RESUMEN
N-Acetyl-D-mannosamine (ManNAc) is an endogenous monosaccharide and precursor of N-acetylneuraminic acid (Neu5Ac), a critical sialic acid. ManNAc is currently under clinical development to treat GNE myopathy, a rare muscle-wasting disease. In this randomized, open-label, 2-sequence, crossover study, 16 healthy women and men were administered a single oral dose of ManNAc under fasting and fed conditions. Blood samples were collected for 48 hours after dosing for quantification of plasma ManNAc and Neu5Ac concentrations. Noncompartmental pharmacokinetic and deconvolution analyses were performed using baseline-corrected plasma concentration data. Administration of ManNAc in the fed state resulted in a 1.6-fold increase in ManNAc exposure, compared to fasting conditions. A concurrent increase in Neu5Ac exposure was observed in the presence of food. Deconvolution analysis indicated that the findings were attributed to prolonged absorption rather than an enhanced rate of absorption. The impact of food on ManNAc pharmacokinetics was greater in women than men (fed/fasted area under the concentration-time curve from time 0 to infinity mean ratio: 198% compared to 121%). It is hypothesized that the presence of food slows gastric emptying, allowing a gradual release of ManNAc into the small intestine, translating into improved ManNAc absorption. The results suggest that taking ManNAc with food may enhance its therapeutic activity and/or reduce the daily dosage requirement.
Asunto(s)
Estudios Cruzados , Interacciones Alimento-Droga , Hexosaminas , Ácido N-Acetilneuramínico , Humanos , Femenino , Masculino , Adulto , Hexosaminas/administración & dosificación , Hexosaminas/farmacocinética , Administración Oral , Adulto Joven , Ácido N-Acetilneuramínico/administración & dosificación , Ácido N-Acetilneuramínico/farmacocinética , Ácido N-Acetilneuramínico/sangre , Persona de Mediana Edad , Ayuno , Voluntarios Sanos , Área Bajo la Curva , Absorción IntestinalRESUMEN
BACKGROUND: It is known that SARS-CoV-2 mostly infects the respiratory system causing pneumonia; although it can also affect the gastrointestinal tract (GIT), which covered with a bi-layer of mucus rich in glycosylated proteins that terminated by sialic acid. Therefore; this study aimed to evaluate serum total sialic acid (TSA) in moderate COVID-19 patients with and without GIT manifestations. METHODS: A total of 161 moderate COVID-19 patients without and with GIT manifestations and 50 controls were enrolled into our study. Serum electrolytes levels were measured by using colorimetric or turbidmetric commercial assay kits, while the level of serum TSA was measured by using a commercial ELISA kit. RESULTS: Our results showed that serum TSA level was highly significantly increased in moderate COVID-19 patients with GIT manifestations (81.43 ± 8.91) when compared with controls (61.24 ± 6.41) or even moderate COVID-19 patients without GIT manifestations (69.46 ± 7.03). ROC curve analysis showed that AUC for TSA is 0.84 with 76.2 % sensitivity and 73.7 % specificity in discrimination between moderate COVID-19 patients with and without GIT manifestations. Serum potassium and sodium levels were highly significantly decreased in moderate COVID-19 patients with GIT manifestations when compared with controls or even moderate COVID-19 patients without GIT manifestations; while serum calcium level was found to be significantly decreased in moderate COVID-19 patients with GIT manifestations when compared with controls. CONCLUSION: Finally, we can conclude that SA plays a crucial role in the pathogenesis of GIT complications associated with COVID-19 and could be a potential biomarker for the COVID-19 gastrointestinal complications.
Asunto(s)
COVID-19/patología , Tracto Gastrointestinal/patología , Ácido N-Acetilneuramínico/sangre , Adulto , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Tracto Gastrointestinal/virología , Humanos , Masculino , Persona de Mediana Edad , Moco/metabolismo , Moco/virología , SARS-CoV-2RESUMEN
BACKGROUND: Cardiac sialylation is involved in a variety of physiological processes in the heart. Altered sialylation has been implicated in heart failure (HF) mice. However, its role in patients with HF is unclear, and the potential effect of modulation of cardiac sialylation is worth exploring. METHODS: We first assessed the association between plasma N-acetylneuraminic acid levels and the incidence of adverse cardiovascular events in patients with HF over a median follow-up period of 2 years. Next, immunoblot analysis and lectin histochemistry were performed in cardiac tissue to determine the expression levels of neuraminidases and the extent of cardiac desialylation. Finally, the therapeutic impact of a neuraminidase inhibitor was evaluated in animal models of HF. RESULTS: Among 1699 patients with HF, 464 (27%) died of cardiovascular-related deaths or underwent heart transplantation. We found that the elevated plasma N-acetylneuraminic acid level was independently associated with a higher risk of incident cardiovascular death and heart transplantation (third tertile adjusted hazard ratio, 2.11 [95% CI, 1.67-2.66], P<0.001). In addition, in cardiac tissues from patients with HF, neuraminidase expression was upregulated, accompanied by desialylation. Treatment with oseltamivir, a neuraminidase inhibitor, in HF mice infused with isoproterenol and angiotensin II significantly inhibited desialylation and ameliorated cardiac dysfunction. CONCLUSIONS: This study uncovered a significant association between elevated plasma N-acetylneuraminic acid level and an increased risk of a poor clinical outcome in patients with HF. Our data support the notion that desialylation represents an important contributor to the progression of HF, and neuraminidase inhibition may be a potential therapeutic strategy for HF.
Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Corazón/efectos de los fármacos , Ácido N-Acetilneuramínico/sangre , Ácido N-Acetilneuramínico/uso terapéutico , Anciano , Animales , Femenino , Corazón/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Volumen Sistólico/efectos de los fármacos , Volumen Sistólico/fisiologíaRESUMEN
Endometriosis is an inflammatory disease which diagnostics is difficult and often invasive, therefore non-invasive diagnostics methods and parameters are needed for endometriosis detection. The aim of our study was to analyse the glycosylation of native serum IgG and IgG isolated from sera of women classified as: with endometriosis, without endometriosis but with some benign ginecological disease, and control group of healthy women, in context of its utility for differentiation of advanced endometriosis from the group of healthy women. IgG sialylation and galactosylation/agalactosylation degree was determined using specific lectins: MAA and SNA detecting sialic acid α2,3- and α2,6-linked, respectively, RCA-I and GSL-II specific to terminal Gal and terminal GlcNAc, respectively. The results of ROC and cluster analysis showed that the serum IgG MAA-reactivity, sialylation and agalactosylation factor may be used as supplementary parameters for endometriosis diagnostics and could be taken into account as a useful clinical tool to elucidate women with high risk of endometriosis development. Additionally, we have shown that the analysis of native serum IgG glycosylation, without the prior time-consuming and expensive isolation of the protein, is sufficient to differentiation endometriosis from a group of healthy women.
Asunto(s)
Endometriosis/sangre , Inmunoglobulina G/sangre , Ácido N-Acetilneuramínico/sangre , Adulto , Femenino , Glicosilación , HumanosRESUMEN
Sialic acid and its associated metabolic enzymes have emerged as important components of the pathophysiology of type 2 diabetes (T2D). There is an elevation in the serum concentration of sialic acid in humans and animals with T2D. The present study investigated the modulation of mRNA expression level of UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) and neuraminidase 1 (NEU1) genes in some organs of type 2 diabetic rats. T2D was induced using fructose-streptozotocin model and eight weeks after the induction of diabetes, sialic acid was assayed in the blood and organs (adipose tissue, brain, colon, kidney, liver, pancreas, skeletal muscle and spleen) followed by quantification of mRNA expression level of GNE and NEU1 genes by qPCR. The results showed a significant (P < 0.05) increase in sialic acid level in the serum and all the afore-mentioned organs investigated except in the adipose tissue and skeletal muscle of the diabetic rats compared the normal control. The expression GNE gene was only increased in the pancreas (1.8-fold) of the diabetic rats while there was a decrease in the expression of the gene in the colon. In contrast, the expression of NEU1 gene was increased in the spleen (3.5-fold), brain (2.2-fold), liver (1.9-fold), colon (1.5-fold) and kidney of the diabetic rats. It was concluded that the elevated level of sialic acid in the organs of diabetic rats, except the pancreas, might not be due to increased endogenous synthesis of sialic acid.
Asunto(s)
Diabetes Mellitus Tipo 2/enzimología , Complejos Multienzimáticos/genética , Animales , Encéfalo/enzimología , Colon/enzimología , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Regulación Enzimológica de la Expresión Génica , Hígado/enzimología , Ácido N-Acetilneuramínico/sangre , Ácido N-Acetilneuramínico/metabolismo , Neuraminidasa/genética , Páncreas/enzimología , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Bazo/enzimologíaRESUMEN
In this pilot study, we carried out metabolic profiling of patients with rheumatoid arthritis (RA) starting therapy with biological disease-modifying antirheumatic drugs (bDMARDs). The main aim of the study was to assess the occurring metabolic changes associated with therapy success and metabolic pathways involved. In particular, the potential of the metabolomics profiles was evaluated as therapeutically valuable prognostic indicators of the effectiveness of bDMARD treatment to identify responders versus non-responders prior to implementing treatment. Plasma metabolomic profiles of twenty-five patients with RA prior bDMARD treatment and after three months of therapy were obtained by 1H NMR, liquid chromatography - mass spectrometry, and gas chromatography - mass spectrometry and evaluated by statistical and multivariate analyses. In the group of responders, significant differences in their metabolic patterns were seen after three months of the bDMARD therapy compared with profiles prior to treatment. We identified 24 metabolites that differed significantly between these two-time points mainly belonging to amino acid metabolism, peptides, lipids, cofactors, and vitamins and xenobiotics. Eleven metabolites differentiated responders versus non-responders before treatment. Additionally, N-acetylglucosamine and N-acetylgalactosamine (GlycA) and N-acetylneuraminic acid (GlycB) persisted significant in comparison responders to non-responders after three months of therapy. Moreover, those two metabolites indicated prediction of response potential by results of receiver-operating characteristic (ROC) curve analysis. The applied analysis provides novel insights into the metabolic pathways involved in RA patient's response to bDMARD and therapy effectiveness. GlycA and GlycB are promising biomarkers to identify responding patients prior onset of bDMARD therapy.
Asunto(s)
Acetilgalactosamina/sangre , Artritis Reumatoide/sangre , Biomarcadores/sangre , Metabolómica , Ácido N-Acetilneuramínico/sangre , Adulto , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Cromatografía Líquida de Alta Presión , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Resultado del TratamientoRESUMEN
BACKGROUND: Early diagnosis of sepsis is very important. It is necessary to find effective and adequate biomarkers in order to diagnose sepsis. In this study, we compared the value of sialic acid and procalcitonin for diagnosing sepsis. METHODS: Newly admitted intensive care unit patients were enrolled from January 2019 to June 2019. We retrospectively collected patient data, including presence of sepsis or not, procalcitonin level and sialic acid level. Receiver operating characteristic curves for the ability of sialic acid, procalcitonin and combination of sialic acid and procalcitonin to diagnose sepsis were carried out. RESULTS: A total of 644 patients were admitted to our department from January 2019 to June 2019. The incomplete data were found in 147 patients. Finally, 497 patients data were analyzed. The sensitivity, specificity and area under the curve for the diagnosis of sepsis with sialic acid, procalcitonin and combination of sialic acid and procalcitonin were 64.2, 78.3%, 0.763; 67.9, 84.0%, 0.816 and 75.2, 84.6%, 0.854. Moreover, sialic acid had good values for diagnosing septic patients with viral infection, with 87.5% sensitivity, 82.2% specificity, and 0.882 the area under the curve. CONCLUSIONS: Compared to procalcitonin, sialic acid had a lower diagnostic efficacy for diagnosing sepsis in critically ill patients. However, the combination of sialic acid and procalcitonin had a higher diagnostic efficacy for sepsis. Moreover, sialic acid had good value for diagnosing virus-induced sepsis.
Asunto(s)
Enfermedad Crítica , Ácido N-Acetilneuramínico/sangre , Polipéptido alfa Relacionado con Calcitonina/sangre , Sepsis/diagnóstico , Anciano , Biomarcadores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sepsis/sangreRESUMEN
BACKGROUND: N-acetylneuraminic acid (Neu5Ac) is a functional metabolite involved in coronary artery disease (CAD). We aimed to evaluate the relationship between serum Neu5Ac and the risk and prognosis of acute coronary syndrome (ACS) in a real-world prospective study. METHODS: Patients with suspected ACS who underwent coronary angiography were included. Serum Neu5Ac was measured at admission. Coronary lesion severity was evaluated by Gensini Score. GRACE risk stratification was performed at admission. Major adverse cardiac events (MACEs) were recorded during follow-up. RESULTS: A total of 766 patients, including 537 with unstable angina (UAP), 100 with myocardial infarction (MI), and 129 without CAD were included. The circulating Neu5Ac level was significantly higher in patients with MI (median [1QR]: 297[220, 374] ng/ml) than in those with UAP (227 [114, 312] ng/ml) or without CAD (207 [114, 276] ng/ml; both p < 0.001). Serum level of Neu5Ac was positively correlated with age, hypertension, serum uric acid, creatinine, MB isoform of creatine kinase (CK-MB), and Gensini score (all p < 0.05). Receiver operating characteristic curve analysis showed that a higher serum Neu5Ac was potentially associated with MI and high-risk GRACE stratification in ACS patients. Logistic analysis identified only elevated serum Neu5Ac as an independent predictor of MACEs in these patients (odds ratio [OR]: 1.003, 95% confidence interval [CI]: 1.002-1.005, p < 0.001). CONCLUSIONS: Serum Neu5Ac is associated with myocardial injury, GRACE risk category, and prognosis in ACS patients.
Asunto(s)
Síndrome Coronario Agudo/sangre , Ácido N-Acetilneuramínico/sangre , Síndrome Coronario Agudo/diagnóstico por imagen , Anciano , Biomarcadores/sangre , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Admisión del Paciente , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Regulación hacia ArribaRESUMEN
BACKGROUND: There is growing evidence that oxidative stress (OS) is a critical factor linking obesity with its associated comorbidities, such as cardiovascular diseases. AIM: To evaluate the degree of OS in people with morbid obesity and its relationship with glycoproteins, determined using 1H-NMR spectroscopy, before and after bariatric surgery (BS). METHODS: In this observational cohort study, plasma from 24 patients with BMI ≥ 40 kg/m2 (age: 21-65 years) was used to measure metabolites implicated in OS. We measured glycoprotein (GlycA, GlycB and GlycF) areas and shape factors (H/W = height/width). RESULTS: One year after BS, oxidized low-density lipoprotein had decreased by 49% (P < .0001), malondialdehyde by 32% (P = .0019) and lipoprotein (a) by 21% (P = .0039). The antioxidant enzymes paraoxonase-1 and catalase increased after BS (43%, P < .0001 and 54%, P = .0002, respectively). Superoxide dismutase-2 had fallen 1 year after BS (32%, P = .0052). After BS, both the glycoprotein areas and shape factors decreased by 20%-26%. These glycoproteins were significantly correlated with OS parameters. The plasma atherogenic index was 63% higher in obese individuals than 1 year after BS and correlated positively with glycoproteins. CONCLUSION: For the first time, we here demonstrate the relationship between OS parameters and glycoproteins in people with morbid obesity. So glycoproteins could therefore be a good indicator, together with the oxidative state to assess patient prognosis after BS.
Asunto(s)
Glicoproteínas/sangre , Obesidad Mórbida/cirugía , Estrés Oxidativo , Acetilgalactosamina/sangre , Acetilglucosamina/sangre , Adulto , Anciano , Arildialquilfosfatasa/sangre , Cirugía Bariátrica , Catalasa/sangre , Estudios de Cohortes , Femenino , Glicosilación , Humanos , Lipoproteína(a)/sangre , Lipoproteínas LDL/sangre , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Ácido N-Acetilneuramínico/sangre , Obesidad Mórbida/sangre , Espectroscopía de Protones por Resonancia Magnética , Superóxido Dismutasa/sangre , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Periodontal diseases are inflammatory chronic infections. Sialic acid (SA) is an acute phase reactant by itself. The aim of this study is to investigate the relationship between salivary and serum SA levels and clinical parameters in different forms of periodontal diseases. SUBJECT AND METHODS: Systemically healthy subjects were included in the study; patients with chronic gingivitis (CG) (n = 10), chronic periodontitis (CP) (n = 10), and aggressive periodontitis (AgP) (n = 10), and ten volunteers with healthy periodontium as the control group. Total SA levels were determined by Warren's thiobarbituric acid method in whole saliva, parotis saliva, and serum samples of subjects before and 3 months after nonsurgical periodontal treatment. Full mouth clinical parameters including plaque index, gingival index, probing depth, and bleeding on probing were also recorded. RESULTS: Before treatment, in both periodontitis groups salivary and serum SA levels were higher than those of controls (P = 0.001). Both salivary and serum SA levels decreased significantly in the patient groups after treatment (P < 0.001). Multiple comparisons of baseline clinical parameters in all groups revealed significant differences (P = 0.001) and these parameters decreased significantly on the 90th day (P < 0.01). There were positive correlations between SA levels and periodontal indices of the CG, CP, and AgP groups (P < 0.05). CONCLUSION: Our results suggest that SA level in both saliva and serum may be a potentially useful marker to determine inflammatory changes and investigate different forms of periodontal diseases.
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Biomarcadores/análisis , Ácido N-Acetilneuramínico/sangre , Enfermedades Periodontales/sangre , Saliva/química , Adulto , Periodontitis Agresiva/sangre , Biomarcadores/sangre , Periodontitis Crónica/sangre , Femenino , Gingivitis/sangre , Humanos , Masculino , Persona de Mediana Edad , Índice PeriodontalRESUMEN
Identifying biomolecules for disease diagnosis requires simple, accurate, and reliable analytical techniques. Multiple signal transduction pathways have promoted the development of various biological analysis systems. However, most systems are largely limited by a single mechanism or model analysis, which can easily lead to false-positive/negative results. Herein, we report a covalent organic framework (COF) (TpPa-1) functionalized with a dye (fluorescein sodium) and design this hybrid material (TpPa-1@Dye) to fabricate hydrogels for subsequent analysis with the indicator displacement assay (IDA) method. Selecting a suitable metal cation (Cr3+) for the preparation of hydrogels can reduce the background fluorescence, improve the detection sensitivity, and increase the corresponding sensing selectivity. The TpPa-1@Dye functions as an indicator in the IDA-in-COF system, and Cr3+ is a receptor of the analyte (sialic acid (SA), a biomarker for ovarian cancer diagnosis). Based on the above studies, the integrative logic operations (AND + IMP) are further established, it helps in elucidating the design rules of the IDA-in-COF approach. This work represents the first effort in designing IDA-in-COF luminescent sensors with an On-Off-On mechanism to determine biomarkers and provides a new approach for developing hybrid COF luminescent materials as analysis platforms for human health monitoring.
Asunto(s)
Biomarcadores de Tumor/sangre , Estructuras Metalorgánicas/química , Ácido N-Acetilneuramínico/sangre , Neoplasias Ováricas/diagnóstico , Animales , Femenino , Fluoresceína/química , Colorantes Fluorescentes/química , Humanos , Sensibilidad y Especificidad , Espectrometría de Fluorescencia/métodosRESUMEN
Purpose: COPD is a multisystem disease and there is a need for clinical serum markers that can assess the decline in lung and muscle function in COPD. The goal of this study was to evaluate the potential association of serum club-cell protein 16 (CC16), α-1 acid glycoprotein (AGP) and total sialic acid (TSA) with spirometry, hand-grip strength and quality of life to assess important disease outcomes. Methods: This is a population-based cross-sectional study and data were collected from the patients at teaching hospitals of Gomal University and the University of Health Sciences in Pakistan. The study population included 1582 participants (Non-COPD; N = 788, COPD; N = 845) >55 years of age from both sexes, with data from structural interviews, clinical examinations, laboratory investigations, spirometry and hand-grip strength measurements. Results: Serum TSA and CC16 were significant predictors of FEV1% (p < 0.05) and hand-grip strength in advanced stages of COPD (p < 0.05 each) in both sexes. Men had higher absolute and adjusted hand-grip strength than women in all groups (p < 0.05). Hand-grip strength was significantly associated with FEV1% in both genders (p < 0.05) with stronger effect in women (r2 = 0.075). Serum HDL-C was an independent predictor of hand-grip strength and FEV1% (p < 0.05) in both genders. Participants with extreme problem on EQ-5D parameters had more severe COPD and reduced hand-grip strength (all p values < 0.05). Conclusion: Taken together, these studies show that the serum expressions of TSA and CC16 have correlations with spirometry and muscle decline in COPD. Further studies should be conducted to establish their efficacy in monitoring disease progression in COPD.
Asunto(s)
Fuerza de la Mano , Indicadores de Salud , Pulmón/fisiopatología , Ácido N-Acetilneuramínico/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Uteroglobina/sangre , Anciano , Biomarcadores/sangre , Estudios Transversales , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Pakistán , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida , Índice de Severidad de la Enfermedad , Espirometría , Encuestas y CuestionariosRESUMEN
BACKGROUND: Different from the diagnosis of bacterial infections, Mycoplasma pneumoniae pneumonia (MPP) is still lacking of convenient non-specific laboratory parameters. METHOD: A total of 125 children with MPP were included in the MPP group and 89 children with Mycoplasma-negative pneumonia were included in the control group, and the sera were collected from the children at both the acute and recovery stages in the two groups. RESULTS: The sialic acid and C3 in the MPP group were significantly higher than those in the control group both at the acute and at the recovery stage. On the other hand, the sialic acid and C3 at the acute stage were significantly higher than those at the recovery stage in the MPP group. However, in the control group, the sialic acid and C3 demonstrated IgG exhibited no significant change between the acute stage and the recovery stage. Lastly, positive correlations between sialic acid level and C3 level were identified in the MPP group at both acute and recovery stages. CONCLUSION: Our study demonstrated that the serum sialic acid correlated with C3 specifically increased in children with MPP, indicating that it might be the important non-specific parameters in the diagnosis of MPP.
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Complemento C3/metabolismo , Mycoplasma pneumoniae/fisiología , Ácido N-Acetilneuramínico/sangre , Neumonía por Mycoplasma/sangre , Neumonía por Mycoplasma/microbiología , Adolescente , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Complemento C4/metabolismo , Femenino , Humanos , Inmunoglobulina G/sangre , Lactante , MasculinoRESUMEN
Multifactorial mechanisms leading to diminished platelet counts in immune thrombocytopaenia (ITP) might condition the ability of patients with ITP to respond to treatments. Examining their platelet and immune features, we aimed to detect singular characteristics of patients with ITP who do not respond to any treatment. We studied patients with chronic primary ITP who had been without treatment, or untreated (UT-ITP), for at least six months; included were responders to agonists of thrombopoietin receptors (TPO-RA), patients who showed no response to first- and second-line treatments (NR-ITP), and healthy controls. Platelets from NR-ITP patients exposed a reduced amount of sialic acid residues. Increased loss of platelet surface sialic acid residues was associated with increased platelet apoptosis. NR-ITP patients had an increased fraction of naive lymphocyte (L) B cells and a reduced LTreg (Lymphocyte T-regulator) subset. They also presented an anomalous monocyte and NK (Natural Killer) cells distribution. TPO-RA-treated patients seemed to recover an immune homeostasis similar to healthy controls. In conclusion, our results indicate a severe deregulation of the immune system of NR-ITP. The inverse correlation between loss of sialic acid and LTreg count suggests a potential relationship between glycan composition on the platelet surface and immune response, positing terminal sugar moieties of the glycan chains as aetiopathogenic agents in ITP.
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Plaquetas/patología , Polisacáridos/sangre , Púrpura Trombocitopénica Idiopática/inmunología , Adulto , Anciano , Apoptosis , Plaquetas/química , Caspasas/sangre , Estudios Transversales , Citocinas/sangre , Femenino , Humanos , Células Asesinas Naturales/inmunología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Ácido N-Acetilneuramínico/sangre , Activación Plaquetaria , Estudios Prospectivos , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Receptores de Trombopoyetina/antagonistas & inhibidores , Linfocitos T Reguladores/inmunología , Insuficiencia del TratamientoRESUMEN
AIM: The aim of this study was to compare the preoperative and postoperative (48th hour) total serum sialic acid levels of the patients with colon cancer and to investigate if the total serum sialic acid levels can be used as a tumor marker in colon cancer. METHODS: Preoperative and postoperative (48th hour) total serum sialic acid levels of 100 patients that were diagnosed with colon cancer and 70 healthy individuals were examined. All total serum sialic acid levels were determined by the methods of Warren. RESULTS: Total sialic acid levels of both patient groups were significantly higher when compared to the control group (p<0.0001). Also, highly significant difference was found between preoperative and postoperative total serum sialic acid levels (p<0.001). CONCLUSION: Evaluation of total serum sialic acid levels may play a critical role in colon cancers. Total serum sialic acid levels may serve as a non-invasive tool for early diagnosis of colon cancer. KEY WORDS: Colon cancer, Preoperative, Postoperative, Total sialic acid.
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Neoplasias del Colon , Ácido N-Acetilneuramínico , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Neoplasias del Colon/sangre , Neoplasias del Colon/cirugía , Humanos , Ácido N-Acetilneuramínico/sangreRESUMEN
The profiles of polytraumatized patients in intensive care units were characterized. Serum and salivary markers were compared with normality between Classes I and II of APACHE II and between periods of hospitalization; these results were correlated. This was a prospective study on saliva charts and collection (n = 70). Profile: male, 27 years old, blunt traumas and collisions. Serum parameters with normality: decrease in pH, creatinine at admission to Class I, and at 48 and 72 hours in both classes; K+ at 48 h in Class II; Ca+ on admission in both classes and at 72 h in Class I. Increase in urea at 72 h in Class II, glucose at all times and in all classes, and Ca+ at 48 h in both classes. Class II had high Na+ at 48 and 72 h compared to Class I. In Class I, creatinine reduction occurred in 48 h and 72 h compared to admission and an increase of Ca+ at 48 h with admission. In Class II, pH and Na+ increased at 48 h and 72 h compared to admission. K+ decreased from admission to 48 h and increased from 48 h to 72 h. Urea increased from 48 to 72 hours. Creatinine decreased from admission to 48 and 72 hours. Ca+ increased from admission to 48 hours and decreased from 48 to 72 hours. There was an increase in the saliva levels in both classes and times in relation to normality. There was an increase in urea at admission, glucose at 72 h, and Ca+ at 48 h in Class II compared with Class I. Class I urea increased from admission to 48 h and Ca+ decreased from admission to 48 h. Class II urea decreased from 48 h to 72 h. Strong or very strong positive correlation was identified between blood and creatinine saliva at all times and regular and negative Ca+ at 72 h. This study provides evidence that salivary and serum biomarkers can be used together to monitor the evolution of the clinical symptoms of ICU patients.
Asunto(s)
Biomarcadores/sangre , Traumatismo Múltiple/sangre , Ácido N-Acetilneuramínico/sangre , APACHE , Adolescente , Adulto , Anciano , Femenino , Hospitales Universitarios , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Saliva/metabolismo , Adulto JovenRESUMEN
Sialic acid (SA), a family of acetylated derivatives of neuraminic acid, an acute phase reactant by itself. It usually occurs as a terminal component at the non-reducing end of carbohydrate chains of glycoproteins and glycolipids. SA participates in multiple physiological functions, such as cell-to-cell interactions, cell migration and proliferation. Diabetes mellitus (DM) is a chronic metabolic disorder characterized by rise in blood glucose level. Periodontitis is a chronic inflammatory disease of the periodontal tissue, leading to destruction of bone surrounding the tooth and ultimately tooth loss. There is a two way relationship between diabetes mellitus and periodontitis. Periodontitis is the sixth complication of diabetes along with retinopathy, nephropathy, neuropathy, macrovascular disease, and altered wound healing. Inflammatory mediators like interleukin-6 and tumor necrosis factor-alpha produced during periodontal inflammation can interfere with the actions of insulin receptors and worsen the glycemic control of diabetic patients. Periodontitis is a major cause of tooth loss, affecting over 300 million people and bacteria associated with periodontitis are also linked with systemic problems like endocarditis, atherosclerosis. Recent work has highlighted a major role for the host sugar sialic acid in the biofilm physiology and host-pathogen interactions of T. forsithya, a key periodontal pathogen. There exists a need for a biomarker, for early detection of disease evolution and more robust therapy efficacy measurements. Serum sialic acids were estimated in Indian population by diphenylamine method and Thiobarbituric acid method. The average values were 68 ± 2.6 mg percent by DPA method and 56 ± 5 mg percent by TBA (thiobarbituric acid assay) method. Age and sex showed no influence on serum sialic acid level. Objectives of the present study was to compare (TSSA) level in healthy subjects, subjects with (CMP) with and without (NIDDM) and its effect on non-surgical periodontal therapy. In the present study, the participants were divided into three groups: Group A, B and C. Group A consists of systemically healthy subjects, Group B consists of subjects with (CMP) while Group C consists of subjects with (CMP) with (NIDDM) and results of this study indicated that, at baseline, there were significant differences between Group A, B and Group C with respect to all the clinical parameters, including (GI), (OHI-S), (PPD), (CAL), (TSSA) and (HbA1c) levels. Thus (TSSA) level could be considered as novel biomarker in the progression of periodontal disease and diabetic status. Periodontitis could be considered as a potential, modifiable, and independent risk factor for the development of diabetes. Early detection of elevated (TSSA) level may help in interpreting the progression of periodontitis, risk of development of diabetes mellitus in future and also to prevent complications.
Asunto(s)
Complicaciones de la Diabetes/sangre , Diabetes Mellitus Tipo 2/sangre , Ácido N-Acetilneuramínico/sangre , Periodontitis/sangre , Periodontitis/terapia , Adulto , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodontitis/complicacionesRESUMEN
Dengue virus (DENV) causes the most prevalent arboviral infection of humans, resulting in a spectrum of outcomes, ranging from asymptomatic infection to dengue fever to severe dengue characterized by vascular leakage and shock. Previously, we determined that DENV nonstructural protein 1 (NS1) induces endothelial hyperpermeability, disrupts the endothelial glycocalyx layer (EGL) in vitro and triggers shedding of structural components, including sialic acid (Sia) and heparan sulfate. Here, using a murine model of dengue disease disease, we found high levels of Sia and NS1 circulating in mice with DENV-induced morbidity and lethal DENV infection. Further, we developed a liquid chromatography/mass spectrometry-based method for quantifying free Sia in serum and determined that the levels of free N-glycolylneuraminic acid were significantly higher in DENV-infected mice than in uninfected controls. These data provide additional evidence that DENV infection disrupts EGL components in vivo and warrant further research assessing Sia as a biomarker of severe dengue disease.
Asunto(s)
Biomarcadores/sangre , Dengue/patología , Ácido N-Acetilneuramínico/sangre , Suero/química , Animales , Cromatografía Liquida , Modelos Animales de Enfermedad , Espectrometría de Masas , Ratones , Análisis de Supervivencia , Proteínas no Estructurales Virales/sangreRESUMEN
BACKGROUND: Coronary Artery Disease (CAD) has long been recognized as a global health issue. Inflammation, Fibrinolysis and Oxidative Stress play an important role in the disruption of plaques leading to CAD. Markers that reflect this pathophysiologic mechanism may have prognostic value. OBJECTIVE: To estimate the serum concentrations of high-sensitivity C-reactive protein (hs-CRP), sialic acid (SA), vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), oxidized low density lipoprotein (OX-LDL) and malondialdehyde (MDA) with significant prognostic value in patients with CAD. METHODS: The markers included, hs-CRP, SA, VN, PAI-1, OX-LDL and MDA, were compared between 160 angiographically diagnosed CAD patients and 20 age- and sex-matched healthy individuals. The subjects were divided into 4 groups according to angiography results, and association between all risk factors of CAD was studied. Serum levels of SA, VN, PAI-1, and OX-LDL were measured by enzyme-linked immunosorbent assay (ELISA); MDA was measured based on reaction with thiobarbituric acid (TBA); and hs-CRP level was estimated by immunoturbidimetry using a commercial kit. The diagnostic value of these variables was further assessed by ROC curve analysis. Multiple logistic regression was used to evaluate the diagnostic power of the combination. Furthermore, p < 0.05 was considered as significant. RESULTS: Serum levels of hs-CRP, SA, VN, PAI-1, and OX-LDL were significantly higher in patient groups compared to control group (p < 0.001). Using both normal and CAD patients as subjects, ROC analysis was performed. The cutoff for OX-LDL, MDA, PAI-1, VN, hs-CRP and SA was 2.67 (ug/mL), 5.49 (mmol/mL), 67 (ng/mL), 254 (ng/mL), 3.4 (mg/dL), 7/89 (mg/dL), respectively. Eventually, the complete diagnostic efficacy was classified as: SA, hs-CRP, PAI-1, OX-LDL, MDA and VN. CONCLUSION: Serum levels SA, hs-CRP, VN, PAI-1, OX-LDL and MDA may be predictive of adverse cardiovascular outcomes. Interestingly, these analyses can help as diagnostic and monitoring markers in CAD patients.
Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Fibrinólisis , Estrés Oxidativo , Anciano , Análisis de Varianza , Biomarcadores , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Lipoproteínas LDL/sangre , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Ácido N-Acetilneuramínico/sangre , Inhibidor 1 de Activador Plasminogénico/sangre , Valor Predictivo de las Pruebas , Curva ROC , Valores de Referencia , Factores de Riesgo , Vitronectina/sangreRESUMEN
A delicate dual-readout immunosensor based on tetraphenylporphyrin-polymer dots (TPP-Pdots) with brilliant photoelectrochemical and photothermal performance was first successfully fabricated for the ultrasensitive detection of sialic acid (SA). Herein, TPP-Pdots with good biocompatibility, extraordinary light-harvesting ability and excellent photothermal conversion efficiency was used to capture SA antibody as dual-functional bioprobe for generating photocurrent and temperature signal. Furthermore, the large surface and morphology-mediated of rutile-TiO2 (R-TiO2) was beneficial to load amounts of TPP-Pdots for improved PEC signal and photothermal signal. Importantly, the temperature readout resulted from the variation of target concentration could be easily obtained by a universal thermometer which was time-saving and cost-saving. Under the optimized experimental conditions, the photocurrent densities and temperature changes proportionally increased with the increasing of SA concentrations from 3.5â¯×â¯10-5â¯ng/mL to 35â¯ng/mL (Râ¯=â¯0.996). Impressively, the dual-readout approach proposed here not only featured with good accuracy and high sensitivity for SA detection, but also paved the way for the development of a dual-readout immunoassay based on PEC biosensor.