Circulating Levels of Inflammatory Markers in Intrauterine Growth Restriction

We aimed to investigate possible alterations in circulating levels of the perinatal stress markers high sensitivity (hs)-CRP, PAI-1, and S100B—probably reflecting brain and adipose tissue inflammation—in intrauterine growth-restricted-(IUGR) and appropriate-for-gestational-age-(AGA) pregnancies, given that these groups differ in fat mass and metabolic mechanisms involving aseptic inflammation. Serum hs-CRP, PAI-1, and S100B levels were measured in 40 mothers, and their 20 AGA and 20 IUGR full-term fetuses and neonates on postnatal days 1 and 4. hs-CRP, PAI-1, and S100B levels did not differ at all time points between AGA and IUGR groups. We conclude that the lack of difference in hs-CRP, PAI-1 and S100B levels, between IUGR and AGA fetuses/neonates—despite the lower birth weight, reflecting reduced fat mass in the former—might indicate more intense adipose tissue and nervous system inflammation in IUGRs. However, implication of other inflammation-related mechanisms, common in the IUGR state (e.g. preeclampsia), cannot be excluded

Maternal chronic stress correlates with serum levels of cortisol, glucose and C-peptide in the fetus, and maternal non chronic stress with fetal growth

Introduction: During pregnancy, maternal stressors cause changes in both maternal and fetal HPA axes. We therefore investigated the impact of maternal non chronic and chronic stress on fetal glucose metabolism and growth, and serum levels of cortisol in the fetus. Materials and methods: Normal weight pregnant women (n = 192; mean ± SD 27.9 ± 4.2 years old, and; 26.9 ± 2.4 kg/m²) were assessed during the 2nd and 3rd trimester with anthropometry, fetal ultrasound, blood samples for serum CRH, cortisol and IL6, and STAI trait and state stress questionnaires. We measured serum cortisol, insulin and c-peptide, and plasma glucose from cord blood. Neonates underwent anthropometry at the 3rd post-delivery day. Results: In both 2nd and 3rd trimesters, women with STAI trait scores ≥40 had significantly greater levels of fasting serum CRH and cortisol than those with STAI trait scores<40. 2nd trimester: STAI trait scores correlated positively with cord blood glucose and c-peptide. Maternal serum CRH correlated negatively with U/S fetal biparietal head diameter, while serum cortisol correlated positively with abdominal circumference. Maternal serum IL6, CRH and cortisol all correlated positively with birth waist circumference. 3rd trimester: Women with STAI state scores ≥40 had fetuses with larger U/S abdominal and smaller head circumferences compared to those of women with STAI scores <40. Women with STAI trait scores ≥40 had greater levels of cord blood cortisol, glucose, and c-peptide compared to women with STAI scores <40. STAI state scores ≥40 correlated positively with maternal CRH and U/S fetal abdominal circumference, and negatively with fetal head circumference and biparietal diameter. STAI trait scores correlated positively with cord blood c-peptide, glucose, insulin and cortisol. Maternal serum levels of CRH correlated positively with U/S fetal abdominal circumference and cord blood cortisol, and negatively with fetal head circumference and biparietal head diameter. Maternal serum levels of both CRH and cortisol correlated positively with cord blood c-peptide, glucose, and insulin. STAI trait was the best positive predictor of cord blood cortisol, glucose and c-peptide, whilst STAI state was the best positive and negative predictor, respectively of fetal abdominal circumference and fetal head circumference or biparietal diameter. Conclusions: Increased maternal chronic stress (reflected by the STAI trait score) associates with increased fetal cortisol, glucose, c-peptide secretion and thus, insulin resistance. Maternal non chronic stress (STAI state) in the 3rd trimester associates with changes in fetal growth pattern, including increased and decreased measurements of fetal abdominal and head growth respectively

An assessment of serum leptin levels in patients with chronic viral hepatitis: a prospective study

<p>Abstract</p> <p>Background</p> <p>The role of leptin in the course of liver disease due to chronic viral hepatitis (CVH) remains controversial. Our aims were to investigate the relationship between serum leptin concentrations and the severity of liver disease in a cohort of subjects with HBeAg negative chronic hepatitis B (CHB) and C (CHC) and to analyze the effect of body composition, the leptin system and insulin resistance together with viral factors on virologic response to antiviral treatment.</p> <p>Methods</p> <p>We studied 50 (36 men) consecutive patients suffering from biopsy-proven CVH due to HBV (n = 25) or HCV (n = 25) infection. Thirty-two (17 men) healthy volunteers served as controls. Levels of serum leptin and insulin were determined by immunoassays at baseline and at the end of the treatment.</p> <p>Results</p> <p>A significant association between serum leptin levels and the stage of hepatic fibrosis was noted; patients with cirrhosis presented higher serum leptin levels compared to those with lower fibrosis stage [CHB patients (17436 pg/ml vs 6028.5 pg/ml, p = 0.03), CHC patients (18014 pg/ml vs 4385 pg/ml, p = 0.05]. An inverse correlation between lower leptin levels and response to lamivudine monotherapy was noted in patients with CHB; those with a virologic response presented lower serum leptin levels (5334 vs 13111.5 pg/ml; p-value = 0.003) than non-responders. In genotype 1 CHC patients, insulin resistance played a significant role in the response to antiviral therapy.</p> <p>Conclusion</p> <p>Our data clearly suggest that cirrhosis due to CHB or CHC is associated with higher leptin levels. Increased serum leptin levels represent a negative prognostic factor for response to lamivudine monotherapy in patients with CHB. In CHC patients insulin resistance strongly influences the response to antiviral treatment in patients infected with genotype 1.</p

Circulating visfatin levels in healthy preterm infants are independently associated with high-density lipoprotein cholesterol levels and dietary long-chain polyunsaturated fatty acids

The adipokine visfatin has been proposed to exert insulin-mimicking effects and to play a role in the development of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance and, possibly, for other components of metabolic syndrome. Dietary long-chain polyunsaturated fatty acids (LCPUFAs) during the perinatal period may reduce the risk of metabolic syndrome. The authors’ objective was to study the circulating concentrations of visfatin in preterm infants and to examine associations of visfatin with anthropometric measurements, metabolic indices, and dietary LCPUFAs. Serum visfatin concentrations were determined by enzyme-linked immunosorbent assay at mean (SD) 33.8 (11.7) days of life in 60 healthy preterm infants (gestational age, 32.7 [1.9] weeks) randomly assigned to be fed since birth either a formula containing LCPUFA (arachidonic and docosahexaenoic acid) (+LCPUFA group) or the same formula without LCPUFA (-LCPUFA group). Associations of visfatin with anthropometric parameters, serum glucose, insulin, homeostasis model assessment index of insulin resistance, blood lipids, and adiponectin levels were examined. Serum visfatin levels were significantly higher in the +LCPUFA than in the -LCPUFA group (P &lt; .001) and correlated positively with body weight z score (beta = 0.31, P = .02), total cholesterol (beta = 0.34, P = .01), high-density lipoprotein cholesterol (HDL-C) (beta = 0.47, P &lt; .001), and adiponectin levels (beta = 0.29, P = .03), but not with indices of insulin sensitivity. In multiple regression analysis, HDL-C and dietary LCPUFAs correlated independently with serum visfatin levels. Circulating visfatin levels in preterm infants are independently associated with HDL-C levels and dietary LCPUFAs. Whether the higher visfatin levels in the +LCPUFA preterm infant group are beneficial for the later health of these infants remains to be determined. (C) 2011 Elsevier Inc. All rights reserved

Association of Plasma Irisin Levels with Circulating Endothelial Microparticles (EMPs) and Endothelial Progenitor Cells (EPCs) in Children Born Prematurely

Prematurity has been linked with endothelial dysfunction in later life. The purpose of this study was to evaluate the association between plasma irisin, an adipomyokine reported to protect the functional integrity of vascular endothelium, and circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs), consisting early biomarkers of endothelial dysfunction, in preterm-born children. We studied 131 prepubertal children; 61 preterm and 70 born at term (controls). Plasma irisin was determined by ELISA. Circulating CD62E(+), CD144(+) and CD31(+)/CD42b(-) EMPs, and CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs, were determined by flow cytometry. Body mass index, waist-to-hip ratio, neck circumference, systolic and diastolic blood pressure, and biochemical parameters (glucose, lipids, insulin, HOMA-IR) were also evaluated. Plasma irisin was significantly lower (p = 0.001), whereas circulating EMPs and EPCs were higher, in children born prematurely compared to controls. Irisin was recognized as independent predictor for CD144(+) and CD31(+)/CD42b(-) EMPs, CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs in the total study population, and for CD31(+)/CD42b(-) EMPs in the preterm group. In conclusion, plasma irisin correlates independently with circulating EMP and EPC subpopulations in prepubertal children and in preterm-born ones. Further studies in children will potentially elucidate the link between irisin and the primary stages of prematurity-related endothelial dysfunction

Diagnostic and prognostic utility of serum receptor-binding cancer antigen expressed on SiSo cells (RCAS1) levels in colon cancer patients

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that induces cell-cycle arrest and/or apoptosis in cells bearing the RCAS1 receptor. The aim of the present study was to elucidate the diagnostic and prognostic utility of RCAS1 levels in colon cancer patients. Serum RCAS1 levels were determined using a sandwich enzyme-linked immunosorbent assay in 97 colon cancer patients and 20 healthy individuals. The levels were significantly increased in colon cancer patients compared to healthy individuals (p&lt;0.0001). Increased RCAS1 levels were significantly associated with advanced Dukes’ stage (p=0.0079) and high histopathological tumor grade (p=0.0028). Univariate analysis revealed that colon cancer patients with elevated RCAS1 levels had significantly shorter overall survival times (log-rank test, p=0.027). By multivariate analysis, serum RCAS1 was identified as an independent prognostic factor (Cox regression analysis, p=0.033). In conclusion, colon cancer patients with advanced disease stage and grade and poor prognosis showed elevated serum RCAS1 levels. Assessment of serum RCAS1 levels could therefore be considered as a diagnostic and prognostic marker in colon neoplasia. (Int J Rio Markers 2009; 24: 70-6

Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates with infection

Background: Early diagnosis and treatment of neonatal infection is important to prevent morbidity and mortality. The gastrointestinal tract-derived hormones ghrelin and peptide YY (PYY), which participate in the regulation of food intake and energy balance, may also play roles in the inflammatory response. Their involvement in neonatal infection is not known. Methods: Plasma ghrelin and PYY(3-36) levels were serially measured (by ELISA) on Days 0, 1, 2, 3 and 7 following admission in 36-term neonates with febrile infection (22 of them were septic) and once in 20 healthy term neonates of similar postnatal age and gender distribution, as controls. Associations of ghrelin and PYY(3-36) levels with clinical and laboratory parameters, including anthropometrics, fever, leukocyte and platelet counts, serum glucose, C-reactive protein (CRP) and serum amyloid A levels, were assessed. Results: Plasma ghrelin levels were significantly higher in infected neonates than in controls at each study day (p=0.009), whereas PYY(3-36) levels did not differ significantly between patients and controls at any day. In infected neonates, ghrelin levels on admission correlated negatively with serum glucose levels (p=0.003), whereas fever change during the course of infection was significantly associated with change of ghrelin levels (p=0.01). Receiver operating characteristic analysis of ghrelin levels resulted in significant areas under the curve (AUC) for detecting infected neonates on admission (AUC=0.728, p=0.005). Conclusions: Circulating ghrelin, but not PYY(3-36), levels are increased in neonates with infection, possibly reflecting and/or participating in the inflammatory process

Gender dimorphic increase in RBP-4 and NGAL in children born after IVF: an epigenetic phenomenon?

Background In vitro fertilisation (IVF) has been widely used during the last decades. Recent studies demonstrated some alterations in IVF children’s metabolic profile compared with controls. The recently reported lipocalins retinol-binding protein 4 (RBP-4) and neutrophil gelatinase-associated lipocalin (NGAL), as well as visfatin, which are associated with glucose intolerance and could help in the early detection of metabolic abnormalities, have not been studied in IVF children as yet. We studied the lipocalins RBP-4 and NGAL as well as visfatin in children born after IVF. Subjects and methods A total of 100 children born after IVF (47 boys) and 60 controls born after normal conception (30 boys), aged 414year, were studied cross-sectionally. All children had a physical examination, their fasting glucose, insulin, lipid profile, RBP-4, NGAL, and visfatin were determined and their homoeostasis model assessment (HOMA) index was calculated. Results Children born after IVF had significantly higher RBP-4 (P=0 center dot 009) and NGAL (P=0 center dot 028) levels than controls. When divided by gender, RBP-4 remained higher in IVF girls (P=0 center dot 002), whereas NGAL was higher in IVF boys (P=0 center dot 021). Linear regression analysis had revealed that the differences are attributed to the IVF procedure per se. Conclusions In our study, IVF children had significantly higher RBP-4 and NGAL levels than controls, suggesting early metabolic derangements that could be attributed to an epigenetic phenomenon. These results are in accordance with our earlier findings of higher blood pressure and triglycerides in IVF children than controls. Further prospective studies in IVF children will determine the natural course of their metabolic profile

Serum tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) levels in colorectal cancer patients: associations with clinicopathological variables and patient survival

Tissue inhibitors of metalloproteinases (TIMPs) appear to affect many aspects of cancer biology, playing a crucial role in cell signaling by regulating cell growth, apoptosis, invasion, metastasis, angiogenesis, and genomic instability. The aim of the present study was to elucidate the diagnostic and prognostic utility of TIMP-1 and TIMP-2 in patients with colon cancer. Serum TIMP-1 and TIMP-2 concentrations were quantified using an enzyme-linked immunosorbent assay in 97 colon cancer patients. Elevated serum TIMP-1 levels were found in patients with advanced disease stage (p=0.0512) and poorly differentiated histopathological tumor grade (p=0.0059). Patients with increased TIMP-1 levels had shorter overall survival times (log-rank test, p=0.0143). Multivariate analysis also identified TIMP-1 as an independent prognostic factor (Cox regression analysis, p=0.0149). Serum TIMP-2 levels were not significantly associated with disease stage, histopathological grade or survival. In the subgroup of patients with well and moderately differentiated tumors, TIMP-1 and TIMP-2 were identified as independent prognostic factors (Cox regression analysis, p=0.0379 and p=0.0451, respectively). In conclusion, assessment of serum TIMP-1 can be considered a useful biomarker in colon cancer, whereas TIMP-2 appears to be of limited value. (Int J Biol Markers 2009; 24: 245-52