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1.
Sci Rep ; 11(1): 4930, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654230

RESUMO

Multiple Biomarkers have recently been shown to be elevated in COVID-19, a respiratory infection with multi-organ dysfunction; however, information regarding the prognostic value of cardiac biomarkers as it relates to disease severity and cardiac injury are inconsistent. The goal of this meta-analysis was to summarize the evidence regarding the prognostic relevance of cardiac biomarkers from data available in published reports. PubMed, Embase and Web of Science were searched from inception through April 2020 for studies comparing median values of cardiac biomarkers in critically ill versus non-critically ill COVID-19 patients, or patients who died versus those who survived. The weighted mean differences (WMD) and 95% confidence interval (CI) between the groups were calculated for each study and combined using a random effects meta-analysis model. The odds ratio (OR) for mortality based on cardiac injury was combined from studies reporting it. Troponin levels were significantly higher in COVID-19 patients who died or were critically ill versus those who were alive or not critically ill (WMD 0.57, 95% CI 0.43-0.70, p < 0.001). Additionally, BNP levels were also significantly higher in patients who died or were critically ill (WMD 0.45, 95% CI - 0.21-0.69, p < 0.001). Cardiac injury was independently associated with significantly increased odds of mortality (OR 6.641, 95% CI 1.26-35.1, p = 0.03). A significant difference in levels of D-dimer was seen in those who died or were critically ill. CK levels were only significantly higher in those who died versus those who were alive (WMD 0.79, 95% CI 0.25-1.33, p = 0.004). Cardiac biomarkers add prognostic value to the determination of the severity of COVID-19 and can predict mortality.


Assuntos
Biomarcadores/sangue , /diagnóstico , Miocárdio/metabolismo , /epidemiologia , Cardiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Creatina Quinase/metabolismo , Estado Terminal , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , L-Lactato Desidrogenase/metabolismo , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos/análise , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
2.
PLoS One ; 16(3): e0248230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33740793

RESUMO

BACKGROUND: There is limited data on the markers of coagulation and hemostatic activation (MOCHA) profile in Coronavirus disease 2019 (COVID-19) and its ability to identify COVID-19 patients at risk for thrombotic events and other complications. METHODS: Hospitalized patients with confirmed SARS-COV-2 from four Atlanta hospitals were included in this observational cohort study and underwent admission testing of MOCHA parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer). Clinical outcomes included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, access line thrombosis, ICU admission, intubation and mortality. MAIN RESULTS: Of 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American), 45 (16%) had a thrombotic endpoint. Each MOCHA parameter was independently associated with a thrombotic event (p<0.05) and ≥ 2 abnormalities was associated with thrombotic endpoints (OR 3.3, 95% CI 1.2-8.8) as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6) and ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only ≥ 2 MOCHA abnormalities were associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4). MOCHA and D-dimer cutoffs were not associated with mortality. MOCHA with <2 abnormalities (26% of the cohort) had 89% sensitivity and 93% negative predictive value for a thrombotic endpoint. CONCLUSIONS: An admission MOCHA profile is useful to risk-stratify COVID-19 patients for thrombotic complications and more effective than isolated d-dimer for predicting risk of ICU admission and intubation.


Assuntos
Antitrombina III/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fragmentos de Peptídeos/análise , Peptídeo Hidrolases/análise , Protrombina/análise , Trombose/diagnóstico , Idoso , Área Sob a Curva , /mortalidade , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Razão de Chances , Admissão do Paciente , Curva ROC , Fatores de Risco , Taxa de Sobrevida , Trombose/complicações
3.
Microbiome ; 9(1): 12, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436102

RESUMO

BACKGROUND: Proteolysis regulation allows gut microbes to respond rapidly to dynamic intestinal environments by fast degradation of misfolded proteins and activation of regulatory proteins. However, alterations of gut microbial proteolytic signatures under complex disease status such as inflammatory bowel disease (IBD, including Crohn's disease (CD) and ulcerative colitis (UC)), have not been investigated. Metaproteomics holds the potential to investigate gut microbial proteolysis because semi-tryptic peptides mainly derive from endogenous proteolysis. RESULTS: We have developed a semi-tryptic peptide centric metaproteomic mining approach to obtain a snapshot of human gut microbial proteolysis signatures. This approach employed a comprehensive meta-database, two-step multiengine database search, and datasets with high-resolution fragmentation spectra to increase the confidence of semi-tryptic peptide identification. The approach was validated by discovering altered proteolysis signatures of Escherichia coli heat shock response. Utilizing two published large-scale metaproteomics datasets containing 623 metaproteomes from 447 fecal and 176 mucosal luminal interface (MLI) samples from IBD patients and healthy individuals, we obtain potential signatures of altered gut microbial proteolysis at taxonomic, functional, and cleavage site motif levels. The functional alterations mainly involved microbial carbohydrate transport and metabolism, oxidative stress, cell motility, protein synthesis, and maturation. Altered microbial proteolysis signatures of CD and UC mainly occurred in terminal ileum and descending colon, respectively. Microbial proteolysis patterns exhibited low correlations with ß-diversity and moderate correlations with microbial protease and chaperones levels, respectively. Human protease inhibitors and immunoglobulins were mainly negatively associated with microbial proteolysis patterns, probably because of the inhibitory effects of these host factors on gut microbial proteolysis events. CONCLUSIONS: This semi-tryptic peptide centric mining strategy offers a label-free approach to discover signatures of in vivo gut microbial proteolysis events if experimental conditions are well controlled. It can also capture in vitro proteolysis signatures to facilitate the evaluation and optimization of experimental conditions. Our findings highlight the complex and diverse proteolytic events of gut microbiome, providing a unique layer of information beyond taxonomic and proteomic abundance. Video abstract.


Assuntos
Microbioma Gastrointestinal , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/metabolismo , Proteólise , Proteômica , Tripsina/metabolismo , Adolescente , Adulto , Criança , Escherichia coli/metabolismo , Humanos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/química , Adulto Jovem
4.
Food Chem ; 340: 127923, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889212

RESUMO

Identification of glycomacropeptide (GMP) and ß-lactoglobulin (ß-lg) present in cheese whey is difficult on SDS-PAGE due to their close proximity during electrophoresis and poor sensitivity of commonly used staining dye 'coomassie brilliant blue' (CBB) towards GMP. A simple method has been developed for the detection of GMP and ß-lg by staining acrylamide gel after tricine SDS-PAGE using cationic 'stains all' dye. After staining and destaining major whey proteins, viz. ɑ-lactalbumin (ɑ-la) and ß-lg appear red while GMP stains blue. The method can be used for the identification of these macromolecules in cheese whey and the detection of adulteration of milk with rennet whey.


Assuntos
Caseínas/análise , Eletroforese em Gel de Poliacrilamida/métodos , Contaminação de Alimentos/análise , Lactoglobulinas/análise , Fragmentos de Peptídeos/análise , Animais , Caseínas/química , Quimosina/análise , Glicina/análogos & derivados , Lactoglobulinas/química , Leite/química , Fragmentos de Peptídeos/química , Corantes de Rosanilina
5.
Food Chem ; 340: 127903, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889205

RESUMO

Microbial transglutaminase (mTG) catalyses the formation of protein crosslinks, deamidating glutamine in a side-reaction. Gluten deamidation by human tissue transglutaminase is critical to activate celiac disease pathogenesis making the addition of mTG to wheat-based products controversial. The ability of mTG (0-2000 U.kg-1) to alter gluten's structure, digestibility and the deamidation state of six immunogenic gluten peptides within bread was investigated. Gluten's structure was altered when mTG exceeded 100 U.kg-1, determined by confocal microscopy, extractability and free sulfhydryl assays. The effect of mTG on six immunogenic peptides was investigated by in vitro digestion (INFOGEST) and mass spectrometry. The addition of mTG to bread (0-2000 U.kg-1) did not alter the deamidation state or digestibility of the immunogenic peptides investigated. Overall, this investigation indicated that the addition of mTG to bread does not create activated gluten peptides. This analysis provides evidence for risk assessments of mTG as a food processing aid.


Assuntos
Pão , Glutens/química , Glutens/farmacocinética , Transglutaminases/metabolismo , Pão/análise , Doença Celíaca , Digestão , Glutens/imunologia , Humanos , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/imunologia , Proteólise , Streptomyces/enzimologia , Transglutaminases/química , Triticum/química
6.
Medicine (Baltimore) ; 99(51): e23872, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371174

RESUMO

ABSTRACT: At present, the association between albumin, N-terminal pro-brain natriuretic peptide (NT-proBNP) and long-term prognosis in patients with chronic heart failure (CHF) is unclear. Therefore, the purpose of this study is to explore the relationship between albumin, NT-proBNP and all-cause mortality in CHF patients.Three hundred fifty two CHF patients were recruited in our study, and patients were divided into 2 groups according to the mean (37.16 g/L) of albumin concentration [low group (albumin < 37.16 g/L) and high group (albumin≥37.16 g/L)]. Differences between groups was compared by odds ratio (OR) and 95% confidence interval (CI).NT-proBNP in the high group was significantly lower than that in the low group at baseline [1811.50 (698.75-4037.00) vs 3479.50 (1538.50-7824.25), P < .001]. Spearman correlation analysis showed that there was a negative correlation between albumin and NT-pro BNP log10 transform (ρ= -0.217, P < .001). Furthermore, curve fitting further confirmed that albumin was negatively correlated with NT-proBNP. After a median follow-up of 1726 days, 90 patients in the high group occur all-cause mortality, and 98 patients in the low group occur all-cause mortality (46.88% vs 61.25%, OR = 0.29, 95% CI: 0.08-0.50). After adjusting for the selected confounding covariates by multivariate regression analysis, decreased albumin was still associated with increased all-cause mortality (high group vs low group: OR = 0.62, 95% CI: 0.39-0.97).Decreased albumin is associated with elevated NT-ProBNP and poor long-term prognosis in CHF patients. Clinicians need to pay enough attention to the nutritional status of CHF patients.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos/análise , Prognóstico , Albumina Sérica Humana/análise , Sobreviventes , Idoso , Estudos de Coortes , Feminino , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Retrospectivos
8.
J Proteome Res ; 19(11): 4393-4397, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-32786682

RESUMO

The detection of viral RNA by polymerase chain reaction (PCR) is currently the main diagnostic tool for COVID-19 ( Eurosurveillance 2019, 25 (3), 1). The PCR-based test, however, shows limited sensitivity, especially in the early and late stages of disease development ( Nature 2020, 581, 465-469; J. Formosan Med. Assoc. 2020, 119 (6) 1123), and is relatively time-consuming. Fast and reliable complementary methods for detecting the viral infection would be of help in the current pandemic conditions. Mass spectrometry is one of such possibilities. We have developed a mass-spectrometry-based method for the detection of the SARS CoV-2 virus in nasopharynx epithelial swabs based on the detection of the viral nucleocapsid N protein. Our approach shows confident identification of the N protein in patient samples, even those with the lowest viral loads, and a much simpler preparation procedure. Our main protocol consists of virus inactivation by heating and the addition of isopropanol and tryptic digestion of the proteins sedimented from the swabs followed by MS analysis. A set of unique peptides, produced as a result of proteolysis of the nucleocapsid phosphoprotein of SARS-CoV-2, is detected. The obtained results can further be used to create fast parallel mass-spectrometric approaches for the detection of the virus in the nasopharyngeal mucosa, saliva, sputum and other physiological fluids.


Assuntos
Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Espectrometria de Massas/métodos , Nasofaringe/virologia , Proteínas do Nucleocapsídeo/análise , Pneumonia Viral/diagnóstico , Betacoronavirus/química , Infecções por Coronavirus/virologia , Humanos , Mucosa Nasal/virologia , Pandemias , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/química , Fosfoproteínas , Pneumonia Viral/virologia , Proteômica , Carga Viral
9.
PLoS One ; 15(7): e0236740, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722706

RESUMO

Tryptic digestion of proteins followed by liquid chromatography with tandem mass spectrometry analysis is an extensively used approach in proteomics research and biopharmaceutical product characterization, owing to the high level of cleavage fidelity produced with this technique. However, nonspecific trypsin cleavages have been frequently reported and shown to be related to a number of digestion conditions and predigestion sample treatments. In this work, we reveal that, for a number of commercial trypsins, reconstitution and storage conditions can have a significant impact on the occurrence of trypsin nonspecific cleavages. We analyzed the tryptic digestion of a variety of biotherapeutics, using trypsins reconstituted under different conditions. The results indicate that, for many commercial trypsins, commonly recommended reconstitution/storage conditions (mildly acidic, e.g., 50 mM acetic acid, 1 mM HCl) can actually promote nonspecific trypsin activities, which are time dependent and can be as high as 20% in total relative abundance. In contrast, using water for reconstitution and storage can effectively limit nonspecific cleavages to 1%. Interestingly, the performances of different commercial trypsins were found to be quite distinct in their levels of nonspecific cleavages and responses to the two reconstitution conditions. Our findings demonstrate the importance of choosing the appropriate trypsin for tryptic digestion and the necessity of assessing the impact of trypsin reconstitution and storage on nonspecific cleavages. We advocate for manufacturers of commercial trypsins to reevaluate manufacturing processes and reconstitution/storage conditions to provide good cleavage specificity.


Assuntos
Ácidos/química , Fragmentos de Peptídeos/metabolismo , Proteínas/metabolismo , Proteólise , Proteômica/métodos , Tripsina/metabolismo , Humanos , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/isolamento & purificação
10.
J Proteome Res ; 19(11): 4389-4392, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-32568543

RESUMO

Mass spectrometry (MS) can deliver valuable diagnostic data that complement genomic information and allow us to increase our current knowledge of the COVID-19 disease caused by the SARS-CoV-2 virus. We developed a simple, MS-based method to specifically detect SARS-CoV-2 proteins from gargle solution samples of COVID-19 patients. The protocol consists of an acetone precipitation and tryptic digestion of proteins contained within the gargle solution, followed by a targeted MS analysis. Our methodology identifies unique peptides originating from SARS-CoV-2 nucleoprotein. Building on these promising initial results, faster MS protocols can now be developed as routine diagnostic tools for COVID-19 patients. Data are available via ProteomeXchange with identifier PXD019423.


Assuntos
Betacoronavirus/química , Infecções por Coronavirus/diagnóstico , Espectrometria de Massas/métodos , Boca/virologia , Pneumonia Viral/diagnóstico , Cromatografia Líquida de Alta Pressão , Técnicas de Laboratório Clínico , Infecções por Coronavirus/virologia , Humanos , Nucleoproteínas/análise , Nucleoproteínas/química , Pandemias , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/química , Pneumonia Viral/virologia , Proteínas Virais/análise , Proteínas Virais/química
11.
Medicine (Baltimore) ; 99(21): e20460, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481349

RESUMO

To investigate the different expression of epidermal growth factor receptor 1 (EGFR) and human epidermal growth factor receptor 2 (HER2) in gastric cancer based on tumor locations and its impact on patients survival.Gastric cancer is heterogeneous disease, recent years have established a molecular classification and described distribution of molecular subtypes in stomach. However, the difference of EGFR and HER-2 expression among tumor location is still unknown.Between January 2010 and August 2014, 2477 consecutive patients with gastric cancer were treated in our surgery department. The tumor locations were classified into 4 groups: cardia, fundus, corpus, and antrum. Based on tumor locations, the clinicopathologic characteristics, EGFR and HER-2 expression, and follow-up data were analyzed by univariant analysis and Kaplan-Meier analysis retrospectively.There were difference of gender, age, Borrmann type, pathological type, differentiation, T-stage, tumor size, gastrectomy method, and complications among the locations. The positive rate of EGFR expression in fundus was 18.18%, which was lower than cardia (46.21%), corpus (43.62%), and antrum (48.83%) (P < .001). The 5-year survival rate in EGFR positive patients was 50.8%, which was significantly lower than EGFR negative patients (64.0%, P = .021). The positive rate of HER-2 expression in cardia was 48.15%, which was significantly higher than fundus (37.5%), corpus (35.45%), and antrum (38.54%) (P = .009), but HER-2 expression did not correlate with 5-year survive (P = .548).Our results suggest that there exist difference of EGFR and HER-2 expression based on tumor locations, and the distribution of EGFR impact on patients survival. Emphasizing the role of EGFR and HER-2 in the context of location contribute to make appropriate treatment strategy and improve prognosis of gastric cancer.


Assuntos
Receptores ErbB/análise , Gastrectomia/estatística & dados numéricos , Fragmentos de Peptídeos/análise , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , China/epidemiologia , Receptores ErbB/sangue , Feminino , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/epidemiologia , Análise de Sobrevida
12.
J Surg Res ; 253: 173-184, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32361612

RESUMO

BACKGROUND: Heart chymase rather than angiotensin (Ang)-converting enzyme has higher specificity for Ang I conversion into Ang II in humans. A new pathway for direct cardiac Ang II generation has been revealed through the demonstration that Ang-(1-12) is cleaved by chymase to generate Ang II directly. Herein, we address whether Ang-(1-12), chymase messenger RNA (mRNA), and activity levels can be differentiated in human atrial tissue from normal and diseased hearts and if these measures associate with various pathologic heart conditions. MATERIALS AND METHODS: Atrial appendages were collected from 11 nonfailing donor hearts and 111 patients undergoing heart surgery for the correction of valvular heart disease, resistant atrial fibrillation, or ischemic heart disease. Chymase mRNA was analyzed by real-time polymerase chain reaction and enzymatic activity by high-performance liquid chromatography using Ang-(1-12) as the substrate. Ang-(1-12) levels were determined by immunohistochemical staining. RESULTS: Chymase gene transcripts, chymase activity, and immunoreactive Ang-(1-12) expression levels were higher in left atrial tissue compared with right atrial tissue, irrespective of cardiac disease. In addition, left atrial chymase mRNA expression was significantly higher in stroke versus nonstroke patients and in cardiac surgery patients who had a history of postoperative atrial fibrillation versus nonatrial fibrillation. Correlation analysis showed that left atrial chymase mRNA was positively related to left atrial enlargement, as determined by echocardiography. CONCLUSIONS: As Ang-(1-12) expression and chymase gene transcripts and enzymatic activity levels were positively linked to left atrial size in patients with left ventricular heart disease, an important alternate Ang II forming pathway, via Ang-(1-12) and chymase, in maladaptive atrial and ventricular remodeling in humans is uncovered.


Assuntos
Angiotensinogênio/metabolismo , Fibrilação Atrial/epidemiologia , Quimases/metabolismo , Átrios do Coração/patologia , Fragmentos de Peptídeos/metabolismo , Acidente Vascular Cerebral/epidemiologia , Idoso , Angiotensinogênio/análise , Animais , Fibrilação Atrial/patologia , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Quimases/análise , Quimases/genética , Ecocardiografia , Feminino , Perfilação da Expressão Gênica , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Átrios do Coração/cirurgia , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/cirurgia , Ventrículos do Coração/fisiopatologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Isquemia Miocárdica/cirurgia , Fragmentos de Peptídeos/análise , RNA Mensageiro/isolamento & purificação , RNA Mensageiro/metabolismo , Remodelação Ventricular
13.
Hum Pathol ; 100: 1-9, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32330484

RESUMO

Three types of intracytoplasmic inclusions immunoreactive to fibrinogen are collectively diagnosed as hepatic fibrinogen storage disease. This study aimed to better characterize ground glass (type II) and globular (type III) fibrinogen inclusions by the pathological examination of 3 cases and a literature review. Three adults (age: 32-64 years; male/female = 2:1) were unexpectedly found to have fibrinogen-positive ground glass changes (type II inclusions) by liver needle biopsy, against a background of acute hepatitis E, resolving acute cholangitis, or severe lobular hepatitis of unknown etiology. One patient also had fibrinogen-positive intracytoplasmic globules (type III inclusions) in the first biopsy, but they were not present in a second biopsy. None had coagulation abnormalities or hypofibrinogenemia. On immunostaining, both inclusions were strongly positive for not only fibrinogen but also C-reactive protein and C4d. Ultrastructurally, ground glass changes corresponded to membrane-bound cytoplasmic inclusions containing amorphous, granular material. The pathological features of type II fibrinogen inclusions were identical to those of pale bodies in hepatocellular carcinoma. The literature review suggested that type I fibrinogen inclusions characterized by a polygonal appearance are strongly associated with mutations in fibrinogen genes, coagulopathy, and family history, whereas type II/III inclusions are immunoreactive to multiple proteins and typically develop in cases of other unrelated liver diseases. In conclusion, type II and III fibrinogen inclusions do not represent a true hereditary storage disease but instead the collective retention of multiple proteins. Given the lack of clinical significance, a less specific name (e.g., pale body) may be more appropriate for those inclusions.


Assuntos
Fibrinogênio/análise , Corpos de Inclusão/química , Hepatopatias/metabolismo , Fígado/química , Erros Inatos do Metabolismo/metabolismo , Adulto , Biomarcadores/análise , Biópsia , Proteína C-Reativa/análise , Complemento C4b/análise , Feminino , Fibrinogênio/genética , Humanos , Imuno-Histoquímica , Corpos de Inclusão/genética , Corpos de Inclusão/ultraestrutura , Fígado/ultraestrutura , Hepatopatias/classificação , Hepatopatias/genética , Hepatopatias/patologia , Masculino , Erros Inatos do Metabolismo/classificação , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/patologia , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Terminologia como Assunto
14.
Respir Res ; 21(1): 83, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293449

RESUMO

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020.


Assuntos
Infecções por Coronavirus , Mortalidade Hospitalar , Peptídeo Natriurético Encefálico/análise , Pandemias , Fragmentos de Peptídeos/análise , Pneumonia Viral , Adulto , Idoso , Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Valor Preditivo dos Testes , Prognóstico , Valores de Referência , Estudos Retrospectivos , Fatores de Risco
15.
Medicina (Kaunas) ; 56(3)2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32182690

RESUMO

Background and Objectives: This study evaluated the clinical characteristics of the acute coronary syndromes (ACS) in chronic kidney disease (CKD) patients and established prognostic values of the biomarkers and echocardiography. Materials and Methods: 273 patients admitted to the cardiology department of the Clinical County Emergency Hospital of Oradea, Romania, with ACS diagnosis were studied. Two study groups were formed according to the presence of CKD (137 patients with ACS + CKD and 136 with ACS without CKD). Kidney Disease: Improving Global Outcomes (KDIGO) threshold was used to assess the stages of CKD. Results: Data regarding the medical history, laboratory findings, biomarkers, echocardiography, and coronary angiography were analysed for both groups. ACS parameters were represented by ST-segment elevation myocardial infarction (STEMI), which revealed a greater incidence in subjects without CKD (43.88%); non-ST-segment elevation myocardial infarction (NSTEMI), characteristic for the CKD group (28.47%, with statistically significance p = 0.04); unstable angina and myocardial infarction with nonobstructive coronary arteries (MINOCA). Diabetes mellitus, chronic heart failure, previous stroke, and chronic coronary syndrome were more prevalent in the ACS + CKD group (56.93%, p < 0.01; 41.61%, p < 0.01; 18.25%, p < 0.01; 45.26%, p < 0.01). N-terminal pro b-type natriuretic peptide (NT-proBNP) was statistically higher (p < 0.01) in patients with CKD; Killip class 3 was evidenced more frequently in the same group (p < 0.01). Single-vessel coronary artery disease (CAD) was statistically more frequent in the ACS without CKD group (29.41%, p < 0.01) and three-vessel CAD or left main coronary artery disease (LMCA) were found more often in the ACS + CKD group (27.01%, 14.6%). Conclusions: Extension of the CAD in CKD subjects revealed an increased prevalence of the proximal CAD, and the involvement of various coronary arteries is characteristic in these patients. Biomarkers and echocardiographic elements can outline the evolution and outcomes of ACS in CKD patients.


Assuntos
Síndrome Coronariana Aguda/complicações , Insuficiência Renal Crônica/complicações , Síndrome Coronariana Aguda/classificação , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/análise , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Insuficiência Renal Crônica/classificação , Fatores de Risco , Romênia , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue
17.
J UOEH ; 42(1): 1-12, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32213738

RESUMO

Both brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are established biomarkers that are necessary in the diagnosis and management of heart failure (HF). However, it is difficult to infer BNP concentration from NT-proBNP concentration for a clinician who is familiar with BNP. We investigated whether estimated BNP concentration from NT-proBNP has an equivalent prognostic strength compared with the actual BNP concentration in the prediction of future outcomes. We created a formula for estimating BNP concentration using multivariate analysis in a derivation cohort with known or suspected HF (n = 374). We determined whether the estimated BNP level had a similar prognostic power compared with the actual BNP and NT-proBNP levels in a validation cohort (n = 375). There was a strong correlation between log-transformed BNP and log-transformed NT-proBNP (r = 0.90) in the derivation cohort. We created two types of equation from the derivation cohort. During a median of 1 year of follow up, 49 major adverse cardiac events developed in the validation cohort. Cox proportional analysis revealed that the actual and estimated BNP levels represented equivalent and significant predictors of the future cardiovascular outcome. The estimated BNP levels calculated by our new formula showed a prognostic power similar to the actual BNP levels. This equation will be useful, especially for a physician who is not familiar with NT-proBNP testing.


Assuntos
Biomarcadores/análise , Insuficiência Cardíaca/diagnóstico , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos/análise , Estudos de Coortes , Humanos , Prognóstico
18.
J Am Soc Mass Spectrom ; 31(2): 240-248, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32031395

RESUMO

Enzymatic improvers are enzymes obtained from microbial or fungal cultures, added as technical adjuvants to flour, with the aim of improving the dough characteristics in bakery products. They are used in a low ppm range and, being technical adjuvants, can go undeclared on the label. Many types of enzymatic improvers are present on the market, such as amylases, lipases, proteases, xylanases, glucose oxidases, and others, each with a different function. Analytical methods capable of detecting these enzymes are needed, particularly for bakery companies, in order to monitor the quality of raw materials and to detect any undeclared presence. In the present work, specific peptide markers, obtained by enzymatic digestion, have been used to detect the presence of enzymatic improvers by LC-MS/MS techniques. Promising results were obtained for some enzymes acting on the carbohydrate fraction (glucoamylase, glucose oxidase, xylanase) in which amounts as low as 20 ppm could be identified in blind flour samples. For lipases and proteases the method proved to be very effective in terms of specific identification, even if less sensitive.


Assuntos
Cromatografia Líquida/métodos , Enzimas/análise , Farinha/análise , Fragmentos de Peptídeos/análise , Espectrometria de Massas em Tandem/métodos , Proteínas de Bactérias/análise , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Enzimas/química , Enzimas/metabolismo , Manipulação de Alimentos , Proteínas Fúngicas/análise , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Proteômica , Tripsina/metabolismo
19.
Clin Chim Acta ; 505: 100-107, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32084382

RESUMO

INTRODUCTION: The appropriate use of laboratory diagnostics is increasingly at stake. The aim of this study was to depict some paradigmatic examples of under- and overutilization, as well as possible solutions across Europe. METHODS: We collected six examples from five European countries where a rise or decline of orders for specific laboratory parameters was observed after organizational changes but without evidence of changes in patient collective characteristics as source of this variation. RESULTS: The collected examples were the following: 1-Germany) Switch from a Brain-Natriuretic-Peptide assay to NT-pro Brain-Natriuretic-Peptide assay, resulting in a 374% increase in these analytics; 2-Spain) Implementation of a gatekeeping strategy in tumor marker diagnostics, resulting in a 15-61% reduction of these diagnostics; 3-Croatia) Stepwise elimination of creatine-kinase-MB assay from the laboratory portfolio; 4-UK) Removal of γ-glutamyl transferase from a "liver function" profile, resulting in 82% reduction of orders; 5-Austria) Implementation of a new device for rapid Influenza-RNA detection, resulting in a 450% increase of Influenza testing; 6-Spain) Insourcing of 1,25-(OH)2-Vitamin D measurements, leading to a 378% increase of these analyses. CONCLUSION: The six paradigmatic examples described in this manuscript show that availability of laboratory resources may considerably catalyze the demand, thus underscoring that inappropriate use of laboratory resources may be commonplace in routine laboratories all across Europe and most probably beyond. They also demonstrate that the application of simple strategies may assist in overcoming this issue. We believe that laboratory specialists need to refocus on the extra-analytical parts of the testing process and engage more in interdisciplinary patient-care.


Assuntos
Testes Diagnósticos de Rotina/estatística & dados numéricos , Prescrição Inadequada/estatística & dados numéricos , Laboratórios/estatística & dados numéricos , Biomarcadores Tumorais/análise , Creatina Quinase Forma MB/análise , Europa (Continente) , Humanos , Hidroxicolecalciferóis/análise , Influenza Humana/sangue , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos/análise , gama-Glutamiltransferase/análise
20.
J Neurosci ; 40(7): 1581-1593, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31915254

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disorder, resulting in the progressive decline of cognitive function in patients. Familial forms of AD are tied to mutations in the amyloid precursor protein, but the cellular mechanisms that cause AD remain unclear. Inflammation and amyloidosis from amyloid ß (Aß) aggregates are implicated in neuron loss and cognitive decline. Inflammation activates the protein-tyrosine phosphatase 1B (PTP1B), and this could suppress many signaling pathways that activate glycogen synthase kinase 3ß (GSK3ß) implicated in neurodegeneration. However, the significance of PTP1B in AD pathology remains unclear. Here, we show that pharmacological inhibition of PTP1B with trodusquemine or selective ablation of PTP1B in neurons prevents hippocampal neuron loss and spatial memory deficits in a transgenic AD mouse model with Aß pathology (hAPP-J20 mice of both sexes). Intriguingly, while systemic inhibition of PTP1B reduced inflammation in the hippocampus, neuronal PTP1B ablation did not. These results dissociate inflammation from neuronal loss and cognitive decline and demonstrate that neuronal PTP1B hastens neurodegeneration and cognitive decline in this model of AD. The protective effect of PTP1B inhibition or ablation coincides with the restoration of GSK3ß inhibition. Neuronal ablation of PTP1B did not affect cerebral amyloid levels or plaque numbers, but reduced Aß plaque size in the hippocampus. In summary, our preclinical study suggests that targeting PTP1B may be a new strategy to intervene in the progression of AD.SIGNIFICANCE STATEMENT Familial forms of Alzheimer's disease (AD) are tied to mutations in the amyloid precursor protein, but the cellular mechanisms that cause AD remain unclear. Here, we used a mouse model expressing human amyloid precursor protein bearing two familial mutations and asked whether activation of a phosphatase PTP1B participates in the disease process. Systemic inhibition of this phosphatase using a selective inhibitor prevented cognitive decline, neuron loss in the hippocampus, and attenuated inflammation. Importantly, neuron-targeted ablation of PTP1B also prevented cognitive decline and neuron loss but did not reduce inflammation. Therefore, neuronal loss rather than inflammation was critical for AD progression in this mouse model, and that disease progression could be ameliorated by inhibition of PTP1B.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/fisiologia , Memória Espacial/fisiologia , Peptídeos beta-Amiloides/análise , Animais , Colestanos/farmacologia , Modelos Animais de Doenças , Feminino , Glicogênio Sintase Quinase 3 beta/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Humanos , Inflamação , Resistência à Insulina , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Proteínas do Tecido Nervoso/antagonistas & inibidores , Fragmentos de Peptídeos/análise , Placa Amiloide/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteínas Recombinantes/metabolismo , Memória Espacial/efeitos dos fármacos , Espermina/análogos & derivados , Espermina/farmacologia
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