Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.721
Filtrar
1.
J Chromatogr A ; 1652: 462373, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34246963

RESUMO

Chitosan-modified magnetic Schiff base network composite nanospheres (Fe3O4@SNW@Chitosan) were prepared for the enrichment and detection of hippuric acid (HA) and 4-methyl hippuric acid (4-MHA) via magnetic solid phase extraction (MSPE) connected with HPLC. The SNW was one of the covalent organic framework, which constructed through covalent bonds, shown comprising solvent stability, low density and accessible pores. The obtained Fe3O4@SNW@Chitosan has many merits as a magnetic sorbent, including a hydrophilic surface, uniform pore size, unique ordered channel structure, and superparamagnetism. The favourable linearity of this MSPE-HPLC method was in the range of 1-1000 µg L-1, and LODs of HA and 4-MHA were 0.3 µg L-1 and 0.2 µg L-1, respectively. The recoveries in urine samples were range from 95.3 to 109.0 % with the RSD less than 9.6 %. When employed for the enrichment of HA and 4-MHA, Fe3O4@SNW@Chitosan exhibited great potential as a candidate for preconcentration.


Assuntos
Técnicas de Química Analítica , Quitosana , Hipuratos , Nanosferas , Técnicas de Química Analítica/métodos , Quitosana/química , Cromatografia Líquida de Alta Pressão , Hipuratos/análise , Hipuratos/isolamento & purificação , Humanos , Fenômenos Magnéticos , Nanosferas/química , Bases de Schiff/química , Extração em Fase Sólida
2.
Br J Gen Pract ; 71(708): e528-e537, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34001538

RESUMO

BACKGROUND: Urinary tract infections (UTIs) are often treated with antibiotics and are a source of antibiotic overuse. AIM: To systematically review randomised controlled trials (RCTs) of adult women in the community with a history of recurrent UTIs and who use methenamine hippurate prophylactically. DESIGN AND SETTING: Systematic review of women in the UK, Australia, Norway, and US (aged ≥18 years) with recurrent UTIs receiving methenamine hippurate against placebo or no treatment, and antibiotics. METHOD: The authors searched three databases, clinical trial registries, and performed forward-backward citation analysis on references of included studies. RESULTS: Six studies involving 557 participants were included (447 were analysed). Of the six studies, five were published and one was an unpublished trial record with results, three compared methenamine hippurate against placebo or control, and three compared methenamine hippurate with antibiotics. For the number of patients who remained asymptomatic, methenamine hippurate showed a non-statistically significant trend of benefit versus antibiotics over 12 months (risk ratio [RR] 0.65, 95% confidence interval [CI] = 0.40 to 1.07, I 2 49%), versus control over 6 or 12 months (RR 0.56, 95% CI = 0.13 to 2.35, I 2 93%), and a non-statistically significant trend versus any antibiotic for abacteruria (RR 0.80, 95% CI = 0.62 to 1.03, I 2 23%). A similar non-statistically significant trend of benefits for methenamine hippurate for the number of UTI or bacteriuric episodes was found, and a non-statistically significant difference in the number of patients experiencing adverse events between methenamine hippurate and any comparator, with a trend towards benefit for the methenamine hippurate, was identified. Antibiotic use and resistance were not consistently reported. CONCLUSION: There is insufficient evidence to be certain of the benefits of methenamine hippurate to prevent UTI. Further research is needed to test the drug's effectiveness in preventing UTIs and as an alternative for antibiotic treatment for UTI.


Assuntos
Preparações Farmacêuticas , Infecções Urinárias , Adolescente , Adulto , Antibacterianos/uso terapêutico , Feminino , Hipuratos , Humanos , Metenamina/análogos & derivados , Metenamina/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/prevenção & controle
3.
Molecules ; 26(8)2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920347

RESUMO

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.


Assuntos
Metaboloma , Metabolômica/métodos , Neoplasias da Bexiga Urinária/urina , Idoso , Ácido Benzoico/urina , Estudos de Casos e Controles , Cromatografia Líquida , Ácidos Cumáricos/urina , Feminino , Glicerofosfolipídeos/urina , Hipuratos/urina , Histidina/urina , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fenilalanina/metabolismo , Microextração em Fase Sólida/métodos , Espectrometria de Massas em Tandem , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , beta-Alanina/urina
4.
Ecotoxicol Environ Saf ; 217: 112231, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33862429

RESUMO

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.


Assuntos
Poluentes Ocupacionais do Ar/urina , Hipuratos/urina , Exposição Ocupacional/estatística & dados numéricos , Salas Cirúrgicas , Recursos Humanos em Hospital , Fumaça , Adulto , Poluentes Ocupacionais do Ar/análise , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Creatinina , Atenção à Saúde , Humanos , Exposição Ocupacional/análise , Espectrometria de Massas em Tandem , Tolueno/metabolismo , Xilenos/metabolismo
5.
Commun Biol ; 4(1): 53, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420329

RESUMO

The G protein-coupled receptor 109 A (GPR109A) is robustly expressed in osteoclastic precursor macrophages. Previous studies suggested that GPR109A mediates effects of diet-derived phenolic acids such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA) on promoting bone formation. However, the role of GPR109A in metabolic bone homeostasis and osteoclast differentiation has not been investigated. Using densitometric, bone histologic and molecular signaling analytic methods, we uncovered that bone mass and strength were significantly higher in tibia and spine of standard rodent diet weaned 4-week-old and 6-month-old GPR109A gene deletion (GPR109A-/-) mice, compared to their wild type controls. Osteoclast numbers in bone and in ex vivo bone marrow cell cultures were significantly decreased in GPR109A-/- mice compared to wild type controls. In accordance with these data, CTX-1 in bone marrow plasma and gene expression of bone resorption markers (TNFα, TRAP, Cathepsin K) were significantly decreased in GPR109A-/- mice, while on the other hand, P1NP was increased in serum from both male and female GPR109A-/- mice compared to their respective controls. GPR109A deletion led to suppressed Wnt/ß-catenin signaling in osteoclast precursors to inhibit osteoclast differentiation and activity. Indeed, HA and 3-3-PPA substantially inhibited RANKL-induced GPR109A expression and Wnt/ß-catenin signaling in osteoclast precursors and osteoclast differentiation. Resultantly, HA significantly inhibited bone resorption and increased bone mass in wild type mice, but had no additional effects on bone in GPR109A-/- mice compared with their respective untreated control mice. These results suggest an important role for GPR109A during osteoclast differentiation and bone resorption mediating effects of HA and 3-3-PPA on inhibiting bone resorption during skeletal development.


Assuntos
Reabsorção Óssea/prevenção & controle , Hipuratos/farmacologia , Osteogênese/efeitos dos fármacos , Fenilpropionatos/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Microbioma Gastrointestinal , Hipuratos/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenilpropionatos/uso terapêutico , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Via de Sinalização Wnt
6.
Clin Chim Acta ; 516: 83-91, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33508250

RESUMO

BACKGROUND: Total 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. METHODS: This 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. RESULTS: Multiple regression analysis showed that sex, potassium, systolic blood pressure (SBP), average BP, ß2-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, ß2-microglobulin was independently positively associated with total PCS. Moreover, potassium, diastolic blood pressure, average BP, ß2-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, ß2-microglobulin, average BP, creatinine, and eGFR). CONCLUSION: This study demonstrated that uremic toxins (IS and HA) and HD quality indicators (potassium, ß2-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.


Assuntos
Indicã , Uremia , Cresóis , Hipuratos , Humanos , Indicadores de Qualidade em Assistência à Saúde , Diálise Renal , Ésteres do Ácido Sulfúrico
7.
Am J Ind Med ; 64(4): 245-250, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33512020

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Assuntos
Artrite Reumatoide/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Vigilância da População , Solventes/toxicidade , Tolueno/toxicidade , Adulto , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/urina , Hipuratos/urina , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/urina , Estudos Prospectivos , República da Coreia , Adulto Jovem
8.
Biomarkers ; 26(1): 65-73, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33284648

RESUMO

Aim: Xylenes are aromatic hydrocarbons used for industrial applications such as the production of petrochemicals and plastics. Acute xylene exposures can negatively impact health through neurotoxicity and irritation of respiratory and dermal tissues. We quantified urinary biomarkers of xylene exposure [2-methylhippuric acid (2MHA) and a mixture of 3- and 4-methylhippuric acids (34MH)] in a representative sample of the U.S. population. Methods: Spot urine obtained during the National Health and Nutrition Examination Survey 2005-2006 and 2011-2016 was analysed using ultra-high-performance liquid chromatography/tandem mass spectrometry. Exclusive smokers were distinguished from non-users using a combination of self-report and serum cotinine data. Results: The median 2MHA and 34MH levels were higher for exclusive smokers (100 µg/g and 748 µg/g creatinine, respectively) than for non-users (27.4 µg/g and 168 µg/g creatinine, respectively). Participants who smoked cigarettes had significantly higher 2MHA and 34MH levels (p < 0.0001) than unexposed participants. Smoking 1-10, 11-20, and >20 cigarettes per day (CPD) was significantly associated with 181%, 339% and 393% higher 2MHA levels, respectively. For 34MH, smoking 1-10, 11-20, and >20 CPD was significantly associated with 201%, 398%, and 471% higher 34MH levels, respectively. Conclusion: We confirm that tobacco smoke is a significant source of xylene exposure as measured by urinary 2MHA and 34MH levels.


Assuntos
Monitoramento Biológico , Biomarcadores/sangue , Biomarcadores/urina , Xilenos/toxicidade , Adolescente , Adulto , Criança , Cotinina/sangue , Feminino , Hipuratos/urina , Humanos , Hidrocarbonetos Aromáticos/toxicidade , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Produtos do Tabaco , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto Jovem
9.
Neurosci Lett ; 742: 135515, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33227370

RESUMO

Bipolar disorder (BD) is a debilitating mental disorder with complex clinical manifestations and low diagnostic accuracy. Depressive episodes are most common in the course of BD with high comorbidity and suicide rates, which present greater clinical challenges than mania and hypomania episodes. However, there are no objective biomarkers for bipolar depression. The aim of this study was to detect urinary metabolite biomarkers that could be useful for the diagnosis of bipolar depression. Nuclear magnetic resonance spectroscopy was used to profile urine samples of patients with bipolar depression (n = 37) and healthy volunteers (n = 48). Data were analyzed using Orthogonal Partial Least Square Discriminant Analysis and t-test. Differential metabolites were identified (VIP > 1 and p < 0.05), and further analyzed using Metabo Analyst 3.0 to identify associated metabolic pathways. In total, we identified seven metabolites differentially expressed in patients with BD and healthy controls. Compared with healthy group, the levels of betaine, glycerol, hippuric acid, indole sulfate, trimethylamine oxide, and urea in urine samples of BD patients were significantly higher, while the level of inositol was significantly lower. Most of these small molecules are related to lipid metabolism and gut microbiota metabolism. These differential metabolites could provide critical insight into the pathological mechanisms of bipolar depression. The results of this study provide a meaningful reference for similar and further studies in the future.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/urina , Metabolômica/métodos , Ressonância Magnética Nuclear Biomolecular/métodos , Adolescente , Adulto , Betaína/urina , Biomarcadores/metabolismo , Biomarcadores/urina , Feminino , Hipuratos/urina , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
J Ethnopharmacol ; 269: 113699, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33340600

RESUMO

ETHNOPHARMCOLOGICAL RELEVANCE: Microbial biofilm formation, a quorum sensing (QS) regulated process, is one of the major causes of nosocomial and chronic infections, foodborne diseases, and associated deaths. Various approaches have been used to eradicate the menace of biofilm. Ethnomedicinal plants as potent antibiofilm agents are gaining a lot of interest in an era where the drug resistance is increasing and the availability of potent antibiotics is no longer promised. In this context, the methanol extract of Cuphea carthagenensis (CCMD), an ethno-medicinal and culinary herb, was evaluated as an antibiofilm and anti-QS agent against Pseudomonas aeruginosa. AIM OF THE STUDY: The aim of the study is to evaluate the antibiofilm and anti-QS activity of an ethnomedicinal plant against a strong biofilm forming microorganism, P. aeruginosa. METHODS: Antibiofilm activity of CCMD was demonstrated at different concentrations by Tissue Culture Plate, Test Tube method and other microscopic techniques. The effect of CCMD on QS and QS-related virulence factors viz. Pyocyanin, exopolymeric substance matrix (EPS), total protease, elastase, pyoverdin and swimming motility in P. aeruginosa were also evaluated. Antioxidant activity (DPPH & FRAP), total phenolic and flavonoid content were also checked. In order to determine the composition of the extract HPLC analysis was also performed. RESULTS: In vitro study demonstrated a significant inhibition of biofilm formation (81.88 ± 2.57%) as well as production of QS-dependent virulence factors in P. aeruginosa. The extract also inhibited violacein production (83.31 ± 2.77%) in Chromobacterium violaceum which correlates with the reduction in QS-mediated virulence factors. The extract showed 64.79% ± 0.83% DPPH scavenging activity and reduction of ferricyanide complex (Fe3+) to the ferrous form (Fe2+) in DPPH and FRAP assay, respectively. Furthermore, the extract showed thermal stability and does not have any growth inhibitory effect on P. aeruginosa. The HPLC analysis demonstrated the presence of ellagic acid, ascorbic acid and hippuric acid in the extract. CONCLUSION: This work is the first to demonstrate that C. carthagenensis can attenuate biofilm formation and QS-mediated virulence factors of P. aeruginosa. Further investigation is required to use this ethnomedicinal plant (CCMD) as an important source of antibiofilm agents.


Assuntos
Antibacterianos/farmacologia , Cuphea/química , Medicina Tradicional/métodos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/fisiologia , Fatores de Virulência/antagonistas & inibidores , Antioxidantes/farmacologia , Ácido Ascórbico , Biofilmes/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Chromobacterium/efeitos dos fármacos , Ácido Elágico , Flavonoides/análise , Hipuratos , Indóis/antagonistas & inibidores , Fenóis/análise , Folhas de Planta/química , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Fatores de Virulência/metabolismo
11.
Dalton Trans ; 50(2): 553-561, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33350995

RESUMO

Three novel Cd(ii)/Zn(ii) coordination polymers (CPs), namely [Cd(L)(BPDC)0.5H2O]·0.5H2O (1), [Zn2(L)2(BPDC)]·2H2O (2) and [Cd2(L)(BTC)H2O]·3H2O (3) (L = 4-(tetrazol-5-yl)phenyl-4,2':6',4''-terpyridine, H2BPDC = 4,4'-biphenyldicarboxylic acid, and H3BTC = 1,3,5-benzenetricarboxylic acid), have been successfully synthesized and characterized. CP 1 and CP 2 display new two-dimensional double-layered honeycomb frameworks containing uncoordinated nitrogen atoms from pyridine and tetrazole rings, which can easily form hydrogen bonds with various analytes. CP 3 exhibits a 3D framework also with uncoordinated nitrogen atoms from pyridine and tetrazole rings. The fluorescence explorations indicate that CPs 1-3 exhibit strong blue luminescence and excellent chemical stability under a relatively wide range of pH conditions. It is worth noting that CPs 1-3 can quantitatively detect hippuric acid (HA), which is a metabolite of toluene in human urine, with high selectivity, sensitivity, fast response and relatively low detection limits. Moreover, the sensing mechanism of CPs 1-3 for HA can mainly be ascribed to fluorescence resonance energy transfer (FRET). CPs 1-3 could be ideal candidates as HA sensors in human urine samples for practical applications. Notably, to the best of our knowledge, we report for the first time Cd(ii)/Zn(ii)-based luminescent sensors for detecting HA in simulated urine.


Assuntos
Cádmio/química , Hipuratos/urina , Polímeros/química , Tolueno/toxicidade , Urinálise/métodos , Água/química , Zinco/química , Complexos de Coordenação/química , Humanos , Ligação de Hidrogênio , Limite de Detecção , Luminescência , Modelos Moleculares , Conformação Molecular , Fatores de Tempo
12.
Nutrients ; 12(11)2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33182344

RESUMO

Urinary polyphenol metabolites are potential biomarkers of dietary polyphenol intake. The current study aims to evaluate associations between total diet, vegetable and fruit polyphenol intakes with urinary polyphenol metabolite concentrations in a sample of adults prescribed a diet rich in vegetables and fruit. Thirty-four participants completed a 10-week pre-post study. Participants were asked to consume Australian recommended daily vegetable and fruit serves and attend measurement sessions at baseline and at weeks 2 and 10. Two 24-h diet recalls were collected at each time-point and polyphenol intakes were calculated using the Phenol-Explorer database. Spot urine samples, collected at each time-point, were analyzed for 15 polyphenol metabolites using liquid chromatography-mass spectroscopy. Spearman's correlation analyzes assessed the strength of relationships between urinary and dietary polyphenols. Linear mixed models were used to investigate relationships between polyphenol excretion and intake. Total urinary polyphenols were significantly correlated with total polyphenol intakes at week 10 (rs = 0.47) and fruit polyphenols at week 2 (rs = 0.38). Hippuric acid was significantly correlated with vegetable polyphenols at baseline (rs = 0.39). Relationships were identified between individual polyphenol metabolites and vegetable and fruit polyphenols. Linear mixed model analyzes identified that for every 1 mg increase in polyphenol intakes, urinary polyphenol excretion increased by 16.3 nmol/g creatinine. Although the majority of relationships were not sufficiently strong or consistent at different time-points, promising relationships were observed between total urinary polyphenols and total polyphenol intakes, and hippuric acid and vegetable polyphenols.


Assuntos
Dieta , Polifenóis/administração & dosagem , Polifenóis/urina , Adolescente , Adulto , Austrália , Biomarcadores/urina , Feminino , Frutas/química , Hipuratos/urina , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Verduras/química , Adulto Jovem
13.
Sci Rep ; 10(1): 17223, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057167

RESUMO

Systemic metabolic changes after renal transplantation reflect the key processes that are related to graft accommodation. In order to describe and better understand these changes, the 1HNMR based metabolomics approach was used. The changes of 47 metabolites in the serum samples of 19 individuals were interpreted over time with respect to their levels prior to transplantation. Considering the specific repeated measures design of the experiments, data analysis was mainly focused on the multiple analyses of variance (ANOVA) methods such as ANOVA simultaneous component analysis and ANOVA-target projection. We also propose here the combined use of ANOVA and classification and regression trees (ANOVA-CART) under the assumption that a small set of metabolites the binary splits on which may better describe the graft accommodation processes over time. This assumption is very important for developing a medical protocol for evaluating a patient's health state. The results showed that besides creatinine, which is routinely used to monitor renal activity, the changes in levels of hippurate, mannitol and alanine may be associated with the changes in renal function during the post-transplantation recovery period. Specifically, the level of hippurate (or histidine) is more sensitive to any short-term changes in renal activity than creatinine.


Assuntos
Nível de Saúde , Hipuratos/sangue , Falência Renal Crônica/diagnóstico , Transplante de Rim , Metabolômica/métodos , Monitorização Fisiológica/métodos , Alanina/sangue , Biomarcadores/sangue , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/cirurgia , Espectroscopia de Ressonância Magnética , Manitol/sangue , Sensibilidade e Especificidade
14.
Artigo em Inglês | MEDLINE | ID: mdl-32615535

RESUMO

Acute kidney injury (AKI) is a frequent, serious complication in critically ill patients. Even if renal replacement therapy is rapidly initiated, AKI may lead to the acute accumulation of metabolic waste products called uremic toxins (UTs). Although the accumulation and effects of UTs have been extensively described in the setting of chronic kidney disease (CKD), few data are available for AKI. A rapid, sensitive, specific method with simple sample preparation is required to facilitate routine blood monitoring of UTs in a context of acute accumulation. We have developed and validated two fast liquid chromatography tandem mass spectrometry methods for the quantification of seven UTs in human serum. The first method (in negative ionization mode) enables the quantification of five UTs (hippuric acid (HA), indoxyl sulfate (IxS), para-cresyl sulfate (pCS), para-cresyl glucuronide (pCG), 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)). The second method (in positive ionization mode) enables the quantification of two UTs (indole-3-acetic acid (IAA), and trimethylamine N-oxide (TMAO)). Sample preparation consisted of the deproteinization of a small volume of serum (50 µL). The run-times required to assay all the UTs in negative and positive ionization modes were only 2.5 and 2 min, respectively. In order to obtain a reliable, toxin-free matrix for the preparation of calibration standards and quality controls, serum was pretreated with activated charcoal. We used these methods to determine the time course of UT accumulation in eight patients who developed an AKI after cardiac surgery. The calibration curves ranged from 0.1 to 100 µg mL-1 for all the UTs (except for IAA: 0.5 to 100 µg mL-1), and the correlation coefficients were above 0.999 for all. The methods were reproducible, repeatable, and accurate, with all coefficients of variation and biases below 15%. The highest concentrations measured in patients with AKI were lower than those reported in CKD stages 4 and 5 but higher than those observed in patients with no impairment of renal function (particularly for IxS and pCS). Our results also highlighted low accumulation of the other toxins (IAA, HA, TMAO, pCG, and CMPF). The UT concentrations did not rise earlier than that of creatinine; although the return to baseline took longer than for creatinine for some compounds. Lastly, assessment of the time course of UT accumulation as a prognostic marker for AKI (particularly for pCS and IxS) appears to be promising and should be continued in a larger number of patients.


Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Biomarcadores/sangue , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cresóis/sangue , Feminino , Furanos/sangue , Hipuratos/sangue , Humanos , Indicã/sangue , Limite de Detecção , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Propionatos/sangue , Reprodutibilidade dos Testes
15.
Mol Nutr Food Res ; 64(12): e2000031, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32386352

RESUMO

SCOPE: Blueberries are rich sources of bioactive polyphenols that may provide health benefits when consumed regularly, leading to their increased marketing as dietary supplements. However, the metabolic changes associated with consuming concentrated doses of purified polyphenols, as may be present in dietary supplements, are unknown, especially when considering the colonic metabolites formed. This study aimed to evaluate the pharmacokinetics of high doses of purified blueberry polyphenols. METHODS AND RESULTS: 5-month old, ovariectomized Sprague-Dawley rats are acutely dosed with purified blueberry polyphenols (0, 75, 350, and 1000 mg total polyphenols per kg body weight (bw)) and 45 Ca to measure calcium absorption. Blood and urine are collected for 48 h after dosing and phenolic metabolites measured via ultra high-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The most prominent metabolites are colonically generated cinnamic and hippuric acids. Smaller amounts of other phenolic acids, flavonols, and anthocyanins are also detected. Most metabolites follow a dose-response relationship, though several show saturated absorption. Maximal metabolite concentrations are reached within 12 h for a majority of compounds measured, while some (e.g., hippuric acid) peaked up to 24 h post-dosing. Calcium absorption is significantly increased in the highest dose group (p = 0.03). CONCLUSION: These results indicate that increased doses of blueberry polyphenols induce changes in intestinal phenolic metabolism and increase calcium absorption.


Assuntos
Mirtilos Azuis (Planta)/química , Colo/efeitos dos fármacos , Polifenóis/farmacologia , Animais , Cálcio/farmacocinética , Colo/metabolismo , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Feminino , Flavonoides/urina , Hipuratos/urina , Absorção Intestinal/efeitos dos fármacos , Ovariectomia , Fenóis/metabolismo , Fenóis/urina , Polifenóis/administração & dosagem , Polifenóis/análise , Ratos Sprague-Dawley
16.
Artigo em Inglês | MEDLINE | ID: mdl-32240053

RESUMO

Salicylates are among the most known anti-inflammatory drugs, used both in human and veterinary medicine. They also occur naturally in plants. Residues of salicylic acid in tissues and eggs may occur after drug administration or exposure of animals to feed material with high salicylate content. An animal study was performed on laying hens. The birds received sodium salicylate or acetylsalicylic acid (10 mg/kg b.w.) for 7 days or were given corn containing 1.18 mg/kg of salicylic acid. Samples of liver, muscle and plasma were collected at 0, 4, 8, 24 and 72 h after treatment; eggs were collected daily for 14 days. Salicylic acid and its metabolites: gentisic acid, salicyluric acid and gentisuric acid were determined using liquid chromatography coupled with tandem mass spectrometry. In both liver and muscle, the residues after administration of sodium salicylate were initially higher than for acetylsalicylic acid but they depleted at the same time. The deposition and depletion profile of salicylic acid in eggs was similar for groups receiving both drugs; the plateau level reached 248 ± 61.5 µg/kg and 275 ± 82.1 µg/kg. The concentration of salicylic acid in tissues and eggs of animals receiving salicylic acid was low. Gentisic acid was found in individual samples of liver, muscle and eggs from all treated groups. The exposure of hens to the salicylates at feed additive levels and to naturally occurring salicylates results in low residue concentrations and fast depletion of salicylic acid. The eggs do not pose any risk to consumers sensitive to salicylates.


Assuntos
Resíduos de Drogas/análise , Análise de Alimentos , Contaminação de Alimentos/análise , Hipuratos/química , Óvulo/química , Ácido Salicílico/análise , Administração Oral , Animais , Galinhas , Hipuratos/administração & dosagem , Fígado/química , Músculos/química , Ácido Salicílico/administração & dosagem , Ácido Salicílico/metabolismo
17.
OMICS ; 24(3): 140-147, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32176594

RESUMO

Acute T cell-mediated rejection (TCMR) is a major complication after renal transplantation. TCMR diagnosis is very challenging and currently depends on invasive renal biopsy and nonspecific markers such as serum creatinine. A noninvasive metabolomics panel could allow early diagnosis and improved accuracy and specificity. We report, in this study, on urine metabolome changes in renal transplant recipients diagnosed with TCMR, with a view to future metabolomics-based diagnostics in transplant medicine. We performed urine metabolomic analyses in three study groups: (1) 7 kidney transplant recipients with acute TCMR, (2) 15 kidney transplant recipients without rejection but with impaired kidney function, and (3) 6 kidney transplant recipients with stable renal function, using 1H-nuclear magnetic resonance. Multivariate modeling of metabolites suggested a diagnostic panel where the diagnostic accuracy of each metabolite was calculated by receiver operating characteristic curve analysis. The impaired metabolic pathways associated with TCMR were identified by pathway analysis. In all, a panel of nine differential metabolites encompassing nicotinamide adenine dinucleotide, 1-methylnicotinamide, cholesterol sulfate, gamma-aminobutyric acid (GABA), nicotinic acid, nicotinamide adenine dinucleotide phosphate, proline, spermidine, and alpha-hydroxyhippuric acid were identified as novel potential metabolite biomarkers of TCMR. Proline, spermidine, and GABA had the highest area under the curve (>0.7) and were overrepresented in the TCMR group. Nicotinate and nicotinamide metabolism was the most important pathway in TCMR. These findings call for clinical validation in larger study samples and suggest that urinary metabolomics warrants future consideration as a noninvasive research tool for TCMR diagnostic innovation.


Assuntos
Rejeição de Enxerto/urina , Transplante de Rim , Metaboloma/imunologia , Prolina/urina , Espermidina/urina , Ácido gama-Aminobutírico/urina , Doença Aguda , Difosfato de Adenosina/urina , Adulto , Biomarcadores/urina , Ésteres do Colesterol/urina , Estudos Transversais , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Hipuratos/urina , Humanos , Masculino , Pessoa de Meia-Idade , NAD/urina , Niacina/urina , Niacinamida/análogos & derivados , Niacinamida/urina , Curva ROC , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/cirurgia , Linfócitos T
18.
Clin Lab ; 66(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32162883

RESUMO

BACKGROUND: Campylobacter spp. is one of the leading causes of bacterial foodborne infections worldwide. In this study, we aimed to investigate the genetic diversity of 341 Campylobacter strains isolated in Turkey. METHODS: Campylobacter spp. was identified by phenotypical methods and PCR. Species level identification was carried out by the hippurate hydrolysis test and PCR. C. jejuni and C. coli strains were typed by using flaA-RFLP and PFGE. RESULTS: Of 341 strains, 300 (88%), 37 (10.8%), and four were identified as C. jejuni, C. coli, and non-jejuni/non-coli, respectively. The hippurate hydrolysis test misidentified 12% of 341 strains. The typeabilities of flaA-RFLP and PFGE were 100% for C. coli, whereas those of flaA-RFLP and PFGE for C. jejuni were 99.3% and 99%, respectively. The discriminatory power of the combination of PFGE and flaA-RFLP was determined to be higher than either method alone for both C. jejuni and C. coli. Both of the strains were so diverse that 80% and 64% of C. jejuni and C. coli genotypes included only one strain, respectively. In two patients, Campylobacter strains that were isolated from the first stool samples were C. jejuni where as those isolated from the second samples, collected eight and 20 days after the collection of the first samples, were C. coli. C. jejuni strains that were recovered from two different stool samples of two patients, collected 1 - 2 days apart, were found to be genetically different. CONCLUSIONS: Species identification of Campylobacter strains should be done using molecular methods. Combination of two methods is prerequisite for increasing the accuracy of molecular typing. Mixed or subsequent infection by different Campylobacter species and C. jejuni of different genotypes should not be underestimated.


Assuntos
Infecções por Campylobacter/diagnóstico , Infecções por Campylobacter/metabolismo , Campylobacter coli/genética , Campylobacter jejuni/genética , Tipagem Molecular/métodos , Infecções por Campylobacter/microbiologia , Campylobacter coli/metabolismo , Campylobacter jejuni/metabolismo , Eletroforese em Gel de Campo Pulsado , Hipuratos/metabolismo , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Turquia
19.
Bioorg Chem ; 97: 103640, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32086051

RESUMO

Inhibitors of aldose reductase are rate-limiting enzymes and could play a key role to prevent the complications of diabetes. In our attempt to develop novel inhibitors of aldose reductase, the derivatives of rhodanine-3-hippuric acid-pyrazole hybrid were synthesized and characterised by spectral data. The biological studies reveal that all the compounds show an excellent activity against ALR2 with IC50 values ranging from 0.04 to 1.36 µM. Among these the synthesised compounds 6a-m, 6g and 6e showed specific inhibitory activity with IC50 values of 0.04 and 0.06 µM respectively against ALR2 and found to be more potent than epalrestat (IC50 = 0.87 µM), the only aldose reductase inhibitor currently used in the therapy. Molecular docking analysis using the AR-NADP+ complex as a receptor was performed with all the synthesized compounds. All the compounds exhibit a well-defined binding mode within the AR active site, similarly to previous described AR inhibitors, with the anion head group bound to the catalytic center, blocking thus its activity. By forming hydrogen bonds with Tyr48 and His110 of the protein from ALR2 (PDB ID: 2FZD), the compounds 6g and 6e interrupt the proton donation mechanism, which is necessary for the catalytic activity of ALR2.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Rodanina/análogos & derivados , Rodanina/farmacologia , Aldeído Redutase/química , Aldeído Redutase/metabolismo , Desenho de Fármacos , Descoberta de Drogas , Hipuratos/química , Hipuratos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
20.
Physiol Rep ; 8(4): e14349, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32097533

RESUMO

Measurement of the concentration of hippurate in the inferior vena cava and renal blood samples performed in 13 subjects with normal or near-normal serum creatinine concentrations confirmed the prediction that endogenous hippurate was cleared on a single pass through the kidney with the same avidity as that reported for infused para-amino hippurate. This suggests that a timed urine collection without infusion would provide a measure of effective renal plasma flow. Comparison of the arteriovenous concentration differences for a panel of protein-bound solutes identified solutes that were secreted by the renal tubule and solutes that were subjected to tubular reabsorption.


Assuntos
Hipuratos/sangue , Eliminação Renal , Idoso , Proteínas Sanguíneas/metabolismo , Creatinina/sangue , Feminino , Hipuratos/urina , Humanos , Rim/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Veia Cava Inferior/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...