Urinary Acetic Acid Research Articles

Associations of air PM2.5 level with gut microbiota in Chinese Han preschoolers and effect modification by oxytocin receptor gene polymorphism

Variations in the single nucleotide polymorphisms (SNPs) of the oxytocin receptors (OXTR) indicate individual differences in stress response, social behavior, and psychopathology, but very few paper mentioned OXTR as part of the mechanism linking exposure to air pollution and poor social interactions. The authors investigated the moderating role of Oxytocin receptor (OXTR) rs53576 polymorphism in the relationship between PM2.5 level and gut microbiota in children, in an attempt to provide some reference for the evidence linking biological and environmental factors to children brain development. The study included 86 healthy Chinese preschoolers (50 males, 36 females) from two campuses of a kindergarten with different air PM2.5 levels. Atmospheric PM2.5 values released by air quality monitoring stations where the two campuses are located were collected for 30 days. The genotypes of OXTR rs53576 were determined by PCR and restriction fragment length polymorphism. The gut microbiota situation was evaluated by determining urinary concentrations of short-chain fatty acids. Urinary levels of cortisone and cortisol were determined to assess the impact of air pollution on the HPA axis. Urinary 2′-Deoxy-7,8-dihydro-8-oxoguanosine and 8-oxo-7,8-dihydroguanosine were measured to evaluate the oxidative stress state. The genotype distribution frequency of rs53576 polymorphism was consistent with Hardy-Weinberg equilibrium. The average urinary concentrations of cortisone, cortisol and 8-OHdG in high pollution campus preschoolers were significantly higher than those in low pollution campus preschoolers, while situations were opposite for acetic acid, propionic acid, isobutyric acid, butyric acid and valeric acid. The interaction between OXTR rs53576 and air pollution had a significant effect on urinary acetic acid. Allele G of rs53576 may be a risk factor for gut microbiota disorder caused by air pollution, and children with GA/GG genotype may be more susceptible than those with AA genotype.

Histidine metabolism after Bretschneider cardioplegia in cardiac surgical patients.

Bretschneider (histidine-tryptophan-ketoglutarate) solution with its high histidine concentration (198 mM) is one of many cardioplegic solutions, which are routinely used for cardiac arrest. The aim of this study was to evaluate the physiological biochemical degradation of administered histidine to histamine and its major urinary metabolite N-methylimidazole acetic acid. A total number of thirteen consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass were enrolled in the prospective observational designed study at the Department of Thoracic and Cardiovascular Surgery between 04/2016 and 06/2016. Patients received 1.7 l Bretschneider solution on average. Before and at the end of operation as well as in the postoperative course, urine samples gathered from the urinary catheter bag were analyzed. During the operative period, urinary histidine concentration significantly increased from 29 micromol/mmol creatinine to 9,609 micromol/mmol creatinine. Postoperatively, histidine excretion reduced while histamine as well as N-methylimidazole acetic acid excretion rose significantly. Patients showed elevated levels of histidine, histamine as well as N-methylimidazole acetic acid in urine, but no unmanageable hemodynamic instability possibly arising from the histamine's biological properties. Chemically modified histidine might reduce uptake and metabolization while maintaining the advantages of buffer capacity.

The Activation Effects of Low Level Isopropyl Alcohol Exposure on Arterial Blood Pressures Are Associated with Decreased 5-Hydroxyindole Acetic Acid in Urine.

PurposesThe objectives of this paper are to study the impact of low level isopropyl alcohol exposure on blood pressure and to explore its potential mechanism.MethodsThis cross-sectional study was based on a prospective occupational cohort in south China, which focusing on occupational risk factors related cardiovascular health problems. A total of 283 participants (200 low isopropyl alcohol exposed workers and 83 controls) was finally enrolled in this study. Linear regression models were used to analyze the relationship between arterial blood pressures and low level isopropyl alcohol exposure. We used mediation method to explore possible mediated roles of neurogenic factors.ResultsSystolic blood pressure (SBP, 123±10 vs. 118±11), diastolic blood pressure (DBP, 79±7 vs. 74±7) and mean blood pressure (MBP, 93±8 vs. 89±9) were different between the exposed group and the control group (p < 0.01). After adjusting for covariates, the difference was still significant. Besides, isopropyl alcohol and smoking had an interactive effect on DBP and MBP (p < 0.05). Furthermore, we observed a mediated effect of 5-hydroxyindole acetic acid (5-HIAA) on isopropyl alcohol exposure induced arterial blood pressure increase, which accounted for about 25%.ConclusionsOur results suggest that low level isopropyl alcohol exposure is a potential risk factor for the increased arterial blood pressure and 5-HIAA partly mediates the association between low level isopropyl alcohol exposure and arterial blood pressures.

Changes in urine headspace composition as an effect of strenuous walking.

The present investigation uses proton transfer reaction mass spectrometry (PTR-MS) combined with multivariate and univariate statistical analyses to study potential biomarkers for altered metabolism in urine due to strenuous walking. Urine samples, in concurrence with breath and blood samples, were taken from 51 participants (23 controls, 11 type-1 diabetes, 17 type-2 diabetes) during the Dutch endurance walking event, the International Four Days Marches. Multivariate analysis allowed for discrimination of before and after exercise for all three groups (control, type-1 and type-2 diabetes) and on three out of 4 days. The analysis highlighted 12 molecular ions contributing to this discrimination. Of these, acetic acid in urine is identified as a significant marker for exercise effects induced by walking; an increase is observed as an effect of walking. Analysis of acetone concentration with univariate tools resulted in different information when compared to breath as a function of exercise, revealing an interesting effect of time over the 4 days. In breath, acetone provides an immediate snapshot of metabolism, whereas urinary acetone will result from longer term diffusion processes, providing a time averaged view of metabolism. The potential to use PTR-MS measurements of urine to monitor exercise effects is exhibited, and may be utilized to monitor subjects in mass participation exercise events.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-015-0813-8) contains supplementary material, which is available to authorized users.

Evaluation of Anti Depressant and MAO Inhibitory Activity ofRhodiola rhodantharhizome methanolic extract

The objective of the present study was to evaluate the antidepressant activity of methanolic extract for the rhizomes of Rhodiola rhodantha. Depression is the most common feature and it may range from a very mild condition to even severe depression which is called as psychotic depression. In the traditional systems of medicine many plants and formulations have been used to treat depression for thousands of years. The present study was undertaken to assess the antidepressant effect of crude methanolic extract of Rhodiola rhodantha at doses 100mg/kg, 200mg/kg and 400mg/kg using parameters forced induced swimming test (FST), tail suspension test (TST). Significant dose dependent decline in immobility time was observed in all the three doses in FST and TST and the extract showed dose dependent relation of immobility reduction in mice. In order to understand the probable mechanism of antidepressantlike activity in FST and TST, the levels of 5-hydroxy indole acetic acid in urine was taken as basis for biochemical assessment of anti depressant activity.

Quantitative metabolomics of urine for rapid etiological diagnosis of urinary tract infection: Evaluation of a microbial–mammalian co-metabolite as a diagnostic biomarker

BackgroundWe have previously reported a NMR-based urinalysis for the screening of urinary tract infection (UTI) with high accuracy and reproducibility. Urinary acetic acid per creatinine was found to be a diagnostic marker of bacterial UTI with an area-under-receiver operating characteristic (ROC) curve of 0.97. In addition, we identified trimethylamine (TMA) as a human-microbial marker of Escherichia coli (EC)-associated UTI. Here, we evaluate the clinical application of NMR-based urinalysis in aiding the etiological diagnosis of bacterial UTI. MethodsProton NMR spectroscopy was acquired using a Bruker 600MHz spectroscopy for 88 urine samples from patients with bacterial UTI, confirmed by urine culture. The spectra were analyzed using orthogonal partial least squares-discriminant analysis (OPLS-DA). ROC curve analysis was performed after the quantitation of the urine metabolites. ResultsThe TMA/creatinine (mmol/mmol) level was determined to be a specific marker for EC-associated UTI. It has an area-under-ROC=0.85 (95% confidence interval: 0.75–0.91). For the etiological diagnosis, the cutoff for 97.0% specificity was at 0.0117mmol/mmol creatinine for EC-associated UTI with a sensitivity of 66.7%. The mean of TMA/creatinine of EC is 21-fold that of non-EC. ConclusionsThe co-metabolism of TMA by EC and human cells makes TMA an ideal urine biomarker for UTI. The presence of TMA in a freshly collected sample eliminates the possibility of contamination of urine by bacteria during the collection process resulting in a positive bacterial culture result. We envisage the NMR-based urinalysis of urinary TMA that can be a useful method for the etiological diagnosis of EC-associated UTI.

Spot İdrarda Bakılan 5-Hi̇droksi̇ İndol Aseti̇k Asi̇ti̇n Akut Apandi̇si̇t Tanısında Değeri (The Value of Acute Appendicitis Viewed 5-Hydroxy Indole Acetic Acid in Spot Urine)

Amac: Bu calisma, akut apandisit suphesi nedeniyle acile basvuran hastalarda, idrarda bakilan 5-Hidroksi Indol Asetik Asit seviyesinin tani koymada anlamliligini degerlendirmektedir. Yontem: 2011 Ocak- 2011 Aralik aylari arasinda klinigimize karin agrisi nedeniyle basvuran hastalarda idrarda 5-Hidroksi Indol Asetik Asit ileriye donuk olarak calisma yapilmistir. Sonuclar: Bir yillik surede klinigimize karin agrisi nedeniyle basvuran ve interne edilen, ortalama yaslari 10.4 yil ±3.4 olan toplam 49 hastanin klinik degerlendirme sonrasi, 32 hastada apandisit, 17 hastada apandisit harici karin agrisi tespit edilmistir. Appendektomi yapilan 2 hastada apendiks normal olarak degerlendirilmistir. Tum basvuran hastalardan ilk basvuruda idrar ornekleri alinmistir. Her 2 grup karsilastirildiginda spot idrar 5-Hidroksi Indol Asetik Asit duzeyleri arasindaki fark istatistiksel olarak anlamli bulunmamistir (p>0.05). Spot idrar 5-Hidroksi Indol Asetik Asit duzeylerinde ozgulluk, duyarlilik, pozitif ongoru degeri, negatif ongoru degeri sirasiyla %63, %66, %54 ve %73 olarak bulunmustur. Sonuc: Spot idrar 5-Hidroksi Indol Asetik Asit degeri cocuklarda akut apandisit tanisinda tek tip parametre olarak kullanildiginda sinirli tanisal degeri oldugu saptanmistir. Anahtar Kelimeler: Akut Apandisit, Akut Karin, 5 Indol Asetik Asit, Somatostatin, Cocuk ABSTRACT Backgraund/Aim: This study is to investigate the significance of spot urine 5-hydroxy indol acetic acid levels in patients admitted with the suspicion of acute apendicitis. Material/Method: Between January 2011 and June 2011, patients with the complaints of abdominal pain were evaluated according to levels of 5-hydroxy indol acetic acid in urine at admission. This study was designed as prospectively. Results: Forthy-nine patients with the mean age of 10.4 years ±3.4 who were admitted and interned to our department during the one year period with the complaints of abdominal pain. After the clinical evaluation appendicitis was detected in 32 patients and abdominal pain was found to be due to causes other than appendicitis in 17 patients. Two of the patiens were negatif appendectomy. Spot urine samples were collected in all patients during admission and 5-hydroxy indol acetic acid levels were studied. The differences between the patients with acute appendicitis and other groups were not statistically significant (p>0.05). Sensitivity, specifity, positive predictive value and diagnostic specificity of 5-hydroxy indol acetic acid level in spot urine were 63%, 66%, 54%, 73%, respectively. Conclusion; Spot urine 5-hydroxy indol acetic acid levels in diagnosis of acute appendicitis seems to have limited diagnostic power as a single parameter in children. Key Words: Acut Appendicitis, Acut abdomen, 5-hydroxy indole acetic acid, Somatositatin, Child

Comparison and evaluation of analysis procedures for the quantification of (2-methoxyethoxy)acetic acid in urine

Several extraction and derivatization procedures were evaluated for the quantification of (2-methoxyethoxy)acetic acid (MEAA) in urine. MEAA is a metabolite and a biomarker for exposure to 2-(2-methoxyethoxy)ethanol, a glycol ether with widespread use in various industrial applications and the specific use as an anti-icing additive in the military jet fuel formulation JP-8. Quantification of glycol ether biomarkers is an active area of analytical research. Various sample preparation procedures were evaluated: liquid-liquid extraction (LLE) using ethyl acetate yielded the highest recovery, and solid-phase extraction (SPE) gave low recovery of MEAA. Two derivatization procedures were thoroughly investigated and validated, namely, silylation of MEAA with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), and esterification of MEAA using ethanol. Quantification was performed by gas chromatography (GC) with a mass spectrometer as detector and using a polydimethylsiloxane (HP-1) capillary column. Deuterated 2-butoxyacetic acid (d-BAA) was used as an internal standard. Recovery studies of spiked human urine demonstrated the accuracy and precision of both procedures. The limit of detection (LOD) and other figures of merit for both derivatization procedures will be discussed in detail. Applications of these analysis procedures are also discussed.

Detection of Recent Ethanol Intake With New Markers: Comparison of Fatty Acid Ethyl Esters in Serum and of Ethyl Glucuronide and the Ratio of 5-Hydroxytryptophol to 5-Hydroxyindole Acetic Acid in Urine

At present, recent ethanol consumption can be routinely detected with certainty only by direct measurement of ethanol concentration in blood or urine. Because ethanol is rapidly eliminated from the circulation, however, the time span for this detection is in the range of hours. Several new markers have been proposed to extend the detection interval, but their characteristics have not yet justified their use in routine clinical practice. We therefore investigated three new markers and compared their kinetics and sensitivities: (1) fatty acid ethyl esters (FAEEs) in serum, (2) ethyl glucuronide (EtG) in urine, and (3) the ratio of 5-hydroxytryptophol to 5-hydroxyindole acetic acid (5-HTOL/5-HIAA) in urine. Seventeen healthy men participated in a drinking experiment. Blood and urine samples were collected twice daily on three consecutive days and once daily on days 4 and 5. Ethanol concentration was determined by gas chromatography, FAEE levels, by gas chromatography with mass spectrometry, EtG concentration, by liquid chromatography-tandem mass spectrometry, and 5-HTOL/5-HIAA ratio, by high-performance liquid chromatography. The peak serum ethanol concentrations of the subjects ranged from 5.4 to 44.7 mmol/liter (mean +/- SD, 30.1 +/- 9.1 mmol/liter). In the case of the serum ethanol determination, 100% sensitivity was reached only immediately after the end of the drinking experiment, and in the case of FAEE levels and 5-HTOL/5-HIAA ratio, it tested for 6.7 hr after the end of the ethanol intake. Thereafter, these latter parameters declined until 15.3 hr (FAEEs) and 29.4 hr (5-HTOL/5-HIAA), subsequently remaining in a stable range until 78.5 hr without further decrease. In contrast, EtG concentration showed 100% sensitivity until 39.3 hr and thereafter decreased, falling to below the limit of quantification of 0.1 mg/liter at 102.5 hr. After moderate drinking, EtG in the urine proved to be a superior marker of recent ethanol consumption in healthy subjects. This is because EtG is a direct ethanol metabolite, it occurs in the urine only when ethanol has been consumed, and its sensitivity remains at the level of 100% for 39.3 hr.

A Test Procedure for the Determination of (2-Methoxyethoxy)acetic Acid in Urine from Jet Fuel-Exposed Mice

A test procedure for the determination of (2-methoxyethoxy)acetic acid (MEAA) was adapted and applied to urine samples from jet fuel (JP-8)-exposed mice using capillary gas chromatography with a mass selective detector (MSD). MEAA is a metabolite and proposed biomarker for exposure to 2-(2-methoxyethoxy)ethanol, a glycol ether component in the formulation of JP-8. The collected urine samples were spiked with deuterated butoxyacetic acid internal standard, and extracted with ethyl acetate, and esterified with ethanol and sulfuric acid, and the esters of the glycol ethers were extracted with methylene chloride. The chromatographic conditions used easily separate the MEAA ethyl ester from interferences within mouse urine. The application of this procedure to urine samples collected from mice demonstrated that MEAA was detectable after oral (2000 mg/kg) or dermal (50 μ L) exposure for 7 days to JP-8 at levels as high as 8.5 or 6.5 μ g/mL, respectively. This pilot demonstration indicated that total urinary MEAA was a viable biomarker for the two routes of JP-8 exposure in laboratory mice.

Tryptophan metabolism via serotonin in rats with hexachlorobenzene experimental porphyria

One of the three pathways for the metabolisation of dietary tryptophan is the formation of serotonin. Tryptophan hydroxylase catalyses the formation of 5-hydroxytryptophan, the first and regulatory step of this biosynthesis. The aim of the present work is to study alterations in this tryptophan metabolism in rats with experimental Porphyria Cutanea Tarda induced by hexachlorobenzene. With this purpose, the content of tryptophan and its metabolites related to the serotonin pathway are determined by HPLC techniques, in tissues (brain, liver and gut) and in fluids (blood, plasma and urine) of controls and hexachlorobenzene-porphyric rats. In these experimental-porphyric animals, we determine a significant increase in the excretion of 5-hydroxyindole acetic acid in urine and a decrease in the content of serotonin in small gut, respect to controls. Significant increases in contents of serotonin in 24-hr urine and tryptophan in liver are also found. No other significant variations for the different metabolites are detected in any of the tissues and fluids studied. Brain and liver activities of the rate-limiting enzyme tryptophan hydroxylase can only be measured in porphyric rats. Our results agree with an increased turnover of gastrointestinal serotonin derived from dietary tryptophan and its excretion as urinary 5-hydroxyindole acetic acid, which is formed in liver. An increased serotonin pathway in porphyric livers is confirmed by the measured increase in the activity of hepatic tryptophan hydroxylase. The absence of neurological symptoms in patients with Porphyria Cutanea Tarda could be related to the absence of a statistically significant variation in serotonin content shown in brain.

Disposition, pharmacokinetics, and metabolism of 14C-fotemustine in cancer patients

The pharmacokinetics and metabolism of intravenously infused 14C-fotemustine (about 100 mg/m 2) were examined in 2 cancer patients. Plasma levels of radioactivity increased to a maximum of 4.1 and 5.5 μg equivalents per g when the infusion stopped then declined triexponentially with mean half-lives of about 1 2 , 10 and 80 h for the initial, mid and terminal phases, respectively. Plasma levels of intact drug were lower, with maximum levels of 1.1 and 2.8 μg/ml, and declined monophasically with a half-life of about 24 min. Plasma clearance was high (1426 and 764 ml/min) with the volume of distribution based on areas of 47.7 and 26.4 1. Most of the radioactivity was eliminated in urine (50.1 and 61.3%) over 7 days with smaller amounts in the faeces (6.8 and 0.3%) and only minimal quantities (under 0.1%) as expired carbon dioxide. Metabolites of fotemustine were identified as chloroethanol and N-nitroso-1-imidazolone-ethyl-diethylphosphonate in plasma and as 1-hydantoin-ethyl-diethyl-phosphonate and acetic acid in urine.

The effect of disodium cromoglycate and ketotifen on the excretion of histamine and N tau‐methylimidazole acetic acid in urine of patients with mastocytosis.

Treatment of four mastocytosis patients with the mast cell stabilising drugs, disodium cromoglycate and ketotifen failed to alter significantly the urinary excretion levels of histamine or N tau-methylimidazole acetic acid. No clinical improvement was noted in any subject after treatment by either drug.

The metabolism of 2-ethylhexanol in rats.

1. 2-Ethylhexanol was efficiently absorbed following oral administration to rats. 14C associated with 2-ethyl[1-14C]hexanol was rapidly excreted in respiratory CO2 (6-7%), faeces (8-9%) and urine (80-82%), with essentially complete elimination by 28 h after administration. 2. The amount of label recovered in 14CO2 matched the amount of unlabelled 2-heptanone plus 4-heptanone recovered from urine, suggesting that both types of metabolite may have been derived form the major urinary metabolite, 2-ethylhexanoic acid, by decarboxylation following partial beta-oxidation. The 14CO2 appeared not to be derived from acetate (urinary acetic acid and liver and brain cholesterol were not labelled) or by reductive decarboxylation (heptane was not present.) 3. Other identified metabolites were 2-ethyl-5-hydroxyhexanoic acid, 2-ethyl-5-ketohexanoic acid, and 2-ethyl-1,6-hexanedioic acid. Only about 3% of the ethylhexanol was excreted unchanged. 4. Ethylhexanol was a competitive inhibitor of yeast alcohol dehydrogenase, but a good substrate for horse alcohol dehydrogenase. 5. Other relationships between metabolism and toxicity of 2-ethylhexanol are discussed.

Urinary bacteria: potential source of some organic acidurias

Normal human urine was inoculated with pure cultures of various urinary pathogens, and then incubated at 37°. Organic acids were measured in the urine by gas Chromatographie techniques. Microorganisms of 11different species were found capable of producing large amounts of acetic acid in urine, while 8 species produced propionic acid. Bacteria of 8 different species were able to hydrolyze hippuric acid to benzoic acid. A few organisms also produced butyric, isovaleric, or caproic acid. Thus investigators who study cases of presumed metabolic disorders in man must exclude the possibility that abnormal acids found in urine are only artifacts produced by urinary tract infections.

2-Methyl-4-amino-6-methoxy-s-triazine (CV399)の一般薬理作用，とくに中枢作用を中心として

2-Methyl-4-amino-6-methoxy-s-triazine (CV 399) showed the marked central depressive actions in animal experiments, i. e. sedation in gross behavior, reduction of spontaneous motor activity and of hyperactivity induced by a variety of CNS excitants, potentation of pentobarbital or ethanol hypnosis, inhibition of hyperirritability of septal lesioned rats, analgesic effect, hypothermic effect and anticonvulsive action against electro- and chemoshocks. This agent blocked both of the conditioned avoidance response and the escape response in about the same extent in rats. This agent, however, did not exibit any effect on respiration and blood pressure level, and any change in brain serotonin content and in excretion of 5-hydroxyindole acetic acid in urine at the dose producing the above-mentioned effect.