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1.
J Neurochem ; 168(6): 977-994, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38390627

RESUMO

Alzheimer's disease (AD) is the most common type and accounts for 60%-70% of the reported cases of dementia. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in gene expression regulation. Although the diagnosis of AD is primarily clinical, several miRNAs have been associated with AD and considered as potential markers for diagnosis and progression of AD. We sought to match AD-related miRNAs in cerebrospinal fluid (CSF) found in the GeoDataSets, evaluated by machine learning, with miRNAs listed in a systematic review, and a pathway analysis. Using machine learning approaches, we identified most differentially expressed miRNAs in Gene Expression Omnibus (GEO), which were validated by the systematic review, using the acronym PECO-Population (P): Patients with AD, Exposure (E): expression of miRNAs, Comparison (C): Healthy individuals, and Objective (O): miRNAs differentially expressed in CSF. Additionally, pathway enrichment analysis was performed to identify the main pathways involving at least four miRNAs selected. Four miRNAs were identified for differentiating between patients with and without AD in machine learning combined to systematic review, and followed the pathways analysis: miRNA-30a-3p, miRNA-193a-5p, miRNA-143-3p, miRNA-145-5p. The pathways epidermal growth factor, MAPK, TGF-beta and ATM-dependent DNA damage response, were regulated by these miRNAs, but only the MAPK pathway presented higher relevance after a randomic pathway analysis. These findings have the potential to assist in the development of diagnostic tests for AD using miRNAs as biomarkers, as well as provide understanding of the relationship between different pathophysiological mechanisms of AD.


Assuntos
Doença de Alzheimer , Mineração de Dados , Aprendizado de Máquina , MicroRNAs , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/genética , Doença de Alzheimer/diagnóstico , Humanos , MicroRNAs/líquido cefalorraquidiano , MicroRNAs/genética , Biomarcadores/líquido cefalorraquidiano
2.
Mol Biol Rep ; 51(1): 270, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302810

RESUMO

Dementia is the term used to describe a group of cognitive disorders characterized by a decline in memory, thinking, and reasoning abilities that interfere with daily life activities. Examples of dementia include Alzheimer's Disease (AD), Frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS), Vascular dementia (VaD) and Progressive supranuclear palsy (PSP). AD is the most common form of dementia. The hallmark pathology of AD includes formation of ß-amyloid (Aß) oligomers and tau hyperphosphorylation in the brain, which induces neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal apoptosis. Emerging studies have associated long non-coding RNAs (lncRNAs) with the pathogenesis and progression of the neurodegenerative diseases. LncRNAs are defined as RNAs longer than 200 nucleotides that lack the ability to encode functional proteins. LncRNAs play crucial roles in numerous biological functions for their ability to interact with different molecules, such as proteins and microRNAs, and subsequently regulate the expression of their target genes at transcriptional and post-transcriptional levels. In this narrative review, we report the function and mechanisms of action of lncRNAs found to be deregulated in different types of dementia, with the focus on AD. Finally, we discuss the emerging role of lncRNAs as biomarkers of dementias.


Assuntos
Doença de Alzheimer , Demência Frontotemporal , RNA Longo não Codificante , Humanos , Doença de Alzheimer/genética , RNA Longo não Codificante/genética , Peptídeos beta-Amiloides
3.
BMC Pregnancy Childbirth ; 24(1): 628, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354367

RESUMO

OBJECTIVE: This study introduces the complete blood count (CBC), a standard prenatal screening test, as a biomarker for diagnosing preeclampsia with severe features (sPE), employing machine learning models. METHODS: We used a boosting machine learning model fed with synthetic data generated through a new methodology called DAS (Data Augmentation and Smoothing). Using data from a Brazilian study including 132 pregnant women, we generated 3,552 synthetic samples for model training. To improve interpretability, we also provided a ridge regression model. RESULTS: Our boosting model obtained an AUROC of 0.90±0.10, sensitivity of 0.95, and specificity of 0.79 to differentiate sPE and non-PE pregnant women, using CBC parameters of neutrophils count, mean corpuscular hemoglobin (MCH), and the aggregate index of systemic inflammation (AISI). In addition, we provided a ridge regression equation using the same three CBC parameters, which is fully interpretable and achieved an AUROC of 0.79±0.10 to differentiate the both groups. Moreover, we also showed that a monocyte count lower than 490 / m m 3 yielded a sensitivity of 0.71 and specificity of 0.72. CONCLUSION: Our study showed that ML-powered CBC could be used as a biomarker for sPE diagnosis support. In addition, we showed that a low monocyte count alone could be an indicator of sPE. SIGNIFICANCE: Although preeclampsia has been extensively studied, no laboratory biomarker with favorable cost-effectiveness has been proposed. Using artificial intelligence, we proposed to use the CBC, a low-cost, fast, and well-spread blood test, as a biomarker for sPE.


Assuntos
Biomarcadores , Aprendizado de Máquina , Pré-Eclâmpsia , Humanos , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/sangue , Feminino , Gravidez , Biomarcadores/sangue , Contagem de Células Sanguíneas/métodos , Adulto , Sensibilidade e Especificidade , Brasil , Índice de Gravidade de Doença , Curva ROC , Diagnóstico Pré-Natal/métodos
4.
Alzheimers Dement ; 19(9): 4046-4060, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37204054

RESUMO

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.


Assuntos
Disfunção Cognitiva , Humanos , América Latina , Disfunção Cognitiva/prevenção & controle , Estilo de Vida , Cognição , Projetos de Pesquisa
5.
Immunol Invest ; 51(4): 883-898, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33557640

RESUMO

BACKGROUND: Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1ß, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data. METHODS: Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2). RESULTS: Higher IL-10 levels were observed in the case group compared to controls at T1 (p = .006) and T2 (p = .046). The IL-1ß, IL-6 and TNF levels did not change during treatment in each group (p > .05), nor between the case and control groups. The IL-10 levels were higher at T1 than at T0 and T2 (p < .05 for both) in the cardiotoxicity group. A correlation between IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at T0 and T2 in the cardiotoxicity group was observed (p = .048 and p = .004, respectively). CONCLUSION: Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.


Assuntos
Neoplasias da Mama , Cardiotoxicidade , Interleucina-10 , Biomarcadores , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/etiologia , Doxorrubicina/efeitos adversos , Feminino , Seguimentos , Humanos , Interleucina-10/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue
6.
Mol Biol Rep ; 49(8): 7359-7365, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35576050

RESUMO

BACKGROUND: Atrial fibrillation (AF) is an arrhythmia that involves structural and electrophysiological abnormalities. Many of the AF-related clinical conditions are associated with an increase in inflammatory and oxidative factors. Haptoglobin (Hp) is an acute phase protein whose biological role is to promote clearance of free hemoglobin (Hb). In addition, for being considered an inflammatory marker, Hp represents a protective mechanism against the oxidative effects of Hb. The Hp1-Hp2 polymorphism at Hp locus can lead to three phenotypes related to structural and functional differences in the protein. The objective of this study were to evaluate Hp levels and Hp1-Hp2 polymorphism at Hp locus in patients with AF compared to a control group. METHODS AND RESULTS: This study included 65 patients with AF and 54 individuals without the arrhythmia. Biochemical parameters were determined using Vitros system, plasma levels of Hp were measured in serum samples by using ELISA method and polymorphisms were verified by PCR technique. Plasma Hp levels, as well as allelic and genotypic frequency, were not associated with AF. The levels of Hp also did not differ among the genotypes according to the applied models. CONCLUSIONS: The results suggest that Hp levels and Hp1-Hp2 polymorphism are not associated to AF.


Assuntos
Fibrilação Atrial , Haptoglobinas , Fibrilação Atrial/genética , Genótipo , Haptoglobinas/química , Haptoglobinas/genética , Hemoglobinas , Humanos , Polimorfismo Genético
7.
Mol Biol Rep ; 49(10): 9509-9520, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35980532

RESUMO

BACKGROUND: About 5-10% of breast cancer cases are related to genetic and hereditary factors. The application of Next Generation Sequencing (NGS) in oncology has allowed the identification of genetic variants present in several genes related to the increased risk of breast cancer. This study aimed to determine the frequency of germline genetic variants in patients with a family and/or personal history of breast cancer. METHODS: An analysis of positive reports from NGS panels was carried out in female individuals with a personal and/or family history of breast cancer, present in the database of a private laboratory in Brazil. RESULTS: From about 2000 reports, 183 individuals presented 219 different germline genetic variants. The genes with the highest number of variants were BRCA2 (16.0%), ATM (15.0%) and BRCA1 (12.8%). Among the variants found, 78 were either pathogenic or probably pathogenic, accounting for 35% of all variants discovered. The gene with the highest proportion of pathogenic/probably pathogenic variants was TP53 (80%) and the most frequent pathogenic variant was also reported in this gene (c.1010G > A p.(Arg337His)). Furthermore, the study obtained a high proportion of variants of uncertain significance (VUS) (65%) and approximately 32% of the variants found were in genes of moderate penetrance. CONCLUSIONS: Our results could improve the risk estimation and clinical follow-up of Brazilian patients with a history of breast cancer.


Assuntos
Neoplasias da Mama , Proteína BRCA1/genética , Brasil/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Genes BRCA2 , Predisposição Genética para Doença , Células Germinativas , Mutação em Linhagem Germinativa/genética , Humanos
8.
Adv Exp Med Biol ; 1307: 115-128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32253710

RESUMO

Diabetes mellitus (DM) is a metabolic disorder characterised by hyperglycemia and abnormalities in carbohydrate, fat and protein metabolism. Several studies demonstrated that foods typical of the Mediterranean diet (MedDiet), including vegetables, fruits, oilseeds, extra virgin olive oil and fish, can promote health benefits for individuals at risk of or with type 2 diabetes (T2DM). In this review, we summarised randomised clinical trials, cohort studies, meta-analyses and systematic reviews that evaluated the effects of the MedDiet on metabolic control of T2DM. The data suggest that the MedDiet influences cardiovascular risk factors, including blood pressure, lipid profile, insulin resistance, inflammation and glucose metabolism, in T2DM patients. In conclusion, the MedDiet appears to protect patients from macro- and microangiopathy and should be considering in the management of diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Dieta Mediterrânea , Pressão Sanguínea , Doenças Cardiovasculares/prevenção & controle , Glucose/metabolismo , Humanos , Inflamação , Resistência à Insulina , Lipídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
9.
Cytokine ; 125: 154858, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31557637

RESUMO

INTRODUCTION: Hemodialysis (HD) is associated with high risk for cardiovascular diseases including acute myocardial infarction, stroke and congestive heart failure. C-C Motif Chemokine Ligand 2 (CCL2), also known monocyte chemotactic protein-1 (MCP-1) can be produced by a variety of cells, reaching increased levels in dyslipidemic chronic kidney disease (CKD) patients undergoing HD treatment. The main of this study was to evaluate the association between of CCL2 plasma levels and dyslipidemia in CKD patients undergoing HD. METHODS: A cross-sectional study enrolled 160 Brazilian HD patients. CCL2 plasma levels were measured by capture ELISA. The association between CCL2 levels and dyslipidemia was investigated using linear regression, adjusted for classic and non-classical CVD risk factors. RESULTS: A significant association was observed between CCL2 levels and dyslipidemia (P = 0.029), even after adjustment for possible confounding variables, such as age, gender, body mass index, diabetes mellitus, HD time, urea pre-hemodialysis and interdialytic weight gain (P = 0.045). CONCLUSION: Our findings show that CCL2 levels are associated with dyslipidemia, which suggests a role of this cytokine in the pathogenesis of cardiovascular disease in HD patients. A better understanding of this pathogenesis could contribute to the discovery of new therapeutic targets that would reduce cardiovascular complications in these patients.


Assuntos
Doenças Cardiovasculares/etiologia , Quimiocina CCL2/sangue , Dislipidemias/sangue , Falência Renal Crônica/sangue , Adulto , Brasil , Doenças Cardiovasculares/complicações , Correlação de Dados , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Fatores de Risco
10.
Mol Biol Rep ; 47(12): 9279-9288, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33231818

RESUMO

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by high levels of low-density lipoprotein-cholesterol (LDLc), associated to premature cardiovascular disease. The detection of the variants related to FH is important to improve the early diagnosis in probands / index-cases (ICs) and their relatives. We included ICs with FH and their relatives, living in a small region of Minas Gerais state-Brazil, which were classified according to Dutch Lipid Clinic Network Criteria (DLCNC) and submitted to sequencing of genes related to FH (LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, APOE, ABCG5 e ABCG8). In a total of 143 subjects (32 ICs and 111 relatives), eight variants were identified in 91 individuals. From these variants, five were in LDLR [p.(Asp224Asn), p.(Ser854Gly), p.(Cys34Arg), p.(Asp601His), deletion of exon15 in LDLR)], one in APOB [p.(Met499Val)], one in PCSK9 [p.(Arg237Trp)] and one in APOE [p.(Pro28Leu)] genes. The variants were detected in 100% of those subjects classified as definitive, 87% as probable and 69% as possible FH cases based on DLCNC. The LDLc level was higher in individuals with corneal arch and xanthomas or xanthelasmas, as well as in pathogenic or probably pathogenic variants carriers. This study showed higher frequency of LDLR gene variants compared to other genes related to LDL metabolism in individuals with FH in Minas Gerais - Brazil and the presence of FH in relatives without previous diagnosis. Our data reinforce the importance of molecular and clinical evaluation of FH relatives in order to early diagnosis the FH, as well as cardiovascular diseases prevention.


Assuntos
Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Programas de Rastreamento/métodos , Mutação de Sentido Incorreto , Receptores de LDL/genética , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , LDL-Colesterol/sangue , Análise por Conglomerados , Diagnóstico Precoce , Feminino , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA/métodos , Adulto Jovem
11.
Diabetes Metab Res Rev ; 35(1): e3071, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30160822

RESUMO

C-peptide is a cleavage product of proinsulin that acts on different type of cells, such as blood and endothelial cells. C-peptide biological effects may be different in type 1 and type 2 diabetes. Besides, there are further evidence for a functional interaction between C-peptide and insulin. In this way, C-peptide has ambiguous effects, acting as an antithrombotic or thrombotic molecule, depending on the physiological environment and disease conditions. Moreover, C-peptide regulates interaction of leucocytes, erythrocytes, and platelets with the endothelium. The beneficial effects include stimulation of nitric oxide production with its subsequent release by platelets and endothelium, the interaction with erythrocytes leading to the generation of adenosine triphosphate, and inhibition of atherogenic cytokine release. The undesirable action of C-peptide includes the chemotaxis of monocytes, lymphocytes, and smooth muscle cells. Also, C-peptide was related with increased lipid deposits and elevated smooth muscle cells proliferation in the vessel wall, contributing to atherosclerosis. Purpose of this review is to explore these dual roles of C-peptide on the blood, contributing at one side to haemostasis and the other to atherosclerotic process.


Assuntos
Aterosclerose/metabolismo , Peptídeo C/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Animais , Endotélio Vascular/metabolismo , Eritrócitos/metabolismo , Humanos , Óxido Nítrico/metabolismo
12.
Mol Cell Probes ; 45: 43-47, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31028794

RESUMO

BACKGROUND: Genetic, immune and environmental factors are involved in preeclampsia (PE) etiopathogenesis. Considering that hypertension and poor placental perfusion are important features in PE, polymorphisms in the angiotensin-converting enzyme (ACE) and estrogen nuclear receptor 1 (ESR1) genes could be involved in the predisposition and/or development of the disease. The aim of this study was to evaluate if polymorphisms in ACE and ESR1 genes were associated with PE occurrence. MATERIAL AND METHODS: This case-control study included 209 Brazilian pregnant women (107 with severe PE and 102 normotensive controls). The polymorphisms were investigated by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis. RESULTS: No significant difference between PE versus normotensive pregnant women, as well as early versus late PE, was observed when compared the allelic and genotypic frequencies of insertion/deletion polymorphism in intron 16 of the ACE gene and the single nucleotide polymorphisms (SNPs - rs2234693 and rs9340799) of the ESR1 gene. CONCLUSION: This pioneer study involving Brazilian women showed no association among the studied polymorphisms and PE, which suggests that ins/del ACE and SNPs ESR1 do not contribute to this disease occurrence in Brazil.


Assuntos
Receptor alfa de Estrogênio/genética , Mutação INDEL , Peptidil Dipeptidase A/genética , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genética , Adolescente , Adulto , Brasil/etnologia , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Reação em Cadeia da Polimerase , Pré-Eclâmpsia/etnologia , Gravidez , Adulto Jovem
13.
Gynecol Endocrinol ; 35(2): 146-149, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30182771

RESUMO

This study aimed to investigate the association between vitamin D (VitD) levels, polymorphisms in VDR gene (ApaI, BsmI, FokI, and TaqI) and the polycystic ovary syndrome (PCOS) in a group of Brazilian women. A total of 100 patients with PCOS and 100 control women were included. The quantification of 25-hydroxyvitamin D (25(OH)D) was performed in high-performance liquid chromatography (HPLC). Polymorphisms on VDR gene were performed by PCR-RFLP. The BsmI AG genotype was more frequent in PCOS group, while the GG genotype was more frequent in the control group (p = .007). The frequency of the Taql CC genotype was higher in PCOS group, while the CT genotype was the most frequent in the control group (p = .021). Mean serum VitD levels were similar between the groups. However, there was a negative correlation between VitD levels and Ferriman-Gallwey score (p = .031, r = -.260) in the PCOS group. The TaqI and BsmI polymorphisms were associated with PCOS. Moreover, VitD levels are associated with the clinical hyperandrogenism. The data suggest the role of VitD in PCOS development and its complications.


Assuntos
Síndrome do Ovário Policístico/genética , Receptores de Calcitriol/genética , Vitamina D/análogos & derivados , Adulto , Glicemia/metabolismo , Brasil , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Predisposição Genética para Doença , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/genética , Insulina/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/metabolismo , Polimorfismo Genético , Testosterona/sangue , Vitamina D/sangue , Adulto Jovem
14.
Medicina (Kaunas) ; 55(5)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121922

RESUMO

Background and Objectives: Vitamin D levels have been associated with a diversity of diseases, including obesity. Vitamin D presents a pleiotropic action, and can regulate insulin secretion and inflammatory responses. Vitamin D receptor (VDR) gene polymorphisms are involved in the gene expression regulation and have been associated with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between the polymorphisms ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810), and TaqI (rs731236) in the VDR gene in people diagnosed with T2DM, and plasma 25-hydroxivitamin D levels [25(OH)D]. Materials and Methods: A total of 101 T2DM patients and 62 gender, age, and body mass index (BMI) matched non-diabetic controls were included in this study. Molecular analyzes were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The plasma 25(OH)D levels were measured by high performance liquid chromatography. Results: The plasma 25(OH)D levels were lower in T2DM patients (17.2 (16.6) ng/mL) when compared with the control subjects (30.8 (16.2) ng/mL, p < 0.0001), independently of obesity status. We found no difference between genotypic and allelic frequencies of the VDR polymorphisms when comparing the T2DM group and control group (p > 0.05 for all), and did not show any association with plasma 25(OH)D levels. Conclusions: These results suggest that T2DM is associated with lower plasma 25(OH)D levels, which are not related to BMI and VDR gene polymorphisms.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Polimorfismo Genético/fisiologia , Receptores de Calcitriol/genética , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/genética , Adulto , Idoso , Glicemia/análise , Brasil , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Jejum/sangue , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Receptores de Calcitriol/análise , Receptores de Calcitriol/sangue , Estatísticas não Paramétricas , Vitamina D/análise , Vitamina D/sangue , Deficiência de Vitamina D/sangue
15.
Cytokine ; 96: 24-29, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28282547

RESUMO

BACKGROUND: A common complication in patients undergoing peritoneal dialysis (PD) is a chronic inflammatory state and anemia that can be treating by recombinant human erythropoietin (rHuEPO). Higher required dose of rHuEPO could be expected in patients with higher cytokine levels. Additionally, it is known that peritoneal inflammation can be correlated with systemic inflammation and this could contribute to the compromised rHuEPO required dose in anemic patients with end stage renal disease (ESRD). Thus, the current study aimed to evaluate the association between levels of systemic and local interferon (IFN)-γ, interleukin (IL)-17 and other cytokines and the dose of rHuEPO used by patients undergoing PD for the correction of anemia. METHODS: Thirty-one patients under PD using rHuEPO were evaluated in this cross-sectional study. Plasma and dialysate levels of IL-2, IL-4, IL-6, IL-10, IL-17, tumour necrosis factor (TNF)-α and IFN-γ were determined using the Cytometric Bead Array TM kit (CBA; BD Bioscences, San Jose, CA). The relation between the levels of each cytokine levels and the tertiles of rHuEPO were plotted on box-plot graphics and then the medians of interleukins levels were compared by median comparison test. The significance level adopted was 5% and the analysis was performed by the softwares STATA (version 12.0) and GraphPad Prism 3.0. RESULTS: The median of IL-17 and IFN-γ plasma levels were significant higher in the group with higher rHuEPO dosage. However, this association was not observed in the dialysate levels, as well as was not observed a relationship between the other plasma and dialysate cytokines evaluated in this study and the dose of rHuEPO. CONCLUSIONS: Our study found increased IL-17 and IFN-γ plasma, but no dialysate levels, in patients receiving higher doses of rHuEPO, suggesting may exist a relationship between systemic inflammation of ESRD, and the necessary levels of rHuEPO for the correction of anemia in these patients.


Assuntos
Eritropoetina/administração & dosagem , Interferon gama/sangue , Interleucina-17/sangue , Diálise Peritoneal/efeitos adversos , Idoso , Anemia/tratamento farmacológico , Anemia/etiologia , Estudos Transversais , Citocinas/sangue , Relação Dose-Resposta a Droga , Eritropoetina/genética , Eritropoetina/uso terapêutico , Feminino , Humanos , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/tratamento farmacológico
16.
J Obstet Gynaecol Res ; 43(3): 436-446, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28127831

RESUMO

Polycystic ovary syndrome (PCOS) is the most frequent endocrinological disorder that affects women of reproductive age, leading to metabolic alterations, such as hyperandrogenism, obesity, menstrual irregularities, insulin resistance, and polycystic ovaries. The etiology remains unclear, but several genetic and environmental factors have been correlated with manifestations of this syndrome. Vitamin D plays important roles in metabolic pathways affected by PCOS, including calcium homeostasis, the insulin pathway, and sex hormone synthesis. Vitamin D concentration has been related with the severity of this disorder, and vitamin D receptor polymorphisms have been shown in some studies to have an association with some of the patterns presented by PCOS. The objective of this study is to provide an up-to-date review about vitamin D receptor polymorphisms and their association with PCOS.


Assuntos
Síndrome do Ovário Policístico/genética , Receptores de Calcitriol/genética , Feminino , Humanos , Síndrome do Ovário Policístico/sangue , Polimorfismo Genético , Vitamina D/sangue
17.
Arch Gynecol Obstet ; 296(4): 617-621, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28795250

RESUMO

PURPOSE: The objective of this study was to evaluate the levels of total microparticles (MPs) and microparticles-expressing tissue factor (TFMPs) in women with polycystic ovarian syndrome (PCOS) who use metformin comparing to those who do not take metformin. METHODS: We quantified total MPs and TFMPs in the plasma of 50 patients with PCOS-13 of these women used metformin (850 mg 2×/day during at least 6 months) and the other 37 did not. For this purpose, the microparticles (MPs) were purified by differential centrifugation of the plasma and, subsequently, by flow cytometry, using annexin-V and CD142 as markers. RESULTS: Total MPs levels were lower in treated patients (59.58 ± 28.43 MPs/µL) when compared to untreated group (97.32 ± 59.42; p = 0.033). Plasma levels of TFMPs were also significantly lower in the group of patients who used metformin (1.10 ± 0.94 MPs/µL) when compared to untreated patients (2.20 ± 1.42 MPs/µL) (p = 0.003). CONCLUSIONS: Considering that metformin reduced the levels of total MPs and TFMPs, our results suggest that this mechanism could be involved in the antithrombotic metformin effect, corroborating with the indication of this drug in the PCOS treatment.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Hemostáticos/metabolismo , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Adulto , Feminino , Humanos , Síndrome do Ovário Policístico/sangue , Tromboplastina
18.
Nitric Oxide ; 42: 19-23, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25106888

RESUMO

Preeclampsia (PE) is characterized by hypertension and proteinuria, occurring after the 20th week of pregnancy in women who have had no previous symptoms. The disease progresses with generalized vasoconstriction and endothelial dysfunction. Clinically, it is important to diagnose the severe form of the disease (sPE), in which blood pressure and proteinuria are much higher. Recently, the gestational age (GA) of the onset of PE has led to the classification of this disease as early (GA <34 weeks) and late (GA ≥34 weeks). Several genetic polymorphisms affecting endothelial nitric oxide synthase (eNOS) levels or function were described, including G894T (Glu298Asp), VNTR b/a (variable-number 27-bp tandem repeat) and T-786C (promoter) polymorphisms. Thus, the aim of this study was to compare the distribution of G894T, VNTR b/a and T-786C polymorphisms and their haplotypes in Brazilian early and late sPE, as well as in normotensive pregnant. A total of 201 women were evaluated, 53 with early sPE, 45 with late sPE and 103 as normotensive pregnant women. The frequency of 894T allele was higher in late sPE vs normotensive pregnant, and 894TT genotype was higher in late sPE vs early sPE and normotensive pregnant. For VNTR b/a polymorphism, higher frequencies of aa genotype and a allele were observed in early sPE vs late sPE and normotensive pregnant. Besides, the frequency of haplotype T-b-C was higher in late sPE vs early sPE and normotensive pregnant. Considering the results found for eNOS polymorphisms, it is possible to suggest that the functional alterations induced by these two polymorphisms may influence the time of severe PE onset, although both alterations are putatively associated with low NO bioavailability. However, other studies are necessary to validate these findings and clarify this issue.


Assuntos
Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA , Feminino , Humanos , Reação em Cadeia da Polimerase , Gravidez , Índice de Gravidade de Doença
19.
J Reprod Immunol ; 163: 104248, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703439

RESUMO

Preeclampsia (PE) is the major cause of maternal-fetal mortality and morbidity. Its pathophysiology is not elucidated, but there is evidence for the role of visfatin/nicotinamide phosphoribosyl transferase (NAMPT), mainly due to its relation to endothelial dysfunction, a hallmark of PE. However, there is heterogeneous data regarding visfatin/NAMPT in healthy pregnancy (HP) and PE. Therefore, we performed a search on MEDLINE/PubMed using the terms "visfatin and preeclampsia" and "NAMPT and preeclampsia, and we selected 23 original articles: 12 articles reported increased levels in PE compared to HP, only four articles showed lower levels and eight articles did not find differences regarding visfatin/NAMPT in the groups studied. It is widely acknowledged that levels detected in plasma, serum, or placenta can be influenced by the size of the population and sample analyzed, as well as genetic factors. We further discussed the correlations of visfatin/NAMPT with clinical biomarkers in PE and inflammatory pathways. Considering the common inflammatory mechanisms between PE and visfatin/NAMPT, few studies have recently performed serum or plasma dosages. In conclusion, further studies are needed to highlight the potential role of visfatin/NAMPT in the pathophysiology of PE. This will provide comparative evidence to establish it as a biomarker for disease outcomes and treatment.


Assuntos
Biomarcadores , Citocinas , Nicotinamida Fosforribosiltransferase , Pré-Eclâmpsia , Humanos , Pré-Eclâmpsia/imunologia , Pré-Eclâmpsia/sangue , Nicotinamida Fosforribosiltransferase/sangue , Nicotinamida Fosforribosiltransferase/metabolismo , Gravidez , Feminino , Citocinas/sangue , Citocinas/metabolismo , Biomarcadores/sangue , Placenta/imunologia , Placenta/metabolismo , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/sangue , Inflamação/imunologia
20.
Can J Aging ; : 1-11, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38467581

RESUMO

The relationship between alcohol consumption and cognition is still controversial. This is a cross-sectional population-based study conducted in Caeté (MG), Brazil, where 602 individuals aged 75+ years, 63.6% female, and with a mean education of 2.68 years, were submitted to thorough clinical assessments and categorized according to the number of alcoholic beverages consumed weekly. The prevalence rates of previous and current alcohol consumption were 34.6% and 12.3%, respectively. No association emerged between cognitive diagnoses and current/previous alcohol consumption categories. Considering current alcohol intake as a dichotomous variable, the absence of alcohol consumption was associated with dementia (OR = 2.34; 95%CI: 1.39-3.90) and worse functionality (p = 0.001). Previous consumption of cachaça (sugar cane liquor) increased the risk of dementia by 2.52 (95%CI: 1.25-5.04). The association between the consumption of cachaça and dementia diagnosis has not been described before.

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