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Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the etiology of which has not been clearly determined yet. There is increasing evidence that synaptic and dendritic changes are involved in the etiology of ASD. The aim of this study is to determine whether serum Thrombospondin-1 and Thrombospondin-2 differ between ASD patients and healthy controls. This study also investigates possible correlations between clinical symptomatology of ASD and serum Thrombospondin-1 and Thrombospondin-2 levels. Method: A total of 44 children with ASD and 21 healthy controls under 6 years of age were included in the study. Symptom severity and behavioral problems among children with ASD were evaluated by using Childhood Autism Rating Scale and Abnormal Behavior Checklist. Serum levels of Thrombospondin-1 and Thrombospondin-2 were measured by using commercial enzyme-linked immunosorbent assay kits. Result: No statistically significant differences were found between the two groups in terms of serum Thrombospondin-1 and Thrombospondin-2 levels. In addition, no correlation was determined between Thrombospondin-2 levels and clinical symptomatology and severity of ASD. However, the Thrombospondin-1 level was found to negatively correlated with the total score of Childhood Autism Rating Scale, inappropriate speech and stereotype subscale scores of Aberrant Behavior Checklist scale. Conclusion: Thrombospondin-1 might have a potential role in the etiopathogenesis of ASD. Further studies are required to clearly elucidate the association between Trombospondin-1 and ASD.
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Objective: In this study, we aimed to evaluate subclinical atherosclerosis in patients with obesity who had cardiovascular disease risk indicators such as arterial stiffness, which is evaluated using pulse wave velocity (PWV), carotid intima-media thickness (CIMT), and biomarkers of endothelial dysfunction such as endocan, ADAMTS97, and ADAMTS9. Subjects and methods: Sixty obese subjects, including 23 subjects with body mass index (BMI) ≥ 40, 37 subjects with BMI ≥ 30 but < 40, and 60 age-and sex-matched control subjects, were included in our study. Serum endocan, ADAMTS97, and ADAMTS9 levels as well as PWV and CIMT measurements of the subjects in the obese and control groups were performed. Results: In the obesity group, PWV levels were significantly higher than they were in the control group and endocan levels were significantly lower than they were in the control group. When we compared the obese group with BMI ≥ 40 and the control group, the BMI ≥ 40 group had significantly higher PWV and CIMT levels than the control group had, whereas endocan, ADAMTS7, and ADAMTS9 levels were similar to those of the control group. When we compared the obese group with BMI ≥ 30 < 40 to the control group, endocan levels were lower in the group with BMI ≥30 < 40, and PWV and CIMT levels were similar to the control group. Conclusion: We found that arterial stiffness and CIMT increased in obese patients with BMI ≥ 40 and that increased arterial stiffness was associated with age, systolic blood pressure, and HBA1C. In addition, we found that the endocan levels were lower in obese patients than they were in nonobese control individuals.
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Aterosclerosis , Rigidez Vascular , Humanos , Grosor Intima-Media Carotídeo , Análisis de la Onda del Pulso , Aterosclerosis/etiología , Obesidad/complicaciones , Biomarcadores , Factores de RiesgoRESUMEN
Fabry disease (FD) is associated with inflammation, proteinuria, and chronic kidney disease. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) plays an important role in inflammation in diabetic nephropathy and lupus nephritis. Since there is a close relationship linking serum TWEAK (sTWEAK), inflammation, and carotid intima-media thickness (CIMT) in various kidney diseases, we aimed to determine the relationship between sTWEAK levels and CIMT in subjects with and without proteinuria in a cross-sectional study involving 15 FD patients (seven females, eight males) and seven healthy controls (four females, three males). There were no differences in age, sex, estimated glomerular filtration rate, and biochemical parameters (serum glucose, albumin, creatinine, uric acid, C-reactive protein (CRP), low-density lipoprotein, and high-density lipoprotein) between FD patients and healthy controls. The spot urine protein-creatinine ratios of healthy controls and FD patients were 90 mg/g and 185 mg/g, respectively (P = 0.022). STWEAK levels were higher in FD patients than in healthy controls (P = 0.007). The CIMT of FD patients and healthy controls was 0.55 ± 0.14 mm and 0.42 ± 0.04 mm, respectively (P = 0.007). STWEAK was positively correlated with CRP and CIMT, and negatively with proteinuria (P = 0.005, P = 0.013, and P = 0.018, respectively). In the multivariate analysis, only sTWEAK was an independent variable of increased CIMT. We demonstrated that sTWEAK and CIMT were increased in FD patients. STWEAK might have a role in the pathogenesis of subclinical atherosclerosis in FD.
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Biomarcadores , Grosor Intima-Media Carotídeo , Citocina TWEAK , Enfermedad de Fabry , Humanos , Citocina TWEAK/sangre , Femenino , Masculino , Estudios Transversales , Adulto , Enfermedad de Fabry/sangre , Enfermedad de Fabry/complicaciones , Estudios de Casos y Controles , Biomarcadores/sangre , Persona de Mediana Edad , Proteinuria/etiología , Proteinuria/sangre , Adulto Joven , Valor Predictivo de las Pruebas , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/etiología , Factores de RiesgoRESUMEN
ABSTRACT Objective: In this study, we aimed to evaluate subclinical atherosclerosis in patients with obesity who had cardiovascular disease risk indicators such as arterial stiffness, which is evaluated using pulse wave velocity (PWV), carotid intima-media thickness (CIMT), and biomarkers of endothelial dysfunction such as endocan, ADAMTS97, and ADAMTS9. Subjects and methods: Sixty obese subjects, including 23 subjects with body mass index (BMI) ≥ 40, 37 subjects with BMI ≥ 30 but < 40, and 60 age-and sex-matched control subjects, were included in our study. Serum endocan, ADAMTS97, and ADAMTS9 levels as well as PWV and CIMT measurements of the subjects in the obese and control groups were performed. Results: In the obesity group, PWV levels were significantly higher than they were in the control group and endocan levels were significantly lower than they were in the control group. When we compared the obese group with BMI ≥ 40 and the control group, the BMI ≥ 40 group had significantly higher PWV and CIMT levels than the control group had, whereas endocan, ADAMTS7, and ADAMTS9 levels were similar to those of the control group. When we compared the obese group with BMI ≥ 30 < 40 to the control group, endocan levels were lower in the group with BMI ≥ 30 < 40, and PWV and CIMT levels were similar to the control group. Conclusions: We found that arterial stiffness and CIMT increased in obese patients with BMI ≥ 40 and that increased arterial stiffness was associated with age, systolic blood pressure, and HBA1C. In addition, we found that the endocan levels were lower in obese patients than they were in nonobese control individuals.
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BACKGROUND: Apelin-13 have potential effect on mood because of high expression in the hypothalamus. In this study, we aimed to investigate the serum apelin-13 levels among adolescents with major depressive disorder. SUBJECT AND METHODS: A total of 42 patients between the ages of 12 and 18 with a primary diagnosis of major depressive disorder have been included. Depression scores of both groups were measured by the Children's Depression Inventory. Serum apelin-13 concentrations were measured by a commercially available kit based on enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The mean serum apelin-13 levels in the patients with MDD was 173.08±106.33 pg/ml, whereas it was 251.75±167.82 pg/ml in healthy controls. The difference between groups in terms of mean serum apelin-13 levels was statistically signiï¬cant (p=0.018, Cohen's d=-0.571). CONCLUSION: This is the first study to examine the serum apelin-13 levels in adolescents diagnosed with major depressive disorder. Lower serum apelin-13 levels were found in depressed adolescents.
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Trastorno Depresivo Mayor , Niño , Humanos , Adolescente , Trastorno Depresivo Mayor/diagnóstico , Péptidos y Proteínas de Señalización IntercelularRESUMEN
BACKGROUND: Data on the presence and extent of cardiovascular disease (CVD) risk in primary hyperparathyroidism (PHPT) are conflicting. In our study, we aimed to investigate the increased CVD risk in patients with PHPT by carotid intima-media thickness (CIMT), epicardial adipose tissue (EAT) thickness, and serum levels of endocan and nesfatin-1. METHODS: Patients with PHPT (n = 44) and age- and sex-matched healthy control subjects (n = 40) were enrolled in this study. Demographic data of the participants were questioned. Serum endocan and nesfatin-1 concentrations were assessed using commercially available ELISA kits. Noninvasive measurements of CIMT and EAT thickness were made with high-resolution ultrasonography and B-mode echocardiography. RESULTS: There was no statistically significant difference in serum endocan and nesfatin-1 levels and EAT thickness in the PHPT group compared to controls. CIMT was statistically significantly higher in the PHPT group compared to controls (p = 0.001). A negative correlation was found between PTH and low-density lipoprotein cholesterol level (p = 0.001) but no significant relationship was found between other parameters. DISCUSSION: We found that CIMT is increased in patients with PHPT and consequently, CVD risk is high in these patients. More comprehensive studies are needed to identify other markers that predict increased CVD risk in patients with PHPT.
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Enfermedades Cardiovasculares , Hiperparatiroidismo Primario , Humanos , Grosor Intima-Media Carotídeo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Pericardio/diagnóstico por imagen , Tejido Adiposo/diagnóstico por imagen , Factores de RiesgoRESUMEN
Obesity is a condition of abnormally increased body fat resulting from increased energy intake relative to energy expenditure. Excess body weight is a risk factor for many somatic and psychological disorders, including cardiovascular disease, type 2 diabetes mellitus, osteoarthritis, and cancer types. Bone metabolism, bone turnover, and mineral content are altered in severe obesity. This review will focus on the relationship between inflammation and bone biomarkers in adult obesity.
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Diabetes Mellitus Tipo 2 , Adulto , Humanos , Obesidad/metabolismo , Remodelación Ósea , Metabolismo Energético , InflamaciónRESUMEN
Behçet disease (BD) is an inflammatory, multisystemic vasculitis of unknown etiopathogenesis. However, innate and adaptive immune system involvement and immune-mediated networks play a vital role in the inflammatory cascade. Indoleamine 2,3-dioxygenase 1 (IDO1) is activated in chronic inflammatory states and catalyzes the first and rate-limiting step of tryptophan (TRP) metabolism along the kynurenine pathway (KP). The study aimed to measure KP metabolites levels in patients with BD and investigate the relationship between disease activity and clinical findings with these metabolites. The study included 120 patients with BD and 120 healthy volunteers. Serum TRP, kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), and quinolinic acid (QUIN) levels were measured with the tandem mass spectrometric method. Demographic data, clinical manifestations, and disease activity score (BDCAF) were recorded. Serum KYN, KYNA, 3HK, 3HAA, QUIN levels, and KYN/TRP ratio were higher (p < 0.05) in patients with BD compared to the control group, while TRP levels were lower (p < 0.05). KYN/TRP ratio and QUIN levels were significantly higher in the presence of neuro-Behçet, while serum KYN levels were significantly higher in the presence of arthritis (p < 0.05). In addition, serum QUIN levels were significantly higher in the presence of thrombosis (p < 0.05). BDCAF score positively correlated with KYN/TRP ratio. Our findings showed that serum KP metabolite levels were elevated in patients with BD, and there is a relationship between these metabolites with disease activity, clinical findings, and inflammatory burden.
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Síndrome de Behçet , Quinurenina , Humanos , Ácido Quinurénico/metabolismo , Ácido Quinolínico/metabolismo , Triptófano/metabolismoRESUMEN
OBJECTIVE: Cardiovascular complications such as cardiomyopathy and endothelial dysfunction, which are frequently seen in patients with acromegaly, are among the most important causes of morbidity and mortality. In this study, we aimed to investigate arterial stiffness, carotid intima-media thickness, endocan level, and A disintegrin and metalloproteinase with thrombospondin type I motif 9 level and their relationship with disease activity in patients with acromegaly with and without cardiovascular risk factors. METHODS: A total of 60 patients with acromegaly-25 with active disease, 26 with well-controlled disease, and 9 with newly diagnosed disease-and 60 age-, sex-, and body mass index (BMI)-matched healthy control subjects were enrolled in this study. All the subjects' height, weight, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG) level, insulin, hemoglobin A1C (HbA1C), C-reactive protein , lipid, endocan, A disintegrin and metalloproteinase with thrombospondin type I motif 9 levels, pulse wave velocity (PWV), and carotid intima-media thickness were measured. RESULTS: The SBP, DBP, FPG level, HbA1C level, and PWV of the acromegaly group were higher than those of the control group. In patients with acromegaly with cardiovascular disease (CVD) risk factors, the PWV was higher than that in the control group, and in patients with acromegaly without CVD risk factors, the PWV was similar to that in the control group. In a correlation analysis, a positive correlation was found between PWV and age, BMI, SBP, DBP, FPG level, and HbA1C level in the acromegaly group. CONCLUSION: In our study, we found that arterial stiffness increased in patients with acromegaly with CVD risk factors and that increased arterial stiffness was associated with hemodynamic (SBP and DBP) and metabolic (BMI, FPG level, and HbA1C level) parameters.
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Acromegalia , Enfermedades Cardiovasculares , Rigidez Vascular , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/etiología , Grosor Intima-Media Carotídeo , Desintegrinas , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Metaloproteasas , Análisis de la Onda del Pulso , Factores de Riesgo , TrombospondinasRESUMEN
Background: Acne vulgaris is a common chronic inflammatory skin disease in adolescents and oxidative stress plays an important role in acne pathology. However, the pathology of acne has not yet been fully elucidated. miRNAs are small noncoding RNAs, and there is increasing evidence for their role in the pathogenesis of skin diseases such as psoriasis, atopic dermatitis, and other inflammatory diseases. Aims and Objectives: The aim of the study was to investigate serum malondialdehyde (MDA) and glutathione (GSH) levels with plasma miRNA expression profile related with oxidative stress in patients with severe acne vulgaris. Materials and Methods: Fifty seven female patients with severe acne and 40 healthy women were included in the study. Plasma miRNA-31, miRNA-200a, and miRNA-21 levels were evaluated by using real-time quantitative polymerase chain rection analysis. MDA and GSH levels were measured as per the manufacturer's procedures using commercial ELISA kits. Results: Plasma miRNA-21 levels were statistically significantly higher in patients with severe acne compared to the control group (P =0.003). Plasma miRNA-200a (P =0.303) and miRNA-31 (P =.652) levels were slightly higher in patients with severe acne compared to the control group, but this difference was not statistically significant. Serum MDA levels (P =.047) were higher in patients with severe acne compared to control group, while serum GSH levels (P =.001) were lower. Conclusion: These results show that oxidative damage is involved in acne etiopathogenesis and especially miRNA-21 may have an important role in the pathogenesis of acne vulgaris.
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BACKGROUND: Progranulin (PGRN), endothelial cell-specific molecule-1, clusterin (CLU), and human epididymis protein 4 (HE-4) are novel proteins reported to have diagnostic and prognostic potential in lung cancer. Here, we aimed to identify the markers with high sensitivity and specificity in distinguishing malignant pleural fluids from other pleural fluids. METHODS: This prospective, descriptive study was conducted at a medical faculty hospital between 2016 and 2019. The study population consisted of 90 patients <18 years of age with pleural effusion (PE). Levels of pleural fluids of PGRN, endothelial cell-specific molecule-1, CLU, and HE-4 were measured with enzyme-linked immunosorbent assay kits under the manufacturer's manual. RESULTS: Of 90 patients, 54 were men, and 36 were women (mean age 65â ±â 16 years). Of pleural fluids investigated, 23 (25%) and 67 (74%) were transudates and exudates, respectively. Of exudates, while 27 (40%) and 19 (28%) were parapneumonic PE and tuberculous PE, respectively, 20 (29%) were malignant pleural effusion (MPE). Levels of all biomarkers in exudate fluids were found significantly higher than those of transudate fluids. CLU, HE-4, and PGRN levels in MPE were also found significantly higher than benign fluids (Pâ <â .05). Cutoff values were achieved by receiver operating characteristics analysis for CLU, HE-4, and PGRN to distinguish between malignant and benign groups. For diagnosis of MPE, the sensitivity and specificity values were found as 0.66 and 0.67 for a cutoff value of CLU of 18.29 mg/L (Pâ =â .00), as 0.76 and 0.76 for a cutoff value of HE-4 of 9.33 mg/L (Pâ =â .00), and as 0.66 and 0.67 for a cutoff value of PGRN of 105.91 mg/L (Pâ =â .001). CONCLUSION: HE-4 having high sensitivity and specificity can be a potential diagnostic marker in distinguishing between malignant and benign effusions, and these findings can constitute a basis for future research.
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Derrame Pleural Maligno , Derrame Pleural , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Derrame Pleural Maligno/patología , Diagnóstico Diferencial , Estudios Prospectivos , Clusterina , Derrame Pleural/diagnóstico , Derrame Pleural/metabolismoRESUMEN
Hydroxychloroquine has attracted attention in the treatment of COVID-19. Many conflicting findings have been reported regarding the efficacy and safety of this drug, which has been used safely in the rheumatological diseases for years. However, these studies lacked measurement methods that allow accurate assessment of hydroxychloroquine and its metabolite levels. The aim of this study was to measure hydroxychloroquine and its metabolite levels in whole blood samples of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and scleroderma (Scl) by a robust, simple and accurate validated tandem mass spectrometric method, and to investigate the relationship between these levels with drug-related adverse effects and disease activity scores. The validated LC-MS/MS method was applied to measure blood hydroxychloroquine and its metabolite levels of patients with RA, SLE, SS, Scl. Various haematological and biochemical parameters were measured with Beckman-Coulter AU 5800 and Beckman Coulter LH 780 analyzers, respectively. QTc intervals were calculated with Bazett's formula, and the patients were followed up by clinicians in terms of clinical findings and adverse effects. Hydroxychloroquine levels of patients were similar to previous studies. There was a negative correlation between disease activity scores and hydroxychloroquine levels, while the highest correlation was between QTc interval, creatinine and GFR levels with desethylchloroquine. Bidetylchloroquine had the highest correlation with RBC count and liver function tests. Our findings showed that hydroxychloroquine and its metabolite levels were associated with disease activity scores, renal, hepatic function, QTc prolongation, and hematological parameters.
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Antimaláricos/efectos adversos , Antimaláricos/sangre , COVID-19/complicaciones , Enfermedades del Tejido Conjuntivo/complicaciones , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/sangre , Adulto , Anciano , Cromatografía Líquida de Alta Presión , Creatinina/sangre , Electrocardiografía , Recuento de Eritrocitos , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Pruebas de Función Renal , Pruebas de Función Hepática , Síndrome de QT Prolongado/inducido químicamente , Masculino , Persona de Mediana Edad , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
OBJECTIVES: The study aimed to develop a validated LC-MS / MS method for the measurement of carbamazepine and carbamazepine-10,11-epoxide (CBZE) levels, to compare the carbamazepine concentrations measured by AbSciex API 3200 LC-MS/MS and Beckman Coulter Emit® 2000 immunoassay and to investigate the effect of carbamazepine concentrations on various hematological and biochemical parameters. METHODS: For the measurement of carbamazepine and CBZE levels, a validated LC-MS / MS method was developed. Serum carbamazepine levels of patients were measured by AbSciex API 3200 LC-MS / MS and Beckman Coulter Emit® 2000 immunoassay. Biochemical, hematological parameters, and hormone levels were measured by Beckman-Coulter AU 5800 (Beckman Coulter, Brea, USA), Beckman Coulter LH 780 (Beckman Coulter, Miami, FL, USA), and Cobas 6000 (Roche Diagnostics, Germany) analyzers, respectively. RESULTS: The imprecision values for all analytes were less than 7.0 %. The correlation coefficient between the methods was 0.981 (95 % confidence interval: 0.975 to 0.985). Linear regression analysis demonstrated highly significant associations of carbamazepine concentrations with albumin (B = -0.300, p = 0.040), calcium (B = -0.262, p = 0.004), phosphorus (B = -0.241, p = 0.022), WBC (B = -0.288, p = <0.001), PLT (B = -0.236, p = 0.003), RBC (B = -0.257, p = 0.001), NEU% (B = -0.289, p = <0.001), LYM% (B = -0.268, p = 0.001), D vitamini (B = -0.344, p = 0.006) levels. CONCLUSIONS: A robust, rapid, and simple method has been developed. Our study revealed that carbamazepine and its metabolite have a significant correlation and likely impact on bone metabolism, blood cell counts, serum protein, albumin levels, and electrolyte concentrations.
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Carbamazepina , Espectrometría de Masas en Tándem , Benzodiazepinas , Cromatografía Liquida , Humanos , InmunoensayoRESUMEN
Our aim in this study was to measure serum levels of methylarginines and related metabolites in patients with ankylosing spondylitis (AS), moreover, to investigate the relationship between these parameters and various clinical and laboratory parameters of patients with AS. The study included 60 patients with AS and 60 healthy volunteers. Serum asymmetric dimethylarginine (ADMA), L-N monomethylarginine (L-NMMA), symmetric dimethylarginine (SDMA), arginine (Arg), homoarginine (hArg), ornithine, and citrulline concentrations were measured with tandem mass spectrometry. In addition, participants were divided into three groups according to the treatment regimen: TNF-α inhibitor group (n = 25), conventional therapy group (n = 35), and control group (n = 60). These groups were compared in terms of serum levels of methylarginine pathway metabolites and various biochemical parameters. It was found that total methylated arginine load significantly increased in patients with AS (p < 0.001), and the Arg/ADMA ratio was positively correlated with HDL levels and negatively correlated with glucose, ESR, total cholesterol, triglyceride, and LDL levels. In addition, serum ADMA, SDMA, total methylated arginine load, and CRP levels were lower (p < 0.05) in the TNF-α group compared to the conventional treatment group. To the best of our knowledge, this is the first study to comprehensively investigate serum methylarginine levels in patients with AS. Elevated total methylated arginine load and decreased global arginine bioavailability ratio (GABR) indicate that NO metabolism is impaired in patients with AS. Therefore, the increased cardiovascular risk in patients with AS may be related to the decreased NO production or bioavailability due to the elevated total methylarginine load.
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Arginina/análogos & derivados , Biomarcadores/sangre , Espondilitis Anquilosante/diagnóstico , Espectrometría de Masas en Tándem/métodos , Adulto , Arginina/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Espondilitis Anquilosante/sangreRESUMEN
PROBLEM: The cesarean section (CS) rate has increased significantly in North America, Western Europe, and Latin America. However, it has been reported that the incidence of inflammatory and autoimmune diseases such as asthma and type 1 diabetes increased in parallel with CS in these countries. Our aim was to investigate the expression level of miRNAs associated with inflammatory response and autoimmune diseases in colostrum samples and contribute to elucidating the role of CS in the pathogenesis of immune system-related diseases. METHOD OF STUDY: Colostrum samples were taken from voluntary mothers who had 40 normal and 50 cesarean births. miRNAs were extracted from colostrums and detected to miRNA expression profiling (eighty-four miRNAs) by quantitative real-time PCR with the Fluidigm integrated microfluidic circuit technology. RESULTS: There was a statistically significant change in the expression levels of 17 miRNAs in the colostrums of mothers who had normal and cesarean delivery (p < .05), and all of miRNAs were upregulated in the colostrums of mothers who have had cesarean delivery. CONCLUSION: Our best knowledge is that the study we conducted was the first to investigate the effect of delivery method (CS or normal) on the miRNA profile of colostrum. Cesarean delivery is a potential risk factor for inflammatory and immune system-related diseases in children due to dysregulation in miRNA expression.
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Enfermedades Autoinmunes/metabolismo , Calostro/metabolismo , MicroARNs/metabolismo , Adulto , Enfermedades Autoinmunes/genética , Cesárea , Perfilación de la Expresión Génica , Humanos , MicroARNs/genética , Factores de Riesgo , Adulto JovenRESUMEN
Favipiravir is a broad-spectrum inhibitor of viral RNA polymerase. It is currently used as a possible treatment for coronavirus disease 2019 (COVID-19). Pre-clinical or clinical trials of favipiravir require robust, sensitive, and accurate bioanalytical methods for quantitation of favipiravir levels. Recently, several studies have been reported about developing a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring favipiravir levels. However, these methods were validated predominantly for plasma samples, electrospray ionization was operated only in negative or positive mode, and clinical application of these methods has not been applied for patients with COVID-19. This study aimed was to develop a validated LC-MS/MS method for the measurement of favipiravir levels in positive and negative electrospray ionization mode and to perform a pilot study in patients with COVID-19 receiving favipiravir to demonstrate the applicability of this method in biological samples. Simple protein precipitation was used for the extraction of favipiravir from the desired matrix. Favipiravir levels were quantitated using MS / MS with an electrospray ionization source in positive and negative multiple reaction monitoring (MRM) mode. The chromatographic detection was performed on a reverse-phase Phenomenex C18 column (50 mm × 4.6 mm, 5 µm, 100 Å) with gradient elution using 0.1% formic acid in water and 0.1% formic acid in methanol as mobile phase. The method was linear over the concentration ranges of 0.048-50 µg/mL (in negative ionization mode) and 0.062-50 µg/mL (in positive ionization mode) with a correlation coefficient (r2) better than 0.998. The total run time was 3.5 min. The intra-assay and inter-assay %CV values were less than 7.2% and 8.0%, respectively. A simple, rapid and robust LC-MS / MS method was developed for the measurement of favipiravir and validation studies were performed. The validated method was successfully applied for drug level measurement in COVID-19 patients receiving favipiravir.
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Amidas/sangre , Tratamiento Farmacológico de COVID-19 , Cromatografía Liquida/métodos , Pirazinas/sangre , Espectrometría de Masas en Tándem/métodos , Amidas/administración & dosificación , Amidas/uso terapéutico , Antivirales/administración & dosificación , Antivirales/sangre , Antivirales/uso terapéutico , COVID-19/sangre , Estabilidad de Medicamentos , Humanos , Límite de Detección , Pirazinas/administración & dosificación , Pirazinas/uso terapéutico , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
BACKGROUND & OBJECTIVES: Obesity is known for low-grade inflammatory state with enhanced production of inflammatory mediators in children and adolescents. Soluble urokinase plasminogen activator receptor (suPAR) can be generated as a pro-inflammatory marker. This study was conducted to evaluate the role of suPAR, and its association with leptin, adiponectin, interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP) and fibrinogen in adolescent obesity. METHODS: A total of 98 participants, 55 obese individuals and 43 healthy controls, aged between 10 and 17 yr, were included in the study. Serum suPAR, IL-6, leptin and adiponectin were measured using ELISA method. RESULTS: Serum suPAR, IL-6, fibrinogen, hsCRP and leptin levels in obese individuals were significantly higher than those of controls (P<0.05 & P<0.001). Serum adiponectin levels in obese individuals were significantly lower than those of controls (P<0.01). INTERPRETATION & CONCLUSIONS: Our findings showed that suPAR, IL-6, fibrinogen, hsCRP and leptin were significantly higher in the obese individuals than those of controls. suPAR may be a good novel biomarker for systemic subclinical inflammation and immune activation linked to adolescent obesity.
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Biomarcadores/sangre , Inflamación/sangre , Obesidad Infantil/sangre , Receptores del Activador de Plasminógeno Tipo Uroquinasa/sangre , Adiponectina/sangre , Adolescente , Proteína C-Reactiva/metabolismo , Niño , Femenino , Humanos , Inflamación/patología , Interleucina-6/sangre , Leptina/sangre , Masculino , Obesidad Infantil/patologíaRESUMEN
OBJECTIVE: The Western-type diet is associated with an elevated risk of Alzheimer's disease and other milder forms of cognitive impairment. The aim of the present study was to investigate the effects of the environmental enrichment on amyloid and tau pathology in high-fat and high-sucrose-fed rats. METHODS: In total, 40 adult male rats were categorised into two main groups according to their housing conditions: enriched environment (EE, n=16) and standard housing condition (n=24). The groups were further divided into five subgroups that received standard diet, high-fat diet, and high-sucrose diet. We performed the analysis of amyloid ß-peptide (Aß) (1-40), Aß(1-42), amyloid precursor protein (APP), and tau levels in the hippocampus of rats that were maintained under standard housing conditions or exposed to an EE. RESULTS: The EE decreased the Aß(1-40), Aß(1-42), APP, and tau levels in high-fat and high-sucrose-fed rats. CONCLUSION: This observation shows that EE may rescue diet-induced amyloid and tau pathology.
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Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Dieta Alta en Grasa/efectos adversos , Azúcares de la Dieta/efectos adversos , Ambiente , Proteínas tau/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Hipocampo/metabolismo , Masculino , Fragmentos de Péptidos/metabolismo , Ratas WistarRESUMEN
AIMS: Previous studies demonstrated that the Western diet (WD), which is rich in saturated fat (HFD) and refined sugar (HSU), is related to the impairments of hippocampus-dependent learning and memory and forebrain synaptic plasticity in rodents. The environmental enrichment (EE) has been shown to enhance learning and memory in the HFD-induced cognitive deficits, but the exact mechanism is still not clearly understood. Therefore, the present study aimed to clarify the effects of the EE on spatial memory in WD-fed rats, and to analyze the potential role of corticosteroid receptors in the EE conditioning. MAIN METHODS: Male Wistar albino rats were housed in either an enriched or standard environment and fed with the HFD (35% of energy as fat), HSU (100% of carbohydrate as sucrose) or standard rat chow for 4weeks. We used the Morris' water maze test (MWM) to assess the learning and memory performance, and measured plasma levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH), as well as glucocorticoid (GR) and mineralocorticoid receptor (MR) levels in the hippocampus. KEY FINDINGS: The results showed that HFD-fed rats displayed poorer learning and memory performance evaluated with MWM than controls. The EE reversed the cognitive deficits caused by the HFD. In addition, the EE resulted in an increase of GR and MR levels without affecting plasma CORT and ACTH concentrations. SIGNIFICANCE: Based on these findings, it could be suggested that the EE plays an important role in amelioration of the HFD-induced cognitive impairments, but this intervention is independent of the hypothalamic-pituitary-adrenal axis and hippocampal corticosteroid receptor levels.
Asunto(s)
Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/terapia , Dieta Occidental/efectos adversos , Ambiente , Sistema Hipófiso-Suprarrenal/metabolismo , Receptores de Esteroides/fisiología , Animales , Trastornos del Conocimiento/etiología , Dieta Alta en Grasa/efectos adversos , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Aprendizaje por Laberinto/fisiología , Ratas , Ratas Wistar , Receptores de Mineralocorticoides/fisiologíaRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been associated with increased oxidative stress or reduced antioxidant resources. The main goal of this study was to evaluate the levels of serum ischemia-modified albumin (IMA), oxidized low-density lipoprotein (ox-LDL), total oxidant status (TOS), and total antioxidant status in patients with stable COPD, compared with a control group. METHODS: This study was performed on 51 patients with stable COPD (42 men and 9 women; mean age 56.92 ± 3.0 years) and 45 healthy control participants (32 men and 13 women; 54.8 ± 3.8 years). The levels of serum lipids, IMA, total antioxidant status, TOS, and ox-LDL were measured in all participants. RESULTS: The levels of serum IMA, ox-LDL, and TOS were significantly higher in patients with COPD than those in control individuals. There was no difference between the levels of serum total antioxidant status, triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) of patients with COPD and those of control individuals. Serum high-density lipoprotein cholesterol levels were significantly lower in patients with COPD than in control individuals. CONCLUSION: Our study indicated that serum IMA, ox-LDL, and TOS may be increased as a result of chronic hypoxia, inflammation, and oxidative stress in patients with severe and very severe stable COPD. Our findings also revealed that IMA is higher in patients with Global Initiative for Chronic Obstructive Lung Disease Stages II, III, and IV, while TOS and ox-LDL are higher in patients with Global Initiative for Chronic Obstructive Lung Disease Stage IV. Measurements of serum IMA, TOS, and ox-LDL levels may be useful markers in the evaluation of stable COPD.