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2.
Tumour Biol ; 42(9): 1010428320958603, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32964798

RESUMO

This study aimed to investigate whether changes in progastrin-releasing peptide (ProGRP) levels correlate with treatment response and can be used to optimize clinical management of patients with small-cell lung cancer. Patients with small-cell lung cancer (any stage) receiving chemotherapy were eligible. ProGRP was measured in serum/plasma at baseline and after each chemotherapy cycle using the Elecsys® ProGRP assay (Roche Diagnostics). Treatment response was assessed by computed tomography scan. The primary objective was to examine whether changes in ProGRP levels correlated with computed tomography scan results after two cycles of chemotherapy. The prognostic value of ProGRP among patients receiving first-line chemotherapy was also assessed. Overall, 261 patients from six centers were eligible. Among patients with elevated baseline ProGRP (>100 pg/mL), a ProGRP decline after Cycle 2 was associated with nonprogression (area under the curve: 84%; 95% confidence interval: 72.8-95.1; n = 141). ProGRP changes from baseline to end of Cycle 1 were predictive of response, as determined by computed tomography scan 3 weeks later (area under the curve: 87%; 95% confidence interval: 74.1-99.2; n = 137). This was enhanced by repeat measurements, with a 92% area under the curve (95% confidence interval: 85.3-97.8) among patients with ProGRP data after both Cycles 1 and 2 (n = 123); if a patient experienced a ≥25% decline in ProGRP after Cycle 1, and ProGRP remained stable or decreased after Cycle 2, the probability of finding progression on the interim computed tomography scan at the end of Cycle 2 was almost zero (sensitivity: 100%, specificity: 71%). Both ProGRP levels at baseline and at the end of first-line chemotherapy were prognostic; the latter provided a moderately improved hazard ratio of 2.43 (95% confidence interval: 1.33-4.46; n = 110) versus 1.87 (95% confidence interval: 1.04-3.37; n = 216). In summary, for patients with small-cell lung cancer and elevated baseline ProGRP levels, ProGRP may be a simple, reliable, and repeatable tool for monitoring response to chemotherapy and provide valuable prognostic information.


Assuntos
Neoplasias Pulmonares/sangue , Fragmentos de Peptídeos/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais/sangue , China , Europa (Continente) , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes/sangue , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios X
3.
Acta Odontol Latinoam ; 33(2): 125, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920615

RESUMO

Melatonin (MLT) is a potential signaling molecule in the homeostasis of bone metabolism and may be an important mediator of bone formation and stimulation. The aim of this in vitro study was to evaluate the effect of MLT on the viability, mRNA/protein expression and mineralization of pre-osteoblastic cells. The concentrations 5, 2.5, 1, 0.1 and 0.01 mM MLT were tested on pre-osteoblastic cells (MC3T3) compared to control (no MLT), evaluating proliferation and cell viability (C50), gene expression (RT-PCR) and secretion (ELISA) of COL-I and OPN at 24h, 48h and 72h, and the formation of mineral nodules (alizarin red and fast red) after 10 days of treatment. MLT at 5 and 2.5 mM proved to be cytotoxic (C50), so only 0.01, 0.1 and 1 mM were used for the subsequent analyses. OPN mRNA expression increased with MLT at 0.1 mM - 1 mM, which was followed by increased secretion of OPN both at 24h and 72h compared to the remaining groups (p <0.05). COL-I mRNA and COL-1 secretion followed the same pattern as OPN at 0.1 mM MLT at 72h of treatment (p <0.05). Regarding mineralization, all MLT doses (except 1mM) caused an increase (p <0.05) in the formation of mineral nodules compared to the control. Melatonin at 0.01mM - 1mM had a stimulatory effect on osteoblasts by upregulating COL-I and OPN expression/ secretion and mineralization, thereby fostering osteogenesis.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Metaloproteinase 2 da Matriz/metabolismo , Melatonina/farmacologia , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteopontina/metabolismo , Fragmentos de Peptídeos/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/genética , Osteoblastos/metabolismo , Osteopontina/genética , Fragmentos de Peptídeos/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real
4.
Ecotoxicol Environ Saf ; 203: 111044, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888613

RESUMO

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) is associated with various adverse health outcomes. Although several mechanisms have been proposed including oxidative stress and inflammatory responses, the exact mechanism is still unknown. Few studies have investigated the mechanism linking PM2.5 and blood pressure (BP). In this study, we measured urinary metabolites and BP -related renin-angiotensin-aldosterone system (RAAS) to investigate the associations between ambient PM2.5 exposure and BP in healthy C57BL/6 mice. METHODS: The C57BL/6 mice were exposed to ambient concentrated PM2.5 or filtered air (FA) for 16 weeks. Systolic BP and diastolic BP were measured by noninvasive BP system. The urine metabolites were quantified using the untargeted metabolomics approach. The expression of RAAS-related proteins angiotensin-converting enzyme (ACE)2, angiotensin (Ang) II, Ang (1-7) and aldosterone (ALD) were measured using Western blot and ELISA kits. RESULTS: The metabolomics analysis demonstrated that PM2.5 exposure induced significant changes of some metabolites in urine, including stress hormones, amino acids, fatty acids, and lipids. Furthermore, there was an elevation of BP, increase of serous Ang II and ALD, along with the decrease of ACE2 and Ang (1-7) in kidney in the PM2.5-exposed mice compared with FA-exposed mice. CONCLUSIONS: The results demonstrated that PM2.5 exposure-induced BP elevation might be associated with RAAS activation. Meanwhile, PM2.5 exposure-induced changes of stress hormone and lipid metabolism might mediate the activation of RAAS. The results suggested that the systemic stress hormone and lipid metabolism was associated with the development of hypertension.


Assuntos
Poluentes Atmosféricos/toxicidade , Angiotensina I/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/induzido quimicamente , Material Particulado/toxicidade , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Acetilglucosaminidase/urina , Angiotensina I/sangue , Animais , Biomarcadores/sangue , Biomarcadores/urina , Hipertensão/urina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , beta-Galactosidase/urina
5.
Emerg Med Clin North Am ; 38(4): 931-944, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981627

RESUMO

Emergency physicians must be prepared to rapidly diagnose and resuscitate patients with pulmonary embolism (PE). Certain aspects of PE resuscitation run counter to typical approaches. A specific understanding of the pathophysiology of PE is required to avoid cardiovascular collapse potentially associated with excessive intravenous fluids and positive pressure ventilation. Once PE is diagnosed, rapid risk stratification should be performed and treatment guided by patient risk class. Although anticoagulation remains the mainstay of PE treatment, emergency physicians also must understand the indications and contraindications for thrombolysis and should be aware of new therapies and models of care that may improve outcomes.


Assuntos
Embolia Pulmonar/terapia , Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Angiografia por Tomografia Computadorizada , Estado Terminal , Ecocardiografia , Eletrocardiografia , Serviço Hospitalar de Emergência , Oxigenação por Membrana Extracorpórea , Hidratação , Humanos , Intubação Intratraqueal , Ácido Láctico/sangue , Trombólise Mecânica , Peptídeo Natriurético Encefálico/sangue , Óxido Nítrico/uso terapêutico , Oxigenoterapia , Fragmentos de Peptídeos/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Respiração com Pressão Positiva , Embolia Pulmonar/classificação , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/fisiopatologia , Ressuscitação/métodos , Medição de Risco , Índice de Gravidade de Doença , Terapia Trombolítica , Troponina/sangue , Vasoconstritores/uso terapêutico
6.
Int Heart J ; 61(5): 1079-1083, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32879264

RESUMO

A Japanese girl with polycystic kidney disease (PKD) developed normally, but at 8 months of age, she was hospitalized for acute onset dyspnea. On the day after admission to hospital, her general condition suddenly became worse. An echocardiogram showed left ventricular dilatation with thin walls, severe mitral valve regurgitation, and a reduced ejection fraction. She died of acute cardiac failure 3 hours after the sudden change. Postmortem analysis with light microscopy showed disarray of cardiomyocytes without obvious infiltration of lymphocytes, and we diagnosed her heart failure as idiopathic dilated cardiomyopathy (DCM). Clinical exome sequencing showed compound heterozygous variants in JPH2 (p.T237A/p.I414L) and a heterozygous nonsense mutation in PKD1 (p.Q4193*). To date, several variants in the JPH2 gene have been reported to be pathogenic for adult-onset hypertrophic cardiomyopathy or DCM in an autosomal dominant manner and infantile-onset DCM in an autosomal recessive manner. Additionally, autosomal dominant polycystic kidney disease is a systemic disease associated with several extrarenal manifestations, such as cardiomyopathy. Here we report a sudden infant death case of DCM and discuss the genetic variants of DCM and PKD.


Assuntos
Cardiomiopatia Dilatada/genética , Proteínas de Membrana/genética , Proteínas Musculares/genética , Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genética , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/patologia , Morte Súbita Cardíaca/etiologia , Evolução Fatal , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Heterozigoto , Humanos , Lactente , Insuficiência da Valva Mitral/etiologia , Miocárdio/patologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue
7.
Mol Genet Genomics ; 295(6): 1529-1535, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32894358

RESUMO

Lanthipeptides are a subgroup of ribosomally encoded and post-translationally modified peptides (RiPPs) which frequently possess potent biological activity. Here we provide the first comprehensive bioinformatic analysis of the lanthipeptide-producing capability of the Salinispora genus, a marine actinomycete. One hundred twenty-two Salinispora arenicola, tropica, and pacifica genomic sequences were analyzed for lanthipeptide gene clusters, and the resulting 182 clusters were divided into seven groups based on sequence similarities. Group boundaries were defined based on LanB and LanM sequences with greater than 80% similarity within groups. Of the seven groups, six are predicted to encode class I lanthipeptides while only one group is predicted to encode class II lanthipeptides. Leader and core peptides were predicted for each cluster along with the number of possible lanthionine bridges. Notably, all of the predicted products of these clusters would represent novel lanthipeptide scaffolds. Of the 122 Salinispora genomes analyzed in this study, 92% contained at least one lanthipeptide gene cluster suggesting that Salinispora is a rich, yet untapped, source of lanthipeptides.


Assuntos
Alanina/análogos & derivados , Proteínas de Bactérias/metabolismo , Genoma Bacteriano , Micromonosporaceae/metabolismo , Fragmentos de Peptídeos/metabolismo , Sulfetos/metabolismo , Alanina/isolamento & purificação , Alanina/metabolismo , Proteínas de Bactérias/genética , Genômica , Micromonosporaceae/genética , Micromonosporaceae/crescimento & desenvolvimento , Fragmentos de Peptídeos/isolamento & purificação , Sulfetos/isolamento & purificação
8.
Proc Natl Acad Sci U S A ; 117(39): 24384-24391, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32913053

RESUMO

An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8+ T cell memory to peptides presented by common HLA types like HLA-A2, which enhances recovery and diminishes clinical severity upon reinfection. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the clonal expansion of SARS-CoV-2-specific CD8+ and CD4+ T cells in vitro, with CD4+ T cells being robust. We identified two HLA-A*02:01-restricted SARS-CoV-2-specfic CD8+ T cell epitopes, A2/S269-277 and A2/Orf1ab3183-3191 Using peptide-HLA tetramer enrichment, direct ex vivo assessment of A2/S269 +CD8+ and A2/Orf1ab3183 +CD8+ populations indicated that A2/S269 +CD8+ T cells were detected at comparable frequencies (∼1.3 × 10-5) in acute and convalescent HLA-A*02:01+ patients. These frequencies were higher than those found in uninfected HLA-A*02:01+ donors (∼2.5 × 10-6), but low when compared to frequencies for influenza-specific (A2/M158) and Epstein-Barr virus (EBV)-specific (A2/BMLF1280) (∼1.38 × 10-4) populations. Phenotyping A2/S269 +CD8+ T cells from COVID-19 convalescents ex vivo showed that A2/S269 +CD8+ T cells were predominantly negative for CD38, HLA-DR, PD-1, and CD71 activation markers, although the majority of total CD8+ T cells expressed granzymes and/or perforin. Furthermore, the bias toward naïve, stem cell memory and central memory A2/S269 +CD8+ T cells rather than effector memory populations suggests that SARS-CoV-2 infection may be compromising CD8+ T cell activation. Priming with appropriate vaccines may thus be beneficial for optimizing CD8+ T cell immunity in COVID-19.


Assuntos
Betacoronavirus/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/imunologia , Antígeno HLA-A2/imunologia , Pneumonia Viral/imunologia , Linfócitos T CD4-Positivos/imunologia , Epitopos de Linfócito T , Feminino , Humanos , Memória Imunológica , Imunofenotipagem , Leucócitos Mononucleares/imunologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Pandemias , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Proteínas Virais/química , Proteínas Virais/imunologia
10.
Nat Commun ; 11(1): 4790, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963242

RESUMO

Preventing aggregation of amyloid beta (Aß) peptides is a promising strategy for the treatment of Alzheimer's disease (AD), and gold nanoparticles have previously been explored as a potential anti-Aß therapeutics. Here we design and prepare 3.3 nm L- and D-glutathione stabilized gold nanoparticles (denoted as L3.3 and D3.3, respectively). Both chiral nanoparticles are able to inhibit aggregation of Aß42 and cross the blood-brain barrier (BBB) following intravenous administration without noticeable toxicity. D3.3 possesses a larger binding affinity to Aß42 and higher brain biodistribution compared with its enantiomer L3.3, giving rise to stronger inhibition of Aß42 fibrillation and better rescue of behavioral impairments in AD model mice. This conjugation of a small nanoparticle with chiral recognition moiety provides a potential therapeutic approach for AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/efeitos dos fármacos , Ouro/farmacologia , Transtornos da Memória/tratamento farmacológico , Nanopartículas Metálicas/química , Fragmentos de Peptídeos/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Fragmentos de Peptídeos/metabolismo , Estereoisomerismo
11.
Trials ; 21(1): 769, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895056

RESUMO

OBJECTIVES: To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. TRIAL DESIGN: This is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization. EXCLUSION CRITERIA: pregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent. INTERVENTION AND COMPARATOR: The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: As a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio. RANDOMISATION: After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. BLINDING (MASKING): Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group). TRIAL STATUS: The local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28th June and is expected to end in November 2020. TRIAL REGISTRATION: The protocol is registered before starting subject recruitment under the title: "Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial" in ClinicalTrials.org with the registration number: NCT04445935 . Registered on 24 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Antitrombinas/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/terapia , Anticoagulantes/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/sangue , Estado Terminal , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Hirudinas , Humanos , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/sangue , Catar , Proteínas Recombinantes/uso terapêutico
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(7): 1023-1028, 2020 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895169

RESUMO

OBJECTIVE: To investigate the effects of stachydrine (STA) on apoptosis of Aß25-35-induced PC12 cells mimicking Alzheimer's disease and explore the mechanisms. METHODS: The differential genes of STA were analyzed based on GSE85871 data, and the target genes of STA were identified using STITCH database. PC12 cells were treated with Aß25-35 to establish a cell model of Alzheimer's disease, and the changes in cell viability and cell cycle in response to STA treatment were assessed using MTT assay and flow cytometry, respectively. RT-PCR and Western blotting were used to detect the relevant gene or protein expressions in the treated cells. RESULTS: GSE85871 data showed 37 up-regulated genes and 48 down-regulated genes in cells following treatment with STA. Analysis of the data from the STITCH database indicated that RPS8 and EED were the target genes of STA. Treatment of PC12 cells with Aß25-35 significantly lowered the cell viability (P < 0.05) and the expressions of RPS8 and EED at both the mRNA and protein levels (P < 0.05), and obviously inhibited the expression of apoptosis-related proteins Bcl-2 and p53 (P < 0.05). STA treatment of the cells significantly reversed the effect of Aß25-35 and induced cell cycle arrest in G2/M phase, causing also significantly increases in the expression levels of RPS8, EED, Bcl-2 and p53 (P < 0.05). CONCLUSIONS: STA plays an important role in inhibiting the apoptosis of PC12 cells induced by Aß25-35 possibly by regulating RPS8 and EED expression to promote the expressions of Bcl-2 and p53.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Animais , Apoptose , Sobrevivência Celular , Células PC12 , Fragmentos de Peptídeos , Ratos
14.
Medicine (Baltimore) ; 99(31): e21460, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756167

RESUMO

Volume status is a key parameter for cardiovascular-related mortality in dialysis patients. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP), myeloperoxidase, copeptin, and pro-adrenomedullin have been reported as volume markers, the relationship between body fluid status and volume markers in dialysis patients is uncertain. Therefore, we investigated the utility of volume status biomarkers based on body composition monitor (BCM) analyses.We enrolled pre-dialysis, hemodialysis (HD), and peritoneal dialysis (PD) patients and age- and gender-matched healthy Korean individuals (N = 80). BCM and transthoracic echocardiography were performed and NT-proBNP, myeloperoxidase, copeptin, and pro-adrenomedullin concentrations were measured. Relative hydration status (ΔHS, %) was defined in terms of the hydration status-to-extracellular water ratio with a cutoff of 15%, and hyperhydrated status was defined as ΔHS > 15%.Although there were no significant differences in total body water, extracellular water, or intracellular water among groups, mean amount of volume overload and hyperhydrated status were significantly higher in HD and PD patients compared with control and pre-dialysis patients. Mean amount of volume overload and hyperhydrated status were also significantly associated with higher NT-proBNP and pro-adrenomedullin levels in HD and PD patients, although not with myeloperoxidase or copeptin levels. Furthermore, they were significantly associated with cardiac markers (left ventricular mass index, ejection fraction, and left atrial diameter) in HD and PD patients compared with those in the control and pre-dialysis groups.On the basis of increased plasma NT-proBNP and pro-adrenomedullin concentrations, we might be able to make predictions regarding the volume overload status of dialysis patients, and thereby reduce cardiovascular-related mortality through appropriate early volume control.


Assuntos
Biomarcadores/sangue , Líquidos Corporais/metabolismo , Doenças Cardiovasculares/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia , Adrenomedulina/sangue , Adulto , Composição Corporal/fisiologia , Doenças Cardiovasculares/diagnóstico por imagem , Estudos de Casos e Controles , Diálise/métodos , Diálise/tendências , Ecocardiografia/métodos , Feminino , Glicopeptídeos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Diálise Peritoneal/estatística & dados numéricos , Peroxidase/sangue , Precursores de Proteínas/sangue , Diálise Renal/estatística & dados numéricos , República da Coreia/epidemiologia , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem
15.
Medicine (Baltimore) ; 99(31): e21492, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756181

RESUMO

Activation of the renin angiotensin system and renal oxidative stress (OS) are critical contributors in the progression of chronic kidney disease(CKD). Recent studies have confirmed that the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas(ACE2/Ang(1-7)/Mas) axis, the important components of renin angiotensin system, protected kidneys against damage by antagonizing angiotensin II and attenuating OS in rats with several nephropathy models, but its effect needs to be further evaluated in clinic. In this study, we aimed to detected serum ACE2/Ang (1-7)/Mas axis, OS conditions and described its clinical associations in patients with CKD at different stages.A total of 48 patients with CKD and 6 healthy controls (CT) were enrolled, and serum angiotensin converting enzyme (ACE), ACE2, Ang (1-7), 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined by ELISA. Serum extracellular glutathione peroxidase(eGSH-Px) activity and renal functions were determined by the biochemical method.Serum ACE and ACE2 levels in CKD stages 3 to 5 and serum Ang(1-7) levels in CKD stages 4 to 5 without Ang II receptor blockers treatment significantly increased compared to those in the CT group. However, ACE2 was decreased and Ang(1-7) level increased in early CKD stage with Ang II receptor blockers treatment. Higher serum 8-OHdG levels and lower eGSH-Px activity were noted in CKD stages 4 to 5. Serum 8-OHdG level was correlated with serum ACE2, Ang(1-7) expression. Estimated glomerular filtration rate (eGFR) was correlated with serum ACE, ACE2, Ang(1-7), 8-OHdG, Hcy levels and serum eGSH-Px activity. Multiple-regression analysis eGFR was predicted by ACE, Hcy, eGSH-Px, and also can be predicted by ACE2, Ang(1-7), Hcy in CT subgroup.The ACE2/Ang(1-7)/Mas axis is associated with OS, and both them were associated with eGFR in the progression of CKD. Activation of ACE2/Ang(1-7)/Mas axis may have renoprotective effect and can be a potential therapeutic target in patients with early CKD stages.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Insuficiência Renal Crônica/sangue , 8-Hidroxi-2'-Desoxiguanosina/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sistema Renina-Angiotensina/fisiologia
16.
Redox Biol ; 36: 101655, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32738789

RESUMO

Nox2 is responsible for artery dysfunction via production of reactive oxidant species. RNA viruses may activate Nox2, but it is unknown if this occurs in coronavirus 2019(Covid-19). Nox2 activation by soluble Nox2-derived peptide(sNox2-dp) was measured in patients hospitalized for Covid-19 (n = 182) and controls (n = 91). sNox2-dp values were higher in Covid-19 patients versus controls and in severe versus non severe Covid-19. Patients with thrombotic events(n = 35,19%) had higher sNox2-dp than thrombotic event-free ones. A logistic regression analysis showed that sNox2 and coronary heart disease predicted thrombotic events. Oxidative stress by Nox2 activation is associated severe disease and thrombotic events in Covid-19 patients.


Assuntos
Infecções por Coronavirus/metabolismo , NADPH Oxidase 2/metabolismo , Pneumonia Viral/metabolismo , Trombose/sangue , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Oxidase 2/química , Estresse Oxidativo , Pandemias , Fragmentos de Peptídeos/sangue , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Trombose/etiologia
17.
Front Immunol ; 11: 1714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793244

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus leading to a global health outbreak. Despite the high mortality rates from SARS-CoV-1 and Middle-East respiratory syndrome (MERS)-CoV infections, which both sparked the interest of the scientific community, the underlying physiopathology of the SARS-CoV-2 infection, remains partially unclear. SARS-CoV-2 shares similar features with SARS-CoV-1, notably the use of the angiotensin conversion enzyme 2 (ACE2) as a receptor to enter the host cells. However, some features of the SARS-CoV-2 pandemic are unique. In this work, we focus on the association between obesity, metabolic syndrome, and type 2 diabetes on the one hand, and the severity of COVID-19 infection on the other, as it seems greater in these patients. We discuss how adipocyte dysfunction leads to a specific immune environment that predisposes obese patients to respiratory failure during COVID-19. We also hypothesize that an ACE2-cleaved protein, angiotensin 1-7, has a beneficial action on immune deregulation and that its low expression during the SARS-CoV-2 infection could explain the severity of infection. This introduces angiotensin 1-7 as a potential candidate of interest in therapeutic research on CoV infections.


Assuntos
Adipocinas/imunologia , Angiotensina I/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Fragmentos de Peptídeos/imunologia , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Adipocinas/sangue , Diabetes Mellitus Tipo 2/imunologia , Humanos , Síndrome Metabólica/imunologia , Obesidade/imunologia , Pandemias , Peptidil Dipeptidase A/metabolismo
19.
BMC Infect Dis ; 20(1): 580, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762658

RESUMO

BACKGROUND: Dengue virus (DENV) causes the hospitalisation of an estimated 500,000 people every year. Outbreaks can severely stress healthcare systems, especially in rural settings. It is difficult to discriminate patients who need to be hospitalized from those that do not. Earlier work identified thrombocyte count and subsequent function as a promising prognostic marker of DENV severity. Herein, we investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using Multiplate™ multiple-electrode aggregometry to explore its potential in triage. METHODS: In this prospective cohort study all patients aged ≥13 admitted to Universitas Airlangga Hospital in Surabaya, Indonesia with a fever (≥38 °C) between 25 January and 1 August 2018 and with a clinical suspicion of DENV, were eligible for inclusion. Exclusion criteria were a thrombocyte count below 100 × 109/L and the use of any medication with a known anticoagulant effect, nonsteroidal anti-inflammatory drugs and acetyl salicylic acid. Clinical data was collected and blood was taken on admission, day 1 and day 7. Samples were tested for acute DENV, using Panbio NS1 ELISA. Platelet aggregation using ADP-, TRAP- and COL-test were presented as Area Under the aggregation Curve (AUC). Significance was tested between DENV+, probably DENV, fever of another origin, and healthy controls (HC). RESULTS: A total of 59 patients (DENV+ n = 10, DENV probable n = 25, fever other origin n = 24) and 20 HC were included. We found a significantly lower thrombocyte aggregation in the DENV+ group, compared with both HCs and the fever of another origin group (p < .001). Low ADP AUC values on baseline correlated to a longer hospital stay in DENV+ and probable DENV cases. CONCLUSION: Thrombocyte aggregation induced by Adenosine diphosphate, Collagen and Thrombin receptor activating peptide-6 is impaired in human DENV cases, compared with healthy controls and other causes of fever. This explorative study provides insights to thrombocyte function in DENV patients and could potentially serve as a future marker in DENV disease.


Assuntos
Plaquetas/metabolismo , Vírus da Dengue/imunologia , Dengue/diagnóstico , Dengue/epidemiologia , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Difosfato de Adenosina/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Colágeno/metabolismo , Dengue/virologia , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/diagnóstico , Humanos , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Agregação Plaquetária , Contagem de Plaquetas , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
20.
Nat Commun ; 11(1): 3820, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732919

RESUMO

Supercentenarians (those aged ≥110 years) are approaching the current human longevity limit by preventing or surviving major illness. Identifying specific biomarkers conducive to exceptional survival might provide insights into counter-regulatory mechanisms against aging-related disease. Here, we report associations between cardiovascular disease-related biomarkers and survival to the highest ages using a unique dataset of 1,427 oldest individuals from three longitudinal cohort studies, including 36 supercentenarians, 572 semi-supercentenarians (105-109 years), 288 centenarians (100-104 years), and 531 very old people (85-99 years). During follow-up, 1,000 participants (70.1%) died. Overall, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6, cystatin C and cholinesterase are associated with all-cause mortality independent of traditional cardiovascular risk factors and plasma albumin. Of these, low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age. Only low albumin is associated with high mortality across age groups. These findings expand our knowledge on the biology of human longevity.


Assuntos
Envelhecimento/sangue , Biomarcadores/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Albumina Sérica/análise , Inquéritos e Questionários/estatística & dados numéricos , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Feminino , Humanos , Longevidade/fisiologia , Estudos Longitudinais , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida
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