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1.
Food Funct ; 14(2): 810-821, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36617886

RESUMO

Ascophyllum nodosum polysaccharide (ANP) can protect against colonic inflammation but the underlying mechanism is still unclear. This study has determined the metabolites of gut microbiota regulated by ANP to reveal the mechanism of the anti-inflammation effect of ANP. Using an in vitro colonic fermentation model, the results indicate that gut microbiota could utilize a proportion of ANP to increase the concentrations of short-chain fatty acids (SCFAs) and decrease ammonia content. Metabolomics revealed that 46 differential metabolites, such as betaine, L-carnitine, and aminoimidazole carboxamide ribonucleotide (AICAR), could be altered by ANP. Metabolic pathway analysis showed that ANP mainly up-regulated the phenylalanine, tyrosine, and tryptophan biosynthesis and aminoacyl-tRNA biosynthesis, which were negatively correlated with inflammation progression. Interestingly, these metabolites associated with inflammation were also up-regulated by ANP in colitis mice, including betaine, L-carnitine, AICAR, N-acetyl-glutamine, tryptophan, and valine, which were mainly associated with amino acid metabolism and aminoacyl-tRNA biosynthesis. Furthermore, the metabolites modulated by ANP were associated with the relative abundances of Akkermansia, Bacteroides, Blautia, Coprobacillus, Enterobacter, and Klebsiella. Additionally, based on VIP values, betaine is a key metabolite after the ANP supplement in vitro and in vivo. As indicated by these findings, ANP can up-regulate the production of SCFAs, betaine, L-carnitine, and AICAR and aminoacyl-tRNA biosynthesis to protect against colonic inflammation and maintain intestinal health.


Assuntos
Ascophyllum , Microbioma Gastrointestinal , Camundongos , Animais , Betaína/farmacologia , Triptofano/farmacologia , Inflamação , Ácidos Graxos Voláteis/farmacologia , Carnitina , Polissacarídeos/farmacologia , RNA de Transferência/farmacologia
2.
Toxicol Ind Health ; 39(2): 115-126, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36650049

RESUMO

The fungicide mancozeb increases oxygen-free radicals in the central nervous system. As an antioxidant, L-carnitine protects DNA and cell membranes from damage caused by oxygen-free radicals. The present study investigated how L-carnitine affected the acoustic startle response (ASR) in rats exposed to mancozeb. In this experimental study, male Wistar rats were gavaged orally with mancozeb (500, 1000, and 2000 mg/kg), L-carnitine (100, 200, and 400 mg/kg), or L-carnitine (200 mg/kg) + mancozeb (500 mg/kg) three times in 1 week. In the sham group, saline (0.9%, 10 mL/kg) was gavaged at a volume equivalent to that of the drugs. The control group did not receive any treatment. The results showed that locomotor activity and the percentage of prepulse inhibition in the mancozeb groups decreased compared to the sham group while these parameters increased in the L-carnitine group (200 mg/kg) compared to sham rats. In conclusion, mancozeb may increase the risk factor for cognitive diseases such as schizophrenia in people exposed to it while pretreatment with L-carnitine can attenuate the toxic effect.


Assuntos
Maneb , Reflexo de Sobressalto , Ratos , Animais , Masculino , Reflexo de Sobressalto/fisiologia , Ratos Wistar , Carnitina/farmacologia , Maneb/toxicidade
3.
Braz J Biol ; 82: e267633, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36629544

RESUMO

Carnitine is a conditionally necessary vitamin that aids in energy creation and fatty acid metabolism. Its bioavailability is higher in vegetarians than in meat-eaters. Deficits in carnitine transporters occur because of genetic mutations or in conjunction with other illnesses. Carnitine shortage can arise in health issues and diseases-including hypoglycaemia, heart disease, starvation, cirrhosis, and ageing-because of abnormalities in carnitine control. The physiologically active form of L-carnitine supports immunological function in diabetic patients. Carnitine has been demonstrated to be effective in the treatment of Alzheimer's disease, several painful neuropathies, and other conditions. It has been used as a dietary supplement for the treatment of heart disease, and it also aids in the treatment of obesity and reduces blood glucose levels. Therefore, L-carnitine shows the potential to eliminate the influences of fatigue in COVID-19, and its consumption is recommended in future clinical trials to estimate its efficacy and safety. This review focused on carnitine and its effect on tissues, covering the biosynthesis, metabolism, bioavailability, biological actions, and its effects on various body systems and COVID-19.


Assuntos
COVID-19 , Cardiopatias , Humanos , Carnitina/farmacologia , Carnitina/uso terapêutico , Suplementos Nutricionais , Cirrose Hepática , Cardiopatias/tratamento farmacológico
4.
PLoS One ; 18(1): e0279931, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36607993

RESUMO

BACKGROUND: The study was conducted to determine reference interval (RI) and evaluate the effect of preanalytical variables on Dried blood spot (DBS)-amino acids, acylcarnitines and succinylacetone of neonates. METHODOLOGY: DBS samples were collected within 48-72 hours of life. Samples were analyzed for biochemical markers on tandem mass spectrometer at the University of Iowa. Comparison of RI across various categorical variables were performed. RESULTS: A total of 610 reference samples were selected based on exclusion criteria; 53.2% being females. Mean gestational age (GA) of mothers at the time of delivery was 38.7±1.6 weeks; 24.5% neonates were of low birth weight and 14.3% were preterm. Out of the total 610 neonates, 23.1% were small for GA. Reference intervals were generated for eleven amino acids, thirty-two acylcarnitines and succinylacetone concentrations. Markers were evaluated with respect to the influence of gender, GA, weight and time of sampling and statistically significant minimal differences were observed for some biomarkers. CONCLUSION: RI for amino acids, succinylacetone and acylcarnitine on DBS has been established for healthy neonates, which could be of use in the clinical practice. Clinically significant effect of GA, weight, gender and time of sampling on these markers were not identified.


Assuntos
Aminoácidos , Saúde do Lactente , Recém-Nascido , Feminino , Humanos , Lactente , Masculino , Carnitina , Recém-Nascido de Baixo Peso , Aminas
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(2): 161-165, 2023 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-36709933

RESUMO

OBJECTIVE: To analyze the blood free carnitine (C0) level and SLC22A5 gene variants in 17 neonates with Primary carnitine deficiency (PCD) and to determine its incidence in local area and explore the correlation between C0 level and genotype. METHODS: 148 043 newborns born in 9 counties (cities and districts) of Ningde city from September 2016 to June 2021 were selected as study subjects. Blood free carnitine and acyl carnitine of 148 043 neonates were analyzed. Variants of the SLC22A5 gene were screened in those with blood C0 < 10 µmol/L, or C0 between 10 ∼ 15 µmol/L. Correlation between the free carnitine level and genetic variants was analyzed. RESULTS: In total 17 neonates were diagnosed with PCD, which yielded a prevalence of 1/8 707 in the region. Twelve variants of the SLC22A5 gene were identified, with the common ones including c.760C>T, c.1400C>G and c.51C>G. Compared with those carrying other variants of the gene, children carrying the c.760C>T variant had significantly lower C0 values (P < 0.01). CONCLUSION: The prevalence of PCD is relatively high in Ningde area, and intervention measures should be taken to prevent and control the disease. The c. 760C>T variant is associated with lower level of C0, which can provide a clue for the diagnosis.


Assuntos
Cardiomiopatias , Hiperamonemia , Doenças Musculares , Humanos , Recém-Nascido , Cardiomiopatias/genética , Cardiomiopatias/diagnóstico , Carnitina , Hiperamonemia/genética , Hiperamonemia/diagnóstico , Doenças Musculares/genética , Membro 5 da Família 22 de Carreadores de Soluto/genética
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(2): 155-160, 2023 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-36709932

RESUMO

OBJECTIVE: To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening. METHODS: A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development. RESULTS: Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development. CONCLUSION: SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Triagem Neonatal , Humanos , Recém-Nascido , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/genética , Carnitina , Triagem Neonatal/métodos
7.
Jt Dis Relat Surg ; 34(1): 84-91, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36700268

RESUMO

OBJECTIVES: In this experimental study, we aimed to analyze the effects of levocarnitine (L-carnitine) on tendon healing after surgical repair of Achilles tendon rupture in a rat model. MATERIALS AND METHODS: The study included 40 Wistar Albino rats divided into four groups: Group 1, neither surgical intervention nor substance applications were performed for the Achilles tendons. In the other groups, the right Achilles tendons were cut using a scalpel and repaired with a modified Kessler-type technique with 3/0 monofilament polydioxanone suture. In Group 2, the rats did not receive any additional treatment, except for surgical repair. In Group 3, the same volume similar to Group 4 of saline solution was administered intraperitoneally for seven days. In Group 4, each rat received 300 mg/kg of L-carnitine intraperitoneally for seven days. At Week 6, all rats were sacrificed. All right Achilles tendons were used for biomechanical tests and histopathological evaluations. Biochemical analysis of the matrix metalloproteinase was also performed using the blood specimens. RESULTS: There were no significant differences among the groups in terms of the histopathological parameters. Although the mean matrix metalloproteinase level was low in the L-carnitine group, it did not reach statistical significance. A significant increase in maximum force, tensile strength, and strength to 2-mm gap was observed in the L-carnitine group. CONCLUSION: The significant effects of L-carnitine on biomechanical parameters may indicate favorable effects on Achilles tendon healing in rats by reducing matrix metalloproteinase 2 and 9. To improve Achilles tendon healing, further investigation for these markers is needed. Since the effects of L-carnitine on the Achilles tendon cannot be clearly distinguished histopathologically, further studies involving L-carnitine-induced effects are warranted.


Assuntos
Tendão do Calcâneo , Carnitina , Cicatrização , Animais , Ratos , Tendão do Calcâneo/efeitos dos fármacos , Tendão do Calcâneo/cirurgia , Metaloproteinase 2 da Matriz , Ratos Wistar , Ruptura , Cicatrização/efeitos dos fármacos , Carnitina/farmacologia
8.
Trials ; 24(1): 3, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597167

RESUMO

BACKGROUND: Critically ill patients must be monitored constantly in intensive care units (ICUs). Among many laboratory variables, nutritional status indicators are a key role in the prognosis of diseases. We investigated the effects of L-carnitine adjunctive therapy on monitoring variables in critical illness. METHOD: A prospective, double-blind, randomized controlled trial was implemented in a medical ICU. Participants were 54 patients, aged > 18 years, with multiple conditions, randomly assigned to receive 3 g L-carnitine per day or placebo, along with enteral feeding, for 1 week. Primary outcomes included monitoring variables related to nutritional status. RESULT: Of 54 patients randomly assigned, 51 completed the trial. Serum albumin (Alb) (P-value: 0.001), total protein (P-value: 0.003), and calcium (Ca) (0.044) significantly increased in the intervention vs. control group. Alanine transaminase (ALT) (0.022), lactate (<0.001), creatinine (Cr) (0.005), and international normalized ratio (INR) (0.049) decreased meaningfully in the intervention vs. control group. CONCLUSION: L-Carnitine supplementation in critically ill patients can improve several parameters including INR, Cr, ALT, lactate, Ca, Alb, and total protein. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT 20151108024938N2. This trial was approved by the Research Ethics Committee of Mashhad University of Medical Sciences (registration code: IR.MUMS.fm.REC.1396.671) (available at https://en.irct.ir/trial/30748 , May 2018).


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Carnitina/efeitos adversos , Estado Terminal , Irã (Geográfico) , Estudos Prospectivos , Unidades de Terapia Intensiva , Lactatos
9.
Magn Reson Med ; 89(4): 1314-1322, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36573435

RESUMO

PURPOSE: Acetylcarnitine can be assessed in vivo using proton MRS (1 H-MRS) with long TEs and this has been previously applied successfully in muscle. The aim of this study was to evaluate a 1 H-MRS technique for liver acetylcarnitine quantification in healthy humans before and after l-carnitine supplementation. METHOD: Baseline acetylcarnitine levels were quantified using a STEAM sequence with prolonged TE in 15 healthy adults. Using STEAM with four different TEs was evaluated in phantoms. To assess reproducibility of the measurements, five of the participants had repeated 1 H-MRS without receiving l-carnitine supplementation. To determine if liver acetylcarnitine could be changed after l-carnitine supplementation, acetylcarnitine was quantified 2 h after intravenous l-carnitine supplementation (50 mg/kg body weight) in the other 10 participants. Hepatic lipids were also quantified from the 1 H-MRS spectra. RESULTS: There was good separation between the acetylcarnitine and fat in the phantoms using TE = 100 ms. Hepatic acetylcarnitine levels were reproducible (coefficient of reproducibility = 0.049%) and there was a significant (p < 0.001) increase in the relative abundance after a single supplementation of l-carnitine. Hepatic allylic, methyl, and methylene peaks were not altered by l-carnitine supplementation in healthy volunteers. CONCLUSION: Our results demonstrate that our 1 H-MRS technique could be used to measure acetylcarnitine in the liver and detect changes following intravenous supplementation in healthy adults despite the presence of lipids. Our techniques should be explored further in the study of fatty liver disease, where acetylcarnitine is suggested to be altered due to hepatic inflexibilities.


Assuntos
Acetilcarnitina , Carnitina , Adulto , Humanos , Reprodutibilidade dos Testes , Músculo Esquelético , Fígado/diagnóstico por imagem , Suplementos Nutricionais , Lipídeos
10.
Food Funct ; 14(1): 206-214, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36476928

RESUMO

L-Carnitine can be metabolized to trimethylamine (TMA) by gut microbiota and further converted into trimethylamine N-oxide (TMAO) in the liver, leading to liver damage. This study aimed to investigate the protective effect of quercetin against high L-carnitine-induced liver toxicity in mice. 3% L-carnitine drinking water was used to feed mice in this study. The formation of TMAO in the blood circulation of the tested mice was down-regulated following quercetin treatment. Administration of quercetin could also effectively antagonize the liver injury caused by high L-carnitine intake, which was proved by the decreased serum AST and ALT activities and the reduced levels of inflammatory liver cytokines (IL-1, IL-6, TNF-α, and TNF-ß). Moreover, quercetin exhibited a rebalancing effect on dyslipidemia (TC, TG, HDL, and LDL) and antioxidant abilities (SOD, GSH-Px, MDA, and RAHFR) in L-carnitine-treated mice. The results of hepatic H&E and Oil Red O staining further verified the liver injury of high L-carnitine-treated mice and the protective effects of quercetin. These findings suggested that quercetin could attenuate the hepatotoxic effects of the mice fed with a high L-carnitine diet via inhibiting the circulating TMAO formation.


Assuntos
Carnitina , Quercetina , Camundongos , Animais , Carnitina/metabolismo , Quercetina/farmacologia , Camundongos Endogâmicos C57BL , Metilaminas , Dieta , Óxidos
11.
Food Res Int ; 162(Pt A): 111946, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36461202

RESUMO

The quality of pork, such as intramuscular fat (IMF) content and flavor, can affect the acceptance of the consumer. Many studies have reported on the pork quality of Chinese local and commercial pigs (for example Large White (LW) pigs). The Jianhe White Xiang (JWX) pig, one of the Chinese Xiang pigs, is known for its high IMF and pork flavor. However, studies investigating the characterization and difference of lipids and metabolites between the JWX and LW pork are limited. Herein, we performed metabolomic and lipidomic profiling of JWX and LW pork by high-performance liquid chromatography-tandem mass spectrometry. The IMF and meat redness (a*) of the JWX pork were significantly higher than those of the LW pork. Metabolomic profiling revealed that 118 out of 501 polar metabolites, such as carnitine, amino acids, sugar, and dipeptide, were significantly different between the two types of pork. Additionally, the screened metabolites were mainly related to carnitine synthesis, phospholipid metabolism, sugar metabolism, and amino acid metabolism. Lipidomic profiling identified 100 of 376 lipids, which contained carnitine, diglyceride, triglyceride (TG), sphingomyelin, cardiolipin, fatty acid, phosphatidylcholine (PC), and phosphatidylethanolamine (PE), which were significantly different between the two types of pork under the positive and negative ion modes (variable importance in projection (VIP) > 1, p < 0.05, and fold change (FC) > 2 or FC < 0.5). All of the different TG substances were up-regulated in the JWX pork, and their carbon chain length was longer than that of the residual TGs. In addition, the JWX pork had more double bonds of PC and PE substances than LW pork. Thus, our findings provide comprehensive metabolomic and lipidomic profiles between the JWX and LW pork and a basic understanding on increasing the pork quality.


Assuntos
Carne de Porco , Carne Vermelha , Suínos , Animais , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Carnitina , Lecitinas , Triglicerídeos , Açúcares
12.
World J Surg Oncol ; 20(1): 380, 2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36464703

RESUMO

OBJECTIVE: To screen out potential biomarkers by analyzing fundamental nutrients in the bronchoalveolar lavage fluid (BALF) before confirming the lung cancer. METHODS: In this study, 44 patients were enrolled with clinical information. The concentrations of 23 amino acids and 35 carnitines in their BALF were detected with the high-performance liquid chromatography-mass spectrometry (HPLC-MS). Combined with clinicopathological diagnosis, the patients were divided into the lung cancer group (grades I & II and III & IV) and the non-cancer group for standard statistical analysis. RESULTS: The partial least squares-discriminant analysis (PLS-DA), the Shapiro-Wilk test, and the Bonferroni correction results showed that the serine concentration was higher and the butane-diacyl-carnitine (C4DC) concentration was lower in the lung cancer group, further showing the same changing trend continuously through the non-cancer stage, grades I & II stage and grades III & IV stage. Those two potential biomarkers have been identified. CONCLUSION: The HPLC-MS target detection in clinic for nutrient concentration levels is a promising technique to find the changing concentration of serine and C4DC in BALF, which provides an economical and practical way for early warning of lung cancer.


Assuntos
Carnitina , Neoplasias Pulmonares , Humanos , Aminoácidos , Líquido da Lavagem Broncoalveolar , Serina
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(12): 1339-1343, 2022 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-36453955

RESUMO

OBJECTIVE: To detect variants of IVD gene among 4 neonates with suspected isovalerate acidemia in order to provide a guidance for clinical treatment. METHODS: 111 986 newborns and 7461 hospitalized children with suspected metabolic disorders were screened for acyl carnitine by tandem mass spectrometry. Those showing a significant increase in serum isovaleryl carnitine (C5) were analyzed for urinary organic acid and variants of the IVD gene. RESULTS: Four cases of isovalerate acidemia were detected, which included 2 asymptomatic newborns (0.018‰, 2/111 986) and 2 children suspected for metabolic genetic diseases (0.268‰, 2/7461). The formers had no obvious clinical symptoms. Analysis of acyl carnitine has suggested a significant increase in C5, and urinary organic acid analysis has shown an increase in isovaleryl glycine and 3-hydroxyisovalerate. Laboratory tests of the two hospitalized children revealed high blood ammonia, hyperglycemia, decreased red blood cells, white blood cells, platelets and metabolic acidosis. The main clinical manifestations have included sweaty foot-like odor, feeding difficulty, confusion, drowsiness, and coma. Eight variants (5 types) were detected, which included c.158G>A (p.Arg53His), c.214G>A (p.Asp72Asn), c.548C>T (p.Ala183Val), c.757A>G (p.Thr253Ala) and 1208A>G (p.Tyr403Cys). Among these, c.548C>T and c.757A>G were unreported previously. None of the variants was detected by next generation sequencing of 2095 healthy newborns, and all variants were predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION: The incidence of isovalerate acidemia in Liuzhou area is quite high. Screening of metabolic genetic diseases is therefore recommended for newborns with abnormal metabolism. The discovery of novel variants has enriched the mutational spectrum of the IVD gene.


Assuntos
Acidose , Recém-Nascido , Criança , Humanos , Carnitina , Eritrócitos , Sequenciamento de Nucleotídeos em Larga Escala
14.
Artigo em Russo | MEDLINE | ID: mdl-36537638

RESUMO

OBJECTIVE: Evaluation of the antiasthenic effect of sequential therapy with levocarnitine (LC) and acetylcarnitine (ALC) in patients with arterial hypertension and/or ischemic heart disease (CHD) with asthenic syndrome (AS). MATERIAL AND METHODS: An open comparative study included 120 patients aged 54-67 years in patients with arterial hypertension and/or coronary artery disease with AS. Patients of group1 (n=60), in addition to basic therapy for the underlying disease, received LC (Elcar solution for intravenous and intramuscular injection of 100 mg/ml, the company PIQ-PHARMA) intravenously for 10 days at a dose of 1000 mg/day, followed by a transition to oral administration of ALC (Carnicetine, the company PIQ-PHARMA) 500 mg (2 capsules) 2 times a day for 2 months. Group2 patients (n=60) received only basic therapy for major diseases. The duration of observation was 70 days. The severity of AS was assessed using the MFI-20 questionnaire (MultidiMensional Fatigue Inventory) and the visual analog scale VAS-A (Visual Analog Scale Measuring fatigue). RESULTS: In patients of group1, a statistically significant decrease in various manifestations of AS was noted. The differences were significant both in comparison with the baseline level and in comparison with the 2nd group. The endothelium-protective effect of LC and ALC has been established. CONCLUSION: The results obtained indicate that in such comorbid patients, the use of LC and ALC reduces the severity of AS manifestations, and the established endotheliotropic properties of the drugs allow them to be recommended as part of the complex personalized therapy of patients with cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Hipertensão , Humanos , Acetilcarnitina/uso terapêutico , Carnitina , Doenças Cardiovasculares/induzido quimicamente , Astenia/tratamento farmacológico , Síndrome , Hipertensão/tratamento farmacológico
15.
BMJ Case Rep ; 15(12)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36535739

RESUMO

The neonatal form of carnitine palmitoyltransferase II (CPT II) deficiency is a rare lethal inherited disorder of fatty acid oxidation. Carnitine essentially transfers long-chain fatty acids across the mitochondrial membranes for ß-oxidation, where CPT II plays a key role. CPT II deficiency phenotypical forms include lethal neonatal, severe infantile and myopathic forms. We present a term small-for-gestational-age neonate with hypoglycaemia, seizures, refractory cardiac arrhythmias and intracranial haemorrhage. Plasma acylcarnitine profile and the genetic study confirmed CPT II deficiency. Additionally, likely pathogenic variants in the SLC22A5 gene point to primary carnitine deficiency. Antenatal findings of polycystic kidney disease and cardiomegaly were confirmed postnatally. All supportive measures, including extracorporeal life support, failed to improve the clinical course, and the baby succumbed. Major renal, cerebral and cardiac anomalies were reported with CPT II deficiency. In our case, fetal polycystic nephromegaly and cardiomegaly with parental consanguinity should have signalled the possibility of this disorder.


Assuntos
Carnitina O-Palmitoiltransferase , Erros Inatos do Metabolismo Lipídico , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , Carnitina O-Palmitoiltransferase/genética , Erros Inatos do Metabolismo Lipídico/genética , Ácidos Graxos , Cardiomegalia , Feto , Carnitina , Membro 5 da Família 22 de Carreadores de Soluto
16.
Nutrients ; 14(23)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36501029

RESUMO

BACKGROUND: The effect of serum L-carnitine (LC) concentrations on cancer risk remains unclear. This study aims to explore the association between serum LC and the risk of incident cancer. METHODS: This is a case-control study, including 574 patients with incident cancer and 574 controls matched in a 1:1 ratio by age, sex, and residence, nested within the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analysis was used to assess the association of serum LC and incident cancer risk. RESULTS: When LC was assessed as quartiles, compared with patients with low LC (Q1), patients in the highest quartile (Q4) had a 33% (OR = 0.67, 95% CI: 0.46 to 0.99), 52% (OR = 0.48, 95% CI: 0.23 to 0.99), and 39% (OR = 0.61, 95% CI: 0.38 to 0.99) decreased risk of overall, digestive system, and non-digestive system cancer in the adjusted models, respectively. In subgroup analyses, an inverse association of LC with cancer risk was observed in individuals who were overweight (obese), who never drink, who never smoke, and who were female. In the mediation analysis, serum trimethylamine-N-oxide (TMAO) concentrations did not mediate the reversed association of LC with cancer risk. CONCLUSIONS: This study showed that serum LC concentrations had a protective impact on overall, digestive system, and non-digestive system cancer risk.


Assuntos
Hipertensão , Neoplasias , Adulto , Humanos , Feminino , Masculino , Carnitina , Estudos de Casos e Controles , Metilaminas , Hipertensão/complicações , Hipertensão/epidemiologia , Neoplasias/epidemiologia , Fatores de Risco
17.
Int J Mol Sci ; 23(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36555822

RESUMO

Several common ocular diseases are leading causes of irreversible visual impairment. Over the last decade, various mainly untargeted metabolic studies have been performed to show that metabolic dysfunction plays an important role in the pathogenesis of ocular diseases. A number of metabolites in plasma/serum, aqueous or vitreous humor, or in tears have been found to differ between patients and controls; among them are L-carnitine and acylcarnitines, which are essential for mitochondrial fatty acid oxidation. The metabolic profile of carnitines regarding a variety of diseases has attracted researchers' interest. In this review, we present and discuss recent advances that have been made in the identification of carnitines as potential metabolic biomarkers in common ocular diseases, such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, central retinal vein occlusion, primary open-angle glaucoma, rhegmatogenous retinal detachment, and dry eye syndrome.


Assuntos
Glaucoma de Ângulo Aberto , Oftalmologia , Recém-Nascido , Humanos , Glaucoma de Ângulo Aberto/metabolismo , Carnitina/metabolismo , Corpo Vítreo/metabolismo , Biomarcadores/metabolismo
18.
Proc Natl Acad Sci U S A ; 119(48): e2214941119, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36409888

RESUMO

Colocalization of enzymes is a proven approach to increase pathway flux and the synthesis of nonnative products. Here, we develop a method for enzyme colocalization using the yeast peroxisomal membrane as an anchor point. Pathway enzymes were fused to the native Pex15 anchoring motif to enable display on the surface of the peroxisome facing the cytosol. The peroxisome is the sole location of ß-oxidation in Saccharomyces cerevisiae, and acetyl-CoA is a by-product that is exported in the form of acetyl-carnitine. To access this untapped acetyl-CoA pool, we surface-anchored the native peroxisomal/mitochondrial enzyme Cat2 to convert acetyl-carnitine to acetyl-CoA directly upon export across the peroxisomal membrane; this increased acetyl-CoA levels 3.7-fold. Subsequent surface attachment of three pathway enzymes - Cat2, a high stability Acc1 (for conversion of acetyl-CoA to malonyl-CoA), and the type III PKS 2-pyrone synthase - demonstrated the success of peroxisomal surface display for both enzyme colocalization and access to acetyl-CoA from exported acetyl-carnitine. Synthesis of the polyketide triacetic acid lactone increased by 21% over cytosolic expression at low gene copy number, and an additional 11-fold (to 766 mg/L) after further optimization. Finally, we explored increasing peroxisomal membrane area through overexpression of the peroxisomal biogenesis protein Pex11. Our findings establish peroxisomal surface display as an efficient strategy for enzyme colocalization and for accessing the peroxisomal acetyl-CoA pool to increase synthesis of acetyl-CoA-based products.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Acetilcoenzima A/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Peroxissomos/metabolismo , Carnitina/metabolismo , Peroxinas/metabolismo , Proteínas de Membrana/metabolismo
19.
Proc Natl Acad Sci U S A ; 119(46): e2210247119, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36343260

RESUMO

Genetic variants in SLC22A5, encoding the membrane carnitine transporter OCTN2, cause the rare metabolic disorder Carnitine Transporter Deficiency (CTD). CTD is potentially lethal but actionable if detected early, with confirmatory diagnosis involving sequencing of SLC22A5. Interpretation of missense variants of uncertain significance (VUSs) is a major challenge. In this study, we sought to characterize the largest set to date (n = 150) of OCTN2 variants identified in diverse ancestral populations, with the goals of furthering our understanding of the mechanisms leading to OCTN2 loss-of-function (LOF) and creating a protein-specific variant effect prediction model for OCTN2 function. Uptake assays with 14C-carnitine revealed that 105 variants (70%) significantly reduced transport of carnitine compared to wild-type OCTN2, and 37 variants (25%) severely reduced function to less than 20%. All ancestral populations harbored LOF variants; 62% of green fluorescent protein (GFP)-tagged variants impaired OCTN2 localization to the plasma membrane of human embryonic kidney (HEK293T) cells, and subcellular localization significantly associated with function, revealing a major LOF mechanism of interest for CTD. With these data, we trained a model to classify variants as functional (>20% function) or LOF (<20% function). Our model outperformed existing state-of-the-art methods as evaluated by multiple performance metrics, with mean area under the receiver operating characteristic curve (AUROC) of 0.895 ± 0.025. In summary, in this study we generated a rich dataset of OCTN2 variant function and localization, revealed important disease-causing mechanisms, and improved upon machine learning-based prediction of OCTN2 variant function to aid in variant interpretation in the diagnosis and treatment of CTD.


Assuntos
Carnitina , Proteínas de Transporte de Cátions Orgânicos , Humanos , Membro 5 da Família 22 de Carreadores de Soluto/genética , Membro 5 da Família 22 de Carreadores de Soluto/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Células HEK293 , Carnitina/genética , Carnitina/metabolismo , Genômica
20.
Nutrients ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364913

RESUMO

Ischemic heart disease (IHD) and type-2 diabetes mellitus (T2DM) remain major health problems worldwide and commonly coexist in individuals. Gut microbial metabolites, such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), have been linked to cardiovascular and metabolic diseases. Previous studies have reported dysbiosis in the gut microbiota of these patients and the prebiotic effects of some components of the Mediterranean diet. Essential oil emulsions of savory (Satureja hortensis), parsley (Petroselinum crispum) and rosemary (Rosmarinus officinalis) were assessed as nutraceuticals and prebiotics in IHD and T2DM. Humanized mice harboring gut microbiota derived from that of patients with IHD and T2DM were supplemented with L-carnitine and orally treated with essential oil emulsions for 40 days. We assessed the effects on gut microbiota composition and abundance, microbial metabolites and plasma markers of cardiovascular disease, inflammation and oxidative stress. Our results showed that essential oil emulsions in mice supplemented with L-carnitine have prebiotic effects on beneficial commensal bacteria, mainly Lactobacillus genus. There was a decrease in plasma TMAO and an increase in fecal SCFAs levels in mice treated with parsley and rosemary essential oils. Thrombomodulin levels were increased in mice treated with savory and parsley essential oils. While mice treated with parsley and rosemary essential oils showed a decrease in plasma cytokines (INFÉ£, TNFα, IL-12p70 and IL-22); savory essential oil was associated with increased levels of chemokines (CXCL1, CCL2 and CCL11). Finally, there was a decrease in protein carbonyls and pentosidine according to the essential oil emulsion. These results suggest that changes in the gut microbiota induced by essential oils of parsley, savory and rosemary as prebiotics could differentially regulate cardiovascular and metabolic factors, which highlights the potential of these nutraceuticals for reducing IHD risk in patients affected by T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Dieta Mediterrânea , Microbioma Gastrointestinal , Isquemia Miocárdica , Óleos Voláteis , Rosmarinus , Camundongos , Animais , Prebióticos , Emulsões/farmacologia , Ácidos Graxos Voláteis/metabolismo , Óleos Voláteis/farmacologia , Carnitina/farmacologia
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