Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS.
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ABSTRACT:
SUBMITTER: Frederiksen H
PROVIDER: S-EPMC7007877 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Project description:BackgroundMass spectrometric-based measurements of the steroid metabolome have been introduced to diagnose disorders featuring abnormal steroidogenesis. Defined reference intervals are important for interpreting such data.MethodsLiquid chromatography-tandem mass spectrometry was used to establish reference intervals for 16 steroids (pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, aldosterone, 18-oxocortisol, 18-hydroxycortisol, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, testosterone) measured in plasma from 525 volunteers with (n=227) and without (n=298) hypertension, including 68 women on oral contraceptives.ResultsWomen showed variable plasma concentrations of several steroids associated with menstrual cycle phase, menopause and oral contraceptive use. Progesterone was higher in females than males, but most other steroids were higher in males than females and almost all declined with advancing age. Using models that corrected for age and gender, body mass index showed weak negative relationships with corticosterone, 21-deoxycortisol, cortisol, cortisone, testosterone, progesterone, 17-hydroxyprogesterone and 11-deoxycorticosterone, but a positive relationship with 18-hydroxycortisol. Hypertensives and normotensives showed negligible differences in plasma concentrations of steroids.ConclusionAge and gender are the most important variables for plasma steroid reference intervals, which have been established here according to those variables for a panel of 16 steroids primarily useful for diagnosis and subtyping of patients with endocrine hypertension.
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Project description:A reliable and fast liquid chromatography-tandem mass spectrometry method has been developed for the simultaneous determination of three oxidized nucleic acid damage products in urine, 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). We applied this method to assess the effect of various urine workup procedures on the urinary concentrations of the oxidized nucleic acid products. Our results showed that frozen urine samples must be warmed (i.e., to 37 °C) to re-dissolve any precipitates prior to analysis. We showed that common workup procedures, such as thawing at room temperature or dilution with deionized water, are not capable of releasing fully the oxidized nucleic acid products from the precipitates, and result in significant underestimation (up to ~ 100% for 8-oxoGua, ~ 86% for both 8-oxodGuo and 8-oxoGuo). With this method, we further assessed and compared the ability of the three oxidized nucleic acid products, as well as malondialdehyde (MDA, a product of lipid peroxidation), to biomonitor oxidative stress in vivo. We measured a total of 315 urine samples from subjects with burdens of oxidative stress from low to high, including healthy subjects, patients with chronic obstructive pulmonary disease (COPD), and patients on mechanical ventilation (MV). The results showed that both the MV and COPD patients had significantly higher urinary levels of 8-oxoGua, 8-oxodGuo, and 8-oxoGuo (P < 0.001), but lower MDA levels, compared to healthy controls. Receiver operating characteristic curve analysis revealed that urinary 8-oxoGuo is the most sensitive biomarker for oxidative stress with area under the curve (AUC) of 0.91, followed by 8-oxodGuo (AUC: 0.80) and 8-oxoGua (AUC: 0.76). Interestingly, MDA with AUC of 0.34 failed to discriminate the patients from healthy controls. Emerging evidence suggests a potential clinical utility for the measurement of urinary 8-oxoGuo, and to a lesser extent 8-oxodGuo, which is strongly supported by our findings.
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2024-05-02 | PXD041400 | Pride
Project description:BACKGROUND:Accumulating evidence links higher circulating asymmetric dimethylarginine (ADMA) to greater risk of cardiovascular disease (CVD). Relatively small differences in ADMA concentrations between healthy individuals and those with disease underscore the need to formulate reference intervals that may aid risk stratification of individuals. METHODS:We formulated reference intervals for plasma ADMA concentrations using a community-based reference sample from the Framingham Offspring Study consisting of 1126 nonsmoking individuals [mean (SD) age 56 (9) years; 60% women] who were free of clinical CVD, hypertension, diabetes, and obesity and who attended a routine examination at which ADMA was assayed. ADMA concentrations were determined using a validated tandem mass spectrometry-liquid chromatography assay. RESULTS:In the study sample, the mean ADMA concentration was 0.52 (0.11) micromol/L, and the reference limits were 0.311 and 0.732 (2.5th and 97.5th percentile). The sex-specific reference limits were 0.310 and 0.745 in men and 0.313 and 0.721 micromol/L in women. In multivariable regression analysis, ADMA plasma concentrations were positively correlated with age and total plasma homocysteine (both P < 0.001). CONCLUSIONS:Reference limits calculated for circulating ADMA in our large community-based healthy reference sample confirm the previous observation of a relatively narrow distribution of concentrations. This suggests a tight physiological control of ADMA plasma concentrations, presumably by dimethylarginine dimethylaminohydrolase (DDAH) metabolism of ADMA.
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Project description:Blood urea nitrogen (BUN) is a nitrogenous end product of protein metabolism. This study aims to explore the age- and sex-specific distribution of BUN among healthy Chinese adults. A total of 24,006 BUN values from healthy adults (14,148 males and 9858 females) were included in the cross-sectional study. Males had a higher median BUN value compared to females (4.6 mmol/L vs. 4.1 mmol/L). BUN values showed a positive correlation with body mass index (BMI), cholesterol, and blood sugar (P < 0.0001). However, eGFR showed a negative correlation with the BUN reference value (P < 0.0001) in both sexes. Multiple linear regression analysis confirmed that the positive associations of BUN levels and age were statistically significant after adjusting confounding factors (P < 0.001). Thus, the serum BUN values increased by 0.21 mmol/L for males and 0.282 mmol/L for females per 10 years. The BUN values corresponding to the 1st, 2.5th, 50th, 97.5th, and 99th percentiles for any specific age in both sex were also calculated. These results indicate that the serum BUN reference value is significantly affected by age and gender, and thus, its interpretation is age- and sex-dependent.
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Project description:Clonorchiasis is an important zoonotic parasitic disease worldwide. In view of the fact that parasite infection affects host metabolism, and there is an intricate relationship between metabolism and immunity. Metabolic analysis of the spleen could be helpful for understanding the pathophysiological mechanisms in clonorchiasis. A non-targeted ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF MS) approach was employed to investigate the metabolic profiles of spleen in rats at 4 and 8 weeks post infection with Clonorchis sinensis (C. sinensis). Then a targeted ultra-high performance liquid chromatography multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS/MS) approach was used to further quantify amino acid metabolism. Multivariate data analysis methods, such as principal components analysis and orthogonal partial least squares discriminant analysis, were used to identify differential metabolites. Finally, a total of 396 and 242 significant differential metabolites were identified in ESI+ and ESI- modes, respectively. These metabolites included amino acids, nucleotides, carboxylic acids, lipids and carbohydrates. There were 38 significantly different metabolites shared in the two infected groups compared with the control group through the Venn diagram. The metabolic pathways analysis revealed that pyrimidine metabolism, aminoacyl-tRNA biosynthesis, purine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis were significantly enriched in differential metabolites, which was speculated to be related to the disease progression of clonorchiasis. Furthermore, 15 amino acids screened using untargeted profiling can be accurately quantified and identifed by targeted metabolomics during clonrochiasis. These results preliminarily revealed the perturbations of spleen metabolism in clonorchiasis. Meanwhile, this present study supplied new insights into the molecular mechanisms of host-parasite interactions.
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Project description:Food allergies are the result of immune responses that cause adverse reactions to foods. Immune responses to foods may produce a spectrum of symptoms and disorders, including acute allergic reactions and anaphylaxis, food protein-induced allergic proctocolitis, food protein-induced enterocolitis syndrome, food-dependent, exercise-induced anaphylaxis, and oral allergy syndrome (pollen-food allergy syndrome). Food-allergic responses also contribute to chronic inflammatory disorders such as eosinophilic esophagitis and atopic dermatitis. Although food allergy affects people from infancy through adulthood, there are allergic features that differ according to age (ie, presentation, triggers, and natural course) and have important implications for diagnosis, prognosis, and management. New food allergies can develop at any age, and we propose similarities in the etiology of de novo food allergy whether in infancy or adulthood. The approach to managing food allergy changes dramatically over the life course, and physicians and patients must respond accordingly to optimize care. Food allergy therapies are emerging, and the efficacy and safety of these interventions could differ by age group of those treated. In this review, we highlight interesting observations on the etiology and characteristics of food allergy presenting at different ages and discuss clinical management as it relates to life stage.
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Project description:Introduction:The aim of this nested study is to provide the reference intervals for already published measurements of salivary cortisol from the Croatian Adolescence Stress Study (CLASS). Material and methods:A total of 969 individuals (372 males and 597 females) were included in the reference sample (age range: 18-21 years). Salivary cortisol concentrations were determined by the enzyme immunoassay (LUCIO-Medical ELISA Salivary Cortisol Kit, Nal von Minden, Germany) in the Department of Medical Laboratory Diagnostics, University Hospital Split. Nonparametric statistics were used for calculating the reference intervals (RIs) and 90% confidence intervals (90% CIs). Results:The lower limits of RIs determined by the direct method were higher in females (> 10%) than in males for the cortisol concentrations at awakening (SCC0), 30 to 45 after awakening (SCC30-45) and at bedtime (SCCbedtime). The upper limits of RIs for the SCCbedtime were higher (> 10%) in males than in females. Females also had higher upper limits of RIs for the cortisol awakening response (CAR) and the diurnal cortisol slope (DCS) and higher lower limits of RIs for the CAR and the area under the curve with respect to ground (AUCG). The lower limits of RIs for the DCS were higher in males than in females. Conclusions:Obtained reference values open the arena for introducing salivary bioscience in Croatian clinical laboratory practice and provide important data for better understanding of gender differences in adaptation to stress during late adolescence.
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