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This study investigated the association between the IFITM3 rs12252 polymorphism and the severity and mortality of COVID-19 in hospitalized Brazilian patients. A total of 102 COVID-19 patients were included, and the outcomes of interest were defined as death and the need for mechanical ventilation. Genotypes were assessed using Taqman probes. No significant associations were found between the rs12252 polymorphism and COVID-19 outcomes in the original sample, both for death and the need for mechanical ventilation. A meta-analysis, incorporating previous studies that used death as a severity indicator, revealed no association in the allelic and C-recessive models. However, due to the rarity of the T allele and its absence in the sample, further replication studies in larger and more diverse populations are needed to clarify the role of rs12252 in COVID-19 prognosis.
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COVID-19 , Proteínas de Membrana , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/genética , COVID-19/mortalidade , Brasil/epidemiologia , Proteínas de Membrana/genética , SARS-CoV-2/genética , Masculino , Feminino , Proteínas de Ligação a RNA/genética , Polimorfismo de Nucleotídeo Único/genética , Pessoa de Meia-Idade , Pandemias , Betacoronavirus/genética , Pneumonia Viral/genética , Pneumonia Viral/mortalidade , Genótipo , Idoso , Predisposição Genética para Doença/genética , Respiração Artificial , AdultoRESUMO
Cadmium is a heavy metal that is widespread in the environment and has been described as a metalloestrogen and a cardiovascular risk factor. Experimental studies conducted in male animals have shown that cadmium exposure induces vascular dysfunction, which could lead to vasculopathies caused by this metal. However, it is necessary to investigate the vascular effects of cadmium in female rats to understand its potential sex-dependent impact on the cardiovascular system. While its effects on male rats have been studied, cadmium may act differently in females due to its potential as a metalloestrogen. In vitro studies conducted in a controlled environment allow for a direct assessment of cadmium's impact on vascular function, and the use of female rats ensures that sex-dependent effects are evaluated. Therefore, the aim of this study was to investigate the in vitro effects of Cadmium Chloride (CdCl2, 5 µM) exposure on vascular reactivity in the isolated aorta of female Wistar rats. Exposure to CdCl2 damaged the architecture of the vascular endothelium. CdCl2 incubation increased the production and release of O2â¢-, reduced the participation of potassium (K+) channels, and increased the participation of the angiotensin II pathway in response to phenylephrine. Moreover, estrogen receptors alpha (Erα) modulated vascular reactivity to phenylephrine in the presence of cadmium, supporting the hypothesis that cadmium could act as a metalloestrogen. Our results demonstrated that in vitro cadmium exposure induces damage to endothelial architecture and an increase in oxidative stress in the isolated aorta of female rats, which could precipitate vasculopathies. Graphical Abstract. Own source from Canva and Servier Medical Art servers.
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Cádmio , Metais Pesados , Ratos , Masculino , Feminino , Animais , Cádmio/metabolismo , Ratos Wistar , Fenilefrina/metabolismo , Fenilefrina/farmacologia , Aorta/metabolismo , Metais Pesados/farmacologia , Estresse OxidativoRESUMO
The 3p21.31 locus has been associated with severe COVID-19 prognosis in GWAS studies. Here, we evaluated whether three polymorphisms (LZTFL1 rs10490770, CXCR6 rs2234355 and rs2234358) in the reported locus were associated with the need for mechanical ventilation, hospitalization length and death in 102 COVID-19 hospitalized Brazilian subjects. No genetic association was found with the need for mechanical ventilation and hospitalization length. CXCR6 rs2234355 was associated with mortality under the codominance model, with carriers of the A/A genotype having a greater chance of death than A/G (OR: 10.5; 95% CI: 1.55-70.76). Our results further suggest that the CXCR6 genetic variant contributes to COVID-19 outcomes.
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COVID-19 , Humanos , Brasil/epidemiologia , Genótipo , Hospitalização , Fatores de Transcrição , Receptores CXCR6RESUMO
NEW FINDINGS: What is the central question of this study? The current literature indicates that oxidative stress plays a major role in iron overload. Although exercise is a well-established approach to treat/prevent cardiovascular diseases, its effects on iron overload are not known. What is the main finding and its importance? Moderate-intensity aerobic training had benefits in a rodent model of iron-overload cardiomyopathy by improving the antioxidant capacity of the heart. After further confirmation by translational and clinical studies, we should consider using this non-pharmacological, highly accessible and easily executable adjuvant approach allied to other therapies to improve the quality of life of iron-overloaded patients. ABSTRACT: Iron is an essential micronutrient for several life processes, but its excess can damage organs owing to oxidative stress, with cardiomyopathy being the leading cause of death in iron-overloaded patients. Although exercise has long been considered as a cardioprotective tool, its effects on iron overload are not known. This study was designed to investigate the effects of moderate-intensity aerobic training in rats previously submitted to chronic iron overload. Wistar rats received i.p. injections of iron dextran (100 mg/kg, 5 days/week for 4 weeks); thereafter, the rats were kept sedentary or exercised (60 min/day, progressive aerobic training, 60-70% of maximal speed, 5 days/week on a treadmill) for 8 weeks. At the end of the experimental period, haemodynamics were recorded and blood samples, livers and hearts harvested. Myocardial mechanics of papillary muscles were assessed in vitro, and cardiac remodelling was evaluated by histology and immunoblotting. Iron overload led to liver iron deposition, liver fibrosis and increased serum alanine aminotransferase and aspartate aminotransferase. Moreover, cardiac iron accumulation was accompanied by impaired myocardial mechanics, increased cardiac collagen type I and lipid peroxidation (TBARS), and release of creatine phosphokinase-MB to the serum. Although exercise did not influence iron levels, tissue injury markers were significantly reduced. Likewise, myocardial contractility and inotropic responsiveness were improved in exercised rats, in association with an increase in the endogenous antioxidant enzyme catalase. In conclusion, moderate-intensity aerobic exercise was associated with attenuated oxidative stress and cardiac damage in a rodent model of iron overload, thereby suggesting its potential role as a non-pharmacological adjuvant therapy for iron-overload cardiomyopathy.
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Sobrecarga de Ferro , Qualidade de Vida , Animais , Coração , Humanos , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Miocárdio/metabolismo , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
OBJECTIVE: Major depression (MD) is a condition associated with both hepatitis C virus (HCV) infection and pegylated interferon (IFN)-α treatment. IFN induces a depressive syndrome that is associated with an inflammatory profile. We aimed to investigate whether there is any specific alteration in plasma biomarkers associated with MD. METHODS: HCV-monoinfected patients, with and without IFN treatment, were followed up for 18 months and went through structured psychiatric evaluation. We assessed plasma levels of brain-derived neurotrophic factor, tumor necrosis factor (TNF) and its soluble type 1 and type 2 receptors (sTNFR1 and sTNFR2, respectively), and adipokines (adiponectin, leptin and resistin) using ELISA. RESULTS: Among the 50 patients included in the study, 14 were treated with IFN during the follow-up. Being older, not married, presenting higher body mass index, higher liver inflammatory activity, lower baseline adiponectin levels and use of IFN were associated with MD development. Higher levels of sTNFR1 during IFN treatment were associated with sustained virological response. The lack of a control group without HCV infection did not allow any assumption of a biomarker change exclusively due to the infection itself. CONCLUSION: Adiponectin may be a resilience biomarker for MD in HCV-infected patients.
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Adiponectina/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/diagnóstico , Hepatite C Crônica/sangue , Resiliência Psicológica , Adulto , Antivirais/uso terapêutico , Biomarcadores/sangue , Transtorno Depressivo Maior/psicologia , Feminino , Seguimentos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/psicologia , Humanos , Interferon-alfa/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Pro-resolving molecules may curb disease caused by viruses without altering the capacity of the host to deal with infection. AP1189 is a melanocortin receptor-biased agonist endowed with pro-resolving and anti-inflammatory activity. We evaluated the preclinical and early clinical effects of treatment with AP1189 in the context of COVID-19. METHODS: C57BL/6j mice were infected intranasally with MHV-A59 or hK18-ACE2 mice with SARS-CoV-2. AP1189 (10 mg·kg-1, BID, s.c.) was given to the animals from day 2 and parameters evaluated at day 5. Human PBMCs from health donors were infected with SARS-CoV-2 in presence or absence of AP1189 and production of cytokines quantified. In the clinical study, 6 patients were initially given AP1189 (100 mg daily for 14 days) and this was followed by a randomized (2:1), placebo-controlled, double-blind trial that enrolled 54 hospitalized COVID-19 patients needing oxygen support. The primary outcome was the time in days until respiratory recovery, defined as a SpO2 ≥ 93% in ambient air. RESULTS: Treatment with AP1189 attenuated pulmonary inflammation in mice infected with MHV-A59 or SARS-CoV-2 and decreased the release of CXCL10, TNF-α and IL-1ß by human PBMCs. Hospitalized COVID-19 patients already taking glucocorticoids took a median time of 6 days until respiratory recovery when given placebo versus 4 days when taking AP1189 (P = 0.017). CONCLUSION: Treatment with AP1189 was associated with less disease caused by beta-coronavirus infection both in mice and in humans. This is the first demonstration of the effects of a pro-resolving molecule in the context of severe infection in humans.
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OBJECTIVE: The aim of this study was to investigate the effectiveness of a modified version of the Duke Somatic Algorithm Treatment for Geriatric Depression (STAGED) in a Brazilian sample of older patients with major depression. Besides, we aimed to investigate possible baseline predictive factors for remission in this sample. METHODS: Sixty-seven depressed individuals were treated according to STAGED over 24 weeks in a prospective cohort design with follow-up. All patients had criteria for major depression and were at least 60 years of age at baseline enrollment. RESULTS: During this follow-up, 56 patients could be classified in remitted or not remitted group, 42.85% reached remission, and 57.14% did not reach remission. These results are even better than those found in the original study, probably due to the lower baseline depression severity of our sample. When baseline characteristics were compared between remitted and not remitted groups, scores of Mini Mental State Examination and Cambridge Cognitive Examination (CAMCOG) were the only variables with statistical significant difference (p < 0.05) between groups. Logistic regression analysis was carried out to try to predict remission and statistical significance (p < 0.05) was found only for baseline MMSE scores. It may mean that patients with mixed cognitive disorders and mood disorders have a worse course of depression. CONCLUSIONS: This version of STAGED seems to be a useful strategy for treatment of depression in late life. Baseline general cognitive performance might be useful to predict remission of depression in older patients with mild to moderate depression. Further research with different population characteristics should be conducted in order to evaluate its usefulness and feasibility in different settings.
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Algoritmos , Transtorno Depressivo Maior/terapia , Terapias Somáticas em Psiquiatria , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Brasil , Feminino , Humanos , Modelos Logísticos , Masculino , Estudos ProspectivosRESUMO
Introduction: Clinical studies have shown that low levels of endogenous testosterone are associated with cardiovascular diseases. Considering the intimate connection between oxidative metabolism and myocardial contractility, we determined the effects of testosterone deficiency on the two spatially distinct subpopulations of cardiac mitochondria, subsarcolemmal (SSM) and interfibrillar (IFM). Methods: We assessed cardiac function and cardiac mitochondria structure of SSM and IFM after 12 weeks of testosterone deficiency in male Wistar rats. Results and Discussion: Results show that low testosterone reduced myocardial contractility. Orchidectomy increased total left ventricular mitochondrial protein in the SSM, but not in IFM. The membrane potential, size and internal complexity in the IFM after orchidectomy were higher compared to the SHAM group. However, the rate of oxidative phosphorylation with all substrates in the IFM after orchidectomy was lower compared to the SHAM group. Testosterone replacement restored these changes. In the testosterone-deficient SSM group, oxidative phosphorylation was decreased with palmitoyl-L-carnitine as substrate; however, the mitochondrial calcium retention capacity in IFM was increased. There was no difference in swelling of the mitochondria in either group. These changes in IFM were followed by a reduction in phosphorylated form of AMP-activated protein kinase (p-AMPK-α), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) translocation to mitochondria and decreased mitochondrial transcription factor A (TFAM). Testosterone deficiency increased NADPH oxidase (NOX), angiotensin converting enzyme (ACE) protein expression and reduced mitochondrial antioxidant proteins such as manganese superoxide dismutase (Mn-SOD) and catalase in the IFM. Treatment with apocynin (1.5 mM in drinking water) normalized myocardial contractility and interfibrillar mitochondrial function in the testosterone depleted animals. In conclusion, our findings demonstrate that testosterone deficiency leads to reduced myocardial contractility and impaired cardiac interfibrillar mitochondrial function. Our data suggest the involvement of reactive oxygen species, with a possibility of NOX as an enzymatic source.
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Mitocôndrias Cardíacas , Miocárdio , Ratos , Animais , Masculino , Ratos Wistar , Miocárdio/metabolismo , Estresse Oxidativo , Testosterona/farmacologia , Testosterona/metabolismoRESUMO
BACKGROUND: Studies on functional capacity in community-dwelling older people have shown associations between declines in instrumental activities of daily living (IADL) and several factors. Among these, age has been the most consistently related to functional capacity independent of other variables. We aimed at evaluating the performance of a sample of healthy and cognitively intact Brazilian older people on activities of daily living and to analyze its relation to social-demographic variables. METHODS: We conducted a secondary analysis of data collected for previous epidemiological studies with community-dwelling subjects aged 60 years or more. We selected subjects who did not have dementia or depression, and with no history of neurological diseases, heart attack, HIV, hepatitis or arthritis (n = 1,111). Functional capacity was assessed using the Brazilian version of the Older American Resources and Services Questionnaire (BOMFAQ). ADL performance was analyzed according to age, gender, education, and marital status (Pearson's χ2, logistic regression). RESULTS: IADL difficulties were present in our sample, especially in subjects aged 80 years or more, with lower levels of education, or widowed. The logistic regression analysis results indicated that "higher age" and "lower education" (p ≤ 0.001) remained significantly associated with IADL difficulty. CONCLUSIONS: Functional decline was present in older subjects even in the absence of medical conditions and cognitive impairment. Clinicians and researchers could benefit from knowing what to expect from older people regarding IADL performance in the absence of medical conditions.
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Atividades Cotidianas/psicologia , Idoso/psicologia , Fatores Etários , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Distribuição de Qui-Quadrado , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Escolaridade , Feminino , Humanos , Modelos Logísticos , Masculino , Estado Civil , Pessoa de Meia-Idade , Testes Psicológicos , Psicologia , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Although iron is a metal involved in many vital processes due to its redox capacity, body iron overloads lead to tissue damage, including the cardiovascular system. While cardiomyopathy was the focus since the 1960s, the impact on the vasculature was comparatively neglected for about 40 years, when clinical studies correlating iron overload, oxidative stress, endothelial dysfunction, arterial stiffness and atherosclerosis reinforced an "iron hypothesis". Due to controversial results from some epidemiological studies investigating atherosclerotic events and iron levels, well-controlled trials and animal studies provided essential data about the influence of iron, per se, on the vasculature. As a result, the pathophysiology of vascular dysfunction in iron overload have been revisited. This review summarizes the knowledge obtained from epidemiological studies, animal models and "in vitro" cellular systems in recent decades, highlighting a more harmful than innocent role of iron excess for the vascular homeostasis, which supports our proposal to hereafter denominate "iron overload vasculopathy". Additionally, evidence-based potential therapeutic targets are pointed out to be tested in pre-clinical research that may be useful in cardiovascular protection for patients with iron overload syndromes.
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Aterosclerose , Sobrecarga de Ferro , Animais , Humanos , Ferro , Modelos Animais , Estresse OxidativoRESUMO
In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells. In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1, ACE2, and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu287bp polymorphism was not associated with any of the outcomes. Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions.
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Ageusia , Enzima de Conversão de Angiotensina 2/genética , COVID-19 , Transtornos do Olfato , Ageusia/etiologia , Anosmia , COVID-19/genética , Cognição , Expressão Gênica , Humanos , Transtornos do Olfato/genética , Receptores de Angiotensina , SARS-CoV-2RESUMO
OBJECTIVES: COVID-19 has been associated with long-term consequences to patient wellness and quality of life. Data on post-COVID-19 conditions are scarce in developing countries. This study aimed to investigate long COVID in a cohort of hospitalized patients in Brazil. METHODS: Surviving patients discharged from the hospital between July 1, 2020 and March 31, 2021 were assessed between 2 and 12 months after acute onset of COVID-19. The outcomes were the prevalence of persistent symptoms, risk factors associated with long COVID, and quality of life as assessed by the EuroQol 5D-3L questionnaire. RESULTS: Of 439 participants, most (84%) reported at least one long COVID symptom, at a median of 138 days (interquartile range [IQR] 90-201) after disease onset. Fatigue (63.1%), dyspnea (53.7%), arthralgia (56.1%), and depression/anxiety (55.1%) were the most prevalent symptoms. In multivariate analysis, dysgeusia (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.18-3.44, P <0.001) and intensive care unit (ICU) admission (OR 2.6, 95% CI 1.19-6.56, P = 0.03) were independently associated with long COVID. Fifty percent of patients reported a worsened clinical condition and quality of life. CONCLUSION: Long-term outcomes of SARS-CoV-2 infection in a low- to middle-income country were relevant. Fatigue was the most common persistent symptom. ICU admission was an independent factor associated with long COVID. Dysgeusia could be a potential predictor of long COVID.
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COVID-19 , Brasil/epidemiologia , COVID-19/complicações , COVID-19/epidemiologia , Estudos Transversais , Disgeusia , Fadiga/epidemiologia , Fadiga/etiologia , Humanos , Qualidade de Vida , Fatores de Risco , SARS-CoV-2 , Síndrome de COVID-19 Pós-AgudaRESUMO
Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain. Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days. Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed. Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia. Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.
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INTRODUCTION: Cardiac involvement seems to impact prognosis of COVID-19, being more frequent in critically ill patients. We aimed to assess the prognostic value of right ventricular (RV) and left ventricular (LV) dysfunction, evaluated by bedside echocardiography (echo), in patients hospitalized with COVID-19. METHODS: Patients admitted in 2 reference hospitals in Brazil from Jul to Sept/2020 with confirmed COVID-19 and moderate/severe presentations underwent clinical and laboratory evaluation, and focused bedside echo (GE Vivid-IQ), at the earliest convenience, with remote interpretation. The association between demographics, clinical comorbidities and echo variables with all-cause hospital mortality was assessed, and factors significant at p<0.10 were put into multivariable models. RESULTS: Total 163 patients were enrolled, 59% were men, mean age 64±16 years, and 107 (66%) were admitted to intensive care. Comorbidities were present in 144 (88%) patients: hypertension 115 (71%), diabetes 61 (37%) and heart failure 22 (14%). In-hospital mortality was 34% (N=56). In univariate analysis, echo variables significantly associated with death were: LV ejection fraction (LVEF, OR=0.94), RV fractional area change (OR=0.96), tricuspid annular plane systolic excursion (TAPSE, OR=0.83) and RV dysfunction (OR=5.3). In multivariate analysis, after adjustment for clinical and demographic variables, independent predictors of mortality were age≥63 years (OR=5.53, 95%CI 1.52-20.17), LVEF<64% (OR=7.37, 95%CI 2.10-25.94) and TAPSE<18.5 mm (OR=9.43, 95% CI 2.57-35.03), and the final model had good discrimination, with C-statistic=0.83 (95%CI 0.75-0.91). CONCLUSION: Markers of RV and LV dysfunction assessed by bedside echo are independent predictors of mortality in hospitalized COVID-19 patients, after adjustment for clinical variables.
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COVID-19 , Disfunção Ventricular Direita , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Volume SistólicoRESUMO
ACE2 and TMPRSS2 are key players on SARS-CoV-2 entry into host cells. However, it is still unclear whether expression levels of these factors could reflect disease severity. Here, a case-control study was conducted with 213 SARS-CoV-2 positive individuals where cases were defined as COVID-19 patients with respiratory distress requiring oxygen support (N = 38) and controls were those with mild to moderate symptoms of the disease who did not need oxygen therapy along the entire clinical course (N = 175). ACE2 and TMPRSS2 mRNA levels were evaluated in nasopharyngeal swab samples by RT-qPCR and logistic regression analyzes were applied to estimate associations with respiratory outcomes. ACE2 and TMPRSS2 levels positively correlated with age, which was also strongly associated with respiratory distress. Increased nasopharyngeal ACE2 levels showed a protective effect against this outcome (adjOR = 0.30; 95% CI 0.09-0.91), while TMPRSS2/ACE2 ratio was associated with risk (adjOR = 4.28; 95% CI 1.36-13.48). On stepwise regression, TMPRSS2/ACE2 ratio outperformed ACE2 to model COVID-19 severity. When nasopharyngeal swabs were compared to bronchoalveolar lavages in an independent cohort of COVID-19 patients under mechanical ventilation, similar expression levels of these genes were observed. These data suggest nasopharyngeal TMPRSS2/ACE2 as a promising candidate for further prediction models on COVID-19.
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Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , Síndrome do Desconforto Respiratório/genética , Serina Endopeptidases/genética , Adulto , Idoso , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/terapia , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/metabolismo , RNA Mensageiro/genética , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Regulação para CimaRESUMO
Physical exercise is a well-recognized effective non-pharmacological therapy for cardiovascular diseases. However, because iron is essential element in many physiological processes including hemoglobin and myoglobin synthesis, thereby playing a role on oxygen transport, many athletes use iron supplement to improve physical performance. Regarding this, iron overload is associated with oxidative stress and damage to various systems, including cardiovascular. Thus, we aimed to identify the vascular effects of aerobic exercise in a rat model of iron overload. Male Wistar rats were treated with 100 mg/kg/day iron-dextran, i.p., 5 days a week for 4 weeks, and then underwent aerobic exercise protocol on a treadmill at moderate intensity, 60 min/day, 5 days a week for 8 weeks. Exercise reduced vasoconstrictor response of isolated aortic rings by increasing participation of nitric oxide (NO) and reducing oxidative stress, but these benefits to the vasculature were not observed in rats previously subjected to iron overload. The reduced vasoconstriction in the exercised group was reversed by incubation with superoxide dismutase (SOD) inhibitor, suggesting that increased SOD activity by exercise was lost in iron overload rats. Iron overload groups increased serum levels of iron, transferrin saturation, and iron deposition in the liver, gastrocnemius muscle, and aorta, and the catalase was overexpressed in the aorta probably as a compensatory mechanism to the increased oxidative stress. In conclusion, despite the known beneficial effects of aerobic exercise on vasculature, our results indicate that previous iron overload impeded the anticontractile effect mediated by increased NO bioavailability and endogenous antioxidant response due to exercise protocol.
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Sobrecarga de Ferro , Condicionamento Físico Animal , Animais , Complexo Ferro-Dextran , Masculino , Óxido Nítrico , Estresse Oxidativo , Ratos , Ratos Wistar , Superóxido DismutaseRESUMO
OBJECTIVE: To analyze the degree of knowledge of Brazilian adolescents regarding emergency contraception (EC) such as correct administration, frequency of use, efficacy, mechanism of action, adverse effects, and complications. METHODS: Cross-sectional study. Adolescents aged 11-19 years answered a questionnaire containing questions about sexuality, knowledge, and use of EC. RESULTS: Out of 148 adolescents who were interviewed 8% did not know about the EC. Among the sexually active, 56.7% used EC at least once. The chance of obtaining EC information with friends triples between 15-19 years old [p=0.04; OR=3.18 (1.08-10.53)]. Most used single-dose EC. They said that EC prevents 80% of pregnancy and should be used within 72 hours after unprotected sex. Only 41.2% between 10-14 years old and 82.4% between 15-19 years old know that it prevents fertilization. As reasons for using they cited: rape and unprotected sex in 58.3% of those aged 10-14 years old and 79.6% between 15-19 years old. About side effects, 58.8% of 10-14 years old and 17.6% of those aged ≥15 years old could not answer, but 60.5% between 15-19 years old mentioned nausea and vomiting. A significant portion (17.6-41.2%) believes that EC causes abortion, cancer, infertility, and fetal malformations. Over 80% of the girls agree that it can cause menstrual irregularity. CONCLUSION: Knowledge regarding EC is not satisfactory, especially regarding its risks, regardless of the age and education of the groups evaluated. Improved knowledge may lead to greater adherence to EC and lead to a reduction in unplanned pregnancies.
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Anticoncepção Pós-Coito , Contracepção Hormonal , Gravidez na Adolescência , Adolescente , Brasil , Anticoncepção , Estudos Transversais , Emergências , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Gravidez , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Damage to the vasculature caused by chronic iron-overload in both humans and animal models, is characterized by endothelial dysfunction and reduced compliance. In vitro, blockade of the angiotensin II AT1 receptors reversed functional vascular changes induced by chronic iron-overload. In this study, the effect of chronic AT1 receptor blockade on aorta stiffening was assessed in iron-overloaded rats. EXPERIMENTAL APPROACH: Male Wistar rats were treated for 15 days with saline as control group, iron dextran 200 mg·kg-1 ·day-1 , 5 days a week (iron-overload group), losartan (20 mg·kg-1 ·day-1 in drinking water), and iron dextran plus losartan. Mechanical properties of the aorta were assessed in vivo. In vitro, aortic geometry and biochemical composition were assessed with morphometric and histological methods. KEY RESULTS: Thoracoabdominal aortic pulse wave velocity (PWV) increased significantly, indicating a decrease in aortic compliance. Co-treatment with losartan prevented changes on PWV, ß-index, and elastic modulus in iron-overloaded rats. This iron-related increase in PWV was not related to changes in aortic geometry and wall stress. but to increased elastic modulus/wall stress ratio, suggesting that a change in the composition of the wall was responsible for the stiffness. Losartan treatment also ameliorated the increase in aorta collagen content of the iron-overload group, without affecting circulating iron or vascular deposits. CONCLUSIONS AND IMPLICATIONS: Losartan prevented the structural and functional indices of aortic stiffness in iron-overloaded rats, implying that inhibition of the renin-angiotensin system would limit the vascular remodelling in chronic iron-overload.
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Análise de Onda de Pulso , Receptores de Angiotensina , Angiotensinas , Animais , Pressão Sanguínea , Ferro , Losartan/farmacologia , Masculino , Ratos , Ratos Wistar , Receptor Tipo 1 de AngiotensinaRESUMO
BACKGROUND: Yellow fever (YF) is a viral hemorrhagic disease caused by an arbovirus from the Flaviviridae family. Data on the clinical profile of severe YF in intensive care units (ICUs) are scarce. This study aimed to evaluate factors associated with YF mortality in patients admitted to a Brazilian ICU during the YF outbreaks of 2017 and 2018. METHODS: This was a longitudinal cohort case series study that included YF patients admitted to the ICU. Demographics, clinical and laboratory data were analyzed. Cox regression identified independent predictors of death risk. RESULTS: A total of 114 patients were studied. The median age was 48 years, and 92.1% were males. In univariate analysis, jaundice, leukopenia, bradycardia, prothrombin time, expressed as a ratio to the international normalized ratio-(PT-INR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, lactate, arterial pH and bicarbonate, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score 3 (SAPS 3) severity scores, transfusion of fresh frozen plasma, acute renal failure (Acute Kidney Injury Network stage III (AKIN III)), hemodialysis, cumulative fluid balance at 72 h of ICU, vasopressor use, seizures and grade IV encephalopathy were significantly associated with mortality. In multivariate analysis, factors independently associated with YF mortality were PT-INR, APACHE II, and grade IV hepatic encephalopathy. CONCLUSIONS: In the large outbreak in Brazil, factors independently associated with death risk in YF were: PT-INR, APACHE II, and grade IV hepatic encephalopathy. Early identification of patients with YF mortality risk factors may be very useful. Once these patients with a poor prognosis have been identified, proper management should be promptly implemented.
Assuntos
Unidades de Terapia Intensiva , Febre Amarela/mortalidade , APACHE , Injúria Renal Aguda/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Surtos de Doenças , Feminino , Encefalopatia Hepática/diagnóstico , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Escore Fisiológico Agudo Simplificado , Febre Amarela/diagnóstico , Febre Amarela/epidemiologia , Adulto JovemRESUMO
Despite the strong evidence on the cardiac and renal damages after chronic exposure to cigarette smoke, there is a paucity of data on its short-term effects. The study evaluated the short-term effects of cigarette smoking on left ventricular (LV) remodeling, in vitro myocardial and renal function. Female Wistar rats were randomized to control (C) and cigarette smoking rats for eight weeks. Physical capacity was assessed using an adapted model of exhaustive swim; left ventricle (LV) morphology and function were also evaluated. Renal function was assessed by creatinine clearance and urine protein. The in vitro myocardial performance was analyzed in isolated papillary muscles. Rats exhibited reduced physical capacity after short-term cigarette smoking. Although there was no change on LV function, reduced chamber diameter was found in the smoking group associated with an increased LV wall thickness. There was augmented cardiac mass compared to C that was confirmed by increased cardiomyocyte nucleus volume, but in vitro myocardial performance and renal function were unchanged. A short-term cigarette smoking induces cardiac remodeling without abnormalities in function. The smoking group still preserved renal function and in vitro myocardial performance. However, the reduced physical capacity may suggest an impairment of the cardiac reserve.