Neutrophil function in women with pre-eclampsia.

OBJECTIVE: To investigate the function of neutrophils in normal pregnancy and pre-eclampsia. DESIGN: Baseline levels and activated responses of peripheral blood neutrophils were measured in response to the physiological agonists, n-formyl-met-leu-phe (fMLP) and zymosan activated serum. SAMPLE: Neutrophils of 16 pre-eclamptic, 17 normal pregnant (third trimester) and 15 nonpregnant age-matched control women were calculated. SETTING: Antenatal Clinic, City Hospital, Nottingham. METHODS: Neutrophil superoxide anion production was determined by lucigenin-enhanced chemiluminescence; the release of secondary granule lactoferrin by ELISA; and the expression of cell surface adhesion molecules CD11b, CD18 and L-selectin (CD62L) by flow cytometric analysis. RESULTS: Superoxide anion generation was reduced in the pregnant group compared with nonpregnant controls [fMLP by 51% (P = 0.03) and zymosan activated serum by 56% (P = 0.01)] but pre-eclamptic measurements did not show a similar reduction. There were no differences between the three study groups in the plasma levels of lactoferrin, or in the stimulated expression and release of CD11b and CD18, or lactoferrin and L-selectin. The base-line levels for the production of superoxide anions; the expression of CD11b or CD18 or L-selectin; and the release of lactoferrin showed no significant differences. CONCLUSIONS: Circulating neutrophils in pregnancy and pre-eclampsia are neither activated nor primed in vivo, however the release of reactive oxygen species is diminished in normal pregnancy. In comparison, an elevation of reactive oxygen generation in pre-eclampsia may highlight a role for neutrophils in the oxidative stress and pathophysiology of this disease.     

Impaired vascular function in women with pre-eclampsia observed with orthogonal polarisation spectral imaging

Objective To investigate in vivo the function of the microcirculation of the skin in pregnancy and pregnancy complicated with pre-eclampsia.
Design Case–control study.
Setting Academic Medical Centre.
Participants A group of 10 women with pre-eclampsia and a healthy control group of 10 pregnant women.
Methods The microcirculation of the skin of the finger at rest and during venous occlusion was studied with laser Doppler fluxmetry and orthogonal polarisation spectral imaging. By inflating a cuff around the upper arm to a pressure of 50mmHg, causing venous occlusion, the local sympathetic veno-arteriolar reflex was provoked. With laser Doppler fluxmetry the blood flow of the skin at a depth of 1–2mm was measured at rest and during venous occlusion. Orthogonal polarisation spectral imaging was used to assess red blood cell velocity at rest and during venous occlusion of the nutritive capillaries of the skin.
Results Laser Doppler fluxmetry showed no significant difference between the normotensive group and the group with pre-eclampsia. Using orthogonal polarisation spectral imaging, venous occlusion produced a significantly greater decrease in red blood cell velocity in the control group than in the women with pre-eclampsia: (84% (81–88)(median and interquartile range) vs 58% (45–88), P =0.0029). No differences in absolute red blood cell velocities were observed between groups either at rest or during venous occlusion.
Conclusion This study shows an impaired local veno-arteriolar reflex in pre-eclampsia at the nutritive, but not at the thermoregulatory, level of the microcirculation of the skin.     

Relationship between cardiovascular function and fetal growth restriction in women with pre-eclampsia

Objective

To investigate the relationship between cardiovascular function in women with pre-eclampsia and fetal growth restriction (FGR) using impedance cardiography.

Method

This retrospective study was performed with 639 participants allocated to one of 4 groups, a pre-eclampsia (PE) with FGR group, a PE without FGR group, a pregnancy-induced hypertension (PIH) without FGR group, and normal pregnancy (NP) group. Hemodynamic monitoring was performed noninvasively using impedance cardiography.

Results

Mean arterial pressure and peripheral resistance were significantly higher, and cardiac output and maternal systolic function were significantly lower, in the 2 PE groups than in the PIH and NP groups, and these differences were the greatest between the NP and the PE with FGR groups.

Conclusion

Impedance cardiography allowed to observe a gradual increase in peripheral resistance and cardiac output from the NP group to the PIH, the PE without FGR, and the PE with FGR groups. The most reduced systolic function and cardiac output and the most increased peripheral resistance was observed in the PE with FGR group.     

Increased serum phosphodiesterase activity in women with pre-eclampsia

OBJECTIVE: To measure the activity of serum phosphodiesterase (PDE) in pre-eclampsia. DESIGN: Case-control study. SETTING: Nephrology Laboratory and Obstetrics Unit at S?o Lucas Hospital from Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil. SAMPLE: Twenty-nine normal and 28 pregnant women with pre-eclampsia. METHODS: Serum was collected from women with pre-eclampsia, at the time of diagnosis, and from gestation-matched controls. Circulating PDE activity was assessed by measuring consumption of the substrate thymidine 5'-monophosphate p-nitrophenyl ester and expressed as PDE units/l. MAIN OUTCOME MEASURES: Serum PDE Activity. RESULTS: Mean substrate consumption was higher in pre-eclamptic condition (V(max)= 15.8 +/- 1.4 versus 12.7 +/- 0.9 U/L, P= 3.7 x 10(-14)). CONCLUSION: These data suggest that altered PDE activity may play a role in pre-eclampsia endothelial dysfunction.     

Impaired antioxidant activity in women with pre-eclampsia.

OBJECTIVE: To investigate antioxidant activity of sera and the plasma blood levels of two potent antioxidant in women with pre-eclampsia and normotensive pregnancies. STUDY DESIGN: The antioxidant activity of sera and the blood levels of ascorbic acid and alpha-tocopherol were assayed in women with normal pregnancies (n = 33), mild pre-eclampsia (n = 8), and severe pre-eclampsia (n = 16) between 20 and 40 weeks' gestation. Ascorbic acid and alpha-tocopherol concentrations were analyzed by high-performance liquid chromatography. Antioxidant activity of sera was measured as the percent inhibition of spontaneous autoxidation of a standard brain homogenate. RESULTS: Plasma levels of ascorbic acid in women with mild and severe pre-eclampsia were significantly lower than normal pregnancies (P < 0.05). Sera alpha-tocopherol levels were significantly decreased only in severe pre-eclampsia (P < 0.05). Sera antioxidant activity were significantly decreased in mild (73%) and severe (51%) pre-eclampsia compared with normal (86%) pregnancies (P = 0.02, P = 0.000, respectively). CONCLUSIONS: In women with pre-eclampsia, sera antioxidant activity and antioxidant level of plasma are decreased when compared with normotensive pregnancies. Impaired antioxidant activity and the reduction of antioxidant levels which increase the level of lipid peroxidation products may cause peroxidative damage of vascular endothelium and result in clinical symptoms of pre-eclampsia.     

Serum adenosine deaminase activity in women with pre-eclampsia

The present study investigated serum adenosine deaminase (ADA) activity and the patterns of two ADA isoenzymes, ADA1 and ADA2, and to evaluate the possible role of cell-mediated immunity as causes of the changes in ADA activity in pre-eclampsia. We measured serum activities of total ADA, ADA1 and ADA2 in pre-eclampsia (n = 22) and normal pregnancy (n = 22). Peripheral blood monocyte counts and neopterin levels, reflecting the activation of the monocyte-macrophage cell system, were also measured. In pre-eclampsia, serum total ADA and ADA2 activities were significantly increased compared with normal pregnancy (p < 0.05), which were accompanied by increases in serum neopterin levels. These results suggest that increased total ADA activity reflects increases in ADA2 activity, which may be in part related to enhanced cell-mediated immunity during pre-eclampsia.     

Thyroid function in pre-eclampsia

Summary. Thyroid function was studied in 24 proteinuric pre-eclamptic patients and 24 gestation-matched controls. The pre-eclamptic patients had significantly lower mean total (TT4) and free thyroxine (FT4), and thyroxine-binding globulin (TBG) concentrations, and the concentration of thyroid-stimulating hormone was significantly higher. The mean total triiodothyronine (TT3) concentration, however, was similar to the controls. This is at variance with the classical low T3 syndrome reported previously for pre-eclamptic patients. Compared to the controls, 33·3% and 29·2% of the pre-eclamptic patients had low TT4 and TT3 concentrations respectively. Pre-eclamptic patients with low TT4/ TT3 had significantly higher plasma urate concentrations. Thyroid hormone concentrations may reflect the severity of pre-eclampsia.     

Thyroid function in pre-eclampsia

Thyroid function was studied in 24 proteinuric pre-eclamptic patients and 24 gestation-matched controls. The pre-eclamptic patients had significantly lower mean total (TT4) and free thyroxine (FT4), and thyroxine-binding globulin (TBG) concentrations, and the concentration of thyroid-stimulating hormone was significantly higher. The mean total triiodothyronine (TT3) concentration, however, was similar to the controls. This is at variance with the classical low T3 syndrome reported previously for pre-eclamptic patients. Compared to the controls, 33.3% and 29.2% of the pre-eclamptic patients had low TT4 and TT3 concentrations respectively. Pre-eclamptic patients with low TT4/TT3 had significantly higher plasma urate concentrations. Thyroid hormone concentrations may reflect the severity of pre-eclampsia.     

Serum humanin concentrations in women with pre-eclampsia compared to women with uncomplicated pregnancies

Purpose: To compare serum humanin concentrations in pregnant women with and without pre-eclampsia (PE).

Materials and methods: A case-control study where pregnant women (PE group, n?=?37; control group, n?=?34) studied through history parameters (gynecological, obstetrical, personal, and family), physical and sonographic examination parameters [body mass index (BMI), blood pressure obstetrical ultrasound], and biochemical/hormonal assays [creatinine, urea, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), uric acid, platelets, urinary protein, and humanin].

Results: There was no difference in basic characteristics between women with PE and control, except in parity and gravidity. Humanin concentrations were higher in women with PE compared to controls (422.2?±?33.5 vs. 319.1?±?28.1?pg/ml, p?=?0.023). In a binary logistic analysis, humanin was associated with the presence of PE [odds ratio 1.003, 95% confidence interval (CI); 1.000–1.006]. The ability of humanin to discriminate between women with PE and controls was evaluated by receiver operation characteristics (ROC) analysis [area under the curve (AUC) 0.639, 95% CI; 0.510–0.768, p?=?0.045].

Conclusions: Serum humanin concentrations are increased in women with PE, compared to women with uncomplicated pregnancies, suggesting a potential protective role of humanin against the oxidative stress and endothelial dysfunction occurring in PE.     

Dietary supplementation with L-arginine or placebo in women with pre-eclampsia

BACKGROUND: To investigate the effect of dietary intake of the NO-donor L-arginine on the diastolic blood pressure in women with pre-eclampsia. METHODS: A randomized double-blind study was designed to compare the effect of L-arginine and placebo in pre-eclamptic women with gestational length ranging from 28+0 to 36+0 weeks. The women received orally 12 g of L-arginine or placebo daily for up to 5 days. The primary end-point was to identify a difference in diastolic blood pressure alteration between the two groups after 2 days of intervention. Secondary end-points included the interval from study start to delivery, the proportion of women delivered after 2, 5 or 10 days from treatment start and mean birth weight. RESULTS: There was no statistically significant alteration in diastolic blood pressure in the L-arginine group compared with the placebo group after 2 days of treatment (p = 0.4). No differences in the proportions of women delivered by day 2, 5 or 10 after study start, in the mean interval from study start to delivery, or in mean birth weight percentile were observed between the two groups. CONCLUSIONS: Oral L-arginine supplementation did not reduce mean diastolic blood pressure after 2 days of treatment compared with placebo in pre-eclamptic patients with gestational length varying from 28 to 36 weeks. Whether L-arginine treatment could be clinically beneficial for the mother or the fetus if started earlier in the disease process than for the women in our study remains to be seen.     

Endothelin-l in feto-placental tissues from normotensive pregnant women and women with pre-eclampsia

AIMS: The pathogenesis of pre-eclampsia is still unclear. Placental hypoperfusion, which precedes the maternal manifestations of pre-eclampsia, could be due to some vasoconstrictor factor/s like endothelin-1. The aim of the study therefore was to estimate the levels of endothelin-1 in feto-placental tissue homogenates from normotensive pregnant women and women with pre-eclampsia. METHOD AND MATERIAL: Fresh, vaginally delivered placentae from ten normotensive pregnant women and nine women with pre-eclampsia were carefully dissected and 4 gm each of amnion, chorion laeve, placental plate chorion, fetal placenta (fetal surface of the placenta) and maternal placenta (surface of the placenta attached to the uterine wall) were obtained. These tissues were then thoroughly washed in a 0.5 M phosphate buffer, pH 7.5, at room temperature and then individually homogenized for one minute in 4 ml of the same buffer. After centrifugation the supernatant was removed. The pellet was re-suspended in buffer, re-homogenized and then centrifuged. The supernatant was removed and the procedure was repeated once again and the three supernatants of each tissue were pooled. Endothelin-1 was estimated by RIA. All results are presented as mean+/-SEM. Statistical analysis was performed using students 't' test for unpaired samples and a 'p' value of <0.05 was considered significant. RESULTS: In tissues from normotensive pregnant women, no significant differences were evident in endothelin-1 concentrations in the chorion laeve, fetal placenta and maternal placenta but were significantly higher than those in the amnion and placental plate chorion (p<0.01). In tissues from pre-eclamptic women, no significant differences were evident between endothelin-1 concentrations in the chorion laeve, placental plate chorion and fetal placenta. Mean endothelin-1 concentration in the amnion and maternal placenta were significantly lower than those in chorion laeve, placental plate chorion and fetal placenta (p<0.01). Endothelin-1 concentrations were significantly higher in the amnion, chorion laeve, placental plate chorion and fetal placenta from women with pre-eclampsia when compared to tissues from normotensive pregnant women (p<0.01). CONCLUSIONS: Endothelin-1 levels were significantly higher in the placental tissues from women with pre-eclampsia. Endothelin-1, being a powerful vasoconstrictor, could cause significant vasoconstriction in the placental vasculature, and alterations in endothelin-1 levels in placental vasculature may therefore have a role in the pathogenesis of pre-eclampsia.     

Abnormal platelet function in pre-eclampsia

Platelet behaviour was studied in groups of women suffering from mild and severe pre-eclampsia, and compared with normal pregnant and non-pregnant controls. Platelets from women with severe pre-eclampsia were less responsive than normal to a variety of aggregating agents, and this impairment was significant in response to collagen and vasopressin. Women with severe pre-eclampsia had raised plasma adenine nucleotide levels and lowered platelet 5-hydroxytryptamine levels compared with the controls. Platelets from women with mild pre-eclampsia showed only a slight difference from normal. These findings may be the result of platelets having undergone aggregation and disaggregation within the circulation, and suggest that platelets may be involved in the pathogenesis of pre-eclampsia.     

Lipoprotein(a) levels in women with pre-eclampsia and in normotensive pregnant women

AIM: To determine if plasma lipoprotein(a) levels are elevated in pre-eclampsia and if so, their association with the severity of the disease. METHODS: Ninety-one pre-eclamptic (48 mild, 43 severe) and 40 healthy normotensive pregnant women at more than 32 gestational weeks were recruited into study. Plasma levels of lipoprotein(a), lipids, total protein, albumin and fibrinogen were measured in all subjects. RESULTS: All groups were comparable with respect to maternal age, maternal weight, gravidity and parity. Platelet count, total serum protein and albumin levels were significantly decreased, whereas fibrinogen levels significantly increased in the pre-eclamptic group. There was no difference between the groups with respect to total cholesterol and low-density lipoprotein levels. In the pre-eclampsic group, triglyceride and very-low-density lipoprotein concentrations were significantly higher, whereas high-density lipoprotein levels were significantly lower. No difference in serum lipoprotein(a) levels was found between the three groups. CONCLUSIONS: No statistically significant difference existed between normotensive pregnant, and pre-eclamptic women, with regard to plasma lipoprotein(a) levels. It is improbable that high serum lipoprotein(a) levels are risk factors for the development of pre-eclampsia; however, elevated triglyceride-rich lipoproteins might cause endothelial damage leading to pre-eclampsia.