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Journal of Molecular and Cellular Cardiology 11/2012; 53(5):744. · 5.17 Impact Factor
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Journal of Molecular and Cellular Cardiology 11/2012; 53(5):743. · 5.17 Impact Factor
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Journal of Molecular and Cellular Cardiology 11/2012; 53(5):745. · 5.17 Impact Factor
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Journal of Molecular and Cellular Cardiology 11/2012; 53(5):742. · 5.17 Impact Factor
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ABSTRACT: The present study examined the efficacy of using longevinex, a commercially available resveratrol formulation, to lower blood
cholesterol in hypercholesteromic rabbits. New Zealand white rabbits were randomly divided into two groups (n=6 per group), one group was given high cholesterol diet for 3months while the other group fed regular diet served as control.
The high cholesterol diet fed group was further subdivided into two groups (n=6 per group), one group was given longevinex resveratrol while the other group given vehicle only served as control. Longevinex
was given by gavaging up to a period of 6months. Longevinex-treated rabbits exhibited lowering of plasma cholesterol level.
Inhibition of arterial plaque formation was noticed even after 1month. Longevinex-treated hearts demonstrated improved ventricular
recovery when isolated working hearts were subjected to 30min of ischemia followed by 2h of reperfusion. Aortic flow and
developed pressure during post-ischemic reperfusion period were significantly higher for the longevinex-treated hearts compared
to those in control group of hearts. Myocardial infarct size was also lower in the treated group compared to that for the
untreated group. These results indicate cholesterol-lowering ability of longevinex, which appears to reflect in its ability
to protect the hypercholesteromic hearts from ischemic reperfusion injury.
KeywordsLongevinex–Resveratrol–Hypercholesteromia–Ischemia/reperfusion
Molecular and Cellular Biochemistry 05/2012; 348(1):199-203. · 2.06 Impact Factor
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ABSTRACT: The microstructure and oxidation resistance of NbSi2 coating formed on Nb-based alloy C-103 by a pack siliconization process have been studied. The as-formed coating consists
of an outer NbSi2 layer and an inner Nb5Si3 layer. A NbSi2–Nb5Si3 two-phase zone is also present between the above two layers. Weight-change data obtained under isothermal and cyclic oxidation
in air at 1100 and 1300°C, suggests that the coating gives oxidation protection up to about 4h. The oxide scale that formed
on the coating during oxidation exposure consists of an outer glassy silica layer and an inner Nb2O5-silica mixed layer. Nb2O5 phase is also present in the outer silica scale in the form of elongated particles. Oxidation protection is achieved primarily
by the presence of the glassy silica layer on the surface. Spallation of this layer during thermal cycling causes significant
reduction in the protective life of the coating.
KeywordsSilicide-Oxidation-Coatings-Niobium alloy
Oxidation of Metals 05/2012; 73(5):513-530. · 1.40 Impact Factor
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ABSTRACT: The tensile behavior of a directionally solidified (DS) Ni-base superalloy, namely, CM-247LC, was evaluated in the presence
of a Pt-aluminide bond coat. The effect of the thermal cycling exposure of the coated alloy at 1373K (1100°C) on its tensile
properties was examined. The tensile properties were evaluated at a temperature of 1143K (870°C). The presence of the bond
coating caused an approximately 8pct drop in the strength of the alloy in the as-coated condition. However, the coating did
not appreciably affect the tensile ductility of the substrate alloy. The bond coat prevented oxidation-related surface damage
to the superalloy during thermal cycling exposure in air at 1373K (1100°C). Such cyclic oxidation exposure (up to 750hours)
did not cause any further reduction in yield strength (YS) of the coated alloy. There was a marginal decrease in the ultimate
tensile strength (UTS) with increased exposure duration. Because of the oxidation protection provided by the bond coat, the
drastic loss in ductility of the alloy, which would have happened in the absence of the coating, was prevented.
Metallurgical and Materials Transactions A 05/2012; 42(13):4064-4074. · 1.54 Impact Factor
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ABSTRACT: The formation of secondary reaction zones (SRZs) beneath aluminide coatings in several Ru-bearing single-crystal Ni-base superalloys
has been investigated. The presence of significant amounts of Ru in the superalloys did not prevent the formation of the secondary
reaction zone. However, the Ru content of the alloys affected the type of refractory element-rich phase formed during the
transformation. As the Ru content increased, the phase involved in the transformation shifted from the orthorhombic P to the
β-RuAl phase. A differential tendency to SRZ formation was observed between the dendritic and interdendritic regions of the
alloys. Significant growth of the SRZ was also observed during the high-temperature oxidation exposure of the coated alloys.
The effects of the alloying elements on SRZ formation are discussed.
Metallurgical and Materials Transactions A 04/2012; 39(7):1647-1657. · 1.54 Impact Factor
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Journal of Agricultural and Food Chemistry 03/2012; 60(10):2767. · 2.82 Impact Factor
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Journal of Agricultural and Food Chemistry 03/2012; 60(10):2768. · 2.82 Impact Factor
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Journal of Agricultural and Food Chemistry 03/2012; 60(10):2766. · 2.82 Impact Factor
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ABSTRACT: Controversy is common during efforts to define the role of nutrition in health, but few modern reflections of such controversy are as vivid as the debate over wine. There exists no query that chronic alcohol abuse, a leading worldwide problem, causes neuronal dysfunction and brain damage. However, various epidemiologic studies in recent years have indicated that in comparisons with abstainers or never drinkers, light/moderate alcohol/wine consumers have lower risks of age-dependent cognitive decline and/or dementia, including Alzheimer's disease (AD) Neurodegenerative diseases such as AD and Parkinson's (PD) diseases are defined by a progressive neuronal dysfunction and an ensuing behavioral dysfunction. Epidemiologic studies from numerous disparate populations reveal that individuals with the habit of daily moderate wine consumption enjoy significant reductions in all-cause and particularly cardiovascular and neurodegenerative mortality when compared with individuals who abstain or who drink alcohol in excess. Apart from the alcohol present in the wine, other trace compounds and polyphenolic compounds such as resveratrol naturally present in wine and grapes also exert neuroprotective and cardioprotective activities.
Frontiers in bioscience (Elite edition) 01/2012; 4:1505-12.
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ABSTRACT: Oxidative stress has been considered universally and undeniably implicated in the pathogenesis of all major diseases, including those of the cardiovascular system. Oxidative stress activate transcriptional messengers, such as nuclear factor-κB, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible damage after ischemic reperfusion, and even arrhythmia, such as atrial fibrillation. Evidence is rapidly accumulating to support the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as intracellular signaling molecules. Despite this connection between oxidative stress and cardiovascular disease (CVD), there are currently no recognized therapeutic interventions to address this important unmet need. Antioxidants that provide a broad, "upstream" approach via ROS/RNS quenching or free radical chain breaking seem an appropriate therapeutic option based on epidemiologic, dietary, and in vivo animal model data. Short-term dietary intervention trials suggest that diets rich in fruit and vegetable intake lead to improvements in coronary risk factors and reduce cardiovascular mortality. Carotenoids are such abundant, plant-derived, fat-soluble pigments that functions as antioxidants. They are stored in the liver or adipose tissue, and are lipid soluble by becoming incorporated into plasma lipoprotein particles during transport. For these reasons, carotenoids may represent one plausible mechanism by which fruits and vegetables reduce the risk of chronic diseases as cardiovascular disease (CVD). This review paper outlines the role of carotenoids in maintaining cardiac health and cardioprotection mediated by several mechanisms including redox signaling.
Molecules 01/2012; 17(4):4755-69. · 2.39 Impact Factor
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ABSTRACT: Resveratrol, a constituent of red wine, and γ-tocotrienol, a constituent of palm oil are important for cardioprotection. Although microRNAs are known regulators for genes involved in cardiac remodelling, the regulatory pathway involving microRNA has not been studied so far. We explored the cardioprotection by resveratrol, longevinex and γ-tocotrienol in ischaemia/reperfusion(I/R) model of rat and determined miRNA profile from isolated RNA. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches. Resveratrol and γ-tocotrienol, either alone or in combination, modulated the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 75 miRNAs, some of them, such as miR-21 and miR-20b (anti-angiogenic) were previously implicated in cardiac remodelling. The target genes for the highest differentially expressed miRNA include genes of various molecular functions such as TGFβ1-Smad3 signalling pathway, inflammation and their transcription factors, which may play key role in reducing I/R injury. Administration of antagomiR-20 attenuated I/R induced vascular endothelial growth factor and HIF1α level. All the interventions treated for 3 weeks lead to significant cardioprotection against ischaemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or γ-tocotrienol. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R rat. Interestingly, resveratrol and γ-tocotrienol resulted in synergestic action.
Journal of Cellular and Molecular Medicine 11/2011; 16(10):2504-17. · 4.13 Impact Factor
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ABSTRACT: Most clinical trials with vitamin E could not lower cholesterol and thus, have been deemed unsuccessful. Recently, tocotrienols, isomers of vitamin E have been found to lower LDL levels. To explore if tocotrienols could be the drug target for vitamin E, rabbits were kept on cholesterol diet for 60 days supplemented with tocotrienol-α, tocotrienol-δ, and tocotrienol-γ for the last 30 days. The serum cholesterol levels (in mmol/l) were 24.4 (tocotrienol-α), 34.9 (tocotrienol-δ), 19.8 (tocotrienol-γ) vs. 39.7 (control). Left ventricular function including aortic flow and developed pressure exhibited significantly improved recovery with tocotrienol-γ and -α, but not with tocotrienol-δ. The myocardial infarct size showed a similar pattern: 33% (tocotrienol-α), 23% (tocotrienol-γ), and 47% (tocotrienol-δ). To examine the molecular mechanisms of cardioprotective effects, gene expression profile was determined using Atlas 1.2/1.2II followed by determination of gene profiles using PedQuest 8.3 software. Based on genomic profiles, the following cholesterol-related proteins were examined: FABP, TGF-β (cholesterol suppresses TGF-β), ET-1 (increased by hypercholesterolemia), SPOT 14 (linked with hypercholesterolemia), and matrix metalloproteinase (MMP) 2 and MMP9 (cholesterol regulates MMP2 and MMP9 expression) in the heart. Consistent with the cardioprotective effects of tocotrienol-α and -γ, these two isomers reduced ET-1, decreased MMP2 and MM9, increased TGF-β and reduced SPOT 14, while tocotrienol-δ had no effects. The results of the present study demonstrate that the two isomers of tocotrienols, α and γ, render the hypercholesterolemic hearts resistant to ischemic reperfusion injury by lowering several hypercholesterolemic proteins including MMP2, MMP9, ET-1, and SPOT 14 and upregulating TGF-β.
Molecular and Cellular Biochemistry 09/2011; 360(1-2):35-45. · 2.06 Impact Factor
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Dipak K Das
Current pharmaceutical design 07/2011; 17(21):2145-6. · 4.41 Impact Factor
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ABSTRACT: The worldwide cardiovascular disease (CVD) burden has resulted in an intense interest in pharmaceutical approaches to combat this multifactorial disease. Vitamins are high-flying among natural or endogenous compounds, considered to be beneficial to human health and have become attractive targets for research. Of all the vitamins, tocopherols and tocotrienols, parent congeners in the vitamin E family, are found to be effective in decreasing mortality due to CVD. As understanding of the antioxidant effect of this vitamin evolved, tocotrienols gained eminence in recent years and researchers begun to further study the biological effects of it. Tocotrienols have several cardioprotective effects; including antagonizing the oxidation of low density lipoproteins, anti atherosclerotic, inhibiting platelet aggregation and monocyte adhesion, preventing smooth muscle proliferation and various other cardiovascular disorders. Recent studies have also revealed the molecular targets of the tocotrienols and their roles in cancer, bone resorption, diabetes and neurological diseases at both preclinical and clinical levels. The multitargeted role of tocotrienols in most degenerative diseases proves it to be an ideal candidate as a nutraceutical/pharmaceutical agent for useful exploitation.
Current pharmaceutical design 07/2011; 17(21):2170-5. · 4.41 Impact Factor
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ABSTRACT: Although eggplants are known to be part of a healthy diet, the effects of this fruit on cardioprotection are not known. The present study examined the role of raw and grilled eggplants on cardioprotection using an isolated perfusion heart model. The animals were fed freeze-dried products of either raw or grilled eggplants for 30 days. After 30 days, isolated working hearts were subjected to 30 min ischemia followed by 2 h of reperfusion. Left ventricular function was monitored, and myocardial infarct size and cardiomyocyte apoptosis were assessed. To determine the antioxidant function of eggplants, their DPPH scavenging ability were determined, and polyphenolic components, especially nasunin content, were determined. The chemical composition of raw and grilled eggplants were determined in order to examine whether grilling was associated with major changes in their composition. The results of this study demonstrated eggplants as containing potent cardioprotective compounds judging by their ability to increase left ventricular function, and reduce myocardial infarct size and cardiomyocyte apoptosis. However, there was no difference in cardioprotective ability between the raw and grilled products. The antioxidant vitamins, including vitamin A, vitamin C and β-carotene, were lower and some of the polyphenolic components, especially nasunin content, were higher in grilled eggplants, but they were unable to demonstrate better cardioprotective properties compared to the raw fruit.
Food & function. 07/2011; 2(7):395-9.
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ABSTRACT: Lipid rafts represent a sub-compartment of the plasma membrane that co-ordinate and regulate varieties of signalling processes, whereas caveolins are the integral membrane protein of the lipid raft. Recent evidence demonstrated the pivotal role of caveolins in cardioprotection against ischaemic injury, although their mechanism of action is not clear. However, new understanding of epigenetic modification during ischaemia reperfusion suggests additional targeted approaches that have not been explored before. To study the role of caveolin on epigenetic regulation, isolated mouse heart was prepared from wild-type (WT) and caveolin-1 knockout (Cav-1 KO) mouse and preconditioned them with four cyclic episodes of ischaemia/reperfusion followed by 30 min. global ischaemia and 120 min. reperfusion. We found that Cav-1 KO mouse abolished the acetylation of histone (H3 and H4) and increased the methylation of histone in the preconditioned heart. The increased histone methylation was significantly correlated with an increased level of histone methyltranferase G9a protein and increased the level of histone decaetylase (HDAC) activity. Cav-1 KO mouse also decreased the translocation of forkhead transcription factor (FOXO3a) to the nucleus and reduced the induction of the expression of SIRT-1 in the preconditioned heart. Cardioprotective property of Cav-1 was further confirmed by reduced ventricular function, increased cardiomyocyte apoptosis, increased expression of junas kinase (JNK) and Bax and decreased expression of phospho-adenosine monophosphate-activated protein kinase (AMPK), phospho-AKT and B cell lymphoma-2 (Bcl-2) in Cav-1 KO preconditioned heart. The results clearly indicate that Cav-1 induces cardioprotection through epigenetic regulation.
Journal of Cellular and Molecular Medicine 06/2011; 16(4):888-95. · 4.13 Impact Factor
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ABSTRACT: Caveolae are omega-shaped membrane invaginations present in essentially all cell types of the cardiovascular system, including endothelial cells, smooth muscle cells, macrophages, cardiac myocytes, and fibroblasts. Numerous functions have been ascribed to this omega-shaped structure. Caveolae are enriched with different signaling molecules and ion channel regulatory proteins and function both in protein trafficking and signal transduction in these cell types. Caveolins are the structural proteins that are necessary for the formation of caveola membrane domains. Mechanistically, caveolins interact with a variety of downstream signaling molecules, as, for example, Src-family tyrosine kinase, p42/44 mitogen-activated protein (MAP) kinase, and endothelial nitric oxide synthase (eNOS) and hold the signal transducers in the inactive condition until activated with proper stimulus. Caveolae are gradually acquiring increasing attention as cellular organelles contributing to the pathogenesis of several structural and functional processes including cardiac hypertrophy, atherosclerosis, and heart failure. At present, very little is known about the role of caveolae in cardiac function and dysfunction, although recent studies with caveolin knock-out mouse have shown that caveolae and caveolins play a pivotal role in various human pathobiological conditions. This review will discuss the possible role and mechanism of action of caveolae and caveolins in different cardiac diseases.
Annals of medicine 06/2011; 44(6):530-41. · 3.52 Impact Factor
