Cardiopatia chagásica e insuficiência cardíaca : da epidemiologia ao tratamento

© 2020 Sociedade Portuguesa de Cardiologia. Published by Elsevier España, S.L.U. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Chagas disease is among the neglected tropical diseases recognized by the World Health Organization that have received insufficient attention from governments and health agencies. Chagas disease is endemic in 21 Latin America regions. Due to globalization and increased migration, it has crossed borders and reached other regions including North America and Europe. The clinical presentation of the disease is highly variable, from general symptoms to severe cardiac involvement that can culminate in heart failure. Chagas heart disease is multifactorial, and can include dilated cardiomyopathy, thromboembolic phenomena, and arrhythmias that may lead to sudden death. Diagnosis is by methods such as enzyme-linked immunosorbent assay (ELISA) and the degree of cardiac involvement should be investigated with complementary exams including ECG, chest radiography and electrophysiological study. There have been insufficient studies on which to base specific treatment for heart failure due to Chagas disease. Treatment should therefore be derived from guidelines for heart failure that are not specific for this disease. Heart transplantation is a viable option with satisfactory success rates that has improved survival.A doença de Chagas é uma das reconhecidas pela Organização Mundial de Saúde (OMS) entre um grupo de doenças que receberam atenção insuficiente de governos e órgãos de saúde. A doença de Chagas é endémica em 21 regiões da América Latina. Devido à globalização e ao aumento da migração, a doença de Chagas cruzou fronteiras e atingiu outras regiões como a América do Norte e a Europa. A apresentação clínica da doença pode ser muito variada, pois gera desde sintomas gerais até comprometimento cardíaco grave, capaz de culminar em insuficiência cardíaca. A cardiopatia é multifatorial e, dessa forma, pode expressar-se em miocardiopatia dilatada, fenómenos tromboembólicos e arritmias que podem levar à morte súbita. O diagnóstico deve ser feito utilizando métodos como o estudo imunoenzimático (ELISA) e a investigação do grau de acometimento cardíaco deve ser realizada com outros exames complementares, como ECG, radiografia do tórax, estudo eletrofisiológico, entre outros. Os estudos científicos são insuficientes para propor um tratamento específico para insuficiência cardíaca por doença de Chagas. Portanto, o tratamento deve ser extrapolado das diretrizes para insuficiência cardíaca que não são específicas para essa doença. Atualmente, sabe-se que o transplante cardíaco é uma opção viável que melhora a sobrevida e apresenta taxas de sucesso satisfatória.info:eu-repo/semantics/publishedVersio

Os abcessos pulmonares em revisão

AbstractLung abscesses are cavitating lesions containing necrotic debris caused by microbial infection. Patients with chronic lung disease, bronchial obstruction secondary to cancer, a history of aspiration or risk of aspiration caused by alcoholism, altered mental status, structural or physiologic alterations of the pharynx and esophagus, neuromuscular disorders, anesthesia, are among others at higher risk of developing lung abcess.The main bacteriological characteristics, the diagnosis, therapy and prognosis are considered. The problem of antimicrobial resistance is also referred.Rev Port Pneumol 2008; XIV (1): 141-14

Galectin-3, a prognostic marker - and a therapeutic target?

© 2014 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. Todos os direitos reservadosThe natriuretic peptides BNP and NT-proBNP are currently the most commonly used biomarkers in heart failure, but they have limitations. There is thus a need to identify new biomarkers that may prove useful, alone or in combination, for screening, diagnosis and prognosis. Galectin-3 is a protein involved in a variety of cellular signaling pathways and is found in many tissues. Its expression is low in normal hearts but elevated in fibrotic hearts. Among other effects, it promotes fibroblast proliferation and collagen synthesis, contributing to the cardiac remodeling that is central to the development and progression of heart failure. Heart failure associated with elevated galectin-3 (>17.8 ng/ml) affects 30-50% of patients with chronic heart failure, and is a marker of worse prognosis, with higher rates of short-term rehospitalization and mortality. It is thought that galectin-3 inhibition, or even genetic disruption, may reverse or delay disease progression. Galectin-3 appears to have greater prognostic value than natriuretic peptides when assessed separately, however, when combined their prognostic value is even higher. Galectin-3, associated with BNP or NT-proBNP, may help improve the diagnosis and prognosis of heart failure.Os péptidos natriuréticos BNP e NT-proBNP são atualmente os biomarcadores mais utilizados na insuficiência cardíaca, no entanto, permanecem algumas limitações. Isso justifica a necessidade de identificar novos biomarcadores que possam revelar vantagens, isoladamente ou em associação, no rastreio, diagnóstico e prognóstico. A Galectina-3 é uma proteína envolvida em diversas vias de sinalização celular. Pode ser encontrada em vários tecidos, sendo a sua expressão baixa no coração normal e elevada no coração fibrótico. Entre outros efeitos, é responsável pela proliferação de fibroblastos, promoção da síntese de colagénio, contribuindo para a remodelagem cardíaca que é determinante no desenvolvimento e progressão da insuficiência cardíaca. A insuficiência cardíaca mediada pela Galectina-3 (> 17,8 ng/mL) afeta 30-50% dos doentes com insuficiência cardíaca crónica, apresentando pior prognóstico, com maior taxa de reinternamento a curto prazo e mortalidade. Pensa-se que através da inibição da acção da Galectina-3 ou mesmo através do knock-out genético se possa reverter ou promover um atraso na progressão desta doença. Quando avaliados isoladamente, a Galectina-3 parece ter maior valor prognóstico do que os péptidos natriuréticos, no entanto, quando se combinam, o valor prognóstico é ainda superior. É possível admitir que a Galectina-3, associada ao BNP ou ao NT-proBNP, possa vir a ser considerada no futuro como uma alternativa que permita melhorar o diagnóstico e o prognóstico da insuficiência cardíaca.info:eu-repo/semantics/publishedVersio

Contribution of HFE and HPSE genes and methaemoglobin reductase activity to heart failure

Introduction: Heart failure can be defined as a syndrome caused by a structural anomaly and/or by a committed cardiac function, which leads to an inadequate cardiac output unable to meet the metabolic necessities of the organism. We aim to understand if HFE and HPSE genes as well as methaemoglobin reductase activity, may influence the development of heart failure. Methodology: It was performed a case-control study, in which 252 DNA samples from Portuguese individuals were analysed, 143 derived from subjects with heart failure, and 109 from healthy controls. For HPSE genotyping (rs4693608), we performed endpoint PCR analysis. A multiplex ARMS (Amplification-Refractory Mutation System) assay was used for the simultaneous detection of two HFE polymorphisms (C282Y and H63D). Reductase methaemoglobin activity was determined by spectrophotometric methods. All statistical tests were performed with IBM® SPSS® Statistics 26.0 software. Statistical significance was defined as a p-value < 0.05. Results: Regarding the H63D polymorphism, results show the CG genotype as a risk factor [OR (95% CI) = 2.889 (1.041-8.018); p=0.042]. In what concerns HPSE gene, the GG genotype was found to have a protective effect [OR (95% CI) = 0.435 (0.193-0.982); p=0.045] while the presence of the A allele is a risk factor [OR (95% CI) = 2.297 (1.018-5.179); p=0.045. Considering methaemoglobin reductase, its activity was lower in patients than in healthy controls (p=0.019). Discussion: Intravenous iron supplementation is sometimes considered in heart failure treatment, emphasizing the results presented in the present study. Considering the high prevalence of heart failure in Portugal (400.000 individuals, according to Sociedade Portuguesa de Cardiologia), it is important to identify iron-related markers, since it may allow an earlier and more expert approach, which may provide better prevention and therapeutic strategies for this pathology.N/

Study of the interaction between modulators of iron homeostasis and the ACE gene in heart failure

Introduction: Heart failure (HF) refers to a clinical syndrome composed of a set of symptoms and/or signs that originate from a structural and/or functional cardiac anomaly and that give rise to the inability to pump blood in sufficient quantity, to meet the body's metabolic needs. In the present work, we intend to understand how the interaction between the I/D variation in the ACE gene and possible modulators of iron (Fe) homeostasis influence HF. The modulators under study were: the methemoglobin reductase activity, the Hfe gene and heparanase genes (HPSE) Methodology: A case-control study was carried out with 252 Portuguese people, 143 with HF and 109 healthy controls. To analyze the polymorphism in the HPSE gene (rs4693608) endpoint genotyping (LightCycler480) was performed. To analyze both polymorphisms in the Hfe gene (H63D and C282Y), ARMS Multiplex technique was used. For the analysis of the polymorphism in the ECA gene (rs4646994 - I/D) a regular PCR was performed. Methaemoglobin reductase activity was obtained using spectrophotometric assay. All necessary statistical tests were performed using the IBM® SPSS® Statistics 26.0 software, with values considered significant for p < 0.05. Results: There was an association between HF and: 1) the presence of the D allele of the HFe gene (HH vs HD; p=0.049); 2) the presence of the A allele of the HPSE gene (AA + GA vs GG; p=0.045; 3) lower levels of methemoglobin reductase activity (p=0.019). It was also found that epistasis between the presence of the H or C allele of the Hfe gene and the D allele of the ACE gene are protective in HF (p=0.041 for both). Conclusion: Results of this study highlight the role of iron homeostasis and its interaction with ACE in HF. Iron is an essential component for the proper functioning of mitochondria, which play an important role in providing energy to the heart muscle. Knowledge of the genotype profile of patients, in modulating genes of iron homeostasis in interaction with the ACE gene could be an advantage in the application of a more personalized medicine, allowing preventive counseling and more targeted therapy.info:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19

IntroductionMannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19.MethodsBlood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively.ResultsThe frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p&lt; 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p&lt; 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p&lt; 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed.DiscussionThe results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost