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1.
Biol Trace Elem Res ; 200(1): 281-297, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33624220

RESUMO

Given environmental contamination with toxic metals, diets that promote the elimination of these metals from the body of individuals, including those suffering from obesity, are urgently needed. The aim of this study was to determine the effects of supplementation with resveratrol (Res), L-carnitine (L-Car), tyrosine (Tyr), and tryptophan (Trp) on the content of trace elements in the organs of mice. DBA/2J mice and DBCB tetrahybrid mice received diets high in carbohydrate and fat supplemented with Res, L-Car, Tyr, or Trp for 65 days. In the liver, kidneys, and brain, the contents of 18 elements, including Al, As, Cu, Fe, Mn, Pb, Se, and Zn, were determined by inductively coupled plasma mass spectrometry. Res, L-Car, Tyr, and Trp had minimal or no effect on the essential elements (Fe, Mg, Cu, Zn, Se) in all organs studied. The Mn content notably increased in the organs of mice consuming L-Car and Trp. Mn accumulation was stimulated by Res in organs exclusively in DBCB mice and by Tyr exclusively in livers and brains of DBA/2J mice. Al levels were significantly reduced by L-Car and Trp in all organs of the mice, by Res in only DBCB mice, and by Tyr in only kidneys and livers of DBA/2J mice. In addition, L-Car and Trp decreased Pb accumulation in most organs of mice. Res and Tyr also inhibited Pb accumulation in some cases. Thus, the studied supplements affected the metabolism of trace elements, which may contribute to dietary treatments for obese individuals.


Assuntos
Oligoelementos , Aminoácidos Aromáticos , Animais , Carnitina/farmacologia , Dieta Hiperlipídica , Suplementos Nutricionais/análise , Camundongos , Camundongos Endogâmicos DBA , Obesidade/tratamento farmacológico , Resveratrol/farmacologia
2.
Intern Med ; 60(22): 3533-3542, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776465

RESUMO

Objective In the present study, we prospectively examined the efficacy of levocarnitine in relieving symptoms of fatigue in patients with cirrhosis but without overt hepatic encephalopathy. Methods Twenty-one cirrhotic patients who were able to undergo fatigue symptom evaluations at our institution were enrolled. A total of 12 cirrhotic patients underwent levocarnitine treatment (1,200-1,800 mg/day), while 9 did not undergo levocarnitine treatment. As primary endpoints, we investigated whether or not levocarnitine treatment exerted any beneficial effects by assessing the symptoms of fatigue [8-item Short-Form Health Survey (SF-8) and Fisk Fatigue Severity Score (FFSS)] at baseline and three months after treatment. Furthermore, as exploratory secondary endpoints, we investigated whether or not levocarnitine treatment exerted ameliorative effects on oxidative stress by assessing the serum thioredoxin (TRX) and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Results The median age of the patients was 73 years old. Three men and 18 women were categorized by their Child-Pugh class (A and B in 14 and 7 patients, respectively). There were no significant differences in the clinical laboratory values between the two groups. The FFSS and SF-8 scores were significantly improved in the patients with cirrhosis who underwent levocarnitine treatment (p<0.01) but not in those who did not undergo levocarnitine treatment. Furthermore, three months after levocarnitine treatment, the serum carnitine concentrations were significantly increased, and the serum thioredoxin levels were decreased in the patients with cirrhosis who underwent levocarnitine treatment (p<0.05). Conclusion These results suggest that levocarnitine treatment may relieve symptoms of fatigue in cirrhotic patients by reducing oxidative stress.


Assuntos
Encefalopatia Hepática , Idoso , Carnitina , Fadiga/tratamento farmacológico , Fadiga/etiologia , Feminino , Encefalopatia Hepática/tratamento farmacológico , Encefalopatia Hepática/etiologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Masculino
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(11): 1051-1054, 2021 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-34729741

RESUMO

OBJECTIVE: To analyze the metabolic profile and genetic variants for newborns with primary carnitine deficiency (PCD) from Guangxi, China. METHODS: From January 2014 to December 2019, 400 575 newborns from the jurisdiction of Guangxi Zhuang Autonomous Region Newborn Screening Center were subjected to tandem mass spectrometry (MS/MS) analysis. Newborns with positive results for PCD and their mothers were recalled for retesting. Those who were still positive were subjected to sequencing of the SLC22A5 gene. RESULTS: Twenty-two newborns and 9 mothers were diagnosed with PCD, which gave a prevalence rate of 1/18 208. Sequencing of 18 newborns and 4 mothers have identified 14 types of SLC22A5 gene variants, with the common ones including c.51C>G (10/44, 22.7%), c.1195C>T (9/44, 20.5%) and c.1400C>G (7/44, 15.9%), The c.517delC(p.L173Cfs*3) and c.1031C>T(p.T344I) were unreported previously and predicted to be pathogenic (PVS1+PM2_supporting+PM3+PP4) and likely pathogenic (PM1+PM2_supporting+PM3+PP3+PP4) based on the American College of Medical Genetics and Genomics standards and guidelines. CONCLUSION: c.51C>G, c.1195C>T and c.1400C>G are the most common variants underlying PCD in Guangxi.


Assuntos
Metaboloma , Espectrometria de Massas em Tandem , Cardiomiopatias , Carnitina/deficiência , China , Humanos , Hiperamonemia , Recém-Nascido , Doenças Musculares , Mutação , Membro 5 da Família 22 de Carreadores de Soluto/genética
4.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 589-593, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821089

RESUMO

Objective: To investigate the protective effects of L-carnitine (LC) on lipopolysaccharide (LPS) - injured mouse pulmonary microvascular endothelial cells (PMVECs) and its effects on autophagy and apoptosis. Methods: Cultured mouse PMVECs were divided into three groups: ① Control group, ② LPS group (10 µg/ml, 3, 6, 12, 24 h), ③ LPS (10 µg/ml, 24 h)+LC (2.5, 5.0, 10 µg/ml) (LPS+LC) group. PMVECs apoptosis was examined by Annexin V-FITC/PI double labeling method. Autophagosome was detected by immunofluorescence staining. Levels of autophagy-related protein LC3 and apoptosis-related protein caspase-3 were detected by Western blot. PMVECs viability was measured by CCK-8. Results: ① Compared with the control group, LPS treatment inhibited the PMVECs viability significantly, whereas the apoptosis rate and the expression of autophagy protein LC3 II were markedly increased after LPS treatment for 6 h, 12 h and 24 h. ② Compared with LPS group (10 µg/ml, 24 h), the PMVECs viability, levels of autophagy protein LC3 II and caspase-3 protein expression as well as apoptosis rate in LPS+LC group were increased significantly. Conclusion: LC can increase the activity of PMVECs injuried by LPS, promote autophagy and inhibit apoptosis of PMVECs.


Assuntos
Células Endoteliais , Lipopolissacarídeos , Animais , Apoptose , Autofagia , Carnitina , Camundongos
5.
Arq Bras Cardiol ; 117(4): 715-725, 2021 10.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34709299

RESUMO

BACKGROUND: L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. OBJECTIVES: The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. METHODS: Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. RESULTS: Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). CONCLUSION: The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.


Assuntos
Diabetes Mellitus Experimental , Receptores de Quimiocinas , Animais , Carnitina/farmacologia , Quimiocinas , Diabetes Mellitus Experimental/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico
7.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(4): 481-486, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34704420

RESUMO

To investigate the value of very long chain acylcarnitine (VLCAC) and lysophosphatidylcholine (LPC) in screening of peroxisomal disease in children. Eighteen children with peroxisomal disease, including 14 cases of X-linked adrenoleukodystrophy (X-ALD group) and 4 cases of Zellweger syndrome (ZS group) diagnosed based on clinical symptoms, MRI and genetic tests were enrolled in the study; and 200 healthy children were selected as control group. Samples of dried blood spots were collected from all subjects, VLCAC and LPC in dried blood spots were extracted by solvent containing internal isotopic standards hexacosanoylcarnitine (H-C26) and C26:0 lysophosphatidylcholine (H-C26:0-LPC). The eicosanoylcarnitine (C20), docosanoylcarnitine (C22), tetracosanoylcarnitine (C24), hexacosanoylcarnitine (C26), C20:0 lysophosphatidylcholine (C20:0-LPC), C22:0 lysophosphatidylcholine (C22:0-LPC), C24:0 lysophosphatidylcholine (C24:0-LPC) and C26:0 lysophosphatidylcholine (C26:0-LPC) were detected by tandem mass spectrometry (MS/MS). The above 8 indicators and the ratios were compared among the groups using Kruskal-Wallis test and Mann-Whitney test; the contribution of each index to the disease were analyzed by partial least square method. Except C24:0-LPC/C20:0-LPC, there were significant differences in all indicators and ratios among all groups (<0.05 or <0.01). There were differences in most indicators and ratios between X-ALD group and the control group, as well as between ZS group and the control group, but there was no difference between the X-ALD group and the ZS group. PLS-DA analysis showed that the peroxisome disease group (including X-ALD group and ZS group) and the control group were able to be completely separated, and C26 had the highest variable importance for the projection (VIP) value. MS/MS detection of VLCAC and LPC can be used as a screening method for peroxisomal disease, and C26 may be a sensitive indicator for diagnosis.


Assuntos
Lisofosfatidilcolinas , Espectrometria de Massas em Tandem , Carnitina/análogos & derivados , Criança , Teste em Amostras de Sangue Seco , Humanos
8.
Nutrients ; 13(10)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34684667

RESUMO

Are free carnitine concentrations on newborn screening (NBS) 48-72 h after birth lower in patients who develop type 1 diabetes than in controls? A retrospective case-control study of patients with type 1 diabetes was conducted. NBS results of patients from a Sydney hospital were compared against matched controls from the same hospital (1:5). Multiple imputation was performed for estimating missing data (gestational age) using gender and birthweight. Conditional logistic regression was used to control for confounding and to generate parameter estimates (α = 0.05). The Hommel approach was used for post-hoc analyses. Results are reported as medians and interquartile ranges. A total of 159 patients were eligible (80 females). Antibodies were detectable in 86. Median age at diagnosis was 8 years. Free carnitine concentrations were lower in patients than controls (25.50 µmol/L;18.98-33.61 vs. 27.26; 21.22-34.86 respectively) (p = 0.018). Immunoreactive trypsinogen was higher in this group (20.24 µg/L;16.15-29-52 vs. 18.71; 13.96-26.92) (p = 0.045), which did not persist in the post-hoc analysis. Carnitine levels are lower and immunoreactive trypsinogen might be higher, within 2-3 days of birth and years before development of type 1 diabetes as compared to controls, although the differences were well within reference ranges and provide insight into the pathogenesis into neonatal onset of type 1 diabetes development rather than use as a diagnostic tool. Given trypsinogen's use for evaluation of new-onset type 1 diabetes, larger studies are warranted.


Assuntos
Carnitina/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/imunologia , Triagem Neonatal , Tripsinogênio/imunologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
9.
Int J Mol Sci ; 22(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34639120

RESUMO

Carnitines are quaternary amines involved in various cellular processes such as fatty acid uptake, ß-oxidation and glucose metabolism regulation. Due to their neurotrophic activities, their integrative use has been studied in several different physio-pathological conditions such as anorexia nervosa, chronic fatigue, vascular diseases, Alzheimer's disease and male infertility. Being metabolically active, carnitines have also been proposed to treat reproductive impairment such as functional hypothalamic amenorrhea (FHA) and polycystic ovary syndrome (PCOS) since they improve both hormonal and metabolic parameters modulating the neuroendocrine impairments of FHA. Moreover, they are capable of improving the lipid profile and the insulin sensitivity in patients with PCOS.


Assuntos
Carnitina/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Infertilidade Masculina/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Reprodução , Feminino , Humanos , Masculino
10.
Anal Chem ; 93(38): 12973-12980, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34529423

RESUMO

Acylcarnitines (ACs) play important roles in the fatty acid ß-oxidation and are considered as diagnostic markers for many diseases. Accurate determination of ACs remains challenging due to their low abundance, high structure diversity, and limited availability of standard compounds. In this study, microwave-assisted Tmt-PP (p-[3,5-(dimethylamino)-2,4,6-triazine] benzene-1-sulfonyl piperazine) derivatization was utilized to facilitate the liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) determination of ACs. The result indicated that Tmt-PP labeling enables the prediction of the retention time and MS response of ACs and enhances their MS response up to 4 times. The introduction of the microwave during the derivatization procedure greatly improved the reaction efficiency, demonstrated by the shortened reaction time from 90 to 1 min. Furthermore, we applied a strategy named quantitative analysis of multi-components by a single marker (QAMS) for the assay of 26 ACs with only 5 AC standards, solving the standard availability issue to a large extent. The established workflow was applied to discover dysregulated ACs in xenograft colon cancer mice, and the quantification results were highly comparable with traditional methods where there were the corresponding standards for each AC. Our study demonstrated that chemical derivatization-based LC-MS/MS integrated with the QAMS strategy is robust for the identification and quantification of ACs and has great potential in targeted metabolomics study.


Assuntos
Carnitina , Espectrometria de Massas em Tandem , Animais , Carnitina/análogos & derivados , Cromatografia Líquida , Metabolômica , Camundongos
11.
Cells ; 10(9)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34571942

RESUMO

The Corona Virus Disease 2019 (COVID-19) pandemic represents an ongoing worldwide challenge. The present large study sought to understand independent and overlapping metabolic features of samples from acutely ill patients (n = 831) that tested positive (n = 543) or negative (n = 288) for COVID-19. High-throughput metabolomics analyses were complemented with antigen and enzymatic activity assays on plasma from acutely ill patients collected while in the emergency department, at admission, or during hospitalization. Lipidomics analyses were also performed on COVID-19-positive or -negative subjects with the lowest and highest body mass index (n = 60/group). Significant changes in amino acid and fatty acid/acylcarnitine metabolism emerged as highly relevant markers of disease severity, progression, and prognosis as a function of biological and clinical variables in these patients. Further, machine learning models were trained by entering all metabolomics and clinical data from half of the COVID-19 patient cohort and then tested on the other half, yielding ~78% prediction accuracy. Finally, the extensive amount of information accumulated in this large, prospective, observational study provides a foundation for mechanistic follow-up studies and data sharing opportunities, which will advance our understanding of the characteristics of the plasma metabolism in COVID-19 and other acute critical illnesses.


Assuntos
COVID-19/metabolismo , Prognóstico , Doença Aguda , Adulto , Aminoácidos/sangue , Índice de Massa Corporal , Carnitina/análogos & derivados , Carnitina/sangue , Estudos de Coortes , Ácidos Graxos/sangue , Feminino , Humanos , Cinurenina/sangue , Aprendizado de Máquina , Metabolômica , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Triptofano/sangue
12.
Medicine (Baltimore) ; 100(38): e27333, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559155

RESUMO

RATIONALE: Lipid storage myopathies (LSMs) are a series of genetic disorders of lipid metabolism predominantly affecting muscle. The low incidence and lethal properties of this disease make anesthesia experience limited in such patients. Among all etiologies of LSMs, primary carnitine deficiency (PCD) is now considered highly treatable by early administration of L-carnitine, though it remains unclear whether L-carnitine is effective enough to protect diseased muscle against conventionally used neuromuscular blocking agents (NMBAs) during general anesthesia. Currently, no data are available concerning possible prolonged muscle weakness in these cases. PATIENT CONCERNS: This case presents a 43-year-old female who was diagnosed with a PCD-induced LSM 3 years ago due to fatigability and exertional myalgias and has been treated with L-carnitine ever since. At the time of this report, she was admitted for uterine fibroids and scheduled for selective open gynecologic surgery under general anesthesia. DIAGNOSIS: The patient's diagnosis of PCD-induced LSM was based on the clinical features, muscle biopsy, and diminished organic cation/carnitine transporter 2 (OCTN2) transporter activity in the patient's skin fibroblasts. INTERVENTIONS: L-carnitine was taken by the patient until the morning of surgery. General anesthesia with cisatracurium and sevoflurane was selected as the anesthetic plan during the operation. The train-of-four (TOF) test was adopted as additional monitoring, particularly to track the recovery of neuromuscular function. OUTCOMES: The patient was extubated successfully following a spontaneously restored TOF ratio (TOFR) of 0.9. Nonetheless, we recorded a prolonged efficacy of cisatracurium in the clinical duration and the recovery time with TOFRs of 0.7 and 0.9, respectively. LESSONS: The conventional dose of cisatracurium combined with a low dose of sevoflurane can be safely used in patients with LSMs without additional anesthetic risks. Meanwhile, continuous TOF monitoring is recommended to perform high-quality anesthesia.


Assuntos
Anestesia Geral/métodos , Cardiomiopatias , Carnitina/deficiência , Carnitina/uso terapêutico , Hiperamonemia , Doenças Musculares , Adulto , Anestésicos Inalatórios , Atracúrio/análogos & derivados , Feminino , Humanos , Bloqueadores Neuromusculares , Sevoflurano
13.
Am J Mens Health ; 15(5): 15579883211036790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34515581

RESUMO

The male factor is responsible for infertility in about 35-40% of all cases. Idiopathic oligo- and/or astheno- and/or therato-zoospermia is one of the most common male fertility disorders and remains a significant therapeutic challenge. The primary cause of idiopathic male infertility remains unknown but seems to be associated with oxidative stress. Objective: The use of antioxidative formulation to improve qualitative and quantitative deficiencies in the male gametes.In total, 78 subjects were treated with a combination of 1,725 mg L-carnitine fumarate, 500 mg acetyl-L-carnitine, 90 mg vitamin C, 20 mg coenzyme Q10, 10 mg zinc, 200 µg folic acid, 50 µg selenium, and 1.5 µg vitamin B12 (Proxeed® Plus, Sigma-Tau, Italy) for 6 months; the preparation was taken twice daily from the time idiopathic infertility was diagnosed. Basic seminal parameters were evaluated by a European Society of Human Reproduction and Embryology (ESHRE) -certified embryologist following the fifth edition of the World Health Organisation (2010) guidelines at three time points: at baseline and 3 and 6 months of treatment.Improvements in semen parameters (differing in terms of dynamics) were evident at 3 months and gradually improved over the 6 months of treatment. Each parameter: sperm concentration, total sperm count, sperm total and progressive motility improved significantly after treatment except for the percentage of sperm of abnormal morphology and ejaculate volume.Proxeed Plus was effective for patients with idiopathic infertility; however, a long treatment period is needed to achieve optimal results.


Assuntos
Acetilcarnitina , Infertilidade Masculina , Antioxidantes , Carnitina , Fumaratos , Humanos , Infertilidade Masculina/tratamento farmacológico , Masculino , Motilidade Espermática
14.
Curr Microbiol ; 78(11): 3945-3956, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34542662

RESUMO

The evolution of antimicrobial-resistant pathogens is a global health and development threat. Nanomedicine is rapidly becoming the main driving force behind ongoing changes in antimicrobial studies. Among nanoparticles, silver (AgNPs) have attracted attention due to their versatile properties. The study aimed to investigate the effects of AgNPs and L-carnitine (LC) on mixed Candida albicans and Staphylococcus aureus in the mice vaginitis model. Study of antimicrobial activity of AgNPs evaluated by Minimum Inhibitory Concentration (MIC) and Minimum Biocidal Concentration (MBC) assays. AgNPs inhibited biofilm formation of microbial strains, which was tested by using crystal violet staining. In the current study, we evaluated the effects of AgNPs and LC in NMRI mice infected intravaginally with C. albicans/ S. aureus for two weeks. The proportion of mice in each stage of the estrous cycle (proestrus, estrus, metestrus, and diestrus) was examined. Histological properties were assessed by hematoxylin/ eosin (H&E) staining of formalin-fixed, paraffin-embedded vaginal tissue sections. Based on the results, MICs of AgNPs against S. aureus, C. albicans, and their combination were 252.3, 124.8, and 501.8 ppm, and their minimum biofilm inhibitory concentration (MBIC) was 500, 250, and 1000 ppm, respectively. The estrous cycle in the treated group was similar to the control. Vaginal histology and cytology showed that LC can improve tissue damages caused by vaginitis and AgNPs. This study demonstrates the promising use of AgNPs as antimicrobial agents and the combination of AgNPs/ LC could be a great future alternative in the control of vaginitis.


Assuntos
Nanopartículas Metálicas , Vaginite , Animais , Candida albicans , Carnitina , Feminino , Humanos , Camundongos , Prata/farmacologia , Staphylococcus aureus
15.
J Appl Physiol (1985) ; 131(4): 1241-1250, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34473575

RESUMO

Due to the invasiveness of a muscle biopsy, there is fragmentary information on the existence and possible origin of a sexual dimorphism in the skeletal muscle concentrations of the energy delivery-related metabolites carnosine, creatine, and carnitine. As these metabolites can be noninvasively monitored by proton magnetic resonance spectroscopy, this technique offers the possibility to investigate if sexual dimorphisms are present in an adult reference population and if these dimorphisms originated during puberty using a longitudinal design. Concentrations of carnosine, creatine, and carnitine were examined using proton magnetic resonance spectroscopy in the soleus and gastrocnemius muscles of an adult reference population of female (n = 50) and male adults (n = 50). For the longitudinal follow-up over puberty, 29 boys and 28 girls were scanned prepuberty. Six years later, 24 boys and 24 girls were rescanned postpuberty. A sexual dimorphism was present in carnosine and creatine, but not carnitine, in the adult reference population. Carnosine was 28.5% higher in the gastrocnemius (P < 0.001) and carnosine and creatine were respectively 19.9% (P < 0.001) and 18.2% (P < 0.001) higher in the soleus of male when compared with female adults. Through puberty, carnosine increased more in male subjects compared with female subjects, both in the gastrocnemius (+10.43% and -10.83%, respectively; interaction effect: P = 0.002) and in the soleus (+24.30% and +5.49%, respectively; interaction effect: P = 0.012). No significant effect of puberty was found in either creatine (interaction effect: P = 0.307) or carnitine (interaction effect: P = 0.066). A sexual dimorphism in the adult human muscle is present in carnosine and creatine, but not in carnitine.NEW & NOTEWORTHY This is the first study to investigate sexual dimorphisms in skeletal muscle carnosine, creatine, and carnitine concentrations in a substantial adult reference population (n = 100). A sexual dimorphism is present in both carnosine and creatine at adult age. The origin of the sexual dimorphisms is investigated using a longitudinal design over puberty in 24 males and 24 females. The sexual dimorphism in carnosine originated partly during puberty for carnosine, but not for creatine.


Assuntos
Carnosina , Adulto , Carnitina , Creatina , Feminino , Seguimentos , Humanos , Masculino , Músculo Esquelético , Puberdade
16.
Nutrients ; 13(9)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34579160

RESUMO

Protein imbalance during pregnancy affects women in underdeveloped and developing countries and is associated with compromised offspring growth and an increased risk of metabolic diseases in later life. We studied in a porcine model the glucose and urea metabolism, and circulatory hormone and metabolite profile of offspring exposed during gestation, to maternal isoenergetic low-high (LP-HC), high-low (HP-LC) or adequate (AP) protein-carbohydrate ratio diets. At birth, LP-HC were lighter and the plasma acetylcarnitine to free carnitine ratios at 1 day of life was lower compared to AP offspring. Plasma urea concentrations were lower in 1 day old LP-HC offspring than HP-LC. In the juvenile period, increased insulin concentrations were observed in LP-HC and HP-LC offspring compared to AP, as was body weight from HP-LC compared to LP-HC. Plasma triglyceride concentrations were lower in 80 than 1 day old HP-LC offspring, and glucagon concentrations lower in 80 than 1 day old AP and HP-LC offspring. Plasma urea and the ratio of glucagon to insulin were lower in all 80 than 1 day old offspring. Aminoacyl-tRNA, arginine and phenylalanine, tyrosine and tryptophan metabolism, histidine and beta-alanine metabolism differed between 1 and 80 day old AP and HP-LC offspring. Maternal protein imbalance throughout pregnancy did not result in significant consequences in offspring metabolism compared to AP, indicating enormous plasticity by the placenta and developing offspring.


Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Proteínas na Dieta/administração & dosagem , Fenômenos Fisiológicos da Nutrição Materna , Metaboloma , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Acetilcarnitina/sangue , Animais , Animais Recém-Nascidos/metabolismo , Carnitina/sangue , Carboidratos da Dieta/administração & dosagem , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Masculino , Gravidez , Deficiência de Proteína/metabolismo , Suínos/crescimento & desenvolvimento , Suínos/metabolismo , Triglicerídeos/sangue , Ureia/sangue , Ureia/metabolismo
17.
Nutrients ; 13(9)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34578803

RESUMO

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD/MTPD) and medium chain acyl-CoA dehydrogenase deficiency (MCADD) were included in the expanded neonatal screening program (ENBS) in Czechia in 2009, allowing for the presymptomatic diagnosis and nutritional management of these patients. The aim of our study was to assess the nationwide impact of ENBS on clinical outcome. This retrospective study analysed acute events and chronic complications and their severity in pre-ENBS and post-ENBS cohorts. In total, 28 children (12 before, 16 after ENBS) were diagnosed with LCHADD/MTPD (incidence 0.8/100,000 before and 1.2/100,000 after ENBS). In the subgroup detected by ENBS, a significantly longer interval from birth to first acute encephalopathy was observed. In addition, improvement in neuropathy and cardiomyopathy (although statistically non-significant) was demonstrated in the post-ENBS subgroup. In the MCADD cohort, we included 69 patients (15 before, 54 after ENBS). The estimated incidence rose from 0.7/100,000 before to 4.3/100,000 after ENBS. We confirmed a significant decrease in the number of episodes of acute encephalopathy and lower proportion of intellectual disability after ENBS (p < 0.0001). The genotype-phenotype correlations suggest a new association between homozygosity for the c.1528C > G variant and more severe heart involvement in LCHADD patients.


Assuntos
Acil-CoA Desidrogenase/deficiência , Cardiomiopatias/dietoterapia , Cardiomiopatias/diagnóstico , Erros Inatos do Metabolismo Lipídico/dietoterapia , Erros Inatos do Metabolismo Lipídico/diagnóstico , Miopatias Mitocondriais/dietoterapia , Miopatias Mitocondriais/diagnóstico , Proteína Mitocondrial Trifuncional/deficiência , Triagem Neonatal/métodos , Doenças do Sistema Nervoso/dietoterapia , Doenças do Sistema Nervoso/diagnóstico , Rabdomiólise/dietoterapia , Rabdomiólise/diagnóstico , 3-Hidroxiacil-CoA Desidrogenases/deficiência , Cardiomiopatias/epidemiologia , Carnitina/análogos & derivados , Carnitina/sangue , Criança , Pré-Escolar , República Tcheca/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Erros Inatos do Metabolismo Lipídico/epidemiologia , Masculino , Erros Inatos do Metabolismo/diagnóstico , Miopatias Mitocondriais/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Rabdomiólise/epidemiologia , Índice de Gravidade de Doença
18.
Nutrients ; 13(9)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34578958

RESUMO

Amino acids, fatty acids, and acylcarnitine metabolites play a pivotal role in maternal and fetal health, but profiles of these metabolites over pregnancy are not completely established. We described longitudinal trajectories of targeted amino acids, fatty acids, and acylcarnitines in pregnancy. We quantified 102 metabolites and combinations (37 fatty acids, 37 amino acids, and 28 acylcarnitines) in plasma samples from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (n = 214 women at 10-14 and 15-26 weeks, 107 at 26-31 weeks, and 103 at 33-39 weeks). We used linear mixed models to estimate metabolite trajectories and examined variation by body mass index (BMI), race/ethnicity, and fetal sex. After excluding largely undetected metabolites, we analyzed 77 metabolites and combinations. Levels of 13 of 15 acylcarnitines, 7 of 25 amino acids, and 18 of 37 fatty acids significantly declined over gestation, while 8 of 25 amino acids and 10 of 37 fatty acids significantly increased. Several trajectories appeared to differ by BMI, race/ethnicity, and fetal sex although no tests for interactions remained significant after multiple testing correction. Future studies merit longitudinal measurements to capture metabolite changes in pregnancy, and larger samples to examine modifying effects of maternal and fetal characteristics.


Assuntos
Gravidez/sangue , Adolescente , Adulto , Aminoácidos/sangue , Índice de Massa Corporal , Carnitina/análogos & derivados , Carnitina/sangue , Grupos de Populações Continentais/estatística & dados numéricos , Ácidos Graxos/sangue , Feminino , Humanos , Masculino , Metabolômica , Gravidez/etnologia , Trimestres da Gravidez/sangue , Estudos Prospectivos , Estados Unidos , Adulto Jovem
19.
Biomed Khim ; 67(4): 338-346, 2021 Jul.
Artigo em Russo | MEDLINE | ID: mdl-34414892

RESUMO

Hyperhomocysteinemia is a risk factor for many diseases, including reproductive disorders in men. L-carnitine is used in medical practice to correct impaired bioenergetic conditions; in patients with idiopathic forms of infertility its effects are associated with improvement of the sperm parameters. However, the effect of exogenous L-carnitine on the level of homocysteine in the gonadal tissues, as a risk factor for impaired fertility, has not been investigated yet. The aim of this study was to investigate activity of bioenergetic enzymes in the epididymal mitochondrial fraction, the dynamics of changes in the cytoplasmic and mitochondrial lactate levels and LDH activity, the total carnitine content, as well as the oxidative status of these cells under conditions of oxidative stress caused by hyperhomocysteinemia, and to assess the effect of carnitine chloride on these parameters under conditions of methionine administration to male Wistar rats. Methionine administration to animals for three weeks at a dose of 3 g/kg, resulted in development of the severe forms of hyperhomocysteinemia with serum homocysteine concentrations exceeding 100 µmol/L. This was accompanied by a decrease in the activity of enzymes involved in the bioenergetic processes of the cell: tissue respiration (succinate dehydrogenase) and oxidative phosphorylation (H+-ATPase) in the epididymal head and tail. The change in lactate metabolism included an increase in its level in both the mitochondrial and cytoplasmic fractions of the epididymal head and mitochondria of the epididymal tail, and also simultaneous statistically significant decrease in LDH activity in the mitochondria and cytoplasm of the epididymal head. In male rats with severe hyperhomocysteinemia, an increase in the activity of mitochondrial SOD accompanied by an increase in the carbonylation of mitochondrial proteins in the head and tail of the epididymis was noted. Modeling of hyperhomocysteinemia under conditions of carnitine chloride of administration led to different reactions of the cells of the studied tissues assayed in the epididymal head and tail homogenate. In the epididymal head, carnitine chloride promoted an increase in the mitochondrial lactate concentration and a decrease in the cytoplasmic lactate concentration, as well as an increase in the LDH activity associated with the mitochondrial fraction. These changes were accompanied by an increase in the activity of H+-ATPase in the epididymal, thus suggesting that carnitine chloride stimulated lactate transport of into the mitochondria and its use as an energy substrate under conditions of oxidative stress caused by hyperhomocysteinemia. In the tail tissues, the changes were protective in nature and were associated with a decrease in the formation of oxidatively modified proteins.


Assuntos
Epididimo , Hiper-Homocisteinemia , Animais , Carnitina/metabolismo , Cloretos/metabolismo , Epididimo/metabolismo , Humanos , Hiper-Homocisteinemia/tratamento farmacológico , Hiper-Homocisteinemia/metabolismo , Ácido Láctico/metabolismo , Masculino , Mitocôndrias , Ratos , Ratos Wistar
20.
Epilepsy Behav ; 122: 108220, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371461

RESUMO

BACKGROUND: The benefits of carnitine supplementation in patients treated with valproate (VPA) are not clear. Therefore, we retrospectively explored the benefits of carnitine supplementation by analyzing laboratory data. METHODS: We measured the serum-free carnitine (FC), VPA, aspartate aminotransferase, alanine aminotransferase, amylase, and ammonia levels, and the platelet count, in 69 patients with childhood-onset epilepsy treated with VPA. Eight patients had received carnitine supplementation. The serum FC and acylcarnitine levels were measured using an enzyme cycling method. We compared laboratory values between patients with and without carnitine supplementation and analyzed the correlations between serum FC levels and laboratory values. RESULTS: The serum FC levels were normal (median, 48.8 µmol/L; range: 41.9-68.3 µmol/L) in all eight patients with carnitine supplementation, but below normal in 32 of 61 patients without supplementation. The median serum amylase levels were lower in the patients with carnitine supplementation (median, 48 U/L; range: 27-149 U/L) than in those without (median, 7 U/L; range: 14-234 U/L). The platelet count and serum ammonia levels did not differ significantly between patients with and without supplementation. There was no significant correlation between the serum FC level and the platelet count, serum amylase level, or ammonia level. CONCLUSIONS: Carnitine supplementation helps maintain serum FC levels in patients treated with VPA. The lower serum amylase levels in patients with carnitine supplementation may reflect protective effects of carnitine against latent pancreatic injury.


Assuntos
Epilepsia , Ácido Valproico , Carnitina , Criança , Suplementos Nutricionais , Epilepsia/tratamento farmacológico , Humanos , Estudos Retrospectivos , Ácido Valproico/uso terapêutico
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