Microvascular permeability is related to circulating levels of tumour necrosis factor-alpha in pre-eclampsia

INTRODUCTION: The mechanism for the increased microvascular permeability which, underline many of the complications of pre-eclampsia, remain unexplained. It has been suggested that a factor present in the maternal circulation in pregnancies complicated by the disease may be responsible for increased microvascular permeability. In this study, we have investigated the relationship between filtration capacity (K(f)), an index of microvascular permeability, and maternal levels of VEGF, leptin and TNF-alpha, all of which are known permeability factors whose plasma levels are increased in pre-eclampsia. METHODS: We used a small cumulative pressure step venous congestion plethysmography protocol to compare K(f), an index of microvascular permeability, during the third trimester of 20 women with pre-eclampsia, 18 normal pregnant women and 18 non-pregnant female matched controls. Blood samples were obtained to measure plasma levels of VEGF, leptin, TNF-alpha plasma protein concentrations and full blood count. RESULTS: Microvascular filtration capacity (K(f)) was significantly increased in pre-eclampsia compared to the other groups (P<0.0001, ANOVA). K(f) was also increased in the normal pregnant group when compared to the non-pregnant controls (P=0.02). Plasma levels of VEGF, leptin and TNF-alpha were significantly greater in pre-eclampsia compared to normal pregnancy and non-pregnant controls (P<0.0001, ANOVA, for all three analyses). Total plasma protein and albumin concentrations were significantly lower in the normal pregnant and pre-eclamptic groups, compared to the non-pregnant controls (P<0.0001, ANOVA). K(f) was significantly related to TNF-alpha in pre-eclampsia (r=0.53, P=0.018), and with VEGF in the non-pregnant controls (r=0.6, P=0.02). No significant relationship was observed between K(f) and VEGF, leptin and TNF-alpha during normal pregnancy. There was a significant inverse correlation between plasma albumin concentration and filtration capacity in the normal pregnant (r=-0.94, P<0.0001) and non-pregnant (r=-0.87, P<0.0001) groups but not in the women with pre-eclampsia (r=-0.18, P=0.8). CONCLUSIONS: These data show that that microvascular filtration capacity is significantly increased in pre-eclampsia, and correlates with circulating levels of TNF-alpha but not leptin or VEGF.     

Angiopoietic factors and retinopathy in pregnancies complicated with Type 1 diabetes.

AIMS: To evaluate the role of systemic angiopoietic factors in the progression of diabetic retinopathy during pregnancy. METHODS: In a prospective study of 26 pregnant women with diabetes and eight non-diabetic pregnant women, retinopathy was graded from fundus photographs. Plasma levels of angiopoietin-1, angiopoietin-2, human vascular endothelial growth factor A (hVEGF-A), and total soluble receptor of vascular endothelial growth factor (sVEGF) receptor-1 were measured during the first and third trimester and 3 months postpartum. RESULTS: In diabetic women, levels of angiopoietin-2 were 26.5 ng/ml (12.1-47.7) (median and range) during the first trimester, 2.9 ng/ml (0.6-3.5) during the third trimester, and 0.5 ng/ml (0.3-0.7) 3 months postpartum, compared with 44.3 (38.3-61.9), 5.7 (3.1-8.4) and 0.9 (0.6-4.9) ng/ml, respectively, in non-diabetic women (P = 0.002 between groups). Levels of angiopoietin-1 and sVEGF receptor-1 did not differ between the groups. Postpartum hVEGF-A levels were lowest in women with progression of retinopathy. In logistic regression analyses, progression of retinopathy during pregnancy was not explained by the levels of the angiopoietic factors. CONCLUSIONS: The circulating levels of angiopoietic factors in pregnant diabetic women were either lower than (Ang-2) or similar to (Ang-1, hVEGF-A, VEGFR-1) those levels observed in non-diabetic pregnant women. The levels of angiopoietic factors measured here appear not to be connected with the progression of retinopathy during pregnancy.     

HEPTEST: a suitable method for monitoring heparin during pregnancy.

Methods of monitoring heparin in pregnancy are problematic. The aim of this study was to assess the plasma HEPTEST as a rapid and reliable test for heparin monitoring in pregnancy. HEPTEST, activated partial thromboplastin time (APTT) and chromogenic anti-Xa assays were performed on individual heparin-spiked plasma samples from two groups: normal non-pregnant women (n = 6) and normal pregnant women during the third trimester (n = 6). Heparin activity curves were established in plasma from both groups for low (< 0.3 IU/ml), intermediate (0.3-0.7 IU/ml) and high (> 0.7 IU/ml) heparin concentrations and validated by comparison with the anti-Xa chromogenic assay. Both the APTT and HEPTEST demonstrated good correlation with anti-Xa levels across all heparin concentrations in both plasma groups (r range = 0.879-0.945). In comparison with the APTT, the HEPTEST showed better correlation with anti-Xa levels at low concentrations of heparin (r values 0.933 vs. 0.772, respectively). For both the APTT and HEPTEST there were significant differences between the clotting times in pregnant and non-pregnant plasma at a number of heparin concentrations. This data supports the plasma HEPTEST as an acceptable alternative to the chromogenic anti-Xa assay for monitoring heparin thromboprophylaxis in pregnancy.     

Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor, and delivery

We previously reported that immunoreactive corticotropin-releasing hormone (CRH) is present in human placenta and third trimester maternal plasma, and that such material is very similar to rat CRH and the predicted structure of human CRH. We suggested that maternal plasma immunoreactive CRH may be of placental origin. To further investigate this possibility, we measured plasma immunoreactive CRH in women during pregnancy, labor, and delivery and 1 and 2 h postpartum, and in nonpregnant women. Umbilical cord plasma and placental CRH concentrations were also measured. In the first trimester of pregnancy, the mean maternal plasma level was 5.9 +/- 1.0 pg (+/- SEM)/ml (n = 24), not significantly different from that in 10 nonpregnant women (5.8 +/- 0.8 pg/ml). Plasma CRH concentrations progressively increased during pregnancy (second trimester, 35.4 +/- 5.9 pg/ml (n = 39); early third trimester (28-34 weeks), 263 +/- 41 pg/ml (n = 14); late third trimester (35-40 weeks), 800 +/- 163 pg/ml (n = 20)]. There was a significant correlation between maternal plasma CRH levels and weeks of pregnancy. Plasma CRH concentrations were further elevated (2215 +/- 329 pg/ml; n = 9). During early labor, peaked at delivery (4409 +/- 591 pg/ml; n = 28), and declined rapidly after delivery [1 h postpartum, 1042 +/- (353 pg/ml (n = 13); 2 h postpartum, 346 +/- 91 pg/ml (n = 13)]. There was a significant correlation (r = 0.562; P less than 0.01) between matched maternal plasma and placental CRH concentrations. The mean umbilical cord plasma CRH level (50.6 +/- 6.1 pg/ml; n = 28) was much lower than that in the mother at the time of delivery. Umbilical venous plasma CRH levels were significantly greater than those in simultaneously obtained umbilical arterial plasma (70.8 +/- 11.3 and 41.8 +/- 4.9 pg/ml, respectively; n = 11). There was a significant correlation (r = 0.384; P less than 0.05) between maternal and fetal CRH concentrations. Gel filtration of plasma obtained from women during the third trimester, at delivery, and early postpartum and placental extracts revealed two major peaks of immunoreactive CRH: a high mol wt peak and one at the elution position of rat CRH. In contrast, only rat CRH-sized material was detected in plasma from nonpregnant women and umbilical cord plasma. Maternal plasma immunoreactive CRH-sized material stimulated ACTH release from anterior pituitary tissue in a dose-dependent manner and was equipotent with rat CRH.(ABSTRACT TRUNCATED AT 400 WORDS)     

Evidence for increased metabolism of chloroquine during the early third trimester of human pregnancy

OBJECTIVE: To examine the possibility of a different extent of chloroquine (CQ) metabolism in human pregnancy by determining blood level profiles of the drug and its major metabolite, desethylchloroquine (CQM). METHODS: Five women in the early third trimester of pregnancy and five non-pregnant women received each a single 600 mg oral dose of CQ and blood samples were collected at pre-determined intervals following drug administration. Plasma concentrations of CQ and CQM were analysed by an established HPLC method. RESULTS: The C(max) and AUC(0-48 h) of CQM were significantly higher in the pregnant than the non-pregnant group (P = 0.009). The ratio AUC(CQ)/AUC(CQM) ranged from 0.09 to 0.35 among pregnant women, and from 1.70 to 4.81 among non-pregnant women. CONCLUSION: Results from this preliminary study indicate an occurrence of induction of metabolism of CQ in the early third trimester of pregnancy. In view of toxicological importance of CQ metabolites, it is suggested that caution should be exercised in evaluation of higher dosage regimen of CQ in pregnant women.     

Tissue plasminogen activator levels change with plasma fibrinogen concentrations during pregnancy

To investigate the relationship between coagulation activities and the fibrinolytic system during normal pregnancy, we measured the plasma concentrations of coagulation factors, antithrombin III (AT III), D-dimer, tissue plasminogen activator (tPA), total protein S (TPS), and plasminogen activator inhibitor type 1 (PAI-1) in 436 apparently healthy pregnant, postpartum, and nonpregnant women. There were no significant changes in AT III, TPS, and factor XI concentrations during pregnancy and puerperium. However, factor VII, VIII, IX, and XII activities increased gradually as pregnancy progressed, reached maximum values in the third trimester, and returned to nonpregnant levels by 5-8 weeks postpartum. Plasma D-dimer levels in the third trimester of pregnancy were 1.23+/-0.42 micro g/ml, significantly higher than for the first trimester (0.34+/-0.16 micro g/ml, P<0.01). The tPA antigen levels averaged 1.8-fold higher in the late third trimester than in the first trimester; the plasma fibrinogen concentrations averaged 1.6-fold higher in the late third trimester than in the first trimester. Compared to the peak values during pregnancy, tPA levels averaged 39.8% lower and plasma fibrinogen concentrations averaged 40.0% lower at 5-8 weeks postpartum. The tPA levels correlated strongly with the plasma fibrinogen concentrations ( r=0.52, P<0.01). In short, this study shows that tPA levels change in parallel with plasma fibrinogen concentrations during and after normal pregnancy.     

Radioimmunoassay of plasma ouabain in healthy and pregnant individuals

Ouabain was recently isolated from human plasma, bovine hypothalamus and bovine adrenal in attempts to identify endogenous substances inhibiting the cell membrane sodium pump. A number of radioimmunoassays have been developed in order to study the clinical significance of ouabain. The results have been controversial with regard to the presence and chemical nature of plasma ouabain-like immunoreactivity. We have now measured ouabain in healthy and pregnant individuals using solid-phase extraction of plasma samples followed by a new radioimmunoassay with the extraordinary sensitivity of at least 2 fmol/tube (5 pmol/l). Plasma extracts, a previously isolated human plasma ouabain-like compound and bovine hypothalamic inhibitory factor displaced the tracer in parallel and eluted identically with ouabain in high-performance liquid chromatography. Plasma ouabain immunoreactivity was found to be much lower than reported previously: 12.6+/-1.3 pmol/l in healthy men (mean+/-s.e., n=20) and 9.4+/-0.7 pmol/l in women (n=14). In pregnant women (n=28) plasma ouabain concentration was 16.3+/-4.0 pmol/l during the first trimester, 18.8+/-4.3 pmol/l during the second trimester and 24.3+/-4.0 pmol/l during the third trimester (all P<0.01 compared with non-pregnant women). Plasma ouabain 3-5 days after the delivery was 13.6+/-1.1 pmol/l (n=10, P<0.05-0.01 compared with second and third trimesters). The pregnancy-related changes in the plasma concentrations of ouabain resembled those of cortisol. Therefore cortisol was measured from the same plasma samples and a significant positive correlation was found (r=0.512, P=0.006). The similar profiles of plasma ouabain and cortisol during pregnancy and their rapid decreases postpartum are consistent with the adrenal cortical origin of ouabain and also show that the secretions of these hormones are possibly under the control of same factors.     

Iron status of pregnant Filipino women as measured by serum ferritin.

Iron status of pregnant women at different stages of pregnancy was evaluated by comparing values for hemoglobin (Hb), red cell indices, serum iron (SI), transferrin saturation (TS) and serum ferritin (SF) values with those of a group of non-pregnant women of comparable age and socio-economic status. Mean SF values on the second and third trimesters (9.3 +/- 2.60 ng/ml and 7.1 +/- 2.19 ng/ml) were significantly lower compared to that in the first trimester (22.6 +/- 2.20 ng/ml). These levels were also lower than that found in the non-pregnant controls. The trend was the same for TS. Hemoglobin levels of the pregnant subjects were significantly lower than those of the non-pregnant women. Prevalence of iron deficiency based on SF < 12.0 ng/ml and TS < 16.0% was highest at term and lowest during the first trimester indicating a decrease in iron stores as pregnancy progressed. Sensitivity for each of the iron parameters was computed, and it was found that for the diagnosis of iron deficiency in pregnant women, SF has a greater sensitivity than TS, SI, MCV and MCH.     

DIURNAL SALIVARY CORTISOL PATTERNS DURING PREGNANCY AND AFTER DELIVERY: RELATIONSHIP TO PLASMA CORTICOTROPHIN-RELEASING-HORMONE

The circadian rhythm of salivary cortisol was studied in 10 healthy women every 4 weeks throughout pregnancy. In addition, in 12 women the diurnal patterns of salivary cortisol, serum cortisol, plasma ACTH, plasma CRH and serum progesterone were analysed in late third trimester pregnancy and again 3-5 days after delivery. Salivary cortisol profiles exhibited a clear circadian rhythm during pregnancy with an increase in mean salivary cortisol from the 25th to 28th week onwards reaching concentrations in late pregnancy more than twice as high as in non-pregnant controls, rapidly returning to normal concentrations after delivery. The coefficient of variation of salivary cortisol profiles decreased in third trimester pregnancy due to a parallel upward shift of cortisol concentrations (40.2 +/- 3.4% vs 77.6 +/- 6.6% after delivery, P less than 0.01). A diurnal pattern was also found for plasma ACTH and serum cortisol before and after delivery with lower concentrations post-partum (P less than 0.01). In late pregnancy, progesterone concentrations were significantly higher in the evening (930 +/- 85 nmol/l vs 813 +/- 74 nmol/l at 0900 h, P less than 0.01) but showed no diurnal variation post-partum. Plasma CRH was significantly elevated in late third trimester pregnancy (1.22 +/- 0.23 micrograms/l at 0900 h) but showed no diurnal change (1.30 +/- 0.28 micrograms/l at 1900 h). Moreover, no correlation between the free cortisol increase in late pregnancy and plasma CRH was noted despite a wide range of CRH levels (0.13-3.60 micrograms/l). In contrast, a significant correlation was observed between the serum progesterone increase and the salivary cortisol increase in late pregnancy (r = 0.70, P less than 0.05). These findings demonstrate that placental CRH is not the only regulator of maternal ACTH and cortisol release. Instead, our study suggests that placental CRH has little influence on baseline maternal adrenocortical function in pregnancy. The elevated salivary cortisol levels in pregnancy may be explained by glucocorticoid resistance owing to the antiglucocorticoid action of high progesterone concentrations.     

Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum

OBJECTIVE: To investigate changes in the levels of circulating cytokines with a focus on the Th1/Th2 balance during and after pregnancy in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). METHODS: Plasma and serum samples of 34 pregnant patients, 19 with RA, 6 with JIA, and 9 with AS, and of 30 healthy pregnant women, 20 non-pregnant patients, and 10 non-pregnant healthy women were analysed for levels of interferon gamma (IFNgamma), interleukin (IL) 1beta, IL10, IL1 receptor antagonist (IL1Ra), soluble tumour necrosis factor receptor (sTNFR), and soluble CD30 (sCD30) by ELISA. Clinical assessment and blood sampling in pregnant women was done once in each trimester and 6, 12, and 24 weeks post partum. Disease activity in the patients was evaluated by validated clinical instruments and correlated with circulating levels of cytokines. RESULTS: Low levels of IL10 were found sporadically, whereas IFNgamma and IL1beta were below detection level in the samples tested. Significantly higher concentrations of sTNFR and IL1Ra were measured in pregnant than in non-pregnant subjects. An increase of IL1Ra from the second to the third trimester correlated with improvement of disease activity in patients with RA and AS. Compared with non-pregnant patients and the other pregnant women, patients with RA showed markedly raised levels of sCD30 during pregnancy. CONCLUSIONS: IFNgamma and IL10, markers of a Th1 and Th2 response, respectively, were either low or undetectable in the cohorts analysed. The increase of cytokine inhibitors IL1Ra and sTNFR was related to pregnancy and was independent of an underlying disease. These anti-inflammatory mediators seem to affect disease activity.     

Elevated serum acylated (biologically active) ghrelin and resistin levels associate with pregnancy-induced weight gain and insulin resistance

AIM: To study fasting biologically active serum ghrelin (RIA) and resistin (ELISA) levels in different trimesters of pregnancy (HP, n=45, 15 in each) and in gestational diabetes mellitus (GDM, n=30) compared to non-pregnant healthy women (NP, n=40) in correlation with TNF-alpha, soluble (s)TNF-receptor (R)-1, -2, leptin (ELISA), C-peptide (Cp, RIA) and Cp/blood glucose ratio (bg). STUDY DESIGN: Cross-sectional case control study. RESULTS: Acylated ghrelin levels were significantly increased (p<0.0001) in the 2nd (377+/-38pg/ml, X+/-S.D.) and decreased in the 3rd trimester (252+/-36) and in GDM (226+/-21) compared to NP controls (309+/-20) and HP women in the 1st trimester (314+/-41). Serum resistin levels were higher in the 1st (8.5+/-2.6ng/ml), 2nd (10.2+/-2.1) and 3rd (13.1+/-3.6) trimesters of pregnancy and in GDM (15.7+/-3.5) than in NP controls (6.5+/-2.3). Significant (p<0.01) negative linear correlations were found among fasting serum ghrelin and body mass index (BMI), the fasting C-peptide (Cp) level, C-peptide/blood glucose (Cp/bg) ratio, TNF-alpha, soluble (s)TNFR-2, leptin and resistin concentrations in both, HP and GDM groups. Significant positive correlations were observed between serum acylated ghrelin and adiponectin, and between BMI and fasting Cp, Cp/bg, TNF-alpha, sTNFR-1, -2 and leptin levels in both pregnant groups. CONCLUSION: Increased fasting serum acylated ghrelin concentrations in the 2nd trimester may associate with weight gain during pregnancy. Hyperresistinemia may also be associated with the pregnancy-induced insulin resistance. A negative regulatory feed-back mechanism between resistin, TNF-alpha and ghrelin may be hypothesized.     

Changes in the concentration of 17 alpha,20 alpha-dihydroxypregn-4-en-3-one during pregnancy, labor, and delivery and the effect of dexamethasone treatment during the third trimester of pregnancy

To study whether an alteration of placental steroid metabolism occurs during human pregnancy similar to that in the ewe, we measured the concentration of 17 alpha,20 alpha-dihydroxypregn-4-en-3-one (17,20 alpha-OHP) in peripheral plasma. As the pregnant ewe nears term, the utero-ovarian venous concentrations of 17,20 alpha-OHP increase, suggesting induction of placental 17 alpha-hydroxylase. The mean plasma concentration of 17,20 alpha-OHP measured by RIA in normal menstruating women was 1.1 +/- 0.12 (+/- SE) ng/ml. Similar values were found in plasma from ovariectomized women. In the first and second trimesters of pregnancy, the plasma values of 17,20 alpha-OHP were not significantly different from those in the nonpregnant women, while in the third trimester, the mean plasma concentration was significantly increased (mean +/- SE, 2.6 +/- 0.3 ng/ml). The plasma concentration of 17,20 alpha-OHP was studied in 15 women in late pregnancy, during labor, at delivery, and postpartum. The concentration increased during labor as delivery approached and reached a maximum at the time of delivery, ranging from 4.1-11.2 ng/ml, followed by a significant decrease within 1-4 h postpartum. The mean (+/- SE) 17,20 alpha-OHP concentrations in the venous and arterial cord blood were 8.7 +/- 1.6 and 5.8 +/- 2.0 ng/ml, respectively. To study the effect of increased circulating level of corticosteroids on the serum concentration of progestins, 74 women with premature labor with or without premature rupture of membranes were treated with either placebo or 4 im injections of dexamethasone phosphate (5 mg each) at 12-h intervals. Blood samples were drawn at 0, 14, 26, and 46 h, approximately 2 h after each dexamethasone dose. Plasma progesterone, 17 alpha-hydroxyprogesterone (17-OHP), and 17,20 alpha-OHP values at zero time were 140 +/- 15.8 (+/- SE; n = 21), 7.8 +/- 1.5 ng/ml (n = 16), and 2.3 +/- 0.3 ng/ml (n = 20), respectively. In patients treated with dexamethasone, the plasma progesterone values tended to increase at 14, 20, and 46 h, but 17-OHP and 17,20 alpha-OHP values decreased significantly compared to levels in placebo-treated patients. In conclusion, the concentration of plasma 17,20 alpha-OHP increased during the third trimester of pregnancy, and the increment continued through labor and delivery. During antenatal dexamethasone administration, progesterone in the maternal circulation tended to increase, while 17-OHP and 17,20 alpha-OHP decreased significantly. In the human, in contrast to the ewe, dexamethasone treatment in the third trimester does not appear to stimulate placental 17 alpha-hydroxylase activity.     

妊娠期胃食管反流病的症状特征研究

目的探讨妊娠期胃食管反流病（GERD）症状的发生率及严重程度。 方法选取2018年1月至2019年1月,新疆维吾尔自治区人民医院住院就诊的120例孕妇设定为研究组,进行了一项前瞻性纵向队列研究,通过GerdQ问卷调查妊娠期GERD的患病率。同期选取健康体检者40例非怀孕妇女作为对照组。2组每3个月均记录反流症状的频率和严重程度。 结果妊娠（早、中、晚期）和非孕妇GERD问卷调查结果表示,妊娠晚期的评分范围（3~7分、8~10分、11~14分及15~18分）均明显高于对照组,差异均有统计学意义（P＜0.05）。在孕妇中,5.0%的患者在怀孕前3个月（早期）至少每周有1次反流。在妊娠晚期,15.0%的孕妇每周至少有1次反流,2.50%的非孕妇每周发生1次以上的反流,各组间比较具有统计学意义（P＜0.05）。在孕妇中,5.0%的妊娠早期至少每周有1次烧心。妊娠中期为10.0%,晚期为17.5%,2.5%的非孕妇每周至少有1次烧心,在妊娠晚期,发生烧心的妇女占17.5%,各组间比较具有统计学意义（P＜0.05）。从妊娠早期到妊娠中、晚期,个别症状（反流,烧灼感）的频率与非孕妇组比较均明显增加,在妊娠晚期症状出现的频率达到高峰,与非孕妇组以及妊娠早期比较,具有明显的统计学意义（P＜0.05）。根据症状诊断及发生情况,GERD在妊娠早期发病率为24.5%,在中期为37.5%,在妊娠晚期为52.5%,非孕妇（对照组）GERD患病率为7.5%。 结论妊娠晚期GERD症状发生率明显高于非孕妇,且在妊娠过程中发生率逐渐增高。     

Plasma leptin concentrations in postmenopausal women with osteoporosis

BACKGROUND: The obese are usually protected against osteoporosis and have increased bone mineral density and plasma leptin concentrations. A recent in vitro study demonstrated that leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts, suggesting an influence of leptin on bone mass. However, little is known about the relationship between plasma leptin and bone mass in postmenopausal women with osteoporosis. OBJECTIVE: To investigate plasma leptin concentrations in postmenopausal women with osteoporosis to improve the understanding of the role of leptin in determining bone mass. METHODS: Fifty postmenopausal women with osteoporosis (ages 61.18+/-6.51 years; body mass index (BMI) 28. 91+/-3.44kg/m(2), mean+/-s.d.) and 30 age- and BMI-matched healthy postmenopausal women were included in the study. Bone mineral densities (BMD) were measured by dual energy X-ray absorptiometry. Plasma leptin concentrations were determined using an immunoradiometric assay. RESULTS: The median spine BMD value in the patient group (0.695+/-8.26g/cm(2), median+/-s.e.m.) was significantly lower than that in the control group (1.006+/-1. 29g/cm(2), median+/-s.e.m.; z=-7.454, P<0.001). The median plasma leptin concentration in the patient group (18.70+/-1.78ng/ml, median+/-s.e.m.) was not significantly different from that in the control group (22.35+/-2.20ng/ml, median+/-s.e.m.; z=-1.630, P=0. 103). Plasma leptin concentrations were correlated with BMI in both groups (r(s)=0.394, P=0.031 in controls and r(s)=0.404, P=0.004 in the patient group). There was no correlation between plasma leptin concentrations and BMD values in controls (r(s)=-0.107, P=0.575) but a weak correlation was observed in the patient group (r(s)=0.285, P=0.045). CONCLUSION: Our data suggest that circulating plasma leptin does not have a significant direct influence on bone mass in postmenopausal women.     

Effect of a hypertonic saline load on plasma concentrations of atrial natriuretic peptide in fetal calves and their dams

Plasma concentrations of atrial natriuretic peptide (ANP) were studied in eight adult non-pregnant cows and in two groups of six chronically catheterized bovine fetuses and their mothers in the eighth month of pregnancy. The first group of fetuses was used for studying the effect of an acute i.v. sodium load (240 mmol NaCl/fetus) on fetal ANP; the second group acted as controls. The mean basal ANP levels in the third-trimester bovine fetus were three to four times higher than maternal values (39.5 +/- 5.5 and 9.4 +/- 0.6 pmol/l respectively; P less than 0.01). Basal maternal plasma ANP levels were twice as high in pregnant cows in the third trimester of pregnancy than in non-pregnant cows (9.4 +/- 0.6 and 4.3 +/- 0.7 pmol/l respectively; P less than 0.05). In response to an i.v. hypertonic saline injection, fetal plasma ANP levels increased significantly (P less than 0.01) to a maximum of 86.7 +/- 17.6 pmol/l 10 min after the injection, and returned to baseline within 60 min after the treatment; during the 20 min following the i.v. sodium load, fetal plasma ANP correlated significantly with fetal plasma sodium concentrations (r = 0.96; n = 12) and with fetal plasma osmolality (r = 0.94; n = 12). No significant changes in maternal ANP values were observed in the two groups of animals. These results suggest that ANP secretion is stimulated during pregnancy in cows, and that, in the bovine fetus, a hypertonic sodium load appears to be a potent stimulus for ANP release.     

Paradoxical elevation in adiponectin concentrations in women with preeclampsia

Adiponectin is a recently identified, insulin-sensitizing and anti-inflammatory protein released by adipocytes, which is paradoxically reduced in obesity. It suppresses endothelial activation. Physiological insulin resistance occurs in normal pregnancy and is exaggerated in women with preeclampsia (PE), together with enhanced inflammatory and endothelial activation. Women with increased body mass index (BMI) and insulin resistance are predisposed to PE. We hypothesized that adiponectin concentrations are reduced in normal pregnancy compared with postpartum values and further reduced in women with PE. Fifteen women with PE and 30 control subjects with similar first trimester BMI had adiponectin concentrations measured in the third trimester; postpartum measurements were repeated in 16 control subjects. Adiponectin concentration in healthy pregnant women correlated inversely with early pregnancy BMI (r=-0.47, P=0.01) and fasting insulin concentrations (r=-0.58, P=0.001). However, adiponectin concentrations did not differ significantly in pregnancy and postpartum samples (mean change, -0.15 microg/mL; 95% CI, -2.28 to 1.98, P=0.88). Plasma adiponectin concentrations were markedly elevated (P=0.01) in women with PE (mean, 21.6; SD, 8.18 microg/mL) compared with control subjects (mean, 14.7; SD, 7.06 microg/mL). Moreover, in PE, adiponectin concentrations did not correlate with first trimester BMI or insulin or with serum urate or creatinine concentrations or urinary protein levels. We conclude that plasma adiponectin concentrations are not elevated in normal human pregnancy and paradoxically elevated (by 47%) in women with PE. This may be secondary to exaggerated nonspecific adipocyte lipolysis or as a physiological response to enhance fat utilization and attenuate endothelial damage. Future studies should determine whether adiponectin concentrations help improve prediction of PE.     

HEPTEST: a suitable method for monitoring heparin during pregnancy

Methods of monitoring heparin in pregnancy are problematic. The aim of this study was to assess the plasma HEPTEST as a rapid and reliable test for heparin monitoring in pregnancy. HEPTEST, activated partial thromboplastin time (APTT) and chromogenic anti-Xa assays were performed on individual heparin-spiked plasma samples from two groups; normal non-pregnant women (n = 6) and normal pregnant women during the third trimester (n = 6). Heparin activity curves were established in plasma from both groups for low (<0.3 IU/ml), intermediate (0.3–0.7 IU/ml) and high (>0.7 IU/ml) heparin concentrations and validated by comparison with the anti-Xa chromogenic assay. Both the APTT and HEPTEST demonstrated good correlation with anti-Xa levels across all heparin concentrations in both plasma groups (r range = 0.879–0.945). In comparison with the APTT, the HEPTEST showed better correlation with anti-Xa levels at low concentrations of heparin (r values 0.933 vs 0.772, respectively). For both the APTT and HEPTEST there were significant differences between the clotting times in pregnant and non-pregnant plasma at a number of heparin concentrations. This data supports the plasma HEPTEST as an acceptable alternative to the chromogenic anti-Xa assay for monitoring heparin thromboprophylaxis in pregnancy.     

Significant increase in maternal plasma leptin concentration in induced delivery: a possible contribution of pro-inflammatory cytokines to placental leptin secretion

Maternal plasma leptin concentration is significantly increased during pregnancy. However, its roles in pregnancy, especially in labor, have not been fully clarified. We measured plasma leptin concentrations in pregnant women during the course of induced labor, just after spontaneous vaginal delivery and Cesarean section at term. We also studied the regulation of leptin secretion from term placental tissue and BeWo cells, a trophoblastic cell-line. Plasma leptin concentrations increased significantly during labor (58.9 +/- 9.2 ng/ml) compared to those before labor induction (37.5 +/- 5.8 ng/ml, P<0.05), then decreased 3-6 days postpartum (14 +/- 3 ng/ml, n = 6, P<0.0001) to the levels of normal nonpregnant women. Leptin concentrations within an hour and 24 hours after spontaneous vaginal delivery were significantly higher than those after Cesarean section (P<0.05 for both comparisons). Similarly, leptin mRNA expression in placental tissues obtained after spontaneous vaginal delivery was significantly greater than that in those obtained after Cesarean section without labor (P<0.05). IL-1alpha and TNF-alpha treatment significantly stimulated leptin secretion and leptin mRNA expression in explant culture of human term placental tissue and in BeWo cells as compared with those in vehicle controls (P<0.05, for all comparisons). By contrast, oxytocin and prostaglandin F(2alpha) treatment had no effects on leptin secretion from explant culture of human term placental tissue or from BeWo cells. These data indicate that pro-inflammatory cytokines might stimulate placental leptin secretion, thus finally contributing to the increase in plasma leptin concentration during labor.     

Gender differences in relation to leptin concentration and insulin sensitivity in nondiabetic Chinese subjects.

OBJECTIVE: To investigate the relationship between fasting plasma leptin concentrations and insulin resistance in Chinese men and women. DESIGN: Cross-sectional study design. SUBJECTS: Ninety-six nondiabetic Chinese (51 men and 45 women) with body mass index (BMI) between 18.4-35.8 kg/m2 were studied. MEASUREMENTS: Plasma glucose and insulin concentrations were measured every 30 min for 2 h after a 75 g oral glucose load. The degree of insulin resistance was assessed using a modified insulin suppression test. Plasma leptin values were determined by radioimmunoassay. RESULTS: Fasting plasma glucose, glucose areas, fasting insulin, insulin areas, most of the lipoprotein concentrations and steady state plasma glucose (SSPG) concentrations were relatively similar between men and women. Despite the fact that men had higher BMI values (26.1 +/- 0.5 vs 24.7 +/- 0.5 kg/m2, P < 0.05), fasting plasma leptin concentrations were significantly lower in men than in women (4.9 +/- 0.5 vs 9.0 +/- 0.8 ng/ml, P < 0.001). Fasting leptin values were positively related to SSPG concentrations by simple correlation analysis in both sexes. However, this relationship persisted in men (r = 0.513, P < 0.01) but not in women (r = 0.119, P = NS) after adjustment for BMI. Multiple regression analysis showed that SSPG concentrations, BMI, glucose and insulin responses together accounted for 62.5% and 52.2% of the variation in plasma leptin concentrations in Chinese men and women respectively. CONCLUSION: Fasting plasma leptin concentrations were lower in Chinese men than in Chinese women despite the higher BMI observed in men. After adjustment for BMI, plasma leptin values correlated with the degree of insulin resistance in men but not in women.     

Soluble CD30 in Normal Pregnancy Pre-Eclampsia and Recurrent Pregnancy Loss

Background: Normal pregnancy is thought to be dependent on Th2 deviation, while Recurrent Pregnancy Loss (RPL) and Pre-eclampsia (PE) appear to be biased toward the Th1 immune response. It is believed that the soluble form of CD30 (sCD30) is an index of Th2 immune response or modulator of Th1/Th2 responses. Objective: The aim of this study was determination of the sCD30 level in RPL and PE patients. Methods: The sCD30 level was measured in sera of a group of normal non-pregnant women (N=43) and compared with normal pregnancy at the first (N=42) and third (N=42) trimester. Furthermore, the level of sCD30 in the normal first and third trimester pregnancies were compared with that of RPL (N=38) and severe pre-eclamptic (N=41) patients, respectively. sCD30 levels were measured by ELISA method and student t-test was used for statistical analysis. Results: The mean level of sCD30 at the first trimester in normal pregnancy was significantly elevated as compared with normal non-pregnant women (21.4 vs. 15.2 ng/ml, p<0.0001). A significant difference between sCD30 concentration at the first and third trimester of normal pregnancies was also observed (21.4 vs. 14.3 ng/ml, p<0.0001). Interestingly, the sCD30 concentration did not show any significant changes at the first trimester of normal pregnancy as compared with RPL (21.4 vs. 20.9 ng/ml) and third trimester of normal pregnancy as compared with PE (14.3 vs. 13.1 ng/ml). Conclusion: The data of this study indicated that the concentration of sCD30 in serum during pregnancy period is not associated with RPL or PE and serum sCD30 is not a good correlate of Th2 immune responses in pregnancy.