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  1 / 4223 MEDLINE  
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[PMID]:29214787
[Au] Autor:Eun LY; Lee YM
[Ad] Endereço:Division of Pediatric Cardiology, Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
[Ti] Título:Myocardial Layer-Specific Strain Analysis in Children with Mitochondrial Disease.
[So] Source:Yonsei Med J;59(1):128-134, 2018 Jan.
[Is] ISSN:1976-2437
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Children with mitochondrial disease (MD) have clinical phenotypes that are more severe than those found in adults. In this study, we assessed cardiac function in children with MD using conventional and advanced echocardiographic measurements, explored any unique patterns present, and investigated the development of early cardiomyopathy (CMP). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 33 children with MD. All patients underwent transthoracic echocardiography with conventional and advanced myocardial analysis. We compared all data between patients and an age-matched healthy control group. RESULTS: Conventional echocardiographic diastolic measurements of mitral E, E/A, and tissue Doppler E' were significantly lower and E/E' was significantly higher in children with MD, compared with the measurements from the control group. There was no significant difference in longitudinal and radial strain between the groups. Circumferential strain in the endocardium (p=0.161), middle myocardium (p=0.008), and epicardium (p=0.042) were lower in patients, compared to the values in controls. Circumferential strain was correlated with E' (p<0.01, r>0.60). CONCLUSION: In children with MD, myocardial circumferential strain may develop early in all three layers, even with normally preserved longitudinal and radial strain. This may be an early diagnostic indicator with which to predict CMP in this patient population.
[Mh] Termos MeSH primário: Doenças Mitocondriais/patologia
Doenças Mitocondriais/fisiopatologia
Miocárdio/patologia
[Mh] Termos MeSH secundário: Fenômenos Biomecânicos
Criança
Ecocardiografia Doppler
Feminino
Seres Humanos
Masculino
Doenças Mitocondriais/diagnóstico por imagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.3349/ymj.2018.59.1.128


  2 / 4223 MEDLINE  
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[PMID]:28463418
[Au] Autor:Liu C; Sekine S; Song B; Ito K
[Ad] Endereço:Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
[Ti] Título:Use of Primary Rat Hepatocytes for Prediction of Drug-Induced Mitochondrial Dysfunction.
[So] Source:Curr Protoc Toxicol;72:14.16.1-14.16.10, 2017 May 02.
[Is] ISSN:1934-9262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondrial dysfunction plays a central role in drug-induced liver injury. To evaluate drug-induced mitochondrial impairment, several isolated mitochondria- or cell line-based assays have been reported. Among them, culturing HepG2 cells in galactose provides a remarkable method to assess mitochondrial toxicity by activating mitochondrial aerobic respiration. We applied this assay to primary rat hepatocytes by culturing cells in galactose and hyperoxia to enhance the evaluation of metabolism-related drug-induced mitochondrial toxicity. Conventional culture of primary hepatocytes under high-glucose and hypoxic conditions could force cells to switch energy generation to glycolysis. By contrast, cells cultured in galactose and hyperoxia could maintain energy generation from mitochondrial aerobic respiration, which is consistent with physiological conditions, and consequently improve the susceptibility of cells to mitochondrial toxicants. Measuring the toxicities of test compounds in primary rat hepatocytes cultured in modified conditions provides a useful model to identify mitochondrial dysfunction-mediated drug-induced hepatotoxicity. © 2017 by John Wiley & Sons, Inc.
[Mh] Termos MeSH primário: Hepatócitos/efeitos dos fármacos
Doenças Mitocondriais/induzido quimicamente
Doenças Mitocondriais/patologia
[Mh] Termos MeSH secundário: Animais
Respiração Celular
Doença Hepática Induzida por Substâncias e Drogas
Meios de Cultura
Metabolismo Energético
Previsões
Galactose/metabolismo
Hepatócitos/enzimologia
Hiperóxia/metabolismo
L-Lactato Desidrogenase/análise
Consumo de Oxigênio
Cultura Primária de Células
Ratos
Ratos Sprague-Dawley
Testes de Toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media); EC 1.1.1.27 (L-Lactate Dehydrogenase); X2RN3Q8DNE (Galactose)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1002/cptx.24


  3 / 4223 MEDLINE  
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[PMID]:29302033
[Au] Autor:Ignatenko O; Chilov D; Paetau I; de Miguel E; Jackson CB; Capin G; Paetau A; Terzioglu M; Euro L; Suomalainen A
[Ad] Endereço:Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, Haartmaninkatu 8, University of Helsinki, Helsinki, 00014, Finland.
[Ti] Título:Loss of mtDNA activates astrocytes and leads to spongiotic encephalopathy.
[So] Source:Nat Commun;9(1):70, 2018 01 04.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Mitochondrial dysfunction manifests as different neurological diseases, but the mechanisms underlying the clinical variability remain poorly understood. To clarify whether different brain cells have differential sensitivity to mitochondrial dysfunction, we induced mitochondrial DNA (mtDNA) depletion in either neurons or astrocytes of mice, by inactivating Twinkle (TwKO), the replicative mtDNA helicase. Here we show that astrocytes, the most abundant cerebral cell type, are chronically activated upon mtDNA loss, leading to early-onset spongiotic degeneration of brain parenchyma, microgliosis and secondary neurodegeneration. Neuronal mtDNA loss does not, however, cause symptoms until 8 months of age. Findings in astrocyte-TwKO mimic neuropathology of Alpers syndrome, infantile-onset mitochondrial spongiotic encephalopathy caused by mtDNA maintenance defects. Our evidence indicates that (1) astrocytes are dependent on mtDNA integrity; (2) mitochondrial metabolism contributes to their activation; (3) chronic astrocyte activation has devastating consequences, underlying spongiotic encephalopathy; and that (4) astrocytes are a potential target for interventions.
[Mh] Termos MeSH primário: Astrócitos/metabolismo
Encefalopatias/genética
DNA Mitocondrial/genética
Doenças Mitocondriais/genética
[Mh] Termos MeSH secundário: Animais
Encéfalo/metabolismo
Encéfalo/ultraestrutura
DNA Helicases/genética
DNA Helicases/metabolismo
DNA Mitocondrial/metabolismo
Camundongos Knockout
Microscopia Eletrônica
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
Mutação
Neurônios/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA, Mitochondrial); 0 (Mitochondrial Proteins); EC 3.6.1.- (Peo1 protein, mouse); EC 3.6.4.- (DNA Helicases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-01859-9


  4 / 4223 MEDLINE  
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[PMID]:29269692
[Au] Autor:Ishikawa T; Nakamura K; Shimasaki R; Goto K; Umehara F
[Ad] Endereço:Department of Neurology, Nishibeppu National Hospital.
[Ti] Título:[A case of mitochondrial disease with multiple mitochondrial DNA deletions suspected amyotrophic lateral sclerosis-frontotemporal dementia].
[So] Source:Rinsho Shinkeigaku;58(1):15-20, 2018 Jan 26.
[Is] ISSN:1882-0654
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:A 76-year-old woman showed a dramatic lowering of her tone of voice in October 2014, followed by muscle weakness of the left arm. The previous attending physician noticed remarkable left dominant frontotemporal lobe atrophy on cranial MRI. Her dysarthria, dysphagia and the muscle weakness of her extremities worsened, and a muscle biopsy revealed mitochondrial abnormality. The mitochondrial DNA from her muscle showed multiple deletions; the previous physician therefore diagnosed the patient with mitochondrial disease. The patient resembled amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD). No other cases of ALS-FTD with mitochondrial disease have been reported in Japan. We therefore consider the present case to be valuable.
[Mh] Termos MeSH primário: DNA Mitocondrial/genética
Deleção de Genes
Doenças Mitocondriais/diagnóstico
Doenças Mitocondriais/genética
[Mh] Termos MeSH secundário: Idoso
Esclerose Amiotrófica Lateral
Arginina/administração & dosagem
Diagnóstico Diferencial
Evolução Fatal
Feminino
Demência Frontotemporal
Seres Humanos
Mitocôndrias Musculares/patologia
Doenças Mitocondriais/tratamento farmacológico
Doenças Mitocondriais/patologia
Músculo Esquelético/ultraestrutura
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Mitochondrial); 94ZLA3W45F (Arginine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE
[do] DOI:10.5692/clinicalneurol.cn-001071


  5 / 4223 MEDLINE  
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[PMID]:28749033
[Au] Autor:Couser NL; Marchuk DS; Smith LD; Arreola A; Kaiser-Rogers KA; Muenzer J; Pandya A; Gucsavas-Calikoglu M; Powell CM
[Ad] Endereço:Department of Pediatrics, Division of Genetics and Metabolism, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
[Ti] Título:Co-occurring Down syndrome and SUCLA2-related mitochondrial depletion syndrome.
[So] Source:Am J Med Genet A;173(10):2720-2724, 2017 Oct.
[Is] ISSN:1552-4833
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondrial DNA depletion syndrome 5 (MIM 612073) is a rare autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the beta subunit of the succinate-CoA ligase gene located within the 13q14 band. We describe two siblings of Hispanic descent with SUCLA2-related mitochondrial depletion syndrome (encephalomyopathic form with methylmalonic aciduria); the older sibling is additionally affected with trisomy 21. SUCLA2 sequencing identified homozygous p.Arg284Cys pathogenic variants in both patients. This mutation has previously been identified in four individuals of Italian and Caucasian descent. The older sibling with concomitant disease has a more severe phenotype than what is typically described in patients with either SUCLA2-related mitochondrial depletion syndrome or Down syndrome alone. The younger sibling, who has a normal female chromosome complement, is significantly less affected compared to her brother. While the clinical and molecular findings have been reported in about 50 patients affected with a deficiency of succinate-CoA ligase caused by pathogenic variants in SUCLA2, this report describes the first known individual affected with both a mitochondrial depletion syndrome and trisomy 21.
[Mh] Termos MeSH primário: Síndrome de Down/genética
Homozigoto
Doenças Mitocondriais/genética
Mutação
Succinato-CoA Ligases/genética
[Mh] Termos MeSH secundário: Adulto
Criança
Pré-Escolar
Síndrome de Down/complicações
Síndrome de Down/diagnóstico
Feminino
Seres Humanos
Masculino
Doenças Mitocondriais/complicações
Doenças Mitocondriais/diagnóstico
Fenótipo
Prognóstico
Síndrome
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
EC 6.2.1.- (Succinate-CoA Ligases); EC 6.2.1.5 (SUCLA2 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1002/ajmg.a.38351


  6 / 4223 MEDLINE  
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[PMID]:27771434
[Au] Autor:James MO; Jahn SC; Zhong G; Smeltz MG; Hu Z; Stacpoole PW
[Ad] Endereço:Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610-0485, United States. Electronic address: mojames@ufl.edu.
[Ti] Título:Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.
[So] Source:Pharmacol Ther;170:166-180, 2017 Feb.
[Is] ISSN:1879-016X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Dichloroacetate (DCA) has several therapeutic applications based on its pharmacological property of inhibiting pyruvate dehydrogenase kinase. DCA has been used to treat inherited mitochondrial disorders that result in lactic acidosis, as well as pulmonary hypertension and several different solid tumors, the latter through its ability to reverse the Warburg effect in cancer cells and restore aerobic glycolysis. The main clinically limiting toxicity is reversible peripheral neuropathy. Although administration of high doses to rodents can result in liver cancer, there is no evidence that DCA is a human carcinogen. In all studied species, including humans, DCA has the interesting property of inhibiting its own metabolism upon repeat dosing, resulting in alteration of its pharmacokinetics. The first step in DCA metabolism is conversion to glyoxylate catalyzed by glutathione transferase zeta 1 (GSTZ1), for which DCA is a mechanism-based inactivator. The rate of GSTZ1 inactivation by DCA is influenced by age, GSTZ1 haplotype and cellular concentrations of chloride. The effect of DCA on its own metabolism complicates the selection of an effective dose with minimal side effects.
[Mh] Termos MeSH primário: Ácido Dicloroacético/administração & dosagem
Glutationa Transferase/metabolismo
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Ácido Dicloroacético/efeitos adversos
Ácido Dicloroacético/farmacologia
Relação Dose-Resposta a Droga
Seres Humanos
Hipertensão Pulmonar/tratamento farmacológico
Doenças Mitocondriais/tratamento farmacológico
Neoplasias/tratamento farmacológico
Neoplasias/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
9LSH52S3LQ (Dichloroacetic Acid); EC 2.5.1.- (GSTZ1 protein, human); EC 2.5.1.18 (Glutathione Transferase); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.2 (pyruvate dehydrogenase (acetyl-transferring) kinase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


  7 / 4223 MEDLINE  
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[PMID]:27774607
[Au] Autor:Ke S; Chen S; Dong Z; Hong CS; Zhang Q; Tang L; Yang P; Zhai J; Yan H; Shen F; Zhuang Z; Wen W; Wang H
[Ad] Endereço:State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
[Ti] Título:Erythrocytosis in hepatocellular carcinoma portends poor prognosis by respiratory dysfunction secondary to mitochondrial DNA mutations.
[So] Source:Hepatology;65(1):134-151, 2017 01.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Erythrocytosis is a common paraneoplastic syndrome associated with hepatocellular carcinoma. Although increased erythropoietin (EPO) is found in these patients, the clinical significance and molecular mechanisms underlying this observation are unclear. We demonstrate an inverse relationship between EPO production and overall prognosis in our cohort of 664 patients as well as in data from The Cancer Genome Atlas. In the subset of hepatocellular carcinoma patients with erythrocytosis, we identified somatic mutations of mitochondrial DNA, resulting in impairment of respiratory metabolism, which sequentially led to depletion of α-ketoglutarate, stabilization of hypoxia inducible factor-α, and expression of target genes such as EPO. Cell lines and patient-derived xenograft models were used to demonstrate that EPO promoted cancer stem cell self-renewal and expansion in an autocrine/paracrine manner through enhanced Janus kinase/signal transducer and activator of transcription signaling both in vitro and in vivo. Furthermore, to explore the therapeutic targeting of EPO-induced tumor changes, we found that blocking EPO signaling with soluble EPO receptor extracellular domain Fc fusion protein could inhibit tumor growth both in vitro and in vivo. CONCLUSION: These findings suggest clinical and therapeutic implications for erythrocytosis in hepatocellular carcinoma. There is an underlying link between mitochondrial function and hypoxia inducible factor alpha signaling, revealing a mechanism of erythrocytosis in a subset of hepatocellular carcinoma patients who may benefit from treatment involving EPO signaling interference. (Hepatology 2017;65:134-151).
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/complicações
Carcinoma Hepatocelular/genética
DNA Mitocondrial/genética
Neoplasias Hepáticas/complicações
Neoplasias Hepáticas/genética
Mutação
Síndromes Paraneoplásicas/etiologia
Policitemia/etiologia
[Mh] Termos MeSH secundário: Carcinoma Hepatocelular/fisiopatologia
Hipóxia Celular
Feminino
Seres Humanos
Neoplasias Hepáticas/fisiopatologia
Masculino
Doenças Mitocondriais/genética
Policitemia/fisiopatologia
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA, Mitochondrial)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180121
[Lr] Data última revisão:
180121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1002/hep.28889


  8 / 4223 MEDLINE  
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[PMID]:29237418
[Au] Autor:Cattaneo M; La Sala L; Rondinelli M; Errichiello E; Zuffardi O; Puca AA; Genovese S; Ceriello A
[Ad] Endereço:Cardiovascular Research Unit, IRCCS MultiMedica, Via G. Fantoli 16/15, 20138, Milan, Italy. monica.cattaneo@multimedica.it.
[Ti] Título:A donor splice site mutation in CISD2 generates multiple truncated, non-functional isoforms in Wolfram syndrome type 2 patients.
[So] Source:BMC Med Genet;18(1):147, 2017 12 13.
[Is] ISSN:1471-2350
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Mutations in the gene that encodes CDGSH iron sulfur domain 2 (CISD2) are causative of Wolfram syndrome type 2 (WFS2), a rare autosomal recessive neurodegenerative disorder mainly characterized by diabetes mellitus, optic atrophy, peptic ulcer bleeding and defective platelet aggregation. Four mutations in the CISD2 gene have been reported. Among these mutations, the homozygous c.103 + 1G > A substitution was identified in the donor splice site of intron 1 in two Italian sisters and was predicted to cause a exon 1 to be skipped. METHODS: Here, we employed molecular assays to characterize the c.103 + 1G > A mutation using the patient's peripheral blood mononuclear cells (PBMCs). 5'-RACE coupled with RT-PCR were used to analyse the effect of the c.103 + 1G > A mutation on mRNA splicing. Western blot analysis was used to analyse the consequences of the CISD2 mutation on the encoded protein. RESULTS: We demonstrated that the c.103 + 1G > A mutation functionally impaired mRNA splicing, producing multiple splice variants characterized by the whole or partial absence of exon 1, which introduced amino acid changes and a premature stop. The affected mRNAs resulted in either predicted targets for nonsense mRNA decay (NMD) or non-functional isoforms. CONCLUSIONS: We concluded that the c.103 + 1G > A mutation resulted in the loss of functional CISD2 protein in the two Italian WFS2 patients.
[Mh] Termos MeSH primário: Senilidade Prematura/genética
Perda Auditiva Neurossensorial/genética
Proteínas de Membrana/genética
Doenças Mitocondriais/genética
Mutação
Atrofia Óptica/genética
Sítios de Splice de RNA/genética
[Mh] Termos MeSH secundário: Sequência de Bases
Células Sanguíneas
Códon sem Sentido
Éxons/genética
Feminino
Seres Humanos
Íntrons/genética
Leucócitos Mononucleares
Proteínas de Membrana/química
Isoformas de Proteínas/genética
Sítios de Splice de RNA/fisiologia
Processamento de RNA
RNA Mensageiro/genética
Análise de Sequência
Deleção de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Codon, Nonsense); 0 (ERIS protein, human); 0 (Membrane Proteins); 0 (Protein Isoforms); 0 (RNA Splice Sites); 0 (RNA, Messenger)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171231
[Lr] Data última revisão:
171231
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1186/s12881-017-0508-2


  9 / 4223 MEDLINE  
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[PMID]:29252954
[Au] Autor:Vollmer JP; Haen S; Wolburg H; Lehmann R; Steiner J; Reddersen S; Fend F; Fallier-Becker P
[Ad] Endereço:Institute of Anaesthesiology, Klinikum Stuttgart, Germany.
[Ti] Título:Propofol Related Infusion Syndrome: Ultrastructural Evidence for a Mitochondrial Disorder.
[So] Source:Crit Care Med;46(1):e91-e94, 2018 Jan.
[Is] ISSN:1530-0293
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The objective of this report of a fatal propofol-related infusion syndrome in a young adult was to present-to our knowledge for the first time-direct ultrastructural evidence for the central role of mitochondrial damage in the pathogenesis of this syndrome. DATA SOURCES: Histological and electron microscopical analysis of liver, skeletal, and heart muscle obtained by autopsy and blood obtained from patient. STUDY SELECTION: Case report. DATA EXTRACTION: In addition to conventional macroscopical and histological investigations, electron-microscopical analysis of myocardial- and skeletal muscle and liver tissue obtained at autopsy from a young man was performed in order to search for ultrastructural changes of mitochondria. Acylcarnitine concentrations of his blood were determined by ultra-high performance liquid chromatography mass spectrometry. DATA SYNTHESIS: A 19-year-old male was admitted with acute left-side hemiparesis. The patient was intubated, then propofol infusion started, and a craniotomy was performed to remove an intracerebral hematoma. In the postoperative period, the patient presented with elevated intracranial pressure and brain edema. After repeat surgery, the patient showed impaired systolic left ventricular function, increasing fever, anuria, hyperkalemia, and metabolic acidosis, and he finally expired. Electron microscopy revealed dark, electron dense amorphous structures associated with mitochondria in heart muscle and liver tissue obtained at autopsy. Peripheral blood analysis revealed increased levels of acetyl-, propionyl-, butyryl-, malonyl-, and valeryl-carnitine as an indicator for propofol-related infusion syndrome, as well as for propofol-mediated inhibition of free fatty acid uptake into mitochondria, affecting beta-oxidation. CONCLUSIONS: Electron dense bodies found in association with mitochondria in muscle and liver cells probably correspond to accumulation of free fatty acid provide direct morphological evidence for the mitochondrial damage in propofol-related infusion syndrome.
[Mh] Termos MeSH primário: Doenças Mitocondriais/induzido quimicamente
Doenças Mitocondriais/patologia
Síndrome da Infusão de Propofol/patologia
[Mh] Termos MeSH secundário: Carnitina/análogos & derivados
Carnitina/sangue
Craniotomia
Hematoma Subdural Intracraniano/cirurgia
Seres Humanos
Infusões Intravenosas
Masculino
Microscopia Eletrônica
Mitocôndrias Cardíacas/efeitos dos fármacos
Mitocôndrias Cardíacas/patologia
Mitocôndrias Hepáticas/efeitos dos fármacos
Mitocôndrias Hepáticas/patologia
Mitocôndrias Musculares/efeitos dos fármacos
Mitocôndrias Musculares/patologia
Complicações Pós-Operatórias/induzido quimicamente
Complicações Pós-Operatórias/patologia
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (acylcarnitine); S7UI8SM58A (Carnitine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE
[do] DOI:10.1097/CCM.0000000000002802


  10 / 4223 MEDLINE  
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[PMID]:28987347
[Au] Autor:Tabebi M; Khabou B; Boukadi H; Ben Hamad M; Ben Rhouma B; Tounsi S; Maalej A; Kamoun H; Keskes-Ammar L; Abid M; Mnif M; Fakhfakh F
[Ad] Endereço:Human Molecular Genetics Laboratory, Faculty of Medicine of Sfax, University of Sfax, Tunisia. Electronic address: mounamouna62@yahoo.fr.
[Ti] Título:Association study of apoptosis gene polymorphisms in mitochondrial diabetes: A potential role in the pathogenicity of MD.
[So] Source:Gene;639:18-26, 2018 Jan 10.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia and is maternally transmitted. Syndromic MD is a subgroup of MD including diabetic microangiopathy and macroangiopathy, in addition to extrapancreatic disorder. MD is caused by genetic mutations and deletions affecting mitochondrial DNA. This mitochondrial damage initiates apoptosis. In this study, we hypothesized that functional polymorphisms in genes involved in apoptotic pathway could be associated with the development of apoptosis in MD disease and increased its risk. Detection of apoptosis was confirmed on muscle biopsies taken from MD patients using the TUNEL method and the Cytochrome c protein expression level. We genotyped then 11 published SNPs from intrinsic and extrinsic apoptotic pathway and assessed the signification of these polymorphisms in 43 MD patients and 100 healthy controls. We found 10 selected polymorphisms (p53 (rs1042522 and rs17878362), BCL2 (rs2279115), BAX (rs1805419), BAK1 (rs210132 and rs2227925), CASP3 (rs1405937), CASP7 (rs2227310), CASP8 (rs1045485) and CASP10 (rs13006529)) with a potential apoptosis effect in MD patients compared to control population. Specifically, SNPs involved in the intrinsic pathway (p53, BCL2, BAK1 and CASP3) presented the highest risk of apoptosis. Our result proved that apoptosis initiated by mtDNA mutations, can be emphasized by a functional apoptotic polymorphisms associated with high expression of cytochrome c protein and more myofibers with apoptosis in syndromic MD subgroup compared with non-syndromic MD subgroup.
[Mh] Termos MeSH primário: Apoptose/genética
Diabetes Mellitus/genética
Estudo de Associação Genômica Ampla
Doenças Mitocondriais/genética
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Adulto
Estudos de Casos e Controles
Citocromos c/metabolismo
Diabetes Mellitus/patologia
Feminino
Seres Humanos
Desequilíbrio de Ligação
Masculino
Doenças Mitocondriais/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9007-43-6 (Cytochromes c)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171009
[St] Status:MEDLINE



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