Selected cytokines and glycodelin A levels in serum and peritoneal fluid in girls with endometriosis

Aim: The aim of this study was to determine the role of serum and peritoneal interleukin (IL)-6, tumor necrosis factor (TNF)-α and glycodelin A levels as diagnostic markers of endometriosis in adolescent girls. Material and Methods: The study encompassed 50 adolescent girls, aged 13-19?years, after menarche and with chronic pelvic pain who qualified for diagnostic laparoscopy. The patients were allocated into two groups: group I (endometriosis group) consisted of subjects with diagnosed endometriosis (n?=?33, 66%) and group II (control group) included those whose laparoscopic examinations revealed no evidence of endometriosis (n?=?17, 34%). IL-6, TNF-α and glycodelin A concentrations in serum and peritoneal samples were assessed using commercially available human enzyme-linked immunosorbent assay kits. The value of P?相似文献   

Serum and peritoneal fluid immunological markers in adolescent girls with chronic pelvic pain

The aim of this study was to determine serum and peritoneal interleukin (IL)-2, IL-4, and monocyte chemotactic protein-1 levels as diagnostic markers of endometriosis in adolescent girls. The design of the study encompassed 50 adolescent girls, aged 13 to 19 years after menarche, with chronic pelvic pain who qualified for diagnostic laparoscopy. The patients were allocated into 2 groups: group I (endometriosis) consisted of subjects with diagnosed endometriosis (n = 33, 66%) and group II (control) whose laparoscopic examinations revealed no evidence of endometriosis (n = 17, 34%). IL-2, IL-4, and Monocyte chemotactic protein 1 concentrations in serum and peritoneal samples were assessed using commercially available human enzyme-linked immunosorbent assay kits. The results were analyzed statistically with the Statistica 8.0 computer software. The value of P < 0.05 was the level of statistical significance. The results in adolescents with endometriosis had significantly higher concentrations of serum IL-4 (3.90 ± 1.58 pg/mL vs. 3.04 ± 1.72 pg/mL; P = 0.04) and peritoneal fluid IL-4 (5.03 ± 8.92 pg/mL vs. 2.74 ± 1.11 pg/mL; P = 0.03), and lower peritoneal fluid IL-2 (92.44 ± 292.75 pg/mL vs. 174.23 ± 389.77 pg/mL; P = 0.01) compared with the control. In a receiver-operating characteristic analysis, serum IL-4 as well as peritoneal fluid IL-2 and IL-4 provided the best discriminative ability between subjects with endometriosis and controls. Using cutoff points for serum IL-4 (3.00 pg/mL), peritoneal fluid IL-2 (21.00 pg/mL) and IL-4 (2.7 pg/mL), relatively high odd ratios were obtained in the prediction of endometriosis in adolescents (3.2; 6.4; 3.3). The Serum IL-4, peritoneal IL-2 and IL-4 provided a good method of discrimination between subjects with endometriosis and controls.     

Relative expression of 1,25-dihydroxyvitamin D3 receptor, vitamin D 1 alpha-hydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers

The authors demonstrate expression of the vitamin D receptor (VDR) and its hydroxylases in the endometrium and ovaries of women with and without endometriosis and endometrial or ovarian cancer. Immunohistochemistry showed strong staining of the VDR in endometriosis and endometrial cancer, with the most intense staining in epithelial cells. The VDR mRNA was significantly increased in patients with endometrial and ovarian cancer compared to the control group. There was a significantly higher 1 alpha-hydroxylase expression in the endometrium of patients with endometriosis compared to healthy controls. The observed differences in VDR and 1 alpha -hydroxylase mRNA levels were maintained at the protein level. The authors found no differences in 25-OH vitamin D levels between the serum of patients with endometriosis (25.7 +/- 2.1 ng/mL, n = 46) and healthy controls (22.6 +/- 2.0 ng/mL, n = 33, P = .31). They hypothesize that vitamin D might influence the local activity of immune cells and cytokines thought to play important pathogenic roles in the development and maintenance of endometriosis.     

Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis

OBJECTIVE: To evaluate soluble Fas ligand concentrations in serum and peritoneal fluid from women with endometriosis and from fertile controls without endometriosis, and to study levels of soluble Fas ligand in conditioned media of cultured endometrial stromal cells. DESIGN: Prospective, experimental trial. SETTING: Two academic IVF centers. PATIENT(S): Twenty-nine fertile women without endometriosis and 57 infertile women with endometriosis (32 with stage I or II disease and 25 with stage III or IV disease). MAIN OUTCOME MEASURE(S): Enzyme-linked immunosorbent assay was used to measure soluble Fas ligand concentrations in paired samples of serum and peritoneal fluid from women with and without endometriosis. Concentrations were also measured in conditioned media of cultured endometrial stromal cells at basal conditions and after stimulation with interleukin-8 (0.001-10 ng/mL) and tumor necrosis factor-alpha (1-10 ng/mL). RESULT(S): Compared with fertile controls and women with early-stage of endometriosis, women with moderate to severe endometriosis had elevated serum (87.2 +/- 6.4, 88.2 +/- 6.9, and 162.3 +/- 7.8 pg/mL, respectively) and peritoneal fluid (81.0 +/- 6.0, 80.5 +/- 6.8, and 166.2 +/- 10.3 pg/mL, respectively) concentrations of soluble Fas ligand. Serum levels of soluble Fas ligand positively correlated with levels in peritoneal fluid. Comparison of patients in the same menstrual cycle in each group revealed that increased levels of soluble Fas ligand in patients with advanced endometriosis were not attributable to the difference in cycle phases. Soluble Fas ligand was not detected in conditioned media of endometrial stromal cells under baseline conditions or after stimulation. CONCLUSION(S): Serum and peritoneal fluid of women with moderate to severe endometriosis contain elevated concentrations of soluble Fas ligand compared to women with minimal or mild endometriosis and women without endometriosis. These findings suggest a role for apoptotic dysregulation in the pathophysiology of endometriosis.     

Serum CA-125 in women with endometriosis and chronic pelvic pain

Since serum CA-125 concentrations are increased in women with endometriosis, the authors evaluated CA-125 levels to determine whether this serum test would be useful in differentiating between pelvic pain due to endometriosis and other causes. During a 30-month period, 163 women who had had pelvic pain for at least 3 months had a CA-125 level obtained prior to surgery. Serum CA-125 was measured by an immunoradiometric assay. Of the 82 women with endometriosis, 66 (80%) had CA-125 concentrations greater than or equal to 16 U/ml (95% upper limit). The frequencies of elevated levels in minimal, mild, moderate, and severe endometriosis were 52, 86, 100, and 100%, respectively. Of the 81 women without endometriosis, 5 (6%) had elevated concentrations. With the use of serum CA-125 determinations for the detection of endometriosis, the sensitivity was 80%, the specificity was 94%, and the accuracy was 93% when the prevalence of endometriosis was 50%. The authors conclude that determination of CA-125 levels may assist in the evaluation and treatment of women with chronic pelvic pain.     

Elevated angiogenin levels in the peritoneal fluid of women with endometriosis correlate with the extent of the disorder

OBJECTIVE: To assess the release of angiogenin into peritoneal fluid in women with and without endometriosis by measuring its concentration with reference to disease stage, presence of red lesions, and phase of the menstrual cycle. DESIGN: Retrospective study. SETTING: Nagoya City University Hospital. PATIENT(S): Sixty-four women with endometriosis (n = 38) and cystadenomas (n = 26) for whom surgery was scheduled in the proliferative or secretory phase of the menstrual cycle. INTERVENTION(S): Peritoneal fluid samples were obtained at laparotomy or laparoscopy. MAIN OUTCOME MEASURE(S): Angiogenin concentrations in the peritoneal fluid, as measured by ELISA. RESULT(S): Angiogenin concentration in the peritoneal fluid was markedly elevated in the endometriosis patients (median 515 ng/mL, interquartile range 151-1763 ng/mL) compared with the cystadenoma (control) patients (195 ng/mL, 98-324 ng/mL), with values correlating with the extent of the disease. No significant differences between the proliferative phase and the secretory phase were observed in either the controls or the endometriosis patients. CONCLUSION(S): The inflammation associated with endometriosis, through increasing levels of peritoneal fluid angiogenin, might promote angiogenesis for progression of the disease and correlate with the extent of the disorder.     

Elevations in peritoneal fluid macrophage migration inhibitory factor are independent of the depth of invasion or stage of endometriosis

OBJECTIVE: To quantify levels of macrophage migration inhibitory factor (MIF) in the peritoneal fluid (PF) of women with endometriosis, and to correlate these levels with the extent of disease. DESIGN: Controlled clinical study. SETTING: Academic medical center. PATIENT(S): Peritoneal fluid samples were collected during laparoscopic surgery in 60 women with endometriosis and 16 controls undergoing tubal ligation; 52 of the women with endometriosis had received no hormonal treatment in the 6 months prior to surgery, while 8 were using gonadotropin-releasing hormone (GnRH) agonists. MAIN OUTCOME MEASURE(S): Peritoneal fluid migration inhibitory factor (PF MIF) levels. RESULT(S): Women with endometriosis had significantly higher PF MIF levels (10.8 +/- 0.9 ng/mL) than controls (3.0 +/- 0.7 ng/mL). However, no correlation existed between MIF levels and the stage of disease (r = 0.05) or the depth of endometriotic invasion (r = 0.08). Moreover, treatment with a GnRH agonist did not suppress PF MIF levels. Peritoneal fluid MIF levels did not vary significantly between the proliferative and secretory phases of the cycle, and did not distinguish women with endometriosis-associated infertility from women with endometriosis-associated pain. CONCLUSION(S): Peritoneal fluid migration inhibitory factor levels are markedly elevated in women with endometriosis but are independent of the extent of disease.     

Peritoneal fluid and serum levels of hepatocyte growth factor may predict the activity of endometriosis

BACKGROUND: The suitable parameter in PF as well as in serum that may predict the activity of endometriosis is not well described. Therefore, we tried to examine the peritoneal fluid (PF) and serum concentrations of hepatocyte growth factor (HGF) in different revised American Society of Reproductive Medicine (r-ASRM) staging and morphologic appearances of endometriosis in an attempt to determine whether HGF can be clinically useful to predict the activity of pelvic endometriosis. METHODS: Peritoneal fluid was collected from 137 women with endometriosis and 57 women without endometriosis during laparoscopy and blood sampling was collected from 37 women with endometriosis and 21 women without endometriosis before laparoscopy. The concentration of HGF in PF and serum was measured by enzyme-linked immunosorbent assay. The ability of isolated macrophages and stroma to secrete HGF in response to lipopolysaccharide (LPS) was evaluated. RESULTS: A significantly increased concentration of HGF in PF was found in women with endometriosis (1451.75 +/- 90.7 pg/mL) than that in non-endometriosis (1120.5 +/- 77.3 pg/mL, p < 0.01) without any remarkable difference in HGF levels between women with stage I-/II endometriosis and stage III-/IV endometriosis. When we distributed serum and PF levels of HGF according to different color appearances of endometriosis, we found a significantly higher serum and PF levels of HGF in women containing dominant red peritoneal lesions in pelvic cavity (740 +/- 109.3 pg/mL for serum; 1685 +/- 183.4 pg/mL for PF) than those having other pigmented lesions (649 +/- 79.5 pg/mL, p < 0.05 for serum; 1224 +/- 67.8 pg/mL, p < 0.05 for PF) or chocolate cysts (485 +/- 43.1 pg/mL, p < 0.05 for serum; 1118 +/- 83.1 pg/mL, p < 0.01 for PF). Exogenous stimulation with LPS significantly increased the production of HGF in the culture media by macrophages and stroma derived from women with endometriosis than that in women without endometriosis. CONCLUSIONS: These results suggest that women with early or advanced endometriosis as measured by r-ASRM scoring system are not associated with an increase in either serum or PF concentrations of HGF. Rather HGF levels in serum and PF were significantly increased in women harboring blood-filled red peritoneal lesions and may be clinically useful to predict the activity of pelvic endometriosis.     

Basic Fibroblast Growth Factor: Peritoneal and Follicular Fluid Levels and its Effect on Early Embryonic Development

Objective: To investigate the effect of basic fibroblast growth factor (FGF) on preimplantation embryos and to evaluate the levels of basic FGF in follicular and peritoneal fluid.

Design: Prospective study.

Setting: University-based laboratory.

Patient(s): Follicular fluids (FFs) were obtained from women undergoing ovulation induction (n = 62) and peritoneal fluids were obtained from women with (n = 49) or without (n = 12) endometriosis.

Intervention(s): The effect of basic FGF on mouse embryos was assessed. Basic FGF concentrations were measured in pre-hCG and post-hCG FFs and in peritoneal fluids.

Main Outcome Measure(s): Two-cell murine embryos were treated with basic FGF and followed for the rate of blastocyst formation and embryo hatching. Follicular and peritoneal fluid basic FGF levels were measured by ELISA.

Result(s): Basic FGF (10 ng/mL) decreased the rate of blastocyst formation and embryo hatching. The level of basic FGF did not change in the FF around ovulation, and there was no correlation between FF basic FGF levels and reproductive parameters, with the exception of age. The levels of basic FGF in the peritoneal fluid of women with or without endometriosis were not different.

Conclusion(s): Basic FGF is present in follicular and peritoneal fluids, but its concentration in these fluids does not change during the menstrual cycle or in the presence of endometriosis. Basic FGF inhibits murine preimplantation embryonic development at concentrations 10–100 times higher than the levels detected in follicular and peritoneal fluids.     

Serum hyaluronic acid levels during pregnancy and labor

OBJECTIVE: To study the changes in concentrations of serum hyaluronic acid in uncomplicated human pregnancies. METHODS: We determined the concentrations of serum hyaluronic acid, using a specific enzyme-linked immunosorbent assay, in 70 nonpregnant women, 250 women during their pregnancies, and 68 women at the time of parturition. Results were analyzed for statistical significance with Scheffé test for multiple comparisons. RESULTS: During pregnancy, mean (+/- standard deviation) serum hyaluronic acid levels were 11.4 +/- 4.5, 13.6 +/- 2.8, 20.6 +/- 1.5, and 46.9 +/- 7.9 ng/mL at 5-14 (n = 47), 15-26 (n = 46), 27-37 (n = 58), and 38-40 (n = 99) weeks' gestation, respectively. Pregnant women in labor (n = 68) had significantly higher levels (100.4 +/- 11.3 ng/mL) than did women at term but not in labor (P < .01). CONCLUSION: Maternal serum hyaluronic acid concentrations increase as pregnancy progresses and serum levels increase significantly at term. Hyaluronic acid may be associated with cervical ripening during parturition.     

High concentrations of activin A in the peritoneal fluid of women with epithelial ovarian cancer

OBJECTIVE: The aim of the present study was to evaluate the concentrations of activin A in the peritoneal fluid of women with epithelial (serous) ovarian cancer. METHODS: A group of 160 women was studied and divided in four subgroups as follows: 1) serous ovarian carcinoma (n = 32); 2) serous ovarian cystadenoma (n = 20); 3) endometriosis (n = 53); and 4) healthy controls (n = 55), including both fertile (n = 32) and postmenopausal women (n = 23). Specimens of peritoneal fluid were collected during surgical interventions, and activin A was quantified using a specific two-site enzyme immunoassay. RESULTS: Peritoneal fluid activin A concentrations in women with ovarian carcinoma were about five-fold higher than those found in the control group (median [interquartile range] = 7.60 [2.85-10.15] and 1.50 [1.00-2.50] ng/mL, respectively, P <.001). In contrast, the women with benign serous cystadenoma had peritoneal fluid activin A concentrations (1.50 [1.0-2.70] ng/mL) similar to those of the control group. High peritoneal fluid activin A levels (>2 multiples of the mean) distinguished carcinoma from cystadenoma with a sensitivity of 72% and a specificity of 80%. The follow-up of nine patients with stage IIIc ovarian cancer showed no apparent relationship between the peritoneal fluid activin A levels and overall survival. No significant difference in peritoneal fluid activin A concentrations between patients with endometriosis and control women was observed. CONCLUSION: Most women with serous ovarian carcinoma had high concentrations of activin A in the peritoneal fluid, supporting a possible role of this growth factor in ovarian cancer.     

Altered expression of interleukin-18 in the peritoneal fluid of women with endometriosis

OBJECTIVE: Peritoneal fluid (PF) inflammatory factors may participate in the pathogenesis of endometriosis. The aim of this study was to investigate PF interleukin (IL)-18 levels in women with and without endometriosis. DESIGN: Controlled clinical study. SETTING: Women undergoing laparoscopy at a university hospital. PATIENT(S): Fifty women with previously untreated endometriosis, 8 women on GnRH agonists for endometriosis, and 18 control women with normal pelvic anatomy who were undergoing tubal ligation. INTERVENTION(S): Peritoneal fluid IL-18 levels as measured by ELISA. MAIN OUTCOME MEASURE(S): Peritoneal fluid IL-18 levels. RESULT(S): Peritoneal fluid IL-18 levels were significantly higher in women with previously untreated endometriosis (mean +/- SEM, 91.1 +/- 6.5 pg/mL) than in control women (59.4 +/- 2.0 pg/mL). Interestingly, women with superficial (100.0 +/- 10.2 pg/mL) and deep peritoneal implants (94.0 +/- 10.8 pg/mL) had significantly higher PF IL-18 levels than did women with endometriomas (57.8 +/- 1.8 pg/mL). Similarly, women with stage I-II endometriosis (97.3 +/- 8.0 pg/mL), but not women with stage III-IV endometriosis (74.9 +/- 9.9 pg/mL), had significantly higher PF IL-18 levels than did control women. Peritoneal fluid IL-18 levels were significantly higher in the luteal phase than in the follicular phase but did not discriminate between women with pelvic pain or infertility. CONCLUSION(S): Peritoneal fluid IL-18 is elevated in women with peritoneal, minimal- to mild-stage endometriosis.     

Monocyte chemotactic protein-1 concentration in peritoneal fluid of women with endometriosis and its modulation of expression in mesothelial cells

Objective: To investigate monocyte chemotactic protein-1 concentrations in the peritoneal fluid (PF) of women with or without endometriosis, then assess peritoneal mesothelial cells as a potential source of monocyte chemotactic protein-1.

Design: Prospective study.

Setting: University medical center.

Patient(s): Women with (n = 60) or without (n = 18) endometriosis.

Intervention(s): First monocyte chemotactic protein-1 levels in PF were measured, then mesothelial cells in culture were treated with cytokines.

Main Outcome Measure(s): In PF and culture supernatants, monocyte chemotactic protein-1 was measured by ELISA. In vitro monocyte chemotactic protein-1 messenger RNA expression was evaluated by Northern analysis.

Result(s): The median concentration of monocyte chemotactic protein-1 in PF of control women was 137 pg/mL (conversion factor to SI unit, 0.115; range, 12 to 418 pg/mL); that of women with moderate endometriosis was 205 pg/mL (range 65 to 6,000 pg/mL); and that of those with severe endometriosis was 1,165 pg/mL (0 to 2,602 pg/mL). Within the moderate to severe endometriosis group, monocyte chemotactic protein-1 levels were higher in women with untreated endometriosis (354 pg/mL range 0 to 6,000 pg/mL) than in women receiving GnRH agonist (128 pg/mL, range 0 to 216 pg/mL). In the control group, monocyte chemotactic protein-1 levels were higher in the proliferative phase than in the secretory phase. Mesothelial cells produced constitutively monocyte chemotactic protein-1; moreover, both interleukin-1 and tumor necrosis factor- induced higher levels of monocyte chemotactic protein-1.

Conclusion(s): Levels of monocyte chemotactic protein-1 in PF were higher during the proliferative phase than secretory phase of control women and increased in moderate to severe endometriosis. The regulated expression of monocyte chemotactic protein-1 may recruit macrophages into PF and contribute to the pathogenesis of endometriosis.     

Cardiac troponin I in pre-eclampsia and gestational hypertension

Objective To investigate serum cardiac troponin I, a sensitive marker of cardiac myocyte damage, in normal pregnancy and pregnancies complicated by hypertension with and without significant proteinuria.
Design Prospective cross sectional study.
Setting University hospital delivery suite.
Sample Serum samples obtained from women in normal pregnancy and in pregnancies complicated by hypertension with and without significant proteinuria.
Method Women with hypertension in pregnancy (at least two readings of systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg) (   n = 26  ) and normotensive women (   n = 43  ) were included in the study. Serum cardiac troponin I was measured using Beckman Access immunoassay.
Main outcome measure Serum cardiac troponin I level in the pregnancies complicated by hypertension (with and without significant proteinuria) compared with the levels measured in normotensive women.
Results The median serum cardiac troponin I level in pregnancies complicated by hypertension was 0.118 ng/mL (   n = 26  ) which was significantly greater than that measured in samples obtained from normotensive women in pregnancy (0.03 ng/mL;   n = 43  ) (   P < 0.0001  ). There were higher median serum cardiac troponin I levels in hypertensive women with significant proteinuria (0.155 ng/mL;   n = 6  ), compared with those without proteinuria (0.089 ng/mL;   n = 20  ;   P = 0.03  ).
Conclusion Serum cardiac troponin I is elevated in women with hypertensive disorders of pregnancy indicating some degree of cardiac myofibrillary damage in these disorders.     

Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology.

OBJECTIVE: To determine if interleukin 6 (IL-6) is a normal constituent of peritoneal fluid (PF), and if various types of pelvic pathology influence its presence within the PF microenvironment. STUDY DESIGN: Peritoneal fluid from 73 women obtained at the time of laparoscopy was examined for the presence of IL-6 using an IL-6 specific sandwich enzyme-linked immunosorbent assay. Thirty-nine patients had pelvic endometriosis, 17 had nonendometriotic pelvic adhesive disease, and 17 subjects undergoing tubal sterilization without evidence of pelvic pathology served as controls. RESULTS: Immunoreactive IL-6 was observed in the PF of all 73 subjects (range 0.26 to 11.16 ng/mL). The mean concentration of IL-6 was higher in women with nonendometriotic pelvic adhesions as compared with control subjects (1.28 +/- 0.16 versus 0.80 +/- 0.06 ng/mL, P less than 0.03). There was no difference in the mean peritoneal concentrations of IL-6 between women with endometriosis (1.16 +/- 0.28 ng/mL) and controls, P = 0.38. Twenty-seven of 73 patients (37%) demonstrated elevated levels (greater than 1.0 ng/mL) of IL-6. Patients with pelvic adhesions were significantly more likely to have elevated concentrations of IL-6 than controls (10/17 [59%] versus 3/17 [18%], P less than 0.02). Alternatively, the percentage of patients with elevated IL-6 concentrations did not differ between patients with endometriosis or controls (14/39 [36%] versus 3/17 [18%], P greater than 0.10). CONCLUSIONS: These findings demonstrate that IL-6 is a normal constituent of PF and that elevated levels are found in many patients with pelvic adhesions.     

Increased serum retinol-binding protein 4 concentrations in women with gestational diabetes mellitus

The authors hypothesized that serum retinol-binding protein 4 (RBP4) concentrations will be higher in gestational diabetes mellitus (GDM) subjects. This study tested both women with GDM and healthy pregnant women and correlated their serum RBP4 concentrations with body mass index (BMI) and a variety of other parameters. Also, since there is no information on the relationship between RBP4 concentrations in maternal and fetal serum, this study measured these at delivery and examined whether there were correlations between the cord serum RBP4 levels and maternal serum RBP4 concentrations, neonatal birth weights, and gestational age at delivery. A total of 40 women were evaluated: 20 women with GDM and 20 healthy pregnant women to serve as control subjects. Serum RBP4 concentrations were analyzed with the use of an enzyme-linked immunosorbent assay kit. Serum RBP4 concentrations at glucose challenge test (GCT) were significantly higher in the GDM group (42.4 +/- 13.8 ng/mL) than in the healthy control group (32.0 +/- 8.7 ng/mL; P = .007). BMI at GCT (P = .003) and GDM/no GDM (P = .014) were significantly correlated to serum RBP4 concentrations at GCT by multiple linear regression analysis. In GDM subjects, serum RBP4 concentrations immediately after delivery were significantly lower than those at GCT (30.1 +/- 11.0 ng/mL, 42.4 +/- 13.8 ng/mL; P < .001), but there was no such difference in normal subjects (30.9 +/- 10.0 ng/mL, 32.0 +/- 8.7 ng/mL; P = .581). Cord serum RBP4 concentrations were significantly lower than maternal serum RBP4 concentrations at delivery (10.9 +/- 3.8 ng/mL, 30.5 +/- 10.4 ng/mL; P < .001). Only fetal birth weight (P = .049) was independently related to cord serum RBP4 concentrations at delivery by multiple linear regression analysis. This study found increased serum RBP4 concentrations at GCT in GDM subjects, and GDM was significantly correlated to serum RBP4 levels after adjustment for the effect of BMI. Lower RBP4 concentrations were found at delivery in GDM subjects. Maternal serum RBP4 concentrations were significantly higher than cord serum RBP4 concentrations, and fetal birth weights were independently correlated to cord serum RBP4 concentrations. These findings may indicate that RBP4 plays a role in the pathogenesis of GDM. However, further experiments are required to clarify this role and find a possible regimen for GDM treatment.     

Peritoneal fluid prostaglandins and prostanoids in women with endometriosis, chronic pelvic inflammatory disease, and pelvic pain

Peritoneal fluid obtained at laparoscopy from 49 women was measured for its content of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6-KF), and thromboxane B2 (TxB2) by specific radioimmunoassays. In normal women (n = 10), the concentrations of prostaglandins in peritoneal fluid were (mean +/- SE): PGE2 = 0.79 +/- 0.26, PGF2 alpha = 0.60 +/- 0.18, 6-KF = 0.48 +/- 0.19, and TxB2 = 0.23 +/- 0.09 ng/ml; in women with endometriosis (n = 16): PGE2 = 1.43 +/- 0.72, PGF2 alpha = 1.52 +/- 0.59, 6-KF = 3.32 +/- 0.71, and TxB2 = 1.14 +/- 0.69 ng/ml; in women with chronic pelvic inflammatory disease and/or obstructed tubes (n = 19): PGE2 = 1.94 +/- 1.04, PGF2 alpha = 1.20 +/- 0.61, 6-KF = 1.55 +/- 0.40, and TxB2 = 0.64 +/- 0.24 ng/ml; in women with pelvic pain without any visible pathologic condition (n = 4): PGE2 = 1.11 +/- 0.66, PGF2 alpha = 0.73 +/- 0.55, 6-KF = 1.35 +/- 0.35, and TxB2 = 0.39 +/- 0.17. The mean volumes of peritoneal fluid recovered were 10 to 16 ml and were not significantly different between the groups. Except for a significantly elevated concentration of 6-KF in the peritoneal fluid of women with endometriosis compared to normal women (p = less than 0.02), the prostaglandins measured did not differ significantly between the groups of women studied. The possible significance of elevated 6-KF in the peritoneal fluid of women with endometriosis is discussed.     

Decreased concentrations of pigment epithelium-derived factor in peritoneal fluid of patients with endometriosis

To determine whether patients with endometriosis have altered levels of pigment epithelium-derived factor (PEDF) in peritoneal fluid, concentrations of PEDF in peritoneal fluid collected from 42 patients with endometriosis and 30 patients without endometriosis were measured with enzyme-linked immunosorbent assay. We detected significantly lower levels of peritoneal fluid PEDF in patients with endometriosis compared with patients without endometriosis, suggesting that peritoneal fluid PEDF plays a role in the pathogenesis of this disorder.     

Amniotic fluid--soluble vascular endothelial growth factor receptor-1 in preeclampsia

OBJECTIVE: To measure the levels of the soluble receptor for the potent angiogenic agent vascular endothelial growth factor (VEGF) in amniotic fluid (AF) in healthy and complicated pregnancies, and compare them with levels of erythropoietin, another factor upregulated by hypoxia. METHODS: We assessed amniotic fluid from the second (n = 35, gestational weeks 14-19) and third (n = 29) trimesters of healthy women, and from the third trimesters of preeclamptic (n = 22) and diabetic women with (n = 11) or without preeclampsia (n = 34) and from women with fetal growth restriction (FGR) (n = 14) for soluble VEGF receptor-1 (VEGFR-1) by enzyme-linked immunosorbent assay. RESULTS: In early normal pregnancy, AF-soluble VEGFR-1 levels were higher (median 22 ng/mL, range 2.3-29.5 ng/mL) than in the third trimester (median 13 ng/mL, range 0.5-32 ng/mL; P < .05). In preeclamptic women during the third trimester, levels were higher (median 20 ng/mL, range 10.5-37 ng/mL; P < .05) than healthy controls. The lowest third-trimester levels were in diabetic women (median 11 ng/mL, range 0.5-27 ng/mL). In women with preeclampsia and diabetes, AF-soluble VEGFR-1 levels remained lower (median 13, range 6-32 ng/mL; P < .05) than in women with preeclampsia alone. Amniotic fluid levels of soluble VEGFR-1 in women with FGR (median 19.5 ng/mL, range 5-40 ng/mL) did not statistically differ from those of controls. The AF levels of soluble VEGFR-1 did not correlate with those of erythropoietin. Soluble VEGFR-1 was clearly detectable (median 14 ng/mL, range 9-22 ng/mL) in culture media from placental biopsies (n = 20). CONCLUSION: Preeclampsia is associated with increased levels of soluble VEGFR-1, which are independent of erythropoietin, another hypoxia-inducible factor.     

Correlation of angiogenic cytokines-leptin and IL-8 in stage,type and presentation of endometriosis

Pelvic endometriosis is a chronic inflammatory disease with an immunological background. Yet there is paucity of contemporary research exploring both the angiogenic cytokines, leptin and IL-8 for a possible role in its pathophysiology. Objective: To compare levels of both leptin and IL-8 in peritoneal fluid (PF) in women with endometriosis vs. fertile controls and correlate with disease stage, type and symptoms. Materials and methods: PF from 58 women with endometriosis and 28 women undergoing tubal ligation was collected at laparoscopy and leptin and IL-8 levels were measured using ELISA. Results showed significantly higher levels of both cytokines in women with endometriosis. Significantly higher leptin and IL-8 levels were demonstrated in patients with early peritoneal (ASRM stage I and II) and advancing disease (ASRM stage III and IV), respectively. Levels of leptin/IL-8 were significantly lower in patients with endometrioma (4.8?ng/mL/32 pg/mL) vs. implants (13.0?ng/mL/68 pg/mL). There was no correlation of infertility or chronic pelvic pain with these levels. Conclusion: Both leptin and IL-8 levels are raised in PF of women with endometriosis reflecting inflammation and dysregulated immunomodulation. Higher levels of leptin were seen in early stages; IL-8 seems to stimulate the disease in a dose-dependent manner.