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AC Sim?es e Silva KD Silveira AJ Ferreira MM Teixeira 《British journal of pharmacology》2013,169(3):477-492
Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang-(1-7). Most available evidence supports a counter-regulatory role for Ang-(1-7) by opposing many actions of Ang II on AT1 receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang-(1-7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang-(1-7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang-(1-7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang-(1-7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases. 相似文献
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Hans C. Lee Sikander Ailawadhi Cristina J. Gasparetto Sundar Jagannath Robert M. Rifkin Brian G. M. Durie Mohit Narang Howard R. Terebelo Kathleen Toomey James W. Hardin Lynne Wagner James L. Omel Mazaher Dhalla Liang Liu Prashant Joshi Rafat Abonour Connect® MM Registry 《Blood cancer journal》2021,11(7)
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Steve MM de Castro Lindsey CF de Nes C Yung Nio Daan C Velseboer Fiebo JW Ten Kate Olivier RC Busch Thomas M van Gulik Dirk Jan Gouma 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2010,12(1):15-21
Background:
The determination of the exact nature of a pancreatic head mass in a patient scheduled to undergo a pancreatoduodenectomy can be very difficult. This is important as patients who suffer from benign disease such as pancreatitis do not always require surgery. The aim of the present study was to analyse the incidence of pancreatitis and the signs and symptoms associated with these tumours mistaken for pancreatic cancer and the diagnostic procedures performed.Methods:
A consecutive group of patients who underwent a pancreatoduodenectomy between 1992 and 2005 with histopathologically proven pancreatic adenocarcinoma (PCA) and pancreatitis were analysed.Results:
The incidence of pancreatitis after pancreatoduodenectomy is 63 out of 639 patients who underwent a pancreaticoduodenectomy (9.9%). Of these patients, 24 patients (38%) had lymphoplasmacytic sclerosing pancreatitis (LPSP) and 31 patients (49%) had focal chronic pancreatitis. Eight patients (13%) had an intermediate form with characteristics of both. Pancreatic adenocarcinoma occurred in 227 patients (36%). The presence of pancreatitis without a discrete mass on endoscopic ultrasonography (EUS) seemed to have clinical relevance with a positive likelihood ratio of 5.1. Mortality after resection was nil in both groups.Conclusion:
The incidence of pancreatitis is 9.9% for patients scheduled to undergo a pancreatoduodenectomy. Of these patients, 38% had LPSP, 13% had a intermediate form and 49% had focal chronic pancreatitis. The determination of the exact nature of a pancreatic head mass remains difficult. 相似文献999.
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Summary— Cardiac arrhythmias and sudden death have been associated with both therapeutic and toxic doses of a number of cardiotropic and non-cardiac drugs. Generally the drug-induced electrocardiographic (ECG) alterations have been well described, whereas corresponding cellular electrophysiological effects are poorly documented or lacking. Taking into account the recent advances in the understanding of the mechanisms underlying arrhythmias and antiarrhythmic effects, suitable relationships can be established between ECG alterations and drug effects on cardiac action potential. Thus, a decrease in maximal upstroke velocity (Vmax) and membrane depolarisation leading to cellular inexcitability may slow conduction, prolong QRS interval duration and result in incessant wide QRS ventricular tachycardia. On the other hand, lengthening of the repolarisation phase and early afterdepolarisations (EADs) have been proposed as a mechanism for prolonged QT interval and subsequent Torsades de Pointes. A representative study aimed at detecting the arrhythmogenic potentiality of a drug is given, by examining carefully the concentration- and frequency-dependent effects of four neuroleptics (sultopride, droperidol, thioridazine and clozapine) on Purkinje fibers and comparing them with the reported iatrogenic arrhythmias. The results showed that 10 to 100 μM sultopride and 0.01 to 1 μM droperidol exerted “pure” class III effects. In addition, higher concentrations (3 to 30 μM) of droperidol reversed the prolonging effect on repolarisation concomitantly with a dose- and frequency-dependent decrease in Vmax, action potential amplitude and resting membrane potential (class I effects) resulting in cellular inexcitability at 30 μM. Similar class I effects were induced by thioridazine and clozapine concomitantly with a slight prolonging effect on final repolarisation (class la effects). In the presence of sultopride (30 and 100 μM) and droperidol (0.3 to 3 μM), EADs developed at plateau level. Their incidence, amplitude and number were influenced by extracellular K or Mg concentration, stimulation frequency, modification of Ca entry (by nifedipine or isoproterenol). These experimental results fit well with clinical data although they need further development to precise underlying ionic mechanisms. Therefore, in vitro studies should be considered before clinical prospects for future drug development. 相似文献