@article {2628, title = {Glycosylated tetrahydrosalens as multifunctional molecules for Alzheimer{\textquoteright}s therapy}, journal = {Dalton Transactions}, number = {16}, year = {2009}, note = {ISI Document Delivery No.: 430GYTimes Cited: 8Cited Reference Count: 65Storr, Tim Scott, Lauren E. Bowen, Meryn L. Green, David E. Thompson, Katherine H. Schugar, Harvey J. Orvig, Chris}, pages = {3034-3043}, type = {Article}, abstract = {The tetrahydrosalens N,N{\textquoteright}-bis(2-hydroxybenzyl)-ethane-1,2-diamine (H2L1), N, N{\textquoteright}-bis(2-hydroxybenzyl)-(-)-1,2-cyclohexane-(1R, 2R)-diamine (H2L2), N,N{\textquoteright}-bis(2-hydroxybenzyl)-N,N{\textquoteright}-dimethyl-ethane-1,2-diamine (H2L3), N,N{\textquoteright}-bis(2-hydroxybenzyl)-N,N{\textquoteright}-dibenzyl-ethane-1,2diamine (H2L4), and N,N{\textquoteright}-bis(2-(4-tert-butyl) hydroxybenzyl)-ethane-1,2-diamine (H2L5), as well as their prodrug glycosylated forms, GL(1-5), have been prepared and evaluated in vitro for their potential use as Alzheimer{\textquoteright}s disease (AD) therapeutics. Dysfunctional interactions of metal ions, especially those of Cu, Zn, and Fe, with the amyloid-beta (A beta) peptide are hypothesised to play an important role in the aetiology of AD, and disruption of these aberrant metal-peptide interactions via chelation therapy holds considerable promise as a therapeutic strategy. Tetrahydrosalens such as H2L1-5 have a significant affinity for metal ions, and thus should be able to compete with the A beta peptide for Cu, Zn, and Fe in the brain. This activity was assayed in vitro via a turbidity assay; H2L1 and H2L3 were found to attenuate A beta(1-40) aggregation after exposure to Cu2+ and Zn2+. In addition, H2L1-5 were determined to be potent antioxidants on the basis of an in vitro antioxidant assay. GL(1-5) were prepared as metal binding prodrugs; glycosylation is intended to prevent systemic metal binding, improve solubility, and enhance brain uptake. Enzymatic (beta-glucosidase) deprotection of the carbohydrate moieties was facile, with the exception of GL(4), demonstrating the general feasibility of this prodrug approach. Finally, a representative prodrug, GL(3), was determined to be non-toxic over a large concentration range in a cell viability assay.}, keywords = {A-BETA, ACTIVITY, antioxidant, COMPLEXES, DISEASE, HYDROGEN-PEROXIDE, IN-VITRO, NEURODEGENERATIVE DISORDERS, OXIDATIVE STRESS, TRANSGENIC MICE, zinc}, isbn = {1477-9226}, url = {://000264978300018}, author = {Storr, T. and Scott, L. E. and Bowen, M. L. and Green, D. E. and Thompson, K. H. and Schugar, H. J. and Orvig, Chris} } @article {2350, title = {Rationale, design and baseline characteristics of the PROJECT II study: PROpofol CardioproTECTion for Type II diabetics A randomized, controlled trial of high-dose propofol versus isoflurane preconditioning in patients undergoing on-pump coronary artery b}, journal = {Contemporary Clinical Trials}, volume = {30}, number = {4}, year = {2009}, note = {ISI Document Delivery No.: 456NPTimes Cited: 1Cited Reference Count: 23Ansley, David M. Raedschelders, Koen Chen, David D. Y. Choi, Peter T.}, month = {Jul}, pages = {380-385}, type = {Article}, abstract = {Diabetes mellitus is a leading cause of death globally and results in significant morbidity and mortality following surgery. After cardiac surgery, diabetic patients are especially at risk for low cardiac output syndrome, which can quadruple the risk for postoperative death. Attempts to prevent low cardiac output syndrome have focused on increasing myocardial tolerance to ischemia (preconditioning), which involves the myocardial mitochondrial ATP-regulated K-ATP channel. G-protein initiation, nitric oxide synthase, and protein kinase C. Unfortunately, the signal transduction pathways required for preconditioning are corrupted in diabetes. Effective antioxidant intervention during ischemia-reperfusion appears important for preserving myocardial function: thus, alleviating oxidant-mediated post-ischemic injury by increasing antioxidant defenses (cardioprotection) is an alternative to preconditioning. Our previous work suggests that propofol(2,6-diisopropylphenol), an intravenous anesthetic with antioxidant potential, may confer cardioprotection. In this paper, we describe the rationale and methodology of the Pro-TECT II Study, a Phase II randomized controlled trial designed to explore the relationships of biomarkers of oxidative or nitrosative stress in diabetes, to determine the effect of propofol cardioprotection to counteract these effects in patients undergoing elective primary coronary bypass graft surgery with cardiopulmonary bypass, and to provide feasibility and sample size data needed to conduct Phase III trials. (C) 2009 Elsevier Inc. All rights reserved.}, keywords = {15-F-2T-ISOPROSTANE FORMATION, antioxidant, apoptosis, CAPACITY, Cardiopulmonary bypass, Diabetes mellitus, EXPRESSION, F2-isoprostanes, HYPERGLYCEMIA, INJURY, MORTALITY, MYOCARDIAL-INFARCTION, Nitric oxide synthase type III, PREDICTORS, Propofol, SHORT-TERM}, isbn = {1551-7144}, url = {://000266853900014}, author = {Ansley, D. M. and Raedschelders, K. and Chen, D. D. Y. and Choi, P. T.} } @article {1010, title = {Complementary inhibition of synoviocyte, smooth muscle cell or mouse lymphoma cell proliferation by a vanadyl curcumin complex compared to curcumin alone}, journal = {Journal of Inorganic Biochemistry}, volume = {98}, number = {12}, year = {2004}, note = {ISI Document Delivery No.: 876VBTimes Cited: 20Cited Reference Count: 62}, month = {Dec}, pages = {2063-2070}, type = {Article}, abstract = {A novel vanadyl curcumin complex (VO(cur)2) has been synthesized and and its physicochemical properties characterized. Biological characterization included in vitro testing for anti-rheumatic activity in synoviocytes, angiogenesis inhibition in smooth muscle cells and anti-cancer potential in mouse lymphoma cells; as well as in vivo testing for hypoglycemic activity by oral gavage in streptozotocin (STZ)-diabetic rats. VO(cur)2 was more effective as an anti-cancer agent, compared to uncomplexed curcumin or vanadyl ion alone, was more than twice as effective as curcumin alone as an anti-arthritic agent, and was more than four times as effective as curcumin alone in inhibiting smooth muscle cell proliferation. In both acute and chronic screening tests, VO(cur)2 was ineffective as an insulin mimetic agent; however, it also proved to be exceptionally non-toxic, with no evidence of negative symptornatology during a month-long treatment period, at doses up to and including 2.0 mmol kg(-1) day(-1). (C) 2004 Elsevier Inc. All rights reserved.}, keywords = {antioxidant, apoptosis, arthritis lymphoma, BIS(MALTOLATO)OXOVANADIUM(IV), CELLS, COMPLEX, COORDINATION, curcurnin, DIABETIC-RATS, DIFERULOYL METHANE CURCUMIN, FREE-RADICALS, INDUCED LIPID-PEROXIDATION, INSULIN MIMICS, LEUKEMIA HL-60, METAL-IONS, OXIDATIVE STRESS, vanadyl ion}, isbn = {0162-0134}, url = {://000225525200010}, author = {Thompson, K. H. and Bohmerle, K. and Polishchuk, E. and Martins, C. and Toleikis, P. and Tse, J. and Yuen, V. and McNeill, J. H. and Orvig, Chris} } @article {4610, title = {The metabolites of dietary chlorophylls}, journal = {Phytochemistry}, volume = {50}, number = {2}, year = {1999}, note = {ISI Document Delivery No.: 160EBTimes Cited: 15Cited Reference Count: 70}, month = {Jan}, pages = {195-202}, type = {Review}, abstract = {Chlorophylls, the green pigments responsible for photosynthesis in plants, algae and bacteria, are also part of the daily diet of herbivorous feeders. Numerous metabolic derivatives of the major green pigment, chlorophyll-a, have been found in a wide variety of organisms during the last decade. Studies of these metabolites show that some are antioxidants or cellular signaling mediators in vivo. The metabolites of bacteriochlorophylls-c and d, recently found in the deep-sea dragon fish, Malacosteus niger, function as a visual photosensitizer, enabling the fish to seek their prey in {\textquoteright}the dark{\textquoteright}. Discovery of these metabolites as well as their interesting biological functions raises questions as to the roles of chlorophyll derivatives in the chemical ecology of herbivorous life forms. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.}, keywords = {antioxidant, AUTOXIDATION, cell signaling, CHLORIN, CHLOROPHYLL, DERIVATIVES, DIET, ESTERS, MARINE ORGANISMS, METABOLISM, PHOTOSENSITIZER, PI-CATION RADICALS, porphyrins, PRODUCTS, RUDITAPES-PHILIPPINARUM, TUNICHLORIN}, isbn = {0031-9422}, url = {://000078216500001}, author = {Ma, L. F. and Dolphin, D.} }