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31.
Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named
A1, A2A, A2B and A3 (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding
of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective
agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview
of the recent advancements in identifying potent and selective A2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine
ligands. Nucleoside-based agonists are the result of modifying adenosine by substitution at the N
6-, C2-positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions.
Compounds 1-deoxy-1-{6-[N′-(furan-2-carbonyl)-hydrazino]-9H-purin-9-yl}-N-ethyl-β-D-ribofuranuronamide (19, hA1
K
i = 1050 nM, hA2A
K
i = 1550 nM, hA2B EC50 = 82 nM, hA3
K
i > 5 μM) and its 2-chloro analogue 23 (hA1
K
i = 3500 nM, hA2A
K
i = 4950 nM, hA2B EC50 = 210 nM, hA3
K
i > 5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay
in Chinese hamster ovary (CHO) cells expressing hA2B AR. Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide
(BAY-60–6583, hA1, hA2A, hA3 EC50 > 10 μM; hA2B EC50 = 3 nM) is currently under preclinical-phase investigation for treating coronary artery disorders and atherosclerosis. 相似文献
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Yazdanpanah MJ Mokhtari MB Mostofi K Soleimani M Ebrahimirad M Esmaili H Ahmadi SN 《Acta microbiologica et immunologica Hungarica》2008,55(3):343-350
Oral poliovirus vaccine (OPV) is reported to be effective in treatment of recurrent herpes simplex (RHS). According to our observation during recent years, OPV was not only effective in management of RHS but also in some patients with concomitant recurrent aphthous stomatitis (RAS) reducing its severity and frequency. The purpose of this study was to evaluate the efficacy of OPV in the management of RAS. In a longitudinal, case--control study 48 patients with RAS were recruited. Twenty patients received OPV and 28 patients received placebo. OPV was administered in a dose of 4 drops at monthly intervals for 3 months to the study group while the control group received placebo. The results were registered in 3 months after the last dose. Eight cases (40%) in the OPV group showed significant reduction in the duration of the ulcers, while no change was seen in the control group (P = 0.048). The frequency of recurrence of RAS was reduced in 13 cases (65%) in the OPV group, and in 6 cases (21.4%) of the placebo group (P = 0.006). The severity of attacks was reduced in 12 cases (60%) in the OPV group and in 4 cases (14.3%) in the placebo group (P = 0.008). In conclusion OPV appeared to be effective in the management of RAS. 相似文献
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Tabrizi MA Baraldi PG Preti D Romagnoli R Saponaro G Baraldi S Moorman AR Zaid AN Varani K Borea PA 《Bioorganic & medicinal chemistry》2008,16(5):2419-2430
A new series of 1,3-dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives has been identified as potent A(2B) adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A(2B), A(1), A(2A), and A(3) adenosine receptors. N-(4-chloro-phenyl)-2-[3-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-5-methyl-pyrazol-1-yl] (11c) showed a high affinity for the human A(2B) adenosine receptor K(i)=7nM and good selectivity (A(1), A(2A), A(3)/A(2B)>140). Synthesis and SAR of this novel class of compounds is presented herein. 相似文献
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Mojgan Hessamfar Céline Colin Mathias Bruyand Madeleine Decoin Fabrice Bonnet Patrick Mercié Didier Neau Charles Cazanave Jean-Luc Pellegrin Fran?ois Dabis Philippe Morlat Geneviève Chêne the GECSA study group 《PloS one》2014,9(7)
Objective
To describe trends and determinants of severe morbidity in HIV-infected women and men.Design
A French prospective cohort of HIV-infected patients of both sexes and all transmission categories.Methods
We used hospital admission data from January 2000 to December 2008. A severe morbid event (SME) was defined as a clinical event requiring hospitalization for ≥48 h, several events could be reported during hospitalization. Yearly incidence rates of SME were estimated and compared using Generalized Estimating Equations.Results
Among 4,987 patients (27% women), followed for a median of 8.7 years, 1,473 (30%) were hospitalized (3,049 hospitalizations for 5,963 SME). The yearly incidence rate of hospitalization decreased in men, from 155 in 2000 to 80/1,000 person-years (PY) in 2008 and in women, from 125 to 71/1,000 PY, (p<0.001). This trend was observed for all SME except for hepatic events, stable in men (15 to 13/1,000 PY) and increasing in women (2.5 to 11.5), cardiovascular events increasing in men (6 to 10/1,000 PY) and in women (6 to 14) and non-AIDS non-hepatic malignancies increasing in men (4 to 7/1,000 PY) and stable in women (2.5). Intraveneous drug users, age >50 years, HIV RNA >10,000 copies, CD4 <500/mm3, AIDS stage, hepatitis C co-infection and cardiovascular risk factors (diabetes, high blood pressure, and tobacco use) were associated with SME.Conclusions
HIV-infected individuals in care in France require less and less frequently hospitalization. Women are now presenting with severe hepatic and cardio-vascular events. Disparities in SME between men and women are primarily explained by different exposure patterns to risk factors. Women should be targeted to benefit cardiovascular prevention policies as well as men. 相似文献39.
The remarkable metabolic differences between cancer cells and normal cells result in the potential for targeted cancer therapy. The upregulation of glutaminolysis provides energetic advantages to cancer cells. The recently described link between glutaminolysis and autophagy, mediated by MTORC1, may constitute an attractive target for therapeutic strategies. A combination of therapies targeting simultane-ously cell signaling, cancer metabolism, and autophagy can solve therapy resistance and tumor relapse problems, commonly observed in patients treated with most of the current targeted therapies. In this review we summarize the mechanistic link between glutaminolysis and autophagy, and discuss the impacts of these processes on cancer progression and the potential for therapeutic intervention. 相似文献
40.
Effects of sodium benzoate,a commonly used food preservative,on learning,memory, and oxidative stress in brain of mice 下载免费PDF全文
Mohammad Javad Khoshnoud Asma Siavashpour Mojgan Bakhshizadeh Marzieh Rashedinia 《Journal of biochemical and molecular toxicology》2018,32(2)
Sodium benzoate (SB) is a widely used preservative and antimicrobial substance in many foods and soft drinks. However, this compound is generally recognized as safe food additives, but evidence has suggested that a high intake of SB may link to attention deficit‐hyperactivity disorder in children. Present study investigate the effects of oral administration of different concentrations of SB (0.56, 1.125, and 2.25 mg/mL) for 4 weeks, on the learning and memory performance tests, and also the levels of malondialdehyde (MDA), reduced glutathione (GSH), and acetylcholinesterase activity (AChE) in the mouse brain. The results showed that SB significantly impaired memory and motor coordination. Moreover, SB decreased reduced GSH and increased the MDA level in the brain significantly (P < 0.001). However, nonsignificant alteration was observed in the AChE activity. These findings suggest that short‐term consumption of SB can impair memory performance and increased brain oxidative stress in mice. 相似文献