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排序方式: 共有762条查询结果,搜索用时 15 毫秒
21.
Mouquet F Pfister O Jain M Oikonomopoulos A Ngoy S Summer R Fine A Liao R 《Circulation research》2005,97(11):1090-1092
Tissue-specific progenitor cells contribute to local cellular regeneration and maintain organ function. Recently, we have determined that cardiac side-population (CSP) cells represent a distinct cardiac progenitor cell population, capable of in vitro differentiation into functional cardiomyocytes. The response of endogenous CSP to myocardial injury, however, and the cellular mechanisms that maintain this cardiac progenitor cell pool in vivo remain unknown. In this report we demonstrate that local progenitor cell proliferation maintains CSP under physiologic conditions, with little contribution from extracardiac stem cell sources. Following myocardial infarction in adult mice, however, CSP cells are acutely depleted, both within the infarct and noninfarct areas. CSP pools are subsequently reconstituted to baseline levels within 7 days after myocardial infarction, through both proliferation of resident CSP cells, as well as through homing of bone marrow-derived stem cells (BMC) to specific areas of myocardial injury and immunophenotypic conversion of BMC to adopt a CSP phenotype. We, therefore, conclude that following myocardial injury, cardiac progenitor cell populations are acutely depleted and are reconstituted to normal levels by both self-proliferation and selective homing of BMC. Understanding and enhancing such processes hold enormous potential for therapeutic myocardial regeneration. 相似文献
22.
Angelos Hatzakis Jeffrey V. Lazarus Evangelos Cholongitas Ricardo Baptista‐Leite Charles Boucher Cristian‐Silviu Busoi Sylvie Deuffic‐Burban Jagpreet Chhatwal Gamal Esmat Sharon Hutchinson Minerva‐Melpomeni Malliori Mojca Maticic Antons Mozalevskis Francesco Negro George A. Papandreou George V. Papatheodoridis Markus Peck‐Radosavljevic Homie Razavi Tatjana Reic Eberhard Schatz Nurdan Tozun Zobair Younossi Michael P. Manns 《Liver international》2020,40(2):260-270
The majority of people infected with chronic hepatitis C virus (HCV) in the European Union (EU) remain undiagnosed and untreated. During recent years, immigration to EU has further increased HCV prevalence. It has been estimated that, out of the 4.2 million adults affected by HCV infection in the 31 EU/ European Economic Area (EEA) countries, as many as 580 000 are migrants. Additionally, HCV is highly prevalent and under addressed in Eastern Europe. In 2013, the introduction of highly effective treatments for HCV with direct‐acting antivirals created an unprecedented opportunity to cure almost all patients, reduce HCV transmission and eliminate the disease. However, in many settings, HCV elimination poses a serious challenge for countries’ health spending. On 6 June 2018, the Hepatitis B and C Public Policy Association held the 2nd EU HCV Policy summit. It was emphasized that key stakeholders should work collaboratively since only a few countries in the EU are on track to achieve HCV elimination by 2030. In particular, more effort is needed for universal screening. The micro‐elimination approach in specific populations is less complex and less costly than country‐wide elimination programmes and is an important first step in many settings. Preliminary data suggest that implementation of the World Health Organization (WHO) Global Health Sector Strategy on Viral Hepatitis can be cost saving. However, innovative financing mechanisms are needed to raise funds upfront for scaling up screening, treatment and harm reduction interventions that can lead to HCV elimination by 2030, the stated goal of the WHO. 相似文献
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Georgios Boudouris Ioannis I. Verginadis Yannis V. Simos Andreas Zouridakis Vasilios Ragos Spyridon Ch. Karkabounas Angelos M. Evangelou 《International urology and nephrology》2013,45(4):1137-1144
Purpose
Chronic renal failure patients undergoing peritoneal dialysis (PD) are characterized by increased oxidative stress (OS), which is associated with enhanced cardiovascular risk. Moreover, oxidative stress also contributes to peritoneal membrane changes and ultrafiltration failure. The aim of this study was to evaluate OS in PD patients and the effect of treatment with ascorbic acid and α-tocopherol.Methods
Plasma, erythrocyte, urine, and peritoneal effluent samples from 20 patients on PD were evaluated for glutathione peroxidase and superoxide dismutase activity, total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, as well as protein carbonyl formation, before and after administration of vitamin C, alone or in combination with vitamin E, in comparison with 10 apparently healthy control individuals.Results
All studied markers showed enhanced OS in the PD group, compared to controls. The supplementation of vitamin C and E resulted in improvements of all the OS markers, as indicated by increased erythrocyte antioxidant enzymes activity and TAC levels, as well as decreased MDA concentration and carbonyl compound formation.Conclusions
The oral supplementation of antioxidant vitamins C and E, in combination, can lead to decreased OS, thus providing a useful and cost-effective therapeutic option in PD patients. 相似文献26.
Although the historical background of ethical principles of human subjects research are the same for surgery and nonsurgical fields, surgical clinical trials raise several specific ethical issues. Placebo arms in surgical trials are problematic because the closer the sham surgery is to a real operation, the greater the risks for subjects. In order to ethically enter subjects into a clinical trial, a researcher must have equipoise—that is, uncertainty about which treatment arm is more effective. Surgeons must diligently maintain skepticism about whether new treatments are actually better until objective data are available. The dynamic of informed consent between surgeons and patients may be negatively impacted if patients are convinced that new treatments are better even when there are no objective data. Although clinical trials in surgery often are challenging to develop and complete, there is an ethical and social responsibility for surgeons to participate in clinical trials so that data can be gathered to determine what treatments are safe and effective. 相似文献
27.
Panayiota Papasozomenou Apostolos P. Athanasiadis Menelaos Zafrakas Eleftherios Panteris Themistokles Mikos Angelos Daniilidis 《The journal of maternal-fetal & neonatal medicine》2016,29(20):3368-3373
Objective: To evaluate different methods of defining fetal nasal bone hypoplasia in the second trimester for the detection of trisomy 21.Methods: Prospective study in Greek women undergoing anomaly scan between 18?+?0 and 23?+?6 weeks. The following methods of defining nasal bone hypoplasia were evaluated, either as a single marker or in combination with others: (1) BPD to nasal bone length (NBL) ratio; (2) multiples of the median (MoM) of NBL, according to normal curves from a Greek population; (3–4) NBL?<?2.5 percentile according to normal curves (3) commonly used internationally curves and (4) curves from a Greek population.Results: In total, 1301 singleton fetuses were evaluated???10 with trisomy 21. The best detection rate of trisomy 21 was achieved when the applied method was nasal bone percentiles adjusted to maternal ethnicity, in combination with other markers (<2.5 percentile according to normal curves from a Greek population; p?<?0.001; sensitivity 50%; specificity 94.8%; false-positive rate 5.2%; positive likelihood ratio 9.6).Conclusion: Screening performance of fetal nasal bone hypoplasia in detecting trisomy 21 varies according to the method applied. The best screening performance is achieved by using percentiles adjusted to maternal ethnicity in combination with other markers of aneuploidy. 相似文献
28.
Ohad Ronen K. Thomas Robbins Kerry D. Olsen Ashok R. Shaha Gregory W. Randolph Iain J. Nixon Mark E. Zafereo Dana M. Hartl Luiz P. Kowalski Juan P. Rodrigo Andrs Coca‐Pelaz Antti A. Mkitie Vincent Vander Poorten Alvaro Sanabria Peter Angelos Alessandra Rinaldo Alfio Ferlito 《Head & neck》2020,42(10):3061-3071
Recent modifications in the management of well‐differentiated thyroid cancer have resulted in significant alterations in clinical approach. Utilizing a series of preoperative and postoperative risk factors involving both the patient and the disease pathology, we offer the term “staged thyroidectomy” to help organize these risk factors for patients and the endocrine team to optimize management. This approach is intended to incorporate our latest nuanced understanding of certain endocrine pathology and may serve to optimize patient outcomes. 相似文献
29.
Nonclinical pharmacokinetics and metabolism of EPZ‐5676, a novel DOT1L histone methyltransferase inhibitor
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Aravind Basavapathruni Edward J. Olhava Scott R. Daigle Carly A. Therkelsen Lei Jin P. Ann Boriack‐Sjodin Christina J. Allain Christine R. Klaus Alejandra Raimondi Margaret Porter Scott Angelos Dovletoglou Victoria M. Richon Roy M. Pollock Robert A. Copeland Mikel P. Moyer Richard Chesworth Paul G. Pearson Nigel J. Waters 《Biopharmaceutics & drug disposition》2014,35(4):237-252
(2R,3R,4S,5R)‐2‐(6‐Amino‐9H‐purin‐9‐yl)‐5‐((((1r,3S)‐3‐(2‐(5‐(tert‐butyl)‐1H‐benzo[d]imidazol‐2‐yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran‐3,4‐diol (EPZ‐5676) is a novel DOT1L histone methyltransferase inhibitor currently in clinical development for the treatment of MLL‐rearranged leukemias. This report describes the preclinical pharmacokinetics and metabolism of EPZ‐5676, an aminonucleoside analog with exquisite target potency and selectivity that has shown robust and durable tumor growth inhibition in preclinical models. The in vivo pharmacokinetics in mouse, rat and dog were characterized following i.v. and p.o. administration; EPZ‐5676 had moderate to high clearance, low oral bioavailability with a steady‐state volume of distribution 2–3 fold higher than total body water. EPZ‐5676 showed biexponential kinetics following i.v. administration, giving rise to a terminal elimination half‐life (t1/2) of 1.1, 3.7 and 13.6 h in mouse, rat and dog, respectively. The corresponding in vitro ADME parameters were also studied and utilized for in vitro–in vivo extrapolation purposes. There was good agreement between the microsomal clearance and the in vivo clearance implicating hepatic oxidative metabolism as the predominant elimination route in preclinical species. Furthermore, low renal clearance was observed in mouse, approximating to fu‐corrected glomerular filtration rate (GFR) and thus passive glomerular filtration. The metabolic pathways across species were studied in liver microsomes in which EPZ‐5676 was metabolized to three monohydroxylated metabolites (M1, M3 and M5), one N‐dealkylated product (M4) as well as an N‐oxide (M6). Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
30.
Theodosios D. Filippatos Angelos Liontos Ioanna Papakitsou Moses S. Elisaf 《Postgraduate medicine》2019,131(2):82-88
Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. Two trials have shown significant reductions of cardiovascular (CV) events with empagliflozin and canagliflozin, which could not be attributed solely to their antidiabetic effects. The aim of the review is the critical presentation of suggested mechanisms/hypotheses for the SGLT2 inhibitors' cardioprotection. The search of the literature revealed many possible cardioprotective mechanisms, because SGLT2 inhibitors (i) increase natriuresis and act as diuretics with unique properties leading to a reduction in preload and myocardial stretch (the diuretic hypothesis); (ii) decrease blood pressure and afterload (the blood pressure lowering hypothesis), (iii) favor the production of ketones, which can act as a ‘superfuel’ in the cardiac and renal tissue (the ‘thrifty substrate’ hypothesis), (iv) improve many metabolic variables (the metabolic effects hypothesis), (v) exert many anti-inflammatory effects (the anti-inflammatory effects hypothesis), (vi) can act through the angiotensin II type II receptors in the context of simultaneous renin-angiotensin-aldosterone-system (RAAS) blockade leading to vasodilation and positive inotropic effects (the RAAS hypothesis), (vii) directly decrease the activity of the upregulated in heart failure Na+–H+ exchanger in myocardial cells leading to restoration of mitochondrial calcium handling in cardiomyocytes (the sodium hypothesis). Additionally, some SGLT2 inhibitors exhibit also SGLT1 inhibitory action possibly resulting in an attenuation of oxidative stress in ischemic myocardium (the SGLT1 inhibition hypothesis). Thus, many mechanisms have been suggested (and possibly act cumulatively) for the cardioprotective effects of SGLT2 inhibitors. 相似文献