Angiogenin and vascular endothelial growth factor in pregnancies complicated by preeclampsia.

OBJECTIVE: To investigate the role of the angiogenic factors, vascular endothelial growth factor (VEGF) and angiogenin in the pathophysiology of preeclampsia and how their concentrations correlate with the severity of the disease and fetal outcome. PATIENTS AND METHODS: A prospective study was carried out on 71 pregnant patients with preeclampsia and 20 pregnant normotensive controls. Maternal serum levels of VEGF and angiogenin were determined in all cases by enzyme immunoassay. Assessment of fetal well-being using the Biophysical Profile Score (BPS), umbilical and uterine artery Doppler velocimetry, and infant birthweight were carried out. RESULTS: Maternal serum VEGF and angiogenin levels were significantly increased in cases of mild and severe preeclampsia compared to controls. Their increase was positively correlated with elevated systolic and diastolic blood pressure, as well as poor BPS, abnormal Doppler velocimetry, and low birthweight. CONCLUSION: Elevated levels of both VEGF and angiogenin could confirm the existence of vascular reactivity and endothelial disturbance in preeclampsia. Measurement of these angiogenic factors in maternal serum may be a useful as biomarkers for the assessment of the severity of the disease and of fetal outcome.

Prolactin and calcitropic hormones in preterm premature rupture of membranes.

OBJECTIVES: To investigate the role of prolactin and calcitropic hormones in preterm premature rupture of membranes (PPROM) with intrauterine infection. METHODS: Amniotic fluid was retrieved by transabdominal amniocentesis from 40 patients with PPROM and 36 normal pregnant women of matched gestational age. Microbial state of amniotic cavity included culture for aerobic and anaerobic bacteria, mycoplasmas and ureaplasma. Maternal serum and fetal serum prolactin, parathyroid hormone mid-molecule PTH-M, 1,25-dihydroxyvitamin D3 and calcitonin were determined by the corresponding radioimmunoassay Maternal serum and fetal serum electrolytes were determined by ion-selective electrodes. Chlorides were assayed colorimetrically and osmolality was determined by osmometry. RESULTS: Microbiological evaluation of amniotic fluid PPROM revealed aerobic, anaerobic or mixed aerobic anaerobic infections PPROM was associated with significant elevation of both fetal serum and amniotic fluid prolactin concentrations, increased amniotic fluid osmolality, sodium, chlorides and calcium. Amniotic fluid potassium level was significantly decreased, compared with controls. Maternal serum and fetal serum PTH-M, 1,25-dehydroxyvitamin D3 were significantly higher in patients with PPROM than in controls. CONCLUSIONS: Increased amniotic fluid prolactin leads to impairment of structural integrity of fetal membranes through electrolytes disturbances. Moreover, increased amniotic fluid calcium induced by increased fetal calcitropic hormones evokes myometrial contraction through prostaglandin E2 release. Both mechanisms may combine to trigger the onset of PPROM associated with intrauterine infection.

Maternal serum and amniotic fluid cytokines in patients with preterm premature rupture of membranes with and without intrauterine infection.

OBJECTIVES: To evaluate the role of interleukins (IL-1, IL-6), tumor necrosis factor alpha (TNFalpha) and for the first time interferon gamma (IFNgamma) and epidermal growth factor (EGF) in the pathogenesis of premature rupture of membranes (PROM) with and without confirmed intrauterine infection. METHODS: Amniotic fluid was retrieved by transabdominal amniocentesis from 30 patients with PROM and 20 normal pregnant women with intact membranes of matched gestational age. Microbial state of amniotic cavity included culture for aerobic and anaerobic bacteria, mycoplasmas and ureaplasma whether or not clinical signs of chorioamnionitis were present. Maternal serum and amniotic fluid IL-1, IL-6, TNFalpha and IFNgamma concentrations were determined by the corresponding immunoradiometric assay, whereas EGF concentration was determined by a specific radioimmunoassay. RESULTS: Nearly all cases of PROM with infection revealed elevated amniotic fluid cytokines (IL-1beta, IL-6, TNFalpha, IFNgamma, EGF) whereas half of them revealed elevated serum cytokines. In cases of PROM without confirmed infection, there were no significant changes of maternal serum cytokines, whereas two-thirds of them revealed elevated amniotic fluid cytokines. CONCLUSIONS: The rise of cytokines in amniotic fluid of cases of PROM with infection may represent: (a) enhanced macrophage activity for immunosurveillance of the fetus; (b) a preparatory step for the initiation of labor; and (c) a valuable tests for diagnosing chorioamnioitis. The mechanism responsible for PROM in the presence or absence of infection is likely to be of different nature.

Biomarkers of intrinsic angiogenic and anti-angiogenic activity in patients with endometrial hyperplasia and endometrial cancer.

Serum vascular endothelial growth factor (VEGF) and endostatin were determined in postmenopausal women, including 72 with endometrial cancer, 27 with endometrial hyperplasia and 30 healthy controls. Serum VEGF levels in endometrial hyperplasia (142+/-18 ng/ml, mean +/- SE) and endometrial cancer stages I (291+/-22), II (623+/-68) and stage III-IV (1527+/-119) were significantly higher than the mean for controls (12+/-1.6). Serum endostatin levels in endometrial hyperplasia (149+/-19 ng/ml), endometrial cancer stages I (320+/-41), II (644+/-86) and stage III-IV (1253+/-114) were also significantly higher than the mean for controls (13+/-2.4). Elevated values of VEGF above the non-malignant level were encountered in 7% (stage I), 37% (stage II) and 100% (stage III-IV) of endometrial cancers. The corresponding figures for endostatin were 37%, 59 and 100%, respectively. These results demonstrate that the circulating levels of both markers correlated with tumor stage and apparently tumor burden. Serum VEGF and endostatin levels decreased significantly after treatment, followed by marked elevations at clinical relapse. The VEGF endostatin ratio was higher in the advanced stages ( > 1.0) than in the early stages of endometrial carcinoma (< 1.0). indicating that the balance of angiogenic stimulators and inhibitors may regulate metastasis and access tumor progression.

The clinical value of microtransferrinuria and microalbuminuria in the prediction of pre-eclampsia.

The aim of this study is to determine whether the presence of microtransferrinuria and microalbuminuria detected in pregnant women who are free of symptoms can predict the subsequent development of preeclampsia. One hundred fifty five pregnant women were successfully followed from 10 weeks gestation up till delivery. Pre-eclampsia developed in 31 women (17 mild and 12 severe pre-eclampsia), and eclampsia developed in two cases, whereas 124 women remained normotensive (controls). First morning urine specimens were collected during 10 to 12 weeks gestation and analyzed for microalbuminuria by a specific immunochemical test strip method. Mid-trimester mean arterial blood pressure (MAP) was also measured. Urinary microtransferrin levels in pregnant women who subsequently developed severe pre-eclampsia and eclampsia were significantly higher than those of pregnant women who remained normotensive. Microtransferrinuria as a predictor for pre-eclampsia had a sensitivity 93.5%, specificity 65%, positive predictive value 83% and negative predictive value 98.4%, whereas these values for microalbuminuria were: 50%, 58%, 50% and 91%, respectively. Urinary microtransferrin levels were significantly elevated in women with elevated MAP and in women who delivered low birth weight and low Apgar score babies. In conclusion, microtransferrinuria is a potentially more sensitive predictor of pre-eclampsia than microalbuminuria. Moreover, microtransferrinuria in early pregnancy might be a negative marker of fetal outcome in pre-eclampsia.

Maternal serum transforming growth factor beta-2 in preeclampsia and eclampsia, a potential biomarker for the assessment of disease severity and fetal outcome.

OBJECTIVE: The emerging role of transforming growth factor beta in hypertension, kidney disease, and trophoblast differentiation promoted our interest in evaluating the clinical value of assaying maternal serum TGF-beta2 levels in pregnancies complicated by preeclampsia and eclampsia. We wished to determine these levels in relation to the severity of the disease, the degree of renal involvement, and fetal outcome. METHODS: A prospective study was carried out in 50 pregnant patients with preeclampsia (PE) and eclampsia and these women were compared to 20 pregnant normotensive controls. Preeclamptic patients were subdivided into 20 cases of mild PE, 20 cases of severe PE, and 10 cases of eclampsia. Maternal serum levels of TGF-beta2 were determined in all cases by enzyme immunoassay. Maternal serum creatinine and uric acid were measured, together with an assessment of fetal well being, using the Biophysical Profile Score. RESULTS: Maternal serum TGF-beta2 levels were significantly increased in cases of severe preeclampsia and eclampsia compared to controls. This increase was positively correlated with elevated levels of serum creatinine and uric acid, as well as poor biophysical profile scores (BPS), and low birth weight (LBW). CONCLUSION: Measurement of maternal serum TGF-beta2 levels in preeclampsia may be a useful biomarker for the assessment of the severity of disease and fetal outcome in PE.

Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis.

Thirty healthy perimenopausal women who had normal lumber spine bone mineral density (LS-BMD) measured by dual energy X-ray absorptiometry (DEXA) participated in this study as controls. The pathological group comprised 50 postmenopausal osteoporotic women who had LS-BMD more that 2 SD below the normal mean of healthy perimenopausal women. Postmenopausal osteoporotic patients were allocated to three different therapeutic modalities (hormone replacement therapy HRT, alendronate or combined HRT and alendronate). Blood and urine samples were collected from all groups before and 12 months after treatment. Serum bone sialoprotein (BSP) was measured by a specific radioimmunoassay and urinary pyridinoline (Pyr), deoxy-pyridinoline (DPyr) and N-telopeptide of type 1 collagen (NTX) were determined as biomarkers of bone resorption. In addition, serum IL-11 and TGFbeta2 were measured by enzyme immunoassays. The results obtained showed that serum BSP was significantly elevated in postmenopausal osteoporosis compared to that of healthy perimenopausal controls. Significant positive correlations exist between serum BSP and biomarkers of bone resorption (Pyr,DPyr,NTX) as well as bone resorptive cytokines (IL-11,TGFbeta2). Serum BSP decreased after different antiresorptive treatments and this decrease paralleled the decrease of bone resorption markers and the increase of LS-BMD. Based on these data, circulating BSP appears to be a valuable marker of bone resorption and monitoring therapy with antiresorptive drugs in postmenopausal osteoporosis.

Plasma endothelin-1 and mean arterial pressure in the prediction of pre-eclampsia.

OBJECTIVE: To determine whether increased first trimester plasma endothelin-1 and/or increased midtrimester mean arterial blood pressure detected in pregnant women who are free of symptoms can predict the subsequent development of pre-eclampsia. METHOD: Eighty pregnant women were successfully followed from 10 weeks gestation until delivery. Pre-eclampsia and eclampsia developed in 29 and 2 women, respectively, whereas 49 women remained normotensive. Plasma endothelin-1 was determined in the first trimester (10-12 weeks gestation) by a competitive radioimmunoassay. RESULT: First trimester plasma endothelin-1 levels in pregnant women who subsequently developed mild, severe pre-eclampsia and eclampsia were significantly higher than those of pregnant women who remained normotensive. The release of endothelin-1 increases with the severity of the disease, age, body mass index and mean arterial blood pressure. The predictive values of plasma endothelin-1 for pre-eclampsia were: sensitivity 96.8%, specificity 51%, positive predictive value 55.5% and negative predictive value 91%, whereas those of MAP were 48.4, 45, 35.7 and 58%, respectively. CONCLUSION: Determination of first trimester plasma endothelin level may be a valuable marker to identify 55.5% of individuals at high risk of developing pre-eclampsia, if combined with midtrimester MAP, the positive predictive value increases to 68.2%.

Elevated levels of interleukin-2, soluble interleukin-2 receptor alpha, interleukin-6, soluble interleukin-6 receptor and vascular endothelial growth factor in serum and ascitic fluid of patients with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To investigate the possible role of vascular endothelial growth factor, interleukin-2, soluble interleukin-2 receptor alpha, interleukin-6 and soluble interleukin-6 receptor in the pathogenesis of ovarian hyperstimulation syndrome. STUDY DESIGN: The study group consisted of 10 healthy women who developed severe ovarian hyperstimulation syndrome, group A (n=10), following ovarian stimulation by long GnRHa/hMG protocol for IVF. A control group B=10 patients underwent stimulation with the same protocol and did not develop OHSS. Blood and ascitic fluid samples were assayed for VEGF, IL-2, sIL-2Ralpha, IL-6 and sIL-6R by ELISA. RESULTS: The mean serum levels of IL-2, sIL-2Ralpha, IL-6, sIL-6R and VEGF in OHSS group were 297.5+/-190, 6588+/-5566, 40.6+/-16.6, 5280+/-3326 and 492+/-165 pg/ml as compared to 50.8+/-17.4, 1100+/-391.6, 8.5+/-3.5, 516+/-342 and 167+/-31.3 pg/ml in the control group, respectively, P<0.001. The mean ascitic fluid IL-2, sIL-2Ralpha, IL-6, sIL-6R and VEGF in the OHSS group were 282.5+/-191.5 pg/ml, 26020+/-13 995, 90.5+/-36, 14900+/-2789 and 660+/-359 pg/ml as compared to 32+/-14.8, 1206+/-429.4, 12.6+/-1.7, 614+/-240 and 151+/-20.5 pg/ml, respectively, P<0.001. CONCLUSIONS: The significantly high levels of VEGF in patients with severe OHSS suggest that VEGF is a major capillary permeability agent in OHSS. Elevated levels of IL-6 in serum and peritoneal fluid support the hypothesis that IL-6 may serve as a marker of OHSS. Although serum and ascitic fluid levels of IL-2 were elevated, accumulating evidence does not support a pivotal role for IL-2 in the pathogenesis of OHSS. However, it may have a peripheral role in mediating an increase in vascular permeability. Soluble IL-2Ralpha and sIL-6R may be considered to be involved in OHSS. However, the patho-physiologic mechanism is the subject of further investigations. Clinical application of VEGF-receptors in the management of OHSS is awaited with interest.

Biomarkers of bone turnover and bone mineral density in hyperprolactinemic amenorrheic women.

We tested the hypothesis that biomarkers of bone resorption are increased in hyperprolactinemic amenorrheic patients with estrogen (E) deficiency, augmenting the possible risk of developing osteoporosis. Fifty hyperprolactinemic patients with amenorrhea of more than 12 months and with low serum E2, as well as 30 healthy fertile women (controls), matched for age and body mass index, participated in this study. Bromocriptine was administered orally to hyperprolactinemic patients and blood and urine samples were collected before and 12 weeks after treatment. Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting bone formation, and urinary deoxypridinoline (D-Pyr) and N-telopeptide of type 1 collagen (NTX) excretion, reflecting bone resorption, were measured using direct immunoassays. Hyperprolactinemic patients had higher (p < 0.0005) levels of all the biomarkers compared to control values: (OC, 22+/-1.2 [SE] vs. 14+/-.99 ng/ml (+57 %); B-ALP, 14.2+/-0.7 vs. 7.5+/-0.8 ng/ml (+89 %); D-Pyr, 8.8+/-0.6 vs. 3.2+/-0.3 nmol/mmol creatinine (+175%) and NTX, 65+/-5.1 vs. 25+/-3.2 nmol bone collagen equivalent (BCE)/mmol creatinine (+160%)). These results were associated with significantly decreased lumbar spine bone mineral density (LS-BMD), measured by dual energy X-ray absorptiometry (DEXA). Treatment of hyperprolactinemia with bromocriptine restored normal values of bone formation and resorption markers. In conclusion, hyperprolactinemia with estrogen deficiency exhibits a significant increase of bone resorption which is associated with a significant decrease of LS-BMD. These changes may subject the patient to the possible risk of developing osteoporosis.

Leptin and gestational weight gain: relation of maternal and cord blood leptin to birth weight.

OBJECTIVES: To determine maternal serum leptin concentrations throughout normal pregnancy, as well as cord blood leptin concentration, and to correlate serum and cord blood leptin levels with gestational weight gain and birth weight, respectively. METHODS: This study comprised 52 normal pregnant women, including 11 in the first, 19 in the second, and 22 in the third trimester, in addition to 30 healthy, fertile nonpregnant women of comparable age and with normal body mass index (BMI). Maternal blood and fetal cord blood samples were withdrawn from the normal, healthy pregnant women and the nonpregnant controls for the determination of serum leptin by a specific radioimmunoassay. RESULTS: Maternal serum leptin concentrations in the first trimester did not differ significantly from those of healthy nonpregnant control subjects, whereas leptin concentrations in the second and third trimesters were elevated significantly. There were significant positive correlations between maternal serum leptin concentration and gestational age, gestational weight, and BMI. Cord blood leptin concentration correlated positively with birth weight and third trimester maternal serum leptin. CONCLUSION: Elevated serum leptin is associated with maternal adiposity and risk of developing large for gestational age infants.

Elevated concentrations of angiogenin in serum and ascitic fluid from patients with severe ovarian hyperstimulation syndrome.

This study was conducted to investigate the possible role of angiogenin in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). The study group consisted of 10 healthy women who developed severe OHSS (group A) following ovarian stimulation by a long protocol of gonadotrophin-releasing hormone analogues/human menopausal gonadotrophin for in-vitro fertilization. A control group B (n = 10) underwent stimulation by the same protocol and did not develop OHSS. Blood samples were taken from group A on day of admission to hospital for treatment of OHSS and, in group B, 1 week after oocyte retrieval. In group A, ascitic fluid was routinely aspirated as a treatment for severe OHSS, and a peritoneal fluid sample was aspirated transvaginally before oocyte retrieval in group B. In group A, the mean serum angiogenin, the mean ascitic fluid angiogenin, the mean serum oestradiol concentration on day of human chorionic gonadotrophin and the mean haematocrit were 8390 +/- 6836 ng/ml, 2794 +/- 1024 ng/ml, 6300 +/- 2450 pg/ml and 46.6 +/- 4.4 respectively, as compared with 234 +/- 91 ng/ml, 254 +/- 105 ng/ml, 1850 +/- 1100 pg/ml and 36.8 +/- 4.6 in group B respectively. The differences between groups were highly significant for all parameters. Angiogenin seems to be strongly associated with the formation of neovascularization responsible for the development of OHSS.

Insulin-like growth factor binding protein-3: a novel biomarker for the assessment of the synthetic capacity of hepatocytes in liver cirrhosis.

The liver is the major source of circulating insulin-like growth factor binding protein-3 (IGFBP-3). Because the hepatic tissue is deranged in cirrhotic patients, we measured serum IGFBP-3 concentrations by two-site immunoradiometric assay in sera from 37 cirrhotic patients with different stages of hepatic dysfunction. These were compared with IGFBP-3 levels from 11 healthy controls. Serum IGFBP-3 levels in patients with chronic liver disease were significantly lower than those of the control group (P < 0.0005). The mean percent decrease in cases of early liver cirrhosis, cirrhosis without, and cirrhosis with ascites were 44%, 59%, and 82% respectively, indicating that serum IGFBP-3 levels decrease as the severity of hepatic dysfunction increases. Moreover, the decrease was more pronounced in cases with hyperbilirubinemia, elevated serum transaminases, hypoalbuminemia, and prolonged prothrombin time. There was a significant positive correlation between serum IGFBP-3 and serum albumin, as well as a significant negative correlation between serum IGFBP-3 and prothrombin time. These results indicate the close correlation of IGFBP-3 levels to worsening of hepatic functions. The determination of serum IGFBP-3 level is a clinically useful marker for the assessment of the synthetic capacity of hepatocytes in cirrhotic patients and an early predictor of impending hepatic dysfunction as well.

Radical-scavenging antioxidants in pre-eclampsia and eclampsia.

OBJECTIVE: Increased free-radical activity may be implicated in the pathogenesis of pre-eclampsia and knowledge of the response of the antioxidant systems is limited in pre-eclampsia and lacking in eclampsia. Accordingly, this study was initiated to assess total antioxidant status in pre-eclampsia and eclampsia. METHOD: Thirty-five patients with pre-eclampsia (20 mild and 15 severe), 10 patients with eclampsia and 20 normotensive women (controls) with singleton gestations in the third trimester participated in this study. Their freshly drawn blood was assayed for total antioxidant status colorimetrically using incubation mixture of ABTS, a peroxidase (metmyoglobin) and H2O2. In addition, serum fibronectin was determined by radial immunodiffusion. RESULT: Serum total antioxidant status levels in mild and severe pre-eclampsia and eclampsia were significantly lower than that of healthy pregnant women (controls). The mean percent decreases amounted to 22%, 40% and 59%, respectively, indicating the propensity of these patients to oxidative stress. CONCLUSION: These results demonstrate that radical-scavenging antioxidants are consumed by the increased free-radical activity in pre-eclampsia. The mechanisms by which free radicals are involved in endothelial dysfunction and renal injury are explained as evidenced by significant negative correlation of fibronectin and positive correlation of creatinine clearance with total antioxidants.

The clinical value of assaying maternal serum and amniotic fluid intercellular adhesion molecule 1 (ICAM-1) in cases of premature rupture of membranes.

Intercellular adhesion molecule 1 (ICAM-1) expression and upregulation induced by pro-inflammatory cytokines may be of interest in defining human response to inflammation and infection. This study was initiated to determine the levels of ICAM-1 in sera and amniotic fluid of cases of premature rupture of membranes (PROM). Serum and amniotic fluid ICAM-1 levels were determined by ELISA in 33 cases of PROM and 10 cases of normal pregnancies of matched gestational age (controls). Both serum and amniotic fluid ICAM levels were significantly elevated in 76% and 85% of cases of PROM with mean fold increments of 3.13 and 3.95, respectively. This elevation was associated with intra-amniotic infection which was detected by microbiological culture and histopathological evidence of chorioamnionitis. Increased ICAM-1 in cases of PROM may be attributed to neutrophil activation and ICAM-1 expression on fetal membranes and mononuclear cells of amniotic fluid. These results demonstrate that determination of ICAM-1 may be a valuable biomarker for early detection of acute chorioamnionitis and the possibility of PROM.

The cardiovascular safety of triphasic contraceptive steroids.

It was hypothesized that estrogen-induced cardioprotection is mediated by up-regulation and down-regulation of expression of nitric oxide (NO) and P-selectin, respectively. Published data on circulating levels of the vasodilator NO, atherogenic glycoprotein P-selectin, and lipoprotein-a [Lp(a)] in users of triphasic contraceptive steroids are lacking. A total of 30 healthy women (nonusers, controls) and 82 women using oral triphasic contraceptive steroids (ethinyl estradiol and levonorgestrel: Triovlar, Schering AG) for 18 to 24 cycles participated in this study. Fasting blood samples were obtained from users and nonusers for the determination of P-selectin and Lp(a) by enzyme immunoassay and NO by a colorimetric method. The serum Lp(a) levels in OC users were significantly higher than those of nonusers. On the other hand, the serum NO levels in OC users were significantly elevated when compared to nonusers. Plasma P-selectin was significantly lowered in OC users p < 0.005. These results demonstrate the beneficial effects of ethinyl estradiol in the triphasic contraceptive regimen. Ethinyl estradiol may afford a degree of anti-atherogenic-cardioprotective effect by up-regulation of the expression of the vasodilator NO and down-regulation of the expression of the atherogenic P-selectin. This may outweigh the cardiovascular risk of the increased atherogenic Lp(a). This study may explain the very low rate of mortality from venous thromboembolism in OC users, which compares favorably with the risks that many people accept in daily life.

Circulating nitric oxide levels in galactorrheic, hyperprolactinemic, amenorrheic women.

OBJECTIVE: To test the hypothesis that nitric oxide production is decreased in hyperprolactinemic, amenorrheic patients with estrogen (E) deficiency, augmenting the possible risk of cardiovascular disorders. SETTING: Cairo University Hospitals. DESIGN: Prospective, case-controlled study. PATIENT(S): Twenty-five galactorrheic, hyperprolactinemic patients with amenorrhea of more than 6 months and with low serum E2, as well as 30 healthy, fertile women (controls) matched for age and body mass index. INTERVENTION(S): Bromocriptine was administered orally to hyperprolactinemic patients, and blood samples were collected before and 6 weeks after treatment. MAIN OUTCOME MEASURE(S): Total nitric oxide production was determined photometrically using Greiss reagent after preliminary conversion of nitrate to nitrite by nitrate reductase. RESULT(S): Serum E2 and nitric oxide levels in hyperprolactinemic, amenorrheic patients (62.5 +/- 3.2 [SE] pg/mL [229 +/- 11.7 pmol/L] and 18.4 +/- 2.5 mumol/L, respectively) were significantly lower than E2 (114 +/- 6.4 pg/ml, [418 +/- 23.5 pmol/L]) and nitric oxide (41.2 +/- 4.1 mumol/L) levels observed in normal women during the follicular phase. The decrease of nitric oxide was associated with elevation of blood pressure. Treatment of hyperprolactinemia with bromocriptine restored normal values of serum nitric oxide and E2, and normal blood pressure. CONCLUSION(S): Hyperprolactinemia with E deficiency exhibits a significant decrease in nitric oxide production, and this decrease may subject the patient to certain cardiovascular disorders and disturbed ovarian function.

Clinical significance of urinary human tissue non-specific alkaline phosphatase (hTNAP) in pre-eclampsia and eclampsia.

The aim of this work was to determine the levels of urinary human tissue non-specific alkaline phosphatase (hTNAP) in pre-eclampsia and eclampsia in order to assess renal tubular damage. Urine samples were collected from 26 mild pre-eclamptic, 26 were pre-eclamptic, 20 eclamptic patients and 20 healthy pregnant women (controls) in their late third trimester. Urinary hTNAP/creatinine (hTNAP/cr) in severe pre-eclampsia and eclampsia were significantly higher than in controls. Urinary hTNAP/cr was increased in 23%, 77% and 90% of cases of mild pre-eclampsia, severe pre-eclampsia and eclampsia, respectively, indicating that the increase correlates with the severity of the disease. Marked elevation or urinary hTNAP/cr was also associated with bad fetal outcome. These results provide additional evidence for renal tubular damage in pre-eclampsia and eclampsia.

Enhanced expression of cytokines may play a fundamental role in the mechanisms of immunologically mediated recurrent spontaneous abortion.

OBJECTIVES: To determine circulatory levels of IL-1 beta, TNF alpha, IFN-gamma and Neopterin in immunologically mediated recurrent abortion. DESIGN: Blood samples were withdrawn from both groups of first trimester recurrent abortion and controls for the determination of serum IL-1 beta, TNF alpha, IFN-gamma by the corresponding IRMA and serum neopterin by a double antibody RIA. SETTING: Department of Obstetrics & Gynecology, Cairo University Hospitals. PATIENTS: Thirty pregnant women in their first trimester who presented with inevitable abortion with history of at least 3 prior spontaneous consecutive abortions, in addition to twenty-three pregnant women in their first trimester presented with their first miscarriage due to chromosomal anomalies (controls). Every attempt was made to eliminate the possible known contributing factors of recurrent abortion except for the presence of cervical mucus sperm antibodies which were present in 24 out of 30 cases. INTERVENTIONS: None. RESULTS: Serum IL1 beta, TNF alpha and IFN-gamma levels of the abortion group were significantly elevated when compared to the corresponding levels of controls. The incidence of abnormal high values of these cytokines varied between 40 to 70%. There was no significant difference of serum neopterin between abortion and control groups. The increase of IFN gamma, the most active principle inducing neopterin release, was below the concentration needed for neopterin stimulation. CONCLUSIONS: In view of the proven findings that cytokines do have detrimental effects on implantation, trophoblast proliferation, embryo development and fetal survival, our results suggest a potential mechanism of immunologic recurrent abortion which involves the secretion of IL-1 beta, TNF alpha, IFN gamma and other cytokines by activated endometrial lymphocytes and macrophages in response to either trophoblast or sperm antigens and these cytokines could partially defuse or penetrate into the systemic circulation.

The prevalence of serum antineutrophil cytoplasmic autoantibodies in preeclampsia and eclampsia.

OBJECTIVES: The purpose of this study was to evaluate the prevalence of antineutrophil cytoplasmic autoantibodies (ANCAs) in preeclampsia and eclampsia. METHODS: Blood samples were obtained from 26 mildly preeclamptic, 26 severely preeclamptic, and 20 eclamptic, and 20 normal pregnant women (controls) in the late third trimester for the determination of serum cytoplasmic pattern ANCA (cANCA) and perinuclear pattern ANCA (pANCA) by the corresponding enzyme immunoassay. RESULTS: Significant elevations of serum cANCA and pANCA were found in mild and severe preeclampsia and eclampsia. The extent of rise correlated well with the severity of the disease. Both ANCAs were detected in 80% of eclamptic cases versus 38.5 and 69.3% of mild and severe preeclampsia, respectively. Marked elevations of serum ANCAs were associated with poor fetal outcome. CONCLUSION: ANCAs may be involved in the pathogenesis of glomerulonephritis in preeclampsia and eclampsia and their presence may be attributed to an autoimmune mechanism initiated by autoantibody-mediated activation of neutrophils.