The kidney, subclinical thyroid disease and cardiovascular outcomes in older patients

Objective: Thyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes. Methods: In total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45–4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45–60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke. Results: Mean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24–1.07) comparing subclinical hyperthyroidism and 0.90 (0.58–1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism). Conclusions: In this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction

Quantification of complex mixtures by NMR

NMR has firmly established itself as an analytical tool that can quantify analyte concentrations in complex mixtures in a rapid, cost-effective, accurate and precise manner. Here, the technological advances with respect to instrumentation, sample preparation, data acquisition and data processing over the past decade will be discussed. It will be shown that besides mainstream 1D 1H NMR also homo- and heteronuclear 2D experiments are gaining practical use. An overview will be given of the widespread applications of qNMR in diverse applications areas, ranging from foods, biomedicine to natural and pharmaceutical product analysis. Yet, qNMR is still limited to the quantification of a limited number of target compounds. Considering the current rate of developments in NMR acquisition and data processing, it is envisaged that in the near future a much wider range of analytes can be simultaneously assessed in a routine manner at even lower operational cos

Nutrikinetics: concept, technololgies applications and perspectives

Exposure studies are the first step in predicting bioactivity of phytochemicals in humans. Due to the interaction between phytochemicals, their food matrix, the gut microbiome and the host, the resulting exogenous metabolites in systemic circulation vary largely between individuals. Nutrikinetics is an extension of the classical pharmacokinetic concept with explicit model adaptations. The concept relies on integrated deployment of metabolic profiling, multi-level data analysis and population-based single compartment modelling. Nutrikinetics is expected to make critical contributions in understanding how phenotypes and the food matrix modulate bioactivity of dietary phytochemicals, in particular when gut microbial bioconversions are involved

Chemical fingerprints of emotional body odor

Contains fulltext : 221516.pdf (publisher's version ) (Open Access)Chemical communication is common among animals. In humans, the chemical basis of social communication has remained a black box, despite psychological and neural research showing distinctive physiological, behavioral, and neural consequences of body odors emitted during emotional states like fear and happiness. We used a multidisciplinary approach to examine whether molecular cues could be associated with an emotional state in the emitter. Our research revealed that the volatile molecules transmitting different emotions to perceivers also have objectively different chemical properties. Chemical analysis of underarm sweat collected from the same donors in fearful, happy, and emotionally neutral states was conducted using untargeted two-dimensional (GC×GC) coupled with time of flight (ToF) MS-based profiling. Based on the multivariate statistical analyses, we find that the pattern of chemical volatiles (N = 1655 peaks) associated with fearful state is clearly different from that associated with (pleasant) neutral state. Happy sweat is also significantly different from the other states, chemically, but shows a bipolar pattern of overlap with fearful as well as neutral state. Candidate chemical classes associated with emotional and neutral sweat have been identified, specifically, linear aldehydes, ketones, esters, and cyclic molecules (5 rings). This research constitutes a first step toward identifying the chemical fingerprints of emotion.25 p

GC-MS methods for metabolic profiling of microbial fermentation products of dietary polyphenols in human and in vitro intervention studies

Flavonoids, a subclass of polyphenols, are major constituents of many plant-based foods and beverages, including tea, wine and chocolate. Epidemiological studies have shown that a flavonoid-rich diet is associated with reduced risk of cardiovascular diseases. The majority of the flavonoids survive intact until they reach the colon where they are then extensively metabolized into smaller fragments. Here, we describe the development of GC-MS-based methods for the profiling of phenolic microbial fermentation products in urine, plasma, and fecal water. Furthermore, the methods are applicable for profiling products obtained from in vitro batch culture fermentation models. The methods incorporate enzymatic deconjugation, liquid-liquid extraction, derivatization, and subsequent analysis by GC-MS. At the level of individual compounds, the methods gave recoveries better than 80% with inter-day precision being better than 20%, depending on the matrix. Limits of detection were below 0.1 μg/ml for most phenolic acids. The newly developed methods were successfully applied to samples from human and in-vitro intervention trials, studying the metabolic impact of flavonoid intake. In conclusion, the methods presented are robust and generally applicable to diverse biological fluids. Its profiling character is useful to investigate on a large scale the gut microbiome-mediated bioavailability of flavonoids

SPE-NMR metabolite sub-profiling of urine

NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has been developed using automated solid-phase extraction (SPE) combined with NMR metabolite profiling. SPE-NMR of urine resulted in three fractions with complementary and reproducible sub-profiles. The sub-profile from the wash fraction (100 % water) contained polar metabolites; that from the first eluted fraction (10 % methanol-90 % water) semi-polar metabolites; and that from the second eluted fraction (100 % methanol) aromatic metabolites. The method was validated by analysis of urine samples collected from a crossover human nutritional intervention trial in which healthy volunteers consumed capsules containing a polyphenol-rich mixture of red wine and grape juice extract (WGM), the same polyphenol mixture dissolved in a soy drink (WGM_Soy), or a placebo (PLA), over a period of five days. Consumption of WGM clearly increased urinary excretion of 4-hydroxyhippuric acid, hippuric acid, 3-hydroxyphenylacetic acid, homovanillic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropionic acid. However, there was no difference between the excreted amounts of these metabolites after consumption of WGM or WGM_Soy, indicating that the soy drink is a suitable carrier for WGM polyphenols. Interestingly, WGM_Soy induced a significant increase in excretion of cis-aconitate compared with WGM and PLA, suggesting a higher demand on the tricarboxylic acid cycle. In conclusion, SPE-NMR metabolite sub-profiling is a reliable and improved method for quantification and identification of metabolites in urine to discover dietary effects and markers of phytochemical exposur

SPE-NMR metabolite sub-profiling of urine

NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has been developed using automated solid-phase extraction (SPE) combined with NMR metabolite profiling. SPE-NMR of urine resulted in three fractions with complementary and reproducible sub-profiles. The sub-profile from the wash fraction (100 % water) contained polar metabolites; that from the first eluted fraction (10 % methanol-90 % water) semi-polar metabolites; and that from the second eluted fraction (100 % methanol) aromatic metabolites. The method was validated by analysis of urine samples collected from a crossover human nutritional intervention trial in which healthy volunteers consumed capsules containing a polyphenol-rich mixture of red wine and grape juice extract (WGM), the same polyphenol mixture dissolved in a soy drink (WGM_Soy), or a placebo (PLA), over a period of five days. Consumption of WGM clearly increased urinary excretion of 4-hydroxyhippuric acid, hippuric acid, 3-hydroxyphenylacetic acid, homovanillic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropionic acid. However, there was no difference between the excreted amounts of these metabolites after consumption of WGM or WGM_Soy, indicating that the soy drink is a suitable carrier for WGM polyphenols. Interestingly, WGM_Soy induced a significant increase in excretion of cis-aconitate compared with WGM and PLA, suggesting a higher demand on the tricarboxylic acid cycle. In conclusion, SPE-NMR metabolite sub-profiling is a reliable and improved method for quantification and identification of metabolites in urine to discover dietary effects and markers of phytochemical exposur