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1.
Eur Rev Med Pharmacol Sci ; 25(14): 4762-4772, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34337724

RESUMO

OBJECTIVE:   Various biomarkers have been studied in the early post-kidney transplantation (post-KTx) period in order to identify potential therapeutic targets for improving long-term graft survival. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a biomarker that has recently gained interest in cardiovascular disease but its role still remains to be defined post-KTx. PATIENTS AND METHODS: We prospectively evaluated the levels of PCSK9, interleukin (IL)-6, WBC and C-reactive protein in seventy-three hemodialysis patients undergoing KTx, at 3 time-points; pre-transplantation (day 0) and at 1 and 6-months post-KTx. All data were also analyzed according to donor-type (living or deceased) and compared with hemodialysis patients on transplant waiting list. RESULTS: At Day 0 there was no difference in WBC, CRP, IL-6 and PCSK9 levels between patients scheduled for transplantation and those who remained on hemodialysis. In transplanted patients WBC, CRP and IL-6 levels were significantly reduced early post-KTx [logIL-6 Day 0: 0.68 (0.33, 0.85) vs. 1-month: 0.57 (0.37, 0.75) vs. 6-months: 0.50 (0.32, 0.69) pg/ml, p=0.01], while PCSK9 levels were significantly increased (Day 0: 199.8±63.0 vs. 1-month: 276.2±79.4 vs. 6-months: 245.9±62.5 ng/ml, p<0.001). In contrast, no change of WBC, CRP, IL-6 and PCSK9 levels was observed in hemodialysis patients on follow-up (p=NS for all). Between living-donor and deceased-donor recipients, analysis showed reduced CRP and increased PCSK9 levels in both groups (p<0.05 for all), while IL-6 levels were reduced in living-donor and increased in deceased-donor recipients 1-month post-KTx. PCSK9 levels were not correlated with renal function, delayed graft function, rejection episodes or inflammatory biomarkers. CONCLUSIONS: PCSK9 levels were increased post-KTx independently from renal function and inflammatory biomarkers, in both living and deceased-donor recipients.


Assuntos
Biomarcadores/metabolismo , Inflamação/terapia , Transplante de Rim , Pró-Proteína Convertase 9/metabolismo , Adulto , Biomarcadores/análise , Feminino , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9/análise , Estudos Prospectivos , Diálise Renal
2.
Sci Rep ; 10(1): 19436, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33173147

RESUMO

Pulmonary surfactant forms a sub-micrometer thick fluid layer that covers the surface of alveolar lumen and inhaled nanoparticles therefore come in to contact with surfactant prior to any interaction with epithelial cells. We investigate the role of the surfactant as a protective physical barrier by modeling the interactions using silica-Curosurf-alveolar epithelial cell system in vitro. Electron microscopy displays that the vesicles are preserved in the presence of nanoparticles while nanoparticle-lipid interaction leads to formation of mixed aggregates. Fluorescence microscopy reveals that the surfactant decreases the uptake of nanoparticles by up to two orders of magnitude in two models of alveolar epithelial cells, A549 and NCI-H441, irrespective of immersed culture on glass or air-liquid interface culture on transwell. Confocal microscopy corroborates the results by showing nanoparticle-lipid colocalization interacting with the cells. Our work thus supports the idea that pulmonary surfactant plays a protective role against inhaled nanoparticles. The effect of surfactant should therefore be considered in predictive assessment of nanoparticle toxicity or drug nanocarrier uptake. Models based on the one presented in this work may be used for preclinical tests with engineered nanoparticles.


Assuntos
Células Epiteliais Alveolares/metabolismo , Nanopartículas/metabolismo , Surfactantes Pulmonares/farmacologia , Células A549 , Células Epiteliais Alveolares/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Microscopia Confocal , Microscopia de Fluorescência , Alvéolos Pulmonares/metabolismo
3.
Archaeol Anthropol Sci ; 12(10): 243, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33088349

RESUMO

A Pb-based synthetic mineral referred to as psimythion (pl. psimythia) was manufactured in the Greek world at least since the 6th c BCE and routinely by the 4th c BCE. Theophrastus (On Stones, 56) describes its preparation from metallic Pb suspended over a fermenting liquid. Psimythion is considered the precursor of one of western art's most prominent white pigments, i.e. lead white (basic lead carbonate or synthetic hydrocerussite). However, so far, and for that early period, published analyses of psimythia suggest that they consisted primarily of synthetic cerussite. In this paper, we set out to investigate how it was possible to manufacture pure cerussite, to the near exclusion of other phases. We examined the chemical and mineralogical composition (pXRF/XRD) of a small number of psimythion pellets found within ceramic pots (pyxis) from Athens and Boeotia (5th-4th c BCE) in the collection of the National Archaeological Museum (NAM), Athens. Analyses showed that the NAM pellets consisted primarily of Pb/cerussite with small amounts of Ca (some samples) and a host of metallic trace elements. We highlight the reference in the Theophrastus text to 'spoiled wine' (oxos), rather than 'vinegar', as has been previously assumed, the former including a strong biotic component. We carried out DNA sequencing of the pellets in an attempt to establish presence of microorganisms (Acetic Acid Bacteria). None was found. Subsequently, and as a working hypothesis, we propose a series of (biotic/abiotic) reactions which were likely to have taken place in the liquid and vapour phases and on the metal surface. The hypothesis aims to demonstrate that CO2 would be microbially induced and would increase, as a function of time, resulting in cerussite forming over and above hydrocerussite/other Pb-rich phases. Psimythion has for long been valued as a white pigment. What has perhaps been not adequately appreciated is the depth of empirical understanding from the part of psimythion manufacturers of the reactions between abiotic and biotic components within 'oxos'/pot, as key drivers of minerals synthesis. Ultimately, psimythion manufacture may rest in understanding the nature of 'oxos', antiquity's relatively little researched strongest acid.

4.
Public Health ; 187: 115-119, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32949881

RESUMO

OBJECTIVES: The coronavirus disease 2019 (COVID-19) outbreak, along with implementation of lockdown and strict public movement restrictions, in Greece has affected hospital visits and admissions. We aimed to investigate trends of cardiac disease admissions during the outbreak of the pandemic and possible associations with the applied restrictive measures. STUDY DESIGN: This is a retrospective observational study. METHODS: Data for 4970 patients admitted via the cardiology emergency department (ED) across 3 large-volume urban hospitals in Athens and 2 regional/rural hospitals from February 3, 2020, up to April 12 were recorded. Data from the equivalent (for the COVID-19 outbreak) time period of 2019 and from the postlockdown time period were also collected. RESULTS: A falling trend of cardiology ED visits and hospital admissions was observed starting from the week when the restrictive measures due to COVID-19 were implemented. Compared with the pre-COVID-19 outbreak time period, acute coronary syndrome (ACS) [145 (29/week) vs. 60 (12/week), -59%, P < 0.001], ST elevation myocardial infarction [46 (9.2/week) vs. 21 (4.2/week), -54%, P = 0.002], and non-ST elevation ACS [99 cases (19.8/week) vs. 39 (7.8/week), -60% P < 0.001] were reduced at the COVID-19 outbreak time period. Reductions were also noted for heart failure worsening and arrhythmias. The ED visits in the postlockdown period were significantly higher than in the COVID-19 outbreak time period (1511 vs 660; P < 0.05). CONCLUSION: Our data show significant drops in cardiology visits and admissions during the COVID-19 outbreak time period. Whether this results from restrictive measures or depicts a true reduction of cardiac disease cases warrants further investigation.


Assuntos
Infecções por Coronavirus/epidemiologia , Serviço Hospitalar de Emergência/tendências , Cardiopatias/terapia , Hospitalização/tendências , Pneumonia Viral/epidemiologia , Quarentena/legislação & jurisprudência , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/prevenção & controle , Feminino , Grécia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Estudos Retrospectivos
5.
QJM ; 113(9): 633-642, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32125429

RESUMO

BACKGROUND: It has been long hypothesized that emotional factors and depression may play role in the development of cardiovascular diseases. AIM: The aim of this study was to examine the association between depression, arterial stiffness and atheromatic burden in carotid arteries. DESIGN AND METHODS: Corinthia study is a cross-sectional epidemiological study conducted in subjects aged 40-99 years, inhabitants of the homonym region of Greece. Intima media thickness (IMT) was measured in the left and right common carotid artery, carotid bulb and internal carotid artery. The average of the measurements (mean IMT) and the maximum IMT were determined as the representative value of carotid atherosclerosis burden. Pulse wave velocity was used to evaluate arterial stiffness. The Zung Self-Rating Depression Scale was used to evaluate depressive symptoms in subjects <65 years and the Geriatric Depression Scale in those >65 years. RESULTS: In this analysis, we included data from 1510 participants. In older subjects (i.e. >65 years), maximum IMT was significantly increased in subjects with depression compared to those without (1.57 ± 0.97 mm vs. 1.74 ± 1.05 mm, P = 0.04). Similarly, the prevalence of atheromatic plaques was higher in subjects with depression (46% vs. 34%, P = 0.005). In the younger subgroup (<65years), there was no difference in mean and maximum IMT. Pulse wave velocity was found higher in the presence of depression (8.35 ± 2.36m/s vs. 7.88 ± 1.77m/s, P = 0.007). No differences emerged for the rest of the variables assessed in the individual subgroups. CONCLUSIONS: There is an age-dependent association between depression, arterial stiffness and carotid atheromatic burden highlighting the interplay between cardiovascular diseases and emotional status.


Assuntos
Doenças das Artérias Carótidas/epidemiologia , Depressão/epidemiologia , Rigidez Vascular , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/fisiopatologia , Espessura Intima-Media Carotídea , Estudos Transversais , Depressão/psicologia , Feminino , Grécia/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de Risco
6.
Colloids Surf B Biointerfaces ; 178: 337-345, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30897431

RESUMO

The role of pulmonary surfactant is to reduce the surface tension in the lungs and to facilitate breathing. Surfactant replacement therapy (SRT) aims at bringing a substitute by instillation into the airways, a technique that has proven to be efficient and lifesaving for preterm infants. Adapting this therapy to adults requires to scale the administered dose to the patient body weight and to increase the lipid concentration, whilst maintaining its surface and flow properties similar. Here, we exploit a magnetic wire-based microrheology technique to measure the viscosity of the exogenous pulmonary surfactant Curosurf® in various experimental conditions. The Curosurf® viscosity is found to increase exponentially with lipid concentration following the Krieger-Dougherty law of colloids. The Krieger-Dougherty behavior also predicts a divergence of the viscosity at the liquid-to-gel transition. For Curosurf® the transition concentration is found close to the concentration at which it is formulated (117 g L-1versus 80 g L-1). This outcome suggests that for SRT the surfactant rheological properties need to be monitored and kept within a certain range. The results found here could help in producing suspensions for respiratory distress syndrome adapted to adults. The present work also demonstrates the potential of the magnetic wire microrheology technique as an accurate tool to explore biological soft matter dynamics.


Assuntos
Surfactantes Pulmonares/química , Tensoativos/química , Microscopia Crioeletrônica , Viscosidade
7.
J Colloid Interface Sci ; 525: 206-215, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29705592

RESUMO

HYPOTHESIS: Concentrated fabric softeners are water-based formulations containing around 10-15 wt% of double tailed esterquat surfactants primarily synthesized from palm oil. In recent patents, it was shown that a significant part of the surfactant contained in today's formulations can be reduced by circa 50% and replaced by natural guar polymers without detrimental effects on the deposition and softening performances. We presently study the structure and rheology of these softener formulations and identify the mechanisms at the origin of these effects. EXPERIMENTS: The polymer additives used are guar gum polysaccharides, one cationic and one modified through addition of hydroxypropyl groups. Formulations with and without guar polymers are investigated using optical and cryo-transmission electron microscopy, small-angle light and X-ray scattering and finally rheology. Similar techniques are applied to study the phase behavior of softener and cellulose nanocrystals considered here as a model for cotton. FINDINGS: The esterquat surfactants are shown to assemble into micron-sized vesicles in the dilute and concentrated regimes. In the former, guar addition in small amounts does not impair the vesicular structure and stability. In the concentrated regime, cationic guars induce a local crowding associated to depletion interactions and leads to the formation of a local lamellar order. In rheology, adjusting the polymer concentration at 1/10th that of the surfactant is sufficient to offset the decrease of the elastic property associated with the surfactant reduction. In conclusion, we have shown that through an appropriate choice of natural additives it is possible to lower the concentration of surfactants in fabric conditioners by about half, a result that could represent a significant breakthrough in current home care formulations.

8.
J Phys Chem B ; 121(10): 2299-2307, 2017 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-28225273

RESUMO

There is currently a renewed interest for improving household and personal-care formulations to provide more environment-friendly products. Fabric conditioners used as softeners have to fulfill a number of stability and biodegradability requirements. They should also display significant adsorption on cotton under the conditions of use. The quantification of surfactant adsorption remains however difficult because the fabric-woven structure is complex and deposited amounts are generally small. Here, we propose a method to evaluate cellulose-surfactant interactions with increased detection sensitivity. The method is based on the use of cellulose nanocrystals (CNCs) in lieu of micron-sized fibers or yarns, combined with different techniques, including light scattering, optical and electron microscopy, and electrophoretic mobility. CNCs are rod-shaped nanoparticles in the form of 200 nm laths that are negatively charged and can be dispersed in bulk solutions. In this work, we use a double-tailed cationic surfactant present in fabric softener. Results show that the surfactants self-assemble into unilamellar, multivesicular, and multilamellar vesicles, and the interaction with CNCs is driven by electrostatics. Mutual interactions are strong and lead to the formation of large-scale aggregates, where the vesicles remain intact at the cellulose surface. The technique developed here could be exploited to rapidly assess the fabric conditioner efficiency obtained by varying the nature and content of their chemical additives.

9.
Obes Rev ; 17(10): 989-1000, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27405510

RESUMO

Despite a strong association between body weight and mortality in the general population, clinical evidence suggests better clinical outcome of overweight or obese individuals with established coronary heart disease. This finding has been termed the 'obesity paradox', but its existence remains a point of debate, because it is mostly observed when body mass index (BMI) is used to define obesity. Inherent limitations of BMI as an index of adiposity, as well as methodological biases and the presence of confounding factors, may account for the observed findings of clinical studies. In this review, our aim is to present the data that support the presence of a BMI paradox in coronary heart disease and then explore whether next to a BMI paradox a true obesity paradox exists as well. We conclude by attempting to link the obesity paradox notion to available translational research data supporting a 'healthy', protective adipose tissue phenotype. © 2016 World Obesity.


Assuntos
Índice de Massa Corporal , Doença das Coronárias/metabolismo , Doença das Coronárias/mortalidade , Obesidade/metabolismo , Obesidade/mortalidade , Adiposidade , Distribuição da Gordura Corporal , Comorbidade , Doença das Coronárias/fisiopatologia , Humanos , Obesidade/complicações , Obesidade/fisiopatologia , Fenótipo , Fatores de Risco , Taxa de Sobrevida
10.
Psychiatriki ; 26(2): 116-30, 2015.
Artigo em Grego Moderno | MEDLINE | ID: mdl-26197101

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease affecting 1-2% of the population over 60. Although diagnosed by its characteristic motor manifestations, PD may be preceded, and is frequently accompanied, by a wide range of psychiatric and cognitive symptoms. These symptoms are often more debilitating than its motor complications and it is nowadays appreciated that they can be an important cause of excess disability in PD, frequently necessitating hospitalization and institutionalization. Despite their frequent occurrence, most PD-related neuropsychiatric symptoms remain under-recognized and undertreated in clinical practice and their diagnosis is challenging because of the overlap of the somatic features of the psychiatric disorders and the motor symptoms of PD. Even when identified, there is a common perception that many of these symptoms are untreatable. Their recognition is essential not only for ascertaining the functional status of patients but also for better appreciating the nature of the neurodegenerative process in PD. These symptoms may precede the onset of motor symptoms and can be used as screening tools allowing for very early disease identification and for trials of possible diseasemodifying interventions. The pathophysiology of neuropsychiatric symptoms in PD involves complex and multifactorial mechanisms, including disease-related and psychological factors. Alterations in neurotransmitters like dopamine, serotonin, acetylcholine, involving subcortical projections and synaptic and neuronal changes involving limbic and cortical structures combine to result in these nonmotor symptoms. Potentially earlier evaluation and treatment of comorbid psychiatric and cognitive disorders in PD could improve quality of life and patient productivity, reduce morbidity and caregiver burden, and minimize healthcare costs. Management strategies include adjustment of dopaminergic medication, use of psychotropic treatments and behavioral and psychological interventions. Dopaminergic medication may precipitate neuropsychiatric conditions, such as the dopamine dysregulation syndrome. The choice of psychotropic medication for the neuropsychiatric symptoms of PD is determined by a balance between potential benefit versus side effects, mostly in terms of worsening motor symptoms. Furthermore, treatments used in general psychiatry services may not be as effective in PD. This article provides an overview and focuses on the neuropsychiatric manifestations in PD including depression, anxiety, psychosis, apathy and fatigue, personality, sexual dysfunction, sleep disorders, cognitive impairment and dementia, impulse control disorders and related behaviours. The epidemiology, pathophysiology and risk factors, clinical presentation and management of the most common neuropsychiatric complications in PD are discussed.


Assuntos
Sintomas Comportamentais , Disfunção Cognitiva , Doença de Parkinson , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/etiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Diagnóstico Diferencial , Gerenciamento Clínico , Diagnóstico Precoce , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Doença de Parkinson/terapia
11.
Indoor Air ; 24(6): 639-51, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24713025

RESUMO

UNLABELLED: A number of studies have estimated population exposure to PM2.5 by examining modeled or measured outdoor PM2.5 levels. However, few have taken into account the mediating effects of building characteristics on the ingress of PM2.5 from outdoor sources and its impact on population exposure in the indoor domestic environment. This study describes how building simulation can be used to determine the indoor concentration of outdoor-sourced pollution for different housing typologies and how the results can be mapped using building stock models and Geographical Information Systems software to demonstrate the modifying effect of dwellings on occupant exposure to PM2.5 across London. Building archetypes broadly representative of those in the Greater London Authority were simulated for pollution infiltration using EnergyPlus. In addition, the influence of occupant behavior on indoor levels of PM2.5 from outdoor sources was examined using a temperature-dependent window-opening scenario. Results demonstrate a range of I/O ratios of PM2.5 , with detached and semi-detached dwellings most vulnerable to high levels of infiltration. When the results are mapped, central London shows lower I/O ratios of PM2.5 compared with outer London, an apparent inversion of exposure most likely caused by the prevalence of flats rather than detached or semi-detached properties. PRACTICAL IMPLICATIONS: Population exposure to air pollution is typically evaluated using the outdoor concentration of pollutants and does not account for the fact that people in London spend over 80% of their time indoors. In this article, building simulation is used to model the infiltration of outdoor PM2.5 into the domestic indoor environment for dwellings in a London building stock model, and the results mapped. The results show the variation in relative vulnerability of dwellings to pollution infiltration, as well as an estimated absolute indoor concentration across the Greater London Authority (GLA) scaled by local outdoor levels. The practical application of this work is a better understanding of the modifying effect of the building geometry and envelope design on pollution exposure, and how the London building stock may alter exposure. The results will be used to inform population exposure to PM2.5 in future environmental epidemiological studies.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Habitação , Movimentos do Ar , Simulação por Computador , Humanos , Londres , Modelos Teóricos , Tamanho da Partícula , Material Particulado/análise , Ventilação
12.
Int J Cancer ; 134(10): 2504-11, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24226765

RESUMO

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.


Assuntos
Carcinoma de Células de Transição/epidemiologia , Dieta Mediterrânea , Neoplasias da Bexiga Urinária/epidemiologia , Idoso , Índice de Massa Corporal , Inquéritos sobre Dietas/métodos , Inquéritos sobre Dietas/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Preferências Alimentares , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fumar , Inquéritos e Questionários , Fatores de Tempo
13.
Curr Med Chem ; 20(21): 2641-60, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23627935

RESUMO

Polyphenols are composed of a wide variety of molecules that are classified into several categories, according to their chemical type such as phenolic acids, flavonoids, stilbenes, and lignans. Many studies have proven the beneficial effects of flavonoids in atherosclerosis progression and cardiovascular disease. Dietary flavonoids reduce oxidative stress and exert anti-inflammatory actions. Moreover, flavonoids have the ability to avoid the thrombus formation, improve endothelial function, modify lipid levels and regulate glucose metabolism. In the context of this evidence in this review article we summarize the so far acquired knowledge of the most important mechanisms of action of flavonoids in atherosclerosis progression.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aterosclerose/tratamento farmacológico , Flavonoides/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Aterosclerose/patologia , Progressão da Doença , Flavonoides/química , Humanos , Estresse Oxidativo/efeitos dos fármacos
14.
Curr Med Chem ; 19(16): 2534-47, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22489715

RESUMO

Heart failure (HF) is a complex syndrome with high morbidity and mortality while, myocardial injury, hemodynamic overload, genetic, neurohormonal, inflammatory and biochemical factors are implicated in the development and progression of the disease. Interestingly, despite the development of several diagnostic tests, HF diagnosis remains clinical, based on symptoms and signs, while there is a poor relationship between symptoms and the prognosis of HF. Several biomarkers have recently been examined for their efficacy to predict outcome and assess prognosis of HF patients. The best studied for its prognostic ability sub-group of biomarkers is the neurohormones including the natriuretic peptides, the components of the renin-angiotensin-aldosterone system and the catecholamines. Others sub-groups of biomarkers include inflammatory and oxidative stress markers, extracellular matrix remodeling markers and myocardial injury markers (such as troponins I and T). Nevertheless, it is difficult to access a single biomarker fulfilling our need to evaluate prognosis and guiding treatment in acute or chronic HF patients, thus the predictive ability of combined biomarkers is recently under research. Therefore, further studies are needed to elucidate the clinical significance of these biomarkers. In the present review, we will discuss the usefulness and significance of potentials or established biomarkers in HF patients focusing on their ability to predict adverse events, morbidity and mortality.


Assuntos
Biomarcadores/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/diagnóstico , Traumatismos Cardíacos/metabolismo , Hormônios/metabolismo , Humanos , Miócitos Cardíacos/patologia , Estresse Oxidativo , Prognóstico
15.
Curr Med Chem ; 19(16): 2555-71, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22489717

RESUMO

Cardiovascular disease (CVD) remains the leading cause of premature death in patients with chronic kidney disease (CKD). Recent evidence suggests that the interaction of "classic" and "non-classic" cardiovascular risk factors is an important contributor in excessive and accelerated CVD in patients with CKD. Indeed, the imposing cardiovascular morbidity and mortality of CKD patients corresponds to a significant extent in endothelial dysfunction, inflammation, oxidative stress, vascular calcification and volume overload. In addition, the kidney's function decline is independently associated with CVD in patients with chronic kidney disease. Currently, there is a growing interest in the role of new biomarkers that are closely correlated with CVD in CKD population. In current review, we summarize the so far acquired knowledge of the most promising biomarkers and we discuss the major clinical correlations of novel risk factors and new biomarkers of CVD in CKD patients, their predictive value for future cardiovascular events and their use in the treatment monitoring of this population.


Assuntos
Biomarcadores/metabolismo , Doenças Cardiovasculares/metabolismo , Nefropatias/metabolismo , Doenças Cardiovasculares/complicações , Humanos , Nefropatias/complicações , Estresse Oxidativo , Proteômica , Risco , Calcificação Vascular
16.
Curr Cancer Drug Targets ; 12(7): 873-98, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22515520

RESUMO

Sporadic colorectal cancer develops through a number of functional mutations. Key events are mutually exclusive mutations in BRAF or RAS oncogenes. Signatures for BRAF oncogene have been revealed in melanoma. In a previous study we have reported a molecular signature for HRAS and KRAS mutations in colorectal cell lines that also showed an EMT phenotype for HRAS. In this study we report a molecular profile for a BRAF oncogenic mutation BRAFV600E in colon using the Illumina 45,000 gene microarray. Key differentially expressed genes have been identified from the array analysis further verified by qPCR analysis. Ingenuity pathway analysis such as microsatellite instability, kinase signalling, apoptosis, WNT and Integrin signalling is presented. MutBRAF transforms cells through cross talk with developmental pathways Hedgehog and Wnt, as well as by deregulation of colorectal cancer related kinase pathways, like PI3K. Differential gene expression of BRAFV600E in colon as compared to those associated with RAS oncogenes is presented, as well as similarities and differences between oncogenic BRAF signatures in colon as compared to thyroid and melanoma are highlighted. Novel selected genes/pathways are validated in cell lines and clinical samples bearing BRAFV600E and may serve as markers/targets for personalised diagnosis/therapy/resistance of colorectal cancer.


Assuntos
Neoplasias do Colo/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Células CACO-2 , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Análise em Microsséries/métodos , Oncogenes , Proteínas Proto-Oncogênicas B-raf/metabolismo , Transdução de Sinais , Regulação para Cima
17.
Curr Med Chem ; 19(8): 1193-209, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22257055

RESUMO

Adiponectin is an abundant plasma protein secreted from adipocytes. Its role in energy homeostasis is well-known, including the regulation of hydrocarbons and lipids metabolism as well as the improvement of insulin resistance. It has been thought to be a key molecule in the development of type 2 diabetes mellitus and metabolic syndrome, which are epidemiological targets for preventing cardiovascular disease. In addition to beneficial metabolic effects, adiponectin seems to have anti-inflammatory, anti-atherosclerotic and vasoprotective actions. Furthermore, adiponectin affects signalling in myocardial cells and exerts beneficial actions on the heart after pressure overload and ischemia-reperfusion injury. The ability of adiponectin to reduce insulin resistance in conjunction with its antiinflammatory and cardioprotective properties makes this adipocytokine a promising therapeutic target. On clinical interest, agents that enhance endogenous adiponectin production or action have potential for the treatment of cardiovascular disease. Management strategies that increase adiponectin levels include weight reduction, Mediterranean diet, thiazolidinediones, antihypertensive and lipid lowering drugs. Current knowledge on the main actions of adiponectin and therapeutic approaches for cardiovascular disease is summarized in this review.


Assuntos
Adiponectina/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Adiponectina/química , Animais , Humanos
18.
Curr Med Chem ; 19(6): 901-20, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22229416

RESUMO

Coronary atherosclerosis is the pathophysiologic background of coronary artery disease. Vascular calcification is an actively regulated form of calcified tissue metabolism and a common feature of coronary atherosclerotic plaques. Interestingly, systematic research has revealed that vascular mineralization, is also a strong and independent predictor of cardiovascular morbidity and mortality. Recently, several biomarkers, including osteopontin, fetuin-A, matrix-carboxyglutamic acid protein, pyrophosphates, bone morphogenetic proteins, leptin, osteoprotegerin have emerged as surrogate markers of coronary calcification. Furthermore, biomarkers of vascular calcification can be used as prognostic markers of coronary artery disease and can predict future cardiovascular events and mortality. Nevertheless, there is little knowledge on the usefulness of these biomarkers in evaluating the results of treatments targeting coronary artery disease. Within this context, the present review sets out to discuss the role of new biomarkers assessing calcium deposition in coronary arteries and their role in the prognosis, progression, and treatment of cardiovascular disease.


Assuntos
Cálcio/metabolismo , Doença da Artéria Coronariana/metabolismo , Animais , Biomarcadores/metabolismo , Vasos Coronários/metabolismo , Humanos
19.
QJM ; 104(12): 1035-43, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21764809

RESUMO

BACKGROUND: Regular physical activity (PA) has shown substantial cardiac benefits. We sought to investigate whether habitual PA is associated with changes of the electrical action potential duration, as it is represented by the QT duration on a rest ECG, in a population based sample of middle-aged and elderly individuals of Ikaria island. METHODS: In a cross-sectional survey 1071 inhabitants of Ikaria Island (65 ± 13 years, 47% males) were enrolled. PA was estimated by means of IPAQ classifying the participants into low, moderate and vigorous group. QT duration was measured from a surface electrocardiogram; while using Bazett's formula the heart-rate-corrected QT (QTc) was calculated. RESULTS: Among participants, 85% reported at least moderate PA levels. Women in the 'vigorous' and 'moderate' PA level compared to those in the 'low' PA level had significantly shorter QTc (408 ± 2 ms vs. 411 ± 1 ms vs. 419 ± 2 ms, P = 0.001, respectively). In contrast, no significant difference in QTc according to PA levels was observed in men (P = 0.053). Linear regression analysis revealed that PA level was significantly associated with shorter QTc in women after adjustment for established confounders; while no such association was evident in men. Furthermore, compared to the 'low' PA group, women in the 'vigorous' PA group were 5.5-times less likely to have QTc interval above 450 ms (P = 0.031). CONCLUSION: Increased PA is associated with shorter QTc interval only in middle-aged and elderly women of Ikaria Island irrespectively of participant's habits or medical conditions, illustrating gender differences in the cardioprotective effect of habitual exercise.


Assuntos
Eletrocardiografia , Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Idoso , Algoritmos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Fatores Sexuais
20.
Langmuir ; 27(8): 5054-61, 2011 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-21446711

RESUMO

The association of cetyltrimethylammonium bromide, CTAB, with a series of P(MMAx-co-SSNa) random copolymers of sodium styrene sulfonate (SSNa) with methyl methacrylate (MMA) was explored in aqueous solution as a function of the MMA molar content, x, of the copolymers. The polyelectrolyte/surfactant complexation in aqueous solution was verified through pyrene fluorescence probing. In addition, turbidimetry studies in dilute or more concentrated aqueous solutions elucidated the phase separation behavior of the P(MMAx-co-SSNa)/CTAB systems as a function of the copolymer composition x and the surfactant to polyelectrolyte mixing charge ratio. It is found that practically phase separation is completely suppressed within the studied mixing range when the MMA content of the copolymers is ∼30-40 mol%. For lower MMA contents the polyelectrolyte/surfactant complex separates out from water, while for higher x values the solubility limits of the copolymers in water are attained. For the intermediate MMA contents, viscoelastic systems are obtained in more concentrated polymer/surfactant solutions provided that the polyelectrolyte is fully complexed with the cationic surfactant ((1)H NMR results). Moreover, the (1)H NMR studies indicate that hybrid P(MMAx-co-SSNa)/CTAB wormlike micelles are formed in water under these conditions. Finally, it is shown that addition of salt prevents syneresis problems and facilitates the rheological investigation.

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