Hippuric Acid Research Articles

The relationship between urinary polyphenol metabolites and dietary polyphenol intakes in young adults

Spot urinary polyphenols have potential as a biomarker of polyphenol-rich food intakes. The aim of this study is to explore the relationship between spot urinary polyphenols and polyphenol intakes from polyphenol-rich food sources. Young adults (18-24 years old) were recruited into a sub-study of an online intervention aimed at improving diet quality. Participants' intake of polyphenols and polyphenol-rich foods was assessed at baseline and 3 months using repeated 24-h recalls. A spot urine sample was collected at each session, with samples analysed for polyphenol metabolites using LC-MS. To assess the strength of the relationship between urinary polyphenols and dietary polyphenols, Spearman correlations were used. Linear mixed models further evaluated the relationship between polyphenol intakes and urinary excretion. Total urinary polyphenols and hippuric acid (HA) demonstrated moderate correlation with total polyphenol intakes (rs = 0·29-0·47). HA and caffeic acid were moderately correlated with polyphenols from tea/coffee (rs = 0·26-0·46). Using linear mixed models, increases in intakes of total polyphenols or polyphenols from tea/coffee or oil resulted in a greater excretion of HA, whereas a negative relationship was observed between soya polyphenols and HA, suggesting that participants with higher intakes of soya polyphenols had a lower excretion of HA. Findings suggest that total urinary polyphenols may be a promising biomarker of total polyphenol intakes foods and drinks and that HA may be a biomarker of total polyphenol intakes and polyphenols from tea/coffee. Caffeic acid warrants further investigation as a potential biomarker of polyphenols from tea/coffee.

Exposure to benzene and toluene of gasoline station workers in Khon Kaen, Thailand and adverse effects

This cross-sectional study aimed to assess the adverse effects of benzene and toluene exposure in gasoline station workers via biological screening and health risk assessment. Ambient air benzene and toluene concentrations were monitored and analyzed by gas chromatography (GC-FID). Urinary samples to test trans,trans-muconic acid (tt-MA) and hippuric acid levels were collected after shift work from 158 refueling workers and 34 cashiers; any adverse symptoms were noted in the interview and hazard index (HI) values were estimated for workers’ adverse effects. There was a significant correlation between benzene and toluene concentrations at gasoline stations (r = 0.827). The levels of detected tt-MA and hippuric acid, metabolites of benzene and toluene, respectively, were higher in refueling workers (IQR = 537.88 µg/g creatinine (Cr), 316.41 mg/g Cr) than in cashiers (IQR = 208.68 µg/g Cr, 236.17 mg/g Cr). The concentrations of benzene and locations of stations were associated with detection of tt-MA. Adverse symptoms of benzene and toluene exposure, i.e., sore throat, drowsiness, muscle weakness, and unconsciousness were reported. The hazard index values from exposure to benzene and toluene among refueling workers were found to have statistical significance. The conclusion is that carrying out health surveillance with benzene exposure monitoring and health screening can be an important aspect of a strategy to reduce toluene exposure in gasoline workers.

Green microfluidic liquid-phase microextraction of polar and non-polar acids from urine.

In this work, hippuric acid (log P = 0.5), anthranilic acid (log P = 1.3), ketoprofen (log P = 3.6), and naproxen (log P = 3.0) were simultaneously extracted by a green microfluidic device based on the principles of liquid-phase microextraction (LPME). Different deep eutectic solvents (DESs) were investigated as supported liquid membrane (SLM), and a mixture of camphor and menthol as eutectic solvents in the molar ratio 1:1 was found to be highly efficient for the simultaneous extraction of non-polar and polar acidic drugs. LPME was conducted for 6min per sample. Urine sample was delivered to the system at 1μLmin-1, and target analytes were extracted exhaustively (75-100% recovery) across the DES SLM, and into pure aqueous phosphate buffer pH11.0 delivered as acceptor at 1μLmin-1. The acceptor was analyzed with liquid chromatography-UV detection. Interestingly, the DES enabled extraction of both the polar and non-polar model analytes at the same time; all chemicals were green and non-hazardous, and the chemical waste was less than 1mg per sample.

Toluene and Heavy Metals in Small Automotive Refinishing Shops and Personal Protection of the Workers in Nakhon Si Thammarat, Thailand.

Chemical contamination and safe work practices of workers in automotive refinishing shops have been extensively studied in industrialized countries, but the evidence in developing countries is limited. This study aimed to evaluate chemical contamination and the use of personal protective equipment (PPE) of workers in local small-scale automotive refinishing shops in Nakhon Si Thammarat, Thailand. Airborne toluene and heavy metals, i.e., lead, chromium, and cadmium, were measured in 3 automotive refinishing shops. Toluene exposure assessed by urinary hippuric acid (n = 27) and metal contamination on workers' hands (n = 24) were also determined. Information on the use of PPE and personal hygiene practices of the workers was collected by questionnaires. Average ambient levels of toluene (0.04–18.26 ppm) and the metals (Pb: ND-26.34, Cr: 0.02–4.46, and Cd: ND-1.44 µg/m3) in all sites did not exceed the national standard levels of 200 ppm for toluene (1998) and 50, 12, and 5 µg/m3 for Pb, Cr, and Cd, respectively (2017). The mean ambient levels of these chemicals were highest in paint spray booths followed by nonpainting areas and office rooms, respectively. The highest level of urinary hippuric acid (1.13 g/g creatinine) was found in a painter but did not exceed the recommended biological exposure index of 1.6 g/g creatinine (2014). In contrast, the highest levels of lead and chromium detected on the workers' hands were found in body repair technicians. Direct hand contact without using gloves was suggested as a primary cause of metal contamination.

Use of urinary hippuric acid and o-/p-/m-methyl hippuric acid to evaluate surgical smoke exposure in operating room healthcare personnel

Toluene and xylene are common components of surgical smoke, whereas hippuric acid (HA) and methylhippuric acid (MHA) are the products of toluene and xylene metabolism in humans, respectively. HA and MHA can be used as indicators to evaluate the exposure hazards of toluene and xylene. In this study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to simultaneously analyze the HA, o-/m-/p-MHA, and creatinine contents in the urine of healthcare personnel. Concentrations of HA and o-/m-/p-MHAs were normalized to those of creatinine and used to analyze urine samples of 160 operating room (OR) healthcare personnel, including administrative staff, surgical nurses, nurse anesthetists, and surgeons. The results showed that the five analytes could be accurately separated and exhibited good linearity (r > 0.9992). The rate of recovery was between 86% and 106%, and the relative standard deviation was less than 5%. Urine from administrative staff presented the highest median concentration of hippuric acid (0.25 g/g creatinine); this was significantly higher than that found in the urine of surgeons (0.15 g/g). The concentrations of urinary o-/m-/p-MHAs in surgical nurses were higher than those in administrative staff, nurse anesthetists, and surgeons. Furthermore, the type, sex, and age of healthcare personnel were associated with changes in urine HA and o-/m-/p-MHA concentrations. Healthcare personnel should be aware of the risk of exposure to surgical smoke.

Metabolic Evaluation of Urine from Patients Diagnosed with High Grade (HG) Bladder Cancer by SPME-LC-MS Method.

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.

Benzoic acid formation and its relationship with microbial properties in traditional Turkish cheese varieties

Benzoic acid, the simplest member of the aromatic carboxylic acid family, is a weak acid that is a precursor to the synthesis of many important organic compounds. In addition to being used to prevent microbial spoilage in foods, it can also form due to different factors in foods. Hippuric acid found in the natural content of milk can be converted into benzoic acid naturally and can be found in different levels in dairy products. The present study aimed to determine the naturally-forming benzoic acid values in fresh and ripened traditional type cheese varieties and to determine the effect of some physicochemical and microbiological changes of cheeses on the amount of benzoic acid. In this research, benzoic acid levels of six different cheese types (White pickled cheese (traditional-industrial), Tulum cheese (canned or goat skin-packed), and Kashar cheese (fresh and ripened)) were determined. As a result of the analysis performed by HPLC, the amount of benzoic acid in cheese samples varied between 5.95 and 55.72 mg/kg, and it was determined that the microbiota of cheese significantly affected the formation of benzoic acid (p < 0.05). Especially, a lower benzoic acid level was observed in fresh Kashar and industrial White pickled cheeses with short shelf life, whereas a higher shelf-life was observed in cheese types such as ripened traditional White pickled and skin-packed Tulum cheese (p < 0.05). Although there is a difference according to the cheese types, especially between hippuric acid content and changes in pH, and Lactococcus and Enterococcus, a correlation was found between benzoic acid content and yeast-molds changes.

Phenolic Metabolites in the Urine and Plasma of Healthy Men After Acute Intake of Purple Potato Extract Rich in Methoxysubstituted Monoacylated Anthocyanins

Structurally stable acylated anthocyanins have potential in various food applications but the effects of acylation and methoxysubstitution on anthocyanin metabolism are poorly understood. This is the first study thoroughly investigating phenolic metabolites, their time-wise changes, and pharmacokinetics following an acute intake of methoxysubstituted monoacylated anthocyanins. Healthy male volunteers (n = 17) consumed a yellow potato meal with and without purple potato extract rich in acylated anthocyanins (152mg) and hydroxycinnamic acid conjugates (140mg). Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is used for identification and quantification of metabolites from serially collected urine and plasma. While the parent anthocyanins are not detected, 28 phenolic metabolites from urine and 14 from plasma are quantified, including hydroxybenzoic and hydroxycinnamic acids and protocatechuic acid sulfates and glucuronides; three (catechol, gallic acid-4-O-glucuronide, and 2-methoxybenzoic acid) are detected for the first time after anthocyanin-rich food. Urinary hippuric acid is the most abundant with an increase of 139µM mM-1 creatinine after the treatment. A large additional set of tentatively identified phenolic metabolites are detected. Late urinary peak time values suggest colonic degradation. Acylated anthocyanins are more bioavailable than earlier reported after extensive degradation in human and/or colonial metabolism to phenolic metabolites, which may be further conjugated and demethylated.

Cardiovascular Harm From Egg Yolk and Meat: More Than Just Cholesterol and Saturated Fat.

Cardiovascular Harm From Egg Yolk and Meat: More Than Just Cholesterol and Saturated Fat.

Metabolites Secreted by Bovine Embryos In Vitro Predict Pregnancies That the Recipient Plasma Metabolome Cannot, and Vice Versa.

This work describes the use of mass spectrometry-based metabolomics as a non-invasive approach to accurately predict birth prior to embryo transfer (ET) starting from embryo culture media and plasma recipient. Metabolomics was used here as a predictive platform. Day-6 in vitro produced embryos developed singly in modified synthetic oviduct fluid culture medium (CM) drops for 24 h were vitrified as Day-7 blastocysts and transferred to recipients. Day-0 and Day-7 recipient plasma (N = 36 × 2) and CM (N = 36) were analyzed by gas chromatography coupled to the quadrupole time of flight mass spectrometry (GC-qTOF). Metabolites quantified in CM and plasma were analyzed as a function to predict pregnancy at Day-40, Day-62, and birth (univariate and multivariate statistics). Subsequently, a Boolean matrix (F1 score) was constructed with metabolite pairs (one from the embryo, and one from the recipient) to combine the predictive power of embryos and recipients. Validation was performed in independent cohorts of ETs analyzed. Embryos that did not reach birth released more stearic acid, capric acid, palmitic acid, and glyceryl monostearate in CM (i.e., (p < 0.05, FDR < 0.05, Receiver Operator Characteristic—area under curve (ROC-AUC) > 0.669)). Within Holstein recipients, hydrocinnamic acid, alanine, and lysine predicted birth (ROC-AUC > 0.778). Asturiana de los Valles recipients that reached birth showed lower concentrations of 6-methyl-5-hepten-2-one, stearic acid, palmitic acid, and hippuric acid (ROC-AUC > 0.832). Embryonal capric acid and glyceryl-monostearate formed F1 scores generally >0.900, with metabolites found both to differ (e.g., hippuric acid, hydrocinnamic acid) or not (e.g., heptadecanoic acid, citric acid) with pregnancy in plasmas, as hypothesized. Efficient lipid metabolism in the embryo and the recipient can allow pregnancy to proceed. Changes in phenolics from plasma suggest that microbiota and liver metabolism influence the pregnancy establishment in cattle.

Beverages containing Lactobacillus paracasei LC-37 improved functional dyspepsia through regulation of the intestinal microbiota and their metabolites

Functional dyspepsia (FD) is a common disease of the digestive system and probiotics have been reported to be effective in the treatment of functional gastrointestinal diseases. The aim of this study was to determine the effect of the beverage containing Lactobacillus paracasei LC-37 (LC-37) and its ability to relieve symptoms of FD by a randomized clinical trial. Due to the mechanistic complexity underlying FD, intestinal microbiota and stool metabolomes were also evaluated. The results showed that FD was relieved in participants after treatment with the beverage containing LC-37 for 14 and 28 d. The clinical symptom scores were significantly decreased after these times (abdominal pain and belching were significantly decreased after 14 d and almost absent after 28 d of treatment). Probiotics, such as those containing the Lactobacillus, Lactococcus, and Weissella, significantly increased, and the abundance of harmful bacteria such as Lachnocliostridium significantly decreased. Furthermore, relevant beneficial intestinal metabolites such as pelargonic acid, benzoic acid, and short-chain fatty acids increased, and harmful intestinal metabolites such as hippuric acid decreased. Taken together, these findings suggested that the beverages containing LC-37 can increase the abundance of probiotics and decrease pathogenic bacteria, and thereby improve beneficial intestinal metabolites. Therefore, the beverages containing LC-37 may provide a natural alternative to combat FD.

Effects of harvest date and grass species on silage cell wall components and lactation performance of dairy cows

This study evaluated the effect of harvest date and forage species on the concentration of hydroxycinnamic acids in silage and its relationship to dairy cow performance. Tall fescue and timothy were harvested at a regular date on June 27 and July 8, respectively, or at a late date on July 8 and 25, respectively, in the first regrowth. Forage was treated with a salt-based additive and ensiled in hard-pressed round bales. Forty-seven lactating dairy cows were used in a block design. Cows received 1 of 4 treatments: (1) tall fescue harvested at regular date (RTF), (2) timothy harvested at regular date (RTI), (3) tall fescue harvested at late date (LTF), and (4) timothy harvested at late date (LTI). Diets were formulated to have the same forage-to-concentrate ratio (46:54 on a dry matter basis). Harvesting at late date increased fiber components, but only for timothy, where LTI contained greater neutral detergent fiber, acid detergent fiber, and acid detergent lignin concentrations than the other silages. Concentrations of hydroxycinnamic acids were affected by forage species, where concentrations of esterified ferulic acid and p-coumaric acid were greater for tall fescue silages than for timothy silages. Cows fed the RTI diet showed the greatest intakes of dry matter, organic matter, and crude protein. Feeding diets containing timothy silages increased milk yield and energy-corrected milk yield compared with tall fescue diets when averaged over harvest dates. Cows fed the RTI diet had greater milk protein yield than cows fed the RTF and LTF diets, and milk lactose yield was greater for cows fed diets containing timothy silage compared with tall fescue silage when averaged over harvest dates. Cows fed the LTF diet showed greater urinary N excretion compared with the LTI diet, but RTI showed the lowest urinary N and urea N excretions when calculated as percent of N intake. Cows fed diets containing timothy silage excreted more uric acid than cows fed tall fescue diets. Allantoin excretion was greater for cows eating the RTI and LTI diets compared with cows eating the RTF diet. Cows fed the RTI diet had a greater estimated microbial N flow and a greater excretion of hippuric acid than the RTF and LTF groups. In conclusion, besides the effect of harvest date on increasing the fiber components of timothy, concentrations of hydroxycinnamic acids were mainly affected by forage species; consequently, milk production was only affected by forage species. This indicates that hydroxycinnamic acids, such as ferulic acid, which cross-links to glucuronoarabinoxylans, was a major factor regulating milk production of cows fed tall fescue- and timothy silage-based diets, where lower hydroxycinnamic acid concentrations were responsible for greater milk yield.

Gut microbiota-associated compounds increase lethal prostate cancer risk.

147 Background: Gut-microbiota-mediated metabolism of trimethylamine-associated nutrients and amino acids has been linked to altered cholesterol metabolism and endothelial inflammation. However, the association between these compounds and lethal prostate cancer (PCa) remains unknown. Methods: A nested case-control study was performed using samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial to evaluate the association between baseline serum levels of target metabolites (choline, carnitine, betaine, γ-butyrobetaine, crotonobetaine, trimethylamine N-oxide, phenylacetylglutamine, hippuric acid, and p-cresol sulfate) and lethal PCa risk. Lethal cases were randomly matched to controls at a 1:3 ratio on the basis of age, race, and enrollment date. Multivariable logistic regression, conditioned on case status and adjusted for PSA and BMI, was performed to assess the association between analyte quartile (Q) with lethal PCa. Trend of increasing odd ratios (OR) was evaluated using the Cochran-Armitage test. Results: 173 lethal PCa cases and 519 controls were analyzed. Relative to those in Q1, cases with baseline levels of choline and betaine above the median exhibited increased odds of developing lethal PCa after adjusting for BMI and PSA (Table). Lethal PCa risk increased across quartiles of choline in a dose-dependent fashion ( P-trend: 0.005), but not for betaine (P-trend: 0.08). Higher serum levels of other trimethylamine-associated compounds including γ-butyrobetaine, crotonobetaine, trimethylamine N-oxide were not consistently associated with PCa mortality. Baseline serum levels of phenylacetylglutamine, a gut-microbiota metabolite of phenylalanine, were associated with incident lethal PCa, with risk increasing across quantiles (P-trend: 0.003). Elevations in hippuric acid and p-cresol sulfate levels were not consistently associated with greater lethal PCa risk. Conclusions: Serum levels choline, betaine, and phenylacetylglutamine are associated with PCa mortality, underscoring the potential role of gut-microbiota-mediated metabolism in the biology of lethal PCa. Clinical trial information: NCT00002540. [Table: see text]

Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets.

Chronic kidney disease (CKD) is a progressive loss of renal function. The gradual decline in kidney function leads to an accumulation of toxins normally cleared by the kidneys, resulting in uremia. Uremic toxins are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound solutes, and middle molecules. CKD patients have increased risk of developing cardiovascular disease (CVD), due to an assortment of CKD-specific risk factors. The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of CKD and its co-morbidities, including CVD. Although numerous uremic toxins have been identified to date and many of them are believed to play a role in the progression of CKD and CVD, very few toxins have been extensively studied. The pathophysiological mechanisms of uremic toxins must be investigated further for a better understanding of their roles in disease progression and to develop therapeutic interventions against uremic toxicity. This review discusses the renal and cardiovascular toxicity of uremic toxins indoxyl sulfate, p-cresyl sulfate, hippuric acid, TMAO, ADMA, TNF-α, and IL-6. A focus is also placed on potential therapeutic targets against uremic toxicity.

Synergistic activity of weak organic acids against uropathogens

Urinary tract infections (UTIs) are among the most common hospital-acquired infections, with an estimated 75% of UTIs caused by urinary catheters. In addition to the significant healthcare costs and patient morbidity, the escalating antimicrobial resistance reported among common uropathogens make the investigation of efficacious new antimicrobial strategies of urgent importance. To examine the antibacterial activity of a suite of weak organic acids (WOAs) (citric acid, malic acid, propionic acid, mandelic acid, lactic acid, benzoic acid, pyruvic acid and hippuric acid), alone and in combination, against common nosocomial uropathogens (Proteus mirabilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa). Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm eradication concentration (MBEC), fractional inhibitory concentration index (FICI) values and kinetics of bactericidal activity of WOAs were determined by microdilution and time-kill assays. All tested WOAs displayed bactericidal activities against uropathogens in their planktonic and biofilm modes of growth when used individually. Moreover, WOAs in combination displayed synergistic activity against P.mirabilis, S. aureus and E.coli, with reductions in MIC values of up to 250-fold and significant reductions in biofilm formation. The synergistic multi-mechanistic combinations identified herein are anticipated to play an important role in the treatment and prevention of catheter-associated UTIs.

Effects of Orange Pulp Conservation Methods (Dehydrated or Ensiled Sun-Dried) on the Nutritional Value for Finishing Pigs and Implications on Potential Gaseous Emissions from Slurry.

Simple SummaryUtilization of local by-products in pig nutrition can reduce the environmental impact of feeds and contribute to the sustainable development of the livestock sector. Orange pulp (OP) is the most abundant citrus by-product worldwide, but its seasonal production and perishable nature requires storage and drying procedures that might affect its nutritive value. Conservation process by fuel drying is expensive and can impair feed sustainability. Instead, in the Mediterranean countries, OP is sun-dried in the open-air. This procedure often implies a previous silage (during storage) which occurs naturally, because OP has a high level of sugars available for fermentation. Orange pulp is also rich in soluble fiber, which is highly fermentable at the pig’s caecum and may reduce gas emissions from slurry. In this study, the nutritive value of conventional fuel-dehydrated (DOP) or ensiled-sun dried (ESDOP) was determined for pig diets. Sugars fermentation during ensiling increases fiber level in ESDOP and decreases energy digestibility compared to DOP, but both OP have an appreciable digestible energy content for pigs, around 87 and 94% that of barley, respectively. In addition, they do not differ in the amount of slurry excreted and contribute to reduce potential derived ammonia and methane emissions.The inclusion of orange pulp (OP) in pig diets may promote the circular economy, but drying procedures might influence its nutritional value and environmental impact. The purpose of this study was to determine the energy value and nutrient digestibility of dehydrated (DOP) and ensiled sun dried (ESDOP) orange pulp. The potential ammonia (NH3) and methane (CH4) emissions derived from slurry were also measured. Digestible energies of 14.2 and 13.2 MJ/kg DM for DOP and ESDOP, respectively, were estimated by difference after a 500 g/kg substitution of a basal diet with OPs. A high fiber digestion efficiency was observed for both OPs. Pigs fed the basal diet showed a higher intake and a greater excretion of urine N than pigs fed with OP, but fecal N excretion did not differ among diets. A higher benzoic and hippuric acid content in urine was observed in OP than in basal diet. Altogether, these findings explained a lower pH in slurry of OP diets and a reduction of potential NH3 emissions. The biochemical CH4 potential also decreased, especially with ESDOP. Overall, both OP are relevant sources of energy for pig diets. Their inclusion in feeds generate favorable changes of slurry characteristics that reduce potential NH3 and CH4 emissions.

Rheumatoid arthritis in low-level toluene-exposed workers based on nationwide medical surveillance data in Korea.

There is growing evidence that exposure to organic solvents can play a role in the etiology of rheumatoid arthritis (RA). This prospective cohort study aimed to investigate the association between RA and toluene exposure. The study cohort consisted of Korea Occupational Safety and Health Agency data from male workers exposed to toluene who had undergone a toluene-associated special medical examination at least once between January 1, 2000 and December 31, 2004 (n = 148,870). The morbidity from RA based on hospital admission records was estimated from 2000 to 2005 using National Health Insurance Claim Data. The standardized admission ratio (SAR) for RA was calculated with reference to the general population. Levels of urinary hippuric acid (HA), a metabolite of toluene, were measured and used for exposure assessment. Toluene-exposed workers were at an elevated risk of seropositive rheumatoid arthritis (ICD-10 code M05) with an SAR of 2.38 (95% confidence interval [CI]: 1.14-4.37) and other rheumatoid arthritis (M06) with an SAR of 1.22 (95% CI: 0.91-1.59). When data were stratified according to the duration of toluene exposure and by tertiles of urinary HA level, no significant difference was apparent. SARs of the toluene-exposed workers are higher than that of the general reference population, indicating that exposure to toluene may contribute to an increased risk of RA. Further studies of toluene-exposed workers with longer follow-up are needed.

Free p-cresyl sulfate shows the highest association with cardiovascular outcome in chronic kidney disease.

Several protein-bound uraemic toxins (PBUTs) have been associated with cardiovascular (CV) and all-cause mortality in chronic kidney disease (CKD) but the degree to which this is the case per individual PBUT and the pathophysiological mechanism have only partially been unraveled. We compared the prognostic value of both total and free concentrations of five PBUTs [p-cresyl sulfate (pCS), p-cresyl glucuronide, indoxyl sulfate, indole acetic acid and hippuric acid] in a cohort of 523 patients with non-dialysis CKD Stages G1-G5. Patients were followed prospectively for the occurrence of a fatal or non-fatal CV event as the primary endpoint and a number of other major complications as secondary endpoints. In addition, association with and the prognostic value of nine markers of endothelial activation/damage was compared. After a median follow-up of 5.5 years, 149 patients developed the primary endpoint. In multivariate Cox regression models adjusted for age, sex, systolic blood pressure, diabetes mellitus and estimated glomerular filtration rate, and corrected for multiple testing, only free pCS was associated with the primary endpoint {hazard ratio [HR]1.39 [95% confidence interval (CI) 1.14-1.71]; P = 0.0014}. Free pCS also correlated with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (r = -0.114, P < 0.05), angiopoietin-2 (ANGPT2) (r = 0.194, P < 0.001), matrix metallopeptidase 7 (MMP-7; (r = 0.238, P < 0.001) and syndecan 1 (r = 0.235, P < 0.001). Of these markers of endothelial activation/damage, ANGPT2 [HR 1.46 (95% CI 1.25-1.70); P < 0.0001] and MMP-7 [HR 1.31 (95% CI 1.08-1.59); P = 0.0056] were also predictive of the primary outcome. Among PBUTs, free pCS shows the highest association with CV outcome in non-dialysed patients with CKD. Two markers of endothelial activation/damage that were significantly correlated with free pCS, ANGPT2 and MMP-7 were also associated with CV outcome. The hypothesis that free pCS exerts its CV toxic effects by an adverse effect on endothelial function deserves further exploration.

Associations among total p-cresylsulfate, indoxyl sulfate and hippuric acid levels with hemodialysis quality indicators in maintenance hemodialysis patients

BackgroundTotal p-cresylsulfate (PCS), indoxyl sulfate (IS) and hippuric acid (HA) are harmful uremic toxins known to be elevated in patients with uremia. Serum total PCS, IS and HA levels have been associated with coronary atherosclerosis, left ventricular hypertrophy, metabolic acidosis, neurological symptoms, and accelerated renal damage associated with chronic kidney disease; however, no study has examined the effect of total PCS, IS and HA on hemodialysis (HD) quality indicators. The aim of this study was to examine associations among total PCS, IS and HA with HD quality indicators in patients undergoing HD treatment. MethodsThis study included 264 consecutive patients at a single HD center who assessed using previously demonstrated HD quality indicators including anemia, bone-mineral metabolism, dialysis dose, cardiovascular risk, and middle molecule removal area. Serum HA was measured using a capillary electrophoresis method. Serum total PCS and IS concentrations were measured using an Ultra Performance LC System. ResultsMultiple regression analysis showed that sex, potassium, systolic blood pressure (SBP), average BP, β2-microglobulin, and creatinine were independently positively associated with IS level, and that age, total cholesterol, and estimated glomerular filtration rate (eGFR) was independently negatively associated with IS level. In addition, β2-microglobulin was independently positively associated with total PCS. Moreover, potassium, diastolic blood pressure, average BP, β2-microglobulin, dialysis vintage, and albumin were independently positively associated with HA level, and age, transferrin saturation, fasting glucose, and eGFR were independently negatively associated with HA level. When the patients were stratified by age and sex, serum IS and HA levels were still independently associated with some hemodialysis quality indicators. In addition, canonical correlation analysis also confirmed the relationship between uremic toxins (IS and HA) and HD quality indicators (potassium, β2-microglobulin, average BP, creatinine, and eGFR). ConclusionThis study demonstrated that uremic toxins (IS and HA) and HD quality indicators (potassium, β2-microglobulin, average BP, creatinine, and eGFR) constructs were correlated with each other, and that there were sex and age differences in these associations among maintenance HD patients.

Beverages Based on Second Quality Citrus Fruits and Maqui Berry, a Source of Bioactive (Poly)phenols: Sorting Out Urine Metabolites upon a Longitudinal Study.

The intake of sugar-sweetened beverages has been associated with an augmented prevalence of metabolic diseases, namely, obesity, type II diabetes, and metabolic syndrome. On the other hand, nowadays, it is broadly accepted that foods and beverages rich in (poly)phenols could contribute to reducing the incidence of these pathologies. In this sense, the objective of the work was to revalue second quality citrus fruits for the development of new beverages, rich in anthocyanins and flavanones (maqui berry and second qualities citrus-based), and evaluate the influence of alternative sweeteners (sucralose, sucrose, or stevia), regarding the bioaccessibility and bioavailability of these bioactive compounds in the frame of a chronic (longitudinal) intervention. To fulfill this objective, a longitudinal study of the urinary excretion of anthocyanins and flavanones, after 2-months of ingestion of the developed maqui-citrus beverage, by 138 volunteers (n = 46 per beverage) and the analysis of the resulting phenolic metabolites by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-ESI-QqQ-MS/MS) was carried out. As major results, the bioavailable metabolites of caffeic acid (CA), catechol (CAT), 3,4-di-hydroxyphenylacetic acid (DHPAA), eriodictyol (E), homoeriodictyol (HE), hippuric acid (HA), naringenin (N), trans-ferulic acid (TFA), 2,4,6-tri-hydroxybenzaldehyde (THBA), trans-isoferulic acid (TIFA), and vanillic acid (VA) were detected. Accordingly, significantly different bioavailability was dependent on the sweetener used, allowing proposing stevia and, to a lower extent, sucralose, as valuable alternatives to sucrose.