RESUMO
External quality assurance (EQA) is crucial to monitor and improve the quality of biochemical genetic testing. ERNDIM (www.erndim.org), established in 1994, aims at reliable and standardized procedures for diagnosis, treatment and monitoring of inherited metabolic disease (IMD) by providing EQA schemes and educational activities. Currently, ERNDIM provides 16 different EQA schemes including quantitative schemes for various metabolite groups, and interpretive schemes such as diagnostic proficiency testing (DPT). DPT schemes focus on the ability of laboratories to correctly identify and interpret abnormalities in authentic urine samples across a wide range of IMDs. In the DPT schemes, six samples each year are distributed together with clinical information. Laboratories choose and perform the tests needed to reach a diagnosis. Data were collected on 345 samples, distributed to up to 105 laboratories worldwide. Diagnostic proficiency (the % of total points possible for all participating laboratories within a scheme for analysis and interpretation) ranged widely: amino acid disorders (n = 20), range 33%-100%, mean 84%; organic acid disorders (n = 35), range 14%-100%, mean 84%; lysosomal storage disorders (n = 13), range 20%-97%, mean 73%; purine/pyrimidine disorders (n = 9), range 37%-100%, mean 70%; miscellaneous disorders (n = 8), range 17%-100%, mean 65%; no IMD, range 65%-95%, mean 85%. When a sample with the same disorder was distributed in a subsequent survey, performance improved in 75 cases with no improvement seen in 32, suggesting overall improvement of performance. ERNDIM diagnostic proficiency testing is a valuable activity which can help to assess laboratory performance, identify methodological/technical challenges, be informative during quality audits and contribute to a better clinical appreciation of diagnostic uncertainty.
Assuntos
Doenças por Armazenamento dos Lisossomos , Doenças Metabólicas , Técnicas e Procedimentos Diagnósticos , Humanos , Laboratórios , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/genética , Doenças Metabólicas/urinaRESUMO
Metabolomics has become an important tool for clinical research, especially for analyzing inherited metabolic disorders (IMDs). The purpose of this study was to explore the performance of metabolomics in diagnosing IMDs using an untargeted metabolomic approach. A total of 40 urine samples were collected: 20 samples from healthy children and 20 from pediatric patients, of whom 13 had confirmed IMDs and seven had suspected IMDs. Samples were analyzed by Orbitrap mass spectrometry in positive and negative mode alternately, coupled with ultra-high liquid chromatography. Raw data were processed using Compound Discovery 2.0 ™ and then exported for partial least squares discriminant analysis (PLS-DA) by SIMCA-P 14.1. After comparing with m/zCloud and chemSpider libraries, compounds with similarity above 80% were selected and normalized for subsequent relative quantification analysis. The uncommon compounds discovered were analyzed based on the Kyoto Encyclopedia of Genes and Genomes to explore their possible metabolic pathways. All IMDs patients were successfully distinguished from controls in the PLS-DA. Untargeted metabolomics revealed a broader metabolic spectrum in patients than what is observed using routine chromatographic methods for detecting IMDs. Higher levels of certain compounds were found in all 13 confirmed IMD patients and 5 of 7 suspected IMD patients. Several potential novel markers emerged after relative quantification. Untargeted metabolomics may be able to diagnose IMDs from urine and may deepen insights into the disease by revealing changes in various compounds such as amino acids, acylcarnitines, organic acids, and nucleosides. Such analyses may identify biomarkers to improve the study and treatment of IMDs.
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Doenças Metabólicas/diagnóstico , Doenças Metabólicas/urina , Metabolômica , Aminoácidos/metabolismo , Aminoácidos/urina , Biomarcadores/metabolismo , Biomarcadores/urina , Carnitina/análogos & derivados , Carnitina/metabolismo , Carnitina/urina , Criança , Humanos , Espectrometria de Massas , Doenças Metabólicas/metabolismo , Nucleosídeos/metabolismo , Nucleosídeos/urinaRESUMO
OBJECTIVE: Urinary free cortisol (UFC) is a reliable marker to avoid cortisol fluctuation and the effects of binding proteins. However, UFC levels are affected by fluid intake and urine volume, and the normal levels range widely. METHODS: To discover the utility of the ratio of urinary cortisol to aldosterone excretions, 246 patients in whom daily excretions of UFC and aldosterone (UAC) were measured were retrospectively analyzed. RESULTS: The UFC/UAC ratio showed significant positive and negative correlations with the levels of serum cortisol (R=0.287) and aldosterone (R=-0.762), respectively. The UFC/UAC ratio increased with aging in female patients, while it was not altered by the level of BMI in either gender. Markers for metabolic and inflammatory status, including hemoglobin A1c (R=0.327), albumin (R=-0.331), C-reactive protein (R=0.317), ferritin (R=0.473), and D-dimer (R=0.569), showed correlations with the ratio of UFC/UAC that were more significant than the correlations with the serum level of cortisol or UFC alone. Of note, the UFC/UAC ratio was shown to be an indicator for the risk of diabetes (AUC: 0.765), hypoalbuminemia (0.839), hyper-CRPemia (0.748), and thrombophilia (0.824), in which the cut-off levels of the UFC/UAC ratio were around 12. CONCLUSION: The UFC/UAC ratio is a variable for detecting metabolic and inflammatory complications related to adrenocortical dysfunction.
Assuntos
Aldosterona/urina , Biomarcadores/urina , Hidrocortisona/urina , Inflamação/diagnóstico , Doenças Metabólicas/diagnóstico , Idoso , Testes Diagnósticos de Rotina , Feminino , Seguimentos , Humanos , Inflamação/urina , Masculino , Doenças Metabólicas/urina , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Every year individuals experience symptoms that remain undiagnosed by healthcare providers. In the United States, these rare diseases are defined as a condition that affects fewer than 200,000 individuals. However, there are an estimated 7000 rare diseases, and there are an estimated 25-30 million Americans in total (7.6-9.2% of the population as of 2018) affected by such disorders. The NIH Common Fund Undiagnosed Diseases Network (UDN) seeks to provide diagnoses for individuals with undiagnosed disease. Mass spectrometry-based metabolomics and lipidomics analyses could advance the collective understanding of individual symptoms and advance diagnoses for individuals with heretofore undiagnosed disease. Here, we report the mass spectrometry-based metabolomics and lipidomics analyses of blood plasma, urine, and cerebrospinal fluid from 148 patients within the UDN and their families, as well as from a reference population of over 100 individuals with no known metabolic diseases. The raw and processed data are available to the research community so that they might be useful in the diagnoses of current or future patients suffering from undiagnosed disorders.
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Lipidômica , Doenças Metabólicas/diagnóstico , Metabolômica , Doenças não Diagnosticadas/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Conjuntos de Dados como Assunto , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Espectrometria de Massas , Doenças Metabólicas/sangue , Doenças Metabólicas/líquido cefalorraquidiano , Doenças Metabólicas/urina , Pessoa de Meia-Idade , Doenças não Diagnosticadas/sangue , Doenças não Diagnosticadas/líquido cefalorraquidiano , Doenças não Diagnosticadas/urina , Adulto JovemRESUMO
BACKGROUND: Patients with urolithiasis have a lower bone mineral density (BMD) than those without stones, suggesting a potential correlation between calcium stone formation and bone resorption disorders, including osteopenia and osteoporosis. METHODS: To investigate the influence of BMD on clinical outcomes in urolithiasis, we performed a single-center retrospective cohort study to analyze patients with urolithiasis who underwent both BMD examination and 24-h urine collection between 2006 and 2015. Data from the national cross-sectional surveillance of the Japanese Society on Urolithiasis Research in 2015 were utilized, and additional data related to urinary tract stones were obtained from medical records. The primary outcome was the development of stone-related symptoms and recurrences during follow-up. A total of 370 patients were included in this 10-year study period. RESULTS: Half of the patients had recurrent stones, and the two-thirds were symptomatic stone formers. While only 9% of patients had hypercalciuria, 27% and 55% had hyperoxaluria and hypocitraturia, respectively. There was a positive correlation between T-scores and urinary citrate excretion. Both univariate and multivariate analyses demonstrated that female sex was associated with recurrences (odds ratio = 0.44, p = 0.007), whereas a T-score < - 2.5 and hyperoxaluria were associated with symptoms (odds ratio = 2.59, p = 0.037; odds ratio = 0.45, p = 0.01; respectively). CONCLUSION: These results revealed that low T-scores might cause symptoms in patients with urolithiasis, suggesting the importance of BMD examination for high-risk Japanese patients with urolithiasis having hypocitraturia.
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Doenças Ósseas Metabólicas/complicações , Ácido Cítrico/urina , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologia , Urolitíase/complicações , Adulto , Idoso , Estudos de Coortes , Correlação de Dados , Feminino , Humanos , Masculino , Doenças Metabólicas/urina , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Guanidinoacetic acid (GAA, also known as glycocyamine or betacyamine) is a naturally-occurring derivative of glycine and a direct metabolic precursor of creatine, a key player in high-phosphate cellular bioenergetics. GAA is found in human serum and urine, with circulating GAA likely reflects an equilibrium between its endogenous production and utilization/excretion. GAA deficiency (as indicated by low serum GAA) has been reported in various conditions yet this intriguing clinical entity appears to be poorly characterized as yet, either as a primary deficit or a sequel of secondary disease. This minireview article summarizes the inherited and acquired disorders with apparent GAA deficiency and discusses a possible relevance of GAA shortfall in clinical medicine.
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Glicina/análogos & derivados , Doenças Metabólicas/etiologia , Creatina/metabolismo , Metabolismo Energético , Glicina/sangue , Glicina/deficiência , Glicina/metabolismo , Glicina/urina , Humanos , Doenças Metabólicas/sangue , Doenças Metabólicas/metabolismo , Doenças Metabólicas/urinaRESUMO
A review is made of the basic aspects of creatine/creatinine metabolism and the close relationship between creatinine and muscle mass, which makes the former a biochemical marker of the latter. Emphasis is placed on the current prognostic value of both the low urinary excretion of creatinine and low serum creatinine levels in different clinical settings in which sarcopenia probably plays a significant role in morbidity and mortality.
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Creatinina/sangue , Creatinina/urina , Doenças Metabólicas/sangue , Doenças Metabólicas/urina , Creatinina/metabolismo , Humanos , Fatores de RiscoRESUMO
Background: Iodine is important in both thyroid function and human metabolism. Studies have explored the effect of iodine on metabolic disorders through thyroid function. This study aimed to investigate the relationship between iodine status and metabolic disorders, such as metabolic syndrome (MetS), hypertension, impaired glucose metabolism, central obesity, and dyslipidemia. Methods: A total of 51,795 subjects aged ≥18 years from the TIDE (Thyroid Disorders, Iodine Status and Diabetes, a national epidemiological cross-sectional study) program were included. The prevalence of metabolic disorders and its related diseases was calculated based on the level of urinary iodine concentrations (UICs) using the chi-square method. To further explore whether the prevalence was associated with UIC, quadratic and UIC-stratified logistic regression models were used. Results: The prevalence of metabolic disorders as a function of UIC was found to be U-shaped with a lower prevalence of 76.0% at an UIC of 300-499 µg/L. Participants with an UIC of 300-499 µg/L showed an association with metabolic disorders (odds ratio [OR] = 0.857, 95% confidence interval [CI 0.796-0.922]) and hypertension (OR = 0.873 [CI 0.814-0.936]). An UIC of 300-799 µg/L was found to be associated with the occurrence of MetS and impaired glucose tolerance. An UIC of 500-799 µg/L was associated with the occurrence of prediabetes (OR = 0.883 [CI 0.797-0.978]). An UIC of ≥300 µg/L was associated with the occurrence of hypertriglyceridemia, hypercholesterolemia, and high levels of low-density lipoprotein cholesterol. Furthermore, an UIC of <100 µg/L showed an association with hypertension (OR = 1.097 [CI 1.035-1.162]) and hypercholesterolemia (OR = 1.178 [CI 1.117-1.242]). Conclusions: The association between UICs in adults and metabolic disorders and its related diseases is U-shaped. The association between UIC and metabolic disorders disappears in cases of iodine deficiency (<100 µg/L) or excess (≥500 µg/L).
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Iodo/urina , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , China/epidemiologia , LDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/urina , Feminino , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/urina , Masculino , Doenças Metabólicas/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/urina , Pessoa de Meia-Idade , Estado Nutricional , Prevalência , Adulto JovemRESUMO
PURPOSE OF REVIEW: As the incidence of urinary stone disease in children is increasing, identifying dietary risk factors becomes vitally important, especially in the context of targeting interventions to reduce risk for stone formation. Indiscriminant dietary restrictions are not appropriate for paediatric patients. RECENT FINDINGS: Although large, prospective studies are still needed to better quantify dietary risk factors for paediatric stone formers, a number of smaller studies provide data to identify common risk factors to help prevent stone formation, while minimizing inappropriate dietary restrictions. SUMMARY: Interpretation of 24-h urine samples to identify individualized dietary risk factors is crucial for implementing a strategy for prevention of further urinary stone formation in children. Clinicians should avoid generalized dietary restrictions in stone-forming children uninformed by laboratory data.
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Dieta/efeitos adversos , Cálculos Renais/etiologia , Doenças Metabólicas/diagnóstico , Cálculos Urinários/etiologia , Criança , Humanos , Cálculos Renais/metabolismo , Cálculos Renais/urina , Doenças Metabólicas/complicações , Doenças Metabólicas/urina , Fatores de Risco , Fatores Socioeconômicos , Cálculos Urinários/metabolismo , Cálculos Urinários/urinaRESUMO
Oocyte quality is closely related to female fertility. Nevertheless, core nutritional metabolites influencing oocyte quality are unclear. Herein, comprehensive metabolomics analysis of follicular fluid, serum, and urine from low reproductive performance (LRP) and normal reproductive performance (NRP) sows was conducted. Twenty-seven, fourteen and sixteen metabolites (involved in metabolism of amino acids, fatty acids, purine and pyrimidine) were altered in follicular fluid, serum and urine, respectively, in LRP compared with NRP sows, and could decrease oocyte quality and developmental potential, ultimately leading to low fertility. Deoxyinosine, guanidine acetate, thymidine, 5,6-epoxy-eicosatrienoic acid, carnosine, docosahexaenoic acid and carbamoyl phosphate in follicular fluid, cysteine, carnitine, serotonin, hypoxanthine, valine and arginine in serum, as well as carnitine, phenyl glycine, N-acetyl glutamine, propionyl carnitine and choline in urine could be selected as diagnostic markers to indicate oocyte quality. Consistent with metabolomics data, we confirmed changes in concentrations of fatty acids and amino acids in follicular fluid. Targeting purine metabolism, elevating levels of deoxyinosine in in-vitro maturation medium of porcine oocyte significantly promoted the blastocyst rate. Collectively, this study provided new information of potential targets for predicting oocyte quality and developmental potential, and may help with strategies for early diagnosis or therapeutic/dietary intervention in improving reproductive outcomes.
Assuntos
Aminoácidos , Ácidos Graxos , Doenças Metabólicas , Oócitos/metabolismo , Purinas , Doenças dos Suínos , Suínos , Aminoácidos/sangue , Aminoácidos/urina , Animais , Ácidos Graxos/sangue , Ácidos Graxos/urina , Feminino , Doenças Metabólicas/sangue , Doenças Metabólicas/urina , Purinas/sangue , Purinas/urina , Suínos/sangue , Suínos/urina , Doenças dos Suínos/sangue , Doenças dos Suínos/urinaRESUMO
BACKGROUND: Disorders of primary bile acid synthesis may be life-threatening if undiagnosed, or not treated with primary bile acid replacement therapy. To date, there are few reports on the management and follow-up of patients with Δ4-3-oxosteroid 5ß-reductase (AKR1D1) deficiency. We hypothesized that a retrospective analysis of the responses to oral bile acid replacement therapy with chenodeoxycholic acid (CDCA) in patients with this bile acid synthesis disorder will increase our understanding of the disease progression and permit evaluation of this treatment regimen as an alternative to the Food and Drug Administration (FDA) approved drug cholic acid, which is currently unavailable in China. AIM: To evaluate the therapeutic responses of patients with AKR1D1 deficiency to oral bile acid therapy, specifically CDCA. METHODS: Twelve patients with AKR1D1 deficiency, confirmed by fast atom bombardment ionization-mass spectrometry analysis of urine and by gene sequencing for mutations in AKR1D1, were treated with differing doses of CDCA or ursodeoxycholic acid (UDCA). The clinical and biochemical responses to therapy were monitored over a period ranging 0.5-6.4 years. Dose adjustment, to optimize the therapeutic dose, was based on changes in serum biochemistry parameters, notably liver function tests, and suppression of the urinary levels of atypical hepatotoxic 3-oxo-Δ4-bile acids measured by mass spectrometry. RESULTS: Physical examination, serum biochemistry parameters, and sonographic findings improved in all 12 patients during bile acid therapy, except one who underwent liver transplantation. Urine bile acid analysis confirmed a significant reduction in atypical hepatotoxic 3-oxo-Δ4 bile acids concomitant with clinical and biochemical improvements in those patients treated with CDCA. UDCA was ineffective in down-regulating endogenous bile acid synthesis as evidenced from the inability to suppress the urinary excretion of atypical 3-oxo-Δ4-bile acids. The dose of CDCA required for optimal clinical and biochemical responses varied from 5.5-10 mg/kg per day among patients based on maximum suppression of the atypical bile acids and improvement in serum biochemistry parameters, and careful titration of the dose was necessary to avoid side effects from CDCA. CONCLUSION: The primary bile acid CDCA is effective in treating AKR1D1 deficiency but the therapeutic dose requires individualized optimization. UDCA is not recommended for long-term management.
Assuntos
Ácido Quenodesoxicólico/administração & dosagem , Fármacos Gastrointestinais/administração & dosagem , Doenças Metabólicas/tratamento farmacológico , Oxirredutases/deficiência , Ácido Ursodesoxicólico/administração & dosagem , Administração Oral , Ácido Quenodesoxicólico/efeitos adversos , Análise Mutacional de DNA , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Recém-Nascido , Masculino , Doenças Metabólicas/genética , Doenças Metabólicas/urina , Mutação , Oxirredutases/genética , Estudos Retrospectivos , Resultado do Tratamento , Ácido Ursodesoxicólico/efeitos adversosRESUMO
Recent studies have established that dietary protein restriction improves metabolic health and glucose homeostasis. SLC6A19 (B°AT1) is the major neutral amino acid transporter in the intestine and carries out the bulk of amino acid absorption from the diet. Mice lacking SLC6A19 show signs of protein restriction, have improved glucose tolerance, and are protected from diet-induced obesity. Pharmacological blockage of this transporter could be used to induce protein restriction and to treat metabolic diseases such as type 2 diabetes. A few novel inhibitors of SLC6A19 have recently been identified using in vitro compound screening, but it remains unclear whether these compounds block the transporter in vivo. To evaluate the efficacy of SLC6A19 inhibitors biomarkers are required that can reliably detect successful inhibition of the transporter in mice. A gas chromatography mass spectrometry (GC-MS)-based untargeted metabolomics approach was used to discriminate global metabolite profiles in plasma, urine and faecal samples from SLC6A19ko and wt mice. Due to inefficient absorption in the intestine and lack of reabsorption in the kidney, significantly elevated amino acids levels were observed in urine and faecal samples. By contrast, a few neutral amino acids were reduced in the plasma of male SLC6A19ko mice as compared to other biological samples. Metabolites of bacterial protein fermentation such as p-cresol glucuronide and 3-indole-propionic acid were more abundant in SLC6A19ko mice, indicating protein malabsorption of dietary amino acids. Consistently, plasma appearance rates of [14C]-labelled neutral amino acids were delayed in SLC6A19ko mice as compared to wt after intra-gastric administration of a mixture of amino acids. Receiver operating characteristic (ROC) curve analysis was used to validate the potential use of these metabolites as biomarkers. These findings provide putative metabolite biomarkers that can be used to detect protein malabsorption and the inhibition of this transporter in intestine and kidney.
Assuntos
Sistemas de Transporte de Aminoácidos Neutros/antagonistas & inibidores , Aminoácidos/sangue , Doenças Metabólicas/sangue , Aminoácidos/urina , Animais , Benzotropina/farmacologia , Biomarcadores/metabolismo , Biomarcadores/urina , Proteínas Alimentares/metabolismo , Feminino , Absorção Intestinal , Masculino , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/urina , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Reabsorção RenalRESUMO
Metabonomics has been widely used in disease diagnosis and clinically practical methods often require the detection of multi-class bio-samples. In this work, multi-class classification methods were investigated to simultaneously discriminate among 6 inherited metabolic diseases (IMDs) and the normal instances using gas chromatography-mass spectrometry (GC-MS) of urine samples. Two common multi-class classification strategies, one-against-all (OAA) and one-against-one (OAO) were compared and enhanced using a novel ensemble classification strategy (ECS), which developed a set of sequential sub-classifiers by fusion of OAA and OAO and made the final classification decisions using softmax function. GC-MS data of 240 instances of 6 IMDs and healthy controls were classified by different strategies based on orthogonal partial least squares discriminant analysis (OPLS-DA) and particle swarm optimization (PSO) algorithm was performed for feature selection. By OAA and OAO, the classification accuracies were 70.00% and 82.86%, respectively. Using the two methods based on ECS, the total classification accuracies were 0.9143 and 0.9429. The newly proposed ECS will provide a useful multi-class classification tool for simultaneous detection of clinically similar IMDs and promote practical and reliable diagnosis of IMDs using metabonomics data.
Assuntos
Doenças Metabólicas/diagnóstico , Metabolômica , Algoritmos , Análise Discriminante , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Análise dos Mínimos Quadrados , Doenças Metabólicas/metabolismo , Doenças Metabólicas/urinaRESUMO
This study was undertaken to determine the association of four chlorophenol pesticides with cardiometabolic risk factors and obesity in children and adolescents. This cross-sectional study was conducted in 2016 on 242 children and adolescents, aged 6 to 18 years. The concentrations of 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), 2,4,5-trichlorophenol (2,4,5-TCP), and 2,4,6-trichlorophenol (2,4,6-TCP) in the urine were examined and their association with indices of obesity and cardiometabolic risk factors was determined. Multivariate linear regression and multinomial logistic regression analyses were applied. Overall, 242 participants with mean (SD) ages of 11.3 (2.5) years completed the survey. After adjustment for confounders, a significant positive association was found between body mass index (BMI) z-score and waist circumference (WC) with 2,5-DCP (0.07 (95% CI 0.04, 0.1)) and 0.79 (95% CI 0.54, 1.03), respectively. A significant association of 2,4,5-TCP was only found with WC (0.23 (95% CI 0.0, 0.46), but the relationship with 2,4-DCP was not significant. 2,5-DCP had a significant relationship only with obesity (1.09 (95% CI 1.1, 1.19)), while 2,4-DCP and 2,4,5-TCP showed no significant correlation with overweight or obesity. 2,4-DCP showed a significant positive relationship with high density lipoprotein-cholesterol (HDL-C). Moreover, 2,5-DCP showed a significant negative relationship only with systolic blood pressure and 2,4,5-TCP had a statistically significant inverse association with total cholesterol and HDL-C (-0.71 (95% CI -0.98, -0.45)). This study suggests potential associations of chlorophenol pesticides with overweight, obesity, lipid profile, and blood pressure in children and adolescents. Longitudinal studies are necessary to assess the clinical impact of these findings.
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Doenças Cardiovasculares/etiologia , Clorofenóis/urina , Exposição Ambiental/análise , Doenças Metabólicas/etiologia , Obesidade Infantil/urina , Praguicidas/urina , Adolescente , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/urina , Criança , Clorofenóis/toxicidade , Estudos Transversais , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Irã (Geográfico) , Modelos Lineares , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Doenças Metabólicas/urina , Obesidade Infantil/complicações , Praguicidas/toxicidade , Fatores de RiscoRESUMO
L2-hydroxyglutaric aciduria (L2-HGA) is a rare neurometabolic disease characterized by accumulation of L2-hydroxyglutarate (L2-HG), a potential oncometabolite resulting in significant lifetime risk for cerebral tumors. Herein, we present a case of intraventricular glioblastoma multiforme (GBM) in a 16-year-old child with L2-HGA who presented with rapid functional decline and persistent vomiting. The tumor was completely resected, and the patient remained well at 2-year follow-up. Clinicians should be aware of the usual insidious nature of the disease. Rapid deterioration is unusual and should raise the suspicion of tumor development. This case also illustrates the importance of surveillance neuroimaging in patients with L2-HGA. To the best of our knowledge, only 1 case of GBM has been reported and it was sited in the temporal lobe, unlike the unusual intraventricular location in our case.
Assuntos
Glioblastoma/complicações , Glutamatos/urina , Doenças Metabólicas/complicações , Doenças Metabólicas/urina , Adolescente , Glioblastoma/diagnóstico por imagem , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , MasculinoRESUMO
BACKGROUND: Coffee is an important source of bioactive compounds, including caffeine, phenolic compounds (mainly chlorogenic acids), trigonelline, and diterpenes. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic diseases, but the impact of coffee dosage on markers of cardiometabolic risk is not well understood. Moreover, the pool of coffee-derived circulating metabolites and the contribution of each metabolite to disease prevention still need to be evaluated in real-life settings. The aim of this study will be to define the bioavailability and beneficial properties of coffee bioactive compounds on the basis of different levels of consumption, by using an innovative experimental design. The contribution of cocoa-based products containing coffee to the pool of circulating metabolites and their putative bioactivity will also be investigated. METHODS: A three-arm, crossover, randomized trial will be conducted. Twenty-one volunteers will be randomly assigned to consume three treatments in a random order for 1 month: 1 cup of espresso coffee/day, 3 cups of espresso coffee/day, and 1 cup of espresso coffee plus 2 cocoa-based products containing coffee twice per day. The last day of each treatment, blood and urine samples will be collected at specific time points, up to 24 hours following the consumption of the first product. At the end of each treatment the same protocol will be repeated, switching the allocation group. Besides the bioavailability of the coffee/cocoa bioactive compounds, the effect of the coffee/cocoa consumption on several cardiometabolic risk factors (anthropometric measures, blood pressure, inflammatory markers, trimethylamine N-oxide, nitric oxide, blood lipids, fasting indices of glucose/insulin metabolism, DNA damage, eicosanoids, and nutri-metabolomics) will be investigated. DISCUSSION: Results will provide information on the bioavailability of the main groups of phytochemicals in coffee and on their modulation by the level of consumption. Findings will also show the circulating metabolites and their bioactivity when coffee consumption is substituted with the intake of cocoa-based products containing coffee. Finally, the effect of different levels of 1-month coffee consumption on cardiometabolic risk factors will be elucidated, likely providing additional insights on the role of coffee in the protection against chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03166540 . Registered on May 21, 2017.
Assuntos
Chocolate , Café , Compostos Fitoquímicos/farmacocinética , Disponibilidade Biológica , Biomarcadores/sangue , Biomarcadores/urina , Biotransformação , Protocolos Clínicos , Estudos Cross-Over , Dano ao DNA , Nível de Saúde , Cardiopatias/sangue , Cardiopatias/prevenção & controle , Cardiopatias/urina , Humanos , Mediadores da Inflamação/sangue , Doenças Metabólicas/sangue , Doenças Metabólicas/prevenção & controle , Doenças Metabólicas/urina , Estresse Oxidativo , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/sangue , Compostos Fitoquímicos/urina , Projetos de Pesquisa , Fatores de RiscoRESUMO
BACKGROUND: Several endocrine disruptors (including phthalates) are considered to be a cause of obesity. However, the current evidence has not conclusively established an association between phthalates and metabolic abnormalities, especially in children. The objective of the study was to evaluate the association between urinary phthalate metabolites and metabolic abnormalities in obese Thai children and adolescents. METHODS: This cross-sectional case-control study was conducted in participants aged 7-18 years and divided into two groups: normal weight and overweight/obesity. Spot urine concentrations of two phthalate metabolites (monomethyl phthalate [MMP] and mono-n-buthyl phthalate [MBP]) were measured by high performance liquid chromatography (HPLC). Anthropometric data, including weight, height, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHTR), were measured and calculated. Fasting plasma glucose, insulin, HbA1c, lipid profiles and hepatic transaminase were analyzed, and insulin resistance indices were calculated. RESULTS: One hundred and fifty-five participants were included. The median MMP level in the normal weight and the overweight/obesity groups were 0 (0, 459.83) and 0 (0, 1623.50) µg/g Cr, respectively (p=0.933). The median MBP level in the normal weight and the overweight/obesity groups were 233.6 (118.1, 633.62) and 206.94 (7.4, 427.7) µg/g Cr, respectively (p=0.083). After adjusting for age, gender and puberty, there was no correlation between MBP and all anthropometric data and metabolic profiles. Participants with hypertriglyceridemia had lower MBP levels than those with normal TG level. MMP levels were not significantly different between the participants with normal and abnormal weight of all metabolic parameters. CONCLUSIONS: Participants with hypertriglyceridemia had lower MBP levels than those with normotriglyceridemia. However, it cannot show the correlation between phthalate and metabolic parameters.
Assuntos
Poluentes Ambientais/urina , Doenças Metabólicas/urina , Obesidade/urina , Ácidos Ftálicos/urina , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Tailândia , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
CONTEXT: The incidence of urinary tract stone disease is increasing and the risk of recurrent stone formation is high. Appropriate therapeutic procedures with the aim of counteracting the progress of stone formation are highly desirable. Metabolic work-up is considered essential as a base for optimal design and follow-up of effective recurrence prevention. OBJECTIVE: To scrutinize the current literature with regard to principles of metabolic work-up for this heterogeneous group of patients. EVIDENCE ACQUISITION: Relevant articles in PubMed, guideline documents, consensus reports, and the Cochrane Library published during the past 20 yr were consulted. EVIDENCE SYNTHESIS: Grades of recommendation were used according to the principles applied in the European Association of Urology and American Urological Association guidelines. Medical efforts to prevent recurrent stone formation should be part of the care of patients with urinary tract stone disease (grade of recommendation A). A careful medical history and imaging together with analysis of stone composition, blood, and urine provide the basis for appropriate measures, but the treatment has to be individualized (grade of recommendation D). Whenever possible, stone analysis should be carried out at least once for every patient or each time when a long time has elapsed between two stone episodes because the risk factors explaining stone formation may have changed (clinical principle). The medical history, including information on dietary and drinking habits as well as lifestyle, is necessary for appropriate advice (grade of recommendation C). The medical history, together with imaging and stone composition, is used to estimate the severity of the disease (clinical principle). Identification of specific medical conditions should be supported by blood and/or urine analysis (grade of recommendation B). Pharmacological agents associated with an increased risk of stone formation should be identified (grade of recommendation C). Patients who have formed noncalcium stones should always be given recurrence preventive treatment. Analysis of urine composition for these patients is optional, but might be of value in the follow-up to support decisions on appropriate dosage regimens (grade of recommendation C). For patients with idiopathic calcium stone disease information from 24-h urine samples should be used, although the number of samples to be taken is debated (grade of recommendation C). Information from 24-h urine analysis should be used for selective dietary and drinking advice as well as for selection of the most appropriate pharmacological agent (grade of recommendation B). The treatment effects on the risk of stone formation can be followed by estimates of supersaturation based on urine composition (grade of recommendation C). CONCLUSIONS: It is clear that the metabolic work-up of patients with urinary tract stone disease should be individualized according to stone type and severity of the disease, and that the different therapeutic approaches are closely associated with the availability of therapeutic tools and motivation by the patient. PATIENT SUMMARY: Effective prevention of recurrent stone formation is determined by several factors such as the current and previous stone episodes and surgical procedures, stone composition, medical history, dietary and drinking habits, lifestyle, and ongoing pharmacological therapy. Analysis of blood and urine is an important part of the metabolic evaluation, but how extensive the risk evaluation should be is determined by the type of stone and the severity of the disease.
Assuntos
Algoritmos , Doenças Metabólicas/diagnóstico , Prevenção Secundária/métodos , Urolitíase/prevenção & controle , Humanos , Cálculos Renais/química , Doenças Metabólicas/complicações , Doenças Metabólicas/terapia , Doenças Metabólicas/urina , Urinálise , Urolitíase/sangue , Urolitíase/etiologiaRESUMO
Fabrication of nitrogen-doped carbon dots (N-CDs) electrode for the screening of purine metabolic disorder was described in this paper. Peroxynitrite is a short-lived oxidant species that is a potent inducer of cell death. Uric acid (UA) can scavenge the peroxynitrite to avoid the formation of nitrotyrosine, which is formed from the reaction between peroxynitrite and tyrosine (Try). Scavenging the peroxynitrite avoids the inactivation of cellular enzymes and modification of the cytoskeleton. Reduced level of UA decreases the ability of the body from preventing the peroxynitrite toxicity. On the other hand, the abnormal level of UA leads to gout and hyperuricemia. Allopurinol (AP) is administered in UA lowering therapy. Thus, the simultaneous determination of UA, Try and AP using N-CDs modified glassy carbon (GC) electrode was demonstrated for the first time. Initially, N-CDs were prepared from L-asparagine by pyrolysis and characterized by different spectroscopic and microscopic techniques. The HR-TEM image shows that the average size of the prepared N-CDs was 1.8±0.03nm. Further, the N-CDs were directly attached on GC electrode by simple immersion, follows Micheal's nucleophilic addition. XPS of N-CDs shows a peak at 285.3eV corresponds to the formation of C-N bond. The GC/N-CDs electrode shows higher electrocatalytic activity towards UA, Tyr and AP by not only shifting their oxidation potentials toward less positive potential but also enhanced their oxidation currents in contrast to bare GC electrode. The GC/N-CDs electrode shows the limit of detection of 13×10-10M (S/N=3) and the sensitivity of 924µAmM-1cm-2 towards the determination of UA. Finally, the N-CDs modified electrode was utilized for the determination of UA, Tyr and AP in human blood serum and urine samples.
Assuntos
Técnicas Biossensoriais/métodos , Doenças Metabólicas/sangue , Doenças Metabólicas/urina , Ácido Úrico/sangue , Ácido Úrico/urina , Alopurinol/sangue , Alopurinol/urina , Asparagina/química , Carbono/química , Eletroquímica , Gota/diagnóstico , Gota/metabolismo , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/metabolismo , Nitrogênio/química , Oxirredução , Polímeros/química , Purinas/metabolismo , Tiadiazóis/química , Tirosina/sangue , Tirosina/urinaRESUMO
OBJECTIVE: To determine if 24-hour urinary parameters in children with nephrolithiasis across 4 institutions were influenced by body mass index (BMI). MATERIALS AND METHODS: The 24-hour urinary parameters obtained from children with nephrolithiasis between 2000 and 2013 were stratified by BMI percentile ≥85th and <85th (overweight and obese patients vs healthy weight, respectively). A total of 206 children were included in the study. Exclusion criteria included patients with a history of spina bifida, neurogenic bladder, and cerebral palsy, and patients on medical treatment before the first 24-hour urine collection. RESULTS: Overweight and obese patients consisted of 35.4% of the cohort (n = 73). Metabolic abnormalities were present in 130 children (63.1%). The most common abnormality present in the <85th percentile was hypercalciuria (32.3%), and in the ≥85th percentile, hyperoxaluria (37.0%). Univariable and multivariable analyses revealed that overweight and obese children were more likely to have low urinary volume and elevated uric acid compared to normal-weight children. CONCLUSION: Although there is a link between stone formation and BMI in adults, no definitive conclusions have been proven in the pediatric literature. Our study indicates that stone-forming children who are overweight or obese have low urinary volume and elevated uric acid compared to normal-weight stone-forming children.