Significance of serum c-erbB-2 oncoprotein, insulin-like growth factor-1 and vascular endothelial growth factor levels in ovarian cancer.

OBJECTIVES: Our aim was to determine the predictive values of serum levels of several growth factors in ovarian cancer, including soluble c-erbB-2 oncoprotein, insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF). BACKGROUND: Previous studies have shown that growth factors play an important role in carcinogenesis. METHODS: Two groups were established. One of them was the malignant group which included 41 patients with ovarian carcinoma and the other was the control group that was made up of 28 healthy volunteers. Preoperative serum samples were obtained from the patients, and c-erbB-2, IGF-1 and VEGF levels were measured in these samples using ELISA. Serum CA-125 levels were also determined, by chemiluminescent microparticle immunoassay. RESULTS: VEGF levels of the malignant group were significantly higher than those of the control group (p < 0.01). CA-125 levels were also significantly higher than the in control group (p < 0.001). Area under the ROC curve (AUC) was 0.982 for CA-125, 0.780 for VEGF, 0.603 for c-erbB-2, and 0.467 for IGF-1 in differentiating cancers from controls. CONCLUSION: Serum VEGF levels might be a predictor for diagnosis in ovarian cancer patients, while serum c-erbB-2 and IGF-1 levels do not have a clinical significance in terms of ovarian cancer (Tab. 1, Fig. 1, Ref. 46).

Diagnosis of late-onset congenital adrenal hyperplasia in clinical practice: current evaluation.

AIM: Aim of the study was to investigate the need to perform the adrenocorticotropic hormone (ACTH) stimulation test by recognizing the importance of a second look at basal serum 17-alpha hydroxyprogesterone (17-OHP) levels and calculating new serum 17-OHP cut-off level. METHODS: A total of 142 patients who had hyperandrogenism symptoms and had basal serum 17-OHP levels of higher than 1.3 ng/mL were scheduled to have an ACTH stimulation test performed. Prior to ACTH stimulation, 17-OHP levels were recorded and as second-look levels. RESULTS: Patients were divided to two groups, late-onset congenital adrenal hyperplasia (LOCAH) (25/142), non-LOCAH (117/142). There were statistically significant results related to cycle length and menstrual irregularity between two groups (P=0.042, P=0.041, respectively). In the LOCAH group, basal serum 17 OHP levels were higher than non-LOCAH (P=0.001). When basal serum 17-OHP levels were measured a second time, the need for performing the ACTH stimulation test was decreased. According to cut-off levels of 1.3 ng/mL, 100% of patients needing to take the second serum 17-OHP decreased to 83.1%, a cut-off level of 2 ng/mL decreased numbers from 74.65% to 35.92% and for 2.25 ng/mL 58.42% of patients was decreased to 26.77%. In this study we established 2.25 ng/ml is a superior cut-off level for 17-OHP, its sensitivity is 84% and specifity is 50.4%. CONCLUSION: The incidence of LOCAH is 1.35% among the patients with hyperandrogenism symptoms. We found a single measurement of serum 17-OHP level can be unreliable. Second 17-OHP test reduces the need of performing the ACTH stimulation test by approximately 30%.

Maternal and cord blood apelin, resistin and visfatin levels in gestational diabetes mellitus.

AIM: The aim of this paper was to investigate maternal and cord blood apelin, resistin and visfatin concentrations in pregnant women with and without gestational diabetes mellitus (GDM). METHODS: This case-control study was conducted on 24 women with GDM and 21 women without GDM. Maternal plasma and cord blood apelin, resistin and visfatin levels were measured with ELISA. RESULTS: The cord blood apelin levels were significantly lower in women with GDM than control subjects (111.23±31.53 vs.. 257.48±133.97 pg/mL, P=0.002). However, the decrease of maternal apelin levels in GDM group was not statistically significant (140.76±48.38 vs. 163.53±91.12 pg/mL, P=0.602). Women with GDM had lower maternal and cord blood visfatin concentrations and higher resistin concentrations than control group. Maternal resistin concentrations were significantly correlated with HOMA-IR (r=0.745, P=0.005). The apelin and visfatin levels did not correlate with HbA1c, BMI, HOMA-IR, glucose and birth weight. CONCLUSION: GDM is associated with lower cord blood apelin levels than control subjects. GDM appears to influence fetoplacental apelin metabolism. Apelin may not be directly involved in the regulation of maternal insulin sensitivity. Our results indicate that there is an increase in resistin concentrations and a decrease in visfatin concentrations in maternal serum and cord blood serum with GDM.

Serum microRNA expression in pregnancies with preeclampsia.

Preeclampsia continues to be a mortal disease of pregnant women throughout the world. Recently, geneticists, allied with obstetricians, have opened new frontiers. MicroRNAs (miRNAs) are members of a class of small, noncoding RNA molecules. They are critical posttranscriptional regulators of gene expression. We extracted circulating miRNA from maternal plasma and quantified mir-152 and mir-210. We found up-regulated miR-210 levels as well as down-regulated mir-152 levels in preeclampsia patients.We propose that detection of increased mir-210 levels in maternal serum could be used to improve prediction methods for noninvasive prenatal diagnosis of preeclampsia.

Placental apoptosis and adhesion molecules expression in the placenta and the maternal placental bed of pregnancies complicated by fetal growth restriction with and without pre-eclampsia.

The aim of the study was to examine the expression of adhesion molecules VCAM-1 and ICAM-3 in placental tissue samples and placental bed (maternal decidual tissue) biopsies of pregnancies complicated by pre-eclampsia (PE) and fetal growth restriction (FGR), and to determine whether PE and FGR are associated with an increase in placental apoptosis. We studied placentas and placental bed samples of 49 third trimester pregnancies complicated by FGR (26 with associated PE, 23 without PE) and 25 normotensive healthy pregnant women. Placental apoptosis was assessed by the TUNEL method. Immunohistochemistry was used to assess expression of the VCAM-1 and ICAM-3. There was no significant difference in the staining intensity of VCAM-1 in placentas (p=0.472) and placental bed biopsies (p=0.754) of women delivering appropriate for gestational age and growth restricted fetuses (with and without associated PE). The amount of lymphocytes staining positively with ICAM-3 was significantly higher in both placental and placental bed biopsies of women delivering growth restricted fetuses compared with control pregnancies (p<0.001). Fetal growth restricted pregnancies with associated PE showed higher staining of ICAM-3 in placental compared with placental bed samples (p=0.049). In fetal growth restricted placentas, apoptotic nuclei were more abundant compared with control placentas (p<0.001). Increased expression of ICAM-3 on lymphocyte surface of both maternal and fetal side, suggests lymphocyte overactivation in PE and FGR. Increased placental apoptosis may play an important role in the pathogenesis or sequelae of PE.

Circulating oxidized low-density lipoprotein and paraoxonase activity in preeclampsia.

Preeclampsia is one of the most frequent complications of pregnancy, however, little is known about its etiology. The objective of this study was to investigate the association of oxidized low-density lipoprotein (oxLDL) and paraoxonase (PON1) activity in women with either preeclampsia or normotensive (NT) pregnancy. The study groups included 41 pregnant women with preeclampsia and 33 normotensive pregnant women. In all patients maternal serum total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs) were measured using enzymatic methods. Serum PON1 activities and malondialdehyde (MDA) concentrations were measured by spectrophotometric methods, and oxLDL was measured by enzyme-linked immunoassay (ELISA). Serum concentrations of lipid parameters (TC, LDL, VLDL, and TGs) were significantly higher in preeclampsia compared with NT controls (p < 0.001, p < 0.05, p < 0.05, and p < 0.001, respectively). Serum concentrations of MDA and oxLDL were significantly higher, while PON1 activity was significantly lower in preeclampsia compared with NT controls (p < 0.001, p < 0.001, and p < 0.001, respectively). A positive correlation was detected between oxLDL and MDA (r = 0.876), and a negative correlation was detected between both MDA and oxLDL and PON1 (r = -0.837 and r = -0.759, respectively). Our data demonstrate that preeclampsia is associated with increased oxLDL and decreased PON1 activity. Elevated oxidative stress, oxLDL, dyslipidemia and decreased PON1 activities may cause vascular endothelial damage and contribute to the pathophysiology of preeclampsia.

Oxidative stress in white coat hypertension; role of paraoxonase.

Oxidative stress in sustained hypertension was shown with several biochemical parameters. Oxidized low-density lipoprotein (oxLDL) plays an important role during the atherosclerosis process and paraoxonase (PON1) can significantly inhibit lipid peroxidation. Serum PON1 activity, oxLDL and malondialdehyde (MDA) concentrations and their relationship with serum lipid parameters and systolic and diastolic blood pressures (SBP and DBP) were determined in subjects with white coat hypertension (WCH), sustained hypertension (HT) and normotension (NT). The study group consisted of a total of 86 subjects, 30 with WCH (14 male, 16 female subjects), 30 with HT (13 male, 17 female subjects) and 26 with NT (12 male, 14 female subjects). Both white coat hypertensive and hypertensive subjects had significantly higher levels of MDA than normotensives (P<0.026 and P<0.001, respectively). The oxLDL level of the HT group was significantly higher than the NT group (P<0.023). The WCH group had an oxLDL level similar to both hypertensive and normotensive groups. HT and WCH groups had significantly lower PON1 levels than the normotensive group (P<0.001). oxLDL correlated with MDA positively (P=0.008), and PON1 negatively (P=0.008). A negative correlation between MDA and PON1 (P=0.014) was detected. MDA correlated positively with both SBP and DBP (P=0.001), while PON1 correlated with both of them negatively (P=0.01 and P=0.008, respectively). OxLDL correlated with diastolic blood pressure positively (P=0.008). Our data demonstrate that oxidative stress increase in WCH is associated with a decrease in PON1 activity. The reduction in PON1 activity may be one of the factors leading to an increase in oxidative status in WCH.

Vascular endothelial growth factor in adnexal masses.

OBJECTIVES: To determine cyst fluid and serum vascular endothelial growth factor (VEGF) concentrations in patients with ovarian masses and to investigate the efficiency of this modulator in the clinical management of cystic pelvic masses. METHODS: Needle puncture for cyst fluid aspiration were performed on 88 cystic ovarian masses intraoperatively. Forty-five patients with benign and 43 patients with malignant ovarian pathology were analyzed for cyst fluid and serum VEGF concentrations. Both cystic fluid and serum VEGF concentration were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Cyst fluid VEGF levels of malignant cysts (40.65+/-17.69 ng/ml) were significantly higher than those of benign cysts (12.53+/-6.13 ng/ml; P<0.001). Similarly, higher serum VEGF concentrations were found in patients with malignant disease (0.72+/-0.17 ng/ml) compared with benign cysts (0.33+/-0.11 ng/ml; P<0.001). A statistically significant correlation was observed between cyst fluid and serum VEGF levels in both malignant and benign cysts. For serum VEGF, at a cut-off value of 0.41 ng/ml; sensitivity, specificity, PPV, and NPV were 95%, 78%, 80% and 95%, respectively. No significant correlation between cyst fluid VEGF concentration and tumor stage or grade could be found. CONCLUSIONS: Significantly higher concentrations of VEGF are present in cyst fluid and serum of patients with malignant ovarian cysts compared with benign ovarian ones. There is no relation between VEGF and tumor stage or grade.

The plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in pre-eclampsia.

The aim of the study is to investigate the plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in normotensive and pre-eclamptic pregnancies. Peripheral venous blood samples were collected before labour (35.3 +/- 1.1 and 34.2 +/- 3.4 weeks for normotensive and pre-eclamptic, respectively) and placental tissues was obtained after delivery from 34 pre-eclampsia and 33 normotensive pregnancies. The mean plasma and placental levels of malondialdehyde were significantly higher, glutathione and superoxide dismutase levels were significantly lower in pre-eclamptic compared with normotensive patients (P < 0.01). The plasma and placental levels of malondialdehyde significantly increased, glutathione and superoxide dismutase significantly decreased with the increments in diastolic blood pressure. As a conclusion maternal circulating and placental tissue levels of lipid peroxides increase whereas antioxidants decrease in pre-eclampsia. The magnitude of oxidative stress and antioxidant changes correlate well with diastolic blood pressure.

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.

Vascular cell adhesion molecule-1 (VCAM-1) and leukocyte activation in pre-eclampsia and eclampsia.

OBJECTIVE: To evaluate the levels of VCAM-1 in pre-eclampsia/eclampsia as a possible marker of leukocyte activation and endothelial damage. METHODS: We performed a case-control study on 25 healthy pregnant women and 35 patients diagnosed as pre-eclampsia or eclampsia which were randomly selected. Peripheral venous blood samples were obtained and serum levels of VCAM-1 were measured by enzyme-linked immunoassay (ELISA). RESULTS: In pre-eclampsia/eclampsia, VCAM-1 levels were higher than in normal pregnancy. Serum concentrations of VCAM-1 were significantly higher in severe pre-eclampsia and eclampsia compared to mild pre-eclampsia or healthy controls. ROC analysis detected that VCAM-1 > or = 450 ng/ml had a sensitivity of 0.79 and a specificity of 0.90 in detecting severe pre-eclampsia and eclampsia. CONCLUSION: This is the first study to correlate VCAM-1 levels with severity of disease in pre-eclampsia. Our findings indicate that increasing levels of soluble VCAM-1 are present in the circulation of patients with severe pre-eclampsia/eclampsia compared to mild pre-eclampsia or healthy pregnant women. Elevated VCAM-1 levels may represent a possible mechanism by which endothelial cells attract leukocytes and cause endothelial cell damage.

High-dose medroxyprogesterone acetate for the treatment of dysfunctional uterine bleeding in 24 adolescents.

The objective of the study was to evaluate the effectiveness of high-dose oral medroxyprogesterone acetate therapy in the management of excessive dysfunctional uterine bleeding in adolescents. The study group consisted of 24 adolescents who were hospitalized with the diagnosis of excessive uterine bleeding and anaemia. Oral medroxyprogesterone acetate tablets were administered at a total dose of 60-120 mg during the first day of admission and 20 mg per day for the following 10 days. The blood loss was reduced to acceptable levels in all patients, and actually stopped in 6 (25%) within the first 24 hours of the treatment; bleeding ceased in 29.2%, 20.8% and 25% on the second, third and fourth days respectively. Significant correlation was identified between the initial haemoglobin concentration and the time required for cessation of bleeding (r2 = 0.5, p = 0.001). Rapid saturation of the endometrium with progestogens seems to be an highly effective mode of treatment for excessive dysfunctional uterine bleeding in adolescents.

Mammographic changes in women on hormonal replacement therapy.

OBJECTIVES: In the present retrospective study, we aimed to determine the frequency and the types of mammographic changes of breast parenchyma in women receiving hormone replacement therapy (HRT). We also investigated whether there was an association between mammographic changes and some clinical and hormonal characteristics of the women on HRT. METHODS: One-hundred and eight women were included into the study. Of the 108 women, 19 were climacteric, four premature menopause, 50 spontaneous menopause and 35 surgical menopause. Prior to the start of HRT, an initial mammography was performed and it was repeated at 6- to 18-month intervals according to the women's status. Estrogen alone was started for 35 surgical menopause women and a combination of estrogen plus progesterone for the remaining 73 women. RESULTS: Group I consisted of 96 women with no parenchymal changes or a decrease in parenchymal density on mammography, whereas group II consisted of 12 women with an increase in parenchymal density (11%) during the mean period of 24 months. Endogenous E2 levels were significantly higher in group II than in group I (52.4 +/- 42.3 pg/ml vs. 32.3 +/- 29.3 pg/ml, P < 0.05). Climacterium or types of menopause did not affect the mammographical density changes. Neither the type nor the duration of HRT had an effect on mammographic density increase. CONCLUSIONS: We concluded that the endogenous E2 level might be an important role in screening the women mammographically. Long-term follow-up studies were concluded to be needed in order to evaluate the effects of HRT on mammographic changes.