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felipe chaves

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Felipe J Chaves

INCLIVA

Medical University of Silesia

Kristóf Hirschberg

Lahouaria Hadri

Johannes Waltenberger

University of Münster

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Papers by felipe chaves

DOI: 10.1161/CIRCGENETICS.113.000305 1 Genetic Variants in CCNB1 Associated with Differential Gene Transcription and Risk of Coronary In-Stent Restenosis Running title: Silvestre-Roig et al.; SNPs in CCNB1 and restenosis risk

Background-The development of diagnostic tools to assess restenosis risk after stent deployment m... more Background-The development of diagnostic tools to assess restenosis risk after stent deployment may enable the intervention to be tailored to the individual patient, for example, by targeting the use of drug-eluting stent to highrisk patients, with the goal of improving safety and reducing costs. The CCNB1 gene (encoding cyclin B1) positively regulates cell proliferation, a key component of in-stent restenosis. Therefore, we hypothesized that single-nucleotide polymorphisms in CCNB1 may serve as useful tools in risk stratification for in-stent restenosis. Methods and Results-We identified 3 single-nucleotide polymorphisms in CCNB1 associated with increased restenosis risk in a cohort of 284 patients undergoing coronary angioplasty and stent placement (rs350099: TT versus CC+TC; odds ratio [OR], 1.

Srebf2 Locus Overexpression Reduces Body Weight, Total Cholesterol and Glucose Levels in Mice Fed with Two Different Diets

Nutrients, 2020

Macronutrients represent risk factors for hyperlipidemia or diabetes. Lipid alterations and type ... more Macronutrients represent risk factors for hyperlipidemia or diabetes. Lipid alterations and type 2 diabetes mellitus are global health problems. Overexpression of sterol regulatory element-binding factor (Srebf2) in transgenic animals is linked to elevated cholesterol levels and diabetes development. We investigated the impact of increased Srebf2 locus expression and the effects of control and high-fat, high-sucrose (HFHS) diets on body weight, glucose and lipid metabolisms in transgenic mice (S-mice). Wild type (WT) and S-mice were fed with both diets for 16 weeks. Plasma glucose, insulin and lipids were assessed (n = 25). Immunostainings were performed in liver, pancreas and fat (N = 10). Expression of Ldlr and Hmgcr in liver was performed by RT-PCR (N = 8). Control diet: S-mice showed reduced weight, insulin, total and HDL cholesterol and triglycerides (TG). HFHS diet widened differences in weight, total and HDL cholesterol, insulin and HOMA index but increased TG in S-mice. In S...

Estudo Da Obtenção De Materiais Cerâmicos Provenientes Da Adição De Lodo De Eta À Argila: Caracterização Mecânica

Nos processos de tratamento de aguas, em sua grande maioria realizados nas estacoes de tratamento... more Nos processos de tratamento de aguas, em sua grande maioria realizados nas estacoes de tratamento de agua (ETAs), tem-se a geracao em grande quantidade dos residuos umidos denominados “lodo de ETA”. Este artigo visa fazer uma breve explanacao sobre o lodo, argila e materiais cerâmicos, seguida do detalhamento da metodologia sobre a preparacao de amostras e das analises desenvolvidas de massa especifica e porosidade aparentes, absorcao de agua e analise textural. As amostras foram produzidas variando as proporcoes de 100/0 ate 10/90, referindo-se a porcentagem de argila e lodo em massa, respectivamente. Foi possivel constatar que a adicao de lodo provocou diminuicao da massa especifica aparente das amostras, com aumento dos indices de absorcao de agua e porosidade aparente. Mesmo com este comportamento, os materiais desenvolvidos apresentaram indices de absorcao de agua dentro dos limites estabelecidos pela NBR 15270-1, das proporcoes de 100/0 ate 30/70. Por meio da analise textural,...

Thyroid hormone resistance index and mortality in euthyroid subjects: [email protected] study

European Journal of Endocrinology, 2021

Objective It has been proposed that a mild form of acquired resistance to thyroid hormone may occ... more Objective It has been proposed that a mild form of acquired resistance to thyroid hormone may occur in the general population. Its clinical significance remains largely unknown. The objective of the study was to explore whether a newly described thyroid hormone resistance index is associated with the risk of mortality in a sample of community-dwelling euthyroid subjects representative of the adult population of Spain. Design Longitudinal observational study including 3750 individuals, free of thyroid disease, TPO antibodies-negative (<50 IU/mL) and with TSH levels within the euthyroid range (≥0.5 and ≤5.0 mUI/mL) participating in the nationwide study [email protected] (2008–2010). Methods We used the Thyroid Feedback Quantile-based Index (TFQI) as a marker of resistance to thyroid hormone. The study population was grouped into categories according to their TFQI values at baseline. Fatal events were ascertained from the national death registry (end of follow-up December 2016). Results A t...

Evidenciação do Conteúdo Ambiental e Social nas Demonstrações Contábeis Publicadas na BM no período de 2001 a 2007

Sociedade, Contabilidade e Gestão, 2010

Este artigo tem como objetivo quantificar as ocorrências de expressões ambientais e sociais, por ... more Este artigo tem como objetivo quantificar as ocorrências de expressões ambientais e sociais, por meio da análise das Demonstrações Financeiras Padronizadas (DFP), dos Informativos Anuais (IAN) e das Demonstrações Contábeis e Relatórios Administrativos, no período de 2001 a 2007, das Companhias Abertas atuantes no Brasil, submetidas à Comissão de Valores Mobiliários (CVM), cadastradas na BM&FBOVESPA. Para a execução desse trabalho foram utilizadas 105 empresas dos setores de Bens Industriais; Materiais Básicos; e Petróleo, Gás, e Biocombustíveis. O resultado da pesquisa mostrou que ainda temos baixos índices de evidenciação das expressões ambientais e sociais, apesar de, em média, 49% das empresas analisadas possuirem um Sistema de Gestão Ambiental (SGA). Um ponto positivo foi a constatação que essas evidenciações, ao passar dos anos, estão evoluindo de forma crescente.

Optimization of small RNA library preparation protocol from human urinary exosomes

Journal of Translational Medicine, 2020

Background Sequencing of miRNAs isolated from exosomes has great potential to identify novel dise... more Background Sequencing of miRNAs isolated from exosomes has great potential to identify novel disease biomarkers, but exosomes have low amount of RNA, hindering adequate analysis and quantification. Here, we have assessed several steps in developing an optimized small RNA (sRNA) library preparation protocol for next-generation sequencing (NGS) miRNA analysis from urinary exosomes. Methods A total of 24 urinary exosome samples from donors were included in this study. RNA was extracted by column-based methods. The quality of extracted RNA was assessed by spectrophotometric quantification and Bioanalyzer software analysis. All libraries were prepared using the CleanTag small RNA library preparation protocol and the effect of our additional modifications on adapter-dimer presence, sequencing data and tagged small RNA library population was also analyzed. Results Our results show that good quality sequencing libraries can be prepared following our optimized small RNA library preparation p...

Dairy Product Consumption and Metabolic Diseases in the [email protected] Study

Nutrients, 2019

To date it is not clear what the role of dairy products is in metabolic diseases like diabetes, o... more To date it is not clear what the role of dairy products is in metabolic diseases like diabetes, obesity, and hypertension. Therefore, the aim of this study is to test the association between dairy product consumption and those pathologies. A cross-sectional study was conducted with 5081 adults included in the [email protected] study, from 100 health centers around Spain. Food frequency questionnaires were carried out concerning consumption habits, which included dairy product consumption. Logistic regression models were used for the association analyses between the variables controlling confounding variables. Women had a higher consumption of milk, cheese, or yogurt than men (p < 0.0001), but men consumed more sugar dairy products (p < 0.001). People who live in the North of Spain consume more dairy products than those who live in the East. Dairy product consumption was inversely associated with the presence of hypertension regardless of age, sex, geographical region, and body mass in...

Síndrome medular central parcial associada à plexopatia braquial – anestesia suspensa bilateral e déficit motor em território radicular unilateral

XXXII Congresso Brasileiro de Neurocirurgia, 2018

Diagnóstico diferencial entre glioma de alto grau e AVEI em border zone interna

XXXII Congresso Brasileiro de Neurocirurgia, 2018

Fratura-avulsão de côndilo occipital unilateral com luxação do côndilo contralateral e evolução clínica favorável

XXXII Congresso Brasileiro de Neurocirurgia, 2018

AVEH em trombose venosa encefálica concomitante à TVP – deficiência de proteína S funcional e uso de anticoncepcionais orais resultando em trombogênese sistêmica

XXXII Congresso Brasileiro de Neurocirurgia, 2018

Arsenic exposure, diabetes-related genes and diabetes prevalence in a general population from Spain

Environmental Pollution, 2018

Inorganic arsenic exposure may be associated with diabetes, but the evidence at low-moderate leve... more Inorganic arsenic exposure may be associated with diabetes, but the evidence at low-moderate levels is not sufficient. Polymorphisms in diabetes-related genes have been involved in diabetes risk. We evaluated the association of inorganic arsenic exposure on diabetes in the Hortega Study, a representative sample of a general population from Valladolid, Spain. Total urine arsenic was measured in 1451 adults. Urine arsenic speciation was available in 295 randomly selected participants. To account for the confounding introduced by non-toxic seafood arsenicals, we designed a multiple imputation model to predict the missing arsenobetaine levels. The prevalence of diabetes was 8.3%. The geometric mean of total arsenic was 66.0 mg/g. The adjusted odds ratios (95% confidence interval) for diabetes comparing the highest with the lowest tertile of total arsenic were 1.76 (1.01, 3.09) and 2.14 (1.47, 3.11) before and after arsenobetaine adjustment, respectively. Polymorphisms in several genes including IL8RA, TXN, NR3C2, COX5A and GCLC showed suggestive differential associations of urine total arsenic with diabetes. The findings support the role of arsenic on diabetes and the importance of controlling for seafood arsenicals in populations with high seafood intake. Suggestive arsenic-gene interactions require confirmation in larger studies.

Urinary exosome miR-146a is a potential marker of albuminuria in essential hypertension

Journal of translational medicine, Jan 14, 2018

There is increasing interest in using extracellular vesicle-derived microRNAs (miRNAs) as biomark... more There is increasing interest in using extracellular vesicle-derived microRNAs (miRNAs) as biomarkers in renal dysfunction and injury. Preliminary evidence indicates that miRNAs regulate the progression of glomerular disease. Indeed, exosomes from the renal system have provided novel evidence in the clinical setting of albuminuria. Thus, the aim of this study was to quantify the urinary miRNAs present in exosome and microvesicles (MVs), and to assess their association with the presence of increased urinary albumin excretion in essential hypertension. Exosomes were collected from urine specimens from a cohort of hypertensive patients with (n = 24) or without albuminuria (n = 28), and from 20 healthy volunteers as a control group. Urinary exosomes were phenotyped by Western blot, tunable resistive pulse sensing, and electronic microscopy. Expression of miR-146a and miR-335* was analysed by qRT-PCR and any associations between albuminuria and exosomal miRNAs were analysed. Urinary miRNA...

Urinary levels of sirtuin-1 associated with disease activity in lupus nephritis

Clinical science (London, England : 1979), Jan 15, 2018

Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratif... more Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of the present study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in remission and healthy controls. Association with lupus activity and renal histological features was also analyzed. A significant increase in SIRT1 mRNA levels in patients with active LN was observed compared with those in remission (=0.02) or healthy controls (=0.009). In addition, SIRT-1 protein levels were also augmented in LN group than remission (=0.029...

Immune-unreactive urinary albumin as a predictor of cardiovascular events: the Hortega Study

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 16, 2018

We aimed to determine if immune-unreactive albumin excretion (IURAE) is associated with cardiovas... more We aimed to determine if immune-unreactive albumin excretion (IURAE) is associated with cardiovascular (CV) events in a representative sample of a general population from Spain. We included 1297 subjects (mean age ± standard error 48.0 ± 0.2 years, 48% females), who participated in the Hortega Follow-Up Study. The primary endpoint was incidence of fatal and non-fatal CV events. Urinary albumin excretion (UAE) was measured in spot voided urine, frozen at -80°C, by immunonephelometry [immune-reactive albumin excretion (IRAE)] and by high-performance liquid chromatography (HPLC) [total albumin excretion (AE)]. IURAE was calculated as the difference between HPLC measurements and IRAE. We estimated fully adjusted hazard ratios (HRs) of CV incidence by Cox regression for IRAE, IURAE and total AE. After an average at-risk follow-up of 13 years, we observed 172 CV events. urinary albumin to creatinine ratio (UACR) of ≥30 mg/g assessed by IRAE, IURAE or total AE concentrations was observed i...

Iron deficiency is associated with Hypothyroxinemia and Hypotriiodothyroninemia in the Spanish general adult population: [email protected] study

Scientific reports, Jan 26, 2018

Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, ... more Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, however replication in wide samples of the general adult population has not been performed. We studied 3846 individuals free of thyroid disease, participants in a national, cross sectional, population based study representative of the Spanish adult population. Thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) were analyzed by electrochemiluminescence (E170, Roche Diagnostics). Serum ferritin was analyzed by immunochemiluminescence (Architect I2000, Abbott Laboratories). As ferritin levels decreased (>100, 30-100, 15-30, <15 µg/L) the adjusted mean concentrations of FT4 (p < 0.001) and FT3 (p < 0.001) descended, whereas TSH levels remained unchanged (p = 0.451). In multivariate logistic regression models adjusted for age, sex, UI, BMI and smoking status, subjects with ferritin levels <30 µg/L were more likely to present hypothyroxinemia ...

Urinary podocyte-associated molecules and albuminuria in hypertension

Journal of hypertension, Jan 19, 2018

Hypertension-induced podocyte damage and the relationship with UAE is analyzed in diabetic and no... more Hypertension-induced podocyte damage and the relationship with UAE is analyzed in diabetic and nondiabetic participants. Sixty-four hypertensive patients, 30 diabetics, with glomerular filtration rate (eGFR) greater than 60 ml/min per 1.73 m were included. Urinary albumin excretion was measured in morning urine using a nephelometric immunoassay and expressed as albumin/creatinine ratio. Urinary pellets were obtained from fresh urine and mRNA was assessed by real-time quantitative PCR. Likewise, protein podocyte-specific molecules were measured by western blot using specific antibodies. Fourteen nondiabetics and 20 diabetics had increased UAE greater than 30 mg/g. In individuals with increased EUA, the mRNA expression of nephrin and CD2AP was low in diabetics, whereas only nephrin mRNA in nondiabetics. No differences were observed in podocalyxin and aquaporin-1 mRNA levels. Concerning the protein values, in both nondiabetic and diabetic patients, nephrin, CD2AP and podocalyxin were i...

Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study

BMJ open, Jan 15, 2017

To investigate the association between IL18RAP and body mass index (BMI) and obesity and to verif... more To investigate the association between IL18RAP and body mass index (BMI) and obesity and to verify the effect of a polymorphism in the microRNA136 (MIR136) IL18RAP binding region. We analysed samples from two Spanish cross-sectional studies, VALCAR (Spanish Mediterranean coast) and Hortega (Spanish centre). These studies aimed at analysing cardiovascular risk and development of cardiovascular disease in the general population. Both populations correspond to regions with different characteristics. Five IL18RAP single nucleotide polymorphisms were selected using the SYSNPs web tool and analysed by oligonucleotide ligation assay (SNPlex). For the MIR136 functional study, cells were transfected with plasmids containing different rs7559479 polymorphism alleles and analysed by luciferase reporter assays. 1970 individuals (Caucasian, both genders): VALCAR (468) and Hortega (1502). rs2293225, rs2272127 and rs7559479 showed the following associations: rs7559479 G allele correlated with a hig...

mRNA expression profiles obtained from microdissected pancreatic cancer cells can predict patient survival

Oncotarget, 2017

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating malignancies i... more Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating malignancies in developed countries because of its very poor prognosis and high mortality rates. By the time PDAC is usually diagnosed only 20-25% of patients are candidates for surgery, and the rate of survival for this cancer is low even when a patient with PDAC does undergo surgery. Lymph node invasion is an extremely bad prognosis factor for this disease. Methods: We analyzed the mRNA expression profile in 30 PDAC samples from patients with resectable local disease (stages I and II). Neoplastic cells were isolated by laser-microdissection in order to avoid sample 'contamination' by non-tumor cells. Due to important differences in the prognoses of PDAC patients with and without lymph node involvement (stage IIB and stages I-IIA, respectively), we also analyzed the association between the mRNA expression profiles from these groups of patients and their survival. Results: We identified expression profiles associated with patient survival in the whole patient cohort and in each group (stage IIB samples or stage I-IIA samples). Our results indicate that survival-associated genes are different in the groups with and without affected lymph nodes. Survival curves indicate that these expression profiles can help physicians to improve the prognostic classification of patients based on these profiles.

Antioxidant enzymes in lymphocites from essential hypertension patients

American Journal of Hypertension, 2002

Hypoxia increased LDH release by 4 folds. Exposure to ET-1 (0.1 M) before hypoxia resulted in a 6... more Hypoxia increased LDH release by 4 folds. Exposure to ET-1 (0.1 M) before hypoxia resulted in a 6-fold increase in LDH release (pϽ0.05 vs hypoxia alone). Pretreatment with BQ-123 before hypoxia significantly attenuated LDH release. Morphological assays revealed a severe cytotoxic effect induced by ET-1. Pretreatment with BQ-123 (5 M) prevented the cytotoxic effects. The results were confirmed by electron microscopy. Exposure of myocytes to ET-1 (10-100 nM) caused an increase in the concentration of intracellular free Ca2ϩ in a concentration-dependent manner. The effect was completely inhibited by pretreatment with the ET A antagonist BQ-123 at a concentration of 5 M. Conclusions: ET-1 augments cytotoxic damage in cardiac cells 24 h after exposure to simulated hypoxia. The effect is mediated through activation of the ET A receptor.

DOI: 10.1161/CIRCGENETICS.113.000305 1 Genetic Variants in CCNB1 Associated with Differential Gene Transcription and Risk of Coronary In-Stent Restenosis Running title: Silvestre-Roig et al.; SNPs in CCNB1 and restenosis risk

Background-The development of diagnostic tools to assess restenosis risk after stent deployment m... more Background-The development of diagnostic tools to assess restenosis risk after stent deployment may enable the intervention to be tailored to the individual patient, for example, by targeting the use of drug-eluting stent to highrisk patients, with the goal of improving safety and reducing costs. The CCNB1 gene (encoding cyclin B1) positively regulates cell proliferation, a key component of in-stent restenosis. Therefore, we hypothesized that single-nucleotide polymorphisms in CCNB1 may serve as useful tools in risk stratification for in-stent restenosis. Methods and Results-We identified 3 single-nucleotide polymorphisms in CCNB1 associated with increased restenosis risk in a cohort of 284 patients undergoing coronary angioplasty and stent placement (rs350099: TT versus CC+TC; odds ratio [OR], 1.

Srebf2 Locus Overexpression Reduces Body Weight, Total Cholesterol and Glucose Levels in Mice Fed with Two Different Diets

Nutrients, 2020

Macronutrients represent risk factors for hyperlipidemia or diabetes. Lipid alterations and type ... more Macronutrients represent risk factors for hyperlipidemia or diabetes. Lipid alterations and type 2 diabetes mellitus are global health problems. Overexpression of sterol regulatory element-binding factor (Srebf2) in transgenic animals is linked to elevated cholesterol levels and diabetes development. We investigated the impact of increased Srebf2 locus expression and the effects of control and high-fat, high-sucrose (HFHS) diets on body weight, glucose and lipid metabolisms in transgenic mice (S-mice). Wild type (WT) and S-mice were fed with both diets for 16 weeks. Plasma glucose, insulin and lipids were assessed (n = 25). Immunostainings were performed in liver, pancreas and fat (N = 10). Expression of Ldlr and Hmgcr in liver was performed by RT-PCR (N = 8). Control diet: S-mice showed reduced weight, insulin, total and HDL cholesterol and triglycerides (TG). HFHS diet widened differences in weight, total and HDL cholesterol, insulin and HOMA index but increased TG in S-mice. In S...

Estudo Da Obtenção De Materiais Cerâmicos Provenientes Da Adição De Lodo De Eta À Argila: Caracterização Mecânica

Nos processos de tratamento de aguas, em sua grande maioria realizados nas estacoes de tratamento... more Nos processos de tratamento de aguas, em sua grande maioria realizados nas estacoes de tratamento de agua (ETAs), tem-se a geracao em grande quantidade dos residuos umidos denominados “lodo de ETA”. Este artigo visa fazer uma breve explanacao sobre o lodo, argila e materiais cerâmicos, seguida do detalhamento da metodologia sobre a preparacao de amostras e das analises desenvolvidas de massa especifica e porosidade aparentes, absorcao de agua e analise textural. As amostras foram produzidas variando as proporcoes de 100/0 ate 10/90, referindo-se a porcentagem de argila e lodo em massa, respectivamente. Foi possivel constatar que a adicao de lodo provocou diminuicao da massa especifica aparente das amostras, com aumento dos indices de absorcao de agua e porosidade aparente. Mesmo com este comportamento, os materiais desenvolvidos apresentaram indices de absorcao de agua dentro dos limites estabelecidos pela NBR 15270-1, das proporcoes de 100/0 ate 30/70. Por meio da analise textural,...

Thyroid hormone resistance index and mortality in euthyroid subjects: [email protected] study

European Journal of Endocrinology, 2021

Objective It has been proposed that a mild form of acquired resistance to thyroid hormone may occ... more Objective It has been proposed that a mild form of acquired resistance to thyroid hormone may occur in the general population. Its clinical significance remains largely unknown. The objective of the study was to explore whether a newly described thyroid hormone resistance index is associated with the risk of mortality in a sample of community-dwelling euthyroid subjects representative of the adult population of Spain. Design Longitudinal observational study including 3750 individuals, free of thyroid disease, TPO antibodies-negative (<50 IU/mL) and with TSH levels within the euthyroid range (≥0.5 and ≤5.0 mUI/mL) participating in the nationwide study [email protected] (2008–2010). Methods We used the Thyroid Feedback Quantile-based Index (TFQI) as a marker of resistance to thyroid hormone. The study population was grouped into categories according to their TFQI values at baseline. Fatal events were ascertained from the national death registry (end of follow-up December 2016). Results A t...

Evidenciação do Conteúdo Ambiental e Social nas Demonstrações Contábeis Publicadas na BM no período de 2001 a 2007

Sociedade, Contabilidade e Gestão, 2010

Este artigo tem como objetivo quantificar as ocorrências de expressões ambientais e sociais, por ... more Este artigo tem como objetivo quantificar as ocorrências de expressões ambientais e sociais, por meio da análise das Demonstrações Financeiras Padronizadas (DFP), dos Informativos Anuais (IAN) e das Demonstrações Contábeis e Relatórios Administrativos, no período de 2001 a 2007, das Companhias Abertas atuantes no Brasil, submetidas à Comissão de Valores Mobiliários (CVM), cadastradas na BM&FBOVESPA. Para a execução desse trabalho foram utilizadas 105 empresas dos setores de Bens Industriais; Materiais Básicos; e Petróleo, Gás, e Biocombustíveis. O resultado da pesquisa mostrou que ainda temos baixos índices de evidenciação das expressões ambientais e sociais, apesar de, em média, 49% das empresas analisadas possuirem um Sistema de Gestão Ambiental (SGA). Um ponto positivo foi a constatação que essas evidenciações, ao passar dos anos, estão evoluindo de forma crescente.

Optimization of small RNA library preparation protocol from human urinary exosomes

Journal of Translational Medicine, 2020

Background Sequencing of miRNAs isolated from exosomes has great potential to identify novel dise... more Background Sequencing of miRNAs isolated from exosomes has great potential to identify novel disease biomarkers, but exosomes have low amount of RNA, hindering adequate analysis and quantification. Here, we have assessed several steps in developing an optimized small RNA (sRNA) library preparation protocol for next-generation sequencing (NGS) miRNA analysis from urinary exosomes. Methods A total of 24 urinary exosome samples from donors were included in this study. RNA was extracted by column-based methods. The quality of extracted RNA was assessed by spectrophotometric quantification and Bioanalyzer software analysis. All libraries were prepared using the CleanTag small RNA library preparation protocol and the effect of our additional modifications on adapter-dimer presence, sequencing data and tagged small RNA library population was also analyzed. Results Our results show that good quality sequencing libraries can be prepared following our optimized small RNA library preparation p...

Dairy Product Consumption and Metabolic Diseases in the [email protected] Study

Nutrients, 2019

To date it is not clear what the role of dairy products is in metabolic diseases like diabetes, o... more To date it is not clear what the role of dairy products is in metabolic diseases like diabetes, obesity, and hypertension. Therefore, the aim of this study is to test the association between dairy product consumption and those pathologies. A cross-sectional study was conducted with 5081 adults included in the [email protected] study, from 100 health centers around Spain. Food frequency questionnaires were carried out concerning consumption habits, which included dairy product consumption. Logistic regression models were used for the association analyses between the variables controlling confounding variables. Women had a higher consumption of milk, cheese, or yogurt than men (p < 0.0001), but men consumed more sugar dairy products (p < 0.001). People who live in the North of Spain consume more dairy products than those who live in the East. Dairy product consumption was inversely associated with the presence of hypertension regardless of age, sex, geographical region, and body mass in...

Síndrome medular central parcial associada à plexopatia braquial – anestesia suspensa bilateral e déficit motor em território radicular unilateral

XXXII Congresso Brasileiro de Neurocirurgia, 2018

Diagnóstico diferencial entre glioma de alto grau e AVEI em border zone interna

XXXII Congresso Brasileiro de Neurocirurgia, 2018

Fratura-avulsão de côndilo occipital unilateral com luxação do côndilo contralateral e evolução clínica favorável

XXXII Congresso Brasileiro de Neurocirurgia, 2018

AVEH em trombose venosa encefálica concomitante à TVP – deficiência de proteína S funcional e uso de anticoncepcionais orais resultando em trombogênese sistêmica

XXXII Congresso Brasileiro de Neurocirurgia, 2018

Arsenic exposure, diabetes-related genes and diabetes prevalence in a general population from Spain

Environmental Pollution, 2018

Inorganic arsenic exposure may be associated with diabetes, but the evidence at low-moderate leve... more Inorganic arsenic exposure may be associated with diabetes, but the evidence at low-moderate levels is not sufficient. Polymorphisms in diabetes-related genes have been involved in diabetes risk. We evaluated the association of inorganic arsenic exposure on diabetes in the Hortega Study, a representative sample of a general population from Valladolid, Spain. Total urine arsenic was measured in 1451 adults. Urine arsenic speciation was available in 295 randomly selected participants. To account for the confounding introduced by non-toxic seafood arsenicals, we designed a multiple imputation model to predict the missing arsenobetaine levels. The prevalence of diabetes was 8.3%. The geometric mean of total arsenic was 66.0 mg/g. The adjusted odds ratios (95% confidence interval) for diabetes comparing the highest with the lowest tertile of total arsenic were 1.76 (1.01, 3.09) and 2.14 (1.47, 3.11) before and after arsenobetaine adjustment, respectively. Polymorphisms in several genes including IL8RA, TXN, NR3C2, COX5A and GCLC showed suggestive differential associations of urine total arsenic with diabetes. The findings support the role of arsenic on diabetes and the importance of controlling for seafood arsenicals in populations with high seafood intake. Suggestive arsenic-gene interactions require confirmation in larger studies.

Urinary exosome miR-146a is a potential marker of albuminuria in essential hypertension

Journal of translational medicine, Jan 14, 2018

There is increasing interest in using extracellular vesicle-derived microRNAs (miRNAs) as biomark... more There is increasing interest in using extracellular vesicle-derived microRNAs (miRNAs) as biomarkers in renal dysfunction and injury. Preliminary evidence indicates that miRNAs regulate the progression of glomerular disease. Indeed, exosomes from the renal system have provided novel evidence in the clinical setting of albuminuria. Thus, the aim of this study was to quantify the urinary miRNAs present in exosome and microvesicles (MVs), and to assess their association with the presence of increased urinary albumin excretion in essential hypertension. Exosomes were collected from urine specimens from a cohort of hypertensive patients with (n = 24) or without albuminuria (n = 28), and from 20 healthy volunteers as a control group. Urinary exosomes were phenotyped by Western blot, tunable resistive pulse sensing, and electronic microscopy. Expression of miR-146a and miR-335* was analysed by qRT-PCR and any associations between albuminuria and exosomal miRNAs were analysed. Urinary miRNA...

Urinary levels of sirtuin-1 associated with disease activity in lupus nephritis

Clinical science (London, England : 1979), Jan 15, 2018

Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratif... more Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of the present study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in remission and healthy controls. Association with lupus activity and renal histological features was also analyzed. A significant increase in SIRT1 mRNA levels in patients with active LN was observed compared with those in remission (=0.02) or healthy controls (=0.009). In addition, SIRT-1 protein levels were also augmented in LN group than remission (=0.029...

Immune-unreactive urinary albumin as a predictor of cardiovascular events: the Hortega Study

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 16, 2018

We aimed to determine if immune-unreactive albumin excretion (IURAE) is associated with cardiovas... more We aimed to determine if immune-unreactive albumin excretion (IURAE) is associated with cardiovascular (CV) events in a representative sample of a general population from Spain. We included 1297 subjects (mean age ± standard error 48.0 ± 0.2 years, 48% females), who participated in the Hortega Follow-Up Study. The primary endpoint was incidence of fatal and non-fatal CV events. Urinary albumin excretion (UAE) was measured in spot voided urine, frozen at -80°C, by immunonephelometry [immune-reactive albumin excretion (IRAE)] and by high-performance liquid chromatography (HPLC) [total albumin excretion (AE)]. IURAE was calculated as the difference between HPLC measurements and IRAE. We estimated fully adjusted hazard ratios (HRs) of CV incidence by Cox regression for IRAE, IURAE and total AE. After an average at-risk follow-up of 13 years, we observed 172 CV events. urinary albumin to creatinine ratio (UACR) of ≥30 mg/g assessed by IRAE, IURAE or total AE concentrations was observed i...

Iron deficiency is associated with Hypothyroxinemia and Hypotriiodothyroninemia in the Spanish general adult population: [email protected] study

Scientific reports, Jan 26, 2018

Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, ... more Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, however replication in wide samples of the general adult population has not been performed. We studied 3846 individuals free of thyroid disease, participants in a national, cross sectional, population based study representative of the Spanish adult population. Thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) were analyzed by electrochemiluminescence (E170, Roche Diagnostics). Serum ferritin was analyzed by immunochemiluminescence (Architect I2000, Abbott Laboratories). As ferritin levels decreased (>100, 30-100, 15-30, <15 µg/L) the adjusted mean concentrations of FT4 (p < 0.001) and FT3 (p < 0.001) descended, whereas TSH levels remained unchanged (p = 0.451). In multivariate logistic regression models adjusted for age, sex, UI, BMI and smoking status, subjects with ferritin levels <30 µg/L were more likely to present hypothyroxinemia ...

Urinary podocyte-associated molecules and albuminuria in hypertension

Journal of hypertension, Jan 19, 2018

Hypertension-induced podocyte damage and the relationship with UAE is analyzed in diabetic and no... more Hypertension-induced podocyte damage and the relationship with UAE is analyzed in diabetic and nondiabetic participants. Sixty-four hypertensive patients, 30 diabetics, with glomerular filtration rate (eGFR) greater than 60 ml/min per 1.73 m were included. Urinary albumin excretion was measured in morning urine using a nephelometric immunoassay and expressed as albumin/creatinine ratio. Urinary pellets were obtained from fresh urine and mRNA was assessed by real-time quantitative PCR. Likewise, protein podocyte-specific molecules were measured by western blot using specific antibodies. Fourteen nondiabetics and 20 diabetics had increased UAE greater than 30 mg/g. In individuals with increased EUA, the mRNA expression of nephrin and CD2AP was low in diabetics, whereas only nephrin mRNA in nondiabetics. No differences were observed in podocalyxin and aquaporin-1 mRNA levels. Concerning the protein values, in both nondiabetic and diabetic patients, nephrin, CD2AP and podocalyxin were i...

Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study

BMJ open, Jan 15, 2017

To investigate the association between IL18RAP and body mass index (BMI) and obesity and to verif... more To investigate the association between IL18RAP and body mass index (BMI) and obesity and to verify the effect of a polymorphism in the microRNA136 (MIR136) IL18RAP binding region. We analysed samples from two Spanish cross-sectional studies, VALCAR (Spanish Mediterranean coast) and Hortega (Spanish centre). These studies aimed at analysing cardiovascular risk and development of cardiovascular disease in the general population. Both populations correspond to regions with different characteristics. Five IL18RAP single nucleotide polymorphisms were selected using the SYSNPs web tool and analysed by oligonucleotide ligation assay (SNPlex). For the MIR136 functional study, cells were transfected with plasmids containing different rs7559479 polymorphism alleles and analysed by luciferase reporter assays. 1970 individuals (Caucasian, both genders): VALCAR (468) and Hortega (1502). rs2293225, rs2272127 and rs7559479 showed the following associations: rs7559479 G allele correlated with a hig...

mRNA expression profiles obtained from microdissected pancreatic cancer cells can predict patient survival

Oncotarget, 2017

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating malignancies i... more Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating malignancies in developed countries because of its very poor prognosis and high mortality rates. By the time PDAC is usually diagnosed only 20-25% of patients are candidates for surgery, and the rate of survival for this cancer is low even when a patient with PDAC does undergo surgery. Lymph node invasion is an extremely bad prognosis factor for this disease. Methods: We analyzed the mRNA expression profile in 30 PDAC samples from patients with resectable local disease (stages I and II). Neoplastic cells were isolated by laser-microdissection in order to avoid sample 'contamination' by non-tumor cells. Due to important differences in the prognoses of PDAC patients with and without lymph node involvement (stage IIB and stages I-IIA, respectively), we also analyzed the association between the mRNA expression profiles from these groups of patients and their survival. Results: We identified expression profiles associated with patient survival in the whole patient cohort and in each group (stage IIB samples or stage I-IIA samples). Our results indicate that survival-associated genes are different in the groups with and without affected lymph nodes. Survival curves indicate that these expression profiles can help physicians to improve the prognostic classification of patients based on these profiles.

Antioxidant enzymes in lymphocites from essential hypertension patients

American Journal of Hypertension, 2002

Hypoxia increased LDH release by 4 folds. Exposure to ET-1 (0.1 M) before hypoxia resulted in a 6... more Hypoxia increased LDH release by 4 folds. Exposure to ET-1 (0.1 M) before hypoxia resulted in a 6-fold increase in LDH release (pϽ0.05 vs hypoxia alone). Pretreatment with BQ-123 before hypoxia significantly attenuated LDH release. Morphological assays revealed a severe cytotoxic effect induced by ET-1. Pretreatment with BQ-123 (5 M) prevented the cytotoxic effects. The results were confirmed by electron microscopy. Exposure of myocytes to ET-1 (10-100 nM) caused an increase in the concentration of intracellular free Ca2ϩ in a concentration-dependent manner. The effect was completely inhibited by pretreatment with the ET A antagonist BQ-123 at a concentration of 5 M. Conclusions: ET-1 augments cytotoxic damage in cardiac cells 24 h after exposure to simulated hypoxia. The effect is mediated through activation of the ET A receptor.