Urinary phthalate/DINCH metabolites associations with kisspeptin and reproductive hormones in teenagers: A cross-sectional study from the HBM4EU aligned studies.

BACKGROUND: Exposure to phthalate/DINCH metabolites can induce human reproductive toxicity, however, their endocrine-disrupting mechanisms are not fully elucidated. OBJECTIVE: To investigate the association between concentrations of phthalate/DINCH metabolites, serum kisspeptin, and reproductive hormones among European teenagers from three of the HBM4EU Aligned Studies. METHODS: In 733 Belgian (FLEHS IV study), Slovak (PCB cohort follow-up), and Spanish (BEA study) teenagers, ten phthalate and two DINCH metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry. Serum kisspeptin (kiss54) protein, follicle-stimulating hormone (FSH), total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels were measured by immunosorbent assays. Free Androgen Index (FAI) was calculated as a proxy of free testosterone. Adjusted sex-stratified linear regression models for individual studies, mixed effect models (LME) accounting for random effects for pooled studies, and g-computation and Bayesian kernel machine regression (BKMR) models for the phthalate/DINCH mixture were performed. RESULTS: The LME suggested that each IQR increase in ln-transformed levels of several phthalates was associated with lower kisspeptin [MnBP: %change (95%CI): -2.8 (-4.2;-0.4); MEHP: -1.4 (-3.4,0.2)] and higher FSH [∑DINP: 11.8 (-0.6;25.1)] levels in females from pooled studies. G-computation showed that the phthalates/DINCH mixture was associated with lower kisspeptin [-4.28 (-8.07;-0.34)] and higher FSH [22.13 (0.5;48.4)] also in females; BKMR showed similar although non-significant pattern. In males, higher phthalates metabolites [MEHP: -12.22 (-21.09;-1.18); oxo-MEHP: -12.73 (-22.34;-1.93)] were associated with lower TT and FAI, although higher DINCH [OH-MINCH: 16.31 (6.23;27.35), cx-MINCH: 16.80 (7.03;27.46), ∑DINCH: 17.37 (7.26;29.74)] were associated with higher TT levels. No mixture associations were found in males. CONCLUSION: We observed sex-specific associations between urinary concentrations of phthalate/DINCH metabolites and the panel of selected effect biomarkers (kisspeptin and reproductive hormones). This suggests that exposure to phthalates would be associated with changes in kisspeptin levels, which would affect the HPG axis and thus influence reproductive health. However, further research is needed, particularly for phthalate replacements such as DINCH.

Evaluation of chromogranin A determined by three different procedures in patients with benign diseases, neuroendocrine tumors and other malignancies.

UNLABELLED: CgA is a tumor marker in NET's (neuroendocrine tumors) but different ranges of sensitivity and specificity according to the commercial assay kits used have been reported. Our aim was to compare three commercial available assay kits that use three different methodologies (IRMA, RIA and ELISA) to determine CgA, in a clinical setting: 52 healthy people, 98 patients with benign diseases, 94 patients with non-NET´s malignancies, 20 SCLC and in 79 patients with NET's. RESULTS: Using a cut-off with a 100% specificity in healthy people (6 nmol/L, 60 ng/ml, and 90 ng/ml, for RIA, ELISA and IRMA, respectively), abnormal serum concentrations of CgA were found in a high proportion of patients with renal failure (76.7% ,86,7% and 93.3% with ELISA; IRMA and RIA, respectively) other benign diseases (excluding patients with creatinine concentrations > 1.5 mg/dl)(40,3%, 50% and 53,2% with ELISA, IRMA and RIA, respectively) or in patients with non-NET´s malignancies (excluding SCLC and patients with renal failure) (59,8% ELISA, 55,4%% IRMA, 37% RIA). The highest CgA sensitivity in SCLC was obtained with ELISA (100%) and in NET´s with ELISA (83.3%) and IRMA (80.3%) (RIA 65.2%). ROC curves comparing healthy people and NET´s or NET´s- benigns showed a significantly higher area under the curve (AUC) with ELISA (0.964 and 0.774), or IRMA (0.955 and 0.785), and smaller with RIA (0,806 and 0.691). CONCLUSIONS: CgA is not a specific tumormarker and abnormal concentrations may be found in non-NET´s. The higher AUC, sensitivity and specificity obtained with the ELISA and IRMA indicates that these are the best techniques to determine CgA.

A specific protein-enriched enteral formula decreases cortisolemia and improves plasma albumin and amino acid concentrations in elderly patients.

BACKGROUND: Old age is associated with an involuntary and progressive but physiological loss of muscle mass. The aim of this study was to evaluate the effects of exclusive consumption for 6 months of a protein-enriched enteral diet with a relatively high content of branched-chain amino acids on albuminemia, cortisolemia, plasma amino acids, insulin resistance, and inflammation biomarkers in elderly patients. METHODS: Thirty-two patients from the Clinical Nutrition Outpatient Unit at our hospital exclusively consumed a protein-enriched enteral diet for 6 months. Data were collected at baseline and at 3 and 6 months on anthropometric and biochemical parameters and on plasma concentrations of amino acids, cortisol, adrenocorticotropic hormone, urea, creatinine, insulin resistance, and inflammation biomarkers. RESULTS: The percentage of patients with albumin concentration below normal cut-off values decreased from 18% to 0% by the end of the study. At 6 months, concentrations of total plasma (p = 0.008) and essential amino acids (p = 0.011), especially branched-chain amino acids (p = 0.031), were higher versus baseline values, whereas 3-methylhistidine (p = 0.001), cortisol (p = 0.001) and adrenocorticotropic hormone (p = 0.004) levels were lower. CONCLUSIONS: Regular intake of specific protein-enriched enteral formula increases plasma essential amino acids, especially branched-chain amino acids, and decreases cortisol and 3-methylhistidine, while plasma urea and creatinine remain unchanged.