eclamptic women. Moreover, when exogenous recombinant human activin A was administered in female rats arterial pressure or frequency of heart rate did not change. The present study showed that maternal serum activin A concentration is abnormally high in patients with pre-eclampsia. Thus, since the patients with chronic hypertension or pregnancy-induced hypertension have activin A concentration in the normal range of values, activin A may be a prognostic marker of hypertension in pregnancy.

Relevance of Prostaglandins in True Menstrual Migraine

SYNOPSIS

Blood pressure patterns in normal pregnancy and in pregnancy-induced hypertension, preeclampsia, and chronic hypertension

Objective To compare the 24-hour blood pressure (BP) pattern in physiologic pregnancy, pregnancy-induced hypertension, preeclampsia, and chronic hypertension. Methods We investigated four groups of women with singleton pregnancy: 73 controls, 48 patients with pregnancy-induced hypertension, 38 with preeclampsia, and 53 with mild to moderate chronic hypertension. The 24-hour BP monitoring was performed longitudinally in controls and in patients with chronic hypertension, and at the time of diagnosis in those with pregnancy-induced hypertension or preeclampsia. Results Nineteen thousand eight hundred seventy-two BP measurements were analyzed. In controls, the mean values of BP indices were lower than those first reported in nonpregnant women, and the acrophase was always localized in the first part of the afternoon. In pregnancy-induced hypertension and especially in preeclampsia, besides the obvious quantitative increase in BP, circadian BP oscillations were less pronounced than in controls, and the severity of hypertension seemed to favor the loss of diurnal rhythm. Conversely, in chronic hypertension, circadian oscillations were the same as in controls. Conclusion Standardized 24-hour BP monitoring during pregnancy allows quantitative and qualitative evaluations of the hypertensive status. However, if such a technique is used routinely in every clinical setting, we should establish specific thresholds of normality for pregnancy.

Vitamin E supplementation in preeclampsia.

An oxidant/antioxidant imbalance has been suggested among the pathogenetic factors involved in preeclampsia. As vitamin E is one of the most important antioxidant body components, a nonrandomized controlled trial was undertaken in 36 preeclamptic patients in order to evaluate the effect of vitamin E supplementation (100-300 mg/day per os) on fetal and maternal outcome. Fetal mortality was similar in 14 patients treated with conventional therapy plus oral vitamin E supplementation (35%) and in 22 patients treated with conventional therapy only (36%). Furthermore, in both groups of patients proteinuria increased, and increased dosages of antihypertensive drugs were called for in order to control blood pressure. We conclude that, with these dosages and in case of an already established disease, vitamin E does not improve fetal outcome in severe preeclampsia. Furthermore, it does not show favorable effects on maternal hypertension and proteinuria.

Naproxen sodium in short-term prophylaxis of pure menstrual migraine: pathophysiological and clinical considerations.

We investigated the biological and clinical effects of naproxen sodium (NxS) in the short-term prophylaxis of pure menstrual migraine (PMM) in 25 women suffering from migraine without aura, occurring exclusively from 2 days before to 5 days after menstruation onset. Daily oral NxS (550 mg) from 7 days before menstruation to 7 days after menstruation onset was given for 3 menstrual cycles, and 5 days before menstruation to 5 days after menstruation onset over the next 3 menstrual cycles. In the month before initiation of treatment and in the third month of treatment, 6-keto-PGF1α, TXB2 and PGE2 were measured in plasma before menstruation (day –2) and on the second day (day +2) after bleeding onset. In the 20 women analysed, 6-keto-PGF1α was 17% lower (p<0.0001) and TXB2 was 30% lower (p<0.0001) on day –2 during treatment than the same day pretreatment; TXB2 was also lower (p<0.02) on day +2 during treatment than day +2 pretreatment. The 6-keto-PGF1α/TXB2 ratio was higher (p<0.01) on day –2 treatment than day –2 pretreatment. PGE2 levels were significantly lower (p<0.002) on day +2 than pre-treatment values on the same day. The number of attacks reduced from 1.7±0.11 pretreatment to 1.2±0.10 at the 3rd month (p<0.001), to 1.1±0.06 at the 6th month (p<0.0001). The duration reduced from 25.6±4.42 h pretreatment to 15.5±4.43 h in the 3rd month (p<0.02), to 13.35±4.26 h in the 6th month (p<0.001). The intensity reduced from 2.4±0.11 pretreatment, to 1.2±0.10 in the 3rd month of treatment (p<0.0001), and 1.1±0.07 in the 6th month (p<0.0001).

Increased activity of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase in purified cell suspensions and single cells from the uterine cervix in cervical intraepithelial neoplasia

The activities of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase have been measured in squamous epithelial cells of the uterine cervix from normal patients and cases of cervical intraepithelial neoplasia (CIN). A biochemical cycling method, which uses only simple equipment and is suited to routine use and to automation, was applied to cells separated by gradient centrifugation. In addition, cells were examined cytochemically, and the intensity of staining in the cytoplasm of single whole cells was measured using computerised microcytospectrophotometry. Twenty per cent of cells in samples from normal patients (n=61) showed staining intensities above an extinction of 0.15 at 540 nm, compared to 71% of cases of CIN 1 (n=14), 91% of cases of CIN 2 (n=11) and 67% of cases of CIN 3 (n=15). The cytochemical data do not allow definitive distinctions to be made between different grades of CIN whereas the biochemical assay applied to cell lysates shows convincing differences between normal samples and cases of CIN. There are no false negatives for CIN 3 (n=14) and CIN 2 (n=10) and 11% false negatives for CIN 1 (n=9) and 14% of false positives for normal cases (n=21). The results of this preliminary study with reference to automation are discussed [corrected].

Production of prostacyclin, 6-keto-PGFlα and thromboxane B2 by human umbilical vessels increases from the placenta towards the fetus

Summary. The aim of this study was to investigate the production of prostacyclin (PGI2) and thromboxane B2 (TXB2) by incubated samples of umbilical arteries and veins taken at different distances (2, 10,20,30 cm) from the placenta to provide additional information relevant to the haemodynamics of umbilical blood flow. The production of PGI2, and 6‐keto‐PGF1α (the stable metabolite of PGI2), was higher in both veins and arteries as the distance from the placenta at which the vessels were sampled was increased. A similar correlation between production by venous rings and distance from the placenta was observed for TXB2, but there was no apparent gradient of TXB2 production by the samples of arterial rings. No statistically significant variations were discernible in the ratio of 6‐keto‐PGF1α:TXB2 (∼50 in the veins and ∼20 in the arteries) in relation to the sampling distance. The significance of these high ratios is discussed in relation to umbilical blood flow and fetal well‐being and development.

Platelet sensitivity to prostacyclin in normal subjects, and in patients with benign and malignant tumours of the breast

Platelet sensitivity to prostacyclin (PG12) was determined in normal male and female subjects, and in patients with benign and malignant tumours of the breast. The IC50 overall mean values for PG12 on ADP-induced platelet aggregation were similar for normal men and women, being 0.97 +/- 0.05 ng ml-1 and 0.83 +/- 0.07 ng ml-1 respectively. However, there were significant differences in the IC50 values for women in the 1st (0.81 +/- 0.06 ng ml-1) vs. 2nd (1.37 +/- 0.13 ng ml-1) phase of the menstrual cycle; post-menopausal women gave similar values to normal males and to pre-menopausal women in the 1st phase of the cycle. No significant differences were found between normal subjects and patients with benign or malignant tumours of the breast when account was taken of the status of the patient in relation to the phase of the menstrual cycle and the menopause. The importance of the hormonal status in evaluating changes in platelet sensitivity in patients with breast cancer is strongly emphasised.

24-hour blood pressure monitoring to evaluate the effects of nifedipine in pre-eclampsia and in chronic hypertension in pregnancy

Objective To investigate the effect of 7 to 14 days of therapy with nifedipine (sustained‐release preparation) on the 24‐hour blood pressure patterns of pregnant women with pre‐eclampsia or chronic hypertension, and to test the utility of blood pressure monitoring in modulating the timing and dosage of the drug.

Menstrual migraine: A possible pathogenic implication of platelet function

It has been suggested that migraine is a blood disorder caused by a primary abnormality of platelet behaviour. We have studied in different phases of the cycle of 11 healthy normal women and 13 patients suffering from menstrual migraine: 1. The platelet aggregation induced in vitro by ADP, collagen and ristocetin; 2. The platelet sensitivity to prostacyclin (PSP); 3. The platelet content of 5-hydroxytryptimine (5-HT); 4. The possible correlation between these parameters and the plasma concentration of progesterone. The results demonstrate that in patients with menstrual migraine the platelet response to various aggregating agents is not modified compared to the controls, whereas there is a different response of the PSP to the modulating effect of plasma progesterone. Moreover, in the same patients the platelets have an increased capability of accumulating 5-HT during the perimenstrual phase of the cycle. This suggests that platelet dysfunction may play a role in the pathogenesis of menstrual migraine.