RESUMEN
INTRODUCTION: Recent studies have implicated acetyl-L-carnitine as well as other acylcarnitines in depression. To our knowledge, no untargeted metabolomics studies have been conducted among US mainland Puerto Ricans. OBJECTIVES: We conducted untargeted metabolomic profiling on plasma from 736 participants of the Boston Puerto Rican Health Study. METHODS: Using Weighted Gene Co-expression Network Analysis, we identified metabolite modules associated with depressive symptomatology, assessed via the Center for Epidemiologic Studies Depression scale. We identified metabolites contributing to these modules and assessed the relationship between these metabolites and depressive symptomatology. RESULTS: 621 annotated metabolites clustered into eight metabolite modules, of which one, the acylcarnitine module, was significantly inversely associated with depressive symptomatology (ß = - 27.7 (95% CI (- 54.5-0.8); p = 0.043). Several metabolite hub features in the acylcarnitine module were significantly associated with depressive symptomatology, after correction for multiple comparisons. CONCLUSIONS: In this untargeted plasma metabolomics study among mainland Puerto Rican older adults, acylcarnitines, as a metabolite module were inversely associated with depressive symptomatology.
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Carnitina , Depresión , Metabolómica , Humanos , Carnitina/análogos & derivados , Carnitina/sangre , Carnitina/metabolismo , Femenino , Masculino , Depresión/sangre , Depresión/metabolismo , Metabolómica/métodos , Persona de Mediana Edad , Anciano , Puerto Rico , Estudios de Cohortes , Hispánicos o Latinos , Boston/epidemiologíaRESUMEN
This study aims to apply machine learning models to identify new biomarkers associated with the early diagnosis and prognosis of SARS-CoV-2 infection.Plasma and serum samples from COVID-19 patients (mild, moderate, and severe), patients with other pneumonia (but with negative COVID-19 RT-PCR), and healthy volunteers (control) from hospitals in four different countries (China, Spain, France, and Italy) were analyzed by GC-MS, LC-MS, and NMR. Machine learning models (PCA and PLS-DA) were developed to predict the diagnosis and prognosis of COVID-19 and identify biomarkers associated with these outcomes.A total of 1410 patient samples were analyzed. The PLS-DA model presented a diagnostic and prognostic accuracy of around 95% of all analyzed data. A total of 23 biomarkers (e.g., spermidine, taurine, L-aspartic, L-glutamic, L-phenylalanine and xanthine, ornithine, and ribothimidine) have been identified as being associated with the diagnosis and prognosis of COVID-19. Additionally, we also identified for the first time five new biomarkers (N-Acetyl-4-O-acetylneuraminic acid, N-Acetyl-L-Alanine, N-Acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate) that are also associated with the severity and diagnosis of COVID-19. These five new biomarkers were elevated in severe COVID-19 patients compared to patients with mild disease or healthy volunteers.The PLS-DA model was able to predict the diagnosis and prognosis of COVID-19 around 95%. Additionally, our investigation pinpointed five novel potential biomarkers linked to the diagnosis and prognosis of COVID-19: N-Acetyl-4-O-acetylneuraminic acid, N-Acetyl-L-Alanine, N-Acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate. These biomarkers exhibited heightened levels in severe COVID-19 patients compared to those with mild COVID-19 or healthy volunteers.
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Biomarcadores , COVID-19 , Humanos , COVID-19/sangre , COVID-19/diagnóstico , Biomarcadores/sangre , Masculino , Femenino , Persona de Mediana Edad , Italia , Aprendizaje Automático , Carnitina/sangre , Carnitina/análogos & derivados , Francia/epidemiología , SARS-CoV-2 , Adulto , China , Pronóstico , España , MultiómicaRESUMEN
Spinocerebellar ataxia type 7 (SCA7), a neurodegenerative disease characterized by cerebellar ataxia and retinal degeneration, is caused by an abnormal CAG repeat expansion in the ATXN7 gene coding region. The onset and severity of SCA7 are highly variable between patients, thus identification of sensitive biomarkers that accurately diagnose the disease and monitoring its progression are needed. With the aim of identified SCA7-specific metabolites with clinical relevance, we report for the first time, to the best of our knowledge, a metabolomics profiling of circulating acylcarnitines and amino acids in SCA7 patients. We identified 21 metabolites with altered levels in SCA7 patients and determined two different sets of metabolites with diagnostic power. The first signature of metabolites (Valine, Leucine, and Tyrosine) has the ability to discriminate between SCA7 patients and healthy controls, while the second one (Methionine, 3-hydroxytetradecanoyl-carnitine, and 3-hydroxyoctadecanoyl-carnitine) possess the capability to differentiate between early-onset and adult-onset patients, as shown by the multivariate model and ROC analyses. Furthermore, enrichment analyses of metabolic pathways suggest alterations in mitochondrial function, energy metabolism, and fatty acid beta-oxidation in SCA7 patients. In summary, circulating SCA7-specific metabolites identified in this study could serve as effective predictors of SCA7 progression in the clinics, as they are sampled in accessible biofluid and assessed by a relatively simple biochemical assay.
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Aminoácidos/sangre , Carnitina/análogos & derivados , Ataxias Espinocerebelosas/sangre , Adulto , Biomarcadores/sangre , Carnitina/sangre , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Recent analyses have described metabolomic markers for depression and suicidal ideation in non-pregnant adults. We examined the metabolomic profile of antepartum depression and suicidal ideation during mid-pregnancy, a time of high susceptibility to mood disorders. METHODS: We collected fasting blood from 100 pregnant Peruvian women and profiled 307 plasma metabolites using liquid chromatography-mass spectrometry. We used the Patient Health Questionnaire 9 to define antepartum depression (score â¯≥â¯10) and suicidal ideation (having thoughts that you would be better off dead, or of hurting yourself). Logistic regression was used to calculate odds ratios (ORs). RESULTS: Three triacylglycerol metabolites (C48:5 triacylglycerol [OR = =1.89; 95% confidence interval (CI): 1.14-3.14], C50:6 triacylglycerol [OR = =1.88; 95%CI: 1.13-3.14], C46:4 triacylglycerol [OR = =1.89; 95%CI: 1.11-3.21]) were associated with higher odds of antepartum depression and 4 metabolites (betaine [OR = =0.56; 95%CI:0.33-0.95], citrulline [OR = =0.58; 95%CI: 0.34-0.98], C5 carnitine [OR = =0.59; 95%CI: 0.36-0.99], C5:1 carnitine [OR = =0.59; 95%CI: 0.35-1.00]) with lower odds of antepartum depression. Twenty-six metabolites, including 5-hydroxytryptophan (OR = =0.52; 95%CI: 0.30-0.92), phenylalanine (OR = =0.41; 95%CI: 0.19-0.91), and betaine (OR = =0.53; 95%CI: 0.28-0.99) were associated with lower odds of suicidal ideation. LIMITATIONS: Our cross-sectional study could not determine whether metabolites prospectively predict outcomes. No metabolites remained significant after multiple testing correction; these novel findings should be replicated in a larger sample. CONCLUSIONS: Antepartum suicidal ideation metabolomic markers are similar to markers of depression among non-pregnant adults, and distinct from markers of antepartum depression. Findings suggest that mood disorder in pregnancy shares metabolomic similarities to mood disorder at other times and may further understanding of these conditions' pathophysiology.
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Depresión/sangre , Complicaciones del Embarazo/sangre , Segundo Trimestre del Embarazo/sangre , Mujeres Embarazadas/psicología , Ideación Suicida , 5-Hidroxitriptófano/sangre , Adulto , Betaína/sangre , Biomarcadores/sangre , Carnitina/sangre , Citrulina/sangre , Estudios Transversales , Depresión/psicología , Femenino , Humanos , Modelos Logísticos , Metabolómica , Oportunidad Relativa , Cuestionario de Salud del Paciente , Perú , Fenilalanina/sangre , Embarazo , Complicaciones del Embarazo/psicología , Estudios Prospectivos , Factores de Riesgo , Triglicéridos/sangre , Adulto JovenRESUMEN
Approximately 255 million people consume illicit drugs every year, among which 18 million use cocaine. A portion of this drug is represented by crack, but it is difficult to estimate the number of users since most are marginalized. However, there are no recognized efficacious pharmacotherapies for crack-cocaine dependence. Inflammation and infection in cocaine users may be due to behavior adopted in conjunction with drug-related changes in the brain. To understand the metabolic changes associated with the drug abuse disorder and identify biomarkers, we performed a 1H NMR-based metabonomic analysis of 44 crack users' and 44 healthy volunteers' blood serum. The LDA model achieved 98% of accuracy. From the water suppressed 1H NMR spectra analyses, it was observed that the relative concentration of lactate was higher in the crack group, while long chain fatty acid acylated carnitines were decreased, which was associated with their nutritional behavior. Analyses of the aromatic region of CPMG 1H NMR spectra demonstrated histidine and tyrosine levels increased in the blood serum of crack users. The reduction of carnitine and acylcarnitines and the accumulation of histidine in the serum of the crack users suggest that histamine biosynthesis is compromised. The tyrosine level points to altered dopamine concentration.
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Trastornos Relacionados con Cocaína , Cocaína Crack/farmacología , Espectroscopía de Resonancia Magnética/métodos , Metaboloma/efectos de los fármacos , Recolección de Muestras de Sangre , Carnitina/sangre , Estudios de Casos y Controles , Histidina/sangre , Humanos , Ácido Láctico/sangre , Tirosina/sangreAsunto(s)
Trastorno Bipolar/sangre , Esquizofrenia/sangre , Adolescente , Adulto , Biomarcadores/sangre , Carnitina/análogos & derivados , Carnitina/sangre , Femenino , Humanos , Lisofosfatidilcolinas/sangre , Masculino , Fosfatidilcolinas/sangre , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/sangre , Adulto JovenRESUMEN
Coronary artery bypass grafting reduces plasma L-carnitine and may impair the production of myocardial energy. L-carnitine supplementation may elevate plasma L-carnitine and increase cardiac mechanical efficiency. The objective of this study was to verify the recovery of preoperative plasma LC in patients with heart failure undergoing coronary artery bypass grafting supplemented with a daily oral dose of 50 mg / kg. Volunteers with ischemic heart failure who underwent surgery were randomized into a supplemented group (A-received 50 mg / kg L-carnitine) or placebo group (B) for 60 days. Supplementation was started on the third postoperative day. The spectrophotometric enzymatic method was used to quantify plasma L-carnitine. In the preoperative period, both groups had plasma L-carnitine adequate to the reference range (18.9-71.1 µM). On the second postoperative day, there was a reduction in plasma L-carnitine in groups A (17.4%) and B (14.4%). In the comparison between the groups, plasma L-carnitine was higher in group A than B in 10º (p = 0.024), 30º (p = 0.001), and 60º postoperative day (p = 0.008). Supplementation of L-carnitine at a daily oral dose of 50 mg / kg in patients with heart failure undergoing coronary artery bypass grafting may recover preoperative plasma L-carnitine within 10 days.
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Carnitina/administración & dosificación , Carnitina/sangre , Puente de Arteria Coronaria/efectos adversos , Suplementos Dietéticos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/cirugía , Método Doble Ciego , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Persona de Mediana Edad , Placebos , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the association between cord blood amino acid and acylcarnitine profiles and measures of adiposity and hyperinsulinemia in healthy newborns. STUDY DESIGN: A cross-sectional study of 118 full-term infants born to mothers without gestational diabetes was performed. Cord blood leptin, C-peptide, acylcarnitine, and amino acid levels were measured. Body composition was measured by air displacement plethysmography. Multivariate linear regression and principal component analysis were used to analyze associations of cord blood metabolites with newborn anthropometrics, leptin, and C-peptide. RESULTS: Acylcarnitines AC C2, AC C4-DC/Ci4-DC, and AC C8:1-OH/C6:1-DC were positively associated with leptin, and AC C14, AC C14:2, AC C16, AC C18, and AC C18:2 were negatively associated with C-peptide (P ≤ .0016). Principal component analysis revealed a positive association between factor 1(AC C2, AC C3, AC C5, AC C4/Ci4, AC C4-OH, AC C4-DC/Ci4-DC, glutamate/glutamine, and glycine) and adiposity measures. CONCLUSIONS: The positive association of AC C2 and AC C4-DC/Ci4-DC levels with leptin may reflect excess fat stores, higher fatty acid oxidation rate, and mitochondrial dysfunction leading to accumulation of acylcarnitine intermediates. Principal component analysis revealed a positive association between branched chain amino acid and ketone body metabolites and adiposity, confirming prior findings in adults. Cord blood acylcarnitine profiles may identify at-risk children before obesity or insulin resistance develops.
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Adiposidad , Sangre Fetal/metabolismo , Hiperinsulinismo/sangre , Adulto , Aminoácidos/sangre , Péptido C/sangre , Carnitina/análogos & derivados , Carnitina/sangre , Estudios Transversales , Femenino , Humanos , Recién Nacido , Leptina/sangre , Masculino , Análisis Multivariante , Análisis de Componente PrincipalRESUMEN
Citrus juices, especially orange juice, constitute rich sources of bioactive compounds with a wide range of health-promoting activities. Data from epidemiological and in vitro studies suggest that orange juice (OJ) may have a positive impact on lipid metabolism. However, the effect of orange juice intake on blood lipid profile is still poorly understood. We have used two different blood samples, Dried Blood Spots (DBS) and plasma, to assess the effect of two-week orange juice consumption in healthy volunteers by a mass-spectrometry based metabolomics approach. DBS were analysed by liquid chromatography mass spectrometry (LC-MS) and plasma samples were analysed by the gas chromatography mass spectrometry (GC-MS). One hundred sixty-nine lipids including acylcarnitines (AC), lysophosphatidylcholines (LysoPC), (diacyl- and acyl-alkyl-) phosphatidylcholines (PC aa and PC ae) and sphingomyelins (SM) were identified and quantified in DBS. Eighteen fatty acids were identified and quantified in plasma. Multivariate analysis allowed to identify an increase in C3:1, C5-DC(C6-OH), C5-M-DC, C5:1-DC, C8, C12-DC, lysoPC18:3, myristic acid, pentadecanoic acid, palmitoleic and palmitic acid and a decrease in nervonic acid, C0, C2, C10, C10:1, C16:1, C16-OH, C16:1-OH, C18-OH, PC aa C40:4, PC ae C38:4, PC ae C42:3, PC ae C42:4 and cholesterol levels after orange juice intake. A two-week period of orange juice intake could affect fatty acids ß-oxidation through mitochondrial and peroxisomal pathways, leading to an increase of short-chain acylcarnitines and a decrease of medium and long-chain acylcarnitines. This is the first report analyzing the effect of orange juice intake in healthy volunteers using a dried blood spot-based metabolomics approach.
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Carnitina/análogos & derivados , Citrus sinensis/metabolismo , Jugos de Frutas y Vegetales , Espectrometría de Masas/métodos , Metabolómica/métodos , Adulto , Carnitina/sangre , Carnitina/metabolismo , Cromatografía Liquida , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Adulto JovenRESUMEN
BACKGROUND: Structural equation modeling (SEM) can help understanding complex functional relationships among obesity, non-alcoholic fatty liver disease (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty acids that increase oxidative stress and mitochondrial dysfunction, there would be an increase of serum acylcarnitines, amino acids and cytokines in obese subjects. Acylcarnitines would be related to non-alcoholic fatty disease that will induce insulin resistance. 2) If a positive family history of obesity and type 2 diabetes are the major determinants of the metabolomic profile, there would be higher concentration of amino acids and acylcarnitines in patients with this background that will induce obesity and NAFLD which in turn will induce insulin resistance. METHODS/RESULTS: 137 normoglycemic subjects, mean age (SD) of 30.61 (8.6) years divided in three groups: BMI<25 with absence of NAFLD (G1), n = 82; BMI>30 with absence of NAFLD (G2), n = 24; and BMI>30 with NAFLD (G3), n = 31. Family history of obesity (any) was present in 53%. Both models were adjusted in SEM. Family history of obesity predicted obesity but could not predict acylcarnitines and amino acid concentrations (effect size <0.2), but did predict obesity phenotype. CONCLUSION: Family history of obesity is the major predictor of obesity, and the metabolic abnormalities on amino acids, acylcarnitines, inflammation, insulin resistance, and NAFLD.
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Aminoácidos/sangre , Carnitina/análogos & derivados , Anamnesis , Metabolómica , Modelos Biológicos , Enfermedad del Hígado Graso no Alcohólico/sangre , Obesidad/sangre , Adolescente , Adulto , Carnitina/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/genética , Obesidad/genéticaRESUMEN
INTRODUCTION: Inborn errors of metabolism (IEM) represent an important public health problem due to current diagnosis and treatment limitations, poor life quality of affected patients, and consequent untimely child death. In contrast to classical methods, tandem mass spectrometry (MS/MS) has allowed simultaneous evaluation of multiple metabolites associated with IEM offering higher sensitivity, low false positive rates and high throughput. AIMS: Determine concentration levels for amino acids and acylcarnitines in blood of newborns from Colombia, to establish reference values for further use in diagnosis of IEM. METHODS: Implementation of a method to determine amino acids, acylcarnitines and succinylacetone in newborn dried blood spots using MS/MS, and its application in a cross-sectional study conducted in 891 healthy neonates from Cali and Quibdo cities is described. RESULTS: fifty-seven analytes that allow the diagnosis of more than 40 different pathologies were tested. The method showed to be linear, precise and accurate. Healthy neonates 1-18 days of age were included, 523 from Cali and 368 from Quibdo; 52% male and 48% female. Age-related differences on the concentration levels of amino acids and acylcarnitines were observed whereas no significant differences by gender were found. CONCLUSION: The study has contributed to reveal the usual concentration levels of amino acids, acylcarnitines and succinylacetone that could be used as reference for the establishment of a newborn metabolic screening program in Colombia.
INTRODUCCIÓN: Los Errores Innatos del metabolismo (EIM) representan un importante problema de salud pública debido a limitaciones en el tratamiento y diagnóstico oportuno, la pobre calidad de vida de los pacientes afectados, así como la muerte infantil prematura. Comparada con los métodos clásicos, la espectrometría de masas en tándem (MS/MS) ha permitido la evaluación simultánea de múltiples metabolitos asociados con EIM, con una alta sensibilidad, baja proporción de falsos positivos y alto rendimiento. OBJETIVOS: Determinar los niveles de concentración de aminoácidos y acilcarnitinas en sangre de recién nacidos de Colombia, para establecer los valores normales para usarlos como referencia en el diagnóstico de EIM. MÉTODOS: Aquí, se describe la implementación de un método para determinar aminoácidos, acilcarnitinas y succinilacetona en gotas de sangre seca de recién nacidos usando MS/MS, y su aplicación en un estudio de corte transversal realizado en 891 neonatos sanos de las ciudades de Cali y Quibdó. RESULTADOS: Se evaluaron 57 analitos que permiten el diagnóstico de más de 40 patologías diferentes. El método mostró ser lineal, preciso y exacto. Se incluyeron neonatos sanos de 1-18 días de edad, 523 de Cali y 368 de Quibdó, 52% hombres y 48% mujeres. Se observaron diferencias en los niveles de concentración de aminoácidos y acilcarnitinas relacionadas con la edad, mientras que no se encontraron diferencias significativas por sexo. CONCLUSIÓN: El estudio ha contribuido a revelar los niveles usuales de concentración de aminoácidos, acilcarnitinas y succinilacetona que pueden ser usados como referencia para el establecimiento del programa de tamizaje neonatal metabólico en Colombia.
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Aminoácidos/sangre , Carnitina/análogos & derivados , Heptanoatos/sangre , Errores Innatos del Metabolismo/diagnóstico , Espectrometría de Masas en Tándem/métodos , Biomarcadores/sangre , Carnitina/sangre , Colombia , Estudios Transversales , Reacciones Falso Positivas , Humanos , Recién Nacido , Errores Innatos del Metabolismo/sangre , Valores de Referencia , Sensibilidad y EspecificidadRESUMEN
Abstract Introduction: Inborn errors of metabolism (IEM) represent an important public health problem due to current diagnosis and treatment limitations, poor life quality of affected patients, and consequent untimely child death. In contrast to classical methods, tandem mass spectrometry (MS/MS) has allowed simultaneous evaluation of multiple metabolites associated with IEM offering higher sensitivity, low false positive rates and high throughput. Aims: Determine concentration levels for amino acids and acylcarnitines in blood of newborns from Colombia, to establish reference values for further use in diagnosis of IEM. Methods: Implementation of a method to determine amino acids, acylcarnitines and succinylacetone in newborn dried blood spots using MS/MS, and its application in a cross-sectional study conducted in 891 healthy neonates from Cali and Quibdo cities is described. Results: fifty-seven analytes that allow the diagnosis of more than 40 different pathologies were tested. The method showed to be linear, precise and accurate. Healthy neonates 1-18 days of age were included, 523 from Cali and 368 from Quibdo; 52% male and 48% female. Age-related differences on the concentration levels of amino acids and acylcarnitines were observed whereas no significant differences by gender were found. Conclusion: The study has contributed to reveal the usual concentration levels of amino acids, acylcarnitines and succinylacetone that could be used as reference for the establishment of a newborn metabolic screening program in Colombia.
Resumen Introducción: Los Errores Innatos del metabolismo (EIM) representan un importante problema de salud pública debido a limitaciones en el tratamiento y diagnóstico oportuno, la pobre calidad de vida de los pacientes afectados, así como la muerte infantil prematura. Comparada con los métodos clásicos, la espectrometría de masas en tándem (MS/MS) ha permitido la evaluación simultánea de múltiples metabolitos asociados con EIM, con una alta sensibilidad, baja proporción de falsos positivos y alto rendimiento. Objetivos: Determinar los niveles de concentración de aminoácidos y acilcarnitinas en sangre de recién nacidos de Colombia, para establecer los valores normales para usarlos como referencia en el diagnóstico de EIM. Métodos: Aquí, se describe la implementación de un método para determinar aminoácidos, acilcarnitinas y succinilacetona en gotas de sangre seca de recién nacidos usando MS/MS, y su aplicación en un estudio de corte transversal realizado en 891 neonatos sanos de las ciudades de Cali y Quibdó. Resultados: Se evaluaron 57 analitos que permiten el diagnóstico de más de 40 patologías diferentes. El método mostró ser lineal, preciso y exacto. Se incluyeron neonatos sanos de 1-18 días de edad, 523 de Cali y 368 de Quibdó, 52% hombres y 48% mujeres. Se observaron diferencias en los niveles de concentración de aminoácidos y acilcarnitinas relacionadas con la edad, mientras que no se encontraron diferencias significativas por sexo. Conclusión: El estudio ha contribuido a revelar los niveles usuales de concentración de aminoácidos, acilcarnitinas y succinilacetona que pueden ser usados como referencia para el establecimiento del programa de tamizaje neonatal metabólico en Colombia.
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Humanos , Recién Nacido , Carnitina/análogos & derivados , Espectrometría de Masas en Tándem/métodos , Aminoácidos/sangre , Heptanoatos/sangre , Errores Innatos del Metabolismo/diagnóstico , Valores de Referencia , Biomarcadores/sangre , Carnitina/sangre , Estudios Transversales , Sensibilidad y Especificidad , Colombia , Reacciones Falso Positivas , Errores Innatos del Metabolismo/sangreRESUMEN
During cardiac failure, cardiomyocytes have difficulty in using the substrates to produce energy. L-carnitine is a necessary nutrient for the transport of fatty acids that are required for generating energy. Coronary artery graft surgery reduces the plasma levels of L-carnitine and increases the oxidative stress. This study demonstrates the effect of L-carnitine supplementation on the reverse remodeling of patients undergoing coronary artery bypass graft. Patients with ischemic heart failure who underwent coronary graft surgery were randomized to group A - supplemented with L-carnitine or group B controls. Left ventricular ejection fraction, left ventricular systolic and diastolic diameters were assessed preoperatively, 60 and 180 days after surgery. Our study included 28 patients (26 [93.0%] males) with a mean age ± SD of 58.1 ± 10.5 years. The parameters for the evaluation of reverse remodeling did not improve after 60 and 180 days of coronary artery bypass grafting in comparison between groups (p > 0.05). Evaluation within the L-carnitine group showed a 37.1% increase in left ventricle ejection fraction (p = 0.002) and 14.3% (p = 0.006) and 3.3% (p > 0.05) reduction in systolic and diastolic diameters, respectively. L-carnitine supplementation at a dose of 50 mg/kg combined with artery bypass surgery did not demonstrate any additional benefit in reverse remodeling. However, evaluation within the L-carnitine group may indicate a clinical benefit of L-carnitine supplementation.
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Carnitina/administración & dosificación , Puente de Arteria Coronaria , Suplementos Dietéticos , Isquemia Miocárdica/tratamiento farmacológico , Remodelación Ventricular , Anciano , Índice de Masa Corporal , Carnitina/sangre , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Conducta Sedentaria , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
OBJECTIVE: To evaluate the association between newborn acylcarnitine profiles and the subsequent development of necrotizing enterocolitis (NEC) with the use of routinely collected newborn screening data in infants born preterm. STUDY DESIGN: A retrospective cohort study was conducted with the use of discharge records for infants born preterm admitted to neonatal intensive care units in California from 2005 to 2009 who had linked state newborn screening results. A model-development cohort of 94 110 preterm births from 2005 to 2008 was used to develop a risk-stratification model that was then applied to a validation cohort of 22 992 births from 2009. RESULTS: Fourteen acylcarnitine levels and acylcarnitine ratios were associated with increased risk of developing NEC. Each log unit increase in C5 and free carnitine /(C16 + 18:1) was associated with a 78% and a 76% increased risk for developing NEC, respectively (OR 1.78, 95% CI 1.53-2.02, and OR 1.76, 95% CI 1.51-2.06). Six acylcarnitine levels, along with birth weight and total parenteral nutrition, identified 89.8% of newborns with NEC in the model-development cohort (area under the curve 0.898, 95% CI 0.889-0.907) and 90.8% of the newborns with NEC in the validation cohort (area under the curve 0.908, 95% CI 0.901-0.930). CONCLUSIONS: Abnormal fatty acid metabolism was associated with prematurity and the development of NEC. Metabolic profiling through newborn screening may serve as an objective biologic surrogate of risk for the development of disease and thus facilitate disease-prevention strategies.
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Carnitina/análogos & derivados , Enterocolitis Necrotizante/diagnóstico , Enterocolitis Necrotizante/metabolismo , Recien Nacido Prematuro , Biomarcadores/análisis , California , Carnitina/análisis , Carnitina/sangre , Estudios de Cohortes , Intervalos de Confianza , Enterocolitis Necrotizante/epidemiología , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Incidencia , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , Análisis Multivariante , Tamizaje Neonatal/métodos , Oportunidad Relativa , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Poblaciones VulnerablesRESUMEN
OBJECTIVE: To examine the clinical features and risk factors of secondary carnitine deficiency due to long-term use of pivalate-conjugated antibiotics (PCAs). STUDY DESIGN: We retrospectively investigated the age, clinical manifestations, PCA administration period, and background of 22 patients who showed a decrease in free carnitine (C0; ≤20 µmol/L) concomitant with an increase in pivaloyl carnitine (detected as C5-acylcarnitine) on acylcarnitine analysis with tandem mass spectrometry. Administration of PCAs was confirmed in all cases. RESULTS: The patients ranged in age from 2 months to 42 years (median, 1 year, 11 months). One patient was aged <1 year, 10 patients were aged 1 year, 1 patient was aged 2 years, and 10 patients were aged ≥3 years. Nine patients had known underlying disease. Fourteen patients developed acute encephalopathy, 13 with accompanying hypoglycemia. Four patients presented with hypoglycemia without signs of encephalopathy. C0 values ranged from 0.25 to 19.66 µmol/L (median, 1.31 µmol/L); C5-acylcarnitine values, from 0.43 to 11.92 µmol/L (median, 3.23 µmol/L). There was no correlation between the PCA administration period and C0 level. Ten patients developed the symptoms after PCA administration for ≥14 days, whereas 6 patients showed symptoms after PCA administration for <14 days. CONCLUSION: Carnitine deficiency resulting from PCA treatment was most frequently observed in 1-year-old infants. Most patients manifested acute encephalopathy and/or hypoglycemia. Some patients developed carnitine deficiency after PCA administration for <14 days.
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Antibacterianos/efectos adversos , Carnitina/deficiencia , Adolescente , Adulto , Antibacterianos/farmacología , Encefalopatías/etiología , Carnitina/análogos & derivados , Carnitina/sangre , Niño , Preescolar , Femenino , Humanos , Hipoglucemia/etiología , Lactante , Masculino , Estudios Retrospectivos , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
Blood carnitine and/or acetylcarnitine deficiencies are postulated in the literature as possible causes of higher ammonia levels. The aim of this study was to investigate if the use of valproic acid, the age of the patients, or certain central nervous system pathologies can cause carnitine and/or acetylcarnitine deficiency leading to increased ammonia levels. Three groups of patients were studied: (A) epileptic under phenytoin monotherapy (n = 31); (B) with bipolar disorder under valproic acid treatment (n = 28); (C) elderly (n = 41). Plasma valproic acid and blood carnitine and acyl carnitine profiles were determined using a validated HPLC and LC-MS/MS method, respectively. Blood ammonia concentration was determined using an enzymatic automated assay. Higher ammonia levels were encountered in patients under valproic acid treatment and in the elderly. This may be due to the lower carnitine and/or acetylcarnitine found in these patients. Patients with controlled seizures had normal carnitine and acetylcarnitine levels. Further studies are necessary in order to conclude if the uncontrolled bipolar disorder could be the cause of higher carnitine and/or acetylcarnitine levels.
Asunto(s)
Acetilcarnitina , Amoníaco/sangre , Trastorno Bipolar , Carnitina , Epilepsia , Fenitoína/administración & dosificación , Ácido Valproico/administración & dosificación , Acetilcarnitina/sangre , Acetilcarnitina/deficiencia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Trastorno Bipolar/sangre , Trastorno Bipolar/tratamiento farmacológico , Carnitina/sangre , Carnitina/deficiencia , Epilepsia/sangre , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: To test whether follow-up testing for very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency uncovers a diagnosis in patients with elevations of C14:1 and C14:2 plasma acylcarnitines after a controlled fasting study performed for clinically suspected hypoglycemia and to compare the acylcarnitine profiles from fasted patients without VLCAD deficiency vs patients with known VLCAD deficiency to determine whether metabolite testing distinguishes these groups. STUDY DESIGN: We performed a retrospective chart review and identified 17 patients with elevated C14:1 and C14:2 plasma acylcarnitine levels after a controlled fast and with testing for VLCAD deficiency (ACADVL sequencing or fibroblast fatty acid oxidation studies). The follow-up testing in all patients was inconsistent with a diagnosis of VLCAD deficiency. We compared the plasma acylcarnitine profiles from these fasted patients vs patients with VLCAD deficiency. RESULTS: C14:1/C12:1 was significantly lower (P < .001) in fasted patients vs patients with VLCAD deficiency. Metabolomics analysis performed in 2 fasted patients and 1 patient with VLCAD deficiency demonstrated evidence for up-regulated lipolysis and ß-oxidation in the fasted state. CONCLUSIONS: Elevations of plasma C14:1 and C14:2 acylcarnitines appear to be a physiologic result of lipolysis that occurs with fasting. Both metabolomics analysis and/or C14:1/C12:1 may distinguish C14:1 elevations from physiologic fasting-induced lipolysis vs VLCAD deficiency.
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Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Carnitina/análogos & derivados , Ayuno/sangre , Errores Innatos del Metabolismo Lipídico/sangre , Errores Innatos del Metabolismo Lipídico/diagnóstico , Enfermedades Mitocondriales/sangre , Enfermedades Mitocondriales/diagnóstico , Enfermedades Musculares/sangre , Enfermedades Musculares/diagnóstico , Acil-CoA Deshidrogenasa de Cadena Larga/sangre , Adolescente , Carnitina/sangre , Niño , Preescolar , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Femenino , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
A rapid, sensitive and specific method for quantifying piracetam in human plasma using Piracetam d-8 as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by one-step precipitation of protein using an acetonitrile (100%). The extracts were analyzed by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). The method had a chromatographic run time of 3.8 min and a linear calibration curve over the range 0.5-50 µg/mL (r > 0.99). This LC-MS-MS procedure was used to assess the bioavailability of two piracetam formulations: piracetam + l-carnitine (Piracar®; 270/330 mg tablet) and piracetam (Nootropil®; 800 mg tablet) in healthy volunteers of both sexes. The geometric means with corresponding 90% confidence interval (CI) for test/reference percentage ratios were 88.49% (90% CI = 81.19 - 96.46) for peak concentration/dose and 102.55% (90% CI = 100.62 - 104.51) for AUCinf /dose. The limit of quantitation of 0.5 µg/mL is well suited for pharmacokinetic studies in healthy volunteers. It was concluded that piracetam (Piracar®; 270/330 mg tablet) has a bioavailability equivalent to the piracetam (Nootropil®; 800 mg tablet) formulation with regard to both the rate and the extent of absorption.
Asunto(s)
Carnitina/sangre , Fármacos Neuroprotectores/sangre , Piracetam/sangre , Administración Oral , Adolescente , Adulto , Disponibilidad Biológica , Carnitina/administración & dosificación , Cromatografía Líquida de Alta Presión/métodos , Femenino , Voluntarios Sanos , Humanos , Límite de Detección , Masculino , Persona de Mediana Edad , Fármacos Neuroprotectores/administración & dosificación , Piracetam/administración & dosificación , Espectrometría de Masa por Ionización de Electrospray/métodos , Comprimidos , Espectrometría de Masas en Tándem/métodos , Adulto JovenRESUMEN
BACKGROUND: Free amino acids and acylcarnitines circulating in the blood can be used for diagnosis for metabolic illness and imbalances. To date, the normal reference ranges of amino acids and acylcarnitines in horse peripheral blood have not been established. In this study, the concentrations of 12 amino acids and 26 acylcarnitines were determined by tandem mass spectrometry in complete blood from 100 healthy horses (50 Quarter horses (QH) [23 males and 27 females] and 50 American Miniature horses (AMH) [15 males and 35 females]) with no signs of metabolic disease. The means and standard deviations were determined and data statistically analyzed. FINDINGS: Concentrations of short, medium, and long chain acylcarnitines were significantly higher in male AMH than in male QH. The concentrations of the amino acids alanine, arginine, glycine, proline (glycogenic), and leucine (ketogenic) were higher in the QH than in the AMH. Female AMH had higher concentrations of propionylcarnitine, leucine, proline, arginine, and ornithine than female QH. CONCLUSIONS: Normal reference ranges of amino acids and acylcarnitines were established for AMH and QH. Significant differences were found in concentration of these compounds between breeds and gender.