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1.
Food Chem ; 327: 127002, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32438262

RESUMO

This study was designed to investigate proteome changes in Japanese puffer fish (Takifugu rubripes) during short- and long-term frozen storage. In total, 1484 proteins were quantified, and 164 proteins were identified as differential abundance proteins (DAPs) in Japanese puffer fish from two frozen storage treatment groups (14 days and 60 days) compared with the fresh control group. Correlation analysis between the DAPs and quality traits of the puffer fish muscle showed that 106 proteins were correlated closely with colour and texture (hardness, elasticity, and chewiness). Bioinformatics analysis revealed and Western blot analysis verified that Putative prothymosin alpha species, Bridging integrator 3, NADH: the ubiquinone oxidoreductase subunit and Mx species are candidate biomarkers for puffer fish properties. This study offers valuable evidence to improve the quality control and monitoring of Japanese puffer fish during transportation and storage.


Assuntos
Biomarcadores/análise , Produtos Pesqueiros/análise , Proteínas de Peixes/análise , Takifugu , Animais , Cor , Biologia Computacional/métodos , Análise de Alimentos/métodos , Qualidade dos Alimentos , Armazenamento de Alimentos , Congelamento , Músculo Esquelético/química , Precursores de Proteínas/análise , Timosina/análogos & derivados , Timosina/análise
2.
Proc Natl Acad Sci U S A ; 117(19): 10609-10613, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32341146

RESUMO

Autism spectrum disorder (ASD) is a brain disorder characterized by social impairments. ASD is currently diagnosed on the basis of behavioral criteria because no robust biomarkers have been identified. However, we recently found that cerebrospinal fluid (CSF) concentration of the "social" neuropeptide arginine vasopressin (AVP) is significantly lower in pediatric ASD cases vs. controls. As an initial step in establishing the direction of causation for this association, we capitalized upon a rare biomaterials collection of newborn CSF samples to conduct a quasi-prospective test of whether this association held before the developmental period when ASD first manifests. CSF samples had been collected in the course of medical care of 0- to 3-mo-old febrile infants (n = 913) and subsequently archived at -70 °C. We identified a subset of CSF samples from individuals later diagnosed with ASD, matched them 1:2 with appropriate controls (n = 33 total), and quantified their AVP and oxytocin (OXT) concentrations. Neonatal CSF AVP concentrations were significantly lower among ASD cases than controls and individually predicted case status, with highest precision when cases with comorbid attention-deficit/hyperactivity disorder were removed from the analysis. The associations were specific to AVP, as ASD cases and controls did not differ in neonatal CSF concentrations of the structurally related neuropeptide, OXT. These preliminary findings suggest that a neurochemical marker of ASD may be present very early in life, and if replicated in a larger, prospective study, this approach could transform how ASD is detected, both in behaviorally symptomatic children, and in infants at risk for developing it.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Transtorno Autístico/diagnóstico , Vasopressinas/análise , Arginina Vasopressina/análise , Arginina Vasopressina/líquido cefalorraquidiano , Transtorno do Espectro Autista/líquido cefalorraquidiano , Transtorno Autístico/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Registros Médicos , Neuropeptídeos , Neurofisinas/análise , Neurofisinas/líquido cefalorraquidiano , Ocitocina , Estudos Prospectivos , Precursores de Proteínas/análise , Precursores de Proteínas/líquido cefalorraquidiano , Comportamento Social , Vasopressinas/líquido cefalorraquidiano
3.
Comput Biol Chem ; 84: 107168, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31791808

RESUMO

The cyclotides are the largest known family of cyclic proteins, which are found in several plant families including Violaceae. They are circular bioactive peptides consisting of 28-37 amino acids, which possess a cyclic cystine knot (CCK) motif and could be useful in biotechnology and drug design as scaffolds for peptide-based drugs. This study describes our finding of a potentially novel gene transcript from the petals of the Iranian Viola tricolor (V. tricolor) flowers. This study is based on the cDNA screening method employed for isolation of cyclotide precursor genes and in silico analysis. Our study resulted in the finding of a novel cyclotide-like precursor from V. tricolor, which is documented in the NCBI by GenBank accession number: KP065812. The in silico analysis revealed that there are lots of similar sequences in many other plant families and they all exhibit some different features from previously discovered cyclotide precursors. The differences occur particularly in the main cyclotide domain that exists without the usual CCK structure. All of these hypothetical precursors have a conserved ER-signal sequence, a Cysteine (C)-rich sequence forming two zinc finger motifs and a cyclotide-like region containing several conserved elements including two highly conserved C residues. In conclusion, using the cDNA screening method we found a potentially new cyclotide-like precursor gene and in silico studies revealed its significant characteristics that may open up a new research line on the distribution and evolution of cyclotides.


Assuntos
Ciclotídeos/análise , Proteínas de Plantas/análise , Precursores de Proteínas/análise , Viola/química , Sequência de Aminoácidos , Ciclotídeos/química , Ciclotídeos/genética , Flores/química , Genes de Plantas , Irã (Geográfico) , Folhas de Planta/química , Proteínas de Plantas/química , Proteínas de Plantas/genética , Precursores de Proteínas/química , Precursores de Proteínas/genética , Alinhamento de Sequência , Análise de Sequência de DNA
4.
Dis Markers ; 2019: 2804091, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781297

RESUMO

Introduction: Zonulin is a protein that reversibly modulates the permeability of tight junction of the small intestine wall. As the serum concentration of "zonulin family peptides" (ZFPs) is considered to be a sensitive and useful marker of intestinal wall permeability, its serum level may affect the volume of ascites fluid and change in gut microbiota. The aim of the study was to assess the association between concentrations of ZFPs in serum and ascites in relation to the severity of liver cirrhosis. Methods: The preliminary study included 24 adult patients diagnosed with alcoholic or viral liver cirrhosis. 18 healthy adult subjects were enrolled as the control group. In patients and controls, there were measured serum and ascites (only in patients) ZFPs, serum bilirubin, creatinine, alanine aminotransferase, total protein, and C-reactive protein (CRP). Results: Cirrhotic patients had lower serum hemoglobin (11.6 vs. 14.3 mg/dL; p < 0.001), platelet count (178 vs. 305 × 103/mm3; p < 0.01), total protein and albumin (58.6 vs. 74.3 g/dL; p < 0.001, 26.6 vs. 42.3 g/dL; p < 0.001, respectively), and serum ZFPs (30.5 vs. 62.0 ng/mL; p < 0.001) in comparison to controls. In patients with cirrhosis serum bilirubin, C-reactive protein level and INR were higher than in controls (3.07 vs. 0.96 mg/dL; 36.9 vs. 5 mg/L; 1.53 vs. 0.95; p < 0.001, respectively). Patients with low ZFP levels were characterized with lower ascites ZFP levels (0.25 vs. 16.4 ng/mL; p < 0.001) and ascites/serum index (0.011 vs. 0.462; p < 0.001). There were negative correlations between ascites ZFPs and platelet count (R = -0.497; p < 0.01) and positive correlation with INR (R = 0.640; p < 0.001). ZFP index positively correlated with platelet count (R = 0.726; p < 0.001) and negatively with INR (R = -0.392; p = 0.06). Conclusions: Decrease serum ZFP levels seem to reflect their decreased liver synthesis but not increased gut permeability in patients with liver cirrhosis. The physiologically low level of ZFPs in transudate is increased in exudate.


Assuntos
Líquido Ascítico/metabolismo , Biomarcadores/análise , Haptoglobinas/análise , Cirrose Hepática/patologia , Fragmentos de Peptídeos/análise , Precursores de Proteínas/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença
5.
BMC Endocr Disord ; 19(1): 128, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775768

RESUMO

BACKGROUND: Nerves and neurotrophic growth factors are emerging promoters of cancer growth. The precursor for Nerve Growth Factor (proNGF) is overexpressed in thyroid cancer, but its potential role as a clinical biomarker has not been reported. Here we have examined the value of proNGF as a serum and biopsy-rinse biomarker for thyroid cancer diagnosis. METHODS: Patients presenting for thyroid surgery or biopsy were enrolled in separate cohorts examining serum (n = 204, including 46 cases of thyroid cancer) and biopsy-rinse specimens (n = 188, including 26 cases of thyroid cancer). ProNGF levels in clinical samples were analysed by ELISA. Univariate and multivariate statistical analyses were used to compare proNGF levels with malignancy status and clinicopathological parameters. RESULTS: ProNGF was not detected in the majority of serum samples (176/204, 86%) and the detection of proNGF was not associated with thyroid cancer diagnosis. In the few cases where proNGF was detected in the serum, thyroidectomy did not affect proNGF concentration, demonstrating that the thyroid was not the source of serum proNGF. Intriguingly, an association between hyperthyroidism and serum proNGF was observed (OR 3.3, 95% CI 1.6-8.7 p = 0.02). In biopsy-rinse, proNGF was detected in 73/188 (39%) cases, with no association between proNGF and thyroid cancer. However, a significant positive association between follicular lesions and biopsy-rinse proNGF was found (OR 3.3, 95% CI 1.2-8.7, p = 0.02). CONCLUSIONS: ProNGF levels in serum and biopsy-rinse are not increased in thyroid cancer and therefore proNGF is not a clinical biomarker for this condition.


Assuntos
Biomarcadores Tumorais/análise , Biópsia , Fator de Crescimento Neural/análise , Fator de Crescimento Neural/sangue , Precursores de Proteínas/análise , Precursores de Proteínas/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
6.
Clin Chem ; 65(12): 1543-1553, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31672853

RESUMO

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients remains a challenge, especially in China. We sought to create an online calculator of serum biomarkers to detect HCC among patients with chronic hepatitis B (CHB). METHODS: Participants with HBV-HCC, CHB, HBV-related liver cirrhosis (HBV-LC), benign hepatic tumors, and healthy controls (HCs) were recruited at 11 Chinese hospitals. Potential serum HCC biomarkers, protein induced by vitamin K absence or antagonist-II (PIVKA-II), α-fetoprotein (AFP), lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and α-l-fucosidase (AFU) were evaluated in the pilot cohort. The calculator was built in the training cohort via logistic regression model and validated in the validation cohort. RESULTS: In the pilot study, PIVKA-II and AFP showed better diagnostic sensitivity and specificity compared with AFP-L3 and AFU and were chosen for further study. A combination of PIVKA-II and AFP demonstrated better diagnostic accuracy in differentiating patients with HBV-HCC from patients with CHB or HBV-LC than AFP or PIVKA-II alone [area under the curve (AUC), 0.922 (95% CI, 0.908-0.935), sensitivity 88.3% and specificity 85.1% for the training cohort; 0.902 (95% CI, 0.875-0.929), 87.8%, and 81.0%, respectively, for the validation cohort]. The nomogram including AFP, PIVKA-II, age, and sex performed well in predicting HBV-HCC with good calibration and discrimination [AUC, 0.941 (95% CI, 0.929-0.952)] and was validated in the validation cohort [AUC, 0.931 (95% CI, 0.909-0.953)]. CONCLUSIONS: Our results demonstrated that a web-based calculator including age, sex, AFP, and PIVKA-II accurately predicted the presence of HCC in patients with CHB. CLINICALTRIALSGOV IDENTIFIER: NCT03047603.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Hepatite B/complicações , Adulto , Idoso , Algoritmos , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Biomarcadores/análise , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , China , Feminino , Hepatite B/sangue , Vírus da Hepatite B , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Precursores de Proteínas/análise , Precursores de Proteínas/sangue , Protrombina/análise , Curva ROC , Sensibilidade e Especificidade , alfa-Fetoproteínas/análise , alfa-L-Fucosidase/análise , alfa-L-Fucosidase/sangue
7.
Medicina (Kaunas) ; 55(10)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640273

RESUMO

BACKGROUND AND OBJECTIVES: The causative factors or conditions leading to increased intestinal permeability (IIP) have only been partly elucidated, suggesting excessive zonulin release to be a key factor among them. Likewise, it is known that athletic activity predisposes individuals towards the development of IIP; however, little is understood about the nature of this phenomenon. We decided to test the actual coincidence between IIP and increased stool zonulin (ISZ) in actively training athletes. Materials and Methods: We compared intestinal permeability tested with lactulose/mannitol differential absorption (lactulose/mannitol (L/M) test) and zonulin concentration in stool in 20 professional athletes (PRO), 9 amateur athletes (AMA), and 9 non-athletes (CTR). Results: The results confirmed that professional athletic activity showed significant positive association with intestinal permeability. ISZ was observed exclusively in athletes (CTR vs. AMA vs. PRO, respectively, 0% vs. 22% vs. 55%), and its prevalence was significantly higher in PRO than CTR. When we divided the participants into four categories related to exceeding the upper reference limits for both tested parameters (ISZ + or - and IIP + or -), significant differences were found between CTR and PRO; however, no significant differences were found between CTR and AMA or AMA and PRO. Conclusions: Our trial confirmed previous findings that professional athletic activity predisposes individuals to IIP. We also demonstrated that although ISZ was associated with intense training, there was no statistically significant association between ISZ and IIP in the tested group of professional athletes, which suggests the existence of additional mechanisms causing IIP.


Assuntos
Atletas , Fezes/química , Haptoglobinas/análise , Mucosa Intestinal/metabolismo , Permeabilidade , Precursores de Proteínas/análise , Adulto , Água Corporal , Pesos e Medidas Corporais , Exercício Físico/fisiologia , Haptoglobinas/metabolismo , Humanos , Lactulose/metabolismo , Masculino , Manitol/metabolismo , Precursores de Proteínas/metabolismo , Estatísticas não Paramétricas , Urinálise , Circunferência da Cintura/fisiologia , Adulto Jovem
8.
Crit Care ; 23(1): 335, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665092

RESUMO

BACKGROUND: The performance of blood biomarkers (mid-regional proadrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and lactate) and clinical scores (Sequential Organ Failure Assessment (SOFA), National Early Warning Score (NEWS), and quick SOFA) was compared to identify patient populations at risk of delayed treatment initiation and disease progression after presenting to the emergency department (ED) with a suspected infection. METHODS: A prospective observational study across three EDs. Biomarker and clinical score values were calculated upon presentation and 72 h, and logistic and Cox regression used to assess the strength of association. Primary outcomes comprised of 28-day mortality prediction and delayed antibiotic administration or intensive care (ICU) admission, whilst secondary outcomes identified subsequent disease progression. RESULTS: Six hundred eighty-four patients were enrolled with hospitalisation, ICU admission, and infection-related 28-day mortality rates of 72.8%, 3.4%, and 4.4%, respectively. MR-proADM and NEWS had the strongest association with hospitalisation and the requirement for antibiotic administration, whereas MR-proADM alone had the strongest association with ICU admission (OR [95% CI]: 5.8 [3.1 - 10.8]) and mortality (HR [95% CI]: 3.8 [2.2 - 6.5]). Patient subgroups with high MR-proADM concentrations (≥ 1.77 nmol/L) and low NEWS (< 5 points) values had significantly higher rates of ICU admission (8.1% vs 1.6%; p < 0.001), hospital readmission (18.9% vs. 5.9%; p < 0.001), infection-related mortality (13.5% vs. 0.2%; p < 0.001), and disease progression (29.7% vs. 4.9%; p < 0.001) than corresponding patients with low MR-proADM concentrations. ICU admission was delayed by 1.5 [0.25 - 5.0] days in patients with high MR-proADM and low NEWS values compared to corresponding patients with high NEWS values, despite similar 28-day mortality rates (13.5% vs. 16.5%). Antibiotics were withheld in 17.4% of patients with high MR-proADM and low NEWS values, with higher subsequent rates of ICU admission (27.3% vs. 4.8%) and infection-related hospital readmission (54.5% vs. 14.3%) compared to those administered antibiotics during ED treatment. CONCLUSIONS: Patients with low severity signs of infection but high MR-proADM concentrations had an increased likelihood of subsequent disease progression, delayed antibiotic administration or ICU admission. Appropriate triage decisions and the rapid use of antibiotics in patients with high MR-proADM concentrations may constitute initial steps in escalating or intensifying early treatment strategies.


Assuntos
Antibacterianos/administração & dosagem , Biomarcadores/análise , Adrenomedulina/análise , Adrenomedulina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Área Sob a Curva , Biomarcadores/sangue , Proteína C-Reativa/análise , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/sangue , Pró-Calcitonina/análise , Pró-Calcitonina/sangue , Modelos de Riscos Proporcionais , Estudos Prospectivos , Precursores de Proteínas/análise , Precursores de Proteínas/sangue , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Sepse/tratamento farmacológico , Sepse/psicologia , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Tempo para o Tratamento
9.
J Korean Med Sci ; 34(17): e133, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31050223

RESUMO

BACKGROUND: There have been few studies to evaluate the prognostic implications of guideline-directed therapy according to the temporal course of heart failure. This study assessed the relationship between adherence to guideline-directed therapy at discharge and 60-day clinical outcomes in de novo acute heart failure (AHF) and acute decompensated chronic heart failure (ADCHF) separately. METHODS: Among 5,625 AHF patients who were recruited from a multicenter cohort registry of Korean Acute Heart Failure, 2,769 patients with reduced ejection fraction were analyzed. Guideline-directed therapies were defined as the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), ß-blocker, and mineralocorticoid receptor antagonist. RESULTS: In de novo AHF, ACEI or ARB reduced re-hospitalization (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.34-0.95), mortality (HR, 0.41; 95% CI, 0.24-0.69) and composite endpoint (HR, 0.52; 95% CI, 0.36-0.77) rates. Beta-blockers reduced re-hospitalization (HR, 0.62; 95% CI, 0.41-0.95) and composite endpoint (HR, 0.65; 95% CI, 0.47-0.90) rates. In ADCHF, adherence to ACEI or ARB was associated with only mortality and ß-blockers with composite endpoint. CONCLUSION: The prognostic implications of adherence to guideline-directed therapy at discharge were more pronounced in de novo heart failure. We recommend that guideline-directed therapy be started as early as possible in the course of heart failure with reduced ejection fraction.


Assuntos
Fidelidade a Diretrizes , Insuficiência Cardíaca/diagnóstico , Doença Aguda , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Fator Natriurético Atrial/análise , Estudos de Coortes , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Alta do Paciente , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Precursores de Proteínas/análise , Sistema de Registros , Taxa de Sobrevida
10.
Crit Care ; 23(1): 140, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31018868

RESUMO

Overuse of empiric antibiotic therapy in the ICU is responsible for promoting the dissemination of multidrug-resistant (MDR) bacteria. Shortened antibiotic treatment duration could contribute to palliating the emergence of MDR. Uncertainty about patient evolution is a major concern for deciding to stop antibiotics. Biomarkers could represent a complementary tool to identify those patients for whom antibiotic treatment could be safely discontinued. The biomarker most extensively studied to guide antibiotic withdrawal is procalcitonin (PCT), but its real impact on decreasing the duration of antibiotic treatment is a matter of controversy. Combining biomarkers to rule out complicated outcomes in sepsis patients could represent a better option. Some candidate biomarkers, including mid-regional proadrenomedullin, the percentage of human leukocyte antigen DR (HLA-DR)-positive monocytes, means of fluorescence intensities of HLA-DR on monocytes, interleukin-7 receptor expression levels, immunoglobulin M levels in the serum or the absence of increased proteolysis, have already demonstrated the potential to exclude the risk of progression to septic shock, nosocomial infections, and mortality when tested along the sepsis course. Other promising biomarkers to rule out complicated outcomes are neutrophil protease activity, the adaptive/coagulopathic signatures identified by whole transcriptome analysis by Sweeney et al., and the SRS1 signature identified by Davenport et al. In conclusion, there are a number of promising biomarkers involved in proteolytic, vascular, immunological, and coagulation alterations that could be useful to build composed endotypes to predict uncomplicated outcomes in sepsis. These endotypes could help to identify patients deserving the discontinuation of antibiotics.


Assuntos
Antibacterianos/administração & dosagem , Biomarcadores Farmacológicos/análise , Sepse/tratamento farmacológico , Fatores de Tempo , Adrenomedulina/análise , Adrenomedulina/sangue , Antibacterianos/uso terapêutico , Biomarcadores Farmacológicos/sangue , Humanos , Unidades de Terapia Intensiva/organização & administração , Pró-Calcitonina/análise , Pró-Calcitonina/sangue , Precursores de Proteínas/análise , Precursores de Proteínas/sangue , Resultado do Tratamento
11.
BMC Infect Dis ; 19(1): 161, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764769

RESUMO

BACKGROUND: A reduction in duration of antibiotic therapy is crucial in minimizing the development of antimicrobial resistance, drug-related side effects and health care costs. The minimal effective duration of antimicrobial therapy for febrile urinary tract infections (fUTI) remains a topic of uncertainty, especially in male patients, those of older age or with comorbidities. Biomarkers have the potential to objectively identify the optimal moment for cessation of therapy. METHODS: A secondary analysis of a randomized placebo-controlled trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlands. Women and men aged ≥18 years with a diagnosis of fUTI were randomly assigned to receive antibiotic treatment for 7 or 14 days. Patients indicated to receive antimicrobial treatment for more than 14 days were excluded from randomization. The biomarkers procalcitonin (PCT), mid-regional proadrenomedullin (MR-proADM), and C-reactive protein (CRP) were compared in their ability to predict clinical cure or failure through the 10-18 day post-treatment visit. RESULTS: Biomarker concentrations were measured in 249 patients, with a clinical cure rate of 94% in the 165 randomized and 88% in the 84 non-randomized patients. PCT, MR-proADM and CRP concentrations did not differ between patients with clinical cure and treatment failure, and did not predict treatment outcome, irrespective of 7 or 14 day treatment duration (ROCAUC 0.521; 0.515; 0.512, respectively). PCT concentrations at presentation were positively correlated with bacteraemia (τ = 0.33, p < 0.001) and presence of shaking chills (τ = 0.25, p < 0.001), and MR-proADM levels with length of hospital stay (τ = 0.40, p < 0.001), bacteraemia (τ = 0.33, p < 0.001), initial intravenous treatment (τ = 0.22, p < 0.001) and time to defervescence (τ = 0.21, p < 0.001). CRP did not display any correlation to relevant clinical parameters. CONCLUSIONS: Although the biomarkers PCT and MR-proADM were correlated to clinical parameters indicating disease severity, they did not predict treatment outcome in patients with community acquired febrile urinary tract infection who were treated for either 7 or 14 days. CRP had no added value in the management of patients with fUTI. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov [ NCT00809913 ; December 16, 2008] and trialregister.nl [ NTR1583 ; December 19, 2008].


Assuntos
Adrenomedulina/sangue , Biomarcadores Farmacológicos/sangue , Proteína C-Reativa/metabolismo , Infecções Comunitárias Adquiridas/diagnóstico , Febre/diagnóstico , Pró-Calcitonina/sangue , Precursores de Proteínas/sangue , Infecções Urinárias/diagnóstico , Adrenomedulina/análise , Idoso , Antibacterianos/uso terapêutico , Biomarcadores Farmacológicos/análise , Proteína C-Reativa/análise , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Feminino , Febre/sangue , Febre/tratamento farmacológico , Febre/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Pró-Calcitonina/análise , Prognóstico , Precursores de Proteínas/análise , Estudos Retrospectivos , Resultado do Tratamento , Infecções Urinárias/sangue , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia
12.
Crit Care ; 23(1): 40, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736862

RESUMO

BACKGROUND: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. METHODS: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. RESULTS: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. CONCLUSIONS: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.


Assuntos
Biomarcadores/análise , Diagnóstico Precoce , Infecções/diagnóstico , Adolescente , Adrenomedulina/análise , Adrenomedulina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Proteína C-Reativa/análise , Progressão da Doença , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Inglaterra , Feminino , França , Humanos , Itália , Ácido Láctico/análise , Ácido Láctico/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/sangue , Modelos de Riscos Proporcionais , Precursores de Proteínas/análise , Precursores de Proteínas/sangue , Espanha , Estatísticas não Paramétricas , Suécia , Suíça , Estudos de Validação como Assunto
13.
Am J Emerg Med ; 37(6): 1013-1019, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30122508

RESUMO

INTRODUCTION: It is difficult to differentiate whether coronary or non-coronary causes in patients with elevated troponin I (TnI) in emergency department (ED). The aim of this study was to develop a clinical decision tool for differentiating a coronary cause in the patients with elevated TnI. METHODS: This was a retrospective observational study that enrolled consecutive ED patients. Patients were included in the study if they were ≥16 years of age, had admitted through ED with a medical illness, and TnI levels at initial evaluation in the ED were ≥0.2 ng/mL. Patients diagnosed with ST elevation myocardial infarction or congestive heart failure were excluded. Coronary angiography, electrocardiogram, laboratory results, echocardiography, and clinical characteristics were analyzed. RESULTS: Among the included 1441 patients, 603 and 838 patients were categorized into an acute coronary syndrome (ACS) group and non-acute coronary syndrome (non-ACS) group, respectively. The ratio of N-terminal pro-Btype natriuretic peptide (NT-proBNP) to TnI was significantly higher in the non-ACS group compared to the ACS group. The AUC of NT-proBNP/TnI (0.805, 95% CI, 0.784-0.826) was significantly superior to that of NT-proBNP/creatinine kinase-MB, TnI, and NT-proBNP. The patients of the non-ACS group with high levels of TnI and BNP showed more critically ill manifestation at the time of presentation and higher mortality. CONCLUSION: NT-proBNP/TnI may help to distinguish medical patients with elevated TnI whether the elevated TnIs were caused from ACSs or from conditions other than ACS.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Fator Natriurético Atrial/classificação , Precursores de Proteínas/classificação , Troponina I/classificação , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Fator Natriurético Atrial/análise , Fator Natriurético Atrial/sangue , Biomarcadores/análise , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Precursores de Proteínas/análise , Precursores de Proteínas/sangue , Estudos Retrospectivos , Medição de Risco/métodos , Troponina I/análise , Troponina I/sangue
14.
J Med Virol ; 91(5): 886-889, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30570750

RESUMO

Latency associated peptide (LAP) is a protein expressed on the membrane of some regulatory T cells (Treg). LAP+ Treg have a greater immunomodulatory effect than that of their negative counterparts. In this study, we presented the data on the proportion of LAP+ Treg out of CD4+ cells in mice with viral myocarditis, which we believed was more sensitive and specific than that of the ratio of total Treg in CD4+ cells. Comparing with the previously recognized total Treg, LAP+ Treg was a better biomarker on myocardial inflammation.


Assuntos
Infecções por Coxsackievirus/diagnóstico , Miocardite/diagnóstico , Peptídeos/análise , Precursores de Proteínas/análise , Subpopulações de Linfócitos T/química , Linfócitos T Reguladores/química , Fator de Crescimento Transformador beta/análise , Animais , Infecções por Coxsackievirus/patologia , Modelos Animais de Doenças , Contagem de Linfócitos , Masculino , Camundongos Endogâmicos BALB C , Miocardite/patologia
15.
World J Surg ; 43(4): 1085-1093, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30478681

RESUMO

BACKGROUND: The aim was to evaluate the prognoses and clinicopathological characteristics of solitary hepatocellular carcinoma (HCC) originating from the caudate lobe (HCC-CL). METHODS: We analyzed 584 patients with a solitary tumor <10 cm from January 1990 to November 2014. Patients were classified into a caudate lobe group (CL; n = 39) and a non-caudate lobe group (NCL; n = 545). We investigated the prognoses and clinicopathological characteristics of solitary HCC-CL. We compared the surgical procedures performed in these cases. RESULTS: HCC-CL had a similar rate of portal venous invasion (PVI) as HCC-NCL (21% vs. 19%); however, the frequency of tumor thrombus at the first branch of the portal vein (PV) or extension to the trunk or the opposite side of the PV was significantly higher in HCC-CL (8% vs. 2%). HCC-CL had similar OS rates compared to HCC-NCL; however, HCC-CL showed significantly poorer RFS. Although there were no significant differences among the three surgical procedures, blood loss and complication rates tended to be higher in cases who underwent an isolated caudate lobectomy. Tumor size ≥5 cm, PVI, and liver fibrosis or cirrhosis (LF or LC) were independent unfavorable factors for both OS and RFS. PIVKA-II ≥120 mAU/ml was an independent unfavorable factor for RFS. CONCLUSION: HCC-CL presented a poorer RFS rate. Patients with a tumor size ≥5 cm, PIVKA-II ≥120 mAU/ml, portal venous invasion, and LF or LC should be diligently followed up as these cases have a high risk of recurrence.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/patologia , Idoso , Biomarcadores/análise , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia/efeitos adversos , Humanos , Cirrose Hepática/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Veia Porta/patologia , Complicações Pós-Operatórias , Prognóstico , Precursores de Proteínas/análise , Protrombina/análise , Estudos Retrospectivos , Fatores de Risco , Trombose Venosa/patologia
16.
Peptides ; 108: 7-13, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30121362

RESUMO

Cardiac myocytes express the cholecystokinin gene (CCK) at propeptide level. We recently reported that cardiac CCK expression is acutely regulated by isoprenaline in a porcine model. The regulation of CCK expression after myocardial infarction, in exercise, and in severe heart failure is, however, unknown. Cardiac tissue was obtained from healthy new-born and adolescent farm pigs. Myocardial infarction was induced by coronary artery occlusion in adult minipigs. Healthy male subjects performed a 3-hour exercise test, and patients with severe heart failure referred for right heart catheterization were included. Extracts of porcine cardiac tissue and human plasma were analysed with specific proCCK radioimmunoassays. Cardiac proCCK expression shifted from the right atrium in new-born piglets to include the left atrium in adolescent pigs. Regional proCCK expression in the adolescent pig heart was mainly confined to the atria without different expression in sinus node tissue. In adult minipigs with myocardial infarction, no changes in overall left ventricular function or proCCK expression were observed after 8 weeks. In healthy adults, proCCK in circulation increased markedly during exercise in parallel with pro-B-type natriuretic peptide. Finally, patients with severe heart failure displayed markedly increased proCCK - but not CCK - concentrations in plasma. Taken together, our data shows that regional proCCK expression reflects haemodynamic changes in the mammalian heart. The data supports the notion that cardiac CCK expression resembles that of cardiac natriuretic peptides in atria. The ventricular content of proCCK, however, differs from natriuretic peptides and suggests a distinct secretory pathway in ventricular cardiomyocytes.


Assuntos
Colecistocinina/genética , Insuficiência Cardíaca/metabolismo , Hemodinâmica , Miocárdio/metabolismo , Precursores de Proteínas/genética , Animais , Colecistocinina/análise , Colecistocinina/sangue , Feminino , Regulação da Expressão Gênica , Coração/fisiopatologia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/análise , Precursores de Proteínas/sangue , Suínos
17.
Expert Opin Biol Ther ; 18(sup1): 199-203, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30063862

RESUMO

OBJECTIVES: We reevaluated a lyophilized sample of thymosin fraction 5, stored for 37 years at room temperature, by high-resolution mass spectrometry in terms of stability and yet uncharacterized polypeptides that could be biological important substances. METHODS: A top-down proteomic platform based on high-performance liquid chromatography (HPLC) coupled to high-resolution LTQ-Orbitrap mass spectrometry (MS) was applied to molecular characterization of polypeptides present in thymosin fraction 5. RESULTS: We detected more than 100 monoisotopic masses corresponding to thymosin ß4 and truncated forms of ubiquitin, prothymosin α, thymosin ß4, and thymosin ß9. Additionally, we discovered a new polypeptide present in thymosin fraction 5 and identified it as intact SH3 domain-binding glutamic acid-rich-like protein 3. CONCLUSION: In spite of the well-known proteolytic processes inherent to the preparation of thymosin fraction 5, still uncharacterized polypeptides as well as truncated forms of already well-known thymosins are present in fraction 5 after long-term storage. Therefore, continuing characterization of thymosin fraction 5 is even nowadays highly promising.


Assuntos
Espectrometria de Massas/métodos , Timosina/análogos & derivados , Animais , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Liofilização , Humanos , Precursores de Proteínas/análise , Precursores de Proteínas/isolamento & purificação , Proteômica/métodos , Timosina/análise , Timosina/química , Timosina/isolamento & purificação , Fatores de Tempo , Ubiquitina/análise , Ubiquitina/isolamento & purificação
18.
Andrology ; 6(6): 854-859, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29984477

RESUMO

BACKGROUND: A-kinase anchor protein 4 (AKAP4) and its precursor pro-AKAP4 are two major proteins in spermatozoa of rodents and mammals. Although researchers have characterized the AKAP4 expression in various species, the protein's expression in humans has not been described in detail. OBJECTIVES: The objective of this study was to characterize human pro-AKAP4 more precisely (notably the definition of its localization and expression levels in human spermatozoa and testes). MATERIALS AND METHODS: pro-AKAP4 protein expression levels were assessed by Western blotting. The pro-AKAP4's localization in spermatozoa and testes was determined using immunofluorescence staining and immunogold electron microscopy. Furthermore, pro-AKAP4 protein expression levels were assessed in a series of 77 human semen samples, and associations with semen parameters were evaluated. RESULTS: Western blotting revealed a 100-kDa band in human sperm protein extracts. The pro-AKAP4 was immunolocalized in the fibrous sheath of the flagellum of ejaculated spermatozoa and in elongated spermatids in human testes. A Western blot analysis of 77 normozoospermic semen samples evidenced striking differences in pro-AKAP4 levels from one to another sample (median [interquartile range] integrated optical density = 305 [49-1038]). No correlations were found for pro-AKAP4 levels on one hand and semen volume, sperm concentration, sperm count, sperm motility, or sperm morphology on the other (p > 0.05 for all). However, pro-AKAP4 levels were positively correlated with motility after density gradient centrifugation of the semen (r = 0.224, p = 0.049). DISCUSSION: AKAP4 protein might be activated as an alternative pathway to rescue sperm motility. In human spermatozoa, pro-AKAP4 might therefore be a 'reservoir' of mature AKAP4. CONCLUSION: This study generated new knowledge about pro-AKAP4 in human semen, which may be of interest in the management of male infertility.


Assuntos
Proteínas de Ancoragem à Quinase A/análise , Precursores de Proteínas/análise , Espermatozoides/química , Biomarcadores/análise , Western Blotting , Forma Celular , Centrifugação com Gradiente de Concentração , Imunofluorescência , Humanos , Masculino , Microscopia Imunoeletrônica , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides/ultraestrutura
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