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Sample records for pretreatment protects myocardium

  1. Protective effect of pretreatment with the calcium antagonist anipamil on the ischemic-reperfused rat myocardium: a phosphorus-31 nuclear magnetic resonance study

    SciTech Connect

    Kirkels, J.H.; Ruigrok, T.J.; Van Echteld, C.J.; Meijler, F.L.

    1988-05-01

    To assess whether the prophylactic administration of anipamil, a new calcium antagonist, protects the heart against the effects of ischemia and reperfusion, rats were injected intraperitoneally twice daily for 5 days with 5 mg/kg body weight of this drug. The heart was then isolated and perfused by the Langendorff technique. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to monitor myocardial energy metabolism and intracellular pH during control perfusion and 30 min of total ischemia (37/sup 0/C), followed by 30 min of reperfusion. Pretreatment with anipamil altered neither left ventricular developed pressure under normoxic conditions nor the rate and extent of depletion of adenosine triphosphate (ATP) and creatine phosphate during ischemia. Intracellular acidification, however, was attenuated. On reperfusion, hearts from anipamil-pretreated animals recovered significantly better than untreated hearts with respect to replenishment of ATP and creatine phosphate stores, restitution of low levels of intracellular inorganic phosphate and recovery of left ventricular function and coronary flow. Intracellular pH recovered rapidly to preischemic levels, whereas in untreated hearts a complex intracellular inorganic phosphate peak indicated the existence of areas of different pH within the myocardium. It is concluded that anipamil pretreatment protects the heart against some of the deleterious effects of ischemia and reperfusion. Because this protection occurred in the absence of a negative inotropic effect during normoxia, it cannot be attributed to an energy-sparing effect during ischemia. Therefore, alternative mechanisms of action are to be considered.

  2. Coenzyme Q10 protects ischemic myocardium in an open-chest swine model.

    PubMed

    Atar, D; Mortensen, S A; Flachs, H; Herzog, W R

    1993-01-01

    Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion, may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this study was to test the hypothesis that pretreatment with coenzyme Q10 (ubiquinone), believed to act as a free radical scavenger, reduces myocardial stunning in a porcine model. Twelve swine were randomized to receive either oral supplementation with coenzyme Q10 or placebo for 20 days. A normothermic open-chest model was used with short occlusion (8 min) of the distal left descending coronary artery followed by reperfusion. Regional contractile function was measured with epicardial Doppler crystals in ischemic and nonischemic segments by measuring thickening fraction of the left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility until return to baseline. Coenzyme Q10 concentrations were measured in blood and homogenized myocardial tissue by high performance liquid chromatography. Plasma levels of reduced coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations, however, did not show any changes (mean 0.79 micrograms/mg dry weight versus 0.74 micrograms/mg). Stunning time was significantly reduced in coenzyme Q10 pretreated animals (13.7 +/- 7.7 min versus 32.8 +/- 3.1 min, P < 0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated by a humoral rather than intracellular mechanism. PMID:8241692

  3. Activation of Notch-Mediated Protective Signaling in the Myocardium

    PubMed Central

    Gude, Natalie A.; Emmanuel, Gregory; Wu, Weitao; Cottage, Christopher T.; Fischer, Kimberlee; Quijada, Pearl; Muraski, John A.; Alvarez, Roberto; Rubio, Marta; Schaefer, Eric; Sussman, Mark A.

    2013-01-01

    The Notch network regulates multiple cellular processes, including cell fate determination, development, differentiation, proliferation, apoptosis, and regeneration. These processes are regulated via Notch-mediated activity that involves hepatocyte growth factor (HGF)/c-Met receptor and phosphatidylinositol 3-kinase/Akt signaling cascades. The impact of HGF on Notch signaling was assessed following myocardial infarction as well as in cultured cardiomyocytes. Notch1 is activated in border zone cardiomyocytes coincident with nuclear c-Met following infarction. Intramyocardial injection of HGF enhances Notch1 and Akt activation in adult mouse myocardium. Corroborating evidence in cultured cardiomyocytes shows treatment with HGF or insulin increases levels of Notch effector Hes1 in immunoblots, whereas overexpression of activated Notch intracellular domain prompts a 3-fold increase in phosphorylated Akt. Infarcted hearts injected with adenoviral vector expressing Notch intracellular domain treatment exhibit improved hemodynamic function in comparison with control mice after 4 weeks, implicating Notch signaling in a cardioprotective role following cardiac injury. These results indicate Notch activation in cardiomyocytes is mediated through c-Met and Akt survival signaling pathways, and Notch1 signaling in turn enhances Akt activity. This mutually supportive crosstalk suggests a positive survival feedback mechanism between Notch and Akt signaling in adult myocardium following injury. PMID:18369158

  4. Ghrelin protects infarcted myocardium by induction of autophagy and AMP-activated protein kinase pathway.

    PubMed

    Yuan, Ming-Jie; Kong, Bin; Wang, Tao; Wang, Xin; Huang, He; Maghsoudi, Taneen

    2016-08-01

    The majority of studies have reported that enhancing autophagy in the myocardium is cardioprotective. Here, we tested the hypothesis that ghrelin, a growth hormone-releasing peptide, will protect infarcted myocardium by inducing of autophagy. Myocardial infarction was induced in mice by left coronary artery ligation the surviving mice 24 h after surgical were started on 2 week treatments with one of the following: vehicle, acylated ghrelin(50 mg/kg per day) or acylated ghrelin plus 3-MA(an autophagy inhibitor, 15 mg/kg, per day). We found that ghrelin significantly improved the cardiac function, and autophagy was enhanced by elevated LC3-II/LC-I ratio and mRNA expression of autophagy related protein. In vitro, cultured neonatal rat ventricular cardiomyocytes were subjected to simulate ischemia/reperfusion, 3-MA significantly attenuated ghrelin-induced autophagy, which was associated with activated AMP-activated protein kinase (AMPK) signal pathway. Moreover, ghrelin reduced cell death, and RNAi-mediated knockdown of autophagy protein 5 (Atg5) partly abolished ghrelin's cardioprotective effect. It is the first time to demonstrate that the cardioprotective effect of ghrelin on ischemia myocardium in part through regulating of autophagy signal pathway. PMID:27235554

  5. Salusins protect myocardium against ischemic injury by alleviating endoplasmic reticulum stress.

    PubMed

    Wang, Jianfei; Wang, Yin; Shan, Shifu; Hu, Tiantian; Chen, Huyan; Tian, Jing; Ren, Anjing; Zhou, Xu; Yuan, Wenjun; Lin, Li

    2012-04-01

    Salusins are regulatory peptides that affect cardiovascular function. We previously reported that salusin-α and -β protected cultured cardiomyocytes from serum deprivation-induced cell death through upregulating glucose-regulated protein 78 (GRP78), an endoplasmic reticulum (ER) resident protein whose overexpression acts as a marker and suppressor of ER stress. The present study examined whether salusin-α and -β inhibit ER stress in ischemic myocardium. In a rat model of myocardial infarction created by ligating the left anterior descending coronary artery (LAD), salusin-α or -β was intravenously injected at 5 or 15 nmol kg(-1) 15 min prior to 2 h of LAD occlusion. The high dose of salusin-α and -β significantly improved heart function and hemodynamics in LAD-occluded rats, but had no effects in sham-operated rats. The arrhythmias caused by LAD occlusion were markedly attenuated by salusin-α and -β. The apoptotic rate in ischemic myocardium was reduced from 31.5%±3.7% to 19.8%±2.2% and 12.3%±2.2%, and the infarct size was reduced from 53.4%±4.0% of the risk area to 26.5%±9.7% and 23.7%±8.9% by 15 nmol kg(-1) salusin-α and -β, respectively. Furthermore, salusin-α and -β prevented the activation of GRP78 and ER stress-specific apoptotic effectors caspase-12 and CHOP (C/EBP homologous protein), and attenuated the reduction of an ER stress-associated antiapoptotic protein Bcl-2 in ischemic cardiac tissue. The salusins also inhibited the ER stress induced by tunicamycin in cultured rat H9c2 cardiomyocytes. These results indicate that salusins protect myocardium against ischemic injury by inhibiting ER stress and ER stress-associated apoptosis. PMID:22566093

  6. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    SciTech Connect

    Chen, Lijuan; Wang, Yingjie; Pan, Yaohua; Zhang, Lan; Shen, Chengxing; Qin, Gangjian; Ashraf, Muhammad; Weintraub, Neal; Ma, Genshan; Tang, Yaoliang

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  7. Study of possible mechanism of protective effect of phosphocreatine on ischemic myocardium

    SciTech Connect

    Preobrazhenskii, A.N.; Dzhavadov, S.A.; Saks, V.A.

    1986-10-20

    The accumulation of (/sup 32/P)phosphocreatine by control and isolated perfused ischemic rat hearts was studied. It was found that at phosphocreatine concentrations of 0.5-10 mM in the perfusing solution the rate of phosphocreatine accumulation was twice as high in hearts subjected to ischemia for 35 min as in the control hearts and constituted 182 nmoles/min/g dry weight tissue at a phosphocreatine concentrations in the perfusate of 10 mM. 5'-Nucleotidase and phosphatase activities were found in the crude plasma membrane fraction from rat hearts. The pH-dependence of the activity of these enzymes was studied. The 5'-nucleotidase activity decreased 4- to 5-fold with a drop in the pH from 8.0 to 6.0. The phosphatase activity of the preparations increased 2-fold with a drop in the pH from 8.0 to 6.0. The 5'-nucleotidase activity was inhibited by 10 mM phosphocreatine in the presence of 5 mM Mg/sup 2 +/, and the degree of the inhibition depended on the pH. Maximum inhibition by phosphocreatine (58%) was observed at pH 6.0. The inhibition of phosphatase by phosphocreatine did not depend on the pH and reached 20% in the presence of 10 mM phosphocreatine. Some possible mechanisms of the protective effect of phosphocreatine on an ischemic myocardium are discussed.

  8. Acute treatment with Danshen-Gegen decoction protects the myocardium against ischemia/reperfusion injury via the redox-sensitive PKCɛ/mK(ATP) pathway in rats.

    PubMed

    Chiu, Po Yee; Wong, Sze Man; Leung, Hoi Yan; Leong, Pou Kuan; Chen, Na; Zhou, Limin; Zuo, Zhong; Lam, Philip Y; Ko, Kam Ming

    2011-08-15

    Danshen-Gegen (DG) decoction, an herbal formulation comprising Radix Salvia Miltiorrhiza and Radix Puerariae Lobatae, is prescribed for the treatment of coronary heart disease in Chinese medicine. Experimental and clinical studies have demonstrated that DG decoction can reduce the extent of atherosclerosis. In the present study, using an ex vivo rat model of myocardial ischemia/reperfusion (I/R) injury, we investigated the myocardial preconditioning effect of an aqueous DG extract prepared from an optimized weight-to-weight ratio of Danshen and Gegen. Short-term treatment with DG extract at a daily dose of 1 g/kg and 2 g/kg for 3 days protected against myocardial I/R injury in rats. The cardioprotection afforded by DG pretreatment was paralleled by enhancements in mitochondrial antioxidant status and membrane structural integrity, as well as a decrease in the sensitivity of mitochondria to Ca²⁺-stimulated permeability transition in vitro, particularly under I/R conditions. Short-term treatment with the DG extract also enhanced the translocation of PKCɛ from the cytosol to mitochondria in rat myocardium, and this translocation was inhibited by α-tocopherol co-treatment with DG extract in rats. Short-term DG treatment may precondition the myocardium via a redox-sensitive PKCɛ/mK(ATP) pathway, with resultant inhibition of the mitochondrial permeability transition through the opening of mitochondrial K(ATP) channels. Our results suggest that clinical studies examining the effectiveness of DG extract given prophylactically in affording protection against myocardial I/R injury would be warranted. PMID:21855786

  9. Effective components of Panax quinquefolius and Corydalis tuber protect the myocardium by inhibiting platelet activation and improving the hypercoagulable state

    PubMed Central

    XUE, MEI; LIU, MEI-LIN; ZHU, XIN-YUAN; SHI, DA-ZHUO; YIN, HUI-JUN

    2015-01-01

    The aim of the present study was to investigate the effects of extract of Panax quinquefolius and Corydalis tuber (EPC) on platelet activation and the hypercoagulable state in rats with acute myocardial infarction (AMI). The MI model in Wistar rats was induced by coronary artery ligation. Sham surgery was performed as a control. The surviving rats that underwent MI surgery were divided into control (administered normal saline), metoprolol (9 mg/kg) and low-, moderate- and high-dose EPC groups (0.54, 1.08 g/kg and 2.16 g/kg, respectively). Saline, metoprolol and EPC were administered by gastrogavage for two consecutive weeks. The morphological changes of the myocardium were assessed by hematoxylin and eosin and nitroblue tetrazolium staining. Serum von Willebrand factor (vWF), D-dimer (DD), platelet membrane glycoproteins IIb-IIIa (GPIIb-IIIa) and CD62P levels were assessed using enzyme-linked immunosorbent assay. EPC attenuated the pathological changes of the myocardium. High-dose EPC decreased the serum concentration of vWF when compared with control group. Moderate and high doses of EPC decreased the DD and GPIIb-IIIa levels, and the CD62P level was gradually decreased with EPC dose escalation. The results therefore demonstrated that EPC protects the myocardium by inhibiting platelet activation and improving the hypercoagulable state in a rat model of AMI. PMID:25780455

  10. Ginsenoside-Rb3 protects the myocardium from ischemia-reperfusion injury via the inhibition of apoptosis in rats

    PubMed Central

    LIU, XIAOMIN; JIANG, YICHUAN; YU, XIAOFENG; FU, WENWEN; ZHANG, HONG; SUI, DAYUN

    2014-01-01

    Ginsenoside-Rb3 (G-Rb3) has been previously demonstrated to attenuate myocardial ischemia-reperfusion injury (MIRI). The aim of the present study was to investigate this further and determine whether G-Rb3 protects the myocardium from ischemia-reperfusion injury via the inhibition of apoptosis. Adult male Sprague Dawley rats were randomly divided into four groups: Sham, MIRI, G-Rb3 treatment (orally, 20 mg/kg) and ischemic postconditioning (as the positive control). The drug or placebo treatment was administered to the rats once a day for three consecutive days, and MIRI was then induced by subjecting the rats to left anterior descending coronary artery ligation for 30 min and reperfusion for 2 h. The results showed that G-Rb3 treatment significantly reduced the number of apoptotic cells in the myocardium and the expression of B-cell lymphoma 2-associated X protein, and increased the expression of B-cell lymphoma 2. The activities of aspartate aminotransferase, lactate dehydrogenase and creatine kinase-MB in the serum were also reduced significantly by the G-Rb3 treatment. These findings suggest that G-Rb3 inhibits apoptosis in the early stage of MIRI, and attenuates MIRI when the reperfusion continues. G-Rb3 was also shown to significantly reduce the level of malondialdehyde and increase the activity of superoxide dismutase in the myocardium, which suggests that attenuating reactive oxygen species accumulation and oxidative stress may be the major mechanism underlying the anti-apoptotic effects of G-Rb3. The release of inflammatory factors was significantly attenuated by G-Rb3, which may also be associated with its anti-apoptotic effects. PMID:25371727

  11. Lipopolysaccharide Pretreatment Protects from Renal Ischemia/Reperfusion Injury

    PubMed Central

    Heemann, Uwe; Szabo, Attila; Hamar, Peter; Müller, Veronika; Witzke, Oliver; Lutz, Jens; Philipp, Thomas

    2000-01-01

    In vivo administration of low doses of lipopolysaccharide (LPS) to rodents can protect these animals from subsequently administrated, usually lethal doses of endotoxin or LPS. In this study we tested the effects of LPS pretreatment on ischemia/reperfusion injury in the kidney. Male C57/B1 mice were pretreated with different doses of LPS or phosphate-buffered saline on days −4 and −3. The right kidney was removed, and the vessels of the left kidney were clamped for 30 or 45 minutes on day 0. Creatinine levels and survival of animals were monitored. To test the involvement of cytokines, additional animals were harvested before (“time 0”) and 15 minutes, 1, 2, 8, and 16 hours after reperfusion for histology, immunohistochemistry, terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay, and reverse transcriptase-polymerase chain reaction analysis (including tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, inducible nitric oxide synthase (iNOS), and interferon (IFN)-γ messenger RNA (mRNA)). In controls, renal ischemia of 30 minutes was nonlethal, whereas 73% of the animals died within 48 ± 18 hours, after 45 minutes of ischemia. All different doses of LPS protected the animals from lethal renal ischemia/reperfusion injury. Starting at similar levels, serum creatinine increased significantly in controls but not in LPS-pretreated animals over time. As early as 2 hours after reperfusion, tubular cell damage was significantly more pronounced in controls than in LPS-treated mice. In controls, tubules deteriorated progressively until 8 hours of reperfusion. At this time, more than 50% of tubular cells were destroyed. This destruction was accompanied by a pronounced leukocytic infiltration, predominantly by macrophages. In contrast, LPS pretreatment prevented the destruction of kidney tissue and infiltration by leukocytes. The terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay revealed significantly more apoptotic cells in

  12. Involvement of Bcl-2 Signal Pathway in the Protective Effects of Apigenin on Anoxia/Reoxygenation-induced Myocardium Injury.

    PubMed

    Chen, Chuanjun; He, Huan; Luo, Yong; Zhou, Min; Yin, Dong; He, Ming

    2016-02-01

    Apigenin is a type of flavonoids, which has been demonstrated to protect myocardium against ischemia/reperfusion (I/R) injury. However, the mechanism is still unclear. We hypothesized that the mechanism of cardioprotective action of apigenin on the I/R-induced injury might be caused via B-cell lymphoma (Bcl) signaling pathway. In this study, an in vitro I/R model was replicated on Langendorff-perfused heart and H9c2 cardiomyocytes by anoxia/reoxygenation (A/R) treatment. The recovery of cardiac contractile function, infarct size, lactate dehydrogenase (LDH) and creatine kinase (CK) in the perfusate, the expression and activity of Bcl-2 and caspase-3, and cardiomyocyte apoptosis were measured in the Langendorff heart undergoing A/R injury. In addition, the cell viability, LDH release, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), expression of cytochrome c in the cytosol, and cell apoptosis were examined in the culture of H9c2 cardiomyocytes after the A/R. The results showed that apigenin significantly improved rat heart contractile function, reduced LDH release, infarct size and apoptotic rate, upregulated the expression of Bcl-2 and caspase-3, and downregulated the expression of cleaved caspase-3 after the A/R. Moreover, apigenin increased the cell viability and decreased the release of LDH, production of reactive oxygen species, release of mitochondrial cytochrome c into the cytosol, and cell apoptosis in the culture of H9c2 cardiomyocytes after the A/R. In addition, inhibition of Bcl-2 activity by ABT-737 markedly attenuated the protective effect of apigenin on the A/R-induced myocardium injury. Taken together, we firstly demonstrated that the effect of apigenin against A/R injury in cardiomyocytes involves Bcl-2 signal pathway and at least partly depends on its effect of upregulating the expression of Bcl-2. PMID:26466327

  13. RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway

    PubMed Central

    Gu, Anxin; Jie, Yamin; Sun, Liang; Zhao, Shuping; E, Mingyan; You, Qingshan

    2015-01-01

    Radiation-induced heart disease (RIHD), which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF)-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway. PMID:26332771

  14. Activated Protein C Protects Myocardium Via Activation of Anti-apoptotic Pathways of Survival in Ischemia-reperfused Rat Heart

    PubMed Central

    Ding, Jia-Wang; Yang, Jun; Liu, Zhao-Qi; Zhang, Yan; Yang, Jian; Li, Song; Li, Li

    2010-01-01

    Activated protein C (APC) is known to be beneficial on ischemia reperfusion injury in myocardium. However, the protection mechanism of APC is not fully understood. The purpose of this study was to investigate the effects and possible mechanisms of APC on myocardial ischemic damage. Artificially ventilated anaesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 hr of reperfusion. Rats were randomly divided into four groups; Sham, I/R, APC preconditioning and postconditioning group. Myocardial infarct size, apoptosis index, the phosphorylation of ERK1/2, Bcl-2, Bax and cytochrome c genes and proteins were assessed. In APC-administrated rat hearts, regardless of the timing of administration, infarct size was consistently reduced compared to ischemia/reperfusion (I/R) rats. APC improved the expression of ERK1/2 and anti-apoptotic protein Bcl-2 which were significantly reduced in the I/R rats. APC reduced the expression of pro-apoptotic genes, Bax and cytochrome c. These findings suggest that APC produces cardioprotective effect by preserving the expression of proteins and genes involved in anti-apoptotic pathways, regardless of the timing of administration. PMID:21060750

  15. [Effectiveness of protecting the myocardium against ischemia with a normothermic cardioplegic solution and creatine phosphate].

    PubMed

    Popov, Iu V; Saprygin, D B; Egorova, I F; Kashtélian, L S; Bakuleva, N P

    1985-01-01

    The protective effects of cardioplegic solutions (CS) containing creatine phosphate (CP) were studied in a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest. Isolated rat hearts were subjected to a 3-minute coronary infusion with CS containing CP in normothermic (37 degrees C) and hypothermic (4-6 degrees C) regimes. In the normothermia group, the postischemic functional recovery was 70-75% of the preischemic control value, while the cellular ATP and CP content was reduced but insignificantly. By contrast, in the hypothermia group, the postischemic functional recovery was markedly depressed, with the tissue high-energy phosphate content being appreciably lowered. The data obtained confirm high efficacy of CP-containing cardioplegic solutions administered under normothermia conditions. PMID:3967061

  16. Protective effect of the combinations of glycyrrhizic, ferulic and cinnamic acid pretreatment on myocardial ischemia-reperfusion injury in rats

    PubMed Central

    GAO, YUQIN; HAO, JIPING; ZHANG, HONGKAO; QIAN, GUOQIANG; JIANG, RENWANG; HU, JING; WANG, JIANING; LEI, ZHANG; ZHAO, GUOPING

    2015-01-01

    The aim of this study was to find an effective drug cocktail pretreatment to protect myocardial tissue of the heart from ischemia-reperfusion (I/R) injury. The mechanisms underlying the effects of the drug cocktail were subsequently explored in order to expand the application of Dang-gui-si-ni-tang (DGSN), a Traditional Chinese Medicine. The active components of DGSN in the serum following oral administration were investigated using high-performance liquid chromatography. The activity of superoxide dismutase (SOD) and malondialdehyde (MDA) levels were then analyzed to show the effect of the active components in the treatment of myocardial I/R injury. An L16 (44) orthogonal experiment was utilized to determine the most effective cocktail mix and the mechanism underlying the effect of this mix on myocardial I/R injury was investigated. It was observed that FCG, a mixture of glycyrrhizic (50 mg/kg), cinnamic (200 mg/kg) and ferulic (300 mg/kg) acid, was the optimal drug cocktail present in DGSN. This was absorbed into the blood following oral administration and was shown to decrease MDA levels and increase the activity of SOD. In conclusion, the findings suggest that FCG, a combination of active ingredients in the DGSN decoction, can be absorbed into the blood and protect the myocardium from I/R injury. PMID:25574212

  17. No Evidence for Activated Autophagy in Left Ventricular Myocardium at Early Reperfusion with Protection by Remote Ischemic Preconditioning in Patients Undergoing Coronary Artery Bypass Grafting

    PubMed Central

    Gedik, Nilgün; Thielmann, Matthias; Kottenberg, Eva; Peters, Jürgen; Jakob, Heinz; Heusch, Gerd; Kleinbongard, Petra

    2014-01-01

    Objective Remote ischemic preconditioning (RIPC) by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG). Activation of signal transducer and activator of transcription 5 (STAT5) in left ventricular (LV) myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy. Methods CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation) or placebo (cuff deflated) before skin incision (n = 10/10). Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline) and at early (5–10 min) reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p = 0.002). Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5–12 (ATG5-12) complex, light chain 3 (LC3), parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2)-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion. Results Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p = 0.02). STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (≥2.7-fold versus baseline, p≤0.05). Conclusion Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion. PMID:24797938

  18. Improved myocardium transducer

    NASA Technical Reports Server (NTRS)

    Culler, V. H.; Feldstein, C.; Lewis, G. W.

    1979-01-01

    Method of implanting myocardium transducer uses special indented pins that are caught and securely held by epicardial fibers. Pins are small enough to cause minimum of trauma to myocardium during implantation or removal.

  19. Growth differentiation factor 15 may protect the myocardium from no-reflow by inhibiting the inflammatory-like response that predominantly involves neutrophil infiltration

    PubMed Central

    ZHANG, MEI; PAN, KUNYING; LIU, QIANPING; ZHOU, XIN; JIANG, TIEMIN; LI, YUMING

    2016-01-01

    significant no-reflow in ischemic myocardium. GDF-15 may protect the I/R myocardium from no-reflow by inhibiting the inflammatory-like response, which involves neutrophil infiltration and transendothelial migration. PMID:26647773

  20. Docosahexaenoic Acid Pretreatment Confers Protection and Functional Improvements after Acute Spinal Cord Injury in Adult Rats

    PubMed Central

    Figueroa, Johnny D.; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I.; Walker, Robert L.; Miranda, Jorge D.

    2012-01-01

    Abstract Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  1. Docosahexaenoic acid pretreatment confers protection and functional improvements after acute spinal cord injury in adult rats.

    PubMed

    Figueroa, Johnny D; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I; Walker, Robert L; Miranda, Jorge D; Leon, Marino De

    2012-02-10

    Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  2. The effect of various cosmetic pretreatments on protecting hair from thermal damage by hot flat ironing.

    PubMed

    Zhou, Y; Rigoletto, R; Koelmel, D; Zhang, G; Gillece, T W; Foltis, L; Moore, D J; Qu, X; Sun, C

    2011-01-01

    Hot flat irons are used to create straight hair styles. As these devices operate at temperatures over 200 °C they can cause significant damage to hair keratin. In this study, hair thermal damage and the effect of various polymeric pretreatments were investigated using FTIR imaging spectroscopy, DSC, dynamic vapor sorption (DVS), AFM, SEM, and thermal image analysis. FTIR imaging spectroscopy of hair cross sections provides spatially resolved molecular information such as protein distribution and structure. This approach was used to monitor thermally induced modification of hair protein, including the conversion of α-helix to β-sheet and protein degradation. DSC measurements of thermally treated hair also demonstrated degradation of hair keratin. DVS of thermally treated hair shows the reduced water regain and lower water retention, compared to the non-thermally treated hair, which might be attributed to the protein conformation changes due to heat damage. The protection of native protein structure associated with selected polymer pretreatments leads to improved moisture restoration and water retention of hair. This contributes to heat control on repeated hot flat ironing. Thermally stressing hair led to significantly increased hair breakage when subjected to combing. These studies indicate that hair breakage can be reduced significantly when hair is pretreated with selected polymers such as VP/acrylates/lauryl methacrylate copolymer, polyquaternium-55, and a polyelectrolyte complex of PVM/MA copolymer and polyquaternium-28. In addition, polymeric pretreatments provide thermal protection against thermal degradation of keratin in the cortex as well as hair surface damage. The morphological improvement in cuticle integrity and smoothness with the polymer pretreatment plays an important role in their anti-breakage effect. Insights into structure-property relationships necessary to provide thermal protection to hair are presented. PMID:21635854

  3. Assessment of membrane protection by /sup 31/P-NMR effects of lidocaine on calcium-paradox in myocardium

    SciTech Connect

    Sakai, Hirosumi; Yoshiyama, Minoru; Teragaki, Masakazu; Takeuchi, Kazuhide; Takeda, Takeda; Ikata, Mari; Ishikawa, Makoto; Miura, Iwao

    1989-01-01

    In studying calcium paradox, perfused rat hearts were used to investigate the myocardial protective effects of lidocaine. Intracellular contents of phosphates were measured using the /sup 31/P-NMR method. In hearts reexposed to calcium, following 3 minute calcium-free perfusion, a rapid contracture occurred, followed by rapid and complete disappearance of intracellular phosphates with no resumption of cardiac function. In hearts where lidocaine was administered from the onset of the calcium-free perfusion until 2 minutes following the onset of reexposure to calcium, both intracellular phosphates and cardiac contractility were maintained. Therefore, it can be said that cell membranes were protected by lidocaine.

  4. Hydrophilic bile salt ursodeoxycholic acid protects myocardium against reperfusion injury in a PI3K/Akt dependent pathway.

    PubMed

    Rajesh, Katare Gopalrao; Suzuki, Ryoko; Maeda, Hironori; Yamamoto, Murio; Yutong, Xing; Sasaguri, Shiro

    2005-11-01

    The opening of mitochondrial permeability transition pore (PTP) during reperfusion injury of heart has been well demonstrated and thus controlling PTP would attenuate the myocardial damage and cell death. Ursodeoxycholic acid (UDCA) is a hydrophilic bile salt and has been shown to prevent apoptosis in hepatocytes by inhibiting the opening of PTP. Here we demonstrate the role of UDCA in preventing the reperfusion injury of heart through its ability to inhibit PTP. Wistar rats underwent 30 min left coronary artery occlusion (LCA) followed by 180 min reperfusion after treatment with 40 mg/kg per iv infusion of UDCA over 30 min before LCA occlusion. Other groups of rats were treated with PTP agonist atractyloside(5 mg/kg) or PI3 kinase inhibitor wortmannin (16 ug/kg) before UDCA treatment. UDCA treatment prior to LCA occlusion, activated phosphorylation of Akt and Bad. Phosphorylating Bad prevented its translocation in to mitochondria, there by preventing the down regulation of Bcl-2 expression and PTP opening. This was confirmed by reduced cytochrome C release from intramitochondrial space in to the cytosol and hence reduced cell death either by apoptosis (4.8 vs 11.8%, P<0.001, UDCA treated against control group) or necrosis (reduced MI area in UDCA treated group (22.1%) compared to control group(46.4%), P<0.001). In contrast, inhibition of Akt activation with PI3K inhibitor wortmannin or opening the PTP with atractyloside abolished, UDCA mediated cytoprotective effects. Studies on primary culture cardiomyocytes also confirmed our in vivo results of UDCA on cell survival. These results altogether demonstrate that UDCA protect the heart against reperfusion injury by inhibiting the PTP in a PI3K/Akt dependent pathway. PMID:16171810

  5. Over-expression of HSPA12B protects mice against myocardium ischemic/reperfusion injury through a PPARγ-dependent PI3K/Akt/eNOS pathway

    PubMed Central

    Sun, Yanjun; Ye, Lincai; Jiang, Chuan; Jiang, Jun; Hong, Haifa; Qiu, Lisheng

    2015-01-01

    Acute myocardial ischemia/reperfusion (MIR) injury leads to severe arrhythmias and a high lethality. We aim to determine the effect of heat shock protein A12B (HSPA12B), a newly discovered member of the Hsp70 family, on heart injury parameters following MIR surgery. We used HSPA12B transgenic mice to determine its effects on heart function parameters, infarct size and cellular apoptosis following MIR surgery. Proinflammatory cytokines, oxidative products and anti-oxidative enzymes in the myocardium were measured to evaluate the anti-inflammatory and anti-oxidative effects of HSPA12B over-expression. The role of PPARs/eNOS/PI3k/Akt pathway was investigated using their inhibitors. The alteration of hemodynamic parameters, histopathological, apoptotic and infarct size caused by MIR was greatly attenuated in HSPA12B over-expressed mice. HSPA12B also greatly mitigated the inflammatory response, demonstrated by the decrease in the levels of IL-1β, IL-6, TNF-a and MPO. Anti-oxidative enzymes (SOD, Catalase and GPx) were restored by HSPA12B; oxidative products (8-OHdG, MDA and protein carbonyl) were decreased. HSPA12B activated the PPARγ-dependent eNOS/PI3k/Akt pathway, and the influence of HSPA12B on cardiac function was reversed by the inhibitors of eNOS, PPARγ, Akt and PI3K. Our results present a novel signaling mechanism that HSPA12B protects MIR injury through a PPARγ-dependent PI3K/Akt/eNOS pathway. PMID:26885270

  6. Salicylic acid and heat acclimation pretreatment protects Laminaria japonica sporophyte (Phaeophyceae) from heat stress

    NASA Astrophysics Data System (ADS)

    Zhou, Bin; Tang, Xuexi; Wang, You

    2010-07-01

    Possible mediatory roles of heat acclimation and salicylic acid in protecting the sporophyte of marine macroalga Laminaria japonica (Phaeophyceae) from heat stress were studied. Heat stress resulted in oxidative injury in the kelp blades. Under heat stress significant accumulation of hydrogen peroxide (H2O2) and malonaldehyde (MDA), a membrane lipid peroxidation product, and a drastic decrease in chlorophyll a content were recorded. Activity of the enzymatic antioxidant system was drastically affected by heat stress. The activity of superoxide dismutase (SOD) was significantly increased while peroxidase (POD), catalase (CAT) and glutathione peroxidase (GPX) were greatly inhibited and, simultaneously, phenylalanine ammonia-lyase was activated while polyphenol oxidase (PPO) was inhibited. Both heat acclimation pretreatment and exogenous application of salicylic acid alleviated oxidative damage in kelp blades. Blades receiving heat acclimation pretreatment and exogenous salicylic acid prior to heat stress exhibited a reduced increase in H2O2 and MDA content, and a lower reduction in chlorophyll a content. Pretreatment with heat acclimation and salicylic acid elevated activities of SOD, POD, CAT, GPX and PPO. Considering these results collectively, we speculate that the inhibition of antioxidant enzymes is a possible cause of the heat-stress-induced oxidative stress in L. japonica, and enhanced thermotolerance may be associated, at least in part, with the elevated activity of the enzymatic antioxidant system.

  7. Waterborne chitosan-epoxysilane hybrid pretreatments for corrosion protection of zinc.

    PubMed

    Fernández-Solis, Christian; Erbe, Andreas

    2016-06-01

    Biopolymer-based systems are extensively studied as green alternatives for traditional polymer coatings, e.g., in corrosion protection. Chitosan-epoxysilane hybrid films are presented in this work as a chitosan-based protective system, which could, e.g., be applied in a pretreatment step. For the preparation of the chitosan-epoxysilane hybrid systems, a sol-gel procedure was applied. The function of the silane is to ensure adhesion to the substrate. On zinc substrates, homogeneous thin films with thickness of 50-70 nm were obtained after thermal curing. The hybrid-coated zinc substrates were characterized by infrared spectroscopy, ellipsometry, and x-ray photoelectron spectroscopy. As model corrosion experiments, linear polarization resistance was measured, and cathodic delamination of the weak polymer coating poly(vinylbutyral) (PVB) was studied using scanning Kelvin probe. Overall, chitosan-epoxysilane hybrid pretreated samples showed lower delamination rates than unmodified chitosan coatings and pure PVB. Electrochemical impedance spectroscopy confirmed a reduced ion permeability and water uptake by chitosan-epoxysilane films compared to that of a nonmodified chitosan coating. Even though the coatings are hydrophobic and contain water, they slow down cathodic delamination by limiting ion transport. PMID:27009436

  8. Pretreatment with Apoaequorin Protects Hippocampal CA1 Neurons from Oxygen-Glucose Deprivation

    PubMed Central

    Detert, Julia A.; Adams, Erin L.; Lescher, Jacob D.; Lyons, Jeri-Anne; Moyer, James R.

    2013-01-01

    Ischemic stroke affects ∼795,000 people each year in the U.S., which results in an estimated annual cost of $73.7 billion. Calcium is pivotal in a variety of neuronal signaling cascades, however, during ischemia, excess calcium influx can trigger excitotoxic cell death. Calcium binding proteins help neurons regulate/buffer intracellular calcium levels during ischemia. Aequorin is a calcium binding protein isolated from the jellyfish Aequorea victoria, and has been used for years as a calcium indicator, but little is known about its neuroprotective properties. The present study used an in vitro rat brain slice preparation to test the hypothesis that an intra-hippocampal infusion of apoaequorin (the calcium binding component of aequorin) protects neurons from ischemic cell death. Bilaterally cannulated rats received an apoaequorin infusion in one hemisphere and vehicle control in the other. Hippocampal slices were then prepared and subjected to 5 minutes of oxygen-glucose deprivation (OGD), and cell death was assayed by trypan blue exclusion. Apoaequorin dose-dependently protected neurons from OGD – doses of 1% and 4% (but not 0.4%) significantly decreased the number of trypan blue-labeled neurons. This effect was also time dependent, lasting up to 48 hours. This time dependent effect was paralleled by changes in cytokine and chemokine expression, indicating that apoaequorin may protect neurons via a neuroimmunomodulatory mechanism. These data support the hypothesis that pretreatment with apoaequorin protects neurons against ischemic cell death, and may be an effective neurotherapeutic. PMID:24244400

  9. Pretreatment of Gymnema sylvestre revealed the protection against acetic acid-induced ulcerative colitis in rats

    PubMed Central

    2014-01-01

    Background Overproduction of free radicals and decreased antioxidant capacity are well-known risk factors for inflammatory bowel diseases. Gymnema sylvestre (GS) leaves extract is distinguished for its anti-diabetic, antioxidant and anti-inflammatory properties. Present study is designed to evaluate the preventative activities of GS against acetic acid (AA)-induced ulcerative colitis in Wistar rats. Methods Experimentally ulcerative colitis (UC) was induced by AA in animals pretreated with three different doses of GS leaves extract (50, 100, 200 mg/kg/day) and a single dose of mesalazine (MES, 300 mg/kg/day) for seven days. Twenty four hours later, animals were sacrificed and the colonic tissues were collected. Colonic mucus content was determined using Alcian blue dye binding technique. Levels of thiobarbituric acid reactive substances (TBARS), total glutathione sulfhydryl group (T-GSH) and non-protein sulfhydryl group (NPSH) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were estimated in colon tissues. Colonic nucleic acids (DNA and RNA) and total protein (TP) concentrations were also determined. Levels of pro-inflammatory cytokines including interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) as well as prostaglandin E2 (PGE2) and nitric oxide (NO) were estimated in colonic tissues. The histopathological changes of the colonic tissues were also observed. Results In AA administered group TBARS levels were increased, while colonic mucus content, T-GSH and NP-SH, SOD and CAT were reduced in colon. Pretreatment with GS inhibited TBARS elevation as well as mucus content, T-GSH and NP-SH reduction. Enzymatic activities of SOD and CAT were brought back to their normal levels in GS pretreated group. A significant reduction in DNA, RNA and TP levels was seen following AA administration and this inhibition was significantly eliminated by GS treatment. GS pretreatment also inhibited

  10. Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania somnifera Leaf Extract

    PubMed Central

    Khalil, Md. Ibrahim; Ahmmed, Istiyak; Ahmed, Romana; Tanvir, E. M.; Afroz, Rizwana; Paul, Sudip; Gan, Siew Hua; Alam, Nadia

    2015-01-01

    We investigated the protective role of Withania somnifera leaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO-induced MI in rats. PMID:26539517

  11. Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania somnifera Leaf Extract.

    PubMed

    Khalil, Md Ibrahim; Ahmmed, Istiyak; Ahmed, Romana; Tanvir, E M; Afroz, Rizwana; Paul, Sudip; Gan, Siew Hua; Alam, Nadia

    2015-01-01

    We investigated the protective role of Withania somnifera leaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO-induced MI in rats. PMID:26539517

  12. Pulmonary delivery of an aerosolized recombinant human butyrylcholinesterase pretreatment protects against aerosolized paraoxon in macaques.

    PubMed

    Rosenberg, Yvonne J; Laube, Beth; Mao, Lingjun; Jiang, Xiaoming; Hernandez-Abanto, Segundo; Lee, Keunmyoung D; Adams, Robert

    2013-03-25

    Butyrylcholinesterase (BChE) is the leading pretreatment candidate against exposure to organophosphates (OPs), which pose an ever increasing public and military health. Since respiratory failure is the primary cause of death following acute OP poisoning, an inhaled BChE therapeutic could prove highly efficacious in preventing acute toxicity as well as the associated delayed neuropathy. To address this, studies have been performed in mice and macaques using Chinese Hamster Ovary cells (CHO)-derived recombinant (r) BChE delivered by the pulmonary route, to examine whether the deposition of both macaque (Ma) and human (Hu) rBChE administered as aerosols (aer) favored the creation and retention of an efficient protective "pulmonary bioshield" that could scavenge incoming (inhaled) OPs in situ thereby preventing entry into the circulation and inhibition of plasma BChE and AChE on red blood cells (RBC-AChE) and in cholinergic synapses. In contrast to parenteral delivery of rBChE, which currently requires posttranslational modification for good plasma stability, an unmodified aer-rBChE pretreatment given 1-40 h prior to >1 LD50 of aer-paraoxon (Px) was able to prevent inhibition of circulating cholinesterase in a dose-dependent manner. These studies are the first to show protection by rBChE against a pesticide such as paraoxon when delivered directly into the lung and bode well for the use of a non-invasive and consumer friendly method of rHuBChE delivery as a human treatment to counteract OP toxicity. PMID:23178380

  13. Cobalt Protoporphyrin Pretreatment Protects Human Embryonic Stem Cell-Derived Cardiomyocytes From Hypoxia/Reoxygenation Injury In Vitro and Increases Graft Size and Vascularization In Vivo

    PubMed Central

    Luo, Jun; Weaver, Matthew S.; Cao, Baohong; Dennis, James E.; Van Biber, Benjamin; Laflamme, Michael A.

    2014-01-01

    Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) can regenerate infarcted myocardium. However, when implanted into acutely infarcted hearts, few cells survive the first week postimplant. To improve early graft survival, hESC-CMs were pretreated with cobalt protoporphyrin (CoPP), a transcriptional activator of cytoprotective heme oxygenase-1 (HO-1). When hESC-CMs were challenged with an in vitro hypoxia/reoxygenation injury, mimicking cell transplantation into an ischemic site, survival was significantly greater among cells pretreated with CoPP versus phosphate-buffered saline (PBS)-pretreated controls. Compared with PBS-pretreated cells, CoPP-pretreated hESC-CM preparations exhibited higher levels of HO-1 expression, Akt phosphorylation, and vascular endothelial growth factor production, with reduced apoptosis, and a 30% decrease in intracellular reactive oxygen species. For in vivo translation, 1 × 107 hESC-CMs were pretreated ex vivo with CoPP or PBS and then injected intramyocardially into rat hearts immediately following acute infarction (permanent coronary ligation). At 1 week, hESC-CM content, assessed by quantitative polymerase chain reaction for human Alu sequences, was 17-fold higher in hearts receiving CoPP- than PBS-pretreated cells. On histomorphometry, cardiomyocyte graft size was 2.6-fold larger in hearts receiving CoPP- than PBS-pretreated cells, occupying up to 12% of the ventricular area. Vascular density of host-perfused human-derived capillaries was significantly greater in grafts composed of CoPP- than PBS-pretreated cells. Taken together, these experiments demonstrate that ex vivo pretreatment of hESC-CMs with a single dose of CoPP before intramyocardial implantation more than doubled resulting graft size and improved early graft vascularization in acutely infarcted hearts. These findings open the door for delivery of these, or other, stem cells during acute interventional therapy following myocardial infarction or ischemia. PMID

  14. Fracture resistance behaviour of gamma-irradiation sterilized cortical bone protected with a ribose pre-treatment

    NASA Astrophysics Data System (ADS)

    Woodside, Carman Mitchell

    Structural bone allograft reconstructions are often implemented to repair large skeletal defects. To ensure the biological safety of the patient, allograft material is routinely sterilized with gamma-irradiation prior to implantation. The sterilization process damages the tissue, specifically the collagen protein network, leading to severe losses in the mechanical properties of the bone. Our lab has begun developing a ribose pre-treatment that can protect bone from these harmful effects. The goals of the present study were to develop a method to measure the fracture toughness of bone, an important clinical failure mode, and implement it to determine the effectiveness of the ribose pre-treatment on fracture toughness. We have shown that the ribose pre-treatment is successful at protecting some of the original fracture toughness of sterilized bone, and that the connectivity of the collagen network is an important contributor to the fracture resistance of bone.

  15. Use of cholinesterases as pretreatment drugs for the protection of rhesus monkeys against soman toxicity. (Reannouncement with new availability information)

    SciTech Connect

    Wolfe, A.D.; Blick, D.W.; Murphy, M.R.; Miller, S.A.; Gentry, M.K.

    1992-12-31

    Purified fetal bovine serum acetylcholinesterase (FBS AChE) and horse serum butyrylcholinesterase (BChE) were successfully used as single pretreatment drugs for the prevention of pinacolyl methylphosphonofluoridate (soman) toxicity in nonhuman primates. Eight rhesus monkeys, trained to perform Primate Equilibrium Platform (PEP) tasks, were pretreated with FBS AChE or BChE and challenged with a cumulative level of five median lethal doses (LD 50) of soman. All ChE-pretreated monkeys survived the soman challenge and showed no symptoms of soman toxicity. A quantitative linear relation was observed between the soman dose and the neutralization of blood ChE. None of the four AChE-pretreated animals showed PEP task decrements, even though administration of soman irreversibly inhibited nearly all of the exogenously administered AChE. In two of four BChE pretreated animals, a small transient PEP performance decrement occurred when the cumulative soman dose exceeded 4 LD 50. Performance decrements observed under BCh E protection mete modest by the usual standards of organophosphorus compound toxicity. No residual or delayed performance decrements or other untoward effects were observed during 6 weeks of postexposure testing with either ChE.... Cholinesterases, Pretreatment, Soman, AChE, BChE, Toxicity.

  16. Prolonged contraction duration in aged myocardium.

    PubMed

    Lakatta, E G; Gerstenblith, G; Angell, C S; Shock, N W; Weisfeldt, M L

    1975-01-01

    Isometric performance at 29degreesC was measured in left ventricular trabeculae carneae from young adult (6-mo) and aged (25-mo) rats (n equals 18 in each group). Active tension and maximal rate of tension development did not differ with age, but contraction duration was 255plus or minus6 ms in the young adult and 283plus or minus6 ms in the aged group (P less than0.001). Although catecholamine content per gram heart weight was less in the aged myocardium, additional experiments showed that neither 1 times 10-6 M propranolol nor pretreatment with 6-hydroxydopamine eliminated the age difference in contraction duration. To determine if this age difference resulted from a prolonged active state, electromechanical dissociation and the overshoot of contraction duration during recovery from hypoxia were measured. During paired stimulation greater mechanical refractoriness was found in aged muscles (P less than0.01), but intracellular action potential recordings showed no age difference in the electrical refractory period. On recovery from hypoxia, contraction duration overshoot was 117plus or minus 4percent of control in the young and 138plus or minus 4percent of control in the aged muscles (P less than0.01). The greater electromechanical dissociation and greater overshoot in contraction duration following hypoxia in aged myocardium suggests that prolonged contraction duration in aged myocardium results from a prolonged active state rather than changes in passive properties or myocardial catecholamine content. PMID:1109181

  17. Protection against paraoxon toxicity by an intravenous pretreatment with polyethylene-glycol-conjugated recombinant butyrylcholinesterase in macaques

    PubMed Central

    Rosenberg, Yvonne J.; Gearhart, Jeffery; Mao, Lingjun; Jiang, Xiaoming; Hernandez-Abanto, Segundo

    2014-01-01

    Recombinant (r) butyrylcholinesterase (rBChE) produced in CHO cells is being developed as a prophylactic countermeasure against neurotoxicity resulting from exposure to organophosphates (OPs) in the form of pesticides and nerve agents. To evaluate the efficacy of a parenteral pretreatment, a PEGylated macaque (Ma) form of rBChE was administered into homologous animals to ensure good plasma retention without immunogenicity. Thus, macaques were administered PEG-rMaBChE at either 5 or 7 mg/kg intravenously (i.v.) and exposed subcutaneously to 12 µg/kg of the potent pesticide paraoxon (Px) at 1 hr or at 1 and 72 hr respectively. Protection was measured by the ability of rBChE prophylaxis to prevent the inhibition of circulating acetylcholinesterase on red blood cells (RBC-AChE). In rBChE-pretreated animals, no inhibition of RBC-AChE activity after the first Px exposure and only a 10–20% reduction after the second exposure were observed as compared to a 75% RBC-AChE inhibition usually obtained without pretreatment. In addition, these studies raised other interesting issues. The lipophilic nature of Px, appears to result in early and transient inhibition of RBC-AChE as a result of transfer of OP bound to RBC even in BChE-pretreated animals. The protection by a single injection of rBChE against two administrations of Px represents the first example of protection by an i.v. rBChE pretreatment against a pesticide such as Px and bodes well for a parenteral rHuBChE pretreatment as an OP countermeasure in humans. PMID:24384224

  18. Carnosine pretreatment protects against hypoxia-ischemia brain damage in the neonatal rat model.

    PubMed

    Zhang, Xiangmin; Song, Lili; Cheng, Xiuyong; Yang, Yi; Luan, Bin; Jia, Liting; Xu, Falin; Zhang, Zhan

    2011-09-30

    Perinatal hypoxia-ischemia brain injury is a major cause of mortality and morbidity in neonates and lacks an effective treatment thus far. Carnosine has been demonstrated to play a neuroprotective role in the adult brain injuries. However, there is no information available concerning its neuroprotective role in the immature brains after hypoxia-ischemia insults. Therefore, we investigated whether carnosine could also confer neuroprotective effects in a neonatal rat hypoxia-ischemia model. Hypoxia-ischemia was induced in rats on postnatal day 7 (P7). Carnosine (250 mg/kg) was administered intraperitoneally, 30 min prior to hypoxia-ischemia induction. Morphological brain injury and biochemical markers of apoptosis and oxidative stress were evaluated 24 h after hypoxia-ischemia induction. Cognitive performance was evaluated by the Morris Water Maze test on P28-P33. We found that pretreatment with carnosine significantly reduced the infarct volume and the number of terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hypoxia-ischemia brain. Carnosine also inhibited mRNA expression of apoptosis-inducing factor(AIF) and caspase-3, which was accompanied by an increase in superoxide dismutase(SOD)activity and a decrease in the malondialdehyde(MDA)level in carnosine-treated rats. Furthermore, carnosine also improved the spatial learning and memory abilities of rats declined due to hypoxia-ischemia. These results demonstrate that carnosine can protect rats against hypoxia-ischemia-induced brain damage by antioxidation. PMID:21693116

  19. Protection of Rhesus monkeys against Soman and prevention of performance decrement by pretreatment with acetylcholinesterase. (Reannouncement with new availability information)

    SciTech Connect

    Maxwell, D.M.; Castro, C.A.; De La Hoz, D.M.; Gentry, M.K.; Gold, M.B.

    1992-12-31

    The ability of acetylcholinesterase from fetal bovine serum (FBS AChE) to protect against soman, a highly toxic organophosphorus (OP) compound, was tested in rhesus monkeys. Intravenous administration of FBS AChE produced a minimal behavioral effect on the serial probe recognition task, a sensitive test of cognitive function and short-term memory. Pharmacokinetic studies of injected FBS AChE indicated a plasma half-life of 40 hr for FBS AChE in monkeys. Both in vitro and in vivo titration of FBS AChE with soman produced a 1:1 stoichiometry between organophosphate-inhibited FBS AChE and the cumulative dose of the toxic stereoisomers of soman. Administration of FBS AChE protected monkeys against the lethal effects of up to 2.7 LD50 of soman and prevented any signs of organophosphate intoxication, e.g., excessive secretions, respiratory depression, muscle fasciculations, or convulsions. In addition, monkeys pretreated with FBS AChE were devoid of any behavioral incapacitation after soman challenge, as measured by the serial probe recognition task. Compared to the current multicomponent drug treatment against soman, which does not prevent the signs or the behavioral deficits resulting from OP intoxication, use of FBS AChE as a single pretreatment drug provides significantly effective protection against both the lethal and the behavioral effects of soman. Acetylcholinesterase; protection; non-human primates; soman; pretreatment.

  20. Comparative study of pre-treatment procedures for (3)H monitoring in water samples from environmental protection programs.

    PubMed

    Tarancón, A; Bagán, H; Rauret, G; García, J F

    2010-04-15

    The determination of tritium activity in water samples is included in most environmental protection programs, and the recommended procedure consists of sample distillation and further measurement by liquid scintillation. Distillation is a simple but time consuming pre-treatment, especially in routine analysis. Here we evaluate alternative pre-treatments for tritium activity determination, such as filtration or the use of multiple selective ion exchange columns. 52 samples from different water sources (rain, surface, underground, sea and drinking water) in Spanish environmental protection programs, together with an IAEA reference material were analyzed. Results show that both pre-treatments can be applied as a preliminary tool to discriminate between tritium active and non active waters in environmental monitoring programs. In addition, filtration and multiple selective ion exchange column pre-treatments can be used as alternative procedures for tritium activity determination in the routine analyses of water samples with known and reproducible chemical and isotopic composition. Both methods are less time consuming than distillation and, in the case of filtration, extremely cheap. For waters with complex matrices, especially sea water, distillation is the recommended procedure due to the interference from salts contained in the sample. PMID:20167352

  1. Protection of rhesus monkeys against Soman and prevention of performance decrement by pretreatment with acetylcholinesterase. (Reannouncement with new availability information)

    SciTech Connect

    Maxwell, D.M.; Castro, C.A.; De La Hoz, D.M.; Gentry, M.K.; Gold, M.B.

    1992-12-31

    The ability of acetylcholinesterase from fetal bovine serum (FBS AChE) to protect against soman, a highly toxic organophosphorus (OP) compound, was tested in rhesus monkeys. Intravenous administration of FBS AChE produced a minimal behavioral effect on the serial probe recognition task, a sensitive test of cognitive function and short-term memory. Pharmacokinetic studies of injected FBS AChE indicated a plasma half-life of 40 hr for FBS AChE in monkeys. Both in vitro and in vivo titration of FBS AChE with soman produced a 1:1 stoichiometry between organophosphate-inhibited FBS AChE and the cumulative dose of the toxic stereoisomers of soman. Administration of FBS AChE protected monkeys against the lethal effects of up to 2.7 LD50 of soman and prevented any signs of organophosphate intoxication, e.g., excessive secretions, respiratory depression, muscle fasciculations, or convulsions. In addition, monkeys pretreated with FBS AChE were devoid of any behavioral incapacitation after soman challenge, as measured by the serial probe recognition task. Compared to the current multicomponent drug treatment against soman, which does not prevent the signs or the behavioral deficits resulting from OP intoxication, use of FBS AChE as a single pretreatment drug provides significantly effective protection against both the lethal and the behavioral effects of soman.... Pretreatment, Nonhuman primate, Performance decrements, Acetylcholinesterase, Soman, Nerve agents.

  2. Antioxidative Peptides Derived from Enzyme Hydrolysis of Bone Collagen after Microwave Assisted Acid Pre-Treatment and Nitrogen Protection

    PubMed Central

    Lin, Yun-Jian; Le, Guo-Wei; Wang, Jie-Yun; Li, Ya-Xin; Shi, Yong-Hui; Sun, Jin

    2010-01-01

    This study focused on the preparation method of antioxidant peptides by enzymatic hydrolysis of bone collagen after microwave assisted acid pre-treatment and nitrogen protection. Phosphoric acid showed the highest ability of hydrolysis among the four other acids tested (hydrochloric acid, sulfuric acid and/or citric acid). The highest degree of hydrolysis (DH) was 9.5% using 4 mol/L phosphoric acid with a ratio of 1:6 under a microwave intensity of 510 W for 240 s. Neutral proteinase gave higher DH among the four protease tested (Acid protease, neutral protease, Alcalase and papain), with an optimum condition of: (1) ratio of enzyme and substrate, 4760 U/g; (2) concentration of substrate, 4%; (3) reaction temperature, 55 °C and (4) pH 7.0. At 4 h, DH increased significantly (P < 0.01) under nitrogen protection compared with normal microwave assisted acid pre-treatment hydrolysis conditions. The antioxidant ability of the hydrolysate increased and reached its maximum value at 3 h; however DH decreased dramatically after 3 h. Microwave assisted acid pre-treatment and nitrogen protection could be a quick preparatory method for hydrolyzing bone collagen. PMID:21151439

  3. Radiation Pretreatment Does Not Protect the Rat Optic Nerve From Elevated Intraocular Pressure–Induced Injury

    PubMed Central

    Johnson, Elaine C.; Cepurna, William O.; Choi, Dongseok; Choe, Tiffany E.; Morrison, John C.

    2015-01-01

    Purpose. Optic nerve injury has been found to be dramatically reduced in a genetic mouse glaucoma model following exposure to sublethal, head-only irradiation. In this study, the same radiation treatment was used prior to experimental induction of elevated intraocular pressure (IOP) to determine if radiation is neuroprotective in another glaucoma model. Methods. Episcleral vein injection of hypertonic saline was used to elevate IOP unilaterally in two groups of rats: (1) otherwise untreated and (2) radiation pretreated, n > 25/group. Intraocular pressure histories were collected for 5 weeks, when optic nerves were prepared and graded for injury. Statistical analyses were used to compare IOP history and nerve injury. The density of microglia and macrophages in two nerve head regions was determined by Iba1 immunolabeling. Results. Mean and peak IOP elevations were not different between the two glaucoma model groups. Mean optic nerve injury grades were not different in glaucoma model optic nerves and were equivalent to approximately 35% of axons degenerating. Nerves selected for lower mean or peak IOP elevations did not differ in optic nerve injury. Similarly, nerves selected for lower injury grade did not differ in IOP exposure. By multiple regression modeling, nerve injury grade was most significantly associated with mean IOP (P < 0.002). There was no significant effect of radiation treatment. Iba1+ cell density was not altered by radiation treatment. Conclusions. In contrast to previous observations in a mouse genetic glaucoma model, head-only irradiation offers the adult rat optic nerve no protection from optic nerve degeneration due to chronic, experimentally induced IOP elevation. PMID:25525172

  4. Protection against carbon tetrachloride-induced hepatotoxicity by pretreating rats with the hemisuccinate esters of tocopherol and cholesterol.

    PubMed Central

    Fariss, M W; Bryson, K F; Hylton, E E; Lippman, H R; Stubin, C H; Zhao, X G

    1993-01-01

    Previous studies have demonstrated that alpha-tocopheryl hemisuccinate (TS) protects hepatocyte suspensions from chemical-induced toxicity. It has been suggested that TS cytoprotection is related to unique properties of the TS molecule or is dependent on the cellular release and activity of unesterified alpha-tocopherol (T). To test the unique cytoprotective nature of TS in vivo, the protective ability of T and tocopherol esters against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats was examined. Hepatoprotection [determined by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and histopathology] was not observed after T (or tocopheryl acetate and tocopheryl nicotinate) administration, even though this treatment resulted in a fivefold elevation in hepatic T content. Only pretreatment with TS (100 mg/kg, intraperitoneally) resulted in partial hepatoprotection against CCl4 (2.9 g/kg, orally) toxicity. These findings suggest that hepatoprotection results not from the cellular accumulation of T but rather from the intact TS molecule. To test this hypothesis, the hepatoprotective capacity of cholesteryl hemisuccinate (CS), unesterified cholesterol, and cholesteryl acetate (CA) was examined against CCl4 toxicity. As observed with the tocopherol derivatives, pretreatment with unesterified cholesterol or CA demonstrated no protective ability. However, when rats were pretreated with CS (100 mg/kg), the hepatotoxic effects of CCl4 (elevated serum AST and ALT levels and centrilobular necrosis) were completely prevented. The prevention of CCl4-induced hepatotoxicity by CS and TS do not appear to result from an alteration in hepatic drug metabolism. These data clearly demonstrate that CS and TS are unique and powerful cytoprotective agents against CCl4 hepatotoxicity in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. a Figure 1. b Figure 1. c Figure 1. d Figure 2. a Figure 2. b Figure 2. c PMID:8137782

  5. Partial Protection of PC12 Cells from Cellular Stress by Low-Dose Sodium Nitroprusside Pre-treatment.

    PubMed

    Varga, Judit; Bátor, Judit; Nádasdi, Gergő; Árvai, Zita; Schipp, Renáta; Szeberényi, József

    2016-10-01

    The PC12 rat pheochromocytoma cell line is an in vitro model system widely used for the investigation of intracellular signaling events contributing to neuronal differentiation and cell death. We found earlier that the nitric oxide donor compound sodium nitroprusside (SNP) induced apoptosis of PC12 cells if it was applied in high concentration (400 µM). Yoshioka et al. (J Pharmacol Sci 101:126-134, 2006) reported that cell death evoked by cytotoxic concentrations of SNP could be prevented by a 100 µM SNP pre-treatment in a murine macrophage cell line. The apoptosis caused by toxic-dose SNP treatment (400 µM) could be partially overcome in PC12 cells as well by the low-dose SNP pre-treatment. The partial inhibition of apoptosis was accompanied by reduced phosphorylation of certain proteins (such as stress-activated protein kinases, the p53, and the eIF2α proteins), decreased caspase activation, and less intense internucleosomal DNA fragmentation. The 100 µM SNP pre-treatment reduced the pro-apoptotic potential of certain other stress stimuli (serum withdrawal, cisplatin and tunicamycin treatments) as well, although the underlying biochemical changes were not entirely uniform. On the contrary, the 100 µM SNP pre-treatment was unable to prevent cell death caused by the protein synthesis inhibitor anisomycin. Further clarification of the above-mentioned processes may be important in understanding the mechanisms by which mild nitrosative stress protects cells against certain forms of cellular stress conditions. PMID:26626595

  6. Adolescent pre-treatment with oxytocin protects against adult methamphetamine-seeking behavior in female rats.

    PubMed

    Hicks, Callum; Cornish, Jennifer L; Baracz, Sarah J; Suraev, Anastasia; McGregor, Iain S

    2016-03-01

    The neuropeptide oxytocin (OT), given acutely, reduces self-administration of the psychostimulant drug methamphetamine (METH). Additionally, chronic OT administration to adolescent rats reduces levels of alcohol consumption in adulthood, suggesting developmental neuroplasticity in the OT system relevant to addiction-related behaviors. Here, we examined whether OT exposure during adolescence might subsequently inhibit METH self-administration in adulthood. Female Sprague-Dawley rats were administered vehicle or OT (1 mg/kg, i.p.) once daily from postnatal days (PND) 28 to 37 (adolescence). At PND 62 (adulthood), rats were trained to self-administer METH (intravenous, i.v.) in daily 2-hour sessions for 10 days under a fixed ratio 1 (FR1) reinforcement schedule, followed by determination of dose-response functions (0.01-0.3 mg/kg/infusion, i.v.) under both FR1 and progressive ratio (PR) schedules of reinforcement. Responding was then extinguished, and relapse to METH-seeking behavior assessed following priming doses of non-contingent METH (0.1-1 mg/kg, i.p.). Finally, plasma was collected to determine pre-treatment effects on OT and corticosterone levels. Results showed that OT pre-treatment did not significantly inhibit the acquisition of METH self-administration or FR1 responding. However, rats pre-treated with OT responded significantly less for METH under a PR reinforcement schedule, and showed reduced METH-primed reinstatement with the 1 mg/kg prime. Plasma OT levels were also significantly higher in OT pre-treated rats. These results confirm earlier observations that adolescent OT exposure can subtly, yet significantly, inhibit addiction-relevant behaviors in adulthood. PMID:25402719

  7. Rosiglitazone pretreatment protects against lipopolysaccharide-induced fetal demise through inhibiting placental inflammation.

    PubMed

    Bo, Qing-Li; Chen, Yuan-Hua; Yu, Zhen; Fu, Lin; Zhou, Yan; Zhang, Gui-Bin; Wang, Hua; Zhang, Zhi-Hui; Xu, De-Xiang

    2016-03-01

    Peroxisome proliferator-activated receptor (PPAR)-γ is highly expressed in human and rodent placentas. Nevertheless, its function remains obscure. The present study investigated the effects of rosiglitazone, a PPAR-γ agonist, on LPS-induced fetal death. All pregnant mice except controls were intraperitoneally injected with LPS (150 μg/kg) daily from gestational day (GD)15 to GD17. As expected, maternal LPS injection caused placental inflammation and resulted in 63.6% fetal death in dams that completed the pregnancy. Interestingly, LPS-induced fetal mortality was reduced to 16.0% when pregnant mice were pretreated with RSG. Additional experiment showed that rosiglitazone pretreatment inhibited LPS-induced expressions of tumor necrosis factor (Tnf)-α, interleukin (Il)-1β, Il-6, macrophage inflammatory protein (Mip)-2 and keratinocyte-derived chemokine (Kc) in mouse placenta. Although rosiglitazone had little effect on LPS-evoked elevation of IL-10 in amniotic fluid, it alleviated LPS-evoked release of TNF-α and MIP-2 in amniotic fluid. Further analysis showed that pretreatment with rosiglitazone, which activated placental PPAR-γ signaling, simultaneously suppressed LPS-evoked nuclear factor kappa B (NF-κB) activation and blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth layer. These results provide a mechanistic explanation for PPAR-γ-mediated anti-inflammatory activity in the placentas. Overall, the present study provides additional evidence for roles of PPAR-γ as an important regulator of placental inflammation. PMID:26773728

  8. Impact of Sn/F Pre-Treatments on the Durability of Protective Coatings against Dentine Erosion/Abrasion

    PubMed Central

    Ganss, Carolina; Lussi, Adrian; Peutzfeldt, Anne; Naguib Attia, Nader; Schlueter, Nadine

    2015-01-01

    For preventing erosive wear in dentine, coating with adhesives has been suggested as an alternative to fluoridation. However, clinical studies have revealed limited efficacy. As there is first evidence that Sn2+ increases bond strength of the adhesive Clearfil SE (Kuraray), the aim of the present study was to investigate whether pre-treatment with different Sn2+/F− solutions improves the durability of Clearfil SE coatings. Dentine samples (eight groups, n=16/group) were freed of smear layer (0.5% citric acid, 10 s), treated (15 s) either with no solution (control), aminefluoride (AmF, 500 ppm F−, pH 4.5), SnCl2 (800/1600 ppm Sn2+; pH 1.5), SnCl2/AmF (500 ppm F−, 800 ppm Sn2+, pH 1.5/3.0/4.5), or Elmex Erosion Protection Rinse (EP, 500 ppm F−, 800 ppm Sn2+, pH 4.5; GABA International), then rinsed with water (15 s) and individually covered with Clearfil SE. Subsequently the specimens were subjected to an erosion/abrasion protocol consisting of 1320 cycles of immersion in 0.5% citric acid (5°C/55°C; 2 min) and automated brushing (15 s, 200 g, NaF-toothpaste, RDA 80). As the coatings proved stable up to 1320 cycles, 60 modified cycles (brushing time 30 min/cycle) were added. Wear was measured profilometrically. After SnCl2/AmF, pH 4.5 or EP pre-treatment all except one coating survived. In the other groups, almost all coatings were lost and there was no significant difference to the control group. Pre-treatment with a Sn2+/F− solution at pH 4.5 seems able to improve the durability of adhesive coatings, rendering these an attractive option in preventing erosive wear in dentine. PMID:26075906

  9. Impact of Sn/F Pre-Treatments on the Durability of Protective Coatings against Dentine Erosion/Abrasion.

    PubMed

    Ganss, Carolina; Lussi, Adrian; Peutzfeldt, Anne; Naguib Attia, Nader; Schlueter, Nadine

    2015-01-01

    For preventing erosive wear in dentine, coating with adhesives has been suggested as an alternative to fluoridation. However, clinical studies have revealed limited efficacy. As there is first evidence that Sn(2+) increases bond strength of the adhesive Clearfil SE (Kuraray), the aim of the present study was to investigate whether pre-treatment with different Sn(2+)/F(-) solutions improves the durability of Clearfil SE coatings. Dentine samples (eight groups, n=16/group) were freed of smear layer (0.5% citric acid, 10 s), treated (15 s) either with no solution (control), aminefluoride (AmF, 500 ppm F(-), pH 4.5), SnCl2 (800/1600 ppm Sn(2+); pH 1.5), SnCl2/AmF (500 ppm F(-), 800 ppm Sn(2+), pH 1.5/3.0/4.5), or Elmex Erosion Protection Rinse (EP, 500 ppm F-, 800 ppm Sn(2+), pH 4.5; GABA International), then rinsed with water (15 s) and individually covered with Clearfil SE. Subsequently the specimens were subjected to an erosion/abrasion protocol consisting of 1320 cycles of immersion in 0.5% citric acid (5 °C/55 °C; 2 min) and automated brushing (15 s, 200 g, NaF-toothpaste, RDA 80). As the coatings proved stable up to 1320 cycles, 60 modified cycles (brushing time 30 min/cycle) were added. Wear was measured profilometrically. After SnCl2/AmF, pH 4.5 or EP pre-treatment all except one coating survived. In the other groups, almost all coatings were lost and there was no significant difference to the control group. Pre-treatment with a Sn(2+)/F(-) solution at pH 4.5 seems able to improve the durability of adhesive coatings, rendering these an attractive option in preventing erosive wear in dentine. PMID:26075906

  10. Exercise preconditioning of the myocardium.

    PubMed

    Kavazis, Andreas N

    2009-01-01

    Diseases of the heart (e.g. myocardial ischaemia reperfusion injury) remain the major cause of death in the industrialized world. Therefore, developing a pragmatic countermeasure to reduce myocardial ischaemia reperfusion injury is vital. In this regard, a plethora of evidence indicates that regular exercise can protect the heart during an ischaemia reperfusion insult (i.e. cardioprotection). This review summarizes studies indicating that both short-term (i.e. 1-5 days) and long-term (i.e. weeks to months) endurance exercise provides cardioprotection. Data are presented showing that exercise duration and exercise intensity are both important factors in achieving a cardioprotective phenotype. Importantly, it appears that the exercise duration of a single exercise session should last for 60 minutes and should be performed at about 75% maximum oxygen consumption in order to achieve exercise-induced cardioprotection. Furthermore, data are presented showing that exercise-induced cardioprotection against myocardial stunning can persist for at least 9 days after the cessation of exercise training, but is lost 18 days after exercise. This review also summarizes the exercise-induced adaptations that occur to the myocardium. In particular, extrinsic changes observed in human and animal models include neural, hormonal, humoral, vascular and reduced body fat. Other anatomical and biochemical/molecular changes that have been studied as putative mechanisms in exercise-induced cardioprotection include alterations in anatomic coronary arteries, induction of myocardial heat shock proteins, increased myocardial cyclooxygenase-2 activity, elevated endoplasmic reticulum stress proteins, nitric oxide production, improved function of sarcolemmal and/or mitochondrial adenosine triphosphate (ATP)-sensitive potassium channels and increased myocardial antioxidant capacity. However, the most compelling evidence for exercise-induced cardioprotection is the fact that exercise training

  11. GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage.

    PubMed

    Ballough, G P; Cann, F J; Smith, C D; Forster, J S; Kling, C E; Filbert, M G

    1998-05-01

    The effects of GM1 monosialoganglioside pretreatment on brain damage resulting from soman-induced seizure activity were examined in this study. Male Sprague-Dawley rats were infused with GM1 via an osmotic minipump connected through a permanent cannula implanted intracerebroventricularly and challenged with soman (83 micrograms/kg, i.e., 1.25 x LD50) 4 d after initiation of GM1 infusion. Electrocorticographic recordings were monitored via indwelling cortical electrodes. Twenty-seven hours after soman administration, anesthetized rats were euthanized via transcardial perfusion with buffered paraformaldehyde. Brains were processed for hematoxylin and eosin (H&E), cresyl violet (CV), and acetylcholinesterase (AChE) histochemistry, and glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) immunohistochemistry. All soman-challenged rats not infused with GM1 (n = 14) developed status epilepticus (SE). PMID:9778643

  12. Mucuna pruriens Linn. seed extract pretreatment protects against cardiorespiratory and neuromuscular depressant effects of Naja sputatrix (Javan spitting cobra) venom in rats.

    PubMed

    Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Marinello, Enrico; Guerranti, Roberto; Aguiyi, John Chinyere

    2011-04-01

    Mucuna pruriens has been used by native Nigerians as a prophylactic for snakebite. The protective effects of M. pruriens seed extract (MPE) were investigated against the pharmacological actions of N. sputatrix (Javan spitting cobra) venom in rats. The results showed that MPE-pretreatment protected against cardiorespiratory and, to a lesser extent, neuromuscular depressant effects of N. sputatrix venom. These may be explained at least in part by the neutralisation of the cobra venom toxins by anti-MPE antibodies elicited by the MPE pretreatment. PMID:21614888

  13. Trivalent chromium pre-treatment for corrosion protection of aluminum alloys -- an electrochemical evaluation

    SciTech Connect

    Agarwala, V.S.; Beckert, D.W.; Fabiszewski, A.S.; Pearlstein, F.

    1994-12-31

    A corrosion resistant chemical conversion coating on aluminum alloys was developed using a trivalent chromium bath. Electrochemical impedance spectroscopy and dc-polarization measurements were made to determine the nature of the surface films formed. The results showed a 10 to 100 fold increase in the polarization resistance of the surface films compared to the untreated aluminum alloy. These electrochemical results compared well with the corrosion behavior in salt spray tests. The trivalent chromium-treated surfaces showed no corrosion for up to 200 hours in 5% salt spray. A post-treatment with an oxidizer even further improved its resistance which almost doubled its corrosion protection.

  14. Protection of intestinal injury during heat stroke in mice by interleukin-6 pretreatment

    PubMed Central

    Phillips, Neil A; Welc, Steven S; Wallet, Shannon M; King, Michelle A; Clanton, Thomas L

    2015-01-01

    The role of interleukin-6 (IL-6) in hyperthermia and heat stroke is poorly understood. Plasma IL-6 is elevated following hyperthermia in animals and humans, and IL-6 knockout mice are more intolerant of severe hyperthermia. We evaluated the effect of IL-6 supplementation on organ injury following severe hyperthermia exposure in anaesthetized mice. Two hours prior to hyperthermia, mice were treated with 0.6 μg intraperitoneal IL-6, or identical volumes of saline in controls. Mice were anaesthetized, gavaged with FITC–dextran for measures of gastrointestinal permeability, and exposed to incremental (0.5°C every 30 min) increases in temperature. Heating stopped when maximum core temperature (Tc) of 42.4°C was attained (Tc,max). The mice recovered at room temperature (≈22°C) for 30 or 120 min, at which time plasma and tissues were collected. IL-6-treated mice, on average, required ≈25 min longer to attain Tc,max. Injury and swelling of the villi in the duodenum was present in untreated mice after 30 min of recovery. These changes were blocked by IL-6 treatment. IL-6 also reduced gastrointestinal permeability, assayed by the accumulation of FITC–dextran in plasma. Plasma cytokines were also attenuated in IL-6-treated animals, including significant reductions in TNFα, MCP-1 (CXCL2), RANTES (CCL5) and KC (CCL5). The results demonstrate that IL-6 has a protective influence on the pattern of physiological responses to severe hyperthermia, suggesting that early endogenous expression of IL-6 may provide a protection from the development of organ damage and inflammation. PMID:25433073

  15. Short-term pretreatment with atorvastatin attenuates left ventricular dysfunction, reduces infarct size and apoptosis in acute myocardial infarction rats

    PubMed Central

    Chen, Tie-Long; Zhu, Guang-Li; He, Xiao-Long; Wang, Jian-An; Wang, Yu; Qi, Guo-An

    2014-01-01

    Background: Atorvastatin showed a number of cardiovascular benefits, however, the role and underlying molecular mechanisms of short-term atorvastatin-mediated protection remain unclear. Methods: 30 rats were randomly divided into 3 groups: sham group, acute myocardial infarction model group and atorvastatin group. The rats of acute myocardial infarction model were established by ligation of the left anterior descending of coronary arteries. Before surgery, rats in the atorvastatin group received 20 mg/kg/d atorvastatin for 7 days in atorvastatin group. After 4 hours of model established, changes in hemodynamics parameters were recorded and myocardial infarct size was achieved by Evans blue-TTC staining. Myocardium apoptosis was evaluated by TUNEL. The expression of FAS, FAS-L, Bcl-2, Bax, p-BAD, Caspase-8 and Caspase-3 in myocardium were examined by Western blot. Results: In the atorvastatin group, left ventricular function was elevated and infarct size was decreased compared with the model group. Moreover, in the atorvastatin group, the cell apoptosis index was reduced in response to myocardial infarction. The expressions of Bcl-2 were increased and Bax, p-BAD, Fas, Fas-L, caspase-8 and caspase-3 in myocardium were decreased in atorvastatin group. Conclusions: Short-term atorvastatin pretreatment restored left ventricular function and limited infarct size in acute myocardial infarction, which were associated with reduction of the apoptosis in myocardium through Bcl-2 and Fas pathway. PMID:25663976

  16. Pretreatment by low-dose fibrates protects against acute free fatty acid-induced renal tubule toxicity by counteracting PPAR{alpha} deterioration

    SciTech Connect

    Takahashi, Kyoko; Kamijo, Yuji; Hora, Kazuhiko; Hashimoto, Koji; Higuchi, Makoto; Nakajima, Takero; Ehara, Takashi; Shigematsu, Hidekazu; Gonzalez, Frank J.; Aoyama, Toshifumi

    2011-05-01

    Development of a preventive strategy against tubular damage associated with proteinuria is of great importance. Recently, free fatty acid (FFA) toxicities accompanying proteinuria were found to be a main cause of tubular damage, which was aggravated by insufficiency of peroxisome proliferator-activated receptor alpha (PPAR{alpha}), suggesting the benefit of PPAR{alpha} activation. However, an earlier study using a murine acute tubular injury model, FFA-overload nephropathy, demonstrated that high-dose treatment of PPAR{alpha} agonist (0.5% clofibrate diet) aggravated the tubular damage as a consequence of excess serum accumulation of clofibrate metabolites due to decreased kidney elimination. To induce the renoprotective effects of PPAR{alpha} agonists without drug accumulation, we tried a pretreatment study using low-dose clofibrate (0.1% clofibrate diet) using the same murine model. Low-dose clofibrate pretreatment prevented acute tubular injuries without accumulation of its metabolites. The tubular protective effects appeared to be associated with the counteraction of PPAR{alpha} deterioration, resulting in the decrease of FFAs influx to the kidney, maintenance of fatty acid oxidation, diminution of intracellular accumulation of undigested FFAs, and attenuation of disease developmental factors including oxidative stress, apoptosis, and NF{kappa}B activation. These effects are common to other fibrates and dependent on PPAR{alpha} function. Interestingly, however, clofibrate pretreatment also exerted PPAR{alpha}-independent tubular toxicities in PPAR{alpha}-null mice with FFA-overload nephropathy. The favorable properties of fibrates are evident when PPAR{alpha}-dependent tubular protective effects outweigh their PPAR{alpha}-independent tubular toxicities. This delicate balance seems to be easily affected by the drug dose. It will be important to establish the appropriate dosage of fibrates for treatment against kidney disease and to develop a novel PPAR

  17. Protection of dichlorvos induced oxidative stress and nigrostriatal neuronal death by chronic Coenzyme Q{sub 10} pretreatment

    SciTech Connect

    Binukumar, BK; Gupta, Nidhi; Bal, Amanjit; Gill, Kiran Dip

    2011-10-01

    Numerous epidemiological studies have shown an association between pesticide exposure and increased risk of developing Parkinson's diseases. Oxidative stress generated as a result of mitochondrial dysfunction has been implicated as an important factor in the etiology of Parkinson's disease. Previously, we reported that chronic dichlorvos exposure causes mitochondrial impairments and nigrostriatal neuronal death in rats. The present study was designed to test whether Coenzyme Q{sub 10} (CoQ{sub 10}) administration has any neuroprotective effect against dichlorvos mediated nigrostriatal neuronal death, {alpha}-synuclein aggregation, and motor dysfunction. Male albino rats were administered dichlorvos by subcutaneous injection at a dose of 2.5 mg/kg body weight over a period of 12 weeks. Results obtained there after showed that dichlorvos exposure leads to enhanced mitochondrial ROS production, {alpha}-synuclein aggregation, decreased dopamine and its metabolite levels resulting in nigrostriatal neurodegeneration. Pretreatment by Coenzyme Q{sub 10} (4.5 mg/kg ip for 12 weeks) to dichlorvos treated animals significantly attenuated the extent of nigrostriatal neuronal damage, in terms of decreased ROS production, increased dopamine and its metabolite levels, and restoration of motor dysfunction when compared to dichlorvos treated animals. Thus, the present study shows that Coenzyme Q{sub 10} administration may attenuate dichlorvos induced nigrostriatal neurodegeneration, {alpha}-synuclein aggregation and motor dysfunction by virtue of its antioxidant action. - Highlights: > CoQ{sub 10} administration attenuates dichlorvos induced nigrostriatal neurodegenaration. > CoQ{sub 10} pre treatment leads to preservation of TH-IR neurons. > CoQ{sub 10} may decrease oxidative damage and {alpha}-synuclin aggregation. > CoQ{sub 10} treatment enhances motor function and protects rats from catalepsy.

  18. Microleakage in Resin Composite Restoration following Antimicrobial Pre-treatments with 2% Chlorhexidine and Clearfil Protect Bond

    PubMed Central

    Hameed, Hisham; Babu, Biju P; Sagir, V M Mohammed; Chiriyath, Kennet J; Mathias, Jones; Shaji, A P

    2015-01-01

    Aim: To evaluate microleakage in resin composite restorations after antimicrobial pre – treatments Materials and Methods: Forty freshly extracted non carious human premolars were procured. In all forty premolar specimens, class V preparation of standard dimension were prepared and were randomly divided into three experimental and one control group. In all control and experimental groups the class V preparations were restored with FILTEK Z350 composite restorative material. The experimental groups included different self etching primers and 2% Chlorhexidine gluconate. The control group included Xeno III and no antimicrobial pre-treatment was done for the control group. Thereafter these specimens were thermocycled, dried and sealed with nail varnish, leaving 1mm around the restoration and immersed in 0.5% basic fuchsin for 24 hours and then the specimens were subjected for microleakage evaluation. The results were statistically analyzed by Kruskal Wallis Test and Mann Whitney ‘U’ test. Results: Results indicate that group II (2% chlorhexidine gluconate group) had the minimum mean value (15.05) and group III(Clearfil protect Bond group) and IV(control group) had the maximum mean microleakage at the enamel margin (23.00). At the gingival margin the lowest mean microleakage values were obtained with group I (Clearfil SE bond group) and group II (2% chlorhexidine gluconate) (20.25) and highest with group III and group IV (20.85). The difference was not statistically significant both at the enamel margin and the dentin margin (p>0.05). Interpretation & Conclusions: Within the limitations of this in-vitro study, we conclude that: None of the materials tested in this study completely eliminated microleakage at the enamel and at the gingival margin.All of the tested materials provided better sealing at the enamel margin than at the gingival margin. PMID:26229374

  19. Angiogenesis in the Infarcted Myocardium

    PubMed Central

    Cochain, Clement; Channon, Keith M.

    2013-01-01

    Abstract Significance: Proangiogenic therapy appeared a promising strategy for the treatment of patients with acute myocardial infarction (MI), as de novo formation of microvessels, has the potential to salvage ischemic myocardium at early stages after MI, and is also essential to prevent the transition to heart failure through the control of cardiomyocyte hypertrophy and contractility. Recent Advances: Exciting preclinical studies evaluating proangiogenic therapies for MI have prompted the initiation of numerous clinical trials based on protein or gene transfer delivery of growth factors and administration of stem/progenitor cells, mainly from bone marrow origin. Nonetheless, these clinical trials showed mixed results in patients with acute MI. Critical Issues: Even though methodological caveats, such as way of delivery for angiogenic growth factors (e.g., protein vs. gene transfer) and stem/progenitor cells or isolation/culture procedure for regenerative cells might partially explain the failure of such trials, it appears that delivery of a single growth factor or cell type does not support angiogenesis sufficiently to promote cardiac repair. Future Directions: Optimization of proangiogenic therapies might include stimulation of both angiogenesis and vessel maturation and/or the use of additional sources of stem/progenitor cells, such as cardiac progenitor cells. Experimental unraveling of the mechanisms of angiogenesis, vessel maturation, and endothelial cell/cardiomyocyte cross talk in the ischemic heart, analysis of emerging pathways, as well as a better understanding of how cardiovascular risk factors impact endogenous and therapeutically stimulated angiogenesis, would undoubtedly pave the way for the development of novel and hopefully efficient angiogenesis targeting therapeutics for the treatment of acute MI. Antioxid. Redox Signal. 18, 1100–1113. PMID:22870932

  20. Biomass pretreatment

    SciTech Connect

    Hennessey, Susan Marie; Friend, Julie; Elander, Richard T; Tucker, III, Melvin P

    2013-05-21

    A method is provided for producing an improved pretreated biomass product for use in saccharification followed by fermentation to produce a target chemical that includes removal of saccharification and or fermentation inhibitors from the pretreated biomass product. Specifically, the pretreated biomass product derived from using the present method has fewer inhibitors of saccharification and/or fermentation without a loss in sugar content.

  1. Comparative transcriptome analyses indicate enhanced cellular protection against FMDV in PK15 cells pretreated with IFN-γ.

    PubMed

    Fu, Yin; Zhu, Zesen; Chang, Huiyun; Liu, Zaixin; Liu, Jing; Chen, Huiyong

    2016-07-25

    Interferon gamma (IFN-γ) can induce a host antiviral response to foot and mouth disease virus (FMDV) in vivo and in vitro. To elucidate the mechanism of IFN-γ anti FMDV infection in host cells, high-throughput RNA sequencing was analyzed for systemic changes in gene expression profiles in PK15 cells infected by FMDV with or without IFN-γ pretreatment. More than 25 million reads, covering 1.2-1.5 Gb, were analyzed from each experiment panel. FMDV challenge altered the transcription of genes involved in positively and negatively regulating cell death or apoptosis; however, the expected immune suppression response was not obvious. IFN-γ pretreatment combined with FMDV infection normalized the increase in apoptosis. Furthermore, the transcription factors required for IFN-γ functioning, STAT1 and IRF1 were up-regulated by IFN-γ pretreatment and stimulated downstream IFN-stimulated genes (ISGs). These induced ISGs are mainly responsible for antigen processing, antigen presentation or antiviral defense. Interestingly, a synergistic effect on some ISGs, including OAS1, OAS2, MX1, MX2, RIG-I and IFIT1, was observed in the combined treatment compared to the IFN-γ treatment alone. The suggested effects identified by RNA sequencing were consistent with cellular morphology changes and confirmed by related protein markers. This is the first report exploring transcriptome alterations introduced by FMDV infection with or without IFN-γ pretreatment. The identified key host genes that control cell survival in vitro broaden our comprehensive understanding of how IFN-γ inhibits FMDV infection and may shed light on developing improved FMD control approaches. PMID:27018244

  2. Cardioprotective Effect of Electroacupuncture Pretreatment on Myocardial Ischemia/Reperfusion Injury via Antiapoptotic Signaling

    PubMed Central

    Lu, Sheng-feng; Huang, Yan; Wang, Ning; Shen, Wei-xing; Fu, Shu-ping; Li, Qian; Yu, Mei-ling; Liu, Wan-xin; Chen, Xia; Jing, Xin-yue; Zhu, Bing-mei

    2016-01-01

    Objectives. Our previous study has used RNA-seq technology to show that apoptotic molecules were involved in the myocardial protection of electroacupuncture pretreatment (EAP) on the ischemia/reperfusion (I/R) animal model. Therefore, this study was designed to investigate how EAP protects myocardium against myocardial I/R injury through antiapoptotic mechanism. Methods. By using rats with myocardial I/R, we ligated the left anterior descending artery (LAD) for 30 minutes followed by 4 hr of reperfusion after EAP at the Neiguan (PC6) acupoint for 12 days; we employed arrhythmia scores, serum myocardial enzymes, and cardiac troponin T (cTnT) to evaluate the cardioprotective effect. Heart tissues were harvested for western blot analyses for the expressions of pro- and antiapoptotic signaling molecules. Results. Our preliminary findings showed that EAP increased the survival of the animals along with declined arrhythmia scores and decreased CK, LDH, CK-Mb, and cTnT levels. Further analyses with the heart tissues detected reduced myocardial fiber damage, decreased number of apoptotic cells and the protein expressions of Cyt c and cleaved caspase 3, and the elevated level of Endo G and AIF after EAP intervention. At the same time, the protein expressions of antiapoptotic molecules, including Xiap, BclxL, and Bcl2, were obviously increased. Conclusions. The present study suggested that EAP protected the myocardium from I/R injury at least partially through the activation of endogenous antiapoptotic signaling. PMID:27313648

  3. Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis

    SciTech Connect

    El-Naga, Reem N.

    2014-01-01

    Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30 mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7 mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1β, TNF-α, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is

  4. Myocardium wall thickness transducer and measuring method

    NASA Technical Reports Server (NTRS)

    Feldstein, C.; Lewis, G. W.; Silver, R. H.; Culler, V. H. (Inventor)

    1976-01-01

    A miniature transducer for measuring changes of thickness of the myocardium is described. The device is easily implantable without traumatizing the subject, without affecting the normal muscle behavior, and is removable and implantable at a different muscle location. Operating features of the device are described.

  5. Influence of the surface pre-treatment of aluminum on the processes of formation of cerium oxides protective films

    NASA Astrophysics Data System (ADS)

    Andreeva, R.; Stoyanova, E.; Tsanev, A.; Stoychev, D.

    2016-03-01

    It is known that there is special interest in the contemporary investigations on conversion treatment of aluminum aimed at promoting its corrosion stability, which is focused on electrolytes on the basis of salts of metals belonging to the group of rare-earth elements. Their application is especially attractive, as it enables a successful substitution of the presently applied highly efficient, but at the same time toxic Cr6+-containing electrolytes. The present paper presents a study on the influence of the preliminary alkaline activation and acidic de-oxidation of the aluminum surface on the processes of immersion formation of protective cerium oxides films on Al 1050. The results obtained show that their deposition from simple electrolytes (containing only salts of Ce3+ ions) on the Al surface, treated only in alkaline solution, occurs at a higher rate, which leads to preparing thicker oxide films having a better protective ability. In the cases when the formation of oxide films is realized in a complex electrolyte (containing salts of Ce3+ and Cu2+ ions), better results are obtained with respect to the morphology and protective action of cerium oxides film on samples that have been consecutively activated in alkaline solution and deoxidized in acidic solution. Electrochemical investigations were carried out in a model corrosion medium (0.1 M NaCl); it was shown that the cerium protective films, deposited by immersion, have a cathodic character with regard to the aluminum support and inhibit the occurrence of the depolarizing corrosion process -- the reaction of oxygen reduction.

  6. Small vessel hematocrit in ischemic myocardium

    SciTech Connect

    Gumm, D.C.; Cooper, S.M.; Marcus, M.L.; Chilian, W.M.; Harrison, D.G.

    1986-03-01

    As blood enters the microvasculature of normally perfused myocardium, there is a progressive decrease in small vessel hematocrit (SV Hct) due to RBC streaming in smaller branching vessels and the Fahraeus-Lindqvist effect. We hypothesized that if the coronary collateral circulation was composed of very small vessels branching from large parent vessels, plasma streaming would result in a further decrease of SV Hct in ischemic myocardium. Six open chest anesthetized dogs were studied. Plasma was labelled with /sup 59/FeCl siderophilin and RBC's with /sup 99/mTc to estimate SV Hct from myocardial biopsies. The LAD was occluded and cannulated for measurement of retrograde flow (arising presumably from proximal collaterals). The ischemic region was identified using the microsphere shadow technique. Collateral flow after LAD occlusion was 30 +- 12 ml/min 100g (x +- SE). Systemic Hct was 40 +- 1%. The Hct of blood from retrograde flow was 39 +- 1% (p = NS). Activity of /sup 59/FeCl and /sup 99/mTc in known quantities of blood were compared to myocardial biopsies to estimate SV Hct. Ischemic SV Hct was 23 +- 2% and non-ischemic SV Hct was 21 +- 1% (p = NS). We conclude that the size and branching pattern of coronary collaterals is such that plasma streaming in collaterals does not result in an additional decrease in SV Hct in ischemic myocardium.

  7. Effect of pre-treatment of the substrate surface by energetic C+ ion bombardment on structure and nano-tribological characteristics of ultra-thin tetrahedral amorphous carbon (ta-C) protective coatings

    NASA Astrophysics Data System (ADS)

    Rismani, E.; Sinha, S. K.; Tripathy, S.; Yang, H.; Bhatia, C. S.

    2011-03-01

    Depositing an ultra-thin tetrahedral amorphous carbon (ta-C) protective coating on the surface of the recording heads in magnetic tape drives can improve the tribological problems at the head/tape interface. In this work the effect of pre-treatment of the surface of AlTiC substrate (main bearing surface of head in contact with tape) by C+ ions of moderate energy (smaller than 400 eV) on the structural and tribo-mechanical behaviours of the coated surfaces is studied. Sample preparation consisted of two separate stages of surface pre-treatment and deposition of the protective film, and was done by means of filtered cathodic vacuum arc. Structure of the ta-C film and its interface with the substrate were studied by transmission electron microscopy and time-of-flight secondary ion mass spectrometry depth profiling. The results revealed the formation of a broader, dense atomically mixed layer at the ta-C film-substrate interface of the pre-treated samples comparing with that of the samples without pre-treatment. Chemical characterization of thin diamond-like carbon coatings was conducted by means of x-ray photoelectron spectroscopy and the surface pre-treatment was found to have a remarkable effect on increasing the sp3 hybridization fraction in the ta-C overcoat. Nano-tribological properties of the treated surfaces were examined using ball-on-flat wear test at very low load (20 mN). There was a good correlation between the surface and structure characteristics of the film, and the tribological results and the pre-treated surfaces presented a very low coefficient of friction and higher wear life. The experimental results demonstrate the effectiveness of bombardment of the surface with C+ ions of moderate ion energy to improve the structural and tribo-mechanical properties of the protective ta-C films on the magnetic head substrate material.

  8. Backscatter and attenuation characterization of ventricular myocardium

    NASA Astrophysics Data System (ADS)

    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

  9. Enhanced self-cleaning, antibacterial and UV protection properties of nano TiO2 treated textile through enzymatic pretreatment.

    PubMed

    Montazer, Majid; Seifollahzadeh, Samira

    2011-01-01

    Textile materials can be treated with some enzymes to improve their functionality. The usual enzymatic treatment hydrolyzes the textile surfaces that leads to increase the functional groups. Here, the polyester/wool fabric as a blend of fibers fabric was selected and treated with the two different types of enzymes to increase the surface activity with a propose of higher nano-TiO(2) adsorption. The fabric was first treated with proteases and lipases to hydrolyze the wool and the polyester surfaces, respectively. It has been then dipped into an ultrasound bath containing nano TiO(2) and cross-linking agent followed by curing. The cross-linking agent, butane tetracarboxylic acid (BTCA), also assisted to enhance the nano-particles adsorption and stabilization on the fabric surface. The self-cleaning properties of the fabrics were examined through evaluating the color removal from the stained fabric with Acid Blue 113. The antibacterial properties were determined by reduction growth of a Gram-negative bacteria E. coli. and the UV protection was assessed by UV-reflectance spectrum. The SEM pictures and EDX spectrums of some samples were also reported. PMID:21388383

  10. Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.

    PubMed Central

    Potten, C. S.; Booth, D.; Haley, J. D.

    1997-01-01

    The gastrointestinal tract, with its rapid cell replacement, is sensitive to cytotoxic damage and can be a site of dose-limiting toxicity in cancer therapy. Here, we have investigated the use of one growth modulator to manipulate the cell cycle status of gastrointestinal stem cells before cytotoxic exposure to minimize damage to this normal tissue. Transforming growth factor beta-3 (TGF-beta3), a known inhibitor of cell cycle progression through G1, was used to alter intestinal crypt stem cell sensitivity before 12-16 Gy of gamma irradiation, which was used as a model cytotoxic agent. Using a crypt microcolony assay as a measure of functional competence of gastrointestinal stem cells, it was shown that the administration of TGF-beta3 over a 24-h period before irradiation increased the number of surviving crypts by four- to six-fold. To test whether changes in crypt survival are reflected in the well-being of the animal, survival time analyses were performed. After 14.5 Gy of radiation, only 35% of the animals survived within a period of about 12 days, while prior treatment with TGF-beta3 provided significant protection against this early gastrointestinal animal death, with 95% of the treated animals surviving for greater than 30 days. PMID:9166937

  11. Pretreatment with Fucoidan from Fucus vesiculosus Protected against ConA-Induced Acute Liver Injury by Inhibiting Both Intrinsic and Extrinsic Apoptosis

    PubMed Central

    Li, Jingjing; Chen, Kan; Li, Sainan; Liu, Tong; Wang, Fan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

    2016-01-01

    This study aimed to explore the effects of fucoidan from Fucus vesiculosus on concanavalin A (ConA)-induced acute liver injury in mice. Pretreatment with fucoidan protected liver function indicated by ALT, AST and histopathological changes by suppressing inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). In addition, intrinsic and extrinsic apoptosis mediated by Bax, Bid, Bcl-2, Bcl-xL and Caspase 3, 8, and 9 were inhibited by fucoidan and the action was associated with the TRADD/TRAF2 and JAK2/STAT1 signal pathways. Our results demonstrated that fucoidan from Fucus vesiculosus alleviated ConA-induced acute liver injury via the inhibition of intrinsic and extrinsic apoptosis mediated by the TRADD/TRAF2 and JAK2/STAT1 pathways which were activated by TNF-α and IFN-γ. These findings could provide a potential powerful therapy for T cell-related hepatitis. PMID:27035150

  12. Prolonged Cardiac Dysfunction After Intraparenchymal Hemorrhage and Neurogenic Stunned Myocardium.

    PubMed

    Krishnamoorthy, Vijay; Wilson, Thomas; Sharma, Deepak; Vavilala, Monica S

    2016-01-01

    Cardiac dysfunction occurring secondary to neurologic disease, termed neurogenic stunned myocardium, is an incompletely understood phenomenon that has been described after several distinct neurologic processes. We present a case of neurogenic stunned myocardium, discovered intraoperatively after anesthetic induction, in a patient who presented to our operating room with a recent intraparenchymal hemorrhage. We discuss the longitudinal cardiac functional course after neurogenic stunned myocardium. Finally, we discuss the pathophysiology of neurogenic stunned myocardium, as well as its implications for anesthesiologists caring for neurosurgical patients. PMID:26462162

  13. Clinical study of the stunned myocardium.

    PubMed

    Sone, T; Tsuboi, H; Sassa, H

    1991-09-01

    Clinical features of 37 cases of stunned myocardium were studied. Mean duration of asynergy was 22.6 +/- 15.7 days. In all 11 cases of unstable angina without any significant serum creatine kinase leakage, the duration of asynergy was within 14 days. Related coronary lesions were reperfused (spontaneously or by interventional therapy) to TIMI grade II or higher. Transient Q waves were observed in 39% of all cases. Negative T waves tended to be prolonged, and persisted after disappearance of asynergy in 74% of all cases. 201Tl uptake in the stunned area varied widely between individual cases (ranging from "absent" to "normal"), although it became normal in all cases in the chronic stage. Mal-distribution of 99mTc-pyrophosphate (PYP) to the endocardial side of the stunned area was observed in 33%. In 186 cases of acute coronary syndrome, we studied whether or not reversibility of ischemia-disturbed myocardium could be predicted by simultaneous dual isotope SPECT, and found that 201Tl-uptake in the chronic stage significantly improved in the region showing absence of 99mTc-PYP accumulation or maldistribution of 99mTc-PYP to the endocardial side, while reversibility of the region showing transmural 99mTc-PYP accumulation and a dought pattern was poor. Ischemia-associated myocardial damage recovered to various degrees, and dual isotope SPECT was useful in evaluating the reversibility of such damage already at the acute stage. PMID:1834873

  14. OCT imaging of myocardium extending to pulmonary vein

    NASA Astrophysics Data System (ADS)

    Li, Zhifang; Dickfeld, Timm; Tang, Qinggong; Wang, Bohan; Chen, Yu

    2016-02-01

    In this study, we propose to use optical coherence tomography to enable a direct visualization of myocardium extending into the pulmonary vein (PV). The results showed that there are obvious differences in the morphology of myocardium and fibrous tissue in the transition region of myocardial sleeve, which is in agreement with the histological analysis. In addition, the myocardial area in transition point has three layers in the depth of 1 mm, and the depth-resolved myocardial fiber show different orientation in the different layers. This characteristic was applied for segmentation of the structures of myocardium extending into PV.

  15. Heat shock proteins, end effectors of myocardium ischemic preconditioning?

    PubMed Central

    Guisasola, María Concepcion; Desco, Maria del Mar; Gonzalez, Fernanda Silvana; Asensio, Fernando; Dulin, Elena; Suarez, Antonio; Garcia Barreno, Pedro

    2006-01-01

    The purpose of this study was to investigate (1) whether ischemia-reperfusion increased the content of heat shock protein 72 (Hsp72) transcripts and (2) whether myocardial content of Hsp72 is increased by ischemic preconditioning so that they can be considered as end effectors of preconditioning. Twelve male minipigs (8 protocol, 4 sham) were used, with the following ischemic preconditioning protocol: 3 ischemia and reperfusion 5-minute alternative cycles and last reperfusion cycle of 3 hours. Initial and final transmural biopsies (both in healthy and ischemic areas) were taken in all animals. Heat shock protein 72 messenger ribonucleic acid (mRNA) expression was measured by a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method using complementary DNA normalized against the housekeeping gene cyclophilin. The identification of heat shock protein 72 was performed by immunoblot. In our “classic” preconditioning model, we found no changes in mRNA hsp72 levels or heat shock protein 72 content in the myocardium after 3 hours of reperfusion. Our experimental model is valid and the experimental techniques are appropriate, but the induction of heat shock proteins 72 as end effectors of cardioprotection in ischemic preconditioning does not occur in the first hours after ischemia, but probably at least 24 hours after it, in the so-called “second protection window.” PMID:17009598

  16. Model dependent behaviour of pressure hypertrophied myocardium.

    PubMed

    Cooper, G; Tomanek, R J

    1987-05-01

    Two animal models with contrasting responses to pressure overloading were used to determine whether cardiac dysfunction is a general property of pressure hypertrophied myocardium or a specific property of a particular model. Chronic progressive cardiac pressure overload was compared in (a) the left ventricle of the adult and aged spontaneously hypertensive rat, in which pressure overloading begins in the pup, and (b) the right ventricle of the adult cat, in which pressure overloading was initiated surgically in the kitten. Nine hypertensive and nine control rats were studied at 1 year of age, when hypertension is stable in this model; five hypertensive and five control rats were then studied at 2 years of age, when both groups of rats are beginning to show appreciable senile mortality. Systolic blood pressure was similarly increased in both hypertensive groups; compared with the normotensive control groups, the ratio of left ventricular to body weight was 36% and 76% higher in the 1 and 2 year old hypertensive groups respectively. During isotonic contractions of left ventricular papillary muscles the extent and velocity of shortening in muscles from the control and hypertensive rats in each group were the same, but shortening and relaxation times were prolonged in muscles from the hypertensive rats in both age groups. During isometric contractions developed tension and the rate of tension rise were the same throughout, but the time integral of active tension was increased in muscles from the hypertensive rats in both age groups. The ratio of oxygen consumption to either external work or developed tension was decreased in muscles from the hypertensive rats. In contrast to these data, previous data from the hypertrophied cat model showed reductions in both the velocity and the extent of isotonic shortening as well as in the rate and amount of isometric tension development, and prolongation of contraction was not observed. A similar but smaller decrease in the oxygen

  17. Computational Modeling of Healthy Myocardium in Diastole.

    PubMed

    Nikou, Amir; Dorsey, Shauna M; McGarvey, Jeremy R; Gorman, Joseph H; Burdick, Jason A; Pilla, James J; Gorman, Robert C; Wenk, Jonathan F

    2016-04-01

    In order to better understand the mechanics of the heart and its disorders, engineers increasingly make use of the finite element method (FEM) to investigate healthy and diseased cardiac tissue. However, FEM is only as good as the underlying constitutive model, which remains a major challenge to the biomechanics community. In this study, a recently developed structurally based constitutive model was implemented to model healthy left ventricular myocardium during passive diastolic filling. This model takes into account the orthotropic response of the heart under loading. In-vivo strains were measured from magnetic resonance images (MRI) of porcine hearts, along with synchronous catheterization pressure data, and used for parameter identification of the passive constitutive model. Optimization was performed by minimizing the difference between MRI measured and FE predicted strains and cavity volumes. A similar approach was followed for the parameter identification of a widely used phenomenological constitutive law, which is based on a transversely isotropic material response. Results indicate that the parameter identification with the structurally based constitutive law is more sensitive to the assigned fiber architecture and the fit between the measured and predicted strains is improved with more realistic sheet angles. In addition, the structurally based model is capable of generating a more physiological end-diastolic pressure-volume relationship in the ventricle. PMID:26215308

  18. Shock-induced arrhythmogenesis in the myocardium

    NASA Astrophysics Data System (ADS)

    Trayanova, Natalia; Eason, James

    2002-09-01

    The focus of this article is the investigation of the electrical behavior of the normal myocardium following the delivery of high-strength defibrillation shocks. To achieve its goal, the study employs a complex three-dimensional defibrillation model of a slice of the canine heart characterized with realistic geometry and fiber architecture. Defibrillation shocks of various strengths and electrode configurations are delivered to the model preparation in which a sustained ventricular tachycardia is induced. Instead of analyzing the post-shock electrical events as progressions of transmembrane potential maps, the study examines the evolution of the postshock phase singularities (PSs) which represent the organizing centers of reentry. The simulation results demonstrate that the shock induces numerous PSs the majority of which vanish before the reentrant wavefronts associated with them complete half of a single rotation. Failed shocks are characterized with one or more PSs that survive the initial period of PS annihilation to establish a new postshock arrhythmia. The increase in shock strength results in an overall decrease of the number of PSs that survive over 200 ms after the end of the shock; however, the exact behavior of the PSs is strongly dependent on the shock electrode configuration.

  19. Impaired oxidative phosphorylation in overtrained rat myocardium

    PubMed Central

    Kadaja, Lumme; Eimre, Margus; Paju, Kalju; Roosimaa, Mart; Põdramägi, Taavi; Kaasik, Priit; Pehme, Ando; Orlova, Ehte; Mudist, Margareeta; Peet, Nadezhda; Piirsoo, Andres; Seene, Teet; Gellerich, Frank N; Seppet, Enn K

    2010-01-01

    The present study was undertaken to characterize and review the changes in energy metabolism in rat myocardium in response to chronic exhaustive exercise. It was shown that a treadmill exercise program applied for six weeks led the rats into a state characterized by decreased performance, loss of body weight and enhanced muscle catabolism, indicating development of overtraining syndrome. Electron microscopy revealed disintegration of the cardiomyocyte structure, cellular swelling and appearance of peroxisomes. Respirometric assessment of mitochondria in saponin-permeabilized cells in situ revealed a decreased rate of oxidative phosphorylation (OXPHOS) due to diminished control over it by ADP and impaired functional coupling of adenylate kinase to OXPHOS. In parallel, reduced tissue content of cytochrome c was observed, which could limit the maximal rate of OXPHOS. The results are discussed with respect to relationships between the volume of work and corresponding energy metabolism. It is concluded that overtraining syndrome is not restricted to skeletal muscle but can affect cardiac muscle as well. PMID:21264069

  20. The venous drainage of the human myocardium.

    PubMed

    von Lüdinghausen, M

    2003-01-01

    New cardiological techniques such as coronary sinus catheterization and selective catheterization of the cardiac veins permit the opening of new experimental and clinical fields, for instance in venous angiography and the reverse nourishment of myocardium which is endangered by ischemia,and also in the electrophysiological study of the components of the conduction system. New approaches in heart surgery, such as the removal of accessory pathways of the conduction system (as in WPW syndrome), necessitate the realization of the topographical relationships of the vessels in the various sections of the coronary sulci in a different way. The objective of this work is, therefore, to present comprehensive and almost new macro- and microanatomical data about the venous drainage of the myocardium via the coronary sinus and its related and unrelated (non-coronary) cardiac veins. Examination of meticulously dissected heart specimens (of individuals who had achieved old or extreme old age at the time of their death in Germany: n=250) as well as corrosion casts of adult cardiac vessels (of individuals of all ages, n=25) formed the basis for the exact description and documentation of the occurrence, frequency, origin, and courses of both the normal and anomalously developed human coronary sinus and cardiac veins. A wide range of morphological and experimental references was consulted in order to enable thorough discussion of the anatomical findings in the light of modern cardiological diagnostics and treatment. The anatomical and clinical nomenclature is presented and there is a brief comment on modern diagnostic techniques and their applications where the cardiac veins are concerned. The two principal and one compound cardiac venous system are defined and discussed with reference to the existence of both the normal and anomalous coronary sinus and cardiac vein. 1. The greater (major) cardiac venous system (2) The smaller (minor) cardiac venous system (3)The compound cardiac

  1. Murine myocardium OCT imaging with a blood substitute

    NASA Astrophysics Data System (ADS)

    Kim, Jeehyun; Villard, Joseph W.; Lee, Ho; Feldman, Marc D.; Milner, Thomas E.

    2002-06-01

    Imaging of the in vivo murine myocardium using optical coherence tomography (OCT) is described. Application of conventional techniques (e.g. MRI, Ultrasound imaging) for imaging the murine myocardium is problematic because the wall thickness is less than 1.5mm (20g mouse), and the heart rate can be as high as six-hundred beats per minute. To acquire a real-time image of the murine myocardium, OCT can provide sufficient spatial resolution (10 micrometers ) and imaging speed (1000 A-Scans/s). Strong light scattering by blood in the heart causes significant light attenuation making delineation of the endocardium-chamber boundary problematic. By replacing whole blood in the mouse with an artificial blood substitute we demonstrate significant reduction of light scattering in the murine myocardium. The results indicate a significant reduction in light scattering as whole blood hematocrit is diminished below 5%. To measure thickness change of the myocardium during one cycle, a myocardium edge detection algorithm is developed and demonstrated.

  2. 40 CFR 463.26 - Pretreatment for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Pretreatment for new sources. 463.26 Section 463.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Cleaning Water Subcategory § 463.26 Pretreatment for new sources. Any new...

  3. 40 CFR 35.907 - Municipal pretreatment program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Municipal pretreatment program. 35.907 Section 35.907 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act § 35.907 Municipal pretreatment program. (a)...

  4. 40 CFR 405.66 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Pretreatment standards for new sources. 405.66 Section 405.66 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Natural and Processed Cheese Subcategory § 405.66 Pretreatment...

  5. 40 CFR 405.64 - Pretreatment standards for existing sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... comply with 40 CFR part 403. In addition, the following pretreatment standard establishes the quantity or... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for existing sources. 405.64 Section 405.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...

  6. 40 CFR 405.66 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources. 405.66 Section 405.66 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Natural and Processed Cheese Subcategory § 405.66 Pretreatment...

  7. 40 CFR 467.35 - Pretreatment standards for existing sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Pretreatment standards for existing sources. 467.35 Section 467.35 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ALUMINUM FORMING POINT SOURCE CATEGORY Extrusion Subcategory § 467.35 Pretreatment standards for existing sources....

  8. 40 CFR 467.36 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Pretreatment standards for new sources. 467.36 Section 467.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ALUMINUM FORMING POINT SOURCE CATEGORY Extrusion Subcategory § 467.36 Pretreatment standards for new sources. (a)...

  9. 40 CFR 403.2 - Objectives of general pretreatment regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Objectives of general pretreatment regulations. 403.2 Section 403.2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PRE-TREAT-MENT REGULATIONS FOR EXIST-ING AND NEW SOURCES...

  10. Fatty acid uptake in normal human myocardium

    SciTech Connect

    Vyska, K.; Meyer, W.; Stremmel, W.; Notohamiprodjo, G.; Minami, K.; Machulla, H.J.; Gleichmann, U.; Meyer, H.; Koerfer, R. )

    1991-09-01

    Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an unstirred layer were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 {plus minus} 0.024 mumol/g and 0.37 {plus minus} 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells.

  11. Protective effect of Guaraná (Paullinia cupana var. sorbilis) pre-treatment on cadmium-induced damages in adult Wistar testis.

    PubMed

    Leite, Rodrigo Paula; Wada, Ronaldo Seichi; Monteiro, Juliana Castro; Predes, Fabrícia Souza; Dolder, Heidi

    2011-06-01

    Guaraná (Paullinia cupana) is an Amazonian plant. Its antioxidant potential was demonstrated to be due to the high polyphenol concentration. On the other hand, one of the mechanisms underlying cadmium-induced cellular damage is free radical mediated, resulting in increased oxidative processes. This study investigated P. cupana's potential to attenuate cadmium-induced damages in Wistar rat testis. Adult male Wistar rats were either pre-treated with 2 mg/g body weight (BW) of powdered P. cupana seed during 56 days and/or injected with cadmium chloride at a dose of 1.15 mg/kg BW. After cadmium exposition (48 h), testes samples were evaluated by histological and stereological analyses. Both groups exposed to cadmium presented evident morphological alterations relative to control animals. A few rodents showed massive cell death in the seminiferous epithelium and intertubular space, indicating that some animals are more sensitive to cadmium. Despite the alterations observed in both groups, pre-treatment with P. cupana was effective in attenuating morphological changes in Leydig cells, as well as reducing inflammatory response, relative to animals exclusively exposed to the metal. Animals treated only with P. cupana presented a significant increase in plasma testosterone levels and a significant increase in volumetric proportions of seminiferous tubules, which are indicative of spermatogenic stimulation. PMID:20495888

  12. System of scale-selective tomography of myocardium birefringence

    NASA Astrophysics Data System (ADS)

    Ushenko, O. G.; Boichuk, T. M.; Bachinskiy, V. T.; Vanchuliak, O. Ya.; Minzer, O. P.; Ushenko, Yu. O.; Dubolazov, O. V.; Savich, V. O.

    2015-09-01

    This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

  13. Pre-treatment of a single high-dose of atorvastatin provided cardioprotection in different ischaemia/reperfusion models via activating mitochondrial KATP channel.

    PubMed

    Zhao, Zhifang; Cui, Wei; Zhang, Hailin; Gao, Haixia; Li, Xuze; Wang, Yuanyuan; Hu, Haijuan; Li, Bo

    2015-03-15

    A number of clinical trials have shown that a high loading dose of atorvastatin (Ator) within 24h before percutaneous coronary intervention (PCI) exerts protective effects on the cardiovascular system. However, the potential mechanisms regarding this rapid benefit of Ator remain elusive. Our study introduced three different ischaemia/reperfusion (I/R) models: I/R in vivo, I/R in vitro and oxygen-glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes to observe the protective effect of a single loading dose of Ator pre-treatment and further to explore the potential mechanisms of this protective effect with confocal laser scanning microscopy, flow cytometry, biochemical and morphology methods. We found that the pre-treatment of high-dose Ator decreased the cardiac injury and maintained the integrity of mitochondria in all three of the I/R models, which was similar to ischaemic pre-conditioning (IPC). We used the mitochondrial K(ATP) channels (mitoKATP channels) inhibitor 5-hydroxydecanoate (5-HD) and the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) to analyse the underlying mechanisms. The results showed that the pre-treatment of Ator significantly decreased I/R-induced injury, and maintained the functional integrity of mitochondria through alleviating Ca(2+) overload, reactive oxygen species burst, inhibiting the opening of mPTP and preventing mitochondrial membrane potential (ΔΨm) depolarisation. The present results demonstrated that a single dose of Ator might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening through activating the mitoKATP channels. This result may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury. PMID:25641746

  14. Regeneration of infarcted myocardium with resveratrol-modified cardiac stem cells

    PubMed Central

    Gorbunov, Nikolai; Petrovski, Goran; Gurusamy, Narasimman; Ray, Diptarka; Kim, Do Han; Das, Dipak K

    2012-01-01

    Abstract The major problem in stem cell therapy includes viability and engraftment efficacy of stem cells after transplantation. Indeed, the vast majority of host-transfused cells do not survive beyond 24–72 hrs. To increase the survival and engraftment of implanted cardiac stem cells in the host, we developed a technique of treating these cells with resveratrol, and tested it in a rat model of left anterior descending (LAD) occlusion. Multi-potent clonogenic cardiac stem cells isolated from rat heart and stably transfected with EGFP were pre-treated with 2.5 μM resveratrol for 60 min. Rats were anaesthetized, hearts opened and the LAD occluded to induce heart attack. One week later, the cardiac reduced environment was confirmed in resveratrol treated rat hearts by the enhanced expression of nuclear factor-E2-related factor-2 (Nrf2) and redox effector factor-1 (Ref-1). M-mode echocardiography after stem cell therapy, showed improvement in cardiac function (left ventricular ejection fraction, fractional shortening and cardiac output) in both, the treated and control group after 7 days, but only resveratrol-modified stem cell group revealed improvement in cardiac function at the end of 1, 2 and 4 months time. The improvement of cardiac function was accompanied by enhanced stem cell survival and engraftment as demonstrated by the expression of cell proliferation marker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as demonstrated by the expression of EGFP up to 4 months after LAD occlusion in the resveratrol-treated stem cell group. Expression of stromal cell-derived factor and myosin conclusively demonstrated homing of stem cells in the infarcted myocardium, its regeneration leading to improvement of cardiac function. PMID:21352470

  15. Three-dimensional imaging of the myocardium with isotopes

    NASA Technical Reports Server (NTRS)

    Budinger, T. F.

    1975-01-01

    Three methods of imaging the three-dimensional distribution of isotopes in the myocardium are discussed. Three-dimensional imaging was examined using multiple Anger-camera views. Longitudinal tomographic images with compensation for blurring were studied. Transverse-section reconstruction using coincidence detection of annihilation gammas from positron emitting isotopes was investigated.

  16. Stereology of the myocardium in Leontopithecus (Lesson, 1840) callitrichidae - primates.

    PubMed

    Pissinatti, A; Burity, C H F; Mandarim-de-Lacerda, C A

    2003-06-01

    Rare morphological features of the Leontopithecus cardiovascular system have been reported in the literature. The samples analyzed in this study came from 33 specimens of Leontopithecus from the collection of the Center of Primatology of Rio de Janeiro-FEEMA (CPRJ-FEEMA). Morphometry and stereological data were obtained from all animals. Adult body weights of L. rosalia were the lowest, the greatest being those of L. chrysopygus caissara; body weights of L. chrysomelas and L. c. chrysopygus were similar and in between those of the two former species. Cardiomyocytes (left ventricular myocardium) were bigger in adults than in infants. The myocardium of L. rosalia showed focal fibrosis, fatty vacuoles, and hyalinization. In L. chrysomelas the myocardium showed areas of fibrosis and presence of mononuclear cells. Fibrosis and areas of congestion were observed in L. c. chrysopygus; areas of disorganization and vascular congestion were found in L. c. caissara. In L. rosalia infants, a greater density of vessels per myocardial area and a greater length density of vessels were observed as compared with those of L. chrysomelas. In adults, L. chrysomelas showed greater density of connective tissue in the myocardium than L. c. chrysopygus and L. c. caissara did. In L. rosalia, cardiomyocyte nuclei had a greater area density than those of the other forms of Leontopithecus. These characteristics may explain the faster development of L. rosalia infants as compared with that of L. chrysomelas and L. c. chrysopygus kept under the same handling conditions at the CPRJ-FEEMA. PMID:12823624

  17. Improved Protective Effect of Umbilical Cord Stem Cell Transplantation on Cisplatin-Induced Kidney Injury in Mice Pretreated with Antithymocyte Globulin

    PubMed Central

    Večerić-Haler, Željka; Erman, Andreja; Cerar, Anton; Motaln, Helena; Kološa, Katja; Lah Turnšek, Tamara; Sodin Šemrl, Snežna; Lakota, Katja; Mrak-Poljšak, Katjuša; Škrajnar, Špela; Kranjc, Simona; Arnol, Miha; Perše, Martina

    2016-01-01

    Mesenchymal stem cells (MSCs) are recognised as a promising tool to improve renal recovery in experimental models of cisplatin-induced acute kidney injury. However, these preclinical studies were performed on severely immunodeficient animals. Here, we investigated whether human umbilical cord derived MSC treatment could equally ameliorate acute kidney injury induced by cisplatin and prolong survival in mice with a normal immune system and those with a suppressed immune system by polyclonal antithymocyte globulin (ATG). We demonstrated that ATG pretreatment, when followed by MSC transplantation, significantly improved injured renal function parameters, as evidenced by decreased blood urea nitrogen and serum creatinine concentration, as well as improved renal morphology. This tissue restoration was also supported by increased survival of mice. The beneficial effects of ATG were associated with reduced level of inflammatory protein serum amyloid A3 and induced antioxidative expression of superoxide dismutase-1 (SOD-1), glutathione peroxidase (GPx), and hem oxygenase-1 (HO-1). Infused MSCs became localised predominantly in peritubular areas and acted to reduce renal cell death. In conclusion, these results show that ATG diminished in situ inflammation and oxidative stress associated with cisplatin-induced acute kidney injury, the effects that may provide more favourable microenvironment for MSC action, with consequential synergistic improvements in renal injury and animal survival as compared to MSC treatment alone. PMID:26880955

  18. Functional antagonism of β-adrenoceptor subtypes in the catecholamine-induced automatism in rat myocardium

    PubMed Central

    Boer, DC; Bassani, JWM; Bassani, RA

    2011-01-01

    BACKGROUND AND PURPOSE Myocardial automatism and arrhythmias may ensue during strong sympathetic stimulation. We sought to investigate the relevant types of adrenoceptor, as well as the role of phosphodiesterase (PDE) activity, in the production of catecholaminergic automatism in atrial and ventricular rat myocardium. EXPERIMENTAL APPROACH The effects of adrenoceptor agonists on the rate of spontaneous contractions (automatic response) and the amplitude of electrically evoked contractions (inotropic response) were determined in left atria and ventricular myocytes isolated from Wistar rats. KEY RESULTS Catecholaminergic automatism was Ca2+-dependent, as it required a functional sarcoplasmic reticulum to be exhibited. Although both α- and β-adrenoceptor activation caused inotropic stimulation, only β1-adrenoceptors seemed to mediate the induction of spontaneous activity. Catecholaminergic automatism was enhanced and suppressed by β2-adrenoceptor blockade and stimulation respectively. Inhibition of either PDE3 or PDE4 (by milrinone and rolipram, respectively) potentiated the automatic response of myocytes to catecholamines. However, only rolipram abolished the attenuation of automatism produced by β2-adrenoceptor stimulation. CONCLUSIONS AND IMPLICATIONS α- and β2-adrenoceptors do not seem to be involved in the mediation of catecholaminergic stimulation of spontaneous activity in atrial and ventricular myocardium. However, a functional antagonism of β1- and β2-adrenoceptor activation was identified, the former mediating catecholaminergic myocardial automatism and the latter attenuating this effect. Results suggest that hydrolysis of cAMP by PDE4 is involved in the protective effect mediated by β2-adrenoceptor stimulation. PMID:21091648

  19. Genetic Modification of Mesenchymal Stem Cells Overexpressing CCR1 Increases Cell Viability, Migration, Engraftment and Capillary Density in the Injured Myocardium

    PubMed Central

    Huang, Jing; Zhang, Zhiping; Guo, Jian; Ni, Aiguo; Deb, Arjun; Zhang, Lunan; Mirotsou, Maria; Pratt, Richard E; Dzau, Victor J

    2010-01-01

    Rationale Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly due to poor cell viability and low engraftment in the ischemic myocardium. Specific chemokines are upregulated in the infarcted myocardium. However the expression levels of the corresponding chemokine receptors (e.g. CCR1, CXCR2) in MSCs are very low. We hypothesized that this discordance may account for the poor MSC engraftment and survival. Objective To determine whether overexpression of CCR1 or CXCR2 chemokine receptors in MSCs augments their cell survival, migration and engraftment after injection in the infarcted myocardium. Methods and Results Overexpression of CCR1, but not CXCR2, dramatically increased chemokine-induced murine MSC migration and protected MSC from apoptosis in vitro. Moreover, when MSCs were injected intramyocardially one hour after coronary artery ligation, CCR1-MSCs accumulated in the infarcted myocardium at significantly higher levels than control-MSCs or CXCR2-MSCs three days post-myocardial infarction (MI). CCR1-MSC injected hearts exhibited a significant reduction in infarct size, reduced cardiomyocytes apoptosis and increased capillary density in injured myocardium three days post-MI. Furthermore, intramyocardial injection of CCR1-MSCs prevented cardiac remodeling and restored cardiac function 4 weeks post-MI. Conclusions Our results demonstrate the in vitro and in vivo salutary effects of genetic modification of stem cells. Specifically, overexpression of chemokine receptor enhances the migration, survival and engraftment of MSCs, and may provide a new therapeutic strategy for the injured myocardium. PMID:20378860

  20. MiR-22/Sp-1 Links Estrogens With the Up-Regulation of Cystathionine γ-Lyase in Myocardium, Which Contributes to Estrogenic Cardioprotection Against Oxidative Stress.

    PubMed

    Wang, Long; Tang, Zhi-Ping; Zhao, Wei; Cong, Bing-Hai; Lu, Jian-Qiang; Tang, Xiao-Lu; Li, Xiao-Han; Zhu, Xiao-Yan; Ni, Xin

    2015-06-01

    Hydrogen sulfide, generated in the myocardium predominantly via cystathionine-γ-lyase (CSE), is cardioprotective. Our previous study has shown that estrogens enhance CSE expression in myocardium of female rats. The present study aims to explore the mechanisms by which estrogens regulate CSE expression, in particular to clarify the role of estrogen receptor subtypes and the transcriptional factor responsible for the estrogenic effects. We found that either the CSE inhibitor or the CSE small interfering RNA attenuated the protective effect of 17β-estradiol (E2) against H2O2- and hypoxia/reoxygenation-induced injury in primary cultured neonatal cardiomyocytes. E2 stimulates CSE expression via estrogen receptor (ER)-α both in cultured cardiomyocytes in vitro and in the myocardium of female mice in vivo. A specificity protein-1 (Sp-1) consensus site was identified in the rat CSE promoter and was found to mediate the E2-induced CSE expression. E2 increases ERα and Sp-1 and inhibits microRNA (miR)-22 expression in myocardium of ovariectomized rats. In primary cardiomyocytes, E2 stimulates Sp-1 expression through the ERα-mediated down-regulation of miR-22. It was confirmed that both ERα and Sp-1 were targeted by miR-22. In the myocardium of ovariectomized rats, the level of miR-22 inversely correlated to CSE, ERα, Sp-1, and antioxidant biomarkers and positively correlated to oxidative biomarkers. In summary, this study demonstrates that estrogens stimulate Sp-1 through the ERα-mediated down-regulation of miR-22 in cardiomyocytes, leading to the up-regulation of CSE, which in turn results in an increase of antioxidative defense. Interaction of ERα, miR-22, and Sp-1 may play a critical role in the control of oxidative stress status in the myocardium of female rats. PMID:25825815

  1. Influence of viscosity on myocardium mechanical activity: a mathematical model.

    PubMed

    Katsnelson, Leonid B; Nikitina, Larissa V; Chemla, Denis; Solovyova, Olga; Coirault, Catherine; Lecarpentier, Yves; Markhasin, Vladimir S

    2004-10-01

    We have previously proposed and validated a mathematical model of myocardium contraction-relaxation cycle based on current knowledge of regulatory role of Ca2+ and cross-bridge kinetics in cardiac cell. That model did not include viscous elements. Here we propose a modification of the model, in which two viscous elements are added, one in parallel to the contractile element, and one more in parallel to the series elastic element. The modified model allowed us to simulate and explain some subtle experimental data on relaxation velocity in isotonic twitches and on a mismatch between the time course of sarcomere shortening/lengthening and the time course of active force generation in isometric twitches. Model results were compared with experimental data obtained from 28 rat LV papillary muscles contracting and relaxing against various loads. Additional model analysis suggested contribution of viscosity to main inotropic and lusitropic characteristics of myocardium performance. PMID:15302547

  2. Oxygen diffusion distance in thyroxine-induced hypertrophic rabbit myocardium.

    PubMed

    Seiden, D; Navidad, P; Weiss, H R

    1988-10-01

    We studied the oxygen diffusion distance in the rabbit myocardium in untreated animals and in animals treated with thyroxine (T4) for 3 days and 16 days. The subepicardial and subendocardial regions were studied separately. Sixteen days of T4 treatment results in significant cardiac hypertrophy. After 16 days, the percentage of the myocardium occupied by myocytes decreases as the volume of extracellular matrix increases. After 3 days, the number of myocyte mitochondria per unit volume of myocardium increases without an increase in mitochondrial volume. After 16 days the volume density of the myocyte mitochondria increases. Oxygen diffusion distance was determined by measuring the distance between the myocardial capillaries and the cardiomyocyte mitochondria. The deposition of extracellular matrix results in an increase in the distance between the myocardial capillaries and the myocytes. The distribution of the mitochondria within the myocytes remains unchanged resulting in an increased distance between the capillaries and the mitochondria, hence, an increased oxygen diffusion distance. There is some evidence that the mitochondria most distant from the capillaries are the mitochondria in which division is most frequent with T4 stimulation. This may be related to the relative deprivation of oxygen of these mitochondria. PMID:2975340

  3. Protective effect of PNU-120596, a selective alpha7 nicotinic acetylcholine receptor-positive allosteric modulator, on myocardial ischemia-reperfusion injury in rats.

    PubMed

    Li, Hui; Zhang, Zong-Ze; Zhan, Jia; He, Xiang-Hu; Song, Xue-Min; Wang, Yan-Lin

    2012-06-01

    The cholinergic anti-inflammatory pathway has been found to exert a protective role in myocardial ischemia-reperfusion injury (MIRI). Alpha7 nicotinic acetylcholine receptor (α7nAChR) is a regulator of cholinergic anti-inflammatory pathway; however, little information is available on the effect of α7nAChR on MIRI. In the present study, we hypothesized that 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxanol-3-yl)-urea (PNU-120596), a potent positive allosteric modulator of α7nAChR, could play a protective role on MIRI. Fifty-five rats were randomly assigned into 4 groups: Sham group, ischemia-reperfusion group, PNU-120596 group, α-bungarotoxin group. Compared with ischemia-reperfusion group, PNU-120596 treatment markedly decreased infarct size, ultrastructural damage, serum creatine kinase, and lactate dehydrogenase. Serum proinflammatory cytokine production, myocardium endothelial activation and neutrophil infiltration, myocardium malondialdehyde were also significantly decreased, accompanied by increased myocardium superoxide dismutase production, in the PNU-120596 group compared with the ischemia-reperfusion group. Meanwhile, we observed a significant inhibition of nuclear factor kappa B activation in PNU-120596 group compared with ischemia-reperfusion group. Pretreatment of α7nAChR-selective antagonist, α-bungarotoxin, abolished all the protective effects of PNU-120596 on MIRI. In conclusion, PNU might have a protective effect against MIRI. Its action mechanisms might be involved in the inhibition of inflammatory responses, attenuation of lipid peroxidation, and suppression of nuclear factor kappa B activity. PMID:22343370

  4. Ultrastructural and functional effects of lead poisoning on adult canine myocardium: assessment of thiamin treatment

    SciTech Connect

    Kincaid, N.G.

    1985-01-01

    The effects of lead (Pb) poisoning on the adult canine myocardium were assessed quantitatively using stereological techniques, functional testing, and blood analyses as well as qualitatively by morphological investigation. Relative measurements using stereological techniques compared the volume fractions of cellular components of the three groups. Blood was analyzed for lead, hemoglobin, hematocrit, total erythrocytes, total leukocytes, thiamin pyrophosphate (TPP), delta-aminolevulinic acid dehydratase activity (ALAD), and zinc protoporphyrin (ZPP). The major finding of the stereological analysis was the statistically significant increase of 3.2% in myofilament volume in the Pb treated group and the significant decrease in mitochondrial volume in both the Pb treated and Pb + B/sub 1/ treated groups. A statistically significant decrease in the mitochondria/myofilament volume ratio was found in the Pb treated, but no Pb + B/sub 1/ treated group. This may indicate either a protective effect of thiamin on mitochondria or a reduced compensatory need of the myocyte to increase myofilament volume.

  5. Gold nanoparticle loaded hybrid nanofibers for cardiogenic differentiation of stem cells for infarcted myocardium regeneration.

    PubMed

    Ravichandran, Rajeswari; Sridhar, Radhakrishnan; Venugopal, Jayarama Reddy; Sundarrajan, Subramanian; Mukherjee, Shayanti; Ramakrishna, Seeram

    2014-04-01

    Heart disease is the leading cause of mortality in many industrialized nations and is often related to irregularities in electrical function that can radically damage cardiac functioning. The aim of this study is to develop a novel therapeutic hybrid scaffold that can couple electrical, mechanical, and biological properties, desirable for cardiac tissue regeneration. BSA/PVA scaffolds are fabricated in the ratio 2:1 and gold nanoparticles (AuNPs) embedded scaffolds in the ratios BSA/PVA/Au of 2:1:0.1 (lower concentration) and BSA/PVA/Au of 2:1:0.4 (higher concentration) by electrospinning. The scaffolds are characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), contact angle, Fourier transform infrared (FTIR) spectroscopy, and tensile testing to analyze the fiber morphology, AuNP distribution, hydrophilicity, surface functional groups, and mechanical properties of the scaffolds, respectively. Results show that ex vivo pretreatment of MSCs using 5-aza and AuNPs loaded conductive nanofibrous construct could lead to enhanced cardiomyogenic differentiation and result in superior biological and functional effects on infarcted myocardium regeneration. PMID:24327549

  6. Partial protection and abomasal cytokine expression in sheep experimentally infected with Haemonchus contortus and pre-treated with Taenia hydatigena vesicular concentrate.

    PubMed

    Buendía-Jiménez, J A; Muñoz-Guzmán, M A; Vega-López, M A; Cuenca-Verde, C; Martínez-Labat, J P; Cuéllar-Ordaz, J A; Alba-Hurtado, F

    2015-06-30

    The abomasal expression of IL-2, IL-4, IL-6, IL-10 and IFNγ in lambs experimentally infected with Haemonchus contortus and its relationship to protection induced by a Taenia hydatigena larvae vesicular concentrate (ThLVC) were evaluated. The lambs that were only infected with H. contortus larvae showed a worm burden greater (p<0.05) than the lambs that received ThLVC prior to infection. Moreover, the lambs that received ThLVC showed a greater (p<0.05) number of blood eosinophils than the lambs that did not receive the ThLVC. In general, the lambs that received ThLVC prior to infection had a greater amount of eosinophils and mast cells and higher in situ expression of IFNγ, IL-2, IL-4, IL-6 and IL-10 in the abomasal wall than the lambs that were infected with H. contortus only or that received ThLVC (p<0.05) only. A higher expression of IL-2 and IFNγ in the submucosa compared to the abomasal mucosa and a higher expression of IL-4 in the abomasal mucosa compared to the submucosa was observed (p<0.05). These results suggest that there is a Th1 type response in the abomasal submucosa and a Th2 type response in in the abomasal mucosa. The amount of eosinophils and mast cells and the in situ expression of IFNγ, IL-2, IL-4 and IL-6 in the abomasal walls were negatively correlated with the worm burden (p<0.05). These results suggest that ThLVC is a non-specific immune stimulator for the abomasal immune response, and it is likely that the protection observed is the result of this effect. PMID:25959643

  7. Alpha-1-Adrenergic Receptor Subtypes in Non-Failing and Failing Human Myocardium

    PubMed Central

    Jensen, Brian C.; Swigart, Philip M; DeMarco, Teresa; Hoopes, Charles; Simpson, Paul C.

    2009-01-01

    Background Alpha-1-adrenergic receptors (α1-ARs) play adaptive roles in the heart and protect against the development of heart failure (HF). The three α1-AR subtypes,α1A, α1B, and α1D, have distinct physiological roles in mouse heart, but very little is known about α1-subtypes in human heart. Here we test the hypothesis that the α1A and α1B subtypes are present in human myocardium, similar to the mouse, and are not down-regulated in heart failure. Methods and Results Hearts from transplant recipients and unused donors were failing (n = 12; mean EF 24%) or non-failing (n = 9; mean EF 59%), and similar in age (~44 years) and sex (~70% male). We measured the α1-AR subtypes in multiple regions of both ventricles by quantitative real-time reverse transcription PCR and radioligand binding. All three α1-AR subtype mRNAs were present, and α1A mRNA was most abundant (~65% of total α1-AR mRNA). However, only α1A and α1B binding were present, and the α1B was most abundant (60% of total). In failing hearts, α1A and α1B binding were not down-regulated, in contrast with β1-ARs. Conclusions Our data show for the first time that the α1A and α1B subtypes are both present in human myocardium, but α1D binding is not, and that the α1-subtypes are not down-regulated in HF. Since α1-subtypes in the human heart are similar to mouse, where adaptive and protective effects of α1-subtypes are most convincing, it might become feasible to treat HF with a drug targeting the α1A and/or α1B. PMID:19919991

  8. Erythropoietin pretreatment suppresses inflammation by activating the PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury

    PubMed Central

    RONG, REN; XIJUN, XIAO

    2015-01-01

    Erythropoietin (EPO), a glycoprotein originally known for its important role in the stimulation of erythropoiesis, has recently been shown to have significant protective effects in animal models of kidney and intestinal ischemia-reperfusion injury (IRI). However, the mechanism underlying these protective effects remains unclear. The aim of the current study was to evaluate the effects of EPO on myocardial IRI and to investigate the mechanism underlying these effects. A total of 18 male Sprague Dawley rats were randomly divided into three groups, namely the sham, IRI-saline and IRI-EPO groups. Rats in the IRI-EPO group were administered 5,000 U/kg EPO intraperitoneally 24 h prior to the induction of IRI. IRI was induced by ligating the left descending coronary artery for 30 min, followed by reperfusion for 3 h. Pathological changes in the myocardial tissue were observed and scored. The levels of the proinflammatory cytokines, interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, were evaluated in the serum and myocardial tissue. Furthermore, the effects of EPO on phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling and EPO receptor (EPOR) phosphorylation were measured. Pathological changes in the myocardial tissue, increased expression levels of TNF-α, IL-6 and IL-1β in the myocardium, and increased serum levels of these mediators, as a result of IRI, were significantly decreased by EPO pretreatment. The effects of EPO were found to be associated with the activation of PI3K/Akt signaling, which suppressed the inflammatory responses, following the initiation of EPOR activation by EPO. Therefore, EPO pretreatment was demonstrated to decrease myocardial IRI, which was associated with activation of EPOR, subsequently increasing PI3K/Akt signaling to inhibit the production and release of inflammatory mediators. Thus, the results of the present study indicated that EPO may be useful for preventing myocardial IRI. PMID:26622330

  9. Pretreatment of microbial sludges

    DOEpatents

    Rivard, Christopher J.; Nagle, Nicholas J.

    1995-01-01

    Methods are described for pretreating microbial sludges to break cells and disrupt organic matter. One method involves the use of sonication, and another method involves the use of shear forces. The pretreatment of sludge enhances bioconversion of the organic fraction. This allows for efficient dewatering of the sludge and reduces the cost for final disposal of the waste.

  10. Pretreatment of microbial sludges

    DOEpatents

    Rivard, C.J.; Nagle, N.J.

    1995-01-10

    Methods are described for pretreating microbial sludges to break cells and disrupt organic matter. One method involves the use of sonication, and another method involves the use of shear forces. The pretreatment of sludge enhances bioconversion of the organic fraction. This allows for efficient dewatering of the sludge and reduces the cost for final disposal of the waste.

  11. [Effect of adaptation to hypoxia on expression of NO synthase isoforms in rat myocardium].

    PubMed

    Goryacheva, A V; Terekhina, O L; Abramochkin, D V; Budanova, O P; Belkina, L M; Smirin, B V; Downey, H F; Malyshev, I Yu; Manukhina, E B

    2015-01-01

    Previously we have shown that adaptation to hypoxia (AH) is cardio- and vasoprotective in myocardial ischemic and reperfusion injury and this protection is associated with restriction of nitrosative stress. The present study was focused on further elucidation of NO-dependent mechanisms of AH by identifying specific NO synthases (NOS) that could play the major role in AH protection. AH was performed in a normobaric hypoxic chamber by breathing hypoxic gas mixture (9.5-10% O2) for 5-10 min with intervening 4 min normoxia (5-8 cycles daily for 21 days). Expression of neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) protein was measured in the left ventricular myocardium using Western blot analysis with respective antibodies. AH educed iNOS protein expression by 71% (p < 0.05) whereas eNOS protein expression tended to be reduced by 41% compared to control (p < 0.05). nNOS protein expression remained unchanged after AH. Selective iNOS inhibition can mimic the AH-induced protection. Therefore protective effects of AH could be at least partially due to restriction of iNOS and, probably, eNOS expression. PMID:27116881

  12. GREET Pretreatment Module

    SciTech Connect

    Adom, Felix K.; Dunn, Jennifer B.; Han, Jeongwoo

    2014-09-01

    A wide range of biofuels and biochemicals can be produced from biomass via different pretreatment technologies that yield sugars. This report documents the material and energy flows that occur when fermentable sugars from four lignocellulosic feedstocks (corn stover, miscanthus, switchgrass, and poplar) are produced via dilute acid pretreatment and ammonia fiber expansion. These flows are documented for inclusion in the pretreatment module of the Greenhouses Gases, Regulated Emissions, and Energy Use in Transportation (GREET) model. Process simulations of each pretreatment technology were developed in Aspen Plus. Material and energy consumption data from Aspen Plus were then compiled in the GREET pretreatment module. The module estimates the cradle-to-gate fossil energy consumption (FEC) and greenhouse gas (GHG) emissions associated with producing fermentable sugars. This report documents the data and methodology used to develop this module and the cradle-to-gate FEC and GHG emissions that result from producing fermentable sugars.

  13. Potent In Vitro Protection Against PM[Formula: see text]-Caused ROS Generation and Vascular Permeability by Long-Term Pretreatment with Ganoderma tsugae.

    PubMed

    Tseng, Chia-Yi; Chung, Meng-Chi; Wang, Jhih-Syuan; Chang, Yu-Jung; Chang, Jing-Fen; Lin, Chin-Hung; Hseu, Ruey-Shyang; Chao, Ming-Wei

    2016-04-01

    Epidemiological studies show increased particulate matter (PM[Formula: see text]) particles in ambient air are correlated with increased myocardial infarctions. Given the close association of capillaries and alveoli, the dysfunction is caused when inhaled PM[Formula: see text] particles come in close proximity to capillary endothelial cells. We previously suggested that the inhalation of PM[Formula: see text] diesel exhaust particles (DEP) induces oxidative stress and upregulates the Nrf2/HO-1 pathway, inducing vascular permeability factor VEGFA secretion, which results in cell-cell adherens junction disruption and PM[Formula: see text] transmigratation into circulation. Here, we minimized the level that PM[Formula: see text] traveled in the bloodstream by pre-supplementing with a traditional Chinese medicine (TCM) Ganoderma tsugae DMSO extract (GTDE) prior to PM[Formula: see text] exposure. Our results show that PM[Formula: see text] caused alterations in enzyme activities and cellular anti-oxidant balance. We found decreased glutathione levels, a reduced cellular redox ratio, increased ROS generation and cytotoxicity in the cellular fractions. The oxidative stress caused DNA damage and apoptosis, likely causing downstream molecular events that trigger vasculature permeabilization and, eventually, cardiovascular disorders. Our results show long-term GTDE treatment increased endogenous glutathione level, while PM[Formula: see text]-reduced glutathione levels and the cellular redox ratio. GTDE was protective against the genotoxic and apoptotic effects initiated by PM[Formula: see text] oxidative stress. Vascular permeability revealed that PM[Formula: see text] only accumulated on the surface of cells after GTDE treatment; no penetration was detected. After two weeks of GTDE treatment, VEGFA secretion was significantly reduced in human umbilical vein endothelial cells (HUVEC) and endothelial cell migration was blocked. Our results suggest GTDE prevents PM

  14. [The effect of helium-neon laser radiation on the energy metabolic indices of the myocardium].

    PubMed

    Chizhov, G K; Koval'skaia, N I; Kozlov, V I

    1991-03-01

    It was shown in experiments on white rats, that intravenous and direct myocardium helium-neon laser irradiation leads to the some activation of lactate, glucose-6-phosphate, succinate and reduced NAD degydrogenases. During direct myocardium irradiation these changes are in a less degree. It is suggested that helium-neon laser irradiation displays some active influence on the energy metabolism enzymes of the myocardium, and the mechanisms of this action are discussed. PMID:2054512

  15. Solids Control in Sludge Pretreatment

    SciTech Connect

    Beahm, E.C., Weber, C.F., Hunt, R.D., Dillow, T.A.

    1997-12-31

    Sludge pretreatment will likely involve washing, followed by caustic or acidic leaching and washing of sludge residues after leaching. The principal goal of pretreatment is to obtain a low-volume high-activity waste stream and a high-volume low-activity waste stream. Also, some waste constituents such as chromium and phosphate can be included in glass formulations only at very low concentrations; therefore, it is desirable to remove them from high-level waste streams. Two aspects of sludge treatment and subsequent separations should be well delineated and predictable: (1) the distribution of chemical species between aqueous solutions and solids and (2) potential problems due to chemical interactions that could result in process difficulties or safety concerns.Before any treatment technology is adopted, it must be demonstrated that the process can be carried out as planned. Three pretreatment methods were considered in the Tri-Party (Washington State Ecology, U.S. Environmental Protection Agency, and U.S. Department of Energy) negotiations: (1) sludge washing with corrosion- inhibiting water, (2) Enhanced Sludge Washing, and (3)acidic dissolution with separations processes. Enhanced Sludge Washing is the baseline process. In Enhanced Sludge Washing, sludge is first washed with corrosion-inhibiting water; it is then leached with caustic (sodium hydroxide solution) and washed again with corrosion- inhibiting water. The initial concern is whether a pretreatment technique is effective in separating sludge components. This can be evaluated by bench-scale tests with sludge specimens from underground storage tanks. The results give data on the distribution of important species such as aluminum, phosphate, and radionuclides between wash and leach solutions and solid sludge residues.

  16. Myocardium proteome remodelling after nutritional deprivation of methyl donors.

    PubMed

    Martinez, Emilie; Gérard, Nicolas; Garcia, Maira M; Mazur, Andrzej; Guéant-Rodriguez, Rosa-Maria; Comte, Blandine; Guéant, Jean-Louis; Brachet, Patrick

    2013-07-01

    Methyl donor (MD: folate, vitamin B12 and choline) deficiency causes hyperhomocysteinemia, a risk factor for cardiovascular diseases. However, the mechanisms of the association between MD deficiency, hyperhomocysteinemia, and cardiomyopathy remain unclear. Therefore, we performed a proteomic analysis of myocardium of pups from rat dams fed a MD-depleted diet to understand the impact of MD deficiency on heart at the protein level. Two-dimension gel electrophoresis and mass spectrometry-based analyses allowed us to identify 39 proteins with significantly altered abundance in MD-deficient myocardium. Ingenuity Pathway Analysis showed that 87% of them fitted to a single protein network associated with developmental disorder, cellular compromise and lipid metabolism. Concurrently increased protein carbonylation, the major oxidative post-translational protein modification, could contribute to the decreased abundance of many myocardial proteins after MD deficiency. To decipher the effect of MD deficiency on the abundance of specific proteins identified in vivo, we developed an in vitro model using the cardiomyoblast cell line H9c2. After a 4-day exposure to a MD-deprived (vs. complete) medium, cells were deficient of folate and vitamin B12, and released abnormal amounts of homocysteine. Western blot analyses of pup myocardium and H9c2 cells yielded similar findings for several proteins. Of specific interest is the result showing increased and decreased abundances of prohibitin and α-crystallin B, respectively, which underlines mitochondrial injury and endoplasmic reticulum stress within MD deficiency. The in vitro findings validate the MD-deficient H9c2 cells as a relevant model for studying mechanisms of the early metabolic changes occurring in cardiac cells after MD deprivation. PMID:23318136

  17. Neurogenic stunned myocardium and cardiac transplantation: a case report.

    PubMed

    Hernández-Caballero, C; Martín-Bermúdez, R; Revuelto-Rey, J; Aguilar-Cabello, M; Villar-Gallardo, J

    2012-09-01

    We present the case of a 46-year-old woman referred to our center for urgent heart transplantation assessment, initially diagnosed as having cardiogenic shock of uncertain etiology. Some hours before she had suffered syncope without regaining consciousness. When she arrived at our hospital, the objective examination revealed bilateral unreactive mydriasis and absent brain-stem reflexes, and echocardiography showed global left ventricle wall hypokinesis sparing the apex. An urgent computed tomography (CT) imaging of the head was performed, which showed a massive subarachnoid hemorrhage and extensive cerebral edema. In the following hours, she fulfilled the criteria of brain-stem death and indeed became a multiorgan donor. The heart was rejected for transplantation because of the existence of left ventricle wall motion abnormalities associated with neurogenic stunned myocardium. Neurogenic stunned myocardium is a stress-related cardiomyopathy that occurs after an acute brain injury. It is especially frequent in subarachnoid hemorrhage, where it reaches an incidence of up to 40% of patients. It is characterized by acute electrocardiographic changes and regional hypokinesis of the left ventricle wall not consistent with the coronary artery distribution, and is thought to be a transient condition. For this reason it should not constitute an absolute contraindication to cardiac donation in young donors with no previous cardiac disease. In our hospital during the last year one third of the potential heart donors had regional left ventricle wall motion abnormalities compatible with neurogenic stunned myocardium. With the aim of improving the number of cardiac donors, several strategies have been described to try to demonstrate the reversibility of this entity, such as dobutamine stress echocardiography. PMID:22974925

  18. Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window.

    PubMed

    Polizzotti, Brian D; Ganapathy, Balakrishnan; Walsh, Stuart; Choudhury, Sangita; Ammanamanchi, Niyatie; Bennett, David G; dos Remedios, Cristobal G; Haubner, Bernhard J; Penninger, Josef M; Kühn, Bernhard

    2015-04-01

    Therapies developed for adult patients with heart failure have been shown to be ineffective in pediatric clinical trials, leading to the recognition that new pediatric-specific therapies for heart failure must be developed. Administration of the recombinant growth factor neuregulin-1 (rNRG1) stimulates regeneration of heart muscle cells (cardiomyocytes) in adult mice. Because proliferation-competent cardiomyocytes are more abundant in growing mammals, we hypothesized that administration of rNRG1 during the neonatal period might be more effective than in adulthood. If so, neonatal rNRG1 delivery could be a new therapeutic strategy for treating heart failure in pediatric patients. To evaluate the effectiveness of rNRG1 administration in cardiac regeneration, newborn mice were subjected to cryoinjury, which induced myocardial dysfunction and scar formation and decreased cardiomyocyte cell cycle activity. Early administration of rNRG1 to mice from birth to 34 days of age improved myocardial function and reduced the prevalence of transmural scars. In contrast, administration of rNRG1 from 4 to 34 days of age only transiently improved myocardial function. The mechanisms of early administration involved cardiomyocyte protection (38%) and proliferation (62%). We also assessed the ability of rNRG1 to stimulate cardiomyocyte proliferation in intact cultured myocardium from pediatric patients. rNRG1 induced cardiomyocyte proliferation in myocardium from infants with heart disease who were less than 6 months of age. Our results identify an effective time period within which to execute rNRG1 clinical trials in pediatric patients for the stimulation of cardiomyocyte regeneration. PMID:25834111

  19. Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo

    PubMed Central

    Lei, Biao; Matsuo, Ken; Labinskyy, Volodymyr; Sharma, Naveen; Chandler, Margaret P.; Ahn, Anna; Hintze, Thomas H.; Stanley, William C.; Recchia, Fabio A.

    2005-01-01

    Nitric oxide (NO) inhibits myocardial glucose transport and metabolism, although the underlying mechanism(s) and functional consequences of this effect are not clearly understood. We tested the hypothesis that NO inhibits the activation of AMP-activated protein kinase (AMPK) and translocation of cardiac glucose transporters (GLUTs; GLUT-4) and reduces lactate production. Ischemia was induced in open-chest dogs by a 66% flow reduction in the left anterior descending coronary artery (LAD). During ischemia, dogs were untreated (control) or treated by direct LAD infusion of (i) nitroglycerin (NTG) (0.5 μg·kg–1·min–1); (ii) 8-Br-cGMP (50 μg·kg–1·min–1); or (iii) NO synthase inhibitor l-nitro-argininemethylester (40 μg·kg–1·min–1; n = 9 per group). Cardiac substrate oxidation was measured with isotopic tracers. There were no differences in myocardial blood flow or oxygen delivery among groups; however, at 45 min of ischemia, the activation of AMPK was significantly less in NTG (77 ± 12% vs. nonischemic myocardium) and 8-Br-cGMP (104 ± 13%), compared with control (167 ± 17%). Similarly, GLUT-4 translocation was significantly reduced in NTG (74 ± 7%) and 8-Br-cGMP (120 ± 11%), compared with control (165 ± 17%). Glucose uptake and lactate output were 30% and 60% lower in NTG compared with control. Inhibition of NO synthesis stimulated glucose oxidation (67% increase compared with control) but did not affect AMPK phosphorylation, GLUT-4 translocation and glucose uptake. Contractile function in the ischemic region was significantly improved by NTG and l-nitro-argininemethylester. In conclusion, in ischemic myocardium an NO donor inhibits glucose uptake and lactate production via a reduction in AMPK stimulation of GLUT-4 translocation, revealing a mechanism of metabolic modulation and myocardial protection activated by NO donors. PMID:15870202

  20. 40 CFR 445.3 - General pretreatment standards.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... subject to this part that introduces wastewater pollutants into a publicly owned treatment works (POTW) must comply with 40 CFR part 403. ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false General pretreatment standards....

  1. 40 CFR 410.86 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources (PSNS). 410.86 Section 410.86 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS TEXTILE MILLS POINT SOURCE CATEGORY Nonwoven Manufacturing Subcategory § 410.86 Pretreatment standards for...

  2. 40 CFR 410.86 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Pretreatment standards for new sources (PSNS). 410.86 Section 410.86 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS TEXTILE MILLS POINT SOURCE CATEGORY Nonwoven Manufacturing Subcategory § 410.86 Pretreatment standards for...

  3. 40 CFR 410.84 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources (PSES). 410.84 Section 410.84 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS TEXTILE MILLS POINT SOURCE CATEGORY Nonwoven Manufacturing Subcategory § 410.84 Pretreatment standards...

  4. 40 CFR 410.84 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Pretreatment standards for existing sources (PSES). 410.84 Section 410.84 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS TEXTILE MILLS POINT SOURCE CATEGORY Nonwoven Manufacturing Subcategory § 410.84 Pretreatment standards...

  5. 40 CFR 410.84 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for existing sources (PSES). 410.84 Section 410.84 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS TEXTILE MILLS POINT SOURCE CATEGORY Nonwoven Manufacturing Subcategory § 410.84 Pretreatment standards...

  6. 40 CFR 414.75 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources (PSES). 414.75 Section 414.75 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS Bulk Organic Chemicals § 414.75 Pretreatment standards...

  7. 40 CFR 414.85 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources (PSES). 414.85 Section 414.85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS Specialty Organic Chemicals § 414.85 Pretreatment...

  8. 40 CFR 430.67 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Pretreatment standards for new sources (PSNS). 430.67 Section 430.67 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS THE PULP, PAPER, AND PAPERBOARD POINT SOURCE CATEGORY Semi-Chemical Subcategory § 430.67 Pretreatment standards...

  9. 40 CFR 433.17 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Pretreatment standards for new sources (PSNS). 433.17 Section 433.17 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS METAL FINISHING POINT SOURCE CATEGORY Metal Finishing Subcategory § 433.17 Pretreatment standards for new sources...

  10. 40 CFR 433.15 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Pretreatment standards for existing sources (PSES). 433.15 Section 433.15 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS METAL FINISHING POINT SOURCE CATEGORY Metal Finishing Subcategory § 433.15 Pretreatment standards for...

  11. 40 CFR 461.75 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Pretreatment standards for new sources (PSNS). 461.75 Section 461.75 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS BATTERY MANUFACTURING POINT SOURCE CATEGORY Zinc Subcategory § 461.75 Pretreatment standards for new sources...

  12. 40 CFR 468.15 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for new sources (PSNS). 468.15 Section 468.15 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS COPPER FORMING POINT SOURCE CATEGORY Copper Forming Subcategory § 468.15 Pretreatment standards for new sources...

  13. 40 CFR 468.14 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for existing sources (PSES). 468.14 Section 468.14 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS COPPER FORMING POINT SOURCE CATEGORY Copper Forming Subcategory § 468.14 Pretreatment standards for...

  14. 40 CFR 403.20 - Pretreatment Program Reinvention Pilot Projects Under Project XL.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment Program Reinvention Pilot Projects Under Project XL. 403.20 Section 403.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PRE-TREAT-MENT REGULATIONS FOR EXIST-ING AND...

  15. 40 CFR 403.20 - Pretreatment Program Reinvention Pilot Projects Under Project XL.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment Program Reinvention Pilot Projects Under Project XL. 403.20 Section 403.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PRE-TREAT-MENT REGULATIONS FOR EXIST-ING AND...

  16. 40 CFR 419.47 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources (PSNS). 419.47 Section 419.47 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PETROLEUM REFINING POINT SOURCE CATEGORY Lube Subcategory § 419.47 Pretreatment standards for new sources...

  17. 40 CFR 419.57 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources (PSNS). 419.57 Section 419.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PETROLEUM REFINING POINT SOURCE CATEGORY Integrated Subcategory § 419.57 Pretreatment standards for new sources...

  18. 40 CFR 419.17 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources (PSNS). 419.17 Section 419.17 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PETROLEUM REFINING POINT SOURCE CATEGORY Topping Subcategory § 419.17 Pretreatment standards for new sources...

  19. 40 CFR 423.16 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources (PSES). 423.16 Section 423.16 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS STEAM ELECTRIC POWER GENERATING POINT SOURCE CATEGORY § 423.16 Pretreatment standards for existing sources...

  20. 40 CFR 419.37 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources (PSNS). 419.37 Section 419.37 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PETROLEUM REFINING POINT SOURCE CATEGORY Petrochemical Subcategory § 419.37 Pretreatment standards for new sources...

  1. 40 CFR 419.27 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources (PSNS). 419.27 Section 419.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PETROLEUM REFINING POINT SOURCE CATEGORY Cracking Subcategory § 419.27 Pretreatment standards for new sources...

  2. 40 CFR 423.17 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources (PSNS). 423.17 Section 423.17 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS STEAM ELECTRIC POWER GENERATING POINT SOURCE CATEGORY § 423.17 Pretreatment standards for new sources (PSNS)....

  3. Pretreatment with low-dose gadolinium chloride attenuates myocardial ischemia/reperfusion injury in rats

    PubMed Central

    Chen, Min; Zheng, Yuan-yuan; Song, Yun-tao; Xue, Jing-yi; Liang, Zheng-yang; Yan, Xin-xin; Luo, Da-li

    2016-01-01

    Aim: We have shown that low-dose gadolinium chloride (GdCl3) abolishes arachidonic acid (AA)-induced increase of cytoplasmic Ca2+, which is known to play a crucial role in myocardial ischemia/reperfusion (I/R) injury. The present study sought to determine whether low-dose GdCl3 pretreatment protected rat myocardium against I/R injury in vitro and in vivo. Methods: Cultured neonatal rat ventricular myocytes (NRVMs) were treated with GdCl3 or nifedipine, followed by exposure to anoxia/reoxygenation (A/R). Cell apoptosis was detected; the levels of related signaling molecules were assessed. SD rats were intravenously injected with GdCl3 or nifedipine. Thirty min after the administration the rats were subjected to LAD coronary artery ligation followed by reperfusion. Infarction size, the release of serum myocardial injury markers and AA were measured; cell apoptosis and related molecules were assessed. Results: In A/R-treated NRVMs, pretreatment with GdCl3 (2.5, 5, 10 μmol/L) dose-dependently inhibited caspase-3 activation, death receptor-related molecules DR5/Fas/FADD/caspase-8 expression, cytochrome c release, AA release and sustained cytoplasmic Ca2+ increases induced by exogenous AA. In I/R-treated rats, pre-administration of GdCl3 (10 mg/kg) significantly reduced the infarct size, and the serum levels of CK-MB, cardiac troponin-I, LDH and AA. Pre-administration of GdCl3 also significantly decreased the number of apoptotic cells, caspase-3 activity, death receptor-related molecules (DR5/Fas/FADD) expression and cytochrome c release in heart tissues. The positive control drug nifedipine produced comparable cardioprotective effects in vitro and in vivo. Conclusion: Pretreatment with low-dose GdCl3 significantly attenuates I/R-induced myocardial apoptosis in rats by suppressing activation of both death receptor and mitochondria-mediated pathways. PMID:26948086

  4. Innate immune inflammatory response in the acutely ischemic myocardium.

    PubMed

    Deftereos, Spyridon; Angelidis, Christos; Bouras, Georgios; Raisakis, Konstantinos; Gerckens, Ulrich; Cleman, Michael W; Giannopoulos, Georgios

    2014-01-01

    The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing. PMID:25102201

  5. Lipofuscin accumulation in ageing myocardium & its removal by meclophenoxate.

    PubMed

    Patro, N; Sharma, S P; Patro, I K

    1992-06-01

    A study was undertaken on the age-associated histochemical changes in the ventricular myocardium and the influence of meclophenoxate hydrochloride (MPH) on the age pigment lipofuscin. Sixty Wistar albino rats in three age-groups (3, 15 and 30 months old) were treated with meclophenoxate hydrochloride (100 mg/kg body wt/day, ip) for a period of 2-8 wk. Five animals each from the three age-groups served as controls. Various histochemical and micromorphometric studies were carried out on the myocardial tissue. A linear increase in the myocardial volume occupied by the pigment was observed with advancing age. As a result of meclophenoxate treatment, a gradual decrease in the myocardial volume occupied by the pigment was noted. After 4-6 wk treatment, the pigment bodies were found lodged into the capillary endothelium and the lumen, facilitating the removal of the pigment via blood stream. Histochemical and micromorphometric analyses of ventricular myocardium of albino rats have shown thus that deposition of the age-pigment, lipofuscin, can be accepted as an index of cellular ageing. PMID:1512044

  6. Ultrastructural morphometry of the myocardium of Thunnus alalunga.

    PubMed

    Breisch, E A; White, F; Jones, H M; Laurs, R M

    1983-01-01

    The common ventricle in the heart of the Thunnus alalunga was studied. The ventricular myocardium consists of an outer compact layer and a thick inner spongy layer. The compact layer has slightly larger cells (4-6 microns diameter) than the spongy layer (2.5-5 microns diameter). Ultrastructurally the myocardium displays normal arrangements of myofibrils and mitochondria. The sarcoplasmic reticulum is poorly developed. The intercalated discs are simple with the fascia adherens being the most frequent junctional type observed; occasionally a desmosome was seen. Nexus type junctions are present but are unassociated with the intercalated discs. There are no t-tubules evident but the plasmalemma exhibits numerous caveolae which rarely form couplings with the sarcoplasmic reticulum. A morphometric analysis of the volume percent of mitochondria and myofibrils showed that the myocardial cells in the spongy layer of the heart have a significantly greater volume percentage of mitochondria than the compact layer. No significant differences were found between myocardial regions when the volume percentages of myofibrils were compared. The physiological studies revealed that the albacore tuna has heart rates (120 bpm) and ventricular blood pressures (100 mmHg) that are among the highest reported for fish. PMID:6616575

  7. Pretreatment and Enzymatic Hydrolysis

    SciTech Connect

    2006-06-01

    Activities in this project are aimed at overcoming barriers associated with high capital and operating costs and sub-optimal sugar yields resulting from pretreatment and subsequent enzymatic hydrolysis of biomass.

  8. 40 CFR 425.04 - Applicability of sulfide pretreatment standards.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Applicability of sulfide pretreatment standards. 425.04 Section 425.04 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS LEATHER TANNING AND FINISHING POINT SOURCE CATEGORY General...

  9. 40 CFR 425.04 - Applicability of sulfide pretreatment standards.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Applicability of sulfide pretreatment standards. 425.04 Section 425.04 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) LEATHER TANNING AND FINISHING POINT SOURCE CATEGORY...

  10. 40 CFR 425.04 - Applicability of sulfide pretreatment standards.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Applicability of sulfide pretreatment standards. 425.04 Section 425.04 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS LEATHER TANNING AND FINISHING POINT SOURCE CATEGORY General...

  11. 40 CFR 425.04 - Applicability of sulfide pretreatment standards.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Applicability of sulfide pretreatment standards. 425.04 Section 425.04 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) LEATHER TANNING AND FINISHING POINT SOURCE CATEGORY...

  12. 40 CFR 420.28 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards compliance dates. 420.28 Section 420.28 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Sintering Subcategory §...

  13. 40 CFR 417.166 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources. 417.166 Section 417.166 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Liquid Detergents Subcategory §...

  14. 40 CFR 417.166 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Pretreatment standards for new sources. 417.166 Section 417.166 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Liquid Detergents Subcategory §...

  15. 40 CFR 35.907 - Municipal pretreatment program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Municipal pretreatment program. 35.907 Section 35.907 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act §...

  16. 40 CFR 35.907 - Municipal pretreatment program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Municipal pretreatment program. 35.907 Section 35.907 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act §...

  17. 40 CFR 35.907 - Municipal pretreatment program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Municipal pretreatment program. 35.907 Section 35.907 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act §...

  18. 40 CFR 35.907 - Municipal pretreatment program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Municipal pretreatment program. 35.907 Section 35.907 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act §...

  19. 40 CFR 426.126 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Pretreatment standards for new sources. 426.126 Section 426.126 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GLASS MANUFACTURING POINT SOURCE CATEGORY Incandescent Lamp Envelope Manufacturing Subcategory §...

  20. 40 CFR 426.116 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Pretreatment standards for new sources. 426.116 Section 426.116 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GLASS MANUFACTURING POINT SOURCE CATEGORY Television Picture Tube Envelope Manufacturing Subcategory...

  1. 40 CFR 426.126 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Pretreatment standards for new sources. 426.126 Section 426.126 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GLASS MANUFACTURING POINT SOURCE CATEGORY Incandescent Lamp Envelope Manufacturing Subcategory §...

  2. 40 CFR 426.86 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Pretreatment standards for new sources. 426.86 Section 426.86 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GLASS MANUFACTURING POINT SOURCE CATEGORY Glass Container Manufacturing Subcategory § 426.86...

  3. 40 CFR 426.116 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Pretreatment standards for new sources. 426.116 Section 426.116 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GLASS MANUFACTURING POINT SOURCE CATEGORY Television Picture Tube Envelope Manufacturing Subcategory...

  4. 40 CFR 426.86 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Pretreatment standards for new sources. 426.86 Section 426.86 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GLASS MANUFACTURING POINT SOURCE CATEGORY Glass Container Manufacturing Subcategory § 426.86...

  5. 40 CFR 427.76 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... process wastewater pollutants into a publicly owned treatment works must comply with 40 CFR part 403. ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Pretreatment standards for new sources. 427.76 Section 427.76 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)...

  6. 40 CFR 418.56 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 30 2013-07-01 2012-07-01 true Pretreatment standards for new sources. 418.56 Section 418.56 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS FERTILIZER MANUFACTURING POINT SOURCE CATEGORY Nitric Acid Subcategory §...

  7. 40 CFR 418.56 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources. 418.56 Section 418.56 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS FERTILIZER MANUFACTURING POINT SOURCE CATEGORY Nitric Acid Subcategory §...

  8. 40 CFR 418.56 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources. 418.56 Section 418.56 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS FERTILIZER MANUFACTURING POINT SOURCE CATEGORY Nitric Acid Subcategory §...

  9. 40 CFR 418.56 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Pretreatment standards for new sources. 418.56 Section 418.56 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS FERTILIZER MANUFACTURING POINT SOURCE CATEGORY Nitric Acid Subcategory §...

  10. 40 CFR 418.56 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for new sources. 418.56 Section 418.56 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS FERTILIZER MANUFACTURING POINT SOURCE CATEGORY Nitric Acid Subcategory §...

  11. 40 CFR 412.3 - General pretreatment standards.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false General pretreatment standards. 412.3 Section 412.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES... publicly owned treatment works (POTW) must comply with 40 CFR part 403....

  12. 40 CFR 405.64 - Pretreatment standards for existing sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Pretreatment standards for existing sources. 405.64 Section 405.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Natural and Processed Cheese Subcategory § 405.64...

  13. 40 CFR 405.76 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources. 405.76 Section 405.76 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Fluid Mix for Ice Cream and Other Frozen Desserts Subcategory §...

  14. 40 CFR 420.48 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards compliance dates. 420.48 Section 420.48 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Steelmaking Subcategory §...

  15. 40 CFR 420.18 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards compliance dates. 420.18 Section 420.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Cokemaking Subcategory §...

  16. 40 CFR 420.48 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Pretreatment standards compliance dates. 420.48 Section 420.48 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY...

  17. 40 CFR 420.18 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Pretreatment standards compliance dates. 420.18 Section 420.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Cokemaking...

  18. 40 CFR 420.28 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards compliance dates. 420.28 Section 420.28 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Sintering Subcategory §...

  19. 40 CFR 420.28 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 30 2013-07-01 2012-07-01 true Pretreatment standards compliance dates. 420.28 Section 420.28 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Sintering Subcategory §...

  20. 40 CFR 420.18 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards compliance dates. 420.18 Section 420.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Cokemaking Subcategory §...

  1. 40 CFR 420.18 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards compliance dates. 420.18 Section 420.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Cokemaking Subcategory §...

  2. 40 CFR 420.18 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 30 2013-07-01 2012-07-01 true Pretreatment standards compliance dates. 420.18 Section 420.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Cokemaking Subcategory §...

  3. 40 CFR 420.28 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Pretreatment standards compliance dates. 420.28 Section 420.28 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Sintering...

  4. 40 CFR 420.48 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards compliance dates. 420.48 Section 420.48 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Steelmaking Subcategory §...

  5. 40 CFR 420.28 - Pretreatment standards compliance dates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards compliance dates. 420.28 Section 420.28 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Sintering Subcategory §...

  6. 40 CFR 405.66 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... introduces process wastewater pollutants into a publicly owned treatment works must comply with 40 CFR part... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for new sources. 405.66 Section 405.66 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)...

  7. 40 CFR 405.64 - Pretreatment standards for existing sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 405.64 Section 405.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Natural and Processed Cheese Subcategory § 405.64...

  8. 40 CFR 429.96 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... owned treatment works must comply with 40 CFR part 403 and achieve the following pretreatment standards... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Pretreatment standards for new sources... Subcategory § 429.96 Pretreatment standards for new sources (PSNS). Except as provided in 40 CFR 403.7,...

  9. 40 CFR 429.86 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... owned treatment works must comply with 40 CFR part 403 and achieve the following pretreatment standards... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Pretreatment standards for new sources... Subcategory § 429.86 Pretreatment standards for new sources (PSNS). Except as provided in 40 CFR 403.7,...

  10. 40 CFR 423.17 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources... Pretreatment standards for new sources (PSNS). Except as provided in 40 CFR 403.7, any new source subject to... CFR part 403 and the following pretreatment standards for new sources (PSNS). (a) There shall be...

  11. 40 CFR 455.11 - Compliance date for pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) PESTICIDE CHEMICALS Organic Pesticide Chemicals Manufacturing Subcategory § 455.11 Compliance date for pretreatment standards...

  12. 40 CFR 455.11 - Compliance date for pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) PESTICIDE CHEMICALS Organic Pesticide Chemicals Manufacturing Subcategory § 455.11 Compliance date for pretreatment standards...

  13. 40 CFR 455.11 - Compliance date for pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) PESTICIDE CHEMICALS Organic Pesticide Chemicals Manufacturing Subcategory § 455.11 Compliance date for pretreatment standards...

  14. Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats

    PubMed Central

    Karim, Nurul; Hossain, Md. Sabir; Alam, Nadia

    2016-01-01

    The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium. PMID:27294126

  15. Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats.

    PubMed

    Afroz, Rizwana; Tanvir, E M; Karim, Nurul; Hossain, Md Sabir; Alam, Nadia; Gan, Siew Hua; Khalil, Md Ibrahim

    2016-01-01

    The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium. PMID:27294126

  16. Probability mapping of scarred myocardium using texture and intensity features in CMR images

    PubMed Central

    2013-01-01

    Background The myocardium exhibits heterogeneous nature due to scarring after Myocardial Infarction (MI). In Cardiac Magnetic Resonance (CMR) imaging, Late Gadolinium (LG) contrast agent enhances the intensity of scarred area in the myocardium. Methods In this paper, we propose a probability mapping technique using Texture and Intensity features to describe heterogeneous nature of the scarred myocardium in Cardiac Magnetic Resonance (CMR) images after Myocardial Infarction (MI). Scarred tissue and non-scarred tissue are represented with high and low probabilities, respectively. Intermediate values possibly indicate areas where the scarred and healthy tissues are interwoven. The probability map of scarred myocardium is calculated by using a probability function based on Bayes rule. Any set of features can be used in the probability function. Results In the present study, we demonstrate the use of two different types of features. One is based on the mean intensity of pixel and the other on underlying texture information of the scarred and non-scarred myocardium. Examples of probability maps computed using the mean intensity of pixel and the underlying texture information are presented. We hypothesize that the probability mapping of myocardium offers alternate visualization, possibly showing the details with physiological significance difficult to detect visually in the original CMR image. Conclusion The probability mapping obtained from the two features provides a way to define different cardiac segments which offer a way to identify areas in the myocardium of diagnostic importance (like core and border areas in scarred myocardium). PMID:24053280

  17. Ramipril-induced delayed myocardial protection against free radical injury involves bradykinin B2 receptor-NO pathway and protein synthesis

    PubMed Central

    Jin, Zhu-Qiu; Chen, Xiu

    1998-01-01

    The aim of the present study was to examine whether ramipril induces delayed myocardial protection against free radical injuries ex vivo and to determine the possible role of the bradykinin B2–nitric oxide (NO) pathway, prostaglandins(PGs) and protein synthesis in this delayed adaptive response.Rats were pretreated with ramipril (10 or 50 μg kg−1, i.v.) and hearts were isolated after 24, 48 and 72 h. Langendorff hearts were subjected to 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical-induced injury.Left ventricular developed pressure (LVDP) and its maximal increase velocity (+dP/dtmax), coronary flow (CF), heart rate (HR), lactate dehydrogenase (LDH) in coronary effluent and thiobarbituric acid reactive substances (TBARS) in the myocardium were measured.The results showed that in the DPPH control group, 20 min after free radical-induced injury, LVDP, +dP/dtmax, CF, HR declined, whereas TBARS and LDH increased significantly. The above cardiac function parameters were significantly improved in RAM-pretreated rats after 24 and 48 h.Pretreatment with HOE 140, the selective bradykinin B2 receptor antagonist, NG-nitro-L-arginine, the NO synthase inhibitor, and actinomycin D, the RNA transcription inhibitor, prior to ramipril injection abolished the beneficial effects of ramipril at 24 h while indomethacin, a cyclooxygenase inhibitor, pretreatment had no effect on ramipril-induced delayed protection.In conclusion, ramipril induces delayed myocardial protection against free radical injury in the rat heart. This delayed protection was sustained for 48 h, is associated with the bradykinin B2 receptor–NO pathway and depends on protein but not prostaglandin synthesis. PMID:9806340

  18. Tumor necrosis factor-alpha gene and protein expression in adult feline myocardium after endotoxin administration.

    PubMed Central

    Kapadia, S; Lee, J; Torre-Amione, G; Birdsall, H H; Ma, T S; Mann, D L

    1995-01-01

    TNF alpha mRNA and protein biosynthesis were examined in the adult feline heart after stimulation with endotoxin. When freshly isolated hearts were stimulated with endotoxin in vitro, de novo TNF alpha mRNA expression occurred within 30 min, and TNF alpha protein production was detected within 60-75 min; however, TNF alpha mRNA and protein production were not detected in diluent-treated hearts. Immunohistochemical studies localized TNF alpha to endothelial cells, smooth muscle cells, and cardiac myocytes in the endotoxin-treated hearts, whereas TNF alpha immunostaining was absent in the diluent-treated hearts. To determine whether the cardiac myocyte was a source for TNF alpha production, two studies were performed. First, in situ hybridization studies, using highly specific biotinylated probes, demonstrated TNF alpha mRNA in cardiac myocytes from endotoxin-stimulated hearts; in contrast, TNF alpha mRNA was not expressed in myocytes from diluent-treated hearts. Second, TNF alpha protein production was observed when cultured cardiac myocytes were stimulated with endotoxin, whereas TNF alpha protein production was not detected in the diluent-treated cells. The functional significance of the intramyocardial production of TNF alpha was determined by examining cell motion in isolated cardiac myocytes treated with superfusates from endotoxin- and diluent-stimulated hearts. These studies showed that cell motion was depressed in myocytes treated with superfusates from the endotoxin-treated hearts, but was normal with the superfusates from the diluent-treated hearts; moreover, the negative inotropic effects of the superfusates from the endotoxin-treated hearts could be abrogated completely by pretreatment with an anti-TNF alpha antibody. Finally, endotoxin stimulation was also shown to result in the intramyocardial production of TNF alpha mRNA and protein in vivo. Thus, this study shows for the first time that the adult mammalian myocardium synthesizes biologically active

  19. Muscarinic receptor stimulation and cyclic AMP-dependent effects in guinea-pig ventricular myocardium.

    PubMed Central

    Schmied, R.; Korth, M.

    1990-01-01

    1. The effect of carbachol on force of contraction, contraction duration, intracellular Na+ activity and cyclic AMP content was studied in papillary muscles of the guinea-pig exposed to isoprenaline or the phosphodiesterase inhibitor 3-isobutyl, 1-methyl xanthine (IBMX). The preparations were obtained from reserpine-pretreated animals and were electrically driven at a frequency of 0.2 Hz. 2. Isoprenaline (10 nM) and IBMX (100 microM) produced comparable positive inotropic effects of 9.8 and 9.7 mN, respectively. Carbachol (3 microM) attenuated the inotropic effects by 82% (isoprenaline) and by 79% (IBMX). The shortening of contraction duration which accompanied the positive inotropic effect of isoprenaline (by 14.9%) and of IBMX (by 22.4%) was not significantly affected by 3 microM carbachol. 3. The positive inotropic effect of 10 nM isoprenaline and of 100 microM IBMX was accompanied by an increase in cellular cyclic AMP content of 58 and 114%, respectively. Carbachol (3 microM) failed to reduce significantly the elevated cyclic AMP content of muscles exposed to either isoprenaline or IBMX. 4. In the quiescent papillary muscle, isoprenaline (10 nM) and IBMX (100 microM) reduced the intracellular Na+ activity by 28 and 17%, respectively. This decline was not influenced by the additional application of 3 microM carbachol. 5. The results demonstrate that muscarinic antagonism in guinea-pig ventricular myocardium exposed to cyclic AMP-elevating drugs is restricted to force of contraction. The underlying mechanism does not apparently involve the cytosolic signal molecule cyclic AMP. PMID:1691677

  20. Proto-oncogene expression in porcine myocardium subjected to ischemia and reperfusion.

    PubMed

    Brand, T; Sharma, H S; Fleischmann, K E; Duncker, D J; McFalls, E O; Verdouw, P D; Schaper, W

    1992-12-01

    The molecular basis of myocardial adaptation to ischemia and reperfusion is poorly understood. It is thought that nuclear proto-oncogenes act as third messengers, converting cytoplasmic signal transduction into long-term changes of gene expression. We studied the expression of six nuclear proto-oncogenes (Egr-1, c-fos, fosB, c-jun, junB, and c-myc) in myocardium subjected to ischemia and reperfusion in anesthetized pigs. Stunning was achieved by two 10-minute left anterior descending coronary artery occlusions separated by 30 minutes of reperfusion. Hearts were excised after the first occlusion, after the first reperfusion, and at 30, 120, 150, and 210 minutes of reperfusion after the second occlusion. Total RNA was prepared from stunned as well as normally perfused myocardial tissue and subjected to Northern blotting. The response of the six nuclear proto-oncogenes varied.fosB gene expression was never detected. The c-myc gene was expressed, but its level was unchanged by ischemia. c-jun expression was slightly increased by ischemia (3.1 +/- 0.6-fold). The c-fos, Egr-1, and junB genes were highly induced, being fivefold to sevenfold higher in experimental than in control tissue. In three animals pretreated with the beta 1-antagonist metoprolol and then subjected to the above experimental protocol, the induction of proto-oncogenes was similar to that in nonblocked controls. Our results show that the myocardial adaptive response to ischemic stress includes the induction of at least four transcription factors that may be further operative in repair processes and angiogenesis. PMID:1385005

  1. Evidence against a role for dopamine D1 receptors in the myocardium of the pig.

    PubMed Central

    Van Woerkens, L. J.; Duncker, D. J.; Den Boer, M. O.; McFalls, E. O.; Sassen, L. M.; Saxena, P. R.; Verdouw, P. D.

    1991-01-01

    1. We investigated the presence of dopamine D1 receptors in the myocardium of anesthetized pigs using intravenous infusions of dopamine, alone and after alpha- and beta-adrenoceptor blockade and intracoronary infusions of the selective D1 receptor agonist, fenoldopam. 2. Intravenous infusion of dopamine (2.5, 5 and 10 micrograms kg-1 min-1 for 10 min, n = 6) caused dose-dependent changes in heart rate (from 94 +/- 6 to 132 +/- 10 beats min-1, P less than 0.05), the maximal rate of rise of left ventricular pressure (LVdP/dtmax; from 2280 +/- 170 to 4800 +/- 410 mmHgs-1, P less than 0.05), mean arterial blood pressure (from 87 +/- 5 to 62 +/- 3 mmHg) and systemic vascular resistance (from 40 +/- 4 to 28 +/- 2 mmHgl-1 min, P less than 0.05). The increases in heart rate and LVdP/dtmax were abolished when dopamine was infused after alpha- and beta-adrenoceptor blockade. The vasodilator response was, however, only minimally affected. 3. Intravenous infusions of dopamine decreased coronary vascular resistance from 0.90 +/- 0.06 to 0.53 +/- 0.07 mmHg ml-1 min 100 g (P less than 0.05). This action of dopamine was not observed when dopamine was infused after blockade of the alpha- and beta-adrenoceptors. 4. Pretreatment with alpha- and beta-adrenoceptor blockade had no effect or only slightly attenuated the dopamine-induced decrease in vascular resistance of the brain, kidneys, adrenals and small intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1686206

  2. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction.

    PubMed

    Miyahara, Yoshinori; Nagaya, Noritoshi; Kataoka, Masaharu; Yanagawa, Bobby; Tanaka, Koichi; Hao, Hiroyuki; Ishino, Kozo; Ishida, Hideyuki; Shimizu, Tatsuya; Kangawa, Kenji; Sano, Shunji; Okano, Teruo; Kitamura, Soichiro; Mori, Hidezo

    2006-04-01

    Mesenchymal stem cells are multipotent cells that can differentiate into cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet technology, that monolayered mesenchymal stem cells have multipotent and self-propagating properties after transplantation into infarcted rat hearts. We cultured adipose tissue-derived mesenchymal stem cells characterized by flow cytometry using temperature-responsive culture dishes. Four weeks after coronary ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred myocardium. After transplantation, the engrafted sheet gradually grew to form a thick stratum that included newly formed vessels, undifferentiated cells and few cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered mesenchymal stem cells reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Thus, transplantation of monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac tissue regeneration. PMID:16582917

  3. Cardiac magnetic resonance T1 mapping of left atrial myocardium

    PubMed Central

    Beinart, Roy; Khurram, Irfan M.; Liu, Songtao; Yarmohammadi, Hirad; Halperin, Henry R.; Bluemke, David A.; Gai, Neville; van der Geest, Rob J.; Lima, Joao A.C.; Calkins, Hugh; Zimmerman, Stefan L.; Nazarian, Saman

    2013-01-01

    BACKGROUND Cardiac magnetic resonance (CMR) T1 mapping is an emerging tool for objective quantification of myocardial fibrosis. OBJECTIVES To (a) establish the feasibility of left atrial (LA) T1 measurements, (b) determine the range of LA T1 values in patients with atrial fibrillation (AF) vs healthy volunteers, and (c) validate T1 mapping vs LA intracardiac electrogram voltage amplitude measures. METHODS CMR imaging at 1.5 T was performed in 51 consecutive patients before AF ablation and in 16 healthy volunteers. T1 measurements were obtained from the posterior LA myocardium by using the modified Look-Locker inversion-recovery sequence. Given the established association of reduced electrogram amplitude with fibrosis, intracardiac point-by-point bipolar LA voltage measures were recorded for the validation of T1 measurements. RESULTS The median LA T1 relaxation time was shorter in patients with AF (387 [interquartile range 364–428] ms) compared to healthy volunteers (459 [interquartile range 418–532] ms; P < .001) and was shorter in patients with AF with prior ablation compared to patients without prior ablation (P = .035). In a generalized estimating equations model, adjusting for data clusters per participant, age, rhythm during CMR, prior ablation, AF type, hypertension, and diabetes, each 100-ms increase in T1 relaxation time was associated with 0.1 mV increase in intracardiac bipolar LA voltage (P = .025). CONCLUSIONS Measurement of the LA myocardium T1 relaxation time is feasible and strongly associated with invasive voltage measures. This methodology may improve the quantification of fibrotic changes in thin-walled myocardial tissues. PMID:23643513

  4. Pretreatment methods for bioethanol production.

    PubMed

    Xu, Zhaoyang; Huang, Fang

    2014-09-01

    Lignocellulosic biomass, such as wood, grass, agricultural, and forest residues, are potential resources for the production of bioethanol. The current biochemical process of converting biomass to bioethanol typically consists of three main steps: pretreatment, enzymatic hydrolysis, and fermentation. For this process, pretreatment is probably the most crucial step since it has a large impact on the efficiency of the overall bioconversion. The aim of pretreatment is to disrupt recalcitrant structures of cellulosic biomass to make cellulose more accessible to the enzymes that convert carbohydrate polymers into fermentable sugars. This paper reviews several leading acidic, neutral, and alkaline pretreatments technologies. Different pretreatment methods, including dilute acid pretreatment (DAP), steam explosion pretreatment (SEP), organosolv, liquid hot water (LHW), ammonia fiber expansion (AFEX), soaking in aqueous ammonia (SAA), sodium hydroxide/lime pretreatments, and ozonolysis are intensively introduced and discussed. In this minireview, the key points are focused on the structural changes primarily in cellulose, hemicellulose, and lignin during the above leading pretreatment technologies. PMID:24972651

  5. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury.

    PubMed

    Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

    2015-01-01

    Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury. PMID:26103523

  6. PRETREATING THORIUM FOR ELECTROPLATING

    DOEpatents

    Beach, J.G.; Schaer, G.R.

    1959-07-28

    A method is presented for pretreating a thorium surface prior to electroplating the surface. The pretreatment steps of the invention comprise cleaning by vapor blasting the surface, anodically pickling in a 5 to 15% by volume aqueous hydrochloric acid bath with a current of 125 to 250 amp/sq ft for 3 to 5 min at room temperature, chemically pickling the surface in a 5 to 15% by volume of aqueous sulfuric acid for 3 to 5 min at room temperature, and rinsing the surface with water.

  7. Protective effects of remote ischemic preconditioning in isolated rat hearts

    PubMed Central

    Teng, Xiao; Yuan, Xin; Tang, Yue; Shi, Jingqian

    2015-01-01

    To use Langendorff model to investigate whether remote ischemic preconditioning (RIPC) attenuates post-ischemic mechanical dysfunction on isolated rat heart and to explore possible mechanisms. SD rats were randomly divided into RIPC group, RIPC + norepinephrine (NE) depletion group, RIPC + pertussis toxin (PTX) pretreatment group, ischemia/reperfusion group without treatment (ischemia group) and time control (TC) group. RIPC was achieved through interrupted occlusion of anterior mesenteric artery. Then, Langendorff model was established using routine methods. Heart function was tested; immunohistochemistry and ELISA methods were used to detect various indices related to myocardial injury. Compared with ischemia group in which the hemodynamic parameters deteriorated significantly, heart function recovered to a certain degree among the RIPC, RIPC + NE depletion, and RIPC + PTX groups (P<0.05). More apoptotic nuclei were observed in ischemia group than in the other three groups (P<0.05); more apoptotic nuclei were detected in NE depletion and PTX groups than in RIPC group (P<0.05). While, there was no significant difference between NE depletion and PTX groups. In conclusion, RIPC protection on I/R myocardium extends to the period after hearts are isolated. NE and PTX-sensitive inhibitory G protein might have a role in the protection process. PMID:26550168

  8. The alteration of interelemental ratios in myocardium under the congenital heart disease (SRXRF)

    NASA Astrophysics Data System (ADS)

    Trunova, V. A.; Zvereva, V. V.; Okuneva, G. N.; Levicheva, E. N.

    2007-05-01

    It is the myocardium that bears the basic functional loading during heart working, including muscle contractility and enzyme activity. The elemental concentrations in myocardium tissue of heart were determined by SRXRF technique. Our investigation is systematical: the elemental content in each compartment (left and right ventricles, left and right auricles) of hearts of healthy and diseased children (congenital heart diseases, transposition of main vessels (TMV)) was analyzed. The elemental distribution in myocardium of four heart chambers of human fetuses was also analyzed. Following elements were determined: S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb, Sr. It was revealed that the elemental concentrations in myocardium of both ventricles are almost constant in heart of fetuses and healthy children. The transition from pre-natal study (fetus) to post-natal study is accompanied by the redistribution of chemical elements in myocardium. The higher concentrations of S, Fe, Ca, Sr and Cu in myocardium of children are observed, the content of K, Br, Rb and especially Se is lower than in heart of fetuses. The elemental distribution in myocardium of children TMV is considerably different in comparison with the healthy children: the higher levels of Cu are observed. The content of Se is lower.

  9. The antioxidant compound tert-butylhydroquinone activates Akt in myocardium, suppresses apoptosis and ameliorates pressure overload-induced cardiac dysfunction

    PubMed Central

    Zhang, Yongtao; Fang Liu, Fang; Bi, Xiaolei; Wang, Shuangxi; Wu, Xiao; Jiang, Fan

    2015-01-01

    Tert-butylhydroquinone (TBHQ) is an antioxidant compound which shows multiple cytoprotective actions. We evaluated the effects of TBHQ on pathological cardiac remodeling and dysfunction induced by chronic overload. Pressure overload was created by transverse aortic constriction (TAC) in male C57BL/6 mice. TBHQ was incorporated in the diet and administered for 4 weeks. TBHQ treatment prevented left ventricular dilatation and cardiac dysfunction induced by TAC, and decreased the prevalence of myocardial apoptosis. The beneficial effects of TBHQ were associated with an increase in Akt activation, but not related to activations of Nrf2 or AMP-activated protein kinase. TBHQ-induced Akt activation was accompanied by increased phosphorylation of Bad, glycogen synthase kinase-3β (GSK-3β) and mammalian target of rapamycin (mTOR). Mechanistically, we showed that in cultured H9c2 cells and primary cardiac myocytes, TBHQ stimulated Akt phosphorylation and suppressed oxidant-induced apoptosis; this effect was abolished by wortmannin or an Akt inhibitor. Blockade of the Akt pathway in vivo accelerated cardiac dysfunction, and abrogated the protective effects of TBHQ. TBHQ also reduced the reactive aldehyde production and protein carbonylation in stressed myocardium. We suggest that TBHQ treatment may represent a novel strategy for timely activation of the cytoprotective Akt pathway in stressed myocardium. PMID:26260024

  10. [Four-week simulated weightlessness increases the expression of atrial natriuretic peptide in the myocardium].

    PubMed

    Zhang, Wen-Cheng; Lu, Yuan-Ming; Yang, Huai-Zhang; Xu, Peng-Tao; Chang, Hui; Yu, Zhi-Bin

    2013-04-25

    One of the major circulatory changes that occur in human during space flight and simulated weightlessness is a cerebral redistribution of body fluids, which is accompanied by an increase of blood volume in the upper body. Therefore, atrial myocardium should increase the secretion of atrial natriuretic peptide (ANP), but the researches lack common conclusion until now. The present study was to investigate the expression level of ANP in simulated weightlessness rats, and to confirm the changes of ANP by observing the associated proteins of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The tail-suspended rat model was used to simulate weightlessness. Western blots were carried out to examine the expression levels of ANP and SNARE proteins in atrial and left ventricular myocardium. The results showed that ANP expression in atrial myocardium showed an increase in 4-week tail-suspended rats (SUS) compared with that in the synchronous control rats (CON). We only detected a trace amount of ANP in the left ventricular myocardium of the CON, but found an enhanced expression of ANP in left ventricular myocardium of the SUS. Expression of VAMP-1/2 (vesicle associated SNARE) increased significantly in both atrial and left ventricular myocardium in the SUS compared with that in the CON. There was no difference of the expression of syntaxin-4 (target compartment associated SNARE) between the CON and SUS, but the expression of SNAP-23 showed an increase in atrial myocardium of the SUS compared with that in the CON. Synip and Munc-18c as regulators of SNAREs did not show significant difference between the CON and SUS. These results suggest that the expression of ANP shows an increase in atrial and left ventricular myocardium of 4-week tail-suspended rats. Enhanced expression of VAMP-1/2 associated with ANP vesicles confirms the increased expression of ANP in atrial and left ventricular myocardium. PMID:23598869

  11. Longitudinal rotating frame relaxation time measurements in infarcted mouse myocardium in vivo.

    PubMed

    Musthafa, Haja-Sherief N; Dragneva, Galina; Lottonen, Line; Merentie, Mari; Petrov, Lyubomir; Heikura, Tommi; Ylä-Herttuala, Elias; Ylä-Herttuala, Seppo; Gröhn, Olli; Liimatainen, Timo

    2013-05-01

    Longitudinal relaxation time in the rotating frame (T1ρ) was measured using continuous wave irradiation in normal and infarcted mouse myocardium in vivo. Significant increase in T1ρ was found after 7 days of infarction when compared with reference myocardium or in myocardium before infarction. Cine MRI and histology were performed to verify the severity of infarction. The time course of T1ρ in the infarct fits better with granulation and scar tissue formation than necrosis and edema. The results of the study show that T1ρ could potentially be a noninvasive quantitative marker for tissue remodeling after ischemic damage. PMID:22736543

  12. 40 CFR 429.35 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... with 40 CFR part 403. ... sources (PSES). 429.35 Section 429.35 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Subcategory § 429.35 Pretreatment standards for existing sources (PSES). Any existing source subject to...

  13. Streptococcus pneumoniae Translocates into the Myocardium and Forms Unique Microlesions That Disrupt Cardiac Function

    PubMed Central

    Brown, Armand O.; Mann, Beth; Gao, Geli; Hankins, Jane S.; Humann, Jessica; Giardina, Jonathan; Faverio, Paola; Restrepo, Marcos I.; Halade, Ganesh V.; Mortensen, Eric M.; Lindsey, Merry L.; Hanes, Martha; Happel, Kyle I.; Nelson, Steve; Bagby, Gregory J.; Lorent, Jose A.; Cardinal, Pablo; Granados, Rosario; Esteban, Andres; LeSaux, Claude J.; Tuomanen, Elaine I.; Orihuela, Carlos J.

    2014-01-01

    Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1β was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD. PMID:25232870

  14. Bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs.

    PubMed Central

    Sassen, L. M.; den Boer, M. O.; Rensen, R. J.; Saxena, P. R.; Verdouw, P. D.

    1988-01-01

    1. The ability of the cardioselective beta-adrenoceptor antagonist bisoprolol ((+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropyl-amino -2-propanol hemifumarate, EMD 33512) to suppress isoprenaline-induced increases in heart rate and maximal rate of rise in left ventricular pressure (LVdP/dtmax) was studied in 6 anaesthetized pigs given 4 cumulative doses (16, 64, 256 and 1024 micrograms kg-1). Bisoprolol was about 2 times more effective in suppressing isoprenaline-induced increases in LVdP/dtmax than those in heart rate. 2. In 8 animals which had a partial stenosis of the left anterior descending coronary artery (LADCA), the effects of 3 consecutive doses (50, 200 and 750 micrograms kg-1) of bisoprolol were studied on systemic haemodynamics, regional myocardial perfusion and function. The effects of the drug were compared with those obtained in a group of 9 animals with LADCA stenosis which did not receive any treatment. 3. The lowest dose of bisoprolol (50 micrograms kg-1) increased perfusion of the ischaemic myocardium (which had been reduced from 123 +/- 20 ml min-1 100 g-1 to 42 +/- 11 ml min-1 100 g-1) by 21 +/- 10 ml min-1 100 g-1 (P less than 0.05). In particular the subendocardial layers, which were most severely affected by the stenosis (a decrease from 128 +/- 19 ml min-1 100 g-1 to 20 +/- 6 ml min-1 100 g-1) benefited from the administration of the drug (an increase of 30 +/- 10 ml min-1 100 g-1). Perfusion of the subepicardium was not significantly affected. With the higher dose only a minor additional improvement in perfusion of the ischaemic myocardium was observed. 4. The negative chronotropic response is the most likely factor leading to the improvement in perfusion. 5. Myocardial wall thickening, which decreased from 41 +/- 2% to 9 +/- 4% (P less than 0.05) due to the hypoperfusion, did not improve after administration of the drug. This lack of improvement may possibly be due to the duration of ischaemia before and the magnitude of the

  15. Client Perceptions of Pretreatment Change

    ERIC Educational Resources Information Center

    Kindsvatter, Aaron; Osborn, Cynthia J.; Bubenzer, Donald; Duba, Jill D.

    2010-01-01

    The authors suggest that when counselors have a rich understanding of pretreatment changes, they are better able to assist clients in capitalizing on such changes. The current study examined client perceptions of pretreatment changes. Thirty-six clients completed Q-sorts pertaining to pretreatment changes they experienced. Four factors pertaining…

  16. Secretogranin II; a Protein Increased in the Myocardium and Circulation in Heart Failure with Cardioprotective Properties

    PubMed Central

    Røsjø, Helge; Stridsberg, Mats; Florholmen, Geir; Stensløkken, Kåre-Olav; Ottesen, Anett Hellebø; Sjaastad, Ivar; Husberg, Cathrine; Dahl, Mai Britt; Øie, Erik; Louch, William E.; Omland, Torbjørn; Christensen, Geir

    2012-01-01

    Background Several beneficial effects have been demonstrated for secretogranin II (SgII) in non-cardiac tissue. As cardiac production of chromogranin A and B, two related proteins, is increased in heart failure (HF), we hypothesized that SgII could play a role in cardiovascular pathophysiology. Methodology/Principal Findings SgII production was characterized in a post-myocardial infarction heart failure (HF) mouse model, functional properties explored in experimental models, and circulating levels measured in mice and patients with stable HF of moderate severity. SgII mRNA levels were 10.5 fold upregulated in the left ventricle (LV) of animals with myocardial infarction and HF (p<0.001 vs. sham-operated animals). SgII protein levels were also increased in the LV, but not in other organs investigated. SgII was produced in several cell types in the myocardium and cardiomyocyte synthesis of SgII was potently induced by transforming growth factor-β and norepinephrine stimulation in vitro. Processing of SgII to shorter peptides was enhanced in the failing myocardium due to increased levels of the proteases PC1/3 and PC2 and circulating SgII levels were increased in mice with HF. Examining a pathophysiological role of SgII in the initial phase of post-infarction HF, the SgII fragment secretoneurin reduced myocardial ischemia-reperfusion injury and cardiomyocyte apoptosis by 30% and rapidly increased cardiomyocyte Erk1/2 and Stat3 phosphorylation. SgII levels were also higher in patients with stable, chronic HF compared to age- and gender-matched control subjects: median 0.16 (Q1–3 0.14–0.18) vs. 0.12 (0.10–0.14) nmol/L, p<0.001. Conclusions We demonstrate increased myocardial SgII production and processing in the LV in animals with myocardial infarction and HF, which could be beneficial as the SgII fragment secretoneurin protects from ischemia-reperfusion injury and cardiomyocyte apoptosis. Circulating SgII levels are also increased in patients with chronic

  17. Erythropoietin protects myocardin-expressing cardiac stem cells against cytotoxicity of tumor necrosis factor-{alpha}

    SciTech Connect

    Madonna, Rosalinda; Shelat, Harnath; Xue, Qun; Willerson, James T.; De Caterina, Raffaele; Geng, Yong-Jian

    2009-10-15

    Cardiac stem cells are vulnerable to inflammation caused by infarction or ischemic injury. The growth factor, erythropoietin (Epo), ameliorates the inflammatory response of the myocardium to ischemic injury. This study was designed to assess the role of Epo in regulation of expression and activation of the cell death-associated intracellular signaling components in cardiac myoblasts stimulated with the proinflammatory cytokine tumor necrosis factor (TNF)-{alpha}. Cardiac myoblasts isolated from canine embryonic hearts characterized by expression of myocardin A, a promyogenic transcription factor for cardiovascular muscle development were pretreated with Epo and then exposed to TNF-{alpha}. Compared to untreated cells, the Epo-treated cardiac myoblasts exhibited better morphology and viability. Immunoblotting revealed lower levels of active caspase-3 and reductions in iNOS expression and NO production in Epo-treated cells. Furthermore, Epo pretreatment reduced nuclear translocation of NF-{kappa}B and inhibited phosphorylation of inhibitor of kappa B (I{kappa}B) in TNF-{alpha}-stimulated cardiac myoblasts. Thus, Epo protects cardiac myocyte progenitors or myoblasts against the cytotoxic effects of TNF-{alpha} by inhibiting NF-{kappa}B-mediated iNOS expression and NO production and by preventing caspase-3 activation.

  18. PROJECT W-551 INTERIM PRETREATMENT SYSTEM PRECONCEPTUAL CANDIDATE TECHNOLOGY DESCRIPTIONS

    SciTech Connect

    MAY TH

    2008-08-12

    The Office of River Protection (ORP) has authorized a study to recommend and select options for interim pretreatment of tank waste and support Waste Treatment Plant (WTP) low activity waste (LAW) operations prior to startup of all the WTP facilities. The Interim Pretreatment System (IPS) is to be a moderately sized system which separates entrained solids and 137Cs from tank waste for an interim time period while WTP high level waste vitrification and pretreatment facilities are completed. This study's objective is to prepare pre-conceptual technology descriptions that expand the technical detail for selected solid and cesium separation technologies. This revision includes information on additional feed tanks.

  19. Nonhazardous Urine Pretreatment Method

    NASA Technical Reports Server (NTRS)

    Akse, James R.; Holtsnider, John T.

    2012-01-01

    A method combines solid phase acidification with two non-toxic biocides to prevent ammonia volatilization and microbial proliferation. The safe, non-oxidizing biocide combination consists of a quaternary amine and a food preservative. This combination has exhibited excellent stabilization of both acidified and unacidified urine. During pretreatment tests, composite urine collected from donors was challenged with a microorganism known to proliferate in urine, and then was processed using the nonhazardous urine pre-treatment method. The challenge microorganisms included Escherichia coli, a common gram-negative bacteria; Enterococcus faecalis, a ureolytic gram-positive bacteria; Candida albicans, a yeast commonly found in urine; and Aspergillus niger, a problematic mold that resists urine pre-treatment. Urine processed in this manner remained microbially stable for over 57 days. Such effective urine stabilization was achieved using non-toxic, non-oxidizing biocides at higher pH (3.6 to 5.8) than previous methods in use or projected for use aboard the International Space Station (ISS). ISS urine pretreatment methods employ strong oxidants including ozone and hexavalent chromium (Cr(VI)), a carcinogenic material, under very acidic conditions (pH = 1.8 to 2.4). The method described here offers a much more benign chemical environment than previous pretreatment methods, and will lower equivalent system mass (ESM) by reducing containment volume and mass, system complexity, and crew time needed to handle pre-treatment chemicals. The biocides, being non-oxidizing, minimize the potential for chemical reactions with urine constituents to produce volatile, airborne contaminants such as cyanogen chloride. Additionally, the biocides are active under significantly less acidic conditions than those used in the current system, thereby reducing the degree of required acidification. A simple flow-through solid phase acidification (SPA) bed is employed to overcome the natural buffering

  20. Probing myocardium biomechanics using quantitative optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Wang, Shang; Lopez, Andrew L.; Morikawa, Yuka; Tao, Ge; Li, Jiasong; Larina, Irina V.; Martin, James F.; Larin, Kirill V.

    2015-03-01

    We present a quantitative optical coherence elastographic method for noncontact assessment of the myocardium elasticity. The method is based on shear wave imaging optical coherence tomography (SWI-OCT), where a focused air-puff system is used to induce localized tissue deformation through a low-pressure short-duration air stream and a phase-sensitive OCT system is utilized to monitor the propagation of the induced tissue displacement with nanoscale sensitivity. The 1-D scanning of M-mode OCT imaging and the application of optical phase retrieval and mapping techniques enable the reconstruction and visualization of 2-D depth-resolved shear wave propagation in tissue with ultra-high frame rate. The feasibility of this method in quantitative elasticity measurement is demonstrated on tissue-mimicking phantoms with the estimated Young's modulus compared with uniaxial compression tests. We also performed pilot experiments on ex vivo mouse cardiac muscle tissues with normal and genetically altered cardiomyocytes. Our results indicate this noncontact quantitative optical coherence elastographic method can be a useful tool for the cardiac muscle research and studies.

  1. Colored microspheres reveal interarterial microvascular anastomoses in canine myocardium.

    PubMed

    Cicutti, N; Rakusan, K; Downey, H F

    1992-01-01

    While the presence of microvascular intercommunication within an individual myocardial arterial bed is well documented, there is a paucity of data to support the existence of anastomoses emanating from independent arterial beds. Simultaneous in-vivo infusion of two different colored microsphere suspensions into the left anterior descending (LAD) and left circumflex (LCx) coronary arteries identified a specific interface region of canine myocardium that was perfused by both arterial branches. Subsequent microscopic/morphometric analysis of 40 microns serial sections in eight hearts revealed clustering of microspheres in their respective perfusion territories (red microspheres in the LAD region away from the interface, blue microspheres in the LCx field away from the interface), along with a mutually perfused borderzone. In each tissue section, two regions within this zone were identified and their maximum widths measured. One region was defined as the Interface Transition Zone (ITZ) (mean width = 5251 +/- 770 microns; mean +/- SD). This region was formed by an intermingling of microvessels supplied by the parent arteries of the adjacent perfusion territories; it separated tissue containing only one or the other colored microspheres. The second region was defined as the Boundary Watershed Zone (BWZ) (mean zone width = 3151 +/- 611 microns; mean +/- SD). This region was formed by capillaries containing sphere aggregates of both colors; it was located exclusively within the ITZ. In addition, the ITZ and BWZ were significantly wider in subepicardial than in subendocardial regions (p less than 0.001). PMID:1417709

  2. Free radical metabolites in myocardium during ischemia and reperfusion.

    PubMed

    Ruuge, E K; Ledenev, A N; Lakomkin, V L; Konstantinov, A A; Ksenzenko MYu

    1991-10-01

    Low-temperature electron paramagnetic resonance (EPR) spectroscopy and spin traps were used to measure paramagnetic species generation in rat hearts and isolated mitochondria. The hearts were freeze-clamped at 77 K during control perfusion by the Langendorff procedure, after 20-30 min of normothermic ischemia or 10-30 s of reperfusion with oxygenated perfusate. All EPR spectra measured at 4.5-50 K exhibited signals of both mitochondrial free radical centers and FeS proteins. The analysis of spectral parameters measured at 243 K showed that free radicals in heart tissue were semiquinones of coenzyme Q10 and flavins. The appearance of a typical "doublet" signal at g = 1.99 in low-temperature spectra indicated that a part of ubisemiquinones formed a complex with a high potential FeS protein of succinate dehydrogenase. Ischemia decreased the free radical species in myocardium approximately 50%; the initiation of reflow of perfusate resulted in quick increase of the EPR signal. Mitochondria isolated from hearts during control perfusion and after 20-30 min of ischemia were able to produce superoxide radicals in both the NADH-coenzyme Q10 reductase and the bc1 segments of the respiratory chain. The rate of oxyradical generation was significantly higher in mitochondria isolated from ischemic heart. PMID:1656795

  3. [Dynamics of lesions to the myocardium in experimental hyper- cholesterolemia].

    PubMed

    Rózycka, Z; Lewicki, Z; Wutzen, J

    1989-04-10

    Dynamics of changes in the myocardium of rabbits subjected to food hypercholesterolemia lasting from 6 to 16 weeks was investigated. An intensification of coronary atheromatosis was proportional to the duration of the high-cholesterol diet. There were observed focal and growing in time damages of cardiomyocytes. They were sharply outlined in atherosclerotically changed coronary arteries. The following morphological and histochemical changes have been observed: increased acidophilia and fuchsinophilia in the single and grouped muscle fibres, foci of infiltrations by mononuclear cells, contraction bands, and outlines of myocardial fibres, separation of myofibrils, granular disintegration of cardiomyocytes, healed infarcts, depletion and excessive accumulation of glycogen in muscle fibres, presence of neutral fats, cholesterol and its esters in atheromatous plaques of coronary arteries, presence of neutral fats in some cardiomyocytes: focal acid phosphates, loss of activity of Mg- and Ca-dependent ATPases and SDH: oedema of mitochondria with disorganization of cristae, disorganisation of fibres and lysis of myofilaments, margination of chromatin in cardiomyocyte nuclei, increased number of lysosomes, intensified symptoms of egzocytosis, widening of channels of sarcoplasmatic reticulum, oedema of endothelium of capillary vessels and increased number of the collagenous fibres in the interstitial space. The results of histological, histochemical and microscopic-electron investigations correlated with each other. It may be considered that the observed damages of cardiomyocytes precede myocardial infarction and result from progressive and increasing ischemia, hypoxia and accumulation of fat substances and cholesterol and its esters in intima of coronary arterioles as well as in cardiomyocytes. PMID:2813156

  4. Microvasculature of the Dog Left Ventricular Myocardium1

    PubMed Central

    Bassingthwaighte, James B.; Yipintsoi, Tada; Harvey, Rodney B.

    2010-01-01

    One of the main branches of the left main coronary artery of normally beating dog hearts was perfused with a silicone elastomer which solidified within the vasculature. Prolonged immersion in increasingly concentrated ethanol and in methyl salicylate rendered the tissue translucent and the vasculature clearly visible. Surfaces were photographed by reflected or transmitted light microscopy, showing large groups of capillaries running parallel to muscle fibers and extending for up to a few centimeters. The arrangement of arteriolar inflows to the capillary network and venular outflows (two to four times as frequent) suggested that functional capillary lengths were 500–1000 μm. Estimates of capillary diameters, presumably at maximal dilatation, were 5.6 ± 1.3 μm. Capillary densities within muscle groups were 3100–3800/mm2, giving intercapillary distances of 19–17.5 μm. With the lesser density value, the capillary surface area is estimated to be 500 cm2/g of myocardium. Inclusion of interfascial spaces lowered the average density to about 2500/mm2. Unbranched capillary lengths averaged 100 μm, with a strongly right-skewed distribution. The anatomic arrangement provides a basis mainly for concurrent flow in neighboring capillaries, and also for some diffusional exchange between inflow and outflow regions. PMID:4596001

  5. Autophagy and mitophagy in the myocardium: therapeutic potential and concerns.

    PubMed

    Jimenez, Rebecca E; Kubli, Dieter A; Gustafsson, Åsa B

    2014-04-01

    The autophagic-lysosomal degradation pathway is critical for cardiac homeostasis, and defects in this pathway are associated with development of cardiomyopathy. Autophagy is responsible for the normal turnover of organelles and long-lived proteins. Autophagy is also rapidly up-regulated in response to stress, where it rapidly clears dysfunctional organelles and cytotoxic protein aggregates in the cell. Autophagy is also important in clearing dysfunctional mitochondria before they can cause harm to the cell. This quality control mechanism is particularly important in cardiac myocytes, which contain a very high volume of mitochondria. The degradation of proteins and organelles also generates free fatty acids and amino acids, which help maintain energy levels in myocytes during stress conditions. Increases in autophagy have been observed in various cardiovascular diseases, but a major question that remains to be answered is whether enhanced autophagy is an adaptive or maladaptive response to stress. This review discusses the regulation and role of autophagy in the myocardium under baseline conditions and in various aetiologies of heart disease. It also discusses whether this pathway represents a new therapeutic target to treat or prevent cardiovascular disease and the concerns associated with modulating autophagy. PMID:24148024

  6. Failure of interventions to maintain mitochondrial function in ischemic myocardium.

    PubMed

    Clements, I P; Dewey, J D; Harrison, C E

    1980-10-01

    The purpose of this study was to investigate whether pyruvate (2.5 mmol/kg), the combination of glucose (3.9 mmol/kg) and insulin (0.13 unit/kg) with potassium (9.27 meq/kg), or sodium dichloroacetate (120 mg/kg) infused for 15 minutes before and 20 minutes after ligation of the left anterior descending coronary arterv in anesthetized dogs restricted the depression in mitochondrial respiratory function induced by ischemia. Myocardial blood flow after ligation in the three groups was o.2 ml/min per gram or less in ischemic subendocardium and was similar to that in saline-infused controls that had also undergone coronary artery ligation. The depressions induced in mitochondrial respiratory control index and state 3 respiration by ischemia in the subendocardium and subepicardium of the three treatment groups, when compared with corresponding nonischemic tissue, were not significantly improved from the control values. It was concluded that these three interventions fail to preserve mitochondrial respiration in ischemic myocardium. PMID:6997645

  7. Coagulating activity of the blood, vascular wall, and myocardium under hypodynamia conditions

    NASA Technical Reports Server (NTRS)

    Petrovskiy, B. V. (Editor); Chazov, E. I. (Editor); Andreyev, S. V. (Editor)

    1980-01-01

    In order to study the effects of hypodynamia on the coagulating properties of the blood, vascular wall, and myocardium, chinchilla rabbits were kept for varying periods in special cages which restricted their movements. At the end of the experiment, blood samples were taken and the animals were sacrificed. Preparations were made from the myocardium venae cavae, and layers of the aorta. Two resultant interrelated and mutually conditioned syndromes were discovered: thrombohemorrhagic in the blood and hemorrago-thrombotic in the tissues.

  8. Drinking to near death--acute water intoxication leading to neurogenic stunned myocardium.

    PubMed

    Losonczy, Lia I; Lovallo, Emily; Schnorr, C Daniel; Mantuani, Daniel

    2016-01-01

    Neurogenic stunned myocardium is a rare disease entity that has been typically described as a consequence of subarachnoid hemorrhage and, less commonly, seizures. Here we describe a case of a healthy young woman who drank excessive free water causing acute hyponatremia complicated by cerebral edema and seizure, leading to cardiogenic shock from neurogenic stunned myocardium. Two days later, she had complete return of her normal cardiac function. PMID:26238098

  9. Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway.

    PubMed

    Zhang, Xue-Jiao; Xiong, Zi-Bo; Tang, An-Li; Ma, Hong; Ma, Yue-Dong; Wu, Jing-Guo; Dong, Yu-Gang

    2010-02-01

    1. Rosiglitazone is widely used in the treatment of Type 2 diabetes. However, in recent years it has become evident that the therapeutic effects of peroxisome proliferator-activated receptor gamma ligands reach far beyond their use as insulin sensitizers. Recently, the ability of rosiglitazone pretreatment to induce cardioprotection following ischaemia-reperfusion (I/R) has been well documented; however, the protective mechanisms have not been elucidated. In the present study, examined the role of the phosphatidylinositol 3-kinase (PI3-K)/Akt signalling pathway in rosiglitazone cardioprotection following I/R injury. 2. Mice were pretreated with 3 mg/kg per day rosiglitazone for 14 days before hearts were subjected to ischaemia (30 min) and reperfusion (2 h). Wortmannin (1.4 mg/kg, i.p.), an inhibitor of PI3-K, was administered 10 min prior to myocardial I/R. Then, activation of the PI3-K/Akt/glycogen synthase kinase (GSK)-3alpha signalling pathway was examined. The effects of PI3-K inhibition on rosiglitazone-induced cardioprotection were also evaluated. 3. Compared with control rats, the ratio of infarct size to ischaemic area (area at risk) and the occurrence of sustained ventricular fibrillation in rosiglitazone-pretreated rats was significantly reduced (P < 0.05). Rosiglitazone pretreatment attenuated cardiac apoptosis, as assessed by ELISA to determine cardiomyocyte DNA fragmentation. Rosiglitazone pretreatment significantly increased levels of phosphorylated (p-) Akt and p-GSK-3alpha in the rat myocardium. Pharmacological inhibition of PI3-K by wortmannin markedly abolished the cardioprotection induced by rosiglitazone. 4. These results indicate that rosiglitazone-induced cardioprotection in I/R injury is mediated via a PI3-K/Akt/GSK-3alpha-dependent pathway. The data also suggest that modulation of PI3-K/Akt/GSK-3alpha-dependent signalling pathways may be a viable strategy to reduce myocardial I/R injury. PMID:19566839

  10. Biomass shock pretreatment

    DOEpatents

    Holtzapple, Mark T.; Madison, Maxine Jones; Ramirez, Rocio Sierra; Deimund, Mark A.; Falls, Matthew; Dunkelman, John J.

    2014-07-01

    Methods and apparatus for treating biomass that may include introducing a biomass to a chamber; exposing the biomass in the chamber to a shock event to produce a shocked biomass; and transferring the shocked biomass from the chamber. In some aspects, the method may include pretreating the biomass with a chemical before introducing the biomass to the chamber and/or after transferring shocked biomass from the chamber.

  11. Detection of ischemic myocardium with a new hypoxic tissue targeting tracer 99Tc(m)-HL91.

    PubMed

    Lü, Jiagao; Liu, Gang; Fang, Ya; Wu, Hua

    2006-01-01

    The imaging appearances of 99Tc(m)-HL91, a new hypoxic imaging agent, in ischemic myocardium were studied and the value of 99Tc(m)-HL91 in the evaluation of regional ischemic viable myocardium was explored. Acute myocardial ischemia models were made by coronary artery legations in 18 rats and randomly divided into 2 groups: 99Tc(m)-HL91 group and 99Tc(m)-MIBI group. Evan blue infusion during ischemia and TTC staining after operation were used to delineate the area of ischemic and viable myocardium. The isolated heart was sliced in the short axis and then autoradiography was performed. The electron microscopic examination was also done for the myocardial samples. 99Tc(m)-HL91 and 99Tc(m)-MIBI uptake activities (counts/g) were measured in the area of ischemic myocardium (T) and normal myocardium (NT) separately. The uptake ratios of 99Tc(m)-HL91 and that of 99Tc(m)-MIBI in ischemic myocardium were calculated as T/NT. It was found that the normal myocardium was blue and ischemic or infarct myocardium was negative with Evans blue in all experiment rats. Both the normal and ischemic myocardium was in red color with TTC staining. In the 99Tc(m)-HL91 group the ischemic myocardium showed much higher uptake over normal myocardium, that was demonstrated both in the autoradiography and quantitative analysis. The ischemic/normal activity ratios were 1.634 +/- 0.354. It was suggested that 99Tc(m)-HL91 might accumulate in ischemic and viable myocardium, which is helpful in the evaluation of hypoxic but viable myocardium and potentially used as a imaging agent to assess myocardial viability. PMID:16961269

  12. Muscarinic receptors mediate negative and positive inotropic effects in mammalian ventricular myocardium: differentiation by agonists.

    PubMed Central

    Korth, M.; Kühlkamp, V.

    1987-01-01

    The concentration-dependence of the negative and positive inotropic effect of choline esters and of oxotremorine was studied in isometrically contracting papillary muscles of the guinea-pig. The preparations were obtained from reserpine-pretreated animals and were electrically driven at a frequency of 0.2 Hz. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine (IBMX, 100 mumol l-1), choline esters and oxotremorine produced concentration-dependent negative inotropic effects. Oxotremorine exhibited the highest negative inotropic potency (with a half-maximal effective concentration, EC50, of 20 nmol l-1) followed by carbachol (139 nmol l-1), methacholine (490 nmol l-1), acetylcholine in the presence of 10 mumol l-1 physostigmine (1.36 mumol l-1) and bethanechol (10 mumol l-1). Atropine was a competitive antagonist of the negative inotropic effects. Carbachol and oxotremorine decreased Vmax, overshoot and duration of slow Ca2+-dependent action potentials which had been elicited in the presence of 100 mumol l-1 IBMX. Choline esters produced a concentration-dependent positive inotropic effect. With an EC50 of 32 mumol l-1, carbachol was the most potent compound, followed by methacholine (35 mumol l-1), acetylcholine in the presence of 10 mumol l-1 physostigmine (46 mumol l-1) and bethanechol (142 mumol l-1). Compared to carbachol and methacholine which increased force by 100% of control, the increase induced by acetylcholine and bethanechol was only 64 and 58%, respectively. Atropine shifted the concentration-effect curves of all choline esters to higher concentrations. Choline esters caused intracellular Na+ activity to increase in the quiescent papillary muscle. This effect was reversed by atropine. Oxotremorine produced a small concentration-dependent positive inotropic effect (about 30% of the maximal effect of carbachol) which was resistant to atropine. Oxotremorine was a potent inhibitor of the positive inotropic effect of choline esters

  13. Structure and vascularization of the ventricular myocardium in Holocephali: their evolutionary significance.

    PubMed

    Durán, Ana C; López-Unzu, Miguel A; Rodríguez, Cristina; Fernández, Borja; Lorenzale, Miguel; Linares, Andrea; Salmerón, Francisca; Sans-Coma, Valentín

    2015-06-01

    It was generally assumed that the ventricle of the primitive vertebrate heart was composed of trabeculated, or spongy, myocardium, supplied by oxygen-poor luminal blood. In addition, it was presumed that the mixed ventricular myocardium, consisting of a compacta and a spongiosa, and its supply through coronary arteries appeared several times throughout fish evolution. Recent work has suggested, however, that a fully vascularized, mixed myocardium may be the primitive condition in gnathostomes. The present study of the heart ventricles of four holocephalan species aimed to clarify this controversy. Our observations showed that the ventricular myocardium of Chimaera monstrosa and Harriotta raleighana consists of a very thin compacta overlying a widespread spongiosa. The ventricle of Hydrolagus affinis is composed exclusively of trabeculated myocardium. In these three species there is a well-developed coronary artery system. The main coronary artery trunks run along the outflow tract, giving off subepicardial ventricular arteries. The trabeculae of the spongiosa are irrigated by branches of the subepicardial arteries and by penetrating arterial vessels arising directly from the main coronary trunks at the level of the conoventricular junction. The ventricle of Rhinochimaera atlantica has only spongy myocardium supplied by luminal blood. Small coronary arterial vessels are present in the subepicardium, but they do not enter the myocardial trabeculae. The present findings show for the first time that in a wild living vertebrate species, specifically H. affinis, an extensive coronary artery system supplying the whole cardiac ventricle exists in the absence of a well-developed compact ventricular myocardium. This is consistent with the notion derived from experimental work that myocardial cell proliferation and coronary vascular growth rely on distinct developmental programs. Our observations, together with data in the literature on elasmobranchs, support the view that

  14. Urine Pretreat Injection System

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A new method of introducing the OXONE (Registered Trademark) Monopersulfate Compound for urine pretreat into a two-phase urine/air flow stream has been successfully tested and evaluated. The feasibility of this innovative method has been established for purposes of providing a simple, convenient, and safe method of handling a chemical pretreat required for urine processing in a microgravity space environment. Also, the Oxone portion of the urine pretreat has demonstrated the following advantages during real time collection of 750 pounds of urine in a Space Station design two-phase urine Fan/Separator: Eliminated urine precipitate buildup on internal hardware and plumbing; Minimized odor from collected urine; and Virtually eliminated airborne bacteria. The urine pretreat, as presently defined for the Space Station program for proper downstream processing of urine, is a two-part chemical treatment of 5.0 grams of Oxone and 2.3 ml of H2SO4 per liter of urine. This study program and test demonstrated only the addition of the proper ratio of Oxone into the urine collection system upstream of the Fan/Separator. This program was divided into the following three major tasks: (1) A trade study, to define and recommend the type of Oxone injection method to pursue further; (2) The design and fabrication of the selected method; and (3) A test program using high fidelity hardware and fresh urine to demonstrate the method feasibility. The trade study was conducted which included defining several methods for injecting Oxone in different forms into a urine system. Oxone was considered in a liquid, solid, paste and powered form. The trade study and the resulting recommendation were presented at a trade study review held at Hamilton Standard on 24-25 October 94. An agreement was reached at the meeting to continue the solid tablet in a bag concept which included a series of tablets suspended in the urine/air flow stream. These Oxone tablets would slowly dissolve at a controlled rate

  15. Harnessing the potential of ligninolytic enzymes for lignocellulosic biomass pretreatment.

    PubMed

    Masran, Ruqayyah; Zanirun, Zuraidah; Bahrin, Ezyana Kamal; Ibrahim, Mohamad Faizal; Lai Yee, Phang; Abd-Aziz, Suraini

    2016-06-01

    Abundant lignocellulosic biomass from various industries provides a great potential feedstock for the production of value-added products such as biofuel, animal feed, and paper pulping. However, low yield of sugar obtained from lignocellulosic hydrolysate is usually due to the presence of lignin that acts as a protective barrier for cellulose and thus restricts the accessibility of the enzyme to work on the cellulosic component. This review focuses on the significance of biological pretreatment specifically using ligninolytic enzymes as an alternative method apart from the conventional physical and chemical pretreatment. Different modes of biological pretreatment are discussed in this paper which is based on (i) fungal pretreatment where fungi mycelia colonise and directly attack the substrate by releasing ligninolytic enzymes and (ii) enzymatic pretreatment using ligninolytic enzymes to counter the drawbacks of fungal pretreatment. This review also discusses the important factors of biological pretreatment using ligninolytic enzymes such as nature of the lignocellulosic biomass, pH, temperature, presence of mediator, oxygen, and surfactant during the biodelignification process. PMID:27115758

  16. Efficiency of single stage- and two stage pretreatment in biomass with different lignin content.

    PubMed

    Kärcher, M A; Iqbal, Y; Lewandowski, I; Senn, T

    2016-07-01

    In current study the enzymatic glucose yields of miscanthus and wheat straw were compared after single stage- and two stage pretreatment with dilute sulfuric acid at different pretreatment severities. Glucose yields after two stage pretreatment were higher than after single stage pretreatment in miscanthus. Whereas wheat straw had higher glucose yields after single stage pretreatment. The study shows that two stage pretreatment has a negative effect on glucose yield in biomass with low not-acid-degradable lignin content and a positive one in biomass with high not-acid-degradable lignin content. The not-acid-degradable lignin fraction offers a higher degree of protection of the whole lignin structure against chemical attacks by mineral acids. More severe pretreatment conditions were needed to achieve a sufficient breakup of the lignin structure. But more severe conditions enhance resin formation, leading to lower enzyme activity and reduced carbohydrate yields. PMID:27067673

  17. [Possible reasons for the variability of the inotropic insulin effect in papillary muscles of ground squirrel myocardium].

    PubMed

    Nakipova, O V; Chumaeva, L A; Andreeva, L A; Anufriev, A I; Kukushkin, N I

    2012-01-01

    The effects of insulin (0.1-50 nM) on isometric twitch force (0.1 to 1.0 Hz; 30 +/- 1 degree C; 1.8 mM Ca(2+)) were studied in right ventricular papillary muscles from active ground squirrels of different seasons (summer, n = 14; autumn, n = 16 and winter interbout, n = 16) in control conditions and after one-hour pretreatment of PM with 2 mkM nifedipine (an L-type Ca(2+)-channel inhibitor) and 1.0 mM orthovanadate (a tyrosine phosphatase inhibitor). In active animals of different seasonal periods insulin causes both positive and negative inotropic effects. At low frequencies (0.1-0.5 Hz), insulin of low concentrations (0.1-1.0 nM) induces a transient (within the first 20 min after application) positive effect (about 15-25%). Application of high hormone concentration (10 nM) in a low range of stimulation frequencies causes a biphasic effect (a small initial positive inotropic effect followed by a marked negative one). At frequencies above 0.5-Hz stimulation, insulin of 10 nM concentration causes presumably a negative inotropic effect. It was proposed that ICaL is possibly involved in the insulin-induced negative inotropy in ground squirrels hearts. Alteration of protein phosphorylation in tyrosine residues is known to be a major link in the mechanism of insulin action. We performed a study on orthovanadate action (a known inhibitor of tyrosine phosphatase) on the inotropic insulin effect. In the group of summer animals the pretreatment of papillary muscles with orthovanadate (100 mkM) does not change the negative inotropic effect of insulin in a low range of stimulation frequencies but almost completely removes this effect at stimulation frequencies above 0.3 Hz (n = 4). Nifedipine (1-1.5 hr pretreatment), a blocker of L-type calcium channel, reduces the inhibitory effect of insulin in autumn and winter animals, and on the contrary intensifies it in summer animals. This fact indicates that different mechanisms must be involved in insulin actions in animals of

  18. Effect of Shen-Fu Injection Pretreatment to Myocardial Metabolism During Untreated Ventricular Fibrillation in a Porcine Model

    PubMed Central

    Yuan, Wei; Wu, Jun-Yuan; Wang, Guo-Xing; Zhang, Qian; Li, Chun-Sheng

    2015-01-01

    Background: Shen-Fu injection (SFI) can attenuate ischemia-reperfusion injury, protect cardiac function, and improve microcirculation during cardiopulmonary resuscitation. We hypothesized that SFI may also have an influence on myocardial metabolism during ventricular fibrillation (VF). In this study, we used SFI pretreatment prior to VF to discuss the changes of myocardial metabolism and catecholamine (CA) levels during untreated VF, trying to provide new evidence to the protection of SFI to myocardium. Methods: Twenty-four pigs were divided into three groups: Saline group (SA group), SFI group, and SHAM operation group (SHAM group). Thirty minutes prior to the induction of VF, the SFI group received 0.24 mg/ml SFI through an intravenous injection; the SA group received an equal amount of sodium chloride solution. The interstitial fluid from the left ventricle (LV) wall was collected through the microdialysis tubes during VF. Adenosine diphosphate (ADP), adenosine triphosphate (ATP), and Na+ -K+ -ATPase and Ca2+ -ATPase enzyme activities were measured after untreated VF. Peak-to-trough VF amplitude and median frequency were analyzed for each of these 5-s intervals. Results: The levels of glucose and glutamate were lower after VF in both the SA and SFI groups, compared with baseline, and the levels in the SFI group were higher than those in the SA group. Compared with baseline, the levels of lactate and the lactate/pyruvate ratio increased after VF in both SA and SFI groups, and the levels in the SFI group were lower than those in the SA group. In both the SA and SFI groups, the levels of dopamine, norepinephrine, and epinephrine increased significantly. There were no statistical differences between the two groups. The content of ATP, ADP, and phosphocreatine in the SFI group was higher than those in the SA group. The activity of LV Na+ -K+ -ATPase was significantly higher in the SFI group than in the SA group. Amplitude mean spectrum area (AMSA) was significantly

  19. Electrolytic pretreatment of urine

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Electrolysis has been under evaluation for several years as a process to pretreat urine for ultimate recovery of potable water in manned spacecraft applications. The conclusions that were drawn from this investigation are the following: (1) A platinum alloy containing 10 percent rhodium has been shown to be an effective, corrosion-resistant anode material for the electrolytic pretreatment of urine. Black platinum has been found to be suitable as a cathode material. (2) The mechanism of the reactions occurring during the electrolysis of urine is two-stage: (a) a total Kjeldahl nitrogen and total organic carbon (TOC) removal in the first stage is the result of electrochemical oxidation of urea to CO2, H2O, and ammonia followed by chloride interaction to produce N2 from ammonia, (b) after the urea has been essentially removed and the chloride ions have no more ammonia to interact with, the chloride ions start to oxidize to higher valence states, thus producing perchlorates. (3) Formation of perchlorates can be suppressed by high/low current operation, elevated temperature, and pH adjustment. (4) UV-radiation showed promise in assisting electrolytic TOC removal in beaker tests, but was not substantiated in limited single cell testing. This may have been due to non-optimum configurations of the single cell test rig and the light source.

  20. Peroxisome Proliferator-Activated Receptor-α Inhibition Protects Against Doxorubicin-Induced Cardiotoxicity in Mice.

    PubMed

    Rahmatollahi, Mahdieh; Baram, Somayeh Mahmoodi; Rahimian, Reza; Saeedi Saravi, Seyed Soheil; Dehpour, Ahmad Reza

    2016-07-01

    Doxorubicin is an effective chemotherapeutic drug against a considerable number of malignancies. However, its toxic effects on myocardium are confirmed as major limit of utilization. PPAR-α is highly expressed in the heart, and its activation leads to an increased cardiac fatty acid oxidation and cardiomyocyte necrosis. This study was performed to adjust the hypothesis that PPAR-α receptor inhibition protects against doxorubicin-induced cardiac dysfunction in mice. Male Balb/c mice were used in this study. Left atria were isolated, and their contractility was measured in response to electrical field stimulation in a standard organ bath. PPAR-α activity was measured using specific PPAR-α antibody in an ELISA-based system coated with double-strand DNA containing PPAR-α response element sequence. Moreover, cardiac MDA and TNF-α levels were measured by ELISA method. Following incubation with doxorubicin (35 µM), a significant reduction in atrial contractility was observed (P < 0.001). Pretreatment of animals with a selective PPAR-α antagonist, GW6471, significantly improved doxorubicin-induced atrial dysfunction (P < 0.001). Furthermore, pretreatment of the mice with a non-selective cannabinoid agonist, WIN55212-2, significantly decreased PPAR-α activity in cardiac tissue, subsequently leading to significant improvement in doxorubicin-induced atrial dysfunction (P < 0.001). Also, GW6471 and WIN significantly reduced cardiac MDA and TNF-α levels compared with animals receiving doxorubicin (P < 0.001). The study showed that inhibition of PPAR-α is associated with protection against doxorubicin-induced cardiotoxicity in mice, and cannabinoids can potentiate the protection by PPAR-α blockade. Moreover, PPAR-α may be considered as a target to prevent cardiotoxicity induced by doxorubicin in patients undergoing chemotherapy. PMID:26082188

  1. Pre-treatment of synthetic elastomeric scaffolds by cardiac fibroblasts improves engineered heart tissue.

    PubMed

    Radisic, Milica; Park, Hyoungshin; Martens, Timothy P; Salazar-Lazaro, Johanna E; Geng, Wenliang; Wang, Yadong; Langer, Robert; Freed, Lisa E; Vunjak-Novakovic, Gordana

    2008-09-01

    Native myocardium consists of several cell types, of which approximately one-third are myocytes and most of the nonmyocytes are fibroblasts. By analogy with monolayer culture in which fibroblasts were removed to prevent overgrowth, early attempts to engineer myocardium utilized cell populations enriched for cardiac myocytes (CMs; approximately 80-90% of total cells). We hypothesized that the pre-treatment of synthetic elastomeric scaffolds with cardiac fibroblasts (CFs) will enhance the functional assembly of the engineered cardiac constructs by creating an environment supportive of cardiomyocyte attachment and function. Cells isolated from neonatal rat ventricles were prepared to form three distinct populations: rapidly plating cells identified as CFs, slowly plating cells identified as CMs, and unseparated initial population of cells (US). The cell fractions (3 x 10(6) cells total) were seeded into poly(glycerol sebacate) scaffolds (highly porous discs, 5 mm in diameter x 2-mm thick) using Matrigeltrade mark, either separately (CM or CF), concurrently (US), or sequentially (CF pre-treatment followed by CM culture, CF + CM), and cultured in spinner flasks. The CF + CM group had the highest amplitude of contraction and the lowest excitation threshold, superior DNA content, and higher glucose consumption rate. The CF + CM group exhibited compact 100- to 200-mum thick layers of elongated myocytes aligned in parallel over layers of collagen-producing fibroblasts, while US and CM groups exhibited scattered and poorly elongated myocytes. The sequential co-culture of CF and CM on a synthetic elastomer scaffold thus created an environment supportive of cardiomyocyte attachment, differentiation, and contractile function, presumably due to scaffold conditioning by cultured fibroblasts. When implanted over the infarcted myocardium in a nude rat model, cell-free poly(glycerol sebacate) remained at the ventricular wall after 2 weeks of in vivo, and was vascularized. PMID

  2. Brain-Derived Neurotrophic Factor Regulates TRPC3/6 Channels and Protects Against Myocardial Infarction in Rodents

    PubMed Central

    Hang, Pengzhou; Zhao, Jing; Cai, Benzhi; Tian, Shanshan; Huang, Wei; Guo, Jing; Sun, Chuan; Li, Yue; Du, Zhimin

    2015-01-01

    Background: Brain-derived neurotrophic factor (BDNF) is associated with coronary artery diseases. However, its role and mechanism in myocardial infarction (MI) is not fully understood. Methods: Wistar rat and Kunming mouse model of MI were induced by the ligation of left coronary artery. Blood samples were collected from MI rats and patients. Plasma BDNF level, protein expression of BDNF, tropomyosin-related kinase B (TrkB) and its downstream transient receptor potential canonical (TRPC)3/6 channels were examined by enzyme-linked immunosorbent assay and Western blot. Infarct size, cardiac function and cardiomyocyte apoptosis were measured after intra-myocardium injection with recombinant human BDNF. Protective role of BDNF against cardiomyocyte apoptosis was confirmed by BDNF scavenger TrkB-Fc. The regulation of TRPC3/6 channels by BDNF was validated by pretreating with TRPC blocker (2-Aminoethyl diphenylborinate, 2-APB) and TRPC3/6 siRNAs. Results: Circulating BDNF was significantly enhanced in MI rats and patients. Protein expression of BDNF, TrkB and TRPC3/6 channels were upregulated in MI. 3 days post-MI, BDNF treatment markedly reduced the infarct size and serum lactate dehydrogenase activity. Meanwhile, echocardiography indicated that BDNF significantly improved cardiac function of MI mice. Furthermore, BDNF markedly inhibited cardiomyocyte apoptosis by upregulating Bcl-2 expression and downregulating caspase-3 expression and activity in ischemic myocardium. In neonatal rat ventricular myocytes, cell viability was dramatically increased by BDNF in hypoxia, which was restored by TrkB-Fc. Furthermore, protective role of BDNF against hypoxia-induced apoptosis was reversed by 2-APB and TRPC3/6 siRNAs. Conclusion: BDNF/TrkB alleviated cardiac ischemic injury and inhibited cardiomyocytes apoptosis by regulating TRPC3/6 channels, which provides a novel potential therapeutic candidate for MI. PMID:25892961

  3. Exendin-4 Pretreated Adipose Derived Stem Cells Are Resistant to Oxidative Stress and Improve Cardiac Performance via Enhanced Adhesion in the Infarcted Heart

    PubMed Central

    Yin, Yujing; Wang, Liman; Liu, Zhiqiang; Yang, Junjie; Chen, Yundai; Wang, Changyong

    2014-01-01

    Reactive oxygen species (ROS), which were largely generated after myocardial ischemia, severely impaired the adhesion and survival of transplanted stem cells. In this study, we aimed to determine whether Exendin-4 pretreatment could improve the adhesion and therapeutic efficacy of transplanted adipose derived stem cells (ADSCs) in ischemic myocardium. In vitro, H2O2 was used to provide ROS environments, in which ADSCs pretreated with Exendin-4 were incubated. ADSCs without pretreatment were used as control. Then, cell adhesion and viability were analyzed with time. Compared with control ADSCs, Exendin-4 treatment significantly increased the adhesion of ADSCs in ROS environment, while reduced intracellular ROS and cell injury as determined by dihydroethidium (DHE) staining live/Dead staining, lactate dehydrogenase-release assay and MTT assay. Western Blotting demonstrated that ROS significantly decreased the expression of adhesion-related integrins and integrin-related focal adhesion proteins, which were significantly reversed by Exendin-4 pretreatment and followed by decreases in caspase-3, indicating that Exendin-4 may facilitate cell survival through enhanced adhesion. In vivo, myocardial infarction (MI) was induced by the left anterior descending artery ligation in SD rats. Autologous ADSCs with or without Exendin-4 pretreatment were injected into the border area of infarcted hearts, respectively. Multi-techniques were used to assess the beneficial effects after transplantation. Longitudinal bioluminescence imaging and histological staining revealed that Exendin-4 pretreatment enhanced the survival and differentiation of engrafted ADSCs in ischemic myocardium, accompanied with significant benefits in cardiac function, matrix remodeling, and angiogenesis compared with non-pretreated ADSCs 4 weeks post-transplantation. In conclusion, transplantation of Exendin-4 pretreated ADSCs significantly improved cardiac performance and can be an innovative approach in the

  4. Exendin-4 pretreated adipose derived stem cells are resistant to oxidative stress and improve cardiac performance via enhanced adhesion in the infarcted heart.

    PubMed

    Liu, Jianfeng; Wang, Haibin; Wang, Yan; Yin, Yujing; Wang, Liman; Liu, Zhiqiang; Yang, Junjie; Chen, Yundai; Wang, Changyong

    2014-01-01

    Reactive oxygen species (ROS), which were largely generated after myocardial ischemia, severely impaired the adhesion and survival of transplanted stem cells. In this study, we aimed to determine whether Exendin-4 pretreatment could improve the adhesion and therapeutic efficacy of transplanted adipose derived stem cells (ADSCs) in ischemic myocardium. In vitro, H2O2 was used to provide ROS environments, in which ADSCs pretreated with Exendin-4 were incubated. ADSCs without pretreatment were used as control. Then, cell adhesion and viability were analyzed with time. Compared with control ADSCs, Exendin-4 treatment significantly increased the adhesion of ADSCs in ROS environment, while reduced intracellular ROS and cell injury as determined by dihydroethidium (DHE) staining live/Dead staining, lactate dehydrogenase-release assay and MTT assay. Western Blotting demonstrated that ROS significantly decreased the expression of adhesion-related integrins and integrin-related focal adhesion proteins, which were significantly reversed by Exendin-4 pretreatment and followed by decreases in caspase-3, indicating that Exendin-4 may facilitate cell survival through enhanced adhesion. In vivo, myocardial infarction (MI) was induced by the left anterior descending artery ligation in SD rats. Autologous ADSCs with or without Exendin-4 pretreatment were injected into the border area of infarcted hearts, respectively. Multi-techniques were used to assess the beneficial effects after transplantation. Longitudinal bioluminescence imaging and histological staining revealed that Exendin-4 pretreatment enhanced the survival and differentiation of engrafted ADSCs in ischemic myocardium, accompanied with significant benefits in cardiac function, matrix remodeling, and angiogenesis compared with non-pretreated ADSCs 4 weeks post-transplantation. In conclusion, transplantation of Exendin-4 pretreated ADSCs significantly improved cardiac performance and can be an innovative approach in the

  5. Unique Transcriptional Profile of Sustained Ligand-Activated Preconditioning in Pre- and Post-Ischemic Myocardium

    PubMed Central

    Ashton, Kevin J.; Tupicoff, Amanda; Williams-Pritchard, Grant; Kiessling, Can J.; See Hoe, Louise E.; Headrick, John P.; Peart, Jason N.

    2013-01-01

    Background Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. Methodology/Principal Findings Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (≥1.3-fold change, FDR≤5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip. Conclusions Protection via SLP is associated with transcriptional repression of inflammation/immunity, up

  6. VEGF-C/VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium

    PubMed Central

    Zhao, Tieqiang; Zhao, Wenyuan; Meng, Weixin; Liu, Chang; Chen, Yuanjian; Gerling, Ivan C; Weber, Karl T; Bhattacharya, Syamal K; Kumar, Rahul; Sun, Yao

    2015-01-01

    Background: Numerous studies have shown that in addition to angio/lymphangiogenesis, the VEGF family is involved in other cellular actions. We have recently reported that enhanced VEGF-C and VEGFR-3 in the infarcted rat myocardium, suggesting the paracrine/autocrine function of VEGF-C on cardiac remodeling. The current study was designed to test the hypothesis that VEGF-C regulates cardiomyocyte growth and survival in the infarcted myocardium. Methods and results: Gene profiling and VEGFR-3 expression of cardiomyocytes were assessed by laser capture microdissection/microarray and immunohistochemistry in the normal and infarcted myocardium. The effect of VEGF-C on myocyte hypertrophy and apoptosis during normoxia and hypoxia was detected by RT-PCR and western blotting in cultured rat neonatal cardiomyocytes. VEGFR-3 was minimally expressed in cardiomyocytes of the normal and noninfarcted myocardium, while markedly elevated in the surviving cardiomyocytes of the infarcted myocardium and border zone. Genes altered in the surviving cardiomyocytes were associated with the networks regulating cellular growth and survival. VEGF-C significantly increased the expression of atrial natriuretic factor (ANP), brain natriuretic factor (BNP), and β-myosin heavy chain (MHC), markers of hypertrophy, in neonatal cardiomyocytes. Hypoxia caused neonatal cardiomyocyte atrophy, which was prevented by VEGF-C treatment. Hypoxia significantly enhanced apoptotic mediators, including cleaved caspase 3, 8, and 9, and Bax in neonatal cardiomyocytes, which were abolished by VEGF-C treatment. Conclusion: Our findings indicate that VEGF-C/VEGFR-3 pathway exerts a beneficial role in the infarcted myocardium by promoting compensatory cardiomyocyte hypertrophy and survival. PMID:26064438

  7. Enhanced effect of gap junction uncouplers on macroscopic electrical properties of reperfused myocardium.

    PubMed

    Rodriguez-Sinovas, Antonio; García-Dorado, David; Ruiz-Meana, Marisol; Soler-Soler, Jordi

    2004-08-15

    Transient inhibition of gap junction (GJ)-mediated communication with heptanol during myocardial reperfusion limits infarct size. However, inhibition of cell coupling in normal myocardium may be arrhythmogenic. The purpose of this study was to test the hypothesis that the consequences of GJ inhibition may be magnified in reperfused myocardium compared with normal tissue, thus allowing the inhibition of GJs in reperfused tissue while only minimally modifying overall macroscopic cell coupling in normal myocardium. Concentration-response curves were defined for the effects of heptanol, 18alpha-glycyrrhetinic acid, halothane, and palmitoleic acid on conduction velocity, tissue electrical impedance, developed tension and lactate dehydrogenase (LDH) release in normoxically perfused rat hearts (n= 17). Concentrations lacking significant effects on tissue impedance were added during the initial 15 min of reperfusion in hearts submitted to 60 min (n= 43) or 30 min (n= 35) of ischaemia. These concentrations markedly increased myocardial electrical impedance (resistivity and phase angle) in myocardium reperfused after either 30 or 60 min of ischaemia, and reduced reperfusion-induced LDH release after 1 h of ischaemia by 83.6, 57.9, 51.7 and 52.5% for heptanol, 18alpha-glycyrrhetinic acid, halothane and palmitoleic acid, respectively. LDH release was minimal in hearts submitted to 30 min of ischaemia, independently of group allocation. In conclusion, the present results strongly support the hypothesis that intercellular communication in postischaemic myocardium may be effectively reduced by concentrations of GJ inhibitors affecting only minimally overall electrical impedance in normal myocardium. Reduction of cell coupling during initial reperfusion was consistently associated with attenuated lethal reperfusion injury. PMID:15218064

  8. Enhanced effect of gap junction uncouplers on macroscopic electrical properties of reperfused myocardium

    PubMed Central

    Rodriguez-Sinovas, Antonio; García-Dorado, David; Ruiz-Meana, Marisol; Soler-Soler, Jordi

    2004-01-01

    Transient inhibition of gap junction (GJ)-mediated communication with heptanol during myocardial reperfusion limits infarct size. However, inhibition of cell coupling in normal myocardium may be arrhythmogenic. The purpose of this study was to test the hypothesis that the consequences of GJ inhibition may be magnified in reperfused myocardium compared with normal tissue, thus allowing the inhibition of GJs in reperfused tissue while only minimally modifying overall macroscopic cell coupling in normal myocardium. Concentration–response curves were defined for the effects of heptanol, 18α-glycyrrhetinic acid, halothane, and palmitoleic acid on conduction velocity, tissue electrical impedance, developed tension and lactate dehydrogenase (LDH) release in normoxically perfused rat hearts (n = 17). Concentrations lacking significant effects on tissue impedance were added during the initial 15 min of reperfusion in hearts submitted to 60 min (n = 43) or 30 min (n = 35) of ischaemia. These concentrations markedly increased myocardial electrical impedance (resistivity and phase angle) in myocardium reperfused after either 30 or 60 min of ischaemia, and reduced reperfusion-induced LDH release after 1 h of ischaemia by 83.6, 57.9, 51.7 and 52.5% for heptanol, 18α-glycyrrhetinic acid, halothane and palmitoleic acid, respectively. LDH release was minimal in hearts submitted to 30 min of ischaemia, independently of group allocation. In conclusion, the present results strongly support the hypothesis that intercellular communication in postischaemic myocardium may be effectively reduced by concentrations of GJ inhibitors affecting only minimally overall electrical impedance in normal myocardium. Reduction of cell coupling during initial reperfusion was consistently associated with attenuated lethal reperfusion injury. PMID:15218064

  9. Sewage sludge pretreatment and disposal. (Latest citations from the NTIS bibliographic database). Published Search

    SciTech Connect

    1995-06-01

    The bibliography contains citations concerning techniques and equipment used in the pretreatment and disposal of sewage sludges. Citations discuss sludge digestion, dewatering, disinfection, stabilization, chlorination, and desulfurization. Topics include pretreatment programs, land disposal, incineration, and waste utilization. Environmental monitoring and protection, federal regulations, and legal aspects are examined. (Contains 50-250 citations and includes a subject term index and title list.)

  10. Protective Effects of Cardamom in Isoproterenol-Induced Myocardial Infarction in Rats

    PubMed Central

    Goyal, Sameer N.; Sharma, Charu; Mahajan, Umesh B.; Patil, Chandragouda R.; Agrawal, Yogeeta O.; Kumari, Santosh; Arya, Dharamvir Singh; Ojha, Shreesh

    2015-01-01

    Cardamom is a popular spice that has been commonly used in cuisines for flavor since ancient times. It has copious health benefits such as improving digestion, stimulating metabolism, and exhibits antioxidant and anti-inflammatory effects. The current study investigated the effect of cardamom on hemodynamic, biochemical, histopathological and ultrastructural changes in isoproterenol (ISO)-induced myocardial infarction. Wistar male albino rats were randomly divided and treated with extract of cardamom (100 and 200 mg/kg per oral) or normal saline for 30 days with concomitant administration of ISO (85 mg/kg, subcutaneous) on 29th and 30th days, at 24 h interval. ISO injections to rats caused cardiac dysfunction evidenced by declined arterial pressure indices, heart rate, contractility and relaxation along with increased preload. ISO also caused a significant decrease in endogenous antioxidants, superoxide dismutase, catalase, glutathione peroxidase, depletion of cardiomyocytes enzymes, creatine kinase-MB, lactate dehydrogenase and increase in lipid peroxidation. All these changes in cardiac and left ventricular function as well as endogenous antioxidants, lipid peroxidation and myocyte enzymes were ameliorated when the rats were pretreated with cardamom. Additionally, the protective effects were strengthened by improved histopathology and ultrastructural changes, which specifies the salvage of cardiomyocytes from the deleterious effects of ISO. The present study findings demonstrate that cardamom significantly protects the myocardium and exerts cardioprotective effects by free radical scavenging and antioxidant activities. PMID:26593900