ABSTRACT
Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Subject(s)
Creatine/metabolism , Extracellular Vesicles , Muscle, Skeletal/metabolism , Myoblasts/metabolism , Regeneration , Connexins/metabolismABSTRACT
Creatine (Cr) plays an important role in storage and transmissionof phosphate-bound energy. Cerebral creatine deficiencysyndromes comprise three inherited defects in Cr biosynthesis andtransport. The aim of this study was to investigate whether Cr andGuanidinoacetate (GAA) can be detected in saliva of healthysubjects and to establish the relationship between salivary andplasma levels of these molecules. An adapted gas chromatography(GC) method is described for the quantification of Cr and GAAbiomarkers in saliva. Reference values were established for GAAand Cr in saliva. These values were age dependent (p= 0.001). Nodifference between genders was observed. We detected a differencebetween GAA and Cr concentrations in saliva and in plasma. TheGC method for simultaneous determination of GAA and Cr inhuman saliva is fast, reliable, sensitive, non-invasive and preciseto use as a biochemical approach in early detection of cerebralcreatine deficiency syndromes.
La creatina (Cr) juega un importante rol en el almacenamiento y el transporte de energía unida al fosfato. Los síndromes de deficiencia de creatina cerebral comprenden tres defectos genéticos en la biosíntesis y transporte de creatina. Es propósito de este estudio investigar si el guanidinoacetato (GAA) y la Crpueden ser detectados en saliva de sujetos sanos e investigar la relación entre los valores de GAA y Cr en saliva con los niveles en plasma de estas moléculas. Se describe un método modificado de cromatografía gaseosa para la cuantificación de los biomarca -dores, Cr y GAA en este biofluído. Se establecieron valores de referencia para GAA y Cr. Estos valores dependen de la edad (P=0.001). No se observaron diferencias entre género. Se detectóuna diferencia entre la concentración de GAA y Cr en saliva con respecto al plasma. El método adaptado de cromatografía gaseosa para la determinación simultánea de GAA y Cr en saliva humana es fácil, seguro, sensible, no invasivo y preciso para utilizar como aproximación bioquímica en la detección temprana de lossíndromes de deficiencia de creatina cerebral.
Subject(s)
Humans , Male , Adolescent , Adult , Female , Infant, Newborn , Infant , Child, Preschool , Child , Young Adult , Middle Aged , Biomarkers , Creatine/metabolism , Guanidinoacetate N-Methyltransferase/isolation & purification , Saliva/chemistry , Age Factors , Argentina , Chromatography, Gas/methods , Plasma , Data Interpretation, StatisticalABSTRACT
PURPOSE: Mitochondrial encephalopathy (ME) is a rare disorder of energy metabolism. The disease course can roughly be evaluated by clinical findings. The purpose of this study was to evaluate metabolic spectral changes using proton MR spectroscopy (MRS), and to establish a way to monitor ME by neuroimaging. MATERIALS AND METHODS: Proton MRS data were retrospectively reviewed in 12 patients with muscle biopsy-confirmed ME (M : F = 7 : 5, Mean age = 4.8 years). All received 1H-MRS initially and also after a ketogenic diet and mitochondrial disease treatment cocktail (follow up average was 10.2 months). Changes of N-acetylaspartate/creatine (NAA/Cr) ratio, choline/creatine (Cho/Cr) ratio, and lactate peak in basal ganglia at 1.2 ppm were evaluated before and after treatment. Findings on conventional T2 weighted MR images were also evaluated. RESULTS: On conventional MRI, increased basal ganglia T2 signal intensity was the most common finding with ME (n = 9, 75%), followed by diffuse cerebral atrophy (n = 8, 67%), T2 hyperintense lesions at pons and midbrain (n = 4, 33%), and brain atrophy (n = 2, 17%). Lactate peak was found in 4 patients; 2 had disappearance of the peak on follow up MRS. Quantitative analysis showed relative decrease of Cho/Cr ratio on follow up MRS (p = 0.0058, paired t-test, two-tailed). There was no significant change in NAA/Cr ratio. CONCLUSION: MRS is a useful tool for monitoring disease progression or impro-vement in ME, and decrease or disappearance of lactate peak and reduction of Cho/Cr fraction were correlated well with improvement of clinical symptoms.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Choline/metabolism , Creatine/metabolism , Magnetic Resonance Spectroscopy , Mitochondrial Encephalomyopathies/pathology , Retrospective StudiesABSTRACT
In denervation, there was loss of protein in gastrocnemius muscles and this loss of was more in prednisolone treated animals. There was significant change of protein loss between tenotomy and tenotomy with prednisolone treatment. The reduction of protein in denervation and denervation with prednisolone treatment were also highly significant. Significant loss of muscle creatine was observed in denervation with prednisolone treatment. It was about 50% of the normal control group and about 40% when compared to other limb. In denervation alone, the creatine loss was about 24%. In tenotomy and in tenotomy with prednisolone treatment, the loss of creatine was also significantly high. All these figures regarding the reduction of muscle creatine in different experiments were highly significant. The reduction of muscle weight, protein and creatine content of muscle in denervation were due to inactivation of the muscle and due to trophic changes caused by loss of motor supply to the muscle. But in tenotomy, the reductions were only due to inactivation.
Subject(s)
Animals , Creatine/metabolism , Glucocorticoids/pharmacology , Male , Muscles/drug effects , Organ Size/drug effects , Proteins/metabolism , RatsABSTRACT
As alterações impostas ao metabolismo de ATP, CP e glicogênio são, frequentemente, associadas à menorfadiga muscular periférica aguda após o exercício físico crônico. Contudo, os metabolismos de Ca2 mais e K mais também são apontados como influenciadores dos mecanismos de fadiga muscular periférica. Tomadas separadamente, estas vias metabólicas conseguem explicar o fenômeno de maneira reduzida. Modelos multifatoriais de catástrofe ou de complexidade propõem a integração de diferentes vias metabólicas para a explicação da fadiga muscular periférica. Esta revisão apresenta algumas possíveis vias que integram os metabolismos de ATP, CP e glicogênio aos metabolismos de Ca2 mais e K mais (pontos de convergência), bem como suas alterações após o exercício crônico.
The alterations in ATP, CP and glycogen metabolisms are frequently related to high performance after chronic exercise. However, the Ca2 more and K more metabolisms should be considerate because these variables are also associated with the peripheral muscle fatigue mechanisms. When took into account separately, these two metabolic pathways just explain the phenomenon partially. Catastrophe and complexity multifactorials models try to connect different metabolic pathways in order to explain the peripheral muscle fatigue. This review presents some possible pathways that integrate the ATP, CP, and glycogen metabolisms to Ca2 more and K more metabolisms (convergence points), as well as yours adaptations to training.
Subject(s)
Creatine/metabolism , Exercise/physiology , Muscle Fatigue/physiology , Glycogen/metabolism , Adenosine Triphosphate/metabolismABSTRACT
OBJECTIVE@#The purpose of our study was to evaluate the postmortem interval with multi-voxel 1H-MR spectroscopy.@*METHODS@#Twelve healthy rabbits were studied and the quantities of N-acetylaspartate, total choline, phosphocreatine and creatine were measured by 1H-MR spectroscopy after death at 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 h.@*RESULTS@#The levels of Naa/Cr and Naa/Ch decreased following death, while the level of Ch/Cr increased initially and then decreased following death.@*CONCLUSION@#Multi-voxel proton MR spectroscopy for Naa/Cr and Ch/Cr metabolic ratio could be used in future postmortem interval studies.
Subject(s)
Animals , Female , Male , Rabbits , Aspartic Acid/metabolism , Biomarkers/metabolism , Brain/pathology , Choline/metabolism , Creatine/metabolism , Disease Models, Animal , Embolism, Air , Magnetic Resonance Spectroscopy/methods , Phosphocreatine/metabolism , Postmortem Changes , Protons , Regression Analysis , Time FactorsABSTRACT
As determinações de creatinina e uréia têm sido utilizadas para avaliar o impacto do treinamento físico. Portanto, o principal objetivo do presente estudo foi verificar o comportamento das concentrações séricas e urinárias de creatinina e uréia em futebolistas profissionais ao longo de uma periodização. Participaram do estudo 18 jogadores de futebol que foram avaliados no início (T1), meio (T2) e fim (T3) de uma periodização específica. Os atletas foram submetidos às avaliações antropométrica e de determinação da capacidade aeróbia e da eficiência do metabolismo anaeróbio alático. As concentrações de creatinina e uréia dos atletas foram mensuradas no soro e na urina, além da taxa de filtração glomerular (TFG), determinada por três métodos distintos, sendo um independente e dois dependentes do volume urinário. A análise das respostas das variáveis em T1, T2 e T3 foi realizada por Anova one-way, seguida de post hoc de Newman-Keuls, assim como foi aplicado teste de correlação de Pearson. Para todos os casos o nível de significância prefixado foi de 5 por cento. Houve melhora nos parâmetros aeróbio (p < 0,01) e anaeróbio alático (p < 0,01) ao longo da periodização, assim como foi verificada diminuição do volume urinário (p < 0,05) ao longo do estudo. As concentrações de creatinina apresentaram comportamento oposto quando determinadas no soro (p < 0,05) e na urina (p < 0,01) ao longo da periodização, não apresentando correlações significativas. Todos os métodos de determinação de TFG mostraram redução dos valores (p < 0,05) em resposta ao treinamento periodizado. Foram observadas correlações significativas entre todos os métodos em T1, e também em T2 e T3 apenas entre os métodos dependentes do volume urinário. De acordo com os resultados, é possível concluir que as concentrações de creatinina determinadas no soro e na urina de futebolistas profissionais foram sensíveis ao programa de treinamento desenvolvido; contudo, apresentaram comportamentos...
The creatinine and urea responses have been extensively used to evaluate the physical training impact. Therefore, the purpose of this study was to investigate the behavior of serum and urinary creatinine and urea concentrations during a soccer training program. Eighteen Brazilian soccer players were evaluated at the beginning (T1), in the middle (T2) and at the end (T3) of a soccer training program. The athletes had their anthropometric characteristics, aerobic capacity and alactic anaerobic metabolism efficiency assessed. Besides the measurement of serum and urinary creatinine and urea concentrations, the athletes had their creatinine clearance evaluated by three different methods. While the first method was independent from the urinary volume, the others were dependent. Anova one-way test followed by Newman-Keuls and Pearson product-moment coefficient were used to verify the responses and correlations of the data to the soccer training program. A significance level of 5 percent was chosen. The soccer training program led to an increase in aerobic (p < 0.01) and alactic anaerobic (p < 0.01) performances, however, the urinary volume diminished along the experiment (p < 0.05). The serum (p < 0.05) and urinary (p < 0.01) creatinine concentrations presented an opposite behavior during the soccer training program, in addition, there were not observed significant correlations between this parameters in any period of the study. The creatinine clearance assessed by the three different methods decreased in response to the training (p < 0.05). Significant correlations for all methods were observed only in T1. However, the urinary volume dependent methods were statistically correlated in T2 and T3. According to results, it can concluded that the serum and urinary creatinine concentrations were sensible to the training program developed, but presented opposite behaviour. This probably occurred due the limitations of the urinary method to assay creatinine...
Las respuestas de urea y creatinina han sido extensamente usadas para evaluar el impacto del entrenamiento físico. De ahí que el propósito de nuestro estudio ha sido el de investigar el comportamiento del suero y la creatinina urinaria y las concentraciones de urea durante el entrenamiento de fútbol. Fueron evaluados 18 jugadores brasileños de fútbol al inicio (T1), a la mitad (T2) y en el final (T3) de un programa de entrenamiento de fútbol. En los atletas se midieron la eficiencia de sus características antropométricas, capacidad aeróbica y metabolismo anaeróbico alatico. Sumadas a las medidas de suero y creatinina urinaria y concentraciones de urea, también se evaluó en los atletas la eliminación de creatinina mediante tres métodos diferentes. Mientras que el primer método fue independiente del volumen urinario, los otros fueron dependientes. Para verificar las respuestas y la correlación de datos en el programa de entrenamiento de fútbol se utilizó el test de ANOVA (one-way), seguido del coeficiente de Newman-Keuls y Pearson, producto-momento y escogimos un nivel de significancia de 5 por ciento. El programa de entrenamiento de fútbol midió un incremento en el desempeño aeróbico (p < 0.01) y un desempeño alatico anaeróbico (p < 0.01), más aún, el volumen de orina disminuyó a lo largo de la experiencia (p < 0.05). Las concentraciones de suero (p < 0.05) y creatinina urinaria (p < 0.01) presentaron un comportamiento opuesto durante el programa de entrenamiento, en contrapartida, no se observó correlación significativa entre los parámetros durante el periodo de estudio. La medición hecha de la eliminación de creatinina por los tres métodos disminuyó como respuesta al entrenamiento. Se observó correlación significativa para T1 en todos los métodos. Sin embargo, el volumen de orina dependiente del método fue correlacionado estadísticamente en T2 y T3. De acuerdo a nuestros resultados, podemos concluir que las concentraciones séricas y...
Subject(s)
Humans , Male , Young Adult , Analysis of Variance , Athletes , Creatine/metabolism , Athletic Performance , Soccer , Anaerobic Threshold , Blood Proteins/metabolism , Glomerular Filtration Rate , Kidney Function TestsABSTRACT
OBJETIVO: Descrever os achados da espectroscopia de prótons (¹H-ERM) na doença de Alzheimer (DA) e no comprometimento cognitivo sem demência (CIND) em uma amostra da comunidade. MÉTODO: Foram avaliados seis pacientes com DA, sete com CIND e sete controles normais, originários da comunidade. ¹H-ERM foi realizada com voxel de 8 cm³ nas regiões temporal direita, parietal esquerda e occipital medial e estudados os metabólitos: N-acetilaspartato (NAA), creatina (Cr), colina (Cho) e mio-inositol (mI). RESULTADOS: O NAA foi maior nos indivíduos controles do que nos DA e intermediário no CIND. Análise de função discriminante mostrou que as associações Cr parietal-Cr occipital e Cr parietal-Cho occipital identificaram corretamente 92,3 por cento da amostra comparando Controle vs DA. Na comparação Controle vs CIND O mI temporal identificou corretamente 78,6 por cento dos indivíduos. CONCLUSÃO: A espectroscopia pode contribuir para o diagnóstico e seguimento de indivíduos com comprometimento cognitivo; avaliações de pacientes da comunidade podem revelar achados diferentes quanto à distribuição dos metabólitos cerebrais.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Alzheimer Disease/metabolism , Cognition Disorders/metabolism , Magnetic Resonance Spectroscopy , Protons , Aspartic Acid/analysis , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Case-Control Studies , Choline/analysis , Choline/metabolism , Creatine/analysis , Creatine/metabolism , Educational Status , Inositol/analysis , Inositol/metabolism , Neuropsychological TestsABSTRACT
OBJETIVO: Comparar dados de espectroscopia de prótons por ressonância magnética com clínicos e propor um estadiamento espectroscópico da doença de Alzheimer(DA).MÉTODO: Sujeitos (n=46), normais (12) e com DA (34), emparelhados por idade (CDR0-CDR3); diagnóstico de DA de acordo com os critérios DSM-IV/NINCDS-ADRDA; 1H-MRS com Signa Horizon LX-GE, 1.5T; voxel único em região hipocampal/RHC e área posterior do cíngulo/APC. RESULTADOS: Redução estatisticamente significativa (p<0.01) apenas de Naa/Cr - na RHC entre CDR0, CDR1+CDR2 e CDR3, e na APC entre CDR0 e CDR1+CDR2 em relação a CDR3. CONCLUSÃO: A RHC é a primeira a apresentar redução de Naa (CDR1). A APC é acometida mais tardiamente (CDR3). Esses valores declinam progressivamente de acordo com os estágios de gravidade. Considerando as disparidades entre a RHC e a APC é possível sugerir um estadiamento espectroscópico (metabólico) (MS) da DA como segue: MS0 (CDR0)=RHC e APC ambos normais, MS1-2 (CDR1-2)=RHC anormal e APC normal e MS3 (CDR3)=RHC e APC ambos anormais. Esses resultados permitem um diagnóstico precoce, o seguimento do processo degenerativo ao longo da evolução e sugerir um estadiamento espectroscópico relacionado aos estágios clínicos da DA.
Subject(s)
Aged , Aged, 80 and over , Animals , Female , Humans , Male , Middle Aged , Alzheimer Disease/diagnosis , Limbic System/metabolism , Analysis of Variance , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Case-Control Studies , Creatine/metabolism , Magnetic Resonance Spectroscopy , Psychiatric Status Rating Scales , Severity of Illness IndexABSTRACT
This study was conducted to investigate the metabolic changes in the motor and motor association cortices following axonal injury in the internal capsule that was caused by deep intracerebral hematoma. Using proton magnetic resonance spectroscopy (1H MRS), the authors studied the primary motor cortices (M-1) and sup-plementary motor areas (SMA) of 9 hemiparetic patients with documentable hemi-paresis of varying severity, and we studied 10 normal volunteers as controls. To measure the M-1 and SMA biochemical changes, 4 separate single volumes of inter-est(VOIs) were located bilaterally in the affected and unaffected hemisphere (AH and UH).1H MRS provided a neuronal and axonal viability index by measuring levels of N-acetylaspartate (NAA) and creatine/phosphocreatine (Cr). The M-1/SMA NAA/Cr ratios of the AH and UH in patients, and the AH and normal volunteers were com-pared. The NAA/Cr ratios of the M-1 and SMA in AH, and the SMA in UH were sig-nificantly lower than those of normal volunteers. These 1H MRS findings indicate that axonal injury in the descending motor pathway at the level of internal capsule could induce metabolic changes in the higher centers of the motor pathway.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Aspartic Acid/analogs & derivatives , Basal Ganglia Hemorrhage/metabolism , Creatine/metabolism , Magnetic Resonance Spectroscopy , Motor Cortex/metabolism , Paresis/metabolism , Phosphocreatine/metabolism , Protons , Pyramidal Tracts/metabolismABSTRACT
We report the clinical and MR manifestations of an 18 year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Recurrent status epilepticus caused reversible cytotoxic edema on diffusion-weighted images (DWI). Initial and one month follow-up MR spectroscopy, after seizure control, showed some discrepancies in the ratio of metabolites. N-acetylaspartate (NAA) partially recovered (NAA/creatine (Cr) ratio: 1.27-->1.84). This was because of a normalization of decreased NAA due to cellular dysfunction as a result of status epilepticus. A low ratio of NAA/Cr due to abnormal mitochondria remained in the decreased state. Reversible NAA/Cr ratios in the acute lesion suggested that NAA reflects the neuronal function as well as the level of neuronal structural damage. The altered NAA/Cr ratio better correlated with the abnormal signal intensity area of T2-weighted images (T2WI) and DWI than the lactate (Lac)/Cr ratio. With conservative treatment with anti-epileptics not accompanied by coenzyme Q or sodium dichloroacetate, lactate persistently increased (Lac/Cr ratio: 1.01-->1.21) because of the continued production of lactate in cells with respiratory deficiency, which is the main pathology of MELAS.
Subject(s)
Female , Humans , Adolescent , Aspartic Acid/metabolism , Aspartic Acid/analogs & derivatives , Brain/metabolism , Creatine/metabolism , Diffusion , MELAS Syndrome/metabolism , MELAS Syndrome/diagnosis , Magnetic Resonance Imaging , Magnetic Resonance SpectroscopyABSTRACT
O magnésio e a creatina são substâncias fundamentais para a produção de energia. O magnésio tem um papel importante na contração muscular, assim como no equilíbrio do metabolismo de energia e no equilíbrio eletroquímico. A creatina, por outro lado, proporciona elevada síntese de ATP, além disso retarda o aparecimento da fadiga e facilita a recuperação muscular. Os benefícios musculares, tanto do magnésio, quanto da creatina, também podem ser estendidos ao músculo cardíaco. O composto magnésio bis-creatina quelato garante que a creatina e o magnésio alcancem a célula muscular simultaneamente, o que é decisivo para a otimização da performance de ambos nutrientes.
Subject(s)
Humans , Animals , Rats , Chelating Agents , Muscle Contraction/physiology , Heart/physiology , Creatine/physiology , Magnesium/physiology , Adenosine Triphosphate/metabolism , Chelating Agents/metabolism , Creatine/metabolism , Dietary Supplements , Exercise/physiology , Magnesium Deficiency/metabolism , Magnesium/metabolismABSTRACT
Creatina é um nutriente natural, encontrado em alimento de origem animal, como carnes e peixes, sendo também sintetizada endogenamente no fígado, pâncreas e rins, a partir dos aminoácidos glicina, arginina e metionina. A creatina total (TCr) existente no músculo apresenta-se em duas formas: creatina livre (Cr) e fosfocreatina (PCr). Creatina é importante reservatório de energia para a contração muscular, pois pode sofrer fosforilação, formando fosfocreatina e, reversivelmente, pode doar o grupo fosfato para adenosina difosfato (ADP) com a finalidade de sintetizar adenosina trifosfato (ATP). Esta reação é fonte rápida de energia para o desempenho de atividades físicas de alta intensidade e curta duração...
Subject(s)
Creatine/metabolism , Dietary Supplements , Exercise , Nutritional Sciences , Adenosine Triphosphate/biosynthesis , Electric Power Supplies , SportsABSTRACT
A evoluçäo da cirurgia para epilepsia vem sendo acompanhada por novos métodos de neuroimagem, näo só morfológicos, como, também, funcionais. Dentre esses últimos, destacamos a espectroscopia por ressonância magnética (ERM), de especial interesse deste artigo. A ERM parece ser promissora na definiçäo da identificaçäo do foco epileptogênico, pela demonstraçäo das alteraçöes dos metabólicos do fósforo (31P-ERM) e avaliaçäo pelo próton de H+ (1H-ERM). Reconhece-se a variaçäo da 1H-ERM normal, segundo alteraçöes idade-relacionadas, para localizaçäo do foco epileptogênico, no período interictal, pelas taxas de NAA (N-acetilaspartato), Cr (creatina) e Co (colina), e relaçöes NAA: Co e NAA: Cr; e no ictal, pelas mesmas taxas e pela avaliaçäo do lactato. A estimativa de aminoácidos neurotransmissores também auxilia nessa topografia. A ERM, em especial, a 1H-ERM, é de grande potencialidade no estudo bioquímico do cérebro, in vivo, e poderá vir a ter crescente importância no diagnóstico topográfico da regiäo epileptogênica dos pacientes com epilepsia, na dependência da idade e do local do foco