Preparation and Characterization of Hyaluronic Acid-Polycaprolactone Copolymer Micelles for the Drug Delivery of Radioactive Iodine-131 Labeled Lipiodol.

Micelles, with the structure of amphiphilic molecules including a hydrophilic head and a hydrophobic tail, are recently developed as nanocarriers for the delivery of drugs with poor solubility. In addition, micelles have shown many advantages, such as enhanced permeation and retention (EPR) effects, prolonged circulation times, and increased endocytosis through surface modification. In this study, we measured the critical micelle concentrations, diameters, stability, and cytotoxicity and the cell uptake of micelles against hepatic cells with two kinds of hydrophilic materials: PEG-PCL and HA-g-PCL. We used 131I as a radioactive tracer to evaluate the stability, drug delivery, and cell uptake activity of the micelles. The results showed that HA-g-PCL micelles exhibited higher drug encapsulation efficiency and stability in aqueous solutions. In addition, the 131I-lipiodol loaded HA-g-PCL micelles had better affinity and higher cytotoxicity compared to HepG2 cells.

Proteomic Profiling of Neuroblastoma Cells Adhesion on Hyaluronic Acid-Based Surface for Neural Tissue Engineering.

The microenvironment of neuron cells plays a crucial role in regulating neural development and regeneration. Hyaluronic acid (HA) biomaterial has been applied in a wide range of medical and biological fields and plays important roles in neural regeneration. PC12 cells have been reported to be capable of endogenous NGF synthesis and secretion. The purpose of this research was to assess the effect of HA biomaterial combining with PC12 cells conditioned media (PC12 CM) in neural regeneration. Using SH-SY5Y cells as an experimental model, we found that supporting with PC12 CM enhanced HA function in SH-SY5Y cell proliferation and adhesion. Through RP-nano-UPLC-ESI-MS/MS analyses, we identified increased expression of HSP60 and RanBP2 in SH-SY5Y cells grown on HA-modified surface with cotreatment of PC12 CM. Moreover, we also identified factors that were secreted from PC12 cells and may promote SH-SY5Y cell proliferation and adhesion. Here, we proposed a biomaterial surface enriched with neurotrophic factors for nerve regeneration application.

Activation of the ubiquitin proteasome pathway by silk fibroin modified chitosan nanoparticles in hepatic cancer cells.

Silk fibroin (SF) is a protein with bulky hydrophobic domains and can be easily purified as sericin-free silk-based biomaterial. Silk fibroin modified chitosan nanoparticle (SF-CSNP), a biocompatible material, has been widely used as a potential drug delivery system. Our current investigation studied the bio-effects of the SF-CSNP uptake by liver cells. In this experiment, the characterizations of SF-CSNPs were measured by particle size analysis and protein assay. The average size of the SF-CSNP was 311.9 ± 10.7 nm, and the average zeta potential was +13.33 ± 0.3 mV. The SF coating on the SF-CSNP was 6.27 ± 0.17 µg/mL. Moreover, using proteomic approaches, several proteins involved in the ubiquitin proteasome pathway were identified by analysis of differential protein expressions of HepG2 cell uptake the SF-CSNP. Our experimental results have demonstrated that the SF-CSNP may be involved in liver cancer cell survival and proliferation.

Characterization of silk fibroin modified surface: a proteomic view of cellular response proteins induced by biomaterials.

The purpose of this study was to develop the pathway of silk fibroin (SF) biopolymer surface induced cell membrane protein activation. Fibroblasts were used as an experimental model to evaluate the responses of cellular proteins induced by biopolymer material using a mass spectrometry-based profiling system. The surface was covered by multiwalled carbon nanotubes (CNTs) and SF to increase the surface area, enhance the adhesion of biopolymer, and promote the rate of cell proliferation. The amount of adhered fibroblasts on CNTs/SF electrodes of quartz crystal microbalance (QCM) greatly exceeded those on other surfaces. Moreover, analyzing differential protein expressions of adhered fibroblasts on the biopolymer surface by proteomic approaches indicated that CD44 may be a key protein. Through this study, utilization of mass spectrometry-based proteomics in evaluation of cell adhesion on biopolymer was proposed.

Utilizing isotope dilution-matrix-assisted laser desorption ionization-time of flight mass spectrometry as a reference procedure for the radioimmunoassay of serum thyroxine.

BACKGROUND: The thyroid hormone, thyroxine (T4), is a tyrosine-based hormone produced by the thyroid gland, which is essential in regulating a number of biological processes, including growth, neurodevelopment, carbohydrate metabolism, oxygen consumption and protein synthesis. Data on human thyroid hormone metabolism were gathered since the middle of the 1970s mainly by the use of radioactive iodinated ((125)I or (131)I) hormones. METHODS: We describe an isotope dilution-matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) method for the simultaneous determination of endogenous thyroid hormone and its (13)C6-labeled analogue in serum. The (13)C6-thyroxine ((13)C6-T4) was used as an internal standard; T4 and its isotopically labeled analogue were measured in the selected reaction monitoring mode for the transitions from m/z 777.8 to 732.1 and from m/z 784.2 to 738.1, respectively. RESULTS: Serum samples were prepared and concentrated by a solid-phase extraction chromatography method. The recovery rate was measured by (125)I-T4 and can be up to 82.8±2.8%. The detection limit and linear range for T4 were 5 ng/ml and 5-400 ng/ml, respectively. The correlation coefficient (R(2)) between radioimmunoassay (RIA) and isotope dilution-MALDI-TOF MS for detection of serum T4 was 0.982. CONCLUSION: This assay has a good relationship against a commercial RIA and the isotope dilution-mass spectrometry method and may serve as a reference method for quantitative analysis of T4.

Assessing human urinary proteome using a mass spectrometry-based profiling system combined with magnetic nanoparticles.

BACKGROUND: Samples originating from body fluids often contain a complex mixture of inorganic salts, buffers, chaotropic agents, surfactant/detergents, preservatives, and other solubilizing agents. The presence of those contaminants often precludes direct analysis by mass spectrometry. Urine, a blood filtrate produced by the urinary system, is an ideal bio-sample and a rich source of biomarkers for diagnostic information. METHODS: To enhance our understanding of urinary proteome, the urine proteins were prepared by magnetic nanoparticles (MNPs) combined with MACS separation column system and then identified by reverse phase nano-high performance liquid chromatography electrospray ionization tandem mass spectrometry (RP-nano-HPLC-ESI-MS/MS) followed by peptide fragmentation pattern. RESULTS: Experimental results have revealed that the better protein identification for the demonstration of bovine serum albumin (BSA) in artificial urine. Using this cleanup approach, a total of 542 peptides, corresponding to 282 unique proteins, were identified from human urine samples, in which 54 proteins have higher confidence levels. Indeed, this study has revealed that some biological factors might be increased along with aging, such as up-regulation of immunoproteins. CONCLUSIONS: The present study was designed to establish optimal techniques to develop a proteomic map of urinary proteins, and a cleanup method that greatly simplifies this sample preparation process was proposed.

Assessing the responses of cellular proteins induced by hyaluronic acid-modified surfaces utilizing a mass spectrometry-based profiling system: over-expression of CD36, CD44, CDK9, and PP2A.

The cell responses to biopolymer surface at the early adhesion stages can be critical for cell survival. The purpose of this research was to assess formation of hyaluronic acid (HA) biopolymer surface, the fibroblasts were used as an experimental model to evaluate the responses of cellular proteins induced by biopolymer materials using a mass spectrometry-based profiling system. Surfaces were covered by multi-walled carbon nanotubes (CNT), chitosan (CS), and HA to increase the surface area, enhance the adhesion of biopolymer and promote the rate of cell proliferation. The amount of adhered fibroblasts on CNT/CS/HA electrodes of quartz crystal microbalance (QCM) were greatly exceeded those on other surfaces that were consistent with cell-count technique. Moreover, analyzing differential protein expressions of adhered fibroblasts on those biopolymer surfaces by proteomic approaches identified CD36, CD44, PP2A, and CDK9 as key proteins. To validate the influences of those four proteins on adhesions of fibroblasts on biopolymers, the cells were blocked by antibodies of the proteins and the adhesions of cells on the tested biopolymer surfaces were examined using a QCM technique, flow cytometric analysis and morphological observations. The results of significantly decreasing the weights and densities of the blocked fibroblasts adhering to CNT/CS/HA surfaces were obtained, and validate those proteins found by proteomic approaches. Utilizing mass spectrometry-based proteomics to evaluate cell adhesions on biopolymers is proposed.

Activity-dependent neuroprotector homeobox protein: A candidate protein identified in serum as diagnostic biomarker for Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia of late life. To enhance our understanding of AD proteome, the serum proteins were analyzed using two-dimensional gel electrophoresis (2DE) combined with nano-high performance liquid chromatography electrospray ionization tandem mass spectrometry (nano-HPLC-ESI-MS/MS) followed by peptide fragmentation patterning. In this study, six protein spots with differential expression were identified. Five up-regulated proteins were identified as actin, apolipoprotein A-IV (Apo A-IV), inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), alpha-1-antitrypsin (AAT), and antithrombin-III (AT-III); one protein, activity-dependent neuroprotector homeobox protein (ADNP) was down-regulated in AD patients. These proteins with differential expression in the serum may serve as potential indicators of AD. Our results suggested that ADNP may play an important role in slowing the progression of clinical symptoms of AD.

Urinary protein profiling by liquid chromatography/tandem mass spectrometry: ADAM28 is overexpressed in bladder transitional cell carcinoma.

Bladder cancer is the most common urological cancer with higher incidence rate in the endemic areas of Blackfoot disease (BFD) in southern Taiwan. The aim of this study was to utilize the proteomic approach to establish urinary protein patterns of bladder cancer. The experimental results showed that most patients with bladder cancer had proteinuria or albuminuria. The urine arsenic concentrations of bladder cancer patients in BFD areas were significantly higher than those patients from non-BFD areas. In the proteomic analysis, the urinary proteome was identified by nano-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (nano-HPLC/ESI-MS/MS) followed by peptide fragmentation pattern analysis. We categorized 2782 unique proteins of which 89 proteins were identified with at least three unique matching peptide sequences. Among these 89 proteins, thirteen of them were not found in the control group and may represent proteins specific for bladder cancer. In this study, three proteins, SPINK5, ADAM28 and PTP1, were also confirmed by Western blotting and showed significant differential expression compared with the control group. ADAM28 may be used as a possible biomarker of bladder cancer.

Protein profiling of human nonpigmented ciliary epithelium cell secretome: the differentiation factors characterization for retinal ganglion cell line.

The purpose of this paper was to characterize proteins secreted from the human nonpigmented ciliary epithelial (HNPE) cells, which have differentiated a rat retinal ganglion cell line, RGC-5. Undifferentiated RGC-5 cells have been shown to express several marker proteins characteristic of retinal ganglion cells. However, RGC-5 cells do not respond to N-methyl-D aspartate (NMDA), or glutamate. HNPE cells have been shown to secrete numbers of neuropeptides or neuroproteins also found in the aqueous humor, many of which have the ability to influence the activity of neuronal cells. This paper details the profile of HNPE cell-secreted proteins by proteomic approaches. The experimental results revealed the identification of 132 unique proteins from the HNPE cell-conditioned SF-medium. The biological functions of a portion of these identified proteins are involved in cell differentiation. We hypothesized that a differentiation system of HNPE cell-conditioned SF-medium with RGC-5 cells can induce a differentiated phenotype in RGC-5 cells, with functional characteristics that more closely resemble primary cultures of rat retinal ganglion cells. These proteins may replace harsh chemicals, which are currently used to induce cell differentiation.

Characterization of surface modification on self-assembled monolayer-based piezoelectric crystal immunosensor for the quantification of serum α-fetoprotein.

Self-assembled monolayers (SAMs) on coinage metallic material can provide versatile modeling systems for studies of interfacial electron transfer, biological interactions, molecular recognition and other interfacial phenomena. Recently, a bio-sensing system has been produced by analysis of the attachment of antibody using alkanethiols, to form SAMs on the face of Au-quartz crystal microbalance (QCM) surfaces. In this study, the attachment of anti-α-fetoprotein monoclonal antibody to a SAMs surface of 11-mercaptoundecanoic acid was achieved using water-soluble N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide as coupling agents. Surface analyses were utilized by X-ray photoelectron spectroscopy and atomic force microscopy. The quantization of immobilized antibody was characterized by the frequency shift of QCM and the radioactivity change of ¹²5I labeled antibody. The limit of detection and linear range of the calibration curve of the QCM method were 15 ng/ml and 15-850 ng/ml. The correlation coefficients of α-fetoprotein concentration between QCM and radioimmunoassay were 0.9903 and 0.9750 for the standards and serum samples, respectively. This report illustrates an investigation of SAMs for the preparation of covalently immobilized antibody biosensors.

Melamine contamination.

In the summer of 2008, serious illnesses and deaths of babies in China were linked to melamine-tainted powdered infant formula. Melamine contains several metabolites, such as ammeline, ammelide, and cyanuric acid, and has been used for the adulteration of foods or milk to increase their apparent protein content. It is assumed that melamine and its metabolites are absorbed in the gastrointestinal tract, and precipitate in the kidney to form crystals. A new tolerable daily intake of 0.2 mg kg(-1) body weight was adapted by the World Health Organization in 2008. This paper reviews the variety of analytical methods that have been used for the analysis of melamine in food. The limit of detection of these various methods is 0.05-100 ppm. The maximum acceptable concentration in food has been set at 50 ppb by the US FDA. A fast and ultrasensitive procedure for screening, detection, and characterization of melamine and its derivative compounds needs to be established. Currently, mass-spectrometry technologies provide an alternative to derivatization for regulatory analysis of food.

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.

Serum resistin level is a predictor of ovarian response in in vitro fertilisation cycle.

OBJECTIVES: To measure serum resistin levels in infertile women undergoing in vitro fertilisation-embryo transfer (IVF-ET), and to find any correlations between serum resistin levels and body weight, body mass index, the number of oocytes retrieved, and the outcome of IVF-ET. In addition, to assess whether there is any difference in serum resistin levels between infertility caused by polycystic ovary syndrome (PCOS) and infertility caused by other female factors. METHODS: We designed a case-control study, and a total of 44 infertile women were enrolled. The blood samples for resistin measurement were collected on day 3 of the menstrual cycle prior to the administration of gonadotropin during in vitro fertilisation. These cases were then divided into 2 subgroups (PCOS group versus non-PCOS group) and a number of variables were measured and compared, including serum resistin levels. RESULTS: Serum resistin levels were inversely correlated with the number of oocytes retrieved (r=-0.371, p=0.013). No significant correlation was found between serum resistin levels and body mass index or body weight, either in the whole group or in the 2 subgroups. Serum resistin levels in the non-PCOS group were significantly higher than in the PCOS group (p=0.049). Serum resistin levels in the non-PCOS group were inversely correlated to the number of oocytes retrieved (r=-0.386, p=0.039), but no similar correlation was found in the PCOS group. There was no correlation between serum resistin levels and fertility rate or clinical pregnancy rate in either subgroup. CONCLUSIONS: We observed a negative correlation between serum resistin levels and the number of oocytes retrieved during IVF. However, this phenomenon was only present in the non-PCOS group. This result suggests that serum resistin levels might be a good predictor of ovarian response in infertile women without PCOS during IVF. The role of serum resistin in response to inflammation caused by endometriosis or chronic pelvic infection, both of which are major causes of female infertility, should be examined in a further study.

Identification of human hepatocellular carcinoma-related proteins by proteomic approaches.

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. Analysis of human serum from HCC patients using two-dimensional gel electrophoresis (2DE) combined with nano-high-performance liquid chromatography electrospray ionization tandem mass spectrometry (nano-HPLC-ESI-MS/MS) identified fourteen different proteins differentially expressed between HCC patients and the control group. Twelve proteins were up-regulated and two down-regulated. By using nano-HPLC-MS/MS system to analyze proteome in human serum, 317 proteins were identified, twenty-nine of which to high confidence levels (protein matched at last two unique peptide sequences). Of these twenty-nine proteins, six were present only in HCC patients and may serve as biomarkers for HCC.

Increased plasma visfatin concentrations in women with polycystic ovary syndrome.

OBJECTIVE: To test the hypothesis that plasma visfatin concentrations will be higher in women with polycystic ovary syndrome (PCOS) than in women without PCOS. DESIGN: Clinical study. SETTING: University hospital. PATIENT(S): A total of 52 women were evaluated. Twenty-six had PCOS, and the remaining 26 were healthy women with regular menstrual cycles who served as control subjects. INTERVENTION(S): Plasma visfatin concentrations were analyzed with the use of RIA. MAIN OUTCOME MEASURE(S): Serum concentrations of FSH, LH, TSH, PRL, T, insulin, E(2), and visfatin. RESULT(S): Plasma visfatin concentrations were significantly higher in the PCOS group (336.8 +/- 50.2 ng/mL) than in the healthy control group (282.4 +/- 43.3 ng/mL). Logistic regression analysis indicated a significant association between odds ratio (OR) values of PCOS and visfatin levels (OR = 2.81; 95% confidence interval [CI], 2.74-2.90), T (OR = 3.39; 95% CI, 2.85-4.16), and LH levels (OR = 3.49; 95% CI, 2.79-4.56). There was no correlation between plasma visfatin concentrations and T, insulin, and LH levels or age in either the PCOS group or the control group. We observed that plasma visfatin levels were positively correlated with body mass index in the PCOS group (r = 0.396, r(2) = 0.157) but not in the control group (r = -0.328, r(2) = 0.108). CONCLUSION(S): Our data show that women with PCOS exhibit higher plasma visfatin levels than control subjects of similar body mass index. Further studies are required to clarify the etiology and effects of hypervisfatinemia in women with PCOS.

Decreased plasma visfatin concentrations in women with gestational diabetes mellitus.

OBJECTIVE: To test the hypothesis that plasma visfatin concentrations will be lower in women with gestational diabetes mellitus, we evaluated women with gestational diabetes mellitus and healthy pregnant women, and then correlated their plasma visfatin concentrations with body mass index (BMI) and various other parameters. METHODS: A total of 40 women were evaluated: 20 women with gestational diabetes mellitus and 20 healthy pregnant women to serve as control subjects. Plasma visfatin concentrations were analyzed using an enzyme-linked immunosorbent assay. RESULTS: Plasma visfatin concentrations were significantly lower in the gestational diabetes mellitus group (9.4 +/- 3.8 ng/mL) than in the healthy control group (12.6 +/- 4.5 ng/mL) (P = .023). A negative correlation was found between plasma visfatin concentrations and maternal age (r = -0.399, P = .011), first trimester body weight (r = -0.350, P = .027), and first trimester BMI (r = -0.336, P = .034). Multiple linear regression analysis revealed that maternal age (P = .017) and gestational diabetes mellitus/no gestational diabetes mellitus (P = .044) were independently related to plasma visfatin concentrations. However, no relationship was found with either gestational age at the time of sampling or first trimester BMI. CONCLUSIONS: Our results show that there are decreased concentrations of plasma visfatin in gestational diabetes mellitus subjects and this may indicate that visfatin plays a role in the pathogenesis of gestational diabetes mellitus. However, further experiments are needed to clarify this role.

Adiponectin and glucose levels in women with negative or false positive glucose challenge test.

OBJECTIVE: To determine whether there is a correlation between adiponectin levels and glucose levels in women screened for gestational diabetes mellitus by means of a 50-g oral glucose challenge test, and to examine the difference in adiponectin levels between women who tested negative, and those who tested false positive. We further calculated the correlations between adiponectin levels and glucose levels, body mass index, gestational age and maternal age. METHODS: A case control study included 171 mothers with negative or false positive results in the 1-h 50-g glucose challenge test at 24-28 gestational weeks. Serum adiponectin levels were determined by radioimmunoassay at the time of the glucose challenge test. RESULTS: There was a significant difference between women who tested negative at screening, and those who tested false positive with respect to age, prepregnancy body weight and body mass index, and adiponectin levels. Correlation analysis showed adiponectin levels to be negatively correlated to glucose levels (r=-0.193, P=0.011). To examine the association between glucose levels, adiponectin levels and demographic variables, multiple linear regression analysis was carried out. Prepregnancy body mass index and age accounted for 14.6% of the variance in the glucose challenge test. Adiponectin levels did not contribute independently to the variation in glucose levels. A further multiple linear regression analysis was undertaken to investigate the association between adiponectin levels and age, prepregnancy body mass index and glucose levels in the glucose challenge test. In this regression model, prepregnancy body mass index and age explained 12.1% of the variance in adiponectin levels. CONCLUSIONS: In conclusion, our study indicated a negative correlation between adiponectin and glucose levels in women screened for gestational diabetes mellitus by a glucose challenge test. We further found that maternal age and body mass index were independent risk factors for a false positive glucose challenge test. Reduced adiponectin levels in women who tested false positive on the glucose challenge test were dependent on advanced age and higher body mass index.

Serum adiponectin levels increase after human chorionic gonadotropin treatment during in vitro fertilization.

AIMS: To determine whether or not serum adiponectin concentrations are influenced by ovarian hyperstimulation during in vitro fertilization (IVF). METHODS: This study involved 52 women who were participating in IVF-ET cycles. Adiponectin levels in serum were determined by radioimmunoassay and compared. RESULTS: Serum adiponectin levels fell from Day-basal to Day-hCG (p = 0.047), and then rose on Day-OR and again on Day-7ET (p < 0.001; p < 0.001). Estradiol levels on Day-hCG were significantly and positively correlated with serum adiponectin levels on Day-OR and Day-7ET (r = 0.325, p = 0.019; r = 0.372, p = 0.007). Progesterone levels on Day-OR positively correlated with serum adiponectin levels on Day-basal (r = 0.278, p = 0.046). There was also a positive correlation between progesterone levels on Day-7ET and serum adiponectin levels on Day-OR (r = 0.289, p = 0.038). Multiple linear regression analysis revealed that adiponectin levels on Day-OR and Day-7ET were negatively correlated with age and body mass index after adjustment was made for concomitant diseases. CONCLUSIONS: To sum up, following gonadotropin treatment, serum adiponectin levels decrease as a result of the negative effect of high estradiol levels on adiponectin production. Conversely, serum adiponectin levels increase following human chorionic gonadotropin treatment.

In utero exposure to dioxins and polychlorinated biphenyls and its relations to thyroid function and growth hormone in newborns.

The aim of this study is to examine the association between transplacental exposure to dioxins/polychlorinated biphenyls (PCBs) and thyroid and growth hormones in newborns. We recruited 118 pregnant women, between 25 and 34 years of age, at the obstetric clinic. Personal data collected included reproductive and medical histories and physical factors. Clinicians gathered placental and umbilical cord serum upon delivery and carefully scored the 118 newborns, making both structural and functional assessments. We analyzed placentas for 17 polychlorinated dibenzo-p-dioxins and dibenzofurans and 12 dioxin-like PCB congeners with the World Health Organization-defined toxic equivalent factors, and six indicator PCBs by high-resolution gas chromatography and high-resolution mass spectrometry. We analyzed thyroid and growth hormones from cord serum using radioimmunoassay. Insulin-like growth factor (IGF)-1, IGF-binding globulin-3, and thyroxine x thyroid-stimulating hormone (T4 x TSH) were significantly associated with increased placental weight and Quetelet index (in kilograms per square meter; correlation coefficient r = 0.2-0.3; p < 0.05). Multivariate analyses showed independently and significantly decreased free T4 (FT4) x TSH with increasing non-ortho PCBs (r = -0.2; p < 0.05). We suggest that significant FT4 feedback alterations to the hypothalamus result from in utero exposure to non-ortho PCBs. Considering the vast existence of bioaccumulated dioxins and PCBs and the resultant body burden in modern society, we suggest routine screening of both thyroid hormone levels and thyroid function in newborns.