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  1. Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation.

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    Emil D Bartels

    Full Text Available Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and beta-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP; the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease.

  2. Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation

    DEFF Research Database (Denmark)

    Bartels, Emil D; Nielsen, Jan M; Hellgren, Lars I;

    2009-01-01

    Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and beta-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via...... secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism...... remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression...

  3. Breath-hold CT attenuation correction for quantitative cardiac SPECT

    OpenAIRE

    Koshino, Kazuhiro; Fukushima, Kazuhito; Fukumoto, Masaji; Sasaki, Kazunari; Moriguchi, Tetsuaki; Hori, Yuki; Zeniya, Tsutomu; Nishimura, Yoshihiro; Kiso, Keisuke; Iida, Hidehiro

    2012-01-01

    Background Attenuation correction of a single photon emission computed tomography (SPECT) image is possible using computed tomography (CT)-based attenuation maps with hybrid SPECT/CT. CT attenuation maps acquired during breath holding can be misaligned with SPECT, generating artifacts in the reconstructed images. The purpose of this study was to investigate the effects of respiratory phase during breath-hold CT acquisition on attenuation correction of cardiac SPECT imaging. Methods A series o...

  4. Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

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    Marcos Minicucci

    2016-01-01

    Full Text Available Abstract Background: Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. Objective: The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Methods: Wistar rats were distributed in four groups: Control (C, Pentoxifylline (PX, Tobacco Smoke (TS, and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. Results: TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt, and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA and citrate synthase (CS. PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. Conclusion: TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

  5. Dietary long-chain, but not medium-chain, triglycerides impair exercise performance and uncouple cardiac mitochondria in rats

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    Murray Andrew J

    2011-08-01

    Full Text Available Abstract Short-term consumption of a high-fat diet impairs exercise capacity in both rats and humans, and increases expression of the mitochondrial uncoupling protein, UCP3, in rodent cardiac and skeletal muscle via activation of the transcription factor, peroxisome proliferator-activated receptor α (PPARα. Unlike long-chain fatty acids however, medium-chain fatty acids do not activate PPARα and do not increase muscle UCP3 expression. We therefore investigated exercise performance and cardiac mitochondrial function in rats fed a chow diet (7.5% kcal from fat, a long-chain triglyceride (LCT rich diet (46% kcal from LCTs or a medium-chain triglyceride (MCT rich diet (46% kcal from MCTs. Rats fed the LCT-rich diet for 15 days ran 55% less far than they did at baseline, whereas rats fed the chow or MCT-rich diets neither improved nor worsened in their exercise capacities. Moreover, consumption of an LCT-rich diet increased cardiac UCP3 expression by 35% and decreased oxidative phosphorylation efficiency, whereas consumption of the MCT-rich diet altered neither UCP3 expression nor oxidative phosphorylation efficiency. Our results suggest that the negative effects of short-term high-fat feeding on exercise performance are predominantly mediated by long-chain rather than medium-chain fatty acids, possibly via PPARα-dependent upregulation of UCP3.

  6. CXCR4 Antagonism Attenuates the Development of Diabetic Cardiac Fibrosis.

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    Po-Yin Chu

    Full Text Available Heart failure (HF is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice or type II diabetes (Israeli Sand-rats and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach.

  7. Patient position alters attenuation effects in multipinhole cardiac SPECT

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    Timmins, Rachel; Ruddy, Terrence D.; Wells, R. Glenn, E-mail: gwells@ottawaheart.ca [Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7 (Canada)

    2015-03-15

    Purpose: Dedicated cardiac cameras offer improved sensitivity over conventional SPECT cameras. Sensitivity gains are obtained by large numbers of detectors and novel collimator arrangements such as an array of multiple pinholes that focus on the heart. Pinholes lead to variable amounts of attenuation as a source is moved within the camera field of view. This study evaluated the effects of this variable attenuation on myocardial SPECT images. Methods: Computer simulations were performed for a set of nine point sources distributed in the left ventricular wall (LV). Sources were placed at the location of the heart in both an anthropomorphic and a water-cylinder computer phantom. Sources were translated in x, y, and z by up to 5 cm from the center. Projections were simulated with and without attenuation and the changes in attenuation were compared. A LV with an inferior wall defect was also simulated in both phantoms over the same range of positions. Real camera data were acquired on a Discovery NM530c camera (GE Healthcare, Haifa, Israel) for five min in list-mode using an anthropomorphic phantom (DataSpectrum, Durham, NC) with 100 MBq of Tc-99m in the LV. Images were taken over the same range of positions as the simulations and were compared based on the summed perfusion score (SPS), defect width, and apparent defect uptake for each position. Results: Point sources in the water phantom showed absolute changes in attenuation of ≤8% over the range of positions and relative changes of ≤5% compared to the apex. In the anthropomorphic computer simulations, absolute change increased to 20%. The changes in relative attenuation caused a change in SPS of <1.5 for the water phantom but up to 4.2 in the anthropomorphic phantom. Changes were larger for axial than for transverse translations. These results were supported by SPS changes of up to six seen in the physical anthropomorphic phantom for axial translations. Defect width was also seen to significantly increase. The

  8. Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression

    Institute of Scientific and Technical Information of China (English)

    Bing-yan GUO; Yong-jun LI; Rui HAN; Shao-1ing YANG; Ying-hui SHI; De-rong HAN; Hong ZHOU; Mei WANG

    2011-01-01

    Aim:To investigate whether telmisartan(Telm)pretreatment attenuates isoproterenol(Iso)-induced postinfarction remodeling(PIR)in rats, and whether the effect of Telm is associated with cardiac expression of adiponectin.Methods:PIR was induced in male Wistar rats with two consecutive injections of Iso(80 mg/kg,sc)at an interval of 24 h.Primary Culture of ventricular myocytes from neonatal rats was prepared.Iso-induced cardiomyocyte injury was assessed based on cell growth and lactate dehydrogenase(LDH)activity.Cardiac adiponectin expression was measured using qRT-PCR and immunoblot analysis.Results:In the rats with PIR.Telm(10 mg·kg-1·d-1,po for 65 d)suppressed lso-induced increases in gravimetric parameters.cardiomyocyte diameter and collagen volume fraction,but had no effect on Iso-induced myocardial hypertrophy and interstitial fibrosis.The protective effect of Telm was associated with enhanced protein expression of cardiac adiponectin.In cultured cardiomyocytes,Telm (5-20 μmol/L)inhibited the celI death and LDH release induced by lSO(10 μmol/L).and reversed Iso-induced reduction in adiponectinprotein expression.In cardiomyocytes exposed to Iso(20 μmol/L).GW9662(30 μmol/L),a selective antagonist of PPAR-v,blocked the effects of Telm Dretreatment on adiponectin protein expression,as well as the protective effects of Telm on Iso-induced celI injUry.Conclusion:Telm attenuates Iso-induced cardiac remodeling and cell injury,which is associated with induction of cardiac adiponectin expression.

  9. Transdermal Nicotine Application Attenuates Cardiac Dysfunction after Severe Thermal Injury

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    Leif Claassen

    2015-01-01

    Full Text Available Background. Severe burn trauma leads to an immediate and strong inflammatory response inciting cardiac dysfunction that is associated with high morbidity and mortality. The aim of this study was to determine whether transdermal application of nicotine could influence the burn-induced cardiac dysfunction via its known immunomodulatory effects. Material and Methods. A standardized rat burn model was used in 35 male Sprague Dawley rats. The experimental animals were divided into a control group, a burn trauma group, a burn trauma group with additional nicotine treatment, and a sham group with five experimental animals per group. The latter two groups received nicotine administration. Using microtip catheterization, functional parameters of the heart were assessed 12 or 24 hours after infliction of burn trauma. Results. Burn trauma led to significantly decreased blood pressure (BP values whereas nicotine administration normalized BP. As expected, burn trauma also induced a significant deterioration of myocardial contractility and relaxation parameters. After application of nicotine these adverse effects were attenuated. Conclusion. The present study showed that transdermal nicotine administration has normalizing effects on burn-induced myocardial dysfunction parameters. Further research is warranted to gain insight in molecular mechanisms and pathways and to evaluate potential treatment options in humans.

  10. Variable linesource response in attenuation corrected cardiac SPECT

    International Nuclear Information System (INIS)

    Full text: Varying line source response can result in errors due to the reference scan being inappropriate. The incidence of this problem and its effect on cardiac perfusion SPECT was investigated. Acquisitions of transmission data without the bed or a patient were used to determine the variation in global sensitivity and uniformity of the transmission with respect to camera position over a period of 4 months. The average variations for various parameters were: Influence of variations in regional sensitivity on the reconstructed attenuation map and ultimately the patient study was investigated. Counts in selected sections of patient transmission images were reduced by 5 to 30 percent and then reconstructed in the patient study with iterative reconstruction for 30 iterations (Butterworth 0.66 nyquist frequency order 10). The reconstructed scans were compared to the original study which had minimal linesource misalignment and the percentage differences were calculated to determine the effect of regional sensitivity differences with angle. At the level of variation of regional sensitivity (5-10%) it was found data varied by up to 20% in portions of the patient myocardium compared to the original data. Additional line source quality control is essential and variation in transmission counts with rotation minimised. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  11. Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease.

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    Wei Zhao

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients.

  12. Cine CT for Attenuation Correction in Cardiac PET/CT

    OpenAIRE

    Alessio, Adam M.; Kohlmyer, Steve; Branch, Kelley; Chen, Grace; Caldwell, James; Kinahan, Paul

    2007-01-01

    In dual-modality PET/CT systems, the CT scan provides the attenuation map for PET attenuation correction. The current clinical practice of obtaining a single helical CT scan provides only a snapshot of the respiratory cycle, whereas PET occurs over multiple respiratory cycles. Misalignment of the attenuation map and emission image because of respiratory motion causes errors in the attenuation correction factors and artifacts in the attenuation-corrected PET image. To rectify this problem, we ...

  13. Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation

    Institute of Scientific and Technical Information of China (English)

    Yong-nan FU; Han XIAO; Xiao-wei MA; Sheng-yang JIANG; Ming XU; You-yi ZHANG

    2011-01-01

    Aim: To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect.Methods: Wild type and AMPKα2 knockout (AMPKα2-/-) littermates were subjected to left ventricular pressure overload caused by evaluated using echocardiography and anatomic and histological methods. The antihypertrophic mechanism of metformin was analyzed using Western blotting.Results: Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKx2-/- mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKα2-/-mice.Conclusion: Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.

  14. Incretin attenuates diabetes-induced damage in rat cardiac tissue.

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    AbdElmonem Elbassuoni, Eman

    2014-09-01

    Glucagon-like peptide-1 (GLP-1), as a member of the incretin family, has a role in glucose homeostasis, its receptors distributed throughout the body, including the heart. The aim was to investigate cardiac lesions following diabetes induction, and the potential effect of GLP-1 on this type of lesions and the molecular mechanism driving this activity. Adult male rats were classified into: normal, diabetic, 4-week high-dose exenatide-treated diabetic rats, 4-week low-dose exenatide-treated diabetic rats, and 1-week exenatide-treated diabetic rats. The following parameters were measured: in blood: glucose, insulin, lactate dehydrogenase (LDH), total creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), and CK-MB relative index; in cardiac tissue: lipid peroxide (LPO) and some antioxidant enzymes. The untreated diabetic group displayed significant increases in blood level of glucose, LDH, and CK-MB, and cardiac tissue LPO, and a significant decrease in cardiac tissue antioxidant enzymes. GLP-1 supplementation in diabetic rats definitely decreased the hyperglycemia and abolished the detrimental effects of diabetes on the cardiac tissue. The effect of GLP-1 on blood glucose and on the heart also appeared after a short supplementation period (1 week). It can be concluded that GLP-1 has beneficial effects on diabetes-induced oxidative cardiac tissue damage, most probably via its antioxidant effect directly acting on cardiac tissue and independent of its hypoglycemic effect. PMID:25011640

  15. Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome.

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    Gao, Ling; Cao, Jia-Tian; Liang, Yan; Zhao, Yi-Chao; Lin, Xian-Hua; Li, Xiao-Cui; Tan, Ya-Jing; Li, Jing-Yi; Zhou, Cheng-Liang; Xu, Hai-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-05-01

    Polycystic ovary syndrome (PCOS) is a complex reproductive and metabolic disorder affecting 10 % of reproductive-aged women, and is well associated with an increased prevalence of cardiovascular risk factors. However, there are few data concerning the direct association of PCOS with cardiac pathologies. The present study aims to investigate the changes in cardiac structure, function, and cardiomyocyte survival in a PCOS model, and explore the possible effect of calcitriol administration on these changes. PCOS was induced in C57BL/6J female mice by chronic dihydrotestosterone administration, as evidenced by irregular estrous cycles, obesity and dyslipidemia. PCOS mice progressively developed cardiac abnormalities including cardiac hypertrophy, interstitial fibrosis, myocardial apoptosis, and cardiac dysfunction. Conversely, concomitant administration of calcitriol significantly attenuated cardiac remodeling and cardiomyocyte apoptosis, and improved cardiac function. Molecular analysis revealed that the beneficial effect of calcitriol was associated with normalized autophagy function by increasing phosphorylation levels of AMP-activated protein kinase and inhibiting phosphorylation levels of mammalian target of rapamycin complex. Our findings provide the first evidence for the presence of cardiac remodeling in a PCOS model, and vitamin D supplementation may be a potential therapeutic strategy for the prevention and treatment of PCOS-related cardiac remodeling.

  16. Cardiac Effects of Attenuating Gsα - Dependent Signaling.

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    Marcus R Streit

    Full Text Available Inhibition of β-adrenergic signalling plays a key role in treatment of heart failure. Gsα is essential for β-adrenergic signal transduction. In order to reduce side-effects of beta-adrenergic inhibition diminishing β-adrenergic signalling in the heart at the level of Gsα is a promising option.We analyzed the influence of Gsα on regulation of myocardial function and development of cardiac hypertrophy, using a transgenic mouse model (C57BL6/J mice overexpressing a dominant negative Gsα-mutant under control of the α-MHC-promotor. Cardiac phenotype was characterized in vivo and in vitro and under acute and chronic β-adrenergic stimulation. At rest, Gsα-DN-mice showed bradycardia (602 ± 13 vs. 660 ± 17 bpm, p<0.05 and decreased dp/dtmax (5037 ± 546- vs. 6835 ± 505 mmHg/s, p = 0.02. No significant differences were found regarding ejection fraction, heart weight and cardiomyocyte size. β-blockade by propranolol revealed no baseline differences of hemodynamic parameters between wildtype and Gsα-DN-mice. Acute adrenergic stimulation resulted in decreased β-adrenergic responsiveness in Gsα-DN-mice. Under chronic adrenergic stimulation, wildtype mice developed myocardial hypertrophy associated with increase of LV/BW-ratio by 23% (4.4 ± 0.2 vs. 3.5 ± 0.1 mg/g, p<0.01 and cardiac myocyte size by 24% (14927 ± 442 px vs. 12013 ± 583 px, p<0.001. In contrast, both parameters were unchanged in Gsα-DN-mice after chronic isoproterenol stimulation.Overexpression of a dominant negative mutant of Gsα leads to decreased β-adrenergic responsiveness and is protective against isoproterenol-induced hypertrophy. Thus, Gsα-DN-mice provide novel insights into β-adrenergic signal transduction and its modulation in myocardial overload and failure.

  17. Proteasome inhibitors attenuated cholesterol-induced cardiac hypertrophy in H9c2 cells

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    Lee, Hyunjung; Park, Jinyoung; Kim, Eunice EunKyeong; Yoo, Young Sook; Song, Eun Joo

    2016-01-01

    The Ubiquitin proteasome system (UPS) plays roles in protein degradation, cell cycle control, and growth and inflammatory cell signaling. Dysfunction of UPS in cardiac diseases has been seen in many studies. Cholesterol acts as an inducer of cardiac hypertrophy. In this study, the effect of proteasome inhibitors on the cholesterol-induced hypertrophic growth in H9c2 cells is examined in order to observe whether UPS is involved in cardiac hypertrophy. The treatment of proteasome inhibitors MG132 and Bortezomib markedly reduced cellular surface area and mRNA expression of β-MHC in cholesterol-induced cardiac hypertrophy. In addition, activated AKT and ERK were significantly attenuated by MG132 and Bortezomib in cholesterol-induced cardiac hypertrophy. We demonstrated that cholesterol-induced cardiac hypertrophy was suppressed by proteasome inhibitors. Thus, regulatory mechanism of cholesterol-induced cardiac hypertrophy by proteasome inhibitors may provide a new therapeutic strategy to prevent the progression of heart failure. [BMB Reports 2016; 49(5): 270-275] PMID:26592933

  18. Montelukast attenuates lipopolysaccharide-induced cardiac injury in rats.

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    Khodir, A E; Ghoneim, H A; Rahim, M A; Suddek, G M

    2016-04-01

    This study investigates the possible protective effects of montelukast (MNT) against lipopolysaccharide (LPS)-induced cardiac injury, in comparison to dexamethasone (DEX), a standard anti-inflammatory. Male Sprague Dawley rats (160-180 g) were assigned to five groups (n = 8/group): (1) control; (2) LPS (10 mg/kg, intraperitoneal (i.p.)); (3) LPS + MNT (10 mg/kg, per os (p.o.)); (4) LPS + MNT (20 mg/kg, p.o.); and (5) LPS + DEX (1 mg/kg, i.p.). Twenty-four hours after LPS injection, heart/body weight (BW) ratio and percent survival of rats were determined. Serum total protein, creatine kinase muscle/brain (CK-MB), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities were measured. Heart samples were taken for histological assessment and for determination of malondialdehyde (MDA) and glutathione (GSH) contents. Cardiac tumor necrosis factor α (TNF-α) expression was evaluated immunohistochemically. LPS significantly increased heart/BW ratio, serum CK-MB, ALP, and LDH activities and decreased percent survival and serum total protein levels. MDA content increased in heart tissues with a concomitant reduction in GSH content. Immunohistochemical staining of heart specimens from LPS-treated rats revealed high expression of TNF-α. MNT significantly reduced percent mortality and suppressed the release of inflammatory and oxidative stress markers when compared with LPS group. Additionally, MNT effectively preserved tissue morphology as evidenced by histological evaluation. MNT (20 mg/kg) was more effective in alleviating LPS-induced heart injury when compared with both MNT (10 mg/kg) and DEX (1 mg/kg), as evidenced by decrease in positive staining by TNF-α immunohistochemically, decrease MDA, and increase GSH content in heart tissue. This study demonstrates that MNT might have cardioprotective effects against the inflammatory process during endotoxemia. This effect can be attributed to its antioxidant and/or anti-inflammatory properties. PMID:26089034

  19. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin induced cardiac injury in mice

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    Yousif Nasser

    2011-10-01

    Full Text Available Abstract Background Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin induced cardiac toxicity. Toll-like receptors (TLRs are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity. Methods Seven days after a single injection of herceptin (2 mg/kg; i.p., left ventricular pressure volume loops were measured in HeN compotent (TLR4+/+ and HeJ mutant (TLR4-/- treated with trastuzumab and control mice. Immunofluorescent staining for monocyte infiltration and analyses of plasma by (ELISAs for different chemokines including: MCP-1and tumor necrosis factor-α (TNF-α, Western immunoblotting assay for ICAM-1, and used troponin I for cardiac injury marker. Results Trastuzumab injection resulted in an impairment of left ventricular function in TLR-4 competent (HeN, in contrast TLR4-/- trastuzumab mice showed improved left ventricular function EF%, CO; p -/-; p -/-, marked reduction of myocardial troponin-I levels in TLR4-deficient mice. Data are presented as means ± SE; n = 8 in each group p Conclusions Treatment with trastuzumab induces an inflammatory response that contributes to myocardial tissue TLR4 mediates chemokine expression (TNF-α, MCP-1and ICAM-1, so in experimental animals TLR4 deficiency improves left ventricular function and attenuates pathophysiological key mechanisms in trastuzumab induced cardiomyopathy.

  20. Attenuated muscle metaboreflex-induced increases in cardiac function in hypertension.

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    Sala-Mercado, Javier A; Spranger, Marty D; Abu-Hamdah, Rania; Kaur, Jasdeep; Coutsos, Matthew; Stayer, Douglas; Augustyniak, Robert A; O'Leary, Donal S

    2013-11-15

    Sympathoactivation may be excessive during exercise in subjects with hypertension, leading to increased susceptibility to adverse cardiovascular events, including arrhythmias, infarction, stroke, and sudden cardiac death. The muscle metaboreflex is a powerful cardiovascular reflex capable of eliciting marked increases in sympathetic activity during exercise. We used conscious, chronically instrumented dogs trained to run on a motor-driven treadmill to investigate the effects of hypertension on the mechanisms of the muscle metaboreflex. Experiments were performed before and 30.9 ± 4.2 days after induction of hypertension, which was induced via partial, unilateral renal artery occlusion. After induction of hypertension, resting mean arterial pressure was significantly elevated from 98.2 ± 2.6 to 141.9 ± 7.4 mmHg. The hypertension was caused by elevated total peripheral resistance. Although cardiac output was not significantly different at rest or during exercise after induction of hypertension, the rise in cardiac output with muscle metaboreflex activation was significantly reduced in hypertension. Metaboreflex-induced increases in left ventricular function were also depressed. These attenuated cardiac responses caused a smaller metaboreflex-induced rise in mean arterial pressure. We conclude that the ability of the muscle metaboreflex to elicit increases in cardiac function is impaired in hypertension, which may contribute to exercise intolerance.

  1. Triglyceride level

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    ... page: //medlineplus.gov/ency/article/003493.htm Triglyceride level To use the sharing features on this page, ... and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Nursing; Council on the Kidney ...

  2. Carbamazepine alone and in combination with doxycycline attenuates isoproterenol-induced cardiac hypertrophy

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    Harold Ray Garner

    2010-02-01

    Full Text Available β-adrenergic signaling is involved in the development of cardiac hypertrophy (CH, justifying the use of β-blockers as a therapy to minimize and postpone the consequences of this disease. Evidence suggests that adenylate cyclase, a downstream effector of the β-adrenergic pathway, might be a therapeutic target. We examined the effects of the anti-epileptic drug carbamazepine (CBZ, an inhibitor of adenylate cyclase. In a murine cardiac hypertrophy model, carbamazepine significantly attenuates isoproteronol (ISO-induced cardiac hypertrophy. Carbamazepine also has an effect in transverse aortic banding induced cardiac hypertrophy (TAB (P=0.07. When carbamazepine was given in combination with the antibiotic doxycycline (DOX, which inhibits matrix metalloproteinases (MMPs, therapeutic outcome measured by heart weight-to-body weight and heart weight-to-tibia length ratios was improved compared to either drug alone. Additionally, the combination therapy resulted in an increase in the survival rate over a 56-day period compared to that of untreated mice with cardiac hypertrophy or either drug used alone. Moreover, in support of a role for carbamaze­pine as a β-adrenergic antagonist via cAMP inhibition, a lower heart rate and a lower level of the activated phosphorylated form of the cAMP Response Element-Binding (CREB were observed in heart extracts from mice treated with carbamazepine. Gene expression analysis identified 19 genes whose expression is significantly altered in treated animals and might be responsible for the added benefit provided by the combination therapy. These results suggest that carbamazepine acts as a β-adrenergic antagonist. Carbamazepine and doxycycline are approved by the US Food and Drug Administration (FDA as drugs that might complement medications for cardiac hypertrophy or serve as an alternative therapy to traditional β-blockers. Furthermore, these agents reproducibly impact the expression of genes that may serve as

  3. Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

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    Xiao-Bing Ji

    2015-07-01

    Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

  4. Insulin-like growth factor 1 treatment of MSCs attenuates inflammation and cardiac dysfunction following MI.

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    Guo, Jun; Zheng, Dong; Li, Wen-feng; Li, Hai-rui; Zhang, Ai-dong; Li, Zi-cheng

    2014-12-01

    It has been reported that insulin-like growth factor 1 (IGF-1) promoted migration of endothelial cells and cardiac resident progenitor cells. In the previous study, we found the time-dependent and dose-dependent effects of IGF-1 treatment on the CXCR4 expression in MSCs in vitro, but it is still not clear whether IGF-1 pretreatment of MSCs may play anti-apoptotic and anti-inflammation role in myocardial infarction. In this study, we demonstrated that IGF-1-treated MSCs' transplantation attenuate cardiac dysfunction, increase the survival of engrafted cells in the ischemic heart, decrease myocardium cells apoptosis, and inhibit protein production and gene expression of inflammation cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6. IGF-1 pretreatment of MSCs may play anti-apoptotic and anti-inflammation roles in post-myocardial infarction.

  5. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

    International Nuclear Information System (INIS)

    We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

  6. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Xiao-Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Jia, Lin-Lin; Qi, Jie; Song, Xin-Ai; Tan, Hong [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China)

    2015-05-01

    We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

  7. Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure.

    Science.gov (United States)

    Sinha-Hikim, Indrani; Shen, Ruoqing; Nzenwa, Ify; Gelfand, Robert; Mahata, Sushil K; Sinha-Hikim, Amiya P

    2011-06-01

    This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15-21 (E15-E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocycline. Pups were killed on postnatal day 15 (P15). Additional pregnant dams received twice daily IP injections of cocaine (from E15-E21) + oral administration of a relatively higher (37.5 mg/kg BW) dose of minocycline. Minocycline treatment continued from E15 until the pups were sacrificed on P15. In utero cocaine exposure resulted in an increase in oxidative stress and fetal cardiac myocyte apoptosis through activation of c-Jun-NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK)-mediated mitochondria-dependent apoptotic pathway. Continued minocycline treatment from E15 through P15 significantly prevented oxidative stress, kinase activation, perturbation of BAX/BCL-2 ratio, cytochrome c release, caspase activation, and attenuated fetal cardiac myocyte apoptosis after prenatal cocaine exposure. These results demonstrate in vivo cardioprotective effects of minocycline in preventing fetal cardiac myocyte death after prenatal cocaine exposure. Given its proven clinical safety and ability to cross the placental barrier and enter into the fetal circulation, minocycline may be an effective therapy for preventing cardiac consequences of in utero cocaine exposure. PMID:21424555

  8. Feasibility of using respiration-averaged MR images for attenuation correction of cardiac PET/MR imaging.

    Science.gov (United States)

    Ai, Hua; Pan, Tinsu

    2015-01-01

    Cardiac imaging is a promising application for combined PET/MR imaging. However, current MR imaging protocols for whole-body attenuation correction can produce spatial mismatch between PET and MR-derived attenuation data owing to a disparity between the two modalities' imaging speeds. We assessed the feasibility of using a respiration-averaged MR (AMR) method for attenuation correction of cardiac PET data in PET/MR images. First, to demonstrate the feasibility of motion imaging with MR, we used a 3T MR system and a two-dimensional fast spoiled gradient-recalled echo (SPGR) sequence to obtain AMR images ofa moving phantom. Then, we used the same sequence to obtain AMR images of a patient's thorax under free-breathing conditions. MR images were converted into PET attenuation maps using a three-class tissue segmentation method with two sets of predetermined CT numbers, one calculated from the patient-specific (PS) CT images and the other from a reference group (RG) containing 54 patient CT datasets. The MR-derived attenuation images were then used for attenuation correction of the cardiac PET data, which were compared to the PET data corrected with average CT (ACT) images. In the myocardium, the voxel-by-voxel differences and the differences in mean slice activity between the AMR-corrected PET data and the ACT-corrected PET data were found to be small (less than 7%). The use of AMR-derived attenuation images in place of ACT images for attenuation correction did not affect the summed stress score. These results demonstrate the feasibility of using the proposed SPGR-based MR imaging protocol to obtain patient AMR images and using those images for cardiac PET attenuation correction. Additional studies with more clinical data are warranted to further evaluate the method. PMID:26218995

  9. Molecular mechanism of carvedilol in attenuating the reversion to fetal energy metabolism during cardiac hypertrophy development

    Institute of Scientific and Technical Information of China (English)

    胡琴; 李隆贵

    2003-01-01

    Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdominal aorta (CAA) in male Wistar rats. Methods: Hemodynamic and ventricular remodeling parameters, free fatty acid content in the serum were measured in the experimental animals at 16 weeks after the surgical CAA, the rats receiving carvedilol intervention (CAR) after CAA, and those with sham operation (SH). The expressions of muscle carnitine palmitoyltransferaseⅠ (M-CPTⅠ) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the cardiac myocytes from every group were studied with RT-PCR. Results: Significant left ventricular hypertrophy were observed in the rats 16 weeks after coarctation operation (P<0.05), together with significant free fatty acids accumulation and downregulation of M-CPTⅠ and MCAD mRNA (P<0.05) in CAA group. Carvedilol at a dose of 30 mg/kg/d for 12 weeks inhibited the left ventricular hypertrophy induced by pressure overload and enhanced the gene expressions of rate-limiting enzyme (M-CPTⅠ) and key enzyme of fatty acid (MCAD) in the CAR group compared with CAA group (P<0.05). Conclusion: Pressure overload-induced hypertrophy in CAA rats causes the reversion back towards fetal enery metabolism, that is, downregulates the expressions of rate-limiting enzyme and key enzyme of fatty acid oxidation. The intervention therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates the reversion of the metabolic gene expression to fetal type through upregulating M-CPTⅠ and MCAD mRNA expressions. Thus, carvedilol may exert cardioprotective effects on heart failure by the mechanism of preserving the adult metabolic gene regulation.

  10. Sodium hydrosulfide attenuates hyperhomocysteinemia rat myocardial injury through cardiac mitochondrial protection.

    Science.gov (United States)

    Wang, Yuwen; Shi, Sa; Dong, Shiyun; Wu, Jichao; Song, Mowei; Zhong, Xin; Liu, Yanhong

    2015-01-01

    Hydrogen sulfide (H2S) plays an important role during rat myocardial injury. However, little is known about the role of H2S in hyperhomocysteinemia (HHcy)-induced cardiac dysfunction as well as the underlying mechanisms. In this study, we investigated whether sodium hydrosulfide (NaHS, a H2S donor) influences methionine-induced HHcy rat myocardial injury in intact rat hearts and primary neonatal rat cardiomyocytes. HHcy rats were induced by methionine (2.0 g/kg) and the daily administration of 80 μmol/L NaHS in the HHcy + NaHS treatment group. At the end of 4, 8, and 12 weeks, the ultrastructural alterations and functions of the hearts were observed using transmission electron microscopy and echocardiography system. The percentage of apoptotic cardiomyocytes, the mitochondrial membrane potential, and the production of reactive oxygen species (ROS) were measured. The expressions of cystathionine-γ-lyase (CSE), Bax and Bcl-2, caspase-3, phospho-endothelial nitric oxide synthase and the mitochondrial NOX4 and cytochrome c were analyzed by Western blotting. The results showed the cardiac dysfunction, the ultrastructural changes, and the apoptotic rate increase in the HHcy rat hearts. In the primary neonatal rat cardiomyocytes of HHcy group, ROS production was increased markedly, whereas the expression of CSE was decreased. However, treatment with NaHS significantly improved the HHcy rat hearts function, the ultrastructural changes, and decreased the levels of ROS in the primary neonatal rat cardiomyocytes administrated with HHcy group. Furthermore, NaHS down-regulated the expression of mitochondrial NOX4 and caspase-3 and Bax and inhibited the release of cytochrome c from mitochondria. In conclusion, H2S is involved in the attenuation of HHcy myocardial injury through the protection of cardiac mitochondria.

  11. Comparison of ordered subsets expectation maximization and Chang's attenuation correction method in quantitative cardiac SPET: a phantom study.

    Science.gov (United States)

    Dey, D; Slomka, P J; Hahn, L J; Kloiber, R

    1998-12-01

    Photon attenuation is one of the primary causes of artifacts in cardiac single photon emission tomography (SPET). Several attenuation correction algorithms have been proposed. The aim of this study was to compare the effect of using the ordered subsets expectation maximization (OSEM) reconstruction algorithm and Chang's non-uniform attenuation correction method on quantitative cardiac SPET. We performed SPET scans of an anthropomorphic phantom simulating normal and abnormal myocardial studies. Attenuation maps of the phantom were obtained from computed tomographic images. The SPET projection data were corrected for attenuation using OSEM reconstruction, as well as Chang's method. For each defect scan and attenuation correction method, we calculated three quantitative parameters: average radial maximum (ARM) ratio of the defect-to-normal area, maximum defect contrast (MDC) and defect volume, using automated three-dimensional quantitation. The differences between the two methods were less than 4% for defect-to-normal ARM ratio, 19% for MDC and 13% for defect volume. These differences are within the range of estimated statistical variation of SPET. The calculation times of the two methods were comparable. For all SPET studies, OSEM attenuation correction gave a more correct activity distribution, with respect to both the homogeneity of the radiotracer and the shape of the cardiac insert. The difference in uniformity between OSEM and Chang's method was quantified by segmental analysis and found to be less than 8% for the normal study. In conclusion, OSEM and Chang's attenuation correction are quantitatively equivalent, with comparable calculation times. OSEM reconstruction gives a more correct activity distribution and is therefore preferred.

  12. Celastrol-Induced Suppression of the MiR-21/ERK Signalling Pathway Attenuates Cardiac Fibrosis and Dysfunction

    Directory of Open Access Journals (Sweden)

    Mian Cheng

    2016-05-01

    Full Text Available Backgroud: Myocardial fibrosis results in myocardial remodelling and dysfunction. Celastrol, a traditional oriental medicine, has been suggested to have cardioprotective effects. However, its underlying mechanism is unknown. This study investigated the ability of celastrol to prevent cardiac fibrosis and dysfunction and explored the underlying mechanisms. Methods: Animal and cell models of cardiac fibrosis were used in this study. Myocardial fibrosis was induced by transverse aortic constriction (TAC in mice. Cardiac hypertrophy and fibrosis were evaluated based on histological and biochemical measurements. Cardiac function was evaluated by echocardiography. The levels of transforming growth factor beta 1 (TGF-β1, extracellular signal regulated kinases 1/2 (ERK1/2 signalling were measured using Western blotting, while the expression of miR-21was analyzed by real-time qRT-PCR in vitro and in vivo. In vitro studies, cultured cardiac fibroblasts (CFs were treated with TGF-β1 and transfected with microRNA-21(miR21. Results: Celastrol treatment reduced the increased collagen deposition and down-regulated α-smooth muscle actin (α-SMA, atrial natriuretic peptide (ANP, brain natriuretic peptides (BNP, beta-myosin heavy chain (β-MHC, miR-21 and p-ERK/ERK. Cardiac dysfunction was significantly attenuated by celastrol treatment in the TAC mice model. Celastrol treatment reduced myocardial fibroblast viability and collagen content and down-regulated α-SMA in cultured CFs in vitro. Celastrol also inhibited the miR-21/ERK signalling pathway. Celastrol attenuated miR-21 up-regulation by TGF-β1 and decreased elevated p-ERK/ERK levels in CFs transfected with miR-21. Conclusion: MiR-21/ERK signalling could be a potential therapeutic pathway for the prevention of myocardial fibrosis. Celastrol ameliorates myocardial fibrosis and cardiac dysfunction, these probably related to miR-21/ERK signaling pathways in vitro and in vivo.

  13. Silencing of miR-34a attenuates cardiac dysfunction in a setting of moderate, but not severe, hypertrophic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Bianca C Bernardo

    Full Text Available Therapeutic inhibition of the miR-34 family (miR-34a,-b,-c, or miR-34a alone, have emerged as promising strategies for the treatment of cardiac pathology. However, before advancing these approaches further for potential entry into the clinic, a more comprehensive assessment of the therapeutic potential of inhibiting miR-34a is required for two key reasons. First, miR-34a has ∼40% fewer predicted targets than the miR-34 family. Hence, in cardiac stress settings in which inhibition of miR-34a provides adequate protection, this approach is likely to result in less potential off-target effects. Secondly, silencing of miR-34a alone may be insufficient in settings of established cardiac pathology. We recently demonstrated that inhibition of the miR-34 family, but not miR-34a alone, provided benefit in a chronic model of myocardial infarction. Inhibition of miR-34 also attenuated cardiac remodeling and improved heart function following pressure overload, however, silencing of miR-34a alone was not examined. The aim of this study was to assess whether inhibition of miR-34a could attenuate cardiac remodeling in a mouse model with pre-existing pathological hypertrophy. Mice were subjected to pressure overload via constriction of the transverse aorta for four weeks and echocardiography was performed to confirm left ventricular hypertrophy and systolic dysfunction. After four weeks of pressure overload (before treatment, two distinct groups of animals became apparent: (1 mice with moderate pathology (fractional shortening decreased ∼20% and (2 mice with severe pathology (fractional shortening decreased ∼37%. Mice were administered locked nucleic acid (LNA-antimiR-34a or LNA-control with an eight week follow-up. Inhibition of miR-34a in mice with moderate cardiac pathology attenuated atrial enlargement and maintained cardiac function, but had no significant effect on fetal gene expression or cardiac fibrosis. Inhibition of miR-34a in mice with severe

  14. Combination of Epinephrine with Esmolol Attenuates Post-Resuscitation Myocardial Dysfunction in a Porcine Model of Cardiac Arrest

    OpenAIRE

    Qian Zhang; Chunsheng Li

    2013-01-01

    BACKGROUND: Recent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of post resuscitation myocardial dysfunction. The aim of the study was to investigate whether the short-acting β₁-selective adrenergic blocking agent, esmolol, would attenuate post resuscitation myocardial dysfunction in a porcine model of cardiac arrest. METHODS AND RESULTS: After 8 min of untreated ventricular fibrillation and 2 min of basic li...

  15. MR-based attenuation correction for cardiac FDG PET on a hybrid PET/MRI scanner: comparison with standard CT attenuation correction

    Energy Technology Data Exchange (ETDEWEB)

    Vontobel, Jan; Liga, Riccardo; Possner, Mathias; Clerc, Olivier F.; Mikulicic, Fran; Veit-Haibach, Patrick; Voert, Edwin E.G.W. ter; Fuchs, Tobias A.; Stehli, Julia; Pazhenkottil, Aju P.; Benz, Dominik C.; Graeni, Christoph; Gaemperli, Oliver; Herzog, Bernhard; Buechel, Ronny R.; Kaufmann, Philipp A. [University Hospital Zurich, Department of Nuclear Medicine, Zurich (Switzerland)

    2015-09-15

    The aim of this study was to evaluate the feasibility of attenuation correction (AC) for cardiac {sup 18}F-labelled fluorodeoxyglucose (FDG) positron emission tomography (PET) using MR-based attenuation maps. We included 23 patients with no known cardiac history undergoing whole-body FDG PET/CT imaging for oncological indications on a PET/CT scanner using time-of-flight (TOF) and subsequent whole-body PET/MR imaging on an investigational hybrid PET/MRI scanner. Data sets from PET/MRI (with and without TOF) were reconstructed using MR AC and semi-quantitative segmental (20-segment model) myocardial tracer uptake (per cent of maximum) and compared to PET/CT which was reconstructed using CT AC and served as standard of reference. Excellent correlations were found for regional uptake values between PET/CT and PET/MRI with TOF (n = 460 segments in 23 patients; r = 0.913; p < 0.0001) with narrow Bland-Altman limits of agreement (-8.5 to +12.6 %). Correlation coefficients were slightly lower between PET/CT and PET/MRI without TOF (n = 460 segments in 23 patients; r = 0.851; p < 0.0001) with broader Bland-Altman limits of agreement (-12.5 to +15.0 %). PET/MRI with and without TOF showed minimal underestimation of tracer uptake (-2.08 and -1.29 %, respectively), compared to PET/CT. Relative myocardial FDG uptake obtained from MR-based attenuation corrected FDG PET is highly comparable to standard CT-based attenuation corrected FDG PET, suggesting interchangeability of both AC techniques. (orig.)

  16. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice

    OpenAIRE

    Yousif Nasser; Al-amran Fadhil G

    2011-01-01

    Abstract Background Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin) induced cardiac toxicity. Toll-like receptors (TLRs) are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity. Methods Seven days after a single injection of herceptin (2 mg/kg; i.p.)...

  17. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway.

    Directory of Open Access Journals (Sweden)

    Chen Li

    Full Text Available Although extracellular-regulated kinases (ERK are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy.In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed.Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

  18. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway

    Science.gov (United States)

    Yang, Hao; Luo, Fangbo; Chen, Lihong; Cai, Huawei; Li, Yajiao; You, Guiying; Long, Dan; Li, Shengfu; Zhang, Qiuping; Rao, Li

    2016-01-01

    Aims Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. Methods and Results In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. Conclusions Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials. PMID:27438013

  19. Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin Ⅱ-induced cardiac diastolic dysfunction in mice

    Institute of Scientific and Technical Information of China (English)

    Yu-qiong LI; Xiao-bo LI; Shu-jie GUO; Shao-li CHU; Ping-jin GAO; Ding-liang ZHU; Wen-quan NIU

    2013-01-01

    Aim:To investigate whether apocynin,a NADPH oxidase inhibitor,produced cardioproteictive effects in Ang Ⅱ-induced hypertensive mice,and to elucidate the underlying mechanisms.Methods:C57BL/6 mice were subcutaneously infused Ang Ⅱ for 4 weeks to mimic cardiac remodeling and fibrosis.Concomitantly the mice were administered apocynin (100 mg· kg-1·d-1) or/and the aldosterone receptor blocker eplerenone (200 mg·kg-1d-1) via gavage for 4 weeks.Systolic blood pressure (SBP) and heart rate were measured,and transthoracic echocardiography was performed.For in vitro study,cardiac fibroblasts were treated with Ang Ⅱ (10 7 mol/L) in the presence of apocynin (105 mol/L) or/and eplerenone (105 mol/L).Immunohistochemistry and Western blotting were used to quantify the expression levels of NADPH oxidase and osteopontin (OPN) proteins in the cells.Results:Both apocynin and eplerenone significantly decreased SBP,and markedly improved diastolic dysfunction in Ang Ⅱ-induced hypertensive mice,accompanied with ameliorated oxidative stress and cardiac fibrosis.In the Ang Ⅱ-treated cardiac fibroblasts,the expression levels of NOX4 and OPN proteins were markedly upregulated.Both Apocynin and eplerenone significantly suppressed the increased expression levels of NOX4 and OPN proteins in the Ang Ⅱ-treated cells.In all the experiments,apocynin and eplerenone produced comparable effects.Co-administration of the two agents did not produce synergic effects.Conclusion:Apocynin produces cardioproteictive effects comparable to those of eplerenone.The beneficial effects of apocynin on myocardial oxidative stress and cardiac fibrosis might be mediated partly through a pathway involving NADPH oxidase and OPN.

  20. Intramyocardial delivery of mesenchymal stem cell-seeded hydrogel preserves cardiac function and attenuates ventricular remodeling after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Eva Mathieu

    Full Text Available BACKGROUND: To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC hydrogel seeded with MSC (MSC+hydrogel could preserve cardiac function and attenuate left ventricular (LV remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDING: Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. CONCLUSION/SIGNIFICANCE: These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium.

  1. Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

    OpenAIRE

    Lee Jung Eun; Yi Chin-ok; Jeon Byeong Tak; Shin Hyun Joo; Kim Soo Kyoung; Jung Tae Sik; Choi Jun Young; Roh Gu Seob

    2012-01-01

    Abstract Background Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA) on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF) rats. Methods Animals were se...

  2. Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

    Directory of Open Access Journals (Sweden)

    Maria E Danoviz

    Full Text Available BACKGROUND: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDINGS: 99mTc-labeled ASCs (1x10(6 cells isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C, or culture medium (ASC/M as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively. Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT and control groups (culture medium, fibrin, or collagen alone. Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW, a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. CONCLUSIONS: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.

  3. Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

    Science.gov (United States)

    Danoviz, Maria E.; Nakamuta, Juliana S.; Marques, Fabio L. N.; dos Santos, Leonardo; Alvarenga, Erica C.; dos Santos, Alexandra A.; Antonio, Ednei L.; Schettert, Isolmar T.; Tucci, Paulo J.; Krieger, Jose E.

    2010-01-01

    Background Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). Methodology/Principal Findings 99mTc-labeled ASCs (1×106 cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by γ-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8±2.0 and 26.8±2.4% vs. 4.8±0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. Conclusions We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers. PMID:20711471

  4. Adenoviral short hairpin RNA targeting phosphodiesterase 5 attenuates cardiac remodeling and cardiac dysfunction following myocardial infarction in mice

    Institute of Scientific and Technical Information of China (English)

    张健

    2014-01-01

    Objective To observe the impact of PDE5shRNA on cardiac remodeling and heart function following myocardial infarction in mice.Methods Myocardial infarction(MI)was induced in mice by left coronary artery ligation.Mice were randomly assigned to sham operation group(n=6),PDE5shRNA group(n=12),common adenovirus group(n=15)and DMEM group(n=8).Four weeks post-MI,the survival rate was evaluated.

  5. Overexpression of junctophilin-2 does not enhance baseline function but attenuates heart failure development after cardiac stress.

    Science.gov (United States)

    Guo, Ang; Zhang, Xiaoying; Iyer, Venkat Ramesh; Chen, Biyi; Zhang, Caimei; Kutschke, William J; Weiss, Robert M; Franzini-Armstrong, Clara; Song, Long-Sheng

    2014-08-19

    Heart failure is accompanied by a loss of the orderly disposition of transverse (T)-tubules and a decrease of their associations with the junctional sarcoplasmic reticulum (jSR). Junctophilin-2 (JP2) is a structural protein responsible for jSR/T-tubule docking. Animal models of cardiac stresses demonstrate that down-regulation of JP2 contributes to T-tubule disorganization, loss of excitation-contraction coupling, and heart failure development. Our objective was to determine whether JP2 overexpression attenuates stress-induced T-tubule disorganization and protects against heart failure progression. We therefore generated transgenic mice with cardiac-specific JP2 overexpression (JP2-OE). Baseline cardiac function and Ca(2+) handling properties were similar between JP2-OE and control mice. However, JP2-OE mice displayed a significant increase in the junctional coupling area between T-tubules and the SR and an elevated expression of the Na(+)/Ca(2+) exchanger, although other excitation-contraction coupling protein levels were not significantly changed. Despite similar cardiac function at baseline, overexpression of JP2 provided significantly protective benefits after pressure overload. This was accompanied by a decreased percentage of surviving mice that developed heart failure, as well as preservation of T-tubule network integrity in both the left and right ventricles. Taken together, these data suggest that strategies to maintain JP2 levels can prevent the progression from hypertrophy to heart failure. PMID:25092313

  6. Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion.Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins,Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion,enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group.Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion,expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl

  7. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    OpenAIRE

    Zhipeng Zeng; Kunwu Yu; Long Chen; Weihua Li; Hong Xiao; Zhengrong Huang

    2016-01-01

    CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significant...

  8. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Zhipeng Zeng

    2016-01-01

    Full Text Available CD4+CD25+Foxp3+ regulatory T cells (Treg cells have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI. We hypothesize that the interleukin- (IL- 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1 attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th cells among the CD4+Foxp3− T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically.

  9. Exogenous nerve growth factor supplementation elevates myocardial immunoreactivity and attenuates cardiac remodeling in pressure-overload rats

    Institute of Scientific and Technical Information of China (English)

    Bing He; and Yuming Li; Fan Ye; Xin Zhou; He Li; Xiaoqing Xun; Xiaoqing Ma; Xudong Liu; Zhihong Wang; Pengxiao Xu

    2012-01-01

    It is postulated that supplementation of exogenous nerve growth factor (NGF) might mediate improvement of the cardiac sympathetic nerve function in heart failure (HF).Local intramuscular injection of NGF near the cardiac sympathetic ganglia could influence the innervation pattern,norepinephrine transporter (NET) gene expression,and improve the cardiac remodeling in experimental HF animals.In this study,we injected NGF into the scalenus medius muscles of Sprague-Dawley rats with abdominal aortic constriction (AC).The nerve innervated pattern,left ventricular morphology,and function following injection in rats with AC were investigated respectively by immunohistochemistry and echocardiography.Levels of mRNA expression of NET,growth associated protein 43 (GAP 43),NGF and its receptors TrkA and p75NTR,and brain natriuretic peptide (BNP) were measured by realtime polymerase chain reaction.The results showed that myocardial NGF mRNA levels were comparable in rats with AC.Short-term supplementation of exogenous NGF raised the myocardial NGF immunoreactivity,but did not cause hyperinnervation and NET mRNA upregulation in the AC rats.Furthermore,myocardial TrkA mRNA was found to be remarkably decreased and p75NTR mRNA was increased.Myocardial TrkA downregulation may play a beneficial effect for avoiding the hyperinnervation,and it is reasonable to postulate that p75NTR can function as an NGF receptor in the absence of TrkA.Interestingly,local NGF administration into the neck muscles near the ganglia could attenuate cardiac remodeling and downregulate BNP mRNA.These results suggest that exogenous NGF can reach the target tissue along the axons anterogradely,and improve the cardiac remodeling.

  10. Inhibition of CaMKII does not attenuate cardiac hypertrophy in mice with dysfunctional ryanodine receptor.

    Directory of Open Access Journals (Sweden)

    Asima Chakraborty

    Full Text Available In cardiac muscle, the release of calcium ions from the sarcoplasmic reticulum through ryanodine receptor ion channels (RyR2s leads to muscle contraction. RyR2 is negatively regulated by calmodulin (CaM and by phosphorylation of Ca2+/CaM-dependent protein kinase II (CaMKII. Substitution of three amino acid residues in the CaM binding domain of RyR2 (RyR2-W3587A/L3591D/F3603A, RyR2ADA impairs inhibition of RyR2 by CaM and results in cardiac hypertrophy and early death of mice carrying the RyR2ADA mutation. To test the cellular function of CaMKII in cardiac hypertrophy, mutant mice were crossed with mice expressing the CaMKII inhibitory AC3-I peptide or the control AC3-C peptide in the myocardium. Inhibition of CaMKII by AC3-I modestly reduced CaMKII-dependent phosphorylation of RyR2 at Ser-2815 and markedly reduced CaMKII-dependent phosphorylation of SERCA2a regulatory subunit phospholamban at Thr-17. However the average life span and heart-to-body weight ratio of Ryr2ADA/ADA mice expressing the inhibitory peptide were not altered compared to control mice. In Ryr2ADA/ADA homozygous mice, AC3-I did not alter cardiac morphology, enhance cardiac function, improve sarcoplasmic reticulum Ca2+ handling, or suppress the expression of genes implicated in cardiac remodeling. The results suggest that CaMKII was not required for the rapid development of cardiac hypertrophy in Ryr2ADA/ADA mice.

  11. A novel method for incorporating respiratory-matched attenuation correction in the motion correction of cardiac PET-CT studies

    Science.gov (United States)

    McQuaid, Sarah J.; Lambrou, Tryphon; Hutton, Brian F.

    2011-05-01

    Mismatches between PET and CT datasets due to respiratory effects can lead to artefactual perfusion defects. To overcome this, we have proposed a method of aligning a single CT with each frame of a gated PET study in a semi-automatic manner, incorporating a statistical shape model of the diaphragm and a rigid registration of the heart. This ensures that the structures that could influence the appearance of the reconstructed cardiac activity are correctly matched between emission and transmission datasets. When tested on two patient studies, it was found in both cases that attenuation correction using the proposed technique resulted in PET images that were closer to the gold standard of attenuation correction with a gated CT, compared with scenarios where only heart matching was considered (and not the diaphragm) or where no transformation was performed (i.e. where a single CT frame was used to attenuation-correct all PET frames). These preliminary results suggest that diaphragm matching between PET and CT improves the quantitative accuracy of reconstructed PET images and that the proposed method of using a statistical shape model to describe the diaphragm shape and motion, in combination with a rigid registration to determine respiratory-induced heart motion, is a feasible method of achieving this.

  12. Combination of epinephrine with esmolol attenuates post-resuscitation myocardial dysfunction in a porcine model of cardiac arrest.

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    Full Text Available BACKGROUND: Recent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of post resuscitation myocardial dysfunction. The aim of the study was to investigate whether the short-acting β₁-selective adrenergic blocking agent, esmolol, would attenuate post resuscitation myocardial dysfunction in a porcine model of cardiac arrest. METHODS AND RESULTS: After 8 min of untreated ventricular fibrillation and 2 min of basic life support, 24 pigs were randomized to three groups (n = 8 per group, which received central venous injection of either epinephrine combined with esmolol (EE group, epinephrine (EP group, or saline (SA group. Hemodynamic status and blood samples were obtained at 0, 30, 60, 120, 240 and 360 min after return of spontaneous circulation (ROSC. Surviving pigs were euthanatized at 24 h after ROSC, and the hearts were removed for analysis by electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay. Compared with the EP and SA groups, EE group had a better outcome in hemodynamic function, (improved dp/dt maxima and minima and cardiac output (P<0.05, and improved oxygen metabolism (oxygen delivery and oxygen consumption (P<0.05, which suggesting that EE can protect myocardial tissue from injury and improve post-resuscitation myocardial dysfunction. The protective effect of EE also correlated with reducing cardiomyocyte apoptosis, evidenced by reducing TUNEL-positive cells, increasing anti-apoptotic Bcl-2/Bax ratio and suppression of caspase-3 activity in myocardium. CONCLUSIONS: Esmolol, a short-acting β₁-selective adrenergic blocking agent, given during CPR has significant effects on attenuating post resuscitation myocardial dysfunction. The current study provides a potential pharmacologic target for post resuscitation myocardial dysfunction.

  13. Desmodium gangeticum root extract attenuates isoproterenol-induced cardiac hypertrophic growth in rats.

    OpenAIRE

    Divya Hitler; Parthasarathy Arumugam; Mathivanan Narayanasamy; Elangovan Vellaichamy

    2014-01-01

    Context: Desmodium gangeticum (L) DC (Fabaceae; DG), a medicinal plant that grows in tropical habitats, is widely used to treat various ailments including digestive and inflammatory disorders. Aims: To investigate the possible cardioprotective activity of a DG root extract against isoproterenol (ISO)-induced left ventricular cardiac hypertrophy (LVH) in adult Wistar rats. Methods: Daily intraperitoneal administration of ISO (10 mg/kg body weight, single injection) for 7 days induced LVH...

  14. Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

    Directory of Open Access Journals (Sweden)

    Lee Jung Eun

    2012-09-01

    Full Text Available Abstract Background Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF rats. Methods Animals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry. Results Western blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1 and connective tissue growth factor (CTGF were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA. Conclusions ALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.

  15. Mitochondria-targeted ROS scavenger improves post-ischemic recovery of cardiac function and attenuates mitochondrial abnormalities in aged rats.

    Science.gov (United States)

    Escobales, Nelson; Nuñez, Rebeca E; Jang, Sehwan; Parodi-Rullan, Rebecca; Ayala-Peña, Sylvette; Sacher, Joshua R; Skoda, Erin M; Wipf, Peter; Frontera, Walter; Javadov, Sabzali

    2014-12-01

    Mitochondria-generated reactive oxygen species (ROS) play a crucial role in the pathogenesis of aging and age-associated diseases. In this study, we evaluated the effects of XJB-5-131 (XJB), a mitochondria-targeted ROS and electron scavenger, on cardiac resistance to ischemia-reperfusion (IR)-induced oxidative stress in aged rats. Male adult (5-month old, n=17) and aged (29-month old, n=19) Fischer Brown Norway (F344/BN) rats were randomly assigned to the following groups: adult (A), adult+XJB (AX), aged (O), and aged+XJB (OX). XJB was administered 3 times per week (3mg/kg body weight, IP) for four weeks. At the end of the treatment period, cardiac function was continuously monitored in excised hearts using the Langendorff technique for 30 min, followed by 20 min of global ischemia, and 60-min reperfusion. XJB improved post-ischemic recovery of aged hearts, as evidenced by greater left ventricular developed-pressures and rate-pressure products than the untreated, aged-matched group. The state 3 respiration rates at complexes I, II and IV of mitochondria isolated from XJB-treated aged hearts were 57% (P<0.05), 25% (P<0.05) and 28% (P<0.05), respectively, higher than controls. Ca(2+)-induced swelling, an indicator of permeability transition pore opening, was reduced in the mitochondria of XJB-treated aged rats. In addition, XJB significantly attenuated the H2O2-induced depolarization of the mitochondrial inner membrane as well as the total and mitochondrial ROS levels in cultured cardiomyocytes. This study underlines the importance of mitochondrial ROS in aging-induced cardiac dysfunction and suggests that targeting mitochondrial ROS may be an effective therapeutic approach to protect the aged heart against IR injury. PMID:25451170

  16. Low-dose interpolated average CT for attenuation correction in cardiac PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tung-Hsin [Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taiwan (China); Zhang, Geoffrey [Department of Radiation Oncology, Moffitt Cancer Center, Florida (United States); Wang, Shyh-Jen [Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taiwan (China); Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Chen, Chih-Hao [Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Yang, Bang-Hung [Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taiwan (China); Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Wu, Nien-Yun [Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Huang, Tzung-Chi, E-mail: tzungchi.huang@mail.cmu.edu.t [Department of Biomedical Imaging and Radiological Science, China Medical University, Taiwan (China)

    2010-07-21

    Because of the advantages in the use of high photon flux and thus the short scan times of CT imaging, the traditional {sup 68}Ge scans for positron emission tomography (PET) image attenuation correction have been replaced by CT scans in the modern PET/CT technology. The combination of fast CT scan and slow PET scan often causes image misalignment between the PET and CT images due to respiration motion. Use of the average CT derived from cine CT images is reported to reduce such misalignment. However, the radiation dose to patients is higher with cine CT scans. This study introduces a method that uses breath-hold CT images and their interpolations to generate the average CT for PET image attenuation correction. Breath-hold CT sets are taken at end-inspiration and end-expiration. Deformable image registration is applied to generate a voxel-to-voxel motion matrix between the two CT sets. The motion is equally divided into 5 steps from inspiration to expiration and 5 steps from expiration to inspiration, generating a total of 8 phases of interpolated CT sets. An average CT image is generated from all the 10 phase CT images, including original inhale/exhale CT and 8 interpolated CT sets. Quantitative comparison shows that the reduction of image misalignment artifacts using the average CT from the interpolation technique for PET attenuation correction is at a similar level as that using cine average CT, while the dose to the patient from the CT scans is reduced significantly. The interpolated average CT method hence provides a low dose alternative to cine CT scans for PET attenuation correction.

  17. Low-dose interpolated average CT for attenuation correction in cardiac PET/CT

    International Nuclear Information System (INIS)

    Because of the advantages in the use of high photon flux and thus the short scan times of CT imaging, the traditional 68Ge scans for positron emission tomography (PET) image attenuation correction have been replaced by CT scans in the modern PET/CT technology. The combination of fast CT scan and slow PET scan often causes image misalignment between the PET and CT images due to respiration motion. Use of the average CT derived from cine CT images is reported to reduce such misalignment. However, the radiation dose to patients is higher with cine CT scans. This study introduces a method that uses breath-hold CT images and their interpolations to generate the average CT for PET image attenuation correction. Breath-hold CT sets are taken at end-inspiration and end-expiration. Deformable image registration is applied to generate a voxel-to-voxel motion matrix between the two CT sets. The motion is equally divided into 5 steps from inspiration to expiration and 5 steps from expiration to inspiration, generating a total of 8 phases of interpolated CT sets. An average CT image is generated from all the 10 phase CT images, including original inhale/exhale CT and 8 interpolated CT sets. Quantitative comparison shows that the reduction of image misalignment artifacts using the average CT from the interpolation technique for PET attenuation correction is at a similar level as that using cine average CT, while the dose to the patient from the CT scans is reduced significantly. The interpolated average CT method hence provides a low dose alternative to cine CT scans for PET attenuation correction.

  18. Low-dose interpolated average CT for attenuation correction in cardiac PET/CT

    Science.gov (United States)

    Wu, Tung-Hsin; Zhang, Geoffrey; Wang, Shyh-Jen; Chen, Chih-Hao; Yang, Bang-Hung; Wu, Nien-Yun; Huang, Tzung-Chi

    2010-07-01

    Because of the advantages in the use of high photon flux and thus the short scan times of CT imaging, the traditional 68Ge scans for positron emission tomography (PET) image attenuation correction have been replaced by CT scans in the modern PET/CT technology. The combination of fast CT scan and slow PET scan often causes image misalignment between the PET and CT images due to respiration motion. Use of the average CT derived from cine CT images is reported to reduce such misalignment. However, the radiation dose to patients is higher with cine CT scans. This study introduces a method that uses breath-hold CT images and their interpolations to generate the average CT for PET image attenuation correction. Breath-hold CT sets are taken at end-inspiration and end-expiration. Deformable image registration is applied to generate a voxel-to-voxel motion matrix between the two CT sets. The motion is equally divided into 5 steps from inspiration to expiration and 5 steps from expiration to inspiration, generating a total of 8 phases of interpolated CT sets. An average CT image is generated from all the 10 phase CT images, including original inhale/exhale CT and 8 interpolated CT sets. Quantitative comparison shows that the reduction of image misalignment artifacts using the average CT from the interpolation technique for PET attenuation correction is at a similar level as that using cine average CT, while the dose to the patient from the CT scans is reduced significantly. The interpolated average CT method hence provides a low dose alternative to cine CT scans for PET attenuation correction.

  19. A knowledge-based method for reducing attenuation artefacts caused by cardiac appliances in myocardial PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Hamill, James J [Siemens Medical Solutions, Molecular Imaging, 810 Innovation Dr., Knoxville, TN (United States); Brunken, Richard C [Department of Molecular and Functional Imaging, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH (United States); Bybel, Bohdan [Department of Molecular and Functional Imaging, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH (United States); DiFilippo, Frank P [Department of Molecular and Functional Imaging, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH (United States); Faul, David D [Siemens Medical Solutions, Molecular Imaging, 810 Innovation Dr., Knoxville, TN (United States)

    2006-06-07

    Attenuation artefacts due to implanted cardiac defibrillator leads have previously been shown to adversely impact cardiac PET/CT imaging. In this study, the severity of the problem is characterized, and an image-based method is described which reduces the resulting artefact in PET. Automatic implantable cardioverter defibrillator (AICD) leads cause a moving-metal artefact in the CT sections from which the PET attenuation correction factors (ACFs) are derived. Fluoroscopic cine images were measured to demonstrate that the defibrillator's highly attenuating distal shocking coil moves rhythmically across distances on the order of 1 cm. Rhythmic motion of this magnitude was created in a phantom with a moving defibrillator lead. A CT study of the phantom showed that the artefact contained regions of incorrect, very high CT values and adjacent regions of incorrect, very low CT values. The study also showed that motion made the artefact more severe. A knowledge-based metal artefact reduction method (MAR) is described that reduces the magnitude of the error in the CT images, without use of the corrupted sinograms. The method modifies the corrupted image through a sequence of artefact detection procedures, morphological operations, adjustments of CT values and three-dimensional filtering. The method treats bone the same as metal. The artefact reduction method is shown to run in a few seconds, and is validated by applying it to a series of phantom studies in which reconstructed PET tracer distribution values are wrong by as much as 60% in regions near the CT artefact when MAR is not applied, but the errors are reduced to about 10% of expected values when MAR is applied. MAR changes PET image values by a few per cent in regions not close to the artefact. The changes can be larger in the vicinity of bone. In patient studies, the PET reconstruction without MAR sometimes results in anomalously high values in the infero-septal wall. Clinical performance of MAR is assessed by

  20. Dasatinib Attenuates Pressure Overload Induced Cardiac Fibrosis in a Murine Transverse Aortic Constriction Model.

    Directory of Open Access Journals (Sweden)

    Sundaravadivel Balasubramanian

    Full Text Available Reactive cardiac fibrosis resulting from chronic pressure overload (PO compromises ventricular function and contributes to congestive heart failure. We explored whether nonreceptor tyrosine kinases (NTKs play a key role in fibrosis by activating cardiac fibroblasts (CFb, and could potentially serve as a target to reduce PO-induced cardiac fibrosis. Our studies were carried out in PO mouse myocardium induced by transverse aortic constriction (TAC. Administration of a tyrosine kinase inhibitor, dasatinib, via an intraperitoneally implanted mini-osmotic pump at 0.44 mg/kg/day reduced PO-induced accumulation of extracellular matrix (ECM proteins and improved left ventricular geometry and function. Furthermore, dasatinib treatment inhibited NTK activation (primarily Pyk2 and Fak and reduced the level of FSP1 positive cells in the PO myocardium. In vitro studies using cultured mouse CFb showed that dasatinib treatment at 50 nM reduced: (i extracellular accumulation of both collagen and fibronectin, (ii both basal and PDGF-stimulated activation of Pyk2, (iii nuclear accumulation of Ki67, SKP2 and histone-H2B and (iv PDGF-stimulated CFb proliferation and migration. However, dasatinib did not affect cardiomyocyte morphologies in either the ventricular tissue after in vivo administration or in isolated cells after in vitro treatment. Mass spectrometric quantification of dasatinib in cultured cells indicated that the uptake of dasatinib by CFb was greater that that taken up by cardiomyocytes. Dasatinib treatment primarily suppressed PDGF but not insulin-stimulated signaling (Erk versus Akt activation in both CFb and cardiomyocytes. These data indicate that dasatinib treatment at lower doses than that used in chemotherapy has the capacity to reduce hypertrophy-associated fibrosis and improve ventricular function.

  1. Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure

    OpenAIRE

    Sinha-Hikim, Indrani; Shen, Ruoqing; Nzenwa, Ify; GELFAND, ROBERT; Mahata, Sushil K.; Sinha-Hikim, Amiya P.

    2011-01-01

    This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15–21 (E15–E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocyc...

  2. Triglycerides and cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Varbo, Anette

    2014-01-01

    After the introduction of statins, clinical emphasis first focussed on LDL cholesterol-lowering, then on the potential for raising HDL cholesterol, with less focus on lowering triglycerides. However, the understanding from genetic studies and negative results from randomised trials that low HDL...... cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides. This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride......-rich lipoproteins as an additional cause of cardiovascular disease and all-cause mortality. Triglycerides can be measured in the non-fasting or fasting states, with concentrations of 2-10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk...

  3. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Suo, Yu-Ping [Department of Obstetrics and Gynecology, Shanxi Provincial People' s Hospital, Taiyuan 030012 (China); Yue, Li-Ying [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China)

    2014-02-01

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

  4. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

  5. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xin-Ai; Jia, Lin-Lin [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Meng [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Yuan, Zu-Yi [Department of Cardiovascular Medicine, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Guo, Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Li, Hui-Hua [Key Laboratory of Remodeling-related Cardiovascular Diseases, Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Liu, Hao, E-mail: haoliu75@163.com [Department of Neurosurgery, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-11-15

    We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

  6. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    International Nuclear Information System (INIS)

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

  7. Respective roles of scatter, attenuation, depth-dependent collimator response and finite spatial resolution in cardiac single-photon emission tomography quantitation: a Monte Carlo study

    Energy Technology Data Exchange (ETDEWEB)

    El Fakhri, G.N.; Buvat, I.; Pelegrini, M.; Benali, H.; Todd-Pokropek, A.; Paola, R. di [Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Necker, 75 - Paris (France); Almeida, P.; Bendriem, B. [SHFJ, Groupe Instrumentation PET/SPET, Orsay (France)

    1999-05-01

    The purpose of this study was to investigate the relative influence of scatter, attenuation, depth-dependent collimator response and finite spatial resolution upon the image characteristics in cardiac single-photon emission tomography (SPET). An acquisition of an anthropomorphic cardiac phantom was performed together with corresponding SPET Monte Carlo simulations. The cardiac phantom and the Monte Carlo simulations were designed so that the effect of scatter, attenuation, depth-dependent collimator response and finite spatial resolution could be studied individually and in combination. The impact of each physical effect and of combinations of effects was studied in terms of absolute and relative quantitative accuracy, spatial resolution and signal-to-noise ratio (SNR) in the resulting images. No corrections for these effects were assessed. Results obtained from Monte Carlo simulations and real acquisitions were in excellent agreement. Attenuation introduced about 90% activity underestimation in a 10-mm-thick left ventricle wall while finite spatial resolution alone introduced about 30% activity underestimation. Scatter had a negligible impact on quantitative accuracy in the recontructed slices when attenuation was present. Neither bull`s eye map homogeneity nor contrast between a hot and a cold region were affected by depth-dependent collimator response or finite spatial resolution. Bull`s eye map homogeneity was severely affected by attenuation but not by scatter. Attenuation and scatter reduced contrast by about 20% each. Both attenuation and scatter increased the full-width at half-maximum (FWHM) characterizing the spatial resolution of the imaging system by {approx}1 mm each but the main effect responsible for the observed 11-mm FWHM spatial resolution was the depth-dependent collimator response. SNR was reduced by a factor of {approx}2.5 because of attenuation, while scattered counts increased SNR by {approx}10%. In conclusion, the quantification of the

  8. Long-Lived αMUPA Mice Show Attenuation of Cardiac Aging and Leptin-Dependent Cardioprotection.

    Directory of Open Access Journals (Sweden)

    Esther Levy

    Full Text Available αMUPA transgenic mice spontaneously consume less food compared with their wild type (WT ancestors due to endogenously increased levels of the satiety hormone leptin. αMUPA mice share many benefits with mice under caloric restriction (CR including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of αMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, αMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while αMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in αMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in αMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin abrogated the αMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the αMUPA myocardium. αMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of αMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in αMUPA mice, indicating the attenuation of cardiac aging. αMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR.

  9. Prostaglandins attenuate cardiac contractile dysfunction produced by free radical generation but not by hydrogen peroxide.

    Science.gov (United States)

    Zimmer, K M; Karmazyn, M

    1997-11-01

    The aim of this study was to examine and compare the potential influence of cyclooxygenase or lipoxygenase derived metabolites of arachidonic acid on myocardial injury produced either by a free radical generating system consisting of purine plus xanthine oxidase or that produced by hydrogen peroxide. A free radical generating system consisting of purine (2.3 mM) and xanthine oxidase (10 U/L) as well as hydrogen peroxide (75 microM) produced significant functional changes in the absence of either significant deficits in high energy phosphates or ultrastructural damage. Prostaglandin F2 alpha (30 nM) significantly attenuated both the negative inotropic effect of purine plus xanthine oxidase as well as the ability of the free radical generator to elevate diastolic pressure. An identical concentration of prostaglandin 12 (prostacyclin) significantly reduced diastolic pressure elevation only and had no effect on contractile depression. The salutary effects of the two PGs occurred in the absence of any inhibitory influence on superoxide anion generation produced by the purine and xanthine oxidase reaction. None of prostaglandins modulated the response to hydrogen peroxide. In addition, neither prostaglandin E2 nor leukotrienes exerted any effect on changes produced by either type of oxidative stress. A 5 fold elevation in the concentrations of free radical generators or hydrogen peroxide produced extensive injury as characterized by a virtual total loss in contractility, 400% elevation in diastolic pressure, ultrastructural damage and significant depletions in high energy phosphate content. None of these effects were modulated by eicosanoid treatment. Our results therefore demonstrate a selective ability of both prostaglandin F2 alpha and to a lesser extent prostacyclin, to attenuate dysfunction produced by purine plus xanthine oxidase but not hydrogen peroxide. It is possible that these eicosanoids may represent endogenous protective factors under conditions of enhanced

  10. Minocycline attenuates brain tissue levels of TNF-α produced by neurons after prolonged hypothermic cardiac arrest in rats

    Science.gov (United States)

    Drabek, Tomas; Janata, Andreas; Wilson, Caleb D.; Stezoski, Jason; Janesko-Feldman, Keri; Tisherman, Samuel A.; Foley, Lesley M.; Verrier, Jonathan; Kochanek, Patrick M.

    2014-01-01

    Neuro-cognitive disabilities are a well-recognized complication of hypothermic circulatory arrest. We and others have reported that prolonged cardiac arrest (CA) produces neuronal death and microglial proliferation and activation that are only partially mitigated by hypothermia. Microglia, and possibly other cells, are suggested to elaborate tumor necrosis factor alpha (TNF-α) which can trigger neuronal death cascades and exacerbate edema after CNS insults. Minocycline is neuroprotective in some brain ischemia models in part by blunting the microglial response. We tested the hypothesis that minocycline would attenuate neuroinflammation as reflected by brain tissue levels of TNF-α after hypothermic CA in rats. Rats were subjected to rapid exsanguination, followed by a 6 min normothermic CA. Hypothermia (30 °C) was then induced by an aortic saline flush. After a total of 20 min CA, resuscitation was achieved via cardiopulmonary bypass (CPB). After 5 min reperfusion, minocycline (90 mg/kg; n=6) or vehicle (PBS; n=6) were given. Hypothermia (34 °C) was maintained for 6 h. Rats were sacrificed at 6 or 24 h. TNF-α was quantified (ELISA) in four brain regions (cerebellum, CEREB; cortex, CTX; hippocampus, HIP; striatum, STRI). Naïve rats (n=6) and rats subjected to the same anesthesia and CPB but no CA served as controls (n=6). Immunocytochemistry was used to localize TNF-α. Naïve rats and CPB controls had no detectable TNF-α in any brain region. CA markedly increased brain TNF-α. Regional differences were seen, with the highest TNF-α levels in striatum in CA groups (10-fold higher, P<0.05 vs. all other brain regions). TNF-α was undetectable at 24 h. Minocycline attenuated TNF-α levels in CTX, HIP and STRI (P<0.05). TNF-α showed unique co-localization with neurons. In conclusion, we report region-dependent early increases in brain TNF-α levels after prolonged hypothermic CA, with maximal increases in striatum. Surprisingly, TNF-α co-localized in neurons and

  11. Arsenic trioxide attenuated the rejection of major histocompatibility complex fully-mismatched cardiac allografts in mice.

    Science.gov (United States)

    Yan, S; Zhang, Q Y; Zhou, B; Xue, L; Chen, H; Wang, Y; Zheng, S S

    2009-06-01

    We investigated the effects of arsenic trioxide (As(2)O(3)) on allogeneic immune response using a mouse heart transplantation model. Mice were randomly divided into 4 groups of 6 animals each. The control group received phosphate-buffered saline (PBS); the As(2)O(3)-treated group, intraperitoneal (IP) injection of As(2)O(3) (1 mg/kg) from days -3 to 10 after heart transplantation. The cyclosporine (CsA)-treated group was given a subtherapeutic dose of CsA (10 mg/kg) IP, and the As(2)O(3) plus CsA-treated group, a combined protocol of As(2)O(3) and CsA. Six days after transplantation, cardiac allografts were harvested for immunohistology and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The survival of the allografts was significantly improved among the As(2)O(3)-treated group compared with the control group (17.2 +/- 1.9 vs 8.0 +/- 0.9 days; P < .05). A marked prolongation (28.6 +/- 6.0 days) of graft survival was achieved by the combined protocol compared with the CsA-treated group (9.6 +/- 3.0 days; P < .05) or the As(2)O(3)-treated group. Allografts of As(2)O(3)-treated and As(2)O(3) plus CsA-treated mice showed a changing pattern of Th1/Th2 cytokine mRNA expression. Allograft rejection was apparently alleviated by low-dose As(2)O(3), and particularly when combined with a subtherapeutic CsA dose. PMID:19545743

  12. Desmodium gangeticum root extract attenuates isoproterenol-induced cardiac hypertrophic growth in rats.

    Directory of Open Access Journals (Sweden)

    Divya Hitler

    2014-10-01

    Full Text Available Context: Desmodium gangeticum (L DC (Fabaceae; DG, a medicinal plant that grows in tropical habitats, is widely used to treat various ailments including digestive and inflammatory disorders. Aims: To investigate the possible cardioprotective activity of a DG root extract against isoproterenol (ISO-induced left ventricular cardiac hypertrophy (LVH in adult Wistar rats. Methods: Daily intraperitoneal administration of ISO (10 mg/kg body weight, single injection for 7 days induced LVH in rats. The LVH rats were post-treated orally with DG (100 mg/kg body weight for a period of 30 days. Thereafter, changes in heart weight (HW and body weight (BW, HW/BW ratio, percent of hypertrophy, collagen accumulation, activities of matrix metalloproteinase (MMP -2 and -9, superoxide dismutase (SOD and catalase (CAT enzymes, and the level of an oxidative stress marker, lipid peroxide (LPO, were determined. Results: HW/BW ratio, an indicator of hypertrophic growth, was significantly reduced in DG root post-treated LVH rats as compared with that for the non-treated LVH rats. The altered levels of ventricular LPO, collagen, MMPs-2 and -9, and antioxidant enzymes in the ISO-treated animals reverted back to near normal upon DG treatment. Further, the anti-hypertrophic activity of DG was comparable to that of the standard drug losartan (10 mg/kg. Conclusions: The results of the present study suggest that the aqueous root extract of DG exhibited anti-hypertrophic activity in-vivo by inhibiting ISO-induced ROS generation and MMP activities.

  13. Ablation of C/EBP homologous protein increases the acute phase mortality and doesn't attenuate cardiac remodeling in mice with myocardial infarction.

    Science.gov (United States)

    Luo, Guangjin; Li, Qingman; Zhang, Xiajun; Shen, Liang; Xie, Jiahe; Zhang, Jingwen; Kitakaze, Masafumi; Huang, Xiaobo; Liao, Yulin

    2015-08-14

    Endoplasmic reticulum stress is a proapoptotic and profibrotic stimulus. Ablation of C/EBP homologous protein (CHOP) is reported to reverse cardiac dysfunction by attenuating cardiac endoplasmic reticulum stress in mice with pressure overload or ischemia/reperfusion, but it is unclear whether loss of CHOP also inhibits cardiac remodeling induced by permanent-infarction. In mice with permanent ligation of left coronary artery, we found that ablation of CHOP increased the acute phase mortality. For the mice survived to 4 weeks, left ventricular anterior (LV) wall thickness was larger in CHOP knockout mice than in the wildtype littermates, while no difference was noted on posterior wall thickness, LV dimensions, LV fractional shortening and ejection fraction. Similarly, invasive assessment of LV hemodynamics, morphological analysis of heart and lung weight indexes, myocardial fibrosis and TUNEL-assessed apoptosis showed no significant differences between CHOP knockout mice and their wildtype ones, while in mice with ischemia for 45 min and reperfusion for 1 week, myocardial fibrosis and apoptosis in the infarct area were significantly attenuated in CHOP knockout mice. These findings indicate that ablation of CHOP doesn't ameliorate cardiac remodeling induced by permanent-myocardial infarction, which implicates that early reperfusion is a prerequisite for ischemic myocardium to benefit from CHOP inhibition.

  14. Cardiac Shock Wave Therapy Attenuates H9c2 Myoblast Apoptosis by Activating the AKT Signal Pathway

    Directory of Open Access Journals (Sweden)

    Weiwei Yu

    2014-04-01

    Full Text Available Background: Previous studies have demonstrated that Cardiac Shock Wave Therapy (CSWT improves myocardial perfusion and cardiac function in a porcine model of chronic myocardial ischemia and also ameliorates myocardial ischemia in patients with severe coronary artery disease (CAD. Apoptosis plays a key role in ischemic myocardial pathogenesis. However, it remains unclear whether CSWT is beneficial for ischemia/hypoxia (I/H-induced myocardial cell apoptosis and by which mechanism CSWT could improve heart function. We put forward the hypothesis that CSWT might protect heart function during ischemia/hypoxia by decreasing apoptosis. Methods: We generated ischemia/hypoxia (I/H-induced apoptosis in the H9c2 myoblast cell line to examine the CSWT function and possible mechanisms. H9c2 cells were treated under hypoxic serum-starved conditions for 24 h and then treated with or without CSWT (500 shots, 0.06, 0.09, 0.12mJ/mm2. The apoptotic cell rate was determined by flow cytometry assay, cell viability was examined by the MTT assay, nuclear fragmentation was detected by Hoechst 33342 staining, and the mitochondrial-mediated intrinsic pathway of apoptosis was assessed by the expression of Bax and Bcl-2 protein and Caspase3 activation. Results: First, apoptosis could be induced by ischemia/hypoxia in H9c2 cells. Second, CSWT attenuates the cell death and decreases the H9c2 cell apoptosis rate induced by ischemia and hypoxia. Third, CSWT suppresses the expression of apoptosis molecules that regulate the intrinsic pathway of apoptosis in H9c2 cells. Fourth, CSWT increases the phosphorylation of AKT, which indicates the activation of the PI3K-AKT pathway. Conclusions: These results indicate that CSWT exerts a protective effect against I/H-induced cell death, potentially by preventing the activation of components of the mitochondrial-dependent intrinsic apoptotic pathway. We also demonstrate that the PI3K-Akt pathway may be involved in the CSWT effects on

  15. Radix Astragali Improves Dysregulated Triglyceride Metabolism and Attenuates Macrophage Infiltration in Adipose Tissue in High-Fat Diet-Induced Obese Male Rats through Activating mTORC1-PPARγ Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yang Long

    2014-01-01

    Full Text Available Increased levels of free fatty acids (FFAs and hypertriglyceridemia are important risk factors for cardiovascular disease. The effective fraction isolated from radix astragali (RA has been reported to alleviate hypertriglyceridemia. The mechanism of this triglyceride-lowering effect of RA is unclear. Here, we tested whether activation of the mTORC1-PPARγ signaling pathway is related to the triglyceride-lowering effect of RA. High-fat diet-induced obese (DIO rats were fed a high-fat diet (40% calories from fat for 9-10 weeks, and 4 g/kg/d RA was administered by gavage. RA treatment resulted in decreased fasting triglyceride levels, FFA concentrations, and adipocyte size. RA treated rats showed improved triglyceride clearance and fatty acid handling after olive oil overload. RA administration could also decrease macrophage infiltration and expression of MCP-1 and TNFα, but it may also increase the expression of PPARγ in epididymal adipose tissue from RA treated rats. Consistently, expressions of PPARγ and phospho-p70S6K were increased in differentiated 3T3-L1 adipocytes treated with RA. Moreover, RA couldnot upregulate the expression of PPARγ at the presence of rapamycin. In conclusion, the mTORC1-PPARγ signaling pathway is a potential mechanism through which RA exerts beneficial effects on the disturbance of triglyceride metabolism and dysfunction of adipose tissue in DIO rats.

  16. Mechanical ventilation with high tidal volumes attenuates myocardial dysfunction by decreasing cardiac edema in a rat model of LPS-induced peritonitis

    Directory of Open Access Journals (Sweden)

    Smeding Lonneke

    2012-03-01

    Full Text Available Abstract Background Injurious mechanical ventilation (MV may augment organ injury remote from the lungs. During sepsis, myocardial dysfunction is common and increased endothelial activation and permeability can cause myocardial edema, which may, among other factors, hamper myocardial function. We investigated the effects of MV with injuriously high tidal volumes on the myocardium in an animal model of sepsis. Methods Normal rats and intraperitoneal (i.p. lipopolysaccharide (LPS-treated rats were ventilated with low (6 ml/kg and high (19 ml/kg tidal volumes (Vt under general anesthesia. Non-ventilated animals served as controls. Mean arterial pressure (MAP, central venous pressure (CVP, cardiac output (CO and pulmonary plateau pressure (Pplat were measured. Ex vivo myocardial function was measured in isolated Langendorff-perfused hearts. Cardiac expression of endothelial vascular cell adhesion molecule (VCAM-1 and edema were measured to evaluate endothelial inflammation and leakage. Results MAP decreased after LPS-treatment and Vt-dependently, both independent of each other and with interaction. MV Vt-dependently increased CVP and Pplat and decreased CO. LPS-induced peritonitis decreased myocardial function ex vivo but MV attenuated systolic dysfunction Vt-dependently. Cardiac endothelial VCAM-1 expression was increased by LPS treatment independent of MV. Cardiac edema was lowered Vt-dependently by MV, particularly after LPS, and correlated inversely with systolic myocardial function parameters ex vivo. Conclusion MV attenuated LPS-induced systolic myocardial dysfunction in a Vt-dependent manner. This was associated with a reduction in cardiac edema following a lower transmural coronary venous outflow pressure during LPS-induced coronary inflammation.

  17. Elafin, a serine elastase inhibitor, attenuates post-cardiac transplant coronary arteriopathy and reduces myocardial necrosis in rabbits afer heterotopic cardiac transplantation.

    OpenAIRE

    Cowan, B.; Baron, O; Crack, J; Coulber, C; Wilson, G.J.; Rabinovitch, M

    1996-01-01

    We have related experimentally induced post-cardiac transplant coronary arteriopathy to increased elastolytic activity, IL-1beta, fibronectin-mediated inflammatory and smooth muscle cell (SMC) migration, and SMC proliferation. Since our in vitro studies show that a serine elastase releases SMC mitogens and facilitates IL-lbeta induction of fibronectin, we hypothesized that administration in vivo of the specific serine elastase inhibitor, elafin, would decrease the post-cardiac transplant coro...

  18. Zinc deficiency exacerbates while zinc supplement attenuates cardiac hypertrophy in high-fat diet-induced obese mice through modulating p38 MAPK-dependent signaling.

    Science.gov (United States)

    Wang, Shudong; Luo, Manyu; Zhang, Zhiguo; Gu, Junlian; Chen, Jing; Payne, Kristen McClung; Tan, Yi; Wang, Yuehui; Yin, Xia; Zhang, Xiang; Liu, Gilbert C; Wintergerst, Kupper; Liu, Quan; Zheng, Yang; Cai, Lu

    2016-09-01

    Childhood obesity often leads to cardiovascular diseases, such as obesity-related cardiac hypertrophy (ORCH), in adulthood, due to chronic cardiac inflammation. Zinc is structurally and functionally essential for many transcription factors; however, its role in ORCH and underlying mechanism(s) remain unclear and were explored here in mice with obesity induced with high-fat diet (HFD). Four week old mice were fed on either HFD (60%kcal fat) or normal diet (ND, 10% kcal fat) for 3 or 6 months, respectively. Either diet contained one of three different zinc quantities: deficiency (ZD, 10mg zinc per 4057kcal), normal (ZN, 30mg zinc per 4057kcal) or supplement (ZS, 90mg zinc per 4057kcal). HFD induced a time-dependent obesity and ORCH, which was accompanied by increased cardiac inflammation and p38 MAPK activation. These effects were worsened by ZD in HFD/ZD mice and attenuated by ZS in HFD/ZS group, respectively. Also, administration of a p38 MAPK specific inhibitor in HFD mice for 3 months did not affect HFD-induced obesity, but completely abolished HFD-induced, and zinc deficiency-worsened, ORCH and cardiac inflammation. In vitro exposure of adult cardiomyocytes to palmitate induced cell hypertrophy accompanied by increased p38 MAPK activation, which was heightened by zinc depletion with its chelator TPEN. Inhibition of p38 MAPK with its specific siRNA also prevented the effects of palmitate on cardiomyocytes. These findings demonstrate that ZS alleviates but ZD heightens cardiac hypertrophy in HFD-induced obese mice through suppressing p38 MAPK-dependent cardiac inflammatory and hypertrophic pathways. PMID:27346292

  19. Gut triglyceride production.

    Science.gov (United States)

    Pan, Xiaoyue; Hussain, M Mahmood

    2012-05-01

    Our knowledge of how the body absorbs triacylglycerols (TAG) from the diet and how this process is regulated has increased at a rapid rate in recent years. Dietary TAG are hydrolyzed in the intestinal lumen to free fatty acids (FFA) and monoacylglycerols (MAG), which are taken up by enterocytes from their apical side, transported to the endoplasmic reticulum (ER) and resynthesized into TAG. TAG are assembled into chylomicrons (CM) in the ER, transported to the Golgi via pre-chylomicron transport vesicles and secreted towards the basolateral side. In this review, we mainly focus on the roles of key proteins involved in uptake and intracellular transport of fatty acids, their conversion to TAG and packaging into CM. We will also discuss intracellular transport and secretion of CM. Moreover, we will bring to light few factors that regulate gut triglyceride production. Furthermore, we briefly summarize pathways involved in cholesterol absorption. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

  20. Allogeneic cardiospheres delivered via percutaneous transendocardial injection increase viable myocardium, decrease scar size, and attenuate cardiac dilatation in porcine ischemic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Kristine Yee

    Full Text Available Epicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI, but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy.We studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22 post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled ("dose optimization" study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16. Finally, the superior product and dose (150 million cardiospheres were tested in a blinded, randomized, placebo-controlled ("pivotal" study (n = 22. Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo.Dose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration.

  1. Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise.

    Science.gov (United States)

    Willis, Monte S; Min, Jin-Na; Wang, Shaobin; McDonough, Holly; Lockyer, Pamela; Wadosky, Kristine M; Patterson, Cam

    2013-12-01

    The carboxyl terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase/cochaperone critical for the maintenance of cardiac function. Mice lacking CHIP (CHIP-/-) suffer decreased survival, enhanced myocardial injury and increased arrhythmias compared with wild-type controls following challenge with cardiac ischaemia reperfusion injury. Recent evidence implicates a role for CHIP in chaperone-assisted selective autophagy, a process that is associated with exercise-induced cardioprotection. To determine whether CHIP is involved in cardiac autophagy, we challenged CHIP-/- mice with voluntary exercise. CHIP-/- mice respond to exercise with an enhanced autophagic response that is associated with an exaggerated cardiac hypertrophy phenotype. No impairment of function was identified in the CHIP-/- mice by serial echocardiography over the 5 weeks of running, indicating that the cardiac hypertrophy was physiologic not pathologic in nature. It was further determined that CHIP plays a role in inhibiting Akt signalling and autophagy determined by autophagic flux in cardiomyocytes and in the intact heart. Taken together, cardiac CHIP appears to play a role in regulating autophagy during the development of cardiac hypertrophy, possibly by its role in supporting Akt signalling, induced by voluntary running in vivo.

  2. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

    Science.gov (United States)

    Benter, Ibrahim F.; Babiker, Fawzi; Al-Rashdan, Ibrahim; Yousif, Mariam; Akhtar, Saghir

    2013-01-01

    Aims. We evaluated the effects of RU28318 (RU), a selective mineralocorticoid receptor (MR) antagonist, Captopril (Capt), an angiotensin converting enzyme inhibitor, and Losartan (Los), an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R-) induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I) followed by a period of 30 min of reperfusion (R). Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple). Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving −dP/dt (a measure of diastolic function) when administered to diabetic hearts after ischemia. PMID:24066305

  3. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

    Directory of Open Access Journals (Sweden)

    Ibrahim F. Benter

    2013-01-01

    Full Text Available Aims. We evaluated the effects of RU28318 (RU, a selective mineralocorticoid receptor (MR antagonist, Captopril (Capt, an angiotensin converting enzyme inhibitor, and Losartan (Los, an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R- induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I followed by a period of 30 min of reperfusion (R. Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple. Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving -dP/dt (a measure of diastolic function when administered to diabetic hearts after ischemia.

  4. Attenuated Cardiac Mitochondrial-Dependent Apoptotic Effects by Li-Fu Formula in Hamsters Fed with a Hypercholesterol Diet

    Directory of Open Access Journals (Sweden)

    Wei-Wen Kuo

    2011-01-01

    Full Text Available Apoptosis involves in the pathogenesis of various cardiac abnormalities. This study intends to evaluate the effects of Li-Fu formula on cardiac apoptosis induced by hyper-cholesterol diet. Twenty-four male Golden Syrian hamsters were randomly divided into Control, Cholesterol and Li-Fu formula groups. Histopathological analysis, western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assays were performed to measure the effects of Li-Fu formula on left ventricle. Significantly reduced TUNEL-positive cells and mitochondria- dependent apoptosis were observed in the left ventricle of hamsters from Li-Fu formula group compared to the Cholesterol group. Additionally, induced cardiac insulin like growth factor I receptor (IGFIR-dependent survival pathway was detected in the Li-Fu formula group compared to the Cholesterol group. Besides, minor fibrosis, increased collagen deposition, and myofibril disarray was detected in the Cholesterol group, whereas the reductions of collagen deposition and myofibril disarray were observed in the Li-Fu formula group. This study demonstrated that Li-Fu formula not only reduced the mitochondria-dependent apoptosis and fibrosis, but also enhanced the IGF-I survival pathway in the left ventricle from high cholesterol-fed hamsters. We suggest the protective effects of Li-Fu formula on cardiac apoptosis and therapeutic potentials against cardiovascular disease.

  5. Pre-Conditioning with CDP-Choline Attenuates Oxidative Stress-Induced Cardiac Myocyte Death in a Hypoxia/Reperfusion Model

    Directory of Open Access Journals (Sweden)

    Héctor González-Pacheco

    2014-01-01

    Full Text Available Background. CDP-choline is a key intermediate in the biosynthesis of phosphatidylcholine, which is an essential component of cellular membranes, and a cell signalling mediator. CDP-choline has been used for the treatment of cerebral ischaemia, showing beneficial effects. However, its potential benefit for the treatment of myocardial ischaemia has not been explored yet. Aim. In the present work, we aimed to evaluate the potential use of CDP-choline as a cardioprotector in an in vitro model of ischaemia/reperfusion injury. Methods. Neonatal rat cardiac myocytes were isolated and subjected to hypoxia/reperfusion using the coverslip hypoxia model. To evaluate the effect of CDP-choline on oxidative stress-induced reperfusion injury, the cells were incubated with H2O2 during reperfusion. The effect of CDP-choline pre- and postconditioning was evaluated using the cell viability MTT assay, and the proportion of apoptotic and necrotic cells was analyzed using the Annexin V determination by flow cytometry. Results. Pre- and postconditioning with 50 mg/mL of CDP-choline induced a significant reduction of cells undergoing apoptosis after hypoxia/reperfusion. Preconditioning with CDP-choline attenuated postreperfusion cell death induced by oxidative stress. Conclusion. CDP-choline administration reduces cell apoptosis induced by oxidative stress after hypoxia/reperfusion of cardiac myocytes. Thus, it has a potential as cardioprotector in ischaemia/reperfusion-injured cardiomyocytes.

  6. Silencing MicroRNA-155 Attenuates Cardiac Injury and Dysfunction in Viral Myocarditis via Promotion of M2 Phenotype Polarization of Macrophages.

    Science.gov (United States)

    Zhang, Yingying; Zhang, Mengying; Li, Xueqin; Tang, Zongsheng; Wang, Xiangmin; Zhong, Min; Suo, Qifeng; Zhang, Yao; Lv, Kun

    2016-01-01

    Macrophage infiltration is a hallmark feature of viral myocarditis. As studies have shown that microRNA-155 regulates the differentiation of macrophages, we aimed to investigate the role of microRNA-155 in VM. We report that silencing microRNA-155 protects mice from coxsackievirus B3 induced myocarditis. We found that microRNA-155 expression was upregulated and localized primarily in heart-infiltrating macrophages and CD4(+) T lymphocytes during acute myocarditis. In contrast with wildtype (WT) mice, microRNA-155(-/-) mice developed attenuated viral myocarditis, which was characterized by decreased cardiac inflammation and decreased intracardiac CD45(+) leukocytes. Hearts of microRNA-155(-/-) mice expressed decreased levels of the IFN-γ and increased levels of the cytokines IL-4 and IL-13. Although total CD4(+) and regulatory T cells were unchanged in miR-155(-/-) spleen proportionally, the activation of T cells and CD4(+) T cell proliferation in miR-155(-/-) mice were significantly decreased. Beyond the acute phase, microRNA-15(5-/-) mice had reduced mortality and improved cardiac function during 5 weeks of follow-up. Moreover, silencing microRNA-155 led to increased levels of alternatively-activated macrophages (M2) and decreased levels of classically-activated macrophages (M1) in the heart. Combined, our studies suggest that microRNA-155 confers susceptibility to viral myocarditis by affecting macrophage polarization, and thus may be a potential therapeutic target for viral myocarditis. PMID:26931072

  7. Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by the GPER agonist G-1 in female mRen2.Lewis rats.

    Directory of Open Access Journals (Sweden)

    Jewell A Jessup

    Full Text Available INTRODUCTION: The G protein-coupled estrogen receptor (GPER is expressed in various tissues including the heart. Since the mRen2.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days or vehicle (VEH, DMSO/EtOH on cardiac function and structure. METHODS: Intact female mRen2.Lewis rats were fed a normal salt (0.5% sodium; NS diet or a high salt (4% sodium; HS diet for 10 weeks beginning at 5 weeks of age. RESULTS: Prolonged intake of HS in mRen2.Lewis females resulted in significantly increased blood pressure, mildly reduced systolic function, and left ventricular (LV diastolic compliance (as signified by a reduced E deceleration time and E deceleration slope, increased relative wall thickness, myocyte size, and mid-myocardial interstitial and perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte hypertrophy, with nominal effects on blood pressure, LV systolic function, LV compliance and cardiac fibrosis in the HS group. G-1 treatment significantly increased LV lusitropy [early mitral annular descent (e'] independent of prevailing salt, and improved the e'/a' ratio in HS versus NS rats (P<0.05 as determined by tissue Doppler. CONCLUSION: Activation of GPER improved myocardial relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte hypertrophy and wall thickness in those rats fed a high salt diet. Moreover, these advantageous effects of the GPER agonist on ventricular lusitropy and remodeling do not appear to be associated with overt changes in blood pressure.

  8. Diazoxide Attenuates Postresuscitation Brain Injury in a Rat Model of Asphyxial Cardiac Arrest by Opening Mitochondrial ATP-Sensitive Potassium Channels.

    Science.gov (United States)

    Wu, Haidong; Wang, Peng; Li, Yi; Wu, Manhui; Lin, Jiali; Huang, Zitong

    2016-01-01

    Objective. We investigated whether and how diazoxide can attenuate brain injury after cardiopulmonary resuscitation (CPR) by selective opening of mitochondrial ATP-sensitive potassium (mitoKATP) channels. Methods. Adult male Sprague-Dawley rats with induced cerebral ischemia (n = 10 per group) received an intraperitoneal injection of 0.1% dimethyl sulfoxide (1 mL; vehicle group), diazoxide (10 mg/kg; DZ group), or diazoxide (10 mg/kg) plus 5-hydroxydecanoate (5 mg/kg; DZ + 5-HD group) 30 min after CPR. The control group (sham group, n = 5) underwent sham operation, without cardiac arrest. Mitochondrial respiratory control rate (RCR) was determined. Brain cell apoptosis was assessed using TUNEL staining. Expression of Bcl-2, Bax, and protein kinase C epsilon (PKCε) in the cerebral cortex was determined by Western blotting and immunohistochemistry. Results. The neurological deficit scores (NDS) in the vehicle group decreased significantly at 24 h and 48 h after CPR. Diazoxide significantly improved NDS and mitochondrial RCR after CPR at both time points; 5-HD cotreatment abolished these effects. Diazoxide decreased TUNEL-positive cells following CPR, upregulated Bcl-2 and PKCε, downregulated Bax, and increased the Bcl-2/Bax ratio; 5-HD cotreatment reversed these effects. Conclusions. Diazoxide attenuates postresuscitation brain injury, protects mitochondrial function, inhibits brain cell apoptosis, and activates the PKC pathway by opening mitoKATP channels. PMID:27648441

  9. FAK-related nonkinase attenuates hypertrophy induced by angiotensin-Ⅱ in cultured neonatal rat cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    Jin QIN; Zheng-xiang LIU

    2006-01-01

    Aim: To examine the inhibitory effect of FAK-related nonkinase (FRNK) in cardiac hypertrophy in vitro and investigate the possible mechanisms. Methods: A functional fragment of FRNK cDNA was amplified by reverse transcription-polymerase chain reaction and cloned into the vector pcDNA3.1. Hypertrophy in neonatal rat cardiac myocytes was established with angiotensin-Ⅱ stimulation. The pcDNA3.1-FRNK or pcDNA3.1 was respectively transfected into cardiomyocytes by Lipofectamine 2000. The surface area and mRNA expression of atrial natriuretic peptide (ANP) of myocytes were employed to detect cardiac hypertrophy. NF-κB p65 protein in nuclear extracts, phosphorylation levels of ERK1/2 (p-ERK1/2) and AKT (p-AKT), as well as total ERK1/2, and AKT in variant treated cardiomyocytes were determined by Western blot. Results: Under the stimulation of angiotensin Ⅱ, the surface area of myocytes and levels of ANP mRNA were significantly increased. But transient transfection with pcDNA3.1-FRNK in advance may reduce the surface area and expression of ANP mRNA of hypertrophic myocytes. The protein levels of NF-κB p65 in nuclear extracts and p-ERK1/2, p-AKT in FRNK treated cardiomyocytes were significantly decreased compared with that in angiotensin-Ⅱ induced cardiomyocytes, while different treatments had little effect on total ERK1/2 and AKT. Conclusion: FRNK may inhibit angiotensin-Ⅱ-induced cardiomyocyte hypertrophy via decreasing phosphorylation levels at ERK1/2 and AKT, consequently downregulating nuclear translocation of NF-κB p65.

  10. Butanolic fraction of Moringa oleifera Lam. (Moringaceae) attenuates isoprotrenol induced cardiac necrosis and oxidative stress in rats: an EPR study

    OpenAIRE

    Panda, Sunanda

    2015-01-01

    The preventive effect of Moringa oleifera polyphenolic fraction (MOPF) on cardiac damage was evaluated in isoproterenol (ISO) induced cardiotoxicity model of Wistar rats. Male rats in different groups were treated with MOPF orally at the dose of 50, 100 and 150 mg/kg/day for 28 days and were subsequently administered (s.c.) with ISO (85 mg/kg body weight) for the last two days. At the end of the experiment levels of serum troponin-T, creatine kinase-MB, lactate dehydrogenase, content of malon...

  11. Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion.

    Science.gov (United States)

    Yang, Mingzhu; Orgah, John; Zhu, Jie; Fan, Guanwei; Han, Jihong; Wang, Xiaoying; Zhang, Boli; Zhu, Yan

    2016-07-01

    Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects. PMID:27107944

  12. Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion.

    Science.gov (United States)

    Yang, Mingzhu; Orgah, John; Zhu, Jie; Fan, Guanwei; Han, Jihong; Wang, Xiaoying; Zhang, Boli; Zhu, Yan

    2016-07-01

    Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects.

  13. Lipase Based Biosensors for Triglyceride Determination

    OpenAIRE

    Rosli Nurul Huwaida; Mohd Zain Zainiharyati; Ahmad Nor Monica

    2016-01-01

    A review of methods development in lipase based biosensor for triglyceride determination was briefly discussed. This review focuses on the basic principle of triglyceride biosensor that includes performances of triglyceride biosensor such as limit of detection, response time, and optimization.

  14. Olmesartan, an AT1 Antagonist, Attenuates Oxidative Stress, Endoplasmic Reticulum Stress and Cardiac Inflammatory Mediators in Rats with Heart Failure Induced by Experimental Autoimmune Myocarditis

    Directory of Open Access Journals (Sweden)

    Vijayakumar Sukumaran, Kenichi Watanabe, Punniyakoti T. Veeraveedu, Narasimman Gurusamy, Meilei Ma, Rajarajan A. Thandavarayan, Arun Prasath Lakshmanan, Ken'ichi Yamaguchi, Kenji Suzuki, Makoto Kodama

    2011-01-01

    Full Text Available Studies have demonstrated that angiotensin II has been involved in immune and inflammatory responses which might contribute to the pathogenesis of immune-mediated diseases. Recent evidence suggests that oxidative stress may play a role in myocarditis. Here, we investigated whether olmesartan, an AT1R antagonist protects against experimental autoimmune myocarditis (EAM by suppression of oxidative stress, endoplasmic reticulum (ER stress and inflammatory cytokines. EAM was induced in Lewis rats by immunization with porcine cardiac myosin, were divided into two groups and treated with either olmesartan (10 mg/kg/day or vehicle for a period of 21 days. Myocardial functional parameters measured by hemodynamic and echocardiographic analyses were significantly improved by the treatment with olmesartan compared with those of vehicle-treated rats. Treatment with olmesartan attenuated the myocardial mRNA expressions of proinflammatory cytokines, [Interleukin (IL-1β, monocyte chemoattractant protein-1, tumor necrosis factor-α and interferon-γ] and the protein expression of tumor necrosis factor-α compared with that of vehicle-treated rats. Myocardial protein expressions of AT1R, NADPH oxidase subunits (p47phox, p67phox, gp91phox and the expression of markers of oxidative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal, and the cardiac apoptosis were also significantly decreased by the treatment with olmesartan compared with those of vehicle-treated rats. Furthermore, olmesartan treatment down-regulated the myocardial expressions of glucose regulated protein-78, growth arrest and DNA damage-inducible gene, caspase-12, phospho-p38 mitogen-activated protein kinase (MAPK and phospho-JNK. These findings suggest that olmesartan protects against EAM in rats, at least in part via suppression of oxidative stress, ER stress and inflammatory cytokines.

  15. Apigenin Attenuates β-Receptor-Stimulated Myocardial Injury Via Safeguarding Cardiac Functions and Escalation of Antioxidant Defence System.

    Science.gov (United States)

    Buwa, Chhabildas C; Mahajan, Umesh B; Patil, Chandragouda R; Goyal, Sameer N

    2016-07-01

    Apigenin (AP) is a flavone in dietary flavonoids reported as strong antioxidant and elite modulator of PPARγ. The current study evaluated the consequence of AP in isoproterenol (ISO)-induced oxidative stress and myocardial infarction during β-adrenergic receptor stimulus in rats by persistent hemodynamic, biochemical and histopathological changes. Rats received AP (25, 50 and 75 mg/kg/day) or vehicle i.p. for 14 days and ISO (100 mg/kg, s.c.) on 13th and 14th days for initiation of cardiotoxicity. ISO-treated rats showed evidence of significant dwindle in systolic and diastolic arterial pressures, maximal positive rate of developed left ventricular pressure. In totting up, a noteworthy diminution in activities of creatine kinase-MB isoenzyme, reduced glutathione, superoxide dismutase, catalase and level along with rise in malondialdehyde content were observed. The shielding function of AP on isoproterenol-induced myocardial damage was observed by attenuating all the endogenous parameters and the membrane-bound enzymes. It was confirmed by histopathological examinations. The effect of AP at the doses of 50 and 75 mg/kg showed added apparent than at the dose of 25 mg/kg. Current study thus provides confirmation for protective effects of AP on myocardium in experimentally induced myocardial infarction. PMID:26186996

  16. Work flow with manual re-registration of cardiac 18F-FDG PET and attenuation correction CT to compensate for respiratory motion: Effects and inter-operator variability

    DEFF Research Database (Denmark)

    Juhl, Christian; Christensen, Nana Louise; Møller, Lone W.;

    , attenuation artefacts are often observed on the lateral wall of the left ventricle. Many strategies has been proposed to reduce these artefacts, including averaging multiple CTs, respiratory gating and manual re-registration1-3. However, for scanner platform-independent implementation, manual re......Aim: Cardiac PET exams with CT for attenuation correction are increasing in number. However, due to different natures of the PET (average over many respiratory cycles) and the CT exam (snap-shot during one respiratory cycle) and the large difference in density of the cardiac and lung tissue......-registration is currently the most feasible. In this study, we examine both the effect on misalignment artefacts and the inter-operator variability of manual re-registration performed by the technologist in a step before the final image reconstruction and verified by a second technologist before image analysis. Method: 40...

  17. Enzymes involved in triglyceride hydrolysis.

    Science.gov (United States)

    Taskinen, M R; Kuusi, T

    1987-08-01

    The lipolytic enzymes LPL and HL play important roles in the metabolism of lipoproteins and participate in lipoprotein interconversions. LPL was originally recognized to be the key enzyme in the hydrolysis of chylomicrons and triglyceride, but it also turned out to be one determinant of HDL concentration in plasma. When LPL activity is high, chylomicrons and VLDL are rapidly removed from circulation and a concomitant rise of the HDL2 occurs. In contrast, low LPL activity impedes the removal of triglyceride-rich particles, resulting in the elevation of serum triglycerides and a decrease of HDL (HDL2). Concordant changes of this kind in LPL and HDL2 are induced by many physiological and pathological perturbations. Finally, the operation of LPL is also essential for the conversion of VLDL to LDL. This apparently clear-cut role of LPL in lipoprotein interconversions is contrasted with the enigmatic actions of HL. The enzyme was originally thought to participate in the catalyses of chylomicron and VLDL remnants generated in the LPL reaction. However, substantial in vitro and in vivo data indicate that HL is a key enzyme in the degradation of plasma HDL (HDL2) in a manner which opposes LPL. A scheme is presented for the complementary actions of the two enzymes in plasma HDL metabolism. In addition, recent studies have attributed a role to HL in the catabolism of triglyceride-rich lipoproteins, particularly those containing apo E. However, this function becomes clinically important only under conditions where the capacity of the LPL-mediated removal system is exceeded. Such a situation may arise when the input of triglyceride-rich particles (chylomicrons and/or VLDL) is excessive or LPL activity is decreased or absent.

  18. Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

    OpenAIRE

    Shin-Ichi Yokota; Kaai Nakamura; Midori Ando; Hiroyasu Kamei; Fumihiko Hakuno; Shin-Ichiro Takahashi; Shigenobu Shibata

    2014-01-01

    Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepa...

  19. Nitro-Oleic Acid Reduces J774A.1 Macrophage Oxidative Status and Triglyceride Mass: Involvement of Paraoxonase2 and Triglyceride Metabolizing Enzymes.

    Science.gov (United States)

    Rosenblat, Mira; Rom, Oren; Volkova, Nina; Aviram, Michael

    2016-08-01

    Nitro-fatty acids possess anti-atherogenic properties, but their effects on macrophage oxidative status and lipid metabolism that play important roles in atherosclerosis development are unclear. This study compared the effects of nitro-oleic acid (OLA-NO2) with those of native oleic acid (OLA) on intracellular reactive oxygen species (ROS) generation, anti-oxidants and metabolism of triglycerides and cholesterol in J774A.1 macrophages. Upon incubating the cells with physiological concentrations of OLA-NO2 (0-1 µM) or with equivalent levels of OLA, ROS levels measured by 2, 7-dichlorofluorescein diacetate, decreased dose-dependently, but the anti-oxidative effects of OLA-NO2 were significantly augmented. Copper ion addition increased ROS generation in OLA treated macrophages without affecting OLA-NO2 treated cells. These effects could be attributed to elevated glutathione levels and to increased activity and expression of paraoxonase2 that were observed in OLA-NO2 vs OLA treated cells. Beneficial effects on triglyceride metabolism were noted in OLA-NO2 vs OLA treated macrophages in which cellular triglycerides were reduced due to attenuated biosynthesis and accelerated hydrolysis of triglycerides. Accordingly, OLA-NO2 treated cells demonstrated down-regulation of diacylglycerol acyltransferase1, the key enzyme in triglyceride biosynthesis, and increased expression of hormone-sensitive lipase and adipose triglyceride lipase that regulate triglyceride hydrolysis. Finally, OLA-NO2 vs OLA treatment resulted in modest but significant beneficial effects on macrophage cholesterol metabolism, reducing cholesterol biosynthesis rate and low density lipoprotein influx into the cells, while increasing high density lipoprotein-mediated cholesterol efflux from the macrophages. Collectively, compared with OLA, OLA-NO2 modestly but significantly reduces macrophage oxidative status and cellular triglyceride content via modulation of cellular anti-oxidants and triglyceride

  20. Nitro-Oleic Acid Reduces J774A.1 Macrophage Oxidative Status and Triglyceride Mass: Involvement of Paraoxonase2 and Triglyceride Metabolizing Enzymes.

    Science.gov (United States)

    Rosenblat, Mira; Rom, Oren; Volkova, Nina; Aviram, Michael

    2016-08-01

    Nitro-fatty acids possess anti-atherogenic properties, but their effects on macrophage oxidative status and lipid metabolism that play important roles in atherosclerosis development are unclear. This study compared the effects of nitro-oleic acid (OLA-NO2) with those of native oleic acid (OLA) on intracellular reactive oxygen species (ROS) generation, anti-oxidants and metabolism of triglycerides and cholesterol in J774A.1 macrophages. Upon incubating the cells with physiological concentrations of OLA-NO2 (0-1 µM) or with equivalent levels of OLA, ROS levels measured by 2, 7-dichlorofluorescein diacetate, decreased dose-dependently, but the anti-oxidative effects of OLA-NO2 were significantly augmented. Copper ion addition increased ROS generation in OLA treated macrophages without affecting OLA-NO2 treated cells. These effects could be attributed to elevated glutathione levels and to increased activity and expression of paraoxonase2 that were observed in OLA-NO2 vs OLA treated cells. Beneficial effects on triglyceride metabolism were noted in OLA-NO2 vs OLA treated macrophages in which cellular triglycerides were reduced due to attenuated biosynthesis and accelerated hydrolysis of triglycerides. Accordingly, OLA-NO2 treated cells demonstrated down-regulation of diacylglycerol acyltransferase1, the key enzyme in triglyceride biosynthesis, and increased expression of hormone-sensitive lipase and adipose triglyceride lipase that regulate triglyceride hydrolysis. Finally, OLA-NO2 vs OLA treatment resulted in modest but significant beneficial effects on macrophage cholesterol metabolism, reducing cholesterol biosynthesis rate and low density lipoprotein influx into the cells, while increasing high density lipoprotein-mediated cholesterol efflux from the macrophages. Collectively, compared with OLA, OLA-NO2 modestly but significantly reduces macrophage oxidative status and cellular triglyceride content via modulation of cellular anti-oxidants and triglyceride

  1. Omega-3 Fatty Acid Supplementation Appears to Attenuate Particulate Air Pollution-induced Cardiac Effects and Lipid Changes in Healthy Middle-aged Adults.

    Science.gov (United States)

    Context: Air pollution exposure has been associated with adverse cardiovascular effects. A recent epidemiologic study reported that omega-3 fatty acid (fish oil) supplementation blunted the cardiac responses to air pollution exposure. Objective: To evaluate in a randomized contro...

  2. Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

    DEFF Research Database (Denmark)

    Bartels, Emil D; Ploug, Thorkil; Størling, Joachim;

    2014-01-01

    Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design....... In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apo......B transgenic mice accumulated 28% less triglycerides in skeletal myocytes after one year of fat-feeding as compared with WT mice (32 ± 5, n = 10 vs. 44 ± 4 nmol/mg ww, n = 13, p = 0.04). Moreover, expression of human apoB in fat-fed mice was associated with 32% (p = 0.02) and 37% (p = 0.01) lower plasma...

  3. Garlic attenuates cardiac oxidative stress via activation of PI3K/AKT/Nrf2-Keap1 pathway in fructose-fed diabetic rat.

    Directory of Open Access Journals (Sweden)

    Raju Padiya

    Full Text Available BACKGROUND: Cardiovascular complication due to diabetes has remained a major cause of death. There is an urgent need to intervene the cardiac complications in diabetes by nutritional or pharmacological agents. Thus the present study was designed to find out the effectiveness of garlic on cardiac complications in insulin-resistant diabetic rats. METHODS AND RESULTS: SD rats were fed high fructose (65% diet alone or along with raw garlic homogenate (250 mg/kg/day or nutrient-matched (65% corn starch control diet for 8 weeks. Fructose-fed diabetic rats showed cardiac hypertrophy, increased NFkB activity and increased oxidative stress. Administration of garlic significantly decreased (p<0.05 cardiac hypertrophy, NFkB activity and oxidative stress. Although we did not observe any changes in myocardial catalase, GSH and GPx in diabetic heart, garlic administration showed significant (p<0.05 increase in all three antioxidant/enzymes levels. Increased endogenous antioxidant enzymes and gene expression in garlic treated diabetic heart are associated with higher protein expression of Nrf2. Increased myocardial H2S levels, activation of PI3K/Akt pathway and decreased Keap levels in fructose-fed heart after garlic administration might be responsible for higher Nrf2 levels. CONCLUSION: Our study demonstrates that raw garlic homogenate is effective in reducing cardiac hypertrophy and fructose-induced myocardial oxidative stress through PI3K/AKT/Nrf2-Keap1 dependent pathway.

  4. Triglyceride-Rich Lipoproteins and Remnants: Targets for Therapy?

    Science.gov (United States)

    Dallinga-Thie, Geesje M; Kroon, Jeffrey; Borén, Jan; Chapman, M John

    2016-07-01

    It is now evident that elevated circulating levels of triglycerides in the non-fasting state, a marker for triglyceride (TG)-rich remnant particles, are associated with increased risk of premature cardiovascular disease (CVD). Recent findings from basic and clinical studies have begun to elucidate the mechanisms that contribute to the atherogenicity of these apoB-containing particles. Here, we review current knowledge of the formation, intravascular remodelling and catabolism of TG-rich lipoproteins and highlight (i) the pivotal players involved in this process, including lipoprotein lipase, glycosylphosphatidylinositol HDL binding protein 1 (GPIHBP1), apolipoprotein (apo) C-II, apoC-III, angiopoietin-like protein (ANGPTL) 3, 4 and 8, apoA-V and cholesteryl ester transfer protein; (ii) key determinants of triglyceride (TG) levels and notably rates of production of very-low-density lipoprotein 1 (VLDL1) particles; and (iii) the mechanisms which underlie the atherogenicity of remnant particles. Finally, we emphasise the polygenic nature of moderate hypertriglyceridemia and briefly discuss modalities for its clinical management. Several new therapeutic strategies to attenuate hypertriglyceridemia have appeared recently, among which those targeted to apoC-III appear to hold considerable promise. PMID:27216847

  5. Aspects of plasma triglyceride metabolism in children

    NARCIS (Netherlands)

    P.P. Forget

    1975-01-01

    textabstractThis thesis aimed at investigating some aspects of plasma triglyceride metabolism in children. In the introduction general aspects of plasma triglyceride metabolism are presented. Chapter 1 reviews recent litterature data on the intravenous fat tolerance test and on plasma postheparin li

  6. Serum triglycerides and risk of cardiovascular disease.

    NARCIS (Netherlands)

    Boullart, I.; Graaf, J. de; Stalenhoef, A.F.H.

    2012-01-01

    Dyslipidemia, especially elevated serum levels of cholesterol, is causally related to cardiovascular disease. The specific role of triglycerides has long been controversial. In this article we discuss the role of serum triglycerides in relation to the risk of cardiovascular disease. First, the (path

  7. Transgenic Knockdown of Cardiac Sodium/Glucose Cotransporter 1 (SGLT1) Attenuates PRKAG2 Cardiomyopathy, Whereas Transgenic Overexpression of Cardiac SGLT1 Causes Pathologic Hypertrophy and Dysfunction in Mice

    OpenAIRE

    Ramratnam, Mohun; Sharma, Ravi K.; D'Auria, Stephen; Lee, So Jung; Wang, David; Huang, Xue Yin N.; Ahmad, Ferhaan

    2014-01-01

    Background The expression of a novel cardiac glucose transporter, SGLT1, is increased in glycogen storage cardiomyopathy secondary to mutations in PRKAG2. We sought to determine the role of SGLT1 in the pathogenesis of PRKAG2 cardiomyopathy and its role in cardiac structure and function. Methods and Results Transgenic mice with cardiomyocyte‐specific overexpression of human T400N mutant PRKAG2 cDNA (TGT400N) and transgenic mice with cardiomyocyte‐specific RNA interference knockdown of SGLT1 (...

  8. CYP2J2 and its metabolites (EETs) attenuate cardiac hypertrophy by activating AMPKα2 and enhancing nuclear translocation of Akt1

    Institute of Scientific and Technical Information of China (English)

    WANG Bei; ZENG He-song; WEN Zheng; CHEN Chen; WANG Dao-wen

    2016-01-01

    AIM:Cytochrome P450 epoxygenase 2J2 and epoxyeicosatrienoic acids ( EETs) are known to protect against cardiac hypertrophy and heart failure, which involve activation of 5′-AMP-activated protein kinase ( AMPK) and Akt.Although the functional roles of AMPK and Akt are well established , the significance of crosstalk between them in the development of cardiac hypertrophy and anti -hy-pertrophy of CYP2J2 and EETs remains unclear .Here, we investigated whether CYP 2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1.Moreover, we tested whether EETs enhanced crosstalk between AMPKα2 and phosphorylated Akt1 ( p-Akt1), and stimulated the nuclear translocation of p-Akt1, to exert their anti-hypertrophic effects. METHODS:The recombinant rAAV9 vector was coupled to CYP2J2 and the rAAV9-CYP2J2 construct was injected into the caudal vein of AMPKα2-/-and littermate control mice .AMPKα2 -/-and littermate control mice that overexpressed CYP 2J2 in heart were treated with angiotensin II (Ang II) for 2 weeks.Hemodynamic and cardiac functions were also evaluated after 14 days of infusion with Ang II or saline.RESULTS:Interestingly, the overexpression of CYP2J2 suppressed cardiac hypertrophy , including decreased heart size, cross sectional area of cardiomyocytes , markers of cardiac hypertrophy [ brain natriuretic peptide ( BNP) ,β-myosin heavy chain (β-MHC) and skeletal muscle α-actin (ACTA1)] and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild-type mice but not AMPKα2 -/-mice.Measurement of left ventricular ejection fraction and fractional shortening showed that CYP2J2 overexpression prevented Ang II-induced ventricular systolic dysfunction in mice .Moreover, an Ang II-induced reduction in cardiac function, demonstrated by decreased dp/dtmax and dp/dtmin, was prevented by overexpression of CYP2J2.Mechanistically, the CYP2J2 metabolites 11,12-EET activated AMPKα2 to induce the nuclear

  9. HSF1 and NF-κB p65 participate in the process of exercise preconditioning attenuating pressure overload-induced pathological cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Tongyi [Department of Cardiothoracic Surgery, No. 401 Hospital of PLA, Qingdao (China); Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Zhang, Ben [Centre of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Region, Guangzhou (China); Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Yang, Fan; Cai, Chengliang; Wang, Guokun [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Han, Qingqi, E-mail: handoctor@gmail.com [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Zou, Liangjian, E-mail: zouliangjiansh@gmail.com [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2015-05-08

    Pathological cardiac hypertrophy, often accompanied by hypertension, aortic stenosis and valvular defects, is typically associated with myocyte remodeling and cardiac dysfunction. Exercise preconditioning (EP) has been proven to enhance the tolerance of the myocardium to cardiac ischemia-reperfusion injury. However, the effects of EP in pathological cardiac hypertrophy are rarely reported. 10-wk-old male Sprague–Dawley rats (n = 80) were randomly divided into four groups: sham, TAC, EP + sham and EP + TAC. Two EP groups were subjected to 4 weeks of treadmill training, and the EP + TAC and TAC groups were followed by TAC operations. The sham and EP + sham groups underwent the same operation without aortic constriction. Eight weeks after the surgery, we evaluated the effects of EP by echocardiography, morphology, and histology and observed the expressions of the associated proteins. Compared with the respective control groups, hypertrophy-related indicators were significantly increased in the TAC and EP + TAC groups (p < 0.05). However, between the TAC and EP + TAC groups, all of these changes were effectively inhibited by EP treatment (p < 0.05). Furthermore, EP treatment upregulated the expression of HSF1 and HSP70, increased the HSF1 levels in the nuclear fraction, inhibited the expression of the NF-κB p65 subunit, decreased the NF-κB p65 subunit levels in the nuclear fraction, and reduced the IL2 levels in the myocardia of rats. EP could effectively reduce the cardiac hypertrophic responses induced by TAC and may play a protective role by upregulating the expressions of HSF1 and HSP70, activating HSF1 and then inhibiting the expression of NF-κB p65 and nuclear translocation. - Highlights: • EP could effectively reduce the cardiac hypertrophic responses induced by TAC. • EP may play a protective role by upregulating the expressions of HSF1 and HSP70 and then activating HSF1. • EP may play a protective role by inhibiting the expression

  10. Computed tomography calcium score scan for attenuation correction of N-13 ammonia cardiac positron emission tomography : effect of respiratory phase and registration method

    NARCIS (Netherlands)

    Zaidi, Habib; Nkoulou, Rene; Bond, Sarah; Baskin, Aylin; Schindler, Thomas; Ratib, Osman; Declerck, Jerome

    2013-01-01

    The use of coronary calcium scoring (CaScCT) for attenuation correction (AC) of N-13-ammonia PET/CT studies (NH3) is still being debated. We compare standard ACCT to CaScCT using various respiratory phases and co-registration methods for AC. Forty-one patients underwent a stress/rest NH3. Standard A

  11. Reduction of sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure progression and improves cardiac function after myocardial infarction.

    Science.gov (United States)

    Lymperopoulos, Anastasios; Rengo, Giuseppe; Gao, Erhe; Ebert, Steven N; Dorn, Gerald W; Koch, Walter J

    2010-05-21

    Chronic heart failure (HF) is characterized by sympathetic overactivity and enhanced circulating catecholamines (CAs), which significantly increase HF morbidity and mortality. We recently reported that adrenal G protein-coupled receptor kinase 2 (GRK2) is up-regulated in chronic HF, leading to enhanced CA release via desensitization/down-regulation of the chromaffin cell alpha(2)-adrenergic receptors that normally inhibit CA secretion. We also showed that adrenal GRK2 inhibition decreases circulating CAs and improves cardiac inotropic reserve and function. Herein, we hypothesized that adrenal-targeted GRK2 gene deletion before the onset of HF might be beneficial by reducing sympathetic activation. To specifically delete GRK2 in the chromaffin cells of the adrenal gland, we crossed PNMTCre mice, expressing Cre recombinase under the chromaffin cell-specific phenylethanolamine N-methyltransferase (PNMT) gene promoter, with floxedGRK2 mice. After confirming a significant ( approximately 50%) reduction of adrenal GRK2 mRNA and protein levels, the PNMT-driven GRK2 knock-out (KO) offspring underwent myocardial infarction (MI) to induce HF. At 4 weeks post-MI, plasma levels of both norepinephrine and epinephrine were reduced in PNMT-driven GRK2 KO, compared with control mice, suggesting markedly reduced post-MI sympathetic activation. This translated in PNMT-driven GRK2 KO mice into improved cardiac function and dimensions as well as amelioration of abnormal cardiac beta-adrenergic receptor signaling at 4 weeks post-MI. Thus, adrenal-targeted GRK2 gene KO decreases circulating CAs, leading to improved cardiac function and beta-adrenergic reserve in post-MI HF. GRK2 inhibition in the adrenal gland might represent a novel sympatholytic strategy that can aid in blocking HF progression.

  12. Comparison of serum triglyceride levels with propofol in long chain triglyceride and propofol in medium and long chain triglyceride after short term anesthesia in pediatric patients

    OpenAIRE

    Ishwar Bhukal; Gokul Thimmarayan; Indu Bala; Sohan Lal Solanki; Tanvir Samra

    2014-01-01

    Background: Significant increase in serum triglyceride (ST) concentration have been described in adult population after prolonged administration of propofol formulation containing long chain triglyceride (LCT). Though, medium chain triglyceride-LCT (MCT-LCT) propofol when compared with LCT propofol for long-term sedation in adults resulted in identical triglyceride levels, the elimination of triglyceride was faster in patients administered MCT-LCT propofol. Materials and Methods: A total of 4...

  13. Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion

    OpenAIRE

    Fettiplace, Michael R.; Lis, Kinga; Ripper, Richard; Kowal, Katarzyna; Pichurko, Adrian; Vitello, Dominic; Rubinstein, Israel; Schwartz, David; Akpa, Belinda S.; Weinberg, Guy

    2014-01-01

    Triglyceride micro-emulsions such as Intralipid® have been used to reverse cardiac toxicity induced by a number of drugs but reservations about their broad-spectrum applicability remain because of the poorly understood mechanism of action. Herein we report an integrated mechanism of reversal of bupivacaine toxicity that includes both transient drug scavenging and a cardiotonic effect that couple to accelerate movement of the toxin away from sites of toxicity. We thus propose a multi-modal the...

  14. Genomic interval engineering of mice identified a novel modulator of triglyceride production

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Y.; Jong, M.C.; Frazer, K.A.; Gong, E.; Krauss, R.M.; Cheng, J.F.; Boffelli, D.; Rubin, E.M.

    1999-10-01

    To accelerate the biological annotation of novel genes discovered in sequenced of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450 kb region on mouse chromosome 11 which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein (VLDL) triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450 kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine and hepatic triglyceride production is of particular importance due to the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion.

  15. GPIHBP1 and Plasma Triglyceride Metabolism

    DEFF Research Database (Denmark)

    Fong, Loren G; Young, Stephen G; Beigneux, Anne P;

    2016-01-01

    GPIHBP1, a GPI-anchored protein in capillary endothelial cells, is crucial for the lipolytic processing of triglyceride-rich lipoproteins (TRLs). GPIHBP1 shuttles lipoprotein lipase (LPL) to its site of action in the capillary lumen and is essential for the margination of TRLs along capillaries...... of the protein and abolish its capacity to bind and transport LPL. The discovery of GPIHBP1 has substantially revised our understanding of intravascular triglyceride metabolism but has also raised many new questions for future research....

  16. [Nonfasting triglycerides and risk of ischemic stroke--secondary publication

    DEFF Research Database (Denmark)

    Freiberg, J.J.; Tybjaerg-Hansen, A.; Jensen, J.S.;

    2009-01-01

    The role of triglycerides in the risk of ischemic stroke remains controversial. We tested the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population. Men with a nonfasting triglyceride level 5 mmol/l had a multivariable, adjusted...... hazard ratio for ischemic stroke of 2.5 (95% confidence interval: 1.3-4.8) compared with men with a nonfasting triglyceride level triglycerides is associated with risk of ischemic stroke Udgivelsesdato...

  17. Ikkefastende triglycerider og risiko for iskamisk apopleksi--sekundaerpublikation

    DEFF Research Database (Denmark)

    Freiberg, Jacob J; Tybjaerg-Hansen, Anne; Jensen, Jan Skov;

    2009-01-01

    The role of triglycerides in the risk of ischemic stroke remains controversial. We tested the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population. Men with a nonfasting triglyceride level 5 mmol/l had a multivariable, adjusted...... hazard ratio for ischemic stroke of 2.5 (95% confidence interval: 1.3-4.8) compared with men with a nonfasting triglyceride level triglycerides is associated with risk of ischemic stroke...

  18. Central nervous system control of triglyceride metabolism

    NARCIS (Netherlands)

    Geerling, Johanna Janetta (Janine)

    2013-01-01

    This thesis describes the role of the brain in the regulation of peripheral triglyceride metabolism, in the context of the metabolic syndrome. Based on various pharmacological studies we described the role of two hormones, insulin and glucagon-like peptide-1, in the production and clearance of trigl

  19. Mild hypothermia attenuates post-resuscitation brain injury through a V-ATPase mechanism in a rat model of cardiac arrest.

    Science.gov (United States)

    Zhang, J C; Lu, W; Xie, X M; Pan, H; Wu, Z Q; Yang, G T

    2016-01-01

    Although therapeutic hypothermia is an effective treatment for post-resuscitation brain injury after cardiac arrest (CA), the underlying mechanism remains unclear. Vacuolar H(+)-ATPase (V-ATPase) plays a key role in cellular adaption to a hypoxic environment. This study sought to evaluate the effect of mild hypothermia on V-ATPase and its involvement in neuroprotection after CA. Male Sprague-Dawley rats were subjected to a 6-min CA, resuscitated successfully, and then assigned to either the normothermia (NT) group or the hypothermia (HT) group. Rats were further divided into 2 subgroups based on the time of euthanasia, either 3 or 24 h after CA (NT-3 h, HT-3 h; NT-24 h, HT-24 h). Mild hypothermia was induced following CA and maintained at 33°C for 2 h. Neurologic deficit scores were used to determine the status of neurological function. Brain specimens were analyzed by TUNEL assay, western blotting, and immunohistochemistry. V-ATPase activity was estimated by subtracting total ATP hydrolysis from the bafilomycin-sensitive activity. Mild hypothermia improved the neurological outcome (HT-24 h: 34.3 ± 16.4 vs NT-24 h: 50.3 ± 17.4) and significantly decreased neurocyte apoptosis 24 h after resuscitation. Mild hypothermia significantly increased V0a1 compared to NT-3 h; V0a1 expression was associated with a decrease in the cleaved caspase 3 expression. These findings suggested that mild hypothermia inhibits CA-induced apoptosis in the hippocampus, which may be associated with reduced V-ATPase impairment. These data provide new insights into the protective effects of hypothermia in vivo. PMID:27323115

  20. GPIHBP1 and Plasma Triglyceride Metabolism.

    Science.gov (United States)

    Fong, Loren G; Young, Stephen G; Beigneux, Anne P; Bensadoun, André; Oberer, Monika; Jiang, Haibo; Ploug, Michael

    2016-07-01

    GPIHBP1, a GPI-anchored protein in capillary endothelial cells, is crucial for the lipolytic processing of triglyceride-rich lipoproteins (TRLs). GPIHBP1 shuttles lipoprotein lipase (LPL) to its site of action in the capillary lumen and is essential for the margination of TRLs along capillaries - such that lipolytic processing can proceed. GPIHBP1 also reduces the unfolding of the LPL catalytic domain, thereby stabilizing LPL catalytic activity. Many different GPIHBP1 mutations have been identified in patients with severe hypertriglyceridemia (chylomicronemia), the majority of which interfere with folding of the protein and abolish its capacity to bind and transport LPL. The discovery of GPIHBP1 has substantially revised our understanding of intravascular triglyceride metabolism but has also raised many new questions for future research. PMID:27185325

  1. The Role of Triglycerides in Atherosclerosis

    OpenAIRE

    Talayero, Beatriz G.; Sacks, Frank M.

    2011-01-01

    Hypertriglyceridemia is a prevalent risk factor for cardiovascular disease (CVD) and increasingly important in the setting of current obesity and insulin resistance epidemics. High triglyceride (TG) levels are markers for several types of atherogenic lipoproteins. Patients who have hypertriglyceridemia may be at significant risk for CVD even if low-density lipoprotein cholesterol levels are at goal, and therefore warrant treatment that optimizes diet, reduces overweight, and promotes regular ...

  2. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne;

    2011-01-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  3. Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-γ in patients with triglyceride deposit cardiomyovasculopathy

    International Nuclear Information System (INIS)

    Highlights: •Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare severe heart disease. •PPARγ is up-regulated in myocardium in patients with TGCV. •Possible vicious cycle for fatty acid may be involved in pathophysiology of TGCV. -- Abstract: Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, “Triglyceride deposit cardiomyovasculopathy (TGCV)”. Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5′ splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules’ lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients’ passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG

  4. Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-γ in patients with triglyceride deposit cardiomyovasculopathy

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Ken-ichi, E-mail: khirano@cnt-osaka.com [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan); Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Tatsuya [Center for Medical Research and Education, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Ikeda, Yoshihiko [Department of Pathology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita 565-8565 (Japan); Yamaguchi, Satoshi [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan); Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Zaima, Nobuhiro [Department of Applied Biochemistry, Kinki University, 3327-204, Nakamachi, Nara 631-8505 (Japan); Kobayashi, Kazuhiro [Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Suzuki, Akira [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan); Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakata, Yasuhiko [Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1, Seiryo-cho, Aoba-ku, Sendai 980-8574 (Japan); and others

    2014-01-10

    Highlights: •Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare severe heart disease. •PPARγ is up-regulated in myocardium in patients with TGCV. •Possible vicious cycle for fatty acid may be involved in pathophysiology of TGCV. -- Abstract: Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, “Triglyceride deposit cardiomyovasculopathy (TGCV)”. Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5′ splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules’ lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients’ passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG

  5. Patient Guide to the Assessment and Treatment of Hypertriglyceridemia (High Triglycerides)

    Science.gov (United States)

    Assessment and Treatment of Hypertriglyceridemia (High Triglycerides) A Patient’s Guide Having high levels of triglycerides, or hypertriglyceridemia , is a common problem. Triglycerides are fats in ...

  6. Cardiac arrest

    Science.gov (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  7. All-trans retinoic acid attenuates cardiac allograft vasculopathy and myocardial fibrosis%全反式维甲酸减轻大鼠移植心脏血管病变及纤维化

    Institute of Scientific and Technical Information of China (English)

    张明奎; 吴清玉; 胡建国

    2009-01-01

    目的 探讨全反式维甲酸(atRA)对大鼠移植心脏血管病变(CAV)及心肌纤维化的影响及可能机制.方法 以近交系Wistar大鼠为供者,SD大鼠为受者,进行异位心脏移植,一组受者术后接受环孢素A(CsA,10 nag·kg-1·d-1)皮下注射,同时以atRA(10 mg·kg-1·d-1)灌胃(atRA治疗组),另一组受者术后接受CsA皮下注射(慢性排斥组).术后60 d,取移植心脏,行Masson染色观察心肌组织纤维化程度,Van Gieson染色分析血管狭窄程度,免疫组织化学染色(sP法)观察心肌组织中CD68+细胞浸润情况,逆转录聚合酶链反应分析心肌组织中血小板生长因子(PDGF)A mRNA的相对含量.结果 慢性排斥组和atRA治疗组心肌纤维化指数分别为64.0±11.9和34.7±6.3,慢性排斥组纤维化指数明显高于atRA治疗组(P<0.01).慢性排斥组的血管狭窄指数为62.9±17.2,atRA治疗组为40.1±8.2,二者比较,差异有统计学意义(P<0.01).慢性排斥组CD68+细胞数为(32.1±9.3)个,atRA治疗组CD68+细胞数为(17.6±4.2)个,慢性排斥组明显高于atRA治疗组(P<0.01).慢性排斥组PDGF-AmRNA的相对含量为0.94±0.11,atRA治疗组为0.46±0.08,慢性排斥组明显高于atRA治疗组(P<0.01).结论 atRA能减轻大鼠心脏移植后的CAV及心肌纤维化,机制可能与其抑制CD68+细胞浸润及PDGF A mRNA表达有关.%Objective To investigate the mechanism of albtrans retinoic acid (atRA)attenuating cardiac allograft vasculopathy and myocardial fibrosis. Methods With inbred Wistar rats as donors and Sprague Dawley (SD) rats as recipients, heterotopic heart transplantation model was rejection group received same doses of cyclosporine A for 60 days. Grafts were removed on the day 60 post-transplant. Paraffin-embedded sections of cardiac allograft were stained with Masson's trichrome and Van Gieson for examination of myocardial fibrosis and vascular stenosis. Immunohistochemistry was performed to observe CD68 positive cell infiltration. Platelet

  8. Inborn errors of cytoplasmic triglyceride metabolism.

    Science.gov (United States)

    Wu, Jiang Wei; Yang, Hao; Wang, Shu Pei; Soni, Krishnakant G; Brunel-Guitton, Catherine; Mitchell, Grant A

    2015-01-01

    Triglyceride (TG) synthesis, storage, and degradation together constitute cytoplasmic TG metabolism (CTGM). CTGM is mostly studied in adipocytes, where starting from glycerol-3-phosphate and fatty acyl (FA)-coenzyme A (CoA), TGs are synthesized then stored in cytoplasmic lipid droplets. TG hydrolysis proceeds sequentially, producing FAs and glycerol. Several reactions of CTGM can be catalyzed by more than one enzyme, creating great potential for complex tissue-specific physiology. In adipose tissue, CTGM provides FA as a systemic energy source during fasting and is related to obesity. Inborn errors and mouse models have demonstrated the importance of CTGM for non-adipose tissues, including skeletal muscle, myocardium and liver, because steatosis and dysfunction can occur. We discuss known inborn errors of CTGM, including deficiencies of: AGPAT2 (a form of generalized lipodystrophy), LPIN1 (childhood rhabdomyolysis), LPIN2 (an inflammatory condition, Majeed syndrome, described elsewhere in this issue), DGAT1 (protein loosing enteropathy), perilipin 1 (partial lipodystrophy), CGI-58 (gene ABHD5, neutral lipid storage disease (NLSD) with ichthyosis and "Jordan's anomaly" of vacuolated polymorphonuclear leukocytes), adipose triglyceride lipase (ATGL, gene PNPLA2, NLSD with myopathy, cardiomyopathy and Jordan's anomaly), hormone-sensitive lipase (HSL, gene LIPE, hypertriglyceridemia, and insulin resistance). Two inborn errors of glycerol metabolism are known: glycerol kinase (GK, causing pseudohypertriglyceridemia) and glycerol-3-phosphate dehydrogenase (GPD1, childhood hepatic steatosis). Mouse models often resemble human phenotypes but may diverge markedly. Inborn errors have been described for less than one-third of CTGM enzymes, and new phenotypes may yet be identified. PMID:25300978

  9. Inborn errors of cytoplasmic triglyceride metabolism.

    Science.gov (United States)

    Wu, Jiang Wei; Yang, Hao; Wang, Shu Pei; Soni, Krishnakant G; Brunel-Guitton, Catherine; Mitchell, Grant A

    2015-01-01

    Triglyceride (TG) synthesis, storage, and degradation together constitute cytoplasmic TG metabolism (CTGM). CTGM is mostly studied in adipocytes, where starting from glycerol-3-phosphate and fatty acyl (FA)-coenzyme A (CoA), TGs are synthesized then stored in cytoplasmic lipid droplets. TG hydrolysis proceeds sequentially, producing FAs and glycerol. Several reactions of CTGM can be catalyzed by more than one enzyme, creating great potential for complex tissue-specific physiology. In adipose tissue, CTGM provides FA as a systemic energy source during fasting and is related to obesity. Inborn errors and mouse models have demonstrated the importance of CTGM for non-adipose tissues, including skeletal muscle, myocardium and liver, because steatosis and dysfunction can occur. We discuss known inborn errors of CTGM, including deficiencies of: AGPAT2 (a form of generalized lipodystrophy), LPIN1 (childhood rhabdomyolysis), LPIN2 (an inflammatory condition, Majeed syndrome, described elsewhere in this issue), DGAT1 (protein loosing enteropathy), perilipin 1 (partial lipodystrophy), CGI-58 (gene ABHD5, neutral lipid storage disease (NLSD) with ichthyosis and "Jordan's anomaly" of vacuolated polymorphonuclear leukocytes), adipose triglyceride lipase (ATGL, gene PNPLA2, NLSD with myopathy, cardiomyopathy and Jordan's anomaly), hormone-sensitive lipase (HSL, gene LIPE, hypertriglyceridemia, and insulin resistance). Two inborn errors of glycerol metabolism are known: glycerol kinase (GK, causing pseudohypertriglyceridemia) and glycerol-3-phosphate dehydrogenase (GPD1, childhood hepatic steatosis). Mouse models often resemble human phenotypes but may diverge markedly. Inborn errors have been described for less than one-third of CTGM enzymes, and new phenotypes may yet be identified.

  10. Unreliability of triglyceride measurement to predict turbidity induced interference

    OpenAIRE

    Twomey, P J; Don-Wauchope, A C; McCullough, D

    2003-01-01

    Lipaemic specimens are a common problem in clinical chemistry. Most laboratories will measure the concentration of triglycerides and then decide whether the analytical result is valid or not. There is a poor association between the concentration of triglycerides and an objective assessment of turbidity for visually turbid specimens. Extrapolation of triglyceride concentrations derived from the use of intravenous emulsions to visually turbid specimens found in clinical practice will overestima...

  11. Increasing insulin resistance accentuates the effect of triglyceride-associated loci on serum triglycerides during five years

    DEFF Research Database (Denmark)

    Justesen, Johanne M; Andersson, Ehm A; Allin, Kristine H;

    2016-01-01

    Blood concentrations of triglycerides are influenced by genetic factors, as well as a number of environmental factors including adiposity and glucose homeostasis. The aim to investigate the association between a weighted serum triglyceride genetic risk score (wGRS) and changes in fasting serum...... triglyceride level over five years and to test whether the effect of the wGRS was modified by 5-year changes of adiposity, insulin resistance and lifestyle factors. A total of 3,474 non-diabetic individuals from the Danish Inter99 cohort participated in both the baseline and 5-year follow-up physical...... examinations and had information on the wGRS comprising 39 genetic variants. In a linear regression model adjusted for age, sex and baseline serum triglyceride, the wGRS was associated with increased serum triglyceride levels over 5 years (per allele effect=1.3% (1.0;1.6); P=1.0*10(-17)). This triglyceride...

  12. Squalene Modulates Radiation-Induced Structural, Ultrastructural And Biochemical Changes In Cardiac Muscles Of Male Albino Rats

    International Nuclear Information System (INIS)

    The failing heart represents an enormous clinical problem and is a major cause of death throughout the world. Hyperlipidemia and oxidative stress have been shown to contribute to heart failure. Squalene is a remarkable bioactive substance that belongs to a class of antioxidants called isoprenoids, which neutralize the harmful effect of excessive free radicals production in the body.The present study was designed to determine the possible protective effect of squalene against oxidative cardiac muscle damage induced by gamma irradiation.Rats were treated daily by gavage with 0.4 ml/kg squalene for 42 days before whole body gamma irradiation at a dose of 4 Gy and continued until animals were sacrificed 3 days post irradiation.Histological examination of cardiac muscles sections by using light and electron microscopes showed that exposure of rats to ionizing radiation has provoked a severe architecture damage such as necrotic nuclei, nuclei located at the periphery, alteration in chromatin distribution, ruptured cell and mitochondrial membranes, cristae of mitochondria disappeared, sticking mitochondria and ruptured myofibers. Structural and ultra-structural changes were associated with severe oxidative stress. Significant increase of lipid peroxidation products (malondialdehyde) (MDA) along with reduction in the activity of the antioxidant enzymes; superoxide dismutase (SOD) and catalse (CAT), and glutathione content (GSH), were recorded.Treatment of rats with squalene has significantly attenuated the radiation-induced oxidative damage and histopathological changes in cardiac muscle which was substantiated by a significant amelioration in the activity of plasma lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and aspartate transaminase (AST). Furthermore, administration of squalene to rats has adjusted the radiation-induced increase in plasma triglycerides (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). Based on these results, it

  13. Cyclic GMP signaling in cardiomyocytes modulates fatty acid trafficking and prevents triglyceride accumulation.

    Science.gov (United States)

    Khairallah, Ramzi J; Khairallah, Maya; Gélinas, Roselle; Bouchard, Bertrand; Young, Martin E; Allen, Bruce G; Lopaschuk, Gary D; Deschepper, Christian F; Des Rosiers, Christine

    2008-08-01

    While the balance between carbohydrates and fatty acids for energy production appears to be crucial for cardiac homeostasis, much remains to be learned about the molecular mechanisms underlying this relationship. Given the reported benefits of cGMP signaling on the myocardium, we investigated the impact of its chronic activation on cardiac energy metabolism using mice overexpressing a constitutively active cytoplasmic guanylate cyclase (GC(+/0)) in cardiomyocytes. Ex vivo working GC(+/0) heart perfusions with (13)C-labeled substrates revealed an altered pattern of exogenous substrate fuel selection compared to controls, namely a 38+/-9% lower contribution of exogenous fatty acids to acetyl-CoA formation, while that of carbohydrates remains unchanged despite a two-fold increase in glycolysis. The lower contribution of exogenous fatty acids to energy production is not associated with changes in energy demand or supply (contractile function, oxygen consumption, tissue acetyl-CoA or CoA levels, citric acid cycle flux rate) or in the regulation of beta-oxidation (acetyl-CoA carboxylase activity, tissue malonyl-CoA levels). However, GC(+/0) hearts show a two-fold increase in the incorporation of exogenous oleate into triglycerides. Furthermore, the following molecular data are consistent with a concomitant increase in triglyceride hydrolysis: (i) increased abundance of hormone sensitive lipase (HSL) protein (24+/-11%) and mRNA (22+/-4%) as well as (ii) several phosphorylation events related to HSL inhibitory (AMPK) and activation (ERK 1/2) sites, which should contribute to enhance its activity. These changes in exogenous fatty acid trafficking in GC(+/0) hearts appear to be functionally relevant, as demonstrated by their resistance to fasting-induced triglyceride accumulation. While the documented metabolic profile of GC(+/0) mouse hearts is partly reminiscent of hypertrophied hearts, the observed changes in lipid trafficking have not been previously documented, and may

  14. The Protective Effect of Fasudil on the Structure and Function of Cardiac Mitochondria from Rats with Type 2 Diabetes Induced by Streptozotocin with a High-Fat Diet Is Mediated by the Attenuation of Oxidative Stress

    OpenAIRE

    Guo, Rong; Liu, Baoxin; Zhou, Shunping; ZHANG, BUCHUN; XU, YAWEI

    2013-01-01

    Dysfunction of cardiac mitochondria appears to play a substantial role in cardiomyopathy or myocardial dysfunction and is a promising therapeutic target for many cardiovascular diseases. We investigated the effect of the Rho/Rho-associated protein kinase (ROCK) inhibitor fasudil on cardiac mitochondria from rats in which diabetes was induced by a combination of streptozotocin (STZ) and a sustained high-fat diet. Eight weeks after diabetes was induced by a single intraperitoneal injection of 5...

  15. Dicarboxylic aciduria and medium chain triglyceride supplemented milk.

    OpenAIRE

    Henderson, M.J.; Dear, P R

    1986-01-01

    Pronounced dicarboxylic aciduria was observed in preterm infants fed a medium chain triglyceride supplemented milk formula. As many special formulas contain a medium chain triglyceride oil attention needs to be drawn to its metabolic effects, regarding the diagnosis of inborn errors of metabolism and that dicarboxylic acids might be harmful.

  16. Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

    NARCIS (Netherlands)

    Dallinga-Thie, GM; Van Tol, A; Hattori, H; van Vark-van de Zee, LC; Jansen, H; Sijbrands, EJG

    2006-01-01

    Aims/hypothesis: Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in pa

  17. Low Nonfasting Triglycerides and Reduced All-Cause Mortality

    DEFF Research Database (Denmark)

    Thomsen, Mette; Varbo, Anette; Tybjærg-Hansen, Anne;

    2014-01-01

    BACKGROUND: Increased nonfasting plasma triglycerides marking increased amounts of cholesterol in remnant lipoproteins are important risk factors for cardiovascular disease, but whether lifelong reduced concentrations of triglycerides on a genetic basis ultimately lead to reduced all......-cause mortality is unknown. We tested this hypothesis. METHODS: Using individuals from the Copenhagen City Heart Study in a mendelian randomization design, we first tested whether low concentrations of nonfasting triglycerides were associated with reduced all-cause mortality in observational analyses (n = 13 957......); second, whether genetic variants in the triglyceride-degrading enzyme lipoprotein lipase, resulting in reduced nonfasting triglycerides and remnant cholesterol, were associated with reduced all-cause mortality (n = 10 208). RESULTS: During a median 24 and 17 years of 100% complete follow-up, 9991...

  18. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  19. A review of omega-3 ethyl esters for cardiovascular prevention and treatment of increased blood triglyceride levels

    Directory of Open Access Journals (Sweden)

    Clemens von Schacky

    2006-09-01

    Full Text Available Clemens von SchackyMedizinische Klinik and Poliklinik Innenstadt, University of Munich, Munich, GermanyAbstract: The two marine omega-3 fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, prevalent in fish and fish oils, have been investigated as a strategy towards prophylaxis of atherosclerosis. While the results with fish and fish oils have been not as clear cut, the data generated with the purified ethyl ester forms of these two fatty acids are consistent. Although slight differences in biological activity exist between EPA and DHA, both exert a number of positive actions against atherosclerosis and its complications. EPA and DHA as ethyl esters inhibit platelet aggregability, and reduce serum triglycerides, while leaving other serum lipids essentially unaltered. Glucose metabolism has been studied extensively, and no adverse effects were seen. Pro-atherogenic cytokines are reduced, as are markers of endothelial activation. Endothelial function is improved, vascular occlusion is reduced, and the course of coronary atherosclerosis is mitigated. Heart rate is reduced, and heart rate variability is increased by EPA and DHA. An antiarrhythmic effect can be demonstrated on the supraventricular and the ventricular level. More importantly, two large studies showed reductions in clinical endpoints like sudden cardiac death or major adverse cardiac events. As a consequence, relevant cardiac societies recommend using 1 g/day of EPA and DHA for cardiovascular prevention, after a myocardial infarction and for prevention of sudden cardiac death.Keywords: sudden cardiac death, major adverse cardiac events, cardiovascular prevention, eicosapentaenoic acid, docosahexaenoic acid

  20. Comparison of serum triglyceride levels with propofol in long chain triglyceride and propofol in medium and long chain triglyceride after short term anesthesia in pediatric patients

    Directory of Open Access Journals (Sweden)

    Ishwar Bhukal

    2014-01-01

    Full Text Available Background: Significant increase in serum triglyceride (ST concentration have been described in adult population after prolonged administration of propofol formulation containing long chain triglyceride (LCT. Though, medium chain triglyceride-LCT (MCT-LCT propofol when compared with LCT propofol for long-term sedation in adults resulted in identical triglyceride levels, the elimination of triglyceride was faster in patients administered MCT-LCT propofol. Materials and Methods: A total of 40 children were randomized into two groups of 20 each; Group I were induced with 1% LCT propofol (3 mg/kg and Group II with 1% medium and LCT propofol and maintained with descalating dose of 20.15 and 10 mg/kg/h at 10 min intervals. Blood samples for ST concentration were obtained before induction of anesthesia, at the end of propofol infusion and 4 h after terminating propofol infusion. Results: ST levels were raised significantly above the basal values in both the groups but the rise was significantly higher in Group I (P < 0.05. Four hours after stopping propofol infusion the triglyceride levels were similar to the basal values in Group II, whereas in Group I the values were significantly greater than the baseline (P < 0.05 as well as those of Group II (P < 0.05. No clinically significant adverse effect of hypertriglyceridemia was observed. Conclusion: Even short term anesthesia with LCT and MCT-LCT propofol (1% leads to elevated ST levels. The increase in ST levels is less with MCT-LCT propofol and elimination of triglyceride is also rapid after terminating MCT-LCT propofol infusion.

  1. Unreliability of triglyceride measurement to predict turbidity induced interference.

    Science.gov (United States)

    Twomey, P J; Don-Wauchope, A C; McCullough, D

    2003-11-01

    Lipaemic specimens are a common problem in clinical chemistry. Most laboratories will measure the concentration of triglycerides and then decide whether the analytical result is valid or not. There is a poor association between the concentration of triglycerides and an objective assessment of turbidity for visually turbid specimens. Extrapolation of triglyceride concentrations derived from the use of intravenous emulsions to visually turbid specimens found in clinical practice will overestimate the turbidity induced interference in assays (non-turbid interferences are probably the same). The evaluation of turbidity induced interference needs to be standardised using objective assessments of turbidity.

  2. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids

    OpenAIRE

    Huang, Tom Hsun-Wei; Peng, Gang; Kota, Bhavani Prasad; Li, George Qian; Yamahara, Johji; Roufogalis, Basil D.; Li, Yuhao

    2005-01-01

    Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro.Long-term oral administration of PGF extract (500 mg kg−1) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholestero...

  3. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G

    2016-01-01

    Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need...... to reduce levels to no advice on treatment. New insight in epidemiology now suggests that these lipoproteins, marked by high triglycerides, are strong and independent predictors of ASCVD and all-cause mortality, and that their cholesterol content or remnant cholesterol likewise are strong predictors...... of ASCVD. Of all adults, 27% have triglycerides >2 mmol/L (176 mg/dL), and 21% have remnant cholesterol >1 mmol/L (39 mg/dL). For individuals in the general population with nonfasting triglycerides of 6.6 mmol/L (580 mg/dL) compared with individuals with levels of 0.8 mmol/L (70 mg/dL), the risks were 5...

  4. Cardiac rehabilitation

    Science.gov (United States)

    ... attack or other heart problem. You might consider cardiac rehab if you have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery Heart transplant Procedures such as angioplasty and stenting In some ...

  5. Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation.

    Science.gov (United States)

    Kang, Lin-Lin; Zhang, Dong-Mei; Ma, Chun-Hua; Zhang, Jian-Hua; Jia, Ke-Ke; Liu, Jia-Hui; Wang, Rong; Kong, Ling-Dong

    2016-01-01

    Fructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti-inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury, and cardioprotective effects of cinnamaldehyde and allopurinol are not completely understood. In this study, fructose-fed rats displayed metabolic syndrome with elevated serum ox-LDL, cardiac oxidative stress, inflammation and fibrosis. Scavenger receptor CD36, Toll-like receptor 4 (TLR4), TLR6, IL-1R-associated kinase 4/1 (IRAK4/1), nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin-1β, transforming growth factor-β (TGF-β), drosophila mothers against DPP homolog (Smad) 2/3 phosphorylation and Smad4 were increased in animal and H9c2 cell models. These pathological processes were further evaluated in ox-LDL or fructose-exposed H9c2 cells pretreated with ROS scavenger and CD36 specific inhibitor, or IRAK1/4 inhibitor, and transfected with CD36, NLRP3, or IRAK4/1 siRNA, demonstrating that NLPR3 inflammasome activation through CD36-mediated TLR4/6-IRAK4/1 signaling may promote cardiac inflammation and fibrosis. Cinnamaldehyde and allopurinol reduced cardiac oxidative stress to suppress NLPR3 inflammasome activation and TGF-β/Smads signaling by inhibiting CD36-mediated TLR4/6-IRAK4/1 signaling under fructose induction. These results suggest that the blockage of CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation by cinnamaldehyde and allopurinol may protect against fructose-induced cardiac inflammation and fibrosis. PMID:27270216

  6. Gender differences in cardiac hypertrophic remodeling.

    Science.gov (United States)

    Patrizio, Mario; Marano, Giuseppe

    2016-01-01

    Cardiac remodeling is a complex process that occurs in response to different types of cardiac injury such as ischemia and hypertension, and that involves cardiomyocytes, fibroblasts, vascular smooth muscle cells, vascular endothelial cells, and inflammatory cells. The end result is cardiomyocyte hypertrophy, fibrosis, inflammation, vascular, and electrophysiological remodeling. This paper reviews a large number of studies on the influence of gender on pathological cardiac remodeling and shows how sex differences result in different clinical outcomes and therapeutic responses, with males which generally develop greater cardiac remodeling responses than females. Although estrogens appear to have an important role in attenuating adverse cardiac remodeling, the mechanisms through which gender modulates myocardial remodeling remain to be identified. PMID:27364397

  7. Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2011-07-01

    Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

  8. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  9. Decreased expression of natriuretic peptides associated with lipid accumulation in cardiac ventricle of obese mice

    DEFF Research Database (Denmark)

    Bartels, E.D.; Nielsen, J.M.; Bisgaard, L.S.;

    2010-01-01

    -actin) and natriuretic peptide receptor genes were not consistently altered by obesity across the three mouse models. In contrast, cardiac ventricular triglycerides were similarly increased by 60-115% in all three obese mouse models and incubation with oleic acid caused triglyceride accumulation and an approximately 35......Plasma B-type natriuretic peptide (BNP) and proBNP are established markers of cardiac dysfunction. Even though obesity increases the risk of cardiovascular disease, obese individuals have reduced plasma concentrations of natriuretic peptides. The underlying mechanism is not established. We used...... cultured cardiomyocytes and three different mouse models to examine the impact of obesity and cardiac lipid accumulation on cardiac natriuretic peptide expression. The cardiac ventricular expression of atrial natriuretic peptide (ANP) and BNP mRNA and ANP peptide was decreased 36-72% in obese ob/ob, db...

  10. [Residual risk: The roles of triglycerides and high density lipoproteins].

    Science.gov (United States)

    Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

    2016-06-01

    In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target. PMID:27305303

  11. Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver.

    Science.gov (United States)

    Yokota, Shin-Ichi; Nakamura, Kaai; Ando, Midori; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shibata, Shigenobu

    2014-01-01

    Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism. PMID:25383314

  12. Acetylcholinesterase (AChE inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

    Directory of Open Access Journals (Sweden)

    Shin-Ichi Yokota

    2014-01-01

    Full Text Available Although fasting induces hepatic triglyceride (TG accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1 and liver-fatty acid binding-protein (L-FABP. Physostigmine promoted the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism.

  13. [Cardiac amyloidosis].

    Science.gov (United States)

    Hoyer, Caroline; Angermann, Christiane E; Knop, Stefan; Ertl, Georg; Störk, Stefan

    2008-03-15

    Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment. PMID:18344065

  14. Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: Modulation of cardiac PPAR-α-mediated transcription of fatty acid metabolic genes

    International Nuclear Information System (INIS)

    Excess cardiac triglyceride accumulation in diabetes and obesity induces lipotoxicity, which predisposes the myocytes to death. On the other hand, increased cardiac fatty acid (FA) oxidation plays a role in the development of myocardial dysfunction in diabetes. PPAR-α plays an important role in maintaining homeostasis of lipid metabolism. We have previously demonstrated that the extract from Salacia oblonga root (SOE), an Ayurvedic anti-diabetic and anti-obesity medicine, improves hyperlipidemia in Zucker diabetic fatty (ZDF) rats (a genetic model of type 2 diabetes and obesity) and possesses PPAR-α activating properties. Here we demonstrate that chronic oral administration of SOE reduces cardiac triglyceride and FA contents and decreases the Oil red O-stained area in the myocardium of ZDF rats, which parallels the effects on plasma triglyceride and FA levels. Furthermore, the treatment suppressed cardiac overexpression of both FA transporter protein-1 mRNA and protein in ZDF rats, suggesting inhibition of increased cardiac FA uptake as the basis for decreased cardiac FA levels. Additionally, the treatment also inhibited overexpression in ZDF rat heart of PPAR-α mRNA and protein and carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase mRNAs and restored the downregulated acetyl-CoA carboxylase mRNA. These results suggest that SOE inhibits cardiac FA oxidation in ZDF rats. Thus, our findings suggest that improvement by SOE of excess cardiac lipid accumulation and increased cardiac FA oxidation in diabetes and obesity occurs by reduction of cardiac FA uptake, thereby modulating cardiac PPAR-α-mediated FA metabolic gene transcription

  15. The use of medium-chain triglycerides in preterm infants

    NARCIS (Netherlands)

    E.J. Sulkers (Eric)

    1993-01-01

    textabstractFor many years, medium-chain triglycerides (MCTs), with a chain length of eight and ten carbon atoms, have been included in preterm infant formulas. MCTs are manufactured by reesterification of medium-chain fatty acids (MCFAs) from coconut oil, and their intestil1al absorption is assumed

  16. Fatty liver and medium chain triglyceride (MCT) diet.

    OpenAIRE

    Beverley, D; Arthur, R.

    1988-01-01

    A 12 year old boy with intractable epilepsy developed fatty infiltration of the liver after three years' treatment on the medium chain triglyceride (MCT) diet. This was not associated with any hepatic dysfunction and resolved after discontinuing the diet. Three of four other patients on the same diet had evidence of hepatic steatosis.

  17. Triglyceride selectivity of immobilized Thermomyces lanuginosa lipase in interesterification

    DEFF Research Database (Denmark)

    Rønne, Torben Harald; Pedersen, Lars S.; Xu, Xuebing

    2005-01-01

    The triglyceride (fatty acid) selectivity of an immobilized lipase from Thermomyces lanuginosa (Lipozyme TL IM) was investigated in lipase-catalyzed interesterification reactions between two mono-acid TG in n-hexane. Tristearin (tri-C18:0) was used as a reference in a series of TG with saturated FA...

  18. Diagnostic value of postprandial triglyceride testing in healthy subjects

    DEFF Research Database (Denmark)

    Mihas, Constantinos; Kolovou, Genovefa D; Mikhailidis, Dimitri P;

    2011-01-01

    Triglycerides (TGs) are measured in studies evaluating changes in non-fasting lipid profiles after a fat tolerance test (FTT); however, the optimal timing for TG measurements after the oral fat load is unclear. The aim of this study was to evaluate how non-fasting TG levels vary after an oral FTT...

  19. Triglycerides in the human kidney cortex: relationship with body size.

    Directory of Open Access Journals (Sweden)

    Ion Alexandru Bobulescu

    Full Text Available Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04. Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis.

  20. Myocardial triglycerides : magnetic resonance spectroscopy in health and diabetes

    NARCIS (Netherlands)

    Hammer, Sebastiaan

    2008-01-01

    In this thesis we focused on the functional and metabolic consequences of myocardial triglyceride (TG) accumulation in healthy subjects and in patients with diabetes mellitus. Ectopic accumulation of TGs is associated with organ dysfunction in metabolic disease in experimental animal studies. These

  1. Cardiac rhabdomyosarcoma

    OpenAIRE

    Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

    2001-01-01

    Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical stain...

  2. FATTY-ACID COMPOSITION OF HUMAN-MILK TRIGLYCERIDE SPECIES - POSSIBLE CONSEQUENCES FOR OPTIMAL STRUCTURES OF INFANT FORMULA TRIGLYCERIDES

    NARCIS (Netherlands)

    WINTER, CH; HOVING, EB; MUSKIET, FAJ

    1993-01-01

    Human milk triglycerides (TGs) were separated into 14 fractions by silver ion high-performance liquid chromatography (HPLC) with light-scattering detection (LSD). Subsequent fractionation by reversed-phase HPLC-LSD resulted in 75 subfractions. The major 48 were analysed by gas chromatography for the

  3. Fasting versus post-challenge triglycerides and pre-existing cavitating lacunes: a Berlin Cream & Sugar substudy.

    Directory of Open Access Journals (Sweden)

    Christopher O Leonards

    2013-07-01

    Full Text Available Background and Purpose: Although the presence of cavitating lacunes on brain imaging may have prognostic implications, the modifiable risk factors underlying these frequently observed lesions are not completely understood. We sought to determine if fasting and post-challenge triglycerides associate with cavitating lacunes.Methods: All first ischemic stroke patients who completed a novel combined oral triglyceride and glucose tolerance test and MRI between January 2009 and June 2012 were included. Fluid-attenuated inversion recovery or T2 MRI sequences were used to visualize cavitating lacunes and white matter hyperintensities, which were graded using the Wahlund visual scale. Results: 190 patients were included (median age 66, IQR 52-73; 33% female; median National Institute of Health Stroke Scale 2, IQR 1-4. A forward stepwise binary logistical regression analysis applying the Hosmer-Lameshow goodness of fit test adjusted for parameters significant in univariate analyses (at the p<0.10 level revealed that Wahlund scores (Wahlund 0-4: reference; Wahlund 5-10: adjusted odds ratio, 5.1; 95% confidence interval, 1.3-20.0, P=0.019; Wahlund >10: adjusted odds ratio 9.6; 95% CI, 1.55-59.35; P=0.015 and the highest quartile of post-challenge triglycerides (>295 mg/dL; adjusted odds ratio, 7.36; 95% confidence interval 1.24-43.70; P=0.028 independently associated with the presence of cavitating lacunes. Conclusion: Post-challenge serum triglycerides are independently associated with the presence of cavitating lacunes. Clinical Trial Registration Information: The Berlin Cream&Sugar study is registered with EudraCT (2009-010356-97 and clinicaltrials.gov (NCT 01378468.  

  4. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels

    OpenAIRE

    Md. Ibrahim Khalil; E. M. Tanvir; Rizwana Afroz; Siti Amrah Sulaiman; Siew Hua Gan

    2015-01-01

    The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey...

  5. Role of Triglyceride-rich Lipoproteins in Renal Injury

    OpenAIRE

    Ng, Kit Fai; AUNG, HNIN HNIN; Rutledge, John C.

    2011-01-01

    Dyslipidemia is implicated as a risk factor for the development of atherosclerosis. Specifically triglyceride-rich lipoproteins (TGRL) and their lipolysis products are shown to be pro-inflammatory and pro-apoptosis in both in vivo and in vitro studies with endothelium. However the role of TGRL in the progression of kidney diseases is not clear. Epidemiology studies demonstrated a correlation between renal disease and blood lipids. Recent evidence suggests that the mechanism may involve cellul...

  6. Lowering triglycerides to modify cardiovascular risk: will icosapent deliver?

    Directory of Open Access Journals (Sweden)

    Scherer DJ

    2015-03-01

    Full Text Available Daniel J Scherer,1 Stephen J Nicholls2 1Cardiovascular Investigation Unit, Royal Adelaide Hospital, 2South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, SA, Australia Abstract: Despite the clinical benefits of lowering levels of low-density lipoprotein cholesterol, many patients continue to experience cardiovascular events. This residual risk suggests that additional risk factors require aggressive modification to result in more effective prevention of cardiovascular disease. Hypertriglyceridemia has presented a considerable challenge with regard to understanding its role in the promotion of cardiovascular risk. Increasing evidence has established a clear causal role for elevated triglyceride levels in vascular risk. As a result, there is increasing interest in the development of specific therapeutic strategies that directly target hypertriglyceridemia. This has seen a resurgence in the use of omega-3 fatty acids for the therapeutic lowering of triglyceride levels. The role of these agents and other emerging strategies to reduce triglyceride levels in order to decrease vascular risk are reviewed. Keywords: hypertriglyceridemia, omega-3 fatty acid, fish oil, cardiovascular risk, lipids

  7. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

    DEFF Research Database (Denmark)

    Sarwar, Nadeem; Sandhu, Manjinder S; Ricketts, Sally L;

    2010-01-01

    Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality....

  8. Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-β1 expression and fibrosis in minipigs with ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    LU Lin; SHEN Wei-feng; ZHANG Qi; XU Yan; ZHU Zheng-bin; GENG Liang; WANG Ling-jie; JIN Cao; CHEN Qiu-jing; Ann Marie Schmidt

    2010-01-01

    Background The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n=5) or saline (control group, n=5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-β1was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 5.1) to (32.3 5.6) ml, P <0.05) and end-systolic volume (from (8.3 3.2) to (15.2 4.1) ml, P <0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 13.3)% to (50.2 11.9)%, P<0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P<0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P<0.05). Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

  9. Sildenafil and FDP-Sr attenuate diabetic cardiomyopathy by suppressing abnormal expression of myocardial CASQ2,FKBPl2.6,and SERCA2a in rats

    Institute of Scientific and Technical Information of China (English)

    Yu-si CHENG; De-zai DAI; Hui JI; Qi ZHANG; Yin DAI

    2011-01-01

    Alm:To study whether calcium-modulating proteins CASQ2,FKBPl2.6 and SERCA2a participate in diabetic cardiomyopathy,and whether the beneficial actions of testosterone,sildenafil or fructose diphosphate Sr(FDP-Sr)in the treatment of diabetic cardiomyopathy result from suppressing these molecules.Methods:Fifry male Sprague-Dawley(SD)rats were divided into five groups.Except for the normal gmup(non-diabetic), the other four groups were injected with streptozotocin(STZ,60 mg/kg,ip)to induce diabetes.Four weeks after STZ injection,the four groups received sildenafil(12 mg·kg-1·d-1,ig,for 4 week).FDP-Sr(200 mg/kg,ig for 4 week),testosterone propionate(4 mg·kg-1·d-1,sc,for 4 week),or no treatment,respectively.Results:In the diabetic rats.blood glucose.free fatty acids.triglycerides.total cholesterol.and low-density lipoprotein cholesterol (LDL-C)were significantly increased.while high-density lipoprotein cholesterol(HDL-C)was significantly reduced.as compared to the non-dlabetic rats.Cardiac dysfunction and myocardial hypertrophy of the diabetic rats were associated with increased mRNA and protein expression of iNOS,OBRb,and PKCε.while expression of CASQ2,SERCA2a.and FKBPl2.6 was significantly down-regulated.Sildenafil and FDp-St,but not testosterone.significantly attenuated the biomarker abnormalities, without changing the metabolic abnormalities.Conclusion:CASQ2.FKBPl2.6 and SERCA2a were down.regulated in diabetic cardiomyopathy.Sildenafil and FDP-Sr, but not testosterone, attenuated the cardiac dysfunction in diabetic cardiomyopathy,without changing the metabolic abnormalities,which may results from inhibiting oxidative and inflammatory cytokines and improving calcium homeostasis.

  10. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  11. Photonic Crystal Fiber Attenuator

    Institute of Scientific and Technical Information of China (English)

    Joo Beom Eom; Hokyung Kim; Jinchae Kim; Un-Chul Paek; Byeong Ha Lee

    2003-01-01

    We propose a novel fiber attenuator based on photonic crystal fibers. The difference in the modal field diameters of a conventional single mode fiber and a photonic crystal fiber was used. A variable optical attenuator was also achieved by applying macro-bending on the PCF part of the proposed attenuator

  12. Parenteral use of medium-chain triglycerides: a reappraisal.

    Science.gov (United States)

    Ulrich, H; Pastores, S M; Katz, D P; Kvetan, V

    1996-04-01

    Over the last two decades, the clinical use of intravenous fat emulsions for the nutritional support of hospitalized patients has become routine. During this time long-chain triglycerides (LCT) derived from soybean and/or safflower oils were the exclusive lipid source for these emulsions, providing both a safe calorically dense alternative to dextrose and essential fatty acids needed for biologic membranes and the maintenance of immune function. During the past decade, the availability of novel experimental triglycerides for parenteral use has generated interest in the use of these substrates for nutritional and metabolic support. Medium-chain triglycerides (MCT), long advocated as a superior substrate for parenteral use, possess many unique physiochemical and metabolic properties that make them theoretically advantageous over their LCT counterparts. Although not yet approved in the United States, preparations containing MCT have been widely available in Europe. Intravenous MCT preparations, either as physical mixtures or structured lipids, have been used clinically in patients with immunosuppresion, critical illness, liver and pulmonary disease and in premature infants. Despite great promise, the clinical data comparing the efficacy of MCT-based lipid emulsions to their LCT counterparts has been equivocal. This may be due in part to the limited nature of the published clinical trials. Measures of efficacy for parenteral or enteral nutritional products has taken on new meaning, in light of the reported experience using immunomodulatory nutrients. Current concerns about cost of medical care and resource use warrant careful deliberation about the utility of any new and expensive therapy. Until clinical data can fulfill expectations derived from animal studies, it is difficult to advocate the general use of MCT-based lipid emulsions. Future clinical studies with MCT-based emulsions should have clear outcome objectives sufficient to prove their theorized metabolic

  13. Short-term overexpression of DGAT1 or DGAT2 increases hepatic triglyceride but not VLDL triglyceride or apoB production

    NARCIS (Netherlands)

    Millar, John S.; Stone, Scot J.; Tietge, Uwe J. F.; Tow, Bryan; Billheimer, Jeffrey T.; Wong, Jinny S.; Hamilton, Robert L.; Farese, Robert V.; Rader, Daniel J.

    2006-01-01

    Increased triglyceride synthesis resulting from enhanced flux of fatty acids into liver is frequently associated with VLDL overproduction. This has led to the common belief that hepatic triglyceride synthesis can directly modulate VLDL production. We used adenoviral vectors containing either murine

  14. Micro RNA-124a Regulates Lipolysis via Adipose Triglyceride Lipase and Comparative Gene Identification 58

    Directory of Open Access Journals (Sweden)

    Suman K. Das

    2015-04-01

    Full Text Available Lipolysis is the biochemical pathway responsible for the catabolism of cellular triacylglycerol (TG. Lipolytic TG breakdown is a central metabolic process leading to the generation of free fatty acids (FA and glycerol, thereby regulating lipid, as well as energy homeostasis. The precise tuning of lipolysis is imperative to prevent lipotoxicity, obesity, diabetes and other related metabolic disorders. Here, we present our finding that miR-124a attenuates RNA and protein expression of the major TG hydrolase, adipose triglyceride lipase (ATGL/PNPLA2 and its co-activator comparative gene identification 58 (CGI-58/ABHD5. Ectopic expression of miR-124a in adipocytes leads to reduced lipolysis and increased cellular TG accumulation. This phenotype, however, can be rescued by overexpression of truncated Atgl lacking its 3'UTR, which harbors the identified miR-124a target site. In addition, we observe a strong negative correlation between miR-124a and Atgl expression in various murine tissues. Moreover, miR-124a regulates the expression of Atgl and Cgi-58 in murine white adipose tissue during fasting as well as the expression of Atgl in murine liver, during fasting and re-feeding. Together, these results point to an instrumental role of miR-124a in the regulation of TG catabolism. Therefore, we suggest that miR-124a may be involved in the regulation of several cellular and organismal metabolic parameters, including lipid storage and plasma FA concentration.

  15. Pleiotropic Analysis of Lung Cancer and Blood Triglycerides.

    Science.gov (United States)

    Zuber, Verena; Marconett, Crystal N; Shi, Jianxin; Hua, Xing; Wheeler, William; Yang, Chenchen; Song, Lei; Dale, Anders M; Laplana, Marina; Risch, Angela; Witoelar, Aree; Thompson, Wesley K; Schork, Andrew J; Bettella, Francesco; Wang, Yunpeng; Djurovic, Srdjan; Zhou, Beiyun; Borok, Zea; van der Heijden, Henricus F M; de Graaf, Jacqueline; Swinkels, Dorine; Aben, Katja K; McKay, James; Hung, Rayjean J; Bikeböller, Heike; Stevens, Victoria L; Albanes, Demetrius; Caporaso, Neil E; Han, Younghun; Wei, Yongyue; Panadero, Maria Angeles; Mayordomo, Jose I; Christiani, David C; Kiemeney, Lambertus; Andreassen, Ole A; Houlston, Richard; Amos, Christopher I; Chatterjee, Nilanjan; Laird-Offringa, Ite A; Mills, Ian G; Landi, Maria Teresa

    2016-12-01

    Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.1 (rs6904596, ZNF184) was associated with both lung cancer (P = 5.50x10(-6)) and blood triglycerides (P = 1.39x10(-5)). We replicated the association in 6097 lung cancer case patients and 204 657 control subjects (P = 2.40 × 10(-4)) and in 71 113 subjects with triglycerides data (P = .01). rs6904596 reached genome-wide significance in lung cancer meta-analysis (odds ratio = 1.15, 95% confidence interval = 1.10 to 1.21 ,: Pcombined = 5.20x10(-9)). The large sample size provided by the lipid GWAS data and the shared genetic risk factors between the two traits contributed to the uncovering of a hitherto unidentified genetic locus for lung cancer. PMID:27565901

  16. Cardiac perception and cardiac control. A review.

    Science.gov (United States)

    Carroll, D

    1977-12-01

    The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks. PMID:348240

  17. JTT-130, a microsomal triglyceride transfer protein (MTP inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs

    Directory of Open Access Journals (Sweden)

    Shrestha Sudeep

    2005-09-01

    Full Text Available Abstract Background Microsomal transfer protein inhibitors (MTPi have the potential to be used as a drug to lower plasma lipids, mainly plasma triglycerides (TG. However, studies with animal models have indicated that MTPi treatment results in the accumulation of hepatic TG. The purpose of this study was to evaluate whether JTT-130, a unique MTPi, targeted to the intestine, would effectively reduce plasma lipids without inducing a fatty liver. Methods Male guinea pigs (n = 10 per group were used for this experiment. Initially all guinea pigs were fed a hypercholesterolemic diet containing 0.08 g/100 g dietary cholesterol for 3 wk. After this period, animals were randomly assigned to diets containing 0 (control, 0.0005 or 0.0015 g/100 g of MTPi for 4 wk. A diet containing 0.05 g/100 g of atorvastatin, an HMG-CoA reductase inhibitor was used as the positive control. At the end of the 7th week, guinea pigs were sacrificed to assess drug effects on plasma and hepatic lipids, composition of LDL and VLDL, hepatic cholesterol and lipoprotein metabolism. Results Plasma LDL cholesterol and TG were 25 and 30% lower in guinea pigs treated with MTPi compared to controls (P Conclusion These results suggest that JTT-130 could have potential clinical applications due to its plasma lipid lowering effects with no alterations in hepatic lipid concentrations.

  18. Medium-chain triglyceride and n-3 polyunsaturated fatty acid-containing emulsions in intravenous nutrition.

    Science.gov (United States)

    Chan, S; McCowen, K C; Bistrian, B

    1998-03-01

    Medium-chain triglycerides and n-3 polyunsaturated fatty acid emulsions as a physical mixture have attracted increasing interest for use in parenteral nutrition and may play an important role in the development of structured triglycerides in a future generation of new lipids. Over the past two decades, the clinical use of intravenous emulsion for the nutritional support of hospitalized patients has relied exclusively on long-chain triglycerides providing both a safe, calorically dense alternative to dextrose and a source of essential fatty acids needed for biological membranes and maintenance of the immune function. During the past decade, the development of new triglycerides (medium- and long-chain triglyceride emulsions and structured triglyceride emulsions) for parenteral use have provided useful advances and opportunities to enhance nutritional and metabolic support. Medium-chain triglycerides and n-3 polyunsaturated fatty acid emulsions possess unique physical, chemical, and metabolic properties that make them theoretically advantageous over the conventional long-chain triglycerides. The physical mixture of medium- and long-chain triglycerides have been used clinically in patients with critical illness, liver disease, immunosuppression, pulmonary disease, and in premature infants, with good tolerance and the avoidance of some of the problems encountered with long-chain triglycerides alone. PMID:10565343

  19. Lack of triglyceride-lowering properties of fish oil in apolipoprotein e-deficient mice.

    Science.gov (United States)

    Asset, G; Baugé, E; Fruchart, J C; Dallongeville, J

    2001-03-01

    Fish oil is a potent triglyceride (TG)-lowering agent in humans. The goal of the present study was to assess the contribution of decreased triglyceride synthesis and of apoE in mediation of the triglyceride-lowering effect of fish oil. To this end, apoE-deficient mice and wild-type control mice were supplemented with either coconut oil, sunflower oil, or fish oil (20% wt/wt) for 2 weeks. Compared with coconut oil and sunflower oil, fish oil reduced the concentrations of cholesterol and triglycerides in the wild-type mice, whereas it had no effect on cholesterol concentration and it had a triglyceride-raising effect in apoE-deficient mice. The latter was due to increased triglyceride concentrations in the doil than after a sunflower oil load. These data indicate an impairment of triglyceride metabolism in the fish oil-fed apoE-deficient mice. Compared with coconut oil and sunflower oil, fish oil lowered triglyceride production rates measured with the Triton method in both wild-type (Poil-fed wild-type and apoE-deficient mice, suggesting an alteration in VLDL lipolysis independent of the mice genotype. In conclusion, fish oil does not decrease triglyceride concentrations in apoE-deficient mice despite reducing triglyceride production rates, suggesting that decreased triglyceride synthesis is not sufficient to lower triglyceride concentrations in mice. ApoE appears to be necessary for fish oil to lower plasma triglyceride concentrations, indicating a critical role of apoE in this process.

  20. Cardiac metastasis from colorectal cancer: A case report

    Institute of Scientific and Technical Information of China (English)

    Pyong Wha Choi; Chul Nam Kim; Sun Hee Chang; Woo Ik Chang; Chang Young Kim; Hyun Min Choi

    2009-01-01

    The heart is an unusual site of metastasis from any malignancy. We report a case of cardiac metastasis from colorectal cancer. A 70-year-old woman was referred with a presumptive diagnosis of sigmoid colon cancer with cardiac myxoma. Two-dimensional echocardiography showed a 4 cm × 4.5 cm mobile mass on the lateral right atrial wall, and computed tomography revealed a low attenuated lobulating mass in the right atrium. The patient underwent anterior resection for sigmoid colon cancer (T4N2). Thereafter, she experienced progressive shortness of breath. Therefore, a cardiac operation was performed 2 wk after the colorectal operation.Histological examination revealed adenocarcinoma,which was identical to the primary lesion. Although twodimensional echocardiography has become the diagnostic test of choice for detecting cardiac tumors, in patients with colorectal cancer showing a cardiac mass, further diagnostic evaluation such as a magnetic resonance imaging might be necessary.

  1. Variable laser attenuator

    Science.gov (United States)

    Foltyn, Stephen R.

    1988-01-01

    The disclosure relates to low loss, high power variable attenuators comprng one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength.

  2. Therapeutic Targets of Triglyceride Metabolism as Informed by Human Genetics.

    Science.gov (United States)

    Bauer, Robert C; Khetarpal, Sumeet A; Hand, Nicholas J; Rader, Daniel J

    2016-04-01

    Human genetics has contributed to the development of multiple drugs to treat hyperlipidemia and coronary artery disease (CAD), most recently including antibodies targeting PCSK9 to reduce LDL cholesterol. Despite these successes, a large burden of CAD remains. Genetic and epidemiological studies have suggested that circulating triglyceride (TG)-rich lipoproteins (TRLs) are a causal risk factor for CAD, presenting an opportunity for novel therapeutic strategies. We discuss recent unbiased human genetics testing, including genome-wide association studies (GWAS) and whole-genome or -exome sequencing, that have identified the lipoprotein lipase (LPL) and hepatic lipogenesis pathways as important mechanisms in the regulation of circulating TRLs. Further strengthening the causal relationship between TRLs and CAD, findings such as these may provide novel targets for much-needed potential therapeutic interventions. PMID:26988439

  3. Anatomical relationship between traditional acupuncture point ST 36 and Omura's ST 36 (True ST 36) with their therapeutic effects: 1) inhibition of cancer cell division by markedly lowering cancer cell telomere while increasing normal cell telomere, 2) improving circulatory disturbances, with reduction of abnormal increase in high triglyceride, L-homocystein, CRP, or cardiac troponin I & T in blood by the stimulation of Omura's ST 36--Part 1.

    Science.gov (United States)

    Omura, Yoshiaki; Chen, Yemeng; Lu, Dominic P; Shimotsura, Yasuhiro; Ohki, Motomu; Duvvi, Harsha

    2007-01-01

    for cardio-vascular diseases with hypertriglyceridemia, hyperglycemia, high L-homocystein, and CRP, high cardiac Troponim I & T, and some hypertension. These beneficial effects were accompanied by euphoria, & relaxation with increased alpha waves in EEG. Thus Omura's ST 36 stimulation is a safe, effective and highly desirable supplemental treatment. In addition to manual stimulation, similar beneficial effects can be induced by finger tip stmulation (without any needle) or with electroacupuncture stimulation, (+) Qi Gong energy stored paper and (+) solar energy stored paper which often resulted in significant clinical improvement.

  4. Blood Triglycerides Levels and Dietary Carbohydrate Indices in Healthy Koreans

    Science.gov (United States)

    Kang, Ji Yeon

    2016-01-01

    Objectives: Previous studies have obtained conflicting findings regarding possible associations between indices measuring carbohydrate intake and dyslipidemia, which is an established risk factor of coronary heart disease. In the present study, we examined cross-sectional associations between carbohydrate indices, including the dietary glycemic index (GI), glycemic load (GL), total amount of carbohydrates, and the percentage of energy from carbohydrates, and a range of blood lipid parameters. Methods: This study included 1530 participants (554 men and 976 women) from 246 families within the Healthy Twin Study. We analyzed the associations using a generalized linear mixed model to control for familial relationships. Results: Levels of the Apo B were inversely associated with dietary GI, GL, and the amount of carbohydrate intake for men, but these relationships were not significant when fat-adjusted values of the carbohydrate indices were used. Triglyceride levels were positively associated with dietary GI and GL in women, and this pattern was more notable in overweight participants (body mass index [BMI] ≥25 kg/m2). However, total, low-density lipoprotein and high-density lipoprotein cholesterol levels were not significantly related with carbohydrate intake overall. Conclusions: Of the blood lipid parameters we investigated, only triglyceride levels were positively related with dietary carbohydrate indices among women participants in the Healthy Twin Study, with an interactive role observed for BMI. However, these associations were not observed in men, suggesting that the association between blood lipid levels and carbohydrate intake depends on the type of lipid, specific carbohydrate indices, gender, and BMI. PMID:27255074

  5. Triglyceride kinetics in fasted and fed E. coli septic rats

    Energy Technology Data Exchange (ETDEWEB)

    Lanza-Jacoby, S.; Tabares, A. (Jefferson Medical Coll., Philadelphia, PA (United States))

    1990-02-26

    The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studies by examining the liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess the liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant intravenous infusion of (2-{sup 3}H) glycerol-labeled VLDL in fasted control, fasted E. coli-treated, fed control, and fed E.coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 {times} 10{sup 7} live E.coli colonies per 100 g body weight. Twenty-four hours following E.coli injection serum TG of fasted E.coli-treated rats was elevated by 170% which was attributed to a 67% decrease in the clearance rate of VLDL-TG in fasted E.coli-treated rats compared with their fasted controls. The secretion of VLDL-TG declined by 31% in the livers of the fasted E.coli-treated rats which was accompanied by a 2-fold increase in the composition of liver TG. In a second series of experiments control and E.coli-treated rats were fed intragastrically (IG) a balanced solution containing glucose plus fat as the sources of nonprotein calories. Serum TG were 26% lower in the fed E.coli-treated rats because the clearance rate increased by 86%. The secretion of TG in the fed septic rats increased by 40% but this difference was not significant. In the septic rat the ability to clear triglycerides from the plasma depends upon the nutritional state.

  6. Common variants associated with plasma triglycerides and risk for coronary artery disease

    DEFF Research Database (Denmark)

    Do, R.; Willer, C. J.; Schmidt, E. M.;

    2013-01-01

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common...... variants recently mapped for plasma lipids (P triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations...... with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength...

  7. Cardiac sodium channelopathies

    NARCIS (Netherlands)

    A.S. Amin; A. Asghari-Roodsari; H.L. Tan

    2010-01-01

    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I-Na) during phase 0 of the cardiac action potential. The importance of I-Na for normal cardiac electrical activity is reflected by the high incidence of

  8. Diffuse infiltrative cardiac tuberculosis

    International Nuclear Information System (INIS)

    We present the cardiac magnetic resonance images of an unusual form of cardiac tuberculosis. Nodular masses in a sheet-like distribution were seen to infiltrate the outer myocardium and pericardium along most of the cardiac chambers. The lesions showed significant resolution on antitubercular therapy

  9. Oxidative stabilization of mixed mayonnaises made with linseed oil and saturated medium-chain triglyceride oil

    DEFF Research Database (Denmark)

    Raudsepp, Piret; Brüggemann, Dagmar A.; Lenferink, Aufried;

    2014-01-01

    Mayonnaises, made with either saturated medium chain triglyceride (MCT) oil or unsaturated purified linseed oil (LSO), were mixed. Raman confocal microspectrometry demonstrated that lipid droplets in mixed mayonnaise remained intact containing either MCT oil or LSO. Peroxide formation during...... simply diluting unsaturated triglycerides with saturated triglycerides is causing the oxidative stabilization observed for mixed mayonnaise and mixed oil mayonnaise. © 2013 Elsevier Ltd. All rights reserved....

  10. The role of fasting versus nonfasting triglycerides in ischemicstroke: a systematic review

    Directory of Open Access Journals (Sweden)

    Christopher Leonards

    2010-10-01

    Full Text Available Objective: To synthesize results from pertinent studies and determine if fasting and/or nonfasting triglycerides are a risk factor for ischemic stroke. Method: We performed two independent systematic literature searches using the PubMed and ScienceDirect databases to identify studies examining the relationship between fasting and nonfasting triglyceride concentrations and ischemic stroke risk. A meta-analysis was performed using ischemic stroke as a primary endpoint. Results: Twenty-five reports were identified, including 13 prospective cohort and 12 case-control studies. Baseline characteristics, study samples, methods, and primary outcomes varied. Of 13 prospective cohort studies, 9 assessed triglyceride concentrations in the fasting state. Seven of these identified triglycerides as an independent risk factor for ischemic stroke risk (n=1624 ischemic cases. Three prospective cohort studies identified a positive association between elevated nonfasting triglyceride concentrations and ischemic stroke risk (n=2050 ischemic cases. One prospective cohort study that compared fasting and nonfasting triglycerides identified only nonfasting triglycerides as an independent risk factor for ischemic stroke. Of 12 case-control studies identified, 5 identified a positive relationship between ischemic stroke risk and elevated fasting triglycerides (n=838 cases. Seven case-control studies were included in the metaanalysis (n=1996 ischemic stroke cases, revealing an odds ratio of 1.15 (95% CI, 1.08 to 1.21. Conclusions: The available data are inconsistent. The relationship between triglyceride levels and ischemic stroke needs further investigation under standardized conditions. We recommend a standardized triglyceride tolerance test to further investigate the associations between fasting versus nonfasting triglyceride levels and ischemic stroke.

  11. Cardiac tumours in children

    Directory of Open Access Journals (Sweden)

    Parsons Jonathan M

    2007-03-01

    Full Text Available Abstract Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT and Magnetic Resonance Imaging (MRI of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

  12. Absence of cardiac lipid accumulation in transgenic mice with heart-specific HSL overexpression.

    Science.gov (United States)

    Suzuki, J; Shen, W J; Nelson, B D; Patel, S; Veerkamp, J H; Selwood, S P; Murphy, G M; Reaven, E; Kraemer, F B

    2001-10-01

    Hormone-sensitive lipase (HSL) hydrolyzes triglyceride (TG) in adipose tissue. HSL is also expressed in heart. To explore the actions of cardiac HSL, heart-specific, tetracycline (Tc)-controlled HSL-overexpressing mice were generated. Tc-responsive element-HSL transgenic (Tg) mice were generated and crossed with myosin heavy chain (MHC)alpha-tTA Tg mice, which express the Tc-responsive transactivator (tTA) in the heart. The double-Tg mice (MHC-HSL) were maintained with doxycycline (Dox) to suppress Tg HSL. Upon removal of Dox, cardiac HSL activity and protein increased 12- and 8-fold, respectively, and the expression was heart specific. Although cardiac TG content increased twofold in control mice after an overnight fast, it did not increase in HSL-induced mice. Electron microscopy showed numerous lipid droplets in the myocardium of fasted control mice, whereas fasted HSL-induced mice showed virtually no droplets. Microarray analysis showed altered expression of cardiac genes for fatty acid oxidation, transcription factors, signaling molecules, cytoskeletal proteins, and histocompatibility antigens in HSL-induced mice. Thus cardiac HSL plays a role in controlling accumulation of triglyceride droplets and can affect the expression of a number of cardiac genes.

  13. Triglyceride sensing in the reward circuitry: A new insight in feeding behaviour regulation.

    Science.gov (United States)

    Cansell, Celine; Luquet, Serge

    2016-01-01

    In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Obesity often involves a behavioural component in which, similar to drugs abuse, compulsive consumption of palatable food rich in lipids and sugar drives energy intake far beyond metabolic demands. The hypothalamus is one of the primary integration sites of circulating energy-related signals like leptin or ghrelin and is therefore considered as one of the main central regulators of energy balance. However, food intake is also modulated by sensory inputs, such as tastes and odours, as well as by affective or emotional states. The mesolimbic pathway is well established as a key actor of the rewarding aspect of feeding. Particularly, the hedonic and motivational aspects of food are closely tied to the release of the neurotransmitter dopamine (DA) in striatal structure such as the Nucleus Accumbens (Nacc). In both rodent and humans several studies shows an attenuated activity of dopaminergic signal associated with obesity and there is evidence that consumption of palatable food per se leads to DA signalling alterations. Furthermore impaired cognition in obese mice is improved by selectively lowering triglycerides (TG) and intracerebroventricular administration of TG induces by itself acquisition impairment in several cognitive paradigms in normal body weight mice. Together, these observations raise the possibility that nutritional lipids, particularly TG, directly affect cognitive and reward processes by modulating the mesolimbic pathway and might contribute to the downward spiral of compulsive consumption of palatable food and obesity. This review is an attempt to capture recent evolution in the field that might point toward a direct action of nutritional lipid in the reward circuitry. PMID:26159487

  14. Structure of the human hepatic triglyceride lipase gene

    International Nuclear Information System (INIS)

    The structure of the human hepatic triglyceride lipase gene was determined from multiple cosmid clones. All the exons, exon-intron junctions, and 845 bp of the 5' and 254 bp of the 3' flanking DNA were sequenced. Comparison of the exon sequences to three previously published cDNA sequences revealed differences in the sequence of the codons for residue 133, 193, 202, and 234 that may represent sequence polymorphisms. By primer extension, hepatic lipase mRNA initiates at an adenine 77 bases upstream of the translation initiation site. The hepatic lipase gene spans over 60 kb containing 9 exons and 8 introns, the latter being all located within the region encoding the mature protein. The exons are all of average size (118-234 bp). Exon 1 encodes the signal peptide, exon 4, a region that binds to the lipoprotein substrate, and exon 5, an evolutionarily highly conserved region of potential catalytic function, and exons 6 and 9 encode sequences rich in basic amino acids thought to be important in anchoring the enzyme to the endothelial surface by interacting with acidic domains of the surface glycosaminoglycans. The human lipoprotein lipase gene has been recently reported to have an identical exon-intron organization containing the analogous structural domains. The observations strongly support the common evolutionary origin of these two lipolytic enzymes

  15. Postprandial triglyceride metabolism in elderly men with subnormal testosterone levels

    Institute of Scientific and Technical Information of China (English)

    Ingvild Agledahl; John-Bjarne Hansen; Johan Svartberg

    2008-01-01

    Aim: To investigate the level of postprandial triglycerides (TG)s in elderly men with subnormal testosterone level (≤ 11.0 nmol/L) compared to men with normal testosterone level (> 11.0 nmol/L). Methods: Thirthy-seven men with subnormal and 41 men with normal testosterone aged 60-80 years underwent an oral fat load and TG levels were measured fasting and 2, 4, 6 and 8 h afterwards. Results: Men with subnormal testosterone had significantly higher body mass index (BMI) and waist circumference (P < 0.001) than men with normal testosterone. They had signifi- cantly higher area under curve (AUC, P = 0.037), incremental area under curve (AUCi, P = 0.035) and TG response (TGR, P = 0.014) for serum-TG and significantly higher AUC (P=0.023), AUCi (P=0.023) and TGR (P = 0.014) for chylomicron-TG compared to men with normal testosterone level. Adjusting for waist circumference erased the significant differences between the groups in postprandial triglyceridemia. Conclusion: Men with subnormal test- osterone have increased postprandial TG levels indicating an impaired metabolism of postprandial TG-rich lipoproteins (TRL), which may add to an unfavourable lipid profile and promote development of atherosclerosis. (Asian JAndrol 2008 Jul; 10: 542-549)

  16. Effect of Amphiphiles on the Rheology of Triglyceride Networks

    Science.gov (United States)

    Seth, Jyoti

    2014-11-01

    Networks of aggregated crystallites form the structural backbone of many products from the food, cosmetic and pharmaceutical industries. Such materials are generally formulated by cooling a saturated solution to yield the desired solid fraction. Crystal nucleation and growth followed by aggregation leads to formation of a space percolating fractal-network. It is understood that microstructural hierarchy and particle-particle interactions determine material behavior during processing, storage and use. In this talk, rheology of suspensions of triglycerides (TAG, like tristearin) will be explored. TAGs exhibit a rich assortment of polymorphs and form suspensions that are evidently sensitive to surface modifying additives like surfactants and polymers. Here, a theoretical framework will be presented for suspensions containing TAG crystals interacting via pairwise potentials. The work builds on existing models of fractal aggregates to understand microstructure and its correlation with material rheology. Effect of amphiphilic additives is derived through variation of particle-particle interactions. Theoretical predictions for storage modulus will be compared against experimental observations and data from the literature and micro structural predictions against microscopy. Such a theory may serve as a step towards predicting short and long-term behavior of aggregated suspensions formulated via crystallization.

  17. Efficient phagocytosis requires triacylglycerol hydrolysis by adipose triglyceride lipase.

    Science.gov (United States)

    Chandak, Prakash G; Radovic, Branislav; Aflaki, Elma; Kolb, Dagmar; Buchebner, Marlene; Fröhlich, Eleonore; Magnes, Christoph; Sinner, Frank; Haemmerle, Guenter; Zechner, Rudolf; Tabas, Ira; Levak-Frank, Sanja; Kratky, Dagmar

    2010-06-25

    Macrophage phagocytosis is an essential biological process in host defense and requires large amounts of energy. To date, glucose is believed to represent the prime substrate for ATP production in macrophages. To investigate the relative contribution of free fatty acids (FFAs) in this process, we determined the phagocytosis rates in normal mouse macrophages and macrophages of adipose triglyceride lipase (ATGL)-deficient mice. ATGL was shown to be the rate-limiting enzyme for the hydrolysis of lipid droplet-associated triacylglycerol (TG) in many tissues. Here, we demonstrate that Atgl(-/-) macrophages fail to efficiently hydrolyze cellular TG stores leading to decreased cellular FFA concentrations and concomitant accumulation of lipid droplets, even in the absence of exogenous lipid loading. The reduced availability of FFAs results in decreased cellular ATP concentrations and impaired phagocytosis suggesting that fatty acids must first go through a cycle of esterification and re-hydrolysis before they are available as energy substrate. Exogenously added glucose cannot fully compensate for the phagocytotic defect in Atgl(-/-) macrophages. Hence, phagocytosis was also decreased in vivo when Atgl(-/-) mice were challenged with bacterial particles. These findings imply that phagocytosis in macrophages depends on the availability of FFAs and that ATGL is required for their hydrolytic release from cellular TG stores. This novel mechanism links ATGL-mediated lipolysis to macrophage function in host defense and opens the way to explore possible roles of ATGL in immune response, inflammation, and atherosclerosis.

  18. Landing gear noise attenuation

    Science.gov (United States)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

    2011-01-01

    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  19. Rare ATGL haplotypes are associated with increased plasma triglyceride concentrations in the Greenland Inuit

    DEFF Research Database (Denmark)

    Johansen, Christopher T; Gallinger, Zane R; Wang, Jian;

    2010-01-01

    To genotype common genetic variants found in the adipose triglyceride lipase (ATGL) gene and test them for association with cardiovascular disease risk factors in the Greenland Inuit.......To genotype common genetic variants found in the adipose triglyceride lipase (ATGL) gene and test them for association with cardiovascular disease risk factors in the Greenland Inuit....

  20. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

    NARCIS (Netherlands)

    N. Sarwar; M.S. Sandhu; S.L. Ricketts; A.S. Butterworth; E. Di Angelantonio; S.M. Boekholdt; W. Ouwehand; H. Watkins; N.J. Samani; D. Saleheen; D. Lawlor; M.P. Reilly; A.D. Hingorani; P.J. Talmud; J. Danesh

    2010-01-01

    BACKGROUND: Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. METHODS: We assessed the -1131T>C (rs662799) promoter polymorphism of the apo

  1. Common variants associated with plasma triglycerides and risk for coronary artery disease

    Science.gov (United States)

    Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tõnu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Åsa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Müller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Döring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J.F.; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; März, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njølstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Altshuler, David; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N.A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.

    2013-01-01

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P<5×10−8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064

  2. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  3. Fasting serum triglyceride and high-density lipoprotein cholesterol levels in patients intended to be treated for dyslipidemia

    Directory of Open Access Journals (Sweden)

    Genovefa D Kolovou

    2005-07-01

    Full Text Available Genovefa D Kolovou1, Katherine Anagnostopoulou1, Nektarios D Pilatis1, Klelia D Salpea1, Ioannis S Hoursalas1, Ilias Petropoulos1, Helen I Bilianou2, Dennis V Cokkinos11Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece; 2Cardiology Department, Tzanio State Hospital, Piraeus, GreeceObjective: The aim of the present investigation was to evaluate the influence of serum triglycerides (TG on other plasma lipids in patients to be treated for dyslipidemia.Methodology: Lipid profiles of a cohort of 801 patients (487 males and 314 females aged 57 ± 9 years (mean ± SD were evaluated. Patients were stratified according to their plasma lipid levels. They were divided into various groups on the basis of serum TG (≥ 150 or < 150 mg/dL and high-density lipoprotein cholesterol (HDL-C (≥ 40 or < 40 mg/dL.Results: Patients with TG ≥ 150 mg/dL had a higher total cholesterol and lower HDL-C levels compared with those with TG < 150 mg/dL, (p < 0.001. Patients with HDL-C < 40 mg/dL had a lower serum total cholesterol and higher TG compared with those with HDL-C ≥ 40 mg/dL (p = 0.011 and p < 0.0001, respectively. In all patients as well as in the subgroups, an inverse correlation between TG and HDL-C was found (r = –0.377, p < 0.001.Conclusions: Although, the metabolic pathway for TG and HDL-C is closely linked, an inverse correlation between TG and HDL-C levels seems to exist in the entire sampled population. This correlation also appears to persist in fasting patients with low levels of TG.Keywords: triglycerides, high-density lipoprotein cholesterol, dyslipidemia

  4. The establishment and reproducibility of 1H-MR spectroscopy in the determination of myocardial triglyceride content in vivo

    International Nuclear Information System (INIS)

    Objective: To establish the method of 1H-MRS in the determination of myocardial triglyceride content (MTC) in vivo and test its reproducibility. Methods: Ten healthy volunteers were recruited after routine physical examination. Cardiac images of the four-chamber and short axis views were collected. Spectroscopic volumes of interest were positioned within the interventricular septum on the end- systolic images. PRESS sequence spectroscopic data acquisition was triggered by electrocardiograph-derived R wave and synchronized with respiratory cycle at end-exhalation. MTC was calculated by the ratio of areas of resonances for lipid and water. After three months 1H-MRS of the heart were conducted again to investigate the reproducibility of the method. MTC before and after' three months was compared by using paired t test. The correlation between MTC and clinical data was determined by using correlation analysis. Results: UTC in healthy volunteers were (0.46 ± 0.17)% and (0.48 ± 0.19)% for the baseline and follow-up respectively. No difference was identified (t=-0.569, P=0.583). MTC was not correlated with body mass index [BMI (21.1±2.1) kg/m2, r=0.271, P=0.449], waist circumference [(77.9 ± 4.7) cm, r=0.105,P=0.772], waist-to-hip ratio (WHR 0.81 ± 0.01, r=0.172, P=0.635), systolic blood pressure [SBP(111 ± 16) mm Hg (1 mm Hg=0.133 kPa), r=0.267, P=0.456], diastolic blood pressure [DBP(71±9) mm Hg, r=-0.553, P=0.097], fasting glucose [FPG (4.77 ± 0.44) mmol/L, r=0.568,P=0.087], total cholesterol ITC (4.25 ± 0.55) mmol/L, r=0.067,P=0.854] and triglyceride [TG (1.07±0.48) mmol/L, r=0.478, P=0.162]. Conclusions: Myocardial triglyceride content can be quantitatively determined by 1H-MRS. The reproducibility of myocardial 1H-MRS was good for clinical purpose. (authors)

  5. Relationship between Plasma Triglyceride Level and Severity of Hypertriglyceridemic Pancreatitis

    Science.gov (United States)

    Wang, Sheng-Huei; Chou, Yu-Ching; Shangkuan, Wei-Chuan; Wei, Kuang-Yu; Pan, Yu-Han; Lin, Hung-Che

    2016-01-01

    Background Hypertriglyceridemia is the third most common cause of acute pancreatitis, but whether the level of triglyceride (TG) is related to severity of pancreatitis is unclear. Aim To evaluate the effect of TG level on the severity of hypertriglyceridemic pancreatitis (HTGP). Design Retrospective cohort study. Methods We reviewed the records of 144 patients with HTGP from 1999 to 2013 at Tri-Service General Hospital. Patients with possible etiology of pancreatitis, such as gallstones, those consuming alcohol or drugs, or those with infections were excluded. The classification of severity of pancreatitis was based on the revised Atlanta classification. We allocated the patients into high-TG and low-TG groups based on the optimal cut-off value (2648 mg/dL), which was derived from the receiver operating characteristic (ROC) curve between TG level and severity of HTGP. We then compared the clinical characteristics, pancreatitis severity, and mortality rates of the groups. Results There were 66 patients in the low-TG group and 78 patients in the high-TG group. There was no significant difference in the age, sex ratio, body mass index, and comorbidity between the 2 groups. The high-TG group had significantly higher levels of glucose (P = 0.022), total cholesterol (P = 0.002), and blood urea nitrogen (P = 0.037), and lower levels of sodium (P = 0.003) and bicarbonate (P = 0.002) than the low-TG group. The incidences of local complication (P = 0.002) and severe and moderate form of pancreatitis (P = 0.004) were significantly higher in the high-TG group than in the low-TG group. The mortality rate was higher in the high-TG group than in the low-TG group (P = 0.07). Conclusions Higher TG level in patients with HTGP may be associated with adverse prognosis, but randomized and prospective studies are needed in the future verify this relationship. PMID:27727299

  6. Marketing cardiac CT programs.

    Science.gov (United States)

    Scott, Jason

    2010-01-01

    There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing.

  7. Anti-rat soluble IL-6 receptor antibody down-regulates cardiac IL-6 and improves cardiac function following trauma-hemorrhage.

    Science.gov (United States)

    Yang, Shaolong; Hu, Shunhua; Choudhry, Mashkoor A; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

    2007-03-01

    Although anti-IL-6-mAb down-regulates cardiac IL-6 and attenuates IL-6-mediated cardiac dysfunction following trauma-hemorrhage, it is not known whether blockade of IL-6 receptor will down-regulate cardiac IL-6 and improve cardiac function under those conditions. Six groups of male adult rats (275-325 g) were used: sham/trauma-hemorrhage+vehicle, sham/trauma-hemorrhage+IgG, sham/trauma-hemorrhage+anti-rat sIL-6R. Rats underwent trauma-hemorrhage (removal of 60% of the circulating blood volume and fluid resuscitation after 90 min). Vehicle (V), normal goat IgG or anti-rat sIL-6R (16.7 microg/kg BW) was administered intra-peritoneally in the middle of resuscitation. Two hours later, cardiac function was measured by ICG dilution technique; blood samples collected, cardiomyocytes isolated, and cardiomyocyte nuclei were then extracted. Cardiac IL-6, IL-6R, gp130, IkappaB-alpha/P-IkappaB-alpha, NF-kappaB, and ICAM-1 expressions were measured by immunoblotting. Plasma IL-6 and cardiomyocyte NF-kappaB DNA-binding activity were determined by ELISA. In additional animals, heart harvested and cardiac MPO activity and CINC-1 and -3 were also measured. In another group of rats, cardiac function was measure by microspheres at 24 h following trauma-hemorrhage. Cardiac function was depressed and cardiac IL-6, P-IkappaB-alpha, NF-kappaB and its DNA-binding activity, ICAM-1, MPO activity, and CINC-1 and -3 were markedly increased after trauma-hemorrhage. Moreover, cardiac dysfunction was evident even 24 h after trauma-hemorrhage. Administration of sIL-6R following trauma-hemorrhage: (1) improved cardiac output at 2 h and 24 h (p<0.05); (2) down-regulated both cardiac IL-6 and IL-6R (p<0.05); and (3) attenuated cardiac P-IkappaB-alpha, NF-kappaB, NF-kappaB DNA-binding activity, ICAM-1, CINC-1, -3, and MPO activity (p<0.05). IgG did not significantly influence the above parameters. Thus, IL-6-mediated up-regulation of cardiac NF-kappaB, ICAM-1, CINC-1, -3, and MPO activity likely

  8. Measuring temporal resolution of cardiac CT reconstructions

    Science.gov (United States)

    Matthews, David; Heuscher, Dominic

    2005-04-01

    Multi-slice CT today is capable of imaging the heart with excellent temporal resolution. Algorithms have been developed to perform reconstructions combining data from multiple cardiac cycles. This paper presents a simulation phantom that enables a direct measurement of the actual temporal resolution achieved by these algorithms. This is not only useful for assessing the temporal resolution but also for validating the algorithms themselves. A simulation phantom was developed that consists of a 20 cm. diameter water phantom containing an array of cylinders whose intensities are pulsed for various durations ranging from 10 msec. to 250 msec. The intensity varied between the background value of water (0 HU) and 800 HU. By measuring the nominal attenuation value at the center of each cylinder, a curve can be derived representing the response over the given temporal range. A temporal resolution representing the FWHM value is determined based on the half-max value of this curve. Reconstructions were performed using a multi-cycle cardiac algorithm described previously in the literature. The measured FWHM values agree quite well to the temporal resolution predicted by the cardiac algorithm itself. Even the variation along the longitudinal axis can be accounted for by the predicted values. A simulated phantom can be used to accurately assess the temporal resolution of cardiac reconstruction algorithms. Excellent agreement was achieved between the predicted and measured temporal resolution values for the multi-cycle algorithm used in this study.

  9. Enhancing lysosome biogenesis attenuates BNIP3-induced cardiomyocyte death

    OpenAIRE

    Ma, Xiucui; Godar, Rebecca J.; Liu, Haiyan; Diwan, Abhinav

    2012-01-01

    Hypoxia-inducible pro-death protein BNIP3 (BCL-2/adenovirus E1B 19-kDa interacting protein 3), provokes mitochondrial permeabilization causing cardiomyocyte death in ischemia-reperfusion injury. Inhibition of autophagy accelerates BNIP3-induced cell death, by preventing removal of damaged mitochondria. We tested the hypothesis that stimulating autophagy will attenuate BNIP3-induced cardiomyocyte death. Neonatal rat cardiac myocytes (NRCMs) were adenovirally transduced with BNIP3 (or LacZ as c...

  10. Postprandial Triglyceride Is Associated with Fasting Triglyceride and HOMA-IR in Korean Subjects with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Seo Hee Lee

    2011-08-01

    Full Text Available BackgroundRecent studies indicate postprandial triglyceride (TG had a better association with cardiovascular events and metabolic syndrome than fasting TG. The authors of the present study investigated the metabolic and clinical relevance of postprandial TG.MethodsIn a cross-sectional retrospective study, the authors of the present study compared fasting and postprandial TG and analyzed the relationship between postprandial TG and various demographic and metabolic parameters in 639 Korean subjects with type 2 diabetes (T2D, group I, n=539 and impaired fasting glucose (IFG, group II, n=100 after ingestion of a standardized liquid meal (total 500 kcal, 17.5 g fat, 68.5 g carbohydrate, and 17.5 g protein.ResultsFasting and postprandial TG were significantly correlated (r=0.973, r=0.937, P<0.001 in group I and II, respectively. Of the variables, total cholesterol, waist circumference and body mass index were significantly correlated with fasting and postprandial TG in both groups. Only postprandial TG showed a significant correlation with glucose metabolic parameters (e.g., postprandial glucose, homeostatic model assessment of insulin resistance [HOMA-IR], and fasting C-peptide in subjects with T2D. Multiple regression analysis showed fasting TG and HOMA-IR could be predictable variables for postprandial TG in subjects with T2D.ConclusionPostprandial TG was very strongly correlated with fasting TG. The authors of the present study suggest insulin resistance may be more associated with postprandial TG than fasting TG in Korean T2D patients on a low-fat diet.

  11. Dietary ω-3 Fatty Acids Alter Cardiac Mitochondrial Phospholipid Composition and Delay Ca2+-Induced Permeability Transition

    OpenAIRE

    O’Shea, Karen M.; Khairallah, Ramzi J.; Sparagna, Genevieve C.; Xu, Wenhong; Hecker, Peter A; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Kristian, Tibor; Robert C. Murphy; Fiskum, Gary; Stanley, William C.

    2009-01-01

    Consumption of ω-3 fatty acids from fish oil, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), decreases risk for heart failure and attenuates pathologic cardiac remodeling in response to pressure overload. Dietary supplementation with EPA+DHA may also impact cardiac mitochondrial function and energetics through alteration of membrane phospholipids. We assessed the role of EPA+DHA supplementation on left ventricular (LV) function, cardiac mitochondrial membrane phospho...

  12. Cardiomyocyte Triglyceride Accumulation and Reduced Ventricular Function in Mice with Obesity Reflect Increased Long Chain Fatty Acid Uptake and De Novo Fatty Acid Synthesis

    Directory of Open Access Journals (Sweden)

    Fengxia Ge

    2012-01-01

    Full Text Available A nonarteriosclerotic cardiomyopathy is increasingly seen in obese patients. Seeking a rodent model, we studied cardiac histology, function, cardiomyocyte fatty acid uptake, and transporter gene expression in male C57BL/6J control mice and three obesity groups: similar mice fed a high-fat diet (HFD and db/db and ob/ob mice. At sacrifice, all obesity groups had increased body and heart weights and fatty livers. By echocardiography, ejection fraction (EF and fractional shortening (FS of left ventricular diameter during systole were significantly reduced. The Vmax for saturable fatty acid uptake was increased and significantly correlated with cardiac triglycerides and insulin concentrations. Vmax also correlated with expression of genes for the cardiac fatty acid transporters Cd36 and Slc27a1. Genes for de novo fatty acid synthesis (Fasn, Scd1 were also upregulated. Ten oxidative phosphorylation pathway genes were downregulated, suggesting that a decrease in cardiomyocyte ATP synthesis might explain the decreased contractile function in obese hearts.

  13. Planetary Ices Attenuation Properties

    Science.gov (United States)

    McCarthy, Christine; Castillo-Rogez, Julie C.

    In this chapter, we review the topic of energy dissipation in the context of icy satellites experiencing tidal forcing. We describe the physics of mechanical dissipation, also known as attenuation, in polycrystalline ice and discuss the history of laboratory methods used to measure and understand it. Because many factors - such as microstructure, composition and defect state - can influence rheological behavior, we review what is known about the mechanisms responsible for attenuation in ice and what can be inferred from the properties of rocks, metals and ceramics. Since attenuation measured in the laboratory must be carefully scaled to geologic time and to planetary conditions in order to provide realistic extrapolation, we discuss various mechanical models that have been used, with varying degrees of success, to describe attenuation as a function of forcing frequency and temperature. We review the literature in which these models have been used to describe dissipation in the moons of Jupiter and Saturn. Finally, we address gaps in our present knowledge of planetary ice attenuation and provide suggestions for future inquiry.

  14. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment

    DEFF Research Database (Denmark)

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei;

    2015-01-01

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study...... cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs...

  15. Acute administration of n-3 rich triglyceride emulsions provides cardioprotection in murine models after ischemia-reperfusion.

    Directory of Open Access Journals (Sweden)

    Hylde Zirpoli

    Full Text Available Dietary n-3 fatty acids (FAs may reduce cardiovascular disease risk. We questioned whether acute administration of n-3 rich triglyceride (TG emulsions could preserve cardiac function and decrease injury after ischemia/reperfusion (I/R insult. We used two different experimental models: in vivo, C57BL/6 mice were exposed to acute occlusion of the left anterior descending coronary artery (LAD, and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff technique (LT. In the LAD model, mice treated with n-3 TG emulsion (1.5 g/kg body weight, immediately after ischemia and 1 h later during reperfusion, significantly reduced infarct size and maintained cardiac function (p<0.05. In the LT model, administration of n-3 TG emulsion (300 mg TG/100 ml during reperfusion significantly improved functional recovery (p<0.05. In both models, lactate dehydrogenase (LDH levels, as a marker of injury, were significantly reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs protects hearts from I/R injury, we investigated changes in key pathways linked to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased phosphorylation of AKT and GSK3β proteins (p<0.05. Acute n-3 TG emulsion treatment also increased Bcl-2 protein level and reduced an autophagy marker, Beclin-1 (p<0.05. Additionally, cardioprotection by n-3 TG emulsion was linked to changes in PPARγ protein expression (p<0.05. Rosiglitazone and p-AKT inhibitor counteracted the positive effect of n-3 TG; GSK3β inhibitor plus n-3 TG significantly inhibited LDH release. We conclude that acute n-3 TG injection during reperfusion provides cardioprotection. This may prove to be a novel acute adjunctive reperfusion therapy after treating patients with myocardial infarction.

  16. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone

    2014-01-01

    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  17. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc

    2015-01-01

    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  18. Chronic vagal stimulation for the treatment of low ejection fraction heart failure : results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

    NARCIS (Netherlands)

    Zannad, Faiez; De Ferrari, Gaetano M; Tuinenburg, Anton E; Wright, David; Brugada, Josep; Butter, Christian; Klein, Helmut; Stolen, Craig; Meyer, Scott; Stein, Kenneth M; Ramuzat, Agnes; Schubert, Bernd; Daum, Doug; Neuzil, Petr; Botman, Cornelis; Castel, Maria Angeles; D'Onofrio, Antonio; Solomon, Scott D; Wold, Nicholas; Ruble, Stephen B

    2015-01-01

    AIM: The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure p

  19. Frequency Dependent Attenuation Revisited

    CERN Document Server

    Richard, Kowar; Xavier, Bonnefond

    2009-01-01

    The work is inspired by thermo-and photoacoustic imaging, where recent efforts are devoted to take into account attenuation and varying wave speed parameters. In this paper we study causal equations describing propagation of attenuated pressure waves. We review standard models like frequency power laws and and the thermo-viscous equation. The lack of causality of standard models in the parameter range relevant for photoacoustic imaging requires to derive novel equations. The main ingredients for deriving causal equations are the Kramers-Kronig relation and the mathematical concept of linear system theory. The theoretical results of this work are underpined by numerical experiments.

  20. Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

    Directory of Open Access Journals (Sweden)

    Ken Shinmura

    2013-01-01

    Full Text Available The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

  1. Lapacho tea (Tabebuia impetiginosa) extract inhibits pancreatic lipase and delays postprandial triglyceride increase in rats.

    Science.gov (United States)

    Kiage-Mokua, Beatrice Nyanchama; Roos, Nils; Schrezenmeir, Jürgen

    2012-12-01

    Earlier work in our laboratory indicated that ethanolic extracts of Tabebuia impetiginosa, Arctium lappa L., Calendula officinalis, Helianthus annuus, Linum usitatissimum and L. propolis, inhibit pancreatic lipase in vitro. In a follow-up study we assessed their effects on plasma triglycerides in rats fed on a fatty meal. Extracts, orlistat or only ethanol were given orally to the rats together with the test meal and the rate of increase of postprandial triglycerides was assessed over 4 h. Clearing of the triglycerides from the blood compartment was abolished by inhibiting lipoprotein lipase with Triton WR-1339. Our results showed that out of all the extracts, the bark of Tabebuia impetiginosa led to a significant delay in the postprandial increase of plasma triglycerides. However, lapachol, which is contained in the bark of Tabebuia impetiginosa and soluble in ethanol, had no lipase inhibitory effect in vitro and hence this substance did not seem to mediate the pertinent effect. PMID:22431070

  2. Oxidative stabilization of mixed mayonnaises made with linseed oil and saturated medium-chain triglyceride oil

    NARCIS (Netherlands)

    Raudsepp, P.; Brüggemann, D.A.; Lenferink, A.T.M.; Otto, C.; Andersen, M.L.

    2014-01-01

    Mayonnaises, made with either saturated medium chain triglyceride (MCT) oil or unsaturated purified linseed oil (LSO), were mixed. Raman confocal microspectrometry demonstrated that lipid droplets in mixed mayonnaise remained intact containing either MCT oil or LSO. Peroxide formation during storage

  3. Nonfasting Triglycerides and Risk of Ischemic Stroke in the General Population

    DEFF Research Database (Denmark)

    Freiberg, J.J.; Tybjaerg-Hansen, A.; Jensen, J.S.;

    2008-01-01

    Context The role of triglycerides in the risk of ischemic stroke remains controversial. Recently, a strong association was found between elevated levels of nonfasting triglycerides, which indicate the presence of remnant lipoproteins, and increased risk of ischemic heart disease. Objective To test...... the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population. Design, Setting, and Participants The Copenhagen City Heart Study, a prospective, Danish population - based cohort study initiated in 1976, with follow- up through July 2007....... Participants were 13 956 men and women aged 20 through 93 years. A cross- sectional study included 9637 individuals attending the 1991- 1994 examination of the prospective study. Main Outcome Measures Prospective study: baseline levels of nonfasting triglycerides, other risk factors at baseline and at follow...

  4. Elevated triglycerides and risk of myocardial infarction in HIV-positive persons

    DEFF Research Database (Denmark)

    Worm, Signe W; Kamara, David Alim; Reiss, Peter;

    2011-01-01

    Objectives: To explore the relationship between elevated triglyceride levels and the risk of myocardial infarction (MI) in HIV-positive persons after adjustment for total cholesterol (TC), high-density lipoprotein–cholesterol (HDL-C) and nonlipid risk factors. Background: Although elevated...... triglyceride levels are commonly noted in HIV-positive individuals, it is unclear whether they represent an independent risk factor for MI. Methods: The incidence of MI during follow-up was stratified according to the latest triglyceride level. Multivariable Poisson regression models were used to describe...... the independent association between the latest triglyceride level and MI risk after adjusting for TC and HDL-C, nonlipids cardiovascular disease (CVD) risk factors, HIV and treatment-related factors. Results: The 33 308 persons included in the study from 1999 to 2008 experienced 580 MIs over 178 835 person...

  5. Ultrasonographic diagnosis of fatty liver and relations with body index, serum lipid, and serum triglyceride

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Young Deog; Lee, S. H.; Lee, H. K.; Kim, D. H.; Kwon, K. H.; Kim, K. C. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1989-12-15

    Hepatic fatty infiltration appears as an area of increased echogenicity. And many factors concerned to fatty infiltration. With 65 cases of fatty liver and 42 cases of normal group, we analyzed fatty liver with grading and attempt to find relations between grade of fatty liver and levels of body index, serum triglyceride, and serum lipid. And compared fatty liver with normal control group. Patients with fatty liver are higher percentage of supra-normal value in body index, serum lipid, and serum triglyceride than normal control group. As fatty infiltration progressed, serum lipid, serum trig-lyceride and body index are also increased. Conclusively ultrasonographic examination of liver with serum triglyceride, serum lipid, and body index are simple method, useful follow-up examination of fatty liver, and preventive routine check-up of chronic liver disease

  6. [Cardiac evaluation before non-cardiac surgery].

    Science.gov (United States)

    Menzenbach, Jan; Boehm, Olaf

    2016-07-01

    Before non-cardiac surgery, evaluation of cardiac function is no frequent part of surgical treatment. European societies of anesthesiology and cardiology published consensus-guidelines in 2014 to present a reasonable approach for preoperative evaluation. This paper intends to differentiate the composite of perioperative risk and to display the guidelines methodical approach to handle it. Features to identify patients at risk from an ageing population with comorbidities, are the classification of surgical risk, functional capacity and risk indices. Application of diagnostic means, should be used adjusted to this risk estimation. Cardiac biomarkers are useful to discover risk of complications or mortality, that cannot be assessed by clinical signs. After preoperative optimization and perioperative cardiac protection, the observation of the postoperative period remains, to prohibit complications or even death. In consideration of limited resources of intensive care department, postoperative ward rounds beyond intensive care units are considered to be an appropriate instrument to avoid or recognize complications early to reduce postoperative mortality. PMID:27479258

  7. ADIPOSE TRIGLYCERIDE LIPASE REGULATES BASAL LIPOLYSIS AND LIPID DROPLET SIZE IN ADIPOCYTES

    OpenAIRE

    Miyoshi, Hideaki; Perfield, James W.; Obin, Martin S.; Greenberg, Andrew S.

    2008-01-01

    In adipocytes, lipid droplet (LD) size reflects a balance of triglyceride synthesis (lipogenesis) and hydrolysis (lipolysis). Perilipin A (Peri A), is the most abundant phosphoprotein on the surface of adipocyte LDs and has a crucial role in lipid storage and lipolysis. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are the major rate-determining enzymes for lipolysis in adipocytes. Each of these proteins (Peri A, ATGL and HSL) have been demonstrated to regulate lipid s...

  8. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology.

    Science.gov (United States)

    Nordestgaard, Børge G

    2016-02-19

    Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need to reduce levels to no advice on treatment. New insight in epidemiology now suggests that these lipoproteins, marked by high triglycerides, are strong and independent predictors of ASCVD and all-cause mortality, and that their cholesterol content or remnant cholesterol likewise are strong predictors of ASCVD. Of all adults, 27% have triglycerides >2 mmol/L (176 mg/dL), and 21% have remnant cholesterol >1 mmol/L (39 mg/dL). For individuals in the general population with nonfasting triglycerides of 6.6 mmol/L (580 mg/dL) compared with individuals with levels of 0.8 mmol/L (70 mg/dL), the risks were 5.1-fold for myocardial infarction, 3.2-fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate that triglyceride-rich lipoproteins are causally associated with ASCVD and all-cause mortality. Finally, genetic evidence also demonstrates that high concentrations of triglyceride-rich lipoproteins are causally associated with low-grade inflammation. This suggests that an important part of inflammation in atherosclerosis and ASCVD is because of triglyceride-rich lipoprotein degradation and uptake into macrophage foam cells in the arterial intima. Taken together, new insights now strongly suggest that elevated triglyceride-rich lipoproteins represent causal risk factors for low-grade inflammation, ASCVD, and all-cause mortality. PMID:26892957

  9. Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.; Krauss, Ronald M.; Rubin, Edward M.; Cohen, Jonathan C.

    2002-09-16

    The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

  10. Absence of adipose triglyceride lipase protects from hepatic endoplasmic reticulum stress in mice

    OpenAIRE

    Fuchs, Claudia D.; Claudel, Thierry; Kumari, Pooja; Haemmerle, Guenter; Pollheimer, Marion J.; Stojakovic, Tatjana; Scharnagl, Hubert; Halilbasic, Emina; Gumhold, Judith; Silbert, Dagmar; Koefeler, Harald; Trauner, Michael

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by triglyceride (TG) accumulation and endoplasmic reticulum (ER) stress. Because fatty acids (FAs) may trigger ER stress, we hypothesized that the absence of adipose triglyceride lipase (ATGL/PNPLA2)-the main enzyme for intracellular lipolysis, releasing FAs, and closest homolog to adiponutrin (PNPLA3) recently implicated in the pathogenesis of NAFLD-protects against hepatic ER stress. Wild-type (WT) and ATGL knockout (KO) mice were ch...

  11. An insight on acyl migration in solvent-free ethanolysis of model triglycerides using Novozym 435.

    Science.gov (United States)

    Sánchez, Daniel Alberto; Tonetto, Gabriela Marta; Ferreira, María Luján

    2016-02-20

    In this work, the ethanolysis of triglycerides catalyzed by immobilized lipase was studied, focusing on the secondary reaction of acyl migration. The catalytic tests were performed in a solvent-free reaction medium using Novozym 435 as biocatalyst. The selected experimental variables were biocatalyst loading (5-20mg), reaction time (30-90min), and chain length of the fatty acids in triglycerides with and without unsaturation (short (triacetin), medium (tricaprylin) and long (tripalmitin/triolein)). The formation of 2-monoglyceride by ethanolysis of triglycerides was favored by long reaction times and large biocatalyst loading with saturated short- to medium-chain triglycerides. In the case of long-chain triglycerides, the formation of this monoglyceride was widely limited by acyl migration. In turn, acyl migration increased the yield of ethyl esters and minimized the content of monoglycerides and diglycerides. Thus, the enzymatic synthesis of biodiesel was favored by long-chain triglycerides (which favor the acyl migration), long reaction times and large biocatalyst loading. The conversion of acylglycerides made from long-chain fatty acids with unsaturation was relatively low due to limitations in their access to the active site of the lipase. PMID:26795690

  12. Serum Triglyceride Level: A Predictor of Complications and Outcomes in Acute Pancreatitis?

    Directory of Open Access Journals (Sweden)

    Hassan Tariq

    2016-01-01

    Full Text Available Aim. To study serum triglyceride level as a predictor of complications and outcomes in acute pancreatitis. Methods. In this retrospective observational study, 582 patients admitted with acute pancreatitis, who had serum triglyceride levels measured within the first 24 hours, were divided into two groups. The study group consisted of patients with a triglyceride level ≥2.26 mmol/L (group 2 and the control group consisted of triglyceride level of <2.26 mmol/L (group 1. We collected data for baseline demographics, laboratory values, incidence of complications (local and systemic, admission to the intensive care unit (ICU, ICU length of stay, length of total hospital stay, and death in the two groups. Results. A triglyceride level of ≥2.26 mmol/L was found to be an independent predictor of developing altered mental status (p: 0.004, pancreatic necrosis (p: 0.001, acute respiratory distress syndrome (p: 0001, systemic Inflammatory response syndrome (p: 0.001, acute kidney injury (p: 0.001, hospital length of stay (LOS (p: 0.002, admission to intensive care unit (ICU (p: 0.002, and ICU LOS (p: 0.003. Conclusion. A triglyceride level of ≥2.26 mmol/L on admission in acute pancreatitis is an independent predictor of developing local and systemic complications, hospital LOS, admission to ICU, and ICU LOS.

  13. Structured triglyceride vehicles for oral delivery of halofantrine: examination of intestinal lymphatic transport and bioavailability in conscious rats

    DEFF Research Database (Denmark)

    Holm, René; Porter, Christopher J H; Müllertz, Anette;

    2002-01-01

    triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol backbone. The two structured triglycerides were abbreviated MLM and LML to reflect the structural position on the glycerol. The concentration...... animals, and this was most pronounced for the animals dosed with the structured triglycerides. CONCLUSIONS: Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption...... in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil....

  14. Cardiac metabolism and arrhythmias

    OpenAIRE

    Barth, Andreas S.; Tomaselli, Gordon F.

    2009-01-01

    Sudden cardiac death remains a leading cause of mortality in the Western world, accounting for up to 20% of all deaths in the U.S.1, 2 The major causes of sudden cardiac death in adults age 35 and older are coronary artery disease (70–80%) and dilated cardiomyopathy (10–15%).3 At the molecular level, a wide variety of mechanisms contribute to arrhythmias that cause sudden cardiac death, ranging from genetic predisposition (rare mutations and common polymorphisms in ion channels and structural...

  15. Comprehensive cardiac rehabilitation

    DEFF Research Database (Denmark)

    Kruse, Marie; Hochstrasser, Stefan; Zwisler, Ann-Dorthe O;

    2006-01-01

    OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed. METHODS: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed...... and may be as high as euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective....

  16. Evaluation of respiratory and cardiac motion correction schemes in dual gated PET/CT cardiac imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lamare, F., E-mail: frederic.lamare@chu-bordeaux.fr; Fernandez, P. [Univ. Bordeaux, INCIA, UMR 5287, F-33400 Talence (France); CNRS, INCIA, UMR 5287, F-33400 Talence (France); Service de Médecine Nucléaire, Hôpital Pellegrin, CHU de Bordeaux, 33076 Bordeaux (France); Le Maitre, A.; Visvikis, D. [INSERM, UMR1101, LaTIM, Université de Bretagne Occidentale, 29609 Brest (France); Dawood, M.; Schäfers, K. P. [European Institute for Molecular Imaging, University of Münster, Mendelstr. 11, 48149 Münster (Germany); Rimoldi, O. E. [Vita-Salute University and Scientific Institute San Raffaele, Milan, Italy and CNR Istituto di Bioimmagini e Fisiologia Molecolare, Milan (Italy)

    2014-07-15

    Purpose: Cardiac imaging suffers from both respiratory and cardiac motion. One of the proposed solutions involves double gated acquisitions. Although such an approach may lead to both respiratory and cardiac motion compensation there are issues associated with (a) the combination of data from cardiac and respiratory motion bins, and (b) poor statistical quality images as a result of using only part of the acquired data. The main objective of this work was to evaluate different schemes of combining binned data in order to identify the best strategy to reconstruct motion free cardiac images from dual gated positron emission tomography (PET) acquisitions. Methods: A digital phantom study as well as seven human studies were used in this evaluation. PET data were acquired in list mode (LM). A real-time position management system and an electrocardiogram device were used to provide the respiratory and cardiac motion triggers registered within the LM file. Acquired data were subsequently binned considering four and six cardiac gates, or the diastole only in combination with eight respiratory amplitude gates. PET images were corrected for attenuation, but no randoms nor scatter corrections were included. Reconstructed images from each of the bins considered above were subsequently used in combination with an affine or an elastic registration algorithm to derive transformation parameters allowing the combination of all acquired data in a particular position in the cardiac and respiratory cycles. Images were assessed in terms of signal-to-noise ratio (SNR), contrast, image profile, coefficient-of-variation (COV), and relative difference of the recovered activity concentration. Results: Regardless of the considered motion compensation strategy, the nonrigid motion model performed better than the affine model, leading to higher SNR and contrast combined with a lower COV. Nevertheless, when compensating for respiration only, no statistically significant differences were

  17. Identification of a novel phosphorylation site in adipose triglyceride lipase as a regulator of lipid droplet localization.

    Science.gov (United States)

    Xie, Xitao; Langlais, Paul; Zhang, Xiaodong; Heckmann, Bradlee L; Saarinen, Alicia M; Mandarino, Lawrence J; Liu, Jun

    2014-06-15

    Adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triacylglycerol (TG) hydrolysis, has long been known to be a phosphoprotein. However, the potential phosphorylation events that are involved in the regulation of ATGL function remain incompletely defined. Here, using a combinatorial proteomics approach, we obtained evidence that at least eight different sites of ATGL can be phosphorylated in adipocytes. Among them, Thr³⁷² resides within the hydrophobic region known to mediate lipid droplet (LD) targeting. Although it had no impact on the TG hydrolase activity, substitution of phosphorylation-mimic Asp for Thr³⁷² eliminated LD localization and LD-degrading capacity of ATGL expressed in HeLa cells. In contrast, mutation of Thr³⁷² to Ala gave a protein that bound LDs and functioned the same as the wild-type protein. In nonstimulated adipocytes, the Asp mutation led to decreased LD association and basal lipolytic activity of ATGL, whereas the Ala mutation produced opposite effects. Moreover, the LD translocation of ATGL upon β-adrenergic stimulation was also compromised by the Asp mutation. In accord with these findings, the Ala mutation promoted and the Asp mutation attenuated the capacity of ATGL to mediate lipolysis in adipocytes under both basal and stimulated conditions. Collectively, these studies identified Thr³⁷² as a novel phosphorylation site that may play a critical role in determining subcellular distribution as well as lipolytic action of ATGL.

  18. Identification of a novel phosphorylation site in adipose triglyceride lipase as a regulator of lipid droplet localization.

    Science.gov (United States)

    Xie, Xitao; Langlais, Paul; Zhang, Xiaodong; Heckmann, Bradlee L; Saarinen, Alicia M; Mandarino, Lawrence J; Liu, Jun

    2014-06-15

    Adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triacylglycerol (TG) hydrolysis, has long been known to be a phosphoprotein. However, the potential phosphorylation events that are involved in the regulation of ATGL function remain incompletely defined. Here, using a combinatorial proteomics approach, we obtained evidence that at least eight different sites of ATGL can be phosphorylated in adipocytes. Among them, Thr³⁷² resides within the hydrophobic region known to mediate lipid droplet (LD) targeting. Although it had no impact on the TG hydrolase activity, substitution of phosphorylation-mimic Asp for Thr³⁷² eliminated LD localization and LD-degrading capacity of ATGL expressed in HeLa cells. In contrast, mutation of Thr³⁷² to Ala gave a protein that bound LDs and functioned the same as the wild-type protein. In nonstimulated adipocytes, the Asp mutation led to decreased LD association and basal lipolytic activity of ATGL, whereas the Ala mutation produced opposite effects. Moreover, the LD translocation of ATGL upon β-adrenergic stimulation was also compromised by the Asp mutation. In accord with these findings, the Ala mutation promoted and the Asp mutation attenuated the capacity of ATGL to mediate lipolysis in adipocytes under both basal and stimulated conditions. Collectively, these studies identified Thr³⁷² as a novel phosphorylation site that may play a critical role in determining subcellular distribution as well as lipolytic action of ATGL. PMID:24801391

  19. Cardiac Risk Assessment

    Science.gov (United States)

    ... to assess cardiac risk include: High-sensitivity C-reactive protein (hs-CRP) : Studies have shown that measuring ... LDL-C but does not respond to typical strategies to lower LDL-C such as diet, exercise, ...

  20. Sudden Cardiac Arrest

    Science.gov (United States)

    ... Heart Risk Factors & Prevention Heart Diseases & Disorders Atrial Fibrillation (AFib) Sudden Cardiac Arrest (SCA) SCA: Who's At Risk? Prevention of SCA What Causes SCA? SCA Awareness Atrial Flutter Heart Block Heart Failure Sick Sinus Syndrome Substances & Heart Rhythm Disorders Symptoms & ...

  1. Socially differentiated cardiac rehabilitation

    DEFF Research Database (Denmark)

    Meillier, Lucette Kirsten; Nielsen, Kirsten Melgaard; Larsen, Finn Breinholt;

    2012-01-01

    to a standard rehabilitation programme (SRP). If patients were identified as socially vulnerable, they were offered an extended version of the rehabilitation programme (ERP). Excluded patients were offered home visits by a cardiac nurse. Concordance principles were used in the individualised programme elements......%. Patients were equally distributed to the SRP and the ERP. No inequality was found in attendance and adherence among referred patients. Conclusions: It seems possible to overcome unequal referral, attendance, and adherence in cardiac rehabilitation by organisation of systematic screening and social......Aim: The comprehensive cardiac rehabilitation (CR) programme after myocardial infarction (MI) improves quality of life and results in reduced cardiac mortality and recurrence of MI. Hospitals worldwide face problems with low participation rates in rehabilitation programmes. Inequality...

  2. Calcium Sensing Receptor Promotes Cardiac Fibroblast Proliferation and Extracellular Matrix Secretion

    Directory of Open Access Journals (Sweden)

    Xinying Zhang

    2014-02-01

    Full Text Available Aims: Calcium-sensing receptor (CaR acts as a G protein coupled receptor that mediates the increase of the intracellular Ca2+ concentration. The expression of CaR has been confirmed in various cell types, including cardiomyocytes, smooth muscle cells, neurons and vascular endothelial cells. However, whether CaR is expressed and functions in cardiac fibroblasts has remained unknown. The present study investigated whether CaR played a role in cardiac fibroblast proliferation and extracellular matrix (ECM secretion, both in cultured rat neonatal cardiac fibroblasts and in a model of cardiac hypertrophy induced by isoproterenol (ISO. Methods and Results: Immunofluorescence, immunohistochemistry and Western blot analysis revealed the presence of CaR in cardiac fibroblasts. Calcium and calindol, a specific activator of CaR, elevated the intracellular calcium concentration in cardiac fibroblasts. Pretreatment of cardiac fibroblasts with calhex231, a specific inhibitor of CaR, U73122 and 2-APB attenuated the calindol- and extracellular calcium-induced increase in intracellular calcium ([Ca2+]i. Cardiac fibroblast proliferation and migration were assessed by MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, cell count and the cell scratch assay. ECM production was detected by expression of matrix metalloproteinase-3 and -9 (MMP-3 and -9. Activation of CaR promoted cardiac fibroblast proliferation and migration and ECM secretion. More importantly, calhex231, suppressed cardiac fibroblast proliferation and migration and MMP-3 and -9 expression. To further investigate the effect of CaR on cardiac fibrosis, a model of ISO-induced cardiac hypertrophy was established. Pretreatment with calhex231 prevented cardiac fibrosis and decreased the expression of MMP-3 and -9 expression. Conclusions: Our results are the first report that CaR plays an important role in Ca2+ signaling involved in cardiac fibrosis through the phospholipase C- inositol 3

  3. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi

    2014-01-01

    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  4. A multiresolution restoration method for cardiac SPECT

    Science.gov (United States)

    Franquiz, Juan Manuel

    Single-photon emission computed tomography (SPECT) is affected by photon attenuation and image blurring due to Compton scatter and geometric detector response. Attenuation correction is important to increase diagnostic accuracy of cardiac SPECT. However, in attenuation-corrected scans, scattered photons from radioactivity in the liver could produce a spillover of counts into the inferior myocardial wall. In the clinical setting, blurring effects could be compensated by restoration with Wiener and Metz filters. Inconveniences of these procedures are that the Wiener filter depends upon the power spectra of the object image and noise, which are unknown, while Metz parameters have to be optimized by trial and error. This research develops an alternative restoration procedure based on a multiresolution denoising and regularization algorithm. It was hypothesized that this representation leads to a more straightforward and automatic restoration than conventional filters. The main objective of the research was the development and assessment of the multiresolution algorithm for compensating the liver spillover artifact. The multiresolution algorithm decomposes original SPECT projections into a set of sub-band frequency images. This allows a simple denoising and regularization procedure by discarding high frequency channels and performing inversion only in low and intermediate frequencies. The method was assessed in bull's eye polar maps and short- axis attenuation-corrected reconstructions of a realistic cardiac-chest phantom with a custom-made liver insert and different 99mTc liver-to-heart activity ratios. Inferior myocardial defects were simulated in some experiments. The cardiac phantom in free air was considered as the gold standard reference. Quantitative analysis was performed by calculating contrast of short- axis slices and the normalized chi-square measure, defect size and mean and standard deviation of polar map counts. The performance of the multiresolution

  5. Protective Effect of Quercetin on Posttraumatic Cardiac Injury.

    Science.gov (United States)

    Jing, Zehao; Wang, Zhuorun; Li, Xiujie; Li, Xintao; Cao, Tingting; Bi, Yue; Zhou, Jicheng; Chen, Xu; Yu, Deqin; Zhu, Liang; Li, Shuzhuang

    2016-01-01

    Quercetin is an important dietary flavonoid present in fruits and vegetables and has attracted attention because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play important roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This study investigates the protective effect of quercetin on trauma-induced secondary cardiac injury and the mechanisms involved. Widely accepted nonlethal mechanical trauma models were established. In vivo, cardiomyocyte apoptosis and cardiac dysfunction in rats were assessed using TUNEL staining and a biological mechanic experiment system. In vitro, cell viability, tumour necrosis factor-α (TNF-α), reactive oxygen species (ROS) and [Ca(2+)]i of H9c2 cells were detected using an MTT assay, ELISA, and 2',7'-dichlorofluorescin diacetate and fluo-4 acetoxymethyl ester assays respectively. Quercetin pretreatment (20 mg/kg i.p.; 0.5 h before trauma) significantly improved posttraumatic cardiomyocyte apoptosis and cardiac dysfunction. Pretreatment with quercetin (20 μM; 24 h before trauma plasma addition) significantly attenuated trauma-induced viability decreases, TNF-α increases, ROS overproduction and [Ca(2+)]i overload in H9c2 cells. In conclusion, quercetin may reverse posttraumatic cardiac dysfunction by reducing cardiomyocyte apoptosis through the suppression of TNF-α increases, ROS overproduction and Ca(2+) overload in cardiomyocytes, representing a potential preventive approach for the treatment of secondary cardiac injury after mechanical trauma. PMID:27470932

  6. Awareness in cardiac anesthesia.

    LENUS (Irish Health Repository)

    Serfontein, Leon

    2010-02-01

    Cardiac surgery represents a sub-group of patients at significantly increased risk of intraoperative awareness. Relatively few recent publications have targeted the topic of awareness in this group. The aim of this review is to identify areas of awareness research that may equally be extrapolated to cardiac anesthesia in the attempt to increase understanding of the nature and significance of this scenario and how to reduce it.

  7. Cardiac rehabilitation in Germany.

    Science.gov (United States)

    Karoff, Marthin; Held, Klaus; Bjarnason-Wehrens, Birna

    2007-02-01

    The purpose of this review is to give an overview of the rehabilitation measures provided for cardiac patients in Germany and to outline its legal basis and outcomes. In Germany the cardiac rehabilitation system is different from rehabilitation measures in other European countries. Cardiac rehabilitation in Germany since 1885 is based on specific laws and the regulations of insurance providers. Cardiac rehabilitation has predominantly been offered as an inpatient service, but has recently been complemented by outpatient services. A general agreement on the different indications for offering these two services has yet to be reached. Cardiac rehabilitation is mainly offered after an acute cardiac event and bypass surgery. It is also indicated in severe heart failure and special cases of percutaneous coronary intervention. Most patients are men (>65%) and the age at which events occur is increasing. The benefits obtained during the 3-4 weeks after an acute event, and confirmed in numerous studies, are often later lost under 'usual care' conditions. Many attempts have been made by rehabilitation institutions to improve this deficit by providing intensive aftercare. One instrument set up to achieve this is the nationwide institution currently comprising more than 6000 heart groups with approximately 120000 outpatients. After coronary artery bypass grafting or acute coronary syndrome cardiac rehabilitation can usually be started within 10 days. The multidisciplinary rehabilitation team consists of cardiologists, psychologists, exercise therapists, social workers, nutritionists and nurses. The positive effects of cardiac rehabilitation are also important economically, for example, for the improvement of secondary prevention and vocational integration. PMID:17301623

  8. Cardiac tumours in infancy

    OpenAIRE

    Yadava, O.P.

    2012-01-01

    Cardiac tumours in infancy are rare and are mostly benign with rhabdomyomas, fibromas and teratomas accounting for the majority. The presentation depends on size and location of the mass as they tend to cause cavity obstruction or arrhythmias. Most rhabdomyomas tend to regress spontaneously but fibromas and teratomas generally require surgical intervention for severe haemodynamic or arrhythmic complications. Other relatively rare cardiac tumours too are discussed along with an Indian perspect...

  9. Infected cardiac hydatid cyst

    OpenAIRE

    Ceviz, M; Becit, N; Kocak, H.

    2001-01-01

    A 24 year old woman presented with chest pain and palpitation. The presence of a semisolid mass—an echinococcal cyst or tumour—in the left ventricular apex was diagnosed by echocardiography, computed tomography, and magnetic resonance imaging. The infected cyst was seen at surgery. The cyst was removed successfully by using cardiopulmonary bypass with cross clamp.


Keywords: cardiac hydatid cyst; infected cardiac hydatid cyst

  10. Cardiac applications of optogenetics.

    Science.gov (United States)

    Ambrosi, Christina M; Klimas, Aleksandra; Yu, Jinzhu; Entcheva, Emilia

    2014-08-01

    In complex multicellular systems, such as the brain or the heart, the ability to selectively perturb and observe the response of individual components at the cellular level and with millisecond resolution in time, is essential for mechanistic understanding of function. Optogenetics uses genetic encoding of light sensitivity (by the expression of microbial opsins) to provide such capabilities for manipulation, recording, and control by light with cell specificity and high spatiotemporal resolution. As an optical approach, it is inherently scalable for remote and parallel interrogation of biological function at the tissue level; with implantable miniaturized devices, the technique is uniquely suitable for in vivo tracking of function, as illustrated by numerous applications in the brain. Its expansion into the cardiac area has been slow. Here, using examples from published research and original data, we focus on optogenetics applications to cardiac electrophysiology, specifically dealing with the ability to manipulate membrane voltage by light with implications for cardiac pacing, cardioversion, cell communication, and arrhythmia research, in general. We discuss gene and cell delivery methods of inscribing light sensitivity in cardiac tissue, functionality of the light-sensitive ion channels within different types of cardiac cells, utility in probing electrical coupling between different cell types, approaches and design solutions to all-optical electrophysiology by the combination of optogenetic sensors and actuators, and specific challenges in moving towards in vivo cardiac optogenetics.

  11. Cardiac sympathetic denervation preceding motor signs in Parkinson disease

    OpenAIRE

    Goldstein, David S.; Sharabi, Yehonatan; Karp, Barbara I.; Bentho, Oladi; Saleem, Ahmed; Pacak, Karel; Eisenhofer, Graeme

    2007-01-01

    There is substantial interest in identifying biomarkers to detect early Parkinson disease (PD). Cardiac noradrenergic denervation and attenuated baroreflex-cardiovagal function occur in de novo PD, but whether these abnormalities can precede PD has been unknown. Here we report the case of a patient who had profoundly decreased left ventricular myocardial 6-[18F]fluorodopamine-derived radioactivity and low baroreflex-cardiovagal gain, 4 years before the onset of symptoms and signs of PD. The r...

  12. APJ ACTS AS A DUAL RECEPTOR IN CARDIAC HYPERTROPHY

    OpenAIRE

    Scimia, Maria Cecilia; Hurtado, Cecilia; Ray, Saugata; Metzler, Scott; Wei, Ke; Wang, Jianming; Woods, Chris E.; Purcell, Nicole H.; Catalucci, Daniele; Akasaka, Takashi; Bueno, Orlando F.; Vlasuk, George P.; Kaliman, Perla; Bodmer, Rolf; Smith, Layton H.

    2012-01-01

    Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues 1 . Here we report that genetic loss of APJ confers resistance to chronic pressure overload by dramatically reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to s...

  13. Cardiac CT for planning redo cardiac surgery: effect of knowledge-based iterative model reconstruction on image quality

    Energy Technology Data Exchange (ETDEWEB)

    Oda, Seitaro [MedStar Washington Hospital Center, Department of Cardiology, Washington, DC (United States); Kumamoto University, Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto (Japan); Weissman, Gaby; Weigold, W. Guy [MedStar Washington Hospital Center, Department of Cardiology, Washington, DC (United States); Vembar, Mani [Philips Healthcare, CT Clinical Science, Cleveland, OH (United States)

    2015-01-15

    The purpose of this study was to investigate the effects of knowledge-based iterative model reconstruction (IMR) on image quality in cardiac CT performed for the planning of redo cardiac surgery by comparing IMR images with images reconstructed with filtered back-projection (FBP) and hybrid iterative reconstruction (HIR). We studied 31 patients (23 men, 8 women; mean age 65.1 ± 16.5 years) referred for redo cardiac surgery who underwent cardiac CT. Paired image sets were created using three types of reconstruction: FBP, HIR, and IMR. Quantitative parameters including CT attenuation, image noise, and contrast-to-noise ratio (CNR) of each cardiovascular structure were calculated. The visual image quality - graininess, streak artefact, margin sharpness of each cardiovascular structure, and overall image quality - was scored on a five-point scale. The mean image noise of FBP, HIR, and IMR images was 58.3 ± 26.7, 36.0 ± 12.5, and 14.2 ± 5.5 HU, respectively; there were significant differences in all comparison combinations among the three methods. The CNR of IMR images was better than that of FBP and HIR images in all evaluated structures. The visual scores were significantly higher for IMR than for the other images in all evaluated parameters. IMR can provide significantly improved qualitative and quantitative image quality at in cardiac CT for planning of reoperative cardiac surgery. (orig.)

  14. Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

    2003-08-15

    Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting Apo

  15. Control algorithms for dynamic attenuators

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Scott S., E-mail: sshsieh@stanford.edu [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Pelc, Norbert J. [Department of Radiology, Stanford University, Stanford California 94305 and Department of Bioengineering, Stanford University, Stanford, California 94305 (United States)

    2014-06-15

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  16. Hypoxia-induced mobilization of stored triglycerides in the euryoxic goby Gillichthys mirabilis.

    Science.gov (United States)

    Gracey, Andrew Y; Lee, Tsung-Han; Higashi, Richard M; Fan, Teresa

    2011-09-15

    Environmental hypoxia is a common challenge that many aquatic organisms experience in their habitat. Responding to hypoxia requires metabolic reprogramming so that energy-demanding processes are regulated to match available energy reserves. In this study we explored the transcriptional control of metabolic reorganization in the liver of a hypoxia-tolerant burrow-dwelling goby, Gillichthys mirabilis. Gene expression data revealed that pathways associated with triglyceride hydrolysis were upregulated by hypoxia whereas pathways associated with triglyceride synthesis were downregulated. This finding was supported by tissue histology, which showed that the size of hepatic lipid droplets declined visibly during exposure to hypoxia. Proton nuclear magnetic resonance analysis confirmed the mobilization of hepatic triglycerides, which declined 2.7-fold after 5 days of hypoxia. The enzyme, adipose triglyceride lipase, was implicated in the mobilization of triglycerides because its expression increased at the level of both transcript and protein. This observation raises questions regarding the regulation of fat metabolism during hypoxia and the role played by the hypoxia-responsive gene leptin.

  17. Biopolymer from microbial assisted in situ hydrolysis of triglycerides and dimerization of fatty acids.

    Science.gov (United States)

    Kavitha, V; Radhakrishnan, N; Madhavacharyulu, E; Sailakshmi, G; Sekaran, G; Reddy, B S R; Rajkumar, G Suseela; Gnanamani, Arumugam

    2010-01-01

    The present study demonstrates biopolymer production by in situ bio-based dimerization of fatty acids by microorganism isolated from marine sediments. Microbial isolate grown in Zobell medium in the presence of triglycerides for the period of 24-240 h at 37 degrees C, hydrolyze the applied triglycerides and sequentially dimerized the hydrolyzed products and subsequently polymerized and transformed to a biopolymer having appreciable adhesive properties. Physical (nature, odour, stickyness and tensile strength), chemical (instrumentation) and biochemical (cell free broth) methods of analyses carried out provided the hypotheses involved in the formation of the product as well as the nature of the product formed. Results revealed, lipolytic enzymes released during initial period of growth and the biosurfactant production during later period, respectively, hydrolyze the applied triglycerides and initiate the dimerization and further accelerated when the incubation period extended. The existence and the non-existence of in situ hydrolysis of various triglycerides followed by dimerization and polymerization and the mechanism of transformation of triglycerides to biopolymer are discussed in detail.

  18. Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models.

    Science.gov (United States)

    Laplante, Marc-André; Charbonneau, Alexandre; Avramoglu, Rita Kohen; Pelletier, Patricia; Fang, Xiangping; Bachelard, Hélène; Ylä-Herttuala, Seppo; Laakso, Markku; Després, Jean-Pierre; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André

    2013-09-01

    Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.

  19. The effect of targeted temperature management on coagulation parameters and bleeding events after out-of-hospital cardiac arrest of presumed cardiac cause

    DEFF Research Database (Denmark)

    Jacob, Marrit; Hassager, Christian; Bro-Jeppesen, John;

    2015-01-01

    AIMS: Targeted temperature management (TTM) is part of the standard treatment of comatose patients after out-of-hospital cardiac arrest (OHCA) to attenuate neurological injury. In other clinical settings, hypothermia promotes coagulopathy leading to an increase in bleeding and thrombosis tendency...

  20. Resolvin D1 reduces ER stress-induced apoptosis and triglyceride accumulation through JNK pathway in HepG2 cells.

    Science.gov (United States)

    Jung, Tae Woo; Hwang, Hwan-Jin; Hong, Ho Cheol; Choi, Hae Yoon; Yoo, Hye Jin; Baik, Sei Hyun; Choi, Kyung Mook

    2014-06-25

    Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Resolvins, a novel family derived from ω-3 polyunsaturated fatty acids, have anti-inflammatory and insulin sensitizing properties, and it has been suggested that they play a role in the amelioration of obesity-related metabolic dysfunctions. This study showed that pretreatment with resolvin D1 (RvD1) attenuated ER stress-induced apoptosis and also decreased caspase 3 activity in HepG2 cells. Furthermore, RvD1 significantly decreased tunicamycin-induced triglycerides accumulation as well as SREBP-1 expression. However, tunicamycin-induced ER stress markers were not significantly affected by RvD1 treatment. Moreover, RvD1 treatment did not affect the tunicamycin-induced expression of chaperones that assist protein folding in the ER. These results suggest that RvD1-conferred cellular protection may occur downstream of the ER stress. This was supported by the finding that RvD1 significantly inhibited tunicamycin-induced c-Jun N-terminal kinase (JNK) expression, although P38 and ERK1/2 phosphorylation were not affected. In addition, anisomycin, a JNK activator, increased caspase 3 activity and apoptosis as well as triglycerides accumulation and SREBP1 expression, and RvD1 treatment reversed these changes. In conclusion, RvD1 attenuated ER stress-induced hepatic steatosis and apoptosis via the JNK-mediated pathway. This study may provide insight into a novel underlying mechanism and a strategy for treating NAFLD. PMID:24784707

  1. Genetic variation in SULF2 is associated with postprandial clearance of triglyceride-rich remnant particles and triglyceride levels in healthy subjects.

    Directory of Open Access Journals (Sweden)

    Niina Matikainen

    Full Text Available CONTEXT: Nonfasting (postprandial triglyceride concentrations have emerged as a clinically significant cardiovascular disease risk factor that results from accumulation of remnant triglyceride-rich lipoproteins (TRLs in the circulation. The remnant TRLs are cleared from the circulation by hepatic uptake, but the specific mechanisms involved are unclear. The syndecan-1 heparan sulfate proteoglycan (HSPG pathway is important for the hepatic clearance of remnant TRLs in mice, but its relevance in humans is unclear. OBJECTIVE: We sought to determine whether polymorphisms of the genes responsible for HSPG assembly and disassembly contribute to atherogenic dyslipoproteinemias in humans. PATIENTS AND DESIGN: We performed an oral fat load in 68 healthy subjects. Lipoproteins (chylomicrons and very low density lipoproteins 1 and 2 were isolated from blood, and the area under curve and incremental area under curve for postprandial variables were calculated. Single nucleotide polymorphisms in genes encoding syndecan-1 and enzymes involved in the synthesis or degradation of HSPG were genotyped in the study subjects. RESULTS: Our results indicate that the genetic variation rs2281279 in SULF2 associates with postprandial clearance of remnant TRLs and triglyceride levels in healthy subjects. Furthermore, the SNP rs2281279 in SULF2 associates with hepatic SULF2 mRNA levels. CONCLUSIONS: In humans, mild but clinically relevant postprandial hyperlipidemia due to reduced hepatic clearance of remnant TRLs may result from genetic polymorphisms that affect hepatic HSPG.

  2. Incorporation of medium chain fatty acids into fish oil triglycerides by chemical and enzymatic inter esterification

    Energy Technology Data Exchange (ETDEWEB)

    Feltes, M. M. C.; Oliveira de Pilot, L.; Gomes Correira, F.; Grimaldi, R.; Mara Block, J.; Ninow, J. L.

    2009-07-01

    Structured triglycerides (STs) containing both medium chain fatty acids (MCFA) and polyunsaturated fatty acids (PUFA) in the same molecule offer nutritional and therapeutic benefits. The aim of this work was to establish the incorporation of MCFA into fish oil triglycerides (TAGs), while maintaining substantial levels of docosahexaenoic and eicosapentaenoic acids. The effects of different acyl donors (capric acid methyl ester/MeC10 or medium chain triglyceride/TCM) and of the catalyst (chemical or enzymatic) on the fatty acid composition of the reaction product were studied. The fatty acid composition of the fish oil TAG was modified after inter esterification to contain MCFA, and it depended on the catalyst and on the substrates. Thermo grams obtained by Differential Scanning Calorimetry (DSC) showed that inter esterification promoted noteworthy changes in the melting profile of the samples. STs of clinical nutrition interest containing both EPA and DHA obtained from fish oil along with MCFA were successfully produced. (Author) 70 refs.

  3. High plasma triglyceride levels strongly correlate with low kisspeptin in the arcuate nucleus of male rats

    DEFF Research Database (Denmark)

    Overgaard, A; Axel, A M; Lie, M E;

    2015-01-01

    signals to the GnRH neurons. METHODS: In this study, we measured body weight and plasma concentrations of leptin, insulin, testosterone, and triglycerides after high fat diet exposure and correlated these parameters with the number of kisspeptin-immunoreactive neurons in the arcuate nucleus of male rats...... with increased fat in the diet. Kisspeptin-immunoreactive cells are not correlated with body weight, testosterone, leptin or insulin. However, we find that the number of kisspeptin-immunoreactive cells is strongly and negatively correlated with the level of plasma triglycerides (R2=0.49, p=0.004). CONCLUSION: We...... find a strong negative correlation between plasma triglyceride concentrations and the number of kisspeptin neurons in the rat arcuate nucleus regardless of the percentage of fat in the diet. In line with the lipotoxicity hypothesis, our results suggest that it is the level of hypertriglyceridemia per...

  4. Triglycerides and high-density lipoprotein cholesterol are associated with insulinemia in adolescents

    Directory of Open Access Journals (Sweden)

    Ramírez-López Guadalupe

    2006-01-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the association between lipids and insulin concentration in adolescents. MATERIAL AND METHODS: A cross-sectional study of 350 adolescents aged 14-19 years old from a public high school in Guadalajara, in the state of Jalisco, Mexico, was conducted. Fasting insulin concentration was determined using microparticle enzyme immunoassay; total cholesterol and triglycerides were detected by standard enzymatic procedures; and low- and high-density lipoproteins were found using standard precipitation methods. Statistical analysis included linear multivariate regression. RESULTS: Serum triglycerides were associated positively with insulin fasting (beta= 0.003, p= 0.0001 and high-density lipoprotein cholesterol was negatively associated with insulin fasting in male adolescents 18-19 years old (beta= -0.03, p= 0.012. CONCLUSIONS: The relationships between triglycerides and insulin and between high-density lipoprotein cholesterol and insulin are already present in adolescence.

  5. Glycemic Variability Is Associated With Reduced Cardiac Autonomic Modulation in Women With Type 2 Diabetes

    DEFF Research Database (Denmark)

    Fleischer, Jesper; Lebech Cichosz, Simon; Hoeyem, Pernille;

    2015-01-01

    and 39 women with non-insulin-treated type 2 diabetes and a known duration of diabetes sensor for 3 days, and the mean amplitude of glycemic excursions (MAGE) was calculated to obtain individual glycemic variability. Cardiac......OBJECTIVE: To investigate the sex differences in cardiac autonomic modulation in patients with newly diagnosed type 2 diabetes and to determine whether cardiac autonomic modulation is associated with glycemic variability. RESEARCH DESIGN AND METHODS: We investigated a cohort consisting of 48 men...... variability as assessed by MAGE. This was not the case in men. The association in women persisted in a multivariate regression analysis controlling for weight, mean heart rate, blood pressure (systolic), and triglycerides. CONCLUSIONS: In patients with newly diagnosed and well-controlled type 2 diabetes...

  6. Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Callø, Kirstine; Braunstein, Thomas Hartig;

    2015-01-01

    a significant increase in cardiac triglyceride content (1.93 ± 0.19 (n = 12) vs. 0.77 ± 0.13 nmol/mg (n = 12), p cause electrophysiological changes, which leads to QRS prolongation, decreased conduction velocity and increased arrhythmogenesis during......BACKGROUND: Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model and examines the underlying mechanism. METHODS....... Conduction velocity was examined in isolated tissue strips. Ion channel and gap junction conductances were analyzed by patch-clamp studies in isolated cardiomyocytes. Fibrosis was examined by Masson's Trichrome staining and thin-layer chromatography was used to analyze cardiac lipid content. Connexin43 (Cx43...

  7. Churg-Strauss Syndrome with Cardiac Involvement: A Case Report with CT and MRI Findings

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Seong Joo; Cho, Young Jun; Kim, Keum; Hwang, Cheol Mok; Kim, Dae Ho [Dept. of Radiology, Konyang University College of Medicine, Daegu (Korea, Republic of); Choi, Eu Gene [Dept. of Internal Medicine, Konyang University College of Medicine, Daegu (Korea, Republic of)

    2012-02-15

    This is a case report of Churg-Strauss Syndrome (CSS) associated with cardiac involvement which is demonstrated in chest CT and cardiac MRI (CMR) without specific cardiac symptoms. A 32-year-old woman had a 3-year history of bronchial asthma, chronic sinusitis, and otitis media. The patient had various typical findings of CSS. The patient had no specific cardiac symptoms or signs such as chest pain, palpitations, syncope, or murmur, but she had diffuse low attenuation lesions in the inner wall of the left ventricle (LV) in contrast-enhanced CT. This corresponded to the area of subendocardial hyperenhancement in delayed contrast-enhanced CMR images. She was treated with steroids for 2 months. Follow-up delayed contrast-enhanced CMR of the LV showed a decrease in the size of the subendocardial enhancement area, and she had no symptoms. Therefore, the radiologist and clinician both should pay careful attention to observe possible cardiac involvement in case of CSS.

  8. Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene × gender interaction

    Indian Academy of Sciences (India)

    Ke-Sheng Wang; Liang Wang; Xuefeng Liu; Min Zeng

    2013-12-01

    The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes. We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity $(P \\lt 0.05)$. SNP rs535812 revealed a stronger association with obesity in meta-analysis of these two samples $(P = 0.0105)$. The T–A haplotype from rs878950 and rs9525149 revealed significant association with obesity in the Marshfield sample $(P = 0.012)$. Moreover, nine SNPs showed associations with triglycerides in the Marshfield sample $(P \\lt 0.05)$ and the best signal was rs1927796 $(P = 0.00858)$. In addition, rs7331762 showed a strong gene × gender interaction $(P = 0.00956)$ for obesity while rs1927796 showed a strong gene × gender interaction $(P = 0.000625)$ for triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology.

  9. Colipase enhances hydrolysis of dietary triglycerides in the absence of bile salts.

    Science.gov (United States)

    Bläckberg, L; Hernell, O; Bengtsson, G; Olivecrona, T

    1979-11-01

    This study explores how dietary lipids are digested when intraduodenal bile salts are low or absent. Long-chain triglycerides emulsified with phosphatidylcholine were found to be hydrolyzed very slowly by pancreatic lipase alone, as if the surface layer of phospholipids enveloping the triglycerides impeded the action of the enzyme. Colipase enhanced triglyceride hydrolysis severalfold, both when added before or after the lipase. Hydrolysis became even more rapid when the emulsion was first incubated with pancreatic phospholipase. Hydrolysis of long-chain triglycerides was also severely impeded when other proteins were added to the system, probably because they adsorbed to the oil-water interface of the emulsion droplets. It was previously known that bile salts can relieve such inhibition, presumably by desorbing the adsorbed proteins. Colipase was found to enhance hydrolysis severalfold in a dose-dependent manner even in the absence of bile salts, i.e., it could partially or completely relieve the inhibition depending upon the amount and the type of inhibitory protein added to the system. Prior exposure of a protein-coated triglyceride emulsion to another lipase also enhanced the rate at which pancreatic lipase could then hydrolyze the lipids. Most dietary triglycerides are probably presented for intestinal digestion in emulsions covered by proteins and/or phospholipids. These emulsions would be hydrolyzed slowly by pancreatic lipase alone. However, through the action of the lipase in stomach contents and of pancreatic phospholipase and through the lipolysis-promoting effects of collipase, these triglycerices can be rather efficiently hydrolyzed, even in the absence of bile salts.

  10. Chronic family stress moderates the association between a TOMM40 variant and triglyceride levels in two independent Caucasian samples

    DEFF Research Database (Denmark)

    Jiang, Rong; Brummett, Beverly H; Hauser, Elizabeth R;

    2013-01-01

    TOMM40 SNP rs157580 has been associated with triglyceride levels in genome-wide association studies (GWAS). Chronic caregiving stress moderates the association between triglyceride levels and a nearby SNP rs439401 that is associated with triglyceride levels in GWAS. Here, we report data from two...... independent Caucasian samples (242 U.S. women and men; 466 Danish men) testing the hypothesis that chronic family stress also moderates the association between rs157580 and triglyceride levels. The interaction of rs157580 and family stress in predicting triglyceride levels was statistically significant...... in the U.S. sample (p=0.004) and marginally significant (p=0.075) in the Danish sample. The G allele of rs157580 was associated with increased triglyceride levels among family stressed cases in both samples compared with A/A cases, but not among controls. Chronic family stress moderates the association...

  11. Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

    Directory of Open Access Journals (Sweden)

    Hong SS

    2016-09-01

    Full Text Available Soon-Seok Hong,1 Ju Yeon Choi,2 Jong Oh Kim,2 Mi-Kyung Lee,3 So Hee Kim,4 Soo-Jeong Lim1 1Department of Bioscience and Bioengineering, Sejong University, Seoul, 2College of Pharmacy, Yeungnam University, Gyeongsan, 3College of Pharmacy, Woosuk University, Wanju-gun, Jeollabuk-do, 4College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, Republic of Korea Abstract: Studies have highlighted the challenge of developing injectable liposomes as a paclitaxel (PTX carrier, a challenge attributable to the limitations in liposomal stability caused by PTX loading. Poor stability of PTX-loaded liposomes is caused by PTX-triggered aggregation or fusion of liposomal membranes and is exacerbated in the presence of PEGylated lipid. In the present study, the effect of triglyceride incorporation on the stability of PTX-loaded/PEGylated liposomes was explored. Incorporation of a medium chain triglyceride Captex 300 into saturated phosphatidylcholine (PC-based liposomes (1,2-dimyristoyl-sn-glycero-3-phosphocholine [DMPC]:cholesterol [CHOL]:N-(Carbonyl-methoxypolyethyleneglycol 2000-1, 2-distearoyl-sn-glycero-3-phospho-ethanolamine [PE-PEG], produced a fine, homogeneous, and membrane-filterable PTX-loaded liposomes fulfilling the requirement of an injectable lipid formulation. Triglyceride incorporation also greatly inhibited the time-dependent leakage of PTX from saturated PC-based liposomes, which appears to be mediated by the inhibition of liposome fusion. In contrast, triglyceride incorporation induced the destabilization and PTX leakage of unsaturated PC-based liposomes, indicating the opposite effect of triglyceride depending on the fluidity status of PC constituting the liposomal membrane. PTX release profile and the in vitro and in vivo anticancer efficacy of triglyceride-incorporated DMPC:CHOL:PE-PEG liposomes were similar to Taxol® while the toxicity of liposomal PTX was significantly lower than that of

  12. mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Parker, Benjamin L; Chaudhuri, Rima;

    2016-01-01

    culture. RESULTS: Ric mKO mice exhibited a greater reliance on fat as an energy substrate, a re-partitioning of lean to fat mass and an increase in intramyocellular triglyceride (IMTG) content, along with increases in several lipid metabolites in muscle. Unbiased proteomics revealed an increase...... dependent manner. PLIN3 overexpression was sufficient to increase triglyceride content in muscle cells. CONCLUSIONS: We identified a novel link between mTORC2 and PLIN3, which regulates lipid storage in muscle. While mTORC2 is a negative regulator, we further identified AMPK as a positive regulator of PLIN3...

  13. Composition, structure and properties of POPC–triolein mixtures. Evidence of triglyceride domains in phospholipid bilayers

    DEFF Research Database (Denmark)

    Duelund, Lars; Jensen, Grethe Vestergaard; Hannibal-Bach, Hans Kristian;

    2013-01-01

    We have in this study investigated the composition, structure and spectroscopical properties of multilamellar vesicles composed of a phospholipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and up to 10mol% of triolein (TO), a triglyceride. We found in agreement with previous results......% TO contained pure TO domains. These observations are consistent with an earlier MD simulation study by us and our co-workers suggesting triglycerides to be located in lens shaped, blister-like domains between the two lipid bilayer leaflets (Khandelia et al. (2010) [26])....

  14. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment

    OpenAIRE

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; FUJIMOTO, TOYOSHI

    2015-01-01

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1–coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf–GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD...

  15. Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4-Induced Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Ping-Chun Li

    2012-01-01

    Full Text Available We used the carbon tetrachloride (CCl4 induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE and silymarin against cardiac hypertrophy. We treated male wistar rats with CCl4 and either OGE (0.02 g/kg B.W. or 0.04 g/kg B.W. or silymarin (0.2 g/kg B.W.. Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6 signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy.

  16. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa

    2002-01-01

    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

  17. The cardiac anxiety questionnaire: cross-validation among cardiac inpatients

    NARCIS (Netherlands)

    Beek, M.H. van; Oude Voshaar, R.C.; Deelen, F.M. van; Balkom, A.J. van; Pop, G.A.; Speckens, A.E.

    2012-01-01

    OBJECTIVE: General anxiety symptoms are common in patients with cardiac disease and considered to have an adverse effect on cardiac prognosis. The role of specific cardiac anxiety, however, is still unknown. The aim of this study is to examine the factor structure, reliability, and validity of the D

  18. THE CARDIAC ANXIETY QUESTIONNAIRE : CROSS-VALIDATION AMONG CARDIAC INPATIENTS

    NARCIS (Netherlands)

    van Beek, M. H. C. T.; Voshaar, R. C. Oude; van Deelen, F. M.; van Balkom, A. J. L. M.; Pop, G.; Speckens, A. E. M.

    2012-01-01

    Objective: General anxiety symptoms are common in patients with cardiac disease and considered to have an adverse effect on cardiac prognosis. The role of specific cardiac anxiety, however, is still unknown. The aim of this study is to examine the factor structure, reliability, and validity of the D

  19. Giant Cardiac Cavernous Hemangioma.

    Science.gov (United States)

    Unger, Eric; Costic, Joseph; Laub, Glenn

    2015-07-01

    We report the case of an asymptomatic giant cardiac cavernous hemangioma in a 71-year-old man. The intracardiac mass was discovered incidentally during surveillance for his prostate cancer; however, the patient initially declined intervention. On presentation to our institution 7 years later, the lesion had enlarged significantly, and the patient consented to excision. At surgery, an 8 × 6.5 × 4.8 cm intracardiac mass located on the inferior heart border was excised with an intact capsule through a median sternotomy approach. The patient had an uneventful postoperative course. We discuss the diagnostic workup, treatment, and characteristics of this rare cardiac tumor. PMID:26140782

  20. Perioperative management of cardiac disease.

    Science.gov (United States)

    Aresti, N A; Malik, A A; Ihsan, K M; Aftab, S M E; Khan, W S

    2014-01-01

    Pre-existing cardiac disease contributes significantly to morbidity and mortality amongst patients undergoing non cardiac surgery. Patients with pre-existing cardiac disease or with risk factors for it, have as much as a 3.9% risk of suffering a major perioperative cardiac event (Lee et al 1999, Devereaux 2005). Furthermore, the incidence of perioperative myocardial infarction (MI) is increased 10 to 50 fold in patients with previous coronary events (Jassal 2008).

  1. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids.

    Science.gov (United States)

    Huang, Tom Hsun-Wei; Peng, Gang; Kota, Bhavani Prasad; Li, George Qian; Yamahara, Johji; Roufogalis, Basil D; Li, Yuhao

    2005-07-01

    Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro. Long-term oral administration of PGF extract (500 mg kg(-1)) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholesterol in Zucker diabetic fatty (ZDF) rats, indicating improvement by PGF extract of abnormal cardiac TG accumulation and hyperlipidemia in this diabetic model. Treatment of ZDF rats with PGF extract lowered plasma FA levels. Furthermore, the treatment suppressed cardiac overexpression of mRNAs encoding for FA transport protein, peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase alpha2, and restored downregulated cardiac acetyl-CoA carboxylase mRNA expression in ZDF rats, whereas it showed little effect in Zucker lean rats. The results suggest that PGF extract inhibits increased cardiac FA uptake and oxidation in the diabetic condition. PGF extract and its component oleanolic acid enhanced PPAR-alpha luciferase reporter gene activity in human embryonic kidney 293 cells, and this effect was completely suppressed by a selective PPAR-alpha antagonist MK-886, consistent with the presence of PPAR-alpha activator activity in the extract and this component. Our findings suggest that PGF extract improves abnormal cardiac lipid metabolism in ZDF rats by activating PPAR-alpha and thereby lowering circulating lipid and inhibiting its cardiac uptake. PMID:15880139

  2. Estrogen modulates the influence of cardiac inflammatory cells on function of cardiac fibroblasts

    Directory of Open Access Journals (Sweden)

    McLarty JL

    2013-08-01

    untreated group resulted in: 1 an increased fibroblast proliferation, collagen production and matrix metalloproteinase activity; and 2 a loss of ß1 integrin protein and a reduced ability to contract collagen gels. In contrast, inflammatory cells from the treated group resulted in: 1 an attenuated fibroblast proliferation; 2 a nonsignificant reduction in collagen production; 3 the prevention of matrix metalloproteinase activation and the loss of β1 integrin by fibroblasts and 4 a preservation of the fibroblasts’ ability to contract collagen gels. The TNF-α neutralizing antibody attenuated or prevented the untreated inflammatory cell-induced fibroblast proliferation, collagen production, matrix metalloproteinase activation and loss of β1 integrin protein as well as preserved fibroblast contractile ability. Incubation with TNF-α yielded changes in the cardiac fibroblast parameters that were directionally similar to the results obtained with untreated inflammatory cells. Conclusion: These results and those of our previous in vivo studies suggest that a major mechanism by which estrogen provides cardioprotection is its ability to modulate synthesis of TNF-α by inflammatory cells, thereby preventing inflammatory cell induction of cardiac fibroblast events that contribute to adverse extracellular matrix remodeling. Keywords: tumor necrosis factor-alpha, neutralizing antibody, fibroblast proliferation, matrix metalloproteinase activity, β1 integrin, collagen gel contraction

  3. Uncommon breast tumor attenuation artifact on radionuclide ventriculography.

    Science.gov (United States)

    Metrard, Gilles; Girault, Sylvie; Capitain, Olivier; Jeanguillaume, Christian; Rakotonirina, Hervé; Berthelot, Cécile; Le Jeune, Jean-Jacques; Morel, Olivier

    2008-04-01

    A 39-year-old woman with locally advanced left breast cancer (T4 N0 M0) underwent equilibrium radionuclide ventriculography for baseline assessment of left ventricular function before neoadjuvant chemotherapy. The left ventricular ejection fraction was 76% at 75 beats per minute, without localized wall motion abnormality. In the best septal left anterior oblique projection, a large photopenic "halo" surrounded the cardiac chambers, mimicking a pericardial effusion. In fact, this aspect resulted from an attenuation artifact by a large left breast tumor, as demonstrated by FDG-PET/CT imaging. PMID:18356673

  4. Heterogeneous catalysts for the transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons

    International Nuclear Information System (INIS)

    The results of studies devoted to the catalysts for transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons are presented and described systematically. Various approaches to the use of heterogeneous catalysts for the production of biofuel from these raw materials are considered. The bibliography includes 134 references.

  5. CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance

    NARCIS (Netherlands)

    Goudriaan, [No Value; den Boer, MAM; Rensen, PCN; Febbraio, M; Kuipers, F; Romijn, JA; Havekes, LM; Voshol, PJ

    2005-01-01

    CD36 is involved in high-affinity peripheral FFA uptake. CD36-deficient (cd36(-/-)) mice exhibit increased plasma FFA and triglyceride (TG) levels. The aim of the present study was to elucidate the cause of the increased plasma TG levels in cd36(-/-) mice. cd36(-/-) mice showed no differences in hep

  6. Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Non-alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Poulsen, Marianne K; Nellemann, Birgitte; Stødkilde-Jørgensen, Hans;

    2016-01-01

    CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of VLDL-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: To determine VLDL-TG, glucose and palmitate kinetics during fasting and hyperin...

  7. Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats.

    Science.gov (United States)

    Margolis, Lee M; Rivas, Donato A; Ezzyat, Yassine; Gaffney-Stomberg, Erin; Young, Andrew J; McClung, James P; Fielding, Roger A; Pasiakos, Stefan M

    2016-01-01

    The purpose of this investigation was to assess the influence of calorie restriction (CR) alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL), and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or CR (40% restriction), adequate (10%), or high (32%) protein (PRO) milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β) values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g(-1) lower (p protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p health benefits associated with CR-specifically reduction in intrahepatic triglyceride content-may be enhanced by consuming a higher-protein/lower-carbohydrate diet. PMID:27649241

  8. Changes in the triglyceride-rich lipoproteins and the response to dietary cholesterol in man.

    NARCIS (Netherlands)

    Demacker, P.N.M.; Glatz, J.F.C.; Katan, M.B.

    1988-01-01

    The effect of a cholesterol-enriched diet was studied in nine healthy volunteers with special emphasis to the changes which occurred in the triglyceride-rich lipoproteins (d<1.019 g/ml). Compared to the habitual diet, a moderately increased intake of cholesterol (from 300–900 mg/day) resulted in cha

  9. Comprehensive Experiment--Clinical Biochemistry: Determination of Blood Glucose and Triglycerides in Normal and Diabetic Rats

    Science.gov (United States)

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a…

  10. The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglycerides

    NARCIS (Netherlands)

    Moen, C.J.A.; Tholens, A.P.; Voshol, P.J.; Haan, W. de; Havekes, L.M.; Gargalovic, P.; Lusis, A.J.; Dyk, K.W. van; Frants, R.R.; Hofker, M.H.; Rensen, P.C.N.

    2007-01-01

    The Hyplip2 congenic mouse strain contains part of chromosome 15 from MRL/MpJ on the BALB/cJ background. Hyplip2 mice show increased plasma levels of cholesterol and predominantly triglycerides (TGs) and are susceptible to diet-induced atherosclerosis. This study aimed at elucidation of the mechanis

  11. A report of high triglyceride level in cord blood of Iranian newborns

    Directory of Open Access Journals (Sweden)

    Seyed Ali Naghi Kazemi

    2013-01-01

    Conclusion: The mean and 95 th percentiles of triglyceride levels in cord blood of our newborn infants were higher than other reports. We recommend that larger studies should be conducted in this area to establish preventive ways for increasing epidemic of the metabolic syndrome.

  12. Interference of flavonoids with enzymatic assays for the determination of free fatty acid and triglyceride levels

    NARCIS (Netherlands)

    Hoek-van den Hil, E.F.; Beekmann, K.; Keijer, J.; Hollman, P.C.H.; Rietjens, I.; Schothorst, van E.M.

    2012-01-01

    Flavonoids are bioactive food compounds with potential lipid-lowering effects. Commercially available enzymatic assays are widely used to determine free fatty acid (FFA) and triglyceride (TG) levels both in vivo in plasma or serum and in vitro in cell culture medium or cell lysate. However, we have

  13. Placental triglyceride accumulation in maternal type 1 diabetes is associated with increased lipase gene expression

    DEFF Research Database (Denmark)

    Lindegaard, Marie Louise Skakkebæk; Damm, Peter; Mathiesen, Elisabeth R;

    2006-01-01

    in placenta is largely unknown. To examine whether maternal type 1 diabetes affects placental lipid metabolism, we measured lipids and mRNA expression of lipase-encoding genes in placentas from women with type 1 diabetes (n = 27) and a control group (n = 21). The placental triglyceride (TG) concentration...

  14. Liver protein expression in dairy cows with high liver triglycerides in early lactation

    DEFF Research Database (Denmark)

    Sejersen, Henrik; Sørensen, Martin Tang; Larsen, Torben;

    2012-01-01

    Fatty liver is a frequent subclinical health disorder in dairy cows that may lead to disorders related to the liver function. However, the effect of triglyceride (TG) accumulation on liver metabolic pathways is still unclear. The objective was, therefore, to characterize quantitative differences...

  15. Assessment and clinical relevance of non-fasting and postprandial triglycerides

    DEFF Research Database (Denmark)

    Kolovou, Genovefa D; Mikhailidis, Dimitri P; Kovar, Jan;

    2011-01-01

    An Expert Panel group of scientists and clinicians met to consider several aspects related to non-fasting and postprandial triglycerides (TGs) and their role as risk factors for cardiovascular disease (CVD). In this context, we review recent epidemiological studies relevant to elevated non...

  16. Intramyocellular triglyceride content in man, influence of sex, obesity and glycaemic control

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Mu, Huiling; Vaag, Allan;

    2009-01-01

    It remains unknown whether sex impacts on intramyocellular triglyceride (IMTG) in obesity. as has been shown in non-obese subjects, and if so, whether this may have implications on the association between IMTG and insulin sensitivity. Subject and methods: A Muscle biopsy from vastus lateralis...

  17. Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training

    DEFF Research Database (Denmark)

    Alsted, Thomas J; Schweiger, Martina; Nybo, Lars;

    2009-01-01

    ) is not changed. Recently, adipose triglyceride lipase (ATGL) was identified as a TG-specific lipase in various rodent tissues. To investigate whether human skeletal muscle ATGL protein is regulated by endurance exercise training, 10 healthy young men completed 8 wk of supervised endurance exercise training...

  18. Sympathetic nervous system control of triglyceride metabolism: Novel concepts derived from recent studies

    NARCIS (Netherlands)

    Geerling, J.J.; Boon, M.R.; Kooijman, S.; Parlevliet, E.T.; Havekes, L.M.; Romijn, J.A.; Meurs, I.M.; Rensen, P.C.N.

    2014-01-01

    Abstract Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the collective action of which determine plasma TG levels.

  19. Genetic APOC3 mutation, serum triglyceride concentrations, and coronary heart disease

    Science.gov (United States)

    Recent decades have witnessed an increased awareness of the importance of lowering triglyceride concentrations in conjunction with lowering LDL cholesterol (LDL-C) to achieve optimal reduction of the risk for coronary heart disease (CHD). Historically, LDL-C was the only target of pharmacologic ther...

  20. The cardiac malpositions.

    Science.gov (United States)

    Perloff, Joseph K

    2011-11-01

    Dextrocardia was known in the 17th century and was 1 of the first congenital malformations of the heart to be recognized. Fifty years elapsed before Matthew Baillie published his account of complete transposition in a human of the thoracic and abdominal viscera to the opposite side from what is natural. In 1858, Thomas Peacock stated that "the heart may be congenitally misplaced in various ways, occupying either an unusual position within the thorax, or being situated external to that cavity." In 1915, Maude Abbott described ectopia cordis, and Richard Paltauf's remarkable illustrations distinguished the various types of dextrocardia. In 1928, the first useful classification of the cardiac malpositions was proposed, and in 1966, Elliott et al's radiologic classification set the stage for clinical recognition. The first section of this review deals with the 3 basic cardiac malpositions in the presence of bilateral asymmetry. The second section deals with cardiac malpositions in the presence of bilateral left-sidedness or right-sidedness. Previous publications on cardiac malpositions are replete with an arcane vocabulary that confounds rather than clarifies. Even if the terms themselves are understood, inherent complexity weighs against clarity. This review was designed as a guided tour of an unfamiliar subject.

  1. Hepato-cardiac disorders

    Institute of Scientific and Technical Information of China (English)

    Yasser; Mahrous; Fouad; Reem; Yehia

    2014-01-01

    Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases

  2. Cardiac effects of vasopressin.

    Science.gov (United States)

    Pelletier, Jean-Sébastien; Dicken, Bryan; Bigam, David; Cheung, Po-Yin

    2014-07-01

    Vasopressin is an essential hormone involved in the maintenance of cardiovascular homeostasis. It has been in use therapeutically for many decades, with an emphasis on its vasoconstrictive and antidiuretic properties. However, this hormone has a ubiquitous influence and has specific effects on the heart. Although difficult to separate from its powerful vascular effects in the clinical setting, a better understanding of vasopressin's direct cardiac effects could lead to its more effective clinical use for a variety of shock states by maximizing its therapeutic benefit. The cardiac-specific effects of vasopressin are complex and require further elucidation. Complicating our understanding include the various receptors and secondary messengers involved in vasopressin's effects, which may lead to various results based on differing doses and varying environmental conditions. Thus, there have been contradictory reports on vasopressin's action on the coronary vasculature and on its effect on inotropy. However, beneficial results have been found and warrant further study to expand the potential therapeutic role of vasopressin. This review outlines the effect of vasopressin on the coronary vasculature, cardiac contractility, and on hypertrophy and cardioprotection. These cardiac-specific effects of vasopressin represent an interesting area for further study for potentially important therapeutic benefits. PMID:24621650

  3. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...

  4. Cardiac pacemaker power sources

    International Nuclear Information System (INIS)

    A review of chemical and radioisotope batteries used in cardiac pacemakers is presented. The battery systems are examined in terms of longevity, reliability, cost, size and shape, energy density, weight, internal resistance versus time, end-of-life voltage, chemical compatibility, and potential failure mechanisms

  5. Effect of Low Amphetamine Doses on Cardiac Responses to Emotional Stress in Aged Rats

    NARCIS (Netherlands)

    Nyakas, Csaba; Buwalda, Bauke; Luiten, Paul G.M.; Bohus, Bela

    1992-01-01

    In young Wistar rats conditioned emotional stress can be characterized by a learned bradycardiac response to an inescapable footshock. In aged rats this bradycardiac response is attenuated and accompanied by suppressed behavioral arousal in response to novelty. In the present study, cardiac response

  6. Diuretics Prevent Thiazolidinedione-Induced Cardiac Hypertrophy without Compromising Insulin-Sensitizing Effects in Mice

    Science.gov (United States)

    Chang, Cherng-Shyang; Tsai, Pei-Jane; Sung, Junne-Ming; Chen, Ju-Yi; Ho, Li-Chun; Pandya, Kumar; Maeda, Nobuyo; Tsai, Yau-Sheng

    2015-01-01

    Much concern has arisen regarding critical adverse effects of thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, on cardiac tissue. Although TZD-induced cardiac hypertrophy (CH) has been attributed to an increase in plasma volume or a change in cardiac nutrient preference, causative roles have not been established. To test the hypothesis that volume expansion directly mediates rosiglitazone-induced CH, mice were fed a high-fat diet with rosiglitazone, and cardiac and metabolic consequences were examined. Rosiglitazone treatment induced volume expansion and CH in wild-type and PPARγ heterozygous knockout (Pparg+/−) mice, but not in mice defective for ligand binding (PpargP465L/+). Cotreatment with the diuretic furosemide in wild-type mice attenuated rosiglitazone-induced CH, hypertrophic gene reprogramming, cardiomyocyte apoptosis, hypertrophy-related signal activation, and left ventricular dysfunction. Similar changes were observed in mice treated with pioglitazone. The diuretics spironolactone and trichlormethiazide, but not amiloride, attenuated rosiglitazone effects on volume expansion and CH. Interestingly, expression of glucose and lipid metabolism genes in the heart was altered by rosiglitazone, but these changes were not attenuated by furosemide cotreatment. Importantly, rosiglitazone-mediated whole-body metabolic improvements were not affected by furosemide cotreatment. We conclude that releasing plasma volume reduces adverse effects of TZD-induced volume expansion and cardiac events without compromising TZD actions in metabolic switch in the heart and whole-body insulin sensitivity. PMID:24287404

  7. Colorimetric measurement of triglycerides cannot provide an accurate measure of stored fat content in Drosophila.

    Directory of Open Access Journals (Sweden)

    Bader Al-Anzi

    Full Text Available Drosophila melanogaster has recently emerged as a useful model system in which to study the genetic basis of regulation of fat storage. One of the most frequently used methods for evaluating the levels of stored fat (triglycerides in flies is a coupled colorimetric assay available as a kit from several manufacturers. This is an aqueous-based enzymatic assay that is normally used for measurement of mammalian serum triglycerides, which are present in soluble lipoprotein complexes. In this short communication, we show that coupled colorimetric assay kits cannot accurately measure stored triglycerides in Drosophila. First, they fail to give accurate readings when tested on insoluble triglyceride mixtures with compositions like that of stored fat, or on fat extracted from flies with organic solvents. This is probably due to an inability of the lipase used in the kits to efficiently cleave off the glycerol head group from fat molecules in insoluble samples. Second, the measured final products of the kits are quinoneimines, which absorb visible light in the same wavelength range as Drosophila eye pigments. Thus, when extracts from crushed flies are assayed, much of the measured signal is actually due to eye pigments. Finally, the lipoprotein lipases used in colorimetric assays also cleave non-fat glycerides. The glycerol backbones liberated from all classes of glycerides are measured through the remaining reactions in the assay. As a consequence, when these assay kits are used to evaluate tissue extracts, the observed signal actually represents the amount of free glycerols together with all types of glycerides. For these reasons, findings obtained through use of coupled colorimetric assays on Drosophila samples must be interpreted with caution. We also show here that using thin-layer chromatography to measure stored triglycerides in flies eliminates all of these problems.

  8. Association of Zinc, Copper and triglyceride levels with low birth weight deliveries in central Sudan

    International Nuclear Information System (INIS)

    Objective, to investigate the maternal and cord level of zinc, Copper and triglyceride in mothers with low birth weight babies (LBW; < 2500 gm) in comparison to mothers with normal weight babies. Method, a case control study was conducted in Medani Hospital, Sudan pre-tested questionnaires were used to gather maternal socio-demographic and clinical data. Zinc and cooper were measured by atomic absorption spectrophotometer. And triglyceride was measured by colorimetric method. Results, case and controls (50 in each arm) were matched in their basic clinical data. The median ( 25-75 Th inter quartile) of maternal zinc ( 62.9 ( 36.3-96.8) vs. 96.2 (84,6-125.7) μg/dl; p <0.001) and copper (81.6 ( 23.7- 167.5) vs. 139.8 (319.8 (31.9 - 186.2) μg/dl; p=0.04) and triglyceride (172 (100-227) vs. 195 ( 133.7-320.2) mg/dl; p=0.052) levels were significantly lower in cases than in the controls. Likewise, cord zinc ( 87.1 (43.3 -118.1) vs. 92.2 (62.0-114.5) μg/dl; p=0.02) and triglyceride ( 45 ( 31.5-95) vs. 149.5 (97.5- 174.2) mg/dl; p<0.00) levels were significantly lower in cord serum of the case than in controls. Conclusions, in this study maternal and fetal zinc, copper and triglyceride levels were lower in mothers with LBW babies compared to mothers with normal birth weight babies. Supplementation with zinc and copper might be necessary to prevent LBW deliveries in this setting. (Author)

  9. Cardiac-specific knockout of ETA receptor mitigates low ambient temperature-induced cardiac hypertrophy and contractile dysfunction

    Institute of Scientific and Technical Information of China (English)

    Yingmei Zhang; Linlin Li; Yinan Hua; Jennifer M. Nunn; Feng Dong; Masashi Yanagisawa; Jun Ren

    2012-01-01

    Cold exposure is associated with oxidative stress and cardiac dysfunction.The endothelin (ET) system,which plays a key role in myocardial homeostasis,may participate in cold exposure-induced cardiovascular dysfunction.This study was designed to examine the role of ET-1 in cold stress-induced cardiac geometric and contractile responses.Wild-type (WT) and ETA receptor knockout (ETAKO) mice were assigned to normal or cold exposure (4℃) environment for 2 and 5 weeks prior to evaluation of cardiac geometry,contractile,and intracellular Ca2+ properties.Levels of the temperature sensor transient receptor potential vanlllold (TRPV1),mitochondrlal proteins for biogenesis and oxidative phosphorylatlon,Including UCP2,HSP90,and PGC1α were evaluated.Cold stress triggered cardiac hypertrophy,depressed myocardial contractile capacity,including fractional shortening,peak shortening,and maximal velocity of shortening/relengthening,reduced intracellular Ca2+ release,prolonged intracellular Ca2+ decay and relengthening duration,generation of ROS and superoxide,as well as apoptosls,the effects of which were blunted by ETAKO.Western blotting revealed downregulated TRPV1 and PGC1α as well as upregulated UCP2 and activation of GSK3β,GATA4,and CREB in cold-stressed WT mouse hearts,which were obliterated by ETAKO.Levels of HSP90,an essential regulator for thermotolerance,were unchanged.The TRPV1 agonist SA13353 attenuated whereas TRPV1 antagonist capsazepino mimicked cold stress- or ET-1-induced cardiac anomalies.The GSK3β Inhibitor SB216763 ablated cold stress-induced cardiac contractile (but not remodeling) changes and ET-1-induced TRPV1 downregulation.These data suggest that ETAKO protects against cold exposure-induced cardiac remodeling and dysfunction mediated through TRPV1 and mitochondrlal function.

  10. Parenteral medium-chain triglyceride-induced neutrophil activation is not mediated by a Pertussis Toxin sensitive receptor.

    NARCIS (Netherlands)

    Versleijen, M.W.J.; Esterik, J.C. van; Schaap-Roelofs, H.M.J.; Emst-de Vries, S.E. van; Willems, P.H.G.M.; Wanten, G.J.A.

    2009-01-01

    BACKGROUND & AIMS: Lipid-induced immune modulation might contribute to the increased infection rate that is observed in patients using parenteral nutrition. We previously showed that emulsions containing medium-chain triglycerides (LCT/MCTs or pure MCTs), but not pure long-chain triglycerides (LCTs)

  11. Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids

    DEFF Research Database (Denmark)

    Schoiswohl, Gabriele; Schweiger, Martina; Schreiber, Renate;

    2010-01-01

    Fatty acids (FA) are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGLko)exhibit defective lipolysis and accumulate TG in adipose tissue and muscle suggesting that ATGL deficiency affects energy...

  12. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease

    DEFF Research Database (Denmark)

    Wittrup, Hans H; Andersen, Rolf V; Tybjaerg-Hansen, Anne;

    2006-01-01

    Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD).......Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD)....

  13. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

    NARCIS (Netherlands)

    Schweiger, M.; Paar, M.; Eder, C.; Brandis, J.; Moser, E.; Gorkiewisz, G.; Grond, S.; Radner, F.P.W.; Cerk, I.; Cornaciu, I.; Oberer, M.; Kersten, A.H.; Zechner, R.; Zimmermann, M.B.; Lass, A.

    2012-01-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL)5, which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 sw

  14. Cardiac fusion and complex congenital cardiac defects in thoracopagus twins: diagnostic value of cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Park, Jeong-Jun [University of Ulsan College of Medicine, Asan Medical Center, Department of Pediatric Cardiac Surgery, Seoul (Korea, Republic of); Kim, Ellen Ai-Rhan [University of Ulsan College of Medicine, Asan Medical Center, Division of Neonatology, Department of Pediatrics, Seoul (Korea, Republic of); Won, Hye-Sung [University of Ulsan College of Medicine, Asan Medical Center, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of)

    2014-09-15

    Most thoracopagus twins present with cardiac fusion and associated congenital cardiac defects, and assessment of this anatomy is of critical importance in determining patient care and outcome. Cardiac CT with electrocardiographic triggering provides an accurate and quick morphological assessment of both intracardiac and extracardiac structures in newborns, making it the best imaging modality to assess thoracopagus twins during the neonatal period. In this case report, we highlight the diagnostic value of cardiac CT in thoracopagus twins with an interatrial channel and complex congenital cardiac defects. (orig.)

  15. Backscatter and attenuation characterization of ventricular myocardium

    Science.gov (United States)

    Gibson, Allyson Ann

    2009-12-01

    This Dissertation presents quantitative ultrasonic measurements of the myocardium in fetal hearts and adult human hearts with the goal of studying the physics of sound waves incident upon anisotropic and inhomogeneous materials. Ultrasound has been used as a clinical tool to assess heart structure and function for several decades. The clinical usefulness of this noninvasive approach has grown with our understanding of the physical mechanisms underlying the interaction of ultrasonic waves with the myocardium. In this Dissertation, integrated backscatter and attenuation analyses were performed on midgestational fetal hearts to assess potential differences in the left and right ventricular myocardium. The hearts were interrogated using a 50 MHz transducer that enabled finer spatial resolution than could be achieved at more typical clinical frequencies. Ultrasonic data analyses demonstrated different patterns and relative levels of backscatter and attenuation from the myocardium of the left ventricle and the right ventricle. Ultrasonic data of adult human hearts were acquired with a clinical imaging system and quantified by their magnitude and time delay of cyclic variation of myocardial backscatter. The results were analyzing using Bayes Classification and ROC analysis to quantify potential advantages of using a combination of two features of cyclic variation of myocardial backscatter over using only one or the other feature to distinguish between groups of subjects. When the subjects were classified based on hemoglobin A1c, the homeostasis model assessment of insulin resistance, and the ratio of triglyceride to high-density lipoprotein-cholesterol, differences in the magnitude and normalized time delay of cyclic variation of myocardial backscatter were observed. The cyclic variation results also suggested a trend toward a larger area under the ROC curve when information from magnitude and time delay of cyclic variation is combined using Bayes classification than when

  16. Muscle and liver glycogen, protein, and triglyceride in the rat. Effect of exercise and of the sympatho-adrenal system

    DEFF Research Database (Denmark)

    Richter, E A; Sonne, B; Mikines, K J;

    1984-01-01

    in skeletal muscle was accompanied by increased breakdown of triglyceride and/or protein. Thus, the effect of exhausting swimming and of running on concentrations of glycogen, protein, and triglyceride in skeletal muscle and liver were studied in rats with and without deficiencies of the sympatho......-adrenal system. In control rats, both swimming and running decreased the concentration of glycogen in fast-twitch red and slow-twitch red muscle whereas concentrations of protein and triglyceride did not decrease. In the liver, swimming depleted glycogen stores but protein and triglyceride concentrations did...... not decrease. In exercising rats, muscle glycogen breakdown was impaired by adrenodemedullation and restored by infusion of epinephrine. However, impaired glycogen breakdown during exercise was not accompanied by a significant net breakdown of protein or triglyceride. Surgical sympathectomy of the muscles did...

  17. Acquisition and automated 3-D segmentation of respiratory/cardiac-gated PET transmission images

    International Nuclear Information System (INIS)

    To evaluate the impact of respiratory motion on attenuation correction of cardiac PET data, we acquired and automatically segmented gated transmission data for a dog breathing on its own under gas anesthesia. Data were acquired for 20 min on a CTI/Siemens ECAT EXACT HR (47-slice) scanner configured for 12 gates in a static study, Two respiratory gates were obtained using data from a pneumatic bellows placed around the dog's chest, in conjunction with 6 cardiac gates from standard EKG gating. Both signals were directed to a LabVIEW-controlled Macintosh, which translated them into one of 12 gate addresses. The respiratory gating threshold was placed near end-expiration to acquire 6 cardiac-gated datasets at end-expiration and 6 cardiac-gated datasets during breaths. Breaths occurred about once every 10 sec and lasted about 1-1.5 sec. For each respiratory gate, data were summed over cardiac gates and torso and lung surfaces were segmented automatically using a differential 3-D edge detection algorithm. Three-dimensional visualizations showed that lung surfaces adjacent to the heart translated 9 mm inferiorly during breaths. Our results suggest that respiration-compensated attenuation correction is feasible with a modest amount of gated transmission data and is necessary for accurate quantitation of high-resolution gated cardiac PET data

  18. Computer Generated Cardiac Model For Nuclear Medicine

    Science.gov (United States)

    Hills, John F.; Miller, Tom R.

    1981-07-01

    A computer generated mathematical model of a thallium-201 myocardial image is described which is based on realistic geometric and physiological assumptions. The left ventricle is represented by an ellipsoid truncated by aortic and mitral valve planes. Initially, an image of a motionless left ventricle is calculated with the location, size, and relative activity of perfusion defects selected by the designer. The calculation includes corrections for photon attenuation by overlying structures and the relative distribution of activity within the tissues. Motion of the ventricular walls is simulated either by a weighted sum of images at different stages in the cardiac cycle or by a blurring function whose width varies with position. Camera and collimator blurring are estimated by the MTF of the system measured at a representative depth in a phantom. Statistical noise is added using a Poisson random number generator. The usefulness of this model is due to two factors: the a priori characterization of location and extent of perfusion defects and the strong visual similarity of the images to actual clinical studies. These properties should permit systematic evaluation of image processing algorithms using this model. The principles employed in developing this cardiac image model can readily be applied to the simulation of other nuclear medicine studies and to other medical imaging modalities including computed tomography, ultrasound, and digital radiography.

  19. Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

    Science.gov (United States)

    Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

    2015-04-01

    Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats. PMID:24905340

  20. Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction.

    Science.gov (United States)

    Wang, Jiaxing; Lu, Songhe; Zheng, Qijun; Hu, Nan; Yu, Wenjun; Li, Na; Liu, Min; Gao, Beilei; Zhang, Guoyong; Zhang, Yingmei; Wang, Haichang

    2016-07-01

    Paraquat (1,1'-dim ethyl-4-4'-bipyridinium dichloride), a highly toxic quaternary ammonium herbicide widely used in agriculture, exerts potent toxic prooxidant effects resulting in multi-organ failure including the lung and heart although the underlying mechanism remains elusive. Recent evidence suggests possible involvement of endothelin system in paraquat-induced acute lung injury. This study was designed to examine the role of endothelin receptor A (ETA) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type (WT) and cardiac-specific ETA receptor knockout mice were challenged to paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties, as well as apoptosis and mitochondrial damage. Levels of the mitochondrial proteins for biogenesis and oxidative phosphorylation including UCP2, HSP90 and PGC1α were evaluated. Our results revealed that paraquat elicited cardiac enlargement, mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic and end-diastolic diameters as well as reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, overt apoptosis and mitochondrial damage. ETA receptor knockout itself failed to affect myocardial function, apoptosis, mitochondrial integrity and mitochondrial protein expression. However, ETA receptor knockout ablated or significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) defect, apoptosis and mitochondrial damage. Taken together, these findings revealed that endothelin system in particular the ETA receptor may be involved in paraquat-induced toxic myocardial contractile anomalies possibly related to apoptosis and mitochondrial damage. PMID:26089164

  1. Correlation of CRP, Fasting Serum Triglycerides and Obesity as Cardiovascular Risk Factors

    International Nuclear Information System (INIS)

    Objective: To determine the correlation of C-reactive protein (CRP) with fasting triglycerides (TG) among pre-obese and obese patients without established diagnosis of coronary artery disease (CAD). Study Design: A comparative cross-sectional study. Place and Duration of Study: Mayo Hospital, Lahore, from January to June 2010. Methodology: Patients with BMI > 23 kg/m2 aged between 18 - 65 years were inducted and above variables were studied. Patients with signs of fluid retention, collagen vascular disease, CAD, patients on corticosteroids, immunomodulators or lipid lowering medications and febrile patients were not recruited. Body mass index was also determined. Independent sample t-test was applied to see the mean difference of age, CRP level and triglycerides level in relation to gender. Chisquare test was used to see the association between qualitative variables. ANOVA was applied to see CRP and fasting serum TG level in relation to BMI categories. Pearson correlation and simple linear regression was applied to see the dependency of CRP and triglycerides with BMI. P-value A = 0.05 was taken as significant. Results: Raised CRP was major finding among all groups of BMI. Most of obese and pre-obese patients were young and middle aged and belonged to pre-obese group followed by class-1 and class-2 obesity. CRP level increased with body mass index. No such trend was observed for triglycerides. There was an intermediate positive correlation between CRP and BMI and triglycerides and BMI showed a weak negative correlation. If BMI increases by 1 unit on the average, CRP rises by 0.239 times and this unit rise was significant. Whereas 1 unit rise increase in triglycerides on the average cause CRP to decrease -0.006 times but this value was insignificant. Conclusion: Raised CRP and high fasting TG were major findings in all age groups especially among young and middle aged people. Obesity, hypertriglyceridemia and raised CRP are interrelated suggesting that obesity is not

  2. Sudden Cardiac Death

    Directory of Open Access Journals (Sweden)

    Yipsy María Gutiérrez Báez

    2015-09-01

    Full Text Available Since the second half of the twentieth century, dying suddenly due to heart-related problems has become the main health issue in all countries where infectious diseases are not prevalent. Sudden death from cardiac causes is an important global health problem. Major databases were searched for the leading causes of sudden cardiac death. It has been demonstrated that there is a group of hereditary diseases with structural alterations or without apparent organic cause that explains many cases of sudden death in young people, whether related or not to physical exertion. Certain population groups are at higher risk for this disease. They are relatively easy to identify and can be the target of primary prevention measures.

  3. Inherited cardiac disease

    Directory of Open Access Journals (Sweden)

    Philippe Charron

    2012-06-01

    Full Text Available Major advances have been achieved over the two last decades in the field of genetic cardiovascular diseases, not only through increased recognition and understanding of underlying molecular defects but also through rapid translation of knowledge into clinical practice. Genetic counseling and organization of cardiac family screening has become part of the medical management of these diseases, and these should be performed systematically unless an acquired cause has been diagnosed...

  4. Cardiac Tissue Engineering

    OpenAIRE

    MILICA RADISIC; GORDANA VUNJAK-NOVAKOVIC

    2009-01-01

    We hypothesized that clinically sized (1-5 mm thick),compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3) can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of p...

  5. Cardiac developmental toxicity

    OpenAIRE

    Mahler, Gretchen J.; Jonathan T Butcher

    2011-01-01

    Congenital heart disease is a highly prevalent problem with mostly unknown origins. Many cases of CHD likely involve an environmental exposure coupled with genetic susceptibility, but practical and ethical considerations make nongenetic causes of CHD difficult to assess in humans. The development of the heart is highly conserved across all vertebrate species, making animal models an excellent option for screening potential cardiac teratogens. This review will discuss exposures known to cause ...

  6. Cardiac hybrid imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gaemperli, Oliver [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); University Hospital Zurich, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Kaufmann, Philipp A. [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2014-05-15

    Hybrid cardiac single photon emission computed tomography (SPECT)/CT imaging allows combined assessment of anatomical and functional aspects of cardiac disease. In coronary artery disease (CAD), hybrid SPECT/CT imaging allows detection of coronary artery stenosis and myocardial perfusion abnormalities. The clinical value of hybrid imaging has been documented in several subsets of patients. In selected groups of patients, hybrid imaging improves the diagnostic accuracy to detect CAD compared to the single imaging techniques. Additionally, this approach facilitates functional interrogation of coronary stenoses and guidance with regard to revascularization procedures. Moreover, the anatomical information obtained from CT coronary angiography or coronary artery calcium scores (CACS) adds prognostic information over perfusion data from SPECT. The use of cardiac hybrid imaging has been favoured by the dissemination of dedicated hybrid systems and the release of dedicated image fusion software, which allow simple patient throughput for hybrid SPECT/CT studies. Further technological improvements such as more efficient detector technology to allow for low-radiation protocols, ultra-fast image acquisition and improved low-noise image reconstruction algorithms will be instrumental to further promote hybrid SPECT/CT in research and clinical practice. (orig.)

  7. Seismic attenuation in fractured media

    International Nuclear Information System (INIS)

    The prime objective of this paper is to quantitatively estimate seismic attenuation caused by fractures with different physical parameters. In seismic wave simulation, the fractured media are treated as the anisotropic media and fractures are represented by frequency-dependent elastic constants. Based on numerical experiments with three different parameters, namely viscosity, porosity and the Lamé parameters, this paper has the following observations. First, seismic attenuation is not affected by the viscosity within fractures, although it increases with the increase of porosity and decreases with the increase of the Lamé parameters within fractures. Among the latter two parameters, seismic attenuation is more sensitive to the Lamé parameters than to the porosity. Second, for the attenuation anisotropy, low frequencies have more anisotropic effect than high frequencies. For example, a 50 Hz wavefield has the strongest anisotropy effect if compared to 100 and 150 Hz wavefields. The attenuation anisotropy for low frequency (say 50 Hz) is more sensitive to the viscosity than the porosity and the Lamé parameters have the weakest effect among these three parameters. These observations suggest that low-frequency seismic attenuation, and especially the attenuation anisotropy in low frequency, would have great potential for fluid discrimination within fractured media. (paper)

  8. Anomalous hydrocracking of triglycerides over CoMo-catalyst-influence of reaction intermediates

    Indian Academy of Sciences (India)

    M Anand; M G Sibi; D Verma; A K Sinha

    2014-03-01

    Reaction intermediates have been identified and followed to understand anomalous cracking of jathropha oil triglycerides in the presence of sulphided Co-Mo/Al2O3 catalyst. Undesirable C-C coupling reactions are favoured at temperatures between 320° and 340°C, giving waxy oligomerization products, whereas at temperatures above 340°C, direct hydrocracking of triglycerides to lighter and middle distillates were favoured. To minimize undesirable waxy oligomerization products, higher pressures (>80 bar) and higher H2/feed ratios (>1500) were necessary. Aldol condensation and ketonization reactions between the reaction intermediates are counter-productive as they result in waxy long chain oxygenated products which tend to accumulate on the catalyst surface, choke the reactor and cause rapid catalyst deactivation. Reaction conditions have to be optimized to minimize condensation reaction during this process.

  9. Optimization of conjugated linoleic acid triglycerides via enzymatic esterification in no-solvent system

    Institute of Scientific and Technical Information of China (English)

    YI Dan; SUN Xiuqin; LI Guangyou; LIU Fayi; LIN Xuezheng; SHEN Jihong

    2009-01-01

    We compared four esterifiable enzymes. The lipase Novozym 435 possessed the highest activity for the conjugated linoleic acid esterification during the synthesis of triglycerides. The triglycerides were synthesized by esterification of glycerol and conjugated linoleic acid (CLA) in a no-solvent system using lipase catalysis. We investigated the effects of temperature, enzyme concentration, water content, and time on esterification. Enzyme and water concentrations of up to 1% of the total reaction volume and a system temperature of 60°C proved optimal for esterification. Similarly, when the esterification was carried out for 24 h, the reaction ratio improved to 94.11%. The esterification rate of the rotating screen basket remained high (87.28%) when the enzyme was re-used for the 5th time. We evaluated the substrate selectivity of lipase (NOVO 435) and determined that this lipase prefers the 10,12-octadacadienoic acid to the 9,11-octadecadienoic acid.

  10. High plasma triglyceride levels strongly correlate with low kisspeptin in the arcuate nucleus of male rats

    DEFF Research Database (Denmark)

    Overgaard, A; Axel, A M; Lie, M E;

    2015-01-01

    signals to the GnRH neurons. METHODS: In this study, we measured body weight and plasma concentrations of leptin, insulin, testosterone, and triglycerides after high fat diet exposure and correlated these parameters with the number of kisspeptin-immunoreactive neurons in the arcuate nucleus of male rats....... In this model, a high fat diet (45% or 60% energy from fat, respectively) or a control diet (10% energy from fat) was provided after weaning for three months. RESULTS: We find a significant increase in body weight and plasma leptin concentration, but no change in the number of kisspeptin......-immunoreactive cells with increased fat in the diet. Kisspeptin-immunoreactive cells are not correlated with body weight, testosterone, leptin or insulin. However, we find that the number of kisspeptin-immunoreactive cells is strongly and negatively correlated with the level of plasma triglycerides (R2=0.49, p=0...

  11. Indeterminacy of Spatiotemporal Cardiac Alternans

    CERN Document Server

    Zhao, Xiaopeng

    2007-01-01

    Cardiac alternans, a beat-to-beat alternation in action potential duration (at the cellular level) or in ECG morphology (at the whole heart level), is a marker of ventricular fibrillation, a fatal heart rhythm that kills hundreds of thousands of people in the US each year. Investigating cardiac alternans may lead to a better understanding of the mechanisms of cardiac arrhythmias and eventually better algorithms for the prediction and prevention of such dreadful diseases. In paced cardiac tissue, alternans develops under increasingly shorter pacing period. Existing experimental and theoretical studies adopt the assumption that alternans in homogeneous cardiac tissue is exclusively determined by the pacing period. In contrast, we find that, when calcium-driven alternans develops in cardiac fibers, it may take different spatiotemporal patterns depending on the pacing history. Because there coexist multiple alternans solutions for a given pacing period, the alternans pattern on a fiber becomes unpredictable. Usin...

  12. An overview of cardiac morphogenesis.

    Science.gov (United States)

    Schleich, Jean-Marc; Abdulla, Tariq; Summers, Ron; Houyel, Lucile

    2013-11-01

    Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In this article we review the different steps of heart development, focusing on the processes of alignment and septation. We also show, as often as possible, the links between abnormalities of cardiac development and the main congenital heart defects. The development of animal models has permitted the unraveling of many mechanisms that potentially lead to cardiac malformations. A next step towards a better knowledge of cardiac development could be multiscale cardiac modelling. PMID:24138816

  13. Clinical significance of serum triglyceride elevation at early stage of acute biliary pancreatitis

    OpenAIRE

    Cheng, Long; Luo, Zhulin; Xiang, Ke; Ren, Jiandong; Huang, Zhu; Tang, Lijun; Tian, Fuzhou

    2015-01-01

    Background Pancreatitis induced by hypertriglyceridemia (HTG) has gained much attention. However, very limited numbers of studies have focused on the clinical significance of TG elevation in non-HTG induced pancreatitis, such as acute biliary pancreatitis (ABP). This study aimed to study the clinical significances of triglyceride (TG) elevation in patients with ABP. Methods We retrospectively analyzed a total of 426 ABP cases in our research center. According to the highest TG level within 72...

  14. Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats

    Directory of Open Access Journals (Sweden)

    Lee M. Margolis

    2016-09-01

    Full Text Available The purpose of this investigation was to assess the influence of calorie restriction (CR alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL, and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL or CR (40% restriction, adequate (10%, or high (32% protein (PRO milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g−1 lower (p < 0.05 in CR and 32% PRO compared to AL and 10% PRO, respectively. Gene expression of fatty acid synthase (FASN, stearoyl-CoA destaurase-1 (SCD1 and pyruvate dehydrogenase kinase, isozyme 4 (PDK4 were 45% ± 1%, 23% ± 1%, and 57% ± 1% lower (p < 0.05, respectively, in CR than AL, regardless of protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p < 0.05 in 32% PRO compared to 10% PRO, independent of calorie intake. Results from this investigation provide evidence that the metabolic health benefits associated with CR—specifically reduction in intrahepatic triglyceride content—may be enhanced by consuming a higher-protein/lower-carbohydrate diet.

  15. Adipose Triglyceride Lipase Deficiency Causes Tissue-specific Changes in Insulin Signaling*

    OpenAIRE

    Kienesberger, Petra C.; Lee, Daeho; Pulinilkunnil, Thomas; Brenner, Daniel S.; Cai, Lingzhi; Magnes, Christoph; Koefeler, Harald C.; Streith, Ingo E.; Rechberger, Gerald N.; Haemmerle, Guenter; Flier, Jeffrey S.; Zechner, Rudolf; Kim, Young-Bum; Kershaw, Erin E.

    2009-01-01

    Triacylglycerol accumulation in insulin target tissues is associated with insulin resistance. Paradoxically, mice with global targeted deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme in triacylglycerol hydrolysis, display improved glucose tolerance and insulin sensitivity despite triacylglycerol accumulation in multiple tissues. To determine the molecular mechanisms for this phenotype, ATGL-deficient (ATGL−/−) and wild-type mice were injected with saline or insulin (1...

  16. Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Boerwinkle, E. (Univ. of Texas Health Science Center, Houston, TX (United States)); Brown, S.; Patsch, W. (Methodist Hospital and Baylor College of Medicine, Houston, TX (United States)); Sharrett, A.R. (National Heart, Lung, and Blood Institute, Bethesda, MD (United States)); Heiss, G. (Univ. of North Carolina, Chapel Hill, NC (United States))

    1994-02-01

    To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, the authors have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of postprandial response in plasma was monitored over 8 h by triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B-100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was determined by DNA amplification and digestion. The frequency of the apo E alleles and their effects on fasting lipid levels in this sample with vitamin A was significantly different among apo E genotypes, with delayed clearance in individuals with an [var epsilon]2 allele, compared with [var epsilon]3/3 and [var epsilon]3/4 individuals. In the sample of 397 Caucasians, average retinyl palmitate response was 1,489 [mu]g/dl in [var epsilon]2/3 individuals, compared with 1,037 [mu]g/dl in [var epsilon]3/3 individuals and 1,108 [mu]g/dl in [var epsilon]3/4 individuals. The apo E polymorphism accounted for 7.1% of the interindividual variation in postprandial retinyl palmitate response, a contribution proportionally greater than its well-known effect on fasting LDL-cholesterol. However, despite this effect on postprandial retinyl palmitate, the profile of postprandial triglyceride response was not significantly different among apo E genotypes. The profile of postprandial response was consistent between the sample of Caucasians and a smaller sample of black subjects. While these data indicate that the removal of remnant particles from circulation is delayed in subjects with the [var epsilon]2/3 genotype, there is no reported evidence that the [var epsilon]2 allele predisposes to coronary artery disease (CAD). 82 refs., 6 figs., 4 tabs.

  17. Polymorphisms, de novo lipogenesis, and plasma triglyceride response following fish oil supplementation

    OpenAIRE

    Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

    2013-01-01

    Interindividual variability in the response of plasma triglyceride concentrations (TG) following fish oil consumption has been observed. Our objective was to examine the associations between single-nucleotide polymorphisms (SNPs) within genes encoding proteins involved in de novo lipogenesis and the relative change in plasma TG levels following a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a six-week f...

  18. Fractionation of human serum lipoproteins and simultaneous enzymatic determination of cholesterol and triglycerides

    Energy Technology Data Exchange (ETDEWEB)

    Qureshi, Rashid Nazir [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands); Kok, Wim Th., E-mail: W.Th.Kok@uva.nl [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands); Schoenmakers, Peter J. [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands)

    2009-11-03

    A method based on Asymmetric Flow Field-Flow Fractionation (AF4) was developed to separate different types of lipoproteins from human serum. The emphasis in the method optimization was on the possibilities to characterize the largest lipoprotein fractions (LDL and VLDL), which is usually not possible with the size-exclusion chromatography methods applied in routine analysis. Different channel geometries and flow programs were tested and compared. The use of a short fractionation channel was shown to give less sample dilution at the same fractionation power compared to a conventional, long channel. Different size selectivities were obtained with an exponential decay and a linear cross flow program. The ratio of the UV absorption signal to the light scattering signal was used to validate the relation between retention time and size of the fractionated particles. An experimental setup was developed for the simultaneous determination of the cholesterol and triglycerides distribution over the lipoprotein fractions, based on enzymatic reactions followed by UV detection at 500 nm. Coiled and knitted PTFE tubing reactors were compared. An improved peak sharpness and sensitivity were observed with the knitted tubing reactor. After optimization of the experimental conditions a satisfactory linearity and precision (2-3% rsd for cholesterol and 5-6% rsd for triglycerides) were obtained. Finally, serum samples, a pooled sample from healthy volunteers and samples of sepsis patients, were analyzed with the method developed. Lipoprotein fractionation and cholesterol and triglyceride distributions could be correlated with the clinical background of the samples.

  19. Fluoxetine Decreased Serum Total Cholesterol and Triglyceride Levels in a Hypercholesterolemic Patient with Postpartum Depression

    Directory of Open Access Journals (Sweden)

    Hossein Khalili

    2006-05-01

    Full Text Available Objective: To report the case of a 28-year old hypercholesterolemic female with postpartum depression, whose triglyceride (TG and total cholesterol (TC levels decreased while being treated with fluoxetine. Method: A 28-year old female, with a diagnosis of major depressive disorder with postpartum onset based on DSM-IV criteria, was hospitalized at a mental health hospital. Her past history included another episode of depression 4 months after giving birth to her second child, which was 12 years prior to her recent episode. Her serum total cholestrol and triglyceride levels were measured prior to the initiation of medication. Then fluoxetine was initiated at a daily dose of 20 mg and had been increased to 40 mg per day at the time of discharge. The lipid profile measurements was repeated at week 4 and 8 following treatment. Results: Total cholesterol level was reduced from 242 mg/dL at baseline to 224 mg/dL at week 4 and to 202 mg/dL at week 8; triglyceride level was decreased from 516 mg/dL to 448 mg/dL at week 4 and to 404 mg/dL at week 8. Conclusions: Fluoxetine may be an appropriate treatment for hyperlipidemic women with postpartum depression..

  20. Deranged aortic intima-media thickness, plasma triglycerides and granulopoiesis in Sl/Sld mice

    Directory of Open Access Journals (Sweden)

    Kottarappat N. Dileepan

    2004-01-01

    Full Text Available STUDIES were carried out to evaluate the impact of a high-fat dietary regimen on aortic wall thickness, peripheral blood leukocyte profile, and plasma cholesterol and triglyceride levels in the mast cell-deficient Sl/Sld mouse. The results demonstrated that the mean aortic wall thickness of Sl/Sld mice was significantly higher than their normal littermates, and were increased in both genotypes after a 17-day high-fat regimen. In comparison with normal littermates, Sl/Sld genotypes had elevated levels of plasma triglycerides with normal levels of plasma cholesterol, and the high-fat diet markedly lowered the triglyceride levels. Total peripheral blood leukocytes, the monocyte and granulocyte counts, and hemoglobin levels were significantly lower in Sl/Sld mice, although the number of lymphocytes, eosinophils and basophils were the same in both genotypes. Interestingly, the high-fat diet regimen elevated leukocyte counts and the number of monocytes and granulocytes in Sl/Sld mice.

  1. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment.

    Science.gov (United States)

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-06-15

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf-GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD2 by RNA interference induced an increase in the amount of ATGL existing in LDs and decreased the total cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but palmitoylation was required only for distribution to LDs. An ELMOD2 mutant deficient in palmitoylation failed to reconstitute the ATGL transport after the ELMOD2 knockdown, indicating that distribution in LDs is indispensable to the functionality of ELMOD2. These results indicate that ELMOD2 regulates ATGL transport and cellular lipid metabolism by modulating the Arf1-COPI activity in LDs.

  2. Effect of cholesterol and triglycerides levels on the rheological behavior of human blood

    Science.gov (United States)

    Moreno, Leonardo; Calderas, Fausto; Sanchez-Olivares, Guadalupe; Medina-Torres, Luis; Sanchez-Solis, Antonio; Manero, Octavio

    2015-02-01

    Important public health problems worldwide such as obesity, diabetes, hyperlipidemia and coronary diseases are quite common. These problems arise from numerous factors, such as hyper-caloric diets, sedentary habits and other epigenetic factors. With respect to Mexico, the population reference values of total cholesterol in plasma are around 200 mg/dL. However, a large proportion has higher levels than this reference value. In this work, we analyze the rheological properties of human blood obtained from 20 donors, as a function of cholesterol and triglyceride levels, upon a protocol previously approved by the health authorities. Samples with high and low cholesterol and triglyceride levels were selected and analyzed by simple-continuous and linear-oscillatory shear flow. Rheometric properties were measured and related to the structure and composition of human blood. In addition, rheometric data were modeled by using several constitutive equations: Bautista-Manero-Puig (BMP) and the multimodal Maxwell equations to predict the flow behavior of human blood. Finally, a comparison was made among various models, namely, the BMP, Carreau and Quemada equations for simple shear rate flow. An important relationship was found between cholesterol, triglycerides and the structure of human blood. Results show that blood with high cholesterol levels (400 mg/dL) has flow properties fully different (higher viscosity and a more pseudo-plastic behavior) than blood with lower levels of cholesterol (tendency to Newtonian behavior or viscosity plateau at low shear rates).

  3. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment.

    Science.gov (United States)

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-06-15

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf-GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD2 by RNA interference induced an increase in the amount of ATGL existing in LDs and decreased the total cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but palmitoylation was required only for distribution to LDs. An ELMOD2 mutant deficient in palmitoylation failed to reconstitute the ATGL transport after the ELMOD2 knockdown, indicating that distribution in LDs is indispensable to the functionality of ELMOD2. These results indicate that ELMOD2 regulates ATGL transport and cellular lipid metabolism by modulating the Arf1-COPI activity in LDs. PMID:25904333

  4. [Absorption of medium chain triglycerides in patients with blind loop syndrome].

    Science.gov (United States)

    Pereira Filho, R A; Sevá-Pereira, A; de Magalhães, A F

    1988-01-01

    Absorption of medium chain triglycerides (MCT) was estimated in 10 patients with stagnant loop syndrome (SLS). Six patients had steatorrhea due to gastrojejunal anastomosis and 4 due to diabetic neuropathy. The diagnosis of SLS was confirmed by antibiotic therapeutic test after exclusion of other causes of malabsorption syndrome. Each patient was submitted to 2 types of diet during one week each, differing only in the type of added lipid. In the diet with long chain triglycerides (LCT), soy oil and butter were added. In the diet, with medium chain triglycerides, only MCT oil from babaçu was added. The excretion of lipid was determined in the feces in the last 3 days of each diet. The results showed that the medium fecal lipid excretion was 48.6 (sd = 19.8) g/d in the LCT diet and 26.6 (sd = 13.8) g/d in the MCT [d = 22.0; s(d) = 3.10; t = 7.10; p less than 0.001], which indicates that in patients with SLS, MCT diet was better absorbed than LCT diet. It is suggested that MCT oil may be used as a caloric source during nutritional recovery in SLS.

  5. Programs of Active Aging – A Relation between BMI and Triglycerides

    Directory of Open Access Journals (Sweden)

    Samuel Honório

    2014-03-01

    Full Text Available Objective: To enhance the importance of physical activity programs for elderly and their influence on BMI and triglycerides. Methods: The sample consisted of 91 elderly individuals, 63 females and 28 males aged between 65 and 78 years of age. All seniors practice water activities, including swimming and gymnastics. Were analyzed with respect to two aspects: BMI, Triglycerides and practice time, seniors who were physically active at least 2 months, and seniors who maintained habits of physical activity between 2 and 6 months and still accumulated 30 or more minutes of other activities. We have established contingency tables were confronted where the variables described in the analysis. Results: It was found that elderly who maintained physical activity programs were broader outnumbered those who were overweight and obesity rates in Table I of BMI, and lower triglycerides values. Conclusions: We concluded therefore that physical activity programs that contemplate 2 or more hours per week, duly organized and systematized constitute a positive factor in combating inactivity and turn into a more active and cheerful elderly.

  6. Adipose triglyceride lipase regulates lipid metabolism in dairy goat mammary epithelial cells.

    Science.gov (United States)

    Li, Jun; Luo, Jun; Wang, Hui; Shi, Hengbo; Zhu, Jiangjiang; Sun, Yuting; Yu, Kang; Yao, Dawei

    2015-01-01

    Adipose triglyceride lipase (ATGL) catalyzes the initial step in the lipid lipolysis process, hydrolyzing triglyceride (TG) to produce diacylglycerol (DG) and free fatty acids (FFA). In addition, ATGL regulates lipid storage and release in adipocyte cells. However, its role in mammary gland tissue remains unclear. To assess the role of the ATGL gene in the goat mammary gland, this study analyzed the tissue distribution and expression of key genes together with lipid accumulation after knockdown of the ATGL gene. The mRNA of ATGL was highly expressed in subcutaneous adipose tissue, the lung and the mammary gland with a significant increase in expression during the lactation period compared with the dry period of the mammary gland. Knockdown of the ATGL gene in goat mammary epithelial cells (GMECs) using siRNA resulted in a significant decrease in both ATGL mRNA and protein levels. Silencing of the ATGL gene markedly increased lipid droplet accumulation and intracellular TG concentration (Pfat formation and secretion was down-regulated (PCD36 for fatty acid uptake (P<0.05). In conclusion, these data suggest that the ATGL gene plays an important role in triglyceride lipolysis in GMECs and provides the first experimental evidence that ATGL may be involved in lipid metabolism during lactation. PMID:25307872

  7. FSP27 promotes lipid droplet clustering and then fusion to regulate triglyceride accumulation.

    Directory of Open Access Journals (Sweden)

    Srikarthika Jambunathan

    Full Text Available Fat Specific Protein 27 (FSP27, a lipid droplet (LD associated protein in adipocytes, regulates triglyceride (TG storage. In the present study we demonstrate that FSP27 plays a key role in LD morphology to accumulate TGs. We show here that FSP27 promotes clustering of the LDs which is followed by their fusion into fewer and enlarged droplets. To map the domains of FSP27 responsible for these events, we generated GFP-fusion constructs of deletion mutants of FSP27. Microscopic analysis revealed that amino acids 173-220 of FSP27 are necessary and sufficient for both the targeting of FSP27 to LDs and the initial clustering of the droplets. Amino acids 120-140 are essential but not sufficient for LD enlargement, whereas amino acids 120-210 are necessary and sufficient for both clustering and fusion of LDs to form enlarged droplets. In addition, we found that FSP27-mediated enlargement of LDs, but not their clustering, is associated with triglyceride accumulation. These results suggest a model in which FSP27 facilitates LD clustering and then promotes their fusion to form enlarged droplets in two discrete, sequential steps, and a subsequent triglyceride accumulation.

  8. Sudden Cardiac Death in Athletes.

    Science.gov (United States)

    Wasfy, Meagan M; Hutter, Adolph M; Weiner, Rory B

    2016-01-01

    There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed. PMID:27486488

  9. Current Roles and Future Applications of Cardiac CT: Risk Stratification of Coronary Artery Disease

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Yeonyee Elizabeth [Department of Cardiology, Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of); Lim, Tae-Hwan [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of)

    2014-07-01

    Cardiac computed tomography (CT) has emerged as a noninvasive modality for the assessment of coronary artery disease (CAD), and has been rapidly integrated into clinical cares. CT has changed the traditional risk stratification based on clinical risk to image-based identification of patient risk. Cardiac CT, including coronary artery calcium score and coronary CT angiography, can provide prognostic information and is expected to improve risk stratification of CAD. Currently used conventional cardiac CT, provides accurate anatomic information but not functional significance of CAD, and it may not be sufficient to guide treatments such as revascularization. Recently, myocardial CT perfusion imaging, intracoronary luminal attenuation gradient, and CT-derived computed fractional flow reserve were developed to combine anatomical and functional data. Although at present, the diagnostic and prognostic value of these novel technologies needs to be evaluated further, it is expected that all-in-one cardiac CT can guide treatment and improve patient outcomes in the near future.

  10. Current Roles and Future Applications of Cardiac CT: Risk Stratification of Coronary Artery Disease

    International Nuclear Information System (INIS)

    Cardiac computed tomography (CT) has emerged as a noninvasive modality for the assessment of coronary artery disease (CAD), and has been rapidly integrated into clinical cares. CT has changed the traditional risk stratification based on clinical risk to image-based identification of patient risk. Cardiac CT, including coronary artery calcium score and coronary CT angiography, can provide prognostic information and is expected to improve risk stratification of CAD. Currently used conventional cardiac CT, provides accurate anatomic information but not functional significance of CAD, and it may not be sufficient to guide treatments such as revascularization. Recently, myocardial CT perfusion imaging, intracoronary luminal attenuation gradient, and CT-derived computed fractional flow reserve were developed to combine anatomical and functional data. Although at present, the diagnostic and prognostic value of these novel technologies needs to be evaluated further, it is expected that all-in-one cardiac CT can guide treatment and improve patient outcomes in the near future

  11. Comparison of the effects of enteral feeding with continuous and intermittent parenteral nutrition on hepatic triglyceride secretion in human beings

    International Nuclear Information System (INIS)

    Plasma triglyceride turnover was measured during steady-state conditions in 22 postoperative patients. Nine had received nutritional support with an enteral regimen, seven had received an equivalent regimen as continuous parenteral nutrition, and six received the same parenteral regimen as a cyclical infusion. After 5 days of nutritional support, each patient received an intravenous bolus of tritiated glycerol. Plasma radiolabeled triglyceride content was measured during the subsequent 24 hours. The data were analyzed by means of a simple deterministic model of plasma triglyceride kinetics and compared with the results obtained by stochastic analysis. The rates of hepatic triglyceride secretion obtained by deterministic analysis were higher than those obtained by the stochastic approach. However, the mode of delivery of the nutritional regimen did not affect the rate of hepatic triglyceride secretion regardless of the method of analysis. The results suggest that neither complete nutritional bypass of the gastrointestinal tract nor interruption of parenteral nutrition in an attempt to mimic normal eating has any effect on hepatic triglyceride secretion. Any beneficial effect that enteral feeding or cyclical parenteral nutrition may have on liver dysfunction associated with standard parenteral nutrition appears to be unrelated to changes in hepatic triglyceride secretion

  12. Case Report: Penetrating Cardiac Injury

    Directory of Open Access Journals (Sweden)

    Adem Grbolar

    2013-10-01

    Full Text Available Summary: Penetrating cardiac injurys caused by gunshots and penetrating tools have high mortality rates. The way of injury, how the cardiac area is effected and the presence of cardiac tamponadecauses mortality in different rates. However the better treatment quality of hospitals, increasingoperative techniques, and internel care unit quality has not been change during the years. Searching the literature, we want to present a 42 years old male patient whowas injured by knife and had a 1 cm skin wound on chest with cardiac tamponade. After sternotomy a 7 cm laseration was observed in heart. Cardioraphy was performed.

  13. Cardiac Insulin Resistance and MicroRNA Modulators

    Directory of Open Access Journals (Sweden)

    Lakshmi Pulakat

    2012-01-01

    Full Text Available Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS, and this disorder may be accentuated by chronic alcohol consumption. In conditions of over-nutrition, increased insulin (INS and angiotensin II (Ang II activate mammalian target for rapamycin (mTOR/p70 S6 kinase (S6K1 signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activation of mTOR/S6K1 induces cardiac INS resistance via serine phosphorylation of INS receptor substrates (IRS-1/2, it also renders cardioprotection via increased Ang II receptor 2 (AT2R upregulation and adaptive hypertrophy. In the INS-resistant and hyperinsulinemic Zucker obese (ZO rat, a rodent model for CRS, activation of mTOR/S6K1signaling in cardiac tissue is regulated by protective feed-back mechanisms involving mTOR↔AT2R signaling loop and profile changes of microRNA that target S6K1. Such regulation may play a role in attenuating progressive heart failure. Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy.

  14. Baroreceptor activation attenuates attentional effects on pain-evoked potentials.

    Science.gov (United States)

    Gray, Marcus A; Minati, Ludovico; Paoletti, Giulia; Critchley, Hugo D

    2010-12-01

    Focused attention typically enhances neural nociceptive responses, reflected electroencephalographically as increased amplitude of pain-evoked event-related potentials (ERPs). Additionally, pain-evoked ERPs are attenuated by hypertension and baroreceptor activity, through as yet unclear mechanisms. There is indirect evidence that these two effects may interact, suggesting that baroreceptor-related modulation of nociception is more than a low-level gating phenomenon. To address this hypothesis, we explored in a group of healthy participants the combined effects of cue-induced expectancy and baroreceptor activity on the amplitude of pain-evoked ERPs. Brief nociceptive skin stimuli were delivered during a simple visual task; half were preceded by a visual forewarning cue, and half were unpredictable. Nociceptive stimuli were timed to coincide either with systole (maximum activation of cardiac baroreceptors) or with diastole (minimum baroreceptor activation). We observed a strong interaction between expectancy and cardiac timing for the amplitude of the P2 ERP component; no effects were observed for the N2 component. Cued stimuli were associated with larger P2 amplitude, but this effect was abolished for stimuli presented during baroreceptor activation. No cardiac timing effect was observed for un-cued stimuli. Taken together, these findings suggest a close integration of cognitive-affective aspects of expectancy and baroreceptor influences on pain, and as such may cast further light on mechanisms underlying mental and physiological contributions to clinical pain.

  15. Milk production, peripartal liver triglyceride concentration and plasma metabolites of dairy cows fed diets supplemented with calcium soaps or hydrogenated triglycerides of palm oil.

    Science.gov (United States)

    Karcagi, Roland G; Gaál, Tibor; Ribiczey, Piroska; Huszenicza, Gyula; Husvéth, Ferenc

    2010-05-01

    The aim of the study was to test the effect of rumen-inert fat supplements of different chemical forms or containing different unsaturated/saturated (U/S) fatty acid contents on milk production, milk composition and liver and blood metabolic variables of high-yielding dairy cows in the peripartal period. Thirty Holstein-Friesian dairy cows were divided into three equal groups and fed a corn silage-based diet, without fat supplementation (control) or supplemented with 11.75 MJ NEl per day of calcium soaps of palm oil fatty acids (CAS; U/S=61/39) or with 11.75 MJ NEl per day of hydrogenated palm oil triglyceride (HTG; U/S=6/94). Each diet was fed from 25+/-2 d prior to the expected calving to 100+/-5 d post partum. Compared with the control, both CAS and HTG supplementation resulted in an increase of the average milk yield. Milk fat content and fat-corrected milk yield were higher in the HTG group but lower in the CAS group than in the control group. In all groups liver triglyceride concentrations (TGL) increased from 15 d prepartum to 5 d post partum, and then decreased thereafter. At 5 d TGL was lower in the HTG group than control or CAS cows. No significant differences were detected in TGL among dietary treatments at 15 d prepartum and 25 d post partum. Higher plasma glucose and insulin and lower non-esterified fatty acids and beta-hydroxybutyrate concentrations and aspartate aminotransferase activity were measured in the HTG group than in the control or CAS groups at 5 d or 25 d post partum. Our results show that HTG may provide a better energy supply for high-yielding dairy cows in negative energy balance than CAS around calving.

  16. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review.

    Directory of Open Access Journals (Sweden)

    Marnie L Elizaga

    Full Text Available BACKGROUND: Vaccinia-associated myo/pericarditis was observed during the US smallpox vaccination (DryVax campaign initiated in 2002. A highly-attenuated vaccinia strain, modified vaccinia Ankara (MVA has been evaluated in clinical trials as a safer alternative to DryVax and as a vector for recombinant vaccines. Due to the lack of prospectively collected cardiac safety data, the US Food and Drug Administration required cardiac screening and surveillance in all clinical trials of MVA since 2004. Here, we report cardiac safety surveillance from 6 phase I trials of MVA vaccines. METHODS: Four clinical research organizations contributed cardiac safety data using common surveillance methods in trials administering MVA or recombinant MVA vaccines to healthy participants. 'Routine cardiac investigations' (ECGs and cardiac enzymes obtained 2 weeks after injections of MVA or MVA-HIV recombinants, or placebo-controls, and 'Symptom-driven cardiac investigations' are reported. The outcome measure is the number of participants who met the CDC-case definition for vaccinia-related myo/pericarditis or who experienced cardiac adverse events from an MVA vaccine. RESULTS: Four hundred twenty-five study participants had post-vaccination safety data analyzed, 382 received at least one MVA-containing vaccine and 43 received placebo; 717 routine ECGs and 930 cardiac troponin assays were performed. Forty-five MVA recipients (12% had additional cardiac testing performed; 22 for cardiac symptoms, 19 for ECG/laboratory changes, and 4 for cardiac symptoms with an ECG/laboratory change. No participant had evidence of symptomatic or asymptomatic myo/pericarditis meeting the CDC-case definition and judged to be related to an MVA vaccine. CONCLUSIONS: Prospective surveillance of MVA recipients for myo/pericarditis did not detect cardiac adverse reactions in 382 study participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT00082446 NCT003766090 NCT00252148 NCT00083603

  17. Ubiquitin-Specific Protease 4 Is an Endogenous Negative Regulator of Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    He, Ben; Zhao, Yi-Chao; Gao, Ling-Chen; Ying, Xiao-Ying; Xu, Long-Wei; Su, Yuan-Yuan; Ji, Qing-Qi; Lin, Nan; Pu, Jun

    2016-06-01

    Dysregulation of the ubiquitin proteasome system components ubiquitin ligases and proteasome plays an important role in the pathogenesis of cardiac hypertrophy. However, little is known about the role of another ubiquitin proteasome system component, the deubiquitinating enzymes, in cardiac hypertrophy. Here, we revealed a crucial role of ubiquitin specific protease 4 (USP4), a deubiquitinating enzyme prominently expressed in the heart, in attenuating pathological cardiac hypertrophy and dysfunction. USP4 levels were consistently decreased in human failing hearts and in murine hypertrophied hearts. Adenovirus-mediated gain- and loss-of-function approaches indicated that deficiency of endogenous USP4 promoted myocyte hypertrophy induced by angiotensin II in vitro, whereas restoration of USP4 significantly attenuated the prohypertrophic effect of angiotensin II. To corroborate the role of USP4 in vivo, we generated USP4 global knockout mice and mice with cardiac-specific overexpression of USP4. Consistent with the in vitro study, USP4 depletion exacerbated the hypertrophic phenotype and cardiac dysfunction in mice subjected to pressure overload, whereas USP4 transgenic mice presented ameliorated pathological cardiac hypertrophy compared with their control littermates. Molecular analysis revealed that USP4 deficiency augmented the activation of the transforming growth factor β-activated kinase 1 (TAK1)-(JNK1/2)/P38 signaling in response to hypertrophic stress, and blockage of TAK1 activation abolished the pathological effects of USP4 deficiency in vivo. These findings provide the first evidence for the involvement of USP4 in cardiac hypertrophy, and shed light on the therapeutic potential of targeting USP4 in the treatment of cardiac hypertrophy.

  18. Sustained cardiac remodeling after a short-term very low calorie diet in type 2 diabetes mellitus patients.

    Science.gov (United States)

    Jonker, Jacqueline T; Snel, Marieke; Hammer, Sebastiaan; Jazet, Ingrid M; van der Meer, Rutger W; Pijl, Hanno; Meinders, A Edo; de Roos, Albert; Smit, Johannes W A; Romijn, Johannes A; Lamb, Hildo J

    2014-01-01

    A very low calorie diet (VLCD) results in cardiac remodeling and improved diastolic function. It is unknown how long these effects sustain after reintroduction of a regular diet. We aimed to assess the long-term effects of initial weight loss by VLCD on cardiac dimensions and function in type 2 diabetes mellitus (T2DM) patients. Fourteen insulin-dependent T2DM patients (mean ± SEM: age 53 ± 2 years; BMI 35 ± 1 kg/m(2)) were treated by a VLCD (450 kcal/day) during 16 weeks. Cardiac function and myocardial triglyceride (TG) content were measured by magnetic resonance imaging and spectroscopy at baseline, after a 16-week VLCD and after 14 months of follow-up on a regular diet. BMI decreased from 35 ± 1 to 28 ± 1 kg/m(2) after VLCD and increased again to 32 ± 1 kg/m(2) at 18 months (both P diet.

  19. Antifibrinolytics in cardiac surgery

    Directory of Open Access Journals (Sweden)

    Achal Dhir

    2013-01-01

    Full Text Available Cardiac surgery exerts a significant strain on the blood bank services and is a model example in which a multi-modal blood-conservation strategy is recommended. Significant bleeding during cardiac surgery, enough to cause re-exploration and/or blood transfusion, increases morbidity and mortality. Hyper-fibrinolysis is one of the important contributors to increased bleeding. This knowledge has led to the use of anti-fibrinolytic agents especially in procedures performed under cardiopulmonary bypass. Nothing has been more controversial in recent times than the aprotinin controversy. Since the withdrawal of aprotinin from the world market, the choice of antifibrinolytic agents has been limited to lysine analogues either tranexamic acid (TA or epsilon amino caproic acid (EACA. While proponents of aprotinin still argue against its non-availability. Health Canada has approved its use, albeit under very strict regulations. Antifibrinolytic agents are not without side effects and act like double-edged swords, the stronger the anti-fibrinolytic activity, the more serious the side effects. Aprotinin is the strongest in reducing blood loss, blood transfusion, and possibly, return to the operating room after cardiac surgery. EACA is the least effective, while TA is somewhere in between. Additionally, aprotinin has been implicated in increased mortality and maximum side effects. TA has been shown to increase seizure activity, whereas, EACA seems to have the least side effects. Apparently, these agents do not differentiate between pathological and physiological fibrinolysis and prevent all forms of fibrinolysis leading to possible thrombotic side effects. It would seem prudent to select the right agent knowing its risk-benefit profile for a given patient, under the given circumstances.

  20. Age dependency of myocardial triglyceride content. A 3T high-field {sup 1}H-MR spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Petritsch, B.; Gassenmaier, T.; Kunz, A.S.; Donhauser, J.; Bley, T.A.; Horn, M. [University Hospital of Wuerzburg (Germany). Inst. of Diagnostic and Interventional Radiology; Goltz, J.P. [University Hospital of Schleswig-Holstein, Campus Luebeck (Germany). Clinic for Radiology and Nuclear Medicine

    2015-11-15

    The role of myocardial triglyceride (mTG) content in the aging human heart is not entirely understood. The aim of this study was to measure concentrations of mTG content from healthy volunteers and to determine the association between age, mTG content and systolic heart function. Furthermore, the technical stability of the {sup 1}H-magnetic resonance spectroscopy ({sup 1}H-MRS) and the reliability of peak evaluation at 3 T were evaluated. The total study population of 47 healthy volunteers was divided into 4 age classes, according to the age of the subjects (1{sup st} cohort 20-29 years (yrs.), n=20; 2{sup nd} cohort 30-39 yrs., n=10; 3{sup rd} cohort 40-49 yrs., n=9; 4{sup th} cohort 50-60 yrs., n=8). Cardiac MRI and double triggered {sup 1}H-MRS of the myocardium were consecutively performed using a 3 T scanner. Each participant underwent spectroscopic measurements twice in the same investigation. mTG content increases with age. The correlation of age and mTG is minimal (r=0.48; p<0.001). The following age-averaged mTG content values expressed as % of mTG signal compared to the water signal were determined for each cohort: 1{sup st} cohort 0.25 % (± 0.17); 2{sup nd} cohort 0.48 % (± 0.30); 3{sup rd} cohort 0.48 % (± 0.18); 4{sup th} cohort 0.77 % (± 0.70). There was no significant correlation (r=0.04; p=n.s.) between LV mass and mTG content in healthy volunteers. Within our cohorts, no effects of age or mTG content on systolic heart function were seen (r=-0.01; p=n.s.). The intraclass correlation coefficient of spectroscopic measurements was high (r=0.965; p<0.001). Myocardial TG content increases with age. The normal age-dependent concentration ranges of myocardial lipid metabolites reported in this study may be helpful for the correction of acquired {sup 1}H-MRS data in patients when evaluating metabolic and cardiovascular diseases in future magnetic resonance spectroscopy studies.

  1. Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

    OpenAIRE

    Zannad, Faiez; De Ferrari, Gaetano M.; Tuinenburg, Anton E.; Wright, David; Brugada, Josep; Butter, Christian; Klein, Helmut; Stolen, Craig; Meyer, Scott; Stein, Kenneth M.; Ramuzat, Agnes; Schubert, Bernd; Daum, Doug; Neuzil, Petr; Botman, Cornelis

    2014-01-01

    Aim The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy. Methods: Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or contro...

  2. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: chen919085@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)

    2015-09-01

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  3. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    International Nuclear Information System (INIS)

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  4. Cardiac arrest – cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Basri Lenjani

    2014-01-01

    Conclusions: All survivors from cardiac arrest have received appropriate medical assistance within 10 min from attack, which implies that if cardiac arrest occurs near an institution health care (with an opportunity to provide the emergent health care the rate of survival is higher.

  5. Leadership in cardiac surgery.

    Science.gov (United States)

    Rao, Christopher; Patel, Vanash; Ibrahim, Michael; Ahmed, Kamran; Wong, Kathie A; Darzi, Ara; von Segesser, Ludwig K; Athanasiou, Thanos

    2011-06-01

    Despite the efficacy of cardiac surgery, less invasive interventions with more uncertain long-term outcomes are increasingly challenging surgery as first-line treatment for several congenital, degenerative and ischemic cardiac diseases. The specialty must evolve if it is to ensure its future relevance. More importantly, it must evolve to ensure that future patients have access to treatments with proven long-term effectiveness. This cannot be achieved without dynamic leadership; however, our contention is that this is not enough. The demands of a modern surgical career and the importance of the task at hand are such that the serendipitous emergence of traditional charismatic leadership cannot be relied upon to deliver necessary change. We advocate systematic analysis and strategic leadership at a local, national and international level in four key areas: Clinical Care, Research, Education and Training, and Stakeholder Engagement. While we anticipate that exceptional individuals will continue to shape the future of our specialty, the creation of robust structures to deliver collective leadership in these key areas is of paramount importance. PMID:20884217

  6. Interventional cardiac catheterization.

    Science.gov (United States)

    Pihkala, J; Nykanen, D; Freedom, R M; Benson, L N

    1999-04-01

    Over the past decade, transcatheter interventions have become increasingly important in the treatment of patients with congenital heart lesions. These procedures may be broadly grouped as dilations (e.g., septostomy, valvuloplasty, angioplasty, and endovascular stenting) or as closures (e.g., vascular embolization and device closure of defects). Balloon valvuloplasty has become the treatment of choice for patients in all age groups with simple valvar pulmonic stenosis and, although not curative, seems at least comparable to surgery for congenital aortic stenosis in newborns to young adults. Balloon angioplasty is successfully applied to a wide range of aortic, pulmonary artery, and venous stenoses. Stents are useful in dilating lesions of which the intrinsic elasticity results in vessel recoil after balloon dilation alone. Catheter-delivered coils are used to embolize a wide range of arterial, venous, and prosthetic vascular connections. Although some devices remain investigational, they have been successfully used for closure of many arterial ducts and atrial and ventricular septal defects. In the therapy for patients with complex CHD, best results may be achieved by combining cardiac surgery with interventional catheterization. The cooperation among interventional cardiologists and cardiac surgeons was highlighted in a report of an algorithm to manage patients with tetralogy of Fallot or pulmonary atresia with diminutive pulmonary arteries, involving balloon dilation, coil embolization of collaterals, and intraoperative stent placement. In this setting, well-planned catheterization procedures have an important role in reducing the overall number of procedures that patients may require over a lifetime, with improved outcomes.

  7. Ictal Cardiac Ryhthym Abnormalities.

    Science.gov (United States)

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  8. Pneumothorax in cardiac pacing

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nohr, Ellen Aagaard;

    2012-01-01

    AIM: To identify risk factors for pneumothorax treated with a chest tube after cardiac pacing device implantation in a population-based cohort.METHODS AND RESULTS: A nationwide cohort study was performed based on data on 28 860 patients from the Danish Pacemaker Register, which included all Danish...... patients who received their first pacemaker (PM) or cardiac resynchronization device from 1997 to 2008. Multiple logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals for the association between risk factors and pneumothorax treated with a chest tube. The median...... age was 77 years (25th and 75th percentile: 69-84) and 55% were male (n = 15 785). A total of 190 patients (0.66%) were treated for pneumothorax, which was more often in women [aOR 1.9 (1.4-2.6)], and in patients with age >80 years [aOR 1.4 (1.0-1.9)], a prior history of chronic obstructive pulmonary...

  9. Dietary Supplementation with Docosahexaenoic Acid, but Not Eicosapentanoic Acid, Dramatically Alters Cardiac Mitochondrial Phospholipid Fatty Acid Composition and Prevents Permeability Transition

    OpenAIRE

    Khairallah, Ramzi J.; Sparagna, Genevieve C.; Khanna, Nishanth; O’Shea, Karen M.; Hecker, Peter A; Kristian, Tibor; Fiskum, Gary; Rosiers, Christine Des; Polster, Brian M.; Stanley, William C.

    2010-01-01

    Treatment with the ω-3 polyunsaturated fatty acids (PUFAs) docosahexanoic acid (DHA) and eicosapentanoic acid (EPA) exerts cardioprotective effects, and suppresses Ca2+-induced opening of the mitochondrial permeability transition pore (MPTP). These effects are associated with increased DHA and EPA, and lower arachidonic acid (ARA) in cardiac phospholipids. While clinical studies suggest the triglyceride lowering effects of DHA and EPA are equivalent, little is known about the independent effe...

  10. Triglyceride Blisters in Lipid Bilayers: Implications for Lipid Droplet Biogenesis and the Mobile Lipid Signal in Cancer Cell Membranes

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Duelund, Lars; Pakkanen, Kirsi Inkeri;

    2010-01-01

    Triglycerides have a limited solubility, around 3%, in phosphatidylcholine lipid bilayers. Using millisecond-scale course grained molecular dynamics simulations, we show that the model lipid bilayer can accommodate a higher concentration of triolein (TO) than earlier anticipated, by sequestering...

  11. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction

    DEFF Research Database (Denmark)

    Jørgensen, Anders Berg; Frikke-Schmidt, Ruth; West, Anders Sode;

    2012-01-01

    AimsElevated non-fasting triglycerides mark elevated levels of remnant cholesterol. Using a Mendelian randomization approach, we tested whether genetically increased remnant cholesterol in hypertriglyceridaemia due to genetic variation in the apolipoprotein A5 gene (APOA5) associates with an incr......AimsElevated non-fasting triglycerides mark elevated levels of remnant cholesterol. Using a Mendelian randomization approach, we tested whether genetically increased remnant cholesterol in hypertriglyceridaemia due to genetic variation in the apolipoprotein A5 gene (APOA5) associates...... with an increased risk of myocardial infarction (MI).Methods and resultsWe resequenced the core promoter and coding regions of APOA5 in individuals with the lowest 1% (n = 95) and highest 2% (n = 190) triglyceride levels in the Copenhagen City Heart Study (CCHS, n = 10 391). Genetic variants which differed...... in frequency between the two extreme triglyceride groups (c.-1131T > C, S19W, and c.*31C > T; P-value: 0.06 to...

  12. Disruption of Epac1 protects the heart from adenylyl cyclase type 5-mediated cardiac dysfunction.

    Science.gov (United States)

    Cai, Wenqian; Fujita, Takayuki; Hidaka, Yuko; Jin, Huiling; Suita, Kenji; Prajapati, Rajesh; Liang, Chen; Umemura, Masanari; Yokoyama, Utako; Sato, Motohiko; Okumura, Satoshi; Ishikawa, Yoshihiro

    2016-06-17

    Type 5 adenylyl cyclase (AC5) plays an important role in the development of chronic catecholamine stress-induced heart failure and arrhythmia in mice. Epac (exchange protein activated by cAMP), which is directly activated by cAMP independent of protein kinase A, has been recently identified as a novel mediator of cAMP signaling in the heart. However, the role of Epac in AC5-mediated cardiac dysfunction and arrhythmias remains poorly understood. We therefore generated AC5 transgenic mice (AC5TG) with selective disruption of the Epac1 gene (AC5TG-Epac1KO), and compared their phenotypes with those of AC5TG after chronic isoproterenol (ISO) infusion. Decreased cardiac function as well as increased susceptibility to pacing-induced atrial fibrillation (AF) in response to ISO were significantly attenuated in AC5TG-Epac1KO mice, compared to AC5TG mice. Increased cardiac apoptosis and cardiac fibrosis were also concomitantly attenuated in AC5TG-Epac1KO mice compared to AC5TG mice. These findings indicate that Epac1 plays an important role in AC5-mediated cardiac dysfunction and AF susceptibility. PMID:27117748

  13. Effects of a comprehensive cardiac rehabilitation program on quality of life and exercise tolerance in women: A retrospective analysis

    Directory of Open Access Journals (Sweden)

    Knapik Grant

    2003-04-01

    Full Text Available Abstract Background Currently, there are a lack of investigations that have examined the effect of participating in a comprehensive cardiac rehabilitation program on quality of life and physiological measures in women of different ages. The purpose of this investigation was to examine the effect of participating in a comprehensive cardiac rehabilitation program on quality of life, exercise tolerance, blood pressure and lipids in women between 33 and 82 years of age. Methods The 126 women participated in a 14-week cardiac rehabilitation program that consisted of 7 weeks of formal supervised exercise training and 7 weeks of unsupervised exercise and lifestyle modification. Physiologic and quality of life outcome measures obtained at the outset and after 14 weeks included: 1 exercise treadmill time; 2 resting and peak systolic and diastolic blood pressure; 3 total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and Triglycerides; 4 Cardiac Quality of Life Index questionnaire. Results Significant improvements were found in the following quality of life measures after participating in the cardiac rehabilitation program: physical well being, psychosocial, worry, nutrition and symptoms. No significant differences were seen for any QOL variable between the different age groups. Significant improvements were seen in exercise tolerance (+21% and high density lipoprotein (+5%. Conclusion Cardiac rehabilitation may play an important role in improving quality of life, exercise tolerance and high density lipoprotein cholesterol levels in younger and older women with underlying cardiovascular disease.

  14. Affect intensity and cardiac arousal.

    Science.gov (United States)

    Blascovich, J; Brennan, K; Tomaka, J; Kelsey, R M; Hughes, P; Coad, M L; Adlin, R

    1992-07-01

    Relationships between affect intensity and basal, evoked, and perceived cardiac arousal were investigated in 3 experiments. Affect intensity was assessed using Larsen and Diener's (1987) Affect Intensity Measure (AIM). Cardiac arousal was evoked with exercise in the 1st study and with mental arithmetic in the 2nd and 3rd. Perceived cardiac arousal was measured under optimal conditions using a standard heartbeat discrimination procedure. Women as a group scored higher on the AIM. Affect intensity was unrelated to basal or evoked cardiac arousal and was negatively related to perceived cardiac arousal in all 3 studies. Data suggest that affect intensity, although unrelated to actual physiological arousal, is negatively related to the accuracy with which individuals perceive their own arousal. Results are discussed within the context of an expanded arousal-regulation model (Blascovich, 1990). PMID:1494983

  15. Feasibility and Efficacy of Defatted Human Milk in the Treatment for Chylothorax After Cardiac Surgery in Infants.

    Science.gov (United States)

    Fogg, Kristi L; DellaValle, Diane M; Buckley, Jason R; Graham, Eric M; Zyblewski, Sinai C

    2016-08-01

    Chylothorax is a well-described complication after cardiothoracic surgery in children. Medical nutritional therapy for chylothorax includes medium-chain triglyceride (MCT) formulas and reduction in enteral long-chain triglyceride intake to reduce chyle production. Human milk is usually eliminated from the diet of infants with chylothorax because of its high long-chain triglyceride content. However, given the immunologic properties of human milk, young infants with chylothorax may benefit from using human milk over human milk substitutes. We performed a retrospective cohort study to describe the feasibility and efficacy of defatted human milk (DHM) for the treatment for chylothorax in infants after cardiac surgery and to compare growth outcomes between infants treated with DHM (n = 14) versus MCT formula (n = 21). There were no differences in mortality or length of hospital stay between the DHM and MCT formula treatment groups. The DHM treatment group had a significantly higher weight-for-age z-score at hospital discharge compared to the MCT formula group with median z-scores of -1 (-2 to 0.5) and -1.5 (-2 to 0), respectively (p = 0.02). In infants with chylothorax after cardiac surgery, DHM is a safe and feasible medical nutritional treatment and may have potential benefits for improved nutrition and growth.

  16. Feasibility and Efficacy of Defatted Human Milk in the Treatment for Chylothorax After Cardiac Surgery in Infants.

    Science.gov (United States)

    Fogg, Kristi L; DellaValle, Diane M; Buckley, Jason R; Graham, Eric M; Zyblewski, Sinai C

    2016-08-01

    Chylothorax is a well-described complication after cardiothoracic surgery in children. Medical nutritional therapy for chylothorax includes medium-chain triglyceride (MCT) formulas and reduction in enteral long-chain triglyceride intake to reduce chyle production. Human milk is usually eliminated from the diet of infants with chylothorax because of its high long-chain triglyceride content. However, given the immunologic properties of human milk, young infants with chylothorax may benefit from using human milk over human milk substitutes. We performed a retrospective cohort study to describe the feasibility and efficacy of defatted human milk (DHM) for the treatment for chylothorax in infants after cardiac surgery and to compare growth outcomes between infants treated with DHM (n = 14) versus MCT formula (n = 21). There were no differences in mortality or length of hospital stay between the DHM and MCT formula treatment groups. The DHM treatment group had a significantly higher weight-for-age z-score at hospital discharge compared to the MCT formula group with median z-scores of -1 (-2 to 0.5) and -1.5 (-2 to 0), respectively (p = 0.02). In infants with chylothorax after cardiac surgery, DHM is a safe and feasible medical nutritional treatment and may have potential benefits for improved nutrition and growth. PMID:27090650

  17. Estimation of Water Vapour Attenuation And Rain Attenuation

    Directory of Open Access Journals (Sweden)

    K.Kalyana Srinivas

    2015-04-01

    Full Text Available Attenuation due to and water vapour and rain can severely degrade the radio wave propagation at centimeter or millimeter wavelengths. It restricts the path length of radio communication systems and limits the use of higher frequencies for line-of-sight microwave links and satellite communications. The attenuation will pose a greater problem to communication as the frequency of occurrence of heavy rain increases.In a tropical region, like Malaysia, where excessive rainfall is a common phenomenon throughout the year, the knowledge of the rain attenuation at the frequency of operation is extremely required for the design of a reliable terrestrial and earth space communication link at a particular location.

  18. The triglyceride content in skeletal muscle is associated with hepatic but not peripheral insulin resistance in elderly twins

    DEFF Research Database (Denmark)

    Grunnet, L G; Laurila, Esa; Hansson, Ola;

    2012-01-01

    Total muscle triglyceride (MT) content has been associated with insulin resistance. We investigated the predictors and impact of MT on relevant metabolic parameters including peripheral and hepatic insulin resistance in elderly twins.......Total muscle triglyceride (MT) content has been associated with insulin resistance. We investigated the predictors and impact of MT on relevant metabolic parameters including peripheral and hepatic insulin resistance in elderly twins....

  19. A Sequence Variation (I148M) in PNPLA3 Associated with Nonalcoholic Fatty Liver Disease Disrupts Triglyceride Hydrolysis*

    OpenAIRE

    He, Shaoqing; McPhaul, Christopher; Li, John Zhong; Garuti, Rita; Kinch, Lisa; Nick V Grishin; Cohen, Jonathan C.; Hobbs, Helen H.

    2009-01-01

    Obesity and insulin resistance are associated with deposition of triglycerides in tissues other than adipose tissue. Previously, we showed that a missense mutation (I148M) in PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is associated with increased hepatic triglyceride content in humans. Here we examined the effect of the I148M substitution on the enzymatic activity and cellular location of PNPLA3. Structural modeling predicted that the substitution of methionine for isoleu...

  20. The attenuation and the attenuators: strategies and tactics

    Directory of Open Access Journals (Sweden)

    Antonio Briz

    2013-12-01

    Full Text Available This work is inscribed in a research project (ES.POR.ATENUAÇÃO that seeks to analyze and explain the attenuator activity in different regional varieties of Spanish and Portuguese, in order to perform, subsequently, different contrastive intralinguistic and interlinguistic studies. In this article, we explain some of the theoretical and methodological principles on which are based the qualitative and quantitative analysis. And especially, we will refer to the concept of attenuation (Briz 1995, 2002, 2003, 2005, 2007a, 2012.

  1. Multi-transmitting formula for attenuating waves

    Institute of Scientific and Technical Information of China (English)

    陈少林; 廖振鹏

    2003-01-01

    The MTF is extended to case of attenuating incident wave by introducing an attenuation coefficient. The reflection coefficients of this modified MTF and MTF areevaluated and compared when an attenuating wave impinges on the boundary, and the results demonstrate that MTF can be used to absorb slightly attenuating wavesand the modified MTF is more capable of absorbing heavily attenuating waves than MTF. The accuracy of modified MTF is also tested by numerical examples of fluid saturated porous media.

  2. Photoacoustic Imaging Taking into Account Attenuation

    CERN Document Server

    Kowar, Richard

    2010-01-01

    First, we review existing attenuation models and discuss their causality properties, which we believe to be essential for algorithms for inversion with attenuated data. Then, we survey causality properties of common attenuation models. We also derive integro-differential equations which the attenuated waves are satisfying. In addition we discuss the ill--conditionness of the inverse problem for calculating the unattenuated wave from the attenuated one.

  3. Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

    Science.gov (United States)

    Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

    2007-05-01

    3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function. PMID:17284482

  4. Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

    Science.gov (United States)

    Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

    2007-05-01

    3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

  5. Piromelatine decreases triglyceride accumulation in insulin resistant 3T3-L1 adipocytes: role of ATGL and HSL.

    Science.gov (United States)

    Wang, Ping-Ping; She, Mei-Hua; He, Ping-Ping; Chen, Wu-Jun; Laudon, Moshe; Xu, Xuan-Xuan; Yin, Wei-Dong

    2013-08-01

    Piromelatine, a novel investigational multimodal sleep medicine, is developed for the treatment of patients with primary and co-morbid insomnia. Piromelatine has been shown to inhibit weight gain and improve insulin sensitivity in high-fat/high-sucrose-fed (HFHS) rats. Considering that piromelatine has also been implicated in lowering of triglyceride levels in HFHS rats, this work elucidated whether this effect involves in the regulation of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in triglyceride (TG) metabolism. In this study, we investigated the effects of piromelatine and MT2 receptors inhibition on TG content, insulin-stimulated glucose uptake, and the expressions of ATGL and HSL in 3T3-L1 adipocytes preincubated in high glucose and high insulin (HGI) conditions. Our results showed that culturing 3T3-L1 adipocytes under HGI conditions increased triglyceride accumulation with concomitant decrease of ATGL and HSL expression, inducing insulin resistance in 3T3-L1 adipocytes. We also found that triglyceride accumulation was significantly inhibited and the levels of ATGL/HSL increased after melatonin or piromelatine treatment. The effects of melatonin/piromelatine (10 nM) were counteracted by pretreatment with the relatively selective MT2 receptor antagonist luzindole (100 nM). In this study, our data demonstrate that piromelatine reverses high glucose and high insulin-induced triglyceride accumulation in 3T3-L1 adipocytes, possibly through up-regulating of ATGL and HSL expression via a melatonin-dependent manner.

  6. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis.

    Science.gov (United States)

    He, Shaoqing; McPhaul, Christopher; Li, John Zhong; Garuti, Rita; Kinch, Lisa; Grishin, Nick V; Cohen, Jonathan C; Hobbs, Helen H

    2010-02-26

    Obesity and insulin resistance are associated with deposition of triglycerides in tissues other than adipose tissue. Previously, we showed that a missense mutation (I148M) in PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is associated with increased hepatic triglyceride content in humans. Here we examined the effect of the I148M substitution on the enzymatic activity and cellular location of PNPLA3. Structural modeling predicted that the substitution of methionine for isoleucine at residue 148 would restrict access of substrate to the catalytic serine at residue 47. In vitro assays using recombinant PNPLA3 partially purified from Sf9 cells confirmed that the wild type enzyme hydrolyzes emulsified triglyceride and that the I148M substitution abolishes this activity. Expression of PNPLA3-I148M, but not wild type PNPLA3, in cultured hepatocytes or in the livers of mice increased cellular triglyceride content. Cell fractionation studies revealed that approximately 90% of wild type PNPLA3 partitioned between membranes and lipid droplets; substitution of isoleucine for methionine at position 148 did not alter the subcellular distribution of the protein. These data are consistent with PNPLA3-I148M promoting triglyceride accumulation by limiting triglyceride hydrolysis.

  7. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

    Energy Technology Data Exchange (ETDEWEB)

    Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.]|[Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)

    1997-07-01

    Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

  8. Placental triglyceride accumulation in maternal type 1 diabetes is associated with increased lipase gene expression

    DEFF Research Database (Denmark)

    Lindegaard, Marie Louise Skakkebæk; Damm, Peter; Mathiesen, Elisabeth R;

    2006-01-01

    in placenta is largely unknown. To examine whether maternal type 1 diabetes affects placental lipid metabolism, we measured lipids and mRNA expression of lipase-encoding genes in placentas from women with type 1 diabetes (n = 27) and a control group (n = 21). The placental triglyceride (TG) concentration...... and mRNA expression of endothelial lipase (EL) and hormone-sensitive lipase (HSL) were increased in placentas from women with diabetes. The differences were more pronounced in women with diabetes and suboptimal metabolic control than in women with diabetes and good metabolic control. Placental m...

  9. Fatty acid composition of adipose tissue triglycerides after weight loss and weight maintenance

    DEFF Research Database (Denmark)

    Kunešová, M; Hlavatý, P; Tvrzická, E;

    2012-01-01

    of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI (HP....../HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic (16:1n-7...

  10. FSP27 Promotes Lipid Droplet Clustering and Then Fusion to Regulate Triglyceride Accumulation

    OpenAIRE

    Jambunathan, Srikarthika; Yin, Jun; Khan, Waheed; Tamori, Yoshikazu; Puri, Vishwajeet

    2011-01-01

    Fat Specific Protein 27 (FSP27), a lipid droplet (LD) associated protein in adipocytes, regulates triglyceride (TG) storage. In the present study we demonstrate that FSP27 plays a key role in LD morphology to accumulate TGs. We show here that FSP27 promotes clustering of the LDs which is followed by their fusion into fewer and enlarged droplets. To map the domains of FSP27 responsible for these events, we generated GFP-fusion constructs of deletion mutants of FSP27. Microscopic analysis revea...

  11. Increased plasma free fatty acid and triglyceride levels after single administation of toluene in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Setsunori; Tanabe, Koichi; Shiono, Hiroshi (Shimane Medical Univ., Izumo (Japan)); Maseda, Chikatoshi (Shimane Prefectural Police Headquarters, Matsue (Japan)); Fukui, Yuko (Kyoto Univ. (Japan))

    1988-01-01

    Changes of plasma lipids (triglyceride, TG: total cholesterol, Cho; and phospholipids, PL), free fatty acid (FFA), and blood glucose (BG) were studied in male rabbits after toluene administration (0.5 g/kg per os). Hypertriglyceridemia was observed at and after 2 h. Plasma FFA and BG were elevated temporarily during the early stage and lowered gradually thereafter. Initially, plasma Cho and PL were virtually unchanged, by the Cho levels increased slowly after 6 h. The hypertriglyceridemia observed may have some adverse effects on heart function.

  12. Mixtures of mono-, di- and tri-glycerides as energy supplements to broilers’ diets

    OpenAIRE

    Sara Minieri; Clara Sargentini; Francesco Petacchi,; Mauro Antongiovanni; Arianna Buccioni

    2010-01-01

    Mixtures of mono-, di- and tri-glycerides from olive oil (MDT) were added to: palm oil (PO), olive oil (OO), soybean oil (SO), free fatty acids from palm oil (PFA), free fatty acids from olive oil (OFA). The compound mixtures were used as energy supplements in the diets of broiler chickens in comparison with plain SO and plain animal fat (AF). Two hundred and ten birds were randomly allotted to 7 dietary treatments with the diverse oil sources: 6 birds per cage, 5 cages per treatment. The eff...

  13. Impaired secretion of very low density lipoprotein-triglycerides by apolipoprotein E- deficient mouse hepatocytes.

    OpenAIRE

    Kuipers, F; M. C. De Jong; Lin, Y.; Eck, M; Havinga, R.; Bloks, V; Verkade , H.J.; Hofker, M H; Moshage, H; Berkel, T J; Vonk, R J; Havekes, L M

    1997-01-01

    To explore mechanisms underlying triglyceride (TG) accumulation in livers of chow-fed apo E-deficient mice (Kuipers, F., J.M. van Ree, M.H. Hofker, H. Wolters, G. In't Veld, R.J. Vonk, H.M.G. Princen, and L.M. Havekes. 1996. Hepatology. 24:241-247), we investigated the effects of apo E deficiency on secretion of VLDL-associated TG (a) in vivo in mice, (b) in isolated perfused mouse livers, and (c) in cultured mouse hepatocytes. (a) Hepatic VLDL-TG production rate in vivo, determined after Tri...

  14. Attenuation of mitochondrial, but not cytosolic, Ca2+ overload reduces myocardial injury induced by ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Chun-mei CAO; Wing-yee YAN; Jing LIU; Kenneth WL KAM; Shi-zhong ZHAN; James SK SHAM; Tak-ming WONG

    2006-01-01

    Aim: Attenuation of mitochondrial Ca2+ ([Ca2+]m, but not cytosolic Ca2+ ([Ca2+]c), overload improves contractile recovery. We hypothesized that attenuation of [Ca2+]m, but not [Ca2+]c, overload confers cardioprotection against ischemia/ reperfusion-induced injury. Methods: Infarct size from isolated perfused rat heart, cell viability, and electrically-induced Ca2+ transient in isolated rat ventricular myocytes were measured. We determined the effects of BAPTA-AM, a Ca2+ chelator, at concentrations that abolish the overload of both [Ca2+]c and [Ca2+]m, and ruthenium red, an inhibitor of mitochondrial uniporter of Ca2+ transport, at concentrations that abolish the overload of [Ca2+]m, but not [Ca2+]c, on cardiac injury induced by ischemia/reperfusion. Results: Attenuation of both [Ca2+]m and [Ca2+]c by BAPTA-AM, and attenuation of [Ca2+]m, but not [Ca2+]c, overload by ruthenium red, reduced the cardiac injury observations, indicating the importance of [Ca2+]m in cardioprotection and contractile recovery in response to ischemia/reperfusion. Conclusion: The study has provided unequivocal evidence using a cause-effect approach that attenuation of [Ca2+]m, but not [Ca2+]c, overload is responsible for cardioprotection against ischemia/reperfusion-induced injury. We also confirmed the previous observation that attenuation of [Ca2+]m, but not [Ca2+]c, by ruthenium red improves contractile recovery following ischemia/ reperfusion.

  15. Sound attenuation in magnetorheological fluids

    Science.gov (United States)

    Rodríguez-López, J.; Elvira, L.; Resa, P.; Montero de Espinosa, F.

    2013-02-01

    In this work, the attenuation of ultrasonic elastic waves propagating through magnetorheological (MR) fluids is analysed as a function of the particle volume fraction and the magnetic field intensity. Non-commercial MR fluids made with iron ferromagnetic particles and two different solvents (an olive oil based solution and an Araldite-epoxy) were used. Particle volume fractions of up to 0.25 were analysed. It is shown that the attenuation of sound depends strongly on the solvent used and the volume fraction. The influence of a magnetic field up to 212 mT was studied and it was found that the sound attenuation increases with the magnetic intensity until saturation is reached. A hysteretic effect is evident once the magnetic field is removed.

  16. Josephson tunnel junction microwave attenuator

    DEFF Research Database (Denmark)

    Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.;

    1993-01-01

    A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc biased...... at different points in the current-voltage characteristic. Both numerical calculations based on the Tien-Gordon theory and 70-GHz microwave experiments have confirmed the wide dynamic range (more than 15-dB attenuation for one stage) and the low insertion loss in the ''open'' state. The performance of a fully...... integrated submillimeter receiver circuit which comprises a flux-flow oscillator (FFO) as local oscillator, a superconducting variable attenuator, and a microwave SIS detector with tuned-out capacitance is also reported....

  17. Material-based engineering strategies for cardiac regeneration.

    Science.gov (United States)

    Marion, Mieke H van; Bax, Noortje A M; Spreeuwel, Ariane C C van; van der Schaft, Daisy W J; Bouten, Carlijn V C

    2014-01-01

    Cardiac tissue is composed of muscle and non-muscle cells, surrounded by extracellular matrix (ECM) and spatially organized into a complex three-dimensional (3D) architecture to allow for coordinated contraction and electrical pulse propagation. Despite emerging evidence for cardiomyocyte turnover in mammalian hearts, the regenerative capacity of human cardiac tissue is insufficient to recover from damage, e.g. resulting from myocardial infarction (MI). Instead, the heart 'repairs' lost or injured tissue by ongoing synthesis and remodeling of scar tissue. Conventional therapies and timely (stem) cell delivery to the injured tissue markedly improve short-term function and remodeling, but do not attenuate later stage adverse remodeling, leading to functional deterioration and eventually failure of the heart. Material-based therapies have been successfully used to mechanically support and constrain the post-MI failing heart, preventing it from further remodeling and dilation. When designed to deliver the right microenvironment for endogenous or exogenous cells, as well as the mechanical and topological cues to guide neo-tissue formation, material-based therapies may even reverse remodeling and boost cardiac regeneration. This paper reviews the up-to-date status of material-based cardiac regeneration with special emphasis on 1) the use of bare biomaterials to deliver passive constraints that unload the heart, 2) the use of materials and cells to create engineered cardiac constructs for replacement, support, or regeneration of damaged myocardium, and 3) the development of bio-inspired and bioactive materials that aim to enhance the endogenous regenerative capacity of the heart. As the therapies should function in the infarcted heart, the damaged host environment and engineered in vitro test systems that mimic this environment, are reviewed as well.

  18. Physics of Cardiac Arrhythmogenesis

    Science.gov (United States)

    Karma, Alain

    2013-04-01

    A normal heartbeat is orchestrated by the stable propagation of an excitation wave that produces an orderly contraction. In contrast, wave turbulence in the ventricles, clinically known as ventricular fibrillation (VF), stops the heart from pumping and is lethal without prompt defibrillation. I review experimental, computational, and theoretical studies that have shed light on complex dynamical phenomena linked to the initiation, maintenance, and control of wave turbulence. I first discuss advances made to understand the precursor state to a reentrant arrhythmia where the refractory period of cardiac tissue becomes spatiotemporally disordered; this is known as an arrhythmogenic tissue substrate. I describe observed patterns of transmembrane voltage and intracellular calcium signaling that can contribute to this substrate, and symmetry breaking instabilities to explain their formation. I then survey mechanisms of wave turbulence and discuss novel methods that exploit electrical pacing stimuli to control precursor patterns and low-energy pulsed electric fields to control turbulence.

  19. Mediastinitis after cardiac transplantation

    Directory of Open Access Journals (Sweden)

    Noedir A. G. Stolf

    2000-05-01

    Full Text Available OBJECTIVE: Assessment of incidence and behavior of mediastinitis after cardiac transplantation. METHODS: From 1985 to 1999, 214 cardiac transplantations were performed, 12 (5.6% of the transplanted patients developed confirmed mediastinitis. Patient's ages ranged from 42 to 66 years (mean of 52.3±10.0 years and 10 (83.3% patients were males. Seven (58.3% patients showed sternal stability on palpation, 4 (33.3% patients had pleural empyema, and 2 (16.7% patients did not show purulent secretion draining through the wound. RESULTS: Staphylococcus aureus was the infectious agent identified in the wound secretion or in the mediastinum, or both, in 8 (66.7% patients. Staphylococcus epidermidis was identified in 2 (16.7% patients, Enterococcus faecalis in 1 (8.3% patient, and the cause of mediastinitis could not be determined in 1 (8.3% patient. Surgical treatment was performed on an emergency basis, and the extension of the débridement varied with local conditions. In 2 (16.7% patients, we chose to leave the surgical wound open and performed daily dressings with granulated sugar. Total sternal resection was performed in only 1 (8.3% patient. Out of this series, 5 (41.7% patients died, and the causes of death were related to the infection. Autopsy revealed persistence of mediastinitis in 1 (8.3% patient. CONCLUSION: Promptness in diagnosing mediastinitis and precocious surgical drainage have changed the natural evolution of this disease. Nevertheless, observance of the basic precepts of prophylaxis of infection is still the best way to treat mediastinitis.

  20. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    Jonas S De Jong

    2010-12-01

    Full Text Available Sudden cardiac death remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g. serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

  1. X-Ray Attenuation Cell

    Energy Technology Data Exchange (ETDEWEB)

    Ryutov, D.; Toor, A.

    2000-03-03

    To minimize the pulse-to-pulse variation, the LCLS FEL must operate at saturation, i.e. 10 orders of magnitude brighter spectral brilliance than 3rd-generation light sources. At this intensity, ultra-high vacuums and windowless transport are required. Many of the experiments, however, will need to be conducted at a much lower intensity thereby requiring a reliable means to reduce the x-ray intensity by many orders of magnitude without increasing the pulse-to-pulse variation. In this report we consider a possible solution for controlled attenuation of the LCLS x-ray radiation. We suggest using for this purpose a windowless gas-filled cell with the differential pumping. Although this scheme is easily realizable in principle, it has to be demonstrated that the attenuator can be made short enough to be practical and that the gas loads delivered to the vacuum line of sight (LOS) are acceptable. We are not going to present a final, optimized design. Instead, we will provide a preliminary analysis showing that the whole concept is robust and is worth further study. The spatial structure of the LCLS x-ray pulse at the location of the attenuator is shown in Fig. 1. The central high-intensity component, due to the FEL, has a FWHM of {approx}100 {micro}m. A second component, due to the undulator's broad band spontaneous radiation is seen as a much lower intensity ''halo'' with a FWHM of 1 mm. We discuss two versions of the attenuation cell. The first is directed towards a controlled attenuation of the FEL up to the 4 orders of magnitude in the intensity, with the spontaneous radiation halo being eliminated by collimators. In the second version, the spontaneous radiation is not sacrificed but the FEL component (as well as the first harmonic of the spontaneous radiation) gets attenuated by a more modest factor up to 100. We will make all the estimates assuming that the gas used in the attenuator is Xenon and that the energy of the FEL is 8.25 keV. At

  2. Metoclopramide-induced cardiac arrest

    Directory of Open Access Journals (Sweden)

    Martha M. Rumore

    2011-11-01

    Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

  3. A novel and orally active poly(ADP-ribose) polymerase inhibitor, KR-33889 [2-[methoxycarbonyl(4-methoxyphenyl) methylsulfanyl]-1H-benzimidazole-4-carboxylic acid amide], attenuates injury in in vitro model of cell death and in vivo model of cardiac ischemia.

    Science.gov (United States)

    Oh, Kwang-Seok; Lee, Sunkyung; Yi, Kyu Yang; Seo, Ho Won; Koo, Hyun-Na; Lee, Byung Ho

    2009-01-01

    Blocking of poly(ADP-ribose) polymerase (PARP)-1 has been expected to protect the heart from ischemia-reperfusion injury. We have recently identified a novel and orally active PARP-1 inhibitor, KR-33889 [2-[methoxycarbonyl(4-methoxyphenyl)-methylsulfanyl]-1H-benzimidazole-4-carboxylic acid amide], and its major metabolite, KR-34285 [2-[carboxy(4-methoxyphenyl)methylsulfanyl]-1H-benzimidazole-4-carboxylic acid amide]. KR-33889 potently inhibited PARP-1 activity with an IC(50) value of 0.52 +/- 0.10 microM. In H9c2 myocardial cells, KR-33889 (0.03-30 microM) showed a resistance to hydrogen peroxide (2 mM)-mediated oxidative insult and significantly attenuated activation of intracellular PARP-1. In anesthetized rats subjected to 30 min of coronary occlusion and 3 h of reperfusion, KR-33889 (0.3-3 mg/kg i.v.) dose-dependently reduced myocardial infarct size. KR-34285, a major metabolite of KR-33889, exerted similar patterns to the parent compound with equi- or weaker potency in the same studies described above. In separate experiments for the therapeutic time window study, KR-33889 (3 mg/kg i.v.) given at preischemia, at reperfusion or in both, in rat models also significantly reduced the myocardial infarction compared with their respective vehicle-treated group. Furthermore, the oral administration of KR-33889 (1-10 mg/kg p.o.) at 1 h before occlusion significantly reduced myocardial injury. The ability of KR-33889 to inhibit PARP in the rat model of ischemic heart was confirmed by immunohistochemical detection of poly(ADP-ribose) activation. These results indicate that the novel PARP inhibitor KR-33889 exerts its cardioprotective effect in in vitro and in vivo studies of myocardial ischemia via potent PARP inhibition and also suggest that KR-33889 could be an attractive therapeutic candidate with oral activity for several cardiovascular disorders, including myocardial infarction.

  4. Medium-chain triglycerides and monounsaturated fatty acids potentiate the beneficial effects of fish oil on selected cardiovascular risk factors in rats.

    Science.gov (United States)

    Kondreddy, Vijay Kumar Reddy; Anikisetty, Maheswaraiah; Naidu, Kamatham Akhilender

    2016-02-01

    Fish oil (FO) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is known to reduce the risk of cardiovascular diseases (CVDs). Little information is known regarding the influence of lipid composition in the background diet on the modulatory effect of FO supplementation on CVDs. The present study was designed to investigate the influence of various background dietary lipids and FO on selected cardiovascular risk factors in rats. Adult Wistar rats were fed semisynthetic diet with FO at 1.0% or 2.0% along with other lipids, namely, medium-chain triacylglycerols (MCTs), monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs) and n-3 PUFAs, for 5 weeks. Some of the potent CVD risk factors were estimated in the rats. FO at 1.0% and 2.0% has significantly reduced serum lipid peroxides, total cholesterol, triglycerides (TAGs), tumor necrosis factor-α, interleukin-6 and C-reactive protein; liver and adipose TAG and cholesterol levels in MCT, MUFA and n-6 PUFA diet groups. Notably, these alterations were comparatively higher in 1.0% FO-substituted MCT and MUFA diet groups. Interestingly, feeding of FO along with n-3 PUFAs did not show additive effect in attenuation of these factors. Serum liver EPA and DHA levels were remarkably elevated in rats fed FO-enriched MCT or MUFA diets. Our results suggest that MCTs or MUFAs in the background diet might promote the beneficial effects of FO on CVDs. PMID:26878786

  5. Terbufos-sulfone exacerbates cardiac lesions in diabetic rats: a sub-acute toxicity study.

    Science.gov (United States)

    Nurulain, Syed M; Shafiullah, Mohamed; Yasin, Javed; Adem, Abdu; Kaabi, Juma Al; Tariq, Saeed; Adeghate, Ernest; Ojha, Shreesh

    2016-06-01

    Organophosphorus compounds (OPCs) have a wide range of applications, from agriculture to warfare. Exposure to these brings forward a varied kind of health issues globally. Terbufos is one of the leading OPCs used worldwide. The present study investigates the cardiac effect of no observable dose of a metabolite of terbufos, terbufos-sulfone (TS), under non-diabetic and streptozotocin-induced diabetic condition. One hundred nanomoles per rat (1/20 of LD50) was administered intraperitoneally to adult male Wister rats daily for fifteen days. The left ventricle was collected for ultrastructural changes by transmission electron microscopy. The blood samples were collected for biochemical tests including RBC acetylcholinesterase, creatinine kinase (CK), lactate dehydrogenase (LDH), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, ALT, AST, and GGT. The study revealed about 10 % inhibition of RBC-AChE in two weeks of TS treatment in non-diabetic rats whereas RBC-AChE activity was significantly decreased in diabetic TS treated rats. CK, LDH, and triglycerides were significantly higher in diabetic TS treated rats. Electron microscopy of the heart showed derangement and lesions of the mitochondria of cardiomyocytes in the TS treated groups. The present study concludes that a non-lethal dose of TS causes cardiac lesions which exacerbate under diabetic condition. Biochemical tests confirmed the ultrastructural changes. It is concluded that a non-lethal dose of TS may be a risk factor for a cardiovascular disease, which may be fatal under diabetic condition. PMID:27331300

  6. Epigenetic regulation in cardiac fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li-Ming; Yu; Yong; Xu

    2015-01-01

    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.

  7. Cardiac perioperative complications in noncardiac surgery

    OpenAIRE

    Radovanović Dragana; Kolak Radmila; Stokić Aleksandar; Radovanović Zoran; Jovanović Gordana

    2008-01-01

    Anesthesiologists are confronted with an increasing population of patients undergoing noncardiac surgery who are at risk for cardiac complications in the perioperative period. Perioperative cardiac complications are responsible for significant mortality and morbidity. The aim of the present study was to determine the incidence of perioperative (operative and postoperative) cardiac complications and correlations between the incidence of perioperative cardiac complications and type of surgical ...

  8. Cyclic GMP signaling in cardiomyocytes modulates fatty acid trafficking and prevents triglyceride accumulation

    Science.gov (United States)

    While the balance between carbohydrates and fatty acids for energy production appears to be crucial for cardiac homeostasis, much remains to be learned about the molecular mechanisms underlying this relationship. Given the reported benefits of cGMP signaling on the myocardium, we investigated the im...

  9. Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARα signaling.

    Science.gov (United States)

    Obrowsky, Sascha; Chandak, Prakash G; Patankar, Jay V; Povoden, Silvia; Schlager, Stefanie; Kershaw, Erin E; Bogner-Strauss, Juliane G; Hoefler, Gerald; Levak-Frank, Sanja; Kratky, Dagmar

    2013-02-01

    Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triglyceride (TG) hydrolysis. The lack of ATGL results in TG accumulation in multiple tissues, underscoring the critical role of ATGL in maintaining lipid homeostasis. Recent evidence suggests that ATGL affects TG metabolism via activation of peroxisome proliferator-activated receptor α (PPARα). To investigate specific effects of intestinal ATGL on lipid metabolism we generated mice lacking ATGL exclusively in the intestine (ATGLiKO). We found decreased TG hydrolase activity and increased intracellular TG content in ATGLiKO small intestines. Intragastric administration of [(3)H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [(3)H]oleate also accumulated within TG in ATGLiKO intestines, indicating that ATGL mobilizes fatty acids from the systemic circulation absorbed by the basolateral side from the blood. Down-regulation of PPARα target genes suggested modulation of cholesterol absorption by intestinal ATGL. Accordingly, ATGL deficiency in the intestine resulted in delayed cholesterol absorption. Importantly, this study provides evidence that ATGL has no impact on intestinal TG absorption but hydrolyzes TGs taken up from the intestinal lumen and systemic circulation. Our data support the role of ATGL in modulating PPARα-dependent processes also in the small intestine.

  10. Chronic treatment with bark infusion from Croton cajucara lowers plasma triglyceride levels in genetic hyperlipidemic mice.

    Science.gov (United States)

    Bighetti, Eliete J B; Souza-Brito, Alba R M; de Faria, Eliana C; Oliveira, Helena C F

    2004-06-01

    Aqueous infusion and preparations containing dehydrocrotonin (DHC) and essential oil from Croton cajucara bark were tested for plasma lipid-lowering effects in genetically modified hyperlipidemic mice. Two mouse models were tested: 1) primary hypercholesterolemia resulting from the LDL-receptor gene knockout, and 2) combined hyperlipidemia resulting from crosses of LDL-receptor knockout mice with transgenic mice overexpressing apolipo protein (apo) CIII and cholesteryl ester-transfer protein. Mice treated with bark infusion, DHC, essential oil, or placebos for 25 days showed no signals of toxicity as judged by biochemical tests for liver and kidney functions. The bark infusion reduced triglyceride plasma levels by 40%, while essential oil and DHC had no significant effects on plasma lipid levels. The bark infusion treatment promoted a redistribution of cholesterol among the lipoprotein fractions in combined hyperlipidemic mice. There was a marked reduction in the VLDL fraction and an increase in the HDL fraction, in such a way that the (VLDL + LDL)/HDL ratio was reduced by half. The bark infusion treatment did not modify cholesterol distribution in hypercholesterolemic mice. In conclusion, C. cajucara bark infusion reduced plasma triglycerides levels and promoted a redistribution of cholesterol among lipoproteins in genetically combined hyperlipidemic mice. These changes modify risk factors for the development of atherosclerotic diseases. PMID:15381962

  11. Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia.

    Science.gov (United States)

    Al-Zoughbi, Wael; Pichler, Martin; Gorkiewicz, Gregor; Guertl-Lackner, Barbara; Haybaeck, Johannes; Jahn, Stephan W; Lackner, Carolin; Liegl-Atzwanger, Bernadette; Popper, Helmut; Schauer, Silvia; Nusshold, Elisa; Kindt, Alida S D; Trajanoski, Zlatko; Speicher, Michael R; Haemmerle, Guenther; Zimmermann, Robert; Zechner, Rudolf; Vesely, Paul W; Hoefler, Gerald

    2016-06-01

    Metabolic reprogramming is a hallmark of cancer. Understanding cancer metabolism is instrumental to devise innovative therapeutic approaches. Anabolic metabolism, including the induction of lipogenic enzymes, is a key feature of proliferating cells. Here, we report a novel tumor suppressive function for adipose triglyceride lipase (ATGL), the rate limiting enzyme in the triglyceride hydrolysis cascade.In immunohistochemical analysis, non-small cell lung cancers, pancreatic adenocarcinoma as well as leiomyosarcoma showed significantly reduced levels of ATGL protein compared to corresponding normal tissues. The ATGL gene was frequently deleted in various forms of cancers. Low levels of ATGL mRNA correlated with significantly reduced survival in patients with ovarian, breast, gastric and non-small cell lung cancers. Remarkably, pulmonary neoplasia including invasive adenocarcinoma developed spontaneously in mice lacking ATGL pointing to an important role for this lipase in controlling tumor development.Loss of ATGL, as detected in several forms of human cancer, induces spontaneous development of pulmonary neoplasia in a mouse model. Our results, therefore, suggest a novel tumor suppressor function for ATGL and contribute to the understanding of cancer metabolism. We propose to evaluate loss of ATGL protein expression for the diagnosis of malignant tumors. Finally, modulation of the lipolytic pathway may represent a novel therapeutic approach in the treatment of human cancer.

  12. Different exercise protocols improve metabolic syndrome markers, tissue triglycerides content and antioxidant status in rats

    Directory of Open Access Journals (Sweden)

    Botezelli José D

    2011-12-01

    Full Text Available Abstract Background An increase in the prevalence of obesity entails great expenditure for governments. Physical exercise is a powerful tool in the combat against obesity and obesity-associated diseases. This study sought to determine the effect of three different exercise protocols on metabolic syndrome and lipid peroxidation markers and the activity of antioxidant enzymes in adult Wistar rats (120 days old. Methods Animals were randomly divided into four groups: the control (C group was kept sedentary throughout the study; the aerobic group (A swam1 h per day, 5 days per week, at 80% lactate threshold intensity; the strength group (S performed strength training with four series of 10 jumps, 5 days per week; and the Concurrent group (AS was trained using the aerobic protocol three days per week and the strength protocol two days per week. Results Groups A and S exhibited a reduction in body weight compared to group C. All exercised animals showed a reduction in triglyceride concentrations in fatty tissues and the liver. Exercised animals also exhibited a reduction in lipid peroxidation markers (TBARS and an increase in serum superoxide dismutase activity. Animals in group A had increased levels of liver catalase and superoxide dismutase activities. Conclusions We concluded that all physical activity protocols improved the antioxidant systems of the animals and decreased the storage of triglycerides in the investigated tissues.

  13. EFFECT OF ACUPUNCTURE TREATMENT ON CELLULAR HEMORHEOLOGY,CHOLESTEROL AND TRIGLYCERIDE OF SIMPLE OBESITY PATIENTS

    Institute of Scientific and Technical Information of China (English)

    赵宁侠; 郭瑞林; 任秦有; 张周良; 史恒军

    2004-01-01

    Objective: To observe the effect of acupuncture on simple obesity and cellular hemorheology. Methods: Thirty-two cases of simple obesity patients were enrolled into this study. Acupoints of the Stomach Meridian and Spleen Meridian as Zhongwan (中脘CV 12), Liangmen (梁门ST 21), Tianshu (天枢ST 25), Guanyuan (关元CV 4), etc. were punctured, once daily in the first 5 days, and once every other day afterwards, with 10 sessions being a therapeutic course. Before treatment and after 3 courses of treatment, the body weight, waistline, weight index, serum cholesterol (CH), triglyceride and aggregation index of red blood cell (RBC) were detected. Results: After acupuncture treatment, all the indexes of body weight, waistline, weight index, serum CH, triglyceride and aggregation index of RBC decreased significantly in comparison with those of pre-treatment (P<0.05). Conclusion: Acupuncture can apparently improve cellular hemorheology, reduce body weight, serum cholesterol and TG levels in simple obesity patients.

  14. Long- and medium-chain triglycerides during parenteral nutrition in critically ill patients.

    Science.gov (United States)

    Delafosse, B; Viale, J P; Pachiaudi, C; Normand, S; Goudable, J; Bouffard, Y; Annat, G; Bertrand, O

    1997-04-01

    Due to their special metabolic pathway, medium-chain triglycerides (MCT) have been claimed to be oxidized more extensively, compared with long-chain triglycerides (LCT), when administered as a parenteral nutritional support. This enhanced lipid oxidation rate of MCT emulsions could be particularly disclosed in hyperglycemic and hyperinsulinemic conditions. In an attempt to further elucidate this question, we measured substrate oxidation rates in critically ill patients liable to experience such metabolic conditions, that is to say postoperative patients after esophageal resection receiving 1.5 times their measured energy expenditure (n = 12) or after liver transplantation (n = 8). These patients received either LCT or MCT-LCT emulsions. The metabolic measurements were performed simultaneously by two methods, namely indirect calorimetry and isotopic methods based on natural abundance of nutrients. Although both groups of patients were hyperglycemic and hyperinsulinemic, the measured carbohydrate and lipid oxidation rates were not different with whatever type of lipid was administered. The MCT-LCT emulsions did not offer clear-cut advantages over LCT emulsions in critically ill patients when lipid energetic fate was considered. PMID:9142873

  15. Mfge8 regulates enterocyte lipid storage by promoting enterocyte triglyceride hydrolase activity

    Science.gov (United States)

    Khalifeh-Soltani, Amin; Gupta, Deepti; Ha, Arnold; Iqbal, Jahangir; Hussain, Mahmood; Podolsky, Michael J.

    2016-01-01

    The small intestine has an underappreciated role as a lipid storage organ. Under conditions of high dietary fat intake, enterocytes can minimize the extent of postprandial lipemia by storing newly absorbed dietary fat in cytoplasmic lipid droplets. Lipid droplets can be subsequently mobilized for the production of chylomicrons. The mechanisms that regulate this process are poorly understood. We report here that the milk protein Mfge8 regulates hydrolysis of cytoplasmic lipid droplets in enterocytes after interacting with the αvβ3 and αvβ5 integrins. Mice deficient in Mfge8 or the αvβ3 and αvβ5 integrins accumulate excess cytoplasmic lipid droplets after a fat challenge. Mechanistically, interruption of the Mfge8-integrin axis leads to impaired enterocyte intracellular triglyceride hydrolase activity in vitro and in vivo. Furthermore, Mfge8 increases triglyceride hydrolase activity through a PI3 kinase/mTORC2–dependent signaling pathway. These data identify a key role for Mfge8 and the αvβ3 and αvβ5 integrins in regulating enterocyte lipid processing.

  16. High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease

    Directory of Open Access Journals (Sweden)

    Protasio Lemos da Luz

    2008-01-01

    Full Text Available An abnormal ratio of triglycerides to HDL-cholesterol (TG/HDL-c indicates an atherogenic lipid profile and a risk for the development of coronary disease. OBJECTIVE: To investigate the association between lipid levels, specifically TG/HDL-c, and the extent of coronary disease. METHODS: High-risk patients (n = 374 submitted for coronary angiography had their lipid variables measured and coronary disease extent scored by the Friesinger index. RESULTS: The subjects consisted of 220 males and 154 females, age 57.2 ± 11.1 years, with total cholesterol of 210± 50.3 mg/dL, triglycerides of 173.8 ± 169.8 mg/dL, HDL-cholesterol (HDL-c of 40.1 ± 12.8 mg/dL, LDL-cholesterol (LDL-c of 137.3 ± 46.2 mg/dL, TG/HDL-c of 5.1 ± 5.3, and a Friesinger index of 6.6 ± 4.7. The relationship between the extent of coronary disease (dichotomized by a Friesenger index of 5 and lipid levels (normal vs. abnormal was statistically significant for the following: triglycerides, odds ratio of 2.02 (1.31-3.1; p = 0.0018; HDL-c, odds ratio of 2.21 (1.42-3.43; p = 0.0005; and TG/HDL-c, odds ratio of 2.01(1.30-3.09; p = 0.0018. However, the relationship was not significant between extent of coronary disease and total cholesterol [1.25 (0.82-1.91; p = 0.33] or LDL-c [1.47 (0.96-2.25; p = 0.0842]. The chi-square for linear trends for Friesinger > 4 and lipid quartiles was statistically significant for triglycerides (p = 0.0017, HDL-c (p = 0.0001, and TG/HDL-c (p = 0.0018, but not for total cholesterol (p = 0.393 or LDL-c (p = 0.0568. The multivariate analysis by logistic regression OR gave 1.3 ± 0.79 (p = .0001 for TG/HDL-c, 0.779 ± 0.074 (p = .0001 for HDL-c, and 1.234 ± 0.097 (p = 0.03 for LDL. Analysis of receiver operating characteristic curves showed that only TG/HDL-c and HDL-c were useful for detecting extensive coronary disease, with the former more strongly associated with disease. CONCLUSIONS: Although some lipid variables were associated with the extent of

  17. Compact plasmonic variable optical attenuator

    DEFF Research Database (Denmark)

    Leosson, Kristjan; Rosenzveig, Tiberiu; Hermannsson, Pétur Gordon;

    2008-01-01

    We demonstrate plasmonic nanowire-based thermo-optic variable optical attenuators operating in the 1525-1625 nm wavelength range. The devices have a footprint as low as 1 mm, extinction ratio exceeding 40 dB, driving voltage below 3 V, and full modulation bandwidth of 1 kHz. The polarization...

  18. Robot-assisted cardiac surgery.

    Science.gov (United States)

    Ishikawa, Norihiko; Watanabe, Go

    2015-01-01

    Recognition of the significant advantages of minimizing surgical trauma has resulted in the development of minimally invasive surgical procedures. Endoscopic surgery offers patients the benefits of minimally invasive surgery, and surgical robots have enhanced the ability and precision of surgeons. Consequently, technological advances have facilitated totally endoscopic robotic cardiac surgery, which has allowed surgeons to operate endoscopically rather than through a median sternotomy during cardiac surgery. Thus, repairs for structural heart conditions, including mitral valve plasty, atrial septal defect closure, multivessel minimally invasive direct coronary artery bypass grafting (MIDCAB), and totally endoscopic coronary artery bypass graft surgery (CABG), can be totally endoscopic. Robot-assisted cardiac surgery as minimally invasive cardiac surgery is reviewed. PMID:26134073

  19. Recent developments in cardiac pacing.

    Science.gov (United States)

    Rodak, D J

    1995-10-01

    Indications for cardiac pacing continue to expand. Pacing to improve functional capacity, which is now common, relies on careful patient selection and technical improvements, such as complex software algorithms and diagnostic capabilities.

  20. Robotic Applications in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Alan P. Kypson

    2008-11-01

    Full Text Available Traditionally, cardiac surgery has been performed through a median sternotomy, which allows the surgeon generous access to the heart and surrounding great vessels. As a paradigm shift in the size and location of incisions occurs in cardiac surgery, new methods have been developed to allow the surgeon the same amount of dexterity and accessibility to the heart in confined spaces and in a less invasive manner. Initially, long instruments without pivot points were used, however, more recent robotic telemanipulation systems have been applied that allow for improved dexterity, enabling the surgeon to perform cardiac surgery from a distance not previously possible. In this rapidly evolving field, we review the recent history and clinical results of using robotics in cardiac surgery.

  1. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

    Science.gov (United States)

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T; Komorowski, Richard; Fish, Brian L; Migrino, Raymond Q; Harmann, Leanne; Hopewell, John W; Kronenberg, Amy; Patel, Shailendra; Moulder, John E; Baker, John E

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

  2. Stormwater Attenuation by Green Roofs

    Science.gov (United States)

    Sims, A.; O'Carroll, D. M.; Robinson, C. E.; Smart, C. C.

    2014-12-01

    Innovative municipal stormwater management technologies are urgently required in urban centers. Inadequate stormwater management can lead to excessive flooding, channel erosion, decreased stream baseflows, and degraded water quality. A major source of urban stormwater is unused roof space. Green roofs can be used as a stormwater management tool to reduce roof generated stormwater and generally improve the quality of runoff. With recent legislation in some North American cities, including Toronto, requiring the installation of green roofs on large buildings, research on the effectiveness of green roofs for stormwater management is important. This study aims to assess the hydrologic response of an extensive sedum green roof in London, Ontario, with emphasis on the response to large precipitation events that stress municipal stormwater infrastructure. A green roof rapidly reaches field capacity during large storm events and can show significantly different behavior before and after field capacity. At field capacity a green roof has no capillary storage left for retention of stormwater, but may still be an effective tool to attenuate peak runoff rates by transport through the green roof substrate. The attenuation of green roofs after field capacity is linked to gravity storage, where gravity storage is the water that is temporarily stored and can drain freely over time after field capacity has been established. Stormwater attenuation of a modular experimental green roof is determined from water balance calculations at 1-minute intervals. Data is used to evaluate green roof attenuation and the impact of field capacity on peak flow rates and gravity storage. In addition, a numerical model is used to simulate event based stormwater attenuation. This model is based off of the Richards equation and supporting theory of multiphase flow through porous media.

  3. The transcriptional coactivator PGC-1alpha is essential for maximal and efficient cardiac mitochondrial fatty acid oxidation and lipid homeostasis.

    Science.gov (United States)

    Lehman, John J; Boudina, Sihem; Banke, Natasha Hausler; Sambandam, Nandakumar; Han, Xianlin; Young, Deanna M; Leone, Teresa C; Gross, Richard W; Lewandowski, E Douglas; Abel, E Dale; Kelly, Daniel P

    2008-07-01

    High-capacity mitochondrial ATP production is essential for normal function of the adult heart, and evidence is emerging that mitochondrial derangements occur in common myocardial diseases. Previous overexpression studies have shown that the inducible transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is capable of activating postnatal cardiac myocyte mitochondrial biogenesis. Recently, we generated mice deficient in PGC-1alpha (PGC-1alpha(-/-) mice), which survive with modestly blunted postnatal cardiac growth. To determine if PGC-1alpha is essential for normal cardiac energy metabolic capacity, mitochondrial function experiments were performed on saponin-permeabilized myocardial fibers from PGC-1alpha(-/-) mice. These experiments demonstrated reduced maximal (state 3) palmitoyl-l-carnitine respiration and increased maximal (state 3) pyruvate respiration in PGC-1alpha(-/-) mice compared with PGC-1alpha(+/+) controls. ATP synthesis rates obtained during maximal (state 3) respiration in permeabilized myocardial fibers were reduced for PGC-1alpha(-/-) mice, whereas ATP produced per oxygen consumed (ATP/O), a measure of metabolic efficiency, was decreased by 58% for PGC-1alpha(-/-) fibers. Ex vivo isolated working heart experiments demonstrated that PGC-1alpha(-/-) mice exhibited lower cardiac power, reduced palmitate oxidation, and increased reliance on glucose oxidation, with the latter likely a compensatory response. (13)C NMR revealed that hearts from PGC-1alpha(-/-) mice exhibited a limited capacity to recruit triglyceride as a source for lipid oxidation during beta-adrenergic challenge. Consistent with reduced mitochondrial fatty acid oxidative enzyme gene expression, the total triglyceride content was greater in hearts of PGC-1alpha(-/-) mice relative to PGC-1alpha(+/+) following a fast. Overall, these results demonstrate that PGC-1alpha is essential for the maintenance of maximal, efficient cardiac

  4. Suppressor of IKKɛ is an essential negative regulator of pathological cardiac hypertrophy

    Science.gov (United States)

    Deng, Ke-Qiong; Wang, Aibing; Ji, Yan-Xiao; Zhang, Xiao-Jing; Fang, Jing; Zhang, Yan; Zhang, Peng; Jiang, Xi; Gao, Lu; Zhu, Xue-Yong; Zhao, Yichao; Gao, Lingchen; Yang, Qinglin; Zhu, Xue-Hai; Wei, Xiang; Pu, Jun; Li, Hongliang

    2016-01-01

    Although pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide, our understanding of the molecular mechanisms underlying this disease is still poor. Here, we demonstrate that suppressor of IKKɛ (SIKE), a negative regulator of the interferon pathway, attenuates pathological cardiac hypertrophy in rodents and non-human primates in a TANK-binding kinase 1 (TBK1)/AKT-dependent manner. Sike-deficient mice develop cardiac hypertrophy and heart failure, whereas Sike-overexpressing transgenic (Sike-TG) mice are protected from hypertrophic stimuli. Mechanistically, SIKE directly interacts with TBK1 to inhibit the TBK1-AKT signalling pathway, thereby achieving its anti-hypertrophic action. The suppression of cardiac remodelling by SIKE is further validated in rats and monkeys. Collectively, these findings identify SIKE as a negative regulator of cardiac remodelling in multiple animal species due to its inhibitory regulation of the TBK1/AKT axis, suggesting that SIKE may represent a therapeutic target for the treatment of cardiac hypertrophy and heart failure. PMID:27249321

  5. Cardiac Biomarkers in Hyperthyroid Cats

    OpenAIRE

    Sangster, Jodi Kirsten

    2013-01-01

    Background: Hyperthyroidism has substantial effects on the circulatory system. The cardiac biomarkers NT-proBNP and troponin I (cTNI) have proven useful in identifying cats with myocardial disease but have not been as extensively investigated in hyperthyroidism.Hypothesis: Plasma NT-proBNP and cTNI concentrations are higher in cats with primary cardiac disease than in cats with hyperthyroidism and higher in cats with hyperthyroidism than in healthy control cats.Animals: Twenty-three hyperthyr...

  6. Cardiac manifestations in systemic sclerosis

    Institute of Scientific and Technical Information of China (English)

    Sevdalina; Lambova

    2014-01-01

    Primary cardiac involvement, which develops as a direct consequence of systemic sclerosis(SSc), may manifest as myocardial damage, fibrosis of the conduction system, pericardial and, less frequently, as valvular disease. In addition, cardiac complications in SSc may develop as a secondary phenomenon due to pulmonary arterial hypertension and kidney pathology. The prevalence of primary cardiac involvement in SSc is variable and difficult to determine because of the diversity of cardiac manifestations, the presence of subclinical periods, the type of diagnostic tools applied, and the diversity of patient populations. When clinically manifested, cardiac involvement is thought to be an important prognostic factor. Profound microvascular disease is a pathognomonic feature of SSc, as both vasospasm and structural alterations are present. Such alterations are thought to predict macrovascular atherosclerosis over time. There are contradictory reports regarding the prevalence of atherosclerosis in SSc. According to some authors, the prevalence of atherosclerosis of the large epicardial coronary arteries is similar to that of the general population, in contrast with other rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the level of inflammation in SSc is inferior. Thus, the atherosclerotic process may not be as aggressive and not easily detectable in smaller studies. Echocardiography(especially tissue Doppler imaging), single-photon emission computed tomography, magnetic resonance imaging and cardiac computed tomography are sensitive techniques for earlier detection of both structural and functional scleroderma-related cardiac pathologies. Screening for subclinical cardiac involvement via modern, sensitive tools provides an opportunity for early diagnosis and treatment, which is of crucial importance for a positive outcome.

  7. Computational Modeling of Cardiac Electromechanics

    OpenAIRE

    Krishnamoorthi, Shankarjee

    2013-01-01

    Cardiac arrhythmias are a leading cause of death worldwide. Notably, the electrophysiologiy and microstructural requirements for a fatal ventricular arrhythmia remain incompletely understood, thereby the treatment remains largely empirical. Standard antiarrhythmic drug therapy has failed to reduce, and in some instances has increased, the incidence of Sudden Cardiac Death (SCD). Hence, a more complete understanding of the mechanisms that foment a fatal arrhythmia is needed and computational m...

  8. Current trends in cardiac rehabilitation

    OpenAIRE

    Dafoe, W; Huston, P

    1997-01-01

    Cardiac rehabilitation can reduce mortality and morbidity for patients with many types of cardiac disease cost-effectively, yet is generally underutilized. Rehabilitation is helpful not only for patients who have had a myocardial infarction but also for those with stable angina or congestive heart failure or those who have undergone myocardial revascularization procedures, a heart transplant or heart valve surgery. The beneficial effects of rehabilitation include a reduction in the rate of de...

  9. An overview of cardiac morphogenesis.

    OpenAIRE

    Schleich, Jean-Marc; Abdulla, Tariq; Summers, Ron; Houyel, Lucile

    2013-01-01

    International audience Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In th...

  10. Effects of glucagon and insulin on plasma glucose, triglyceride, and triglyceride-rich lipoprotein concentrations in laying hens fed diets containing different types of fats.

    Science.gov (United States)

    Pál, L; Grossmann, R; Dublecz, K; Husvéth, F; Wagner, L; Bartos, A; Kovács, G

    2002-11-01

    The influence of dietary fat supplementations differing in the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) on the effects of glucagon and insulin on plasma glucose, triglyceride (TG), and TG-rich lipoprotein concentrations was investigated in laying hens. Birds were fed either a low-fat control diet (LF) or diets supplemented with 4% pumpkin seed oil (PO; rich in n-6 PUFA) or 4% cod liver oil (CO; rich in n-3 PUFA). After 4 wk feeding of the experimental diets, hens were implanted with wing vein catheters and injected with porcine glucagon (20 microg/kg BW) and porcine insulin (0.5 IU/kg BW), 2 to 5 h after oviposition. Plasma glucose, TG, and TG-rich lipoprotein concentrations were determined from 10 min pre-injection to 60 min post-injection. PO diet resulted in a prolonged plasma glucose response to glucagon administration and altered hypoglycemic response to insulin. However, CO diet did not influence plasma glucose response to either glucagon or insulin administration compared to LF diet. The effects of glucagon and insulin on plasma TG and TG-rich lipoproteins were similar for all diets regardless of the amount or type of fat. The results suggest that feeding dietary fats with high n-6 to n-3 PUFA ratio alters the glucagon and insulin sensitivity of plasma glucose in laying hens. Fats rich in n-3 PUFA seem to have no influence on the plasma glucose response to glucagon and insulin. PMID:12455597

  11. Physiological and pathological cardiac hypertrophy.

    Science.gov (United States)

    Shimizu, Ippei; Minamino, Tohru

    2016-08-01

    The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy. PMID:27262674

  12. FGF21 and cardiac physiopathology

    Directory of Open Access Journals (Sweden)

    Anna ePlanavila

    2015-08-01

    Full Text Available The heart is not traditionally considered either a target or a site of fibroblast growth factor-21 (FGF21 production. However, recent findings indicate that FGF21 can act as a cardiomyokine; that is, it is produced by cardiac cells at significant levels and acts in an autocrine manner on the heart itself. The heart is sensitive to the effects of FGF21, both systemic and locally generated, owing to the expression in cardiomyocytes of β-Klotho, the key co-receptor known to confer specific responsiveness to FGF21 action. FGF21 has been demonstrated to protect against cardiac hypertrophy, cardiac inflammation, and oxidative stress. FGF21 expression in the heart is induced in response to cardiac insults, such as experimental cardiac hypertrophy and myocardial infarction in rodents, as well as in failing human hearts. Intracellular mechanisms involving PPARα and Sirt1 mediate transcriptional regulation of the FGF21 gene in response to exogenous stimuli. In humans, circulating FGF21 levels are elevated in coronary heart disease and atherosclerosis, and are associated with a higher risk of cardiovascular events in patients with type 2 diabetes. These findings provide new insights into the role of FGF21 in the heart and may offer potential therapeutic strategies for cardiac disease.

  13. [Stem cells and cardiac regeneration].

    Science.gov (United States)

    Perez Millan, Maria Ines; Lorenti, Alicia

    2006-01-01

    Stem cells are defined by virtue of their functional attributes: absence of tissue specific differentitated markers, capable of proliferation, able to self-maintain the population, able to produce a large number of differentiated, functional progeny, able to regenerate the tissue after injury. Cell therapy is an alternative for the treatment of several diseases, like cardiac diseases (cell cardiomyoplasty). A variety of stem cells could be used for cardiac repair: from cardiac and extracardiac sources. Each cell type has its own profile of advantages, limitations, and practicability issues in specific clinical settings. Differentiation of bone marrow stem cells to cardiomyocyte-like cells have been observed under different culture conditions. The presence of resident cardiac stem cell population capable of differentiation into cardiomyocyte or vascular lineage suggests that these cells could be used for cardiac tissue repair, and represent a great promise for clinical application. Stem cells mobilization by cytokines may also offer a strategy for cardiac regeneration. The use of stem cells (embryonic and adult) may hold the key to replacing cells lost in many devastating diseases. This potential benefit is a major focus for stem cell research.

  14. Cardiac Regeneration and Stem Cells.

    Science.gov (United States)

    Zhang, Yiqiang; Mignone, John; MacLellan, W Robb

    2015-10-01

    After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon-14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world.

  15. Cardiac involvement in myotonic dystrophy

    DEFF Research Database (Denmark)

    Lund, Marie; Diaz, Lars Jorge; Ranthe, Mattis Flyvholm;

    2014-01-01

    genetic testing for DM1. Information on incident cardiac diseases was obtained from the NPR. We estimated standardized incidence ratios (SIRs) of cardiac disease compared with the background population, overall and according to selected diagnostic subgroups (cardiomyopathy, heart failure, conduction...... disorders, arrhythmias, and device implantation). In the DM cohort, SIR for any cardiac disease was 3.42 [95% confidence interval (CI) 3.01-3.86]; for a cardiac disease belonging to the selected subgroups 6.91 (95% CI: 5.93-8.01) and for other cardiac disease 2.59 (95% CI: 2.03-3.25). For a cardiac disease...... belonging to the selected subgroups, the risk was particularly high in the first year after DM diagnosis [SIR 15.4 (95% CI: 10.9-21.3)] but remained significantly elevated in subsequent years [SIR 6.07 (95% CI: 5.11-7.16]). The risk was higher in young cohort members [e.g. 20-39 years: SIR 18.1 (95% CI: 12...

  16. Cardiac imaging. A multimodality approach

    Energy Technology Data Exchange (ETDEWEB)

    Thelen, Manfred [Johannes Gutenberg University Hospital, Mainz (Germany); Erbel, Raimund [University Hospital Essen (Germany). Dept. of Cardiology; Kreitner, Karl-Friedrich [Johannes Gutenberg University Hospital, Mainz (Germany). Clinic and Polyclinic for Diagnostic and Interventional Radiology; Barkhausen, Joerg (eds.) [University Hospital Schleswig-Holstein, Luebeck (Germany). Dept. of Radiology and Nuclear Medicine

    2009-07-01

    An excellent atlas on modern diagnostic imaging of the heart Written by an interdisciplinary team of experts, Cardiac Imaging: A Multimodality Approach features an in-depth introduction to all current imaging modalities for the diagnostic assessment of the heart as well as a clinical overview of cardiac diseases and main indications for cardiac imaging. With a particular emphasis on CT and MRI, the first part of the atlas also covers conventional radiography, echocardiography, angiography and nuclear medicine imaging. Leading specialists demonstrate the latest advances in the field, and compare the strengths and weaknesses of each modality. The book's second part features clinical chapters on heart defects, endocarditis, coronary heart disease, cardiomyopathies, myocarditis, cardiac tumors, pericardial diseases, pulmonary vascular diseases, and diseases of the thoracic aorta. The authors address anatomy, pathophysiology, and clinical features, and evaluate the various diagnostic options. Key features: - Highly regarded experts in cardiology and radiology off er image-based teaching of the latest techniques - Readers learn how to decide which modality to use for which indication - Visually highlighted tables and essential points allow for easy navigation through the text - More than 600 outstanding images show up-to-date technology and current imaging protocols Cardiac Imaging: A Multimodality Approach is a must-have desk reference for cardiologists and radiologists in practice, as well as a study guide for residents in both fields. It will also appeal to cardiac surgeons, general practitioners, and medical physicists with a special interest in imaging of the heart. (orig.)

  17. Two meals with different carbohydrate, fat and protein contents render equivalent postprandial plasma levels of calprotectin, cortisol, triglycerides and zonulin.

    Science.gov (United States)

    Ohlsson, Bodil; Darwiche, Gassan; Roth, Bodil; Höglund, Peter

    2016-11-01

    The aim was to compare postprandial plasma levels of calprotectin, cortisol, triglycerides and zonulin between a control breakfast and a moderately low-carbohydrate test breakfast, given randomly after 10-h fast. Blood samples were collected before and repeatedly after the meal. Plasma calprotectin, cortisol, triglycerides and zonulin were analyzed. The total area under the curve (tAUC) and change in AUC from baseline (dAUC) were calculated. Ratios between the test and control values were calculated to investigate equivalence. Healthy volunteers (8 men and 12 women; 46.0 ± 14.5 years) were included. tAUCs of cortisol and triglycerides did not differ between the breakfasts (p = 0.158 versus p = 0.579). Cortisol dAUCs were decreased and triglyceride dAUCs were increased after both breakfasts, with no differences between the breakfasts (p = 0.933 versus p = 0.277). Calprotectin and zonulin levels were unaffected. The meals were bioequivalent for cortisol, triglycerides and zonulin, but not for calprotectin.

  18. Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes.

    Science.gov (United States)

    Bezaire, Véronic; Mairal, Aline; Ribet, Carole; Lefort, Corinne; Girousse, Amandine; Jocken, Johan; Laurencikiene, Jurga; Anesia, Rodica; Rodriguez, Anne-Marie; Ryden, Mikael; Stenson, Britta M; Dani, Christian; Ailhaud, Gérard; Arner, Peter; Langin, Dominique

    2009-07-01

    Lipolysis is the catabolic pathway by which triglycerides are hydrolyzed into fatty acids. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) have the capacity to hydrolyze in vitro the first ester bond of triglycerides, but their respective contributions to whole cell lipolysis in human adipocytes is unclear. Here, we have investigated the roles of HSL, ATGL, and its coactivator CGI-58 in basal and forskolin-stimulated lipolysis in a human white adipocyte model, the hMADS cells. The hMADS adipocytes express the various components of fatty acid metabolism and show lipolytic capacity similar to primary cultured adipocytes. We show that lipolysis and fatty acid esterification are tightly coupled except in conditions of stimulated lipolysis. Immunocytochemistry experiments revealed that acute forskolin treatment promotes HSL translocation from the cytosol to small lipid droplets and redistribution of ATGL from the cytosol and large lipid droplets to small lipid droplets, resulting in enriched colocalization of the two lipases. HSL or ATGL overexpression resulted in increased triglyceride-specific hydrolase capacity, but only ATGL overexpression increased whole cell lipolysis. HSL silencing had no effect on basal lipolysis and only partially reduced forskolin-stimulated lipolysis. Conversely, silencing of ATGL or CGI-58 significantly reduced basal lipolysis and essentially abolished forskolin-stimulated lipolysis. Altogether, these results suggest that ATGL/CGI-58 acts independently of HSL and precedes its action in the sequential hydrolysis of triglycerides in human hMADS adipocytes. PMID:19433586

  19. Contribution of Adipose Triglyceride Lipase and Hormone-sensitive Lipase to Lipolysis in hMADS Adipocytes*

    Science.gov (United States)

    Bezaire, Véronic; Mairal, Aline; Ribet, Carole; Lefort, Corinne; Girousse, Amandine; Jocken, Johan; Laurencikiene, Jurga; Anesia, Rodica; Rodriguez, Anne-Marie; Ryden, Mikael; Stenson, Britta M.; Dani, Christian; Ailhaud, Gérard; Arner, Peter; Langin, Dominique

    2009-01-01

    Lipolysis is the catabolic pathway by which triglycerides are hydrolyzed into fatty acids. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) have the capacity to hydrolyze in vitro the first ester bond of triglycerides, but their respective contributions to whole cell lipolysis in human adipocytes is unclear. Here, we have investigated the roles of HSL, ATGL, and its coactivator CGI-58 in basal and forskolin-stimulated lipolysis in a human white adipocyte model, the hMADS cells. The hMADS adipocytes express the various components of fatty acid metabolism and show lipolytic capacity similar to primary cultured adipocytes. We show that lipolysis and fatty acid esterification are tightly coupled except in conditions of stimulated lipolysis. Immunocytochemistry experiments revealed that acute forskolin treatment promotes HSL translocation from the cytosol to small lipid droplets and redistribution of ATGL from the cytosol and large lipid droplets to small lipid droplets, resulting in enriched colocalization of the two lipases. HSL or ATGL overexpression resulted in increased triglyceride-specific hydrolase capacity, but only ATGL overexpression increased whole cell lipolysis. HSL silencing had no effect on basal lipolysis and only partially reduced forskolin-stimulated lipolysis. Conversely, silencing of ATGL or CGI-58 significantly reduced basal lipolysis and essentially abolished forskolin-stimulated lipolysis. Altogether, these results suggest that ATGL/CGI-58 acts independently of HSL and precedes its action in the sequential hydrolysis of triglycerides in human hMADS adipocytes. PMID:19433586

  20. Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D) interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy

    Science.gov (United States)

    Martin, Tamara P.; Hortigon-Vinagre, Maria P.; Findlay, Jane E.; Elliott, Christina; Currie, Susan; Baillie, George S.

    2014-01-01

    Phosphorylated heat shock protein 20 (HSP20) is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20–phosphodiesterase 4D (PDE4D) complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20–PDE4D interaction leads to attenuation of pathological cardiac remodelling. PMID:25426411

  1. Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy

    Directory of Open Access Journals (Sweden)

    Tamara P. Martin

    2014-01-01

    Full Text Available Phosphorylated heat shock protein 20 (HSP20 is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20–phosphodiesterase 4D (PDE4D complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20–PDE4D interaction leads to attenuation of pathological cardiac remodelling.

  2. Burn-Induced Organ Dysfunction: Vagus Nerve Stimulation Improves Cardiac Function

    OpenAIRE

    Niederbichler, Andreas D; Papst, Stephan; Claassen, Leif; Jokuszies, Andreas; Ipaktchi, Kyros; Reimers, Kerstin; Hirsch, Tobias; Steinstraesser, Lars; Kraft, Theresia; Vogt, Peter M.

    2010-01-01

    Introduction: Many studies have demonstrated the existence of an anti-inflammatory, parasympathetic pathway, termed as the inflammatory reflex. Burn-induced heart failure has been investigated in many previous studies. Proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6, have been shown to play a key pathogenetic role and vagus nerve stimulation attenuates proinflammatory cytokine production. This study was designed to evaluate postburn alterations of cardiac functional parameters after...

  3. Risk factors and the effect of cardiac resynchronization therapy on cardiac and non-cardiac mortality in MADIT-CRT

    DEFF Research Database (Denmark)

    Perkiomaki, Juha S; Ruwald, Anne-Christine; Kutyifa, Valentina;

    2015-01-01

    causes, 108 (63.9%) deemed cardiac, and 61 (36.1%) non-cardiac. In multivariate analysis, increased baseline creatinine was significantly associated with both cardiac and non-cardiac deaths [hazard ratio (HR) 2.97, P ...AIMS: To understand modes of death and factors associated with the risk for cardiac and non-cardiac deaths in patients with cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) vs. implantable cardioverter-defibrillator (ICD) therapy, which may help clarify...... the action and limitations of cardiac resynchronization therapy (CRT) in relieving myocardial dysfunction. METHODS AND RESULTS: In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), during 4 years of follow-up, 169 (9.3%) of 1820 patients died of known...

  4. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jie; Krausz, Kristopher W. [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Feng; Ma, Xiaochao [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Gonzalez, Frank J., E-mail: fjgonz@helix.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

  5. Incorporation of medium chain fatty acids into fish oil triglycerides by chemical and enzymatic interesterification

    Directory of Open Access Journals (Sweden)

    2009-06-01

    Full Text Available Structured triglycerides (STs containing both medium-chain fatty acids (MCFA and polyunsaturated fatty acids (PUFA in the same molecule offer nutritional and therapeutic benefits. The aim of this work was to establish the incorporation of MCFA into fish oil triglycerides (TAGs, while maintaining substantial levels of docosahexaenoic and eicosapentaenoic acids. The effects of different acyl donors (capric acid methyl ester/MeC10 or medium chain triglyceride/TCM and of the catalyst (chemical or enzymatic on the fatty acid composition of the reaction product were studied. The fatty acid composition of the fish oil TAG was modified after interesterification to contain MCFA, and it depended on the catalyst and on the substrates. Thermograms obtained by Differential Scanning Calorimetry (DSC showed that interesterification promoted noteworthy changes in the melting profile of the samples. STs of clinical nutrition interest containing both EPA and DHA obtained from fish oil along with MCFA were successfully produced.

    Triglicéridos estructurados (SL conteniendo ácidos grasos de cadena media (MCFA y ácidos grasos poliinsaturados (PUFA en la misma molécula de glicerol tienen ventajas nutricionales y terapéuticas. Se establece la incorporación de MCFA a los triglicéridos (TAGs de aceite de pescado, conservando un contenido considerable de ácidos docosahexaenóico (DHA y eicosapentaenóico (EPA. El efecto de diferentes acil donadores (éster metílico de ácido cáprico/MeC10 o triglicéridos de cadena media/TCM y de catalizador (químico o enzimático sobre la composición del producto de las reacciones fue estudiado. La composición de ácidos grasos de los TAGs del aceite de pescado fue modificada después de las reacciones para contener MCFA y dependió del catalizador y de los substratos. Los termogramas obtenidos por Calorimetría Diferencial de Barrido (DSC indicaron que la interesterificación provocó alteraciones considerables de

  6. Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat.

    Directory of Open Access Journals (Sweden)

    Miloslava Hodúlová

    Full Text Available The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8-13/strain and two progenitor strains SHR-Lx (n = 13 and BXH2/Cub (n = 18 were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG and cholesterol (C concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl. We have identified 14 loci (encompassing 1 to 65 genes on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b. Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant

  7. Cardiac output during exercise

    DEFF Research Database (Denmark)

    Siebenmann, C; Rasmussen, P.; Sørensen, H.;

    2015-01-01

    Several techniques assessing cardiac output (Q) during exercise are available. The extent to which the measurements obtained from each respective technique compares to one another, however, is unclear. We quantified Q simultaneously using four methods: the Fick method with blood obtained from...... the right atrium (Q(Fick-M)), Innocor (inert gas rebreathing; Q(Inn)), Physioflow (impedance cardiography; Q(Phys)), and Nexfin (pulse contour analysis; Q(Pulse)) in 12 male subjects during incremental cycling exercise to exhaustion in normoxia and hypoxia (FiO2  = 12%). While all four methods reported...... a progressive increase in Q with exercise intensity, the slopes of the Q/oxygen uptake (VO2) relationship differed by up to 50% between methods in both normoxia [4.9 ± 0.3, 3.9 ± 0.2, 6.0 ± 0.4, 4.8 ± 0.2 L/min per L/min (mean ± SE) for Q(Fick-M), Q(Inn), QP hys and Q(Pulse), respectively; P = 0...

  8. Strategies to reduce radiation dose in cardiac PET/CT

    Science.gov (United States)

    Wu, Tung Hsin; Wu, Nien-Yun; Wang, Shyh-Jen; Wu, Jay; S. P. Mok, Greta; Yang, Ching-Ching; Huang, Tzung-Chi

    2011-08-01

    Our aim was to investigate CT dose reduction strategies on a hybrid PET/CT scanner for cardiac applications.MaterialsImage quality and dose estimation of different CT scanning protocols for CT coronary angiography (CTCA), and CT-based attenuation correction for PET imaging were investigated. Fifteen patients underwent CTCA, perfusion PET imaging at rest and under stress, and FDG PET for myocardial viability. These patients were divided into three groups based on the CTCA technique performed: retrospectively gated helical (RGH), ECG tube current modulation (ETCM), and prospective gated axial (PGA) acquisitions. All emission images were corrected for photon attenuation using CT images obtained by default setting and an ultra-low dose CT (ULDCT) scan.ResultsRadiation dose in RGH technique was 22.2±4.0 mSv. It was reduced to 10.95±0.82 and 4.13±0.31 mSv using ETCM and PGA techniques, respectively. Radiation dose in CT transmission scan was reduced by 96.5% (from 4.53±0.5 to 0.16±0.01 mSv) when applying ULDCT as compared to the default CT. No significant difference in terms of image quality was found among various protocols.ConclusionThe proposed CT scanning strategies, i.e. ETCM or PGA for CTCA and ULDCT for PET attenuation correction, could reduce radiation dose up to 47% without degrading imaging quality in an integrated cardiac PET/CT coronary artery examination.

  9. Resistance to leptin action is the major determinant of hepatic triglyceride accumulation in vivo.

    Science.gov (United States)

    Fishman, Sigal; Muzumdar, Radhika H; Atzmon, Gil; Ma, Xiaohui; Yang, Xiaoman; Einstein, Francine H; Barzilai, Nir

    2007-01-01

    Impairment of both insulin and leptin action has been implicated in the pathogenesis of nonalcoholic fatty liver disease. By assessing hepatic triglyceride (TG) stores in response to modulation of leptin action (by leptin infusion), we attempted to determine whether leptin has the major role in hepatic TG accumulation. TG were markedly decreased (by 63%, Pvisceral fat removal (VF-). Enhancement of hepatic insulin action in old VF-rats was associated with reduced hepatic TG stores (by 64% Premoval in a genetically leptin-resistant model (Zucker Diabetic Fatty rats, ZDF). Only in this mode was exclusive improvement of hepatic insulin action by VF removal not associated with reduced hepatic TG stores, suggesting that improved hepatic insulin action is not necessary for modulation of hepatic TG stores. By dissociating action of leptin from that of insulin, we suggest that the failure of leptin action is the major physiological mechanism for hepatic steatosis. PMID:17099068

  10. Low fasting serum triglyceride level as a precocious marker of autoimmune disorders.

    Science.gov (United States)

    Iannello, Silvia; Cavaleri, Antonina; Milazzo, Paolina; Cantarella, Santi; Belfiore, Francesco

    2003-08-01

    The authors recently reported the occurrence of low fasting serum triglyceride (TG) and high free fatty acid (FFA) levels in idiopathic pulmonary fibrosis. TG estimation in diverse groups of patients with autoimmune disease or hyperactive immune response confirmed the occurrence of a similar decrease of TG. In some patients, serum FFA level was also evaluated. TG value in lean and obese patients was compared with that in lean (n = 108) and obese (n = 208) control subjects without autoimmune disease. In patients affected by autoimmune chronic thyroiditis with enhanced concentration of antithyroglobulin antibodies and without thyroidal failure (n = 24), lean and obese patients had reduced TG (-69/%, P autoimmune diseases (scleroderma, APECED [autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy], urticaria or urticarial vasculitis, Reiter or Sjogren syndromes, ulcerative colitis or Crohn's disease, multiple sclerosis or Guillain-Barré syndrome) (n = 14), decreased TG was also observed both in the lean and obese subjects (-59%, P autoimmunity or immune system hyperreactivity. PMID:14600656

  11. Comprehensive experiment-clinical biochemistry: determination of blood glucose and triglycerides in normal and diabetic rats.

    Science.gov (United States)

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a standard clinical biochemistry exercise. The students are not only exposed to techniques and equipment but are also inspired to think more about the biochemical mechanisms of diseases. When linked with lecture topics about the metabolism of carbohydrates and lipids, the students obtain a better understanding of the relevance of abnormal metabolism in relation to diseases. Such understanding provides a solid foundation for the medical students' future research and for other clinical applications.

  12. ENHANCEMENTS TO NATURAL ATTENUATION: SELECTED CASE STUDIES

    Energy Technology Data Exchange (ETDEWEB)

    Vangelas, K; W. H. Albright, W; E. S. Becvar, E; C. H. Benson, C; T. O. Early, T; E. Hood, E; P. M. Jardine, P; M. Lorah, M; E. Majche, E; D. Major, D; W. J. Waugh, W; G. Wein, G; O. R. West, O

    2007-05-15

    In 2003 the US Department of Energy (DOE) embarked on a project to explore an innovative approach to remediation of subsurface contaminant plumes that focused on introducing mechanisms for augmenting natural attenuation to achieve site closure. Termed enhanced attenuation (EA), this approach has drawn its inspiration from the concept of monitored natural attenuation (MNA).

  13. Determination of the triglyceride composition of avocado oil by high-performance liquid chromatography using a light-scattering detector.

    Science.gov (United States)

    Hierro, M T; Tomás, M C; Fernández-Martín, F; Santa-María, G

    1992-08-28

    The triglyceride composition of avocado oil was determined by high-performance liquid chromatography using a light-scattering detector. Two avocado varieties, Fuerte and Hass, were analysed, and the qualitative composition of each was found to be similar, though quantitative differences were detected. The triglyceride composition was predicted using a system of equations based on the relationship between log k' and the molecular variables equivalent carbon number, chain length and number of double bonds for each of the fatty acids in the glycerides. A total of 24 molecular species of triglycerides were identified. The chromatographic system used successfully separated the critical pairs OOO-LOS, PaPaO-LnPP and PaOO-LOP (O = olein; L = linolein; S = stearin; Pa = palmitolein; Ln = linolenin; P = palmitin). Detector response was found to have a linear relationship with the amount of sample injected over the injection range 10-70 micrograms.

  14. Attractancy toOryzaephilus surinamensis (L.), saw-toothed grain beetle, of extracts of carobs, some triglycerides, and related compounds.

    Science.gov (United States)

    O'Donnell, M J; Chambers, J; McFarland, S M

    1983-03-01

    A laboratory method has been devised for testing the attractancy of vapors to adultOryzaephilus surinamensis (L.). Of four solvent extracts prepared from pods of the carob tree [Ceratonia siliqua (L.)], all attractedO. surinamensis, but the least polar extract was the most active. Subdivision of extracts yielded a series of fractions, the most attractive of which contained a mixture of triglycerides with three or more double bonds per molecule. Twelve authentic triglycerides, either synthesized or purchased, elicited responses ranging from high to very low attractancy in a way which appeared to be related to the number, position, and geometrical shape of the double bonds in the molecules. By studying the response of the insects to five glyceride acids, three aldehydes, and three volatile fatty acids, it has been shown that it may be possible to explain the attractancy attributed to the triglycerides, which are involatile, in terms of the response to their volatile breakdown products.

  15. Impact of microemulsion inspired approaches on the formation and destabilisation mechanisms of triglyceride nanoemulsions.

    Science.gov (United States)

    Wooster, Tim J; Labbett, Deanne; Sanguansri, Peerasak; Andrews, Helen

    2016-02-01

    Even after 30+ years of research, there are still few examples of physically stable transparent nanoemulsions despite their high potential to revolutionise pharmaceutical, personal care, and food products. In this study, we examine how low-energy "microemulsion inspired" (co-solvent/co-surfactant) approaches impact the formation and destabilisation mechanisms of homogenised triglyceride nanoemulsions. The addition of n-alcohol co-solvents and Span 80 co-surfactants had two effects on nanoemulsion droplet diameter; a beneficial one that reduced droplet diameter from 120 to 50 nm and a deleterious one that caused destabilisation. The decrease in nanoemulsion droplet diameter facilitated by n-alcohols is thought to arise from changes in: (i) solvent quality near the interface and (ii) interface spontaneous curvature which dramatically reduce interfacial tension. The strength of this effect was magnified by n-alcohol partitioning behaviour and their tendency to associate with the headgroup of POE surfactants. Addition of an excess of n-alcohol led to nanoemulsion destabilisation, unusually for nanoemulsions, destabilisation was not via Ostwald ripening, instead coalescence was found to be the primary destabilisation mechanism. A rapid increase in nanoemulsion droplet growth rate with increasing n-alcohol content was observed for each n-alcohol. Such rapid changes in nanoemulsion instability with composition are reminiscent of PIC/PIT emulsions in the Winsor III region, whose instability has been described to be a function of the activation energy barrier to coalescence. The microemulsion inspired approaches developed in this work highlight a new general approach to the creation of transparent nanoemulsions, and are particularly advantageous for triglyceride oils which are inherently stable against Ostwald ripening. PMID:26620843

  16. Effect of synthetic dietary triglycerides: a novel research paradigm for nutrigenomics.

    Directory of Open Access Journals (Sweden)

    Linda M Sanderson

    Full Text Available BACKGROUND: The effect of dietary fats on human health and disease are likely mediated by changes in gene expression. Several transcription factors have been shown to respond to fatty acids, including SREBP-1c, NF-kappaB, RXRs, LXRs, FXR, HNF4alpha, and PPARs. However, it is unclear to what extent these transcription factors play a role in gene regulation by dietary fatty acids in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Here, we take advantage of a unique experimental design using synthetic triglycerides composed of one single fatty acid in combination with gene expression profiling to examine the effects of various individual dietary fatty acids on hepatic gene expression in mice. We observed that the number of significantly changed genes and the fold-induction of genes increased with increasing fatty acid chain length and degree of unsaturation. Importantly, almost every single gene regulated by dietary unsaturated fatty acids remained unaltered in mice lacking PPARalpha. In addition, the majority of genes regulated by unsaturated fatty acids, especially docosahexaenoic acid, were also regulated by the specific PPARalpha agonist WY14643. Excellent agreement was found between the effects of unsaturated fatty acids on mouse liver versus cultured rat hepatoma cells. Interestingly, using Nuclear Receptor PamChip(R Arrays, fatty acid- and WY14643-induced interactions between PPARalpha and coregulators were found to be highly similar, although several PPARalpha-coactivator interactions specific for WY14643 were identified. CONCLUSIONS/SIGNIFICANCE: We conclude that the effects of dietary unsaturated fatty acids on hepatic gene expression are almost entirely mediated by PPARalpha and mimic those of synthetic PPARalpha agonists in terms of regulation of target genes and molecular mechanism. Use of synthetic dietary triglycerides may provide a novel paradigm for nutrigenomics research.

  17. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Joel Walls; M.T. Taner; Gary Mavko; Jack Dvorkin

    2002-01-01

    In Section 1 of this first report we will describe the work we are doing to collect and analyze rock physics data for the purpose of modeling seismic attenuation from other measurable quantities such as porosity, water saturation, clay content and net stress. This work and other empirical methods to be presented later, will form the basis for ''Q pseudo-well modeling'' that is a key part of this project. In Section 2 of this report, we will show the fundamentals of a new method to extract Q, dispersion, and attenuation from field seismic data. The method is called Gabor-Morlet time-frequency decomposition. This technique has a number of advantages including greater stability and better time resolution than spectral ratio methods.

  18. Chlorine signal attenuation in concrete.

    Science.gov (United States)

    Naqvi, A A; Maslehuddin, M; ur-Rehman, Khateeb; Al-Amoudi, O S B

    2015-11-01

    The intensity of prompt gamma-ray was measured at various depths from chlorine-contaminated silica fume (SF) concrete slab concrete specimens using portable neutron generator-based prompt gamma-ray setup. The intensity of 6.11MeV chloride gamma-rays was measured from the chloride contaminated slab at distance of 15.25, 20.25, 25.25, 30.25 and 35.25cm from neutron target in a SF cement concrete slab specimens. Due to attenuation of thermal neutron flux and emitted gamma-ray intensity in SF cement concrete at various depths, the measured intensity of chlorine gamma-rays decreases non-linearly with increasing depth in concrete. A good agreement was noted between the experimental results and the results of Monte Carlo simulation. This study has provided useful experimental data for evaluating the chloride contamination in the SF concrete utilizing gamma-ray attenuation method.

  19. Effects of aerobic exercise training on cardiac renin-angiotensin system in an obese Zucker rat strain.

    Directory of Open Access Journals (Sweden)

    Diego Lopes Mendes Barretti

    Full Text Available OBJECTIVE: Obesity and renin angiotensin system (RAS hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain. METHODS: THE RATS WERE DIVIDED INTO THE FOLLOWING GROUPS: Lean Zucker rats (LZR; lean Zucker rats plus EXT (LZR+EXT; obese Zucker rats (OZR and obese Zucker rats plus EXT (OZR+EXT. EXT consisted of 10 weeks of 60-min swimming sessions, 5 days/week. At the end of the training protocol heart rate (HR, systolic blood pressure (SBP, cardiac hypertrophy (CH and function, local and systemic components of RAS were evaluated. Also, systemic glucose, triglycerides, total cholesterol and its LDL and HDL fractions were measured. RESULTS: The resting HR decreased (∼12% for both LZR+EXT and OZR+EXT. However, only the LZR+EXT reached significance (p<0.05, while a tendency was found for OZR versus OZR+EXT (p = 0.07. In addition, exercise reduced (57% triglycerides and (61% LDL in the OZR+EXT. The systemic angiotensin I-converting enzyme (ACE activity did not differ regardless of obesity and EXT, however, the OZR and OZR+EXT showed (66% and (42%, respectively, less angiotensin II (Ang II plasma concentration when compared with LZR. Furthermore, the results showed that EXT in the OZR prevented increase in CH, cardiac ACE activity, Ang II and AT2 receptor caused by obesity. In addition, exercise augmented cardiac ACE2 in both training groups. CONCLUSION: Despite the unchanged ACE and lower systemic Ang II levels in obesity, the cardiac RAS was increased in OZR and EXT in obese Zucker rats reduced some of the cardiac RAS components and prevented obesity-related CH. These results show that EXT prevented the heart RAS hyperactivity and cardiac maladaptive morphological alterations in obese Zucker rats.

  20. Apolipoprotein AV Accelerates Plasma Hydrolysis OfTriglyceride-Rich Lipoproteins By Interaction With Proteoglycan BoundLipoprotein Lipase

    Energy Technology Data Exchange (ETDEWEB)

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A.; Laatsch, Alexander; Heeren, Joerg

    2005-02-22

    Apolipoprotein A5 (APOA5) is associated with differences intriglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasmatriglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In hAPOA5 transgenic mice(hAPOA5tr), catabolism of chylomicrons and VLDL was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL).Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by crossbreeding a human LPL transgene with the apoa5 knockout, and the hAPOA5tr to an LPL deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5 deficient mice,however, over expression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr HDL, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line.A direct interaction between LPL and apoAV was found by ligand blotting.It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycans bound LPL for lipolysis.

  1. Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice

    Institute of Scientific and Technical Information of China (English)

    Jian Wang; Dawei Zhan; Lagabaiyila Zha; Yang Cao; Zhenhua Li; Xuan Cheng; Youyi Zhang; XiaoYang; Yao Song; Yan Zhang; Han Xiao; Qiang Sun; Ning Hou; Shuilong Guo; Youliang Wang; Kaiji Fan

    2012-01-01

    Recent studies have begun to reveal critical roles of microRNAs(miRNAs)in the pathogenesis of cardiac hypertrophy and dysfunction.In this study,we tested whether a transforming growth factor-β(TGF-β)-regulated miRNA played a pivotal role in the development of cardiac hypertrophy and heart failure(HF).We observed that miR-27b was upregulated in hearts of cardiomyocyte-specific Smad4 knockout mice,which developed cardiac hypertrophy.In vitro experiments showed that the miR-27b expression could be inhibited by TGF-β1 and that its overexpression promoted hypertrophic cell growth,while the miR-27b suppression led to inhibition of the hypertrophic cell growth caused by phenylephrine(PE)treatment.Furthermore,the analysis of transgenic mice with cardiomyocyte-specific overexpression of miR-27b revealed that miR-27b overexpression was sufficient to induce cardiac hypertrophy and dysfunction.We validated the peroxisome proliferator-activated receptor-γ(PPAR-γ)as a direct target of miR-27b in cardiomyocyte.Consistently,the miR-27b transgenic mice displayed significantly lower levels of PPAR-γ than the control mice.Furthermore,in vivo silencing of miR-27b using a specific antagomir in a pressure-overload-induced mouse model of HF increased cardiac PPAR-γ expression,attenuated cardiac hypertrophy and dysfunction.The results of our study demonstrate that TGF-β1-regulated miR-27b is involved in the regulation of cardiac hypertrophy,and validate miR-27b as an efficient therapeutic target for cardiac diseases.

  2. Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction by Increasing Interleukin 10

    Directory of Open Access Journals (Sweden)

    Varun eKesherwani

    2015-04-01

    Full Text Available Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α and attenuation of anti-inflammatory cytokine such as interleukin10 (IL-10 contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, eight week old, female C57BL/6J mice were fed with HFD and exercised (swimming 1hr/day for 5 days/week for eight weeks. The four treatment groups: normal diet (ND, HFD, HFD + exercise (HFD + Ex and ND + Ex were analyzed for mean body weight, blood glucose level, TNF-α, IL-10, cardiac fibrosis by Masson Trichrome, and cardiac dysfunction by echocardiography. Mean body weights were increased in HFD but comparatively less in HFD + Ex. The level of TNF-α was elevated and IL-10 was downregulated in HFD but ameliorated in HFD + Ex. Cardiac fibrosis increased in HFD and was attenuated by exercise in the HFD + Ex group. The percentage ejection fraction and fractional shortening were decreased in HFD but comparatively increased in HFD + Ex. There was no difference between ND and ND + Ex for the above parameters except an increase in IL-10 level following exercise. Based on these results, we conclude that exercise mitigates HFD- induced cardiomyopathy by decreasing obesity, inducing IL-10, and reducing TNF-α in mice.

  3. Mechanisms of geometrical seismic attenuation

    Directory of Open Access Journals (Sweden)

    Igor B. Morozov

    2011-07-01

    Full Text Available In several recent reports, we have explained the frequency dependence of the apparent seismic quality-factor (Q observed in many studies according to the effects of geometrical attenuation, which was defined as the zero-frequency limit of the temporal attenuation coefficient. In particular, geometrical attenuation was found to be positive for most waves traveling within the lithosphere. Here, we present three theoretical models that illustrate the origin of this geometrical attenuation, and we investigate the causes of its preferential positive values. In addition, we discuss the physical basis and limitations of both the conventional and new attenuation models. For waves in media with slowly varying properties, geometrical attenuation is caused by variations in the wavefront curvature, which can be both positive (for defocusing and negative (for focusing. In media with velocity/density contrasts, incoherent reflectivity leads to geometrical-attenuation coefficients which are proportional to the mean squared reflectivity and are always positive. For «coherent» reflectivity, the geometrical attenuation is approximately zero, and the attenuation process can be described according to the concept of «scattering Q». However, the true meaning of this parameter is in describing the mean reflectivity within the medium, and not that of the traditional resonator quality factor known in mechanics. The general conclusion from these models is that non-zero and often positive levels of geometrical attenuation are common in realistic, heterogeneous media, both observationally and theoretically. When transformed into the conventional Q-factor form, this positive geometrical attenuation leads to Q values that quickly increase with frequency. These predictions show that the positive frequency-dependent Q observed in many datasets might represent artifacts of the transformations of the attenuation coefficients into Q.

  1. Electrophysiological Cardiac Modeling: A Review.

    Science.gov (United States)

    Beheshti, Mohammadali; Umapathy, Karthikeyan; Krishnan, Sridhar

    2016-01-01

    Cardiac electrophysiological modeling in conjunction with experimental and clinical findings has contributed to better understanding of electrophysiological phenomena in various species. As our knowledge on underlying electrical, mechanical, and chemical processes has improved over time, mathematical models of the cardiac electrophysiology have become more realistic and detailed. These models have provided a testbed for various hypotheses and conditions that may not be easy to implement experimentally. In addition to the limitations in experimentally validating various scenarios implemented by the models, one of the major obstacles for these models is computational complexity. However, the ever-increasing computational power of supercomputers facilitates the clinical application of cardiac electrophysiological models. The potential clinical applications include testing and predicting effects of pharmaceutical agents and performing patient-specific ablation and defibrillation. A review of studies involving these models and their major findings are provided.

  2. Complications after cardiac implantable electronic device implantations

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nohr, Ellen Aagaard;

    2013-01-01

    Complications after cardiac implantable electronic device (CIED) treatment, including permanent pacemakers (PMs), cardiac resynchronization therapy devices with defibrillators (CRT-Ds) or without (CRT-Ps), and implantable cardioverter defibrillators (ICDs), are associated with increased patient...

  3. Sudden Cardiac Arrest (SCA) Risk Assessment

    Science.gov (United States)

    ... Find a Specialist Share Twitter Facebook SCA Risk Assessment Sudden Cardiac Arrest (SCA) occurs abruptly and without ... of all ages and health conditions. Start Risk Assessment The Sudden Cardiac Arrest (SCA) Risk Assessment Tool ...

  4. An update on insertable cardiac monitors

    DEFF Research Database (Denmark)

    Olsen, Flemming J; Biering-Sørensen, Tor; Krieger, Derk W

    2015-01-01

    Continuous cardiac rhythm monitoring has undergone compelling progress over the past decades. Cardiac monitoring has emerged from 12-lead electrocardiograms being performed at the discretion of the treating physician to in-hospital telemetry, Holter monitoring, prolonged external event monitoring...

  5. Elevated sensitivity to cardiac ischemia in proteinuric rats is independent of adverse cardiac remodeling

    NARCIS (Netherlands)

    Szymanski, Mariusz K.; Hillege, Hans L.; Danser, A. H. Jan; Garrelds, Ingrid M.; Schoemaker, Regien G.

    2013-01-01

    Objectives: Chronic renal dysfunction severely increases cardiovascular risk. Adverse cardiac remodeling is suggested to play a major role as predisposition for increased cardiac ischemic vulnerability. The aim of the present study was to examine the role of adverse cardiac remodeling in cardiac sen

  6. Apolipoprotein A-V, triglycerides and risk of coronary artery disease : the prospective Epic-Norfolk Population Study

    NARCIS (Netherlands)

    Vaessen, Stefan F C; Schaap, Frank G; Kuivenhoven, Jan-Albert; Groen, Albert K; Hutten, Barbara A; Boekholdt, S Matthijs; Hattori, Hiroaki; Sandhu, Manjinder S; Bingham, Sheila A; Luben, Robert; Palmen, Jutta A; Wareham, Nicholas J; Humphries, Steve E; Kastelein, John J P; Talmud, Philippa J; Khaw, Kay-Tee

    2006-01-01

    In mouse models, apolipoprotein A-V (apoA-V) exhibits triglyceride (TG)-lowering effects. We investigated the apoA-V/TG relationship and the association of apoA-V with coronary artery disease (CAD) risk by determining serum apoA-V levels and genotypes in a nested case-control (n = 1,034/2,031) study

  7. Developmental, hormonal, and nutritional regulation of expression of porcine adipose tissue triglyceride lipase (pATGL) gene

    Science.gov (United States)

    Adipose triglyceride lipase (ATGL) is a newly identified lipase. We report for the first time the porcine ATGL sequence and characterize ATGL gene and protein expression in vitro and in vivo. Adult pig tissue expresses ATGL at high levels in the white adipose and muscle tissue relative to other te...

  8. Efficient lowering of triglyceride levels in mice by human apoAV protein variants associated with hypertriglyceridemia

    NARCIS (Netherlands)

    Vaessen, Stefan F C; Sierts, Jeroen A; Kuivenhoven, Jan Albert; Schaap, Frank G

    2009-01-01

    Variation in the apolipoprotein A5 (APOA5) gene has consistently been associated with increased plasma triglyceride (TG) levels in epidemiological studies. In vivo functionality of these variations, however, has thus far not been tested. Using adenoviral over-expression, we evaluated plasma expressi

  9. Triglycerides, fatty acids, sterols, mono- and disaccharides and sugar alcohols in human milk and current types of infant formula milk

    NARCIS (Netherlands)

    Huisman, M; vanBeusekom, CM; Nijeboer, HJ; Muskiet, FAJ; Boersma, ER

    1996-01-01

    Objective: To investigate differences in the fatty acid composition, sterols, minor carbohydrates and sugar alcohols between human and formula milk. Design: We analyzed the concentrations of triglycerides, sterols, di- and monosaccharides and sugar alcohols, as well as the fatty acid composition of

  10. CD1d-mediated presentation of endogenous lipid antigens by adipocytes requires microsomal triglyceride transfer protein (MTP)

    DEFF Research Database (Denmark)

    Rakhshandehroo, Maryam; Gijzel, Sanne M W; Siersbæk, Rasmus;

    2014-01-01

    microsomal triglyceride transfer protein (MTP), which we show is also under the transcriptional regulation of C/EBPβ and -δ, as a novel player in the presentation of endogenous lipid antigens by adipocytes. Overall, our findings indicate that adipocytes can function as non-professional lipid antigen...

  11. Hypothalamic neuropeptide Y (NPY) controls hepatic VLDL-triglyceride secretion in rats via the sympathetic nervous system

    NARCIS (Netherlands)

    Bruinstroop, E.; Pei, L.; Ackermans, M.T.; Foppen, E.; Borgers, A.J.F.; Kwakkel, J.; Alkemade, A.; Fliers, E.; Kalsbeek, A.

    2012-01-01

    Excessive secretion of triglyceride-rich very low-density lipoproteins (VLDL-TG) contributes to diabetic dyslipidemia. Earlier studies have indicated a possible role for the hypothalamus and autonomic nervous system in the regulation of VLDL-TG. In the current study, we investigated whether the auto

  12. Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-01-01

    To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance...

  13. [Cardiac output monitoring by impedance cardiography in cardiac surgery].

    Science.gov (United States)

    Shimizu, H; Seki, S; Mizuguchi, A; Tsuchida, H; Watanabe, H; Namiki, A

    1990-04-01

    The cardiac output monitoring by impedance cardiography, NCCOM3, was evaluated in adult patients (n = 12) who were subjected to coronary artery bypass grafting. Values of cardiac output measured by impedance cardiography were compared to those by the thermodilution method. Changes of base impedance level used as an index of thoracic fluid volume were also investigated before and after cardiopulmonary bypass (CPB). Correlation coefficient (r) of the values obtained by thermodilution with impedance cardiography was 0.79 and the mean difference was 1.29 +/- 16.9 (SD)% during induction of anesthesia. During the operation, r was 0.83 and the mean difference was -14.6 +/- 18.7%. The measurement by impedance cardiography could be carried out through the operation except when electro-cautery was used. Base impedance level before CPB was significantly lower as compared with that after CPB. There was a negative correlation between the base impedance level and central venous pressure (CVP). No patients showed any signs suggesting lung edema and all the values of CVP, pulmonary artery pressure and blood gas analysis were within normal ranges. From the result of this study, it was concluded that cardiac output monitoring by impedance cardiography was useful in cardiac surgery, but further detailed examinations will be necessary on the relationship between the numerical values of base impedance and the clinical state of the patients. PMID:2362347

  14. Health Literacy Predicts Cardiac Knowledge Gains in Cardiac Rehabilitation Participants

    Science.gov (United States)

    Mattson, Colleen C.; Rawson, Katherine; Hughes, Joel W.; Waechter, Donna; Rosneck, James

    2015-01-01

    Objective: Health literacy is increasingly recognised as a potentially important patient characteristic related to patient education efforts. We evaluated whether health literacy would predict gains in knowledge after completion of patient education in cardiac rehabilitation. Method: This was a re-post observational analysis study design based on…

  15. Regulation of Cardiac Hypertrophy: the nuclear option

    OpenAIRE

    Kuster, Diederik

    2011-01-01

    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, cardiac hypertrophy is an independent risk factor for the development of heart failure and is therefore called pathological hypertrophy. That hypertrophy is not bad per se, is illustrated by the hyp...

  16. Protein kinase C betaII peptide inhibitor exerts cardioprotective effects in rat cardiac ischemia/reperfusion injury.

    Science.gov (United States)

    Omiyi, Didi; Brue, Richard J; Taormina, Philip; Harvey, Margaret; Atkinson, Norrell; Young, Lindon H

    2005-08-01

    Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. A cell-permeable protein kinase C (PKC) betaII peptide inhibitor was used to test the hypothesis that PKC betaII inhibition could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs and increase NO release from vascular endothelium. The effects of the PKC betaII peptide inhibitor were examined in isolated ischemic (20 min) and reperfused (45 min) rat hearts with PMNs. The PKC betaII inhibitor (10 microM; n = 7) significantly attenuated PMN-induced cardiac dysfunction compared with I/R hearts (n = 9) receiving PMNs alone in left ventricular developed pressure (LVDP) and the maximal rate of LVDP (+dP/dt(max)) cardiac function indices (p < 0.01). The PKC betaII inhibitor at 10 microM significantly increased endothelial NO release from a basal value of 1.85 +/- 0.18 pmol NO/mg tissue to 3.49 +/- 0.62 pmol NO/mg tissue from rat aorta. It also significantly inhibited superoxide release (i.e., absorbance) from N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated rat PMNs from 0.13 +/- 0.01 to 0.02 +/- 0.004 (p < 0.01) at 10 microM. Histological analysis of the left ventricle of representative rat hearts from each group showed that the PKC betaII peptide inhibitor-treated hearts experienced a marked reduction in PMN vascular adherence and infiltration into the postreperfused cardiac tissue compared with I/R + PMN hearts (p < 0.01). These results suggest that the PKC betaII peptide inhibitor attenuates PMN-induced post-I/R cardiac contractile dysfunction by increasing endothelial NO release and by inhibiting superoxide release from PMNs. PMID:15878997

  17. Ultra high efficiency/low pressure supercritical fluid chromatography with superficially porous particles for triglyceride separation.

    Science.gov (United States)

    Lesellier, E; Latos, A; de Oliveira, A Lopes

    2014-01-31

    This paper reports the development of the separation of vegetable oil triglycerides (TG) in supercritical chromatography (SFC), using superficially porous particles (SPPs). The SPP, having a small diameter (2-3μm), provide a higher theoretical plate number (N), which allows to improve separation of critical pairs of compounds. However, compared to fully porous particles of larger diameter (5μm), the pressure drop is also increased. Fortunately, supercritical fluids have a low viscosity, which allows coupling several columns to achieve high N values, while maintaining flow rate above 1ml/min, ensuring a ultra high efficiency (UHE) at low pressure (LP) (below 40MPa), with regards to the one reached with liquid and sub-two micron particles (around 100MPa). The use of two detector systems (UV and ELSD) connected in series to the UHE-LP-SFC system provides complementary responses, due to their specific detection principles. Working in a first part with three coupled Kinetex C18 columns (45cm total length), the effect of modifier nature and percentage were studied with two reference oils, argan and rapeseed, chosen for their different and well-known TG composition. The analytical method was developed from previous studies performed with fully porous particles (FPP). Optimized conditions with three Kinetex were as follows: 17°C, 12% of ACN/MeOH (90/10; v/v). With these conditions, and by using an increased length of Kinetex C18 column (60cm), another additional column was selected from ten different commercial SPP C18 bonded phases, by applying a Derringer function on varied parameters: theoretical plate number (TPN), separation index (SI) for critical pairs of peaks (the peaks of compounds difficult to separate due to subtle structural differences), the analysis duration, and the total peak number. This function normalizes the values of any parameters, between 0 and 1, from the worst value to the better, allowing to take account of various parameters in the final

  18. Ultra high efficiency/low pressure supercritical fluid chromatography with superficially porous particles for triglyceride separation.

    Science.gov (United States)

    Lesellier, E; Latos, A; de Oliveira, A Lopes

    2014-01-31

    This paper reports the development of the separation of vegetable oil triglycerides (TG) in supercritical chromatography (SFC), using superficially porous particles (SPPs). The SPP, having a small diameter (2-3μm), provide a higher theoretical plate number (N), which allows to improve separation of critical pairs of compounds. However, compared to fully porous particles of larger diameter (5μm), the pressure drop is also increased. Fortunately, supercritical fluids have a low viscosity, which allows coupling several columns to achieve high N values, while maintaining flow rate above 1ml/min, ensuring a ultra high efficiency (UHE) at low pressure (LP) (below 40MPa), with regards to the one reached with liquid and sub-two micron particles (around 100MPa). The use of two detector systems (UV and ELSD) connected in series to the UHE-LP-SFC system provides complementary responses, due to their specific detection principles. Working in a first part with three coupled Kinetex C18 columns (45cm total length), the effect of modifier nature and percentage were studied with two reference oils, argan and rapeseed, chosen for their different and well-known TG composition. The analytical method was developed from previous studies performed with fully porous particles (FPP). Optimized conditions with three Kinetex were as follows: 17°C, 12% of ACN/MeOH (90/10; v/v). With these conditions, and by using an increased length of Kinetex C18 column (60cm), another additional column was selected from ten different commercial SPP C18 bonded phases, by applying a Derringer function on varied parameters: theoretical plate number (TPN), separation index (SI) for critical pairs of peaks (the peaks of compounds difficult to separate due to subtle structural differences), the analysis duration, and the total peak number. This function normalizes the values of any parameters, between 0 and 1, from the worst value to the better, allowing to take account of various parameters in the final

  19. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels

    Directory of Open Access Journals (Sweden)

    Md. Ibrahim Khalil

    2015-01-01

    Full Text Available The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO- induced myocardial infarction (MI in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI, triglycerides (TG, total cholesterol (TC, lipid peroxidation (LPO products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40 were pretreated orally with Tualang honey (3 g/kg/day for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB, lactate dehydrogenase (LDH, and aspartate transaminase (AST, cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO products (TBARS and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST. Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

  20. Imaging Rayleigh wave attenuation with USArray

    Science.gov (United States)

    Bao, Xueyang; Dalton, Colleen A.; Jin, Ge; Gaherty, James B.; Shen, Yang

    2016-07-01

    The EarthScope USArray provides an opportunity to obtain detailed images of the continental upper mantle at an unprecedented scale. The majority of mantle models derived from USArray data to date contain spatial variations in seismic-wave speed; however, in many cases these data sets do not by themselves allow a non-unique interpretation. Joint interpretation of seismic attenuation and velocity models can improve upon the interpretations based only on velocity and provide important constraints on the temperature, composition, melt content, and volatile content of the mantle. The surface wave amplitudes that constrain upper-mantle attenuation are sensitive to factors in addition to attenuation, including the earthquake source excitation, focusing and defocusing by elastic structure, and local site amplification. Because of the difficulty of isolating attenuation from these other factors, little is known about the attenuation structure of the North American upper mantle. In this study, Rayleigh wave traveltime and amplitude in the period range 25-100 s are measured using an interstation cross-correlation technique, which takes advantage of waveform similarity at nearby stations. Several estimates of Rayleigh wave attenuation and site amplification are generated at each period, using different approaches to separate the effects of attenuation and local site amplification on amplitude. It is assumed that focusing and defocusing effects can be described by the Laplacian of the traveltime field. All approaches identify the same large-scale patterns in attenuation, including areas where the attenuation values are likely contaminated by unmodelled focusing and defocusing effects. Regionally averaged attenuation maps are constructed after removal of the contaminated attenuation values, and the variations in intrinsic shear attenuation that are suggested by these Rayleigh wave attenuation maps are explored.