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1.
Eur Rev Med Pharmacol Sci ; 25(12): 4435-4438, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34227081

RESUMO

OBJECTIVE: We aimed at explaining the mechanism of therapeutic effect of Umbilical Cord Mesenchymal Stem Cells (UC-MSC) in subjects with COVID-19 Acute Respiratory Distress Syndrome (ARDS). Patients with COVID-19 ARDS present with a hyperinflammatory response characterized by high levels of circulating pro-inflammatory mediators, including tumor necrosis factor α and ß (TNFα and TNFß). Inflammatory functions of these TNFs can be inhibited by soluble TNF Receptor 2 (sTNFR2). In patients with COVID-19 ARDS, UC-MSC appear to impart a robust anti-inflammatory effect, and treatment is associated with remarkable clinical improvements. We investigated the levels of TNFα, TNFß and sTNFR2 in blood plasma samples collected from subjects with COVID-19 ARDS enrolled in our trial of UC-MSC treatment. PATIENTS AND METHODS: We analyzed plasma samples from subjects with COVID-19 ARDS (n=24) enrolled in a Phase 1/2a randomized controlled trial of UC-MSC treatment. Plasma samples were obtained at Day 0 (baseline, before UC-MSC or control infusion), and Day 6 post infusion. Plasma concentrations of sTNFR2, TNFα, and TNFß were evaluated using a quantitative multiplex protein array. RESULTS: Our data indicate that at Day 6 after infusion, UC-MSC recipients develop significantly increased levels of plasma sTNFR2 and significantly decreased levels of TNFα and TNFß, compared to controls. CONCLUSIONS: These observations suggest that sTNFR2 plays a mechanistic role in mediating UC-MSC effect on TNFα and TNFß plasma levels, determining a decrease in inflammation in COVID-19 ARDS.


Assuntos
COVID-19/sangue , Linfotoxina-alfa/sangue , Transplante de Células-Tronco Mesenquimais/métodos , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Síndrome do Desconforto Respiratório/sangue , Fator de Necrose Tumoral alfa/sangue , Cordão Umbilical/transplante , Biomarcadores/sangue , COVID-19/terapia , Método Duplo-Cego , Humanos , Síndrome do Desconforto Respiratório/terapia , Cordão Umbilical/citologia
4.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200496

RESUMO

Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal disease caused by mutations in the gene encoding the enzymeN-acetylgalactosamine-6-sulfate sulfatase (GALNS), and is characterized by systemic skeletal dysplasia due to excessive storage of keratan sulfate (KS) and chondroitin-6-sulfate in chondrocytes. Although improvements in the activity of daily living and endurance tests have been achieved with enzyme replacement therapy (ERT) with recombinant human GALNS, recovery of bone lesions and bone growth in MPS IVA has not been demonstrated to date. Moreover, no correlation has been described between therapeutic efficacy and urine levels of KS, which accumulates in MPS IVA patients. The objective of this study was to assess the validity of potential biomarkers proposed by other authors and to identify new biomarkers. To identify candidate biomarkers of this disease, we analyzed plasma samples from healthy controls (n=6) and from untreated (n=8) and ERT-treated (n=5, sampled before and after treatment) MPS IVA patients using both qualitative and quantitative proteomics analyses. The qualitative proteomics approach analyzed the proteomic profile of the different study groups. In the quantitative analysis, we identified/quantified 215 proteins after comparing healthy control untreated, ERT-treated MPSIVA patients. We selected a group of proteins that were dysregulated in MPS IVA patients. We identified four potential protein biomarkers, all of which may influence bone and cartilage metabolism: fetuin-A, vitronectin, alpha-1antitrypsin, and clusterin. Further studies of cartilage and bone samples from MPS IVA patients will be required to verify the validity of these proteins as potential biomarkers of MPS IVA.


Assuntos
Biomarcadores/sangue , Condroitina Sulfatases/deficiência , Terapia de Reposição de Enzimas/métodos , Mucopolissacaridose IV/diagnóstico , Proteoma/metabolismo , Estudos de Casos e Controles , Condroitina Sulfatases/administração & dosagem , Humanos , Mucopolissacaridose IV/sangue , Mucopolissacaridose IV/terapia , Proteoma/análise
5.
Front Immunol ; 12: 619906, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194420

RESUMO

The role of sMAdCAM, an important gut immune migratory marker, remains unexplored in COVID-19 pathogenesis considering recent studies positing the gut as a sanctuary site for SARS-CoV-2 persistence. Thus, assimilating profiles of systemic inflammatory mediators with sMAdCAM levels may provide insights into the progression of COVID-19 disease. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. A cohort (n = 84) of SARS-C0V-2 infected individuals included a group of in-patients (n = 60) at various stages of disease progression together with convalescent individuals (n = 24) recruited between April and June 2020 from Mumbai, India. Follow-up of 35 in-patients at day 7 post diagnosis was carried out. Th1/Th2/Th17 cytokines along with soluble MAdCAM (sMAdCAM) levels in plasma were measured. Also, anti-viral humoral response as measured by rapid antibody test (IgG, IgM), Chemiluminescent Immunoassay (IgG), and antibodies binding to SARS-CoV-2 proteins were measured by Surface Plasmon Resonance (SPR) from plasma. IL-6 and sMAdCAM levels among in-patients inversely correlated with one another. When expressed as a novel integrated marker-sMIL index (sMAdCAM/IL-6 ratio)-these levels were incrementally and significantly higher in various disease states with convalescents exhibiting the highest values. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association response units of receptor binding domain and fold change in binding to spike respectively as measured by SPR. Our results highlight key systemic and gut homing parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.


Assuntos
COVID-19/imunologia , Moléculas de Adesão Celular/sangue , Interleucina-6/sangue , Mucoproteínas/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Estudos de Coortes , Citocinas/sangue , Progressão da Doença , Feminino , Humanos , Intestinos/imunologia , Masculino , Pessoa de Meia-Idade , Ressonância de Plasmônio de Superfície , Adulto Jovem
6.
J Clin Invest ; 131(13)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196300

RESUMO

BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform.RESULTSThis study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways.CONCLUSIONThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.FUNDINGMark and Lisa Schwartz; the National Institutes of Health (U19AI082630); the American Lung Association; the Executive Committee on Research at Massachusetts General Hospital; the Chan Zuckerberg Initiative; Arthur, Sandra, and Sarah Irving for the David P. Ryan, MD, Endowed Chair in Cancer Research; an EMBO Long-Term Fellowship (ALTF 486-2018); a Cancer Research Institute/Bristol Myers Squibb Fellowship (CRI2993); the Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH awards UL1TR001102 and UL1TR002541-01); and by the Harvard University Center for AIDS Research (National Institute of Allergy and Infectious Diseases, 5P30AI060354).


Assuntos
COVID-19/sangue , COVID-19/virologia , SARS-CoV-2 , Viremia/sangue , Viremia/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Pandemias , Prognóstico , Proteoma/metabolismo , Proteômica , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Internalização do Vírus
7.
Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206601

RESUMO

To identify biomarkers of ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A234)- or methyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A232)-inhibited butyrylcholinesterase (BChE), we investigated nonapeptide adducts containing the active site serine, which plays a key role in enzyme activity, using LC-MS/HRMS. Biomarkers were acquired as expected, and they exhibited a significant amount of fragment ions from the inhibiting agent itself, in contrast to the MS2 spectra of conventional nerve agents. These biomarkers had a higher abundance of [M+2H]2+ ions than [M+H]+ ions, making doubly charged ions more suitable for trace analysis.


Assuntos
Butirilcolinesterase/sangue , Agentes Neurotóxicos , Organofosfatos , Plasma , Biomarcadores/sangue , Inibidores da Colinesterase/farmacocinética , Inibidores da Colinesterase/toxicidade , Humanos , Agentes Neurotóxicos/farmacocinética , Agentes Neurotóxicos/toxicidade , Organofosfatos/farmacocinética , Organofosfatos/toxicidade
8.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206780

RESUMO

Vascular calcification (VC) is a risk factor for cardiovascular events and mortality in chronic kidney disease (CKD). Several components influence the occurrence of VC, among which inflammation. A novel uremic toxin, lanthionine, was shown to increase intracellular calcium in endothelial cells and may have a role in VC. A group of CKD patients was selected and divided into patients with a glomerular filtration rate (GFR) of <45 mL/min/1.73 m2 and ≥45 mL/min/1.73 m2. Total Calcium Score (TCS), based on the Agatston score, was assessed as circulating lanthionine and a panel of different cytokines. A hemodialysis patient group was also considered. Lanthionine was elevated in CKD patients, and levels increased significantly in hemodialysis patients with respect to the two CKD groups; in addition, lanthionine increased along with the increase in TCS, starting from one up to three. Interleukin IL-6, IL-8, and Eotaxin were significantly increased in patients with GFR < 45 mL/min/1.73 m2 with respect to those with GFR ≥ 45 mL/min/1.73 m2. IL-1b, IL-7, IL-8, IL-12, Eotaxin, and VEGF increased in calcified patients with respect to the non-calcified. IL-8 and Eotaxin were elevated both in the low GFR group and in the calcified group. We propose that lanthionine, but also IL-8 and Eotaxin, in particular, are a key feature of VC of CKD, with possible marker significance.


Assuntos
Alanina/análogos & derivados , Citocinas/sangue , Insuficiência Renal Crônica/metabolismo , Sulfetos/sangue , Calcificação Vascular/metabolismo , Adulto , Alanina/sangue , Biomarcadores/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Calcificação Vascular/sangue , Calcificação Vascular/etiologia
9.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206927

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder leading to deterioration of kidney function and end stage kidney disease (ESKD). A number of molecular processes are dysregulated in ADPKD but the exact mechanism of disease progression is not fully understood. We measured protein biomarkers being linked to ADPKD-associated molecular processes via ELISA in urine and serum in a cohort of ADPKD patients as well as age, gender and eGFR matched CKD patients and healthy controls. ANOVA and t-tests were used to determine differences between cohorts. Spearman correlation coefficient analysis was performed to assess coregulation patterns of individual biomarkers and renal function. Urinary epidermal growth factor (EGF) and serum apelin (APLN) levels were significantly downregulated in ADPKD patients. Serum vascular endothelial growth factor alpha (VEGFA) and urinary angiotensinogen (AGT) were significantly upregulated in ADPKD patients as compared with healthy controls. Arginine vasopressin (AVP) was significantly upregulated in ADPKD patients as compared with CKD patients. Serum VEGFA and VIM concentrations were positively correlated and urinary EGF levels were negatively correlated with urinary AGT levels. Urinary EGF and AGT levels were furthermore significantly associated with estimated glomerular filtration rate (eGFR) in ADPKD patients. In summary, altered protein concentrations in body fluids of ADPKD patients were found for the mechanistic markers EGF, APLN, VEGFA, AGT, AVP, and VIM. In particular, the connection between EGF and AGT during progression of ADPKD warrants further investigation.


Assuntos
Rim Policístico Autossômico Dominante/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiotensinogênio/urina , Apelina/sangue , Arginina Vasopressina/sangue , Arginina Vasopressina/urina , Biomarcadores/sangue , Biomarcadores/urina , Fator de Crescimento Epidérmico/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/urina , Fator A de Crescimento do Endotélio Vascular/sangue
10.
Int J Med Sci ; 18(13): 2789-2798, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220307

RESUMO

Coronavirus disease 2019 (COVID-19) has spread widely in the communities in many countries. Although most of the mild patients could be cured by their body's ability to self-heal, many patients quickly progressed to severe disease and had to undergo treatment in the intensive care unit (ICU). Thus, it is very important to effectively predict which patients with mild disease are more likely to progress to severe disease. A total of 72 patients hospitalized with COVID-19 in Shandong Provincial Public Health Clinical Center and 1141 patients included in the published papers were enrolled in this study. We determined that the combination of interleukin-6 (IL-6), Neutrophil (NEUT), and Natural Killer (NK) cells had the highest prediction accuracy (with 75% sensitivity and 95% specificity) for progression of COVID-19 infection. A binomial regression equation that accounted for a multiple risk score for the combination of IL-6, NEUT, and NK was also established. The multiple risk score is a good indicator for early stratification of mild patients into risk categories, which is very important for adjusting the treatment plan and preventing death.


Assuntos
Biomarcadores/análise , COVID-19/etiologia , Idoso , Biomarcadores/sangue , Contagem de Células Sanguíneas , COVID-19/epidemiologia , Comorbidade , Progressão da Doença , Humanos , Interleucina-6/sangue , Células Matadoras Naturais , Pessoa de Meia-Idade , Neutrófilos , Estudos Retrospectivos
11.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203775

RESUMO

Mitochondrial disorders (MD) comprise a group of heterogeneous clinical disorders for which non-invasive diagnosis remains a challenge. Two protein biomarkers have so far emerged for MD detection, FGF-21 and GDF-15, but the identification of additional biomarkers capable of improving their diagnostic accuracy is highly relevant. Previous studies identified Gelsolin as a regulator of cell survival adaptations triggered by mitochondrial defects. Gelsolin presents a circulating plasma isoform (pGSN), whose altered levels could be a hallmark of mitochondrial dysfunction. Therefore, we investigated the diagnostic performance of pGSN for MD relative to FGF-21 and GDF-15. Using ELISA assays, we quantified plasma levels of pGSN, FGF-21, and GDF-15 in three age- and gender-matched adult cohorts: 60 genetically diagnosed MD patients, 56 healthy donors, and 41 patients with unrelated neuromuscular pathologies (non-MD). Clinical variables and biomarkers' plasma levels were compared between groups. Discrimination ability was calculated using the area under the ROC curve (AUC). Optimal cut-offs and the following diagnostic parameters were determined: sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and efficiency. Comprehensive statistical analyses revealed significant discrimination ability for the three biomarkers to classify between MD and healthy individuals, with the best diagnostic performance for the GDF-15/pGSN combination. pGSN and GDF-15 preferentially discriminated between MD and non-MD patients under 50 years, whereas FGF-21 best classified older subjects. Conclusion: pGSN improves the diagnosis accuracy for MD provided by FGF-21 and GDF-15.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Gelsolina/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Doenças Mitocondriais/sangue , Doenças Mitocondriais/diagnóstico , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
12.
Molecules ; 26(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204618

RESUMO

There is scientific evidence of the positive effect of polyphenols from plant foods on inflammation and oxidative status. The aim of the present study was to investigate whether treatment with a high-polyphenolic nutraceutical reduces the plasmatic concentration of certain oxidative and inflammatory biomarkers in a healthy population. One hundred and eight subjects were selected and stratified by sex in the intervention group (n = 53) and the placebo group (n = 55). Ninety-two subjects completed the study after two 16-week treatment periods separated by a four-week washout period. The results revealed statistically significant differences in subjects treated with the polyphenolic extract compared to the placebo: A decrease in homocysteine, oxidized low-density lipoprotein (OxLDL), TNF-α, sTNFR1, and C-reactive protein (CRP). The most significant decrease was observed for OxLDL (from 78.98 ± 24.48 to 69.52 ± 15.64; p < 0.05) and CRP (from 1.50 ± 0.33 to 1.39 ± 0.37; p < 0.05), both showing significant differences compared to the placebo (p < 0.001). Moreover, catecholamines increased after the administration of the product under investigation, especially in the case of dopamine (from 15.43 ± 2.66 to 19.61 ± 5.73; p < 0.05). Therefore, the consumption of a nutraceutical based on fruit and vegetables with a high polyphenol content seems to improve the parameters related to health benefits (oxidative and inflammatory biomarkers), including remarkable changes in the expression of catecholamines.


Assuntos
Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Adulto , Antioxidantes/farmacologia , Biomarcadores/sangue , Catecolaminas/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Frutas/metabolismo , Humanos , Lipoproteínas LDL/efeitos dos fármacos , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Placebos , Verduras/metabolismo
13.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207213

RESUMO

Autism spectrum disorder (ASD) is a multifaced neurodevelopmental disorder that becomes apparent during early childhood development. The complexity of ASD makes clinically diagnosing the condition difficult. Consequently, by identifying the biomarkers associated with ASD severity and combining them with clinical diagnosis, one may better factionalize within the spectrum and devise more targeted therapeutic strategies. Currently, there are no reliable biomarkers that can be used for precise ASD diagnosis. Consequently, our pilot experimental cohort was subdivided into three groups: healthy controls, individuals those that express severe symptoms of ASD, and individuals that exhibit mild symptoms of ASD. Using next-generation sequencing, we were able to identify several circulating non-coding RNAs (cir-ncRNAs) in plasma. To the best of our knowledge, this study is the first to show that miRNAs, piRNAs, snoRNAs, Y-RNAs, tRNAs, and lncRNAs are stably expressed in plasma. Our data identify cir-ncRNAs that are specific to ASD. Furthermore, several of the identified cir-ncRNAs were explicitly associated with either the severe or mild groups. Hence, our findings suggest that cir-ncRNAs have the potential to be utilized as objective diagnostic biomarkers and clinical targets.


Assuntos
Transtorno do Espectro Autista/sangue , Ácidos Nucleicos Livres/sangue , RNA Longo não Codificante/sangue , Pequeno RNA não Traduzido/sangue , Adolescente , Transtorno do Espectro Autista/diagnóstico , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino
14.
Nutrients ; 13(6)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207745

RESUMO

It has recently been hypothesized that vitamin K could play a role in COVID-19. We aimed to test the hypotheses that low vitamin K status is a common characteristic of patients hospitalized with COVID-19 compared to population controls and that low vitamin K status predicts mortality in COVID-19 patients. In a cohort of 138 COVID-19 patients and 138 population controls, we measured plasma dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP), which reflects the functional vitamin K status in peripheral tissue. Forty-three patients died within 90 days from admission. In patients, levels of dp-ucMGP differed significantly between survivors (mean 877; 95% CI: 778; 995) and non-survivors (mean 1445; 95% CI: 1148; 1820). Furthermore, levels of dp-ucMGP (pmol/L) were considerably higher in patients (mean 1022; 95% CI: 912; 1151) compared to controls (mean 509; 95% CI: 485; 540). Cox regression survival analysis showed that increasing levels of dp-ucMGP (reflecting low vitamin K status) were associated with higher mortality risk (sex- and age-adjusted hazard ratio per doubling of dp-ucMGP was 1.49, 95% CI: 1.03; 2.24). The association attenuated and became statistically insignificant after adjustment for co-morbidities (sex, age, CVD, diabetes, BMI, and eGFR adjusted hazard ratio per doubling of dp-ucMGP was 1.22, 95% CI: 0.82; 1.80). In conclusion, we found that low vitamin K status was associated with mortality in patients with COVID-19 in sex- and age-adjusted analyses, but not in analyses additionally adjusted for co-morbidities. Randomized clinical trials would be needed to clarify a potential role, if any, of vitamin K in the course of COVID-19.


Assuntos
COVID-19/mortalidade , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Hospitalização , Deficiência de Vitamina K/mortalidade , Vitamina K/sangue , Adulto , Idoso , Biomarcadores/sangue , Coagulação Sanguínea , COVID-19/complicações , COVID-19/metabolismo , Proteínas de Ligação ao Cálcio/sangue , Estudos de Coortes , Proteínas da Matriz Extracelular/sangue , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Regressão , SARS-CoV-2 , Trombose/metabolismo , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/complicações , Adulto Jovem
15.
Emerg Med Clin North Am ; 39(3): 467-478, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34215397

RESUMO

Can laboratory tests that are routinely used in adult patients also be used in pediatric patients? Does the current literature support the routine use of troponin, brain natriuretic peptide, D-dimer, and lactate in children? Adult problems such as acute coronary syndrome and pulmonary embolism are rare in pediatrics, and there is a paucity of literature on how blood tests commonly used to help diagnose these conditions in adults play a role in the diagnosis and management of children. This article presents the literature about 4 common blood tests and examines the clinical applications of each.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Ácido Láctico/sangue , Peptídeo Natriurético Encefálico/sangue , Troponina/sangue , Asma/diagnóstico , Biomarcadores/sangue , Criança , Cardiopatias/diagnóstico , Humanos , Infecções/diagnóstico , Intussuscepção/diagnóstico , Doenças Mitocondriais/diagnóstico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Prognóstico , Embolia Pulmonar/diagnóstico , Síndrome do Desconforto Respiratório/diagnóstico , Sepse/diagnóstico , Ferimentos e Lesões/diagnóstico
16.
Emerg Med Clin North Am ; 39(3): 627-639, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34215406

RESUMO

Pediatric fever is a common complaint in children. The most common cause is self-limited viral infection. However, neonates and young infants are evaluated and treated differently than older, vaccinated, and clinically evaluable children. Neonates should be admitted to the hospital, young infants in the second month of life may be risk stratified, and those deemed low risk on testing may be sent home with close follow-up. Children older than 2 months may be evaluated clinically for signs of bacterial infection that require intervention. Urinary tract infections cause more than 90% of serious bacterial illness in children, and younger children have a higher incidence of infection.


Assuntos
Febre/etiologia , Febre/terapia , Medicina de Emergência Pediátrica , Algoritmos , Anemia Falciforme/complicações , Antibacterianos/uso terapêutico , Antipiréticos/uso terapêutico , Biomarcadores/sangue , Proteína C-Reativa/análise , Criança , Febre/diagnóstico , Humanos , Incidência , Doenças do Prematuro/diagnóstico , Infecções/diagnóstico , Infecções/tratamento farmacológico , Neutropenia/complicações , Pró-Calcitonina/sangue , Medição de Risco
17.
Pak J Pharm Sci ; 34(1(Supplementary)): 275-281, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275851

RESUMO

This study investigated the significance of difference between presence and absence of different neurological findings in COVID-19, in relation with the biochemistry. Various significant correlations in connection with the disease severity and clinical factors were also identified. 351 COVID-19 patients were included. Different laboratory/ clinical findings were investigated. Correlations Kendall's tau and Pearson Chi-Square were applied to find the correlations between severity and clinical findings. The Mann-Whitney Test was applied for a comparison between two types of neurological groups for each biochemistry parameter. Headache was reported in 28% and dizziness in 13% patients. The impaired smell and impaired taste were reported in 28.5% and 36.2% patients, respectively. The muscle pain was present in 39% patients. 80% patients had low lymphocytes & 70% had high neutrophils. 54.5% were found with high ALP. LDH was elevated in 73%. Severity was found significantly correlated with decreased oxygen saturation, age and raised levels of urea, creatinine and LDH. The groups (with/without CNS involvement) were statistically different in ALP, groups (with/without PNS involvement) in WBC, lymphocytes, neutrophils, ALP, urea, creatinine, CK, CKMB and LDH and groups (with/without MSK involvement) in WBC. Oxygen saturation, age, urea, creatinine and LDH are significant indicators of disease severity in COVID-19. The altered levels of different biochemistry can impact the neurological states of COVID-19 patients.


Assuntos
COVID-19/sangue , COVID-19/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Análise Química do Sangue , COVID-19/diagnóstico por imagem , COVID-19/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Paquistão , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
18.
Sci Rep ; 11(1): 14732, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282210

RESUMO

Research exploring the development and outcome of COVID-19 infections has led to the need to find better diagnostic and prognostic biomarkers. This cross-sectional study used targeted metabolomics to identify potential COVID-19 biomarkers that predicted the course of the illness by assessing 110 endogenous plasma metabolites from individuals admitted to a local hospital for diagnosis/treatment. Patients were classified into four groups (≈ 40 each) according to standard polymerase chain reaction (PCR) COVID-19 testing and disease course: PCR-/controls (i.e., non-COVID controls), PCR+/not-hospitalized, PCR+/hospitalized, and PCR+/intubated. Blood samples were collected within 2 days of admission/PCR testing. Metabolite concentration data, demographic data and clinical data were used to propose biomarkers and develop optimal regression models for the diagnosis and prognosis of COVID-19. The area under the receiver operating characteristic curve (AUC; 95% CI) was used to assess each models' predictive value. A panel that included the kynurenine: tryptophan ratio, lysoPC a C26:0, and pyruvic acid discriminated non-COVID controls from PCR+/not-hospitalized (AUC = 0.947; 95% CI 0.931-0.962). A second panel consisting of C10:2, butyric acid, and pyruvic acid distinguished PCR+/not-hospitalized from PCR+/hospitalized and PCR+/intubated (AUC = 0.975; 95% CI 0.968-0.983). Only lysoPC a C28:0 differentiated PCR+/hospitalized from PCR+/intubated patients (AUC = 0.770; 95% CI 0.736-0.803). If additional studies with targeted metabolomics confirm the diagnostic value of these plasma biomarkers, such panels could eventually be of clinical use in medical practice.


Assuntos
Biomarcadores/sangue , COVID-19/diagnóstico , Metabolômica , Adulto , Teste para COVID-19 , Estudos Transversais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Curva ROC
19.
J Int Soc Sports Nutr ; 18(1): 56, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34246303

RESUMO

BACKGROUND: The effects of low muscle glycogen on molecular markers of protein synthesis and myogenesis before and during aerobic exercise with carbohydrate ingestion is unclear. The purpose of this study was to determine the effects of initiating aerobic exercise with low muscle glycogen on mTORC1 signaling and markers of myogenesis. METHODS: Eleven men completed two cycle ergometry glycogen depletion trials separated by 7-d, followed by randomized isocaloric refeeding for 24-h to elicit low (LOW; 1.5 g/kg carbohydrate, 3.0 g/kg fat) or adequate (AD; 6.0 g/kg carbohydrate, 1.0 g/kg fat) glycogen. Participants then performed 80-min of cycle ergometry (64 ± 3% VO2peak) while ingesting 146 g carbohydrate. mTORC1 signaling (Western blotting) and gene transcription (RT-qPCR) were determined from vastus lateralis biopsies before glycogen depletion (baseline, BASE), and before (PRE) and after (POST) exercise. RESULTS: Regardless of treatment, p-mTORC1Ser2448, p-p70S6KSer424/421, and p-rpS6Ser235/236 were higher (P < 0.05) POST compared to PRE and BASE. PAX7 and MYOGENIN were lower (P < 0.05) in LOW compared to AD, regardless of time, while MYOD was lower (P < 0.05) in LOW compared to AD at PRE, but not different at POST. CONCLUSION: Initiating aerobic exercise with low muscle glycogen does not affect mTORC1 signaling, yet reductions in gene expression of myogenic regulatory factors suggest that muscle recovery from exercise may be reduced.


Assuntos
Metabolismo dos Carboidratos , Exercício Físico/fisiologia , Glicogênio/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Desenvolvimento Muscular/fisiologia , Músculo Esquelético/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Adulto , Biomarcadores/sangue , Metabolismo dos Carboidratos/genética , Estudos Cross-Over , Ergometria/métodos , Glicogênio/deficiência , Humanos , Masculino , Proteína MyoD/metabolismo , Miogenina/metabolismo , Fator de Transcrição PAX7/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Fatores de Tempo , Transcrição Genética , Adulto Jovem
20.
Nat Commun ; 12(1): 4304, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262030

RESUMO

Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer's disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in individuals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73-0.87] and 0.92 [95% CI 0.89-0.95] for the discrimination between asymptomatic individuals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS.


Assuntos
Doença de Alzheimer/diagnóstico , Síndrome de Down/diagnóstico , Proteínas tau/sangue , Adulto , Doença de Alzheimer/sangue , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Área Sob a Curva , Atrofia , Biomarcadores/sangue , Biomarcadores/metabolismo , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Cognição , Estudos Transversais , Progressão da Doença , Síndrome de Down/sangue , Síndrome de Down/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/sangue , Fosforilação , Proteínas tau/metabolismo
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