RESUMO
A label-free electrochemical immunosensor was developed for the rapid and sensitive detection of neuron-specific enolase (NSE). The electropolymerization of dopamine in conjunction with highly conductive carbon nanotubes offers a simple and quick platform for the direct anchoring of antibodies without the assistance of any coupling agent as well as a blocking agent. The developed immunosensor exhibited a wider detection range from 120 pM (9 ng mL-1) to 3 nM (200 ng mL-1) for NSE with a high sensitivity of 3.9 µA pM-1 cm-2 in 0.1 M phosphate-buffered saline (PBS) at physiological pH (7.4). Moreover, the short recognition time (15 min) for the antigen enabled the detection to be fast and less invasive. Additionally, the evaluation of a rate constant at various concentrations of NSE via feedback mode of scanning electrochemical microscopy (SECM) explained the profound effect of antigen concentration on the rate of flow of electrons. Therefore, the proposed immunosensor can be a promising tool for the early detection of small cell lung cancer in a very short period of time with consistent accuracy.
Assuntos
Materiais Biocompatíveis , Técnicas Biossensoriais , Indóis , Nanotubos de Carbono , Fosfopiruvato Hidratase , Polímeros , Nanotubos de Carbono/química , Fosfopiruvato Hidratase/imunologia , Fosfopiruvato Hidratase/metabolismo , Fosfopiruvato Hidratase/análise , Polímeros/química , Indóis/química , Humanos , Imunoensaio/métodos , Materiais Biocompatíveis/química , Teste de Materiais , Tamanho da Partícula , Técnicas EletroquímicasRESUMO
Assessment and prognostic value of serum uric acid (SUA) and neuron-specific enolase (NSE) on the efficacy of intravenous thrombolytic therapy in cerebral infarction. A retrospective analysis was performed on clinical data of 159 patients with acute cerebral infarction who received rt-PA intravenous thrombolytic therapy from 2015 to 2020 and patients with an mRS>2 points were assigned to the poor prognosis group and with mRS≤2 to the good prognosis group. The receiver operating characteristic curve (ROC) was used to examine the prognostic value of SUA and NSE in intravenous thrombolytic therapy for acute cerebral infarction, and logistic regression analysis was utilized to elucidate the predictive features. SUA levels were adversely correlated with prognosis, whereas NSE was positively correlated with prognosis (r=0.465 and -0.501, P=0.000 and 0.000). The ROC curve showed that the predictive accuracy of SUA was 77.4% and of NSE was 71%. SUA≤337.5 mmol/l and NSE≥24.50 ng/ml are considered viable criteria to predict the curative effect and prognostic value of intravenous thrombolytic therapy for acute cerebral infarction. SUA and NSE demonstrate great potential to accurately predict the therapeutic effect and prognosis of intravenous thrombolytic therapy for acute cerebral infarction.
Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Ácido Úrico , Prognóstico , Estudos Retrospectivos , Fibrinolíticos , Terapia Trombolítica , Infarto Cerebral/tratamento farmacológico , Fosfopiruvato HidrataseRESUMO
OBJECTIVE: Identification of the relationship between clinical and neuroimaging data and the content of serum biomarkers (damage marker - neuron-specific enolase (NSE), apoptosis - p53 protein and neuroplasticity - brain-derived neurotrophic factor (BDNF)) in acute, early and late recovery periods of ischemic stroke. MATERIAL AND METHODS: Eighty patients in the acute, early and late recovery periods of ischemic stroke, aged from 49 to 75 years, were examined. The comparison group included 20 patients with chronic cerebral ischemia, comparable to the study group. A clinical assessment was carried out on the following scales: The National Institutes of Health Stroke Scale (NIHSS), the European Stroke Scale (ESS), the modified Rankin scale, the Bartel Index and SS-QOL. In the acute, early and late recovery periods of ischemic stroke, the dynamics of biomarker levels (NSE, p53 protein, BDNF) in blood serum and brain MRI in T1, T2, FLAIR, DWI modes were quantified. RESULTS: In patients with a favorable course in the acute period of stroke, low values of the NSE level and a trend towards increased levels of serum BDNF by the 10th day of the disease were noted. For the first time, it was found that high NSE and stable BDNF levels or a tendency to their decrease were observed in the acute period in patients with an unfavorable course of ischemic stroke. In the early recovery period of ischemic stroke, a strong correlation was established between the degree of independence and disability of patients, and the levels of serum NSE and BDNF. A significant inverse correlation was proved between the severity of neurological deficit, assessed on the ESS, in the late recovery period of ischemic stroke (12 months) and the level of BDNF in blood serum (r=-0.464). CONCLUSION: The selected complex of biochemical methods allowed us to assess the severity of damage, the activity of apoptotic and compensatory neurotrophic capabilities of brain tissue in ischemic stroke, as well as their relationship with clinical and neuroimaging data. We have shown the prognostic significance of the selected markers, which will allow, with an integrated approach, more accurate prediction of the further course and outcome of stroke.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Apoptose , Biomarcadores , Fator Neurotrófico Derivado do Encéfalo , Humanos , Fosfopiruvato Hidratase , Prognóstico , Qualidade de Vida , Proteína Supressora de Tumor p53RESUMO
Aim: To investigate the clinical value of tumor markers in extrapleural tumor metastasis assessment of newly diagnosed lung cancer patients. Materials & methods: This study retrospectively analyzed 306 patients diagnosed with lung cancer accompanied by tumor metastasis. Patients were grouped into extrapleural tumor metastasis and intrapleural tumor metastasis. Seven serum tumor markers were included for analysis. Results: The area under curves of receiver operating characteristic curve based on binning decision tree algorithm were above 0.8 in both training and validation sets. A scorecard with a score below 3 suggested extrapleural tumor metastasis in newly diagnosed lung cancer patients. Conclusion: The serum tumor marker-derived model is a convenient and fast approach for extrapleural cavity metastasis assessment, which may provide positive implications in newly diagnosed lung cancer patients.
Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Pulmonares/patologia , Proteínas de Membrana/sangue , Fosfopiruvato Hidratase/sangue , Idoso , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Curva ROC , Estudos RetrospectivosRESUMO
BACKGROUND: The issue of the diagnostic significance and clinical value of neuron-specific enolase (NSE) and brain-derived neurotropic factor (BDNF) in the acute period of stroke remains controversial. Therefore, it is advisable to study the correlation of biomarkers with the clinical characteristics of stroke in the time period of early recovery. OBJECTIVE: To monitor NSE and BDNF levels in peripheral blood, to analyze the clinical and laboratory correlations in patients with ischemic stroke at the stages of medical rehabilitation in the early recovery period. MATERIAL AND METHODS: Forty-nine patients with ischemic stroke in the middle cerebral artery were examined. The observation period is 90 days. Observation Points are Day 1; Day 14; Day 45; Day 90. The National Institute of Health Stroke Scale (NIHSS), the Fugle-Meyer Scale (FMA), the Modified Rankin Scale (mRS) were administered. NSE was determined in blood serum by enzyme-linked immunosorbent assay, BDNF was analyzed on a multiplex analyzer. RESULTS AND CONCLUSION: NSEDay1 in patients was significantly higher than in the comparison group (pDay1-comparison group<0.001) with a trend to a maximum decrease on the 90th day of stroke (pDay1-90<0.001). BDNFDay1 turned out to be lower than in the comparison group (pDay1-comparison group=0.006) and significantly increased by the 14th day of the stroke (pDay1-14<0.001; pDay14-comparison group=0.637). A negative correlation was found between a decrease in NSEDay14 and an increase in BDNFDay14 (r= -0.349; p=0.05). A positive correlation was found between an increase in BDNFDay14 and a decrease in mRS scores Day90 (r=0.499, p=0.035). Outcomes in patients in group 1 (after stages I and II of rehabilitation) on the assessment scales were significantly better than in patients discharged after stage I for outpatient monitoring - group 2 (p<0.05). In group 1, BDNFDay90 did not differ from BDNFDay14 (pDay14-90-Group1=0.17), and in group 2 it was significantly lower by the end of the early recovery period (pDay14-90-Group2=0.002).
Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Encéfalo , Fator Neurotrófico Derivado do Encéfalo , Humanos , Fosfopiruvato Hidratase , Reabilitação do Acidente Vascular CerebralRESUMO
BACKGROUND: Despite all efforts, spinal cord ischemia (SCI) is a relevant and feared complication after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Besides the established correlation of motor evoked potentials (MEPs) and SCI, the usage of biomarkers for early detection of SCI intraoperatively and postoperatively after TAAA surgery is scarcely described in literature. METHODS: The methods include retrospective assessment of 33 patients (48.48% male) undergoing open and endovascular TAAA repair between January 2017 and January 2018. Levels of the biomarkers neurone-specific enolase (NSE), glial fibrillary acidic protein (GFAP), and S100 B were correlated with a decrease of the amplitude of the MEPs of more than 50%, indicating SCI. Linear mixed models were applied to test for differences in the biomarker levels between open and endovascular surgery and between different times of measurement. Post hoc analyses were performed using Tukey's multiple comparisons test. Logistic regression models were used to investigate the association between GFAP, NSE, and S100 B levels at different times and a significant decrease in MEP or in-hospital mortality. RESULTS: Altogether, 19 patients were treated by endovascular repair; 14 patients were treated by open repair; 5 patients were treated because of a type I TAAA; 7 received treatment because of a type II TAAA; 7, 10, and 4 patients received type III, IV, or V TAAA repair, respectively. In-hospital mortality was 18.18% (n = 6); 5 of these patients were treated because of symptomatic TAAA. MEP decrease could be observed in 18 cases (54.5%), with 16 (48.4%) recovering during the intervention. SCI could be observed in 9.09% (n = 3), 2 endovascular repairs leading to paraplegia and one open repair leading to paraparesis. All biomarkers showed increasing levels over time, with no statistically significant difference between open and endovascular repair. The difference in NSE and S100 B levels between the different times of measurements was statistically significant (P < 0.0001, P = 0.0017, respectively). In a univariable logistic regression analysis, no correlation with the end points "significant decrease in MEP" or "in-hospital mortality" was observed for any of the assessed biomarkers. CONCLUSIONS: SCI-related biomarkers, namely NSE and S100 B, show a relevant increase directly after open and endovascular TAAA surgery, while no clear association between these biomarker levels and an intraoperatively measurable indicator for SCI could be observed.
Assuntos
Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Proteína Glial Fibrilar Ácida/sangue , Fosfopiruvato Hidratase/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Isquemia do Cordão Espinal/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/sangue , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Biomarcadores/sangue , Implante de Prótese Vascular/mortalidade , Procedimentos Endovasculares/mortalidade , Potencial Evocado Motor , Feminino , Mortalidade Hospitalar , Humanos , Monitorização Neurofisiológica Intraoperatória , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Isquemia do Cordão Espinal/diagnóstico , Isquemia do Cordão Espinal/etiologia , Isquemia do Cordão Espinal/mortalidade , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To assess the vitreous and serum levels of neuron-specific enolase (NSE), S100B and malondialdehyde (MDA) in proliferative diabetic retinopathy (PDR) cases and investigate the correlation between preoperative and postoperative anatomical and clinical features. MATERIALS AND METHODS: The study group included patients who had pars plana vitrectomy (PPV) for PDR. The control group included non-diabetic individuals who underwent PPV surgery for vitreoretinal interface disorders. Samples of serum were taken from all participants preoperatively, while vitreous samples were taken during the PPV. Vitreous and serum levels of NSE, S100B and MDA were measured, and comparisons were made between the groups. RESULTS: The study group consisted of 56 eyes of 56 cases with PDR. The control group consisted of 20 eyes of 20 cases. The concentrations of vitreous NSE, S100B and MDA were significantly higher than the control group (p < 0.0001, p < 0.05, p < 0.001, respectively). Serum levels were statistically different for NSE and S100B (p < 0.05). CONCLUSION: Our results clearly show that vitreous levels of S100B, NSE and MDA and serum concentrations of NSE and S100B increased significantly in patients with PDR. The findings may possibly indicate neurodegeneration and oxidative stress; therefore, these markers may have a diagnostic value in patients with PDR.
Assuntos
Retinopatia Diabética/metabolismo , Malondialdeído/metabolismo , Fosfopiruvato Hidratase/metabolismo , Retina/patologia , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Corpo Vítreo/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Prognóstico , Estudos Prospectivos , Tomografia de Coerência Óptica , Vitrectomia , Adulto JovemRESUMO
The acute and chronic consequences of long-distance running on brain function have received little attention. The impact of such a hard-physical burden associated with sleep privation during such events such has never been explored in terms of neuropsychological function and brain damage. METHODS: Blood samples were collected from 4 athletes before, during and at the end of one of two races: Grand Raid de la Réunion 2017 (GRR: 165 km, elevation gain: 9529 m, 2 runners) and Trail de la Bourbon 2017 (TB: 111 km, elevation gain: 6433 m, 2 runners). Serum S100B and NSE levels were measured for each runner before, during and after the race. RESULTS: Serum S100B levels (normal range: < 0.15 µg/L) increased early during the race and remained high up to the end of the race in all 4 runners (range: 0.17-0.59 µg/L). NSE level (normal range: < 15 µg/L) increased in 3 of the 4 runners (range: 16.8-39.2 µg/L). CONCLUSIONS: This preliminary study shows the potential interest of S100B and NSE serum assessment during long-distance races. Further studies are needed to confirm these results and to investigate the origins and significance of this increase in brain injury markers.
Assuntos
Biomarcadores/sangue , Montanhismo/fisiologia , Fosfopiruvato Hidratase/sangue , Resistência Física/fisiologia , Corrida/fisiologia , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Adulto , Desempenho Atlético , Feminino , Humanos , Masculino , Fosfopiruvato Hidratase/análise , Dados Preliminares , Reunião , Subunidade beta da Proteína Ligante de Cálcio S100/análise , Fatores de TempoRESUMO
In the context of omics disciplines and especially proteomics and biomarker discovery, the analysis of a clinical sample using label-based tandem mass spectrometry (MS) can be affected by sample preparation effects or by the measurement process itself, resulting in an incorrect outcome. Detection and correction of these mistakes using state-of-the-art methods based on mixed models can use large amounts of (computing) time. MS-based proteomics laboratories are high-throughput and need to avoid a bottleneck in their quantitative pipeline by quickly discriminating between high- and low-quality data. To this end we developed an easy-to-use web-tool called QCQuan (available at qcquan.net ) which is built around the CONSTANd normalization algorithm. It automatically provides the user with exploratory and quality control information as well as a differential expression analysis based on conservative, simple statistics. In this document we describe in detail the scientifically relevant steps that constitute the workflow and assess its qualitative and quantitative performance on three reference data sets. We find that QCQuan provides clear and accurate indications about the scientific value of both a high- and a low-quality data set. Moreover, it performed quantitatively better on a third data set than a comparable workflow assembled using established, reliable software.
Assuntos
Algoritmos , Proteínas de Bactérias/isolamento & purificação , Confiabilidade dos Dados , Pectobacterium carotovorum/química , Proteômica/estatística & dados numéricos , Software , Animais , Bovinos , Cromatografia Líquida , Misturas Complexas/química , Citocromos c/isolamento & purificação , Conjuntos de Dados como Assunto , Glicogênio Fosforilase/isolamento & purificação , Internet , Fosfopiruvato Hidratase/isolamento & purificação , Proteômica/métodos , Controle de Qualidade , Coelhos , Soroalbumina Bovina/isolamento & purificação , Coloração e Rotulagem/métodos , Espectrometria de Massas em TandemRESUMO
Energy metabolism and bone homeostasis share several regulatory pathways. The AP1 transcription factor ΔFosB and leptin both regulate energy metabolism and bone, yet whether their pathways intersect is not known. Transgenic mice overexpressing ΔFosB under the control of the Enolase 2 (ENO2) promoter exhibit high bone mass, high energy expenditure, low fat mass, and low circulating leptin levels. Because leptin is a regulator of bone and ΔFosB acts on leptin-responsive ventral hypothalamic (VHT) neurons to induce bone anabolism, we hypothesized that regulation of leptin may contribute to the central actions of ΔFosB in the VHT. To address this question, we used adeno-associated virus (AAV) expression of ΔFosB in the VHT of leptin-deficient ob/ob mice and genetic crossing of ENO2-ΔFosB with ob/ob mice. In both models, leptin deficiency prevented ΔFosB-triggered reduction in body weight, increase in energy expenditure, increase in glucose utilization, and reduction in pancreatic islet size. In contrast, leptin deficiency failed to prevent ΔFosB-triggered increase in bone mass. Unlike leptin deficiency, galanin deficiency blocked both the metabolic and the bone ΔFosB-induced effects. Overall, our data demonstrate that, while the catabolic energy metabolism effects of ΔFosB require intact leptin and galanin signaling, the bone mass-accruing effects of ΔFosB require galanin but are independent of leptin. © 2019 American Society for Bone and Mineral Research.
Assuntos
Osso e Ossos/anatomia & histologia , Metabolismo Energético , Galanina/metabolismo , Hipotálamo/metabolismo , Leptina/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Animais , Peso Corporal , Deleção de Genes , Glucose/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tamanho do Órgão , Fosfopiruvato Hidratase/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismoRESUMO
OBJECTIVES: To critically review current knowledge on the positive and negative predictive value of blood biomarkers for concussion; to illustrate the clinical and biological contexts that help evaluate the use of these markers in sport-related traumatic brain injuries (TBIs). METHODS: This systematic review was performed in accordance with PRISMA guidelines. We reviewed the measurement, clinical utility, endpoint, and biological significance of blood biomarkers in concussion. RESULTS: A total of 4352 publications were identified. Twenty-six articles relating to blood biomarkers were included in the review. Four common blood biomarkers, namely S100B, tau, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), were examined. Overall, the studies showed S100B measurement and use, either acutely or at several time points, can distinguish injured from noninjured patients with an uncertain degree of utility in predicting mortality. At present, S100B has largely become an acceptable biomarker of TBI; however, studies have begun to highlight the need to incorporate clinical symptoms instead of S100B concentration in isolation on the basis of inconsistent results and lack of specificity across published studies. Further research is needed to evaluate and validate the use of tau, NSE, and GFAP as a diagnostic aid in the management of concussion and TBI. CONCLUSIONS: At present, blood biomarkers have only a limited role in the evaluation and management of concussion. Although several biomarkers of brain injury have been identified, continued research is required. S100B holds promise as the most clinically useful diagnostic biomarker. Blood biomarkers, in combination with other clinical data, such as head computed tomography, would maximize the diagnostic accuracy. The methodological limitations evident in blood biomarker research results in the need for the clinical utility of blood biomarker use in concussion to be further explored.
Assuntos
Traumatismos em Atletas/diagnóstico , Biomarcadores/sangue , Concussão Encefálica/diagnóstico , Traumatismos em Atletas/sangue , Concussão Encefálica/sangue , Proteína Glial Fibrilar Ácida/sangue , Humanos , Fosfopiruvato Hidratase/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Proteínas tau/sangueRESUMO
OBJECTIVE: Increased T2 relaxation time is often seen in temporal lobe epilepsy (TLE) with hippocampal sclerosis. Water content directly affects the effective T2 in a voxel. Our aim was to evaluate the relation between T2 values and two molecules associated with brain water homeostasis aquaporin 4 (AQP4) and chondroitin sulfate proteoglycan (CSPG), as well as cellular populations in the hippocampal region of patients with TLE. METHODS: Hippocampal T2 imaging and diffusion tensor imaging (DTI) were obtained from 42 drug-resistant patients with TLE and 20 healthy volunteers (radiologic controls, RCs). A similar protocol (ex vivo) was applied to hippocampal sections from the same TLE cases and 14 autopsy control hippocampi (histologic and radiologic controls, HRCs), and each hippocampal subfield was evaluated. Hippocampal sections from TLE cases and HRC controls were submitted to immunohistochemistry for neurons (neuron nuclei [NeuN]), reactive astrocytes (glial fibrillary acidic protein [GFAP]), activated microglia (human leukocyte antigen-D-related [HLA-DR]), polarized AQP4, and CSPG. RESULTS: Patients with TLE had higher in vivo and ex vivo hippocampal T2 relaxation time. Hippocampi from epilepsy cases had lower neuron density, higher gliosis, decreased AQP4 polarization, and increased CSPG immunoreactive area. In vivo relaxation correlated with astrogliosis in the subiculum and extracellular CSPG in the hilus. Ex vivo T2 relaxation time correlated with astrogliosis in the hilus, CA4, and subiculum, and with microgliosis in CA1. The difference between in vivo and ex vivo relaxation ratio correlated with mean diffusivity and with the immunopositive area for CSPG in the hilus. SIGNIFICANCE: Our data indicate that astrogliosis, microgliosis, and CSPG expression correlate with the increased T2 relaxation time seen in the hippocampi of patients with TLE.
Assuntos
Aquaporina 4/metabolismo , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Epilepsia do Lobo Temporal/patologia , Gliose/etiologia , Hipocampo/metabolismo , Hipocampo/patologia , Adulto , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Epilepsia do Lobo Temporal/complicações , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/patologia , Antígenos HLA/metabolismo , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Neuroglia/metabolismo , Neurônios/metabolismo , Fosfopiruvato Hidratase/metabolismo , Esclerose/diagnóstico por imagem , Estatística como Assunto , Fatores de TempoRESUMO
INTRODUCTION: The pathophysiology of spinal cord injury (SCI) has a classically bad prognosis. It has been demonstrated that human umbilical cord blood stem cells (hUCBSCs) and Melissa officinalis (MO) are useful for the prevention of neurological disease. METHODS: Thirty-six adult male rats were randomly divided into intact, sham, control (SCI), MO, hUCBSC, and MO-hUCBSC groups. Intraperitoneal injection of MO (150 mg/kg) was commenced 24 hr post-SCI and continued once a day for 14 days. Intraspinal grafting of hUCBSCs was commenced immediately in the next day. The motor and sensory functions of all animals were evaluated once a week after the commencement of SCI. Electromyography (EMG) was performed in the last day in order to measure the recruitment index. Immunohistochemistry, reverse transcription-polymerase chain reaction, and transmission electron microscopy evaluations were performed to determine the level of astrogliosis and myelination. RESULTS: The results revealed that motor function (MO-hUCBSC: 15 ± 0.3, SCI: 8.2 ± 0.37, p < .001), sensory function (MO-hUCBSC: 3.57 ± 0.19, SCI: 6.38 ± 0.23, p < .001), and EMG recruitment index (MO-hUCBSC: 3.71 ± 0.18, SCI: 1.6 ± 0.1, p < .001) were significantly improved in the MO-hUCBSC group compared with SCI group. Mean cavity area (MO-hUCBSC: 0.03 ± 0.03, SCI: 0.07 ± 0.004, p < .001) was reduced and loss of lower motor neurons (MO-hUCBSC: 7.6 ± 0.43, SCI: 3 ± 0.12, p < .001) and astrogliosis density (MO-hUCBSC: 3.1 ± 0.15, SCI: 6.25 ± 1.42, p < 0.001) in the ventral horn of spinal cord were prevented in MO-hUCBSC group compared with SCI group. CONCLUSION: The results revealed that the combination of MO and hUCBSCs in comparison with the control group has neuroprotective effects in SCI.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Melissa/química , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/cirurgia , Animais , Antígenos CD/metabolismo , Bromodesoxiuridina/metabolismo , Modelos Animais de Doenças , Eletromiografia , Potencial Evocado Motor/fisiologia , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Masculino , Melissa/fisiologia , Proteína Básica da Mielina/genética , Proteína Básica da Mielina/metabolismo , Exame Neurológico , Fosfopiruvato Hidratase/metabolismo , Ratos , Ratos Wistar , Medula Espinal/metabolismo , Medula Espinal/patologia , Medula Espinal/ultraestrutura , Fatores de TempoRESUMO
RATIONALE: We have previously identified six serum tumor markers (TMs) (carcinoembryonic antigen, carbohydrate antigen 15.3, squamous cell carcinoma-associated antigen, cytokeratin-19 fragment, neuron-specific enolase, and pro-gastrin-releasing peptide) related to the presence of lung cancer (LC). OBJECTIVES: To validate their individual performance in an independent cohort, and to explore if their combined assessment (≥1 abnormal TM value) is a more accurate marker for LC presence. METHODS: We determined these six TMs in 3,144 consecutive individuals referred to our institution by their primary care physician because of the clinical suspicion of LC. MEASUREMENTS AND MAIN RESULTS: LC was excluded in 1,316 individuals and confirmed in 1,828 patients (1,563 with non-small cell LC and 265 with small cell LC). This study validated the previously reported performance of each individual TM. We also showed that their combined assessment (≥1 abnormal TM) had a better sensitivity, specificity, negative predictive value, and positive predictive value (88.5, 82, 83.7, and 87.3%, respectively) than each TM considered individually and that it increased the diagnostic performance (area under the curve) of a clinical model that included tumor size, age, and smoking status. In patients with radiographic nodules less than 3 cm, the negative predictive value of the TM panel was 71.8%, hence providing some support for a more conservative diagnostic approach. Finally we identified two TMs (neuron-specific enolase and pro-gastrin-releasing peptide) that differentiate the risk of non-small cell LC from that of small cell LC. CONCLUSIONS: The combined assessment of a panel of six serum TMs is a more accurate marker for LC presence than these same TMs considered individually. The potential of these TMs in the diagnostic and screening settings deserves further research.
Assuntos
Neoplasias Pulmonares/sangue , Idoso , Antígenos de Neoplasias/sangue , Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Estudos de Coortes , Feminino , Humanos , Queratina-19/sangue , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Fosfopiruvato Hidratase/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Proteínas Recombinantes/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Serpinas/sangueRESUMO
The aim of this study is to evaluate the incidence and predictors of silent neuronal injury (SNI) after coronary angiography (CAG) and intervention by serial measurement of serum neuron-specific enolase (NSE) in patients presented with acute coronary syndrome (ACS). Ninety-eight consecutive patients presented with ACS and underwent CAG and intervention were included in the study. The NSE levels significantly increased after CAG and intervention compared to baseline levels (22.03 ± 27.70 and 10.08 ± 3.15 consecutively). Left ventricular ejection fraction in the SNI+ group was significantly lower than that in the SNI- group (43.71% ± 12.51%, 50.84% ± 9.34%, P = .002). Maximal creatinine kinase myocardial band, troponin I, and SYNTAX score of the SNI+ group were significantly higher than those of the SNI- group (103.83 ± 99.22, 51.92 ± 78.33, P = .006; 50.04 ± 66.18, 19.18 ± 30.50, P = .002; 103.83 ± 99.22, 51.92 ± 78.33, P = .006; and 50.04 ± 66.18, 19.18 ± 30.50, P = .002 successively). SYNTAX score and performing percutaneous coronary intervention were the independent predictors of SNI (P = .009, odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.014-1.107, P = .036, OR = 4.262, 95% CI = 1.097-16.56). Percutaneous coronary intervention and coronary artery lesion complexity may increase the risk of SNI in patients with ACS.
Assuntos
Síndrome Coronariana Aguda , Transtornos Cerebrovasculares , Angiografia Coronária/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias , Função Ventricular Esquerda , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/fisiopatologia , Síndrome Coronariana Aguda/cirurgia , Idoso , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios , Fosfopiruvato Hidratase/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Fatores de RiscoRESUMO
Schistosomiasis is a common zoonoses affecting humans. The atypical clinical symptoms, low morbidity, and low degree of infection impede diagnosis and assessment of epidemics. Detecting circulating antigens from adult worms in patients' body fluids should be diagnostically superior to examining eggs in feces. Herein, the excretory-secretory proteins of adult worms were analyzed by using 2-D protein electrophoresis and mass spectrometry. The Schistosoma japonicum enolase (Sj enolase) was identified as the most abundant excretory-secretory antigen. Purified recombinant Sj enolase was prepared, and specific monoclonal and polyclonal antibodies were raised against it. A sandwich enzyme-linked immunoassay (sandwich ELISA) was established that used the monoclonal antibody as a capture antibody and the polyclonal antibody as a detection antibody. The linear detection range was 0.7-1000 ng/ml (minimum 700 pg/ml). Sj enolase could be detected in the sera of infected rabbits and disappeared rapidly postpraziquantel treatment. The sensitivity and specificity of this sandwich ELISA to detect field serum samples of schistosomiasis were 84.61 and 95.83 %, respectively. The cross-reaction rates for clonorchiasis and paragonimiasis were 3.33 and 5 %, respectively. This ELISA assay was used to test 45 matching sera of schistosomiasis patients before treatment and at 3, 6, 9, and 12 months posttreatment. Among the sera, 88.89 % were positive before treatment. At 3, 6, 9, and 12 months postpraziquantel treatment, 93.33, 97.78, 100, and 100 % tested negative, respectively. Therefore, Sj enolase can be used to indicate active Schistosoma infection, and detecting serum Sj enolase is important for diagnosis and evaluating treatment effect.
Assuntos
Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/sangue , Fosfopiruvato Hidratase/sangue , Schistosoma japonicum/enzimologia , Esquistossomose Japônica/diagnóstico , Animais , Anticorpos Anti-Helmínticos/sangue , Anticorpos Monoclonais/imunologia , Antígenos de Helmintos/genética , Clonorchis sinensis/enzimologia , Clonorchis sinensis/imunologia , Eletroforese em Gel Bidimensional , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Paragonimus westermani/imunologia , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/imunologia , Coelhos , Schistosoma japonicum/imunologia , Sensibilidade e Especificidade , Caramujos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo-R2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that S-NF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further studies, with volume quantification of axonal injury, and a prolonged sampling time, in order to better determine the connection between NF-L and DAI.
Assuntos
Lesões Encefálicas/sangue , Lesões Encefálicas/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/análise , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Adulto , Idoso , Idoso de 80 Anos ou mais , Axônios/patologia , Dano Encefálico Crônico/epidemiologia , Dano Encefálico Crônico/etiologia , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/mortalidade , Feminino , Seguimentos , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Fosfopiruvato Hidratase/sangue , Prognóstico , Reflexo Pupilar , Estudos Retrospectivos , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Tomografia Computadorizada por Raios X , Índices de Gravidade do TraumaRESUMO
STUDY DESIGN: An analytical cohort study. OBJECTIVE: This study aimed to evaluate severity of traumatic spinal cord injury (SCI) based on the serum levels of phosphorylated form of heavy subunit of neurofilament (pNF-H), neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), which are axonal, neural cell body, and glial cell injury markers, respectively. SUMMARY OF BACKGROUND DATA: Prior studies have reported elevated serum levels of pNF-H, NSE, and GFAP as biomarkers for the detection of traumatic SCI in animals. However, in this study, these biomarkers were studied in humans and with an extended level of timing. METHODS: The study included 35 patients with SCI with a mean age of 36.5 years. All patients were evaluated using the American Spinal Injury Association Impairment Scale, followed by examinations including radiography and spinal computed tomography for determining the injury level. Serum levels of NSE, pNF-H, and GFAP were determined using enzyme-linked immunosorbent assay. RESULTS: The mean serum level of GFAP was significantly higher in patients with SCI than in the control group. Mean serum levels of pNF-H and NSE were significantly higher during 24 and 48 hours after injury in patients with SCI than in the control group. The serum level of GFAP was appropriate for estimating the severity of SCI in the first 24 hours after injury. CONCLUSION: Our findings suggest that increased serum levels of GFAP, NSE, and pNF-H can be used for the diagnosis and degree of SCI severity in trauma patients. During 48 hours after injury, estimation of serum levels of pNF-H, NSE, and GFAP, combined with neurological testing, could predict the presence of SCI and severity prior to spinal computed tomography and surgical or conservative interventions. LEVEL OF EVIDENCE: 2.
Assuntos
Biomarcadores/sangue , Proteína Glial Fibrilar Ácida/sangue , Proteínas de Neurofilamentos/sangue , Fosfopiruvato Hidratase/sangue , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos da Medula Espinal/diagnóstico , Adulto JovemRESUMO
Alzheimer's disease (AD) affects 13% of the population over the age of 65. Behavioral and neuropsychiatric symptoms are frequent and affect 80% of patients. Adult hippocampal neurogenesis, which is impaired in AD, is involved in learning and memory. It remains unclear, however, whether increasing adult neurogenesis improves behavioral symptoms in AD. We report that in the 3xTgAD mouse model of AD, chronic Wnt3a overexpression in the ventral hippocampus dentate gyrus (DG) restored adult neurogenesis to physiological levels. The restoration of adult neurogenesis led to full recovery of danger assessment impairment and the effect was blocked by ablation of neurogenesis with X-irradiation. Finally, using a bed nucleus of stria terminalis (BNST) mRNA expression array, we found that the expression of the 5-HT1A receptor in 3xTgAD mice is selectively decreased and normalized by Wnt3a overexpression in the ventral hippocampus DG, and this normalization is neurogenesis dependent. These findings indicate that reestablishing a functional population of hippocampal newborn neurons in adult AD mice rescues behavioral symptoms, suggesting that adult neurogenesis may be a promising therapeutic target for alleviating behavioral deficits in AD patients.
Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Regulação da Expressão Gênica/fisiologia , Hipocampo/metabolismo , Neurogênese/fisiologia , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Modelos Animais de Doenças , Comportamento Exploratório/fisiologia , Regulação da Expressão Gênica/genética , Vetores Genéticos/fisiologia , Hipocampo/citologia , Humanos , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação/genética , Neurônios/metabolismo , Fosfopiruvato Hidratase/metabolismo , Presenilina-1/genética , Proteína Wnt3/biossíntese , Proteína Wnt3/metabolismo , Proteínas tau/genéticaRESUMO
Staphylococcal strains (CoNS) were speciated in this study. Digests of proteins released from whole cells were converted to tryptic peptides for analysis. Liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI MS/MS, Orbitrap) was employed for peptide analysis. Data analysis was performed employing the open-source software X!Tandem which uses sequenced genomes to generate a virtual peptide database for comparison to experimental data. The search database was modified to include the genomes of the 11 Staphylococcus species most commonly isolated from man. The number of total peptides matching each protein along with the number of peptides specifically matching to the homologue (or homologues) for strains of the same species were assessed. Any peptides not matching to the species examined were considered conflict peptides. The proteins typically identified with the largest percentage of sequence coverage, number of matched peptides and number of peptides corresponding to only the correct species were elongation factor Tu (EF Tu) and enolase (Enol). Additional proteins with consistently observed peptides as well as peptides matching only homologues from the same species were citrate synthase (CS) and 1-pyrroline-5-carboxylate dehydrogenase (1P5CD). Protein markers, previously identified from gel slices, (aconitate hydratase and oxoglutarate dehydrogenase) were found to provide low confidence scores when employing whole cell digests. The methodological approach described here provides a simple yet elegant way of identification of staphylococci. However, perhaps more importantly the technology should be applicable universally for identification of any bacterial species.