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1.
Int J Mol Sci ; 21(12)2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32570774

RESUMO

INTRODUCTION: The global burden of chronic airway diseases represents an important public health concern. The role of oxidative stress and inflammation in the pathogenesis of these diseases is well known. The aim of this study is to evaluate the behavior of both inflammatory and oxidative stress biomarkers in patients with chronic bronchitis, current asthma and past asthma in the frame of a population-based study. METHODS: For this purpose, data collected from the Gene Environment Interactions in Respiratory Diseases (GEIRD) Study, an Italian multicentre, multicase-control study, was evaluated. Cases and controls were identified through a two-stage screening process of individuals aged 20-65 years from the general population. Out of 16,569 subjects selected from the general population in the first stage of the survey, 2259 participated in the clinical evaluation. Oxidative stress biomarkers such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-isoprostane and glutathione and inflammatory biomarkers such as Fractional Exhaled Nitric Oxide (FENO) and white blood cells were evaluated in 1878 subjects. RESULTS: Current asthmatics presented higher levels of FENO (23.05 ppm), leucocytes (6770 n/µL), basophils (30.75 n/µL) and eosinophils (177.80 n/µL), while subjects with chronic bronchitis showed higher levels of GSH (0.29 mg/mL) and lymphocytes (2101.6 n/µL). The multivariable multinomial logistic regression confirmed high levels of leucocytes (RRR = 1.33), basophils (RRR = 1.48), eosinophils (RRR = 2.39), lymphocytes (RRR = 1.26) and FENO (RRR = 1.42) in subjects with current asthma. Subjects with past asthma had a statistically significant higher level of eosinophils (RRR = 1.78) with respect to controls. Subjects with chronic bronchitis were characterized by increased levels of eosinophils (RRR = 2.15), lymphocytes (RRR = 1.58), GSH (RRR = 2.23) and 8-isoprostane (RRR = 1.23). CONCLUSION: In our study, current asthmatics show a greater expression of the inflammatory profile compared to subjects who have had asthma in the past and chronic bronchitis. On the other hand, chronic bronchitis subjects showed a higher rate of expression of oxidative stress biomarkers compared to asthmatic subjects. In particular, inflammatory markers such as circulating inflammatory cells and FENO seem to be more specific for current asthma, while oxidative stress biomarkers such as glutathione and 8-isoprostane appear to be more specific and applicable to patients with chronic bronchitis.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/sangue , Asma/sangue , Biomarcadores/sangue , Bronquite Crônica/sangue , Dinoprosta/análogos & derivados , Glutationa/sangue , Adulto , Idoso , Estudos de Casos e Controles , Dinoprosta/sangue , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Adulto Jovem
2.
Curr Atheroscler Rep ; 19(8): 33, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28573503

RESUMO

PURPOSE OF REVIEW: This short review is intended primarily to summarize the understanding of the interrelated roles of endoplasmic reticulum (ER) stress, oxidative stress and inflammation in cardiovascular diseases. RECENT FINDINGS: Insults interfering with ER function lead to the accumulation of unfolded and misfolded proteins in the ER. An excess of proteins folding in the ER is known as ER stress. This condition initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signalling is induced. Moreover, the role of the protective nuclear erythroid-related factor 2 (Nrf2)/antioxidant-related element (ARE) and the activation of the pro-inflammatory nuclear factor-kappa B (NF-kB) are analysed. Authors summarize evidence that oxidative stress, inflammation and ER stress are closely entwined phenomena. They are involved in the pathogenesis of different cardiovascular diseases. Current literature data are presented, focusing on three topics of related pathologies: atherosclerotic plaque, coronary artery disease and diabetes. This review will provide a basic platform for study and application to several other conditions in which oxidative stress, ER stress and inflammation are key features. Future studies in this area may identify the most promising molecules to be investigated as common targets for cardiovascular diseases.


Assuntos
Doenças Cardiovasculares/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Estresse Oxidativo/fisiologia , Resposta a Proteínas não Dobradas/fisiologia , Animais , Retículo Endoplasmático/metabolismo , Humanos , Inflamação/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais
3.
Radiol Med ; 118(8): 1294-308, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23716289

RESUMO

PURPOSE: This study evaluated the incremental value and cost-effectiveness ratio of introducing coronary angiography (CA) with multidetector computed tomography (MDCT-CA) in the diagnostic management of patients with suspected coronary artery disease (CAD) compared with the traditional diagnostic workup. MATERIAL AND METHODS: Five hundred and fifty consecutive patients who underwent MDCT-CA between January 2009 and June 2011 were considered. Patients with atypical chest pain and suspected obstructive CAD were directed to one of two diagnostic pathways: the traditional protocol (examination, stress test, CA) and the current protocol (examination, stress test, MDCT-CA, and CA, if necessary). The costs of each protocol and for the individual method were calculated. Based on the results, the cost-effectiveness ratio of the two diagnostic pathways was compared. A third, modified, diagnostic pathway has been proposed with its relative cost-effectiveness ratio (examination, MDCT-CA, stress test, and CA, if necessary). RESULTS: Stress test vs. MDCT-CA had an accuracy of 66%, a sensitivity and specificity of 21% and 87%, respectively, and a positive (PPV) and negative (NPV) predictive value of 40% and 70%, respectively. Comparison between conventional CA (CCA) and MDCT-CA showed a sensitivity and specificity of 92% and 89%, respectively, a PPV and NPV of 89%, and an accuracy of 92%. The traditional protocol has higher costs than the second protocol: 1,645 euro against 322 euro (mean), but it shows a better cost-effectiveness ratio. The new proposed protocol has lower costs, mean 261 euro, with a better costeffectiveness ratio than the traditional protocol. CONCLUSIONS: The diagnostic protocol for patients with suspected CAD has been modified by the introduction of MDCT-CA. Our study confirms the greater diagnostic performance of MDCT-CA compared with stress test and its similar accuracy to CCA. The use of MDCT-CA to select patients for CCA has a favourable cost-effectiveness profile.


Assuntos
Angiografia Coronária/economia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/economia , Tomografia Computadorizada Multidetectores/economia , Idoso , Análise Custo-Benefício , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Sensibilidade e Especificidade
4.
Antioxidants (Basel) ; 12(4)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37107265

RESUMO

Chronic diseases and cancer are worldwide health problems which result in death and disability for millions of people [...].

5.
Cells ; 12(6)2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36980208

RESUMO

Cardiovascular diseases (CVDs) are the principal cause of disease burden and death worldwide. Ferroptosis is a new form of regulated cell death mainly characterized by altered iron metabolism, increased polyunsaturated fatty acid peroxidation by reactive oxygen species, depletion of glutathione and inactivation of glutathione peroxidase 4. Recently, a series of studies have indicated that ferroptosis is involved in the death of cardiac and vascular cells and has a key impact on the mechanisms leading to CVDs such as ischemic heart disease, ischemia/reperfusion injury, cardiomyopathies, and heart failure. In this article, we reviewed the molecular mechanism of ferroptosis and the current understanding of the pathophysiological role of ferroptosis in ischemic heart disease and in some cardiomyopathies. Moreover, the comprehension of the machinery governing ferroptosis in vascular cells and cardiomyocytes may provide new insights into preventive and therapeutic strategies in CVDs.


Assuntos
Cardiomiopatias , Doenças Cardiovasculares , Ferroptose , Isquemia Miocárdica , Humanos , Morte Celular , Ferro/metabolismo , Peroxidação de Lipídeos
6.
Antioxidants (Basel) ; 11(3)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35326099

RESUMO

Oxidative stress (OS) is an imbalance between the formation of reactive oxygen and nitrogen species and antioxidant defenses [...].

7.
Antioxidants (Basel) ; 11(10)2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36290778

RESUMO

Moderate wine consumption has been associated with several benefits to human health due to its high polyphenol content. In this study, we investigated whether polyphenols contained in a particular red wine, rich in polyphenols, can pass the cell membrane and switch the oxidant/antioxidant balance toward an antioxidant pattern of THP-1 cells and human cardiomyocytes through a gene regulatory system. First, we identified which metabolite polyphenols present in red wine extract cross cell membranes and may be responsible for antioxidant effects. The results showed that the wine metabolites in treated cells belonged mainly to stilbenes, flavan-3-ols derivatives, and flavonoids. Other metabolites present in cells were not typical wine metabolites. Then, we found that red wine extract dose-dependently lowered reactive oxygen species (ROS) induced by tert-butyl hydroperoxide (TBHP) up to 50 ± 7% in both cell lines (p < 0.01). Furthermore, wine extract increased nuclear Nrf2 of about 35 ± 5% in both cell lines (p < 0.01) and counteracted its reduction induced by TBHP (p < 0.01). The rise in Nrf2 was paralleled by the increase in hemeoxygenase-1 and glutamate-cysteine ligase catalytic subunit gene expression (both mRNA and protein) (p < 0.01). These results could help explain the healthful activity of wine polyphenols within cells.

8.
Front Physiol ; 13: 932013, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860651

RESUMO

Peripheral blood smear is a simple laboratory tool, which remains of invaluable help for diagnosing primary and secondary abnormalities of blood cells despite advances in automated and molecular techniques. Red blood cells (RBCs) abnormalities are known to occur in many viral infections, typically in the form of mild normo-microcytic anemia. While several hematological alterations at automated complete blood count (including neutrophilia, lymphopenia, and increased red cell distribution width-RDW) have been consistently associated with severity of COVID-19, there is scarce information on RBCs morphological abnormalities, mainly as case-reports or small series of patients, which are hardly comparable due to heterogeneity in sampling times and definition of illness severity. We report here a systematic evaluation of RBCs morphology at peripheral blood smear in COVID-19 patients within the first 72 h from hospital admission. One hundred and fifteen patients were included, with detailed collection of other clinical variables and follow-up. A certain degree of abnormalities in RBCs morphology was observed in 75 (65%) patients. Heterogenous alterations were noted, with spiculated cells being the more frequent morphology. The group with >10% RBCs abnormalities had more consistent lymphopenia and thrombocytopenia compared to those without abnormalities or <10% RBCs abnormalities (p < 0.018, and p < 0.021, respectively), thus underpinning a possible association with an overall more sustained immune-inflammatory "stress" hematopoiesis. Follow-up analysis showed a different mortality rate across groups, with the highest rate in those with more frequent RBCs morphological alterations compared to those with <10% or no abnormalities (41.9%, vs. 20.5%, vs. 12.5%, respectively, p = 0.012). Despite the inherent limitations of such simple association, our results point out towards further studies on erythropoiesis alterations in the pathophysiology of COVID-19.

9.
Antioxidants (Basel) ; 10(3)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669036

RESUMO

Over the last few decades, many efforts have been put into fields that explore the potential benefits of antioxidants, especially with regards to aging, cancer, cardiovascular diseases, and neurodegenerative diseases. [...].

10.
Antioxidants (Basel) ; 10(2)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578849

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Here, we review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress (OS) and inflammation. Furthermore, we analyze the potential role of antioxidant and anti-inflammatory therapies to prevent severe complications. OS has a potential key role in the COVID-19 pathogenesis by triggering the NOD-like receptor family pyrin domain containing 3 inflammasome and nuclear factor-kB (NF-kB). While exposure to many pro-oxidants usually induces nuclear factor erythroid 2 p45-related factor2 (NRF2) activation and upregulation of antioxidant related elements expression, respiratory viral infections often inhibit NRF2 and/or activate NF-kB pathways, resulting in inflammation and oxidative injury. Hence, the use of radical scavengers like N-acetylcysteine and vitamin C, as well as of steroids and inflammasome inhibitors, has been proposed. The NRF2 pathway has been shown to be suppressed in severe SARS-CoV-2 patients. Pharmacological NRF2 inducers have been reported to inhibit SARS-CoV-2 replication, the inflammatory response, and transmembrane protease serine 2 activation, which for the entry of SARS-CoV-2 into the host cells through the angiotensin converting enzyme 2 receptor. Thus, NRF2 activation may represent a potential path out of the woods in COVID-19 pandemic.

11.
Antioxidants (Basel) ; 10(11)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34829548

RESUMO

Even though COVID-19 is mostly well-known for affecting respiratory pathology, it can also result in several extrapulmonary manifestations, leading to multiorgan damage. A recent reported case of SARS-CoV-2 myocarditis with cardiogenic shock showed a signature of myocardial and kidney ferroptosis, a novel, iron-dependent programmed cell death. The term ferroptosis was coined in the last decade to describe the form of cell death induced by the small molecule erastin. As a specific inducer of ferroptosis, erastin inhibits cystine-glutamate antiporter system Xc-, blocking transportation into the cytoplasm of cystine, a precursor of glutathione (GSH) in exchange with glutamate and the consequent malfunction of GPX4. Ferroptosis is also promoted by intracellular iron overload and by the iron-dependent accumulation of polyunsaturated fatty acids (PUFA)-derived lipid peroxides. Since depletion of GSH, inactivation of GPX4, altered iron metabolism, and upregulation of PUFA peroxidation by reactive oxygen species are peculiar signs of COVID-19, there is the possibility that SARS-CoV-2 may trigger ferroptosis in the cells of multiple organs, thus contributing to multiorgan damage. Here, we review the molecular mechanisms of ferroptosis and its possible relationship with SARS-CoV-2 infection and multiorgan damage. Finally, we analyze the potential interventions that may combat ferroptosis and, therefore, reduce multiorgan damage.

12.
Biogerontology ; 11(1): 111-22, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19526322

RESUMO

We used an in vitro model to evaluate the effects of cellular aging and inflammation on the gene expression and protein secretion profiles of adipocytes. 3T3-L1 mouse preadipocytes were cultured according to standard conditions and analyzed at different time points both at the basal state and after an acute stimulation with LPS. The mRNA levels of CCAAT/enhancer-binding protein (C/EBP)alpha, peroxisome proliferator-activated receptor (PPAR)gamma and S100A1 were maximal during adipocyte differentiation and then significantly decreased. The expression of the GLUT4 and IRS-1 genes peaked during differentiation and then decreased in aged cells. The mRNA levels and secretion of adiponectin, quickly rose as adipocytes matured and then declined. The mRNA levels of IL6, as well as its secretion, increased as preadipocytes matured and became old cells; a similar trend was also found for MCP-1. LPS decreased the mRNA levels of C/EBPalpha and PPARgamma at all time points, as well as those of GLUT4, IRS-1 and adiponectin. LPS significantly increased the mRNA levels of IL-6, as well as its secretion, with a similar trend also observed for MCP-1. These data suggest that aging adipocytes in vitro show a decline in pro-adipogenic signals, in genes involved in glucose metabolism and cytoskeleton maintenance and in adiponectin. These changes are paralleled by an increase in inflammatory cytokines; inflammation seems to mimic and amplify the effects of cellular aging on adipocytes.


Assuntos
Adipócitos/metabolismo , Envelhecimento/metabolismo , Citocinas/metabolismo , Fatores Imunológicos/metabolismo , Inflamação/metabolismo , Células 3T3-L1 , Animais , Regulação da Expressão Gênica , Camundongos
13.
Antioxidants (Basel) ; 9(4)2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32340270

RESUMO

BACKGROUND: While reperfusion is crucial for survival after an episode of ischemia, it also causes oxidative stress. Nuclear factor-E2-related factor 2 (Nrf2) and unfolded protein response (UPR) are protective against oxidative stress and endoplasmic reticulum (ER) stress. Ezetimibe, a cholesterol absorption inhibitor, has been shown to activate the AMP-activated protein kinase (AMPK)/Nrf2 pathway. In this study we evaluated whether Ezetimibe affects oxidative stress and Nrf2 and UPR gene expression in cellular models of ischemia-reperfusion (IR). METHODS: Cultured cells were subjected to simulated IR with or without Ezetimibe. RESULTS: IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). Ezetimibe significantly decreased the cellular ROS formation and apoptosis induced by IR. These effects were paralleled by the up-regulation of Nrf2/ARE and ATF6 gene expression and by a down-regulation of CHOP. We also found that Nrf2 activation was dependent on AMPK, since Compound C, a pan inhibitor of p-AMPK, blunted the activation of Nrf2. CONCLUSIONS: Ezetimibe counteracts IR-induced oxidative stress and induces Nrf2 and UPR pathway activation.

14.
Mediators Inflamm ; 2008: 367590, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18437228

RESUMO

The endothelium plays a key role in the development of atherogenesis and its inflammatory and proliferative status influences the progression of atherosclerosis. The aim of this study is to compare the effects of two beta blockers such as nebivolol and atenolol on gene expression in human umbilical vein endothelial cells (HUVECs) following an oxidant stimulus. HUVECs were incubated with nebivolol or atenolol (10 micromol/L) for 24 hours and oxidative stress was induced by the addition of oxidized (ox)-LDL. Ox-LDL upregulated adhesion molecules (ICAM-1, ICAM-2, ICAM-3, E-selectin, and P-selectin); proteins linked to inflammation (IL-6 and TNFalpha), thrombotic state (tissue factor, PAI-1 and uPA), hypertension such as endothelin-1 (ET-1), and vascular remodeling such as metalloproteinases (MMP-2, MMP-9) and protease inhibitor (TIMP-1). The exposure of HUVECs to nebivolol, but not to atenolol, reduced these genes upregulated by oxidative stress both in terms of protein and RNA expression. The known antioxidant properties of the third generation beta blocker nebivolol seem to account to the observed differences seen when compared to atenolol and support the specific potential protective role of this beta blocker on the expression of a number of genes involved in the initiation and progression of atherosclerosis.


Assuntos
Atenolol/farmacologia , Benzopiranos/farmacologia , Células Endoteliais/efeitos dos fármacos , Etanolaminas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Antígenos CD/genética , Antígenos CD/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Selectina E/genética , Selectina E/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Ensaio de Imunoadsorção Enzimática , Expressão Gênica/efeitos dos fármacos , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Nebivolol , Análise de Sequência com Séries de Oligonucleotídeos , Selectina-P/genética , Selectina-P/metabolismo , Veias Umbilicais/citologia
15.
Intern Emerg Med ; 13(5): 699-707, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29858968

RESUMO

This study aims at assessing NF-kB activity in unstable angina (UA) patients free of symptoms after a 1 year follow-up (1YFU). Plasma oxidized low-density lipoproteins (oxLDL), circulating NF-kB, Interleukin 6 (IL-6) and Interleukin 1ß (IL-1ß), high-sensitivity C-reactive protein (hs-CRP), as markers of oxidative stress and inflammation and plasma double-stranded DNA (ds-DNA), as marker of Neutrophil Extracellular Traps (NETs), were measured in 23 of the previously enrolled 27 UA patients. These measurements were compared to the UA data at baseline, and then compared to the data derived from the stable angina (SA) and controls (C) enrolled in our previous study (we demonstrated that UA had higher levels of NF-kB compared to SA and C). After a 1YFU, UA patients show a significant decrease in NF-kB, IL-6, hs-CRP, oxLDL, and ds-DNA plasma levels (p < 0.001) and in IL-1ß and White Blood Cells (WBC) (p < 0.005), without differences in lipid and glucose assessment. If compared to SA and C, UA after a 1YFU have higher levels of NF-kB, IL-6, ds-DNA, WBC, and oxLDL compared to C (p < 0.001), but only IL-6 is higher than SA (p < 0.001). No differences are found in lipid and glucose assessment. After a 1YFU, patients with a history of UA improve their oxidative and inflammatory status, such as the levels of circulating ds-DNA, without achieving the status of C. They become comparable to SA subjects. This study provides new insight on the multiple and apparently contradictory facets of NF-kB in UA and on its possible role as mediator in NETs' formation.


Assuntos
Angina Instável/sangue , NF-kappa B/sangue , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , DNA/sangue , Feminino , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Contagem de Leucócitos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo
16.
Intern Emerg Med ; 13(1): 27-33, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28803375

RESUMO

Lung ultrasound (LUS) is a valid tool for the assessment of heart failure (HF) through the quantification of the B-lines. This study in HF patients aims to evaluate if LUS: (1) can accelerate the discharge time; (2) can efficiently drive diuretic therapy dosage; and (3) may have better performance compared to the amino-terminal portion of B type natriuretic peptide (NT-proBNP) levels in monitoring HF recovery. A consecutive sample of 120 HF patients was admitted from the Emergency Department (ED) to the Internal Medicine Department (Verona University Hospital). The Chest X-ray (CXR) group underwent standard CXR examination on admission and discharge. The LUS group underwent LUS on admission, 24, 48 and 72 h later, and on discharge. The Inferior Cava Vein Collapsibility Index, ICVCI, and the NT-proBNP were assessed. LUS discharge time was significantly shorter if compared to CXR group (p < 0.01). During hospitalization, the LUS group underwent an increased number of diuretic dosage modulations compared to the CXR group (p < 0.001). There was a stronger association between partial pressure of oxygen in arterial blood (PaO2) and B-lines compared to the association between PaO2 and NT-proBNP both on admission and on discharge (p < 0.001). The B-lines numbers were significantly higher on admission in patients with more severe HF, and the ICVCI was inversely associated with B-lines number (p < 0.001). The potential of LUS in tailoring diuretic therapy and accelerating the discharge time in HF patients is confirmed. Until the technique comes into common use in different departments, it is plausible that LUS will evolve with different facets.


Assuntos
Insuficiência Cardíaca/diagnóstico , Tempo de Internação/estatística & dados numéricos , Pulmão/diagnóstico por imagem , Ultrassonografia/tendências , Idoso , Idoso de 80 Anos ou mais , Gerenciamento Clínico , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Itália , Masculino , Alta do Paciente/estatística & dados numéricos , Análise de Regressão , Estatísticas não Paramétricas , Fatores de Tempo , Ultrassonografia/métodos
17.
J Atheroscler Thromb ; 25(9): 808-820, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29540636

RESUMO

AIM: Ischemia-reperfusion (I-R) produces reactive oxygen species (ROS) that damage cells and favour cytotoxicity and apoptosis in peripheral artery disease (PAD) patients. Since brief episodes of I-R (ischemic conditioning) protect cells against ischemic harms, we evaluated whether a short-course of supervised treadmill training, characterized by repeated episodes of I-R, makes peripheral blood mononuclear cells (PBMCs) from PAD patients with intermittent claudication more resistant to I-R injuries by reducing oxidative stress and by inducing an adaptative response of unfolded protein response (UPR) and nuclear factor-E2-related factor (Nrf2) pathway expression. METHODS: 24 PAD patients underwent 21 sessions of treadmill training and a treadmill test as indicator of acute response to I-R. RESULTS: Maximal and pain free walking distance improved (p<0.01), whereas LDH leakage and apoptosis of PBMCs decreased (p<0.01); plasma malondialdehyde and ROS generation in PBMCs declined, while plasma glutathione augmented (p<0.01). Moreover we demonstrated an up-regulation of UPR and Nrf2 expression in PBMCs (p<0.01). To understand whether treadmill training may act as a trigger of ischemic conditioning, we examined the effect of repeated episodes of I-R on adaptative response in PBMCs derived from the patients. We showed an up-regulation of UPR and Nrf2 gene expression (p<0.01), while oxidative stress and cytotoxicity, after an initial increase, declined (p<0.01). This positive effect on cytotoxicity was reduced after inhibition of UPR and Nrf2 pathways. CONCLUSIONS: Treadmill training in PAD patients through UPR and Nrf2 up-regulation may trigger hypoxic adaptation similar to conditioning, thus modifying cell survival.


Assuntos
Exercício Físico , Fator 2 Relacionado a NF-E2/sangue , Doença Arterial Periférica/sangue , Resposta a Proteínas não Dobradas , Idoso , Idoso de 80 Anos ou mais , Apoptose , Núcleo Celular/metabolismo , Endorribonucleases/metabolismo , Teste de Esforço , Feminino , Humanos , Precondicionamento Isquêmico , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estresse Oxidativo , Desnaturação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição/metabolismo , Regulação para Cima , Caminhada , eIF-2 Quinase/metabolismo
18.
J Breath Res ; 12(2): 026012, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29167414

RESUMO

BACKGROUND: There is a need for easily measurable biomarkers that are able to identify different levels of asthma severity. AIM: To assess the association between peripheral blood cell counts, fractional nitric oxide in exhaled air (FeNO), urinary biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and 8-isoprostane), and asthma severity in adult patients from the general population. METHODS: In the Gene Environment Interactions in Respiratory Diseases study, 287 subjects with asthma (aged 20-64) were identified from the general population in Verona (Italy) (2008-2010). Self-reported asthma attacks, asthma-like symptoms and the use of hospital services in the past year were synthesized in a score of respiratory symptoms (SRS). The association of biomarkers with SRS and lung function measures (pre-bronchodilator FEV1% predicted and FEV1/FVC) was assessed using quasi-Poisson and Gaussian regression models, respectively. RESULTS: Eosinophils (ratio of expected scores: RES[95%CI] = 1.19[1.09,1.30]), basophils (RES[95%CI] = 1.24[1.10,1.40]), lymphocytes (RES[95%CI] = 1.27[1.12,1.45]) and FeNO (RES[95%CI] = 1.18[1.02,1.37]) were positively associated with SRS. However, only eosinophils (RES[95%CI] = 1.15[1.02,1.30]) and lymphocytes (RES[95%CI] = 1.25[1.06,1.47]) showed an independent association. Furthermore, eosinophils (change in the expected outcome for 1-SD increase: CEO[95%CI] = -1.18[-2.09, -0.27]%), basophils (CEO[95%CI] = -1.24[-2.16, -0.33]%) and lymphocytes (CEO[95%CI] = -1.07[-1.99, -0.14]%) were individually, but not independently, associated with FEV1/FVC. Finally, neutrophils were negatively associated with FEV1% predicted (CEO[95%CI] = -2.22[-4.00, -0.44]%). CONCLUSIONS: We identified a pattern of association between a set of biomarkers and asthma endotypes in adult patients from the general population, which could improve understanding of the heterogeneity and severity of the disease and could be useful in defining targeted therapeutic approaches.


Assuntos
Asma/diagnóstico , Asma/fisiopatologia , Biomarcadores/análise , Respiração , Adulto , Testes Respiratórios , Dinoprosta/análogos & derivados , Dinoprosta/análise , Expiração , Feminino , Humanos , Masculino , Óxido Nítrico/análise , Testes de Função Respiratória , Índice de Gravidade de Doença
19.
Am J Hypertens ; 20(4): 443-50, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17386354

RESUMO

BACKGROUND: Oxidative inactivation of nitric oxide (NO) is regarded as an important cause of reduced endothelium-dependent vasodilation in essential hypertension. Because zofenopril, an angiotensin-converting enzyme (ACE) inhibitor with a sulfhydryl (SH) group, has demonstrated antioxidant properties and to reduce adhesion molecule expression in vitro, in this study we evaluated the effect of this drug in comparison with the carboxylic ACE inhibitor ramipril and the beta-adrenoreceptor blocker atenolol on (1) circulating adhesion molecules and some oxidative stress parameters and (2) endothelium-dependent vasodilation in essential mildly hypertensive patients. METHODS: A total of 45 healthy subjects and 45 matched hypertensive patients participated in the study. Hypertensive patients were randomly treated with zofenopril (15 to 30 mg/d), ramipril (2.5 to 5 mg/d), and atenolol (50 to 100 mg/d). At baseline and after an 8-week therapy we evaluated blood pressure (BP) values, plasma and LDL hydroperoxides, plasma 8-isoprostanes, circulating levels of oxidized-(ox)LDL and of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1], and E-selectin). Furthermore, all patients underwent ultrasound detection of brachial artery reactivity and endothelium-dependent dilation (flow-mediated dilation, FMD) was evaluated. RESULTS: All the treatments determined similar significant (P < .001) reduction of both systolic and diastolic BP values. Plasma (P < .01) and LDL hydroperoxides (P < .01), plasma 8-isoprostanes (P < .05), circulating oxLDL (P < .05), and adhesion molecules (P < .05) were significantly reduced only in patients receiving zofenopril. Similarly FMD was significantly increased (P < .001) in the zofenopril-treated group. CONCLUSIONS: Our results suggest that in mildly hypertensive patients without organ damage zofenopril, beyond its BP-lowering effects and through its sustained antioxidant activity, offers important advantages in reducing endothelial activation.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/análogos & derivados , Endotélio Vascular/fisiopatologia , Hipertensão/tratamento farmacológico , Ramipril/uso terapêutico , Compostos de Sulfidrila/uso terapêutico , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Atenolol/farmacologia , Atenolol/uso terapêutico , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Captopril/farmacologia , Captopril/uso terapêutico , Moléculas de Adesão Celular/sangue , Moléculas de Adesão Celular/efeitos dos fármacos , HDL-Colesterol/sangue , Endotélio Vascular/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ramipril/farmacologia , Compostos de Sulfidrila/farmacologia , Triglicerídeos/sangue , Vasodilatação/efeitos dos fármacos
20.
Am J Case Rep ; 18: 1058-1065, 2017 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-28974669

RESUMO

BACKGROUND Heatstroke (HS) is a life-threatening condition characterized by an elevation of the core body temperature above 40°C, central nervous system dysfunction, and possible multi-organ failure. HS can trigger systemic inflammation, disseminated intravascular coagulation (DIC), rhabdomyolysis, cerebral edema and seizures, pulmonary edema, heart dysfunctions, and renal and hepatic failure. CASE REPORT We report the case of a 41-year-old Romanian woman with a history of alcoholism who developed HS after arriving by bus in Verona, Italy in June 2016. The patient developed consecutive multi-organ dysfunction, including liver and renal failure, rhabdomyolysis, DIC, and arrhythmia. The patient was successfully treated with conservative measures. After 17 days, she recovered completely. CONCLUSIONS The exact mechanism of HS-related multiple organ dysfunction is not completely understood and its pathogenesis is complex. It involves inflammation, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Development of a model in which chronic alcohol abuse alters oxidative, inflammatory, and ER stress response could also be a conceivable solution to the positive prognosis of severe HS patients, in which liver failure has a prominent role.


Assuntos
Golpe de Calor/complicações , Adulto , Alcoolismo/complicações , Arritmias Cardíacas/etiologia , Coagulação Intravascular Disseminada/etiologia , Feminino , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Rabdomiólise/etiologia
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