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1.
J Am Heart Assoc ; 10(16): e021428, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34365798

RESUMO

Background Cardiac dysfunction is a prominent feature of multisystem inflammatory syndrome in children (MIS-C), yet the etiology is poorly understood. We determined whether dysfunction is global or regional, and whether it is associated with the cytokine milieu, microangiopathy, or severity of shock. Methods and Results We analyzed echocardiographic parameters of myocardial deformation and compared global and segmental left ventricular strain between 43 cases with MIS-C ≤18 years old and 40 controls. Primary outcomes included left ventricular global longitudinal strain, right ventricular free wall strain), and left atrial strain. We evaluated relationships between strain and profiles of 10 proinflammatory cytokines, microangiopathic features (soluble C5b9), and vasoactive-inotropic requirements. Compared with controls, cases with MIS-C had significant impairments in all parameters of systolic and diastolic function. 65% of cases with MIS-C had abnormal left ventricular function (|global longitudinal strain|<17%), although elevations of cytokines were modest. All left ventricular segments were involved, without apical or basal dominance to suggest acute stress cardiomyopathy. Worse global longitudinal strain correlated with higher ratios of interleukin-6 (ρ -0.43) and interleukin-8 (ρ -0.43) to total hypercytokinemia, but not absolute levels of interleukin-6 or interleukin-8, or total hypercytokinemia. Similarly, worse right ventricular free wall strain correlated with higher relative interleukin-8 expression (ρ -0.59). There were no significant associations between function and microangiopathy or vasoactive-inotropic requirements. Conclusions Myocardial function is globally decreased in MIS-C and not explained by acute stress cardiomyopathy. Cardiac dysfunction may be driven by the relative skew of the immune response toward interleukin-6 and interleukin-8 pathways, more so than degree of hyperinflammation, refining the current paradigm of myocardial involvement in MIS-C.


Assuntos
Função do Átrio Esquerdo , COVID-19/complicações , Síndrome da Liberação de Citocina/etiologia , Citocinas/sangue , Cardiopatias/etiologia , Mediadores da Inflamação/sangue , Síndrome de Resposta Inflamatória Sistêmica/complicações , Função Ventricular Esquerda , Função Ventricular Direita , Adolescente , Fatores Etários , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Criança , Estudos Transversais , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/imunologia , Ecocardiografia , Feminino , Cardiopatias/diagnóstico por imagem , Cardiopatias/imunologia , Cardiopatias/fisiopatologia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/imunologia
2.
Nutr Metab Cardiovasc Dis ; 31(9): 2619-2627, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34353699

RESUMO

BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). METHODS AND RESULTS: We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. CONCLUSION: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.


Assuntos
COVID-19/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/terapia , Regulação para Baixo , Dislipidemias/diagnóstico , Dislipidemias/mortalidade , Dislipidemias/terapia , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espanha , Fatores de Tempo
3.
Biomed Res Int ; 2021: 5822259, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34423037

RESUMO

Background: COVID-19 patients can present with neurological manifestations in the form of headache, dizziness, hyposmia, myalgia, peripheral neuropathy, acute cerebrovascular disease, and encephalopathy. Neurological involvement could be due to virus-induced brain hypoxia, brain infection, or immune reaction. We aim to describe the neurological presentation of COVID-19 patients and study their neuroimaging findings and disease outcome. Method: The study is a single-centre, retrospective, observational study in Sheikh Shakhbout Medical City (SSMC), Abu Dhabi, UAE. Patients diagnosed with COVID-19 between March and May 2020 who presented with neuropathological features with or without respiratory manifestations of COVID-19 were enrolled. Electronic records were studied for age, sex, duration of hospitalization, detailed neurological presentation, history or documented concomitant fever and respiratory features of COVID-19, inflammatory markers, neuroimaging, progress, and disease outcome. Results: Thirty-three patients of 10 nationalities presented with neurological manifestations. Mean (range) age was 51.4 (21-86) years. Twenty-four had comorbidities, and 18 had no prior or concomitant respiratory symptoms. Ten patients presented with encephalopathy and exhibited altered behavior/sensorium: 7 presented with myositis, 8 with stroke, and 4 with seizures, and 4 had peripheral and cranial nerve involvement. The mean (average) duration of hospital stay was 11.4 days (1-38) with the longest observed in stroke patients. Fifteen patients (45%) died and 3 (9%) had residual weakness. Serum ferritin, CRP, and procalcitonin were higher in the severe disease group and correlated with risk of death. Twelve of 22 brain images showed abnormalities including haemorrhage, infarcts, small vessel ischemia, and oedema. Risk of death was higher in older age but did not differ based on the underlying neuropathology. Conclusion: COVID-19 patients who present with neurological involvement have a higher risk of mortality which is aggravated by older age and higher inflammatory markers. The type of neurological pathology does not seem to influence the risk of mortality.


Assuntos
COVID-19/complicações , COVID-19/diagnóstico , Doenças do Sistema Nervoso/etiologia , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Encéfalo/diagnóstico por imagem , COVID-19/epidemiologia , Feminino , Hospitalização , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/diagnóstico por imagem , Neuroimagem , Pandemias , Prognóstico , Terapia Respiratória , Estudos Retrospectivos , SARS-CoV-2/patogenicidade , Emirados Árabes Unidos/epidemiologia , Adulto Jovem
4.
Nutrients ; 13(7)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34371834

RESUMO

In postmenopausal women (PW), estrogen depletion may predispose to cognitive decline through an increased risk of chronic inflammation. Unhealthy diets also appear to have an impact on the cognitive health of these women. The aim of this study was to investigate the association between inflammatory potential of the diet, levels of inflammatory biomarkers, and cognitive function in PW. In a population of 222 PW, energy intake-adjusted Dietary Inflammatory Index (E-DII) was used to assess the dietary inflammatory potential. Cognitive function was estimated using the Polish version of Mini-Mental State Examination (MMSE), corrected by age and educational level. Selected biochemical inflammatory markers (C-reactive protein, CRP; interleukin-6, IL-6; and tumor necrosis factor alpha, TNF-α) were measured by ELISA tests. PW with an anti-inflammatory diet (first tercile) had significantly higher MMSE, while BMI, percentage fat mass and TNFα concentration were significantly lower compared to those with the most proinflammatory diets (third tercile). Women with cognitive impairment had significantly higher IL-6 concentrations (4.1 (0.8) pg/mL vs. 2.5 (0.2) pg/mL, p = 0.004), and were less educated (12.7 (0.7) years vs. 14.1 (0.2) years, p = 0.03) and less physically active compared to cognitively normal women. PW with the most proinflammatory diets had increased odds of cognitive impairment compared to those with the most anti-inflammatory diets, even after adjustment (OR = 11.10, 95% confidence level; 95%CI: 2.22; 55.56; p = 0.002). Each one-point increase in E-DII (as a continuous value) was also associated with 1.55-times greater odds of cognitive impairment (95%Cl: 1.19; 2.02 p = 0.003) in this population. Dietary inflammation may increase the risk of cognitive impairment in PW, but future studies should include a more sensitive battery of tests to assess cognitive function in this population. Implementation of an anti-inflammatory dietary pattern in PW may help prevent cognitive decline.


Assuntos
Cognição , Dieta/efeitos adversos , Mediadores da Inflamação/sangue , Pós-Menopausa/sangue , Pós-Menopausa/psicologia , Biomarcadores/sangue , Proteína C-Reativa/análise , Disfunção Cognitiva/etiologia , Feminino , Humanos , Inflamação , Interleucina-6/sangue , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Polônia , Fator de Necrose Tumoral alfa/sangue
5.
Nutrients ; 13(7)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34371837

RESUMO

It has been theorized that folic acid supplementation improves inflammation. However, its proven effects on inflammatory markers are unclear as clinical studies on this topic have produced inconsistent results. To bridge this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of folic acid supplementation on serum concentrations of the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Methods: To identify eligible RCTs, a systematic search up to April 2021 was completed in PubMed/Medline, Scopus, Web of Science, EMBASE, Cochrane databases, and Google Scholar using relevant keywords. A fix or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Results: Twelve RCTs were included in the present meta-analysis. The pooled analysis revealed that serum concentrations of CRP (WMD: -0.59 mg/L, 95% CI -0.85 to -0.33, p < 0.001) were significantly reduced following folic acid supplementation compared to placebo, but did not affect serum concentrations of IL-6 (WMD: -0.12, 95% CI -0.95 to 0.72 pg/mL, p = 0.780) or TNF-α (WMD: -0.18, 95% CI -0.86 to 0.49 pg/mL, p = 0.594). The dose-response analysis demonstrated a significant relationship between an elevated dosage of folic acid supplementation and lower CRP concentrations (p = 0.002). Conclusions: We found that folic acid supplementation may improve inflammation by attenuating serum concentrations of CRP but without significant effects on IL-6 and TNF-α. Future RCTs including a larger number of participants and more diverse populations are needed to confirm and expand our findings.


Assuntos
Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Mediadores da Inflamação/sangue , Complexo Vitamínico B/administração & dosagem , Adulto , Biomarcadores/sangue , Proteína C-Reativa , Feminino , Humanos , Inflamação , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/sangue
6.
Nutrients ; 13(7)2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34371884

RESUMO

The dietary supplement, trans-resveratrol and hesperetin combination (tRES-HESP), induces expression of glyoxalase 1, countering the accumulation of reactive dicarbonyl glycating agent, methylglyoxal (MG), in overweight and obese subjects. tRES-HESP produced reversal of insulin resistance, improving dysglycemia and low-grade inflammation in a randomized, double-blind, placebo-controlled crossover study. Herein, we report further analysis of study variables. MG metabolism-related variables correlated with BMI, dysglycemia, vascular inflammation, blood pressure, and dyslipidemia. With tRES-HESP treatment, plasma MG correlated negatively with endothelial independent arterial dilatation (r = -0.48, p < 0.05) and negatively with peripheral blood mononuclear cell (PBMC) quinone reductase activity (r = -0.68, p < 0.05)-a marker of the activation status of transcription factor Nrf2. For change from baseline of PBMC gene expression with tRES-HESP treatment, Glo1 expression correlated negatively with change in the oral glucose tolerance test area-under-the-curve plasma glucose (ΔAUGg) (r = -0.56, p < 0.05) and thioredoxin interacting protein (TXNIP) correlated positively with ΔAUGg (r = 0.59, p < 0.05). Tumor necrosis factor-α (TNFα) correlated positively with change in fasting plasma glucose (r = 0.70, p < 0.001) and negatively with change in insulin sensitivity (r = -0.68, p < 0.01). These correlations were not present with placebo. tRES-HESP decreased low-grade inflammation, characterized by decreased expression of CCL2, COX-2, IL-8, and RAGE. Changes in CCL2, IL-8, and RAGE were intercorrelated and all correlated positively with changes in MLXIP, MAFF, MAFG, NCF1, and FTH1, and negatively with changes in HMOX1 and TKT; changes in IL-8 also correlated positively with change in COX-2. Total urinary excretion of tRES and HESP metabolites were strongly correlated. These findings suggest tRES-HESP counters MG accumulation and protein glycation, decreasing activation of the unfolded protein response and expression of TXNIP and TNFα, producing reversal of insulin resistance. tRES-HESP is suitable for further evaluation for treatment of insulin resistance and related disorders.


Assuntos
Hesperidina/administração & dosagem , Resistência à Insulina , Obesidade/terapia , Sobrepeso/terapia , Resveratrol/administração & dosagem , Adulto , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Proteínas de Transporte/sangue , Correlação de Dados , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/terapia , Feminino , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/terapia , Glicosilação/efeitos dos fármacos , Humanos , Inflamação , Mediadores da Inflamação/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Obesidade/sangue , Sobrepeso/sangue , Aldeído Pirúvico/sangue , Fator de Necrose Tumoral alfa/sangue
7.
Cell Death Dis ; 12(8): 773, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354045

RESUMO

The pathophysiology of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and especially of its complications is still not fully understood. In fact, a very high number of patients with COVID-19 die because of thromboembolic causes. A role of plasminogen, as precursor of fibrinolysis, has been hypothesized. In this study, we aimed to investigate the association between plasminogen levels and COVID-19-related outcomes in a population of 55 infected Caucasian patients (mean age: 69.8 ± 14.3, 41.8% female). Low levels of plasminogen were significantly associated with inflammatory markers (CRP, PCT, and IL-6), markers of coagulation (D-dimer, INR, and APTT), and markers of organ dysfunctions (high fasting blood glucose and decrease in the glomerular filtration rate). A multidimensional analysis model, including the correlation of the expression of coagulation with inflammatory parameters, indicated that plasminogen tended to cluster together with IL-6, hence suggesting a common pathway of activation during disease's complication. Moreover, low levels of plasminogen strongly correlated with mortality in COVID-19 patients even after multiple adjustments for presence of confounding. These data suggest that plasminogen may play a pivotal role in controlling the complex mechanisms beyond the COVID-19 complications, and may be useful both as biomarker for prognosis and for therapeutic target against this extremely aggressive infection.


Assuntos
COVID-19/sangue , COVID-19/mortalidade , Plasminogênio/análise , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Coagulação Sanguínea , COVID-19/diagnóstico , Regulação para Baixo , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo
8.
Front Immunol ; 12: 678661, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335580

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear. Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators. Methods: Ninety-two proteins were quantified in 315 plasma samples from 118 asthmatics, 99 COPD patients and 98 healthy controls (age 40-90 years), who were recruited in Colombia before the COVID-19 pandemic. Protein levels were compared between each disease group and healthy controls. Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the "COVID-19 Drug and Gene Set Library" and with experimentally tested protein biomarkers of severe COVID-19. Results: Forty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database. An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been experimentally detected in patients with severe COVID-19. Conclusions: COPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19. Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19. Also, that IL-6 levels are increased in some asthmatic patients (especially in females) and this may influence their response to COVID-19. The findings in this study depict a novel panel of inflammatory plasma proteins in COPD patients that may potentially associate with increased susceptibility to severe COVID-19 and might be useful as a biomarker signature after future experimental validation.


Assuntos
Asma/imunologia , COVID-19/imunologia , Mediadores da Inflamação/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , SARS-CoV-2/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/diagnóstico , Biomarcadores/sangue , COVID-19/diagnóstico , Quimiocina CXCL9/sangue , Feminino , Fator de Crescimento de Hepatócito/sangue , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Índice de Gravidade de Doença , Regulação para Cima
9.
Br J Anaesth ; 127(3): 424-434, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34218905

RESUMO

BACKGROUND: Postoperative delirium has eluded attempts to define its complex aetiology and describe specific risk factors. The role of neuroinflammation as a risk factor, determined by measuring blood levels of preoperative 'innate' inflammatory mediator levels, has been investigated. However, results have been conflicting. We conducted a systematic review and meta-analysis of the evidence on associations between preoperative blood levels of inflammatory mediators and postoperative delirium in the older person. Influence of type of surgery was also assessed. METHODS: Original, low risk of bias studies, published in peer-reviewed journals, which fulfilled the eligibility criteria were included. Seventeen articles fulfilled study criteria. Data extraction, synthesis, and risk of bias analysis were guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and quality in prognostic studies guidelines. Meta-analyses used a random-effects model. Inflammatory mediators included C-reactive protein, interleukin-6, -8, and -10, tumour necrosis factor-α, insulin-like growth factor-1, cortisol, and neopterin. Surgical groups were cardiac, noncardiac, and hip fracture. RESULTS: Higher preoperative interleukin-6 was associated with postoperative delirium with a standardised mean difference (95% confidence interval) of 0.33 (0.11-0.56) and P=0.003. Higher neopterin was also associated with postoperative delirium. CONCLUSIONS: The association of preoperative blood levels of inflammatory mediators with postoperative delirium may be influenced by the type of surgery and the specific mediator. The potential modulating effect of type of surgery, intrinsic brain vulnerability, and the complex interactions between inflammatory mediators and binding proteins will need to be considered in future studies. CLINICAL TRIAL REGISTRATION: CRD42019159471 (PROSPERO).


Assuntos
Delírio/etiologia , Mediadores da Inflamação/sangue , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Delírio/sangue , Delírio/diagnóstico , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Neopterina/sangue , Cuidados Pré-Operatórios , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Regulação para Cima
10.
Arterioscler Thromb Vasc Biol ; 41(9): 2509-2511, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34261329
11.
Int J Mol Sci ; 22(13)2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34281260

RESUMO

Males have a higher risk for cardiovascular diseases (CVDs) than females. Ambient fine particulate matter (PM) exposure increases CVD risk with increased reactive oxygen species (ROS) production and oxidative stress. Endothelial progenitor cells (EPCs) are important to vascular structure and function and can contribute to the development of CVDs. The aims of the present study were to determine if sex differences exist in the effect of PM exposure on circulating EPCs in mice and, if so, whether oxidative stress plays a role. Male and female C57BL/6 mice (8-10 weeks old) were exposed to PM or a vehicle control for six weeks. ELISA analysis showed that PM exposure substantially increased the serum levels of IL-6 and IL-1ß in both males and females, but the concentrations were significantly higher in males. PM exposure only increased the serum levels of TNF-α in males. Flow cytometry analysis demonstrated that ROS production was significantly increased by PM treatment in males but not in females. Similarly, the level of circulating EPCs (CD34+/CD133+ and Sca-1+/Flk-1+) was significantly decreased by PM treatment in males but not in females. Antioxidants N-acetylcysteine (NAC) effectively prevented PM exposure-induced ROS and inflammatory cytokine production and restored circulating EPC levels in male mice. In sharp contrast, circulating EPC levels remained unchanged in female mice with PM exposure, an effect that was not altered by ovariectomy. In conclusion, PM exposure selectively decreased the circulating EPC population in male mice via increased oxidative stress without a significant impact on circulating EPCs in females independent of estrogen.


Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Material Particulado/toxicidade , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Citocinas/sangue , Células Progenitoras Endoteliais/patologia , Estrogênios/metabolismo , Feminino , Mediadores da Inflamação/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fatores Sexuais
12.
Anaesthesiol Intensive Ther ; 53(2): 108-114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34284551

RESUMO

INTRODUCTION: Infection with SARS-CoV-2 in its most severe form leads to acute respiratory distress syndrome requiring mechanical ventilation under the conditions of the Intensive Care Unit (ICU). The state of hypercoagulation described in COVID-19 may deepen respiratory failure, leading to increased mortality. The aim of the presented study is to characterise the haemostatic profile based on the results of clotting system parameters and risk assessment of thromboembolic complications of patients hospitalised in the ICU. MATERIAL AND METHODS: This retrospective study covered the first 10 adult patients hospitalised in the ICU of the Hospital for Infectious Diseases in Warsaw in the second quarter of 2020. Demographic, clinical and laboratory parameters of the coagulation system and the risk of thromboembolic complications were assessed. Well known criteria of haemostatic disorders were used to classify the observed derangements. RESULTS: The most frequently observed deviations in the coagulation system were high concentrations of D-dimer and fibrinogen. In select cases the clotting time was prolonged. No severe thrombocytopenia was observed. All patients presented a high risk of thromboembolic complications as assesed by the Padua score. The observed clotting abnormalities did not meet the criteria for DIC (disseminated intravascular coagulation) and SIC (sepsis-induced coagulopathy) diagnosis. CONCLUSIONS: The main elements of coagulopathy that were observed in our cases differ from those usually seen in patients with recognised sepsis. The unique haemostatic profile of COVID-19 patients treated in the ICU has been described as CAC (COVID-19-associated coagulopathy).


Assuntos
COVID-19/complicações , COVID-19/terapia , Coagulação Intravascular Disseminada/diagnóstico , Sepse/diagnóstico , Adulto , Testes de Coagulação Sanguínea/métodos , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Mediadores da Inflamação/sangue , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Polônia , Estudos Retrospectivos , Sepse/sangue , Sepse/etiologia
13.
Clin Interv Aging ; 16: 1223-1230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234422

RESUMO

Purpose: The occurrence and predictors of delirium in older adults hospitalized for coronavirus disease 2019 (COVID-19) have not been well described. Highlighting the association with inflammatory markers may be useful for identifying delirium. This study aimed to determine the prevalence and incidence of delirium and explore its association with the C-reactive protein (CRP). Patients and Methods: This cohort study of adults aged 65 and older with a COVID-19 diagnosis took place at an academic healthcare institution between April and May 2020. COVID-19 was diagnosed by positive nasopharyngeal swab. Serum levels of CRP were collected as a marker of systemic inflammation. The primary outcome was the prevalence and incidence of delirium. Delirium was diagnosed primarily during a patient's stay in hospital based on the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5). To ensure that no delirium diagnosis was missed during hospital stay, clinical records were reviewed by clinicians with geriatric medicine training for retrospective diagnoses. Results: A total of 127 patients aged 65 and older were hospitalized with a diagnosis of COVID-19. The median age was 82 years (IQR: 74-88), with 54 (43%) females. Overall, delirium was present in 62 (49%) patients: manifestations of delirium were present on the first day of hospitalization in 53 of these cases (86%), while 9 cases (14%) developed delirium during hospitalization. After controlling for age and sex, the mean CRP value over the first 3 days since arrival was associated with a higher risk of delirium (OR 1.35; 95% CI: 1.01-1.85) for every 50 mg/L increase. Conclusion: In this cohort of older adults hospitalized for COVID-19, delirium was highly prevalent. An early increase in CRP levels should raise suspicion about the occurrence of delirium and could improve its diagnosis.


Assuntos
Proteína C-Reativa/análise , COVID-19/epidemiologia , Delírio/sangue , Delírio/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos de Coortes , Feminino , Hospitalização , Humanos , Incidência , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Tempo de Internação , Masculino , Prevalência , Estudos Retrospectivos , SARS-CoV-2
14.
Aging (Albany NY) ; 13(14): 17961-17977, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282057

RESUMO

We intend to evaluate the differences of the clinical characteristics, cytokine profiles and immunological features in patients with different severity of COVID-19, and to develop novel nomograms based on inflammatory cytokines or lymphocyte subsets for the differential diagnostics for severe or critical and non-severe COVID-19 patients. We retrospectively studied 254 COVID-19 patients, 90 of whom were severe or critical patients and 164 were non-severe patients. Severe or critical patients had significantly higher levels of inflammatory cytokines than non-severe patients as well as lower levels of lymphocyte subsets. Significantly positive correlations between cytokine profiles were observed, while they were all significantly negatively correlated with lymphocyte subsets. Two effective nomograms were developed according to two multivariable logistic regression cox models based on inflammatory cytokine profiles and lymphocyte subsets separately. The areas under the receiver operating characteristics of two nomograms were 0.834 (95% CI: 0.779-0.888) and 0.841 (95% CI: 0.756-0.925). The bootstrapped-concordance indexes of two nomograms were 0.834 and 0.841 in training set, and 0.860 and 0.852 in validation set. Calibration curves and decision curve analyses demonstrated that the nomograms were well calibrated and had significantly more clinical net benefits. Our novel nomograms can accurately predict disease severity of COVID-19, which may facilitate the identification of severe or critical patients and assist physicians in making optimized treatment suggestions.


Assuntos
COVID-19/diagnóstico , Citocinas/sangue , Técnicas de Apoio para a Decisão , Mediadores da Inflamação/sangue , Subpopulações de Linfócitos/imunologia , Nomogramas , Idoso , Biomarcadores/sangue , COVID-19/sangue , COVID-19/imunologia , COVID-19/terapia , Tomada de Decisão Clínica , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Regulação para Cima
16.
Pak J Pharm Sci ; 34(1(Special)): 429-433, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275790

RESUMO

SARS-Covid-19 infection got spread in many countries and WHO declared it as a serious global Pandemic. Pro-inflammatory cytokines storm generated by Covid-19 infection hyper-activates inflammatory response in host body, resulting in elevated release of inflammatory biomarkers. Present article describes the characteristic profile of these inflammatory and related biomarkers in a total of 48 critically ill Covid-19 patients, (Male = 38, F = 10), with mildly ill to severe, critically ill status and thus grouped accordingly. Inflammatory Biomarkers, Ferritin, ProCalcitonin, C-Reactive Protein, coagulation marker-D-Dimer, chemical analytes, Protein, Albumin, BUN, Bilirubin, Creatinine, and enzymes, Lactate Dehydrogenase, γ-Glutamyl transpeptidases, Alkaline phosphatase were routine analyzed by standard methods described earlier. D-dimer, Ferritin, CRP and Procalcitonin exhibited variable alterations (P<0.05 to P<0.001), more markedly in critically ill patients than in the mild and severe. Biochemical analytes and enzymatic parameters showed elevated levels (P<0.05 to P<0.01) mostly in critically ill category of patients when compared with mild or severe, except total protein and albumin, which remained non-significant. It is concluded that cytokine, chemokines and pro-inflammatory markers, which released in abnormally high concentrations in Covid-19 patients of variable syndrome intensity, are significant indicators of disease severity, progression and success of treatments. As the pharmacological options may vary with the different stages of the disease therefore identifying the correct stage of the disease may be very useful in selecting the best option.


Assuntos
COVID-19/sangue , Citocinas/sangue , Mediadores da Inflamação/sangue , Biomarcadores/sangue , COVID-19/virologia , Estado Terminal , Feminino , Humanos , Masculino , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
17.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299301

RESUMO

Metformin can reduce cardiovascular risk independent of glycemic control. The mechanisms behind its non-glycemic benefits, which include decreased energy intake, lower blood pressure and improved lipid and fatty acid metabolism, are not fully understood. In our study, metformin treatment reduced myocardial accumulation of neutral lipids-triglycerides, cholesteryl esters and the lipotoxic intermediates-diacylglycerols and lysophosphatidylcholines in a prediabetic rat model (p < 0.001). We observed an association between decreased gene expression and SCD-1 activity (p < 0.05). In addition, metformin markedly improved phospholipid fatty acid composition in the myocardium, represented by decreased SFA profiles and increased n3-PUFA profiles. Known for its cardioprotective and anti-inflammatory properties, metformin also had positive effects on arachidonic acid metabolism and CYP-derived arachidonic acid metabolites. We also found an association between increased gene expression of the cardiac isoform CYP2c with increased 14,15-EET (p < 0.05) and markedly reduced 20-HETE (p < 0.001) in the myocardium. Based on these results, we conclude that metformin treatment reduces the lipogenic enzyme SCD-1 and the accumulation of the lipotoxic intermediates diacylglycerols and lysophosphatidylcholine. Increased CYP2c gene expression and beneficial effects on CYP-derived arachidonic acid metabolites in the myocardium can also be involved in cardioprotective effect of metformin.


Assuntos
Ácido Araquidônico/metabolismo , Metformina/farmacologia , Miocárdio/metabolismo , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/metabolismo , Animais , Metabolismo Basal/efeitos dos fármacos , Biomarcadores/sangue , Cardiotônicos/farmacologia , Modelos Animais de Doenças , Ácidos Graxos Dessaturases/metabolismo , Coração/efeitos dos fármacos , Hiperlipoproteinemia Tipo IV/tratamento farmacológico , Hiperlipoproteinemia Tipo IV/metabolismo , Hipoglicemiantes/farmacologia , Mediadores da Inflamação/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Fatores de Risco
18.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202017

RESUMO

BACKGROUND: Diabetic patients have prolonged cardiac repolarization and higher risk of arrhythmia. Besides, diabetes activates the innate immune system, resulting in higher levels of plasmatic cytokines, which are described to prolong ventricular repolarization. METHODS: We characterize a metabolic model of type 2 diabetes (T2D) with prolonged cardiac repolarization. Sprague-Dawley rats were fed on a high-fat diet (45% Kcal from fat) for 6 weeks, and a low dose of streptozotozin intraperitoneally injected at week 2. Body weight and fasting blood glucose were measured and electrocardiograms of conscious animals were recorded weekly. Plasmatic lipid profile, insulin, cytokines, and arrhythmia susceptibility were determined at the end of the experimental period. Outward K+ currents and action potentials were recorded in isolated ventricular myocytes by patch-clamp. RESULTS: T2D animals showed insulin resistance, hyperglycemia, and elevated levels of plasma cholesterol, triglycerides, TNFα, and IL-1b. They also developed bradycardia and prolonged QTc-interval duration that resulted in increased susceptibility to severe ventricular tachycardia under cardiac challenge. Action potential duration (APD) was prolonged in control cardiomyocytes incubated 24 h with plasma isolated from diabetic rats. However, adding TNFα and IL-1b receptor blockers to the serum of diabetic animals prevented the increased APD. CONCLUSIONS: The elevation of the circulating levels of TNFα and IL-1b are responsible for impaired ventricular repolarization and higher susceptibility to cardiac arrhythmia in our metabolic model of T2D.


Assuntos
Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Suscetibilidade a Doenças , Mediadores da Inflamação/sangue , Animais , Arritmias Cardíacas/diagnóstico , Citocinas/sangue , Diabetes Mellitus Tipo 2/etiologia , Modelos Animais de Doenças , Insulina/metabolismo , Resistência à Insulina , Canais de Potássio/metabolismo , Ratos , Remodelação Ventricular
19.
Front Immunol ; 12: 624821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149688

RESUMO

Kidney disease affects 10% of the world population and is associated with increased mortality. Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children, often failing standard immunosuppression. Here, we report the results of a prospective study to investigate the immunological impact and safety of a gluten-free and dairy-free (GF/DF) diet in children with SRNS. The study was organized as a four-week summer camp implementing a strict GF/DF diet with prospective collection of blood, urine and stool in addition to whole exome sequencing WES of DNA of participants. Using flow cytometry, proteomic assays and microbiome metagenomics, we show that GF/DF diet had a major anti-inflammatory effect in all participants both at the protein and cellular level with 4-fold increase in T regulatory/T helper 17 cells ratio and the promotion of a favorable regulatory gut microbiota. Overall, GF/DF can have a significant anti-inflammatory effect in children with SRNS and further trials are warranted to investigate this potential dietary intervention in children with SRNS.


Assuntos
Laticínios/efeitos adversos , Dieta Livre de Glúten , Síndrome Nefrótica/congênito , Adolescente , Biomarcadores/sangue , Biomarcadores/urina , Criança , Pré-Escolar , Citocinas/sangue , Dieta Livre de Glúten/efeitos adversos , Estudos de Viabilidade , Feminino , Microbioma Gastrointestinal , Humanos , Lactente , Mediadores da Inflamação/sangue , Intestinos/microbiologia , Masculino , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/dietoterapia , Síndrome Nefrótica/imunologia , Síndrome Nefrótica/microbiologia , Projetos Piloto , Estudo de Prova de Conceito , Estudos Prospectivos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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