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1.
Artigo em Inglês | MEDLINE | ID: mdl-32248046

RESUMO

The present study is the first report of in-situ growth and application of nanorods-flower like Co3O4 nanosorbent coated on the anodized aluminum substrate for thin film microextraction (TFME) approach. The flower like Co3O4 was successfully fabricated by conversion of Co-Al layered double hydroxide (LDH) precursor to Co3O4 using the simple calcinations process. The cheap and available aluminum foil was electrochemically anodized and used as a porous substrate. Response surface methodology (RSM) was explored for optimization step. Different acidic drugs, including: paracetamol, ibuprofen, aspirin and diclofenac were extracted from biological fluids in order to investigate the capability of the prepared sorbent. The extracted analytes were then analyzed using high performance liquid chromatography-ultraviolet detection (HPLC-UV). Under the optimized conditions, the limits of detection were between 0.2 and 1.7 µg L-1 in different selected matrices. The obtained limits of quantification were also calculated to be between 0.8 and 5.1 µg L-1 in the selected matrices. In addition the enrichment factors were also in the range of 105-169. Batch-to-batch reproducibility at 100 µg L-1 concentration level was also evaluated to be lower than 5.2% (n = 3). Finally, the method was successfully used for analysis of these compounds in the biological fluids.


Assuntos
Ácidos/urina , Alumínio/química , Cobalto/química , Nanotubos/química , Óxidos/química , Acetaminofen/urina , Adsorção , Adulto , Aspirina/urina , Cromatografia Líquida de Alta Pressão , Diclofenaco/urina , Técnicas Eletroquímicas , Eletrodos , Feminino , Humanos , Hidróxidos/química , Ibuprofeno/urina , Limite de Detecção , Masculino , Reprodutibilidade dos Testes , Microextração em Fase Sólida , Propriedades de Superfície
2.
Am J Clin Nutr ; 109(5): 1279-1287, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30997510

RESUMO

BACKGROUND: Reduced net acid excretion (NAE) capacity indicates a decrease in renal function. This reduction manifests as a disproportionally low 24-h urine pH in relation to the sum of actually excreted ammonium and titratable acidity by the kidney. OBJECTIVE: The aim of this study was to test the hypothesis that higher body fatness is one determinant of kidney function impairment with a lowered urine pH even at a young age. METHODS: NAE, pH, urea, and creatinine were measured in 24-h urine samples from 524 healthy children and adolescents (aged 6-17 y) participating in the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. Body fatness was assessed anthropometrically by body mass index-standard deviation score (BMI-SDS), fat mass index (FMI), body fat % (BF%), and waist circumference (WC). Multivariable linear and mixed linear regressions were used to examine cross-sectionally (n = 524 urine samples; age groups: 6-8, 9-11, 12-14, 15-17 y) and longitudinally (n = 1999 urine samples) the associations of body fatness with 24-h urine pH as the outcome variable, respectively. RESULTS: After adjusting for the kidneys' total net acid load (24-h urinary NAE) and further relevant covariates, FMI showed significant inverse relations with urinary pH in all 4 age groups, and BMI-SDS, BF%, and WC each in 3 out of these 4 groups (P ≤ 0.02). Longitudinal results substantiated these interindividual relations and further showed intraindividual increases in body fatness to be paralleled by urine pH decreases (P ≤ 0.0002). CONCLUSIONS: Independent of underlying acid load, an early increase in body fatness is associated with increased free proton excretion, and thus with a decline in the kidney's acid excretion function, which could potentiate the risk of renal nephrolithiasis.


Assuntos
Ácidos/urina , Tecido Adiposo , Composição Corporal , Rim/fisiopatologia , Obesidade Pediátrica/fisiopatologia , Eliminação Renal , Adolescente , Antropometria , Índice de Massa Corporal , Criança , Creatinina/urina , Feminino , Humanos , Concentração de Íons de Hidrogênio , Rim/fisiologia , Masculino , Obesidade Pediátrica/patologia , Ureia/urina , Circunferência da Cintura
3.
Nutr Res ; 61: 31-40, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30683437

RESUMO

Childhood asthma prevalence continues to rise despite advancements in prevention and medical management strategies. The purpose of this study was to investigate correlations between urinary organic acids and pulmonary diagnostic tests, asthma control in Greek asthmatic children. We hypothesized that urinary organic acids are positively associated with poor pulmonary function in children with asthma. Seventy-two children, 5 to 12 years old with asthma were recruited from a pediatric asthma clinic in Athens, Greece. Pulmonary function was assessed using spirometry and exhaled nitric oxide analysis. Asthma control was measured qualitatively using the Asthma Control Questionnaire. Targeted metabolomic analysis of 34 urinary organic acids in children was conducted by gas chromatography-mass spectrometry. A statistically significant difference between girls and boys was found for asthma control score (P = .02), lactic acid (P = .03), but not for any other organic acids (P > .05). Statistically significant correlations were found between lactic acid and Forced Expiratory Volume in 1 second (FEV1) (P = .02), Forced Vital Capacity (FVC) (P = .03); 4- hydroxyphenylacetic acid and FEV1 (P = .01), FVC (P = .01); 5-hydroxyindoleacetic acid and FEV1/FVC (P = .03), eNO (P = .05); glycolic acid with Peak Expiratory Flow (PEF) (P = .03); and malic acid with asthma control (P = .02). In conclusion, metabolomics was used to determine correlations between urinary organic acids and conventional pulmonary diagnostic tests in Greek asthmatic children. Metabolomics could be a promising approach for asthma research and in detection of novel biomarkers for asthma monitoring and therapeutic targets for childhood asthma. This study contributes towards a better understanding of the biochemical pathways involved in asthma.


Assuntos
Ácidos/urina , Asma/diagnóstico , Testes Respiratórios , Volume Expiratório Forçado , Pulmão/fisiopatologia , Espirometria , Capacidade Vital , Asma/fisiopatologia , Asma/urina , Biomarcadores/urina , Criança , Pré-Escolar , Feminino , Glicolatos/urina , Grécia , Humanos , Ácido Hidroxi-Indolacético/urina , Ácido Láctico/urina , Malatos/urina , Masculino , Metabolômica
4.
Nephrology (Carlton) ; 24(11): 1131-1141, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30582257

RESUMO

AIM: Metabolic acidosis occurs due to insufficient urinary ammonium excretion as chronic kidney disease (CKD) advances. Because obese subjects tend to have excessive consumption of protein and sodium chloride, they are prone to chronic acid loading and may therefore be predisposed to acid-induced kidney injury. We investigated the involvement of obesity in ammoniagenesis within damaged kidneys. METHODS: In the clinical study, urinary ammonium excretion was compared between 13 normal-weight and 15 overweight/obese CKD outpatients whose creatinine clearance was higher than 25 mL/min. For animal experiments, NH4 Cl was loaded to KKAy/TaJcl (KKAy), a metabolic syndrome model, and control BALB/c mice for 20 weeks. Kidney injury was evaluated through histological analysis and the expression of proinflammatory markers. RESULTS: Urinary ammonium excretion was lower in overweight/obese patients than in normal-weight patients, while intakes of protein and sodium chloride were higher in overweight/obese patients, implying that subclinical metabolic acidosis occurs in overweight/obese patients. The increase in urinary ammonium excretion induced by NH4 Cl loading was attenuated in KKAy mice after 16 weeks, whereas the increase was maintained in BALB/c mice throughout the study period. Histological study and real-time polymerase chain reaction analysis showed proximal tubular injury and enhanced expression levels of neutrophil gelatinase-associated lipocalin (NGAL) protein and messenger RNA, respectively, in KKAy mice but not in BALB/c mice. Finally, urinary NGAL concentration was higher in overweight/obese patients than in normal-weight patients in the early stage of CKD. CONCLUSION: Obesity could facilitate the induction of subclinical metabolic acidosis and acid accumulation in the kidney, which may potentially exacerbate kidney injury in CKD patients.


Assuntos
Amônia/urina , Túbulos Renais/patologia , Obesidade/urina , Sobrepeso/urina , Insuficiência Renal Crônica/urina , Acidose/etiologia , Ácidos/urina , Idoso , Animais , Feminino , Humanos , Lipocalina-2/urina , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade
5.
Clin Sci (Lond) ; 132(11): 1179-1197, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29650676

RESUMO

Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1 M NaCl) or NaHCO3 (0.1 M) solutions as well as in Dahl SS rats lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3 reduced tubular NH4+ production, tubular cast formation, and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury, or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients.


Assuntos
Glomerulosclerose Segmentar e Focal/prevenção & controle , Túbulos Renais/patologia , Proteinúria/prevenção & controle , Bicarbonato de Sódio/uso terapêutico , Ácidos/urina , Animais , Glicemia/metabolismo , Modelos Animais de Doenças , Fibrose , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/metabolismo , Hemodinâmica/efeitos dos fármacos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Canais Iônicos/deficiência , Canais Iônicos/genética , Canais Iônicos/fisiologia , Masculino , Proteinúria/metabolismo , Ratos Endogâmicos Dahl , Ratos Mutantes , Bicarbonato de Sódio/farmacologia , Cloreto de Sódio na Dieta/farmacologia , Cloreto de Sódio na Dieta/toxicidade
6.
Malar J ; 17(1): 128, 2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29566677

RESUMO

BACKGROUND: In severe falciparum malaria metabolic acidosis and acute kidney injury (AKI) are independent predictors of a fatal outcome in all age groups. The relationship between plasma acids, urine acids and renal function was investigated in adult patients with acute falciparum malaria. METHODS: Plasma and urinary acids which previously showed increased concentrations in proportion to disease severity in patients with severe falciparum malaria were quantified. Patients with uncomplicated malaria, sepsis and healthy volunteers served as comparator groups. Multiple regression and multivariate analysis were used to assess the relationship between organic acid concentrations and clinical syndromes, in particular AKI. RESULTS: Patients with severe malaria (n = 90), uncomplicated malaria (n = 94), non-malaria sepsis (n = 19), and healthy volunteers (n = 61) were included. Univariate analysis showed that both plasma and creatinine-adjusted urine concentrations of p-hydroxyphenyllactic acid (pHPLA) were higher in severe malaria patients with AKI (p < 0.001). Multiple regression analysis, including plasma or creatinine-adjusted urinary acids, and PfHRP2 as parasite biomass marker as independent variables, showed that pHPLA was independently associated with plasma creatinine (ß = 0.827) and urine creatinine (ß = 0.226). Principal component analysis, including four plasma acids and seven urinary acids separated a group of patients with AKI, which was mainly driven by pHPLA concentrations. CONCLUSIONS: Both plasma and urine concentrations of pHPLA closely correlate with AKI in patients with severe falciparum malaria. Further studies will need to assess the potential nephrotoxic properties of pHPLA.


Assuntos
Acidose/metabolismo , Lesão Renal Aguda/metabolismo , Malária Falciparum/complicações , Fenilpropionatos/sangue , Fenilpropionatos/urina , Sepse/complicações , Acidose/parasitologia , Acidose/fisiopatologia , Ácidos/sangue , Ácidos/urina , Lesão Renal Aguda/parasitologia , Lesão Renal Aguda/fisiopatologia , Adulto , Bangladesh , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
J Inherit Metab Dis ; 41(6): 985-995, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29435782

RESUMO

BACKGROUND: Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). GSDIa patients are at higher risk of developing insulin-resistance (IR). Mitochondrial dysfunction has been implicated in the development of IR. Mitochondrial dysfunction can demonstrate abnormalities in plama acylcarnitines (ACs) and urine organic acids (UOA). The aim of the study was to investigate the presence of mitochondrial impairment in GSDI patients and its possible connection with IR. METHODS: Fourteen GSDIa, seven GSDIb patients, 28 and 14 age and sex-matched controls, were enrolled. Plasma ACs, UOA, and surrogate markers of IR (HOMA-IR, QUICKI, ISI, VAI) were measured. RESULTS: GSDIa patients showed higher short-chain ACs and long-chain ACs levels and increased urinary excretion of lactate, pyruvate, 2-ketoglutarate, 3-methylglutaconate, adipate, suberate, aconitate, ethylmalonate, fumarate, malate, sebacate, 4-octenedioate, 3OH-suberate, and 3-methylglutarate than controls (p < 0.05). GSDIb patients showed higher C0 and C4 levels and increased urinary excretion of lactate, 3-methylglutarate and suberate than controls (p < 0.05). In GSDIa patients C18 levels correlated with insulin serum levels, HOMA-IR, QUICKI, and ISI; long-chain ACs levels correlated with cholesterol, triglycerides, ALT serum levels, and VAI. DISCUSSION: Increased plasma ACs and abnormal UOA profile suggest mitochondrial impairment in GSDIa. Correlation data suggest a possible connection between mitochondrial impairment and IR. We hypothesized that mitochondrial overload might generate by-products potentially affecting the insulin signaling pathway, leading to IR. On the basis of the available data, the possible pathomechanism for IR in GSDIa is proposed.


Assuntos
Doença de Depósito de Glicogênio Tipo I/complicações , Resistência à Insulina , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/etiologia , Ácidos/urina , Adolescente , Adulto , Antiporters/genética , Biomarcadores/sangue , Carnitina/análogos & derivados , Carnitina/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Glucose-6-Fosfatase/genética , Humanos , Insulina/sangue , Modelos Lineares , Masculino , Proteínas de Transporte de Monossacarídeos/genética , Análise Multivariada , Urinálise , Adulto Jovem
8.
FASEB J ; 32(4): 2046-2059, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29196502

RESUMO

The investigation of orphan GPCRs (GPRs) has the potential to uncover novel insights into whole animal physiology. In this study, our goal was to determine the renal localization of Gprc5c, a receptor that we previously reported to be highly expressed in murine whole kidney, and to examine physiologic parameters in Gprc5c knockout (KO) mice to gain insight into function. Gprc5c localized to the apical membrane of renal proximal tubules (PTs) in mice, rats, and humans. With the comparison of Gprc5c wild-type (WT) and KO mice, we found that Gprc5c KO mice have altered acid-base homeostasis. Specifically, Gprc5c KO mice have lower blood pH and higher urine pH compared with WT mice, with a reduced level of titratable acids in their urine. In an in vitro GPCR internalization assay, we observed that Gprc5c internalization (an index of activation) was triggered by alkaline extracellular pH. Furthermore, with the use of an in vitro BCECF assay, we observed that Gprc5c increases Na+/H+ exchanger 3 (NHE3) activity at alkaline pH. We also find that the NHE3 activity is reduced in Gprc5c KO mice by 2 photon imaging in seminaphthorhodafluors (SNARF)-4F-loaded kidney sections. NHE3 is a primary contributor to apical transport of H+ in the renal PT. Together, these data imply that Gprc5c modulates the renal contribution to systemic pH homeostasis, at least in part, by taking part in the regulation of NHE3.-Rajkumar, P., Cha, B., Yin, J., Arend, L. J., Paunescu, T. G., Hirabayashi, Y., Donowitz, M., Pluznick, J. L. Identifying the localization and exploring a functional role for Gprc5c in the kidney.


Assuntos
Túbulos Renais Proximais/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Ácidos/sangue , Ácidos/urina , Álcalis/sangue , Álcalis/urina , Animais , Células HEK293 , Humanos , Túbulos Renais Proximais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Transporte Proteico , Receptores Acoplados a Proteínas-G/genética , Trocador 3 de Sódio-Hidrogênio/metabolismo , Equilíbrio Hidroeletrolítico
9.
Int J Mol Med ; 40(1): 112-120, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28498405

RESUMO

Metabolomics, a 'budding' discipline, may accurately reflect a specific phenotype which is sensitive to genetic and epigenetic interactions. This rapidly evolving field in science has been proposed as a tool for the evaluation of the effects of epigenetic factors, such as nutrition, environment, drug and lifestyle on phenotype. Urine, being sterile, is easy to obtain and as it contains metabolized or non­metabolized products, is a favored study material in the field of metabolomics. Urine organic acids (OAs) reflect the activity of main metabolic pathways and have been used to assess health status, nutritional status, vitamin deficiencies and response to xenobiotics. To date, a limited number of studies have been performed which actually define reference OA values in a healthy population and as reference range for epigenetic influences, and not as a reference to congenital metabolic diseases. The aim of the present study was thus the determination of reference values (RVs) for urine OA in a healthy adult population. Targeted metabolomics analysis of 22 OAs in the urine of 122 healthy adults by gas chromatography­mass spectrometry, was conducted. Percentile distributions of the OA concentrations in urine, as a base for determining the RVs in the respective population sample, were used. No significant differences were detected between female and male individuals. These findings can facilitate the more sensitive determination of OAs in pathological conditions. Therefore, the findings of this study may contribute or add to the information already available on urine metabolite databases, and may thus promote the use of targeted metabolomics for the evaluation of OAs in a clinical setting and for pathophysiological evaluation. However, further studies with well­defined patients groups exhibiting specific symptoms or diseases are warranted in order to discern between normal and pathological values.


Assuntos
Ácidos/urina , Bases de Dados Factuais , Metabolômica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Eur J Clin Nutr ; 71(3): 420-424, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27759073

RESUMO

BACKGROUND/OBJECTIVES: Acid-producing diets have been associated with adverse health conditions. Dietary acid load can be estimated from dietary intake data, but the available methods require a full dietary assessment. We sought to identify a simpler means to estimate 24-h urinary net acid excretion (NAE), a robust measure of net endogenous acid production, using self-reported intakes of fruits, vegetables (acid-neutralizing foods), grain and/or protein (acid-producing foods) acquired by two different methods in community-dwelling older adults. Identifying food groups associated with NAE by using a method not requiring a full diet assessment could have a broad clinical application. SUBJECTS/METHODS: Fruit, vegetable, protein and grain servings/day were estimated with a widely used food frequency questionnaire (study A, n=162, 63±8 years). Differences in their intakes across NAE categories (<5, ⩾5 to <15, ⩾15 to <50, ⩾50 milliequivalents (mEq)/day) were analyzed using analysis of variance. The findings were verified in a second study, which estimated dietary intakes, using a more detailed record-assisted 24-h recall (study B, n=232, 67±6 years). RESULTS: Fruit intake was significantly associated with NAE in both studies. In study A, fruit intake was 9% lower with each categorical NAE increase (unstandardized beta=-0.21, P=0.01) and 7% lower with each categorical NAE increase in study B (unstandardized beta=-0.18; P=0.02). Grain intake was positively associated with NAE in study B only (unstandardized beta=+0.14; P=0.01). Vegetable and protein intake were not associated with NAE in either study. CONCLUSIONS: The inverse association between fruit intake and NAE suggests low self-reported fruit intake may be an indicator of acid-producing diets in older adults.


Assuntos
Equilíbrio Ácido-Base , Ácidos/urina , Dieta , Idoso , Estudos Transversais , Proteínas na Dieta/administração & dosagem , Feminino , Frutas , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Inquéritos e Questionários , Verduras , Grãos Integrais
11.
Epilepsy Res ; 118: 1-4, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26555630

RESUMO

PURPOSE: Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder caused by mutations of the ALDH7A1 gene. We aimed to analyze the relations between the clinical diagnosis and treatment of PDE and ALDH7A1 gene mutations in Chinese PDE patients. METHODS: The clinical manifestations, diagnosis and treatment were observed in a cohort of PDE patients with early onset of seizure. Video-electroencephalogram (VEEG) and magnetic resonance imaging (MRI) were performed. The mutation of ALDH7A1 gene was analyzed. RESULTS: Of eight patients, six were males and two were females. Age of seizure onset ranged from 1 to 100 days and 75% patients presented with seizures in the neonatal period. All patients showed different degrees of developmental delay. EEGs showed focal or multifocal discharges, or were normal. Molecular analysis revealed 10 ALDH7A1 mutations, including 2 splice site mutations. Five patients had mutation at IVS11+1G>A site, six patients had missense mutations, one with nonsense mutation and another patient had 9-bp genomic deletion mutation. Among them, two mutations were first time reported. CONCLUSIONS: Seizure onset was in neonatal or early infantile period in our PDE patients. Early recognition and diagnosis of the disease is necessary for early intervention and improve cognitive development in the later life. In this study, on the molecular level, we also identified the splice site mutation IVS11+1G>A as a high prevalence mutation site with a frequency of 31.25% (5 of 16 alleles) in Chinese PDE patients.


Assuntos
Aldeído Desidrogenase/genética , Epilepsia/genética , Mutação/genética , Ácidos/urina , Aminoácidos/sangue , Grupo com Ancestrais do Continente Asiático/genética , Pré-Escolar , Estudos de Coortes , Eletroencefalografia , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Epilepsia/urina , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Prevalência , Piridoxina/uso terapêutico , Gravação em Vídeo , Complexo Vitamínico B/uso terapêutico
12.
J Bone Miner Res ; 30(11): 2103-11, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25990255

RESUMO

The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bicarbonate (KHCO3 ) compared with placebo on biochemical markers of bone turnover, and calcium and nitrogen (N) excretion. In this double-blind, randomized, placebo-controlled study, 244 men and women age 50 years and older were randomized to placebo or 1 mmol/kg or 1.5 mmol/kg of KHCO3 daily for 3 months; 233 completed the study. The primary outcomes were changes in 24-hour urinary N-telopeptide (NTX) and N; changes in these measures were compared across the treatment groups. Exploratory outcomes included 24-hour urinary calcium excretion, serum amino-terminal propeptide of type I procollagen (P1NP), and muscle strength and function assessments. The median administered doses in the low-dose and high-dose groups were 81 mmol/day and 122 mmol/day, respectively. When compared with placebo, urinary NTX declined significantly in the low-dose group (p = 0.012, after adjustment for baseline NTX, gender, and change in urine creatinine) and serum P1NP declined significantly in the low-dose group (p = 0.004, adjusted for baseline P1NP and gender). Urinary calcium declined significantly in both KHCO3 groups versus placebo (p < 0.001, adjusted for baseline urinary calcium, gender, and changes in urine creatinine and calcium intake). There was no significant effect of either dose of KHCO3 on urinary N excretion or on the physical strength and function measures. KHCO3 has favorable effects on bone turnover and calcium excretion and the lower dose appears to be the more effective dose. Long-term trials to assess the effect of alkali on bone mass and fracture risk are needed.


Assuntos
Bicarbonatos/farmacologia , Remodelação Óssea/efeitos dos fármacos , Cálcio/urina , Suplementos Nutricionais , Compostos de Potássio/farmacologia , Ácidos/urina , Idoso , Colágeno Tipo I/urina , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Músculos/efeitos dos fármacos , Fragmentos de Peptídeos/sangue , Peptídeos/urina , Pró-Colágeno/sangue
13.
Drug Test Anal ; 7(1): 65-74, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25421420

RESUMO

Iso-α-acids (IAAs) can be used as markers for the consumption of beer. Postmortem specimens from a range of coronial cases were analyzed for IAAs in order to determine the prevalence of beer consumption and any correlation to blood alcohol concentrations (BAC). A total of 130 cases were included in this study including those where beer was mentioned in the case circumstances, cases where beer was not mentioned specifically but alcohol was detected, and cases where neither beer was mentioned nor a positive BAC was present. Available blood, serum, vitreous humour and urine specimens were analyzed. Of the 50 cases where beer was mentioned, 86% had one or more IAAs detected. In cases that only had a positive BAC (n = 60), 57% of these cases also showed the presence of these beer markers. IAAs were detected in specimens obtained from traumatized, burnt, and decomposed cases with a mention of beer consumption or where BAC was positive in blood. No IAAs were detected in cases where BAC was negative. There was little or no correlation between blood IAA concentrations and BAC. This study demonstrates the possible detection of IAAs as a marker for beer consumption.


Assuntos
Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/urina , Cerveja , Ácidos/sangue , Ácidos/urina , Adulto , Idoso , Autopsia , Cerveja/análise , Biomarcadores/sangue , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Feminino , Medicina Legal , Humanos , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Espectrometria de Massas em Tandem , Corpo Vítreo/química
14.
Artigo em Inglês | MEDLINE | ID: mdl-24480519

RESUMO

In the current paper the analytical conditions for the determination of ten free organic acids by GC-MS are studied with the aim to establish a method for organic acid profiling in human urine to be used as a tool for the detection of metabolic or other health disorders. Studies included the GC-MS method development, the derivatization (trimethylsilylation) reaction conditions, the stability of the standard solutions during storage in the freezer, and the stability of the formed trimethylsilyl derivatives. Best results were obtained at a derivatization temperature of 50°C, and a reaction time of 30 min. Standard solutions were stable for 22 days, derivatized samples were stable at least for 30 h when stored at -24°C. GC-MS analysis achieved sensitive determination of the organic acids under study with limits of detection ranging from 0.03 mmol/mol creatinine for glutaric acid, to 0.34 mmol/mol creatinine for glycolic acid. Within-day and day-to-day assay imprecision was found satisfactory with relative standard deviations being below 10%. The developed method was successfully applied to the quantitative analysis of free organic acids in urine samples obtained from hospitalized children. Creatinine-corrected excretion rates of all analyzed organic acids were within reference intervals.


Assuntos
Ácidos/urina , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Orgânicos/urina , Pré-Escolar , Humanos , Limite de Detecção , Erros Inatos do Metabolismo/urina
15.
J Bone Miner Res ; 29(2): 500-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23873776

RESUMO

High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: (1) evaluate the cross-sectional relation between DAL and BMD; and (2) determine whether calcium intake modifies this association. Men (n = 1218) and women (n = 907) aged ≥60 years were included from the National Health and Nutrition Examination Survey 2005-2008. Nutrient intake from 2, 24-hour recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet ) and diet + supplemental calcium (PRALtotal ). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy-adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3 years. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend = 0.04). No associations were observed with PRALtotal at any BMD site (p range, 0.38-0.82). Among men, no significant associations were observed between BMD and NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p = 0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men with <800 mg/d dietary calcium (p = 0.02); no associations were found among men with ≥800 mg/d (p = 0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intake in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.


Assuntos
Ácidos/urina , Densidade Óssea , Cálcio na Dieta/administração & dosagem , Suplementos Nutricionais , Cabeça do Fêmur/metabolismo , Vértebras Lombares/metabolismo , Idoso , Cálcio/deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Artigo em Inglês | MEDLINE | ID: mdl-24210941

RESUMO

Chromatographic methods find application in the diagnostics and prognosis of diseases. They are used in finding new biomarkers, which may result in early medical intervention. Early diagnosis and intervention are especially important in the case of diseases of unknown etiology. One of these is autism. Autism is a neurodevelopmental disorder characterized by severe impairment in reciprocal social interaction and communication and a pattern of repetitive or stereotyped behavior. Organic acids are intermediate metabolites of all major groups of organic cellular components and can play a role in the pathogenesis of autism. This review presents information about abnormal levels of some organic acids observed in the urine of children with autism and determination of acids with the use of chromatographic techniques. 342 literature sources on frequency (2005-2012) of the use of chromatographic methods in the determination of organic compounds in various body fluids were searched.


Assuntos
Ácidos/sangue , Ácidos/urina , Transtorno Autístico/sangue , Transtorno Autístico/urina , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Animais , Biomarcadores/sangue , Biomarcadores/urina , Humanos , Compostos Orgânicos/sangue , Compostos Orgânicos/urina
17.
J Chromatogr A ; 1305: 234-43, 2013 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-23890555

RESUMO

A comprehensive analytical method was developed for the profiling of biogenic amines in human urine using GC/MS in SIM mode. Biogenic amines and their acidic metabolites were converted into their volatile O-trimethylsilyl/N-heptafluorobutyryl (OTMS/-NHFBA) derivatives for GC/MS analysis. Dual hexamethyldisilazane (HMDS)/-N-methyl-bis-heptafluorobutyramide (MBHFBA) derivatizations have been shown to be quite effective, with high derivatization yields and the absence of side products for primary biogenic amines. In this study, selective derivatization conditions by HMDS/MBHFBA were optimized in terms of the reagent amount, reaction temperature and reaction time period. The highest derivatization reaction yield was obtained at 40°C for 10min for OTMS derivatization and 80°C for 5min for N-HFBA derivatization. The use of MCX SPE cartridges with different SPE elution solvents was effective for the pre-concentration and selective cleanup of the biogenic amines and their acidic metabolites in human urine. The selection of appropriate ions in SIM mode provided reliable quantification and identification and a reduction in background effects. The established method was validated in terms of linearity, limits of detection (LOD), limits of quantification (LOQ), precision, and accuracy. The present method was linear (r(2)>0.996), reproducible (relative standard deviation range 1.1-6.9%), and accurate (range 87.9-111.9%), with LOQs of 0.17-17.84ng/mL. The biogenic amine profiling of human urine was successfully accomplished by GC/MS in SIM mode combined with selective HMDS/MBHFBA derivatization and MCX SPE cleanup.


Assuntos
Ácidos/urina , Aminas Biogênicas/urina , Cromatografia Gasosa-Espectrometria de Massas/métodos , Adulto , Feminino , Humanos , Limite de Detecção , Masculino , Extração em Fase Sólida
18.
J Agric Food Chem ; 61(27): 6763-8, 2013 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23777193

RESUMO

The analysis of food components and their metabolome in urine has recently found a growing interest due their potential ability to reflect specific dietary intakes. In the present work, a fast, simple, and environmentally friendly method based on liquid chromatography coupled to electrospray ionization tandem mass spectrometry was developed for the analysis of main wine organic acids in human urine. The proposed method was evaluated in terms of linearity, precision, accuracy, and limits of detection. Quantitative recovery (96-102%) and satisfactory interday precision (RSD <6%) were achieved for all target compounds. To demonstrate the applicability of the method, urine samples from five male volunteers were analyzed before and after consumption of a single moderate dose (200 mL) of red wine. A significant increase (p < 0.01) in the urinary concentration of tartaric and malic acids was observed.


Assuntos
Ácidos/urina , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Vinho/análise , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Nefrología (Madr.) ; 33(3): 289-296, abr.-jun. 2013. ilus
Artigo em Espanhol | IBECS | ID: ibc-114512

RESUMO

La acidosis tubular renal distal (ATRD) o ATR tipo I se caracteriza por una disminución en la excreción urinaria de los hidrogeniones H+ y del amonio. En los niños afectados por ATRD hay retraso en el crecimiento, vómito, estreñimiento, falta de apetito, polidipsia y poliuria, nefrocalcinosis, debilidad y hasta parálisis muscular por la hipopotasemia. En este trabajo se resumen los avances en el estudio genético de la ATRD en las poblaciones hasta ahora estudiadas. La ATRD es heterogénea, por lo que también se analizan los transportadores y canales iónicos que se han identificado hasta ahora en las células intercaladas alfa del túbulo colector, y que podrían explicar los casos de ATRD que no se asocian con los genes hasta ahora estudiados. La ATRD puede ser autosómica dominante o autosómica recesiva. La ATRD autosómica recesiva se manifiesta en los primeros meses de vida, cursa con nefrocalcinosis y sordera temprana o tardía. La ATRD autosómica dominante es menos severa y aparece en la adolescencia o en la etapa adulta, y puede o no presentar nefrocalcinosis. En las células intercaladas alfa de los túbulos colectores se lleva a cabo la excreción urinaria de la carga ácida: los ácidos titulables (fosfatos) y el amonio. La ATRD autosómica recesiva se asocia con mutaciones en los genes ATP6V1B1, ATP6V0A4 y SLC4A1, los cuales codifican las subunidades a4 y B1 de la V-ATPasa y el intercambiador de bicarbonato/cloruro AE1, respectivamente. En contraste, la ATRD autosómica dominante se relaciona con mutaciones solo en AE1 (AU)


Distal renal tubular acidosis (dRTA) or RTA type I is characterised by reduced H+ hydrogen ions and ammonium urinary excretion. In children affected by dRTA there is stunted growth, vomiting, constipation, loss of appetite, polydipsia and polyuria, nephrocalcinosis, weakness and muscle paralysis due to hypokalaemia. This work summarises progress made in dRTA genetic studies in populations studied so far. DRTA is heterogeneous and as such, transporters and ion channels are analysed which have been identified in alpha-intercalated cells of the collecting duct, which could explain cases of dRTA not associated with the hitherto studied genes. DRTA can be autosomal dominant or autosomal recessive. Autosomal recessive dRTA appears in the first months of life and progresses with nephrocalcinosis and early or late hearing loss. Autosomal dominant dRTA is less severe and appears during adolescence or adulthood and may or may not develop nephrocalcinosis. In alpha-intercalated cells of the collecting duct, the acid load is deposited into the urine as titratable acids (phosphates) and ammonium. Autosomal recessive dRTA is associated with mutations in genes ATP6V1B1, ATP6V0A4 and SLC4A1, which encode subunits a4 and B1 of V-ATPase and the AE1 bicarbonate/chloride exchanger respectively. By contrast, autosomal dominant dRTA is only related to mutations in AE1 (AU)


Assuntos
Humanos , Acidose Tubular Renal/fisiopatologia , Nefrocalcinose/fisiopatologia , Amônia/urina , Ácidos/urina , Taxa de Filtração Glomerular , Polidipsia/etiologia , Poliúria/etiologia , Hipopotassemia/etiologia , Predisposição Genética para Doença , ATPases Vacuolares Próton-Translocadoras/fisiologia
20.
Heart Vessels ; 28(6): 735-41, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23274576

RESUMO

Renal dysfunction is reported to be associated with poor outcomes in patients with chronic heart failure (CHF). A recent study showed that acidic urine is related to chronic kidney disease, which is a risk factor for the development of CHF. However, it remains to be determined whether acidic urine is associated with poor outcomes in patients with CHF. We measured urine pH using dipsticks in 537 patients with CHF. Acidic urine was defined as urine pH ≤5.5. Patients were prospectively followed during a median follow-up period of 556 days. There were 145 cardiac events. Prevalence of acidic urine was increased with advancing stage of chronic kidney disease. Patients with acidic urine had a more severe New York Heart Association functional class compared with those with normal urine. In the multivariate Cox proportional hazard analysis, acidic urine was independently associated with poor outcomes in patients with CHF after adjustment of confounding factors. A Kaplan-Meier analysis demonstrated that the rate of cardiac events was higher in patients with acidic urine than in those with normal urine. The presence of acidic urine can reliably identify patients at high risk of future cardiac events in patients with CHF.


Assuntos
Ácidos/urina , Insuficiência Cardíaca/urina , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Distribuição de Qui-Quadrado , Doença Crônica , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Concentração de Íons de Hidrogênio , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fitas Reagentes , Fatores de Risco , Fatores de Tempo , Urinálise/instrumentação
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