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1.
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
2.
J Chromatogr A ; 1627: 461422, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823117

RESUMO

Sialylation, an important form of glycosylation, is involved in many biological processes and plays an important role in the development of diseases. However, due to the low abundance among various glycosylation and lack of efficient enrichment method with high specificity, the study of sialylation remains a challenge. Herein, multi-histidine modified microspheres (MHM) were synthesized to enrich sialylated glycopeptides. It was found that MHM could selectively enrich sialylated glycopeptides from over 100 times of non-sialylated glycopeptides, which indicated MHM possessed good enrichment specificity towards sialylated glycopeptides. Furthermore, MHM were utilized to the large-scale analysis of protein sialylation, and 510 intact glycopeptides were identified with over 94.5% sialylated glycopeptide specificity from 4 µL human serum. The good specificity could be attributed to the synergistic effect by the electrostatic interaction and hydrophilic interaction. Hence, MHM could provide an alternative approach for the analysis of site-specific sialylation at proteome level from complex biological samples.


Assuntos
Glicopeptídeos/análise , Histidina/química , Ácido N-Acetilneuramínico/química , Sequência de Aminoácidos , Avidina/química , Fetuínas/química , Glicopeptídeos/sangue , Glicosilação , Humanos , Microesferas , Padrões de Referência , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
3.
Am J Emerg Med ; 38(9): 1910-1914, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32745922

RESUMO

PURPOSE: The purpose of this study was to investigate the clinical use of copeptin to evaluate migraine attacks in the Emergency Department. An additional aim was to detect changes in serum copeptin levels in migraine patients during attack and attack-free periods. METHODS: This prospective case-control study included 52 migraine patients and 51 healthy individuals with similar demographic characteristics. Blood samples were collected from migraine patients both in attack and attack-free periods. RESULTS: The mean copeptin levels in the patients group in the attack and attack-free periods were 689.28 and 576.68 pg/ml, respectively, whereas they were 608.68 pg/ml in the control group. There was a significant difference in the mean copeptin level in the attack period and attack-free periods (p = 0.026). The sensitivity and specificity of copeptin in detecting headache episodes in migraine patients were 58.8% and 60.7%, respectively, at a cut-off value of 388.67 pg/ml. CONCLUSION: This is the first study to investigate the diagnostic efficacy of serum copeptin levels in migraine patients. Although the diagnostic efficacy of serum copeptin levels for migraines was unsatisfactory, it could be helpful at management of migraine patients in ED.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Glicopeptídeos/sangue , Transtornos de Enxaqueca/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/diagnóstico , Estudos Prospectivos , Sensibilidade e Especificidade
4.
Folia Med Cracov ; 60(1): 5-14, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32658207

RESUMO

BACKGROUND: Today no established biomarkers are available for the early diagnosis of takotsubo syndrome and its differentiation from ST-segment elevation myocardial infarction. We hypothesized that copeptin and copeptin/NT-proBNP ratio may serve a routine marker combination for non-invasive differentiation. METHODS: The study compared the serum concentrations of copeptin, troponin I (TnI) and NT-proBNP in 19 consecutive women diagnosed with takotsubo syndrome according to the Mayo Clinic criteria and 10 consecutive women diagnosed with ST-segment elevation myocardial infarction. RESULTS: Copeptin concentrations were significantly lower in patients with takotsubo syndrome than in patients with ST-segment elevation myocardial infarction. The diagnostic accuracy to distinguish takotsubo syndrome from ST-segment elevation myocardial infarction is highest for copeptin/NTproBNP ratio, copeptin/TnI at admission ratio and copeptin alone (AUC 0.8713, 0.8538, 0.8480, respectively). CONCLUSIONS: The serum copeptin to NTproBNP ratio could be an additional tool in the non-invasive differentiation between takotsubo syndrome and ST-segment elevation myocardial infarction. However, further researches are needed.


Assuntos
Biomarcadores/sangue , Diagnóstico Precoce , Glicopeptídeos/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Cardiomiopatia de Takotsubo/diagnóstico , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Cardiomiopatia de Takotsubo/sangue
5.
West Afr J Med ; 37(3): 231-236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32476116

RESUMO

BACKGROUND: Hypertensive disorders of pregnancy associated with potentially fatal outcomes are common obstetrics occurrences. Early diagnosis, management and prediction of outcomes are challenges to be surmounted especially in developing countries. Biomarkers are emerging as useful tools for diagnosis and prognostication in varying health conditions. Elevated levels of serum copeptin and Brain Natriuretic Peptide (BNP) are associated with adverse perinatal outcomes and may serve as potential biomarkers utilized during routine antenatal care. OBJECTIVE: To determine the level and clinical value of copeptin and BNP as biomarkers of hypertensive disorders of pregnancy among Nigerian pregnant women. METHODS: This case-control study comprised 156 consenting pregnant women equally grouped into those with chronic hypertension (CH), gestational hypertension (GH), and preeclampsia (PE) as cases and normotensives as controls. Pregnant women were recruited from the antenatal clinic, University College Hospital, Nigeria. Blood pressures were measured and blood (10ml) was drawn from patients, serum and plasma obtained accordingly while other data were collected using interviewer administered questionnaire and medical records. Serum copeptin and plasma BNP levels were measured using enzyme-linked immunosorbent assay. Data was analysed with SPSS version 20.0 and statistical significance was set at p < 0.05. RESULTS: The mean levels of SBP and DBP were significantly higher in CH (155.41±2.14; 102.36±2.0 mmHg), GH (150.49±0.82; 98.67±0.56 mmHg), and PE (153.92±1.47; 98.92±0.61 mmHg), compared to controls (101.85±1.9; 66.77±1.24 mmHg). Mean serum copeptin and plasma BNP were significantly higher in women with GH (21.25±1.31pmol/L; 223.05±14.95pg/mL) and PE (22.47±1.01pmol/L; 253.99±17.69pg/mL) compared with controls (9.05±1.01pmol/L; 48.63±2.50pg/mL) (p<0.05). There was no significant difference in the mean levels of copeptin and BNP in CH compared with controls (p>0.05). The ROC curve for copeptin gave an AUC of 0.829 (p= 0.000) with a cut off value of 10.15pmol/ L while the AUC for BNP was 0.902 (p= 0.000) with a cut off value of 50.81pg/mL. CONCLUSION: Serum copeptin and plasma BNP levels were significantly higher in GH and PE and may be used as markers of hypertensive disorders of pregnancy among Nigerian pregnant women.


Assuntos
Glicopeptídeos/sangue , Hipertensão Induzida pela Gravidez/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Pré-Eclâmpsia/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/epidemiologia , Nigéria/epidemiologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/epidemiologia , Valor Preditivo dos Testes , Gravidez
6.
Arch Med Res ; 51(6): 548-555, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32505416

RESUMO

BACKGROUND: Arginine vasopressin (AVP) plays an important role in the pathophysiology of Diabetes Mellitus (DM) and its related complications like diabetic nephropathy. Copeptin is considered as a reliable surrogate biomarker of AVP. If raised levels of copeptin in diabetic patients are detected earlier, prognosis of DM can be improved by timely modulating the treatment strategy. AIMS OF THE STUDY: The study is therefore planned to assess copeptin levels in different groups of DM and in healthy controls to suggest a better and reliable biomarker for progressive stages of DM. METHODS: Subjects were recruited as controls, pre diabetes, DM without nephropathy and diabetic nephropathy. Serum copeptin levels were measured by ELISA. While, Blood Urea Nitrogen (BUN), creatinine, Glycosylated Hemoglobin (HbA1c) and spot urinary albumin creatinine ratio (UACR) were done using spectrophotometry. Statistical analysis was done using ANOVA and Pearson's correlation tests on SPSS. RESULTS: The average copeptin levels were 215.096 pg/mL. Copeptin levels were significantly elevated in subjects with positive family history of DM (p = 0.025), levels were also raised in pre diabetes kpatients (252.85 pg/mL) as compared to other groups. Copeptin levels were also correlated with HbA1c r = 0.171 (p = 0.101), BUN r = 0.244 (p = 0.007), creatinine r = 0.215 (p = 0.018), UACR r = 0.375 (p = <0.001) and GFR r = 0.215 (p = <0.019). CONCLUSION: The significant correlation of copeptin with diabetic and renal biomarkers, along with its positive association with family history of DM support its' role as an early and reliable biomarker of DM and its associated nephropathy.


Assuntos
Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Glicopeptídeos/efeitos adversos , Testes de Função Renal/métodos , Rim/patologia , Neurofisinas/metabolismo , Precursores de Proteínas/metabolismo , Vasopressinas/metabolismo , Adolescente , Adulto , Idoso , Feminino , Glicopeptídeos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
7.
Biomarkers ; 25(2): 137-143, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31902247

RESUMO

Background: Takotsubo cardiomyopathy (TTC) is a syndrome of acute non-coronary heart failure with similar symptoms and electrocardiograms to acute anterior ST-elevation myocardial infarction (STEMI). Little is known about the pathophysiology of TTC. We assessed admission plasma concentrations of biomarkers reflecting neuroendocrine response (copeptin, mid-regional-pro-adrenomedullin, pro-atrial-natriuretic-peptide, soluble thrombomodulin (sTM), syndecan-1) and inflammation (suppression-of-tumorigenicity 2 (ST2), high-sensitive C-reactive-protein) in TTC patients and compared to patients with acute anterior STEMI.Materials and methods: Twenty TTC patients were matched with 40 STEMI patients by age, gender and left ventricular ejection fraction. Blood was sampled upon hospital admission immediately before acute coronary angiography.Results: The groups had similar comorbidities. TTC patients had higher plasma concentrations of sTM: 7.94 (5.89;9.61) vs. 6.42 (5.50;7.82)ng/ml, p = 0.04 and ST2 (53 (32;157) vs. 45 (31;55)ng/ml, p = 0.008) and higher heart rate: 101 ([Formula: see text]33) vs. 76([Formula: see text]14)bpm, p = 0.0001, but lower concentrations of copeptin (10.4 (7.6;39) vs. 92.3 (13;197)pmol/l, p < 0.05) and troponin T (348 (98;759) vs. 1190 (261;4105)ng/l, p = 0.04).Conclusion: TTC patients had higher plasma concentrations of sTM and ST2, higher heart rate and lower copeptin and troponin T concentrations compared to acute anterior STEMI patients. This study contributes to the hypothesis that TTC patients have endothelial cell damage and are hemodynamically more stable than patients with acute anterior STEMI on admission.


Assuntos
Biomarcadores/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Cardiomiopatia de Takotsubo/diagnóstico , Idoso , Diagnóstico Diferencial , Células Endoteliais/patologia , Feminino , Glicopeptídeos/sangue , Frequência Cardíaca , Hemodinâmica , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Cardiomiopatia de Takotsubo/sangue , Trombomodulina/sangue , Troponina T/sangue
8.
J Chromatogr A ; 1610: 460546, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31570191

RESUMO

Selective enrichment of glycopeptides from complex sample with hydrophilic interaction liquid chromatography (HILIC) method, followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites is used extensively as a sample preparation for comprehensive glycoproteome analysis. However, the coenrichment of hydrophilic nonglycosylated peptides and the released N-glycans seriously affect the identification of deglycopeptides with nano-LC-MS/MS. Here, we developed a new method for highly efficient and specific enrichment of human plasma N-glycopeptides using HILIC-PNGaseF-HILIC workflow (HPH). The first HILIC enriches the N-glycopeptides from the complex peptide mixtures. After the enriched N-glycopeptides are deglycosylated with PNGase F, the second HILIC captures the coenrichment of hydrophilic nonglycosylated peptides and the N-glycans, and then further enriches the deglycosylated peptides. The glycopeptide enrichment efficiency can be notably improved by employing HPH, evaluated by the highly recovery (more than 93.6%) and specific capturing glycopeptides from tryptic digest of IgG and BSA up to the molar ratios of 1:200. Meanwhile, we found that the alkylated proteins with IAA can affect the enrichment efficiency for N-glycopeptides with HILIC method. Moreover, after optimism the protein digestion, this novel HPH strategy allowed for the identified 722 N-glycopeptides within 202 unique glycoproteins from 1 µL human plasma digest using PNGase F in H216O. Meanwhile, this new HPH strategy identified an average 501 N-glycopeptides within averagely 134 unique glycoproteins from 1 µL human plasma digest using PNGase F in H218O. The enhanced glycopeptide detection was promoted by a substantial depletion of nonglycosylated peptides in the second HILIC. It was found that 52.2% more N-glycosylation peptides were identified by the HPH strategy compared with the using one HILIC enrichment alone.


Assuntos
Cromatografia Líquida/métodos , Glicopeptídeos/sangue , Glicoproteínas/sangue , Proteoma/análise , Glicopeptídeos/isolamento & purificação , Glicoproteínas/isolamento & purificação , Humanos , Interações Hidrofóbicas e Hidrofílicas , Proteoma/isolamento & purificação , Proteômica
9.
Ann Lab Med ; 40(1): 7-14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31432633

RESUMO

BACKGROUND: Rapid and accurate diagnosis of acute myocardial infarction (AMI) is critical for initiating effective treatment and achieving better prognosis. We investigated the performance of copeptin for early diagnosis of AMI, in comparison with creatine kinase myocardial band (CK-MB) and troponin I (TnI). METHODS: We prospectively enrolled 271 patients presenting with chest pain (within six hours of onset), suggestive of acute coronary syndrome, at an emergency department (ED). Serum CK-MB, TnI, and copeptin levels were measured. The diagnostic performance of CK-MB, TnI, and copeptin, alone and in combination, for AMI was assessed by ROC curve analysis by comparing the area under the curve (AUC). Sensitivity, specificity, negative predictive value, and positive predictive value of each marker were obtained, and the characteristics of each marker were analyzed. RESULTS: The patients were diagnosed as having ST elevation myocardial infarction (STEMI; N=43), non-ST elevation myocardial infarction (NSTEMI; N=25), unstable angina (N=78), or other diseases (N=125). AUC comparisons showed copeptin had significantly better diagnostic performance than TnI in patients with chest pain within two hours of onset (AMI: P=0.022, ≤1 hour; STEMI: P=0.017, ≤1 hour and P=0.010, ≤2 hours). In addition, TnI and copeptin in combination exhibited significantly better diagnostic performance than CK-MB plus TnI in AMI and STEMI patients. CONCLUSIONS: The combination of TnI and copeptin improves AMI diagnostic performance in patients with early-onset chest pain in an ED setting.


Assuntos
Glicopeptídeos/sangue , Infarto do Miocárdio/diagnóstico , Doença Aguda , Idoso , Angina Instável/diagnóstico , Área Sob a Curva , Creatina Quinase Forma MB/sangue , Diagnóstico Precoce , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Estudos Prospectivos , Curva ROC , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Troponina I/sangue
10.
Mediators Inflamm ; 2019: 1939740, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31736654

RESUMO

Copeptin was found to be a stable biomarker of inflammation and stress response in cardiac, renal, metabolic, and respiratory conditions such as pneumonia. The aim of this study was to investigate the copeptin levels in biological fluids (serum and sputum supernatant) of cystic fibrosis pediatric patients during pulmonary exacerbation and remission and to investigate the possible influence of copeptin levels on disease severity and quality of life. Copeptin serum concentrations were measured in 28 pediatric cystic fibrosis (CF) patients: 13 in stable condition and 15 during pulmonary exacerbation. In 10 CF patients, copeptin was also measured in the sputum. In all the patients, we assessed complete blood count, BMI, sputum culture, lung function, and chest imaging (with Brasfield score). The severity of symptoms was assessed using the Shwachman-Kulczycki (SK) score, and the quality of life was assessed with the Cystic Fibrosis Quality of Life Questionnaire-Revised (CFQ-R). Copeptin concentrations in serum and sputum supernatant was measured using an ELISA kit. Statistical analysis was done in Statistica v.12. Serum and sputum copeptin levels were higher in CF patients during pulmonary exacerbation than in a stable period, but the differences were not significant (p = 0.58 and p = 0.13, respectively). Copeptin did not correlate significantly with any clinical, laboratory, or spirometry markers of exacerbation. There was, however, a significant inverse correlation between the serum copeptin level and symptoms severity (r = -0.77, p = 0.008) and radiological changes (r = -0.5626, p = 0.036) during pulmonary exacerbation in pediatric CF patients. Copeptin also inversely correlated with the quality of life domains in CF patients: vitality and eating habits, mostly loss of appetite (p = 0.031 and p = 0.016, respectively). Copeptin may be useful to identify patients with a higher risk of deterioration to improve their outcomes.


Assuntos
Fibrose Cística/sangue , Fibrose Cística/patologia , Glicopeptídeos/sangue , Análise de Variância , Fibrose Cística/diagnóstico por imagem , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Estudos Prospectivos , Testes de Função Respiratória , Inquéritos e Questionários
11.
BMC Pregnancy Childbirth ; 19(1): 403, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690271

RESUMO

BACKGROUND: To better understand the profound multisystem changes in maternal physiology triggered by parturition, in particular in the underexplored neuronal system, by deploying a panel of pre- vs post-delivery maternal serum biomarkers, most notably the neuronal cytoskeleton constituent neurofilament light chain (NfL). This promising fluid biomarker is not only increasingly applied to investigate disease progression in numerous brain diseases, particularly in proteopathies, but also in detection of traumatic brain injury or monitoring neuroaxonal injury after ischemic stroke. METHODS: The study was nested within a prospective cohort study of pregnant women at risk of developing preeclampsia at the University Hospital of Basel. Paired ante- and postpartum levels of progesterone, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin (CT-proAVP), and NfL were measured in 56 women with complete clinical data. RESULTS: Placental delivery significantly decreased all placental markers: progesterone 4.5-fold, PlGF 2.2-fold, and sFlt-1 1.7-fold. Copeptin and MR-proANP increased slightly (1.4- and 1.2-fold, respectively). Unexpectedly, NfL levels (median [interquartile range]) increased significantly post-partum: 49.4 (34.7-77.8) vs 27.7 (16.7-31.4) pg/ml (p < 0.0001). Antepartum NfL was the sole independent predictor of NfL peri-partum change; mode of delivery, duration of labor, clinical characteristics and other biomarkers were all unrelated. Antepartum NfL levels were themselves independently predicted only by maternal age. CONCLUSIONS: Parturition per se increases maternal serum NfL levels, suggesting a possible impact of parturition on maternal neuronal integrity.


Assuntos
Proteínas de Neurofilamentos/sangue , Parto/sangue , Gravidez de Alto Risco/sangue , Adulto , Fator Natriurético Atrial/sangue , Biomarcadores/sangue , Sistema Cardiovascular , Parto Obstétrico/métodos , Feminino , Glicopeptídeos/sangue , Humanos , Fenômenos Fisiológicos do Sistema Nervoso , Fator de Crescimento Placentário/sangue , Período Pós-Parto/sangue , Pré-Eclâmpsia/etiologia , Gravidez , Progesterona/sangue , Estudos Prospectivos , Fatores de Risco , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue
12.
Neuropeptides ; 78: 101975, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31645268

RESUMO

Vasopressin and apelin are reciprocally regulated hormones which are implicated in the pathophysiology of heart failure and the regulation of metabolism; however, little is known about their interactions under pathological conditions. In this study, we determined how post-infarct heart failure (HF) and a high fat diet (HFD) affect expression of the apelin APJ receptor (APJR) and the V1a (V1aR) and V1b (V1bR) vasopressin receptors in the hypothalamus, the heart, and the retroperitoneal adipose tissue. We performed experiments in male 4-week-old Sprague Dawley rats. The animals received either a normal fat diet (NFD) or a HFD for 8 weeks, then they underwent left coronary artery ligation to induce HF or sham surgery (SO), followed by 4 weeks of NFD or HFD. The HF rats showed higher plasma concentration of NT-proBNP and copeptin. The HF reduced the APJR mRNA expression in the hypothalamus. The APJR and V1aR protein levels in the hypothalamus were regulated both by HF and HFD, while the V1bR protein level in the hypothalamus was mainly influenced by HF. APJR mRNA expression in the heart was significantly higher in rats on HFD, and HFD affected the reduction of the APJR protein level in the right ventricle. The regulation of APJR, V1aR and V1bR expression in the heart and the retroperitoneal adipose tissue were affected by both HF and HFD. Our study demonstrates that HF and HFD cause significant changes in the expression of APJR, V1aR and V1bR, which may have an important influence on the cardiovascular system and metabolism.


Assuntos
Receptores de Apelina/metabolismo , Dieta Hiperlipídica , Insuficiência Cardíaca/metabolismo , Hipotálamo/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Receptores de Vasopressinas/metabolismo , Animais , Modelos Animais de Doenças , Glicopeptídeos/sangue , Insuficiência Cardíaca/etiologia , Masculino , Infarto do Miocárdio/complicações , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Ratos , Ratos Sprague-Dawley
13.
Stroke ; 50(12): 3632-3635, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31630623

RESUMO

Background and Purpose- Prognostic value of copeptin in acute ischemic stroke has been widely reported. This study aimed to evaluate copeptin temporal profile according to revascularization strategies and the development of brain edema and hemorrhagic transformation. Methods- Plasma copeptin and brain edema and hemorrhagic transformation assessed by computed tomography/magnetic resonance imaging were evaluated upon admission (T0), at 24 hours (T1), and between the third and fifth day of hospitalization (T2) in 34 acute ischemic stroke patients. Results- Median copeptin concentration was 50.71 pmol/L at T0, 18.31 pmol/L at T1, and 10.92 pmol/L at T2. Copeptin at T1 was higher in patients with medium/severe brain edema at T2 (32.25 versus 13.67 pmol/L; P=0.038) and hemorrhagic transformation at T1 (93.10 versus 13.67 pmol/L; P<0.003) and T2 (85.70 versus 14.45 pmol/L; P=0.024). Copeptin level drop (CopΔT1-T0) was significantly steeper in patients receiving revascularization, particularly in those undergoing combined therapy (-129.34 versus -5.43 pmol/L; P=0.038). ΔT1-T0 also correlated with Thrombolysis in Cerebral Infarction score (P<0.001). Conclusions- Copeptin resulted associated with brain edema and hemorrhagic transformation in acute ischemic stroke, and its drop at 24 hours may mirror effective brain vessel recanalization.


Assuntos
Edema Encefálico/sangue , Isquemia Encefálica/sangue , Glicopeptídeos/sangue , Hemorragias Intracranianas/sangue , Acidente Vascular Cerebral/sangue , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/epidemiologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Estudos de Coortes , Terapia Combinada , Tratamento Conservador , Feminino , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/epidemiologia , Cinética , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Trombectomia , Terapia Trombolítica , Tomografia Computadorizada por Raios X
14.
Pregnancy Hypertens ; 17: 20-27, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31487641

RESUMO

OBJECTIVE: To evaluate the combination of plasma activated endothelial microparticles (CD62e), serum Copeptin (CPP) and placental growth factor (PlGF) levels at 18-23 weeks of gestation for prediction of preeclampsia (PE) in primigravid women. METHODS: This was a nested case-control study from a prospective cohort of 1115 primigravid women attending antenatal care clinic. Plasma levels of CD62e and serum Copeptin, PlGF levels were measured by flow cytometry and ELISA, respectively. Data were presented as median (Interquartile range) and biomarker levels were compared between patients and controls using Mann-Whitney Test. Using binary logistic regression, predictive potential of a combination of biomarkers for PE prediction was determined. RESULTS: Women who developed PE 41 (3.97%) showed significantly increased levels of plasma CD62e [799.33 (546.86-1249.29) versus 384.08 (245.03-576.00), p < 0.0001], serum Copeptin [303.42 (226.01-484.18) versus 207.24 (169.73-276.46), p < 0.0001] and reduced level of PlGF [238.38 (161.36-312.62) versus 947.21 (466.7-1428.56), p < 0.0001] compared to controls at 18-23 weeks of gestation. None of the marker showed statistically significant alteration in levels in fetal growth restriction (FGR) group 68 (6.58%) compared to controls. Using binary logistic regression analysis, AUC, Sensitivity, specificity, PLR, NLR, PPV, and NPV of combination of CD62e, Copeptin and PlGF for prediction of PE at 18-23 weeks of gestation was 0.969, 92.3%, 90.3%, 9.73, 0.08, 79.17%, and 96.94%, respectively. CONCLUSION: At 18-23 weeks, Combination of CD62e microparticles, copeptin, and PlGF levels can effectively identify women at risk of developing PE later in gestation.


Assuntos
Biomarcadores/sangue , Pré-Eclâmpsia/diagnóstico , Diagnóstico Pré-Natal , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Selectina E/sangue , Feminino , Idade Gestacional , Glicopeptídeos/sangue , Humanos , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/sangue , Valor Preditivo dos Testes , Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos
15.
Pol Merkur Lekarski ; 47(279): 114-117, 2019 Sep 25.
Artigo em Polonês | MEDLINE | ID: mdl-31557142

RESUMO

Recently there has been an increasing amount of research on copeptin as a novel biomarker for stress response and homeostasis disorders in a wide spectrum of morbidities. Copeptin is a stable and easily measured surrogate marker of arginine vasopressin and is increasingly included as a part of routine patient assessment tests in selected clinical scenarios. Such tests are also performed in the perioperative period, in which complication risk assessment is of exceptional importance. This review is an attempt to appraise up to date publications on use of copeptin as a biomarker.


Assuntos
Biomarcadores , Glicopeptídeos , Homeostase , Arginina Vasopressina , Biomarcadores/sangue , Glicopeptídeos/sangue , Humanos
16.
Am J Clin Nutr ; 110(6): 1344-1352, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31562496

RESUMO

BACKGROUND: Epidemiological studies in humans show increased concentrations of copeptin, a surrogate marker of arginine vasopressin (AVP), to be associated with increased risk for type 2 diabetes. OBJECTIVES: To examine the acute and independent effect of osmotically stimulated AVP, measured via the surrogate marker copeptin, on glucose regulation in healthy adults. METHODS: Sixty subjects (30 females) participated in this crossover design study. On 2 trial days, separated by ≥7 d (males) or 1 menstrual cycle (females), subjects were infused for 120 min with either 0.9% NaCl [isotonic (ISO)] or 3.0% NaCl [hypertonic (HYPER)]. Postinfusion, a 240-min oral-glucose-tolerance test (OGTT; 75 g) was administered. RESULTS: During HYPER, plasma osmolality and copeptin increased (P < 0.05) and remained elevated during the entire 6-h protocol, whereas renin-angiotensin-aldosterone system hormones were within the lower normal physiological range at the beginning of the protocol and declined following infusion. Fasting plasma glucose did not differ between trials (P > 0.05) at baseline and during the 120 min of infusion. During the OGTT the incremental AUC for glucose from postinfusion baseline (positive integer) was greater during HYPER (401.5 ± 190.5 mmol/L·min) compared with the ISO trial (354.0 ± 205.8 mmol/L·min; P < 0.05). The positive integer of the AUC for insulin during OGTT did not differ between trials (HYPER 55,850 ± 36,488 pmol/L·min compared with ISO 57,205 ± 31,119 pmol/L·min). Baseline values of serum glucagon were not different between the 2 trials; however, the AUC of glucagon during the OGTT was also significantly greater in HYPER (19,303 ± 3939 ng/L·min) compared with the ISO trial (18,600 ± 3755 ng/L·min; P < 0.05). CONCLUSIONS: The present data indicate that acute osmotic stimulation of copeptin induced greater hyperglycemic responses during the oral glucose challenge, possibly due to greater glucagon concentrations.This study was registered at clinicaltrials.gov as NCT02761434.


Assuntos
Glicemia/metabolismo , Cloreto de Sódio/administração & dosagem , Vasopressinas/metabolismo , Adulto , Estudos Cross-Over , Feminino , Glucagon/sangue , Teste de Tolerância a Glucose , Glicopeptídeos/sangue , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Osmose , Plasma/química , Cloreto de Sódio/análise
17.
Scand J Trauma Resusc Emerg Med ; 27(1): 72, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387626

RESUMO

BACKGROUND: Dizziness is a frequent reason for visiting emergency departments (EDs). Differentiating stroke from other causes is challenging for physicians. The role of biomarkers has been poorly assessed. We evaluated whether copeptin and S100b protein (PS100b) assessment, alone or in combination, could rule out stroke in patients visiting EDs for dizziness. METHODS: We included patients 18 years of age or older, visiting the adult ED of a French university hospital for a new episode of dizziness evolving for less than 72 h. All patients underwent standardized physical examination (HINT [Head Impulse test, Nystagmus, test of skew deviation] maneuvers), copeptin and S-100b protein (PS100) measurement and injected brain imaging. Stroke diagnosis involved diffusion-weighted magnetic resonance imaging or, if not available, neurological examination and contrast brain CT scan compatible with the diagnosis. RESULTS: Of the 135 patients participating in the study, 13 (10%) had stroke. The sensitivity, specificity and positive and negative predictive values of copeptin/PS100 combination were 100% (95%CI, 77-100%), 48% (40-57%), 14% (11-27%) and 100% (94-100%), respectively. Values for copeptin alone were 77% (CI95% 0.50-0.91), 50% (CI95% 0.49-0.58), 14% (CI95% 0.08-0.24), 93% (CI95% 0.87-0.98), and for PS100 alone were 54% (CI95% 0.29-0.77), 97% (CI95% 0.92-0.99), 64% (CI95% 0.35-0.84), 95% (CI95% 0.90-0.98). CONCLUSIONS: Absence of copeptin and PS100 elevation seems to ruling out the diagnosis of stroke in patients visiting the ED for a new episode of dizziness. These results need to be confirmed in a large-scale study.


Assuntos
Tontura/diagnóstico , Serviço Hospitalar de Emergência , Glicopeptídeos/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Acidente Vascular Cerebral/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Imagem de Difusão por Ressonância Magnética/métodos , Tontura/sangue , Tontura/etiologia , Feminino , Humanos , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia
18.
Int J Nanomedicine ; 14: 4293-4307, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354261

RESUMO

Purpose: Antibodies are key reagents in the development of immunoassay. We attempted to develop high-performance CPP immunoassays using high-affinity monoclonal antibodies prepared via cytokine-assisted immunization. Methods: We used fetal liver tyrosine kinase 3 ligand (Flt3L), CC subtype chemokine ligand 20 (CCL20), and granulocyte-macrophage colony-stimulating factor (GM-CSF) to assist traditional subcutaneous immunization of preparing high-affinity monoclonal antibodies, and further to develop high-performance immunoassay methods for CPP. Results: This novel immune strategy significantly enhanced immune response against CPP. Six anti-CPP monoclonal antibodies (mAbs) with high affinity were successfully screened and selected for application in a fully automated magnetic chemiluminescence immunoassay (CLIA). This robust and rapid assay can efficiently detect CPP in the range of 1.2-1250 pmol L-1 with a detection limit of 6.25 pmol L-1. Significantly, the whole incubation process can be completed in 30 min as compared to about 4.5 hr for the control ELISA kit. Furthermore, this assay exhibited high sensitivity and specificity, low intra-assay and inter-assay coefficients of variation (CVs < 15%). The developed assay was applied in the detection of CPP in 115 random serum samples and results showed a high correlation with data obtained using a commercially available ELISA kit (correlation coefficient, 0.9737). Conclusion: Our assay could be applied in the point-of-care testing of CPP in the serum samples, and also the method developed in this study could be adopted to explore the detection and diagnosis of other biomarkers for various diseases.


Assuntos
Anticorpos Monoclonais/imunologia , Citocinas/metabolismo , Glicopeptídeos/sangue , Imunização , Imunoensaio/métodos , Medições Luminescentes/métodos , Testes Imediatos , Animais , Anticorpos Monoclonais/biossíntese , Feminino , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Nanopartículas de Magnetita/química , Camundongos Endogâmicos BALB C , Sensibilidade e Especificidade
19.
Talanta ; 204: 446-454, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357319

RESUMO

A mercaptosuccinic acid functionalized hydrophilic magnetic metal-organic framework nanocomposite (denoted as mMOF@Au-MSA) was proposed and synthesized to provide an excellent platform for glycopeptide analysis. The novel nanomaterial integrated favorable advantages such as robust magnetic response from Fe3O4 magnetic nanoparticles, large surface area contributed by MOF, abundant ultra-high hydrophilic carboxylic groups from mercaptosuccinic acid, as well as unbiased affinity toward different types of glycopeptides. This nanocomposite was successfully utilized to capture glycopeptides from standard protein digests with the high selectivity and great sensitivity of 0.5 fmol µL-1. Notably, 307 glycopeptides assigned to 96 glycoproteins were identified from only 2 µL serum of breast cancer patient. The satisfying achievement indicated that the as-prepared nanopartical had promising potential in exploring the knowledge of glycoproteins in breast cancer.


Assuntos
Glicopeptídeos/sangue , Estruturas Metalorgânicas/química , Sequência de Aminoácidos , Neoplasias da Mama/sangue , Sequência de Carboidratos , Ouro/química , Humanos , Nanopartículas de Magnetita/química , Nanocompostos/química , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Tiomalatos/química
20.
Lancet ; 394(10198): 587-595, 2019 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-31303316

RESUMO

BACKGROUND: Differential diagnosis of diabetes insipidus is challenging. The most reliable approach is hypertonic saline-stimulated copeptin measurements. However, this test is based on the induction of hypernatraemia and requires close monitoring of plasma sodium concentrations. Arginine-stimulated copeptin measurements might provide an alternative, simple, and safe test. METHODS: In this prospective diagnostic study, we recruited a development cohort from University Hospital Basel, Basel, Switzerland, and a validation cohort from five centres in Basel, Aarau, Luzern, Bern, and St Gallen, Switzerland, and the University Hospital Würzburg, Würzburg, Germany. For both cohorts, patients were eligible for inclusion if they were aged 18 years or older, were newly referred with polyuria (>50 mL/kg bodyweight per day) or had a known diagnosis of central diabetes insipidus or primary polydipsia. We also recruited a comparator cohort of healthy controls in parallel to each cohort, comprising adults (aged 18 years and older, with normal drinking habits, and no history of polyuria) and children who underwent arginine stimulation to diagnose growth hormone deficiency (children were only included in the comparator cohort to the development cohort as proof of concept). Patients and healthy controls underwent arginine stimulation with measurement of plasma copeptin at baseline and 30, 45, 60, 90, and 120 min. The primary objective in the development cohort was to determine the diagnostic accuracy of plasma copeptin concentrations to discriminate between diabetes insipidus and primary polydipsia, and in the validation cohort was to confirm those results. Adverse effects of the test were monitored in all participants, with tolerability of the test rated using a visual analogue scale (VAS) that ranged from no (0) to maximum (10) discomfort. This trial is registered with ClinicalTrials.gov, number NCT00757276. FINDINGS: Between May 24, 2013, and Jan 11, 2017, 52 patients were enrolled in the development cohort (12 [23%] with complete diabetes insipidus, nine [17%] with partial diabetes insipidus, and 31 [60%] with primary polydipsia) alongside 20 healthy adults and 42 child controls. Between Oct 24, 2017, and June 27, 2018, 46 patients were enrolled in the validation cohort (12 [26%] with complete diabetes insipidus, seven [15%] with partial diabetes insipidus, and 27 [59%] with primary polydipsia) alongside 30 healthy adult controls (two patients in this cohort were excluded from the main analysis because of early vomiting during the test). In the pooled patient and control datasets, median arginine-stimulated copeptin concentrations increased in healthy adult controls (from 5·2 pM [IQR 3·3-10·9] to a maximum of 9·8 pM [6·4-19·6]) and in participants with primary polydipsia (from 3·6 pM [IQR 2·4-5·7] to a maximum of 7·9 pM [5·1-11·8]), but only minimally in those with diabetes insipidus (2·1 pM [IQR 1·9-2·7] to a maximum of 2·5 pM [1·9-3·1]). In the development cohort, a cutoff of 3·5 pM at 60 min provided the highest diagnostic accuracy of 94% (95% CI 84-98). The accuracy of this cutoff in the validation cohort was 86% (95% CI 73-94). By pooling the data from both cohorts, an optimal accuracy of 93% (95% CI 86-97) was reached at a cutoff of 3·8 pM copeptin at 60 min (sensitivity 93%, 95% CI 86-98; specificity 92%, 95% CI 84-100). The test was safe and well tolerated, with median VAS scores of 3·5 (IQR 2-4) in patients with diabetes insipidus, 3 (2-4) in those with primary polydipsia, 1 (1-3) in healthy adults, and 1 (0-5) in healthy children in the pooled participant dataset. INTERPRETATION: Arginine-stimulated copeptin measurements are an innovative test for diabetes insipidus with high diagnostic accuracy, and could be a simplified, novel, and safe diagnostic approach to diabetes insipidus in clinical practice. FUNDING: Swiss National Science Foundation and University Hospital Basel.


Assuntos
Arginina/administração & dosagem , Diabetes Insípido Nefrogênico/diagnóstico , Glicopeptídeos/sangue , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Insípido Nefrogênico/sangue , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto Jovem
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