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1.
Addict Behav ; 103: 106222, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31838445

RESUMO

INTRODUCTION: Electronic cigarettes (e-cigarettes) might be a valid and safe device to support smoking cessation. However, the available evidence is divergent. The aim of the present work was to assess the effects of an e-cigarette program on pulmonary health (cough, breath shortness, catarrh) and to evaluate the effectiveness of e-cigarettes in reducing tobacco consumption. METHODS: The study is a double-blind randomized controlled trial. Two hundred and ten smokers were randomized into three groups: nicotine e-cigarette (8 mg/mL nicotine concentration), nicotine-free e-cigarettes (placebo), and control with 1:1:1 ratio. All participants received a 3 months cessation program that included a cognitive-behavioral intervention aimed at supporting people in changing their behavior and improving motivation to quit. RESULTS: Pulmonary health, assessed with self-reported measures, clinical evaluations and the Leicester Cough Questionnaire, improved in participants who stopped smoking compared to their own baseline. No differences in pulmonary health were found between groups. Statistical tests showed a significant effect of Group (F (2, 118) = 4.005, p < .020) on daily cigarette consumption: after 6 months participants in the nicotine e-cigarette group smoked fewer cigarettes than any other group. Moreover, participants in this group showed the lowest level of exhaled carbon monoxide (CO) (M = 12.012, S.D. = 8.130), and the lowest level of dependence (M = 3.12, S.D. = 2.29) compared to the nicotine-free e-cigarette and control conditions. CONCLUSIONS: After 6 months about 20% of the entire sample stopped smoking. Participants who used e-cigarettes with nicotine smoked fewer tobacco cigarettes than any other group after 6 months (p < .020). Our data add to the efficacy and safety of e-cigarettes in helping smokers reducing tobacco consumption and improving pulmonary health status.

2.
Nicotine Tob Res ; 21(1): 119-126, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29660034

RESUMO

Introduction: E-cigarettes may be positively used in tobacco cessation treatments. However, neither the World Health Organization nor the American Food and Drug Administration has recognized them as effective cessation aids. Data about the efficacy and safety of e-cigarettes are still limited and controversial. Methods: This was a double-blind randomized controlled study. The main focus of this article is on a secondary outcome of the study, that is, the assessment of effectiveness and safety of e-cigarettes in achieving smoking cessation in a group of chronic smokers voluntarily involved in long-term lung cancer screening. Participants were randomized into three arms with a 1:1:1 ratio: e-cigarettes (Arm 1), placebo (Arm 2), and control (Arm 3). All subjects also received a low-intensity counseling. Results: Two hundred ten smokers were randomized (70 to nicotine e-cigarettes, 70 nicotine-free placebo e-cigarettes, and 70 to control groups). About 25% of participants who followed a cessation program based on the use of e-cigarettes (Arm 1 and Arm 2) were abstinent after 3 months. Conversely, only about 10% of smokers in Arm 3 stopped. A Kruskal-Wallis test showed significant differences in daily cigarettes smoking across the three arms (K-W = 6.277, p = .043). In particular, participants in Arm 1 reported a higher reduction rate (M = -11.6441, SD = 7.574) than participants in Arm 2 (M = -10.7636, SD = 8.156) and Arm 3 (M = -9.1379, SD = 8.8127). Conclusions: Our findings support the efficacy and safety of e-cigarettes in a short-term period. E-cigarettes use led to a higher cessation rate. Furthermore, although all participants reported a significant reduction of daily cigarette consumption compared to the baseline, the use of e-cigarettes (including those without nicotine) allowed smokers to achieve better results. Implications: E-cigarettes increased the stopping rate as well as the reduction of daily cigarettes in participants who continued smoking. In fact, although all participants reported a significant reduction of tobacco consumption compared to the baseline, the use of e-cigarettes allowed smokers to achieve a better result. It could be worthwhile to associate this device with new ICT-driven models of self-management support in order to enable people to better handle behavioral changes and side effects. This is true for ready-to-quit smokers (such as our participants) but can also be advantageous for less motivated smokers engaged in clinical settings.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Nicotina/administração & dosagem , Fumantes/psicologia , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar/métodos , Fumar Tabaco/psicologia , Aconselhamento/métodos , Método Duplo-Cego , Detecção Precoce de Câncer , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Nicotina/efeitos adversos , Fumar Tabaco/epidemiologia
4.
Maturitas ; 99: 1-9, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28364860

RESUMO

BACKGROUND: Estetrol (E4) is a natural estrogen produced solely during human pregnancy. E4 is suitable for clinical use since it acts as a selective estrogen receptor modulator. In clinical trials E4 has been seen to have little or no effect on coagulation. Hence, it is interesting to investigate whether E4 alters endothelial-dependent fibrinolysis. OBJECTIVES: We studied the effects of E4 on the fibrinolytic system and whether this could influence the ability of endothelial cells to migrate. In addition, we compared the effects of E4 with those of 17ß-estradiol (E2). STUDY DESIGN: Human umbilical vein endothelial cells (HUVEC) were obtained from healthy women. Expression of plasminogen-activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (u-PA) and tissue plasminogen activator (t-PA) proteins was evaluated by Western blot analysis. Endothelial cell migration was studied by razor-scrape horizontal and multiwell insert systems assays. RESULTS: E4 increased the expression of t-PA, u-PA and PAI-1 in HUVEC, but less so than did equimolar amounts of E2. The effects of E4 on t-PA, u-PA and PAI-1 were mediated by the induction of the early-immediate genes c-Jun and c-Fos. E4 in combination with E2 antagonized the effects induced by pregnancy-like E2 concentrations but did not impair the effects of postmenopausal-like E2 levels. We also found that the increased synthesis of PAI-1, u-PA and t-PA induced by E2 and E4 is important for horizontal and three-dimensional migration of HUVEC. CONCLUSIONS: These results support the hypothesis that E4 acts as an endogenous selective estrogen receptor modulator (SERM), controlling the fibrinolytic system and endothelial cell migration.


Assuntos
Movimento Celular/efeitos dos fármacos , Estetrol/farmacologia , Fibrinólise/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/efeitos dos fármacos , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Ativador de Plasminogênio Tecidual/efeitos dos fármacos , Ativador de Plasminogênio Tipo Uroquinase/efeitos dos fármacos , Western Blotting , Células Cultivadas , Células Endoteliais , Endotélio Vascular/efeitos dos fármacos , Estradiol/farmacologia , Estrogênios/farmacologia , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
5.
JMIR Res Protoc ; 5(1): e21, 2016 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-26842790

RESUMO

BACKGROUND: Smoking is a global public health problem. For this reason, experts have called smoking dependence a global epidemic. Over the past 5 years, sales of electronic cigarettes, or e-cigarettes, have been growing strongly in many countries. Yet there is only partial evidence that e-cigarettes are beneficial for smoking cessation. In particular, although it has been proven that nicotine replacement devices may help individuals stop smoking and tolerate withdrawal symptoms, e-cigarettes' power to increase the quitting success rate is still limited, ranging from 5% to 20% dependent on smokers' baseline conditions as shown by a recent Cochrane review. Consequently, it is urgent to know if e-cigarettes may have a higher success rate than other nicotine replacement methods and under what conditions. Furthermore, the effects of the therapeutic setting and the relationship between individual characteristics and the success rate have not been tested. This protocol is particularly innovative, because it aims to test the effectiveness of electronic devices in a screening program (the COSMOS II lung cancer prevention program at the European Institute of Oncology), where tobacco reduction is needed to lower individuals' lung cancer risks. OBJECTIVE: This protocol was designed with the primary aim of investigating the role of tobacco-free cigarettes in helping smokers improve lung health and either quit smoking or reduce their tobacco consumption. In particular, we aim to investigate the impact of a 3-month e-cigarettes program to reduce smoking-related respiratory symptoms (eg, dry cough, shortness of breath, mouth irritation, and phlegm) through reduced consumption of tobacco cigarettes. Furthermore, we evaluate the behavioral and psychological (eg, well-being, mood, and quality of life) effects of the treatment. METHODS: This is a prospective, randomized, placebo-controlled, double-blind, three-parallel group study. The study is organized as a nested randomized controlled study with 3 branches: a nicotine e-cigarettes group, a nicotine-free e-cigarettes group, and a control group. The study is nested in a screening program for early lung cancer detection in heavy smokers. RESULTS: The study is open and is still recruiting. CONCLUSIONS: Stopping or reducing tobacco consumption should be a main goal of any health organization. However, traditional antismoking programs are expensive and not always effective. Therefore, favoring a partial or complete shift to e-cigarettes in heavy smokers (eg, persons at high risk for a number of diseases) could be considered a moral imperative. However, before following this path, sound and reliable data on large samples and in a variety of contexts are required. TRIAL REGISTRATION: Clinicaltrials.gov NCT02422914; https://clinicaltrials.gov/ct2/show/NCT02422914 (Archived by WebCite at http://www.webcitation.org/6etwz1bPL).

6.
Artigo em Inglês | MEDLINE | ID: mdl-24904530

RESUMO

Estetrol (E4) is a natural human estrogen present at high concentrations during pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is particularly suitable for therapeutic applications. E4 acts as a selective estrogen receptor (ER) modulator, exerting estrogenic actions on the endometrium or the central nervous system, while antagonizing the actions of estradiol in the breast. We tested the effects of E4 on its own or in the presence of 17ß-estradiol (E2) on T47-D ER+ breast cancer cell migration and invasion of three-dimensional matrices. E4 administration to T47-D cells weakly stimulated migration and invasion. However, E4 decreased the extent of movement and invasion induced by E2. Breast cancer cell movement requires a remodeling of the actin cytoskeleton. During exposure to E4, a weak, concentration-dependent, re-distribution of actin fibers toward the cell membrane was observed. However, when E4 was added to E2, an inhibition of actin remodeling induced by E2 was seen. Estrogens stimulate ER+ breast cancer cell movement through the ezrin-radixin-moesin family of actin regulatory proteins, inducing actin and cell membrane remodeling. E4 was a weak inducer of moesin phosphorylation on Thr(558), which accounts for its functional activation. In co-treatment with E2, E4 blocked the activation of this actin controller in a concentration-related fashion. These effects were obtained through recruitment of estrogen receptor-α. In conclusion, E4 acted as a weak estrogen on breast cancer cell cytoskeleton remodeling and movement. However, when E2 was present, E4 counteracted the stimulatory actions of E2. This contributes to the emerging hypothesis that E4 may be a naturally occurring ER modulator in the breast.

7.
Maturitas ; 78(2): 123-30, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24796498

RESUMO

G-protein-coupled estrogen receptors (GPERs) have been proposed to mediate estrogen-mediated vasodilation. The presence of GPER-dependent vasodilation in human resistance-sized arteries (HRAs) or its signal transduction pathways have not been investigated. HRAs in subcutaneous fat tissues (biopsies from postmenopausal women (PMW), age-matched men (M) and pregnant women (PGW)) were mounted for in vitro isometric force recording. Vasodilation induced by G-1 (selective GPER-agonist, 3 µM) from HRAs pre-contracted with norepinephrine amounted to 40±5% in PMW, significantly larger than those obtained from M (20±5%) or PGW (20±5%). L-NAME (nitric oxide (NO) synthase inhibitor) abolished these relaxations in PGW, attenuated them in PMW and had no effect in M. Immunohistochemical analysis confirmed the presence of GPER in both smooth muscle and endothelial cells of HRA with maximum expression in PGW. In cultured human umbilical vein endothelial cells (HUVECs), G-1 increased NO-synthesis concentration-dependently through higher expressions of endothelial NO-synthase (eNOS) and through enhanced phosphorylation of eNOS on Ser(1177). In conclusion, GPER vasodilates human resistance arteries through various activating mechanisms of the eNOS-signaling pathway.


Assuntos
Artérias/efeitos dos fármacos , Estrogênios/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Pós-Menopausa/metabolismo , Receptores Estrogênicos/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Vasodilatação/efeitos dos fármacos , Idoso , Artérias/metabolismo , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Norepinefrina , Fosforilação , Gravidez/metabolismo , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais , Vasoconstrição/efeitos dos fármacos
8.
Mol Hum Reprod ; 18(8): 410-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22389473

RESUMO

Endothelial plasminogen activator inhibitor (PAI-1) controls vascular remodeling, angiogenesis and fibrinolysis. PAI-1 blood levels in women are related to estrogen. The aim of this study was to characterize the signaling pathways through which estrogen regulates PAI-1 in endothelial cells. Furthermore, we aimed to investigate whether PAI-1 is implicated in the control of endothelial migration by estrogen. Cultured human umbilical vein endothelial cells (HUVECs) and ovariectomized rats were used to test the effects of 17ß-estradiol (E(2)) on PAI-1 expression and its role on endothelial migration. At physiological concentrations, E(2) increases the expression of PAI-1 in HUVEC within 6-12 h through activation of a signaling cascade initiated by estrogen receptor α and involving G proteins, phosphatidylinositol-3-OH kinase and Rho-associated kinase II. ROCK-II activation turns into an over-expression of c-Jun and c-Fos that is required for E(2)-induced expression of PAI-1. Estrogen-induced PAI-1 expression is implicated in HUVEC horizontal migration. PAI-1 regulation is found also in vivo, in female rats, where ovariectomy is associated with reduced PAI-1 expression, while estrogen replacement counteracts this change. In conclusion, E(2) increases PAI-1 synthesis in human endothelial cells and in rodent aorta through a G protein-initiated signaling that targets early-immediate gene expression. This regulatory pathway is implicated in endothelial cell migration. These findings describe new mechanisms of action of estrogens in the vessels, which may be important for vascular remodeling and hemostasis.


Assuntos
Aorta/metabolismo , Movimento Celular , Estradiol/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Animais , Células Cultivadas , Estradiol/sangue , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Estrogênios/sangue , Estrogênios/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/biossíntese , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Ovariectomia , Fosfatidilinositol 3-Quinase/metabolismo , Inibidor 1 de Ativador de Plasminogênio/sangue , Proteínas Proto-Oncogênicas c-fos/biossíntese , Proteínas Proto-Oncogênicas c-fos/genética , Interferência de RNA , RNA Interferente Pequeno , Ratos , Ratos Wistar , Transdução de Sinais , Quinases Associadas a rho/metabolismo
9.
Mol Hum Reprod ; 18(1): 44-51, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21971309

RESUMO

Clinical observations and basic studies show that progesterone and progestins have a variable influence on endothelial function. Dydrogesterone (DG) is a widely used progestin, but its endothelial actions have not been thoroughly assessed. In this study, we investigated the effects of DG and its metabolite 20-α-dihydro-dydrogesterone (DHD), natural progesterone as well as medroxyprogesterone acetate, on the expression of leukocyte adhesion molecules in human endothelial cells using an in vitro experimental endothelial inflammation system. Our findings show that all progestins significantly suppress endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and inter-cellular adhesion molecule-1 (ICAM-1) induced by bacterial lypopolysaccharide (LPS). These inhibitory effects of DG and DHD require activation of progesterone receptor. DG and DHD decrease adhesion molecule expression associated with LPS administration by preventing nuclear translocation of the pro-inflammatory transcription factor nuclear factor-κB. In addition, DG and DHD do not alter the anti-inflammatory effects of 17ß-estradiol. In conclusion, DG and DHD decrease endothelial inflammatory responses induced by LPS, via reduced expression of the pro-atherogenic adhesion molecules VCAM-1 and ICAM-1. These actions may be relevant for the vascular effects of DG.


Assuntos
Anti-Inflamatórios/farmacologia , Moléculas de Adesão Celular/metabolismo , Didrogesterona/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Progestinas/farmacologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Didrogesterona/análogos & derivados , Células Endoteliais/citologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo
10.
J Plant Physiol ; 165(10): 1107-19, 2008 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-18439710

RESUMO

The cherry rootstock 'Colt' line was transformed with a phytochrome A rice gene with the aim of altering light perception. Three transgenic events were chosen because of a modified developmental behavior. When red enriched light was supplied horizontally to stems, the PD3 transgenic line showed an increased rate of phytomer formation associated to a superior rate of plant growth compared to wild type (WT). Under the same light conditions, the PO1 and PA lines were less altered in morphology and development. When far-red enriched light was supplied, all transgenic lines had a reduced rate of growth, with the PD3 line being the most similar to the WT. The influence of the alien gene on root and leaf-associated bacteria was studied for a duration of 1 year. Significantly more culturable bacteria were recovered from PA lines than from PO1, PD3 and WT lines. On average, significantly more fluorescent pseudomonads were recovered from the rhizosphere of PA and PO1 lines than from PD3 and WT. No significant differences were detected in the number of bacteria recovered from the phyllosphere of transgenic and WT plant lines. A total of 143 Pseudomonas fluorescens strains isolated from rhizosphere of transgenic and WT lines were tested for their antagonistic activity against Phytophthora nicotianae and differences between bacteria derived from transgenic and WT were not detected. Fluorescent pseudomonads strains isolated from phyllosphere of PA and PO1 lines showed antagonistic activity against P. syringae pv. syringae, whereas no difference among the transgenic and WT lines was detected when fluorescent Pseudomonas strains were tested against P. syringae pv. mors-prunorum. Pathogenicity tests were conducted on rooted and micropropagated plants with P. s. pv. syringae and P. s. pv. mors-prunorum: in all assays, the PO1 lines were the most tolerant to P. s. pv. Syringae, and the PO1 and PD3 were tolerant to P. s. pv. mors-prunorum.


Assuntos
Predisposição Genética para Doença , Fitocromo A/genética , Doenças das Plantas/genética , Raízes de Plantas/microbiologia , Prunus/microbiologia , Prunus/fisiologia , Genes de Plantas , Engenharia Genética , Luz , Oryza/genética , Fitocromo A/metabolismo , Doenças das Plantas/microbiologia , Folhas de Planta/microbiologia , Folhas de Planta/fisiologia , Prunus/genética , Prunus/efeitos da radiação , Pseudomonas , Microbiologia do Solo , Técnicas de Cultura de Tecidos
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