RESUMO
OBJECTIVE: In neonates on total parenteral nutrition (TPN), amino acids may be a risk factor for developing total parenteral nutrition-associated cholestasis (TPNAC). We aimed, first, to compare methionine, cysteine, and taurine plasma levels between neonates on TPN who were receiving an intravenous amino acid solution based on a breast milk aminogram and those on an intravenous solution of pediatric amino acids based on an umbilical cord aminogram, and second, to determine the frequency of TPNAC. METHODS: A double-blind randomized controlled trial was conducted. Ninety-four neonates with a birthweight of 1000g or more and a gestational age of 30 wk or older were admitted and enrolled. Blood samples were obtained at 0, 7, and 14 d of TPN, and plasma amino acid concentrations were determined by ultra-high-resolution liquid chromatography. Continuous variables were compared using the Wilcoxon rank-sum test or Student's t test; categorical variables were compared using the Fisher exact test. RESULTS: Thirty-five neonates completed the study (Primene, nâ¯=â¯14; TrophAmine, nâ¯=â¯21). On day 14, methionine plasma concentrations were significantly lower in the Primene group than in the TrophAmine group (27 µmol/L versus 32.9 µmol/L, Pâ¯=â¯0.044); the taurine concentration was significantly higher in the same group (72.4 µmol/L versus 45.3 µmol/L, P < 0.0001). There were no differences in TPNAC incidence. CONCLUSIONS: Administering an intravenous solution of pediatric amino acids based on the umbilical cord aminogram yielded a higher taurine and lower methionine plasma concentration than did administering a similar solution based on the breast milk aminogram.
Assuntos
Aminoácidos/administração & dosagem , Colestase/epidemiologia , Cisteína/sangue , Metionina/sangue , Nutrição Parenteral/efeitos adversos , Taurina/sangue , Peso ao Nascer , Colestase/etiologia , Método Duplo-Cego , Eletrólitos/administração & dosagem , Feminino , Idade Gestacional , Glucose/administração & dosagem , Humanos , Incidência , Recém-Nascido , Masculino , Leite Humano/química , Soluções/administração & dosagem , Cordão Umbilical/químicaRESUMO
A protocol for harvesting and extracting extracellular metabolites from an in vitro model of human renal cell lines was developed to profile the exometabolome by means of a discovery-based metabolomics approach using ultraperformance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry. Metabolic footprints provided by conditioned media (CM) samples ( n = 66) of two clear cell Renal Cell Carcinoma (ccRCC) cell lines with different genetic backgrounds and a nontumor renal cell line, were compared with the human serum metabolic profile of a pilot cohort ( n = 10) comprised of stage IV ccRCC patients and healthy individuals. Using a cross-validated orthogonal projection to latent structures-discriminant analysis model, a panel of 21 discriminant features selected by iterative multivariate classification, allowed differentiating control from tumor cell lines with 100% specificity, sensitivity, and accuracy. Isoleucine/leucine, phenylalanine, N-lactoyl-leucine, and N-acetyl-phenylalanine, and cysteinegluthatione disulfide (CYSSG) were identified by chemical standards, and hydroxyprolyl-valine was identified with MS and MS/MS experiments. A subset of 9 discriminant features, including the identified metabolites except for CYSSG, produced a fingerprint of classification value that enabled discerning ccRCC patients from healthy individuals. To our knowledge, this is the first time that N-lactoyl-leucine is associated with ccRCC. Results from this study provide a proof of concept that CM can be used as a serum proxy to obtain disease-related metabolic signatures.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/sangue , Neoplasias Renais/sangue , Leucina/sangue , Metaboloma , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Cromatografia Líquida , Cisteína/análogos & derivados , Cisteína/sangue , Análise Discriminante , Feminino , Glutationa/análogos & derivados , Glutationa/sangue , Células HEK293 , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Leucina/análogos & derivados , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenilalanina/análogos & derivados , Fenilalanina/sangue , Projetos Piloto , Espectrometria de Massas em TandemRESUMO
In this study, an acute overloading of methionine (MetLo) was used to investigate the trassulfuration pathway response comparing healthy controls and HIV+ patients under their usual diet and dietary N-acetyl-L-cysteine (NAC) supplementation. MetLo (0.1 g Met/kg mass weight) was given after overnight fasting to 20 non-HIV+ control subjects (Co) and 12 HIV+ HAART-treated patients. Blood samples were taken before and after the MetLo in two different 7-day dietary situations, with NAC (1 g/day) or with their usual diet (UD). The amino acids (Met, Hcy, Cys, Tau, Ser, Glu and Gln) and GSH were determined by HPLC and their inflow rate into circulation (plasma) was estimated by the area under the curve (AUC). Under UD, the HIV+ had lower plasma GSH and amino acids (excepting Hcy) and higher oxidative stress (GSSG/GSH ratio), similar remethylation (RM: Me/Hcy + Ser ratio), transmethylation (TM; Hcy/Met ratio) and glutaminogenesis (Glu/Gln ratio), lower transsulfuration (TS: Cys/Hcy + Ser ratio) and Cys/Met ratio and, higher synthetic rates of glutathione (GG: GSH/Cys ratio) and Tau (TG: Tau/Cys ratio). NAC supplementation changed the HIV pattern by increasing RM above control, normalizing plasma Met and TS and, increasing plasma GSH and GG above controls. However, plasma Cys was kept always below controls probably, associatively to its higher consumption in GG (more GSSG than GSH) and TG. The failure of restoring normal Cys by MetLo, in addition to NAC, in HIV+ patients seems to be related to increased flux of Cys into GSH and Tau pathways, probably strengthening the cell-antioxidant capacity against the HIV progression (registered at http://www.clinicaltrials.gov , NCT00910442).
Assuntos
Acetilcisteína/administração & dosagem , Cisteína/sangue , Suplementos Nutricionais , Glutationa/sangue , Infecções por HIV , HIV-1 , Metionina/sangue , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/sangue , Infecções por HIV/terapia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: This article aimed to identify the influence of high serum homocysteine (Hcy) and cysteine (Cys) levels, alone or in conjunction, on changes in anthropometric parameters in children and adolescents over a 12-month follow-up period. METHODS: This is a cohort study involving 483 boys and girls 7-15 years of age. The outcome variables were body mass index (BMI)-for-age and waist circumference (WC) and the principal exposure variables were serum Hcy and Cys levels, alone or in conjunction. A generalized estimating equation (GEE) approach was used to identify longitudinal changes in the outcome variables. RESULTS: Irrespective of age, sex, socioeconomic conditions, dietary intake, or the practice of physical activity, the children and adolescents in the fifth quintile of distribution of Hcy levels had a z-score increase of 0.50 (p < 0.01) and a 3.62 cm increase (p < 0.01) in mean BMI-for-age and WC, respectively, over the period of the study. In individuals with Cys values above the fifth quintile, a z-score increase of 0.59 (p < 0.01) and a 5 cm increase (p < 0.01) were found in BMI-for-age and WC, respectively. When serum Hcy and Cys levels were both above the fifth quintile of distribution, a z-score increase of 0.87 (p < 0.01) and a 6.57 cm increase (p < 0.01) were found in mean BMI-for-age and WC, respectively, over the 12-month follow-up. CONCLUSION: High serum Hcy and Cys levels contributed to an increase in BMI-for-age and WC in children and adolescents over a 12-month follow-up period, with these increases being even greater when these 2 biochemical parameters were simultaneously high.
Assuntos
Índice de Massa Corporal , Cisteína/sangue , Homocisteína/sangue , Circunferência da Cintura/fisiologia , Adolescente , Antropometria , Brasil , Criança , Feminino , Humanos , Estudos Longitudinais , MasculinoRESUMO
OBJECTIVES: Acetaminophen toxicity is a common cause of pediatric liver failure. The diagnosis may be limited by the short window of detection of acetaminophen in serum. Recently acetaminophen protein adducts (APAP-CYS) have been used as a biomarker with a longer duration of detection. The objective of this study was to describe the serum concentrations of APAP-CYS in pediatric patients with and without reported therapeutic acetaminophen exposure. METHODS: A cross-sectional study of children age 1 to <12 years presenting to a pediatric emergency department. Subjects were stratified by recent acetaminophen use and had serum APAP-CYS measured using LC/MS. RESULTS: One hundred patients were enrolled. All of the patients whose caregivers denied acetaminophen exposure had nondetectable APAP-CYS. Fifty-two percent of subjects who were reported to have taken acetaminophen in the preceding 2 weeks had detectable serum APAP-CYS. The APAP-CYS concentrations were positively correlated with higher overall dose and more recent ingestion. CONCLUSIONS: APAP-CYS is detectable in the majority of children taking acetaminophen and not detected in the majority of children who are not exposed to acetaminophen.
Assuntos
Acetaminofen/sangue , Analgésicos não Narcóticos/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Cisteína/sangue , Overdose de Drogas/diagnóstico , Serviço Hospitalar de Emergência , Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Biomarcadores/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Criança , Pré-Escolar , Estudos Transversais , Overdose de Drogas/sangue , Overdose de Drogas/etiologia , Feminino , Humanos , Lactente , Masculino , Valores de ReferênciaRESUMO
Hyperhomocysteinemia has been considered a risk factor for neuropsychiatric disorders, but the mechanisms involved in this process have not been completely elucidated. The aim of this study was to analyze the influence of hyperhomocysteinemia induction by methionine supplementation considering different levels and periods of exposure in mice. For this purpose, methionine supplementation at concentrations of 0.5 and 1% were administered in water to increase homocysteinemia in male C57BL/6 mice, and was maintained for 3 time periods (2, 4 and 6 months of treatment). The results from one-carbon metabolism parameters, brain-derived neurotrophic factor (BDNF) concentrations and behavioral evaluation were compared. The 0.5% supplementation was efficient in increasing plasma homocysteine levels after 2 and 6 months. The 1% supplementation, increased plasma homocysteine after 2, 4 and 6 months. Little influence was observed in cysteine and glutathione concentrations. Frontal cortex BDNF levels showed a lack of treatment influence in all periods; only the expected decrease due to increasing age was observed. Moreover, the only behavioral alteration observed using a novel object recognition task was that which was expected with increasing age. We found that responses to hyperhomocysteinemia varied based on how it was reached, and the length of toxicity. Moreover, hyperhomocysteinemia can affect the normal pattern of one carbon metabolism during age increase in mice. These findings allow the establishment of a reliable animal model for studies in this field.
Assuntos
Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/metabolismo , Hiper-Homocisteinemia/metabolismo , Metionina/administração & dosagem , Animais , Cisteína/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Glutationa/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/induzido quimicamente , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Reconhecimento Psicológico/efeitos dos fármacos , Fatores de TempoRESUMO
OBJECTIVE: To evaluate the presence of dyslipidemia and plasma concentrations of homocysteine (Hcy) and cysteine (Cys) in adolescents with juvenile systemic lupus erythematosus (SLE) and relate these findings to disease activity (Systemic Lupus Erythematosus Disease Activity Index, SLEDAI) and cardiovascular risk factors. METHODS: A cross-sectional controlled study including 26 female adolescents with SLE and 26 healthy controls was conducted. We evaluated SLEDAI, medications, anthropometric data, dietary intake, lipid profile, proteinuria, Hcy, Cys, folic acid, vitamin B12, and high-sensitivity C-reactive protein levels. RESULTS: Dyslipidemia was observed in 46.2% of the patients and in 19.2% of the controls. The SLE group had a higher Cys concentration and a lower high-density lipoprotein cholesterol concentration compared with the controls. In the multivariate analysis only Hcy was significantly and independently associated with the presence of dyslipidemia in the juvenile SLE group; an increase of 1 µmol/l in the Hcy concentration doubled the chance of dyslipidemia (OR: 2.1; 95% CI: 1.1-4.9; p = 0.030). The Cys concentration was correlated with Hcy, total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations. CONCLUSION: We observed the presence of cardiovascular risk factors in adolescents with juvenile SLE. The early identification of biochemical alterations allows the development of intervention strategies that may lower the risk of cardiovascular disease.
Assuntos
Cisteína/sangue , Dislipidemias/sangue , Homocisteína/sangue , Lúpus Eritematoso Sistêmico/sangue , Adolescente , Corticosteroides/administração & dosagem , Adulto , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Criança , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/complicações , Dislipidemias/epidemiologia , Ingestão de Energia , Feminino , Ácido Fólico/sangue , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Análise Multivariada , Estado Nutricional , Puberdade/fisiologia , Fatores de Risco , Triglicerídeos/sangue , Vitamina B 12/sangue , Circunferência da Cintura , Adulto JovemRESUMO
A nanohybrid platform built with multi-walled carbon nanotubes and gold nanorods, prepared via a cationic surfactant-containing seed-mediated sequential growth process, in aqueous solution, on a glassy carbon substrate has been successfully developed to be used in the electrocatalytic oxidation of L-cysteine (Cys). The nanohybrid was characterized by transmission electron microscopy, Raman spectroscopy and electrochemical measurements. Cyclic voltammetry results had shown that the modified electrode allows the oxidation of Cys at a very low anodic potential (0.00 V vs. Ag/AgCl). The kinetic constant kcat for the catalytic oxidation of Cys was evaluated by chronoamperometry and provided a value of 5.6×10(4) L mol(-1) s(-1). The sensor presents a linear response range from 5.0 up to 200.0 µmol L(-1), detection limit of 8.25 nmol L(-1) and a sensitivity of 120 nA L µmol(-1).
Assuntos
Técnicas Biossensoriais/instrumentação , Carbono/química , Cisteína/sangue , Técnicas Eletroquímicas/instrumentação , Ouro/química , Eletrodos , Vidro/química , Humanos , Limite de Detecção , Nanotubos/química , Nanotubos/ultraestrutura , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestruturaRESUMO
There is an important set of cirrhotic and diabetic patients that present both diseases. However, information about metabolic and cellular blood markers that are altered, in conjunction or distinctively, in the 3 pathological conditions is scarce. The aim of this project was to evaluate several indicators of prooxidant reactions and the membrane composition of blood samples (serum and red blood cells (RBCs)) from patients clinically classified as diabetic (n = 60), cirrhotic (n = 70), and diabetic with liver cirrhosis (n = 25) as compared to samples from a similar population of healthy individuals (n = 60). The results showed that levels of TBARS, nitrites, cysteine, and conjugated dienes in the RBC of cirrhotic patients were significantly increased. However, the coincidence of diabetes and cirrhosis partially reduced the alterations promoted by the cirrhotic condition. The amount of total phospholipids and cholesterol was greatly enhanced in the patients with both pathologies (between 60 and 200% according to the type of phospholipid) but not in the patients with only one disease. Overall, the data indicate that the cooccurrence of diabetes and cirrhosis elicits a physiopathological equilibrium that is different from the alterations typical of each individual malady.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Membrana Eritrocítica/metabolismo , Lipídeos/análise , Hepatopatias/complicações , Hepatopatias/metabolismo , Oxidantes/metabolismo , Estudos de Casos e Controles , Colesterol/metabolismo , Cisteína/sangue , Diabetes Mellitus Tipo 2/sangue , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Hepatopatias/sangue , Óxido Nítrico/metabolismo , Nitritos/sangue , Oxirredução , Estresse Oxidativo , Fosfolipídeos/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The role of the phase angle in hyperhomocysteinemia has yet to be assessed. Classical homocystinuria is a rare genetic disease characterized by severe hyperhomocysteinemia, as well as increased levels of methionine and reduced levels of cysteine. The objective of this study was to investigate the potential relationship between phase angle and homocysteine, cysteine, and methionine levels in patients with classical homocystinuria. Eight patients were included in the study. Phase angle was measured with a tetrapolar bioimpedance analyzer. Serum homocysteine, cysteine, and methionine levels were measured by HPLC. Only three patients had adequate metabolic control of their disease. Median phase angle was 5.9° (range = 5.4°-8.5°). There was a significant correlation between phase angle and levels of homocysteine (r = -0.807, p = 0.015), methionine (r = -0.711, p = 0.048), and cysteine (r = 0.836, p = 0.010). Was also positively correlated with BMI and arm muscle circumference (p < 0.05). Two patients had phase angles below the 5th percentile, and only one above the 50th percentile. Our findings suggest that cellular integrity is affected in patients with high homocysteine levels, thus indicating that phase angle could be a valuable indicator of prognosis and classical homocystinuria. It also suggests a role for this indicator in other forms of hyperhomocysteinemia and other inborn errors of metabolism.