Apical hypertrophic cardiomyopathy: A case series at a Brazilian referral center with a maximal follow-up of 15 years.

BACKGROUND: Apical hypertrophic cardiomyopathy (AHCM) is a rare cardiomyopathy, in which hypertrophy occurs predominantly in the ventricular apex, and in some cases with a high risk of sudden cardiac death. OBJECTIVE: The aim of this paper is to present a case series of patients with AHCM and describe their main clinical, echocardiographic and electrocardiographic characteristics, the recommendation for an implantable cardioverter-defibrillator (ICD) and the frequency of sudden cardiac death (SCD). METHODS: A retrospective case series was conducted at the referral center of a federal teaching hospital, between the years 2005 to 2020, involving patients with an echocardiographic diagnosis of AHCM. The parameters of the American College of Cardiology and the European Society of Cardiology were used to assess the risk of SCD. RESULTS: A total of 11 individuals were assessed with a mean age of 55.3 years, mean follow-up of 41.2 months, most of whom were symptomatic at diagnosis (72.7%). The most frequent symptom was dyspnea (27.3%). A family history of SCD was described in 45.5% of cases. Due to a high risk of SCD, four patients received ICDs. One patient presented sudden cardiac death after having refused the ICD. CONCLUSIONS: Symptoms and alterations in the imaging exams are significant factors in the clinical and prognostic assessment of patients with AHCM.

MDGC-MS analysis of essential oils from Protium heptaphyllum (Aubl. ) and their antifungal activity against Candida specie / Análise MDGC-MS de óleos essenciais de Protium heptaphyllum (Aubl. ) e sua atividade antifúngica contra espécies de Candida

ABSTRACT Protium heptaphyllum is found in the Amazon region, and in various Brazilian states and South American countries. Also Known as almecega, it produces an oil resin used in traditional medicine as analgesic, anti-inflammatory, cicatrizant and expectorant, it is rich in pentacyclic triterpenes and essential oil. The main objective of this study was to analyze the chemical composition of P. heptaphyllumresin (OEPh) over different extraction times and to evaluate their antifungal activity against Candida species, obtained from gardeners with onychomycosis, using the disk diffusion method. The OEPh was obtained by hydrodistillation and analyzed by Multidimensional Gas Chromatography coupled with Mass Spectrometry (MDGC / MS). Candida species were obtained from lesions on the nails of horticulturist from a community garden in the city of Teresina, Piauí, Brazil. The antifungal activity in concentrations of 1000 µg/L, 500 µg/L and 250 µg/L, PROTOCOL M44-A2 (CLSI 2009) OEPh was tested. The main constituents identified were: l-limonene, α-terpineol, p-cineol, o-cymene and α-phellandrene, however, its composition varies significantly with extraction time. All species, except C. rugosa, were inhibited with halo (≥ 14 mm) at 1000 μg / L. C. krusei is naturally resistant to the drug fluconazole, but when tested with OEPh the clinical species (case 9) demonstrated sensitivity in three dilutions (halo ≤ 10 ≥ 14) and the standard strain was inhibited at concentration of 1000 μg/Lg / L (halo 14mm). A similar situation also occurred with the standard strain of C. parapsilosis (halo ≥ 11mm). OEPh has considerable antifungal activity, which merits further investigation for alternative clinical applications, since this species is widely distributed in our community, and it presents good yields, and also has important therapeutic applications.

RESUMO Protium heptaphyllum é encontrada na região amazônica, em vários estados do Brasil e países da América do Sul. Conhecida como almecega produz uma resina oleosa usada na medicina popular como analgésica, antiinflamatória, cicatrizante e expectorante, é rica em triterpenos pentaciclicos e óleo essencial. O objetivo principal do presente trabalho foi analisar a composição química do óleo essencial da resina P. heptaphyllum (OEPh) em diferentes tempo de extração e avaliarsuaatividade antifúngica contra espécies de Candida, isoladas de horticultores com onicomicoses, por método de disco-difusão. O OEPh foi obtido por hidrodestilação, analisado por Cromatografia Gasosa Multidimensinal Acoplada a Espectrometria de Massas (MDGC/MS). As espécies de Candida foram obtidas de lesões nas unhas de horticultores de uma horta comunitária na cidade de Teresina, Piauí, Brasil. Testou-se a atividade antifúngica do OEPhnas concentrações de 1000 μg/L, 500 μg/L e 250 μg/L, protocolo M44-A2 (CLSI 2009). Os principais constituintes identificados foram l- limoneno, α-terpineol, p-cineol, o-cimeno e α-felandreno, entretanto, sua composição varia significativamente em decorrência do tempo de extração. Todas as espécies, exceto a C. rugosa, foram inibidas com halo ( Χ ≥ 14 mm) na concentração de 1000 μg/L. C. krusei é naturalmente resistente ao fármaco fluconazol, mas quando testado com OEPh,a espécie clínico (caso 9) demonstrou sensibilidade nas três diluições (halo Χ ≤ 10 ≥ 14) e a cepa padrão foi inibida na concentração de 1000 μg/L (halo Χ 14mm). Fato semelhante também ocorreu com a cepa padrão de C. parapsilosis (halo Χ ≥ 11mm). O OEPh possui atividade antifúngica considerável, merecendo uma investigação mais aprofundada para aplicações clínicas alternativas, uma vez que esta espécie é amplamente distribuída em nossa comunidade, apresenta bom rendimento e, ainda, aplicações terapêuticas importantes.

Um possível mecanismo de ação para o efeito anticonvulsivante do p-cimeno / A plausible mechanism of action for the anticonvulsant effect of p-cymene

O presente estudo teve como objetivo investigar o efeito anticonvulsivante do p-cimeno (CIM), bem como verificar a concentração das monoaminas (dopamina(DA), noradrenalina (NA), serotonina (5-HT), e seus metabólitos (ácido dihidroxifenilacético (DOPAC), ácidohomovanílico (HVA) e ácido 5-hidroxi-indol-acético (5-HIAA)) no hipocampo de camundongos tratados com cloridrato de pilocarpina 400 mg/kg (P400; i.p.) e nos grupos tratados com a associação de CIM (50, 100 ou150 mg/kg) e P400. Nesse estudo foi avaliada a latência para a primeira crise epiléptica e a taxa de mortalidade. Os resultados revelaram que o CIM produziu um aumento na latência para primeira crise epilética, bem como promoveu uma proteção significativa contra a mortalidade induzida pelo processo convulsivo. O monoterpeno nas doses testadas também foi capaz de produzir um aumento da latência para instalação do estado de mal epilético induzido por pilocarpina. Além disso, durante os estudos para identificar o mecanismo de ação nenhum dos efeitos do p-cimeno nesse modelo foram bloqueados pelo pré-tratamento com atropina. Complementando os estudos para identificar o provável mecanismo de ação do p-cimeno, foi verificado que os efeitos desse monorterpeno foram revertidos pelo flumazenil, um antagonista do sistema GABAérgico, sugerindo que esse monoterpeno pode atuar por meio desse sistema. Também, em nossos resultados também foi visto uma diminuição dos níveis de DA e um aumento do conteúdo de seus metabólitos (DOPAC e HVA) durante as crises epilépticas. Por outro lado foi detectado um aumento na concentração de NA e 5-HT, e uma diminuição no metabólito da 5-HT (5-HIAA) durante as crises epilépticas. Dessa forma, o CIM na presença do estímulo convulsivo, reverte os efeitos produzidos nos níveis das monoaminas e seus metabólitos observados durante as crises epilépticas, sugerindo que este monoterpeno produz efeito anticonvulsivante por meio da modulação direta do sistema GABAérgico e indiretamente por...

The aim of this study was to investigate the anticonvulsant effect of p-cymene (CYM) and to determine the concentrations of monoamines (dopamine (DA), noradrenaline (NA) and serotonin (5-HT)), and their metabolites (dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA)) in the hippocampus of mice treated with pilocarpine hydrochloride 400 mg/kg (P400; i.p.) and in groups treated with a combination of CYM (50,100 or 150 mg/kg) and P400. We assessed the latency to the first epileptic seizure and the mortality rate. Results showed that CYM produced an increase in latency to the first seizure, as well as providing significant protection against mortality induced by seizures. Higher doses of the monoterpene were also able to prolong the latency to the onset of status epilepticus induced by pilocarpine. Moreover, in an experiment to throw light on the mechanism of action of p-cymene, none of its effects was blocked by pretreatment with atropine. In further studies to identify the probable mechanism of CYM, it was observed that the effectsof this monoterpene were reversed by flumazenil, anantagonist of the GABAergic system, suggesting that it may act through this cerebral system. Furthermore, our results also showed a fall in DA levels and an increase in the contents of its metabolites (DOPAC and HVA) during seizures. On the other hand, increases in NA and 5-HT concentrations and a decrease in that of the 5-HTmetabolite (5-HIAA) were detected during seizures. Thus, CYM, in the presence of a convulsant stimulus, reverses the effects on levels of monoamines and their metabolites observed during seizure activity, suggesting that this monoterpene produces its anticonvulsant effect by modulating the GABAergic system directly and/or indirectly, through changes in monoamine (DA, NA and 5-HT) contents opposite to those observed during the convulsive process in the hippocampal region. However,further studies are necessary to...

Exaggerated blood pressure response during the exercise treadmill test as a risk factor for hypertension.

Exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) has been considered to be a risk factor for hypertension. The relationship of polymorphisms of the renin-angiotensin system gene with hypertension has not been established. Our objective was to evaluate whether EBPR during exercise is a clinical marker for hypertension. The study concerned a historical cohort of normotensive individuals. The exposed individuals were those who presented EBPR. At the end of the observation period (41.7 months = 3.5 years), the development of hypertension was analyzed within the two groups. Genetic polymorphisms and blood pressure behavior were assessed as independent variables, together with the classical risk factors for hypertension. The I/D gene polymorphism of the angiotensin-converting enzyme and M235T of angiotensinogen were ruled out as risk factors for hypertension. EBPR during ETT is not an independent influence on the chances of developing hypertension. No differences were observed between the hypertensive and normotensive individuals regarding gender (P = 0.655), skin color (P = 0.636), family history of hypertension (P = 0.225), diabetes mellitus (P = 0.285), or hypertriglyceridemia (P = 0.734). The risk of developing hypertension increased with increasing body mass index (BMI) and advancing age. The risk factors, which independently influenced the development of hypertension, were age and BMI. EBPR did not constitute an independent risk factor for hypertension and is probably a preclinical phase in the spectrum of normotension and hypertension.

Exaggerated blood pressure response during the exercise treadmill test as a risk factor for hypertension

Exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) has been considered to be a risk factor for hypertension. The relationship of polymorphisms of the renin-angiotensin system gene with hypertension has not been established. Our objective was to evaluate whether EBPR during exercise is a clinical marker for hypertension. The study concerned a historical cohort of normotensive individuals. The exposed individuals were those who presented EBPR. At the end of the observation period (41.7 months = 3.5 years), the development of hypertension was analyzed within the two groups. Genetic polymorphisms and blood pressure behavior were assessed as independent variables, together with the classical risk factors for hypertension. The I/D gene polymorphism of the angiotensin-converting enzyme and M235T of angiotensinogen were ruled out as risk factors for hypertension. EBPR during ETT is not an independent influence on the chances of developing hypertension. No differences were observed between the hypertensive and normotensive individuals regarding gender (P = 0.655), skin color (P = 0.636), family history of hypertension (P = 0.225), diabetes mellitus (P = 0.285), or hypertriglyceridemia (P = 0.734). The risk of developing hypertension increased with increasing body mass index (BMI) and advancing age. The risk factors, which independently influenced the development of hypertension, were age and BMI. EBPR did not constitute an independent risk factor for hypertension and is probably a preclinical phase in the spectrum of normotension and hypertension.

Revising the M235T polymorphism position for the AGT gene and reporting a modifying variant in the Brazilian population with potential cardiac and neural impact.

There is a growing need to curate the overwhelming amount of sequencing data which is available in many public databases. For instance, new information shows that the M235T polymorphism at the angiotensinogen gene (AGT) is actually positioned at the position corresponding to the amino acid 268 and not 235. This polymorphism is filled as rs699 in the NCBI SNP database and results in the synthesis of a threonine (T) instead of a methionine (M). It has been widely studied and associated as an important risk factor for several vascular and neuropsychiatric conditions. We faced this new situation during the targeted sequencing of 360 chromosomes from Brazilian subjects studied for the M235T polymorphism, leading to the identification of a novel variation (rs141900991). This report explores the potential impact of such a dinucleotide variation, which promotes the change of alanine (A) to serine (S) at the AGT protein structure (A237S). Considering the previous M268T variation at the four possible haplotypes combined (MA, MS, TA and TS), we performed a comparative hydrophobicity simulation, using the Kyte-Doolittle algorithm, available at the CLB Bio workbench, in the four possible haplotypes. Additional simulations were performed using the programs PolyPhen, I-Mutant and SIFT, in order to evaluate the pathogenicity of both mutations. The predicted hydrophobicity decreases of a similar magnitude, with both MS and TA haplotypes, but the presence of both variations induces a major decrease in hydrophobicity, suggesting a cumulative effect, with possible modifying effect since that this variation per se would limit the hydrophobicity range and the latter chances in finding significant phenotype differences. A better characterization of this kind of variant is particularly important because the current genome wide scan analyses in complex disorders with cardiac or neural etiology are not generating reliable findings, especially if we consider the huge investment with such approach. Additional and unknown variations like this one, with potential modifying effect, might be more common than previously expected.

Effects of immature cashew nut-shell liquid (Anacardium occidentale) against oxidative damage in Saccharomyces cerevisiae and inhibition of acetylcholinesterase activity.

The cashew tree (Anacardium occidentale) represents one of the major cheapest sources of non-isoprenoid phenolic lipids, which have a variety of biological properties: they can act as molluscicides, insecticides, fungicides, have anti-termite properties, have medicinal applications, and demonstrate antioxidant activity in vitro. Immature cashew nut-shell liquid (iCNSL) is a unique natural source of unsaturated long-chain phenols. Their use has stimulated much research in order to prepare drug analogues for application in several fields. The objective of the present study was to determine whether iCNSL has antioxidant properties when used in strains of the yeast Saccharomyces cerevisiae and to measure the inhibitory activity of acetylcholinesterase. The constituents were identified using thin-layer chromatography, gas chromatography-mass spectrometry, Fourier transform infrared spectroscopy, and (1)H and (13)C nuclear magnetic resonance. The iCNSL contains anacardic acid, cardanol, cardol, and 2-methyl cardol. Immature cashew nut oil contains triacylglycerols, fatty acids, alkyl-substituted phenols, and cholesterol. The main constituents of the free fatty acids are palmitic (C(16:0)) and oleic acid (C(18:1)). iCNSL has excellent protective activities in strains of S. cerevisiae against oxidative damage induced by hydrogen peroxide and inhibits acetylcholinesterase activity. iCNSL may have an important role in protecting DNA against damage induced by reactive oxygen species, as well as hydrogen peroxide, generated by intra- and extracellular mechanisms.

Morphological Study of the Liver in the Teleost Oreochromis niloticus / Estudio Morfológico del Hígado en el Teleósteo Oreochromis niloticus

Liver samples of Oreochromis niloticus cultivated in floating net cages were fixed for histological and ultrastructural studies with the objective of describing the hepatic parenchymal structure and the intrahepatic exocrine pancreatic tissue. Anatomically, the liver showed only two hepatic lobes. Histological analysis demonstrated that the hepatocytes were spread out as anastomotic cords, arranged in two cellular layers and surrounded by sinusoids. The intrahepatic exocrine pancreatic tissue exhibited an acinar arrangement and was diffused in the hepatic parenchyma. Structural analysis showed that the hepatocytes had a rounded nucleus and a rough endoplasmic reticulum with a parallel disposition to the nuclear membrane. The exocrine pancreatic cells showed secretion granules at the apical portion and the rough endoplasmic reticulum was concentrically distributed.

Con el objetivo de describir la estructura del parénquima hepático y del páncreas exocrino intrahepático del Oreochromis niloticus, fueron fijados para estudios histológicos y ultraestructurales fragmentos de hígado de peces cultivados en jaulas flotantes. Se evidenciaron sólo 2 lóbubos hepáticos. El análisis histológico demostró que los hepatocitos se encontraban organizados en forma de cordones anastomosados, dispuestos en dos capas celulares y cercados por sinusoides. El tejido pancreático exocrino intrahepático se encontró difuso en el parénquima hepático y se destacó por su organización acinar. El análisis ultraestructural demostró que los hepatocitos presentaban núcleos redondos y el retículo endoplasmático rugoso estaba dispuesto paralelamente a la membrana nuclear. Las células pancreáticas exocrinas presentaban gránulos de secreción localizados en la porción apical y el retículo endoplasmático rugoso estaba organizado de manera concéntrica.