MSCs-derived apoptotic extracellular vesicles promote muscle regeneration by inducing Pannexin 1 channel-dependent creatine release by myoblasts / 国际口腔科学杂志·英文版

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.

The risk prediction value of paraquat poisoning dose, urine protein and myocardial enzymes / 中华劳动卫生职业病杂志

Objective: To explore the value of paraquat (PQ) intake, urine protein and myocardial enzyme indexes in judging the prognosis of patients with acute PQ poisoning. Methods: From September to December 2021, all 201 patients with acute PQ poisoning admitted to Guangzhou Twelfth People's Hospital from January 2010 to December 2019 were selected as the research objects. Based on follow-up results 60 days after poisoning, the research objects were divided into survival group (n=78) and death group (n=123) . The differences in information about poisoning, treatment plan, PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase between the two groups of patients were compared and analyzed. Logistic regression and Cox regression were used to analyze the correlation between poisoning outcome and PQ intake, urine protein and myocardial enzymes. ROC curve and principal component analysis were used to explore high-efficiency indicators for predicting the outcome of acute PQ poisoning. Results: The PQ intake[50 (20, 100) ml], urine protein (total rank 15570.50) , creatine kinase[ (336.36±261.96) U/L], creatine kinase isoenzyme[ (43.91±43.74) U/L], lactate dehydrogenase [ (346.01±196.50) U/L], α-hydroxybutyrate dehydrogenase content[ (271.23±11.92) U/L] of patients in the death group were all higher than the survival group[15 (10, 20) ml, 4730.50, (187.78±178.06) U/L, (18.88±15.50) U/L, (190.92±60.50) U/L, (152.60±48.34) U/L, respectively] (P<0.05) . The outcome of acute PQ poisoning was positively correlated with PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase (P<0.05) . Multivariate logistic regression and multivariate Cox regression analysis showed that creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase and α-hydroxybutyrate dehydrogenase was positively correlated with the prognosis of patients with acute PQ poisoning (P<0.05) . ROC curve analysis and principal component analysis showed that the combined indexes of PQ intake, urine protein and myocardial enzymes had the highest efficacy and weight in judging the prognosis of patients (AUC=0.91, weight coefficient=0.19, sensitivity=0.76, specificity=0.89) . When the combined score was ≥4, the probability of accurately predicting the death of patients was as high as 91% (positive predictive value=0.91) . Conclusion: PQ intake, urine protein combined with creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase has high value in predicting the prognosis of patients with acute PQ poisoning.

Clinical characterization and genetic testing for a patient with creatine deficiency syndrome 1 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child affected with cerebral creatine deficiency syndrome 1 (CCDS1).@*METHODS@#High-throughput sequencing was carried out to screen pathogenic variant associated with the clinical phenotype of the proband. The candidate variant was verified by Sanger sequencing.@*RESULTS@#High-throughput sequencing revealed that the proband has carried heterozygous c.327delG variant of the SLC6A8 gene, which was verified by Sanger sequencing.Neither parent was found to carry the same variant.@*CONCLUSION@#The de novo heterozygous c.327delG variant of the SLC6A8 gene probably underlay the CCDS1 in this child.

Comparación clínica y laboratorial de la fiebre amarilla severa versus dengue grave en Perú / Clinical and laboratory differences between severe yellow fever and severe dengue in emergency patients

En los centros de Emergencia con poco apoyo de laboratorio, es difícil diferenciar a los pacientes con dengue grave y fiebre amarilla severa. El objetivo fue comparar el perfil clínico y de laboratorio de los pacientes con dengue grave y fiebre amarilla severa en Urgencias. Se realizó un estudio observacional retrospectivo de pacientes con diagnóstico confirmado de dengue y fiebre amarilla en el período 2018 a 2020 atendidos en la Unidad de Emergencia del Hospital Carrión, Huancayo-Perú. Se evaluaron un total de 35 pacientes, 11 pacientes (31,4%) fueron diagnosticados con fiebre amarilla severa y 24 pacientes (68,5%) con dengue grave. La media de los resultados de laboratorio con fiebre amarilla severa fueron bilirrubina indirecta 4,7 ml/dL, aspartato transaminasa 4463 UI/L, transaminasa aminotransferasa 4329 UI/L, creatinina 4,9 mg/dl. En pacientes con dengue grave el hematocrito promedio fue 51,8, hemoglobina 17,6 g/dl, plaquetas 24 × 103/mm. En pacientes con síndrome ictérico-febril la presencia de bradicardia, bilirrubina indirecta elevada y transaminasas muy elevadas debe hacer sospechar de fiebre amarilla; mientras que los pacientes que acuden por ascitis, derrame pleural, aumento de hematocrito y deficiencia de plaquetas, se debe tratar como dengue grave sobre todo en Unidades de Emergencia con poco apoyo de laboratorio(AU)

In Emergency centers with little laboratory support, differentiating patients with dengue and yellow fever is difficult. The Aim was to compare the clinical and laboratory profile of patients with severe dengue and severe yellow fever in the Emergency unit. We conducted a retrospective observational study of patients with a confirmed diagnosis of dengue and yellow fever in the period 2018 to 2020 treated in the Emergency Unit of the Carrión hospital, Huancayo-Peru. A total of 35 patients were evaluated, 11 patients (31.4%) were diagnosed with severe yellow fever and 24 patients (68.5%) with severe dengue. The mean laboratory results in patients with severe yellow fever were indirect bilirubin 4.7 ml/dL, aspartate transaminase 4463 IU/L, transaminase aminotransferase 4329 IU/L, creatinine 4.9 mg / dl. In patients with severe dengue were hematocrit 51.8, hemoglobin 17.6 g / dl, platelets 24 × 103 / mm. In patients with syndrome jaundice and fever the presence of bradycardia, elevated indirect bilirubin, and very elevated transaminases should be suspicious for yellow fever; while in patients who come for ascites, pleural effusion, increased hematocrit and platelet deficiency, it should be treated as severe dengue especially in Emergency Units with little laboratory support(AU)

Pharmacological Treatment of Sarcopenia Tratamento medicamentoso da sarcopenia / Tratamento medicamentoso da sarcopenia Pharmacological Treatment of Sarcopenia

Abstract Sarcopenia has been acquiring a growing importance in the scientific literature and in doctors' offices. As the population ages, it becomes increasingly essential to know, prevent, and treat this clinical condition. The purpose of the present review is to bring up the current evidence on the diagnosis of this pathology, in a practical way, as well as the main current treatment options.

Resumo A sarcopenia vem ganhando cada vez mais importância na literatura científica e nos consultórios médicos. Com o envelhecimento da população, essa condição clínica se torna cada vez mais imprescindível de se conhecer, se prevenir e de se tratar. O objetivo desta revisão é trazer as evidências atuais sobre o diagnóstico dessa patologia, de forma prática, bem como as principais opções atuais de tratamento.

The use of a pre-workout supplement containing an amphetamine derivative and its effects on physical performance / Uso de suplemento pre-entrenamiento que contiene un derivado anfetamínico y sus efectos sobre el desempeño físico / Uso de suplemento pré-treino que contém um derivado anfetaminico e seus efeitos sobre o desempenho físico

ABSTRACT Introduction: The quest for better sports performance or simply for esthetic ends has led individuals to seek ergogenic resources indiscriminately to attain their goals. It is believed that nutritional supplements promote better strength, power, focus and better reaction time. Nutritional supplements are used to delay fatigue and increase athletic performance. Also, the anorectics, drugs derived from amphetamines and commonly sought for weight loss, act on the central nervous system by releasing substances that transmit the sensation of not being hungry. Supplements that promise quick solutions to these goals may have compounds in their formulas that compromise health. Objectives: In this study, the potential of creatine and Jack 3D® to boost physical performance and delay muscle fatigue was evaluated in animals that were given the supplements. Methods: The animals underwent 10 weeks of swim training at 80% of the maximum load and received creatine and/or Jack 3D. The muscle contractions were recorded by an electrophysiograph for analysis of muscle fatigue. Results: It was observed that the SED+CR group had significantly different values compared to the SED group and NAT+CR group showed significant differences between groups for the SED, SED+JACK, JACK, NAT and NAT+JACK groups (p <0.05). For the two last parameters, the SED group showed a significant difference in relation to the SED+CR, NAT and NAT+CR groups (p <0.05). Conclusions: These results demonstrate a possible positive influence of physical exercise associated with the use of creatine, delaying muscle fatigue and making an increase in sports performance possible. Level of Evidence III; Development of diagnostic criteria in consecutive patients (with "gold" reference standard applied) .

RESUMEN Introducción: La búsqueda por el mejor desempeño deportivo o simplemente para fines estéticos ha inducido a los individuos a buscar indiscriminadamente recursos ergogénicos para alcanzar el éxito. Se cree que la ingestión de suplementos nutricionales puede proporcionar mayor resistencia, potencia, enfoque y mejor tiempo de reacción. Los suplementos nutricionales son empleados para retardar el surgimiento de la fatiga y aumentar el desempeño atlético. También comúnmente buscados para adelgazamiento están los anorexígenos, medicamentos a base de drogas anfetamínicas, que actúan sobre el sistema nervioso central liberando sustancias que transmiten la sensación de ausencia de hambre. Los suplementos que prometen soluciones rápidas para estos objetivos pueden presentar en sus fórmulas, compuestos que comprometen la salud. Objetivo: En este estudio fue evaluado el potencial de la creatina y del Jack3D® para el desempeño físico y la fatiga muscular de los animales que recibieron la suplementación. Métodos: Los animales fueron sometidos a 10 semanas de entrenamiento de natación a 80% de la carga máxima y recibieron creatina y/o Jack3D. Las contracciones musculares fueron registradas por un electrofisiógrafo para análisis de la fatiga muscular. Resultados: Se observó que el grupo SED+CR presentó valores significativamente diferentes en comparación con el grupo SED y el grupo NAT+CR presentó diferencias significativas con relación a los grupos SED, SED+JACK, NAT y NAT+JACK (p < 0,05). En los dos últimos parámetros, el grupo SED presentó diferencia significativa con relación a los grupos SED+CR, NAT y NAT+CR (p < 0,05). Conclusión: Esos resultados demuestran una posible influencia positiva del ejercicio físico asociado al uso de la creatina, retardando la fatiga muscular y posibilitando un aumento en el desempeño deportivo. Nivel de evidencia III; Desarrollo de criterios diagnósticos en pacientes consecutivos (con estándar de referencia "oro" aplicado) .

RESUMO Introdução: A busca pelo melhor rendimento esportivo ou simplesmente para fins estéticos tem induzido indivíduos a procurarem indiscriminadamente recursos ergogênicos para atingir o êxito. Acredita-se que a ingestão de suplementos nutricionais pode proporcionar maior resistência, potência, foco e melhor tempo de reação. Os suplementos nutricionais são empregados afim de retardar o surgimento da fadiga e aumentar o desempenho atlético. Também comumente procuradas para emagrecimento estão os anorexígenos, medicamentos à base de drogas anfetamínicas, que agem sobre o sistema nervoso central liberando substâncias que transmitem a sensação de ausência de fome. Suplementos que prometem soluções rápidas para estes objetivos podem conter em suas fórmulas compostos que comprometem a saúde. Objetivos: Neste estudo foi avaliado o potencial da creatina e do Jack 3D®para o desempenho físico e fadiga muscular dos animais que receberam a suplementação. Métodos: Os animais foram submetidos a 10 semanas de treinamento de natação a 80% da carga máxima e receberam creatina e/ou Jack 3D. As contrações musculares foram registradas por um eletrofisiógrafo para análise da fadiga muscular. Resultados: Observou-se que o grupo SED+CR apresentou valores significativamente diferentes em comparação com o Grupo SED e o Grupo NAT+CR apresentou diferenças significativas com relação aos grupos SED, SED+JACK, NAT e NAT+JACK (p < 0,05). Nos dois últimos parâmetros, o Grupo SED apresentou diferença significativa com relação aos grupos SED+CR, NAT e NAT+CR (p < 0,05). Conclusão: Esses resultados demonstram uma possível influência positiva do exercício físico associado ao uso da creatina, retardando a fadiga muscular e possibilitando um aumento no desempenho esportivo. Nível de Evidência III; Desenvolvimento de critérios diagnósticos em pacientes consecutivos (com padrão de referência "ouro" aplicado) .

Effect of creatine and sildenafil citrate on the physical performance of mice / Efecto de la creatina y del citrato de sildenafil sobre el desempeño físico de ratones / Efeito da creatina e do citrato de sildenafila sobre o desempenho físico de camundongos

ABSTRACT Introduction: The use of substances to enhance sports performance among professional and amateur athletes is increasing. Such substances may either be included in the group of dietary supplements or fall into pharmacological classes. Every substance used for this purpose is called an ergogenic agent. The number of ergogenic options available increases every day, favoring overuse and use without proper guidance. Among the dietary supplements, we highlight the use of creatine, a substance widespread in sports. Among the pharmacological groups, many drugs are used. Recently the use of sildenafil citrate by professional athletes from various predominantly aerobic sports modalities was reported in the media. Objective: To compare and demonstrate the responses caused by physical training associated with the use of creatine and sildenafil citrate in mice. Methods: A swim training protocol was applied and then an electrophysiograph was used in order to obtain parameters related to contraction intensity, the area under the curve and the percentage drop. Results: The responses obtained demonstrated the ergogenic action of creatine because it altered the parameters used for measurement. The use of sildenafil citrate did not yield satisfactory results to frame the drug as an ergogenic agent. Conclusion: Creatine has an ergogenic effect, reducing the percentage drop after 10 seconds, while sildenafil demonstrated no ergogenic potential and, interestingly, resulted in weaker responses when compared to the exercise groups. Evidence level II; Comparative prospective study .

RESUMEN Introducción: El uso de sustancias con el objetivo de aumentar el rendimiento deportivo entre atletas profesionales y amateurs es creciente. Tales sustancias pueden formar parte del grupo de suplementos alimentarios o integrar clases farmacológicas. Toda sustancia empleada para ese fin es denominada agente ergogénico. El número de opciones entre los agentes ergogénicos aumenta cada día, favoreciendo así su uso excesivo y sin la debida orientación. Entre los suplementos alimentarios, se destaca el uso de creatina, sustancia muy difundida en el medio deportivo. Ya entre los grupos farmacológicos, muchas sustancias son usadas. Recientemente, fue divulgado entre los medios de comunicación el uso de citrato de sildenafil por atletas profesionales, de varias modalidades deportivas, predominantemente las aeróbicas. Objetivos: Comparar y demostrar las respuestas ocasionadas por el entrenamiento físico, asociadas al uso de creatina y citrato de sildenafil en ratones. Métodos: Se aplicó un protocolo de entrenamiento de natación y, a continuación, se usó un electrofisiógrafo con el objetivo de obtener parámetros referentes a la intensidad de contracción, al área bajo la curva y a la caída porcentual. Resultados: Las respuestas obtenidas demuestran acción ergogénica de la creatina, visto que alteraron los parámetros empleados para la medición. Ya el uso de citrato de sildenafil no presentó resultados satisfactorios para encuadrar al fármaco como agente ergogénico. Conclusión: La creatina presenta efecto ergogénico porque reduce la caída porcentual después de 10 segundos, mientras que el sildenafil no presentó potencial ergogénico y, curiosamente, demostró respuestas inferiores cuando comparado a los grupos de ejercicio. Nivel de evidencia II; Estudio prospectivo comparativo .

RESUMO Introdução: O uso de substâncias com o objetivo de aumentar o rendimento esportivo entre atletas profissionais e amadores é crescente. Tais substâncias podem fazer parte do grupo de suplementos alimentares ou integrar classes farmacológicas. Toda substância empregada para esse fim é denominada de agente ergogênico. O número de opções entre os agentes ergogênicos aumenta a cada dia, favorecendo assim o uso em demasia e sem a devida orientação. Entre os suplementos alimentares, salientamos a utilização de creatina, substância muito difundida no meio esportivo. Já entre os grupos farmacológicos, muitas substâncias são utilizadas. Recentemente, foi divulgado entre os meios de comunicação o uso de citrato de sildenafila por atletas profissionais de várias modalidades esportivas, predominantemente as aeróbicas. Objetivos: Comparar e demonstrar as repostas ocasionadas pelo treinamento físico, associadas ao uso de creatina e citrato de sildenafila em camundongos. Métodos: Aplicou-se um protocolo de treinamento de natação e, a seguir, empregou-se um eletrofisiógrafo com objetivo de obter parâmetros referentes à intensidade de contração, à área sob a curva e à queda percentual. Resultados: As respostas obtidas demonstram ação ergogênica da creatina, visto que alteraram os parâmetros empregados para a mensuração. Já a utilização de citrato de sildenafila não apresentou resultados satisfatórios para enquadrar o fármaco como agente ergogênico. Conclusão: A creatina apresenta efeito ergogênico porque reduz a queda percentual após 10 segundos, já a sildenafila não apresentou potencial ergogênico e, curiosamente, demonstrou respostas inferiores quando comparado aos grupos de exercício. Nível de evidência II; Estudo prospectivo comparativo .

Effects of dietary creatine supplementation on kidney and striated skeletal muscles of rats submitted to ischemia and reperfusion of hind limbs

ABSTRACT Purpose To evaluate the effect of creatine supplementation in the diet of rats subjected to ischemia and reperfusion of hind limbs. Methods Eighteen male Wistar rats were randomized to receive dietary creatine supplementation (G1) or no supplementation (G2), before being subjected to 4 h of ischemia followed by 4 h of reperfusion. In addition, 10 rats (G3) underwent the same surgical procedure, without ischemia, but with supplementation. After reperfusion, kidney and musculature were evaluated for histological damage and serum levels of alanine aminotransferase, urea and creatinine were obtained. Results The urea dosage showed significant differences between the groups (averages G1 = 155.1; G2 = 211.27; G3 = 160.42). Histological analysis found significant differences between G1 and G2 (but not between G1 and G3) in renal myoglobin cylinders and vacuolar degeneration variables and in hypereosinophilia and karyopyknosis variables in muscle fibers. There were no significant differences in the other variables studied. Conclusions Creatine supplementation was related to fewer histological lesions, as well as lower levels of plasma urea, which may suggest a protective effect against lesions caused by ischemia and reperfusion of posterior paws muscles in Wistar rats.

Effects of dietary creatine supplementation on kidney and striated skeletal muscles of rats submitted to ischemia and reperfusion of hind limbs

ABSTRACT Purpose To evaluate the effect of creatine supplementation in the diet of rats subjected to ischemia and reperfusion of hind limbs. Methods Eighteen male Wistar rats were randomized to receive dietary creatine supplementation (G1) or no supplementation (G2), before being subjected to 4 h of ischemia followed by 4 h of reperfusion. In addition, 10 rats (G3) underwent the same surgical procedure, without ischemia, but with supplementation. After reperfusion, kidney and musculature were evaluated for histological damage and serum levels of alanine aminotransferase, urea and creatinine were obtained. Results The urea dosage showed significant differences between the groups (averages G1 = 155.1; G2 = 211.27; G3 = 160.42). Histological analysis found significant differences between G1 and G2 (but not between G1 and G3) in renal myoglobin cylinders and vacuolar degeneration variables and in hypereosinophilia and karyopyknosis variables in muscle fibers. There were no significant differences in the other variables studied. Conclusions Creatine supplementation was related to fewer histological lesions, as well as lower levels of plasma urea, which may suggest a protective effect against lesions caused by ischemia and reperfusion of posterior paws muscles in Wistar rats.

Analysis of clinical features and genetic variants in a child with creatine deficiency syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic basis for a patient diagnosed with creatine deficiency syndrome (CDS).@*METHODS@#The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. The level of creatine was determined by using a magnetic resonance spectrum (MRS) method.@*RESULTS@#The patient presented with development delay and poor response to stimuli. No obvious abnormality was found with his muscle tone and strength of his limbs. Borderline EEG was detected. MRI showed abnormal development of the white matter and dysplasia of corpus callosum. Urine organic acid screening has shown increased glycerin-3-phosphate. WES revealed that the patient has carried compound heterozygous variants of the GAMT gene, namely c.412C>T and IVS4-1G>A, which were respectively derived from his mother and father. MRS showed reduced creatine in bilateral basal ganglia. Functional study of the splicing site suggested that the IVS4-1G>A variant has resulted skipping of exon 5 upon splicing.@*CONCLUSION@#The compound variants of the GAMT gene probably underlay the disease in this child. Above finding has enriched the spectrum of GAMT gene variants.

Clinical features and SLC6A8 gene mutations of cerebral creatine deficiency syndrome I: an analysis of two families / 中国当代儿科杂志

This article reports the clinical and genetic features of two cases of cerebral creatine deficiency syndrome I (CCDSI) caused by SLC6A8 gene mutations. Both children were boys. Boy 1 (aged 2 years and 10 months) and Boy 2 (aged 8 years and 11 months) had the clinical manifestations of delayed mental and motor development, and convulsion. Their older brothers had the same symptoms. The mother of the boy 1 had mild intellectual disability. The genetic analysis showed two novel homozygous mutations, c.200G>A(p.Gly67Asp) and c.626_627delCT(p.Pro209Argfs*87), in the SLC6A8 gene on the X chromosome, both of which came from their mothers. These two novel mutations were rated as possible pathogenic mutations and were not reported in the literature before. This study expands the mutation spectrum of the SLC6A8 gene and has great significance in the diagnosis of boys with delayed development, and epilepsy.

Efectos en la función renal de la suplementación de creatina con fines deportivos / Effects of creatine supplementation on renal function

Creatine supplements may transitorily rise serum creatinine levels and mimic a kidney disease. If its use is associated with a high protein diet, the resulting increase in blood urea nitrogen will increase the confusion. Since clinical laboratories usually inform the estimated glomerular filtration rate based on serum creatinine, its elevation may lead to over diagnose a chronic renal failure, with the inherent personal and public health consequences. Creatine supplements are safe and do not cause renal disease. Reports of kidney damage associated with its use are scanty. However, creatine supplements should not be used in people with chronic renal disease or using potentially nephrotoxic medications.

Short-term creatine supplementation changes protein metabolism signaling in hindlimb suspension

The effect of a short-term creatine supplementation on hindlimb suspension (HS)-induced muscle atrophy was investigated. Creatine monohydrate (5 g/kg b.w. per day) or placebo, divided in 2 daily doses, was given by oral gavage for 5 days. Rats were maintained in HS with dietary supplementation concomitantly for 5 days. Body weight, soleus and EDL muscle masses, and cross-sectional areas (CSA) of the muscle fibers were measured. Signaling pathways associated with skeletal muscle mass regulation (FST, MSTN, FAK, IGF-1, MGF, Akt, mTOR, atrogin-1, and MuRF1 expressions, and Akt, S6, GSK3B, and 4EBP1 proteins) were evaluated in the muscles. Soleus muscle exhibited more atrophy than the EDL muscle due to HS. Creatine supplementation attenuated the decrease of wet weight and increased p-4EBP1 protein in the EDL muscle of HS rats. Also, creatine increased mTOR and atrogin-1 expressions in the same muscle and condition. In the absence of HS, creatine supplementation increased FAK and decreased MGF expressions in the EDL muscle. Creatine attenuated the increase in FST expression due to HS in the soleus muscle. MuRF1 expression increased in the soleus muscle due to creatine supplementation in HS animals whereas atrogin-1 expression increased still further in this group compared with untreated HS rats. In conclusion, short-term creatine supplementation changed protein metabolism signaling in soleus and EDL muscles. However, creatine supplementation only slightly attenuated the mass loss of both muscles and did not prevent the CSA reduction and muscle strength decrease induced by HS for 5 days.

Assessment of serum biomarkers and coagulation/fibrinolysis markers for prediction of neurological outcomes of out of cardiac arrest patients treated with therapeutic hypothermia

OBJECTIVE: Despite increased survival in patients with cardiac arrest, it remains difficult to determine patient prognosis at the early stage. This study evaluated the prognosis of cardiac arrest patients using brain injury, inflammation, cardiovascular ischemic events, and coagulation/fibrinolysis markers collected 24, 48, and 72 hours after return of spontaneous circulation (ROSC).METHODS: From January 2011 to December 2016, we retrospectively observed patients who underwent therapeutic hypothermia. Blood samples were collected immediately and 24, 48, and 72 hours after ROSC. Neuron-specific enolase (NSE), S100-B protein, procalcitonin, troponin I, creatine kinase-MB, pro-brain natriuretic protein, D-dimer, fibrin degradation product, antithrombin-III, fibrinogen, and lactate levels were measured. Prognosis was evaluated using Glasgow-Pittsburgh cerebral performance categories and the predictive accuracy of each marker was evaluated. The secondary outcome was whether the presence of multiple markers improved prediction accuracy.RESULTS: A total of 102 patients were included in the study: 39 with good neurologic outcomes and 63 with poor neurologic outcomes. The mean NSE level of good outcomes measured 72 hours after ROSC was 18.50 ng/mL. The area under the curve calculated on receiver operating characteristic analysis was 0.92, which showed the best predictive power among all markers included in the study analysis. The relative integrated discrimination improvement and category-free net reclassification improvement models showed no improvement in prognostic value when combined with all other markers and NSE (72 hours).CONCLUSION: Although biomarker combinations did not improve prognostic accuracy, NSE (72 hours) showed the best predictive power for neurological prognosis in patients who received therapeutic hypothermia.

Defining the Normal Trends of Serum Creatine Kinase Levels Following Spinal Surgery

STUDY DESIGN: Prospective, prognostic study, level II evidence. PURPOSE: To define the normal change in the creatine kinase (CK) levels in patients undergoing prone or supine lumbar or cervical spine surgery and to determine if positioning influences the postoperative changes in the CK levels. OVERVIEW OF LITERATURE: Spine surgery is one of the most commonly performed and fastest growing areas of surgery in the United States. Thus, the various possible complications need to be understood, and risk factors for these complications need to be mitigated. One of the rare complications, reported in the literature as small case series and case reports, is rhabdomyolysis, diagnosed by high CK levels. Thus far, very few studies have examined the rise in CK levels following spine surgery, and to our knowledge, none has assessed the potential association of surgical positioning and the rise in CK levels. METHODS: We retrospectively analyzed 94 patients. We obtained their preoperative CK levels, and re-assessed their CK levels at postoperative day (POD) 1, 2, and 3, as well as at their 2-week follow-up. The data were analyzed with respect to the spine level and positioning to determine if positioning had any effect on the postoperative rise in the CK level. RESULTS: Total 94 consecutive patients were enrolled in this study. The average preoperative CK level was 179.64, and the average CK level was 847.04 on POD 1. Prone positioning showed a greater rise in the CK levels following surgery than the supine positioning. In a similar manner, lumbar procedures led to a larger rise in the CK levels than cervical surgery. Prone/lumbar surgery showed the largest increase among all groups. Finally, revision surgery and instrumentation both increased the postoperative CK levels. CONCLUSIONS: This study demonstrated that positioning can affect the postoperative CK level rise, with patients undergoing prone/lumbar surgery showing the greatest rise in the postoperative CK levels. This rise, however, may be related to paraspinal muscle damage, rather than the positioning itself.

Effects of heme oxygenase-1 upregulation on isoproterenol-induced myocardial infarction

The present study was designed to examine the effect of heme oxygenase-1 (HO-1) induction by cobalt protoporphyrin (CoPP) on the cardiac functions and morphology, electrocardiogram (ECG) changes, myocardial antioxidants (superoxide dismutase [SOD] and glutathione [GSH]), and expression of heat shock protein (Hsp) 70 and connexin 43 (Cx-43) in myocardial muscles in isoproterenol (ISO) induced myocardial infarction (MI). Thirty two adult male Sprague Dawely rats were divided into 4 groups (each 8 rats): normal control (NC) group, ISO group: received ISO at dose of 150 mg/kg body weight intraperitoneally (i.p.) for 2 successive days; ISO + Trizma group: received (ISO) and Trizma (solvent of CoPP) at dose of 5 mg/kg i.p. injection 2 days before injection of ISO, with ISO at day 0 and at day 2 after ISO injections; and ISO + CoPP group: received ISO and CoPP at a dose of 5 mg/kg dissolved in Trizma i.p. injection as Trizma. We found that, administration of ISO caused significant increase in heart rate, corrected QT interval, ST segment, cardiac enzymes (lactate dehydrogenase, creatine kinase-muscle/brain), cardiac HO-1, Hsp70 with significant attenuation in myocardial GSH, SOD, and Cx-43. On the other hand, administration of CoPP caused significant improvement in ECG parameters, cardiac enzymes, cardiac morphology; antioxidants induced by ISO with significant increase in HO-1, Cx-43, and Hsp70 expression in myocardium. In conclusions, we concluded that induction of HO-1 by CoPP ameliorates ISO-induced myocardial injury, which might be due to up-regulation of Hsp70 and gap junction protein (Cx-43).

Evaluation of Transcranial Magnetic Stimulation Efficiency in Major Depressive Disorder Patients: A Magnetic Resonance Spectroscopy Study

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD). This study evaluated the antidepressant effect of rTMS and examined how it affected N-asetyl aspartate (NAA), choline (Cho), creatine (Cr), lactate (Lac), myoinositol (mIns), glutamate (Glu), glutathione (GSH), and glutamine (Gln) metabolite levels in the left dorsolateral prefrontal cortex (DLPFC) of MDD patients who were not receiving antidepressant medication. METHODS: In total, 18 patients (10 female, 8 male) were evaluated. Each patient underwent H magnetic resonance spectroscopy (H-MRS) before and within 3 days of completion of TMS therapy. All patients completed 20 sessions of rTMS directed at the left DLPFC over a 2-week period. The Hamilton Depression Scale (HAMD) scores of patients were calculated, and their responses to treatment were assessed within 1–3 days of completion of TMS. RESULTS: We found statistically significant differences in HAMD scores before and after rTMS. Moreover, the peak metabolite ratios of NAA/Cr, GSH/Cr, and Gln/Cr were significantly higher after rTMS compared to those before rTMS. CONCLUSION: Increased understanding of the mechanism of action of TMS will improve its application and may stimulate development of new-generation therapeutic agents.

Evaluation of Metabolite Changes in the Occipital Cortex of Patients with Idiopathic Infantile Nystagmus or Bilateral Ametropic Amblyopia by Magnetic Resonance Spectroscopy

PURPOSE: To evaluate the effects of idiopathic infantile nystagmus (IN) and bilateral ametropic amblyopia on metabolites in the occipital cortex by magnetic resonance spectroscopy. METHODS: The children included in this prospective study were divided into three groups. Group 1 consisted of 11 patients with idiopathic IN, group 2 consisted of 10 patients with bilateral ametropic amblyopia and group 3 consisted of nine normal children. A single-voxel magnetic resonance spectroscopy examination was performed by placing a region of interest on the occipital cortex of each participant. N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) concentrations were measured in the occipital cortex. This was followed by calculating and comparing the NAA/Cr and Cho/Cr ratios between the three groups. The Kruskal-Wallis test, Mann-Whitney U-test, and chi-square test were used for statistical analysis. RESULTS: There was no statistically significant difference in NAA/Cr ratios between patients with idiopathic IN and normal children, but there was a statistically significant difference between these groups when Cho/Cr ratios were compared; the ratio was higher in the idiopathic IN group. There were no statistically significant differences in NAA/Cr or Cho/Cr ratios between patients with bilateral ametropic amblyopia and normal children. CONCLUSIONS: Our findings suggest that the neurochemical profile of the occipital cortex is partially affected by idiopathic IN, but not by bilateral ametropic amblyopia.