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HO
Terms modified by HO Selected AbstractsCarbon monoxide produced by intrasinusoidally located haem-oxygenase-1 regulates the vascular tone in cirrhotic rat liverLIVER INTERNATIONAL, Issue 5 2009Lien Van Landeghem Abstract Background/Objective: Carbon monoxide (CO) produced by haem-oxygenase isoforms (HO-1 & HO-2) is involved in the regulation of systemic vascular tone. We aimed to elucidate the vasoregulatory role of CO in the microcirculation in normal and thioacetamide cirrhotic rat livers. Methods: Haem-oxygenase expression was examined by Western blot. Total HO enzymatic activity was measured spectrophotometrically. Sensitivity of hepatic stellate cells (HSCs) to CO-mediated relaxation was studied by a stress-relaxed-collagen-lattice model. To define the relative role of CO, the CO-releasing molecule CORM-2, the HO-inhibitor zinc protoporphyrin-IX and the HO-1 inducer hemin were added to an in situ liver perfusion set-up. The topography of vasoactive CO production was evaluated by applying different CO- and nitric oxide-trapping reagents in the liver perfusion set-up and by immunohistochemistry. Results: Western blot showed decreased expression of both HO isoenzymes (P<0.036 for HO-1; P<0.001 for HO-2) in cirrhotic vs normal rat livers, confirmed by the HO-activity assay (P=0.004). HSCs relaxed on exposure to CORM-2 (P=0.013). The increased intrahepatic vascular resistance (IHVR) of cirrhotic rats was attenuated by perfusion with CORM-2 (P=0.016) and pretreatment with hemin (P<0.001). Inhibition of HO caused a dose-related increase in IHVR in normal and cirrhotic liver. In normal liver, the haemodynamically relevant CO production occurred extrasinusoidally, while intrasinusoidally HO-1 predominantly regulated the microcirculation in cirrhotic livers. Conclusion: We demonstrate a role for CO and HO in the regulation of normal and cirrhotic microcirculation. These findings are of importance in the pathophysiology of portal hypertension and establish CO/HO as novel treatment targets. [source] The effectiveness of brief alcohol interventions in primary care settings: A systematic reviewDRUG AND ALCOHOL REVIEW, Issue 3 2009EILEEN F. S. KANER Abstract Issues. Numerous studies have reported that brief interventions delivered in primary care are effective in reducing excessive drinking. However, much of this work has been criticised for being clinically unrepresentative. This review aimed to assess the effectiveness of brief interventions in primary care and determine if outcomes differ between efficacy and effectiveness trials. Approach. A pre-specified search strategy was used to search all relevant electronic databases up to 2006. We also hand-searched the reference lists of key articles and reviews. We included randomised controlled trials (RCT) involving patients in primary care who were not seeking alcohol treatment and who received brief intervention. Two authors independently abstracted data and assessed trial quality. Random effects meta-analyses, subgroup and sensitivity analyses and meta-regression were conducted. Key Findings. The primary meta-analysis included 22 RCT and evaluated outcomes in over 5800 patients. At 1 year follow up, patients receiving brief intervention had a significant reduction in alcohol consumption compared with controls [mean difference: ,38 g week,1, 95%CI (confidence interval): ,54 to ,23], although there was substantial heterogeneity between trials (I2 = 57%). Subgroup analysis confirmed the benefit of brief intervention in men but not in women. Extended intervention was associated with a non-significantly increased reduction in alcohol consumption compared with brief intervention. There was no significant difference in effect sizes for efficacy and effectiveness trials. Conclusions. Brief interventions can reduce alcohol consumption in men, with benefit at a year after intervention, but they are unproven in women for whom there is insufficient research data. Longer counselling has little additional effect over brief intervention. The lack of differences in outcomes between efficacy and effectiveness trials suggests that the current literature is relevant to routine primary care. [Kaner EFS, Dickinson HO, Beyer F, Pienaar E, Schlesinger C, Campbell F, Saunders JB, Burnand B, Heather N. The effectiveness of brief alcohol interventions in primary care settings: A systematic review. Drug Alcohol Rev 2009;28:301,323] [source] Four Simple Tests of Campaign Contributions and Trade Policy PreferencesECONOMICS & POLITICS, Issue 2 2004Eugene Beaulieu This paper uses campaign contribution data to examine trade policy preferences among political action committees. With perfect factor mobility, as the Heckscher,Ohlin (HO) model assumes, interest group trade positions should depend on their factor of production but not on their industry. We show, consistent with the 2 × 2 HO model, that capital groups consistently back representatives supporting trade liberalization while labor groups favor protectionists. Unlike previous work, we also measure the variation in trade policy preferences within capital and labor groups. We find evidence that the industry net export position significantly affects labor unions' trade policy preferences. Industry characteristics have no impact on capital group lobbying. The former result suggests that empirical analyses of labor PAC contributions that exclude industry characteristics may be misspecified. [source] Hydrothermal Synthesis and Structural Characterization of the High-Valent Ruthenium-Containing Polyoxoanion [{PW11O39}2{(HO)RuIV,O,RuIV(OH)}]10,EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 13 2008Su-Wen Chen Abstract The high-valent ruthenium-containing [{PW11O39}2{(HO)RuIV,O,RuIV(OH)}]10, anion (1) has been synthesized by hydrothermal reaction and characterized by X-ray diffraction, IR, multinuclear (31P and 183W) NMR spectroscopy andelectrochemistry. Single-crystal analysis was carried outon Rb10[{PW11O39}2{(HO)RuIV,O,RuIV(OH)}]·21H2O, which crystallizes in the monoclinic system, space group P21/n, with a = 11.1912(14), b = 21.9257(12), c = 38.7310(96) Å, , = 94.682(19)°, V = 9472(3) Å3, Z = 4. Polyanion 1 consists of two lacunary [,-PW11O39]7, anions connected by a linear {(HO)Ru,O,Ru(OH)}4+ unit. Each ruthenium ion achieves six-coordination through interaction with two terminal oxo ligands from the lacuna of each [PW11O39]7, anion.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Two- and Three-Dimensional Hydrogen-Bonded Networks Built from 1,3,5-[(HO)2(O)P]3C6H3 and 4-(Dimethylamino)pyridineEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 16 2004Michael Mehring Abstract Crystallisation of 3,5-bis(phosphonophenyl)phosphonic acid, 1,3,5-[(HO)2(O)P]3C6H3, from MeOH/H2O in the presence of 4-(dimethylamino)pyridine, 4-(Me2N)C5H4N, gave [1-{(HO)2(O)P}-3,5-{(HO)(O)2P}2C6H3]2,[{4-(Me2N)C5H4NH}+]2 (2) and [1,3-{(HO)2(O)P}2 -5-{(HO)(O)2P}C6H3],[4-(Me2N)C5H4NH]+ (3). Single-crystal X-ray diffraction analyses revealed a two- and a three-dimensional hydrogen-bonded network for compounds 2 and 3, respectively. Compound 2 is composed of layers which are formed by hydrogen-bonded motifs of the type R2,2(8) and R4,4(16). These motifs are connected within the layer by additional hydrogen bonds and the benzene spacer. The cation [4-(Me2N)C5H4NH]+ is located between the layers and determines the interlayer separation of approximately 6.5 Å. In compound 3 a layered network of the hydrogen-bonded building units R2,3(10) was observed. These units are interconnected by four additional hydrogen bonds within the network. The benzene spacer links the adjacent layers to give a three-dimensional structure. Within this network, channels with internal dimensions of ca. 8.5 × 11.3 Å2 which are occupied by the [4-(Me2N)C5H4NH]+ cations were observed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Medium Effect on the Reaction of N -Butyl-2,4,6-trinitroaniline with NaOH,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 13 2007María Laura Salum Abstract The kinetics of the reaction of N -butyl-2,4,6-trinitroaniline (3) with NaOH have been studied in 10 and 60,% 1,4-dioxane/H2O at 25 °C. In both cases, several processes were observed. In 10,% 1,4-dioxane/H2O the only product formed was 2,4,6-trinitrophenol (4), whereas in 60,% 1,4-dioxane/H2O a mixture of 4 and 5,7-dinitro-2-propyl-1H -benzimidazole 3-oxide (5) was observed in ratios that depend on the HO, concentration. A mechanism involving the formation of , complexes through the addition of one or two HO, anions to unsubstituted ring positions is proposed for 2,4,6-trinitrophenol formation. The presence of these complexes was confirmed by NMR studies in 60,% [D8]1,4-dioxane/D2O. The mechanism suggested for the formation of the N -oxide includes the cyclization of an N -alkylidene-2-nitrosoaniline-type intermediate as the rate-determining step. The decrease in solvent polarity produces a decrease in the observed rate constant for the formation of 4 of about one order of magnitude making the cyclization reaction a competitive pathway. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Introduction of Aromatic and Heteroaromatic Groups in the 2- and 8-Positions of the Tröger's Base Core by Suzuki, Stille and Negishi Cross-Coupling Reactions , A Comparative StudyEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 16 2005Carlos Solano Abstract A comparative study on the bis(functionalization) of the Tröger's base core by aromatic and heteroaromatic groups using palladium-catalyzed cross-coupling reactions is presented. Three different reactions, the Suzuki, Stille, and Negishi couplings, were investigated using Tröger's base analogues equally substituted in the 2,8-positions with (HO)2B, Bu3Sn and ZnCl groups, respectively, as the metallated component. Six aryl halides with different electronic and steric properties were employed as coupling partners. The presence of the bulky and electron-rich phosphane P(tBu)3 as co-catalyst was found to play an important role. In addition, the palladium source, [Pd(PPh3)4] or [Pd2(dba)3], was also found to be an important factor for the yield of the reactions. The Suzuki coupling was found to be the best method in general, giving excellent yields for most aryl halides, whereas the Stille and Negishi couplings gave moderate to good yields. Finally, the crystal structures of the 4-nitrophenyl- and the 2-pyridyl-appended analogues of Tröger's base, 7d and 7f, are presented in the Supporting Information. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Heme oxygenase-1/p21WAF1 mediates peroxisome proliferator-activated receptor-, signaling inhibition of proliferation of rat pulmonary artery smooth muscle cellsFEBS JOURNAL, Issue 6 2010Manxiang Li Activation of peroxisome proliferator-activated receptor (PPAR)-, suppresses proliferation of rat pulmonary artery smooth muscle cells (PASMCs), and therefore ameliorates the development of pulmonary hypertension in animal models. However, the molecular mechanisms underlying this effect remain largely unknown. This study addressed this issue. The PPAR, agonist rosiglitazone dose-dependently stimulated heme oxygenase (HO)-1 expression in PASMCs, 5 ,m rosiglitazone inducing a 12.1-fold increase in the HO-1 protein level. Cells pre-exposed to rosiglitazone showed a dose-dependent reduction in proliferation in response to serotonin; this was abolished by pretransfection of cells with sequence-specific small interfering RNA against HO-1. In addition, rosiglitazone stimulated p21WAF1 expression in PASMCs, a 2.34-fold increase in the p21WAF1 protein level being achieved with 5 ,m rosiglitazone; again, this effect was blocked by knockdown of HO-1. Like loss of HO-1, loss of p21WAF1 through siRNA transfection also reversed the inhibitory effect of rosiglitazone on PASMC proliferation triggered by serotonin. Taken together, our findings suggest that activation of PPAR, induces HO-1 expression, and that this in turn stimulates p21WAF1 expression to suppress PASMC proliferation. Our study also indicates that rosiglitazone, a medicine widely used in the treatment of type 2 diabetes mellitus, has potential benefits for patients with pulmonary hypertension. [source] Inhibition of heme oxygenase-1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL miceINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Kaeko Hirai Abstract Heme oxygenase (HO)-1 is a key player reducing cytotoxicity and enhancing protumoral effects of nitric oxide (NO). We examined zinc protoporphyrin (ZnPP) IX, an HO-1 inhibitor, to affect tumor growth of LL/2 mouse lung cancer cells. ZnPPIX reduced HO-1 expression and HO activity in LL/2 cells, whereas cobalt PPIX (CoPPIX), an HO-1 activator, increased both. LL/2 cells treated with sodium nitropurusside, an NO donor, showed growth inhibition dose-dependently, which was enhanced by ZnPPIX cotreatment, but was reduced by CoPPIX. In mice tumors, ZnPPIX decreased HO-1 expression. LL/2-tumors were found in 88% (7/8) vehicle-treated mice, whereas tumors were found in 38% (3/8) and 25% (2/8) mice treated with 5 and 20 ,g/mouse ZnPPIX, respectively (p = 0.0302). Tumor growth was inhibited dose-dependently by ZnPPIX. Vascular endothealial growth factor concentration in tumors was reduced by ZnPPIX (p = 0.0341). Microvessel density (MVD) in ZnPPIX-treated tumors was lower than that in vehicle-treated tumors (p = 0.0362). Apoptotic cell count in ZnPPIX-treated tumors was higher than that in vehicle-treated tumors (p = 0.0003). In contrast, CoPPIX treatment increased HO-1 expression, enhanced tumorigenicity and MVD and reduced apoptosis. From these findings, inhibition of HO-1 by ZnPPIX provides relevant antitumoral effects. © 2006 Wiley-Liss, Inc. [source] Kinetics and mechanism of alkaline hydrolysis of 4-nitrophthalimide in the absence and presence of cationic micellesINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 7 2001M. Niyaz Khan Pseudo-first-order rate constants (kobs) for alkaline hydrolysis of 4-nitrophthalimide (NPTH) decreased by nearly 8- and 6-fold with the increase in the total concentration of cetyltrimethyl-ammonium bromide ([CTABr]T) from 0 to 0.02 M at 0.01 and 0.05 M NaOH, respectively. These observations are explained in terms of the pseudophase model and pseudophase ion-exchange model of micelle. The increase in the contents of CH3CN from 1 to 70% v/v and CH3OH from 0 to 80% v/v in mixed aqueous solvents decreases kobs by nearly 12- and 11-fold, respectively. The values of kobs increase by nearly 27% with the increase in the ionic strength from 0.03 to 3.0 M. The mechanism of alkaline hydrolysis of NPTH involves the reactions between HO, and nonionized NPTH as well as between HO, and ionized NPTH. The micellar inhibition of the rate of alkaline hydrolysis of NPTH is attributed to medium polarity effect. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 407,414, 2001 [source] What is a role of haeme oxygenase-1 in psoriasis?INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2007Current concepts of pathogenesis Summary The skin is constantly exposed to endogenous and environmental pro-oxidant agents, which lead to harmful generation of reactive oxygen species (ROS). Healthy skin, being a potential target for oxidative stress, is equipped with a large number of defence mechanisms including antioxidant systems. This protection can be corrupted by an imbalance between ROS and antioxidants with pathological level of oxidants prevailing. There is a great body of evidence indicating that some inflammatory skin diseases, such as psoriasis, are mediated by oxidative stress. Keratinocytes of normal skin, the primary target for pro-oxidant agents, show strong expression of ROS-detoxifying enzymes. In addition, normal keratinocytes express haeme oxygenase (HO), an enzyme which might be involved in the protection of cells against oxidative stress. HO (inducible HO-1, constitutive HO-2 and HO-3) is the rate-limiting enzyme in haeme catabolism, which leads to the generation of biliverdin, iron, and carbon monoxide. HO-1 is a stress-responsive protein whose expression is induced by various oxidative agents. HO-1 is known for its cytoprotective, antioxidant and anti-inflammatory properties. Interestingly, a strong overexpression of HO-1 was observed in psoriatic skin. However, the role of HO-1 in psoriasis remains unclear. In this review, we will discuss some current concepts concerning pathogenesis of psoriasis and the contribution of HO-1 in skin inflammation to show the relationships between HO-1, ROS and cytokine network in psoriatic skin. We will try to answer a question whether enhanced HO-1 expression in keratinocytes results in beneficial or detrimental effect on the development and severity of psoriatic lesions. [source] Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis,INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2004Fabiana Caballero Summary Heme oxygenase (HO) breaks down the pro-oxidant heme into carbon monoxide, iron and the antioxidant biliverdin. The isoform HO-1 plays an effective role to counteract oxidative damage and to control inflammation. Prolonged cellular damage due to chronic inflammation is one of the reasons leading to the development of tumours. The aim of this work was to investigate HO-1 expression and localization along the different stages of chemically induced hepatocarcinogenesis (HCC) and the occurring morphological changes. To provoke sustained oxidative stress and chronic inflammation, CF1 mice received dietary p -dimethylaminoazobenzene (DAB, 0.5%, w/w) during a whole period of 14 months. HO-1 expression increased along the experimental trial in morphologically normal hepatocytes in DAB-treated animals. HO-1 expression diminished in altered hepatic foci (AHF) and oval cells and early preneoplastic lesions. Otherwise, marked HO-1 overexpression was detected in Kupffer cells and macrophages surrounding necrotic and nodular areas. Adenomas showed decreased HO-1 immunostaining. In hepatocellular carcinomas, an inverse relationship was found between the immunohistochemical expression of HO-1 and the degree of tumour differentiation, being negative in poorly differentiated tumours. In our experimental model, down modulation of HO-1 expression correlated with malignancy progression. Thus, our data point to activation of HO-1 as a potential therapeutic tool. [source] Follow-up of serious offender patients in the community: multiple methods of tracingINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2002Elizabeth Jamieson Lecturer Abstract Longitudinal studies of people with mental disorder are important in understanding outcome and intervention effects but attrition rates can be high. This study aimed to evaluate use of multiple record sources to trace, over 12 years, a one-year discharge cohort of high-security hospital patients. Everyone leaving such a hospital in 1984 was traced until a census date of 31 December 1995. Data were collected from several national databases (Office for National Statistics (ONS), Home Office (HO) Offenders' Index, Police National Computer Records, the Electoral Roll) and by hand-searching responsible agency records (HO, National Health Service). Using all methods, only three of the 204 patients had no follow-up information. Home Office Mental Health Unit data were an excellent source, but only for people still under discharge restrictions (<50% after eight years). Sequential tracing of hospital placements for people never or no longer under such restrictions was laborious and also produced only group-specific yield. The best indicator of community residence was ONS information on general practitioner (GP/primary care) registration. The electoral roll was useful when other sources were exhausted. Follow-up of offenders/offender-patients has generally focused on event data, such as re-offending. People untraced by that method alone, however, are unlikely to be lost to follow-up on casting a wider records net. Using multiple records, attrition at the census was 38%, but, after certain assumptions, reduced further to 5%. Copyright © 2002 Whurr Publishers Ltd. [source] Theoretical study on the partial potential energy surface and formation mechanism of the reactive resonance state of HO + CH4 , H2O + CH3 systemINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 2 2008Xi Lu Abstract In the course of an extensive investigation aimed at understanding the detailed mechanism of a prototypical polyatomic reaction, several remarkable observations were uncovered. To interpret these findings, we surmise the existence of a reactive resonance in this polyatomic reaction. The concerned system is HO + CH4 , H2O + CH3, of which the partial potential energy surface is constructed by the coupling between vibrational models and reactive coordinates. Then we explain the formation mechanism of the reactive resonance state by the partial potential energy surface. Finally, we estimated the lifetime of the resonance state, and it is about 45fs. The study of the reactive resonance in a polyatomic reaction is more than just an extension from a typical atom + diatom reaction. As shown here, it holds great promise to disentangle the elusive intramolecular vibrational dynamics of the transient collision complex in the critical transition-state region. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008 [source] Density functional study of HO(H2O)n (n = 1,3) clustersINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4 2005Xiu-Li Dong Abstract The hydrogen bonding complexes HO(H2O)n (n = 1,3) were completely investigated in the present study using DFT and MP2 methods at varied basis set levels from 6-31++G(d,p) to 6-311++G(2d,2p). For n = 1 two, for n = 2 two, and for n = 3 five reasonable geometries are considered. The optimized geometric parameters and interaction energies for various complexes at different levels are estimated. The infrared spectrum frequencies and IR intensities of the most stable structures are reported. Finally, thermochemistry studies are also carried out. The results indicate that the formation and the number of hydrogen bonding have played an important role in the structures and relative stabilities of different complexes. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 [source] Can low densities of carnivores result in genetic depletion?JOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 3 2006An investigation within French polecat populations Summary Carnivores as top predators are commonly found in relatively low densities even in optimal habitats. Despite a lack of empirical studies, it could be suspected that long-term low density could result in genetic depletion. The genetic structure of European polecat Mustela putorius natural populations was investigated by allozyme electrophoresis in five distinct areas. Density estimates significantly differed among sites from 0.17 to 0.83 individuals/km2 with an average of 0.56 individuals per km2, resulting in a scattered distribution. Genetic structure varied among distinct populations both in number of polymorphic loci and heterozygosity. Polecats from Brittany revealed a very low observed heterozygosity (HO = 0.028) whereas mean heterozygosity reached HO = 0.072 in Brière. That the lowest heterozygosity levels and highest inbreeding coefficient FIS were significantly associated with the lowest densities suggests that low densities may affect populations of carnivores. Both the loss of polymorphic loci and the reduction in heterozygosity rates suggest a density-dependent effect and population density can be arguably regarded as a factor affecting genetic diversity in top carnivores. [source] Curcumin-induced fibroblast apoptosis and in vitro wound contraction are regulated by antioxidants and heme oxygenase: implications for scar formationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2009A. Scharstuhl Abstract Fibroblast apoptosis plays a crucial role in normal and pathological scar formation and therefore we studied whether the putative apoptosis-inducing factor curcumin affects fibroblast apoptosis and may function as a novel therapeutic. We show that 25-,M curcumin causes fibroblast apoptosis and that this could be inhibited by co-administration of antioxidants N -acetyl- l -cysteine (NAC), biliverdin or bilirubin, suggesting that reactive oxygen species (ROS) are involved. This is supported by our observation that 25-,M curcumin caused the generation of ROS, which could be completely blocked by addition of NAC or bilirubin. Since biliverdin and bilirubin are downstream products of heme degradation by heme oxygenase (HO), it has been suggested that HO-activity protects against curcumin-induced apoptosis. Interestingly, exposure to curcumin maximally induced HO-1 protein and HO-activity at 10,15 ,M, whereas, at a concentration of >20-,M curcumin HO-1-expression and HO-activity was negligible. NAC-mediated inhibition of 25-,M curcumin-induced apoptosis was demonstrated to act in part via restored HO-1-induction, since the rescuing effect of NAC could be reduced by inhibiting HO-activity. Moreover pre-induction of HO-1 using 5-,M curcumin protected fibroblasts against 25-,M curcumin-induced apoptosis. On a functional level, fibroblast-mediated collagen gel contraction, an in vitro wound contraction model, was completely prevented by 25-,M curcumin, while this could be reversed by co-incubation with NAC, an effect that was also partially HO-mediated. In conclusion, curcumin treatment in high doses (>25 ,M) may provide a novel way to modulate pathological scar formation through the induction of fibroblast apoptosis, while antioxidants, HO-activity and its effector molecules act as a possible fine-tuning regulator. [source] Improved myocardial perfusion in chronic diabetic mice by the up-regulation of pLKB1 and AMPK signalingJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2010Claudia Kusmic Abstract Previous studies related impaired myocardial microcirculation in diabetes to oxidative stress and endothelial dysfunction. Thus, this study was aimed to determine the effect of up-regulating pAMPK-pAKT signaling on coronary microvascular reactivity in the isolated heart of diabetic mice. We measured coronary resistance in wild-type and streptozotocin (STZ)-treated mice, during perfusion pressure changes. Glucose, insulin, and adiponectin levels in plasma and superoxide formation, NOx levels and heme oxygenase (HO) activity in myocardial tissue were determined. In addition, the expression of HO-1, 3-nitrotyrosine, pLKB1, pAMPK, pAKT, and peNOS proteins in control and diabetic hearts were measured. Coronary response to changes in perfusion pressure diverged from control in a time-dependent manner following STZ administration. The responses observed at 28 weeks of diabetes (the maximum time examined) were mimicked by L-NAME administration to control animals and were associated with a decrease in serum adiponectin and myocardial pLKB1, pAMPK, pAKT, and pGSK-3 expression. Cobalt protoporphyrin treatment to induce HO-1 expression reversed the microvascular reactivity seen in diabetes towards that of controls. Up-regulation of HO-1 was associated with an increase in adiponectin, pLKB1, pAKT, pAMPK, pGSK-3, and peNOS levels and a decrease in myocardial superoxide and 3-nitrotyrosine levels. In the present study we describe the time course of microvascular functional changes during the development of diabetes and the existence of a unique relationship between the levels of serum adiponectin, pLKB1, pAKT, and pAMPK activation in diabetic hearts. The restoration of microvascular function suggests a new therapeutic approach to even advanced cardiac microvascular derangement in diabetes. J. Cell. Biochem. 109: 1033,1044, 2010. © 2010 Wiley-Liss, Inc. [source] Dynamic structures of phosphodiesterase-5 active site by combined molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculationsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 8 2008Ying Xiong Abstract Various quantum mechanical/molecular mechanical (QM/MM) geometry optimizations starting from an x-ray crystal structure and from the snapshot structures of constrained molecular dynamics (MD) simulations have been performed to characterize two dynamically stable active site structures of phosphodiesterase-5 (PDE5) in solution. The only difference between the two PDE5 structures exists in the catalytic, second bridging ligand (BL2) which is HO, or H2O. It has been shown that, whereas BL2 (i.e. HO,) in the PDE5(BL2 = HO,) structure can really bridge the two positively charged metal ions (Zn2+ and Mg2+), BL2 (i.e. H2O) in the PDE5(BL2 = H2O) structure can only coordinate Mg2+. It has been demonstrated that the results of the QM/MM geometry optimizations are remarkably affected by the solvent water molecules, the dynamics of the protein environment, and the electronic embedding charges of the MM region in the QM part of the QMM/MM calculation. The PDE5(BL2 = H2O) geometries optimized by using the QM/MM method in different ways show strong couplings between these important factors. It is interesting to note that the PDE5(BL2 = HO - ) and PDE5(BL2 = H2O) geometries determined by the QM/MM calculations neglecting these three factors are all consistent with the corresponding geometries determined by the QM/MM calculations that account for all of these three factors. These results suggest the overall effects of these three important factors on the optimized geometries can roughly cancel out. However, the QM/MM calculations that only account for some of these factors could lead to considerably different geometries. These results might be useful also in guiding future QM/MM geometry optimizations on other enzymes. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008 [source] Ab initio investigation on the reaction path and rate for the gas-phase reaction of HO + H2O , H2O + OHJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 13 2003Tadafumi Uchimaru Abstract This article describes an ab initio investigation on the potential surfaces for one of the simplest hydrogen atom abstraction reactions, that is, HO + H2O , H2O + OH. In accord with the findings in the previously reported theoretical investigations, two types of the hydrogen-bonding complexes [HOHOH] and [H2OHO] were located on the potential energy surface. The water molecule acts as a hydrogen donor in the [HOHOH] complex, while the OH radical acts as a hydrogen donor in the [H2OHO] complex. The energy evaluations at the MP2(FC) basis set limit, as well as those through the CBS-APNO procedure, have provided estimates for enthalpies of association for these complexes at 298 K as ,2.1 , ,2.3 and ,4.1 , ,4.3 kcal/mol, respectively. The IRC calculations have suggested that the [H2OHO] complex should be located along the reaction coordinate for the hydrogen abstraction. Our best estimate for the classical barrier height for the hydrogen abstraction is 7.8 kcal/mol, which was obtained from the CBS-APNO energy evaluations. After fitting the CBS-APNO potential energy curve to a symmetrical Eckart function, the rate constants were calculated by using the transition state theory including the tunneling correction. Our estimates for the Arrhenius parameters in the temperature region from 300 to 420 K show quite reasonable agreement with the experimentally derived values. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1538,1548, 2003 [source] Genetic differentiation and natural hybridization between the Sardinian endemic Maniola nurag and the European Maniola jurtinaJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 4 2007A. GRILL Abstract The Mediterranean island of Sardinia is known for its multitude of unique genetic lineages. We view one of them in a larger phylogeographic context. The endemic Sardinian Meadow Brown butterfly, Maniola nurag, is restricted to the mountainous areas of the island, whereas its widespread close relative, Maniola jurtina, also occurs on the coast. At intermediate altitudes the species' distributions overlap. There, a number of individuals exhibit phenotypic characteristics intermediate between the two species. We examined patterns of intra- and interpopulation variation in 10 M. nurag populations from Sardinia and 16 M. jurtina populations from Sardinia and continental Europe, as well as 17 intermediate individuals, sampled in 1999,2002, by means of allozyme markers, combining it with a morphometric analysis based on 18 wing-characters of 52 males. At the 15 loci studied (aldolase, aat-1, aat-2, g6pdh, gpd, idh-1, idh-2, mdh-1, mdh-2, mpi, me, leu-ala, pgi, pgm, and 6pgdh), 76 different alleles were detected, 63 of which were shared by M. nurag and M. jurtina. None of the loci was found to be alternatively fixed between the two species. In that respect, this study testifies to the difficulties that may arise when trying to identify hybrids from genotypic data. Levels of genetic variation in island populations (M. jurtina: HO = 0.137,0.189; M. nurag: HO = 0.141,0.270) were comparable to those of mainland M. jurtina (HO = 0.141,0.236). A Bayesian admixture analysis supported the hypothesis of mixed (hybrid) ancestry of individuals occurring at intermediate altitudes. Similarly, neighbour-joining and unweighted pair-group method with arithmetic averaging (UPGMA) analyses, as well as morphometrics hinted at the existence of a Maniola -hybrid zone in Sardinia at intermediate altitudes. We discuss the results in the light of the phylogeography of other Sardinian taxa with the aim to reach a general understanding of the biogeographic history of this island's endemic species. [source] Full Characterization and some reactions of 1-(2-adamantyl)-3-(1-adamantyl)aziridin-2-oneJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2008István Lengyel We found that 1-(2-adamantyl)-3- tert -butylaziridin-2-one (5a) is unstable. It slowly decomposes at room temperature, although detectable by IR spectroscopy (1840 cm,1 band in CCl4). On the other hand, a closely related analogue, 1-(2-adamantyl)-3-(1-adamantyl)aziridin-2-one (5b), is very stable, in concurrence with an earlier report [1]. We fully characterized aziridinone 5b, identified its thermal decomposition products (7 and 8) and reacted it with two aprotic ionic (tBuO, and HO,) and one protic non-ionic nucleophile (benzylamine). All three products (9b, 10, and 11) result from exclusive cleavage of the lactam (1-2) bond. [source] One Approach to Formulating and Evaluating Student Work Groups in Legal Environment of Business CoursesJOURNAL OF LEGAL STUDIES EDUCATION, Issue 1 2007Joan E. Camara The principal focus of this study is an investigation of whether students' grade point average (GPA) is a viable criterion for forming student work groups in the undergraduate Legal Environment of Business course. More specifically, the research focuses on the impact of: (1) GPA-homogeneous (HO) and GPA-heterogeneous (HE) groups upon student satisfaction with group processes and (2) the impact on individual student performance in both group and nongroup assignments. Data obtained from fourteen HE and fourteen HO student groups, in four separate Legal Environment of Business classes consisting of a mix of Management, Marketing, Computer Information Systems, International Business, Financial Services, and Accounting majors, generated a number of significant results. The most surprising observations dealt with the behavior of low achievers whose individual grades showed substantial improvement after working in HO groups. Researchers who are assessing pedagogical methods which serve to engage a student's active learning and motivation should find these results to be of interest. In addition, the beneficial impact on task and relationship behaviors observed in this study should provide solace or a sense of reward to the larger set of academicians, across disciplines, who attempt to impart realistic organizational skills to their classes. [source] Up-regulation of heat shock protein HSP 20 in the hippocampus as an early response to hypoxia of the newbornJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Jean-Claude David Abstract Hypoxia is an important challenge for newborn mammals. Stress generated at the brain level under low oxygenation conditions results in up-regulation of heat shock proteins (HSPs) and other stress proteins. The aim of the present work was to determine the effect of hypoxia in the newborn on some newly described small molecular weight HSPs (HSP 20 and B8) in the hippocampus, cortex and cerebellum of newborn piglets. These effects will be compared with those of other closely related proteins such as ,B crystallin, HSP 27, heme oxygenase (HO)-1, HO-2, cyclooxygenase (COX)-1 and COX-2. The piglets were submitted to hypoxia (5% O2; 95% N2) over either 1 or 4 h, with recovery periods ranging from 0 to 68 h. Western blot analysis showed that HSP 20 was rapidly induced only in the hippocampus, long before hypoxia-inducible transcription factor HIF-1,, while HSP 27 was rapidly induced in the cortex and cerebellum. Vascular epithelial growth factor was increased simultaneously in the three regions. Moreover, an increase in the expression of, respectively, HO-1 and COX-2 was observed later, but at the same time, in the three regions tested. It appears that HSP 20 can be an early marker of hypoxia in the hippocampus. The other small HSPs or stress proteins display different temporal patterns of up-regulation (HSP 27 and HO-1, COX-2) or do not show changes in their expressions (,B crystallin, HSP B8, HO-2 and COX-1). [source] Putative heterotopic ossification progenitor cells derived from traumatized muscle,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2009Wesley M. Jackson Abstract Heterotopic ossification (HO) is a frequent complication following combat-related trauma, but the pathogenesis of traumatic HO is poorly understood. Building on our recent identification of mesenchymal progenitor cells (MPCs) in traumatically injured muscle, the goal of this study was to evaluate the osteogenic potential of the MPCs in order to assess the role of these cells in HO formation. Compared to bone marrow-derived mesenchymal stem cells (MSCs), a well-characterized population of osteoprogenitor cells, the MPCs exhibited several significant differences during osteogenic differentiation and in the expression of genes related to osteogenesis. Upon osteogenic induction, MPCs showed increased alkaline phosphatase activity, production of a mineralized matrix, and up-regulated expression of the osteoblast-associated genes CBFA1 and alkaline phosphatase. However, MPCs did not appear to reach terminal differentiation as the expression of osteocalcin was not substantially up-regulated. With the exception of a few genes, the osteogenic gene expression profile of traumatized muscle-derived MPCs was comparable to that of the MSCs after osteogenic induction. These findings indicate that traumatized muscle-derived MPCs have the potential to function as osteoprogenitor cells when exposed to the appropriate biochemical environment and are the putative osteoprogenitor cells that initiate ectopic bone formation in HO. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1645,1651, 2009 [source] Variation in the secreted frizzled-related protein-3 gene and risk of Osteolysis and heterotopic ossification after total hip arthroplastyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2007Andrew Gordon Abstract Secreted frizzled-related protein-3 (sFRP3) antagonizes ligands that promote new bone formation in adult tissues. We examined whether variation in the FRZB gene that encodes sFRP3 is associated with development of osteolysis or heterotopic ossification (HO) after total hip arthroplasty (THA). Genomic DNA was extracted from 609 subjects (osteolysis group n,=,268) at a mean of 11 years following cemented THA for idiopathic osteoarthritis and genotyped for the FRZB Arg200Trp and Arg324Gly polymorphisms. The Brooker classification was used to assess HO following primary THA in 563 of the subjects. The carriage rate of the FRZB 200Trp allele was 14.2% in subjects with osteolysis versus 21.0% in controls (p,=,0.041). The carriage rate of this allele was 21.7% in subjects with HO (n,=,299) versus 12.0% in those without HO (p,=,0.063). The odds ratio for osteolysis with carriage of FRZB 200Trp was 0.62 (95% CI 0.38 to 0.99; p,=,0.049) and for HO was 1.64 (1.05 to 2.54; p,=,0.028), after adjustment for the effects of other risk factors associated with the development of osteolysis or HO. Variants in the FRZB 324 locus alone were not associated with osteolysis or HO. However, the most frequent haplotype (FRZB 200Arg:324Arg) was associated with osteolysis (OR 1.50, 95% CI 1.09 to 2.07; p,=,0.014). Our data suggest that the FRZB Arg200Trp locus may be a marker for pro-osteoblastic activity after THA. Carriage of the FRZB 200Trp allele is associated with a "positive" bone balance phenotype (osteolysis ,: HO+). © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1665,1670, 2007 [source] Comparative study of eight well-known polyphenolic antioxidantsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2003P. Cos ABSTRACT Eight antioxidants from five different polyphenolic classes (cinnamic acids, benzoic acids, flavonoids, proanthocyanidins and stilbenes), and the water-soluble vitamin E derivative trolox were examined for their antioxidant activity in-vitro. In addition, the compounds were tested for their cytotoxicity on growing fibroblasts and their inhibition of the classical pathway of the complement system. Procyanidin C1 was shown to be a good scavenger of both DPPH* and HO*, and a strong inhibitor of lipid peroxidation and the classical pathway of the complement system. Consequently, procyanidin C1 was classified as the most promising antioxidant in-vitro of all compounds tested. In contrast, genistein exhibited a very low antioxidant activity in both the lipid peroxidation and the DPPH* scavenging assay, a high cytotoxicity and a low complement-inhibiting activity. [source] Hyperbranched polyethers by ring-opening polymerization: Contribution of activated monomer mechanismJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 4 2003Przemys, aw Kubisa Abstract Propagation in the cationic ring-opening polymerization of cyclic ethers involves nucleophilic attack of oxygen atoms from the monomer molecules on the cationic growing species (oxonium ions). Such a mechanism is known as the active chain-end mechanism. If hydroxyl groups containing compounds are present in the system, oxygen atoms of HO groups may compete with cyclic ether oxygen atoms of monomer molecules in reaction with oxonium ions. At the proper conditions, this reaction may dominate, and propagation may proceed by the activated monomer mechanism, that is, by subsequent addition of protonated monomer molecules to HO terminated macromolecules. Both mechanisms may contribute to the propagation in the cationic polymerization of monomers containing both functions (i.e., cyclic ether group and hydroxyl groups) within the same molecule. In this article, the mechanism of polymerization of three- and four-membered cyclic ethers containing hydroxymethyl substituents is discussed in terms of competition between two possible mechanisms of propagation that governs the structure of the products,branched polyethers containing multiple terminal hydroxymethyl groups. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 457,468, 2003 [source] Synthesis of hydroxy-terminated, oligomeric poly(silarylene disiloxane)s via rhodium-catalyzed dehydrogenative coupling and their use in the aminosilane,disilanol polymerization reaction,JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 9 2002Craig L. Homrighausen Abstract A series of oligomeric, hydroxy-terminated silarylene,siloxane prepolymers of various lengths were prepared via dehydrogenative coupling between 1,4-bis(dimethylsilyl)benzene [H(CH3)2SiC6H4Si(CH3)2H] and excess 1,4-bis(hydroxydimethylsilyl)benzene [HO(CH3)2SiC6H4Si(CH3)2OH] in the presence of a catalytic amount of Wilkinson's catalyst [(Ph3P)3RhCl]. Attempts to incorporate the diacetylene units via dehydrogenative coupling polymerization between 1,4-bis(dimethylsilyl)butadiyne [H(CH3)2SiCCCCSi(CH3)2H] and the hydroxy-terminated prepolymers were unsuccessful. The diacetylene units were incorporated into the polymer main chain via aminosilane,disilanol polycondensation between 1,4-bis(dimethylaminodimethylsilyl)butadiyne [(CH3)2NSi(CH3)2CCCC(CH3)2SiN(CH3)2] and the hydroxy-terminated prepolymers. Linear polymers were characterized by Fourier transform infrared, 1H and 13C NMR, gel permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis, and they were thermally crosslinked through the diacetylene units, producing networked polymeric systems. The thermooxidative stability of the networked polymers is discussed. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1334,1341, 2002 [source] Stannous(II) trifluoromethane sulfonate: a versatile catalyst for the controlled ring-opening polymerization of lactides: Formation of stereoregular surfaces from polylactide "brushes"JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 20 2001Michael Möller Abstract A general method for the controlled synthesis of polylactide in solution and from solid supports is presented. The evaluation of stannous(II) trifluoromethane sulfonate [Sn(OTf)2] and scandium(III) trifluoromethane sulfonate [Sc(OTf)3] as catalysts for the ring-opening polymerization (ROP) of L -, D -, and L,D -lactide is described as a route to polylactide using mild and highly selective conditions. These triflate catalysts must be used in conjunction with a nucleophilic compound such as an alcohol that is the actual initiating species via the active metal alkoxide species. Consistent with this process, 1H NMR analysis revealed that the ,-chain-end bears the ester from the initiating alcohol, and upon hydrolysis of the active metal alkoxide chain end, a ,-hydroxyl chain end was clearly detected. Polymers of predictable molecular weights and narrow polydispersities were obtained in high yields in accordance with a controlled polymerization process. The addition of base either as a solvent or additive significantly enhanced the polymerization rate with minimal loss to the polymerization control. The ROP of lactide isomers from an initiator, HO(CH2CH2O)3(CH2)11SH, self-assembled onto a gold surface using Sn(OTf)2 produced polylactide brushes under living conditions and provides the opportunity to prepare stereoregular or chiral surfaces by polymerization of enantiomerically pure monomers. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3529,3538, 2001 [source] | |||||||||||||||||||||||||||||||||||||||||||||||||