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Kenneth S. Ramos - One of the best experts on this subject based on the ideXlab platform.
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NF-κB and matrix-dependent regulation of osteopontin promoter activity in Allylamine-activated vascular smooth muscle cells.
Oxidative medicine and cellular longevity, 2012Co-Authors: E. Spencer Williams, Emily Wilson, Kenneth S. RamosAbstract:Repeated cycles of oxidative injury by Allylamine in vivo induce a proliferative rat vascular (aortic) smooth muscle cell (vSMC) phenotype characterized by matrix-dependent enhancement of mitogenic sensitivity, changes in cell surface integrin expression, and osteopontin (opn) overexpression. Here, we show that constitutive and mitogen-stimulated NF-κB DNA binding activity is enhanced in Allylamine vSMCs. Matrix-specific changes in cellular Rel protein expression were observed in Allylamine vSMCs. The NF-κB DNA binding element located at −1943 in the 5′-UTR strongly inhibited opn promoter activity in Allylamine vSMCs, and this response was regulated by the extracellular matrix. Constitutive increases in opn promoter activity were only seen when Allylamine cells were seeded on a fibronectin substrate, and this response was independent of the NF-κB DNA binding sequence within the regulatory region. Thus, NF-κB functions as a critical regulator of the Allylamine-induced proliferative phenotype in vSMCs.
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Collagen suppresses the proliferative phenotype of Allylamine-injured vascular smooth muscle cells.
Atherosclerosis, 2002Co-Authors: Emily Wilson, E. Spencer Williams, Alan R. Parrish, Christopher M. Bral, Kenneth S. RamosAbstract:Abstract Repeated cycles of oxidative injury by Allylamine induce proliferative rat vascular smooth muscle cell (vSMC) phenotypes characterized by enhanced secretion of osteopontin (OPN). The present study was designed to evaluate the role of extracellular matrix (ECM) interactions in the induction of proliferative phenotypes in this model of oxidant injury. Because OPN is involved in ECM/integrin signaling, and may participate in proliferative control, the proliferation profiles of control and Allylamine vSMCs seeded on different matrices were compared. Allylamine cells exhibited a proliferative advantage over controls when seeded on plastic, Pronectin, or fibronectin, but not type I collagen. Addition of GRGDS peptide selectively enhanced [ 3 H]-thymidine incorporation in Allylamine vSMCs, while anti-OPN antibodies nullified their proliferative advantage. Allylamine cells exhibited altered expression of α1, α5 and β3 integrin subunits and enhanced downstream integrin-coupled increases in focal adhesion kinase, AP-1 and NF-κB binding activity. Inhibition of NF-κB by pyrrolidine dithiocarbamate selectively compromised proliferation of Allylamine vSMCs, while seeding on a non-permissive collagen matrix ablated enhancement of NF-κB inducibility. These results implicate ECM interactions in the deregulation of vSMC proliferation following repeated cycles of oxidative chemical injury.
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Differential processing of osteopontin characterizes the proliferative vascular smooth muscle cell phenotype induced by Allylamine.
Journal of cellular biochemistry, 1997Co-Authors: Alan R. Parrish, Kenneth S. RamosAbstract:Repeated cycles of vascular injury by Allylamine induce vascular lesions similar to those seen in atherosclerotic vessels, or following balloon catheterization. Vascular (aortic) smooth muscle cells harvested from Allylamine-treated animals (i.e., Allylamine cells) acquire a proliferative advantage relative to control counterparts that is associated with differential secretion and extracellular matrix sequestration of several proteins. In the present study, we have characterized two of these proteins (M(r) 52 and 36 kDa; pl 5.6 and 5.2, respectively) and their putative role in the expression of a proliferative phenotype. Because the physical properties of these proteins were comparable to those of osteopontin (OPN) and its thrombin-generated fragment(s), initial experiments were conducted to examine the expression and processing of OPN in this cell system. OPN mRNA expression was enhanced during early G1 cell cycle progression in Allylamine cells relative to control counterparts. However, comparable amounts of OPN (M(r) 56, 52, and 50 kDa) were detected by Western analysis in media conditioned by both cell types using the OP-199 or B77-Rat1 antibodies to OPN. Allylamine cells, however, produced increased amounts of a 36 kDa protein recognized by the OP-199 antibody. Incubation of conditioned media from [35S]methionine-labeled Allylamine cells with thrombin decreased the intensity of the 52 kDa protein, while increasing the intensity of a 36 kDa protein. RT-PCR analysis demonstrated expression of a 1.2 kb OPN band in both cell types consistent with the predicted size of OPN mRNA, suggesting that the 36 kDa fragment recognized by OP-199 in Allylamine cells was likely not due to altered splicing of the OPN transcript. To determine if OPN and/or the 36 kDa fragment played a central role in the proliferative capacity of Allylamine cells, the effect of an antibody to an alpha v integin subunit was examined. An antibody to the alpha v subunit, but not alpha 4, nullified the proliferative advantage of Allylamine cells relative to control counterparts, suggesting that integrin-mediated signaling is a key feature of the proliferative phenotype of Allylamine cells. We conclude that enhanced proteolytic cleavage of OPN may characterize the modulation of vascular SMCs to a more proliferative phenotype following chemical injury by Allylamine.
Paul J. Boor - One of the best experts on this subject based on the ideXlab platform.
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Semicarbazide protection from in vivo oxidant injury of vascular tissue by Allylamine.
Toxicology letters, 1993Co-Authors: Sanjay Awasthi, Paul J. BoorAbstract:Abstract Allylamine is a specific cardiovascular toxin that causes vascular and myocardial lesions. Previous studies showed that Allylamine-induced chronic lesions are markedly reduced by semicarbazide, an inhibitor of semicarbazide-sensitive amine oxidase (SSAO), and that Allylamine is metabolized to the aldehyde, acrolein, by SSAO. We hypothesized that inhibitors of SSAO might reduce the acute cardiovascular toxicity of Allylamine. To test our hypothesis, we fed 150 mg kg Allylamine to semicarbazide-pretreated (3 h; 98 mg kg ) rats. Animals were sacrificed 1 h after Allylamine treatment. Aorta, epicardium, and endocardium were assayed for SSAO, glutathione peroxidase, catalase, thiol status and lipid peroxidation. SSAO activity was decreased significantly in aorta, epicardium and endocardium. Activity was 30-times higher in aorta than in epicardium and endocardium. A striking decrease in malonalydehyde level (lipid peroxidation) was found in aorta of pretreated rats as compared to Allylamine-only treated rats. The reduction of free-SH content in aortic mitochondria was also attenuated in pretreated rats. Changes were not so marked in epicardium and endocardium. These results suggest that in vivo pretreatment with semicarbazide at least partially protects aortic mitochondria from Allylamine toxicity. The mechanism can be explained on the basis of the fact that semicarbazide inhibits acrolein formation in Allylamine-treated rats.
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Allylamine and acrolein toxicity in perfused rat hearts.
Toxicology and applied pharmacology, 1991Co-Authors: Jerald L. Sklar, Peter G. Anderson, Paul J. BoorAbstract:We assessed the in vitro toxicity of the cardiovascular toxicant Allylamine, and its presumed in vivo metabolite, acrolein. In dose-response experiments, rat hearts perfused with Allylamine (10–30 mm) or acrolein (0.01–3.0 mm) for 2 hr were assessed by standard histopathology and assay of creatine kinase (CK) in effluent. Allylamine-perfused hearts showed no grossly apparent functional abnormality except at 30 mm, but acrolein-perfused hearts beat irregularly and stopped rapidly (within 15 min at 0.01–0.3 mm, and by 5 min at 3.0 mm). Extensive contraction band necrosis and an apparently dose-dependent loss of CK were evident in Allylamine-perfused hearts, whereas acrolein perfusion resulted in no morphologic lesions or CK loss. Additional experiments, however, suggest that acrolein perfusion results in denaturation of CK, making it undetectable in effluent. In hemodynamic preparations of rat hearts perfused with 10 mm Allylamine, contraction band necrosis and extensive mitochondrial changes were seen by electron microscopy. Allylamine caused a marked rise in left ventricular pressure at 5 and 10 min, followed by a slow decline to a markedly depressed level at the end of 2 hr. End diastolic pressure rose steadily throughout the 2-hr perfusion. Coronary flow was similar in control and Allylamine-perfused hearts for 1 hr, but then declined slowly. These experiments suggest that vascular spasm or alterations in coronary flow are not the cause of Allylamine-induced myocardial damage. Allylamine's toxic effect on myocardium in this model may be mediated through its metabolism and subsequent injurious intracellular events.
J J Leyden - One of the best experts on this subject based on the ideXlab platform.
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overview of topical therapy for common superficial fungal infections and the role of new topical agents update on topical therapy for superficial fungal infections focus on butenafine
Journal of The American Academy of Dermatology, 1997Co-Authors: B Brennan, J J LeydenAbstract:Until recently the treatment options for superficial fungal infections have been limited mainly to the use of fungistatic drugs of the imidazole class, discovered in the 1960s. The recent development of Allylamine and benzylamine compounds provides antifungal agents with fungicidal mechanisms of action. Both imidazole and Allylamine/benzylamine drugs interfere with the production of ergosterol, an essential component of the fungal cell membrane; however, the newer drugs act at an earlier stage of the metabolic pathway than the azoles and cause an accumulation of squalene in the fungal cell, which leads to cell death. In vitro test results show that Allylamine/benzylamine minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) are lower than the MICS and MFCs of azoles tested by the same methods. In studies using animal models of dermatophytosis, results have shown the efficacy of the Allylamine/benzylamine drugs to be superior to that of azole drugs. Clinical trials have also shown significant differences favoring Allylamine/benzylamine drugs over imidazoles in the treatment of dermatophytosis. The fungicidal drugs provide earlier evidence of efficacy, higher cure rates with shorter treatment periods, and lower relapse rates than imidazoles in direct-comparison studies. The Allylamine/benzylamine drugs have also shown high cure rates in patients with candidiasis.
Yuheng Deng - One of the best experts on this subject based on the ideXlab platform.
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Palladium‐Catalyzed Direct Arylation of Allylamines with Simple Arenes
ChemCatChem, 2015Co-Authors: Yichao Lei, Lingjuan Zhang, Ruiying Qiu, Yixiao Pan, Xubo Qin, Yuheng DengAbstract:The Pd(OAc)2-catalyzed direct CH bond olefination of unreactive arenes with Allylamines in the presence of AgOAc was developed. A variety of Allylamines including β-substituted substrates underwent smooth coupling reactions with various arenes to give exclusively the terminal arylation products in high yields with excellent regioselectivities and stereoselectivities. The reaction is compatible with a range of functional groups in both coupling partners. The carbonyl group in the Allylamine substrates is critical to catalysis, and the high regio- and stereocontrol observed is attributed to coordination between the carbonyl O and Pd atoms.
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Palladium‐Catalyzed, Highly Efficient, Regiocontrolled Arylation of Electron‐Rich Allylamines with Aryl Halides
Advanced Synthesis & Catalysis, 2012Co-Authors: Yuheng Deng, Zhen Jiang, Lingjuan Zhang, Min Yao, Weijun TangAbstract:The highly efficient and regioselective palladium-catalyzed Heck coupling of aryl bromides with electron-rich Allylamine derivatives is described. It was found that the choice of solvent, olefin, ligand and additive had a fundamental influence on the regioselectivity and reactivity of the reaction. The combination of palladium acetate [Pd(OAc)2] and 1,3-bis(diphenylphosphino)propane (dppp) in ethylene glycol (EG) constitutes a highly effective catalyst system for internal arylation of N-Boc-Allylamine (tert-butyl methyl allyliminodicarbonate) with aryl bromides to give good to excellent regioselectivities, while the catalyst system consisting of Pd(OAc)2, tetrabutylammonium bromide (TBAB) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) additive allows for a variety of aryl bromides to react efficiently with N,N-(Boc)2-Allylamine (di-tert-butyl allyliminodicarbonate) in water to exclusively afford the linear (E)-Allylamine products in high yields.
Lingjuan Zhang - One of the best experts on this subject based on the ideXlab platform.
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Palladium‐Catalyzed Direct Arylation of Allylamines with Simple Arenes
ChemCatChem, 2015Co-Authors: Yichao Lei, Lingjuan Zhang, Ruiying Qiu, Yixiao Pan, Xubo Qin, Yuheng DengAbstract:The Pd(OAc)2-catalyzed direct CH bond olefination of unreactive arenes with Allylamines in the presence of AgOAc was developed. A variety of Allylamines including β-substituted substrates underwent smooth coupling reactions with various arenes to give exclusively the terminal arylation products in high yields with excellent regioselectivities and stereoselectivities. The reaction is compatible with a range of functional groups in both coupling partners. The carbonyl group in the Allylamine substrates is critical to catalysis, and the high regio- and stereocontrol observed is attributed to coordination between the carbonyl O and Pd atoms.
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Palladium-Catalyzed Highly Regioselective Arylation of Allylamines with Thiophenes and Furans
Advanced Synthesis & Catalysis, 2012Co-Authors: Zhen Jiang, Lingjuan Zhang, Chaonan Dong, Weijun Tang, Zhongzheng Cai, Jianliang XiaoAbstract:A palladium-catalyzed highly regioselective and stereoselective direct arylation of Allylamine derivatives with a wide range of thiophenes and furans has been developed. In the presence of palladium(II) acetate [Pd(OAc)2] catalyst and appropriate oxidants, the coupling reaction proceeded with excellent group compatibility and high efficiency, leading exclusively to γ-arylated linear (E)-Allylamines. It was found that the choice of solvent, olefin substrate and oxidant had an important influence on reaction efficiency, and the use of sterically demanding N,N-diprotected Allylamines bearing a carbamate moiety is crucial for securing high regioselectivity and stereoslectivity. This method provides a straightforward approach for the efficient synthesis of various γ-heteroarylated, linear (E)-Allylamines.
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Palladium‐Catalyzed, Highly Efficient, Regiocontrolled Arylation of Electron‐Rich Allylamines with Aryl Halides
Advanced Synthesis & Catalysis, 2012Co-Authors: Yuheng Deng, Zhen Jiang, Lingjuan Zhang, Min Yao, Weijun TangAbstract:The highly efficient and regioselective palladium-catalyzed Heck coupling of aryl bromides with electron-rich Allylamine derivatives is described. It was found that the choice of solvent, olefin, ligand and additive had a fundamental influence on the regioselectivity and reactivity of the reaction. The combination of palladium acetate [Pd(OAc)2] and 1,3-bis(diphenylphosphino)propane (dppp) in ethylene glycol (EG) constitutes a highly effective catalyst system for internal arylation of N-Boc-Allylamine (tert-butyl methyl allyliminodicarbonate) with aryl bromides to give good to excellent regioselectivities, while the catalyst system consisting of Pd(OAc)2, tetrabutylammonium bromide (TBAB) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) additive allows for a variety of aryl bromides to react efficiently with N,N-(Boc)2-Allylamine (di-tert-butyl allyliminodicarbonate) in water to exclusively afford the linear (E)-Allylamine products in high yields.
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Palladium-catalyzed highly regioselective and stereoselective arylation of electron-rich Allylamines with aryl bromides
Tetrahedron, 2012Co-Authors: Zhen Jiang, Lingjuan Zhang, Chaonan Dong, Weijun Tang, Qing-hua Fan, Jianliang XiaoAbstract:Abstract A palladium-catalyzed, highly efficient Heck arylation of electron-rich N , N -diprotected Allylamine derivatives with a wide range of aryl bromides under ligand-free conditions has been developed. In the presence of Pd(OAc) 2 and an appropriate additive, the reaction proceeds with excellent regioselectivity and stereoselectivity, leading exclusively to the γ-arylated ( E )-Allylamine products in good to excellent yields. It was found that the choice of solvent, olefin, additive and temperature has an important influence on the reaction. Worthy of note is that good results were observed only when using N , N -diprotected Allylamines containing carbamate moiety, and the steric properties of Allylamines also have important impacts on the regiocontrol. The use of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) or HQ (hydroquinone) as the additive is also crucial for securing a faster reaction rate. This method provides a straightforward approach for the efficient synthesis of various γ-arylated, linear ( E )-Allylamines.
