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1.
J Virol Methods ; 287: 114008, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33160015

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the COVID-19 pandemic. Although other diagnostic methods have been introduced, detection of viral genes on oro- and nasopharyngeal swabs by reverse-transcription real time-PCR (rRT-PCR) assays is still the gold standard. Efficient viral RNA extraction is a prerequisite for downstream performance of rRT-PCR assays. Currently, several automatic methods that include RNA extraction are available. However, due to the growing demand, a shortage in kit supplies could be experienced in several labs. For these reasons, the use of different commercial or in-house protocols for RNA extraction may increase the possibility to analyze high number of samples. Herein, we compared the efficiency of RNA extraction of three different commercial kits and an in-house extraction protocol using synthetic ssRNA standards of SARS-CoV-2 as well as in oro-nasopharyngeal swabs from six COVID-19-positive patients. It was concluded that tested commercial kits can be used with some modifications for the detection of the SARS-CoV-2 genome by rRT-PCR approaches, although with some differences in RNA yields. Conversely, EXTRAzol reagent was the less efficient due to the phase separation principle at the basis of RNA extraction. Overall, this study offers alternative suitable methods to manually extract RNA that can be taken into account for SARS-CoV-2 detection.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , RNA Viral/isolamento & purificação , SARS-CoV-2/isolamento & purificação , Testes Diagnósticos de Rotina , Genes Virais/genética , Humanos , Limite de Detecção , Faringe/virologia , RNA Viral/análise , RNA Viral/genética , Reprodutibilidade dos Testes , SARS-CoV-2/genética
2.
Molecules ; 26(1)2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33379366

RESUMO

(1) Background: Nicotine is implicated in the SARS-COV-2 infection through activation of the α7-nAChR and over-expression of ACE2. Our objective was to clarify the role of nicotine in SARS-CoV-2 infection exploring its molecular and cellular activity. (2) Methods: HBEpC or si-mRNA-α7-HBEpC were treated for 1 h, 48 h or continuously with 10-7 M nicotine, a concentration mimicking human exposure to a cigarette. Cell viability and proliferation were evaluated by trypan blue dye exclusion and cell counting, migration by cell migration assay, senescence by SA-ß-Gal activity, and anchorage-independent growth by cloning in soft agar. Expression of Ki67, p53/phospho-p53, VEGF, EGFR/pEGFR, phospho-p38, intracellular Ca2+, ATP and EMT were evaluated by ELISA and/or Western blotting. (3) Results: nicotine induced through α7-nAChR (i) increase in cell viability, (ii) cell proliferation, (iii) Ki67 over-expression, (iv) phospho-p38 up-regulation, (v) EGFR/pEGFR over-expression, (vi) increase in basal Ca2+ concentration, (vii) reduction of ATP production, (viii) decreased level of p53/phospho-p53, (ix) delayed senescence, (x) VEGF increase, (xi) EMT and consequent (xii) enhanced migration, and (xiii) ability to grow independently of the substrate. (4) Conclusions: Based on our results and on evidence showing that nicotine potentiates viral infection, it is likely that nicotine is involved in SARS-CoV-2 infection and severity.


Assuntos
COVID-19/patologia , Células Epiteliais/efeitos dos fármacos , Nicotina/efeitos adversos , Sistema Respiratório/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/virologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/virologia , Humanos , Receptores Nicotínicos/metabolismo , Sistema Respiratório/virologia , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Fumar/efeitos adversos , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
3.
Antioxidants (Basel) ; 9(11)2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33182469

RESUMO

Neuropathic pain is a chronic painful disease. Data have shown that reactive oxygen species (ROS) are implicated in chronic pain. Particularly, the enhanced ROS production alters the mitochondrial genome and proteome through the accumulation of lipid peroxidation products, such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). Sirtuin 3 (SIRT3) is a mitochondrial protein and its activity can reduce ROS levels by modulating key antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Here, we evaluated the role of SIRT3 in the maintenance of basal levels of ROS in a model of chronic constriction injury (CCI) of the sciatic nerve and the protective effects of a natural antioxidant, the bergamot polyphenolic fraction (BPF). Rats were exposed to CCI of the sciatic nerve in the presence or absence of BPF (25-75 mg/kg). Level of acetylation, post-translational modulation on cysteine residues of proteins by HNE and SIRT3 activation, were detected in the spinal cord through western blotting, WES methodology and enzymatic assays. Our results reported that SIRT3 carbonylation and therefore its inactivation contributes to mitochondrial MnSOD hyperacetylation during CCI induced neuropathic pain in rats. In particular, we have demonstrated a close relation between oxidative stress, hyperalgesia, allodynia and sirtuins inactivation reverted by BPF administration.

4.
J Tradit Complement Med ; 10(3): 268-274, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32670822

RESUMO

Background and aim: Non-Alcoholic Fatty Liver Disease (NAFLD) represents a risk factor for cardiovascular diseases. NAFLD is worsened by the simultaneous occurrence of type 2 diabetes mellitus (T2DM) causing an enhancement of inflammatory and fibrotic processes. Although insulin resistance appears the link between NAFLD and T2DM, current pharmacological treatments of T2DM failed to produce relevant benefits in preventing T2DM-related liver dysfunction. In this randomized, double blind, placebo-controlled clinical study, we evaluated the effect of Bergacyn, an innovative formulation originating from the combination of Bergamot Polyphenolic Fraction (BPF) and Cynara cardunculus (CyC). Experimental procedure: 80 adult patients with a history of at least 12 months of T2DM and NAFLD received orally BPF (300 mg/daily) Cyc (300 mg/daily), separately or formulated in combination 50/50% (Bergacyn; 300 mg/daily), or placebo all containing 300 mg of bergamot albedo fibers micronized and co-grinded as excipients. Results and conclusion: Serum measurements and liver ultrasound analyses showed that concomitant administration of BPF and CyC produced significant improvement of NAFLD biomarkers in patients with T2DM. This effect was associated with a substantial reduction of oxidative stress/inflammatory biomarkers, thus contributing to a significant improvement of NO-mediated reactive vasodilation. Furthermore, the effect of Bergacyn showed a synergistic effect of both extracts, thus suggesting that this peculiar formulation represents a novel therapeutic strategy to counteract vascular inflammation and endothelial dysfunction in patients suffering from T2DM and NAFLD. Further studies in larger cohort of diabetic patients are required to better identify the potential of Bergacyn on metabolic disorders accompanying T2DM and NAFLD.

5.
Nutrients ; 12(5)2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32455840

RESUMO

Metabolic syndrome (MetS) represents a set of clinical findings that include visceral adiposity, insulin-resistance, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) levels and hypertension, which is linked to an increased risk of developing type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). The pathogenesis of MetS involves both genetic and acquired factors triggering oxidative stress, cellular dysfunction and systemic inflammation process mainly responsible for the pathophysiological mechanism. In recent years, MetS has gained importance due to the exponential increase in obesity worldwide. However, at present, it remains underdiagnosed and undertreated. The present review will summarize the pathogenesis of MetS and the existing pharmacological therapies currently used and focus attention on the beneficial effects of natural compounds to reduce the risk and progression of MetS. In this regard, emerging evidence suggests a potential protective role of bergamot extracts, in particular bergamot flavonoids, in the management of different features of MetS, due to their pleiotropic anti-oxidative, anti-inflammatory and lipid-lowering effects.


Assuntos
Antioxidantes/farmacologia , Citrus/química , Síndrome Metabólica/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Resistência à Insulina , Obesidade/tratamento farmacológico , Obesidade Abdominal/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico
6.
Pharmacol Res ; 157: 104851, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32423865

RESUMO

Oxidative stress induced post-translational protein modifications are associated with the development of inflammatory hypersensitivities. At least 90% of cellular reactive oxygen species (ROS) are produced in the mitochondria, where the mitochondrial antioxidant, manganese superoxide dismutase (MnSOD), is located. MnSOD's ability to reduce ROS is enhanced by the mitochondrial NAD+-dependent deacetylase sirtuin (SIRT3). SIRT3 can reduce ROS levels by deacetylating MnSOD and enhancing its ability to neutralize ROS or by enhancing the transcription of MnSOD and other oxidative stress-responsive genes. SIRT3 can be post-translationally modified through carbonylation which results in loss of activity. The contribution of post-translational SIRT3 modifications in central sensitization is largely unexplored. Our results reveal that SIRT3 carbonylation contributes to spinal MnSOD inactivation during carrageenan-induced thermal hyperalgesia in rats. Moreover, inhibiting ROS with natural and synthetic antioxidants, prevented SIRT3 carbonylation, restored the enzymatic activity of MnSOD, and blocked the development of thermal hyperalgesia. These results suggest that therapeutic strategies aimed at inhibiting post-translational modifications of SIRT3 may provide beneficial outcomes in pain states where ROS have been documented to play an important role in the development of central sensitization.


Assuntos
Analgésicos/farmacologia , Antioxidantes/farmacologia , Hiperalgesia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sirtuínas/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/enzimologia , Animais , Linhagem Celular Tumoral , Humanos , Hiperalgesia/enzimologia , Hiperalgesia/genética , Hiperalgesia/fisiopatologia , Masculino , Metaloporfirinas/farmacologia , Carbonilação Proteica , Ratos Sprague-Dawley , Resveratrol/farmacologia , Transdução de Sinais , Sirtuínas/genética , Medula Espinal/fisiopatologia , Superóxido Dismutase/metabolismo
7.
Curr Med Chem ; 27(18): 2931-2948, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31838985

RESUMO

The "microbiome" is the operative term to refer to a collection of all taxa constituting microbial communities, such as bacteria, archaea, fungi and protists (originally microbiota). The microbiome consists of the indigenous microbial communities and of the host environment that they inhabit. Actually, it has been shown that there is a close relationship between the microbiome and human health and disease condition. Although, initially, the lung was considered sterile, actually, the existence of a healthy lung microbiome is usually accepted. Lung microbiome changes are reported in Chronic Obstructive Pulmonary Disease (COPD) and in its exacerbation. Viral and bacterial infections of the respiratory system are a major cause of COPD exacerbations (AECOPD) leading to increased local and systemic inflammation. Detection rates of virus in AECOPD are variable between 25-62% according to the detection method. The study of human airway and lung disease virome is quite recent and still very limited. The purpose of this review is to summarize recent findings on the lung microbiome composition with a special emphasis on virome in COPD and in AECOPD. Some drugs of natural origins active against resistant bacteria and virus are described.


Assuntos
Microbiota , Doença Pulmonar Obstrutiva Crônica , Infecções Bacterianas , Produtos Biológicos , Humanos , Pulmão
8.
Int J Psychophysiol ; 146: 133-138, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31648028

RESUMO

Cerebral post-stroke plasticity has been repeatedly investigated via functional neuroimaging techniques mainly based on blood flow/metabolism. However, little is known on predictive value of topological properties of widely distributed neural networks immediately following stroke on rehabilitation outcome and post-stroke recovery measured by early functional outcome. The utility of EEG network parameters (i.e. small world organization) analysis as a potential rough and simple biomarker for stroke outcome has been little explored and needs more validation. A total of 139 consecutive patients within a post-stroke acute stage underwent EEG recording. A group of 110 age paired healthy subjects constituted the control group. All patients were clinically evaluated with 3 scales for stroke: NIHSS, Barthel and ARAT. As a first result, NIHSS, Barthel and ARAT correlated with Small World index as provided by the proportional increment/decrement of low (delta) and viceversa of high (beta2 and gamma) EEG frequency bands. Furthermore, in line with the aim of the present study, we found a strong correlation between NIHSS at follow up and gamma Small World index in the acute post-stroke period, giving SW index a significant weight of recovery prediction. This study aimed to investigate possible correlations between functional abnormalities of brain networks, measured by small world characteristics detected in resting state EEG source investigation, and early post-stroke clinical outcome in order to find a possible predictive index of functional recovery to address and/or correct the rehabilitation program.


Assuntos
Ondas Encefálicas/fisiologia , Córtex Cerebral/fisiopatologia , Conectoma , Eletroencefalografia , Rede Nervosa/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
9.
Mutat Res ; 843: 111-117, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31421732

RESUMO

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by severe respiratory symptoms. COPD shows several hallmarks of aging, and an increased oxidative stress, which is responsible for different clinical and molecular COPD features, including an increased frequency of DNA damage. The current pharmacological treatment options for COPD are mostly symptomatic, and generally do not influence disease progression and survival. In this framework, pulmonary rehabilitation is the most effective therapeutic strategy to improve physical performance, reducing hospital readmissions and mortality. Response to rehabilitation may greatly differ among patients calling for a personalized treatment. In this paper we will investigate in a group of COPD patients those variables that may predict the response to a program of pulmonary rehabilitation, integrating clinical parameters with cellular and molecular measurements, offering the potential for more effective and individualized treatment options. A group of 89 consecutive COPD patients admitted to a 3-weeks Pulmonary Rehabilitation (PR) program were evaluated for clinical and biological parameters at baseline and after completion of PR. DNA fragmentation in cryopreserved lymphocytes was compared by visual scoring and using the Comet Assay IV analysis system. The comparison of DNA damage before and after PR showed a highly significant increase from 19.6 ± 7.3 at admission to 21.8 ± 7.2 after three weeks of treatment, with a significant increase of 2.46 points (p < 0.001). Higher levels of DNA damage were observed in the group of non- responders and in those patients receiving oxygen therapy. The overall variation of %TI during treatment significantly correlated with the level of pCO2 at admission and negatively with the level of IL-6 at admission. Measuring the frequency of DNA damage in COPD patients undergoing pulmonary rehabilitation may provide a meaningful biological marker of response and should be considered as additional diagnostic and prognostic criterion for personalized rehabilitation programs.


Assuntos
Proteína C-Reativa/análise , Ensaio Cometa , Dano ao DNA , Instabilidade Genômica , Interleucina-6/sangue , Doença Pulmonar Obstrutiva Crônica/genética , Terapia Respiratória , Corticosteroides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Broncodilatadores/uso terapêutico , Terapia Combinada , Quebras de DNA de Cadeia Simples , Fragmentação do DNA , Progressão da Doença , Feminino , Humanos , Linfócitos/química , Masculino , Antagonistas Muscarínicos/uso terapêutico , Oxigenoterapia , Medicina de Precisão , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/reabilitação , Doença Pulmonar Obstrutiva Crônica/terapia , Índice de Gravidade de Doença
11.
Int J Mol Sci ; 20(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022961

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient's response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.


Assuntos
Corticosteroides/uso terapêutico , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Proteínas de Ligação a Tacrolimo/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Administração por Inalação , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Glucocorticoides/genética , Resultado do Tratamento
12.
Artigo em Inglês | MEDLINE | ID: mdl-30605063

RESUMO

BACKGROUND: The morbidity and mortality associated with tobacco smoking is well established. Nicotine is the addictive component of tobacco. Nicotine, through the non-neuronal α7nicotinic receptor, induces cell proliferation, neo-angiogenesis, epithelial to mesenchymal transition, and inhibits drug-induced apoptosis. OBJECTIVE: To understand the genetic, molecular and cellular biology of addiction, chronic obstructive pulmonary disease and lung cancer. METHODS: The search for papers to be included in the review was performed during the months of July- September 2018 in the following databases: PubMed (http://www.ncbi.nlm.nih.gov), Scopus (http://www.scopus.com), EMBASE (http://www.elsevier.com/online-tools/embase), and ISI Web of Knowledge (http://apps.webofknowledge.com/). The following searching terms: "nicotine", "nicotinic receptor", and "addiction" or "COPD" or "lung cancer" were used. Patents were retrieved in clinicaltrials.gov (https://clinicaltrials.gov/). All papers written in English were evaluated. The reference list of retrieved articles was also reviewed to identify other eligible studies that were not indexed by the above-mentioned databases. New experimental data on the ability of nicotine to promote transformation of human bronchial epithelial cells, exposed for one hour to Benzo[a]pyrene-7,8-diol-9-10-epoxide, are reported. RESULTS: Nicotinic receptors variants and nicotinic receptors upregulation are involved in addiction, chronic obstructive pulmonary disease and/or lung cancer. Nicotine through α7nicotinic receptor upregulation induces complete bronchial epithelial cells transformation. CONCLUSION: Genetic studies highlight the involvement of nicotinic receptors variants in addiction, chronic obstructive pulmonary disease and/or lung cancer. A future important step will be to translate these genetic findings to clinical practice. Interventions able to help smoking cessation in nicotine dependence subjects, under patent, are reported.


Assuntos
Neoplasias Pulmonares/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Agentes de Cessação do Hábito de Fumar/metabolismo , Fumar Tabaco/metabolismo , Tabagismo/metabolismo , Animais , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Antagonistas Nicotínicos/metabolismo , Antagonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/uso terapêutico , Patentes como Assunto , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Receptores Nicotínicos/metabolismo , Fatores de Risco , Abandono do Hábito de Fumar/métodos , Agentes de Cessação do Hábito de Fumar/farmacologia , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Fumar Tabaco/tratamento farmacológico , Tabagismo/tratamento farmacológico
13.
Curr Med Chem ; 26(10): 1721-1733, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29852859

RESUMO

BACKGROUND: We report a comprehensive overview of current Chronic Obstructive Lung Disease (COPD) therapies and discuss the development of possible new pharmacological approaches based on "new" knowledge. Specifically, sensitivity/resistance to corticosteroids is evaluated with a special focus on the role of gene mutations in drug response. OBJECTIVE: Critically review the opportunities and the challenges occurring in the treatment of COPD. CONCLUSION: Findings from "omics" trials should be used to learn more about biological targeted drugs, and to select more specific drugs matching patient's distinctive molecular profile. Specific markers of inflammation such as the percentage of eosinophils are important in determining sensitivity/resistance to corticosteroids. Specific gene variations (Single nucleotide polymorphisms: SNPs) may influence drug sensitivity or resistance. Clinicians working in a real-world need to have a suitable interpretation of molecular results together with a guideline for the treatment and recommendations. Far more translational research is required before new results from omics techniques can be applied in personalized medicine in realworld settings.


Assuntos
Corticosteroides/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Resistência a Medicamentos/genética , Eosinófilos , Estudo de Associação Genômica Ampla , Humanos , Metabolômica , Mutação , Medicina de Precisão , Proteômica , Doença Pulmonar Obstrutiva Crônica/classificação , Doença Pulmonar Obstrutiva Crônica/terapia
14.
Curr Med Chem ; 26(39): 7048-7058, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29756566

RESUMO

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) and Cardiovascular Diseases (CV) Often Coexist. COPD and CVD are complex diseases characterized by a strict interaction between environment and genetic. The mechanisms linking these two diseases are complex, multifactorial and not entirely understood, influencing the therapeutic approach. COPD is characterized by several comorbidities, it hypothesized the treatment of cardiovascular co-morbidities that may reduce morbidity and mortality. Flavonoids are an important class of plant low molecular weight Secondary Metabolites (SMs). Convincing data from laboratory, epidemiological, and human clinical studies point the important effects on CVD risk prevention. OBJECTIVE: This review aims to provide up-to-date information on the ability of Flavonoids to reduce the CVD risk. CONCLUSION: Current studies support the potential of Flavonoids to prevent the risk of CVD. Well-designed clinical studies are suggested to evaluate advantages and limits of Flavonoids for managing CVD comorbidity in COPD.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Flavonoides/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Humanos
15.
Curr Med Chem ; 26(10): 1734-1745, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30378484

RESUMO

BACKGROUND: We report a comprehensive overview of current COPD therapies from a real-world experience. OBJECTIVE: Critically review the opportunities and the challenges occurring in the real-world treatment of COPD. METHODS: This is a review that also report results from COPD patients treated with standardized therapy including pulmonary rehabilitation (Real World Data - RWD). CONCLUSION: Comprehensive assessment of COPD management requires strategies able to evaluate efficacy and usefulness in a real-world population, that take into account the interaction between experience and academic training, research, adherence to guidelines and judgments in order to plan the appropriate and optimum use of available strategies.


Assuntos
Doença Pulmonar Obstrutiva Crônica/terapia , Adulto , Idoso , Comorbidade , Análise de Dados , Prática Clínica Baseada em Evidências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos
16.
Int J Mol Sci ; 19(9)2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30201915

RESUMO

The main neurovascular unit of the Blood Brain Barrier (BBB) consists of a cellular component, which includes endothelial cells, astrocytes, pericytes, microglia, neurons, and oligodendrocytes as well as a non-cellular component resulting from the extracellular matrix. The endothelial cells are the major vital components of the BBB able to preserve the brain homeostasis. These cells are situated along the demarcation line between the bloodstream and the brain. Therefore, an alteration or the progressive disruption of the endothelial layer may clearly impair the brain homeostasis. The proper functioning of the brain endothelial cells is generally ensured by two elements: (1) the presence of junction proteins and (2) the preservation of a specific polarity involving an apical-luminal and a basolateral-abluminal membrane. This review intends to identify the molecular mechanisms underlying BBB function and their changes occurring in early stages of neurodegenerative processes in order to develop novel therapeutic strategies aimed to counteract neurodegenerative disorders.


Assuntos
Barreira Hematoencefálica/citologia , Proteínas de Membrana/metabolismo , Doenças Neurodegenerativas/metabolismo , Barreira Hematoencefálica/metabolismo , Comunicação Celular , Polaridade Celular , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Humanos , Junções Intercelulares/metabolismo
17.
Mar Drugs ; 16(9)2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30181485

RESUMO

Chronic obstructive pulmonary disease (COPD) is characterized by long-term airflow limitation. Early-onset COPD in non-smoker subjects is ≥60 years and in the elderly is often associated with different comorbidities. Cognitive impairment is one of the most common feature in patients with COPD, and is associated with COPD severity and comorbidities. Cognitive impairment in COPD enhances the assistance requirement in different aspects of daily living, treatment adherence, and effectual self-management.This review describes various bioactive compounds of natural marine sources that modulate different targets shared by both COPD and cognitive impairment and hypothesizes a possible link between these two syndromes.


Assuntos
Organismos Aquáticos/química , Produtos Biológicos/uso terapêutico , Disfunção Cognitiva/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , Produtos Biológicos/isolamento & purificação , Biomarcadores/análise , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Comorbidade , Humanos , Incidência , Fármacos Neuroprotetores/isolamento & purificação , Fatores de Risco
19.
Artigo em Inglês | MEDLINE | ID: mdl-28417609

RESUMO

BACKGROUND: COPD management needs a comprehensive assessment of clinical features (symptoms severity, co-morbidities) together with life-style, behavioural, socio-economic and multi-omics parameters. Among the other issues, psycho-cognitive assessment plays a critical role. Coping strategies are used to manage psychological stress. AIM: To evaluate the association between coping strategies and outcome of Pulmonary Rehabilitation (PR). DESIGN: Observational study. SETTING: Inpatients comprehensive 3 weeks PR programme. POPULATION: Seventy-six patients, 70 years or older affected by COPD GOLD 3-4. METHODS: Disease-specific status was examined using the Medical Research Council Dyspnea Scale, St. George's Respiratory Questionnaire, Maugeri Respiratory Failure, Borg And Barthel Scales. Cognitive And Psychological Clinical Alterations/Disorders Using: Mini-Mental State Examination; Montreal Cognitive Assessment; Center for Epidemiologic Studies Depression Scale; Zung Self-Rating Anxiety Scale. Quality of Life Using Activities of Daily Living; Instrumental Activities of Daily Living; 36-Item Short Form Health Survey General and Mental Health. Functional exercise capacity was measured at baseline and after PR using the Six-Minute Walking Test (6MWT). Coping strategies were measured with the Brief COPE. Internal consistency was determined examining Cronbach's α values. Concurrent validity was determined by examining Spearman r correlations between the single-item and multi-items. Brief-COPE scores after PR between patients who had a different response to respiratory outcomes was evaluated using Student's t and Mann-Whitney U tests. RESULTS: The change in distance (Delta6MWD) between final and baseline value in meters was positively associated with Self-distraction, Active Coping, and Planning strategies. Respiratory disease-specific health status outcomes, as well as the presence of use of long-term oxygen therapy, were not associated with coping strategies. CONCLUSIONS: Self-distraction and Planning strategies are associated to the success of rehabilitation. CLINICAL REHABILITATION IMPACT: Self-distraction and Planning strategies may predict response to pulmonary rehabilitation in elderly patients affected by severe COPD.

20.
Mar Drugs ; 15(3)2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28335527

RESUMO

Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI).


Assuntos
Organismos Aquáticos/química , Fatores Biológicos/química , Fatores Biológicos/farmacologia , Doenças Metabólicas/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Humanos
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