Severe preeclampsia: Association of genes polymorphisms and maternal cytokines production in Brazilian population

IntroductionPreeclampsia (PE) is a multi-system disorder of pregnancy characterized by hypertension and proteinuria. Healthy pregnancy is associated with a controlled inflammatory process, which is exacerbated in PE in response to excessive placental stimuli. Gene expression levels can affect inflammation and immune regulation. It is known that differences in cytokine allele frequencies amongst populations may contribute to difference in the incidence of several diseases.ObjectiveThe aim of this study was to investigate the frequency of TNF-α, IL-6, IFN-γ and IL-10 genes polymorphisms and their relationship with the cytokines plasma levels in PE.MethodsA total of 281 women were included in this study; 116 with severe PE, 107 normotensive pregnant and 58 non-pregnant women. Cytokine genotyping was carried out by the polymerase chain reaction. The analyzed polymorphisms were: TNF-α (−308 G → A), IL-10 (−1082 G → A), IL-6 (−174 G → C), and IFN-γ (+874 A → T). Cytokine plasma levels were measured by Cytometric Bead Array method.ResultsA higher frequency of the IFN-γ (+874) T/T genotype in severe PE comparing to normotensive pregnant women was found (P < 0.001). TNF-α, IL-6 and IFN-γ plasma levels were higher in PE women compared to non-pregnant women (P < 0.001; P < 0.001; P = 0.004). IL-6 and IFN-γ levels were also higher in PE women compared to normotensive pregnant (P < 0.001; P = 0.010). IL-10 levels were higher in normotensive pregnant women compared to PE (P < 0.001). IFN-γ and IL-6 genes polymorphisms influenced the genic expression in PE and normotensive pregnant women, respectively.ConclusionsThese results suggest that IFN-γ seems to play a role in PE occurrence.     

The adipokine preadipocyte factor-1 is downregulated in preeclampsia and expressed in placenta

BackgroundAdipokines contribute to the development of preeclampsia (PE), a severe pregnancy complication which increases the future risk for cardiovascular and metabolic disease in both mother and newborn. Pre-adipocyte factor-1 (Pref-1) was recently introduced as a novel antiangiogenic and antiadipogenic adipokine.Material and methodsPref-1 was quantified in patients with PE (n = 51) and healthy pregnant controls (n = 51) during pregnancy, as well as 6 months after delivery (study population 1). Furthermore, Pref-1 was investigated in the immediate peripartal period and the placenta in 40 healthy pregnant women undergoing elective cesarean section (study population 2).ResultsIn study population 1, median Pref-1 serum concentrations during pregnancy were significantly lower in women with PE (0.5 μg/l) as compared to healthy pregnant controls (0.7 μg/l) (p < 0.001). Furthermore, Pref-1 serum concentrations were independently predicted by PE, leptin levels, and gestational age in this population. In both study populations, Pref-1 serum levels significantly decreased after delivery as compared to prepartal levels. Moreover, significant expression of Pref-1 was detected in placental tissue.ConclusionMaternal Pref-1 serum concentrations are significantly decreased in PE. The pathophysiological significance of this regulation needs to be studied in more detail in future experiments.     

Plasma levels of kisspeptins in postmenopausal Chinese women do not show substantial elevation

The menopause, defined as the permanent cessation of menstruation resulting from ovarian failure, is characterized by elevated levels of serum gonadotropins. Recent studies have demonstrated that the gonadotropin hypersecretion in postmenopausal women is secondary to increase of KiSS-1 mRNA from the hypothalamus neurons, which encoded kisspeptin peptides. The present study was designed to determine whether plasma kisspeptins levels are altered in postmenopausal women. Blood samples were taken from 145 postmenopausal women, 35 young women and 30 pregnant women control in the first trimester. The plasma concentration of kisspeptins, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E₂) was measured using immunoassay kits. Results indicated that plasma kisspeptins levels in postmenopausal women had higher than those in young women (5.25 ± 0.36; 4.48 ± 0.34 pmol/L), but no significant difference was found between the two groups (p = 0.179). Plasma FSH and LH levels were significantly higher in postmenopausal women (124.67 ± 12.78, 57.14 ± 3.57 mIu/mL) than those in young women (9.23 ± 2.78, 7.56 ± 2.71 mIu/mL, p < 0.001). However, Plasma kisspeptins levels were not significantly correlated to FSH and LH in postmenopausal women (r = ?0.23, 0.324; p = 0.927, 0.176, respectively), and also there was no any correlation between plasma kisspeptins and E₂ in postmenopausal women (r = ?0.065; p = 0.792). Collectively, there was no significant difference in plasma kisspeptins levels between postmenopausal and young women. Our result suggested that kisspeptins’ role during menopause might mainly act in central rather than peripheral system and it could not be currently used as a clinical marker for menopause.     

Predictive value of cystatin C and beta-2 microglobulin in preeclampsia

The purpose of this study was to determine whether the levels of cystatin C and beta-2 microglobulin (B2M) are altered during the second trimester in the plasma of women who subsequently develop preeclampsia.Study designWe performed a case control study to compare the levels of cystatin C and B2M in women in whom preeclampsia ultimately developed (n = 30) and in pregnant women who remained normotensive throughout gestation (n = 60). The maternal plasma levels of cystatin C and B2M were measured by enzyme-linked immunosorbent assay. Blood samples were collected between 15 and 20 weeks’ gestation for fetal aneuploidy screening and frozen at ?20 °C until assay after groups had been selected.ResultsThe median concentrations of cystatin C and B2M were significantly higher in those who subsequently developed preeclampsia when compared to those of normal pregnancy (median 668.6 ng/ml and 418.3 μg/ml vs 413.7 ng/ml and 321.2 μg/ml, respectively).ConclusionsIn this study, the maternal plasma levels of cystatin C and B2M were significantly elevated in pregnant women who subsequently developed preeclampsia as compared with normotensive women. Alterations of these proteins antedate clinical symptoms and, thus, they may be useful for early identification of patients at the risk of developing preeclampsia.     

Oxidative stress and apoptosis in preeclampsia

We aimed to determine the oxidative stress and antioxidant status in preeclamptic placenta. Also, we investigated the apoptotic index of villous trophoblast and proliferation index of cytotrophoblasts. The study included 32 pregnant with preeclampsia and 31 normotensive healthy pregnant women. Malondialdehyde (MDA) and total antioxidant status (TAS) levels were measured in the placenta. For detection of apoptosis and proliferation in trophoblast, apoptosis protease activating factor 1 (APAF-1) and Ki-67 were used. Placental MDA levels in preeclamptic women were significantly higher than normal pregnancies (p = 0.002). There was no significant difference between the groups in the TAS levels of placenta (p = 0.773). Also, the apoptotic index in villous trophoblasts increased (p < 0.001), but proliferation index did not change in preeclampsia (p = 0.850). Increased oxidative stress and apoptosis in pathological placenta are not balanced by antioxidant systems and proliferation mechanisms.     

Concentrations of preptin,salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus

This study was undertaken to ascertain whether human milk contains preptin, salusin-alpha (salusin-α) and -beta (salusin-β) and pro-hepcidin and hepcidin-25, and whether there are relationships between plasma and milk preptin, salusin-α and -β and pro-hepcidin and hepcidin-25 concentrations in lactating mothers with and without gestational diabetes mellitus (GDM). Blood was obtained from non-lactating women (n = 12), non-diabetic lactating women (n = 12), and GDM lactating women (n = 12). Colostrum, transitional milk, and mature milk samples were collected just before suckling from healthy and GDM lactating women. Peptides concentrations were determined by ELISA and EIA. Mammary gland tissues were screened immunohistochemically for these peptides. Women with GDM had significantly higher plasma and colostum preptin concentrations than healthy lactating women during the colostral and transitional milk period. Salusin-alpha and -beta levels in milk and plasma were lower in women with GDM. Salusin-α and -β were significantly lower in both plasma and colostrums of GDM than of healthy lactating women. Women with GDM had significantly higher colostum prohepcidin and hepcidin-25 concentrations than healthy lactating women during the colostral period. Plasma prohepcidin was also higher in women with GDM than in healthy lactating women during the colostral period, but plasma prohepcidin and hepcidin-25 levels decreased during mature milk period. Transitional milk pro-hepcidin and hepcidin-25 levels in women with GDM were higher than in healthy lactating women. All these results revealed that the mammary gland produces those peptides, which were present in milk at levels correlating with plasma concentrations.     

The association between serum selenium and gestational diabetes mellitus: A systematic review and meta-analysis

BackgroundResults of the studies about association between serum selenium concentration and gestational hyperglycemia are inconsistent. Some studies have demonstrated that women with gestational diabetes mellitus (GDM) have lower Se concentrations while contrary results are reported in other studies.AimThe aim of this study is to compare the serum Se concentration in women with GDM and normoglycemic pregnant women via a systematic review and meta-analysis.MethodsA computerized literature search on four databases (PubMed, Cochrane register of control trials, Scopus and Google scholar) was performed from inception through August 2013. Necessary data were extracted and random effects model was used to conduct the meta-analysis.ResultsSix observational studies (containing 147 women with GDM and 360 normoglycemic pregnant women) were found, which had compared serum Se concentration in women suffering from GDM with normal pregnant ones. Our meta-analysis revealed that serum Se concentration was lower in women with GDM compared to normoglycemic pregnant women (Hedges = −1.34; 95% CI: −2.33 to −0.36; P < 0.01). Stratified meta-analysis demonstrated that concentration of Se in the sera of women with GDM was lower than normal pregnant women both in second and third trimesters, but the result was not significant in second trimester (second trimester: Hedges = −0.68; 95% CI: −1.60−0.25; P = 0.15, third trimester: Hedges = −2.81; 95% CI: −5.21 to −0.42; P < 0.05). It was also demonstrated that serum Se status was lower in pregnant women with impaired glucose tolerance (IGT) compared to normoglycemic pregnant women (Hedges = −0.85; 95% CI: −1.18 to −0.52).ConclusionThe available evidences suggest that serum Se concentration is significantly lower in pregnant women with gestational hyperglycemia compared to normal pregnant women.     

Association of serum amyloid A levels with adipocyte size and serum levels of adipokines: Differences between men and women

The aim of this study was to characterize the association between adipocyte enlargement and circulating levels of serum amyloid A (SAA). Furthermore, we wanted to search for possible associations with measures of glycemic control and levels of circulating adipokines and/or inflammatory markers in men and women with a large range in body mass index. The study cohort consisted of 167 subjects, 114 non-diabetic and 53 with Type 2 diabetes. Adipocyte diameter as well as circulating levels of SAA, C-reactive protein (CRP), adiponectin, leptin, interleukin-6, tumor necrosis factor alpha, glucose and insulin were measured. Women had higher serum levels of SAA than men (p = 0.044). SAA levels were weakly but positively correlated with BMI (p = 0.043) and % body fat (p = 0.027) in all subjects as well as subcutaneous adipocyte diameter (p = 0.034) in women. Furthermore, in all subjects we found correlations between SAA levels and levels of CRP (p < 0.001), interleukin-6 (p < 0.001), leptin (p = 0.003), insulin (p = 0.006), HbA1c (p = 0.02) and HOMA-IR (p = 0.002). A majority of the correlations were strongest in women. In conclusion, serum levels of SAA are strongly correlated with serum levels of inflammatory markers as well as measures of glycemic control. There seems to be large sex differences in these associations suggesting that sex-specific factors need to be considered when analyzing SAA levels in relation to metabolic disease.     

Weekly iron folic acid supplementation plays differential role in maintaining iron markers level in non-anaemic and anaemic primigravida: A randomized controlled study

Anaemia during pregnancy is most commonly observed and highly prevalent in South-East Asia. Various effective programmes have been laid down for its management, mainly daily supplementation of iron folic acid (IFA) tablets. Following the same, standard obstetrical practice has included the IFA supplementation without requiring the determination of iron deficiency. In this study, a total of 120 primigravida (N = 60; non-anaemic (Hb > 11 g/dl) and N = 60 anaemic (Hb = 8–11 g/dl)) were selected among those attending the Antenatal Clinic in Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. They were supplemented with daily and weekly IFA tablets till 6 weeks postpartum. Corresponding changes in haemoglobin level on advance of pregnancy, side effects and compliance associated with daily and weekly IFA supplementation and its associations with iron status markers were studied. The inflammatory markers were also estimated. The statistical significance level (p < 0.05) between the groups were assessed by applying unpaired t-test using SPSS (version 16.0). The obtained results publicized the salutary role of daily IFA supplementation in improving the haemoglobin level and iron status markers in anaemic pregnant women though the levels could not reach up to the non-anaemic haemoglobin levels. However, weekly IFA supplementation seems to be a better approach in non-anaemic pregnant women where almost comparable results were obtained in terms of haematological parameters, gestation length and birth weight.ConclusionWeekly IFA supplementation found to be as effective as daily supplementation in iron sufficient non-anaemic pregnant women whereas anaemic pregnant women should be prescribed daily IFA supplementation irrespective of iron replete/deplete state.     

Serum vaspin levels in women with and without gestational diabetes mellitus during pregnancy and postpartum

Although vaspin is regarded an insulin-sensitizing adipokine, its role in gestational diabetes mellitus (GDM) is currently unknown. We aimed to evaluate serum vaspin levels and their correlation with insulin resistance in women with and without GDM. Forty-four women with GDM [GDM Group ? 20 managed with diet only (GDM-diet) and 24 with diet plus insulin (GDM-insulin)] and 44 age-matched pregnant women with normal glucose tolerance (Control Group) were studied. Serum glucose, lipids, uric acid, insulin and vaspin were measured at the 2nd and 3rd trimester of pregnancy and postpartum. The quantitative insulin sensitivity check index (QUICKI) and homeostasis model of assessment–insulin resistance (HOMA-IR) were calculated. Circulating vaspin levels decreased significantly postpartum in all groups (p < 0.001), but did not differ between GDM or GDM Subgroups and Control Group in any time point. At the 3rd trimester of pregnancy vaspin was positively correlated to insulin (p = 0.022), HOMA-IR (p = 0.016) and triglycerides (p = 0.033) and negatively correlated to QUICKI (p = 0.016) in the GDM women, but not in the Controls. These correlations were not observed at the 2nd trimester or postpartum. Vaspin, in contrast to HOMA-IR, could not independently predict GDM in binary logistic regression. In patients with GDM, insulin treatment did not affect vaspin levels. In conclusion, our data suggest that vaspin levels gradually decrease from the 2nd trimester to postpartum; however, decreases are similar between women with or without GDM. Serum vaspin cannot independently predict GDM and it is not affected by the degree of glucose metabolism deregulation or the exogenous administration of insulin.     

Relationship between zinc levels and plasma leptin in hemodialysis patients

Recent evidences suggested a possible relationship between zinc deficiency and leptin levels in pathogenesis of anorexia in chronic kidney disease. The present study addressed the relationship between zinc and leptin in hemodialysis (HD) patients.MethodsFifty HD patients (54.3 ± 12.7 years old, 62% men) were studied and compared to 21 healthy volunteers (50.7 ± 15.7 years old, 43% men). Biochemical data, serum zinc, plasma leptin, IL-6, TNF-α and C-Reactive Protein levels were determined. Anthropometric parameters, food intake and appetite score were also assessed.ResultsThe leptin levels were higher in HD patients (16.1 μg/mL (0.21–118.25) vs 6.0 μg/mL (0.50–23.10)) in healthy volunteers (p = 0.04), whereas serum zinc levels were lower (54.5 ± 16.3 μg/dL) compared to healthy volunteers (78.4 ± 9.4 μg/dL) (p = 0.0001). The plasma leptin was correlated negatively with plasma zinc (r = ?0.33; p = 0.007), energy (r = ?0.38; p = 0.002) and protein intake (r = ?0.34; p = 0.006) and, positively correlated with BMI (r = 0.54; p = 0.0001), % body fat (r = 0.70; p = 0.0001) and conicity index (r = 0.46; p = 0.001). Plasma zinc was associated with hemoglobin (r = 0.30; p = 0.04) and negatively associated with TNF-α (r = ?0.37; p = 0.002) and C-Reactive Protein (r = ?0.37; p = 0.004). There was no correlation among Zn, leptin and appetite score in these patients.ConclusionThis study showed that low plasma zinc levels are negatively associated with high leptin levels in HD patients.     

Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women?

Introduction: Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years. Methods: Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Results: Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r = ?0.26, p-value = 0.033; r = 0.42, p = 0.0003), decreasing levels of sex hormone binding globulin (r = 0.38, p = 0.0013; r = ?0.32, p = 0.0076), and increasing body mass index (BMI) (r = ?0.31, p =  < 0.0001; r = 0.39, p =  < 0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users (p = 0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend = 0.43), aPAI-1 (p = 0.78), or resistin (p = 0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p > 0.05). The lack of association with risk may be due to measurement error of the laboratory assays. Discussion: lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk.     

Serum zinc is associated with plasma leptin and Cu–Zn SOD in elite male basketball athletes

This paper investigates the relationship between plasma trace element and plasma leptin, as well as percent fat mass, in 16 male basketball athletes. Blood samples were obtained before intensive training and 24 h after intensive training to measure plasma zinc (Zn), copper (Cu), calcium (Ca), magnesium (Mg), iron (Fe), and leptin levels. High-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride (TG), total and cholesterol (TC) levels were determined using commercially available kits for humans. Subjects presented similar values in terms of age (21.1 ± 2.2 years old), body mass index (23.9 ± 2.00 kg/m²), percent body fat (14.40 ± 1.52%), plasma hemoglobin (150.1 ± 9.4 g/L), plasma Zn (17.47 ± 1.28 μmol/l), plasma Cu (13.42 ± 1.40 μmol/L), plasma Ca (2.41 ± 0.14 mmol/L), and plasma Mg (0.96 ± 0.02 mmol/L). The correlation analysis between degree of plasma leptin and plasma element contents was performed using the SPSS 16.0 software. Plasma Zn correlated positively with plasma leptin (r = 0.746, P < 0.01), Cu–Zn SOD (r = 0.827, P < 0.01), and negatively with percent fat mass (r = –0.598, P < 0.05) under no-training conditions. Meanwhile, plasma Cu, Ca, Mg, and Fe did not correlate with plasma leptin or percent fat mass (P > 0.05). In conclusion, plasma Zn may be involved in the regulation of plasma leptin and may serve as a lipid-mobilizing factor in Chinese men's basketball athletes.     

Elevated plasma levels of soluble (pro)renin receptor in patients with obstructive sleep apnea syndrome: Association with polysomnographic parameters

(Pro)renin receptor ((P)RR) is a specific receptor for both renin and its precursor prorenin. (P)RR was shown to be involved in pathophysiology of cardiovascular and renal diseases. Soluble (pro)renin receptor (s(P)RR), which is generated by furin from full length (P)RR, is present in blood. The aim of the present study is to clarify the association of plasma s(P)RR levels and the severity of OSAS. Plasma levels of s(P)RR were measured by ELISA in 58 male patients diagnosed as OSAS based on polysomnography, and 14 age-matched male control subjects. Blood samples were obtained at 6:00 a.m. just after overnight polysomnography. Plasma s(P)RR levels were significantly higher in patients with OSAS (9.0 ± 2.0 ng/mL, mean ± SD) than in control subjects (7.4 ± 1.5 ng/mL) (P = 0.0026). Plasma s(P)RR levels showed a significant negative correlation with % stage rapid eye movement (REM) sleep (r = −0.377, p < 0.005), and significant positive correlations with % stage 1 (r = 0.374, p < 0.005), arousal index (r = 0.341, p < 0.01), apnea hypopnea index (AHI) (r = 0.352, p < 0.01) and desaturation index (r = 0.302, p < 0. 05). In 12 OSAS patients with AHI ≥20, plasma levels of s(P)RR were studied after 3-month treatment with nasal continuous positive airway pressure (nCPAP). Plasma s(P)RR levels were significantly decreased after the nCPAP treatment (p = 0.0016). The present study has shown for the first time elevated plasma s(P)RR levels in patients with OSAS. Plasma s(P)RR levels were associated with the severity of OSAS. Soluble (P)RR may serve as a plasma marker reflecting the severity of OSAS.     

Serum chemerin levels during normal human pregnancy

During gestation there are important changes in maternal metabolism and an increase in insulin resistance, coinciding with an increase in adiposity. Chemerin is an adipocytokine which is expressed and secreted in various tissues, including placenta, and may play an important role in metabolic regulation during pregnancy. The aim of this study was to determine serum levels of chemerin during gestation and compare them to other indicators of insulin resistance. A cross-sectional study was carried out analyzing serum chemerin levels of 20 pregnant women during three gestational periods, early, middle, and late (between the 10th and 14th, the 23rd and 26th, and the 34th and 37th week) and 20 non-pregnant women were used as a control group. An analysis of chemerin levels during the menstrual cycle was performed in an eumenorrheic group (n = 16) in the early follicular (cycle day 4 ± 1) and the midluteal phase (cycle day 22 ± 1), demonstrating that serum chemerin levels did not fluctuate significantly. Serum levels of chemerin were significantly elevated during late gestation when compared to early (P < 0.001) and middle (P = 0.001) gestation and a negative correlation between serum chemerin and adiponectin levels (r = −0.1643) became more significant when the non-pregnant group was included in the calculations (r = −0.2471). There was no significant association of triglycerides, total cholesterol, LDL, HDL, insulin, and HOMA levels with chemerin. Although chemerin rose significantly and is negatively associated with adiponectin levels, it is not correlated with other markers of insulin sensitivity, suggesting that more study is needed to determine whether chemerin is useful in predicting insulin resistance during gestation.     

Circulating IL-6 concentrations and associated anthropometric and metabolic parameters in South Asian men and women in comparison to European whites

ObjectiveTo determine any ethnic differences in circulating interleukin (IL)-6 concentrations among SAs and Europeans, and to assess their relationship with body composition and insulin resistance measures.MethodsBody composition was assessed among 80 SA and European men and women using anthropometry, dual-energy X-ray absorptiometry and abdominal CT scan. Oral glucose tolerance tests with insulin response were performed to assess insulin resistance measures. IL-6 levels were measured by high sensitivity ELISA.ResultsMedian IL-6 values were higher in SA compared with European women: 1.94 mg/l versus 1.51 mg/l, p = 0.041, but not so in men (1.56 mg/l versus 1.57 mg/l). Only measures of obesity, in particular percentage fat area (r = 0.6, p = 0.003), were positively correlated with IL-6 in SAs. Differences in body fat percentage (visceral and total) could explain up to 30% of the IL-6 difference between Asian and European women.ConclusionSA women have elevated circulating IL-6 levels, in part due to greater visceral and percent fat levels compared with European women. This observation may in part explain why Asians are at elevated cardiovascular disease risk. Future studies should address the effects of lifestyle factors (physical activity, diet) on plasma IL-6 concentrations in SA women.     

Comparison of Different Diagnostic Criteria for Gestational Diabetes Mellitus Based on the 75-G Oral Glucose Tolerance Test: A Cohort Study

ObjectiveTo compare the different diagnostic criteria for gestational diabetes mellitus (GDM) proposed by the American Diabetes Association (ADA), World Health Organization (WHO), and Australian Diabetes in Pregnancy Society (ADIPS) in a 75-g, 2-hour oral glucose tolerance test (OGTT) and to investigate their effects on neonatal birth weight.MethodsHealthy pregnant women were enrolled in a cohort study to undergo a 75-g OGTT during 24 to 28 weeks of pregnancy and then followed up to delivery. ADA criteria and recommendations were used for the management of patients.ResultsAmong 670 pregnant women, GDM was diagnosed in 41 (6.1%), 81 (12.1%), and 126 (18.8%) on the basis of ADA, WHO, and ADIPS criteria, respectively. The kappa value was 0.38 (P < .0001) for the agreement between ADA and WHO criteria, 0.41 (P < .0001) for agreement between ADA and ADIPS criteria, and 0.64 (P < .0001) for agreement between WHO and ADIPS criteria. WHO-only “positive” women had significantly lower fasting plasma glucose (87.9 versus 102.2 mg/dL; P < .0001) and 1-hour plasma glucose levels (146.4 versus 200.5 mg/dL; P < .0001) but higher 2-hour plasma glucose levels (150.1 versus 109.1 mg/dL; P < .0001) than women diagnosed with GDM by only ADA criteria. The correlation coefficient between 1-hour glucose level and neonatal birth weight was 0.09 (P < .02). The adjusted odds ratio of macrosomia associated with GDM according to ADA criteria was 1.34 (95% confidence interval, 0.15 to 12).ConclusionThe frequency of occurrence of GDM was 6.1% in a 75-g OGTT based on ADA criteria, and there was fair agreement between ADA and WHO criteria, moderate agreement between ADA and ADIPS criteria, and strong agreement between WHO and ADIPS criteria. A modest correlation was found between the 1-hour serum glucose value and neonatal birth weight. (Endocr Pract. 2008;14:312-317)     

The impact of acute lung injury,ECMO and transfusion on oxidative stress and plasma selenium levels in an ovine model

The purpose of this study was to determine the effects of smoke induced acute lung injury (S-ALI), extracorporeal membrane oxygenation (ECMO) and transfusion on oxidative stress and plasma selenium levels. Forty ewes were divided into (i) healthy control (n = 4), (ii) S-ALI control (n = 7), (iii) ECMO control (n = 7), (iv) S-ALI + ECMO (n = 8) and (v) S-ALI + ECMO + packed red blood cell (PRBC) transfusion (n = 14). Plasma thiobarbituric acid reactive substances (TBARS), selenium and glutathione peroxidase (GPx) activity were analysed at baseline, after smoke injury (or sham) and 0.25, 1, 2, 6, 7, 12 and 24 h after initiation of ECMO. Peak TBARS levels were similar across all groups. Plasma selenium decreased by 54% in S-ALI sheep (1.36 ± 0.20 to 0.63 ± 0.27 μmol/L, p < 0.0001), and 72% in sheep with S-ALI + ECMO at 24 h (1.36 ± 0.20 to 0.38 ± 0.19, p < 0.0001). PRBC transfusion had no effect on TBARS, selenium levels or glutathione peroxidase activity in plasma. While ECMO independently increased TBARS in healthy sheep to levels which were similar to the S-ALI control, the addition of ECMO after S-ALI caused a negligible increase in TBARS. This suggests that the initial lung injury was the predominant feature in the TBARS response. In contrast, the addition of ECMO in S-ALI sheep exacerbated reductions in plasma selenium beyond that of S-ALI or ECMO alone. Clinical studies are needed to confirm the extent and duration of selenium loss associated with ECMO.     

Prevalence and genotype identification of human papillomavirus in women undergoing voluntary cervical cancer screening in Molise,Central Italy

We examined the prevalence of HR- and LR-HPV by Linear Array genotyping test in 299 women aged 18–63 years who consecutively visited Molise Region main hospitals for routine Pap smear between February and August 2008. Ninety women were positive for any HPV (30.1%), and 66 for any HR-HPV (22.1%). The most prevalent HR-HPV types were HPV 16 (22.2% of all women with HPV infection), HPV 53 (14.4%), and HPV 66 (14.4%). HPV infections increased from 15.8% in the 18–20 years group to 50.0% in the 21–23 years group and then decreased to 9.1% in those aged 50 years or more (p = 0.008). Multiple HPV infections were observed in 15.7% of the study sample (52.2% of all HPV positive). There is a significantly higher prevalence of multiple infections in 18–32 years group women (24.5%) compared with females aged 33 years or more (6.8%) (p < 0.005). Current smokers were at increased risk of HPV infection (44.2% of HPV infections compared with 23.5% in never smokers, and 25.3% of multiple HPV infections compared with 11.3%; p = 0.001). HR-HPV infections were higher in women never been pregnant (27.1% compared with 7.7%; p = 0.001). Oral contraceptive use was completely unrelated to infection. Among the 122 women who had both cytological examination and HPV results, multiple HR-HPV types were found in 36.8% of those with abnormal cervical findings, and in 13.6% of those with normal cervical findings (p = 0.05). The results of the present investigation provide further evidence for the notion that cervical HPV infection is more widespread than previously suggested.     

Cathepsin G activity lowers plasma LDL and reduces atherosclerosis

Cathepsin G (CatG), a serine protease present in mast cells and neutrophils, can produce angiotensin-II (Ang-II) and degrade elastin. Here we demonstrate increased CatG expression in smooth muscle cells (SMCs), endothelial cells (ECs), macrophages, and T cells from human atherosclerotic lesions. In low-density lipoprotein (LDL) receptor-deficient (Ldlr^–/–) mice, the absence of CatG reduces arterial wall elastin degradation and attenuates early atherosclerosis when mice consume a Western diet for 3 months. When mice consume this diet for 6 months, however, CatG deficiency exacerbates atherosclerosis in aortic arch without affecting lesion inflammatory cell content or extracellular matrix accumulation, but raises plasma total cholesterol and LDL levels without affecting high-density lipoprotein (HDL) or triglyceride levels. Patients with atherosclerosis also have significantly reduced plasma CatG levels that correlate inversely with total cholesterol (r = –0.535, P < 0.0001) and LDL cholesterol (r = –0.559, P < 0.0001), but not with HDL cholesterol (P = 0.901) or triglycerides (P = 0.186). Such inverse correlations with total cholesterol (r = –0.504, P < 0.0001) and LDL cholesterol (r = –0.502, P < 0.0001) remain significant after adjusting for lipid lowering treatments among this patient population. Human CatG degrades purified human LDL, but not HDL. This study suggests that CatG promotes early atherogenesis through its elastinolytic activity, but suppresses late progression of atherosclerosis by degrading LDL without affecting HDL or triglycerides.