Fernando BERNARDINO MENDES DA SILVA (original) (raw)

Papers by Fernando BERNARDINO MENDES DA SILVA

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Onco

Immune checkpoint inhibition (ICI) has emerged as a therapeutic option for acute myeloid leukemia... more Immune checkpoint inhibition (ICI) has emerged as a therapeutic option for acute myeloid leukemia (AML) for patients that suffer from relapsed or high-risk disease, or patients ineligible for standard therapy. We aimed to study ICI as monotherapy and/or combined therapy (with chemotherapy (QT), for AML patients. The PRISMA statement was used. The literature used comprised clinical trials, randomized controlled trials, and systematic reviews published within the last 7 years. The blockade of CTLA-4 presented a 42% of complete remission within AML. Nivolumab in high-risk AML showed a median recurrence-free survival (RFS) of 8.48 months. The same drug on relapsed hematologic malignancies after allogenic transplantation shows a 1-year OS of 56%. The use of prophylaxis post allogenic transplantation cyclophosphamide (PTCy), following checkpoint inhibition, demonstrated different baseline disease and transplantation characteristics when compared to no-PCTy patients, being 32% and 10%, res...

Introdução Descoberto em 1911 por Frederick Forssman, a expressão do antigénio (Ag) Forssman (Fs)... more Introdução Descoberto em 1911 por Frederick Forssman, a expressão do antigénio (Ag) Forssman (Fs) varia entre espécies, estando raramente presente nos eritrócitos humanos. Em 1987, três famílias inglesas sem qualquer relação entre si, foram identificadas com um fenótipo designado Apae que, mais tarde, foi classificado como o 31º grupo sanguíneo: FORS. Os anticorpos (Ac) anti-Fs têm ocorrência natural em humanos e podem ter implicações transfusionais e de transplante, uma vez que o Ag está presente na superfície de eritrócitos, fluídos corporais e órgãos. Objetivos O principal objetivo deste trabalho foi avaliar a prevalência de Ab anti-Fs e esclarecer o seu impacto na medicina transfusional, classificando o tipo de imunoglobulina (Ig) envolvida. Materiais e Métodos Neste estudo foi utilizada a técnica standard de tubo para avaliar a presença de Ac anti-Fs em amostras de plasma de uma população de dadores Portugueses e classificar as imunoglobulinas envolvidas. Foi utilizada, para a ...

Molecular Biology Reports

Bladder cancer (BC) is the most common cancer of the urinary tract and despite all innovations, r... more Bladder cancer (BC) is the most common cancer of the urinary tract and despite all innovations, remains a major challenge due to high morbidity and mortality. Genomic and epigenetic analyses allowed the discovery of new genes and pathways involved in the pathogenesis and regulation of BC. However, the effect on mortality has been modest and the development of new targets for BC treatment are needed. Recent evidence suggests that cancer cells are under increased stress associated with oncogenic transformation, with changes in metabolic activity and increased generation of reactive oxygen species (ROS). The increased amounts of ROS in cancer cells are associated with stimulation of cellular proliferation, promotion of mutations and genetic instability, as well as alterations in cellular sensitivity to anticancer agents. Since these mechanisms occur in cancer cells, there is a close link between oxidative stress (OS) and BC with implications in prevention, carcinogenesis, prognosis, and treatment. We address the role of OS as an enemy towards BC development, as well as an ally to fight against BC. This review promises to expand our treatment options for BC with OS-based therapies and launches this approach as an opportunity to improve our ability to select patients most likely to respond to personalized therapy.

Esta pesquisa teve como objetivo indicar a possibilidade de verticalização da produção de cacau n... more Esta pesquisa teve como objetivo indicar a possibilidade de verticalização da produção de cacau na Transamazônica, estado do Pará, buscando-se formas de comercialização com maior valor agregado. Assim, a partir de simulações demonstrou-se como a substituição da venda amêndoa por subprodutos da indústria chocolateira (liquor, manteiga e pó de cacau), podem melhorar a receita nesta atividade. Usou-se como metodologia a análise de indicadores econômicos (relação benefício custo, valor presente líquido e taxa interna de retorno), tendo como base o orçamento para implantação de cada uma das fases do processamento industrial, fazendo as comparações, para uma mesma medida (150 toneladas de matéria-prima), aferindo-se o melhor resultado. Complementou-se o estudo com uma análise de sensibilidade, fazendo-se variações positivas nos custos, negativas nas receitas e custo de oportunidade do capital. Os resultados mostraram que existe viabilidade econômica para a utilização de pequenas plantas i...

O Estado do Pará é um dos maiores produtores e exportadores de madeira em tora no País, tendo est... more O Estado do Pará é um dos maiores produtores e exportadores de madeira em tora no País, tendo esta atividade considerável peso na economia estadual. Para melhor dimensionar esta produção regional oriunda da floresta tropical, fez-se necessário averiguar as localidades onde esta produção ocorre. Para isso, empregou-se o Índice de Concentração Normalizado (ICN), conforme proposto originalmente por Crocco et al. (2003) e ampliando por Santana (2005), construído a partir da Análise de Componentes Principais (ACP). O objetivo do trabalho foi identificar os municípios especializados nas atividades florestal e de madeira e mobiliário com potencial para desenvolver Arranjos Produtivos Locais (APL) no Pará. Os resultados indicaram a existência de nove municípios paraenses especializados, simultaneamente, nas duas atividades, podendo resultar em melhor estruturação desses APL para desenvolver localmente o Pará, via Pólos de Desenvolvimento, mediante ações concretas de políticas públicas para ...

O objetivo deste artigo visa desenvolver uma analise do segmento de frigorificos no Estado do Par... more O objetivo deste artigo visa desenvolver uma analise do segmento de frigorificos no Estado do Para, mais especificamente, seu potencial de geracao de emprego e renda, integracao com os elos a montante e a jusante, alem da sua capacidade de gestao e organizacao competitiva. Para subsidiar a referida analise foram coletados dados primarios junto aos frigorificos, complementados por dados do IBGE e da RAIS. Alem da analise quantitativa dos dados, foi empregada a analise baseada em componentes principais (analise fatorial) no intuito de qualificar as informacoes levantadas, assim como, delimitar parâmetros referentes a gestao e a competitividade. Os resultados identificaram uma relacao de mercado classica com os demais segmentos, refletindo um incipiente grau de integracao, alem de problemas de carater ambiental e tecnologico.

Hepatitis C is an infectious disease caused by hepatitis C virus (HCV) with tropism for liver cel... more Hepatitis C is an infectious disease caused by hepatitis C virus (HCV) with tropism for liver cells, causing severe inflammation with many longterm complications. In most cases an asymptomatic chronic infection progresses, leading to cirrhosis 10 to 20 years after infection, and about 10% to 20% of cases evolve into hepatocellular carcinoma after 30 years of infection (1, 2). The average incubation period of this disease is 15 to 90 days knowing that the asymptomatic individual can transmit the virus before the symptomatic phase, with the acute phase of infection by asymptomatic standard (2). Estimates indicate an overall prevalence of HCV range from 2% to 3%, i.e. a value between 123 million and 170 million people infected worldwide, which is considered a worldwide epidemic (3–6). In Portugal epidemiological data indicate that about 15% (100000–140000) of the population are infected with HCV (7). HCV belongs to the gender Hepacivirus in the Flaviviridae family, about 60 nm in diame...

Results The results suggest that in patients with rheumatoid arthritis, there is a tendency to th... more Results The results suggest that in patients with rheumatoid arthritis, there is a tendency to the decrease of the regulatory T cells frequency in peripheral blood, compared to controls. However, it was observed an increased number of mRNA copies of TGF-β also in these cells. Conclusion: the numeric and functional variation of regulatory T cells in the different study groups suggests a contribution to the etiology and pathophysiology of rheumatoid arthritis.

BMC Health Services Research, 2016

Introduction: Continuous blood pressure (BP) monitoring provides important information about the ... more Introduction: Continuous blood pressure (BP) monitoring provides important information about the cardiovascular system condition. Invasive methods are accurate but denote increased risk. Non-invasive methods are safe but less reliable and don ́t provide continuous information. An alternative approach for a continuous, non-invasive measurement of BP is based on changes in pulse transit time (PTT). PTT is defined as the time delay between the R-wave of the electrocardiogram (ECG) and the peak value of the photoplethysmogram (PPG) signal acquired in the patient finger on the same cardiac cycle.

Biomedicines, 2021

Breast Cancer (BC) is the second most frequent cause of cancer death among women worldwide and, a... more Breast Cancer (BC) is the second most frequent cause of cancer death among women worldwide and, although there have been significant advances in BC therapies, a significant percentage of patients develop metastasis and disease recurrence. Since BC was demonstrated to be an immunogenic tumor, immunotherapy has broken through as a significant therapy strategy against BC. Over the years, immunotherapy has improved the survival rate of HER2+ BC patients due to the approval of some monoclonal antibodies (mAbs) such as Trastuzumab, Pertuzumab and, recently, Margetuximab, along with the antibody-drug conjugates (ADC) Trastuzumab-Emtansine (T-DM1) and Trastuzumab Deruxtecan. Immune checkpoint inhibitors (ICI) showed promising efficacy in triple-negative breast cancer (TNBC) treatment, namely Atezolizumab and Pembrolizumab. Despite the success of immunotherapy, some patients do not respond to immunotherapy or those who respond to the treatment relapse or progress. The main causes of these ad...

Onco, 2021

Bladder cancer (BC) is one of the most common cancers in the world. From an early age, it was obs... more Bladder cancer (BC) is one of the most common cancers in the world. From an early age, it was observed that chronic inflammation is associated with conditions favorable to the development of tumors, as well as the tumor microenvironment. Moreover, regulating tumor progression also interferes with the therapy’s response. The interaction between the tumor and the immune system led to the development of new immune therapies, the immune checkpoint inhibitors. Immunotherapy has shown a better safety profile, survival, and tolerance compared to standard chemotherapy. This therapy offers an effective alternative to patients who are ineligible for cisplatin and patients with advanced disease progression after platinum-based therapy. The first immunotherapy approved for BC was intravesical instillation with Bacillus Calmette–Guérin, for tumors at early stages. Later, immunotherapy focused on immune checkpoint inhibitors, namely, anti-programmed cell death protein 1 (PD1), anti-programmed cel...

Biology, 2021

Antitumor therapies based on Cold Atmospheric Plasma (CAP) are an emerging medical field. In this... more Antitumor therapies based on Cold Atmospheric Plasma (CAP) are an emerging medical field. In this work, we evaluated CAP effects on bladder cancer. Two bladder cancer cell lines were used, HT-1376 (stage III) and TCCSUP (stage IV). Cell proliferation assays were performed evaluating metabolic activity (MTT assay) and protein content (SRB assay). Cell viability, cell cycle, and mitochondrial membrane potential (Δψm) were assessed using flow cytometry. Reactive oxygen and nitrogen species (RONS) and reduced glutathione (GSH) were evaluated by fluorescence. The assays were carried out with different CAP exposure times. For both cell lines, we obtained a significant reduction in metabolic activity and protein content. There was a decrease in cell viability, as well as a cell cycle arrest in S phase. The Δψm was significantly reduced. There was an increase in superoxide and nitric oxide and a decrease in peroxide contents, while GSH content did not change. These results were dependent on...

International braz j urol, 2021

Cancer has become increasingly common worldwide, being the second leading cause of death and an i... more Cancer has become increasingly common worldwide, being the second leading cause of death and an important barrier to increasing life expectancy in all countries in the XXI century (1). The reasons behind these statistic numbers are complex, but they are associated with aging, population growth and the increased prevalence of risk factors (1). Kidney cancers are ranked 14th in the World among the ones with the highest incidence (1-3). The renal cell carcinoma (RCC) represents 80-85% of all kidney cancers, and it is the most common and the third most diagnosed urogenital malignancy (2). It occurs usually in the sixth and seventh decades and most commonly in men (4). The incidence varies globally, with the highest rates in developed countries such as North America and Europe and the lowest rates in Asia and Africa (3). Due to the high incidence and mortality levels of RCC, it is important to find the most appropriate therapeutic strategies, and also to analyse the influence of risk factors. Age (over 85 years), gender (male), smoking habit, analgesics use, obesity, lack of physical activity, exposure to industrial or environmental agents and comorbidities such as hypertension, urinary stones, diabetes, liver and chronic kidney diseases, are known factors related to the incidence of RCC (5). Currently, most of the RCC cases have been diagnosed through computed tomography or abdominal ultrasonography, in asymptomatic subjects (2). RCC is divided into multiple subtypes according to its histological characteristics. The most common subtype is clear cell renal cell carcinoma (ccRCC) (2, 6), responsible for approximately 80% of all cases of RCC. The other major subtypes include papillary (12%), chromophobe (4%), oncocytoma (4%) and collecting duct (<1%). Familial RCC is often seen in the context of an inherited syndrome, such as Von Hippel-Lindau (VHL) syndrome and Birt-Hogg-Dubé syndrome (4, 6). RCC’s treatment can be conducted following two pathways, namely: local treatment with nephrectomy or other ablative strategies (in small masses and older patients), or through systemic therapy; based on the disease staging. In most cases of localized renal cancer, partial or total nephrectomy can be used to eradicate the disease (2). However, the post-operative recurrence rate can be of 20-40% in the first 5 years and 5-10% in late recurrence (4). In cases of recurrence and progression after initial surgical treatment during follow-up or in cases of advanced renal cell carcinoma (aRCC) at presentation, The role of immunotherapy in advanced renal cell carcinoma _______________________________________________

International Journal of Cardiovascular Sciences, 2019

Nutrients, 2020

Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Obesity and hyperlip... more Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Obesity and hyperlipidemia, fueled by unhealthy food habits, are risk factors to glomerular filtration rate (GFR) decline and DN progression. Several studies recommend that diabetic patients should be screened early (in prediabetes) for kidney disease, in order to prevent advanced stages, for whom the current interventions are clearly inefficient. This ambition greatly depends on the existence of accurate early biomarkers and novel molecular targets, which only may arise with a more thorough knowledge of disease pathophysiology. We used a rat model of prediabetes induced by 23 weeks of high-sugar/high-fat (HSuHF) diet to characterize the phenotype of early renal dysfunction and injury. When compared with the control animals, HSuHF-treated rats displayed a metabolic phenotype compatible with obese prediabetes, displaying impaired glucose tolerance and insulin sensitivity, along with hypertriglyceridemia, and...

Revista de Economia e Agronegócio, 2015

O Estado do Pará é o terceiro no ranking das exportações e concentra 75% damadeira extraída de fl... more O Estado do Pará é o terceiro no ranking das exportações e concentra 75% damadeira extraída de floresta nativa no país. Da madeira extraída na Amazônia Legal, 64%destinam-se ao mercado nacional e 36%, à exportação. O objetivo deste trabalho foiidentificar e mapear, por meio do Índice de Concentração Normalizado (ICN), noperíodo de 1998 a 2004, os municípios especializados nas atividades florestais e demadeira e mobiliário, com potencial para se transformar em Arranjos Produtivos Locais(APL). Os resultados indicaram nove municípios especializados, simultaneamente, nasduas atividades, o que sinaliza o desenho de políticas públicas destinadas a apoiar odesenvolvimento local sustentável a partir desses APL de base florestal.

Journal of Immunological Methods, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Medical Research and Innovations, 2017

Carbohydrate histo-blood groups in man include the AB0, H, I, Lewis, P 1 P K , and GLOB systems i... more Carbohydrate histo-blood groups in man include the AB0, H, I, Lewis, P 1 P K , and GLOB systems in which glycoproteins and glycolipids carry immunodominant terminal sugars, defining polymorphic antigens (Ag). Blood group compatibility is one of the most important procedures to correctly transfuse ensuring quality and ensuring patient safety. Forssman glycosphingolipid (FORS) Ag blood group system was demonstrated biochemically on the red blood cells of two blood donors from different families with the A pae phenotype, first described in 1987. Afterwards, a group of Swedish researchers found several criteria that make it up the FORS blood group becomes an independent blood group. In 2012, International Society of Blood Transfusion concluded that subgroup A pae should be abolished and a new histo-blood group should be created. Several antigens, including Fs (Forssman), may act as receptors for certain pathogens, emerging naturally antibody (Ab) against various microorganisms, making these Ab a barrier in transfusion/transplantation medicine. It is known that the Fs synthesis in uroepithelial cells could make such individuals more susceptible to infection by E.coli and the expression of Fs Ag has been reported in cancer cells, being a cancer epitope of interest. Therefore, it's extremely important the study of this histo-blood group, considering all its potentialities, contributing to a better characterization of this histo-blood group.

Blood transfusion = Trasfusione del sangue, Feb 24, 2016

In 1987, three unrelated English families were reported with a putative blood subgroup called Apa... more In 1987, three unrelated English families were reported with a putative blood subgroup called Apae. Swedish researchers later found evidence leading to abolishment of the Apae subgroup and establishment instead of the FORS blood group system (System 31 - ISBT, 2012). It is important to know the prevalence of antibodies in order to make the best decisions in transfusion medicine. Cells expressing the Forssman saccharide, such as sheep erythrocytes, are needed to detect the anti-Forssman antibody. The aim of this study was to define the prevalence of human anti-Forssman antibody. Plasma samples from 800 individuals were studied. Sheep erythrocytes or Forssman "kodecytes" were mixed with the plasma samples using the tube technique. Plasma from an Apae individual was used as a negative control and monoclonal anti-Forssman antibody (M1/22.25.8HL cell line supernatant) was used as the positive control. Of the 800 individuals tested, one was negative for the presence of anti-Fors...