Ca-ATPase Activity of Human Red Cell Ghosts: Preeclampsia,Lipid Peroxidation and MgSO4

The increased level of lipid peroxidation of red blood cells during preclampsia is considered to be responsible for the diminished Ca-ATPase activity in these cells. The level of lipid peroxidation and the Ca-ATPase activity of red blood cells from preeclamptic women, return to their normal values after in vivo and in vitro treatment with MgSO₄ for 24 h. In order to evaluate whether or not cell intactness is essential for these changes, we used either intact red blood cells or red cell ghosts from normotensive pregnant women. The intact red blood cells were treated with Fenton's reagent and then incubated with 4 mM MgSO₄. The red cells ghosts were irradiated with UV light and afterwards incubated with MgSO₄ at 4°C. Lipid peroxidation and Ca-ATPase activity were determined for all the preparations. Both, Fenton's reagent and UV irradiation increased the level of lipid peroxidation and diminished the Ca-ATPase activity of the red cell membranes. Incubation of the cells treated with Fenton's reagent, or the ghosts irradiated with UV, with 4 mM MgSO₄, returned Ca-ATPase activity and lipid peroxidation levels to normal values. The presence of MgSO4 blocked the effects in the ghosts of UV irradiation. MgSO₄ seems to better protect the red cell membrane against lipid peroxidation than other SO₄⁼ and Cl^? salts. These results indicate that the changes in the lipid peroxidation of the red cell ghosts and their Ca-ATPase activity are a result of changes to the cell membranes.     

Comparative study of the calcium adenosine triphosphatase of basal membranes of human placental trophoblasts from normotensive and preeclamptic pregnant women

The Ca-ATPase activity of plasma membranes from human trophoblast is diminished in about 50% in preeclamptic women, as compared to normotensive pregnant women. This diminution is not due to changes in the behavior of the enzyme towards the free calcium concentration, the pH or the temperature of the incubation medium. Neither does it appear to be due to the presence of some condensing factor in the membranes, since the apparent energies of activation for the two tested ranges of temperature (10-20 and 20-37 degrees C) are similar for both normotensive and preeclamptic patients. The possibility of a diminution in the turnover rate of the Ca-ATPase in the plasma membranes from the preeclamptic patients is considered.     

Effect of placental hypoxia on the plasma membrane Ca-ATPase (PMCA) activity and the level of lipid peroxidation of syncytiotrophoblast and red blood cell ghosts

Term placental villous fragments from normotensive pregnant women were incubated under hypoxia in order to induce lipid peroxidation of the placental plasma membranes and, consequently, to increase their release of lipid peroxide products into the incubation medium. The homogenates of the villous fragments were assayed for plasma membrane Ca-ATPase (PMCA) activity and TBARS. The incubation medium, after placental hypoxia, was used to incubate intact red blood cells (RBCs) from normotensive pregnant women. Similarly, intact RBCs from normotensive pregnant women were incubated with deproteinized blood plasma from normotensive pregnant women and women with preeclampsia. In all the cases, red cell ghosts were prepared from the incubated cells and assayed for PMCA and TBARS. The incubation of placental villous fragments under hypoxia led to an increase in the TBARS and a significant reduction in the PMCA activity of their homogenates, as compared to those of villous fragments incubated under normoxia. The exposure of intact RBCs from normotensive pregnant women either to the incubation medium of placental hypoxia or to deproteinized blood plasma from women with preeclampsia, caused a rise of the TBARS and a diminution of PMCA activity of the red cell ghosts. Inside-out vesicles were also prepared from intact RBCs incubated with the medium where the placental hypoxia was carried out. These vesicles were assayed for active calcium transport. Pretreatment of RBCs with the incubation medium of placental hypoxia led to a lower active calcium transport as compared to that of inside-out vesicles from RBCs without any preincubation. These results are in agreement with the idea that the RBCs can be peroxidized when passing through a highly oxidized medium, such as the placental intervillous space from women with preeclampsia. The peroxidized RBCs would contribute then to the propagation of lipid peroxidation from the placenta to nearby and far away tissues.     

Preeclampsia and Calcium‐ATPase Activity of Plasma Membranes from Human Myometrium and Placental Trophoblast

Objective: We determined calcium‐activated adenosine triphosphatase (Ca‐ATPase) activity and thiobarbituric acid‐reactive substances (TBARS) of plasma membranes from myometrium and placental trophoblast of normotensive and preeclamptic pregnant women. Methods: Samples of myometrium were obtained by uterine biopsies taken upon delivery by cesarean section from nulliparous normotensive and preeclamptic pregnant women. Placentas were obtained after full term vaginal delivery from either normotensive or preeclamptic women. Plasma membrane fractions were prepared from both myometrium and placenta and assayed for Ca‐ATPase activity and TBARS. Main Outcome Measure(s): We expected to find a higher level of TBARS and, consequently, a lower activity of Ca‐ATPase of the plasma membrane fractions obtained from both myometrium and placenta of preeclamptic women. Results: The Ca‐ATPase activity of myometrium and placental trophoblast from preeclamptic women was about 50% lower than that from normotensive women, while the TBARS were higher. Conclusions: A reduced Ca‐ATPase activity, caused by an increased level of TBARS, may result in an increase in the cytosolic calcium concentration in the vascular smooth muscle cells of preeclamptic women and thus partially explain the high blood pressure developed by these patients.     

Lipid peroxidation in pregnancy with preeclampsia and diabetes

We studied lipid peroxidation and vitamin E levels in 12 diabetic preeclamptic, 13 nondiabetic preeclamptic, 8 gestational diabetic, 25 normotensive pregnant women, and 25 healthy nonpregnant women. A significant increase in malonaldehyde (MDA) levels was observed in preeclamptic and diabetic preeclamptic women as compared to normotensive pregnant and healthy controls (p<0.001). An increase in MDA levels was observed in gestational diabetics, but the difference was not statistically significant. Likewise, a significant fall in vitamin E levels was noted in preeclamptic and diabetic preeclamptic groups as compared to controls (p<0.001). Gestational diabetics had a slight decrease in vitamin E levels relative to controls. These findings suggest that lipid peroxidation plays a role in the pathogenesis of preeclampsia.     

Functional and structural demonstration of the presence of Ca-ATPase (PMCA) in both microvillous and basal plasma membranes from syncytiotrophoblast of human term placenta

It is known that human syncytiotrophoblast (hSCT) actively transports more than 80% of the Ca(2+) that goes from maternal to fetal circulation. Transepithelial transport of Ca(2+) is carried out through channels, transporters and exchangers located in both microvillous (MVM) and basal (BM) plasma membranes. The plasma membrane Ca-ATPase (PMCA) is the most important mechanism of Ca(2+) homeostasis control in the human placenta. In this work, we reexamined the distribution of PMCA in isolated hSCT of term placenta. The PMCA activity was determined in isolated hSCT plasma membranes. A partial characterization of the PMCA activity was performed, including an evaluation of the sensitivity of this enzyme to an in vitro induced lipid peroxidation. Expression of the PMCA in hSCT plasma membranes and tissue sections was investigated using Western blots and immunohistochemistry, respectively. Our study demonstrates, for the first time, a correlation between the activity and structural distribution of PMCA in both MVM and BM of hSCT. It also demonstrates a higher PMCA activity and expression in MVM as compared to BM. Finally, PMCA4 seems to be preferentially distributed in both hSCT plasma membranes, while PMCA1 is shown to be present in the hSCT homogenate. However, the membrane fractions did not show any PMCA1 labeling. Our results must be taken into account in order to propose a new model for the transport of calcium across the hSCT.     

Osmotic fragility of red blood cells,lipid peroxidation and Ca2+-ATPase activity of placental homogenates and red blood cell ghosts in salt-loaded pregnant rats

Objective: To evaluate the osmotic fragility of red blood cells and the level of lipid peroxidation, the Ca²⁺-ATPase activity of red cell ghosts and placental homogenates from salt-loaded pregnant rats.

Methods: Salt-loaded pregnant rats received 1.8% NaCl solution ad libitum as a beverage for seven days, starting on 15th day of pregnancy. Then, it was evaluated the level of lipid peroxidation and the Ca²⁺-ATPase activity of placental homogenates and red blood cell ghosts from control and experimental rats. Furthermore, the osmotic fragility of the red blood cells was evaluated by measuring the lysis of these cells when incubated with a NaCl solution with different osmolarities.

Results: It was found that placental homogenates and red blood cell ghosts from experimental pregnant rats showed an increased level of lipid peroxidation and a lowered Ca²⁺-ATPase activity, as compared to control pregnant rats. They also presented an increased osmotic fragility of their red blood cells.

Conclusions: Salt-loaded pregnant rats showed, similar to preeclamptic women, an increased level of lipid peroxidation and a lowered Ca²⁺-ATPase activity in placental and red blood cells membranes, as well as an increased osmotic fragility of the red blood cells.     

Preeclampsia,Placenta, Oxidative Stress,and PMCA

Objective: The aim of this study is to summarize the reported evidence on the possible relationship between preeclampsia, placenta, oxidative stress and plasma membrane Ca-ATPase (PMCA) activity, responsible for fine control of intracellular calcium concentration. Methods: Literature search was conducted in MEDLINE/PubMed and several unpublished results from our laboratory were included. Results: Lipid peroxidation in placental and red blood cell plasma membranes during preeclampsia and a concomitant diminution of their PMCA activity are described. Conclusions: Uteroplacental hypoperfusion raises lipid peroxidation by-products in the blood plasma that could alter structure and functionality of the cell membranes of the endothelium and several tissues.     

Lipid peroxidation and antioxidants in preeclampsia

OBJECTIVE: To determine the changes in plasma levels of lipid peroxide, vitamin E and vitamin C in women with preeclampsia and to investigate their relationship with diastolic blood pressure. STUDY DESIGN: Cross sectional study consisting of 22 preeclamptic and 21 healthy pregnant women. Fasting venous blood samples were collected during the antepartum period and plasma levels of malondialdehyde, alpha-tocopherol and ascorbic acid were measured. RESULTS: In the preeclamptic group malondialdehyde, a lipid peroxidation product, was significantly increased, while vitamins E and C were significantly decreased compared to healthy pregnant women. A strong correlation was detected between malondialdehyde and antioxidant factors (vitamins E and C) with blood pressure. CONCLUSION: Our findings are consistent with previous studies suggesting that lipid peroxidation is an important factor in the pathogenesis of preeclampsia. In preeclampsia, antioxidant nutrients are excessively utilised to counteract the cellular changes mediated by free radicals.     

Maternal circulating nitrite levels are decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.

OBJECTIVE: To evaluate whether maternal nitric oxide synthesis in pregnancies with preeclampsia is different from that in normal normotensive pregnancies. MATERIALS: Maternal circulating combined nitrate and nitrite levels or nitrite level were compared between 10 normotensive nonpregnant women, 30 normotensive pregnant women (10 first-trimester, 10 second-trimester, and 10 third-trimester pregnancies), 20 normotensive postpartum women (10 at 1 week after delivery, and 10 at 4 weeks after delivery), and 13 preeclamptic women (32 to 40 weeks' gestation). End-products of nitric oxide synthesis were measured from maternal venous blood samples using a fluorometric assay. RESULTS: Maternal circulating nitrite levels in nonpregnant women (1.13 +/- 0.22 microM) were significantly higher than those in the first-trimester pregnant women (0.68 +/- 0.13 microM), second-trimester pregnant women (0.65 +/- 0.13 microM), third-trimester pregnant women (0.48 +/- 0.17 microM), first puerperal week women (0.36 +/- 0.16 microM), and fourth puerperal week women (0.67 +/- 0.17 microM), respectively (p < 0.05). Maternal circulating nitrite level was decreased with advancing gestation, still remained low just after delivery, and was increased 4 weeks later. There was no significant difference in maternal circulating nitrite level between preeclamptic women (0.40 +/- 0.17 microM) and third-trimester pregnant women (0.48 +/- 0.17 microM). However, there were no significant differences in maternal circulating combined nitrate and nitrite levels among the groups. CONCLUSION: These results suggest that the maternal nitric oxide synthesis is not changed in normal normotensive pregnancies and pregnancies with preeclampsia. However, plasma nitrite level, which has stronger spasmolytic activity than the activity of the nitrate, was decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.     

Elevated amniotic fluid leptin levels in pregnant women who are destined to develop preeclampsia

OBJECTIVE: To analyze whether leptin levels of the amniotic fluid elevate during early pregnancy in women destined to develop preeclampsia and to evaluate the relationship between amniotic fluid leptin levels and gestational age, maternal body mass index, and fetal sex. STUDY DESIGN: Leptin levels of the amniotic fluid were compared in two groups of women, preeclamptic (n = 20) and normotensive pregnant (n = 40), matched for fetal sex, maternal body mass index at sampling, gravidity and fetal gestational age at sampling. Furthermore, amniotic leptin levels in 400 normotensive pregnant women were analyzed for their correlation with gestational age, maternal body mass index, and fetal sex. RESULTS: Median leptin concentrations were significantly higher (p < 0.001) in the women with preeclampsia (7.3+/-0.7 ng/ml) than in the normotensive pregnant women (4.1 +/- 0.3 ng/ml), independent of fetal sex. The leptin levels in the amniotic fluid decreased with advanced gestational age (r = 0.24, p < 0.001). Amniotic fluid leptin levels in the pregnant women carrying a female fetus (5.6+/-0.3ng/ml) were significantly higher than those carrying a male fetus (4.7+/-0.2 ng/ml) (p = 0.004). CONCLUSION: Higher amniotic fluid leptin levels were observed in the preeclamptic pregnant women, and they decreased as gestational age advanced. Furthermore, the women with a female fetus were noted to have higher amniotic fluid leptin levels.     

Localization of alkaline phosphatase and Ca2+-ATPase in the cat placenta

We localized alkaline phosphatase and plasma membrane calcium-ATPase (PMCA) in the cat placental syncytiotrophoblast to address their polarized distribution and their potential as markers for specific plasma membrane purification. We used enzyme- (alkaline phosphatase) and immuno- (PMCA) histochemistry and, for alkaline phosphatase, compared data to observations on the human placenta. Alkaline phosphatase activity in the cat was localized to the decidual cell membranes, to within the associated interstitial space and on the subjacent apical (maternal facing) plasma membrane of the syncytiotrophoblast. Occasional maternal capillaries were positive on their basal surface and there was focal staining within the syncytiotrophoblast. This widespread distribution is less specific than in the human placenta where alkaline phosphatase was restricted to the apical and basal plasma syncytiotrophoblast membranes, with much greater density on the apical membrane. Expression of PMCA in the cat was restricted to the basal membrane of the syncytiotrophoblast only. This specific localization of PMCA is identical to the human placenta and all other species in which its placental localization has been studied. We conclude that the plasma membranes of the cat syncytiotrophoblast show a broadly similar functional polarization to the human and that PMCA would prove a useful marker in isolation of the cat syncytiotrophoblast basal plasma membrane.     

Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia.

AIMS: To evaluate changes in lipid profile, serum levels of malondialdehyde (MDA) and lipoprotein(a) (Lp(a)) and placental MDA in preeclamptic women, and to evaluate the atherogenic role of these changes in the pathophysiology of pre-eclampsia. METHOD: A cross-sectional study was performed in 20 normal pregnant women, 25 women with mild preeclampsia and 28 women with severe preeclampsia in the third trimester. MDA, which is the endproduct of lipid peroxidation, was measured in placental tissue by the thiobarbituric acid (TBA) method of Ohkawa and colleagues and in serum by the TBA method of Asakawa and Matsushita. Serum lipid levels were measured by with an autoanalyzer, serum apolipoprotein (Apo) A-I and Apo B were measured by nephelometric assay and serum Lp(a) level using a nephelometric agglutination assay method. In preeclamptic and normal pregnant women, multiple comparisons between groups were performed by one-way analysis of variance supplemented with Tukey's HSD post hoc test. The association between placental and serum concentrations among groups was analyzed using the Pearson correlation test. RESULTS: Serum levels of MDA, Lp(a), total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and placental MDA were significantly higher, and high-density lipoprotein cholesterol (HDL-C) and Apo A-I levels were significantly lower, in severely preeclamptic and mildly preeclamptic women than in the normal pregnant women, but no difference was observed in Apo B among groups. Serum level of Lp(a) was positively correlated with body mass index in severely preeclamptic women (r=0.489, p=0.008). A significant positive correlation was also found between serum level of MDA and systolic blood pressure in women with severe preeclampsia (r=0.375, p=0.049). CONCLUSIONS: Our findings suggest that high Lp(a), lipid peroxidation, LDL-C and TG, and low HDL-C and Apo A-I levels, are important risk factors for atherosclerosis among preeclamptic women.     

Coagulation inhibitors in preeclamptic pregnant women

Objective Our objective was to detect clinical evaluation of coagulation inhibitors in preeclamptic and normotensive pregnant women and to determine their important role in pathogenesis of preeclampsia.Methods A total of 20 mild, 20 severe preeclamptic and 45 normotensive pregnant women were included in this study. The plasma value of antithrombin III (AT-III) activity, proteins C and S activity, PT, PTT, fibrinogen and platelet counts were determined.Results The values AT-III were lower in women with severe preeclampsia than in controls (p<0.05). In all groups, there was no significantly difference in the concentration of protein C activity, protein S and fibrinogen (p>0.05). The plasma thrombocyte counts were significantly lower in severe preeclamptic women than in normotensive women (p<0.05). There was no significant difference in the prothrombin time value in all groups, but a significantly difference with regard to partial thromboplastin time between severe preeclamptic and the control group (p<0.0001). It was longer than the control.Conclusion The markers of hemostasis activation such as protein S, protein C activity together with fibrinogen levels are not useful tools but the reduction of AT-III and platelet counts would seem useful in different pathological situations in pregnancy to predict and monitor the severity of the condition.     

Evidence of endothelial cytotoxic compounds in placental extracts from preeclamptic women

OBJECTIVE: To determine whether placenta and plasma of preeclamptic women contain factors that cause endothelial cell damage. METHODS: Placental extracts and plasma from preeclamptic and normotensive women were added to cultures of normal human umbilical vein endothelial cells and their effect on their viability, was determined by MTT reduction and 51chromium release. RESULTS: Placental extracts from normotensive and preeclamptic women were cytotoxic to endothelial cells, but not the plasma from both groups. Mean +/- standard deviation values of cytotoxicity index in preeclamptic and normotensive placental extracts using the MTT reduction were 70.3 +/- 6.76% and 51.4 +/- 8.81%, respectively, showing a significant difference (P < .0001). Using the 51chromium-release assay, preeclamptic placental extracts showed cytotoxic effects of 87.6 +/- 13.47% compared with 17 +/- 20.60% in control patients. The cytotoxic activity decreased after trypsin digestion and heat treatment in both groups. CONCLUSIONS: A cytotoxic factor to endothelial cells in placental extracts of preeclamptic women was identified. This compound is thermolabile and sensitive to trypsin digestion.     

Lipid and protein oxidation and antioxidant function in women with mild and severe preeclampsia

OBJECT: The aim of this study was to evaluate the lipid and protein oxidation and antioxidant function in preeclampsia patients and in normotensive pregnant women, as well as, to assess an association with the severity of the disease. METHOD: The study was carried out in 30 patients with mild preeclampsia, 30 with severe preeclampsia, and in 50 normotensive pregnant women during the third trimester of pregnancy. Lipid peroxides in serum, placental and decidual tissues and serum protein carbonyls and some of the antioxidants were measured by spectrophotometric methods. One-way analysis of variance, chi-square test and Pearson correlation test were used for the statistical analyses. Logistic regression procedures were used to calculate odds ratios (OR). RESULTS: Lipid peroxides in serum, placenta and decidua basalis and protein carbonyls in serum were significantly increased, and vitamin E and total carotene levels in serum were significantly decreased especially in women with severe preeclampsia compared with mild preeclampsia and controls. A significant correlation was detected between diastolic blood pressure and lipid peroxides in serum, placental and decidual tissues and serum protein carbonyls. Furthermore, there was significant correlation between antioxidant vitamins and lipid and protein oxidation products in severe preeclamptic patients. Also, logistic regression analysis showed that changes in serum, placental and decidual lipid peroxides and serum protein carbonyls, vitamin E and total carotene concentrations were significantly associated with preeclampsia. CONCLUSION: Our findings suggest that lipid and protein oxidation may be an important factor in the pathogenesis of preeclampsia. Since antioxidant vitamins are significantly decreased in both severe and mild preeclamptic pregnants, early supplementation with antioxidants may be beneficial in preeclamptic patients.     

Auto antibodies against oxidized low density lipoprotein in severe preeclampsia

BACKGROUND: To study autoantibody titres against oxidized low density lipoprotein in preeclamsia. METHODS: Ten millimeters of heparinized blood samples were collected from 20 primigravidae with severe preeclamsia (study group) and 20 gestation-matched normotensive primigravidae (control group). Concentration of malondialdehyde, metabolite of lipid peroxidation were measured in sera by HPLC and autoantibodies against oxidized low density lipoproteins (obtained after oxidation with 2 mm CuSO(4)) were determined by ELISA. Statistical analysis was performed by Student's t-test and chi(2) test. RESULTS: Mean triglyceride levels were significantly (P < 0.001) higher in the study group (193.20 +/- 31.16 mg/dL) compared to the control group (170.60 +/- 23.2 mg/dL). Mean plasma lipid per oxide levels were not significantly different between the study (4.45 +/- 1.28 mmol/mL) and control (3.88 +/- 0.99 mmol/mL) groups. The majority of women in both groups had low antibody titres (<1.32) against low density lipoprotein. Six women (30%) of the study group and four (20%) of the control group had high autoantibody titres (>/=1.32). In preeclamptic women, diastolic blood pressure, the amount of urinary protein excretion and the plasma level of urea were significantly higher (P < 0.05) in patients with higher auto antibody titre. CONCLUSION: Titres of autoantibodies to oxidized low density lipoprotein were similar in normotensive and preeclamptic women. In preeclamptic women, titres correlated positively with the severity of preeclampsia.     

Nitric oxide: does it have an etiological role in pre-eclampsia?

AIM: To determine evidence of nitric oxide (NO) in decidual biopsies and fetal membranes of preeclamptic women. BACKGROUND: Nitric oxide, a potent vasodilator, has been postulated to have a role in the etiology of preeclampsia. Investigations in peripheral blood have led to conflicting results. We therefore decided to study whether immunohistochemically detectable nitric oxide is produced in the decidua and within the fetal membranes. METHODS: Forty-two pregnant women at 28 weeks gestation or more were enrolled. Twenty were normotensive and 22 had preeclampsia. Women with chronic hypertension, diabetes and multiple pregnancies were excluded. Maternal blood samples prior to cesarean section (CS), decidual biopsies during CS, and fetal membrane specimens were obtained. The tissue specimens were fixed immediately (after delivery of the baby and placenta) in formalin, washed, and embedded in paraffin. Immunohistochemical staining for nitric oxide synthases (NOS) I, II, III was performed and reviewed in conjunction with routine hematoxylin and eosin sections, using light microscopy. RESULTS: There was no statistically significant difference in the level of immunostaining of nitric oxide synthases in both normotensive and hypertensive patients. DISCUSSION: The severity of blood pressure did not influence expression of nitric oxide synthases.     

The relation of maternal serum eNOS,NOSTRIN and ADMA levels with aetiopathogenesis of preeclampsia and/or intrauterine fetal growth restriction

Objective: The aim of present study was to assess the maternal serum endothelial nitric oxide synthase (eNOS), NOSTRIN (eNOS-trafficking inducer) and asymmetric dimethylarginine (ADMA) levels in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants.

Patients and methods: The study was performed on 65 normotensive pregnant women with isolated IUGR, 64 preeclamptic women with IUGR, 51 preeclamptic women with normal intrauterine fetal growth and 65 healthy normotensive pregnant women with singleton uncomplicated pregnancies. Severe preeclampsia was defined as blood pressure >?160/110?mmHg with proteinuria >?5?g in a 24-h urinary protein excretion. IUGR were classified when the weight of the fetus was below the 10th centiles with disturbed placental function and abnormal ultrasonographic examination. The diagnosis was confirmed by the infant's weight at birth. The maternal serum eNOS, NOSTRIN and ADMA concentrations were determined using a sandwich enzyme-linked immunosorbent assays.

Results: There were no statistically significant differences in the eNOS and NOSTRIN levels between studied groups of women. Increased levels of ADMA in both preeclamptic groups and in women with pregnancies complicated by isolated IUGR were observed.

Conclusions: Our results allow the conclusion that impaired NO bioavailability in pregnancies complicated by severe preeclampsia and/or IUGR result not from a reduced level or activity of eNOS or from its disturbed intracellular transport, but from increased ADMA levels, an endogenous inhibitor of the enzyme eNOS.     

Evaluation of maternal and umbilical serum TNFalpha levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus.

OBJECTIVE: The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFalpha serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients. PATIENTS AND METHODS: The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFalpha concentrations were estimated using a sandwich ELISA assay. RESULTS AND CONCLUSIONS: Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFalpha levels than those in the normotensive controls. Our findings and other reports indicate that TNFalpha may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor alpha (TNFalpha) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental-fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.