Diferenças entre Duas Condições Cardíacas Hipertróficas Distintas: Doença de Fabry Versus Cardiomiopatia Hipertrófica / Differences Between Two Distinct Hypertrophic Cardiac Conditions: Fabry Disease versus Hypertrophic Cardiomyopathy

Resumo Fundamento A cardiomiopatia hipertrófica (CMH) e a doença de Fabry (DF) são doenças herdadas geneticamente com características fenotípicas de hipertrofia ventricular esquerda (HVE) que causam resultados cardíacos adversos. Objetivos Investigar as diferenças demográficas, clínicas, bioquímicas, eletrocardiográficas (ECG) e ecocardiográficas (ECO) entre CMH e DF. Métodos 60 pacientes com CMH e 40 pacientes com DF foram analisados retrospectivamente como uma subanálise do "estudo LVH-TR" após exclusão de pacientes com fibrilação atrial, ritmo de estimulação, bloqueios de ramo e bloqueios atrioventriculares (AV) de segundo e terceiro graus. O nível de significância foi aceito como <0,05. Resultados O sexo masculino (p=0,048) e a creatinina (p=0,010) são significativamente maiores a favor da DF; entretanto, infradesnivelamento do segmento ST (p=0,028), duração do QT (p=0,041), espessura do septo interventricular (SIVd) (p=0,003), espessura da parede posterior (PWd) (p=0,009), insuficiência mitral moderada a grave (IM) (p=0,013) e o índice de massa ventricular esquerda (IMVE) (p=0,041) são significativamente maiores a favor da CMH nas análises univariadas. Na análise multivariada, a significância estatística apenas permanece na creatinina (p=0,018) e na duração do intervalo QT (0,045). A DF foi positivamente correlacionada com a creatinina (rho=0,287, p=0,004) e a CMH foi positivamente correlacionada com o PWd (rho=0,306, p=0,002), IVSd (rho=0,395, p<0,001), IM moderada-grave (rho= 0,276, p<0,005), IMVE (rho=0,300, p=0,002), espessura relativa da parede (ERP) (rho=0,271, p=0,006), duração do QT (rho=0,213, p=0,034) e depressão do segmento ST (rho =0,222, p=0,026). Conclusão Características bioquímicas, ECG e ECO específicas podem auxiliar na diferenciação e no diagnóstico precoce da CMH e da DF.

Abstract Background Hypertrophic cardiomyopathy (HCM) and Fabry disease (FD) are genetically inherited diseases with left ventricular hypertrophy (LVH) phenotype characteristics that cause adverse cardiac outcomes. Objectives To investigate the demographic, clinical, biochemical, electrocardiographic (ECG), and echocardiographic (ECHO) differences between HCM and FD. Methods 60 HCM and 40 FD patients were analyzed retrospectively as a subanalysis of the 'LVH-TR study' after excluding patients with atrial fibrillation, pace rhythm, bundle branch blocks, and second and third-degree atrioventricular (AV) blocks. The significance level was accepted as <0.05. Results Male gender (p=0.048) and creatinine (p=0.010) are significantly higher in favor of FD; however, ST depression (p=0.028), QT duration (p=0.041), interventricular septum thickness (IVSd) (p=0.003), posterior wall thickness (PWd) (p=0.009), moderate-severe mitral regurgitation (MR) (p=0.013), and LV mass index (LVMI) (p=0.041) are significantly higher in favor of HCM in the univariate analyses. In multivariate analysis, statistical significance only continues in creatinine (p=0.018) and QT duration (0.045). FD was positively correlated with creatinine (rho=0.287, p=0.004) and HCM was positively correlated with PWd (rho=0.306, p=0.002), IVSd (rho=0.395, p<0.001), moderate-severe MR (rho=0.276, p<0.005), LVMI (rho=0.300, p=0.002), relative wall thickness (RWT) (rho=0.271, p=0.006), QT duration (rho=0.213, p=0.034) and ST depression (rho=0.222, p=0.026). Conclusion Specific biochemical, ECG, and ECHO characteristics can aid in the differentiation and early diagnosis of HCM and FD.

Acute dissection of a syphilitic saccular aneurysm of the ascending aorta and arch in a hypertensive patient - a rare phenomenon

ABSTRACT We report the case of a 77-year-old male who suffered from hypertension and died suddenly. At autopsy, he was found to have hypertensive cardiomegaly and a dissecting syphilitic saccular aneurysm of the ascending aorta and arch with tamponade. Chronic aortic regurgitation, which is often seen in syphilitic aortitis, produces an additive effect to the concentric left ventricular hypertrophy seen in hypertension.

Enzima convertidora de angiotensina homóloga (ECA2) y actividad de ROCK en la falla cardíaca experimental

Antecedentes: La ECA2 ha mostrado ser un regulador esencial de la funcionalidad cardíaca. En un modelo experimental de insuficiencia cardíaca (IC) con Fier, modelo de coartación de aorta (COA), se encontró activación de la vía Rho-kinasa. La inhibición de esta vía con fasudil no mejoró el remodelado cardíaco ni la disfunción sistólica. Se desconoce en este modelo, si el deterioro de la función cardíaca y activación de la vía rho-kinasa se asocia con una disminución de la ECA2 cardíaca y si la inhibición de Rho-kinasa tiene un efecto sobre la expresión de ECA2. Objetivo: Nuestro objetivo es determinar si en la falla cardaca experimental por coartación aórtica, los niveles proteicos de ECA2 en el miocardio se asocian a disfunción sistólica y cual es su interacción con la actividad de ROCK en el miocardio. Métodos: Ratones C57BL6J machos de 7-8 semanas se randomizaron en 3 grupos experimentales. Grupo COA por anudación de la aorta + vehículo; Grupo COA + Fasudil (100 mg/Kg día) por bomba osmótica desde la semana 5 post-cirugía; y grupo control o Sham. Se determinaron las dimensiones y función cardíaca por ecocardiografía. Posterior a la eutanasia, se determinaron los niveles de ECA2 del VI por Western-blot y actividad de la Rho-kinasa Resultados: En los grupos COA+vehículo y COA-FAS hubo deterioro de la función cardíaca, reflejada por la reducción de la FE (47,9 ± 1,53 y 45,5 ± 2,10, p < 0,05, respectivamente) versus SHAM (68,6 ± 1,19). Además, aumentaron las dimensiones cardíacas y hubo desarrollo de hipertrofia (0,53 ± 0,02 / 0,53 ± 0,01, p < 0,05) medida por aumento de la masa cardíaca relativa respecto del grupo SHAM (0,40 ± 0,01). En los grupos COA+vehículo y COA-FAS se encontró una disminución significativa del 35% en la expresión de ECA2 cardíaca respecto al grupo control. Conclusiones: La disfunción sistólica por coartación aórtica se asocia con aumento de la actividad de Rho-kinasa y significativa disminución de la expresión de ECA2. La inhibición de Rho-kinasa no mejoró el remodelado cardíaco, la disfunción sistólica y tampoco modificó los niveles de ECA2 cardíaca.

Background: ACE2 has been described as an essential regulator of cardiac function. In an experimental model of heart failure (HF) and heart failure reduced ejection fraction (HFrEF), the aortic coarctation (COA) model, activation of the Rho-kinase pathway of cardiac remodeling was found. Inhibition of this pathway did not improve cardiac remodeling or systolic ventricular dysfunction. It is unknown in this model whether the impairment of cardiac function and activation of the rho-kinase pathway is associated with a decrease in ACE2 and whether rho-kinase inhibition has an effect on ACE2 expression. Objective: To determine if in experimental heart failure due to aortic coarctation, ACE2 protein levels in the myocardium are associated with systolic dysfunction and what is its interaction with ROCK activity in the myocardium. Methods: Male C57BL6J mice aged 7-8 weeks were divided into 3 groups and anesthetized: One group underwent COA+ vehicle; A second group COA + Fasudil (100 mg/Kg/d) by osmotic pump from week 5 post-surgery and; the third group, control(SHAM). Echocardiograms were performed to determine cardiac dimensions and systolic function. Rats were then euthanized. Ventricular expression of ACE2, activity of the Rho-kinase pathway by MYPT-1 phosphorylation, relative cardiac mass, area and perimeter of cardiomyocytes were determined by Western blot. Results: In both COA+vehicle and COA+FAS groups there was deterioration of cardiac function, reflected in the reduction of EF (47.9 ± 1.53 and 45.5 ± 2.10, p < 0.05, respectively) versus the SHAM group (68.6 ± 1.19). In addition, cardiac dimensions and hypertrophy increased (0.53 ± 0.02 / 0.53 ± 0.01, p < 0.05) due to increased relative cardiac mass compared to the SHAM group (0.40 ± 0.01). In the COA+vehicle and COA+FAS groups a significant decrease of 35% in cardiac ACE2 expression was found compared to the control group. Conclusions: Systolic dysfunction due to aortic coarctation is associated with increased Rhokinase activity and a significant decrease in ACE2 expression. Rho-kinase inhibition did not improve cardiac remodeling, systolic dysfunction, nor did it change cardiac ACE2 levels.

Miocardiopatía Hipertrófica en ausencia de criterios de hipertrofia. Serie de casos

La miocardiopatía hipertrófica (MCH) es la miocardiopatía hereditaria más frecuente, su principal expresión fenotípica consiste en hipertrofia ventricular izquierda (HVI) en ausencia de condiciones de carga que la justifiquen. Cuando existe una variante genética patogénica se denomina MCH sarcomérica. Los criterios diagnósticos más aceptados son HVI ≥ 15 mm en cualquier segmento o ≥ 13 en ciertas condiciones, criterios que tienen tres inconvenientes: 1) La HCM es una patología donde la HVI es evolutiva, existiendo otros elementos más precoces, pero menos precisos, como criptas, bandas musculares y alteraciones de la válvula mitral y músculos papilares; 2) Pacientes de baja estatura pueden no alcanzar estos umbrales; 3) La MCH apical no queda siempre bien representada usando estos grosores, requiriendo indexar por tamaño del paciente y/o considerar la HVI relativa (relación grosor apical / basal que no debe superar 1). Presentamos una serie de casos con genotipo confirmado para MCH que no cumplen los criterios de HVI aceptados para MCH y donde se debe individualizar el diagnóstico considerando los tres elementos señalados.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition; its phenotypic expression consists of ventricular hypertrophy (LVH) unrelated to loading conditions. In patients with a genetic pathogenic variant, the condition is termed sarcomeric HCM. Current diagnostic criteria are based on absolute left ventricular thickness, requiring ≥15 mm in any segment or ≥13 mm in particular conditions. These criteria have three pitfalls: 1) HCM is an evolving disease where LVH occurs gradually, with other early -but less precisephenotypic expressions such as myocardial crypts, muscular bands, or mitral and papillary muscle alterations; 2) Patients with short stature tend to have less LVH and do not reach the proposed thickness threshold. 3) Apical HCM is not correctly addressed in this cut-off as the heart tapers from base to apex, warranting indexing wall thickness to body size and using relative LVH in the apex (ratio from apex/base, abnormal,>1). This small case series includes three patients with a pathogenic genetic variant for HCM that doesn't satisfy the current criteria of LVH. For its precise assessment, the aforementioned points must be considered.

Factor de crecimiento análogo a insulina-1 y cardiotrofina-1 inducido por ejercicio y su relación con hipertrofia miocárdica en maratonistas

Antecedentes: El ejercicio de alta intensidad induce hipertrofia miocárdica necesaria para adaptar al corazón a la mayor demanda de trabajo. Se desconoce si correr una maratón induce de forma aguda factores humorales asociados al desarrollo de hipertrofia miocárdica en atletas. Objetivo: Evaluar cardiotrofina-1 (CT1) y el factor de crecimiento análogo a insulina-1 (IGF-1), conocidos inductores de hipertrofia, en maratonistas previo y justo después de correr una maratón y su relación con hipertrofia cardíaca. Métodos: Estudio prospectivo ciego simple de atletas hombres que corrieron la maratón de Santiago. Se incluyó un grupo control sedentario. En todos los sujetos se realizó un ecocardiograma transtorácico estándar. Los niveles de CT1 e IGF-1 se determinaron en plasma obtenidos antes (basal) y justo después de haber terminado (antes de 15 minutos) la maratón, usando test de ELISA. Resultados: Los atletas tenían frecuencias cardíacas menores que los controles, asociado con una mayor hipertrofia miocárdica, determinado por el grosor del septo y pared posterior del corazón, y volúmenes del ventrículo y aurícula izquierda. Los niveles basales de CT1 e IGF-1 fueron similares entre atletas y controles sedentarios. El correr la maratón aumentó los niveles de estas dos hormonas en un subgrupo de atletas. Solo los atletas que incrementaron los niveles de IGF-1, pero no de CT1, tenían volúmenes de ventrículo izquierdo y derecho más grandes que los otros atletas. Conclusiones: IGF-1 que se incrementa de forma aguda por el ejercicio, pero no CT1, estaría asociado con el aumento de los volúmenes ventriculares observado en los atletas.

Background: High intensity exercise induces the development of myocardial hypertrophy necessary to adapt the heart to the increased work demand. Whether running a marathon is associated with acutely induced humoral factors responsible for the development of myocardial hypertrophy observed in athletes is not known. Objective: To evaluate the levels of cardiotrophin-1 (CT1) and insulin-like growth factor-1 (IGF-1), known hypertrophy inducers, in marathon runners before and just after running a marathon and their relationship with cardiac hypertrophy. Methodology: Single-blind prospective study of male athletes who ran the Santiago's marathon. A sedentary control group was included. All subjects underwent a standard transthoracic echocardiogram. CT1 and IGF-1 levels were determined in plasma obtained before (basal) and just after finishing (within 15 min) the marathon using ELISA assays. Results: Athletes had lower heart rates than controls, associated with greater myocardial hypertrophy, as determined by thickness of the heart's septum and posterior wall, and left atrial and ventricular volumes. Basal CT1 and IGF-1 levels were similar between athletes and sedentary controls. Marathon running increased the levels of these two hormones in a subgroup of athletes. Only the athletes who increased IGF-1 levels, but not CT1, had larger left and right ventricular volumes. Conclusion: IGF-1 acutely increased by exercise, but not CT1, was associated with the augmented ventricular volumes observed in athletes.

Hepatotoxicidad por tamsulosina / dutasterida: reporte de un caso probable

La tamsulosina y dutasterida son medicamentos ampliamente usados como tratamiento de la hipertrofia benigna de próstata. teniendo un buen perfil de seguridad. Existen escasos reportes de injuria hepática asociado al uso de tamsulosina; sin embargo, no hay reportes de toxicidad hepática por el uso de dutasterida y del uso combinado de tamsulosina/dutasterida. Se presenta el caso de un varón de 64 años quien desarrolla injuria hepática tras el uso combinado de tamsulosina/dutasterida, desarrollando un patrón de daño hepatocelular y clínica de hepatitis aguda. Se realizo descarte de patología hepática viral, autoinmune y enfermedades metabólicas de depósito, así como de patología biliar mediante ecografía abdominal y colangioresonancia. En la evaluación de causalidad, presentó CIOMS-RUCAM: 6 puntos (probable) y Naranjo: 4 puntos (posible). El paciente presentó respuesta clínica y laboratorial luego de suspender el medicamento.

Tamsulosin and dutasteride are drugs widely used to treat benign prostatic hypertrophy. having a good safety profile. There are few reports of liver injury associated with the use of tamsulosin; however, there are no reports of hepatic toxicity from the use of dutasteride and the combined use of tamsulosin/dutasteride. We present the case of a 64-year-old man who developed liver injury after the combined use of tamsulosin/dutasteride, developing a pattern of hepatocellular damage and acute hepatitis symptoms. Viral, autoimmune, and metabolic storage diseases of the liver were ruled out, as well as biliary pathology by means of abdominal ultrasound and resonance cholangiography. In the causality evaluation, CIOMS-RUCAM presented: 6 points (probable) and Naranjo: 4 points (possible). The patient presented a clinical and laboratory response after discontinuing the drug.

A Comparative Study of Fluticasone Propionate, Mometasone Furoate, and Saline Nasal Spray in the Treatment of Children with Adenoid Hypertrophy

Introduction:Adenoidectomy is currently considered the treatment of choice for relief of the nasal airway obstruction due to adenoid hypertrophy. Evidence suggests that topical nasal steroid sprays can cause a reduction in adenoid size. We aim to compare the effectiveness of fluticasone propionate, mometasone furoate (MF) and saline nasal sprays in relieving the signs and symptoms of adenoid hypertrophy and in reducing the size of the adenoids. MaterialsandMethods: We conducted a randomized comparative study on 60 patients divided into three groups A, B, C (20 each). Group A patients treated with fluticasone propionate nasal spray (400 μg/day), Group B patients treated with MF nasal spray (100 μg/day), and Group C patients treated with saline spray (0.65% w/v in purified water which is made isotonic and buffered). Treatment was given up to 12 weeks with follow‑up at 4, 8, and 12 weeks and at each follow‑up visit assessment was done. Final data were analyzed using SPSS software version 21 and numerical variables associated with different groups were analyzed and analysis of variance test was used. Results: Diagnostic nasal endoscopy and X‑ray grades at day 1 among the study groups were not statistically significant, whereas, at 12 weeks results among fluticasone and mometasone groups were significantly better (P < 0.001) as compared to the saline group. There was a significant improvement in the symptoms under all the categories with the use of fluticasone and mometasone. Conclusion: In our study, both fluticasone propionate and MF were able to effectively reduce symptoms and signs of adenoid hypertrophy as well as help in reducing the size of the enlarged adenoid. Both these drugs were well tolerated by the patients

Restricción parcial de flujo sanguíneo con resistencia, fundamento fisiológico y metodología de entrenamiento

El entrenamiento con restricción del flujo sanguíneo ha resultado ser una alternativa que logra resultados similares a los conseguidos por el entrenamiento de alta intensidad. El presente artículo ofrece el resultado de una investigación, en la que se realizó una revisión bibliográfica para indagar sobre la efectividad en el aumento de fuerza muscular, así como analizar los mecanismos de acción y metodología de aplicación práctica, mediante el método de restricción parcial de flujo sanguíneo con resistencia a bajas cargas. La literatura revisada respalda los efectos positivos de este método para generar hipertrofia y aumento de fuerza muscular, tanto en población sana como en periodo de rehabilitación. Los principales mecanismos propuestos como mediadores de esta adaptación son la elevación en la secreción de hormona del crecimiento, la señalización intracelular vía anabólica y catabólica y la contribución de procesos inflamatorios o edematosos. Se recomendó trabajar con cargas entre el 20 al 40 % de una repetición máxima y con un volumen de 75 repeticiones por sesión con entrenamiento entre 2 a 4 veces por semana, durante un tiempo mínimo de tres semanas. Se discutió sobre los efectos en la adaptación neurológica, sin existir evidencia que lo respalde. Se concluyó que el método de restricción parcial del flujo sanguíneo genera aumento de fuerza e hipertrofia y se recomienda como método complementario y alternativo al ejercicio de alta intensidad, en poblaciones que necesariamente se ven imposibilitadas de entrenar a altas intensidades.

SÍNTESE O treinamento com restrição do fluxo sanguíneo provou ser uma alternativa que alcança resultados similares aos alcançados pelo treinamento de alta intensidade. Este artigo oferece o resultado de uma pesquisa, na qual foi realizada uma revisão de literatura para investigar a eficácia no aumento da força muscular, bem como para analisar os mecanismos de ação e metodologia de aplicação prática, utilizando o método de restrição parcial do fluxo sanguíneo com resistência a cargas baixas. A literatura revisada apóia os efeitos positivos deste método para gerar hipertrofia e aumentar a força muscular, tanto na população saudável quanto no período de reabilitação. Os principais mecanismos propostos como mediadores desta adaptação são a elevada secreção hormonal de crescimento, a sinalização intracelular através de vias anabólicas e catabólicas e a contribuição de processos inflamatórios ou edematosos. Foi recomendado trabalhar com cargas entre 20 a 40% de uma repetição máxima e com um volume de 75 repetições por sessão com treinamento entre 2 a 4 vezes por semana, por um tempo mínimo de três semanas. Os efeitos sobre a adaptação neurológica foram discutidos, mas não há evidências que sustentem isto. Concluiu-se que o método de restrição parcial do fluxo sanguíneo gera maior força e hipertrofia e é recomendado como um método complementar e alternativo ao exercício de alta intensidade, em populações que são necessariamente incapazes de treinar em altas intensidades.

Blood flow restriction training has turned out to be an alternative that achieves results similar to those achieved by high intensity training. The present article offers the result of a research where, a bibliographical review was carried out to inquire about the effectiveness in increasing muscle strength, as well as to analyze the mechanisms of action and methodology of practical application, through the method of partial restriction of blood flow with endurance to low loads. The reviewed literature supports the positive effects of this method to generate hypertrophy and increase muscle strength, both in the healthy population and in the rehabilitation period. The main mechanisms proposed as mediators of this adaptation are increased secretion of growth hormone, intracellular signaling via anabolic and catabolic pathways, and the contribution of inflammatory or edematous processes. It was recommended to work with loads between 20 and 40 % of a maximum repetition and with a volume of 75 repetitions per session with training between 2 and 4 times a week, for a minimum of three weeks. The effects on neurological adaptation were discussed, without supporting evidence. It was concluded that the method of partial restriction of blood flow generates an increase in strength and hypertrophy and is recommended as a complementary and alternative method to high intensity exercise, in populations that are necessarily unable to train at high intensities.

The Prevalence of Isolated Systolic Hypertension at a Tertiary Care Hospital in Eastern India : An Observational Study

Background and Objectives : Hypertension is a significant public health issue. Isolated Systolic Hypertension (ISH) was once considered to be a benign aspect among the aging population, but an association with an increased risk of Cardiovascular Disease is now known. ISH shows an increasing prevalence with increase in age. This study was undertaken to determine the incidence of ISH among adults in Eastern India. Methods : This study evaluated the adult population (aged 18-70 years) attending the NRS Medical College and Hospital, a Tertiary Care Center in East India. The clinical characteristics and echocardiographic findings were also evaluated. Results : A total of 800 patients met the inclusion criteria, of whom 75 (9.37%) had ISH. Blood Pressure increased with age. The most common echocardiographic change observed in ISH patients was increased Left Ventricular Mass Index (LVMI), while concentric Left Ventricular Hypertrophy (LVH) was more common in women than men with isolated Systolic Hypertension. The incidence of LVMI increased as the severity of ISH increased. Furthermore, patients with stage 3 ISH were nearly 4 times more likely to develop Proteinuria. Conclusion : The findings of this study are in line with previous studies evaluating the presence of ISH in the adult Indian population. There is need for effective population screening along with effective treatment for Blood Pressure to reduce morbidity and mortality. Primary prevention strategies may be the need of the hour in the Indian population which is at risk of cardiovascular Disease associated with Hypertension

Cirugía de cornetes inferiores en población pediátrica: ¿Cómo, cuándo y por qué?

La hipertrofia de cornetes inferiores representa una de las principales causas de obstrucción nasal en pacientes pediátricos. En estudios recientes se ha observado un aumento significativo de esta patología en niños que no responden a terapia médica. La evidencia disponible recomienda la cirugía como tratamiento de elección en la obstrucción nasal refractaria en niños con cornetes hipertróficos. Sin embargo, hasta la fecha no existen criterios formales de derivación a cirugía en la población pediátrica y los estudios en infantes son limitados. Al mismo tiempo, la falta de consenso no ha permitido recomendar una técnica quirúrgica en estos pacientes por sobre otras. Por lo tanto, se hace necesario profundizar las diferentes alternativas disponibles, considerando y optando por aquellas que presenten mayores beneficios y menor riesgo de complicaciones. En la presente revisión se estudió la evidencia disponible hasta el momento sobre este tema en la población pediátrica y además se realizó un análisis de la efectividad y complicaciones de las diferentes técnicas disponibles.

Inferior turbinate hypertrophy represents one of the leading causes of nasal obstruction in pediatric patients. Recent studies have observed a significant increase in turbinate hypertrophy in children that does not respond to medical treatment. The latest evidence recommends inferior turbinoplasty for treating nasal obstruction in children with hypertrophic turbinates. However, until today there are no formal criteria for referral to surgery in the pediatric population, and studies in children are limited. At the same time, the absence of consensus has not allowed the recommendation of one surgical technique over others in these patients. This is why it is necessary to deepen the available alternatives and choose those with more significant benefits and a lower risk of complications. In this review, we study available evidence about this topic in the pediatric population and analyze the effectiveness and complications of different known techniques.

Anticoncepção oral e hipotrofia muscular: existe correlação? / Oral contraception and muscle atrophy: is there a correlation?

As pílulas anticoncepcionais consistem na formulação combinada de um estrogênio e um progestagênio ou em apresentações simples de progestagênio isolado com a finalidade de bloquear a ovulação e alterar as condições do útero e das tubas uterinas, bloqueando parcialmente a foliculogênese e a inibição do pico de gonadotrofinas. Desse modo, no que concerne à temática, diversas publicações na mídia de ampla divulgação afirmam que os anticoncepcionais orais têm papel importante na sarcopenia e na hipotrofia, incluindo perda de força muscular e redução do desempenho físico. Assim, o presente trabalho tem por objetivo avaliar, por meio de pesquisas de artigos, a correlação entre anticoncepcionais hormonais orais e hipotrofia muscular. Foi concluído que os artigos científicos especializados no tema são ainda bastante inconclusivos, sugerindo que há indicações de que usuárias de anticoncepcional oral sejam mais suscetíveis ao dano muscular induzido por exercícios, contudo ainda não há consenso.

Anticonception pills consist of a combined formulation of an estrogen and a progestogen or simple presentations of progestogen alone with the purpose of blocking ovulation and altering the conditions of the uterus and uterine tubes, partially blocking folliculogenesis and inhibiting the gonadotropin peak. Thus, with regard to the subject, several widely publicized media publications claim that oral contraceptives play an important role in sarcopenia and hypotrophy, including loss of muscle strength and reduced physical performance. So, the present work aims to evaluate through article searches the correlation between oral hormonal contraceptives and muscle hypotrophy. It was concluded that scientific articles specialized on the subject are still quite inconclusive, suggesting that there are indications that oral contraceptive users are more susceptible to exercise-induced muscle damage, however there is still no consensus.

Effect of histone methylase EZH2 on proliferation and apoptosis of hypertrophic myocardial cells of AC16 / 国际生物医学工程杂志

Objective:To explore the molecular mechanism of the effect of the histone methylase zeste gene enhancer homolog 2 (EZH2) on the proliferation and apoptosis of human hypertrophic cardiomyocytes AC16.Methods:The AC16 hypertrophic cardiomyocyte model was constructed by adding angiotensin Ⅱ to the AC16 cell culture medium. The cells were divided into four groups, including the blank control group, the angiotensin Ⅱ group, the empty vector + angiotensin Ⅱ group, and the EZH2 overexpression + angiotensin Ⅱ group. The expression levels of EZH2 and brain natriuretic peptide ( BNP) genes were measured using fluorescent quantitative PCR. The EZH2, trimethylation of lysine at position 27 of histone H3 (H3K27me3), and BNP proteins expression were detected by Western Blot. The MTS method was used to detect the proliferation of AC16 cell. The Annexin V-FITC/PI double staining method was used to detect the apoptosis of AC16 cell. Results:Compared with the blank control group, the expression levels of EZH2 and H3K27me3 in the angiotensin Ⅱ group were decreased, the expression level of BNP was increased, cell proliferation was decreased, and apoptosis was increased (all P < 0.001). Compared with the empty vector + angiotensin Ⅱ group, the expression levels of EZH2 and H3K27me3 in the EZH2 overexpression + angiotensin Ⅱ group were increased, the expression level of BNP was decreased, the cell proliferation level was increased, and the apoptosis level was decreased (all P < 0.001). There was no significant difference between the angiotensin Ⅱ group and the empty vector + angiotensin Ⅱ group (all P > 0.05). Conclusions:Histone methylase EZH2 has an effect on the proliferation and apoptosis of AC16 cell, providing a reference for the treatment of myocardial hypertrophy and revealing the exact pathogenesis of myocardial hypertrophy.

Inhibitor of growth protein-2 silencing alleviates angiotensin Ⅱ-induced cardiac remodeling in mice by reducing p53 acetylation / 南方医科大学学报

OBJECTIVE@#To investigate the effect of inhibitor of growth protein-2 (Ing2) silencing on angiotensin Ⅱ (AngⅡ)-induced cardiac remodeling in mice and explore the underlying mechanism.@*METHODS@#An adenoviral vector carrying Ing2 shRNA or empty adenoviral vector was injected into the tail vein of mice, followed 48 h later by infusion of 1000 ng · kg-1 · min-1 Ang Ⅱ or saline using a mini-osmotic pump for 42 consecutive days. Transthoracic echocardiography was used to assess cardiac geometry and function and the level of cardiac hypertrophy in the mice. Masson and WGA staining were used to detect myocardial fibrosis and cross-sectional area of cardiomyocytes, and myocardial cell apoptosis was detected with TUNEL assay. Western blotting was performed to detect myocardial expressions of cleaved caspase 3, ING2, collagen Ⅰ, Ac-p53(Lys382) and p-p53 (Ser15); Ing2 mRNA expression was detected using real-time PCR. Mitochondrial biogenesis, as measured by mitochondrial ROS content, ATP content, citrate synthase activity and calcium storage, was determined using commercial assay kits.@*RESULTS@#The expression levels of Ing2 mRNA and protein were significantly higher in the mice with chronic Ang Ⅱ infusion than in saline-infused mice. Chronic infusion of AngⅡ significantly increased the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) and reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the mice. Ing2 silencing obviously alleviated AngⅡ-induced cardiac function decline, as shown by decreased LVEDD and LVESD and increased LVEF and LVFS, improved myocardial mitochondrial damage and myocardial hypertrophy and fibrosis, and inhibited cardiomyocyte apoptosis. Chronic AngⅡ infusion significantly increased myocardial expression levels of Ac-p53(Lys382) and p-p53(Ser15) in the mice, and Ing2 silencing prior to AngⅡ infusion lessened AngⅡ- induced increase of Ac-p53(Lys382) without affecting p53 (ser15) expression.@*CONCLUSION@#Ing2 silencing can inhibit AngⅡ-induced cardiac remodeling and dysfunction in mice by reducing p53 acetylation.

Is the myonuclear domain ceiling hypothesis dead?

Muscle fibres are multinuclear cells, and the cytoplasmic territory where a single myonucleus controls transcriptional activity is called the myonuclear domain (MND). MND size shows flexibility during muscle hypertrophy. The MND ceiling hypothesis states that hypertrophy results in the expansion of MND size to an upper limit or MND ceiling, beyond which additional myonuclei via activation of satellite cells are required to support further growth. However, the debate about the MND ceiling hypothesis is far from settled, and various studies show conflicting results about the existence or otherwise of MND ceiling in hypertrophy. The aim of this review is to summarise the literature about the MND ceiling in various settings of hypertrophy and discuss the possible factors contributing to a discrepancy in the literature. We conclude by describing the physiological and clinical significance of the MND ceiling limit in the muscle adaptation process in various physiological and pathological conditions.

Benefits of progressive resistance training on motor performance and muscular hypertrophy in rats with Parkinson's disease / Beneficios del entrenamiento con ejercicios de resistencia progresiva sobre el rendimiento motor y la hipertrofia muscular en ratas con enfermedad de Parkinson / Benefícios do treinamento com exercícios resistidos progressivos no desempenho motor e na hipertrofia muscular de ratos com doença de Parkinson

ABSTRACT Parkinson's disease (PD) is a progressive neurodegenerative condition defined by the presence of primary debilitating motor symptoms. This study aims to investigate the benefits of high-intensity progressive resistance training on muscle tissue and motor performance before and after the induction of PD in rats. A total of 80 male Wistar rats (Rattus norvegicus, var. albinus) aged 40 days and weighing between 250 and 450g were used. A total of 40 animals were subjected to PD surgery to induce electrolytic injury and were randomly assigned to the following subgroups: animals trained before PD induction (PA-Exa); animals trained after PD induction (PA-Exd); animals trained before and after PD induction (PA-Exad); and sedentary animals with PD induction (PA-Sed). The other 40 animals (control) were subjected to surgical access but not to PD electrolytic injury (Sham) and distributed in the same subgroups described above. For the PD induction surgery, electrolytic stimulation was used at the following coordinates: anteroposterior (AP) −4.9, mid-lateral (ML) 1.7,and dorsoventral (DV) 8.1. High-intensity progressive resistance training was performed on a vertical ladder five days/week from 30 to 45 minutes for four weeks. For our functional evaluation, the parallel bars and the misstep tests were used at the beginning (after surgery) and at the end of the experiment. After euthanasia, the forelimb biceps and hindlimb flexor hallucis longus muscles were removed. Processing, coloration, and histomorphometry analysis of muscle tissue were performed for all groups. To analyze the data, GraphPad Prism 9.4 was used with one-way analysis of variance (ANOVA) and a p<0.05. Data on muscle fiber count and area in forelimb biceps showed no significant differences, with a 0.853 and 0.4122 p-value, respectively. Flexor hallucis longus muscle fiber count showed a significant difference (p=0.0356), and PA-Exa and PA-Exd averaged the highest means. Hindlimb flexor hallucis longus muscle fiber area also evinced a significant difference (p=0.0306), in which PA-Exd, PA-Exad, and Sham-Exad showed the largest areas. Analysis of hindlegs in the parallel bars test showed that PA-Exad evinced the best functional performance. In the misstep test, we observed an increase in the number of errors animals made for almost all the groups, evincing a significant difference in the number of errors before and after the test only for PA-Exa, PA-Exd, and PA-Sed. We concluded that the animals that underwent high-intensity progressive training showed better performance in their hindlegs than in their fore ones and that animals that exercised before and after surgery benefited more from training.

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RESUMO A doença de Parkinson (DP) é uma doença neurodegenerativa progressiva definida pela presença de sintomas motores debilitantes primários. O objetivo deste estudo é investigar os benefícios do treinamento com exercícios físicos progressivos de alta intensidade no tecido muscular e no desempenho motor antes e depois da indução da DP em ratos. Para tanto, foram utilizados 80 ratos Wistar machos (Rattus norvegicus var. albinus) com 40 dias de vida e peso corporal entre 250 e 450g. Quarenta animais foram submetidos à cirurgia de indução da DP por lesão eletrolítica e distribuídos aleatoriamente nos seguintes subgrupos: animais treinados antes da indução da DP (PA-Exa), animais treinados depois da indução da DP (PA-Exd), animais treinados antes e depois da indução da DP (PA-Exad) e animais sedentários com indução da DP (PA-Sed). Os outros 40 animais (controle) foram submetidos ao acesso cirúrgico, mas não à lesão eletrolítica (sham) da DP, e distribuídos nos mesmos subgrupos descritos anteriormente. Para cirurgia de indução da DP, foi utilizada estimulação eletrolítica nas coordenadas: anteroposterior (AP) igual a −4,9, médio-lateral (ML) igual a 1,7 e dorsoventral (DV) igual a 8,1. O treinamento com exercícios físicos progressivos de alta intensidade foi realizado na escada vertical, cinco dias/semana, de 30 a 45 minutos, por quatro semanas. Para avaliação funcional, foi utilizado o teste das barras paralelas e do passo em falso no início, depois da cirurgia e no final do experimento. Após a eutanásia dos animais, foram retirados os músculos bíceps da pata dianteira e flexor longo do hálux da pata traseira. Foi realizado processamento, coloração e análise histomorfométrica do tecido muscular dos grupos de animais. Para análise dos dados, foi utilizado o programa GraphPad Prism 9.4, com a análise de variância (Anova) one-way e p<0,05. Os dados sobre contagem e área das fibras musculares no bíceps da pata dianteira do animal não demonstraram diferenças significativas com valor de p igual a 0,853 e 0,4122, respectivamente. Os resultados da contagem de fibras musculares no flexor longo do hálux demonstraram diferença significativa (p=0,0356), e os grupos que apresentaram maior média de fibras foram PA-Exa e PA-Exd. Sobre a área das fibras do músculo flexor longo do hálux da pata traseira, também foi evidenciada diferença significativa (p=0,0306), e os grupos que apresentaram maiores áreas foram PA-Exd, PA-Exad e o grupo de animais treinados antes e depois da falsa cirurgia (SHAM-Exad). A análise das patas traseiras no teste das barras paralelas demonstrou que os animais do grupo PA-Exad apresentaram melhora do desempenho funcional nesse teste. No teste do passo em falso, foi observado aumento do número de erros cometidos pelos animais em quase todos os grupos, evidenciando diferença significativa no número de erros antes e depois do teste apenas nos grupos PA-Exa, PA-Exd e PA-Sed. Conclui-se que os animais que realizaram o treinamento com exercícios físicos progressivos de alta intensidade apresentaram melhor desempenho nas patas traseiras em comparação com as dianteiras e que os animais que se exercitaram antes e depois da cirurgia foram mais beneficiados com o treinamento.

Relação da Ascensão Matinal da Pressão Arterial com a Hipertrofia Ventricular Esquerda em Hipertensos Obesos / Association between Morning Surge and Left Ventricular Hypertrophy in Obese Hypertensive Patients

Resumo Fundamento O aumento do peso frequentemente desencadeia mecanismos que elevam a pressão arterial. A obesidade causa mudanças estruturais no miocárdio, incluindo aumento da massa ventricular, dilatação atrial, bem como disfunções diastólicas e sistólicas. Além disso, variações pressóricas nos hipertensos obesos, como a ascensão matinal (AM), podem ter relevância clínica na prevenção dos eventos cardiovasculares. A AM da pressão arterial é um fenômeno fisiológico, que quando elevada pode ser considerada um fator de risco independente para eventos cardiovasculares. Objetivo Avaliar valores da elevação da AM e sua associação com a hipertrofia ventricular esquerda (HVE) e com o Descenso do Sono (DS) em obesos e não obesos hipertensos. Métodos Estudo transversal que avaliou medidas pressóricas à monitorização ambulatorial da pressão arterial (MAPA) e a presença de HVE, avaliada pela ecocardiografia, em 203 pacientes hipertensos em tratamento ambulatorial, separados em dois grupos: 109 não obesos e 94 hipertensos obesos. O nível de significância adotado foi de 0,05 em testes bicaudais. Resultados A AM acima de 20 mmHg à MAPA foi detectada em 59,2% dos pacientes do grupo "não obesos" e em 40,6% no grupo "obesos". A HVE foi encontrada em 18,1% no grupo dos não-obesos e em 39,3% no grupo de obesos, p<0,001. No grupo "obesos" foi observado que AM >16 mmHg esteve associada à HVE, com [razão de prevalência: 2,80; IC95% (1,12-6,98), p=0,03]. Para o grupo dos "não obesos", o ponto de corte da AM para essa associação foi >22 mmHg. Conclusão A AM elevada associou-se positivamente com HVE, com comportamento peculiar na população de hipertensos e obesos.

Abstract Background Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass, atrial dilatation, and diastolic and systolic dysfunction. Additionally, blood pressure variations, like morning surge (MS) in obese hypertensive patients may have clinical relevance in cardiovascular events. Although morning blood pressure surge is a physiological phenomenon, excess MS can be considered an independent risk factor for cardiovascular events. Objective To evaluate MS values and their association with left ventricular hypertrophy (LVH) and nocturnal dipping (ND) in obese and non-obese hypertensive patients. Methods A cross-sectional study that evaluated BP measurements by ambulatory blood pressure monitoring (ABPM) and the presence of LVH by echocardiography in 203 hypertensive outpatients, divided into two groups: 109 non-obese and 94 obese hypertensives patients. The significance level was set at 0.05 in two-tailed tests. Results A MS above 20 mmHg by ABPM was detected in 59.2% of patients in the non-obese group and 40.6% in the obese group. LVH was found in 18.1% and 39.3% of patients in the non-obese and obese groups, respectively, p<0.001. In the "obese group", it was observed that a MS>16 mmHg was associated with LVH, [prevalence ratio: 2.80; 95%CI (1.12-6.98), p=0.03]. For the non-obese group, the cut-off point of MS for this association was >22 mmHg. Conclusion High MS was positively associated with LVH, with a particular behavior in the hypertensive obese group.

Validity, reliability and measurement error of quadriceps femoris muscle thickness obtained by ultrasound in healthy adults: a systematic review / Validade, confiabilidade e erro da medida da espessura muscular do quadríceps femoral obtida pela ultrassonografia em adultos saudáveis: uma revisão sistemática

Abstract Due to its low cost and operational simplicity, ultrasound has been used to monitor muscle thickness in laboratory environments, rehabilitation clinics, and sports clubs. However, it is necessary to determine the measurement's quality to infer whether the possible changes observed are derived from the treatment or the measurement error. Therefore, we performed a systematic review to determine the validity, reliability, and measurement error of quadriceps femoris muscle thickness obtained by ultrasound in healthy adults. A search was conducted in the Pubmed, Scopus, and Web of Science databases until April 2022. The study selection process was carried out by two independent researchers, with the presence of a third researcher in case of disagreements. Twenty-six studies were eligible for the review, being 4 of validity, 4 of reliability only, and 18 of reliability and measurement error. The intraclass correlation coefficient ranged from 0.60 to 0.99 in validity studies and from 0.44 to 0.99 in reliability studies. The typical error of measurement ranged from 0.01 to 0.47 cm, and the coefficient of variation was from 0.5 to 17.9%. Four studies received "very good" classification in all the risk of bias analysis criteria. Therefore, it is concluded that the quadriceps femoris muscle thickness obtained by ultrasound was shown to be valid, reliable, and to have low measurement errors in healthy adults. The weighted average of the relative error was 6.5%, less than typical increases in resistance training studies. The raters' experience and methodological care for repeated measurements were necessary to observe low measurement errors.

Resumo Devido ao baixo custo e simplicidade operacional, a ultrassonografia tem sido utilizada para monitorar a espessura muscular em ambientes laboratoriais, clínicas de reabilitação e clubes desportivos. Porém, é necessário determinar a qualidade da medida para inferir se as possíveis modificações observadas são decorrentes do tratamento ou do erro da medida. Portanto, realizamos uma revisão sistemática para determinar a validade, confiabilidade e erro da medida da espessura muscular do quadríceps femoral obtida pela ultrassonografia em adultos saudáveis. Foi realizada busca nas bases de dados Pubmed, Scopus e Web of Science até abril de 2022. O processo de seleção dos estudos foi realizado por dois pesquisadores independentes, com a presença de um terceiro pesquisador em caso de divergências. Vinte e seis estudos foram elegíveis para a revisão, sendo 4 de validade, 4 apenas de confiabilidade e 18 de confiabilidade e erro de medida. O coeficiente de correlação intraclasse variou de 0,60 a 0,99 em estudos de validade e 0,44 a 0,99 em estudos de confiabilidade. O erro típico da medida variou de 0,01 a 0,47 cm e o coeficiente de variação foi de 0,5 a 17,9%. Quatro estudos receberam classificação "muito bom" em todos os critérios na análise de risco de viés. Portanto, concluiu-se que a espessura muscular do quadríceps femoral obtida pela ultrassonografia se mostrou válida, confiável e com baixos erros de medida em adultos saudáveis. A média ponderada do erro relativo foi de 6,5%, menor do que os aumentos típicos em estudos de treinamento resistido. A experiência dos avaliadores e o cuidado metodológico com as medidas repetidas foram necessários para observar baixos erros de medida.