Manejo anestésico perioperatorio de la deficiencia de acil-coenzima A deshidrogenasa de cadena muy larga / Perioperative anesthetic management of very long-chain acyl-coenzyme a dehydrogenase deficiency

La deficiencia de acil-coenzima A deshidrogenasa de cadena muy larga (VLCADD) es un trastorno infrecuente del metabolismo de β-oxidación de los ácidos grasos que origina susceptibilidad a hipoglucemia, fallo hepático, cardiomiopatía y rabdomiólisis durante las situaciones catabólicas. Reportamos el caso de un varón de 10 años de edad programado para la colocación de catéter venoso central totalmente implantado durante su hospitalización por rabdomiólisis, que fue exitosamente gestionada con anestesia general con óxido nitroso, sevoflurano y remifentanilo. No se produjo hipoglucemia y los niveles de creatina quinasa no se incrementaron durante el periodo perioperatorio. Describimos las dificultades a que nos enfrentamos, y las estrategias utilizadas para evitar mayor descompensación de la enfermedad debida al estrés quirúrgico.(AU)

Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare disorder of β-oxidation fatty acid metabolism that results in susceptibility to hypoglycemia, liver failure, cardiomyopathy and rhabdomyolysis during catabolic situations. We report the case of a 10-year-old male undergoing a totally implanted central venous catheter placement during hospitalization for rhabdomyolysis, who was successfully managed with general anesthesia with nitrous oxide, sevoflurane and remifentanil. No hypoglycemia occurred and creatine kinase levels did not increase in the perioperative period. We describe the challenges encountered and the strategies used to avoid further decompensation of the disease due to surgical stress.(AU)

Perioperative anesthetic management of very long-chain acyl-coenzyme a dehydrogenase deficiency.

Very long-chain acyl-coenzyme A dehydrogenase deficiency is a rare disorder of ß-oxidation fatty acid metabolism that results in susceptibility to hypoglycemia, liver failure, cardiomyopathy and rhabdomyolysis during catabolic situations. We report the case of a 10-year-old male undergoing a totally implanted central venous catheter placement during hospitalisation for rhabdomyolysis, who was successfully managed with general anesthesia with nitrous oxide, sevoflurane and remifentanil. No hypoglycemia occurred and creatine kinase levels did not increase in the perioperative period. We describe the challenges encountered and the strategies used to avoid further decompensation of the disease due to surgical stress.

Evidencia del manejo de miopatías asociadas a estatina con coenzima Q10 / Evidence for the management of myopathies associated with statin with coenzyme Q10

Introducción: La incidencia de eventos cardiovasculares fatales es muy elevada y el tratamiento con estatinas es vital para reducir este riesgo en muchos pacientes, sin embargo, sus efectos adversos sobre el músculo esquelético dificultan la adherencia o la continuación del mismo. Se ha propuesto la suplementación de coenzima Q10 para revertir mialgias asociadas a el empleo de estatinas. Los ensayos clínicos que se realizaron en los últimos 10 años obtuvieron resultados contrapuestos. El objetivo de este trabajo es revisar la evidencia sobre la eficacia del empleo de suplementos de coenzima Q10 en para mitigar las miopatías causadas por las estatinas. Metodología: Se realizó una búsqueda sistemática de la literatura publicada hasta Julio de 2020. Las bases de datos consultadas fueron MEDLINE y SCOPUS. También se consultaron instituciones como la Agencia Española del Medicamento y Productos Sanitarios (AEMPS), la European Medicines Agency (EMA) y la Food and Drug Administration (FDA). Resultados: La etiología de las mialgias asociadas a estatinas sigue siendo desconocida y la evidencia encontrada en los ensayos clínicos y metaanalisis obtuvieron conclusiones dispares. La European Medicine Agency (EMA) solo considera el empleo de suplementos en síndrome de deficiencia primaria de coenzima Q10, mientras en Reino Unido el National Institute for Health and Care Excellence (NICE) y el National Institute of Health (NIH) no recomiendan el empleo de estos suplementos para tratar mialgias asociadas al empleo de estatinas. Conclusiones: El conjunto de los estudios analizados no consiguió una evidencia unánime para poder recomendar este empleo de suplementos de coenzima Q10 de modo confiable. Se necesitan estudios mejor diseñados que aporten reproducibilidad y robustez a futuros ensayos clínicos. (AU)

Introduction: The incidence of fatal cardiovascular events is very high and statin treatment is vital to reduce this risk in many patients, however, its adverse effects on skeletal muscle make it difficult to adhere or continue it. Coenzyme Q10 supplementation has been proposed to reverse myalgia associated with the use of statins. The clinical trials carried out in the last 10 years obtained conflicting results. The aim of the present work is to review the evidence on the efficacy of the use of coenzyme Q10 supplements in mitigating myopathies caused by statins. Methodology: A systematic review of the published literature until July 2020 was undertaken. The searched databases were MEDLINE and SCOPUS. Institutions such as the Agencia Española del Medicamento y productos Sanitarios (AEMPS), European Medicines Agency (EMA) and Food and Drug Administration were also consulted. Results: The etiology of statin-associated myalgias remains unknown, and the evidence found in clinical trials and meta-analysis drew disparate conclusions. The European Medicine Agency (EMA) only considers the use of supplements in primary coenzyme Q10 deficiency syndrome, while in the United Kingdom the National Institute for Health and Care Excellence (NICE) and the National Institute of Health (NIH) do not recommend the use of these supplements to treat myalgias associated with the use of statins. Conclusions: The set of studies analyzed did not obtain unanimous evidence to be able to reliably recommend this use of coenzyme Q10 supplements. Better designed studies that provide reproducibility and robustness to future clinical trials are needed. (AU)

Avaliação da influência da Coenzima Q10 sobre o processo de reparo periimplantar de implantes instalados em tíbias de ratos expostos ou não à nicotina / Evaluation of the influence of Coenzyme Q10 on the periimplant repair processo of implants installed in the tíbias of rats exposed or not to nicotine

O propósito do presente estudo foi avaliar a influência da Coenzima Q10 (CoQ10) no reparo periimplantar em implantes instalados em tíbias de ratos modificados sistemicamente ou não pela nicotina. Oitenta ratos machos (Wistar), foram divididos em quatro grupos (n=20). No dia 0 os animais receberam um implante (4 x 2,2mm ­ SLA) na metáfise proximal das tíbias direita e esquerda. Nos 30 dias que antecedem o procedimento cirúrgico e nos 28 que o sucedem, os animais receberam duas injeções subcutâneas diárias de 3mg/kg de hemissulfato de nicotina ou solução salina na região dorsal, com 12 horas de intervalo entre elas. Logo após à cirurgia, o protocolo se constituiu na administração via gavagem gástrica de 1 ml de glicerina vegetal, ou suplementação diária com 120 mg de CoQ10, ambos até o final do experimento. SS (SHAM): o protocolo de aplicação utilizado foi o de solução salina subcutânea, e os animais receberam gavagem gástrica diária de 1 ml de glicerina vegetal. SS-CoQ10: o protocolo de aplicação utilizado foi o de solução salina subcutânea e, como suplementação, receberam 120 mg de Coenzima Q10 via gavagem gástrica. NIC: o protocolo de aplicação utilizado foi o de nicotina, e os animais receberam gavagem gástrica diária de 1 ml de glicerina vegetal. NIC-CoQ10: o protocolo de aplicação utilizado foi o de nicotina e, como suplementação, os animais receberam 120 mg de CoQ10 via gavagem gástrica. As eutanásias foram aos 7 e 28 dias pós-operatórios. As peças coletadas foram processadas com desmineralização para as análises histológica, histométrica (PTON) e imunoistoquímica para detecção de BMP/2, OCN e TRAP; e sem desmineralização para análise da área do contato direto osso/implante (BIC). Após análise de normalidade e homocedasticidade, os dados foram submetidos aos testes mais adequados com significância de 5% (p≤0,05). Com relação ao contato osso implante, o grupo SS, SS-Q10 e NIC- Q10, apresentaram maior BIC em todos os períodos experimentais quando comparado com o grupo NIC. Os grupos SS, SS-Q10 e NIC-Q10 apresentaram também maior PTON em todos os períodos experimentais quando comparado com o grupo NIC. A análise histológica dos tecidos periimplantares mostrou que o grupo NIC-Q10 apresentou características histológicas que se mostraram similares ao grupo controle, no entanto, com maior quantidade de tecido ósseo periimplantar e menor quantidade de tecido conjuntivo. Nos padrões de marcação imunoistoquímica, quando comparado ao grupo SS, o grupo NIC-Q10 apresentou menor imunomarcação para e OCN, menor marcação para TRAP e não houve diferenças quanto a marcação de BMP2. Dentro dos limites do presente estudo, pode-se concluir que a Coenzima Q10 exerceu uma influência positiva na remodelação óssea periimplantar em implantes osseointegrados(AU)

The purpose of the presente study was to evaluate the influence of Coenzyme Q10 (CoQ10) on periimplant repair in implants installed in the tíbia of rats modificated sistemically or not by nicotine. Eighty male rats (Wistar) were divided into four groups(n=20). On day 0 the animals received na implant (4x2,2mm-SLA) in the proximal metaphasys of the right and left tíbias. In the 30 days preceding the surgical procedure and the 28 days following it, the animals received two daily subcutaneous injections of 3 mg/kg of nicotine hemissulfate or saline solution in the dorsal region, with a 12-hour interval between them. Soon after surgery, the protocol consisted of the administration via gastric gavage of 1ml of vegetable glycerin, or daily supplementation with 120 mg of CoQ10, both until the endo f of the experiment. SS (SHAM): the application protocol used was subcutaneous saline solution, and the animals received daily gastric gavage of 1 ml of vegetal glycerin. SS-CoQ10: the application protocol used was subcutaneous saline solution and, as a supplement, they received 120 mg of Coenzyme Q10 via gastric gavage. NIC: the application protocol used was nicotine, and the animals received daily gastric gavage of 1 ml of vegetable glycerin. NIC-CoQ10: the application protocol used was nicotine and, as a supplement, the animals received 120 mg of CoQ10 via gastric gavage. Euthanasias were performed at 7 and 28 days after surgery. The colleted pieces were processed with desmineralization for histological analysis, área of neofomad bone tissue, histomorfometric analysis (PTON) and immunohistochemistry for the detection of BMP2, OCN and TRAP; and without desmineralization for direct bone/implant contat (BIC) analysis. Regarding bonéimplant contact, the SS, SS-Q10 and NIC-Q10 groups showed higher BIC in all experimental periods When compared to the NIC group. The histological analysis of the periimplant tissues showed that the NIC-Q10 group presented histological characteristics that were similar to the control group, however, with a greater amount of periimplant bone tissue and less connective tissue. In immunohistochemical staining patterns, when compared to the SS group, the NICQ10 group showed lower immunostaining for and OCN, lower staining for TRAP and there were no diferences regarding BMP2 staining. Within the limits of the presente study, it can be concluded that Coenzyme Q10 exerted a positive influence on periimplant bone remodeling in osseointegrated implants(AU)

Avaliação dos efeitos da coenzima Q10 utilizada como coadjuvante local e/ou sistêmica ao tratamento mecânico da periodontite experimental em ratos tratados com nicotina / Evaluation of the effects of coenzyme Q10 as local and/or systemic adjuvant to mechanical treatment of experimental periodontitis in rats treated ith nicotine

O propósito do estudo foi avaliar a efetividade da raspagem e alisamento radicular (RAR) associado à coenzima Q10 (CQ10) administrada localmente e/ou sistemicamente no tratamento da periodontite experimental (PE) em ratos tratados sistemicamente com nicotina (NIC). 128 ratos (Wistar) foram divididos em oito grupos (n=16). Durante todo o período experimental, os animais receberam duas injeções subcutâneas diárias de 3mg/kg de hemissulfato de nicotina ou solução salina (SS) na região dorsal, com 12 horas de intervalo entre elas, começando nos 30 dias que antecederam à indução da PE. Após 15 dias da indução da PE, o protocolo de RAR foi realizado bem como o tratamento coadjuvante local e/ou sistêmico com CQ10, com e sem tratamento com a NIC, sendo: SS-PE-RAR e NIC-PE-RAR: irrigação subgengival com SS; SS-PE-RAR/Q10L e NIC-PE-RAR/Q10L: irrigação subgengival com 1ml solução de CQ10; SS-PE-RAR/Q10S e NIC-PE-RAR/Q10S: gavagem gástrica diária com 120 mg de CQ10; SS-PE-RAR/Q10LS e NIC-PE-RAR/Q10LS: irrigação subgengival com 1ml solução de CQ10 e gavagem gástrica diária com 120 mg de CQ10. As eutanásias foram realizadas 7 e 28 dias após tratamento. As peças coletadas foram processadas com desmineralização para as análises histopatológica, histométrica e imunoistoquímica para detecção de TRAP. Os dados foram submetidos ao teste paramétrico Anova two-way e pós-teste de Tukey. O nível de significância adotado foi de 5% (p≤0,05). Na análise histopatológica, pode-se observar que os grupos NIC-PE-RAR-Q10L E NIC-PE-RAR-Q10LS apresentaram tecidos periodontais com aspecto de normalidade, com preservação da inserção conjuntiva e de região de furca preservada aos 7 e 28 dias, de modo distinto do grupo NIC-PE-RAR e NIC-PE-RAR-Q10S em ambos os períodos. Na análise histométrica, pode-se observar maior porcentagem de osso na furca (POF) (p≤0,05) nos grupos NIC-PE-RAR-Q10L, NIC-PE-RAR-Q10S e NIC-PERAR-Q10LS em comparação com o grupo NIC-PE-RAR em ambos os períodos e também com o grupo SS-PE-RAR aos 28 dias. Pode-se observar menor número de células TRAP positivas (p≤0,05) no grupo NIC-PE-RAR-Q10L quando comparado aos grupos SS-PE-RAR E NIC-PE-RAR aos 7 dias e no grupo NIC-PE-RAR-Q10LS quando comparado aos mesmos grupos aos 28 dias. Conclui-se que RAR associado à CQ10 utilizada local e local/sistemicamente no tratamento da PE em ratos tratados sistemicamente com nicotina foram efetivas mostrando resultados favoráveis nas análises histopatológica, histométrica e imunoistoquímica(AU)

The aim of this study was to evaluate the effectiveness of scaling and root planing (SRP) combined with adjunctive local and/or systemic administration of coenzyme Q10 (CQ10) for the treatment of experimental periodontitis (EP) in rats systemically treated with nicotine (NIC). 128 Wistar rats were divided into 8 groups (n=16). Throughout the experiment, animals received two subcutaneous injections of either 3mg/kg nicotine hemissulfate or physiological saline solution (PSS) with 12 h interval between them. These injections were initiated 30 days prior EP induction. 15 days after EP induction, the protocol for SRP was performed together (or not) with local and/or systemic adjunctive CQ10 administration in animals treat with either NIC or PSS, as described: PSS-EP-SRP and NIC-EP-SRP: subgingival irrigation with PSS; PSS-EP-SRP/Q10L and NIC-EP-SRP/Q10L: subgingival irrigation with 1ml of CQ10 solution; PSS-EP-SRP/Q10S and NIC-EP-SRP/Q10S: daily gastric gavage with 120 mg of CQ10; PSS-EP-SRP/Q10LS and NIC-EP-SRP/Q10LS: subgingival irrigation with 1ml of CQ10 solution and daily gastric gavage with 120 mg of CQ10. The euthanasia was performed at 7 and 28 days after treatment. The specimens were collected and processed for histopathologic, histometric and immunochemical for of TRAP analyzes. The data were submitted to the two-way ANOVA and Tukey's post-test. The level of significance adopted was 5% (p≤0.05). In the histopathological analysis, it can be observed that the NIC-PE-RAR-Q10L and NIC-PE-RAR-Q10LS groups presented periodontal tissues with normal aspect, preserving the conjunctival insertion and furca region preserved at 7 and 28 days, differently from the NIC-PE-RAR and NIC-PE-RAR-Q10S groups in both periods. In histometric analysis, a higher percentage of bone in furca (PBF) (p≤0.05) can be observed in the NIC-PE-RAR-Q10L, NIC-PE-RAR-Q10S and NIC-PE-RAR-Q10LS groups compared to the NIC-PE-RAR group in both periods and also with the SS-PE-RAR group at 28 days. A lower number of TRAPpositive cells (p≤0.05) can be observed in the NIC-PE-RAR-Q10L group when compared to the SS-PE-RAR and NIC-PE-RAR groups at 7 days and in the NIC-PE-RAR-Q10LS group when compared to the same groups at 28 days. It was concluded that RAR associated with CQ10 used locally and locally/systemically in the treatment of EP in rats treated systemically with NIC were effective, showing favorable results in histopathological, histometric and immunohistochemical analyses(AU)

¿Reducen las estatinas el riesgo de glaucoma? revisión de las evidencias / Do statins reduce the risk of glaucoma? review of the evidences

Introducción: Los objetivos de este trabajo son revisar y resumir los datos publicados hasta el momento que relacionen el uso de estatinas con el riesgo de aparición o de agravamiento de glaucoma y plantear una hipótesis que explique los efectos protectores de las estatinas y su asociación con un menor riesgo de glaucoma. Método: se realizó una revisión en PubMed usando los términos “statins, hmg coa” o “hmg coa inhibitors” y “glaucoma” o “open angle glaucoma” o “intraocular pressure”. Se seleccionaron todos los artículos que incluían estudios clínicos o meta-análisis y se excluyeron comentarios, cartas a editor, artículos retractados e investigación en modelos animales. Todos los artículos fueron posteriores a 2004. Se emplearon en la revisión 17 artículos. Resultados: la mayor parte de los estudios muestran un efecto protector de las estatinas frente a la aparición y agravamiento del glaucoma de ángulo abierto. Sin embargo, otros estudios no llegan a encontrar una relación significativa e incluso alguno muestra una relación entre el glaucoma y el empleo de estatinas a altas dosis. Los efectos neuroprotectores y la inhibición de la Rho-quinasa podrían explicar los efectos encontrados. Conclusiones: la evidencia publicada no es suficiente como para recomendar el tratamiento con estatinas con el objetivo de prevenir el avance o la aparición del glaucoma. (AU)

Introduction: The objectives of this article are to review and summarize the updated published data that show the relation between treatment with statins and the incidence and progression of glaucoma. We also aimed to pose a hypothesis to explain the protective effects of statins and its association with glaucoma risk. Method: a review of the literature was carried out in the PubMed database considering the MeSH terms “statins, hmg coa” or “hmg coa inhibitors” and “glaucoma” or “open angle glaucoma” or “intraocular pressure”. All articles including clinical studies and meta-analysis were selected. Comments, letters to editors, retracted articles and research on animal models were excluded. All the articles were published from 2004. 17 articles were finally selected for review. Results: most of the studies showed a protective effect of statins on incidence or progression of open angle glaucoma. Nevertheless, other studies did not find a significant association and even one study found association between statin treatment at high doses and more incidence of glaucoma. Neuroprotective effects of statin and inhibition of Rho-kinase may help explain the described effects. Conclusions: The published results are not enough evidence to support statin recommendation as preventive treatment for the incidence or progression of glaucoma. (AU)

Benefits of micronutrient supplementation on nutritional status, energy metabolism, and subjective wellbeing.

INTRODUCTION: The human body, particularly the brain, requires energy, stored in the form of adenosine triphosphate. Energy metabolism during cellular respiration is dependent on the presence of multiple micronutrients, which act as essential components, coenzymes, or precursors at every stage. An adequate supply of multiple micronutrients is vital for efficient energy production. However, micronutrient intakes below the recommended dietary allowance are common, even in industrialized countries. Intakes of vitamins A, D, E, folate, iron, zinc, and selenium are suboptimal across all age groups. Suboptimal micronutrient levels have been shown to contribute to low energy levels, physical and mental fatigue, and impaired cognitive performance and wellbeing - symptoms frequently present in the general population. When supplemented in combination in well-conducted trials, multiple micronutrients ± coenzyme Q10 reduced oxidative stress in chronic fatigue syndrome; in healthy people they increased cerebral blood-flow hemodynamic response, energy expenditure, and fat oxidation; reduced mental and physical fatigue; improved the speed and accuracy of cognitive function during demanding tasks; and reduced stress. The results from these clinical trials suggest that even in industrialized countries, where adults might be assumed to have a healthy, balanced diet, there is a rationale to supplement with multiple micronutrients, including coenzyme Q10, to improve nutritional status, support energy metabolism, and improve subjective wellbeing.

INTRODUCCIÓN: El cuerpo humano, particularmente el cerebro, requiere energía, almacenada en forma de adenosina trifosfato. El metabolismo de la energía durante la respiración celular depende de la presencia de múltiples micronutrientes, que actúan como componentes esenciales, coenzimas o precursores en cada etapa. Un aporte adecuado de múltiples micronutrientes es vital para una producción eficiente de energía. Sin embargo, la ingesta de micronutrientes inferior a la recomendada es frecuente, incluso en los países industrializados. Las ingestas de vitaminas A, D, E, folato, hierro, zinc y selenio son subóptimas en todos los grupos de edad. Se ha demostrado que las situaciones subóptimas en relación con diversos micronutrientes contribuyen a tener niveles bajos de energía, fatiga física y mental, y deterioro del rendimiento cognitivo y el bienestar, síntomas presentes a menudo en la población general. Sin embargo, cuando se suplementa en ensayos bien controlados, con una combinación de diversos micronutrientes ± coenzima Q10, se constata una reducción del estrés oxidativo en el síndrome de fatiga crónica y, en las personas sanas, se observa un aumento de la respuesta hemodinámica del flujo sanguíneo cerebral, el gasto energético y la oxidación de la grasa; una reducción de la fatiga mental y física; una mejora de la velocidad y la precisión de la función cognitiva durante la realización de tareas exigentes, y una reducción del estrés. Los resultados de estos ensayos clínicos sugieren que, incluso en los países industrializados, donde se podría suponer que los adultos tienen una dieta saludable y equilibrada, hay motivos para complementarla con múltiples micronutrientes, incluida la coenzima Q10, con el fin de mejorar el estado nutricional, respaldar el metabolismo energético y mejorar el bienestar subjetivo.

Coenzima Q10versus vitamina D en el manejo de las mialgias asociadas a estatinas / Coenzyme Q10 versus vitamin D when handling myalgias associated to statins

Introducción: Las estatinas han mostrado ser una herramienta esencial en la prevención de eventos cardiovasculares, sin embargo, sus efectos adversos sobre el músculo esquelético conocidos como SAMS (Statin-Associated Muscle Symptoms) son frecuentes y motivan la falta de adherencia al tratamiento. Es necesario superar esta barrera con nuevas estrategias, se ha sugerido en diferentes estudios que la suplementación de vitamina D o de coenzima Q10 (CoQ10) podrían revertir este inconveniente. El objetivo de este trabajo es revisar y comparar la evidencia disponible sobre CoQ10 y la vitamina D como posibles candidatos para el manejo de las SAMS. Método: Se ha realizado una búsqueda bibliográfica de la literatura, las bases de datos consultadas fueron Medline a través de PubMed y Scopus. Resultados: Los ensayos clínicos que evaluaron la suplementación de CoQ10 con este fin obtuvieron conclusiones dispares, la suplementación oral aumentó las concentraciones séricas, pero no se ha confirmado con claridad que este incremento se transfiera al tejido musculo-esquelético ya que pocos ensayos emplearon biopsias, además, cuando se emplearon arrojaron resultados contrapuestos. Respecto a la vitamina D, destacaron estudios transversales y retrospectivos en los que se evidenció que la hipovitaminosis D se asocia a exacerbación de estas miopatías asociadas, en cambio, los ensayos que valoraron la suplementación no obtuvieron una evidencia unánime. Conclusión: No se pueden recomendar suplementos de CoQ10 de modo confiable para tratar SAMS. El estatus de vitamina D al inicio de la terapia con estatinas es un buen marcador de riesgo y mejora el pronóstico de las miopatías asociadas, en cambio, se necesitan más ensayos clínicos controlados con placebo para contrastar la utilidad en suplementación.(AU)

Introduction: Statins have shown to be an essential tool in the prevention of cardiovascular events. However, their adverse effects on skeletal muscle are common and lead to lack of adherence to treatment. Different studies suggest that vitamin D or coenzyme Q10 supplementation could reverse this problem. The aimof this work is to review and compare the available evidence on coenzyme Q10and vitamin D as possible candidates for the management of statin-related myalgias. Method: A bibliographic search of literature was conducted, databases consulted were Medline through Pubmed and Scopus. Results: Clinical trials that evaluated coenzyme Q10 supplementation obtained disparate results. Oral supplementation increased coenzyme Q10 serum concentrations, but it has not been confirmed clearly that this increase is transferred to muscular-skeletal tissue, since few trials used biopsies, and when applied, opposing results were obtained. With regard to vitamin D, some cross-sectional and retrospective studies stand out. They showed hypovitaminosis D is associated with statin-related myalgias exacerbation. However, trials that assessed its supplementation did not obtain unanimous evidence. Conclusion: Coenzyme Q10 supplements cannot be recommended reliably to treat statin-related myalgias. Vitamin D status at the beginning of statin therapy is a good risk marker and improves statin-related myalgias prognosis, but more placebo-controlled clinical trials are needed to prove its supplementation usefulness.(AU)

Benefits of micronutrient supplementation on nutritional status, energy metabolism, and subjective wellbeing / Beneficios de la suplementación con micronutrientes sobre el estado nutricional, el metabolismo energético y el bienestar subjetivo

The human body, particularly the brain, requires energy, stored in the form of adenosine triphosphate. Energy metabolism during cellular respiration is dependent on the presence of multiple micronutrients, which act as essential components, coenzymes, or precursors at every stage. An adequate supply of multiple micronutrients is vital for efficient energy production. However, micronutrient intakes below the recommended dietary allowance are common, even in industrialized countries. Intakes of vitamins A, D, E, folate, iron, zinc, and selenium are suboptimal across all age groups. Suboptimal micronutrient levels have been shown to contribute to low energy levels, physical and mental fatigue, and impaired cognitive performance and wellbeing – symptoms frequently present in the general population. When supplemented in combination in well-conducted trials, multiple micronutrients ± coenzyme Q10 reduced oxidative stress in chronic fatigue syndrome; in healthy people they increased cerebral blood-flow hemodynamic response, energy expenditure, and fat oxidation; reduced mental and physical fatigue; improved the speed and accuracy of cognitive function during demanding tasks; and reduced stress. The results from these clinical trials suggest that even in industrialized countries, where adults might be assumed to have a healthy, balanced diet, there is a rationale to supplement with multiple micronutrients, including coenzyme Q10, to improve nutritional status, support energy metabolism, and improve subjective wellbeing. (AU)

El cuerpo humano, particularmente el cerebro, requiere energía, almacenada en forma de adenosina trifosfato. El metabolismo de la energía durante la respiración celular depende de la presencia de múltiples micronutrientes, que actúan como componentes esenciales, coenzimas o precursores en cada etapa. Un aporte adecuado de múltiples micronutrientes es vital para una producción eficiente de energía. Sin embargo, la ingesta de micronutrientes inferior a la recomendada es frecuente, incluso en los países industrializados. Las ingestas de vitaminas A, D, E, folato, hierro, zinc y selenio son subóptimas en todos los grupos de edad. Se ha demostrado que las situaciones subóptimas en relación con diversos micronutrientes contribuyen a tener niveles bajos de energía, fatiga física y mental, y deterioro del rendimiento cognitivo y el bienestar, síntomas presentes a menudo en la población general. Sin embargo, cuando se suplementa en ensayos bien controlados, con una combinación de diversos micronutrientes ± coenzima Q10, se constata una reducción del estrés oxidativo en el síndrome de fatiga crónica y, en las personas sanas, se observa un aumento de la respuesta hemodinámica del flujo sanguíneo cerebral, el gasto energético y la oxidación de la grasa; una reducción de la fatiga mental y física; una mejora de la velocidad y la precisión de la función cognitiva durante la realización de tareas exigentes, y una reducción del estrés. Los resultados de estos ensayos clínicos sugieren que, incluso en los países industrializados, donde se podría suponer que los adultos tienen una dieta saludable y equilibrada, hay motivos para complementarla con múltiples micronutrientes, incluida la coenzima Q10, con el fin de mejorar el estado nutricional, respaldar el metabolismo energético y mejorar el bienestar subjetivo. (AU)

PCSK9 inhibitors: Ratification of the role of LDL cholesterol in cardiovascular prevention. Towards a convergence of European and North American prevention guidelines? / Inhibidores de PCSK9: ratificación del papel del colesterol LDL en prevención cardiovascular. ¿Hacia la convergencia en las guías de prevención europeas y norteamericanas?

The epidemiological association of cholesterol associated with low density lipoproteins (LDL-c) levels and the development of atherosclerotic vascular disease has been ratified by mendelian randomization studies. Paradoxically, the success of statins led to the underestimation of other lipid-lowering therapies and even the measurement of LDL-c. Recent studies show that the reduction of LDL-c to extraordinarily low levels through absorption inhibition, and, in a particularly intensive manner, with monoclonal antibodies against pro-protein convertase subtilisine Kesine 9 (PCSK9) continues to offer cardiovascular protection. However, the high cost and limited experience with PCSK-9 inhibitors advised a prudent use of them. An appropriate selection of patients most likely to benefit from treatment with PCSK9 inhibitors emerges as the basis for a consensus of international guidelines: the combination of a high absolute vascular risk and a greater expected benefit by the starting LDL-c levels.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes / Estado antioxidante da coenzima Q10 e da vitamina E em crianças com diabetes tipo 1

Abstract Objective: The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. Method: This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Results: Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p < 0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p < 0.05). The platelet redox status showed a negative correlation with the A1c % levels (r = −0.31; p = 0.022) and the duration of type 1 diabetes (r = −0.35, p = 0.012). Conclusion: Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress.

Resumo Objetivo: Avaliar o estado antioxidante da vitamina E no plasma e da coenzima Q10 no plasma e intracelular em crianças com diabetes tipo 1. Método: Este estudo caso-controle realizado em com 72 crianças com diabetes tipo 1 comparadas por idade, sexo e etnia de 58 crianças saudáveis. As crianças diabéticas foram divididas em dois grupos de acordo com sua hemoglobina glicosilada (A1c %): grupos de controle glicêmico bom e baixo. Todas as crianças foram submetidas a anamnese total, exame clínico e laboratorial para hemograma completo, A1c %, colesterol no plasma, triglicerídeos e níveis de vitamina E e níveis de coenzima Q10 no plasma, eritrócitos e plaquetas. Resultados: As crianças com baixo controle glicêmico mostraram nível de vitamina E no plasma significativamente maior, coenzima Q10, triglicerídeos, lipoproteína de baixa densidade, proporção da circunferência da cintura/estatura e níveis de colesterol e menor nível de lipoproteína de alta densidade e estado redox da coenzima Q10 em comparação aos com bom controle glicêmico e com o grupo de controle (p < 0,05). A coenzima Q10 no plasma mostrou correlação positiva com a duração da diabetes tipo 1, triglicerídeos, colesterol, vitamina E e A1c % e correlação negativa com a idade do grupo diabético (p < 0,05). O estado redox das plaquetas mostrou correlação negativa com os níveis de A1c % (r = -0,31; p = 0,022) e a duração da diabetes tipo 1 (r = -0,35, p = 0,012). Conclusão: Os pacientes com diabetes tipo 1, principalmente mal controlados, apresentaram aumento nos níveis de vitamina E no plasma e coenzima Q10 e redução no estado redox das plaquetas da coenzima Q10 que podem indicar aumento do estresse oxidativo.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes.

OBJECTIVE: The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. METHOD: This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. RESULTS: Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=-0.31; p=0.022) and the duration of type 1 diabetes (r=-0.35, p=0.012). CONCLUSION: Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress.

A utilização da coenzima Q10 adjunta à terapia periodontal básica na periodontite crônica / The use of coenzyme Q10 accompanies basic periodontal therapy in chronic periodontitis

A porção inflamatória da resposta imunoinflamatória é mediada por moléculas oxidativas que causam degradação de colágeno e danos às células periodontais. Uma disbiose nessa resposta leva a periodontite. Essas moléculas oxidativas podem ser neutralizadas pela coenzima Q10 (CoQ10), sendo um composto produzido pelo corpo, e apresenta duas formas moleculares, na forma oxidada chamada de Ubiquinona e na reduzida denominada de Ubiquinol. O Ubiquinol é a molécula que confere propriedade antioxidante a esse composto. O objetivo desse estudo é apresentar uma revisão de literatura sobre o uso adjunto da CoQ10 na terapia periodontal básica de pacientes com periodontite crônica. Para tal, foi realizada uma revisão de literatura de ensaios clínicos controlados de pacientes com diagnóstico de periodontite crônica cujo tratamento consistia em raspagem e alisamento radicular (RAR) e CoQ10 adjunta (grupo teste) em comparação a RAR isolado ou associado a um placebo (grupo controle). Os parâmetros periodontais avaliados foram índice de placa (IP), índice gengival (IG), profundidade de bolsa (PB) e nível clínico de inserção (NIC). Foram obtidos 5 estudos e 3 deles não relataram respostas estatisticamente significantes para nenhum parâmetro periodontal avaliado. Entretanto, nos outros dois estudos verificaram-se melhoras estatisticamente significantes para IG e IP após 3 meses e 4 semanas respectivamente utilizando-se CoQ10 adjunta. Após análise dos resultados, pode-se concluir que o uso da CoQ10 adjunta à terapia periodontal básica em paciente com periodontite crônica apresentou melhoras estatisticamente significantes, somente para IG, quando usada em forma de suplementação oral e somente IP quando usada em gel intrabolsa. (AU)

The inflammatory portion of the immune-inflammatory response is mediated by oxidative molecules, which cause collagen degradation and damage to periodontal cells. A dysbiosis in this response leads to periodontitis. These oxidative molecules can be neutralized by coenzyme Q10 (CoQ10), which is a compound produced by the body, and has two molecular forms, in the oxidized form called Ubiquinone and in the reduced form called Ubiquinol. Ubiquinol is the molecule that confers the antioxidant property to this compound. The purpose of this study is to present a literature review on CoQ10 adjunctive use in basic periodontal therapy of patients with chronic periodontitis. A literature review of controlled clinical trials of patients diagnosed with chronic periodontitis, whose treatment consisted of scaling and root planing (SRP) and adjunct CoQ10 (test group) compared to SRP alone or with a placebo associated. The periodontal parameters evaluated were: plaque index (PI) and gingival index (GI), pocket depth (PD) and clinical attachment level (CAL). Five studies were obtained, of which 03 did not report statistically significant responses for any periodontal parameter evaluated. The other two studies showed statistically significant improvements in GI after 3 months of use, and PI after 4 weeks using CoQ10, respectively. After analyzing the results, it can be concluded that the use of CoQ10 adjunct to basic periodontal therapy in patients with chronic periodontitis showed statistically significant improvements, only for GI, when used as oral supplementation, and only PI when applied in intrapocket gel. (AU)

[Regulation of the expression of coenzyme Q-synthesis complex during ageing]. / La expresión del complejo de síntesis de coenzima Q es regulada durante el envejecimiento.

INTRODUCTION: Coenzyme Q is an essential component in the activity of the mitochondrial electron transport chain. Its synthesis involves, at least, a complex of ten different proteins. In this study, an attempt is made to determine the evolution of the expression of the genes involved in coenzyme Q synthesis during mouse ageing. MATERIAL AND METHODS: The messenger RNA (mRNA) of different organs, such as brain, liver, kidney and skeletal muscle from young (8 months), mature (18 months), and old (24 months) mice was extracted by using Trizol and was then analysed by real time PCR (qPCR) using specific primers for all the known components of the coenzyme Q-synthesis complex (COQ genes). RESULTS: Liver showed the highest age-dependent changes in mRNA levels of the different components of Q-synthesis complex, affecting the extent of the variation as well as the significance of the change. In most of the cases, mRNA levels of the different components were higher in mature animals compared to young and old animals. When mRNAs of young and old animals were compared, only minor reductions of mRNA levels were found. Kidney showed a pattern similar to that found in liver as regards the changes in expression, although with lower increases in mature animals than those observed in the liver. Brain and skeletal muscle showed low variations, with muscle being the tissue with less changes, although a pattern similar to that found in liver and kidney was found, with slight increases in mature animals. DISCUSSION: The results of this study indicate that ageing is an important factor affecting COQ gene expression, but its effect depends on the organ, and that mature animals show higher levels of mRNA than young and old animals. Taken into consideration the importance of coenzyme Q in cell metabolism and ageing, a more detailed study is needed to understand the gene regulation of the coenzyme Q-synthesis mechanisms during ageing.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects / Coenzima Q10 e marcadores pró-inflamatórios em crianças com síndrome de Down: aspectos clínicos e bioquímicos

Abstract: Objective: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Methods: Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Results: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p = 0.002), while coenzyme Q10 was significantly decreased (p = 0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Conclusion: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

Resumo: Objetivo: Foram relatadas evidências de estresse oxidativo em indivíduos com a síndrome de Down. Há um interesse cada vez maior na contribuição do sistema imunológico na síndrome de Down. O objetivo deste estudo é avaliar a coenzima Q10 e marcadores pró-inflamatórios selecionados, como interleucina 6 e o fator de necrose tumoral α, em crianças com a síndrome de Down. Métodos: Foram inscritas neste estudo de caso-controle 86 crianças (5-8 anos) de duas instituições públicas. No momento da amostragem, os pacientes e os controles não sofriam de doença aguda ou crônica e não recebiam terapia ou suplementos. Foram medidos os níveis de interleucina 6, fator de necrose tumoral α, coenzima Q10, glicemia de jejum e quociente de inteligência. Resultados: Foram incluídas em oito meses (janeiro-agosto 2014) 43 crianças com síndrome de Down e 43 controles. Em comparação com o grupo de controle, os pacientes com síndrome de Down mostraram aumento significativo na interleucina 6 e no fator de necrose tumoral α (p = 0,002), ao passo que a coenzima Q10 apresentou significativa redução (p = 0,002). Além disso, o índice de massa corporal e a glicemia de jejum eram significativamente maiores nos pacientes. Houve uma correlação significativamente positiva entre os níveis de coenzima Q10 e do quociente de inteligência, bem como entre a interleucina 6 e o fator de necrose tumoral α. Conclusão: Os níveis de interleucina 6 e o fator de necrose tumoral α em crianças mais novas com síndrome de Down podem ser usados como biomarcadores, refletem o processo neurodegenerativo neles. A coenzima Q10 pode ter um papel como bom suplemento em crianças com síndrome de Down para melhorar os sintomas neurológicos.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects.

OBJECTIVE: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. METHODS: Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. RESULTS: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p=0.002), while coenzyme Q10 was significantly decreased (p=0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. CONCLUSION: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

Pravastatin induces cell cycle arrest and decreased production of VEGF and bFGF in multiple myeloma cell line / Pravastatina induz parada no ciclo celular e diminuição na produção de VEGF e bFGF em linhagem de Mieloma Multiplo

Abstract Multiple myeloma (MM) is a B cell bone marrow neoplasia characterized by inflammation with an intense secretion of growth factors that promote tumor growth, cell survival, migration and invasion. The aim of this study was to evaluate the effects of pravastatin, a drug used to reduce cholesterol, in a MM cell line.Cell cycle and viability were determinate by Trypan Blue and Propidium Iodide. IL6, VEGF, bFGF and TGFβ were quantified by ELISA and qRT-PCR including here de HMG CoA reductase. It was observed reduction of cell viability, increase of cells in G0/G1 phase of the cell cycle and reducing the factors VEGF and bFGF without influence on 3-Methyl-Glutaryl Coenzyme A reductase expression.The results demonstrated that pravastatin induces cell cycle arrest in G0/G1 and decreased production of growth factors in Multiple Myeloma cell line.

Resumo O Mieloma Múltiplo é uma neoplasia de linfócitos B da medula óssea, caracterizada por inflamação com uma intensa secreção de fatores de crescimento que promovem o aumento do volume do tumor, sobrevivência celular, migração e invasão. O objetivo deste estudo foi avaliar os efeitos da pravastatina, uma droga usada para reduzir o colesterol, em um linhagem de MM. O ciclo celular e viabilidade foram determinadas por Trypan Blue e iodeto de propídio. IL6, VEGF, bFGF e TGF foram quantificadas por ELISA e qRT-PCR, incluindo aqui de HMG CoA redutase. Observou-se a redução da viabilidade das células, aumento de células na fase G0/G1 do ciclo celular e redução no VEGF e bFGF, sem influência na expressão da enzima 3-Metil-Glutaril Coenzima A redutase. Os resultados demonstraram que a pravastatina induz parada no ciclo celular em G0/G1 e diminuição da produção de fatores de crescimento em várias linhas de células de Mieloma.

The 3-hydroxy-3-methylglutaryl coenzyme-A reductases from fungi: a proposal as a therapeutic target and as a study model.

The enzyme 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) catalyzes the conversion of HMG-Co-A into mevalonate. This step is the limiting point for the synthesis of cholesterol in mammals and ergosterol in fungi. We describe in this article the genome organization of HMGR coding genes and those deduced from different fungi, recount the evidence showing statins as HMGR inhibitors for ergosterol synthesis and its effect in yeast viability, and propose fungal HMGR (HMGRf) as a model to study the use of pharmaceutical compounds to inhibit cholesterol and ergosterol synthesis. Bibliographical search and bioinformatic analyses were performed and discussed. HMGRfs belong to the class I with a high homology in the catalytic region. The sterol biosynthetic pathway in humans and fungi share many enzymes in the initial steps (such as the HMGR enzyme), but in the last steps enzymes are different rendering the two final products: cholesterol in mammals and ergosterol in fungi. With regards to inhibitors such as statins and other compounds, these affect also fungal viability. Since HMGR from Schizosaccharomyces pombe and Ustilago maydis are very similar to the human HMGR in the catalytic regions, we propose that fungal enzymes can be used to test inhibitors for a potential use in humans. We consider that HMGRf is a good therapeutic target to design and test new antifungal compounds. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).

Acidemia propiónica neonatal con deterioro neurológico, rechazo al alimento y emesis reporte de caso y revisión de la literatura / Neonatal-onset propionic acidemia neurologic deficit, poor feeding and vomiting - a case report and literature review

Paciente pretérmino que reingresa a la unidad de recién nacidos de la Clínica Universitaria Colombia, Bogotá DC, por problemas en la alimentación y pobre ganancia ponderal, a quien se le diagnosticó acidemia propiónica mediante cromatografía de ácidos orgánicos en orina. Los errores innatos del metabolismo son entidades que a pesar de tener una baja incidencia, se deben considerar en todo neonato con encefalopatía, problemas en la alimentación o pobre ganancia ponderal, entre otras manifestaciones, ya que el diagnóstico temprano y tratamiento oportuno previenen la aparición de secuelas neurológicas con retardo del desarrollo psicomotor y muerte temprana.

Preterm infant readmitted to the neonatal unit at ClínicaUniversitaria Colombia, Bogotá DC, presenting poor feeding and delays in normal growth velocity, who was diagnosed with propionic acidemiaby means of a urine organic acid profiling by chromatography. Although its low incidence, inborn metabolic disorders must be considered in any newborn presenting with encefalopathy, poor feeding or delays in normal growth velocity, among other manifestations for early diagnosisandprompt treatment preventneurological sequellae including psychomotor retardation and early neonatal death.