RESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) in South Africa and Africa at large is considered a hidden threat. Our local population is burdened with increased metabolic risk factors for NAFLD. Our setting requires a reasonable approach to screen for and aid the diagnosis of NAFLD. OBJECTIVES: To investigate serum fructosamine and random spot urine fructose levels as biomarkers for the screening, diagnosis and monitoring of NAFLD. The primary objective of this study was to compare serum fructosamine and random spot urine fructose levels between groups with different levels of NAFLD severity as measured by ultrasound. A secondary objective was to determine the association, if any, between serum transaminases, the aspartate aminotransferase (AST) to platelet ratio index (APRI) score, serum fructosamine and urine fructose in different groups with steatosis. METHODS: Using a cross-sectional study design, 65 patients with three different levels of NAFLD, as detected by imaging, were enrolled. The primary exposures measured were serum fructosamine with random spot urine fructose, and secondary exposures were the serum transaminases (AST and alanine aminotransferase (ALT)) and the APRI score. Patients identified at the departments of gastroenterology, general internal medicine and diagnostic radiology were invited to participate. RESULTS: There were 38, 17 and 10 patients with mild, moderate and severe steatosis, respectively. There was no significant difference between the groups regarding serum fructosamine, measured as median (interquartile range): mild 257 (241 - 286) µmol/L, moderate 239 (230 - 280) µmol/L and severe 260 (221 - 341) µmol/L, p=0.5; or random spot urine fructose: mild 0.86 (0.51 - 1.30) mmol/L, moderate 0.84 (0.51 - 2.62) mmol/L and severe 0.71 (0.58 - 1.09) mmol/L, p = 0.8. ALT (U/L) differed between groups: mild 19 (12 - 27), moderate 27 (22 - 33), severe 27 (21 - 56), p=0.03, but not AST (U/L) (p=0.7) nor APRI (p=0.9). Urine fructose and ALT were correlated in the moderate to severe steatosis group (R=0.490, p<0.05), but not in the mild steatosis group. Serum fructosamine was associated with age in the mild steatosis group but not the moderate-severe steatosis group (R=0.42, p<0.01). CONCLUSION: Serum fructosamine and random spot urine fructose did not vary with the severity of NAFLD, indicating that they would not be useful biomarkers in this condition.
Assuntos
Alanina Transaminase , Aspartato Aminotransferases , Biomarcadores , Frutosamina , Frutose , Hepatopatia Gordurosa não Alcoólica , Índice de Gravidade de Doença , Humanos , Frutosamina/sangue , Hepatopatia Gordurosa não Alcoólica/urina , Hepatopatia Gordurosa não Alcoólica/sangue , Estudos Transversais , Feminino , Frutose/urina , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Biomarcadores/urina , Adulto , Aspartato Aminotransferases/sangue , Alanina Transaminase/sangue , África do Sul/epidemiologia , UltrassonografiaRESUMO
This study presented a nanoparticle-enhanced aptamer-recognizing homogeneous detection system combined with a portable instrument (NASPI) to quantify lipoarabinomannan (LAM). This system leveraged the high binding affinity of aptamers, the high sensitivity of nanoparticle cascade amplification, and the stabilization effect of dual stabilizers (fructose and histone), and used probe-Cu2+ to achieve LAM detection at concentrations ranging from 10 ag mL-1 to 100 fg mL-1, with a limit of detection of 3 ag mL-1 using a fluorometer. It can also be detected using an independently developed handheld fluorometer or the red-green-blue (RGB) camera of a smartphone, with a minimum detection concentration of 10 ag mL-1. We validated the clinical utility of the biosensor by testing the LAM in the urine of patients. Forty urine samples were tested, with positive LAM results in the urine of 18/20 tuberculosis (TB) cases and negative results in the urine of 6/10 latent tuberculosis infection cases and 10/10 non-TB cases. The assay results revealed a 100% specificity and a 90% sensitivity, with an area under the curve of 0.9. We believe that the NASPI biosensor can be a promising clinical tool with great potential to convert LAM into clinical indicators for TB patients.
Assuntos
Cobre , Frutose , Lipopolissacarídeos , Nanopartículas Metálicas , Smartphone , Tuberculose , Cobre/química , Humanos , Tuberculose/diagnóstico , Tuberculose/urina , Nanopartículas Metálicas/química , Lipopolissacarídeos/urina , Frutose/urina , DNA/química , Técnicas Biossensoriais , FluorometriaRESUMO
BACKGROUND: Developing approaches for the objective assessment of sugars intake in population research is crucial for generating reliable disease risk estimates, and evidence-based dietary guidelines. Twenty-four-hour urinary sucrose and fructose (24uSF) was developed as a predictive biomarker of total sugars intake based on 3 UK feeding studies, yet its performance as a biomarker of total sugars among US participants is unknown. OBJECTIVES: To investigate the performance of 24uSF as a biomarker of sugars intake among US participants, and to characterize its use. METHODS: Ninety-eight participants, aged 18-70 y, consumed their usual diet under controlled conditions of a feeding study for 15 d, and collected 8 nonconsecutive 24-h urines measured for sucrose and fructose. RESULTS: A linear mixed model regressing log 24uSF biomarker on log total sugars intake along with other covariates explained 56% of the biomarker variance. Total sugars intake was the strongest predictor in the model (Marginal R2 = 0.52; P <0.0001), followed by sex (P = 0.0002) and log age (P = 0.002). The equation was then inverted to solve for total sugars intake, thus generating a calibrated biomarker equation. Calibration of the biomarker produced mean biomarker-based log total sugars of 4.79 (SD = 0.59), which was similar to the observed log 15-d mean total sugars intake of 4.69 (0.35). The correlation between calibrated biomarker and usual total sugars intake was 0.59 for the calibrated biomarker based on a single biomarker measurement, and 0.76 based on 4 biomarker repeats spaced far apart. CONCLUSIONS: In this controlled feeding study, total sugars intake was the main determinant of 24uSF confirming its utility as a biomarker of total sugars in this population. Next steps will include validation of stability assumptions of the biomarker calibration equation proposed here, which will allow its use as an instrument for dietary validation and measurement error correction in diet-disease association studies.
Assuntos
Carboidratos da Dieta/urina , Frutose/urina , Sacarose/urina , Adolescente , Adulto , Idoso , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: The study of the involvement of fructose in the pathogenesis of cardiometabolic disease requires accurate and precise measurements of serum and urinary fructose. The aim of the present study was to develop and validate such a method by Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS). METHODS: Fructose was quantified using hydrophilic interaction UPLC-MS/MS with a labelled internal standard. Serum fructose levels were determined in healthy individuals (n = 3) after a 15-gram oral fructose load. Twenty-four hours urinary fructose levels were determined in individuals consuming low (median: 1.4 g/day, interquartile range [IQR]: 0.9-2.0; n = 10), normal (31 g/day, 23-49; n = 15) and high (70 g/day, 55-84; n = 16) amounts of fructose. RESULTS: The calibration curves showed perfect linearity in water, artificial, serum, and urine matrices (r2 > 0.99). Intra- and inter-day assay variation of serum and urinary fructose ranged from 0.3 to 5.1% with an accuracy of ~98%. Fasting serum fructose levels (5.7 ± 0.6 µmol/L) increased 60 min after a 15-gram oral fructose load (to 150.3 ± 41.7 µmol/L) and returned to normal after 180 min (8.4 ± 0.6 µmol/L). Twenty-four hours urinary fructose levels were significantly lower in low fructose consumers when compared to normal and high fructose consumers (median: 36.1 µmol/24 h, IQR: 26.4-64.2; 142.3 µmol/24 h, 98.8-203.0; and 238.9 µmol/24 h, 127.1-366.1; p = 0.004 and p < 0.001, respectively). CONCLUSION: Fructose concentrations can be measured accurately and precisely with this newly-developed UPLC-MS/MS method. Its robustness makes it suitable for assessing the value of fructose in clinical studies.
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Cromatografia Líquida de Alta Pressão/métodos , Frutose/sangue , Frutose/urina , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Feminino , Frutose/farmacocinética , Humanos , Modelos Lineares , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
PURPOSE: Excessive consumption of free sugar increases the risk for non-communicable diseases where a proper assessment of this intake is necessary to correctly estimate its association with certain diseases. Urinary sugars have been suggested as objective biomarkers for total and free sugar intake in adults but less is known about this marker in children and adolescents. Therefore, the aim of this exploratory study is to evaluate the relative validity of self-reported intake using urinary sugars in children and adolescents. METHODS: The study was conducted in a convenience subsample of 228 participants aged 5-18 years of the I.Family study that investigates the determinants of food choices, lifestyle and health in European families. Total, free and intrinsic sugar intake (g/day) and sugar density (g/1000 kcal) were assessed using 24-h dietary recalls (24HDRs). Urinary sucrose (USUC) and urinary fructose (UFRU) were measured in morning urine samples and corrected for creatinine excretion (USUC/Cr, UFRU/Cr). Correlation coefficients, the method of triads and linear regression models were used to investigate the relationship between intake of different types of sugar and urinary sugars. RESULTS: The correlation between usual sugar density calculated from multiple 24HDRs and the sum of USUC/Cr and UFRU/Cr (USUC/Cr + UFRU/Cr) was 0.38 (p < 0.001). The method of triads revealed validity coefficients for the 24HDR from 0.64 to 0.87. Linear regression models showed statistically significant positive associations between USUC/Cr + UFRU/Cr and the intake of total and free sugar. CONCLUSIONS: These findings support the relative validity of total and free sugar intake assessed by self-reported 24HDRs in children and adolescents.
Assuntos
Registros de Dieta , Inquéritos sobre Dietas/métodos , Açúcares da Dieta/urina , Frutose/urina , Autorrelato , Sacarose/urina , Adolescente , Biomarcadores/urina , Criança , Pré-Escolar , Inquéritos sobre Dietas/estatística & dados numéricos , Europa (Continente) , Feminino , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
Epalrestat is an inhibitor of aldose reductase in the polyol pathway and is used for the management of diabetic neuropathy clinically. Our pilot experiments and accumulated evidences showed that epalrestat inhibited polyol pathway and reduced sorbitol production, and suggested the potential renal protection effects of epalrestat on diabetic nephropathy (DN). To evaluate the protective effect of epalrestat, the db/db mice were used and exposed to epalrestat for 8 weeks, both the physiopathological condition and function of kidney were examined. For the first time, we showed that epalrestat markedly reduced albuminuria and alleviated the podocyte foot process fusion and interstitial fibrosis of db/db mice. Metabolomics was employed, and metabolites in the plasma, renal cortex, and urine were profiled using a gas chromatography-mass spectrometry (GC/MS)-based metabolomic platform. We observed an elevation of sorbitol and fructose, and a decrease of myo-inositol in the renal cortex of db/db mice. Epalrestat reversed the renal accumulation of the polyol pathway metabolites of sorbitol and fructose, and increased myo-inositol level. Moreover, the upregulation of aldose reductase, fibronectin, collagen III, and TGF-ß1 in renal cortex of db/db mice was downregulated by epalrestat. The data suggested that epalrestat has protective effects on DN, and the inhibition of aldose reductase and the modulation of polyol pathway in nephritic cells be a potentially therapeutic strategy for DN.
Assuntos
Aldeído Redutase/antagonistas & inibidores , Nefropatias Diabéticas/prevenção & controle , Inibidores Enzimáticos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Rodanina/análogos & derivados , Tiazolidinas/uso terapêutico , Albuminúria/tratamento farmacológico , Animais , Frutose/sangue , Frutose/metabolismo , Frutose/urina , Inositol/sangue , Inositol/metabolismo , Inositol/urina , Rim/metabolismo , Rim/patologia , Masculino , Metabolômica , Camundongos , Rodanina/uso terapêutico , Sorbitol/sangue , Sorbitol/metabolismo , Sorbitol/urinaRESUMO
This study exploits the information potential of comprehensive two-dimensional gas chromatography configured with a parallel dual secondary column-dual detection by mass spectrometry and flame ionization (GC×2GC-MS/FID) to study changes in urinary metabolic signatures of mice subjected to high-fructose diets. Samples are taken from mice fed with normal or fructose-enriched diets provided either in aqueous solution or in solid form and analyzed at three stages of the dietary intervention (1, 6, and 12 weeks). Automated Untargeted and Targeted fingerprinting for 2D data elaboration is adopted for the most inclusive data mining of GC×GC patterns. The UT fingerprinting strategy performs a fully automated peak-region features fingerprinting and combines results from pre-targeted compounds and unknowns across the sample-set. The most informative metabolites, with statistically relevant differences between sample groups, are obtained by unsupervised multivariate analysis (MVA) and cross-validated by multi-factor analysis (MFA) with external standard quantitation by GC-MS. Results indicate coherent clustering of mice urine signatures according to dietary manipulation. Notably, the metabolite fingerprints of mice fed with liquid fructose exhibited greater derangement in fructose, glucose, citric, pyruvic, malic, malonic, gluconic, cis-aconitic, succinic and 2-keto glutaric acids, glycine acyl derivatives (N-carboxy glycine, N-butyrylglycine, N-isovaleroylglycine, N-phenylacetylglycine), and hippuric acid. Untargeted fingerprinting indicates some analytes which were not a priori pre-targeted which provide additional insights: N-acetyl glucosamine, N-acetyl glutamine, malonyl glycine, methyl malonyl glycine, and glutaric acid. Visual features fingerprinting is used to track individual variations during experiments, thereby extending the panorama of possible data elaboration tools. Graphical abstract á .
Assuntos
Açúcares da Dieta/metabolismo , Frutose/metabolismo , Metaboloma , Metabolômica/métodos , Urina/química , Animais , Açúcares da Dieta/urina , Frutose/urina , Cromatografia Gasosa-Espectrometria de Massas/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Despite clinical findings suggesting that the form (liquid versus solid) of the sugars may significantly affect the development of metabolic diseases, no experimental data are available on the impact of their formulations on gut microbiota, integrity and hepatic outcomes. In the present sudy, C57Bl/6j mice were fed a standard diet plus water (SD), a standard diet plus 60% fructose syrup (L-Fr) or a 60% fructose solid diet plus water (S-Fr) for 12 weeks. Gut microbiota was characterized through 16S rRNA phylogenetic profiling and shotgun sequencing of microbial genes in ileum content and related volatilome profiling. Fructose feeding led to alterations of the gut microbiota depending on the fructose formulation, with increased colonization by Clostridium, Oscillospira and Clostridiales phyla in the S-Fr group and Bacteroides, Lactobacillus, Lachnospiraceae and Dorea in the L-Fr. S-Fr evoked the highest accumulation of advanced glycation end products and barrier injury in the ileum intestinal mucosa. These effects were associated to a stronger activation of the lipopolysaccharide-dependent proinflammatory TLR4/NLRP3 inflammasome pathway in the liver of S-Fr mice than of L-Fr mice. In contrast, L-Fr intake induced higher levels of hepatosteatosis and markers of fibrosis than S-Fr. Fructose-induced ex novo lipogenesis with production of SCFA and MCFA was confirmed by metagenomic analysis. These results suggest that consumption of fructose under different forms, liquid or solid, may differently affect gut microbiota, thus leading to impairment in intestinal mucosa integrity and liver homeostasis.
Assuntos
Frutose/química , Frutose/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Cirrose Hepática/induzido quimicamente , Animais , Fezes/química , Frutose/urina , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Transportador de Glucose Tipo 2/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Inflamassomos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Cirrose Hepática/metabolismo , Masculino , Metagenoma/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
Acute kidney injury is associated with high mortality, especially in intensive care unit patients. The polyol pathway is a metabolic route able to convert glucose into fructose. Here we show the detrimental role of endogenous fructose production by the polyol pathway and its metabolism through fructokinase in the pathogenesis of ischaemic acute kidney injury (iAKI). Consistent with elevated urinary fructose in AKI patients, mice undergoing iAKI show significant polyol pathway activation in the kidney cortex characterized by high levels of aldose reductase, sorbitol and endogenous fructose. Wild type but not fructokinase knockout animals demonstrate severe kidney injury associated with ATP depletion, elevated uric acid, oxidative stress and inflammation. Interestingly, both the renal injury and dysfunction in wild-type mice undergoing iAKI is significantly ameliorated when exposed to luteolin, a recently discovered fructokinase inhibitor. This study demonstrates a role for fructokinase and endogenous fructose as mediators of acute renal disease.
Assuntos
Injúria Renal Aguda/prevenção & controle , Frutoquinases/antagonistas & inibidores , Rim/efeitos dos fármacos , Luteolina/farmacologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Aldeído Redutase/metabolismo , Animais , Linhagem Celular , Frutoquinases/genética , Frutoquinases/metabolismo , Frutose/metabolismo , Frutose/urina , Humanos , Isquemia/complicações , Rim/metabolismo , Rim/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ácido Úrico/metabolismoRESUMO
BACKGROUND/AIMS: Hyponatremia associated with high urinary fractional excretion of uric acid which persists after serum sodium is corrected is the cardinal feature of salt losing nephropathy (SLN). We hypothesize that low grade proximal tubular injury is present in SLN because the proximal tubule is the main site of uric acid and sodium transport. METHODS: Five subjects with SLN were compared to four subjects with recurrent hyponatremia and three healthy individuals. Urinary NGAL (neutrophil gelatinase associated lipocalin, a marker of tubular injury) and fasting urinary fructose levels (a marker of proximal tubular injury) were measured. RESULTS: Subjects with SLN (n=5) showed elevated fractional uric acid excretion (22 ± 6 vs 4 ± 2 percent, p<0.0001), elevated urinary NGAL levels (62 ± 37 vs 9 ± 7 ng/mg creatinine, p=0.001) and fasting urinary fructose levels compared with the 7 controls (383 ± 465 vs 60 ± 34µmole/µg creatinine, p <0.001). A strong correlation between urinary NGAL levels and urinary fructose levels was observed (r =0.87, p<0.001). CONCLUSION: High urinary fractional excretion of uric acid in SLN is associated with elevated NGAL and fasting urinary fructose levels suggesting that SLN may involve tubular injury.
Assuntos
Hiponatremia/urina , Túbulos Renais Proximais/lesões , Ácido Úrico/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Frutose/urina , Humanos , Nefropatias , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Sódio/sangue , Adulto JovemRESUMO
OBJECTIVE: Measurement error in self-reported total sugars intake may obscure associations between sugars consumption and health outcomes, and the sum of 24 h urinary sucrose and fructose may serve as a predictive biomarker of total sugars intake. DESIGN: The Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS) was an ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort. Doubly labelled water and 24 h urinary sucrose and fructose were used as biomarkers of energy and sugars intake, respectively. Participants' diets were assessed by up to three 24 h recalls (88 % had two or more recalls). Procedures were repeated approximately 6 months after the initial visit among a subset of ninety-six participants. SETTING: Four centres (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA) across the USA. SUBJECTS: Men and women (n 477) aged 18-74 years. RESULTS: The geometric mean of total sugars was 167·5 (95 % CI 154·4, 181·7) g/d for the biomarker-predicted and 90·6 (95 % CI 87·6, 93·6) g/d for the self-reported total sugars intake. Self-reported total sugars intake was not correlated with biomarker-predicted sugars intake (r=-0·06, P=0·20, n 450). Among the reliability sample (n 90), the reproducibility coefficient was 0·59 for biomarker-predicted and 0·20 for self-reported total sugars intake. CONCLUSIONS: Possible explanations for the lack of association between biomarker-predicted and self-reported sugars intake include measurement error in self-reported diet, high intra-individual variability in sugars intake, and/or urinary sucrose and fructose may not be a suitable proxy for total sugars intake in this study population.
Assuntos
Inquéritos sobre Dietas , Sacarose Alimentar/administração & dosagem , Hispânico ou Latino , Açúcares/administração & dosagem , Adolescente , Adulto , Idoso , Biomarcadores/urina , Sacarose Alimentar/urina , Ingestão de Energia , Feminino , Frutose/urina , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Autorrelato , Estados Unidos , Adulto JovemRESUMO
Recurrent dehydration, such as commonly occurs with manual labor in tropical environments, has been recently shown to result in chronic kidney injury, likely through the effects of hyperosmolarity to activate both vasopressin and aldose reductase-fructokinase pathways. The observation that the latter pathway can be directly engaged by simple sugars (glucose and fructose) leads to the hypothesis that soft drinks (which contain these sugars) might worsen rather than benefit dehydration associated kidney disease. Recurrent dehydration was induced in rats by exposure to heat (36°C) for 1 h/24 h followed by access for 2 h to plain water (W), a 11% fructose-glucose solution (FG, same composition as typical soft drinks), or water sweetened with noncaloric stevia (ST). After 4 wk plasma and urine samples were collected, and kidneys were examined for oxidative stress, inflammation, and injury. Recurrent heat-induced dehydration with ad libitum water repletion resulted in plasma and urinary hyperosmolarity with stimulation of the vasopressin (copeptin) levels and resulted in mild tubular injury and renal oxidative stress. Rehydration with 11% FG solution, despite larger total fluid intake, resulted in greater dehydration (higher osmolarity and copeptin levels) and worse renal injury, with activation of aldose reductase and fructokinase, whereas rehydration with stevia water had opposite effects. In animals that are dehydrated, rehydration acutely with soft drinks worsens dehydration and exacerbates dehydration associated renal damage. These studies emphasize the danger of drinking soft drink-like beverages as an attempt to rehydrate following dehydration.
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Bebidas Gaseificadas/efeitos adversos , Desidratação/induzido quimicamente , Hidratação/efeitos adversos , Nefropatias/induzido quimicamente , Animais , Pressão Sanguínea/efeitos dos fármacos , Desidratação/complicações , Frutose/farmacologia , Frutose/urina , Glicopeptídeos/sangue , Temperatura Alta/efeitos adversos , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/patologia , Testes de Função Renal , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Stevia , Edulcorantes/farmacologia , Ácido Úrico/urina , Água/farmacologia , Equilíbrio HidroeletrolíticoRESUMO
Physical and psychological stress have been shown to modulate multiple aspects of gastrointestinal (GI) physiology, but its molecular basis remains elusive. We therefore characterized the stress-induced metabolic phenotype (metabotype) in soldiers during high-intensity combat training and correlated the metabotype with changes in GI symptoms and permeability. In a prospective, longitudinal study, urinary metabotyping was conducted on 38 male healthy soldiers during combat training and a rest period using gas chromatography-mass spectrometry. The urinary metabotype during combat training was clearly distinct from the rest period (partial least-squares discriminant analysis (PLSDA) Q(2) = 0.581), confirming the presence of a unique stress-induced metabotype. Differential metabolites related to combat stress were further uncovered, including elevated pyroglutamate and fructose, and reduced gut microbial metabolites, namely, hippurate and m-hydroxyphenylacetate (p < 0.05). The extent of pyroglutamate upregulation exhibited a positive correlation with an increase in IBS-SSS in soldiers during combat training (r = 0.5, p < 0.05). Additionally, the rise in fructose levels was positively correlated with an increase in intestinal permeability (r = 0.6, p < 0.005). In summary, protracted and mixed psychological and physical combat-training stress yielded unique metabolic changes that corresponded with the incidence and severity of GI symptoms and alteration in intestinal permeability. Our study provided novel molecular insights into stress-induced GI perturbations, which could be exploited for future biomarker research or development of therapeutic strategies.
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Ansiedade/urina , Depressão/urina , Frutose/urina , Síndrome do Intestino Irritável/urina , Metaboloma , Ácido Pirrolidonocarboxílico/urina , Estresse Psicológico/urina , Ansiedade/diagnóstico , Ansiedade/fisiopatologia , Biomarcadores/urina , Depressão/diagnóstico , Depressão/fisiopatologia , Cromatografia Gasosa-Espectrometria de Massas , Hipuratos/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Intestinos/fisiopatologia , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/fisiopatologia , Análise dos Mínimos Quadrados , Estudos Longitudinais , Masculino , Militares , Permeabilidade , Fenilacetatos/metabolismo , Estudos Prospectivos , Estresse Fisiológico , Estresse Psicológico/diagnóstico , Estresse Psicológico/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: The purpose of this study was to evaluate intestinal absorption, organ distribution, and urinary elimination of the rare sugar D-psicose, a 3-carbon stereoisomer of D-fructose that is currently being investigated and which has been found to be strongly effective against hyperglycemia and hyperlipidemia. METHODS: This study was performed using radioactive D-psicose, which was synthesized enzymatically from radioactive D-allose. Concentrations in whole blood, urine, and organs were measured at different time points until 2 hours after both oral and intravenous administrations and 7 days after a single oral administration (100 mg/kg body weight) to Wistar rats. Autoradiography was also performed by injecting 100 mg/kg body weight of (14)C-labeled D-psicose or glucose intravenously to C3H mice. RESULTS: Following oral administration, D-psicose easily moved to blood. The maximum blood concentration (48.5±15.6 µg/g) was observed at 1 hour. Excretion to urine was 20% within 1 hour and 33% within 2 hours. Accumulation to organs was detected only in the liver. Following intravenous administration, blood concentration was decreased with the half-life=57 minutes, and the excretion to urine was up to almost 50% within 1 hour. Similarly to the results obtained with oral administration, accumulation to organs was detected only in the liver. Seven days after the single-dose oral administration, the remaining amounts in the whole body were less than 1%. Autoradiography of mice showed results similar to those in rats. High signals of (14)C-labeled D-psicose were observed in liver, kidney, and bladder. Interestingly, no accumulation of D-psicose was observed in the brain. CONCLUSION: D-psicose was absorbed well after oral administration and eliminated rapidly after both oral and intravenous administrations, with short duration of action. The study provides valuable pharmacokinetic data for further drug development of D-psicose. Because the findings were mainly based on animal study, it is necessary to implement human trials to study the metabolism pathway, which would give an important guide for human intake and food application of D-psicose.
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Frutose/farmacocinética , Frutose/urina , Absorção Intestinal , Administração Intravenosa , Administração Oral , Animais , Frutose/administração & dosagem , Frutose/sangue , Camundongos , Camundongos Endogâmicos C3H , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
SCOPE: Antiglycative effects of glycyrrhizic acid (GA) in kidney of diabetic mice were examined. METHODS AND RESULTS: GA at 0.05, 0.1, and 0.2% was supplied to diabetic mice for 9 wk. Results showed that GA intake increased its deposit in kidney, raised plasma insulin level, decreased plasma glucose and blood urine nitrogen levels, and improved creatinine clearance rate (p < 0.05). GA intake dose-dependently reduced renal carboxymethyllysine level, and at 0.1 and 0.2% decreased plasma HbA1c, urinary glycated albumin, and renal pentosidine levels (p < 0.05). Dietary GA intake declined renal aldose reductase activity and protein expression, as well as lowered renal fructose and sorbitol levels (p < 0.05). GA intake dose-dependently increased glyoxalase-1 activity and expression, and decreased renal methylglyoxal level (p < 0.05). This compound at 0.1 and 0.2% raised glyoxalase-2 activity and protein expression, and increased d-lactate formation (p < 0.05). GA intake dose-dependently suppressed renal expression of nuclear factor kappa B (NF-κB) p65 and p-p38, decreased reactive oxygen species production, and retained glutathione content (p < 0.05). This compound at 0.1 and 0.2% downregulated renal expression of NF-κB p50 and p-ERK1/2 (p < 0.05), and lowered renal level of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1). CONCLUSIONS: These findings suggest that glycyrrhizic acid is an antiglycative and renal-protective agent.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Ácido Glicirrízico/farmacologia , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Aldeído Redutase/genética , Aldeído Redutase/metabolismo , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Relação Dose-Resposta a Droga , Frutose/urina , Glutationa/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Rim/metabolismo , L-Iditol 2-Desidrogenase/metabolismo , Lactoilglutationa Liase/genética , Lactoilglutationa Liase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Sorbitol/urina , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismoRESUMO
A new strategy is proposed to sensitively and rapidly detect analytes with weak Raman signals in complex media using surface-enhanced Raman spectroscopy (SERS) via detecting the SERS signal changes of the immobilized probe molecules on SERS-active substrates upon binding of the analytes. In this work, 4-mercaptophenylboronic acid (4-MPBA) was selected as the probe molecule which was immobilized on the gold surface of a quasi-three-dimensional plasmonic nanostructure array (Q3D-PNA) SERS substrate to detect fructose. The molecule of 4-MPBA possesses three key functions: molecule recognition and reversible binding of the analyte via the boronic acid group, amplification of SERS signals by the phenyl group and thus shielding of the background noise of complex media, and immobilization on the surface of SERS-active substrates via the thiol group. Most importantly, the symmetry breaking of the 4-MPBA molecule upon fructose binding leads to the change of area ratio between totally symmetric 8a ring mode and nontotally symmetric 8b ring mode, which enables the detection. The detection curves were obtained in phosphate-buffered saline (PBS) and in undiluted artificial urine at clinically relevant concentrations, and the limit of detection of 0.05 mM was achieved.
Assuntos
Frutose/análise , Análise Espectral Raman/métodos , Frutose/urina , Humanos , Limite de Detecção , Propriedades de SuperfícieRESUMO
Urinary sugars excretion has been proposed as a potential biomarker for intake of sugars. In this study, we compared 2 analytical methods (gas chromatography [GC] and enzymatic reactions-UV absorption) for quantifying urinary fructose and sucrose using 24-hour urine samples from a randomized crossover controlled feeding study. All samples were successfully quantified by the GC method; however, 21% and 1.9% of samples were below the detection limit of the enzymatic method for sucrose and fructose, respectively. Although the correlation between the 2 methods was good for fructose (Pearson correlation, 0.71), the correlation was weak for sucrose (Pearson correlation, 0.27). We favor the GC method because of its better sensitivity, simplicity, and the ability to quantify fructose and sucrose directly in the same run. Of the 106 samples from 53 participants with complete urine collection after 2 study diets, 24-hour urinary fructose excretion was significantly associated with fructose intake. The sum of 24-hour urinary fructose and sucrose was significantly associated with total sugars consumption. However, variation in intakes of sugars explained only a modest amount of variation in urinary sugars excretion. In the unadjusted models, fructose intake explained 24.3% of urinary fructose excretion, and intake of total sugars explained 16.3% of the sum of urinary fructose and sucrose. The adjusted models explained 44.3% of urinary fructose excretion and 41.7% of the sum of urinary fructose and sucrose. Therefore, we caution using these biomarkers to predict sugars consumption before other factors that determine urinary sugars excretion are understood.
Assuntos
Biomarcadores/urina , Cromatografia Gasosa/métodos , Frutose/urina , Espectrofotometria Ultravioleta/métodos , Sacarose/urina , Adolescente , Adulto , Índice de Massa Corporal , Estudos Cross-Over , Dieta , Registros de Dieta , Sacarose Alimentar/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
To investigate fructose concentrations in diabetic patients with ketoacidosis or ketosis, serum fructose concentrations and daily urinary fructose excretion were measured in 23 patients with ketoacidosis (n = 16) and ketosis (n = 7) on the first day of admission. Seventeen patients were diagnosed with type 1, one patient with mitochondrial, and 4 patients with atypical diabetes. In 16 of the 23 patients, serum and urinary fructose could be assessed after starting treatments. Mean serum fructose concentration was 71.6 ± 108.1 µmol/l, and mean daily urinary fructose excretion was 352.1 ± 473.7 µmol/day. Serum fructose levels in patients with atypical diabetes were much higher (205.0 ± 213.3 µmol/l) than those in patients with type 1 diabetes (45.1 ± 44.5 µmol/l), while urinary fructose levels in atypical diabetes (249.7 ± 92.4 µmol/day) tended to be lower than those in type 1 diabetes (382.6 ± 533.2 µmol/day). Serum fructose concentrations decreased significantly (P < 0.05) from 88.1 ± 126.3 to 18.0 ± 11.0 µmol/l, and daily urinary fructose excretion also decreased significantly (P < 0.05) from 459.8 ± 530.9 to 75.1 ± 62.0 µmol/day in accordance with glycemic normalization after treatment. Marked and reversible increases in serum and urinary fructose concentrations were observed in diabetics with ketoacidosis and ketosis.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/sangue , Cetoacidose Diabética/urina , Frutose/sangue , Frutose/urina , Adolescente , Adulto , Idoso , Feminino , Humanos , Cetose/sangue , Cetose/urina , Masculino , Pessoa de Meia-Idade , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND/OBJECTIVES: Recently, urinary fructose and sucrose excretion in 24-h urine have been established experimentally as new biomarkers for dietary sugar intake in adults. Our objective was to investigate 1) whether the fructose biomarker is also applicable in free-living children and 2) for what kind of sugar it is standing for. SUBJECTS/METHODS: Intakes of added and total sugar (including additional sugar from fruit and fruit juices) were assessed by 3-day weighed dietary records in 114 healthy prepubertal children; corresponding 24-h urinary fructose excretion was measured photometrically. The associations between dietary sugar intakes and urinary fructose excretion were examined using linear regression models. To determine whether one of the two sugar variables may be better associated with the urinary biomarker, the statistical Pitman's test was used. RESULTS: Added and total sugar correlated significantly with urinary fructose, but the linear regression indicated a weak association between intake of added sugar and urinary log-fructose excretion (ß=0.0026, R(2)=0.055, P=0.01). The association between total sugar intake and log-urinary fructose (ß=0.0040, R(2)=0.181, P<0.001) showed a significantly better fit (P<0.05). CONCLUSIONS: Urinary fructose excretion seems to be rather applicable for the estimation of total sugar intake than for the estimation of added dietary sugar intake in children. However, as excreted fructose stems almost exclusively from the diet (both from food-intrinsic and added intakes), it can be assumed that urinary fructose represents a potential biomarker for total dietary fructose intake, irrespective of its source.
Assuntos
Sacarose Alimentar/urina , Frutose/urina , Biomarcadores/urina , Criança , Dieta , Registros de Dieta , Sacarose Alimentar/administração & dosagem , Feminino , Frutose/administração & dosagem , Humanos , Modelos Lineares , Masculino , Análise de RegressãoRESUMO
Experiments with rats have produced data on the metabolism and energy value of d-psicose; however, no such data have been obtained in humans. The authors assessed the availability of d-psicose absorbed in the small intestine by measuring carbohydrate energy expenditure (CEE) by indirect calorimetry. They measured the urinary excretion rate by quantifying d-psicose in urine for 48 hours. To examine d-psicose fermentation in the large intestine, the authors measured breath hydrogen gas and fermentability using 35 strains of intestinal bacteria. Six healthy subjects participated in the CEE test, and 14 participated in breath hydrogen gas and urine tests. d-Psicose fermentation subsequent to an 8-week adaptation period was also assessed by measuring hydrogen gas in 8 subjects. d-Psicose absorbed in the small intestine was not metabolized into energy, unlike glucose, because CEE did not increase within 3 hours of d-psicose ingestion (0.35 g/kg body weight [BW]). The accumulated d-psicose urinary excretion rates were around 70% for 0.34, 0.17, and 0.08 g/kg BW of ingested d-psicose. Low d-psicose fermentability was observed in intestinal bacteria and breath hydrogen gas tests, in which fructooligosaccharide (0.34, 0.17, and 0.08 g/kg BW) was used as a positive control because its available energy is known to be 8.4 kJ/g. Based on the results of the plot of breath hydrogen concentration vs calories ingested, the energy value of d-psicose was expected to be less than 1.6 kJ/g. Incremental d-psicose fermentability subsequent to an adaptation period was not observed.