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Introduction: Carnitine O-octanoyltransferase (CROT) is a well-established peroxisomal enzyme involved in liver fatty acid oxidation, but less is known about its recently discovered role in promoting vascular calcification, and whether CROT-dependent liver metabolism contributes to the latter. To date, CROT function in the context of calcification potential has been conducted in the dyslipidemic low-density lipoprotein receptor-deficient (Ldlr-/-) mice. Objectives: To differentiate peroxisome and CROT-dependent lipid biology from that of lipoprotein-mediated lipid biology, we therefore conducted a metabolomic analysis of the liver and plasma of normolipidemic CROT-deficient (Crot-/-) mice. Methods: We performed LC-MS-based metabolomics on liver and plasma derived from Crot-/- and Crot +/- mice and sibling Crot+/+ mice, using a dual-phase metabolite extraction protocol, and multiple LC-MS acquisition strategies. Results: We identified between 79 to 453 annotated metabolites from annotated metabolites from liver samples, and 117 to 424 annotated metabolites from plasma samples. Through differential abundance analysis, we determined that omega-3 fatty acids such as EPA, DPA, and DHA were higher in the liver of Crot-/- and Crot +/- mice than Crot+/+ mice. EPA were higher in plasma of Crot-/- mice than Crot+/+ mice. We also determined that the anti-inflammatory dicarboxylic acids, tetradecanedioic acid and azelaic acid, were higher in the plasma of CROT-deficient mice. Conclusion: Our study associated genetic CROT deletion with increased levels of anti-inflammatory molecules in mouse liver and plasma. These results suggest a potential mechanism for anti-calcification effects of CROT suppression and the potential use of omega-3 fatty acids as biomarkers for future CROT inhibition therapies.
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BACKGROUND: Long-chain acyl-carnitines (ACs) are potential arrhythmogenic metabolites. Their role in atrial fibrillation (AF) remains incompletely understood. Using a systems medicine approach, we assessed the contribution of C18:1AC to AF by analysing its in vitro effects on cardiac electrophysiology and metabolism, and translated our findings into the human setting. METHODS AND RESULTS: Human iPSC-derived engineered heart tissue was exposed to C18:1AC. A biphasic effect on contractile force was observed: short exposure enhanced contractile force, but elicited spontaneous contractions and impaired Ca2+ handling. Continuous exposure provoked an impairment of contractile force. In human atrial mitochondria from AF individuals, C18:1AC inhibited respiration. In a population-based cohort as well as a cohort of patients, high C18:1AC serum concentrations were associated with the incidence and prevalence of AF. CONCLUSION: Our data provide evidence for an arrhythmogenic potential of the metabolite C18:1AC. The metabolite interferes with mitochondrial metabolism, thereby contributing to contractile dysfunction and shows predictive potential as novel circulating biomarker for risk of AF.
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Fibrilação Atrial , Humanos , Átrios do Coração , Mitocôndrias , Contração Muscular , RespiraçãoRESUMO
A high-salt diet significantly impacts various diseases, ilncluding cancer and immune diseases. Recent studies suggest that the high-salt/hyperosmotic environment in the body may alter the chronic properties of cancer and immune cells in the disease context. However, little is known about the acute metabolic changes in hyperosmotic stress. Here, we found that hyperosmotic stress for a few minutes induces Warburg-like metabolic remodeling in HeLa and Raw264.7 cells and suppresses fatty acid oxidation. Regarding Warburg-like remodeling, we determined that the pyruvate dehydrogenase phosphorylation status was altered bidirectionally (high in hyperosmolarity and low in hypoosmolarity) to osmotic stress in isolated mitochondria, suggesting that mitochondria themselves have an acute osmosensing mechanism. Additionally, we demonstrate that Warburg-like remodeling is required for HeLa cells to maintain ATP levels and survive under hyperosmotic conditions. Collectively, our findings suggest that cells exhibit acute metabolic remodeling under osmotic stress via the regulation of pyruvate dehydrogenase phosphorylation by direct osmosensing within mitochondria.
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Mitocôndrias , Pressão Osmótica , Oxirredutases , Piruvatos , Humanos , Células HeLa , Mitocôndrias/metabolismo , Oxirredutases/metabolismo , Fosforilação , Piruvatos/metabolismo , Células RAW 264.7 , Animais , CamundongosRESUMO
Metabolite profiles of normal and defective dry, firm and dark (DFD) meat extracts with known ultimate pH (pHu) values were determined by Orbitrap Tribrid ID-X untargeted analysis coupled to chemometrics. An intelligent MS3 AcquireXTM workflow firstly approached the unambiguous characterization of detected features that were subsequently quantified by a complementary MS1 study of biological replicates. Chemometric research revealed how threonylphenylalanine (overexpressed in normal meats) together to tetradecadienoyl- and hydroxydodecanoyl-carnitines (both overexpressed in DFD meats) appropriately grouped meat groups assayed. Robustness of such biomarkers was confirmed through a time-delayed study of a blind set of samples (unknown pHu) and evidenced limitations of pHu as an isolated parameter for accurate meat quality differentiation. Other acyl-carnitines also characterized DFD samples, suggesting interferences induced by pre-slaughter stress (PSS) on lipid catabolism that would explain accumulation of such intermediate metabolites. Results achieved can ease understanding of biochemical mechanisms underlying meat quality defects.
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Quimiometria , Carne , Carne/análise , Biomarcadores , Concentração de Íons de Hidrogênio , MetabolômicaRESUMO
OBJECTIVES: The aim of this study is to determine the plasma free carnitine and acyl-carnitine levels at the time of diabetic ketoacidosis (DKA) diagnosis, and at the end of DKA treatment and to investigate their association with the duration of DKA treatment in children with DKA. METHODS: A total of 40 children with DKA who were treated consecutively in a tertiary health center for DKA were included in the study. The median age of the children was 11.3 years (1.1-17.5) and 25 of them (62.5%) were girls. In addition to routine blood tests, plasma free carnitine and acyl-carnitine levels were measured just before the start of intravenous insulin therapy and at the time of discontinuation of intravenous insulin therapy when DKA therapy was completed. RESULTS: There was no difference in plasma free carnitine and acyl-carnitine levels before and after DKA treatment (p=0.776 and p=0.743 respectively). However, while the frequency of low plasma free carnitine was 30% at the beginning of the treatment, it was observed that this frequency was 20% at the end of the DKA treatment. There was no correlation between duration of DKA treatment and plasma free carnitine or acyl-carnitine levels at admission (p=0.497, r=-0.111 and p=0.474, r=0.116 respectively). CONCLUSIONS: There is no a relationship between duration of DKA treatment and plasma free carnitine or acyl-carnitine level at admission in children with DKA.
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Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Criança , Feminino , Humanos , Masculino , Cetoacidose Diabética/etiologia , Cetoacidose Diabética/terapia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina , CarnitinaRESUMO
Background: The purpose of the study was to investigate the levels of amino acids and acylcarnitines in newborns of the Tibet Autonomous Region for the first time and to provide an experimental basis for the diagnosis of genetic metabolic diseases. Methods: We detected concentrations of 43 kinds of amino acids, acylcarnitines and succinylacetone in the dried blood spots of 18482 newborns using liquid chromatography tandem mass spectrometry and diagnose the case by gene sequencing. We compared the indexes between Tibet and our lab, where most data come from an inland area and Han Chinese people. Then we compared amino acid and acylcarnitine levels of seven regions in Tibet and explored their impact factors. Results: We described the levels of amino acids and acylcarnitines in Tibet newborns using 95% confidence intervals. The distribution of amino acid and acylcarnitines were different in Tibet. Conclusion: This study has contributed to filling in the blanks of Tibet newborn screening, which should be considered in the newborn metabolic disease screening in this area.
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INTRODUCTION: Monitoring metabolic biomarkers could be utilized as an effective tool for the early detection of gastric cancer (GC) risk. OBJECTIVE: We aimed to discover predictive serum biomarkers for GC and investigate biomarker-related metabolism. METHODS: Subjects were randomly selected from the Korean Cancer Prevention Study-II cohort and matched by age and sex. We analyzed baseline serum samples of 160 subjects (discovery set; control and GC occurrence group, 80 each) via nontargeted screening. Identified putative biomarkers were validated in baseline serum samples of 140 subjects (validation set; control and GC occurrence group, 70 each) using targeted metabolites analysis. RESULTS: The final analysis was conducted on the discovery set (control, n = 52 vs. GC occurrence, n = 50) and the validation set (control, n = 43 vs. GC occurrence, n = 44) applying exclusion conditions. Eighteen putative metabolite sets differed between two groups found on nontargeted metabolic screening. We focused on fatty acid-related energy metabolism. In targeted analysis, levels of decanoyl-L-carnitine (p = 0.019), L-carnitine (p = 0.033), and citric acid (p = 0.025) were significantly lower in the GC occurrence group, even after adjusting for age, sex, and smoking status. Additionally, L-carnitine and citric acid were confirmed to have an independently significant relationship to GC development. Notably, alkaline phosphatase showed a significant correlation with these two biomarkers. CONCLUSION: Changes in serum L-carnitine and citric acid levels that may result from alterations of fatty-acid-related energy metabolism are expected to be valuable biomarkers for the early diagnosis of GC risk.
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Neoplasias Gástricas , Fosfatase Alcalina , Biomarcadores , Carnitina , Ácido Cítrico , Humanos , Metabolômica , República da Coreia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismoRESUMO
Objective: This study is designed to investigate the levels of carnitine and acylcarnitines (ACs) in the children with diabetes type 1 compared to the healthy subjects.Methods: Forty-two type 1 diabetic children and healthy subjects were recruited in the study, respectively. In addition to FBS and Hb A1C, free carnitine and ACs in butyl-ester form in the fasting blood samples were assessed by isotope dilution mass spectrometry for all diabetics and controls using the tandem mass spectrometry system.Results: Diabetic patients had a higher level of C, C4, C6, C14, C18:2, and C18:2OH. Females had elevated C14:2 compared to the males. The C18:2 and C18:2OH levels were elevated as the Hb A1C level increased. The C18:2, C14OH were mostly increased in the prediabetic and diabetic patients, respectively.Conclusion: Increased ACs level indicates the increased acyl-CoA intermediates for the fatty acids and amino acids oxidation.
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Diabetes Mellitus Tipo 1 , Aminoácidos , Carnitina/análogos & derivados , Carnitina/metabolismo , Criança , Coenzima A , Ésteres , Ácidos Graxos/metabolismo , Feminino , Hemoglobinas Glicadas , Humanos , Isótopos , MasculinoRESUMO
The western dietary pattern is known for its frequent meals rich in saturated fat and protein, resulting in a postprandial state for a large part of the day. Therefore, our aim was to investigate the postprandial glucose and lipid metabolism in response to high (HP) or normal (NP) protein, high-fat hypercaloric diet and to identify early biomarkers of protein intake and hepatic lipid accumulation. In a crossover design, 17 healthy subjects were randomly assigned to consume a HP or NP hypercaloric diet for two weeks. In parallel, a control group (CD; n = 10) consumed a weight-maintaining control diet. Biomarkers of postprandial lipid and glucose metabolism were measured in 24 h urine and in plasma before and following a meal challenge. The metabolic profile of urine but not plasma, showed increased excretion of 13C, carnitine and short chain acyl-carnitines after adaptation to the HP diet. Urinary excretion of decatrienoylcarnitine and octenoylcarnitine increased after adaptation to the NP diet. Our results suggest that the higher excretion of short-chain urinary acyl-carnitines could facilitate the elimination of excess fat of the HP diet and thereby reduce hepatic fat accumulation previously reported, whereas the higher excretion medium-chains acyl-carnitine could be early biomarkers of hepatic lipid accumulation.
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Carnitina/análogos & derivados , Dieta Hiperlipídica/efeitos adversos , Dieta Rica em Proteínas/efeitos adversos , Dieta Ocidental/efeitos adversos , Síndrome Metabólica/diagnóstico , Adulto , Biomarcadores/urina , Carnitina/metabolismo , Carnitina/urina , Estudos Cross-Over , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Proteínas Alimentares/metabolismo , Ingestão de Energia/fisiologia , Feminino , Glucose/metabolismo , Voluntários Saudáveis , Humanos , Metabolismo dos Lipídeos/fisiologia , Fígado/metabolismo , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/urina , Período Pós-Prandial/fisiologia , Eliminação Renal/fisiologia , Adulto JovemRESUMO
The SLC25A20 transporter, also known as carnitine acyl-carnitine carrier (CAC), catalyzes the transport of short, medium and long carbon chain acyl-carnitines across the mitochondrial inner membrane in exchange for carnitine. The 30-year story of the protein responsible for this function started with its purification from rat liver mitochondria. Even though its 3D structure is not yet available, CAC is one of the most deeply characterized transport proteins of the inner mitochondrial membrane. Other than functional, kinetic and mechanistic data, post-translational modifications regulating the transport activity of CAC have been revealed. CAC interactions with drugs or xenobiotics relevant to human health and toxicology and the response of the carrier function to dietary compounds have been discovered. Exploiting combined approaches of site-directed mutagenesis with chemical targeting and bioinformatics, a large set of data on structure/function relationships have been obtained, giving novel information on the molecular mechanism of the transport catalyzed by this protein.
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Carnitina/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Mitocôndrias/metabolismo , Sítios de Ligação , Carnitina/química , Glutationa/química , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/química , Sulfeto de Hidrogênio/metabolismo , Oxirredução , Especificidade por SubstratoRESUMO
Carnitine acyl-carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of mitochondrial long-chain fatty-acid transport. Most patients present in the first 2 days of life, with hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy or arrhythmia, hepatomegaly and elevated liver enzymes. Multi-centre international retrospective chart review of clinical presentation, biochemistry, treatment modalities including diet, subsequent complications, and mode of death of all patients. Twenty-three patients from nine tertiary metabolic units were identified. Seven attenuated patients of Pakistani heritage, six of these homozygous c.82G>T, had later onset manifestations and long-term survival without chronic hyperammonemia. Of the 16 classical cases, 15 had cardiac involvement at presentation comprising cardiac arrhythmias (9/15), cardiac arrest (7/15), and cardiac hypertrophy (9/15). Where recorded, ammonia levels were elevated in all but one severe case (13/14 measured) and 14/16 had hypoglycaemia. Nine classical patients survived longer-term-most with feeding difficulties and cognitive delay. Hyperammonaemia appears refractory to ammonia scavenger treatment and carglumic acid, but responds well to high glucose delivery during acute metabolic crises. High-energy intake seems necessary to prevent decompensation. Anaplerosis utilising therapeutic d,l-3-hydroxybutyrate, Triheptanoin and increased protein intake, appeared to improve chronic hyperammonemia and metabolic stability where trialled in individual cases. CACTD is a rare disorder of fatty acid oxidation with a preponderance to severe cardiac dysfunction. Long-term survival is possible in classical early-onset cases with long-chain fat restriction, judicious use of glucose infusions, and medium chain triglyceride supplementation. Adjunctive therapies supporting anaplerosis may improve longer-term outcomes.
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Carnitina Aciltransferases/deficiência , Carnitina/uso terapêutico , Dieta com Restrição de Gorduras , Erros Inatos do Metabolismo Lipídico/dietoterapia , Erros Inatos do Metabolismo Lipídico/tratamento farmacológico , Suplementos Nutricionais , Humanos , Recém-Nascido , Internacionalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Biomarker discovery and implementation are at the forefront of the precision medicine movement. Modern advances in the field of metabolomics afford the opportunity to readily identify new metabolite biomarkers across a wide array of disciplines. Many of the metabolites are derived from or directly reflective of mitochondrial metabolism. L-carnitine and acylcarnitines are established mitochondrial biomarkers used to screen neonates for a series of genetic disorders affecting fatty acid oxidation, known as the inborn errors of metabolism. However, L-carnitine and acylcarnitines are not routinely measured beyond this screening, despite the growing evidence that shows their clinical utility outside of these disorders. Measurements of the carnitine pool have been used to identify the disease and prognosticate mortality among disorders such as diabetes, sepsis, cancer, and heart failure, as well as identify subjects experiencing adverse drug reactions from various medications like valproic acid, clofazimine, zidovudine, cisplatin, propofol, and cyclosporine. The aim of this review is to collect and interpret the literature evidence supporting the clinical biomarker application of L-carnitine and acylcarnitines. Further study of these metabolites could ultimately provide mechanistic insights that guide therapeutic decisions and elucidate new pharmacologic targets.
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BACKGROUND: Ketone bodies form a vital energy source for end organs in a variety of physiological circumstances. At different times, the heart, brain and skeletal muscle in particular can use ketones as a primary substrate. Failure to generate ketones in such circumstances leads to compromised energy delivery, critical end-organ dysfunction and potentially death. There are a range of inborn errors of metabolism (IEM) affecting ketone body production that can present in this way, including disorders of carnitine transport into the mitochondrion, mitochondrial fatty acid oxidation deficiencies (MFAOD) and ketone body synthesis. In situations of acute energy deficit, management of IEM typically entails circumventing the enzyme deficiency with replenishment of energy requirements. Due to profound multi-organ failure it is often difficult to provide optimal enteral therapy in such situations and rescue with sodium DL-3-hydroxybutyrate (S DL-3-OHB) has been attempted in these conditions as documented in this paper. RESULTS: We present 3 cases of metabolic decompensation, one with carnitine-acyl-carnitine translocase deficiency (CACTD) another with 3-hydroxyl, 3-methyl, glutaryl CoA lyase deficiency (HMGCLD) and a third with carnitine palmitoyl transferase II deficiency (CPT2D). All of these disorders are frequently associated with death in circumstance where catastrophic acute metabolic deterioration occurs. Intensive therapy with adjunctive S DL-3OHB led to rapid and sustained recovery in all. Alternative therapies are scarce in these situations. CONCLUSION: S DL-3-OHB has been utilised in multiple acyl co A dehydrogenase deficiency (MADD) in cases with acute neurological and cardiac compromise with long-term data awaiting publication. The use of S DL-3-OHB is novel in non-MADD fat oxidation disorders and contribute to the argument for more widespread use.
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Ácidos Graxos , Sódio , Ácido 3-Hidroxibutírico , Carnitina , Humanos , Corpos Cetônicos , CetonasRESUMO
Intoxication by xenobiotics triggers the perturbation of metabolic fingerprints in biofluids, including the accumulation of xenobiotic compounds and the dysregulation of endogenous metabolites. In this work, an untargeted metabolomics workflow was developed to simultaneously profile both xenobiotic and endogenous metabolites for the identification of the xenobiotic origin and an in-depth understanding of the intoxication mechanism. This workflow was demonstrated in a real-world clinical case. Plasma samples were collected from four intoxicated children and another three healthy children. Untargeted metabolomics analysis was performed using ultraperformance liquid chromatography (UPLC) coupled to a high-resolution mass spectrometer (HRMS) with data-independent MSE acquisition. LC-MSE data was processed using an untargeted metabolomics data interpretation workflow, in which the identities of xenobiotics and altered endogenous metabolic features were determined via database searching. Five xenobiotic chemicals and 19 endogenous metabolites were found to be dysregulated. Combined with the clinical evidence, penfluridol was confirmed as the xenobiotic toxin. Furthermore, a mechanistic hypothesis was developed to explain the dysregulation of the four endogenous acyl-carnitines. This workflow can be readily applied to a wide range of clinical toxicology cases, offering a powerful and convenient means of simultaneous discovery of intoxication source and the understanding of intoxication mechanisms.
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Metaboloma , Metabolômica/métodos , Toxicologia/métodos , Xenobióticos , Estudos de Casos e Controles , Pré-Escolar , Cromatografia Líquida/métodos , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Metaboloma/efeitos dos fármacos , Metaboloma/fisiologia , Xenobióticos/sangue , Xenobióticos/metabolismo , Xenobióticos/toxicidadeRESUMO
Liquid chromatography-mass spectrometry (LC-MS) is a widely used methodology for measuring lipids at a global level. Combined with an optimal extraction method LC-MS enables the detection and characterization of a wide range of lipid species even of low abundance. Here, we describe two extraction- and LC-MS-based quantitative analytical methods for lipid, acyl-CoA, and acyl-carnitine analyses from either mouse C2C12 myotubes or mouse skeletal tissue. We also describe the use of 13C16-palmitate and its incorporation into acyl-carnitines to show how stable isotope tracers are metabolized within cells and therefore can be implemented for lipidomic flux analysis.
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Cromatografia Líquida , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Espectrometria de Massas em Tandem , Animais , Camundongos , Fibras Musculares Esqueléticas/citologia , Músculo Esquelético/citologiaRESUMO
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that shown a close association with impaired lipid metabolism. The acyl-carnitine spectrum status in Chinese children with ASD has not been reported. In this study, we assessed the levels of blood acyl-carnitines in Chinese children with ASD and examined the relation between acyl-carnitine profiles and the intelligence levels. Blood levels of acyl-carnitines were determined by tandem mass spectrometry in 60 children with ASD and 30 typically developing children. Chinese Wechsler Young Children Scale of Intelligence (C-WYCSI) was used in ASD group. Blood levels of free carnitine, glutaricyl carnitine, octyl carnitine, twenty four carbonyl carnitine and carnosyl carnitine in the ASD group were significantly lower than those in the control group. Glutaryl carnitine and carnosyl carnitine might be potential biomarkers for diagnosis of ASD. The changes in the acyl-carnitine spectrum indicate potential mitochondrial dysfunction and abnormal fatty acid metabolism in preschool ASD children.
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Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/diagnóstico , Carnitina/análogos & derivados , Transtorno do Espectro Autista/epidemiologia , Biomarcadores/sangue , Carnitina/sangue , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Inteligência/fisiologia , Masculino , Transtornos do Neurodesenvolvimento/sangue , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/epidemiologiaRESUMO
BACKGROUND: Children with long-chain fatty acid ß-oxidation disorders (LCFAOD) presenting with clinical symptoms are treated with a specialist infant formula, with medium chain triglyceride (MCT) mainly replacing long chain triglyceride (LCT). It is essential that the safety and efficacy of any new specialist formula designed for LCFAOD be tested in infants and children. METHODS: In an open-label, 21-day, phase I trial, we studied the safety of a new MCT-based formula (feed 1) in six well-controlled children (three male), aged 7-13 years (median 9 years) with LCFAOD (very long chain acyl CoA dehydrogenase deficiency [VLCADD], n=2; long chain 3-hydroxyacyl CoA dehydrogenase deficiency [LCHADD], n=2; carnitine acyl carnitine translocase deficiency [CACTD], n=2). Feed 1 (Lipistart; Vitaflo) contained 30% energy from MCT, 7.5% LCT and 3% linoleic acid and it was compared with a conventional MCT feed (Monogen; Nutricia) (feed 2) containing 17% energy from MCT, 3% LCT and 1.1% linoleic acid. Subjects consumed feed 2 for 7 days then feed 1 for 7 days and finally resumed feed 2 for 7 days. Vital signs, blood biochemistry, ECG, weight, height, food/feed intake and symptoms were monitored. RESULTS: Five subjects completed the study. Their median daily volume of both feeds was 720 mL (range 500-1900 mL/day). Feed 1 was associated with minimal changes in tolerance, free fatty acids (FFA), acylcarnitines, 3-hydroxybutyrate (3-HB), creatine kinase (CK), blood glucose, liver enzymes and no change in an electrocardiogram (ECG). No child complained of muscle pain or symptoms associated with LCFAOD on either feed. CONCLUSIONS: This is the first safety trial reported of an MCT formula specifically designed for infants and children with LCFAOD. In this short-term study, it appeared safe and well tolerated in this challenging group.
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3-Hidroxiacil-CoA Desidrogenases/deficiência , Acil-CoA Desidrogenase de Cadeia Longa/deficiência , Carnitina Aciltransferases/deficiência , Erros Inatos do Metabolismo Lipídico/dietoterapia , Doenças Mitocondriais/dietoterapia , Doenças Musculares/dietoterapia , Triglicerídeos/administração & dosagem , Adolescente , Criança , Síndrome Congênita de Insuficiência da Medula Óssea , Feminino , Humanos , Masculino , Triglicerídeos/efeitos adversosRESUMO
BACKGROUND: Hard ticks are the main vectors of tick-borne encephalitis virus (TBEV). Free carnitine (FC) and acylcarnitines (AC) have the basic role in ß-oxidation as well as the modulation of immune and nervous system. Homeostasis of carnitines in the TBE patients was not studied so far. OBJECTIVES: This study aimed to evaluate FC and AC serum concentrations in patients with meningitis due to TBEV infection before and after 14 ± 3 days of treatment. MATERIAL AND METHODS: The study was performed in 14 patients aged 48 ± 29 years that were divided a posteriori (based on their FC level before and after treatment) into 2 subgroups: 1-8 and 9-14. Diagnosis was based on the neurological, serological and pleocytosis evaluation. RESULTS: The FC level in patients 1-8 before treatment (24.1 ± 8.1) was significantly lower than in patients post-treatment (34.4 ± 8.3), lower than in the control group (40.5 ± 7.6), and lower than in patients 9-14 before treatment (40.0 ± 13.5) but not lower than in the patients 9-14 after treatment (24.7 ± 7.3 µmol/L), respectively, p < 0.05. AC concentration in the patients 1-8 before treatment (4.7 ± 2.2) was apparently lower than in patients post-treatment (9.5 ± 3.9 µmol/L) but the values were not significantly different. In patients 9-14 before treatment the AC concentration (16.3 ± 12.6) was higher than in patients after treatment (5.3 ± 4.0 µmol/L), but the difference was not statistically significant. CONCLUSIONS: FC and AC homeostasis in circulation was disturbed in the patients with meningitis due to TBEV infection patients. The mean levels of FC and AC in 60% of the patients were below the normal range but normalized after treatment whereas in 40% of the patients they were near or at a normal range and significantly decreased after treatment. Explanation of this intriguing finding and its clinical significance is not easy without further studies.
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Carnitina/análogos & derivados , Carnitina/sangue , Vírus da Encefalite Transmitidos por Carrapatos/isolamento & purificação , Encefalite Transmitida por Carrapatos/sangue , Meningite/sangue , Adulto , Idoso , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vírus da Encefalite Transmitidos por Carrapatos/imunologia , Vírus da Encefalite Transmitidos por Carrapatos/fisiologia , Encefalite Transmitida por Carrapatos/complicações , Encefalite Transmitida por Carrapatos/virologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Meningite/complicações , Meningite/terapia , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
We report three patients with elevations of propionylcarnitine (C3), one without elevations of 2-methylcitrate and 3-hydroxypropionate in urine organic acid analysis, and the other two showing only mild elevations, all of whom were subsequently confirmed to have propionic acidemia by molecular analysis of PCCA and PCCB genes. To date, they have had a mild clinical course. These cases illustrate the importance of considering high C3 as the only biochemical abnormality in a diagnosis of propionic acidemia. Since mild C3 elevations may be overlooked and considered non-diagnostic in isolation, we advise considering a diagnosis of propionic acidemia even in the absence of significant elevations 2-methylcitrate or 3-hydroxypropionate in urine organic acid analysis.
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The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs) and surface-deacetylated (SDA) CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations of CNFs and SDACNFs. Healthy female mice (six-week-old) were fed a normal diet and administered tap water with 0.1% (v/v) CNFs or SDACNFs for 28 days. Oral administration of CNFs increased plasma levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and serotonin (5-hydroxytryptamine, 5-HT). Oral administration of SDACNFs affected the metabolisms of acyl-carnitines and fatty acids. The fecal organic level analysis indicated that oral administration of CNFs stimulated and activated the functions of microbiota. These results indicate that oral administration of CNFs increases plasma levels of ATP and 5-HT via activation of gut microbiota.