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  1. Rotigaptide (ZP123) improves atrial conduction slowing in chronic volume overload-induced dilated atria.

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    Haugan, Ketil; Miyamoto, Takuya; Takeishi, Yasuchika; Kubota, Isao; Nakayama, Jun; Shimojo, Hisashi; Hirose, Masamichi

    2006-07-01

    Chronic atrial dilation is associated with atrial conduction velocity slowing and an increased risk of developing atrial tachyarrhythmias. Rotigaptide (ZP123) is a selective gap junction modifier that increases cardiac gap junctional intercellular communication. We hypothesised that rotigaptide treatment would increase atrial conduction velocity and reduce the inducibility to atrial tachyarrhythmias in a model of chronic volume overload induced chronic atrial dilatation characterized by atrial conduction velocity slowing. Chronic volume overload was created in Japanese white rabbits by arterio-venous shunt formation. Atrial conduction velocity and atrial tachyarrhythmias inducibility were examined in Langendorff-perfused chronic volume overload hearts (n=12) using high-resolution optical mapping before and after treatment with rotigaptide. Moreover, expression levels of atrial gap junction proteins (connexin40 and connexin43) were examined in chronic volume overload hearts (n=6) and compared to sham-operated controls (n=6). Rotigaptide treatment significantly increased atrial conduction velocity in chronic volume overload hearts, however, rotigaptide did not decrease susceptibility to the induction of atrial tachyarrhythmias. Protein expressions of Cx40 and Cx43 were decreased by 32% and 72% (P<0.01), respectively, in chromic volume overload atria compared to control. To conclude, rotigaptide increased atrial conduction velocity in a rabbit model of chromic volume overload induced atrial conduction velocity slowing. The demonstrated effect of rotigaptide on atrial conduction velocity did not prevent atrial tachyarrhythmias inducibility. Whether rotigaptide may possess antiarrhythmic efficacy in other models of atrial fibrillation remains to be determined.

  2. Extracellular Matrix Remodeling During the Progression of Volume Overload-Induced Heart Failure

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    Hutchinson, Kirk R.; Stewart, James A.; Lucchesi, Pamela A.

    2009-01-01

    Volume overload-induced heart failure results in progressive left ventricular remodeling characterized by chamber dilation, eccentric cardiac myocyte hypertrophy and changes in extracellular matrix (ECM) remodeling changes. The ECM matrix scaffold is an important determinant of the structural integrity of the myocardium and actively participates in force transmission across the LV wall. In response to this hemodynamic overload, the ECM undergoes a distinct pattern of remodeling that differs from pressure overload. Once thought to be a static entity, the ECM is now regarded to be a highly adaptive structure that is dynamically regulated by mechanical stress, neurohormonal activation, inflammation and oxidative stress, that result in alterations in collagen and other matrix components and a net change in matrix metalloproteinase (MMP) expression and activation. These changes dictate overall ECM turnover during volume overload hear failure progression. This review will discuss the cellular and molecular mechanisms that dictate the temporal patterns of ECM remodeling during heart disease progression. PMID:19524591

  3. Thallium-201 uptake ratio correlated with myocardial mass ratio in chronically hypertrophied rat hearts induced by preferential pressure or volume overload

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    Taniguchi, Masashi [Kanazawa Univ. (Japan). School of Medicine

    1995-10-01

    Hemodynamic measurements, left to right myocardial ventricular mass ratio and myocardial thallium-201 ({sup 201}Tl) uptake ratio were measured in 6 normal and the following 30 experimental rats (each group, n=6). Right ventricular (RV) pressure overload (PO) was induced by administration of monocrotaline. RV volume overload (VO) was induced by suturing a pulmonary valve to the pulmonary artery. Biventricular (BV) VO was induced by creation of an aortocaval fistula. Left ventricular (LV) PO was induced by constriction of the ascending aorta and LVVO was induced by destruction of the aortic valves. RV mass to body weight (BW) was significantly increased in RPVO, RVVO and BVVO models compared with the control. LV mass to BW was significantly increased in LVPO, LVVO models. RV peak systolic pressure (PSP) was significantly increased in RVPO, BVVO and LVVO models, and LVPSP was significantly increased in LVPO, BVVO and LVVO models. LV/RV mass ratio was significantly decreased in RVPO, RVVO and BVVO models, and was significantly increased in LVPO and LVVO models. LV/RV myocardial {sup 201}Tl uptake ratio was significantly decreased in RVPO and RVVO models, and was significantly increased in LVPO and LVVO models. Linear regression analysis showed an excellent correlation between LV/RV myocardial {sup 201}Tl uptake ratio and LV/RV mass ratio. Although the presence of significant correlation between LV/RV pressure ratio and LV/RV myocardial {sup 201}Tl uptake ratio was confirmed in PO models, rather poor correlation was observed in VO models. Our results suggest that LV/RV myocardial mass ratio as well as LV/RV pressure ratio can be evaluated by LV/RV myocardial {sup 201}Tl uptake ratio in chronic overload models. (S.Y.).

  4. Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload

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    David Sedmera

    2016-08-01

    Full Text Available Volume overload leads to development of eccentric cardiac hypertrophy and heart failure. In our previous report, we have shown myocyte hypertrophy with no fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of aorto-caval fistula at 21 weeks. Here we set to analyze the electrophysiological and protein expression changes in the left ventricle and correlate them with phenotypic severity based upon ventricles to body weight ratio.ECG analysis showed increased amplitude and duration of the P wave, prolongation of PR and QRS interval, ST segment elevation and decreased T wave amplitude in the fistula group. Optical mapping showed a prolongation of action potential duration in the hypertrophied hearts. Minimal conduction velocity (CV showed a bell-shaped curve, with a significant increase in the mild cases and there was a negative correlation of both minimal and maximal CV with heart to body weight ratio. Since the CV is influenced by gap junctional coupling as well as the autonomic nervous system, we measured the amounts of tyrosine hydroxylase (TH and choline acetyl transferase (ChAT as a proxy for sympathetic and parasympathetic innervation, respectively. At the protein level, we confirmed a significant decrease in total and phosphorylated connexin43 that was proportional to the level of hypertrophy, and similarly decreased levels of TH and ChAT.Even at a single time-point, severity of morphological phenotype correlates with progression of molecular and electrophysiological changes, with the most hypertrophied hearts showing the most severe changes that might be related to arrhythmogenesis.

  5. VOLUME OVERLOAD IS ASSOCIATED WITH MALNUTRITION IN PERITONEAL DIALYSIS

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    Jin Joo Cha

    2012-06-01

    Volume overload is associated with malnutrition and seems to be an independent predictor of mortality in PD population. Further study should evaluate the effects of intervention of volume control in PD patients.

  6. Aldosterone and mortality in hemodialysis patients: role of volume overload.

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    Szu-Chun Hung

    Full Text Available BACKGROUND: Elevated aldosterone is associated with increased mortality in the general population. In patients on dialysis, however, the association is reversed. This paradox may be explained by volume overload, which is associated with lower aldosterone and higher mortality. METHODS: We evaluated the relationship between aldosterone and outcomes in a prospective cohort of 328 hemodialysis patients stratified by the presence or absence of volume overload (defined as extracellular water/total body water >48%, as measured with bioimpedance. Baseline plasma aldosterone was measured before dialysis and categorized as low (280 pg/mL. RESULTS: Overall, 36% (n = 119 of the hemodialysis patients had evidence of volume overload. Baseline aldosterone was significantly lower in the presence of volume overload than in its absence. During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred. Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25-0.76 and first cardiovascular event (0.70; 95% confidence interval, 0.33-0.78 in the presence of volume overload. In contrast, high aldosterone was associated with an increased risk for mortality (1.97; 95% confidence interval, 1.69-3.75 and first cardiovascular event (2.01; 95% confidence interval, 1.28-4.15 in the absence of volume overload. CONCLUSIONS: The inverse association of aldosterone with adverse outcomes in hemodialysis patients is due to the confounding effect of volume overload. These findings support treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control.

  7. Avoiding Program-Induced Cumulative Overload (PICO).

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    Orr, Robin; Knapik, Joseph J; Pope, Rodney

    2016-01-01

    This article defines the concept of program-induced cumulative overload (PICO), provides examples, and advises ways to mitigate the adverse effects. PICO is the excessive cumulative physical workload that can be imparted to military personnel by a military training program with an embedded physical training component. PICO can be acute (accumulating within a single day) or chronic (accumulating across the entirety of the program) and results in adverse outcomes for affected personnel, including detrimental fatigue, performance degradation, injuries, or illness. Strategies to mitigate PICO include focusing administration and logistic practices during the development and ongoing management of a trainee program and implementing known musculoskeletal injury prevention strategies. More training is not always better, and trainers need to consider the total amount of physical activity that military personnel experience across both operational training and physical training if PICO is to be mitigated.

  8. Temporal pattern of left ventricular structural and functional remodeling following reversal of volume overload heart failure

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    Hutchinson, Kirk R.; Guggilam, Anuradha; Cismowski, Mary J.; Galantowicz, Maarten L.; West, Thomas A.; Stewart, James A.; Zhang, Xiaojin; Lord, Kevin C.

    2011-01-01

    Current surgical management of volume overload-induced heart failure (HF) leads to variable recovery of left ventricular (LV) function despite a return of LV geometry. The mechanisms that prevent restoration of function are unknown but may be related to the timing of intervention and the degree of LV contractile impairment. This study determined whether reduction of aortocaval fistula (ACF)-induced LV volume overload during the compensatory stage of HF results in beneficial LV structural remodeling and restoration of pump function. Rats were subjected to ACF for 4 wk; a subset then received a load-reversal procedure by closing the shunt using a custom-made stent graft approach. Echocardiography or in vivo pressure-volume analysis was used to assess LV morphology and function in sham rats; rats subjected to 4-, 8-, or 15-wk ACF; and rats subjected to 4-wk ACF followed by 4- or 11-wk reversal. Structural and functional changes were correlated to LV collagen content, extracellular matrix (ECM) proteins, and hypertrophic markers. ACF-induced volume overload led to progressive LV chamber dilation and contractile dysfunction. Rats subjected to short-term reversal (4-wk ACF + 4-wk reversal) exhibited improved chamber dimensions (LV diastolic dimension) and LV compliance that were associated with ECM remodeling and normalization of atrial and brain natriuretic peptides. Load-independent parameters indicated LV systolic (preload recruitable stroke work, Ees) and diastolic dysfunction (tau, arterial elastance). These changes were associated with an altered α/β-myosin heavy chain ratio. However, these changes were normalized to sham levels in long-term reversal rats (4-wk ACF + 11-wk reversal). Acute hemodynamic changes following ACF reversal improve LV geometry, but LV dysfunction persists. Gradual restoration of function was related to normalization of eccentric hypertrophy, LV wall stress, and ECM remodeling. These results suggest that mild to moderate LV systolic

  9. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

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    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  10. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

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    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  11. Temporal evaluation of cardiac myocyte hypertrophy and hyperplasia in male rats secondary to chronic volume overload.

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    Du, Yan; Plante, Eric; Janicki, Joseph S; Brower, Gregory L

    2010-09-01

    The temporal myocardial remodeling induced by chronic ventricular volume overload in male rats was examined. Specifically, left ventricular (LV) cardiomyocyte length and width, sarcomere length, and number of nuclei were measured in male rats (n = 8 to 17) at 1, 3, 5, 7, 21, 35, and 56 days after creation of an infrarenal aortocaval fistula. In contrast to previously published reports of progressive increases in cardiomyocyte length and cross-sectional area at 5 days post-fistula and beyond in female hearts, cardiomyocyte length and width did not increase significantly in males during the first 35 days of volume overload. Furthermore, a significant decrease in cardiomyocyte length relative to age-matched controls, together with a reduced number of sarcomeres per cell, was noted in male hearts at 5 days post-fistula. There was a concurrent increase in the percentage of mononucleated cardiomyocytes from 11.6% to 18% at 5 days post-fistula. These initial differences could not be attributed to cardiomyocyte proliferation, and treatment with a microtubule stabilizing agent prevented them from occurring. The subsequent significant increase in LV weight without corresponding increases in cardiomyocyte dimensions is indicative of hyperplasia. Thus, these findings indicate hyperplasia resulting from cytokinesis of cardiomyocytes is a key mechanism, independent of hypertrophy, that contributes to the significant increase in LV mass in male hearts subjected to chronic volume overload.

  12. Identification of volume overload hospitalizations among hemodialysis patients using administrative claims: a validation study.

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    Assimon, Magdalene M; Nguyen, Thuy; Katsanos, Suzanne L; Brunelli, Steven M; Flythe, Jennifer E

    2016-11-11

    High rates of volume overload hospitalizations may indicate inadequate dialysis facility fluid management. Administrative claims databases are often used to study such outcomes, but these data are generated for billing purposes and may not capture clinical nuance. It is unknown if volume overload admissions can be correctly identified in administrative data and if a single claims-based definition for volume overload can be used across epidemiologic surveillance studies, observational studies of exposure-outcome associations and quality assessments. We conducted a validation study to assess the accuracy of claims-based definitions for volume overload hospitalizations among hemodialysis patients. Data were taken from a random sample of 315 adult hemodialysis patients admitted to University of North Carolina Hospitals from January 2010 through June 2013. Standardized chart reviews were conducted to clinically adjudicate the presence or absence of volume overload at hospital admission. Claims-based definitions were constructed from varying combinations of fluid-related ICD-9 discharge diagnosis codes including fluid overload, pulmonary edema, pleural effusion, and heart failure. Using clinically adjudicated volume overload hospitalizations as the reference standard, validity metrics and their 95 % confidence intervals (CIs) were estimated for each definition. Of the 315 hospital admissions, 77 (24.4 %) were clinically adjudicated as volume overload hospitalizations. The prevalence of claims-identified volume overload admissions varied across definitions, ranging from 1.6 to 37.1 %. When definitions were constructed with discharge diagnosis codes present in any billing position, volume overload hospitalizations defined by fluid overload, pleural effusion or heart failure diagnosis codes had the highest sensitivity, 81.8 % (95 % CI: 71.4 %, 89.7 %). Volume overload hospitalizations defined by pulmonary edema diagnosis codes had the highest specificity, 98.3 % (95

  13. New rat models of iron sucrose-induced iron overload.

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    Vu'o'ng Lê, Bá; Khorsi-Cauet, Hafida; Villegier, Anne-Sophie; Bach, Véronique; Gay-Quéheillard, Jérôme

    2011-07-01

    The majority of murine models of iron sucrose-induced iron overload were carried out in adult subjects. This cannot reflect the high risk of iron overload in children who have an increased need for iron. In this study, we developed four experimental iron overload models in young rats using iron sucrose and evaluated different markers of iron overload, tissue oxidative stress and inflammation as its consequences. Iron overload was observed in all iron-treated rats, as evidenced by significant increases in serum iron indices, expression of liver hepcidin gene and total tissue iron content compared with control rats. We also showed that total tissue iron content was mainly associated with the dose of iron whereas serum iron indices depended essentially on the duration of iron administration. However, no differences in tissue inflammatory and antioxidant parameters from controls were observed. Furthermore, only rats exposed to daily iron injection at a dose of 75 mg/kg body weight for one week revealed a significant increase in lipid peroxidation in iron-treated rats compared with their controls. The present results suggest a correlation between iron overload levels and the dose of iron, as well as the duration and frequency of iron injection and confirm that iron sucrose may not play a crucial role in inflammation and oxidative stress. This study provides important information about iron sucrose-induced iron overload in rats and may be useful for iron sucrose therapy for iron deficiency anemia as well as for the prevention and diagnosis of iron sucrose-induced iron overload in pediatric patients.

  14. Sex-linked differences in the course of chronic kidney disease and congestive heart failure: a study in 5/6 nephrectomized Ren-2 transgenic hypertensive rats with volume overload induced using aorto-caval fistula.

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    Červenka, Luděk; Škaroupková, Petra; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz

    2016-10-01

    The role of hypertension and the renin-angiotensin system (RAS) in sex-related differences in the course of chronic kidney disease (CKD) and congestive heart failure (CHF) remain unclear, especially when the two diseases are combined. In male and female Ren-2 transgenic rats (TGR), a model of hypertension with activation of endogenous RAS, CKD was induced by 5/6 renal mass reduction (5/6 NX) and CHF was elicited by volume overload achieved by creation of an aorto-caval fistula (ACF). The primary aim of the study was to examine long-term CKD- and CHF-related mortality, especially in animals with CKD and CHF combined, with particular interest in the potential sex-related differences. The follow-up period was 23 weeks after the first intervention (5/6 NX). We found, first, that TGR did not exhibit sexual dimorphism in the course of 5/6 NX-induced CKD. Second, in contrast, TGR exhibited important sex-related differences in the course of ACF-induced CHF-related mortality: intact female TGR showed higher survival rate than male TGR. This situation is reversed in the course of combined 5/6 NX-induced CKD and ACF-induced CHF-related mortality: intact female TGR exhibited poorer survival than male TGR. Third, the survival rate in animals with combined 5/6 NX-induced CKD and ACF-induced CHF was significantly worsened as compared with rat groups that were exposed to 'single organ disease'. Collectively, our present results clearly show that CKD aggravates long-term mortality of animals with CHF. In addition, TGR exhibit remarkable sexual dimorphism with respect to CKD- and CHF-related mortality, especially in animals with combined CKD and CHF.

  15. Mechanisms of cardiac hypertrophy in canine volume overload

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    Matsuo, T.; Carabello, B. A.; Nagatomo, Y.; Koide, M.; Hamawaki, M.; Zile, M. R.; McDermott, P. J.

    1998-01-01

    This study tested whether the modest hypertrophy that develops in dogs in response to mitral regurgitation is due to a relatively small change in the rate of protein synthesis or, alternatively, is due to a decreased rate of protein degradation. After 3 mo of severe experimental mitral regurgitation, the left ventricular (LV) mass-to-body weight ratio increased by 23% compared with baseline values. This increase in LV mass occurred with a small, but not statistically significant, increase in the fractional rate of myosin heavy chain (MHC) synthesis (Ks), as measured using continuous infusion with [3H]leucine in dogs at 2 wk, 4 wk, and 3 mo after creation of severe mitral regurgitation. Translational efficiency was unaffected by mitral regurgitation as measured by the distribution of MHC mRNA in polysome gradients. Furthermore, there was no detectable increase in translational capacity as measured by either total RNA content or the rate of ribosome formation. These data indicate that translational mechanisms that accelerate the rate of cardiac protein synthesis are not responsive to the stimulus of mitral regurgitation. Most of the growth after mitral regurgitation was accounted for by a decrease in the fractional rate of protein degradation, calculated by subtracting fractional rates of protein accumulation at each time point from the corresponding Ks values. We conclude that 1) volume overload produced by severe mitral regurgitation does not trigger substantial increases in the rate of protein synthesis and 2) the modest increase in LV mass results primarily from a decrease in the rate of protein degradation.

  16. Regulation of the instantaneous inward rectifier and the delayed outward rectifier potassium channels by Captopril and Angiotensin II via the Phosphoinositide-3 kinase pathway in volume-overload-induced hypertrophied cardiac myocytes

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    Alvin, Zikiar; Laurence, Graham G.; Coleman, Bernell R.; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E.

    2011-01-01

    Summary Background Early development of cardiac hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents can be modulated by the activation of humoral factors, such as angiotensin II (ANG II) through protein kinases. The aim of this work is to assess the regulation of IK and IK1 by ANG II through the PI3-K pathway in hypertrophied ventricular myocytes. Material/Methods Cardiac eccentric hypertrophy was induced through volume-overload in adult male rats by aorto-caval shunt (3 weeks). After one week half of the rats were given captopril (2 weeks; 0.5 g/l/day) and the other half served as control. The voltage-clamp and western blot techniques were used to measure the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity, respectively. Results Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10−6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts, but not in sham. Captopril treatment reversed ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin converting enzyme inhibition, ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Conclusions Thus, captopril treatment reveals a negative effect of ANG II on IK and IK1, which is PI3-K independent, whereas in the absence of angiotensin converting enzyme inhibition IK and IK1 regulation is dependent upon PI3-K. PMID:21709626

  17. Fluid Volume Overload and Congestion in Heart Failure: Time to Reconsider Pathophysiology and How Volume Is Assessed.

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    Miller, Wayne L

    2016-08-01

    Volume regulation, assessment, and management remain basic issues in patients with heart failure. The discussion presented here is directed at opening a reassessment of the pathophysiology of congestion in congestive heart failure and the methods by which we determine volume overload status. Peer-reviewed historical and contemporary literatures are reviewed. Volume overload and fluid congestion remain primary issues for patients with chronic heart failure. The pathophysiology is complex, and the simple concept of intravascular fluid accumulation is not adequate. The dynamics of interstitial and intravascular fluid compartment interactions and fluid redistribution from venous splanchnic beds to central pulmonary circulation need to be taken into account in strategies of volume management. Clinical bedside evaluations and right heart hemodynamic assessments can alert clinicians of changes in volume status, but only the quantitative measurement of total blood volume can help identify the heterogeneity in plasma volume and red blood cell mass that are features of volume overload in patients with chronic heart failure and help guide individualized, appropriate therapy-not all volume overload is the same. © 2016 American Heart Association, Inc.

  18. Time-dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure.

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    Ashikaga, Hiroshi; Omens, Jeffrey H; Covell, James W

    2004-11-01

    To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 +/- 2 wk (means +/- SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 +/- 0.030; P architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture.

  19. A Patient on Peritoneal Dialysis with Refractory Volume Overload

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    2016-01-01

    The management of volume in patients with diabetes on peritoneal dialysis is affected by several factors, including the degree of residual renal function, peritoneal membrane small-solute transport, salt and water intake, blood sugar control, comorbidity, and nutritional status. It requires sequential evaluation of volume status and adjustment of the peritoneal dialysis prescription on the basis of assessments of membrane function and alterations in urine volume. Steps should be taken to preserve residual renal function for as long as possible. Ultimately, in patients who have become anuric and have developed ultrafiltration failure, timely transfer to hemodialysis may be necessary, requiring discussion and planning with the patient. PMID:26185264

  20. Comparative response of right and left ventricles to volume overload.

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    Mathew, R; Thilenius, O G; Arcilla, R A

    1976-08-01

    The cardiac volume data of 49 normal children were compared with those of 23 with secundum atrial septal defect and 24 with patent ductus arteriosus. Significantly smaller ventricular end-diastolic volumes were observed in the normal infants than in older children (right ventricle 53.9 versus 75.5 cm3/m2; left ventricle 46.7 versus 63.6 cm3/m2). "Distensibility" of the right ventricle (DRV), left ventricle (DLV) and left atrium increased normally with age. DRV and DLV were similar shortly after birth; thereafter, DRV increased more rapidly than DLV (mean DRV 12.7; mean DLV 7.8 cm3/m2 per mm Hg, P less than 0.001). In both atrial septal defect and patent ductus arteriosus, the ipsilateral (involved) ventricles had increased volume, increased output, normal ejection fraction and increased distensibility. The contralateral (left) ventricle in atrial septal defect was smaller than normal (39.6 versus 49.7 cm3, P less than 0.001), and had a smaller ejection fraction (0.63 versus 0.71, P less than 0.01) and output (3.70 versus 4.57 liters/min per m2, P less than 0.005). In contrast, the contralateral (right) ventricle in patent ductus arteriosus remained normal. Left atrial maximal volume was larger than normal in atrial septal defect (46.6 versus 35.9 cm3/m2, P less than 0.001). The left atrial and left ventricular volumes in patent ductus arteriosus were, respectively, 152 and 142 percent of normal, indicating comparable response to the volume load. The left head changes in atrial septal defect may be related both to a functionally restrictive defect and to the difference in distensibility of the ventricles.

  1. VARIATION AND SIGNIFICANCE OF C-MYC PROTEIN IN RAT CARDIAC VOLUME-OVERLOAD HYP ERTROPHY

    Institute of Scientific and Technical Information of China (English)

    刘华胜; 马爱群; 王一理; 刘勇; 李恒力; 田红燕

    2002-01-01

    Objective To investigate the change of c-myc protein, which was chosen as the response indicator to volume-overload. Methods The time and spatial course of c-myc protein expressi on on the model of rat cardiac volume-overload hyper trophy was examined by immunohistochemical study. Results The immunohistochemica l study indicated the expression of c-myc protein was increased obviously at 4 -6 hours (62.73%) than that of control (45.41%, P<0.01) after the volume-o verload, then decreased gradually along with development of volume-overload hyp ertrophy and was decreased extremely at 5 months(r=-0.514,P<0.01).Conclusion There are disorders in the signal transduction pathways governing the hypertrophic respon se of cardiomyocytes in hypertrophic myocardium. C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy. Once switching on, c-myc gene and the product of it do not act anymore;While it may be that c-my c gene and the product of it increased following with myocardial hypertrophy, an d have not direct relation to the occurrence and development of myocardial hyper trophy.

  2. Fluoride induced endoplasmic reticulum stress and calcium overload in ameloblasts.

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    Zhang, Ying; Zhang, KaiQiang; Ma, Lin; Gu, HeFeng; Li, Jian; Lei, Shuang

    2016-09-01

    The aim of the study was to evaluate the involvement of endoplasmic reticulum stress and intracellular calcium overload on the development of dental fluorosis. We cultured and exposed rat ameloblast HAT-7 cells to various concentrations of fluoride and measured apoptosis with flow cytometry and intracellular Ca2+ changes using confocal microscopy, investigated the protein levels of GRP78, calreticulin, XBP1 and CHOP by western blotting, and their transcriptional levels with RT-PCR. We also created an in vivo model of dental fluorosis by exposing animals to various concentrations of fluoride. Subsequently, thin dental tissue slices were analyzed with H&E staining, immunohistochemical staining, and transmission electron microscopy, TUNEL assay was also performed on dental tissue slices for assessment of apoptosis. High fluoride concentration was associated with decreased ameloblast proliferation, elevated ameloblast apoptosis, and increased intracellular Ca2+ in vitro. The translation and transcription of the proteins associated with endoplasmic reticulum stress were significantly elevated with high concentrations of fluoride. Based on immunohistochemical staining, these proteins were also highly expressed in animals exposed to high fluoride concentrations. Histologically, we found significant fluorosis-like changes in tissues from animals exposed to high fluoride concentrations. Transmission electron microscopy cytology indicated significant apoptotic changes in tissues exposed to high concentrations of fluoride. These results indicate that exposure to high levels of fluoride led to endoplasmic reticulum stress which induced apoptosis in cultured ameloblasts and in vivo rat model, suggesting an important role of calcium overload and endoplasmic reticulum stress triggered by high concentrations of fluoride in the development of dental fluorosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The Akt-mTOR axis is a pivotal regulator of eccentric hypertrophy during volume overload

    OpenAIRE

    Masataka Ikeda; Tomomi Ide; Takeo Fujino; Yuka Matsuo; Shinobu Arai; Keita Saku; Takamori Kakino; Yasuhiro Oga; Akiko Nishizaki; Kenji Sunagawa

    2015-01-01

    The heart has two major modalities of hypertrophy in response to hemodynamic loads: concentric and eccentric hypertrophy caused by pressure and volume overload (VO), respectively. However, the molecular mechanism of eccentric hypertrophy remains poorly understood. Here we demonstrate that the Akt-mammalian target of rapamycin (mTOR) axis is a pivotal regulator of eccentric hypertrophy during VO. While mTOR in the heart was activated in a left ventricular end-diastolic pressure (LVEDP)-depende...

  4. Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice

    Science.gov (United States)

    Sustained pressure overload causes cardiac hypertrophy and the transition to heart failure. We show here that dietary supplementation with physiologically relevant levels of copper (Cu) reverses pre-established hypertrophic cardiomyopathy in the presence of pressure overload induced by ascending aor...

  5. Natural polyphenols may ameliorate damage induced by copper overload.

    Science.gov (United States)

    Arnal, Nathalie; Tacconi de Alaniz, María J; Marra, Carlos Alberto

    2012-02-01

    The effect of the simultaneous exposure to transition metals and natural antioxidants frequently present in food is a question that needs further investigation. We aimed to explore the possible use of the natural polyphenols caffeic acid (CA), resveratrol (RES) and curcumin (CUR) to prevent damages induced by copper-overload on cellular molecules in HepG2 and A-549 human cells in culture. Exposure to 100μM/24h copper (Cu) caused extensive pro-oxidative damage evidenced by increased TBARS, protein carbonyls and nitrite productions in both cell types. Damage was aggravated by simultaneous incubation with 100μM of CA or RES, and it was also reflected in a decrease on cellular viability explored by trypan blue dye exclusion test and LDH leakage. Co-incubation with CUR produced opposite effects demonstrating a protective action which restored the level of biomarkers and cellular viability almost to control values. Thus, while CA and RES might aggravate the oxidative/nitrative damage of Cu, CUR should be considered as a putative protective agent. These results could stimulate further research on the possible use of natural polyphenols as neutralizing substances against the transition metal over-exposure in specific populations such as professional agrochemical sprayers and women using Cu-intrauterine devices.

  6. Cinnamaldehyde attenuates pressure overload-induced cardiac hypertrophy.

    Science.gov (United States)

    Yang, Liu; Wu, Qing-Qing; Liu, Yuan; Hu, Zhe-Fu; Bian, Zhou-Yan; Tang, Qi-Zhu

    2015-01-01

    Cinnamaldehyde is a major bioactive compound isolated from the leaves of Cinnamomum osmophloeum. Studies have demonstrated that cinnamaldehyde has anti-bacterial activity, anti-tumorigenic effect, immunomodulatory effect, anti-fungal activity, anti-oxidative effect, anti-inflammatory and anti-diabetic effect. It has been proven that Cinnamaldehyde improves ischemia/reperfusion injury of pre-treatment. However, little is known about the effect of cinnamaldehyde on cardiac hypertrophy. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cinnamaldehyde premixed in diets was administered to mice after one week of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed at week 7 after starting cinnamaldehyde (8 weeks after surgery). The extent of cardiac hypertrophy was evaluated by pathological and molecular analyses of heart samples. Meanwhile, the effect of cinnamaldehyde on myocardial hypertrophy, fibrosis and dysfunction induced by AB was investigated, as was assessed by heart weigh/body weight, lung weight/body weight, heart weight/tibia length, echocardiographic and haemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. Our data demonstrated that echocardiography and catheter-based measurements of hemodynamic parameters at week 7 revealed the amelioration of systolic and diastolic abnormalities by cinnamaldehyde intervention. Cardiac fibrosis in AB mice was also decreased by cinnamaldehyde. Moreover, the beneficial effect of cinnamaldehyde was associated with the normalization in gene expression of hypertrophic and fibrotic markers. Further studies showed that pressure overload significantly induced the activation of extracellular signal-regulated kinase (ERK) signaling pathway, which was blocked by cinnamaldehyde. Cinnamaldehyde may be able to retard the progression of cardiac hypertrophy and fibrosis, probably via blocking ERK signaling pathway.

  7. Maternal Cardiovascular Function in Normal Pregnancy: Evidence of Maladaptation to Chronic Volume Overload.

    Science.gov (United States)

    Melchiorre, Karen; Sharma, Rajan; Khalil, Asma; Thilaganathan, Baskaran

    2016-04-01

    The aim of this study was to investigate cardiac functional status in pregnancy using a comprehensive approach taking into account the simultaneous changes in loading and geometry, as well as maternal age and anthropometric indices. This was a prospective cross-sectional study of 559 nulliparous pregnant women assessed at 4 time points during pregnancy and at 1 year postpartum. All women underwent conventional echocardiography and tissue Doppler velocities and strain rate analysis at multiple cardiac sites. Mean arterial pressure and total vascular resistance index significantly decreased (both Ppregnancy and increased thereafter. Stroke volume index and cardiac index showed the opposite trend compared with mean arterial pressure and total vascular resistance index (both Ppregnancy, significant chamber diastolic dysfunction and impaired myocardial relaxation was evident in 17.9% and 28.4% of women, respectively, whereas myocardial contractility was preserved. There was full recovery of cardiac function at 1 year postpartum. Cardiovascular changes during pregnancy are thought to represent a physiological adaptation to volume overload. The findings of a drop in stroke volume index, impaired myocardial relaxation with diastolic dysfunction, and a tendency toward eccentric remodeling in a significant proportion of cases at term are suggestive of cardiovascular maladaptation to the volume-overloaded state in some apparently normal pregnancies. These unexpected cardiovascular findings have important implications for the management of both normal and pathological pregnancy states.

  8. Understanding the heterogeneity in volume overload and fluid distribution in decompensated heart failure is key to optimal volume management: role for blood volume quantitation.

    Science.gov (United States)

    Miller, Wayne L; Mullan, Brian P

    2014-06-01

    This study sought to quantitate total blood volume (TBV) in patients hospitalized for decompensated chronic heart failure (DCHF) and to determine the extent of volume overload, and the magnitude and distribution of blood volume and body water changes following diuretic therapy. The accurate assessment and management of volume overload in patients with DCHF remains problematic. TBV was measured by a radiolabeled-albumin dilution technique with intravascular volume, pre-to-post-diuretic therapy, evaluated at hospital admission and at discharge. Change in body weight in relation to quantitated TBV was used to determine interstitial volume contribution to total fluid loss. Twenty-six patients were prospectively evaluated. Two patients had normal TBV at admission. Twenty-four patients were hypervolemic with TBV (7.4 ± 1.6 liters) increased by +39 ± 22% (range, +9.5% to +107%) above the expected normal volume. With diuresis, TBV decreased marginally (+30 ± 16%). Body weight declined by 6.9 ± 5.2 kg, and fluid intake/fluid output was a net negative 8.4 ± 5.2 liters. Interstitial compartment fluid loss was calculated at 6.2 ± 4.0 liters, accounting for 85 ± 15% of the total fluid reduction. TBV analysis demonstrated a wide range in the extent of intravascular overload. Dismissal measurements revealed marginally reduced intravascular volume post-diuretic therapy despite large reductions in body weight. Mobilization of interstitial fluid to the intravascular compartment with diuresis accounted for this disparity. Intravascular volume, however, remained increased at dismissal. The extent, composition, and distribution of volume overload are highly variable in DCHF, and this variability needs to be taken into account in the approach to individualized therapy. TBV quantitation, particularly serial measurements, can facilitate informed volume management with respect to a goal of treating to euvolemia. Copyright © 2014 American College of Cardiology Foundation. Published

  9. ANG II is required for optimal overload-induced skeletal muscle hypertrophy

    Science.gov (United States)

    Gordon, S. E.; Davis, B. S.; Carlson, C. J.; Booth, F. W.

    2001-01-01

    ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT(1)) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225-250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle (experiment 1) or both the gastrocnemius and plantaris muscles (experiment 2). In experiment 1 (n = 10/group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals (experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT(1) receptor-dependent pathway.

  10. ANG II is required for optimal overload-induced skeletal muscle hypertrophy

    Science.gov (United States)

    Gordon, S. E.; Davis, B. S.; Carlson, C. J.; Booth, F. W.

    2001-01-01

    ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT(1)) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225-250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle (experiment 1) or both the gastrocnemius and plantaris muscles (experiment 2). In experiment 1 (n = 10/group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals (experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT(1) receptor-dependent pathway.

  11. Molten thermoplastic dripping behavior induced by flame spread over wire insulation under overload currents.

    Science.gov (United States)

    He, Hao; Zhang, Qixing; Tu, Ran; Zhao, Luyao; Liu, Jia; Zhang, Yongming

    2016-12-15

    The dripping behavior of the molten thermoplastic insulation of copper wire, induced by flame spread under overload currents, was investigated for a better understanding of energized electrical wire fires. Three types of sample wire, with the same polyethylene insulation thickness and different core diameters, were used in this study. First, overload current effects on the transient one-dimensional wire temperature profile were predicted using simplified theoretical analysis; the heating process and equilibrium temperature were obtained. Second, experiments on the melting characteristics were conducted in a laboratory environment, including drop formation and frequency, falling speed, and combustion on the steel base. Third, a relationship between molten mass loss and volume variation was proposed to evaluate the dripping time and frequency. A strong current was a prerequisite for the wire dripping behavior and the averaged dripping frequency was found to be proportional to the square of the current based on the theoretical and experimental results. Finally, the influence of dripping behavior on the flame propagation along the energized electrical wire was discussed. The flame width, bright flame height and flame spreading velocity presented different behaviors.

  12. Pressure Overload by Transverse Aortic Constriction Induces Maladaptive Hypertrophy in a Titin-Truncated Mouse Model

    Directory of Open Access Journals (Sweden)

    Qifeng Zhou

    2015-01-01

    Full Text Available Mutations in the giant sarcomeric protein titin (TTN are a major cause for inherited forms of dilated cardiomyopathy (DCM. We have previously developed a mouse model that imitates a TTN truncation mutation we found in a large pedigree with DCM. While heterozygous Ttn knock-in mice do not display signs of heart failure under sedentary conditions, they recapitulate the human phenotype when exposed to the pharmacological stressor angiotensin II or isoproterenol. In this study we investigated the effects of pressure overload by transverse aortic constriction (TAC in heterozygous (Het Ttn knock-in mice. Two weeks after TAC, Het mice developed marked impairment of left ventricular ejection fraction (p<0.05, while wild-type (WT TAC mice did not. Het mice also trended toward increased ventricular end diastolic pressure and volume compared to WT littermates. We found an increase in histologically diffuse cardiac fibrosis in Het compared to WT in TAC mice. This study shows that a pattern of DCM can be induced by TAC-mediated pressure overload in a TTN-truncated mouse model. This model enlarges our arsenal of cardiac disease models, adding a valuable tool to understand cardiac pathophysiological remodeling processes and to develop therapeutic approaches to combat heart failure.

  13. Hypo-osmolar intravascular volume overload during anaesthesia for transurethral prostatectomy. A report of 2 cases.

    Science.gov (United States)

    Butt, A D; Wright, I G; Elk, R J

    1985-06-29

    Two cases are reported in which absorption of surgical irrigant into the vascular system during transurethral resection of the prostate gland (TUR) resulted in life-threatening complications due to hypo-osmolar volume overload (also known as water intoxication or the TUR syndrome). Manifestations common to both cases were haemolysis of red cells, cardiac arrhythmias, a drop in the serum sodium level, and an elevated central venous pressure. In addition, one patient developed acute pulmonary oedema and the other hypokalaemia, confusion and visual disturbances due to cerebral oedema. Water as an irrigant for TUR should be superseded by glycine 1,5%, which is safer.

  14. Right ventricular volumes and function in thalassemia major patients in the absence of myocardial iron overload

    Directory of Open Access Journals (Sweden)

    Porter John B

    2010-04-01

    Full Text Available Abstract Aim We aimed to define reference ranges for right ventricular (RV volumes, ejection fraction (EF in thalassemia major patients (TM without myocardial iron overload. Methods and results RV volumes, EF and mass were measured in 80 TM patients who had no myocardial iron overload (myocardial T2* > 20 ms by cardiovascular magnetic resonance. All patients were receiving deferoxamine chelation and none had evidence of pulmonary hypertension or other cardiovascular comorbidity. Forty age and sex matched healthy non-anemic volunteers acted as controls. The mean RV EF was higher in TM patients than controls (males 66.2 ± 4.1% vs 61.6 ± 6%, p = 0.0009; females 66.3 ± 5.1% vs 62.6 ± 6.4%, p = 0.017, which yielded a raised lower threshold of normality for RV EF in TM patients (males 58.0% vs 50.0% and females 56.4% vs 50.1%. RV end-diastolic volume index was higher in male TM patients (mean 98.1 ± 17.3 mL vs 88.4 ± 11.2 mL/m2, p = 0.027, with a higher upper limit (132 vs 110 mL/m2 but this difference was of borderline significance for females (mean 86.5 ± 13.6 mL vs 80.3 ± 12.8 mL/m2, p = 0.09, with upper limit of 113 vs 105 mL/m2. The cardiac index was raised in TM patients (males 4.8 ± 1.0 L/min vs 3.4 ± 0.7 L/min, p Conclusion The normal ranges for functional RV parameters in TM patients with no evidence of myocardial iron overload differ from healthy non-anemic controls. The new reference RV ranges are important for determining the functional effects of myocardial iron overload in TM patients.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  16. Vascular refilling is independent of volume overload in hemodialysis with moderate ultrafiltration requirements.

    Science.gov (United States)

    Kron, Susanne; Schneditz, Daniel; Leimbach, Til; Aign, Sabine; Kron, Joachim

    2016-07-01

    Introduction Blood volume changes and vascular refilling during hemodialysis (HD) and ultrafiltration (UF) have been assumed to depend on volume overload (Vo ). It was the aim to study the magnitude of vascular refilling in stable HD patients with moderate volume expansion in everyday dialysis using novel technical approaches. Methods Patients were studied during routine dialysis and UF based on clinical dry weight assessment. Pre-dialysis Vo was independently measured by bioimpedance spectroscopy. Vascular refilling volume (Vref ) was calculated as: Vref  = Vuf  - ΔV, where ΔV is the absolute blood volume change determined by on-line dialysate dilution using a commercial on-line hemodiafiltration machine incorporating a relative blood volume monitor, and where Vuf is the prescribed UF volume. Findings Thirty patients (dry weight: 81.0 ± 17.8 kg) were studied. Pre-dialysis Vo was 2.46 ± 1.45 L. Vuf was 2.27 ± 0.71 L, specific UF rate was 6.45 ± 2.43 mL/kg/h, and since ΔV was 0.66 ± 0.31 L, Vref was determined as 1.61 ± 0.58 L, corresponding to a constant refilling fraction (Fref ) of 70.6 ± 10.6%. Vref strongly correlated with Vuf (r(2)  = 0.82) but was independent of Vo and other volumes. Fref was also independent of Vo and other volumes normalized for various measures of body size. Discussion While vascular refilling and Fref is independent of Vo in treatments with moderate UF requirements, intravascular volume depletion increases with increasing UF requirements. The relationship between blood volume and Vo needs to be more closely examined in further studies to optimize volume control in everyday dialysis.

  17. Female rats with severe left ventricle volume overload exhibit more cardiac hypertrophy but fewer myocardial transcriptional changes than males.

    Science.gov (United States)

    Beaumont, Catherine; Walsh-Wilkinson, Élisabeth; Drolet, Marie-Claude; Roussel, Élise; Arsenault, Marie; Couet, Jacques

    2017-04-07

    Aortic valve regurgitation (AR) imposes a volume overload (VO) to the left ventricle (LV). Male rats with a pathological heart overload usually progress more quickly towards heart failure than females. We examined whether a sexual dimorphism exists in the myocardial transcriptional adaptations to AR. Adult Wistar male and female rats either underwent a sham operation or were induced with AR and then followed for 26 weeks. Female AR rats gained relatively more LV mass than males (75 vs. 42%). They had a similar increase in LV chamber dimensions compared to males but more wall thickening. On the other hand, fatty acid oxidation (FAO)-related LV enzyme activity was only decreased in AR males. The expression of genes encoding FAO-related enzymes was only reduced in AR males and not in females. A similar situation was observed for the expression of genes involved in mitochondrial biogenesis or function as well as for genes encoding for transcription factors implicated in the control of bioenergetics and mitochondrial function (Errα, Errγ or Pgc1α). Although females develop more LV hypertrophy from severe VO, their myocardial gene expression remains closer to normal. This could provide survival benefits for females with severe VO.

  18. Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

    Directory of Open Access Journals (Sweden)

    Stephanie Puukila

    Full Text Available Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG, a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

  19. Triple Diuretics and Aquaretic Strategy for Acute Decompensated Heart Failure due to Volume Overload

    Directory of Open Access Journals (Sweden)

    Rita Jermyn

    2013-01-01

    Full Text Available Diuretics, including furosemide, metolazone, and spironolactone, have historically been the mainstay of therapy for acute decompensated heart failure patients. The addition of an aquaretic-like vasopressin antagonist may enhance diuresis further. However, clinical experience with this quadruple combination is lacking in the acute setting. We present two hospitalized patients with acute decompensated heart failure due to massive fluid overload treated with a combination strategy of triple diuretics in conjunction with the aquaretic tolvaptan. The first patient lost 72.1 lbs. (32.7 kg with an average urine output of 3.5 to 7.5 L/day over eight days on combined therapy with furosemide, metolazone, spironolactone, and tolvaptan. The second patient similarly achieved a weight loss of 28.2 lbs. (12.8 kg over 4 days on the same treatment. Both patients maintained stable serum sodium, potassium, and creatinine over this period and remained out of the hospital for more than 30 days. Thus, patients hospitalized with acute decompensated heart failure due to volume overload can achieve euvolemia rapidly and without electrolytes disturbances using this regimen, while being under the close supervision of a team of cardiologists and nephrologists. Additionally, this therapy can potentially decrease the need for ultrafiltration and the length of hospital stay.

  20. Triple Diuretics and Aquaretic Strategy for Acute Decompensated Heart Failure due to Volume Overload

    Science.gov (United States)

    Estrada, Chelsea; Patel, Sagar; Weisfelner Bloom, Michelle; Wadhwa, Nand K.

    2013-01-01

    Diuretics, including furosemide, metolazone, and spironolactone, have historically been the mainstay of therapy for acute decompensated heart failure patients. The addition of an aquaretic-like vasopressin antagonist may enhance diuresis further. However, clinical experience with this quadruple combination is lacking in the acute setting. We present two hospitalized patients with acute decompensated heart failure due to massive fluid overload treated with a combination strategy of triple diuretics in conjunction with the aquaretic tolvaptan. The first patient lost 72.1 lbs. (32.7 kg) with an average urine output of 3.5 to 7.5 L/day over eight days on combined therapy with furosemide, metolazone, spironolactone, and tolvaptan. The second patient similarly achieved a weight loss of 28.2 lbs. (12.8 kg) over 4 days on the same treatment. Both patients maintained stable serum sodium, potassium, and creatinine over this period and remained out of the hospital for more than 30 days. Thus, patients hospitalized with acute decompensated heart failure due to volume overload can achieve euvolemia rapidly and without electrolytes disturbances using this regimen, while being under the close supervision of a team of cardiologists and nephrologists. Additionally, this therapy can potentially decrease the need for ultrafiltration and the length of hospital stay. PMID:24829808

  1. Whey protein inhibits iron overload-induced oxidative stress in rats.

    Science.gov (United States)

    Kim, Jungmi; Paik, Hyun-Dong; Yoon, Yoh-Chang; Park, Eunju

    2013-01-01

    In this study, we evaluated the effects of whey protein on oxidative stress in rats that were subjected to oxidative stress induced by iron overload. Thirty male rats were assigned to 3 groups: the control group (regular [50 mg/kg diet] dose of iron+20% casein), iron overload group (high [2,000 mg/kg] dose of iron+20% casein, IO), and whey protein group (high dose of iron+10% casein+10% whey protein, IO+whey). After 6 wk, the IO group showed a reduction in the plasma total radical trapping antioxidant parameter and the activity of erythrocyte superoxide dismutase and an increase in lipid peroxidation (determined from the proportion of conjugated dienes). However, whey protein ameliorated the oxidative changes induced by iron overload. The concentration of erythrocyte glutathione was significantly higher in the IO+whey group than in the IO group. In addition, whey protein supplementation fully inhibited iron overload-induced DNA damage in leukocytes and colonocytes. A highly significant positive correlation was observed between plasma iron levels and DNA damage in leukocytes and colonocytes. These results show the antioxidative and antigenotoxic effects of whey protein in an in vivo model of iron overload-induced oxidative stress.

  2. Thrombopoietin Protects Cardiomyocytes from Iron-Overload Induced Oxidative Stress and Mitochondrial Injury

    Directory of Open Access Journals (Sweden)

    Shing Chan

    2015-07-01

    Full Text Available Background/Aims: Thalassaemia accompanied with iron-overload is common in Hong Kong. Iron-overload induced cardiomyopathy is the commonest cause of morbidity and mortality in patients with β-thalassaemia. Chronic iron-overload due to blood transfusion can cause cardiac failure. Decreased antioxidant defence and increased ROS production may lead to oxidative stress and cell injury. Iron-overload may lead to heart tissue damage through lipid peroxidation in response to oxidative stress, and a great diversity of toxic aldehydes are formed when lipid hydroperoxides break down in heart and plasma. Methods: Iron entry into embryonic heart H9C2 cells was determined by calcein assay using a fluorometer. Reactive oxygen species (ROS production in cells treated with FeCl3 or thrombopoietin (TPO was monitored by using the fluorescent probe H2DCFDA. Changes in mitochondrial membrane potential of H9C2 cells were quantified by using flow cytometry. Results: We demonstrated that iron induced oxidative stress and apoptosis in cardiomyocytes, and that iron increased ROS production and reduced cell viability in a dose-dependent manner. Iron treatment increased the proportion of cells with JC-1 monomers, indicating a trend of drop in the mitochondrial membrane potential. TPO exerted a cardio-protective effect on iron-induced apoptosis. Conclusions: These findings suggest that iron-overload leads to the generation of ROS and further induces apoptosis in cardiomyocytes via mitochondrial pathways. TPO might exert a protective effect on iron-overload induced apoptosis via inhibiting oxidative stress and suppressing the mitochondrial pathways in cardiomyocytes.

  3. Volume overload cleanup: An approach for on-line SPE-GC, GPC-GC, and GPC-SPE-GC

    NARCIS (Netherlands)

    Kerkdijk, H.; Mol, H.G.J.; Nagel, B. van der

    2007-01-01

    A new concept for cleanup, based on volume overloading of the cleanup column, has been developed for on-line coupling of gel permeation chromatography (GPC), solid-phase extraction (SPE), or both, to gas chromatography (GC). The principle is outlined and the applicability demonstrated by the determi

  4. Danshen (Salvia miltiorrhiza injection suppresses kidney injury induced by iron overload in mice.

    Directory of Open Access Journals (Sweden)

    Shengjiang Guan

    Full Text Available OBJECTIVES: Excessive iron can accumulate in the kidney and induce tissue damage. Danshen (Salvia miltiorrhiza injection is a traditional Chinese medicinal preparation used for preventing and treating chronic renal failure. The aim of the present study was to evaluate the effects of treatment with Danshen injection on iron overload-induced kidney damage. METHODS: Mice were mock-treated with saline (control group or given a single dose of iron dextran without treatment (iron overload group, 50 mg/kg/day for 2 weeks or with daily treatments of low-dose Danshen (3 g/kg/day, high-dose Danshen (6 g/kg/day or deferoxamine (100 mg/kg/day. RESULTS: Treatment of iron-overloaded mice with Danshen injection led to significant improvements of body weight and decreased iron levels in the kidney. Danshen injection treatment also reduced concentrations of blood urea nitrogen, creatinine and malondialdehyde and enhanced glutathione peroxidase and superoxide dismutase activities. Histopathological examinations showed that Danshen injection ameliorated pathological changes and reduced iron deposition in kidneys of iron overloaded mice. Furthermore, the treatment was demonstrated to suppress apoptosis in nephrocytes. CONCLUSIONS: These results indicated that Danshen injection exerted significant renal protective effects in iron-overloaded mice, which were closely associated with the decrease of iron deposition and suppression of lipid peroxidation and apoptosis in the kidney.

  5. AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload.

    Science.gov (United States)

    Riedl, Isabelle; Osler, Megan E; Björnholm, Marie; Egan, Brendan; Nader, Gustavo A; Chibalin, Alexander V; Zierath, Juleen R

    2016-03-15

    Mechanisms regulating skeletal muscle growth involve a balance between the activity of serine/threonine protein kinases, including the mammalian target of rapamycin (mTOR) and 5'-AMP-activated protein kinase (AMPK). The contribution of different AMPK subunits to the regulation of cell growth size remains inadequately characterized. Using AMPKγ3 mutant-overexpressing transgenic Tg-Prkag3(225Q) and AMPKγ3-knockout (Prkag3(-/-)) mice, we investigated the requirement for the AMPKγ3 isoform in functional overload-induced muscle hypertrophy. Although the genetic disruption of the γ3 isoform did not impair muscle growth, control sham-operated AMPKγ3-transgenic mice displayed heavier plantaris muscles in response to overload hypertrophy and underwent smaller mass gain and lower Igf1 expression compared with wild-type littermates. The mTOR signaling pathway was upregulated with functional overload but unchanged between genetically modified animals and wild-type littermates. Differences in AMPK-related signaling pathways between transgenic, knockout, and wild-type mice did not impact muscle hypertrophy. Glycogen content was increased following overload in wild-type mice. In conclusion, our functional, transcriptional, and signaling data provide evidence against the involvement of the AMPKγ3 isoform in the regulation of skeletal muscle hypertrophy. Thus, the AMPKγ3 isoform is dispensable for functional overload-induced muscle growth. Mechanical loading can override signaling pathways that act as negative effectors of mTOR signaling and consequently promote skeletal muscle hypertrophy. Copyright © 2016 the American Physiological Society.

  6. Overload-induced skeletal muscle hypertrophy is not impaired in STZ-diabetic rats

    Science.gov (United States)

    Fortes, Marco Aurélio S; Pinheiro, Carlos Hermano J; Guimarães-Ferreira, Lucas; Vitzel, Kaio F; Vasconcelos, Diogo A A; Curi, Rui

    2015-01-01

    The aim of this study was to evaluate the effect of overload-induced hypertrophy on extensor digitorum longus (EDL) and soleus muscles of streptozotocin-induced diabetic rats. The overload-induced hypertrophy and absolute tetanic and twitch forces increases in EDL and soleus muscles were not different between diabetic and control rats. Phospho-Akt and rpS6 contents were increased in EDL muscle after 7 days of overload and returned to the pre-overload values after 30 days. In the soleus muscle, the contents of total and phospho-Akt and total rpS6 were increased in both groups after 7 days. The contents of total Akt in controls and total rpS6 and phospho-Akt in the diabetic rats remained increased after 30 days. mRNA expression after 7 days of overload in the EDL muscle of control and diabetic animals showed an increase in MGF and follistatin and a decrease in myostatin and Axin2. The expression of FAK was increased and of MuRF-1 and atrogin-1 decreased only in the control group, whereas Ankrd2 expression was enhanced only in diabetic rats. In the soleus muscle caused similar changes in both groups: increase in FAK and MGF and decrease in Wnt7a, MuRF-1, atrogin-1, and myostatin. Differences between groups were observed only in the increased expression of follistatin in diabetic animals and decreased Ankrd2 expression in the control group. So, insulin deficiency does not impair the overload-induced hypertrophic response in soleus and EDL muscles. However, different mechanisms seem to be involved in the comparable hypertrophic responses of skeletal muscle in control and diabetic animals. PMID:26197932

  7. Modulation of Pseudomonas aeruginosa lipopolysaccharide-induced lung inflammation by chronic iron overload in rat.

    Science.gov (United States)

    Lê, Bá Vuong; Khorsi-Cauet, Hafida; Bach, Véronique; Gay-Quéheillard, Jérôme

    2012-03-01

    Iron constitutes a critical nutrient source for bacterial growth, so iron overload is a risk factor for bacterial infections. This study aimed at investigating the role of iron overload in modulating bacterial endotoxin-induced lung inflammation. Weaning male Wistar rats were intraperitoneally injected with saline or iron sucrose [15 mg kg(-1) body weight (bw), 3 times per week, 4 weeks]. They were then intratracheally injected with Pseudomonas aeruginosa lipopolysaccharide (LPS) (5 μg kg(-1) bw) or saline. Inflammatory indices were evaluated 4 or 18 h post-LPS/saline injection. At 4 h, LPS-treated groups revealed significant increases in the majority of inflammatory parameters (LPS-binding protein (LBP), immune cell recruitment, inflammatory cytokine synthesis, myeloperoxidase activity, and alteration of alveolar-capillary permeability), as compared with control groups. At 18 h, these parameters reduced strongly with the exception for LBP content and interleukin (IL)-10. In parallel, iron acted as a modulator of immune cell recruitment; LBP, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant 3, and IL-10 synthesis; and alveolar-capillary permeability. Therefore, P. aeruginosa LPS may only act as an acute lung inflammatory molecule, and iron overload may modulate lung inflammation by enhancing different inflammatory parameters. Thus, therapy for iron overload may be a novel and efficacious approach for the prevention and treatment of bacterial lung inflammations.

  8. Iron overload induced death of osteoblasts in vitro: involvement of the mitochondrial apoptotic pathway

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    Qing Tian

    2016-11-01

    Full Text Available Background Iron overload is recognized as a new pathogenfor osteoporosis. Various studies demonstrated that iron overload could induce apoptosis in osteoblasts and osteoporosis in vivo. However, the exact molecular mechanisms involved in the iron overload-mediated induction of apoptosis in osteoblasts has not been explored. Purpose In this study, we attempted to determine whether the mitochondrial apoptotic pathway is involved in iron-induced osteoblastic cell death and to investigate the beneficial effect of N-acetyl-cysteine (NAC in iron-induced cytotoxicity. Methods The MC3T3-E1 osteoblastic cell line was treated with various concentrations of ferric ion in the absence or presence of NAC, and intracellular iron, cell viability, reactive oxygen species, functionand morphology changes of mitochondria and mitochondrial apoptosis related key indicators were detected by commercial kits. In addition, to further explain potential mechanisms underlying iron overload-related osteoporosis, we also assessed cell viability, apoptosis, and osteogenic differentiation potential in bone marrow-derived mesenchymal stemcells(MSCs by commercial kits. Results Ferric ion demonstrated concentration-dependent cytotoxic effects on osteoblasts. After incubation with iron, an elevation of intracelluar labile iron levels and a concomitant over-generation of reactive oxygen species (ROS were detected by flow cytometry in osteoblasts. Nox4 (NADPH oxidase 4, an important ROS producer, was also evaluated by western blot. Apoptosis, which was evaluated by Annexin V/propidium iodide staining, Hoechst 33258 staining, and the activation of caspase-3, was detected after exposure to iron. Iron contributed to the permeabilizatio of mitochondria, leading to the release of cytochrome C (cyto C, which, in turn, induced mitochondrial apoptosis in osteoblasts via activation of Caspase-3, up-regulation of Bax, and down-regulation of Bcl-2. NAC could reverse iron-mediated mitochondrial

  9. Effect of matrine and carvedilol on collagen and MMPs activity of hypertrophy myocardium induced by pressure overload

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To explore the effect and mechanism of matrine (Mt.) on myocardial interstitial fibrosis induced by pressure overload. Methods: Pressure overloaded myocardial hypertrophy was produced by banding of aorta abdominalis in 67 male Sprague-Dawley rats weighing (200± 15) g. The rats were assigned into one of the following groups: sham-operation control,operation control, operation group treated with matrine (15 mg/(kg.d)) and treated with carvedilol (Car.) (3.6 mg/(kg.d)) group.The rats were given drugs one day after operation. Five weeks after treatment, the left ventricular weight (LVW) was measured and the volume of myocardial cells was detected with Hematoxylin-Eosin (H-E) stain and Masson stain was used to assess the level of fibrosis of the myocardial matrix. Myocardial metalloproteinase activity was quantified with zymography, and survival rate was calculated. Results: Survival rate significantly decreased (P<0.05), LVW/BW (body weight), MMP-2 (matrix metalloproteinase-2)activity (P<0.05), size of cardiomyocytes and interstitial fibrosis obviously increased in the operation group compared with sham control group. Mt. and Car. treatment can significantly increase survival rate (P<0.05), decrease LVW/BW (P<0.05) and MMP-2 activity (P<0.05), decrease size of cardiomyocytes and interstitial fibrosis compared with operation group. But there was difference compared with sham group. Conclusion: Matrine was shown to be able to prevent cardiac remodelling of hypertrophy cardium induced by pressure overload including myocardial hypertrophy and fibrosis which may be associated with the decrease in MMP-2 activity of heart.

  10. Blood volume-monitored regulation of ultrafiltration in fluid-overloaded hemodialysis patients: study protocol for a randomized controlled trial

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    Hecking Manfred

    2012-06-01

    Full Text Available Abstract Background Data generated with the body composition monitor (BCM, Fresenius show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR and/or regulation of ultrafiltration and temperature (UTR will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients. Methods/design BCM measurements yield results on fluid overload (in liters, relative to extracellular water (ECW. In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW. Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, ‘final’ dry weight is set to normohydration weight −7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase. In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study

  11. Temporal changes in integrin-mediated cardiomyocyte adhesion secondary to chronic cardiac volume overload in rats

    Science.gov (United States)

    Stewart, James A.; Gardner, Jason D.; Brower, Gregory L.

    2013-01-01

    Previous studies have established integrins as cell surface receptors that mediate cardiomyocyte-extracellular matrix (ECM) attachments. This study sought to determine the contributions of the myocardial β1- and β3-integrin subunits to ventricular dilatation and coronary flow regulation using a blood-perfused isolated heart preparation. Furthermore, cardiomyocyte adhesion to collagen types I and IV, fibronectin, and laminin with and without a β1-integrin subunit neutralizing antibody was assessed during the course of remodeling secondary to a sustained cardiac volume overload, including the onset of heart failure. Isolated cardiomyocytes were obtained during the initial, compensated, and decompensated phases of remodeling resulting from an aortocaval fistula created in 8-wk-old male Sprague-Dawley rats. Blocking the β1-integrin subunit in isolated normal hearts produced ventricular dilatation, whereas this was not the case when the β3-subunit was blocked. Substantial reductions in cardiomyocyte adhesion coincided with the previously documented development of ventricular dilatation and decreased contractility postfistula, with the β1-integrin contribution to adhesion ranging from 28% to 73% over the course of remodeling being essentially substrate independent. In contrast, both integrin subunits were found to be involved in regulating coronary vascular resistance. It is concluded that marked reductions in integrin-mediated cardiomyocyte adhesion to the ECM play a significant role in the progression of adverse myocardial remodeling that leads to heart failure. Furthermore, although both the β1- and β3-integrin subunits were involved in regulating coronary vascular resistance, only inhibition of β1-integrin-mediated adhesion resulted in ventricular dilatation of the normal heart. PMID:24163072

  12. SIRT1 may play a crucial role in overload-induced hypertrophy of skeletal muscle.

    Science.gov (United States)

    Koltai, Erika; Bori, Zoltán; Chabert, Clovis; Dubouchaud, Hervé; Naito, Hisashi; Machida, Shuichi; Davies, Kelvin Ja; Murlasits, Zsolt; Fry, Andrew C; Boldogh, Istvan; Radak, Zsolt

    2017-06-01

    Silent mating type information regulation 2 homologue 1 (SIRT1) activity and content increased significantly in overload-induced hypertrophy. SIRT1-mediated signalling through Akt, the endothelial nitric oxide synthase mediated pathway, regulates anabolic process in the hypertrophy of skeletal muscle. The regulation of catabolic signalling via forkhead box O 1 and protein ubiquitination is SIRT1 dependent. Overload-induced changes in microRNA levels regulate SIRT1 and insulin-like growth factor 1 signalling. Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in silent mating type information regulation 2 homologue 1 (SIRT1) content and activity (P hypertrophied muscles, and SIRT1 levels correlated with muscle mass, paired box protein 7 (Pax7), proliferating cell nuclear antigen (PCNA) and nicotinamide phosphoribosyltransferase (Nampt) levels. Alternatively, decreased forkhead box O 1 (FOXO1) and increased K48 polyubiquitination also suggest that SIRT1 could be involved in the catabolic process of hypertrophy. Furthermore, increased levels of K63 and muscle RING finger 2 (MuRF2) protein could also be important enhancers of muscle mass. We report here that the levels of miR1 and miR133a decrease in hypertrophy and negatively correlate with muscle mass, SIRT1 and Nampt levels. Our results reveal a strong correlation between SIRT1 levels and activity, SIRT1-regulated pathways and overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in

  13. Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload

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    Xian-hui Dong

    2015-01-01

    Full Text Available Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer′s disease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer′s disease patients. An APP swe/PS1ΔE9 double transgenic mouse model of Alzheimer′s disease was used. The intragastric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer′s disease. These compounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer′s disease.

  14. Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload

    Institute of Scientific and Technical Information of China (English)

    Xian-hui Dong; Cong Liu; Jiang-tao Bai; Wei-na Kong; Xiao-ping He; Peng Yan; Tie-mei Shao; Wen-guo Yu; Xi-qing Chai; Yan-hua Wu

    2015-01-01

    Abnormally increased levels of iron in the brain trigger cascade ampliifcation in Alzheimer’s dis-ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer’s disease patients. An APPswe/PS1ΔE9 double transgenic mouse model of Alzheimer’s disease was used. The intragas-tric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer’s disease. These com-pounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer’s disease.

  15. Mitogen-activated protein kinases (p38 and c-Jun NH2-terminal kinase) are differentially regulated during cardiac volume and pressure overload hypertrophy.

    Science.gov (United States)

    Sopontammarak, Somkiat; Aliharoob, Assad; Ocampo, Catherina; Arcilla, Rene A; Gupta, Mahesh P; Gupta, Madhu

    2005-01-01

    Chronic pressure overload (PO) and volume overload (VO) result in morphologically and functionally distinct forms of myocardial hypertrophy. However, the molecular mechanism initiating these two types of hypertrophy is not yet understood. Data obtained from different cell types have indicated that the mitogen-activated protein kinases (MAPKs) comprising c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 play an important role in transmitting signals of stress stimuli to elicit the cellular response. We tested the hypothesis that early induction of MAPKs differs in two types of overload on the heart and associates with distinct expression of hypertrophic marker genes, namely ANF, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. In rats, VO was induced by aortocaval shunt and PO by constriction of the abdominal aorta. The PO animals were further divided into two groups depending on the severity of the constriction, mild (MPO) and severe pressure overload (SPO), having 35 and 85% aortic constriction, respectively. Early changes in MAPK activity (2-120 min and 1 to 2 d) were analyzed by the in vitro kinase assay using kinase-specific antibodies for p38, JNK, and ERK2. The change in expression of hypertrophy marker genes was examined by Northern blot analysis. In VO hypertrophy, the activity of p38 was markedly increased (10-fold), without changing the activity of ERK and JNK. However, during PO hypertrophy, the activity of JNK was significantly increased (two- to sixfold) and depended on the severity of the load. The activity of p38 was not changed in MPO hypertrophy, whereas it was slightly elevated (50%) in hearts with SPO. Similarly, ERK activity was not changed in hearts with MPO, but a transient rise in activity was observed in hearts with SPO. The expression of ANF and beta-MHC genes was elevated in both PO and VO hypertrophy; however, this change was much greater in hearts subjected to PO than VO hypertrophy. Alpha

  16. Attenuation of mitochondrial, but not cytosolic, Ca2+ overload reduces myocardial injury induced by ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Chun-mei CAO; Wing-yee YAN; Jing LIU; Kenneth WL KAM; Shi-zhong ZHAN; James SK SHAM; Tak-ming WONG

    2006-01-01

    Aim: Attenuation of mitochondrial Ca2+ ([Ca2+]m, but not cytosolic Ca2+ ([Ca2+]c), overload improves contractile recovery. We hypothesized that attenuation of [Ca2+]m, but not [Ca2+]c, overload confers cardioprotection against ischemia/ reperfusion-induced injury. Methods: Infarct size from isolated perfused rat heart, cell viability, and electrically-induced Ca2+ transient in isolated rat ventricular myocytes were measured. We determined the effects of BAPTA-AM, a Ca2+ chelator, at concentrations that abolish the overload of both [Ca2+]c and [Ca2+]m, and ruthenium red, an inhibitor of mitochondrial uniporter of Ca2+ transport, at concentrations that abolish the overload of [Ca2+]m, but not [Ca2+]c, on cardiac injury induced by ischemia/reperfusion. Results: Attenuation of both [Ca2+]m and [Ca2+]c by BAPTA-AM, and attenuation of [Ca2+]m, but not [Ca2+]c, overload by ruthenium red, reduced the cardiac injury observations, indicating the importance of [Ca2+]m in cardioprotection and contractile recovery in response to ischemia/reperfusion. Conclusion: The study has provided unequivocal evidence using a cause-effect approach that attenuation of [Ca2+]m, but not [Ca2+]c, overload is responsible for cardioprotection against ischemia/reperfusion-induced injury. We also confirmed the previous observation that attenuation of [Ca2+]m, but not [Ca2+]c, by ruthenium red improves contractile recovery following ischemia/ reperfusion.

  17. Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure

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    Barkoudah Ebrahim

    2015-05-01

    Full Text Available Introduction: Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF, inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF as an alternative strategy for reducing volume overloads in patients with ADHF. Objective: The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. Results: A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI: −2.65 to −0.91 kg; p < 0.001 more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = −0.25 mg/dL; 95% CI: −0.56 to 0.06 mg/dL; p = 0.112. The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64–1.56; p = 0.993. Conclusion: Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed.

  18. G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

    Science.gov (United States)

    White, James P; Wrann, Christiane D; Rao, Rajesh R; Nair, Sreekumaran K; Jedrychowski, Mark P; You, Jae-Sung; Martínez-Redondo, Vicente; Gygi, Steven P; Ruas, Jorge L; Hornberger, Troy A; Wu, Zhidan; Glass, David J; Piao, Xianhua; Spiegelman, Bruce M

    2014-11-04

    Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise.

  19. Cardiac-Specific EPI64C Blunts Pressure Overload-Induced Cardiac Hypertrophy.

    Science.gov (United States)

    Zhu, Xuehai; Fang, Jing; Gong, Jun; Guo, Jun-Hong; Zhao, Guang-Nian; Ji, Yan-Xiao; Liu, Hong-Yun; Wei, Xiang; Li, Hongliang

    2016-05-01

    The calcium-responsive molecule, calcineurin, has been well characterized to play a causal role in pathological cardiac hypertrophy over the past decade. However, the intrinsic negative regulation of calcineurin signaling during the progression of cardiomyocyte hypertrophy remains enigmatic. Herein, we explored the role of EPI64C, a dual inhibitor of both Ras and calcineurin signaling during T-cell activation, in pressure overload-induced cardiac hypertrophy. We generated a cardiac-specific Epi64c conditional knockout mouse strain and showed that loss of Epi64c remarkably exacerbates pressure overload-induced cardiac hypertrophy. In contrast, EPI64C gain-of-function in cardiomyocyte-specific Epi64c transgenic mice exerts potent protective effects against cardiac hypertrophy. Mechanistically, the cardioprotective effects of EPI64C are largely attributed to the disrupted calcineurin signaling but are independent of its Ras suppressive capability. Molecular studies have indicated that the 406 to 446 C-terminal amino acids in EPI64C directly bind to the 287 to 337 amino acids in the catalytic domain of calcineurin, which is responsible for the EPI64C-mediated suppressive effects. We further extrapolated our studies to cynomolgus monkeys and showed that gene therapy based on lentivirus-mediated EPI64C overexpression in the monkey hearts blunted pressure overload-induced cardiac hypertrophy. Our study thus identified EPI64C as a novel negative regulator in cardiac hypertrophy by targeting calcineurin signaling and demonstrated the potential of gene therapy and drug development for treating cardiac hypertrophy. © 2016 American Heart Association, Inc.

  20. Astragalus Polysaccharide Attenuated Iron Overload-Induced Dysfunction of Mesenchymal Stem Cells via Suppressing Mitochondrial ROS

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    Fan Yang

    2016-09-01

    Full Text Available Background/Aims: Bone marrow-derived mesenchymal stem cells (BMSCs have the ability to differentiate into multilineage cells such as osteoblasts, chondrocytes, and cardiomyocytes. Dysfunction of BMSCs in response to pathological stimuli participates in the development of diseases such as osteoporosis. Astragalus polysaccharide (APS is a major active ingredient of Astragalus membranaceus, a commonly used anti-aging herb in traditional Chinese medicine. The aim of this study was to investigate whether APS protects against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Methods: BMSCs were exposed to ferric ammonium citrate (FAC with or without different concentrations of APS. The viability and proliferation of BMSCs were assessed by CCK-8 assay and EdU staining. Cell apoptosis, senescence and pluripotency were examined utilizing TUNEL staining, β-galactosidase staining and qRT-PCR respectively. The reactive oxygen species (ROS level was assessed in BMSCs with a DCFH-DA probe and MitoSOX Red staining. Results: Firstly, we found that iron overload induced by FAC markedly reduced the viability and proliferation of BMSCs, but treatment with APS at 10, 30 and 100 μg/mL was able to counter the reduction of cell proliferation. Furthermore, exposure to FAC led to apoptosis and senescence in BMSCs, which were partially attenuated by APS. The pluripotent genes Nanog, Sox2 and Oct4 were shown to be downregulated in BMSCs after FAC treatment, however APS inhibited the reduction of Nanog, Sox2 and Oct4 expression. Further study uncovered that APS treatment abrogated the increase of intracellular and mitochondrial ROS level in FAC-treated BMSCs. Conclusion: Treatment of BMSCs with APS to impede mitochondrial ROS accumulation can remarkably inhibit apoptosis, senescence, and the reduction of proliferation and pluripotency of BMSCs caused by FAC-induced iron overload.

  1. Deubiquitinase BRCC36 protects heart against chronic pressure overload-induced cardiac remodeling in mice

    Institute of Scientific and Technical Information of China (English)

    LI Ru-jun; FANG Wei; ZHU Hua-jiang; ZHANG Feng-xia; XU Ou-fang; XU Li-juan; ZHANG Zhen-gang; GONG Kai-zheng

    2016-01-01

    Emerging evidence has indicated that BRCC 36-mediated K63-linked ubiquitination modification was involved in diverse cellular functions , including endocytosis , apoptosis and DNA damage repair .We previously showed that activation of cGMP/PKG pathway con-tributed to the binding of BRCC36 and the pro-fibrotic factor Smad3.The current study tested the hypothesis that BRCC 36 functions as a negative regulator of transforming growth factor-beta ( TGF-β)/Smad3 pathway and participates in cardiac remodeling .In isolated adult mouse cardiac fibroblasts , we have demonstrated that TGF-β1 treatment significantly increased the expression of BRCC 36.Over-expression BRCC36 suppressed TGF-β1-induced Smad3 phosphorylation, nuclear translocation, extracellular matrix molecular expres-sion and cell proliferation .On the contrary, silencing BRCC36 by transfection of adenovirus-carrying BRCC36 shRNA potentiated to enhance the pro-fibrotic effect of TGF-β.In vivo, under chronic pressure overload condition-induced by transverse aortic constriction , myocardial pro-survival protein Bcl-2 and Mcl-1 expression were significantly decreased and the pro-apoptosis protein Puma was in-creased.However, the cardiac-specific over-expression of BRCC36 significantly increased myocardial Bcl-2 and Mcl-1 and inhibited Puma expression .Interestingly , we also found that sustained pressure overload resulted in a significant myocardial DNA injury in wild type mice, which was characterized by the increase of γH2AX level.However, cardiac-specific BRCC36 over-expression significantly decreased the level of γH2AX in the pressure overloaded heart in the transgenic mice , while effectively enhanced myocardial RAD 51 expression, a marker of DNA damage repair.Furthermore, BRCC36 over-expression effectively attenuated TAC-induced cardiac fibro-sis and remodeling in the transgenic mice , compared with the wild type mice .Collectively , the results have suggested that BRCC 36 ef-fectively protected heart

  2. Extracellular high-mobility group box 1 mediates pressure overload-induced cardiac hypertrophy and heart failure.

    Science.gov (United States)

    Zhang, Lei; Liu, Ming; Jiang, Hong; Yu, Ying; Yu, Peng; Tong, Rui; Wu, Jian; Zhang, Shuning; Yao, Kang; Zou, Yunzeng; Ge, Junbo

    2016-03-01

    Inflammation plays a key role in pressure overload-induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High-mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload-induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild-type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin-embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up-regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload-induced cardiac hypertrophy and cardiac dysfunction.

  3. Separating plasticity-induced closure and residual stress contributions to fatigue crack retardation following an overload

    Science.gov (United States)

    Salvati, Enrico; Zhang, Hongjia; Fong, Kai Soon; Song, Xu; Korsunsky, Alexander M.

    2017-01-01

    performing comparison between the two loading conditions (R=0.7 and R=0.1), information was extracted regarding the role of residual stress alone, and then, by subtracting this effect for the R=0.1 sample, for crack closure alone. To enable this analysis, we propose a introducing the concept of equivalent effective stress intensity factor range, ∆ K eq , eff proposed by Walker. Afterwards, the SIF range reduction ratio, β , which represents the "knock down" factor with respect to the steady state growth was assessed. It is in terms of these newly introduced parameters that the magnitude and extent of the overload-induced crack growth rate retardation can be plotted, fitted and decomposed into closure and residual stress effects, respectively. It is concluded that although the residual stress effect is present at all values of the load ratio R, its effect is relatively short-lived, whilst the closure effect that is dominant at low values of R causes longer range retardation.

  4. ω-3 Polyunsaturated fatty acids prevent pressure overload-induced ventricular dilation and decrease in mitochondrial enzymes despite no change in adiponectin

    Directory of Open Access Journals (Sweden)

    O'Shea Karen M

    2010-09-01

    Full Text Available Abstract Background Pathological left ventricular (LV hypertrophy frequently progresses to dilated heart failure with suppressed mitochondrial oxidative capacity. Dietary marine ω-3 polyunsaturated fatty acids (ω-3 PUFA up-regulate adiponectin and prevent LV dilation in rats subjected to pressure overload. This study 1 assessed the effects of ω-3 PUFA on LV dilation and down-regulation of mitochondrial enzymes in response to pressure overload; and 2 evaluated the role of adiponectin in mediating the effects of ω-3 PUFA in heart. Methods Wild type (WT and adiponectin-/- mice underwent transverse aortic constriction (TAC and were fed standard chow ± ω-3 PUFA for 6 weeks. At 6 weeks, echocardiography was performed to assess LV function, mice were terminated, and mitochondrial enzyme activities were evaluated. Results TAC induced similar pathological LV hypertrophy compared to sham mice in both strains on both diets. In WT mice TAC increased LV systolic and diastolic volumes and reduced mitochondrial enzyme activities, which were attenuated by ω-3 PUFA without increasing adiponectin. In contrast, adiponectin-/- mice displayed no increase in LV end diastolic and systolic volumes or decrease in mitochondrial enzymes with TAC, and did not respond to ω-3 PUFA. Conclusion These findings suggest ω-3 PUFA attenuates cardiac pathology in response to pressure overload independent of an elevation in adiponectin.

  5. Resistance training using eccentric overload induces early adaptations in skeletal muscle size.

    Science.gov (United States)

    Norrbrand, Lena; Fluckey, James D; Pozzo, Marco; Tesch, Per A

    2008-02-01

    Fifteen healthy men performed a 5-week training program comprising four sets of seven unilateral, coupled concentric-eccentric knee extensions 2-3 times weekly. While eight men were assigned to training using a weight stack (WS) machine, seven men trained using a flywheel (FW) device, which inherently provides variable resistance and allows for eccentric overload. The design of these apparatuses ensured similar knee extensor muscle use and range of motion. Before and after training, maximal isometric force (MVC) was measured in tasks non-specific to the training modes. Volume of all individual quadriceps muscles was determined by magnetic resonance imaging. Performance across the 12 exercise sessions was measured using the inherent features of the devices. Whereas MVC increased (P hypertrophy evident in FW (6.2%) was not statistically greater than that shown in WS (3.0%), all four individual quadriceps muscles of FW showed increased (P exercise supporting the idea that eccentric overload offers a potent stimuli essential to optimize the benefits of resistance exercise.

  6. Loss of Bmx nonreceptor tyrosine kinase prevents pressure overload-induced cardiac hypertrophy.

    Science.gov (United States)

    Mitchell-Jordan, Scherise A; Holopainen, Tanja; Ren, Shuxun; Wang, Sujing; Warburton, Sarah; Zhang, Michael J; Alitalo, Kari; Wang, Yibin; Vondriska, Thomas M

    2008-12-05

    Bmx nonreceptor tyrosine kinase has an established role in endothelial and lymphocyte signaling; however, its role in the heart is unknown. To determine whether Bmx participates in cardiac growth, we subjected mice deficient in the molecule (Bmx knockout mice) to transverse aortic constriction (TAC). In comparison with wild-type mice, which progressively developed massive hypertrophy following TAC, Bmx knockout mice were resistant to TAC-induced cardiac growth at the organ and cell level. Loss of Bmx preserved cardiac ejection fraction and decreased mortality following TAC. These findings are the first to demonstrate a necessary role for the Tec family of tyrosine kinases in the heart and reveal a novel regulator (Bmx) of pressure overload-induced hypertrophic growth.

  7. Carnosine and neocuproine as neutralizing agents for copper overload-induced damages in cultured human cells.

    Science.gov (United States)

    Arnal, Nathalie; de Alaniz, María J T; Marra, Carlos A

    2011-07-15

    Copper is dangerous when it is present in excess, mainly because it can participate in the Fenton reaction, which produces radical species. As a consequence of copper pollution, people are involuntarily exposed to a copper overload under sub-clinical and sub-symptomatological conditions, which may be very difficult to detect. Thus, we investigated (i) the possible use of the chelator molecules carnosine and neocuproine to prevent the Cu overload-induced damage on cellular lipids and proteins, as tested in human cell culture systems, and (ii) the differential response of these two chelating agents in relation to their protective action, and the type of copper ion involved in the process, by using two types of human cultured cells (HepG2 and A-549). Cu treatment clearly enhanced (pcomplexing agent for Cu(II), but also an effective antioxidant that can dismutate superoxide radicals, scavenge hydroxyl radicals and neutralize TBARS formation. Carnosine should be investigated in more detail in order to establish its putative utility as an agent to prevent copper-associated damages in biological systems.

  8. [Preliminary Study of Necroptosis in Cardiac Hypertrophy Induced by Pressure Overload].

    Science.gov (United States)

    Zhao, Mingyue; Qin, Yupei; Lu, Lihui; Tang, Xiaoju; Wu, Wenchao; Fu, Hua; Liu, Xiaojing

    2015-06-01

    The aim of this study was to observe whether necroptosis is involved in the process of cardiac hypertrophy induced by pressure overload. SD rats underwent transverse abdominal aortic constriction (TAC) operation for establishing cardiac hypertrophy model. The structure and function of the left ventricle of rats were evaluated via echocardiography, left ventricular mass index, the expression of markers of cardiac hypertrophy and histological detection. Real-time PCR and Western blot were used to measure the gene and protein expression of receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3, the necroptosis markers) respectively. Four weeks after TAC operation, rat model for cardiac hypertrophy was established. The experimental data showed that the gene and protein expressions of RIPK1 and RIPK3 in the rat heart hypertrophic tissues after TAC for 4 weeks were increased significantly compared with those in the sham group. HE staining showed cardiomyocytes injury and hypertrophy in the hearts of TAC rat models. By transmission electron microscope, we observed that mitochondria of cardiomyocytes were damaged seriously in the TAC models. Treatment with losartan used, the selective antagonist of angiotensin II type I receptor could improve the cardiac function of TAC rats. Moreover, losartan treatment decreased the expression of RIPK1 and RIPK3 in heart tissues of TAC rats. The results suggest that necroptosis occurrs in the process of cardiac hypertrophy with pressure overload, and losartan could alleviate the cardiac hypertrophy and inhibit necroptosis.

  9. Exercise Training Prevents Cardiovascular Derangements Induced by Fructose Overload in Developing Rats.

    Science.gov (United States)

    Farah, Daniela; Nunes, Jonas; Sartori, Michelle; Dias, Danielle da Silva; Sirvente, Raquel; Silva, Maikon B; Fiorino, Patrícia; Morris, Mariana; Llesuy, Susana; Farah, Vera; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2016-01-01

    The risks of chronic diseases associated with the increasing consumption of fructose-laden foods are amplified by the lack of regular physical activity and have become a serious public health issue worldwide. Moreover, childhood eating habits are strongly related to metabolic syndrome in adults. Thus, we aimed to investigate the preventive role of exercise training undertaken concurrently with a high fructose diet on cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in male rats after weaning. Male Wistar rats were divided into 4 groups (n = 8/group): Sedentary control (SC), Trained control (TC), Sedentary Fructose (SF) and Trained Fructose (TF). Training was performed on a treadmill (8 weeks, 40-60% of maximum exercise test). Evaluations of cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in plasma and in left ventricle (LV) were performed. Chronic fructose overload induced glucose intolerance and an increase in white adipose tissue (WAT) weight, in myocardial performance index (MPI) (SF:0.42±0.04 vs. SC:0.24±0.05) and in arterial pressure (SF:122±3 vs. SC:113±1 mmHg) associated with increased cardiac and vascular sympathetic modulation. Fructose also induced unfavorable changes in oxidative stress profile (plasmatic protein oxidation- SF:3.30±0.09 vs. SC:1.45±0.08 nmol/mg prot; and LV total antioxidant capacity (TRAP)- SF: 2.5±0.5 vs. SC:12.7±1.7 uM trolox). The TF group showed reduced WAT, glucose intolerance, MPI (0.35±0.04), arterial pressure (118±2mmHg), sympathetic modulation, plasmatic protein oxidation and increased TRAP when compared to SF group. Therefore, our findings indicate that cardiometabolic dysfunctions induced by fructose overload early in life may be prevented by moderate aerobic exercise training.

  10. Chronic cardiac pressure overload induces adrenal medulla hypertrophy and increased catecholamine synthesis.

    Science.gov (United States)

    Schneider, Johanna; Lother, Achim; Hein, Lutz; Gilsbach, Ralf

    2011-06-01

    Increased activity of the sympathetic system is an important feature contributing to the pathogenesis and progression of chronic heart failure. While the mechanisms and consequences of enhanced norepinephrine release from sympathetic nerves have been intensely studied, the role of the adrenal gland in the development of cardiac hypertrophy and progression of heart failure is less well known. Thus, the aim of the present study was to determine the effect of chronic cardiac pressure overload in mice on adrenal medulla structure and function. Cardiac hypertrophy was induced in wild-type mice by transverse aortic constriction (TAC) for 8 weeks. After TAC, the degree of cardiac hypertrophy correlated significantly with adrenal weight and adrenal catecholamine storage. In the medulla, TAC caused an increase in chromaffin cell size but did not result in chromaffin cell proliferation. Ablation of chromaffin α(2C)-adrenoceptors did not affect adrenal weight or epinephrine synthesis. However, unilateral denervation of the adrenal gland completely prevented adrenal hypertrophy and increased catecholamine synthesis. Transcriptome analysis of microdissected adrenal medulla identified 483 up- and 231 downregulated, well-annotated genes after TAC. Among these genes, G protein-coupled receptor kinases 2 (Grk2) and 6 and phenylethanolamine N-methyltransferase (Pnmt) were significantly upregulated by TAC. In vitro, acetylcholine-induced Pnmt and Grk2 expression as well as enhanced epinephrine content was prevented by inhibition of nicotinic acetylcholine receptors and Ca(2+)/calmodulin-dependent signaling. Thus, activation of preganglionic sympathetic nerves innervating the adrenal medulla plays an essential role in inducing adrenal hypertrophy, enhanced catecholamine synthesis and induction of Grk2 expression after cardiac pressure overload.

  11. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis.

    Science.gov (United States)

    Muthuramu, Ilayaraja; Amin, Ruhul; Postnov, Andrey; Mishra, Mudit; Jacobs, Frank; Gheysens, Olivier; Van Veldhoven, Paul P; De Geest, Bart

    2017-07-18

    Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher (p oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64) during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold (p oil mice than in standard chow mice. Myocardial capillary density (p oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold (p oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower (p oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy.

  12. Effect of ECR on the Expression of Tau from the Brain of the Mice Induced by Overload Aluminum Salt

    Institute of Scientific and Technical Information of China (English)

    YANGSu-Fen; WUZhong-Jun; YANGZheng-Qin; LIYu; WuQin; ZHOUQi-Xin; SHIJing-Shan

    2004-01-01

    Aim: To study the effect of Ecdysterone (ECR) on the expression of Tau from the cerebral cortice and hippocampus and behaviors in passive avoidance reaction and spatial discrimination of the mice induced by overload aluminum salt.Methods Fourty-five NIH mice were randomly divided into five groups, the control group, the model group, the treated

  13. Modifications in nitric oxide and superoxide anion metabolism induced by fructose overload in rat heart are prevented by (-)-epicatechin.

    Science.gov (United States)

    Calabró, Valeria; Piotrkowski, Barbara; Fischerman, Laura; Vazquez Prieto, Marcela A; Galleano, Monica; Fraga, Cesar G

    2016-04-01

    Fructose overload promotes functional and metabolic derangements in humans and in animal experimental models. Evidence suggests that dietary flavonoids have the ability to prevent/attenuate the development of metabolic diseases. In this work we investigated the effects of (-)-epicatechin on the modifications induced by fructose overload in the rat heart in terms of nitric oxide and superoxide metabolism. Male Sprague Dawley rats received 10% (w/v) fructose in the drinking water for 8 weeks, with or without (-)-epicatechin (20 mg per kg body weight per day) in the rat chow diet. These conditions of fructose overload did not lead to overt manifestations of heart hypertrophy or tissue remodeling. However, biochemical and molecular changes were observed and could represent the onset of functional alterations. (-)-Epicatechin prevented a compromised NO bioavailability and the development of oxidative stress produced by fructose overload essentially acting on superoxide anion metabolism. In this line, the increase in superoxide anion production, the overexpression of NOX2 subunit p47phox and of NOX4, the decrease in superoxide dismutase activity, and the higher oxidized/reduced glutathione ratio installed by fructose overload were absent in the rats receiving (-)-epicatechin. These results support the hypothesis that diets rich in (-)-epicatechin could prevent the onset and progression of heart dysfunctions associated with metabolic alterations.

  14. Glucose Transporter 4 (GLUT4) is Not Necessary for Overload-Induced Glucose Uptake or Hypertrophic Growth in Mouse Skeletal Muscle.

    Science.gov (United States)

    McMillin, Shawna L; Schmidt, Denise L; Kahn, Barbara B; Witczak, Carol A

    2017-03-09

    Glucose transporter 4 (GLUT4) is necessary for acute insulin- and contraction-induced skeletal muscle glucose uptake, but its role in chronic muscle loading (overload)-induced glucose uptake is unknown. Our goal was to determine if GLUT4 is required for overload-induced glucose uptake. Overload was induced in mouse plantaris muscle by unilateral synergist ablation. After 5 days, muscle weights and ex vivo [(3)H]-2-deoxy-D-glucose uptake were assessed. Overload-induced muscle glucose uptake and hypertrophic growth were not impaired in muscle-specific GLUT4 knockout mice, demonstrating that GLUT4 is not necessary for these processes. To assess which transporter(s) mediate overload-induced glucose uptake, chemical inhibitors were utilized. The facilitative GLUT inhibitor, cytochalasin B, but not the sodium-dependent glucose-co-transport inhibitor, phloridzin, prevented overload-induced uptake demonstrating that GLUT(s) mediate this effect. To assess which GLUT, hexose competition experiments were performed. Overload-induced [(3)H]-2-deoxy-D-glucose uptake was not inhibited by D-fructose, demonstrating that the fructose-transporting GLUT2, GLUT5, GLUT8, and GLUT12, do not mediate this effect. To assess additional GLUTs, immunoblots were performed. Overload increased GLUT1, GLUT3, GLUT6 and GLUT10 protein levels 2- to 5-fold. Collectively, these results demonstrate that GLUT4 is not necessary for overload-induced muscle glucose uptake or hypertrophic growth, and suggest that GLUT1, GLUT3, GLUT6 and/or GLUT10 mediate overload-induced glucose uptake.

  15. Session Initiation Protocol (SIP) Server Overload Control: Design and Evaluation

    CERN Document Server

    Shen, Charles; Nahum, Erich

    2008-01-01

    A Session Initiation Protocol (SIP) server may be overloaded by emergency-induced call volume, ``American Idol'' style flash crowd effects or denial of service attacks. The SIP server overload problem is interesting especially because the costs of serving or rejecting a SIP session can be similar. For this reason, the built-in SIP overload control mechanism based on generating rejection messages cannot prevent the server from entering congestion collapse under heavy load. The SIP overload problem calls for a pushback control solution in which the potentially overloaded receiving server may notify its upstream sending servers to have them send only the amount of load within the receiving server's processing capacity. The pushback framework can be achieved by either a rate-based feedback or a window-based feedback. The centerpiece of the feedback mechanism is the algorithm used to generate load regulation information. We propose three new window-based feedback algorithms and evaluate them together with two exis...

  16. MicroRNA-145 suppresses ROS-induced Ca{sup 2+} overload of cardiomyocytes by targeting CaMKIIδ

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Min-Ji [Cardiovascular Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Jang, Jin-Kyung [College of Pharmacy, Sookmyung Women’s University, 52 HyoChangWon-Gil, Yongsan-ku, Seoul 140-742 (Korea, Republic of); Ham, Onju; Song, Byeong-Wook; Lee, Se-Yeon [Cardiovascular Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Lee, Chang Yeon; Park, Jun-Hee [Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, 50 Yonsei-ro, Seodamun-gu, Seoul 120-759 (Korea, Republic of); Lee, Jiyun; Seo, Hyang-Hee [Cardiovascular Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Choi, Eunhyun [Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Jeon, Woo-min [Department of Animal Resource, Sahmyook University, Seoul 139-742 (Korea, Republic of); Hwang, Hye Jin [Cardiovascular Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Shin, Hyun-Taek [College of Pharmacy, Sookmyung Women’s University, 52 HyoChangWon-Gil, Yongsan-ku, Seoul 140-742 (Korea, Republic of); and others

    2013-06-14

    Highlights: •CaMKIIδ mediates H{sub 2}O{sub 2}-induced Ca{sup 2+} overload in cardiomyocytes. •miR-145 can inhibit Ca{sup 2+} overload. •A luciferase assay confirms that miR-145 functions as a CaMKIIδ-targeting miRNA. •Overexpression of miR-145 regulates CaMKIIδ-related genes and ameliorates apoptosis. -- Abstract: A change in intracellular free calcium (Ca{sup 2+}) is a common signaling mechanism of reperfusion-induced cardiomyocyte death. Calcium/calmodulin dependent protein kinase II (CaMKII) is a critical regulator of Ca{sup 2+} signaling and mediates signaling pathways responsible for functions in the heart including hypertrophy, apoptosis, arrhythmia, and heart disease. MicroRNAs (miRNA) are involved in the regulation of cell response, including survival, proliferation, apoptosis, and development. However, the roles of miRNAs in Ca{sup 2+}-mediated apoptosis of cardiomyocytes are uncertain. Here, we determined the potential role of miRNA in the regulation of CaMKII dependent apoptosis and explored its underlying mechanism. To determine the potential roles of miRNAs in H{sub 2}O{sub 2}-mediated Ca{sup 2+} overload, we selected and tested 6 putative miRNAs that targeted CaMKIIδ, and showed that miR-145 represses CaMKIIδ protein expression and Ca{sup 2+} overload. We confirmed CaMKIIδ as a direct downstream target of miR-145. Furthermore, miR-145 regulates Ca{sup 2+}-related signals and ameliorates apoptosis. This study demonstrates that miR-145 regulates reactive oxygen species (ROS)-induced Ca{sup 2+} overload in cardiomyocytes. Thus, miR-145 affects ROS-mediated gene regulation and cellular injury responses.

  17. Efferent pathways in sodium overload-induced renal vasodilation in rats.

    Science.gov (United States)

    Amaral, Nathalia O; de Oliveira, Thiago S; Naves, Lara M; Filgueira, Fernando P; Ferreira-Neto, Marcos L; Schoorlemmer, Gerard H M; de Castro, Carlos H; Freiria-Oliveira, André H; Xavier, Carlos H; Colugnati, Diego B; Rosa, Daniel A; Blanch, Graziela T; Borges, Clayton L; Soares, Célia M A; Reis, Angela A S; Cravo, Sergio L; Pedrino, Gustavo R

    2014-01-01

    Hypernatremia stimulates the secretion of oxytocin (OT), but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g) were anesthetized with sodium thiopental (40 mg. kg(-1), i.v.). A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP) and renal blood flow (RBF). Renal vascular conductance (RVC) was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6), OT infusion (0.03 µg • kg(-1), i.v.) induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR) reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1) b.wt., i.v.) was infused over 60 s. In sham rats (n = 6), hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1) • h(-1), i.v.; n = 7) and renal denervation (RX) reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7) completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively), whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

  18. Efferent pathways in sodium overload-induced renal vasodilation in rats.

    Directory of Open Access Journals (Sweden)

    Nathalia O Amaral

    Full Text Available Hypernatremia stimulates the secretion of oxytocin (OT, but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g were anesthetized with sodium thiopental (40 mg. kg(-1, i.v.. A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP and renal blood flow (RBF. Renal vascular conductance (RVC was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6, OT infusion (0.03 µg • kg(-1, i.v. induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1 b.wt., i.v. was infused over 60 s. In sham rats (n = 6, hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1 • h(-1, i.v.; n = 7 and renal denervation (RX reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7 completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively, whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

  19. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis

    Directory of Open Access Journals (Sweden)

    Ilayaraja Muthuramu

    2017-07-01

    Full Text Available Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC in C57BL/6 mice. Mortality rate after TAC was higher (p < 0.05 in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64 during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold (p < 0.01 higher in coconut oil mice than in standard chow mice. Myocardial capillary density (p < 0.001 was decreased, interstitial fibrosis was 1.88-fold (p < 0.001 higher, and systolic and diastolic function was worse in coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold (p < 0.001 higher in coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower (p < 0.05 in coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy.

  20. The Study on Intramyocardial Calcium Overload and Apoptosis Induced by Cosackievirus B3

    Institute of Scientific and Technical Information of China (English)

    HU; Xiufen; WANG; Hongwei; LU; Weiwei; DONG; Yongsui; CHENG; Peixuan

    2001-01-01

    The isolated cardiac myocytes of rats were immediately infected by cosackievirus B3(CVB3) to investigate the effects of such procedure on the cell cycle, apoptosis and intracellular ionized calcium (Ca2+ i) of cardiac myocytes. Newborn Balb/c murine cardiac myocytes were cultivated,then infected by CVB3. Intracellular Ca2+ i was measured by flow cytometer. The calcium in the medium for culturing cardiac myocytes was detected by using atom absorb spectrum test. It was found that CVB3 could markedly inhibit the differentiation and proliferation of the infected cardiac myocytes and induce the apoptosis. The intracellular Ca2+ i level in the infected group was significantly higher than in the control group (P<0. 01). The calcium concentration in the medium for culturing cardiac myocytes in the infected group was significantly lower than in the control group (P<0.05). It was suggested that the apoptosis and intracellular calcium overload of the CVB3-affected cardiac myocytes are likely to play an important role in the pathogenesis of viral myocarditis.

  1. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Ji Zhang

    Full Text Available Fatty acid binding protein 4 (FABP4 is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG mice using α myosin-heavy chain (α-MHC promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.

  2. Effect of miR-29a inhibition on ventricular hypertrophy induced by pressure overload.

    Science.gov (United States)

    Han, Wei; Han, Yancong; Liu, Xiaokun; Shang, Xiaoming

    2015-03-01

    To investigate whether inhibition of miR-29a functioning prevents the hypertension-induced ventricular hypertrophy and fibrosis. Patients diagnosed with hypertension and left ventricular hypertrophy were recruited for the study. Serum levels of miR-29a were determined by RT-PCR. Levels of serum matrix metalloproteinase-9 (MMP-9), collagen type I and III (PINP and PIIINP) were determined by double-antibody enzyme-linked immunosorbent assay. Mouse model of transverse aortic constriction (TAC) was established. 7 days after surgery, TAC mice were injected intraperitoneally with antagomir miR-29a or vehicle once a day for 3 days. After 4 weeks of surgery, animals were sacrificed and cross-sections of the hearts were stained and evaluated for hypertrophy and fibrosis. The expression of the protein markers of hypertrophy and fibrosis was determined by immunoblotting. The serum level of miR-29a in hypertensive patients with left ventricular hypertrophy was significantly higher than those in patients with hypertension alone (p hypertrophy of cardiomyocytes and the expression of ANP and β-MHC, the hypertrophy indices. Also, the ventricular fibrosis and expression of the marker proteins were blocked in antagomir treated mice. The inhibition of miR-29a was found to be effective in improving the ventricular remodeling and hypertrophy caused by pressure overload.

  3. Lead Poisoning Disturbs Oligodendrocytes Differentiation Involved in Decreased Expression of NCX3 Inducing Intracellular Calcium Overload

    Directory of Open Access Journals (Sweden)

    Teng Ma

    2015-08-01

    Full Text Available Lead (Pb poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 μM inhibits OLs precursor cells (OPCs differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3 mRNA expression, one of the major means of calcium (Ca2+ extrusion at the plasma membrane during OPCs differentiation. Also addition of KB-R7943, NCX3 inhibitor, to simulate Pb toxicity, resulted in decreased myelin basic protein (MBP expression and cell branching. Ca2+ response trace with Pb and KB-R7943 treatment did not drop down in the same recovery time as the control, which elevated intracellular Ca2+ concentration reducing MBP expression. In contrast, over-expression of NCX3 in Pb exposed OPCs displayed significant increase MBP fluorescence signal in positive regions and CNPase expression, which recovered OPCs differentiation to counterbalance Pb toxicity. In conclusion, Pb exposure disturbs OLs differentiation via affecting the function of NCX3 by inducing intracellular calcium overload.

  4. Extracellular Volume Overload and Increased Vasoconstriction in Patients With Recurrent Intradialytic Hypertension

    Directory of Open Access Journals (Sweden)

    Peter Noel Van Buren

    2016-11-01

    Full Text Available Background/Aims: Intradialytic hypertension (IH occurs frequently in some hemodialysis patients and increases mortality risk. We simultaneously compared pre-dialysis, post-dialysis and changes in extracellular volume and hemodynamics in recurrent IH patients and controls. Methods: We performed a case-control study among prevalent hemodialysis patients with recurrent IH and hypertensive hemodialysis controls. We used bioimpedance spectroscopy and impedance cardiography to compare pre-dialysis, post-dialysis, and intradialytic change in total body water (TBW and extracellular water (ECW, as well as cardiac index (CI and total peripheral resistance index (TPRI. Results: The ECW/TBW was 0.453 (0.05 pre-dialysis and 0.427 (0.04 post-dialysis in controls vs. 0.478 (0.03 and 0.461 (0.03 in IH patients (p=0.01 post-dialysis. The ECW/TBW change was -0.027 (0.03 in controls and -0.013 (0.02 in IH patients (p=0.1. In controls, pre- and post-dialysis TPRI were 3254 (994 and 2469 (529 dynes/sec/cm2/m2 vs. 2983 (747 and 3408 (980 dynes/sec/cm2/m2 in IH patients (p=0.002 post-dialysis. There were between-group differences in TPRI change (0=0.0001, but not CI (p=0.09. Conclusions: Recurrent intradialytic hypertension is associated with higher post-dialysis extracellular volume and TPRI. Intradialytic TPRI surges account for the vasoconstrictive state post-dialysis, but intradialytic fluid shifts may contribute to post-hemodialysis volume expansion.

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

    Directory of Open Access Journals (Sweden)

    Sundaravadivel Balasubramanian

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

  6. The transcriptional coactivator PGC-1α is dispensable for chronic overload-induced skeletal muscle hypertrophy and metabolic remodeling.

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    Pérez-Schindler, Joaquín; Summermatter, Serge; Santos, Gesa; Zorzato, Francesco; Handschin, Christoph

    2013-12-10

    Skeletal muscle mass loss and dysfunction have been linked to many diseases. Conversely, resistance exercise, mainly by activating mammalian target of rapamycin complex 1 (mTORC1), promotes skeletal muscle hypertrophy and exerts several therapeutic effects. Moreover, mTORC1, along with peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), regulates skeletal muscle metabolism. However, it is unclear whether PGC-1α is required for skeletal muscle adaptations after overload. Here we show that although chronic overload of skeletal muscle via synergist ablation (SA) strongly induces hypertrophy and a switch toward a slow-contractile phenotype, these effects were independent of PGC-1α. In fact, SA down-regulated PGC-1α expression and led to a repression of energy metabolism. Interestingly, however, PGC-1α deletion preserved peak force after SA. Taken together, our data suggest that PGC-1α is not involved in skeletal muscle remodeling induced by SA.

  7. Improvement of cardiac function and reversal of gap junction remodeling by Neuregulin-1β in volume-overloaded rats with heart failure

    Institute of Scientific and Technical Information of China (English)

    Xue-Hui Wang; Xiao-Zhen Zhuo; Ya-Juan Ni; Min Gong; Ting-Zhong Wang; Qun Lu; Ai-Qun Ma

    2012-01-01

    Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 μg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.

  8. Comparison of Volume Overload with Cycler-Assisted versus Continuous Ambulatory Peritoneal Dialysis

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    Davison, Sara N.; Jhangri, Gian S.; Jindal, Kailash; Pannu, Neesh

    2009-01-01

    Background and objectives: Cycler-assisted peritoneal dialysis (CCPD) has been associated with decreased sodium removal compared with continuous ambulatory peritoneal dialysis (CAPD) as a result of peritoneal sodium sieving during the short dwells that are associated with CCPD. This may have adverse consequences for management of extracellular fluid volume (ECFV). This study compared ECFV in patients who received CAPD or CCPD; CCPD dwell times were maximized by limiting the number of exchanges, and the use of icodextrin for the long daytime dwells was widespread. Design, setting, participants, & measurements: This was an observational, cross-sectional study of 158 prevalent patients (90 CAPD, 68 CCPD). Demographic data, blood work, and 24-h dialysate and urine samples were collected from all participants between January 2004 and July 2006. They subsequently underwent assessment of ECFV by multifrequency bioimpedance spectroscopy analysis. Multivariate analysis was used to determine the relationship between peritoneal dialysis modality and ECFV. Potential cofounders including age, comorbidity, time on dialysis, residual renal function, and icodextrin use were identified a priori. Results: There were no differences in BP, use of antihypertensive medications, or the presence of peripheral edema between CAPD and CCPD patients. Similarly, there was no difference in the ratio of ECFV to total body water between CAPD (51.8%) and CCPD (51.9%) patients (P = 0.929). Conclusions: There is no difference in BP, sodium removal, or volume control in patients who use a contemporary approach to CCPD that uses fewer night cycles and liberalizes the use of icodextrin when compared with CAPD. PMID:19406971

  9. Cytosolic CARP promotes angiotensin II- or pressure overload-induced cardiomyocyte hypertrophy through calcineurin accumulation.

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    Ci Chen

    Full Text Available The gene ankyrin repeat domain 1 (Ankrd1 is an enigmatic gene and may exert pleiotropic function dependent on its expression level, subcellular localization and even types of pathological stress, but it remains unclear how these factors influence the fate of cardiomyocytes. Here we attempted to investigate the role of CARP on cardiomyocyte hypertrophy. In neonatal rat ventricular cardiomyocytes (NRVCs, angiotensin II (Ang II increased the expression of both calpain 1 and CARP, and also induced cytosolic translocation of CARP, which was abrogated by a calpain inhibitor. In the presence of Ang-II in NRVCs, infection with a recombinant adenovirus containing rat Ankrd1 cDNA (Ad-Ankrd1 enhanced myocyte hypertrophy, the upregulation of atrial natriuretic peptide and β-myosin heavy chain genes and calcineurin proteins as well as nuclear translocation of nuclear factor of activated T cells. Cyclosporin A attenuated Ad-Ankrd1-enhanced cardiomyocyte hypertrophy. Intra-myocardial injection of Ad-Ankrd1 in mice with transverse aortic constriction (TAC markedly increased the cytosolic CARP level, the heart weight/body weight ratio, while short hairpin RNA targeting Ankrd1 inhibited TAC-induced hypertrophy. The expression of calcineurin was also significantly increased in Ad-Ankrd1-infected TAC mice. Olmesartan (an Ang II receptor antagonist prevented the upregulation of CARP in both Ang II-stimulated NRVCs and hearts with pressure overload. These findings indicate that overexpression of Ankrd1 exacerbates pathological cardiac remodeling through the enhancement of cytosolic translocation of CARP and upregulation of calcineurin.

  10. Expression of renal cubilin and its potential role in tubulointerstitial inflammation induced by albumin overload

    Institute of Scientific and Technical Information of China (English)

    Jurong YANG; Yani HE; Haiying SHEN; Hanlu DING; Kailong LI; Huiming WANG

    2008-01-01

    Sustained proteinuria is an independent risk factor leading to kidney fibrosis and end-stage renal fail-ure. Over-reabsorption of filtered proteins, notably albu-min, has been proved to trigger interstitial inflammation and fibrosis in proteinuric renal disease. Cubilin, an endo-cytic receptor expressed on the renal tubular brush bor-der, is responsible for albumin reabsorption in physiologic condition. However, little is known about whether it is required for activation of tubular cells induced by albu-min overload. In this work, we investigated the change of cubilin expression and its potential role in albumin-induced up-regulation of chemokines synthesis in vivo and in vitro. Twenty-six patients with nephrotic syndrome were enrolled in this study. Proximal tubule uptake of albumin, expression of apical membrane cubilin and infiltrating cells in kidney interstitium were determined by immunocytochemistry. In vitro, the transcription of cubilin in HK2 cells after exposure to albumin was ana-lyzed by real-time PCR. Endocytosis of albumin in HK2 cells was examined by fluorescent microscope. The influ-ence of inhibition of cubilin on albumin-induced expres-sions of monocyte chemoattractant protein 1 (MCP-1) and regulated upon activation normal T-cell expressed and secreted (RANTES) was investigated by Western blot. The intensity of luminal cubilin and tubular accu-mulation of albumin were significantly increased in nephrotic kidneys. The expression of MCP-1 and RANTES was up-regulated, and there were spatial rela-tionships in localization between these chemokines and cubilin as well as intracellular albumin in kidney tissues. Infiltration of CD-3 and ED-1-positive cells was predom-inant in tubulointerstitial areas displaying signs of increases of cubilin expression and albumin accumula-tion. In vitro, the transcription of cubilin mRNA in HK2 cells was enhanced after 24 h exposure to albumin in a dose-dependent manner. Inhibition of endocytosis of albumin by antisense

  11. EGCG inhibits cardiomyocyte apoptosis in pressure overload-induced cardiac hypertrophy and protects cardiomyocytes from oxidative stress in rats

    Institute of Scientific and Technical Information of China (English)

    Rui SHENG; Zhen-lun GU; Mei-lin XIE; Wen-xuan ZHOU; Ci-yi GUO

    2007-01-01

    Aim: To investigate the effects of epigallocatechin gallate (EGCG) on pressure overload and hydrogen peroxide (H2O2) induced cardiac myocyte apoptosis. Methods: Cardiac hypertrophy was established in rats by abdominal aortic constriction. EGCG 25, 50 and 100 mg/kg were administered intragastrically (ig). Cultured newborn rat cardiomyocytes were preincubated with EGCG, and oxidative stress injury was induced by H2O2. Results: In cardiac hypertrophy induced by AC in rats, relative to the model group, EGCG 25, 50 and 100 mg/kg ig for 6weeks dose-dependently reduced systolic blood pressure (SBP) and heart weight indices, decreased malondialdehyde (MDA) content, and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, both in serum and in the myocardium. Also, treatment with EGCG 50 and 100 mg/kg markedly improved cardiac structure and inhibited fibrosis in HE and van Gieson (VG) stain, and reduced apoptotic myocytes in the hypertrophic myocardium detected by terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Inthe Western blot analysis, EGCG significantly inhibited pressure overload-inducedp53 increase and bcl-2 decrease. In H2O2-induced cardiomyocyte injury, when preincubated with myocytes for 6-48 h, EGCG 12.5-200 mg/L increased cell viability determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. EGCG also attenuated H2O2-induced lactate dehydrogenase (LDH) release and MDA formation. Meanwhile, EGCG 50 and 100 mg/L significantly inhibited the cardiomyocyte apoptotic rate in flow cytometry. Conclusion: EGCG inhibits cardiac myocyte apoptosis and oxidative stress in pressure overload in-duced cardiac hypertrophy. Also, EGCG prevented cardiomyocyte apoptosis from oxidative stress in vitro. The mechanism might be related to the inhibitory effects of EGCG on p53 induction and bcl-2 decrease.

  12. Baseline muscle mass is a poor predictor of functional overload-induced gain in the mouse model

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    Audrius Kilikevicius

    2016-11-01

    Full Text Available Genetic background contributes substantially to individual variability in muscle mass. Muscle hypertrophy in response to resistance training can also vary extensively. However, it is less clear if muscle mass at baseline is predictive of the hypertrophic response.The aim of this study was to examine the effect of genetic background on variability in muscle mass at baseline and in the adaptive response of the mouse fast- and slow-twitch muscles to overload. Males of eight laboratory mouse strains: C57BL/6J (B6, n=17, BALB/cByJ (n=7, DBA/2J (D2, n=12, B6.A-(rs3676616-D10Utsw1/Kjn (B6.A, n=9, C57BL/6J-Chr10A/J/NaJ (B6.A10, n=8, BEH+/+ (n=11, BEH (n=12 and DUHi (n=12, were studied. Compensatory growth of soleus and plantaris muscles was triggered by a 4-week overload induced by synergist unilateral ablation. Muscle weight in the control leg (baseline varied from 5.2±07 mg soleus and 11.4±1.3 mg plantaris in D2 mice to 18.0±1.7 mg soleus in DUHi and 43.7±2.6 mg plantaris in BEH (p<0.001 for both muscles. In addition, soleus in the B6.A10 strain was ~40% larger (p<0.001 compared to the B6. Functional overload increased muscle weight, however, the extent of gain was strain-dependent for both soleus (p<0.01 and plantaris (p<0.02 even after accounting for the baseline differences. For the soleus muscle, the BEH strain emerged as the least responsive, with a 1.3-fold increase, compared to a 1.7-fold gain in the most responsive D2 strain, and there was no difference in the gain between the B6.A10 and B6 strains. The BEH strain appeared the least responsive in the gain of plantaris as well, 1.3-fold, compared to ~1.5-fold gain in the remaining strains. We conclude that variation in muscle mass at baseline is not a reliable predictor of that in the overload-induced gain. This suggests that a different set of genes influence variability in muscle mass acquired in the process of normal development, growth and maintenance, and in the process of adaptive

  13. Amelioration of iron overload-induced liver toxicity by a potent antioxidant and iron chelator, Emblica officinalis Gaertn.

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    Sarkar, Rhitajit; Hazra, Bibhabasu; Mandal, Nripendranath

    2015-07-01

    In liver, the major site of iron storage, iron overload is associated with oxidative damage of protein, lipid, and DNA and causes protein oxidation, lipid peroxidation, and rupture of hepatocytes, leading to cell death. Serum ferritin and liver iron content are the main forecasters of moderate to severe iron overload in the liver. The sequels of excess iron deposition in the liver are fibrosis and enhanced levels of serum enzymes and bilirubin markers. Emblica officinalis (EO) fruit extract was found efficient in lessening intraperitoneally injected iron dextran-induced liver toxicity in Swiss albino mice. Mice administered with different doses of 70% methanol extract of EO (50, 100, and 200 mg kg(-1) body weight) showed significant decrease in liver iron, serum ferritin, and serum enzyme levels, along with the decrease in lipid peroxidation, protein oxidation, and collagen content. The activity was further supported by its considerable iron chelation with half-maximal inhibitory concentration of 70.24 ± 2.74 μg ml(-1) and the protection on ferrous ion-mediated DNA breakdown with 50% protection ([P]50) of 1.04 ± 0.01 μg ml(-1). Simultaneously, the extract effectively induced the antioxidant enzyme levels and also exhibited the potential activity of reductive release of ferritin iron. These findings suggest that the EO extract may be used as a potent drug for the treatment of pathological sequences arisen in the iron overload-induced liver damage. © The Author(s) 2013.

  14. Apamin-Sensitive Small Conductance Calcium-Activated Potassium Channels were Negatively Regulated by Captopril in Volume-Overload Heart Failure Rats.

    Science.gov (United States)

    Hongyuan, Bai; Xin, Dong; Jingwen, Zhang; Li, Gao; Yajuan, Ni

    2016-08-01

    In heart failure (HF), the malignant arrhythmias occur frequently; a study demonstrated that upregulation of I KAS resulted in recurrent spontaneous ventricular fibrillation in HF. However, the regulation of SK channels was poorly understood. The activation of SK channels depended on [Ca(2+)]i and PP2A; studies suggested that angiotensin II can regulate them. So, we hypothesized that in HF, the excess of angiotensin may regulate the SK channels and result in the remodeling of SK channels. To test the hypothesis, we used volume-overload-induced HF rat model, treated with captopril, performed whole-cell patch clamp to record apamin-sensitive currents (I KAS), and I-V curve was studied. The sensitivity of I KAS to [Ca(2+)]i was also explored by setting various [Ca(2+)]i (10, 100, 500, 900, 1000, and 10,000 nM), and the steady-state Ca(2+) response of I KAS was attained and performed Hill fitting with the equation (y = 1/[1 + (EC50/x) (n) ]). Immunofluorescent staining, real-time PCR, Western blot were also carried out to furtherly investigate the underlying molecular mechanisms of the regulation. Captopril significantly decreased the mean density of I KAS when [Ca(2+)]i was 500, 900, 1000, and 10000 nM. The Hill fitting showed significantly different EC50 values and the Hill coefficients and showed captopril significantly shifted rightward the steady-state Ca(2+) response of I KAS. The results of real-time PCR and Western blot demonstrated captopril decreased the mRNA and protein expression of SK3 channels. Captopril significantly downregulated the sensitivity of SK channels to [Ca(2+)]i and the SK3 channels expression in HF, and reversed the SK channels remodeling.

  15. Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2

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    Petrak Jiri

    2011-11-01

    Full Text Available Abstract Background Chronic hemodynamic overloading leads to heart failure (HF due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto-caval fistula (ACF and sham-operated rats harvested at the advanced, decompensated stage of HF. Methods We analyzed control and failing myocardium employing iTRAQ labeling, two-dimensional peptide separation combining peptide IEF and nano-HPLC with MALDI-MS/MS. For the transcriptomic analysis we employed Illumina RatRef-12v1 Expression BeadChip. Results In the proteomic analysis we identified 2030 myocardial proteins, of which 66 proteins were differentially expressed. The mRNA expression analysis identified 851 differentially expressed mRNAs. Conclusions The differentially expressed proteins confirm a switch in the substrate preference from fatty acids to other sources in the failing heart. Failing hearts showed downregulation of the major calcium transporters SERCA2 and ryanodine receptor 2 and altered expression of creatine kinases. Decreased expression of two NADPH producing proteins suggests a decreased redox reserve. Overexpression of annexins supports their possible potential as HF biomarkers. Most importantly, among the most up-regulated proteins in ACF hearts were monoamine oxidase A and transglutaminase 2 that are both potential attractive targets of low molecular weight inhibitors in future HF therapy.

  16. The protection of meloxicam against chronic aluminium overload-induced liver injury in rats.

    Science.gov (United States)

    Yang, Yang; He, Qin; Wang, Hong; Hu, Xinyue; Luo, Ying; Liang, Guojuan; Kuang, Shengnan; Mai, Shaoshan; Ma, Jie; Tian, Xiaoyan; Chen, Qi; Yang, Junqing

    2017-04-04

    The present study was designed to observe the protective effect and mechanisms of meloxicam on liver injury caused by chronic aluminium exposure in rats. The histopathology was detected by hematoxylin-eosin staining. The levels of prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases-2, prostaglandin E2 receptors and protein kinase A were measured by western blotting and immunohistochemistry. Our experimental results showed that aluminium overload significantly damaged the liver. Aluminium also significantly increased the expressions of cyclooxygenases-2, prostaglandin E2, cyclic adenosine monophosphate, protein kinase A and the prostaglandin E2 receptors (EP1,2,4) and the levels of inflammation and oxidative stress, while significantly decreased the EP3 expression in liver. The administration of meloxicam significantly improved the impairment of liver. The contents of prostaglandin E2 and cyclic adenosine monophosphate were significantly decreased by administration of meloxicam. The administration of meloxicam also significantly decreased the expressions of cyclooxygenases-2 and protein kinase A and the levels of inflammation and oxidative stress, while significantly increased the EP1,2,3,4 expressions in rat liver. Our results suggested that the imbalance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway is involved in the injury of chronic aluminium-overload rat liver. The protective mechanism of meloxicam on aluminium-overload liver injury is attributed to reconstruct the balance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway.

  17. Epigenetic switch at atp2a2 and myh7 gene promoters in pressure overload-induced heart failure.

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    Tiziana Angrisano

    Full Text Available Re-induction of fetal genes and/or re-expression of postnatal genes represent hallmarks of pathological cardiac remodeling, and are considered important in the progression of the normal heart towards heart failure (HF. Whether epigenetic modifications are involved in these processes is currently under investigation. Here we hypothesized that histone chromatin modifications may underlie changes in the gene expression program during pressure overload-induced HF. We evaluated chromatin marks at the promoter regions of the sarcoplasmic reticulum Ca2+ATPase (SERCA-2A and β-myosin-heavy chain (β-MHC genes (Atp2a2 and Myh7, respectively in murine hearts after one or eight weeks of pressure overload induced by transverse aortic constriction (TAC. As expected, all TAC hearts displayed a significant reduction in SERCA-2A and a significant induction of β-MHC mRNA levels. Interestingly, opposite histone H3 modifications were identified in the promoter regions of these genes after TAC, including H3 dimethylation (me2 at lysine (K 4 (H3K4me2 and K9 (H3K9me2, H3 trimethylation (me3 at K27 (H3K27me3 and dimethylation (me2 at K36 (H3K36me2. Consistently, a significant reduction of lysine-specific demethylase KDM2A could be found after eight weeks of TAC at the Atp2a2 promoter. Moreover, opposite changes in the recruitment of DNA methylation machinery components (DNA methyltransferases DNMT1 and DNMT3b, and methyl CpG binding protein 2 MeCp2 were found at the Atp2a2 or Myh7 promoters after TAC. Taken together, these results suggest that epigenetic modifications may underlie gene expression reprogramming in the adult murine heart under conditions of pressure overload, and might be involved in the progression of the normal heart towards HF.

  18. Assessment of the role of α-lipoic acid against the oxidative stress of induced iron overload

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    Yasser F. Ali

    2015-01-01

    Full Text Available This work was aimed to study the protective role of α-lipoic acid against the oxidative damage of induced iron overload. Iron (Fe overload is a complication of the treatment, by chronic transfusion, of a number of genetic diseases associated with inadequate red cell production (anemias and of other genetic diseases that lead to excessive iron absorption from the diet. Male rats were injected ip with 5 mg/kg body weight ferrous sulfate for 50 days. The animals were injected ip with α-lipoic acid 20 mg per kg body weight for 21 days. Serum iron, Total Iron Binding Capacity (TIBC, Malonyldialdehyde (MDA, Electron paramagnetic resonance (EPR spectroscopy, UV-visible absorption spectrum of hemoglobin and osmotic fragility were studied. Results showed significant increase in serum iron, total iron binding capacity, and malonyldialdehyde levels in iron-loaded rats. Treatment with lipoic acid (LA resulted in decreasing serum iron and TIBC levels by 47%and 29% respectively. At the same time the lipoic acid decreased the level of the MDA in liver, brain and plasma by 54%, 42% and 74% respectively. Also LA diminished the effect of iron-induced free radicals on erythrocyte membrane integrity; it decreased the elevated average osmotic fragility and decreased the elevated rate of hemolysis. Results from UV-visible spectrophotometric measurement of hemoglobin revealed that no oxidative changes of hemoglobin occurred in iron-loaded rats. EPR spectra showed increased in non-heme ferric ions Fe+3 and free radicals in iron-loaded rats. Whereas the injection of the lipoic acid leads to decreased in such toxic result. In conclusion, these observations suggested that lipoic acid might be a beneficial antioxidant that can be effective for limiting damage from oxidative stress of iron overload.

  19. 5-Lypoxygenase products are involved in renal tubulointerstitial injury induced by albumin overload in proximal tubules in mice.

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    Sharon Schilling Landgraf

    Full Text Available The role of albumin overload in proximal tubules (PT in the development of tubulointerstitial injury and, consequently, in the progression of renal disease has become more relevant in recent years. Despite the importance of leukotrienes (LTs in renal disease, little is known about their role in tubulointerstitial injury. The aim of the present work was to investigate the possible role of LTs on tubulointerstitial injury induced by albumin overload. An animal model of tubulointerstitial injury challenged by bovine serum albumin was developed in SV129 mice (wild-type and 5-lipoxygenase-deficient mice (5-LO(-/-. The changes in glomerular morphology and nestin expression observed in wild-type mice subjected to kidney insult were also observed in 5-LO(-/- mice. The levels of urinary protein observed in the 5-LO(-/- mice subjected or not to kidney insult were lower than those observed in respective wild-type mice. Furthermore, the increase in lactate dehydrogenase activity, a marker of tubule damage, observed in wild-type mice subjected to kidney insult did not occur in 5-LO(-/- mice. LTB4 and LTD4, 5-LO products, decreased the uptake of albumin in LLC-PK1 cells, a well-characterized porcine PT cell line. This effect correlated with activation of protein kinase C and inhibition of protein kinase B. The level of proinflammatory cytokines, tumor necrosis factor-α and interleukin (IL-6, increased in mice subjected to kidney insult but this effect was not modified in 5-LO(-/- mice. However, 5-LO(-/- mice subjected to kidney insult presented lower macrophage infiltration and higher levels of IL-10 than wild-type mice. Our results reveal that LTs have an important role in tubulointerstitial disease induced by albumin overload.

  20. 5-Lypoxygenase products are involved in renal tubulointerstitial injury induced by albumin overload in proximal tubules in mice.

    Science.gov (United States)

    Landgraf, Sharon Schilling; Silva, Leandro Souza; Peruchetti, Diogo Barros; Sirtoli, Gabriela Modenesi; Moraes-Santos, Felipe; Portella, Viviane Gomes; Silva-Filho, João Luiz; Pinheiro, Carla Silva; Abreu, Thiago Pereira; Takiya, Christina Maeda; Benjamin, Claudia Farias; Pinheiro, Ana Acacia Sá; Canetti, Claudio; Caruso-Neves, Celso

    2014-01-01

    The role of albumin overload in proximal tubules (PT) in the development of tubulointerstitial injury and, consequently, in the progression of renal disease has become more relevant in recent years. Despite the importance of leukotrienes (LTs) in renal disease, little is known about their role in tubulointerstitial injury. The aim of the present work was to investigate the possible role of LTs on tubulointerstitial injury induced by albumin overload. An animal model of tubulointerstitial injury challenged by bovine serum albumin was developed in SV129 mice (wild-type) and 5-lipoxygenase-deficient mice (5-LO(-/-)). The changes in glomerular morphology and nestin expression observed in wild-type mice subjected to kidney insult were also observed in 5-LO(-/-) mice. The levels of urinary protein observed in the 5-LO(-/-) mice subjected or not to kidney insult were lower than those observed in respective wild-type mice. Furthermore, the increase in lactate dehydrogenase activity, a marker of tubule damage, observed in wild-type mice subjected to kidney insult did not occur in 5-LO(-/-) mice. LTB4 and LTD4, 5-LO products, decreased the uptake of albumin in LLC-PK1 cells, a well-characterized porcine PT cell line. This effect correlated with activation of protein kinase C and inhibition of protein kinase B. The level of proinflammatory cytokines, tumor necrosis factor-α and interleukin (IL)-6, increased in mice subjected to kidney insult but this effect was not modified in 5-LO(-/-) mice. However, 5-LO(-/-) mice subjected to kidney insult presented lower macrophage infiltration and higher levels of IL-10 than wild-type mice. Our results reveal that LTs have an important role in tubulointerstitial disease induced by albumin overload.

  1. Yes-Associated Protein is up-regulated by mechanical overload and is sufficient to induce skeletal muscle hypertrophy.

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    Goodman, Craig A; Dietz, Jason M; Jacobs, Brittany L; McNally, Rachel M; You, Jae-Sung; Hornberger, Troy A

    2015-06-04

    Mechanically-induced skeletal muscle growth is regulated by mammalian/mechanistic target of rapamycin complex 1 (mTORC1). Yes-Associated Protein (YAP) is a mechanically-sensitive, and growth-related, transcriptional co-activator that can regulate mTORC1. Here we show that, in skeletal muscle, mechanical overload promotes an increase in YAP expression; however, the time course of YAP expression is markedly different from that of mTORC1 activation. We also show that the overexpression of YAP induces hypertrophy via an mTORC1-independent mechanism. Finally, we provide preliminary evidence of possible mediators of YAP-induced hypertrophy (e.g. increased MyoD and c-Myc expression, and decreased Smad2/3 activity and muscle ring finger 1 (MuRF1) expression).

  2. Triptolide attenuates pressure overload-induced myocardial remodeling in mice via the inhibition of NLRP3 inflammasome expression.

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    Li, Rujun; Lu, Kuiying; Wang, Yao; Chen, Mingxing; Zhang, Fengyu; Shen, Hui; Yao, Deshan; Gong, Kaizheng; Zhang, Zhengang

    2017-02-12

    Triptolide is the predominant active component of the Chinese herb Tripterygium wilfordii Hook F (TwHF) that has been widely used to treat several chronic inflammatory diseases due to its immunosuppressive, anti-inflammatory, and anti-proliferative properties. In the present study, we elucidated the cardioprotective effects of triptolide against cardiac dysfunction and myocardial remodeling in chronic pressure-overloaded hearts. Furthermore, the potential mechanisms of triptolide were investigated. For this purpose, C57/BL6 mice were anesthetized and subjected to transverse aortic constriction (TAC) or sham operation. Six weeks after the operation, all mice were randomly divided into 4 groups: sham-operated with vehicle group, TAC with vehicle group, and TAC with triptolide (20 or 100 μg/kg/day intraperitoneal injection) groups. Our data showed that the levels of NLRP3 inflammasome were significantly increased in the TAC group and were associated with increased inflammatory mediators and profibrotic factor production, resulting in myocardial fibrosis, cardiomyocyte hypertrophy, and impaired cardiac function. Triptolide treatment attenuated TAC-induced myocardial remodeling, improved cardiac diastolic and systolic function, inhibited the NLRP3 inflammasome and downstream inflammatory mediators (IL-1β, IL-18, MCP-1, VCAM-1), activated the profibrotic TGF-β1 pathway, and suppressed macrophage infiltration in a dose-dependent manner. Our study demonstrated that the protective effect of triptolide against pressure overload in the heart may act by inhibiting the NLRP3 inflammasome-induced inflammatory response and activating the profibrotic pathway.

  3. Long Non-Coding RNA Malat-1 Is Dispensable during Pressure Overload-Induced Cardiac Remodeling and Failure in Mice.

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    Tim Peters

    Full Text Available Long non-coding RNAs (lncRNAs are a class of RNA molecules with diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases and in particular heart failure is still in its infancy. The exceptionally well conserved nuclear lncRNA Metastasis associated in lung adenocarcinoma transcript 1 (Malat-1 is a regulator of mRNA splicing and highly expressed in the heart. Malat-1 modulates hypoxia-induced vessel growth, activates ERK/MAPK signaling, and scavenges the anti-hypertrophic microRNA-133. We therefore hypothesized that Malat-1 may act as regulator of cardiac hypertrophy and failure during cardiac pressure overload induced by thoracic aortic constriction (TAC in mice.Absence of Malat-1 did not affect cardiac hypertrophy upon pressure overload: Heart weight to tibia length ratio significantly increased in WT mice (sham: 5.78±0.55, TAC 9.79±1.82 g/mm; p<0.001 but to a similar extend also in Malat-1 knockout (KO mice (sham: 6.21±1.12, TAC 8.91±1.74 g/mm; p<0.01 with no significant difference between genotypes. As expected, TAC significantly reduced left ventricular fractional shortening in WT (sham: 38.81±6.53%, TAC: 23.14±11.99%; p<0.01 but to a comparable degree also in KO mice (sham: 37.01±4.19%, TAC: 25.98±9.75%; p<0.05. Histological hallmarks of myocardial remodeling, such as cardiomyocyte hypertrophy, increased interstitial fibrosis, reduced capillary density, and immune cell infiltration, did not differ significantly between WT and KO mice after TAC. In line, the absence of Malat-1 did not significantly affect angiotensin II-induced cardiac hypertrophy, dysfunction, and overall remodeling. Above that, pressure overload by TAC significantly induced mRNA levels of the hypertrophy marker genes Nppa, Nppb and Acta1, to a similar extend in both genotypes. Alternative splicing of Ndrg2 after TAC was apparent in WT (isoform ratio

  4. Goal-Directed Fluid Therapy Using Stroke Volume Variation Does Not Result in Pulmonary Fluid Overload in Thoracic Surgery Requiring One-Lung Ventilation

    Directory of Open Access Journals (Sweden)

    Sebastian Haas

    2012-01-01

    Full Text Available Background. Goal-directed fluid therapy (GDT guided by functional parameters of preload, such as stroke volume variation (SVV, seems to optimize hemodynamics and possibly improves clinical outcome. However, this strategy is believed to be rather fluid aggressive, and, furthermore, during surgery requiring thoracotomy, the ability of SVV to predict volume responsiveness has raised some controversy. So far it is not known whether GDT is associated with pulmonary fluid overload and a deleterious reduction in pulmonary function in thoracic surgery requiring one-lung-ventilation (OLV. Therefore, we assessed the perioperative course of extravascular lung water index (EVLWI and paO2/FiO2-ratio during and after thoracic surgery requiring lateral thoracotomy and OLV to evaluate the hypothesis that fluid therapy guided by SVV results in pulmonary fluid overload. Methods. A total of 27 patients (group T were enrolled in this prospective study with 11 patients undergoing lung surgery (group L and 16 patients undergoing esophagectomy (group E. Goal-directed fluid management was guided by SVV (SVV 0.05 in EVLWI during the observation period (BL: 7.8 ± 2.5, 24postop: 8.1 ± 2.4 mL/kg. A subgroup analysis for group L and group E also did not reveal significant changes of EVLWI. The paO2/FiO2-ratio decreased significantly during the observation period (group L: BL: 462 ± 140, OLVterm15: 338 ± 112 mmHg; group E: BL: 389 ± 101, 24postop: 303 ± 74 mmHg but remained >300 mmHg except during OLV. Conclusions. SVV-guided fluid management in thoracic surgery requiring lateral thoracotomy and one-lung ventilation does not result in pulmonary fluid overload. Although oxygenation was reduced, pulmonary function remained within a clinically acceptable range.

  5. Changes and Significance of Matrix Metalloproteinase and Its Tissue Inhibitor in Plasma and Cardiac Muscle of Rats with Chronic Cardiac Failure Induced by Volume Overload%基质金属蛋白酶及其抑制物在容量过负荷致慢性心力衰竭大鼠血浆及心肌组织中的变化及意义

    Institute of Scientific and Technical Information of China (English)

    张超英; 李晓惠; 伏瑾; 崔小岱

    2011-01-01

    目的 观察容量过负荷致慢性心力衰竭大鼠血浆及心肌组织基质金属蛋白酶-8(MMP-8)及其抑制物-1(TIMP-1)的表达变化,探讨其在慢性心力衰竭发病中的病理生理作用.方法 雄性SD大鼠17只,随机分为分流组(n=9)和对照组(n=8).分流组通过腹主动脉下腔静脉穿刺术建立容量过负荷致慢性充血性心力衰竭动物模型,对照组大鼠除不做穿刺外,余操作过程同分流组.分别测定2组大鼠心功能及血流动力学指标,检测血浆MMP-8及TIMP-1水平,实时荧光定量PCR测定大鼠左心室、右心室MMP-8 mRNA、TIMP-1 mRNA的表达.结果 术后8周,分流组大鼠左心室收缩压、左心室舒张压、左心室内压差、左心室内压最大上升速率及最大下降速率较对照组明显降低(Pa<0.05,0.01);左心室舒张末压较对照组明显升高(P<0.05).分流组大鼠血浆MMP-8、TIMP-1水平均较对照组明显升高(Pa<0.05).与对照组相比,分流组大鼠左心室心肌组织MMP-8 mRNA及左、右心室心肌组织TIMP-1 mRNA水平均有升高趋势,右心室MMP-8 mRNA水平有下降趋势,但2组比较差异均无统计学意义(Pa>0.05);左心室和右心室心肌组织中MMP-8/TIMP-1明显降低,右心室较左心室下降更明显.结论 MMP-8与TIMP-1通过影响胶原代谢,参与容量过负荷致慢性充血性心力衰竭的病理生理过程.%Objective To observe the changes of matrix metalloproteinase - 8 ( MMP - 8 ) and its tissue inhibitors of metallopreteinase -1 ( TIMP - 1 ) in plasma and cardiac muscle of rats with chronic cardiac failure induced by volume overload, and to explore those roles in physiology of chronic cardiac failure. Methods Seventeen male SD rats were randomly divided into 2 groups as follows:9 shunt rat models were established by abdominal aorta and inferior vena cava shunt operation and 8 rats after sham operation served as controls. Hemodynamic and echocardiographic measurements were obtained 8 weeks

  6. Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    Qian-yi Peng; Yu Zou; Li-Na Zhang; Mei-Lin Ai; Wei Liu; Yu-Hang Ai

    2016-01-01

    Background:Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality.Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI,and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization.The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown.This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI.Methods:Septic rat models were established by cecal ligation and puncture (CLP).Rats were divided into the sham group,the CLP group,and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group.Nicotinamide adenine dinucleotide (NAD+),cADPR,CD38,and intracellular Ca2+ levels in the lung tissues were measured at 6,12,24,and 48 h after CLP surgery.Lung histologic injury,tumor necrosis factor (TNF)-α,malondialdehyde (MDA) levels,and superoxide dismutase (SOD) activities were measured.Results:NAD+,cADPR,CD38,and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery.Treatment with 8-Br-cADPR,a specific inhibitor of cADPR,significantly reduced intracellular Ca2+ levels (P =0.007),attenuated lung histological injury (P =0.023),reduced TNF-α and MDA levels (P < 0.001 and P =0.002,respectively) and recovered SOD activity (P =0.031) in the lungs of septic rats.Conclusions:The CD38/cADPR pathway is activated in the lungs of septic rats,and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI.

  7. Regulation of L-type inward calcium channel activity by captopril and angiotensin II via the phosphatidyl inositol 3-kinase pathway in cardiomyocytes from volume-overload hypertrophied rat hearts

    Science.gov (United States)

    Alvin, Zikiar; Laurence, Graham G.; Coleman, Bernell R; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E.

    2011-01-01

    Heart failure can be caused by pro-hypertrophic humoral factors such as angiotensin II (Ang II), which regulates protein kinase activities. The intermingled responses of these kinases lead to the early compensated cardiac hypertrophy, but later to the uncompensated phase of heart failure. We have shown that although beneficial, cardiac hypertrophy is associated with modifications in ion channels that are mainly mediated through mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3K) activation. This study evaluates the control of L-type Ca2+ current (ICa,L) by the Ang II/PI3K pathway in hypertrophied ventricular myocytes from volume-overload rats using the perforated patch-clamp technique. To assess activation of the ICa,L in cardiomyocytes, voltages of 350 ms in 10 mV increments from a holding potential of −85 mV were applied to cardiocytes, with a pre-pulse to −45 mV for 300 ms. Volume overload-induced hypertrophy reduces ICa,L, whereas addition of Ang II alleviates the hypertrophic-induced decrease in a PI3K-dependent manner. Acute administration of Ang II (10−6 mol/L) to normal adult cardiomyocytes had no effect; however, captopril reduced their basal ICa,L. In parallel, captopril regressed the hypertrophy and inverted the Ang II effect on ICa,L seemingly through a PI3K upstream effector. Thus, it seems that regression of cardiac hypertrophy by captopril improved ICa,L partly through PI3K. PMID:21423294

  8. Brain Natriuretic Peptide and Body Fluid Composition in Patients with Chronic Kidney Disease: A Cross-Sectional Study to Evaluate the Relationship between Volume Overload and Malnutrition.

    Science.gov (United States)

    Ohashi, Yasushi; Saito, Akinobu; Yamazaki, Keisuke; Tai, Reibin; Matsukiyo, Tatsuru; Aikawa, Atsushi; Sakai, Ken

    2016-08-01

    Fluid volume overload occurs in chronic kidney disease (CKD), leading to the compensatory release of natriuretic peptides. However, the elevated cardiac peptides may also be associated with malnutrition as well as volume overload. Body fluid composition was measured in 147 patients with CKD between 2009 and 2015, and its relationship to brain natriuretic peptide (BNP) levels was examined. Body fluid composition was separated into three components: (a) a water-free mass consisting of muscle, fat, and minerals; (b) intracellular water (ICW) content, and (c) extracellular water (ECW) content. Excess fluid mass was calculated using Chamney's formula. The measured BNP levels in the tertile groups were 10.9 ± 5.4, 36.3 ± 12.5, and 393 ± 542 pg/ml, respectively. Patients in a higher log-transformed BNP level tertile were more likely to be older, to have a higher frequency of cardiac comorbidities, pulse pressure, C-reactive protein levels, and proteinuria, and to have lower serum sodium, kidney function, and serum albumin (p < 0.05). In body fluid composition, decreased body mass was significantly associated with the ECW-to-ICW ratio in relation to the downward ICW slope (r = -0.235, p = 0.004) and was strongly correlated with excess fluid mass (r = -0.701, p < 0.001). The ECW-to-ICW ratio and excess fluid mass was independently associated with the BNP levels. Fluid volume imbalance between intra- and extracellular water regulated by decreased cell mass was independently associated with BNP levels, which may explain the reserve capacity for fluid accumulation in patients with CKD.

  9. Differential effects of chronic overload-induced muscle hypertrophy on mTOR and MAPK signaling pathways in adult and aged rats

    Science.gov (United States)

    We examined activation of the mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) signaling pathways in adult (Y; 6 mo old; n = 16) and aged (O; 30 mo old; n = 16) male rats (Fischer 344 x Brown Norway) subjected to chronic overload-induced muscle hypertrophy of the plan...

  10. Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice

    Energy Technology Data Exchange (ETDEWEB)

    Guenancia, Charles [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Li, Na [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Hachet, Olivier [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Rigal, Eve [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cottin, Yves [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Dutartre, Patrick; Rochette, Luc [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Vergely, Catherine, E-mail: cvergely@u-bourgogne.fr [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France)

    2015-04-15

    Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran–iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran–iron (15 mg/kg) for 3 weeks (D0–D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6 mg/kg of DOX. While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran–iron (125–1000 μg/mL) in combination with DOX, paradoxically limited cytotoxicity in H9c2 and increased it in EMT-6. In mice, IO alone resulted in cardiac hypertrophy (+ 22%) and up-regulation of brain natriuretic peptide and β-myosin heavy-chain (β-MHC) expression, as well as an increase in cardiac nitro-oxidative stress revealed by electron spin resonance spectroscopy. In DOX-treated mice, there was a significant decrease in left-ventricular ejection fraction (LVEF) and an up-regulation of cardiac β-MHC and atrial natriuretic peptide (ANP) expression. However, prior IO did not exacerbate the DOX-induced fall in LVEF and there was no increase in ANP expression. IO did not impair the capacity of DOX to decrease cancer cell viability and could even prevent some aspects of DOX cardiotoxicity in cardiomyocytes and in mice. - Highlights: • The effects of iron on cardiomyocytes were opposite to those on cancer cell lines. • In our model, iron overload did not potentiate anthracycline cardiotoxicity. • Chronic oxidative stress induced by iron could mitigate doxorubicin cardiotoxicity. • The role of iron in

  11. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

    Directory of Open Access Journals (Sweden)

    Natalia Nuño-Lámbarri

    2016-01-01

    Full Text Available Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

  12. ZNF307 (Zinc Finger Protein 307) Acts as a Negative Regulator of Pressure Overload-Induced Cardiac Hypertrophy.

    Science.gov (United States)

    Yu, Chang-Jiang; Liang, Chen; Li, Yu-Xia; Hu, Qing-Qing; Zheng, Wei-Wan; Niu, Na; Yang, Xu; Wang, Zi-Rui; Yu, Xiao-Di; Zhang, Bao-Long; Song, Bin-Lin; Zhang, Zhi-Ren

    2017-04-01

    Pathological cardiac hypertrophy is a key risk factor for heart failure. We found that the protein expression levels of the ZNF307 (zinc finger protein 307) were significantly increased in heart samples from both human patients with dilated cardiomyopathy and mice subjected to aortic banding. Therefore, we aimed to elucidate the role of ZNF307 in the development of cardiac hypertrophy and to explore the signal transduction events that mediate the effect of ZNF307 on cardiac hypertrophy, using cardiac-specific ZNF307 transgenic (ZNF307-TG) mice and ZNF307 global knockout (ZNF307-KO) mice. The results showed that the deletion of ZNF307 potentiated aortic banding-induced pathological cardiac hypertrophy, fibrosis, and cardiac dysfunction; however, the aortic banding-induced cardiac hypertrophic phenotype was dramatically diminished by ZNF307 overexpression in mouse heart. Mechanistically, the antihypertrophic effects mediated by ZNF307 in response to pathological stimuli were associated with the direct inactivation of NF-κB (nuclear factor-κB) signaling and blockade of the nuclear translocation of NF-κB subunit p65. Furthermore, the overexpression of a degradation-resistant mutant of IκBα (IκBα(S32A/S36A)) reversed the exacerbation of cardiac hypertrophy, fibrosis, and dysfunction shown in aortic banding-treated ZNF307-KO mice. In conclusion, our findings demonstrate that ZNF307 ameliorates pressure overload-induced cardiac hypertrophy by inhibiting the activity of NF-κB-signaling pathway. © 2017 American Heart Association, Inc.

  13. Chronic effects of palmitate overload on nutrient-induced insulin secretion and autocrine signalling in pancreatic MIN6 beta cells.

    Science.gov (United States)

    Watson, Maria L; Macrae, Katherine; Marley, Anna E; Hundal, Harinder S

    2011-01-01

    Sustained exposure of pancreatic β cells to an increase in saturated fatty acids induces pleiotropic effects on β-cell function, including a reduction in stimulus-induced insulin secretion. The objective of this study was to investigate the effects of chronic over supply of palmitate upon glucose- and amino acid-stimulated insulin secretion (GSIS and AASIS, respectively) and autocrine-dependent insulin signalling with particular focus on the importance of ceramide, ERK and CaMKII signalling. GSIS and AASIS were both stimulated by >7-fold resulting in autocrine-dependent activation of protein kinase B (PKB, also known as Akt). Insulin release was dependent upon nutrient-induced activation of calcium/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) as their pharmacological inhibition suppressed GSIS/AASIS significantly. Chronic (48 h, 0.4 mM) palmitate treatment blunted glucose/AA-induced activation of CaMKII and ERK and caused a concomitant reduction (~75%) in GSIS/AASIS and autocrine-dependent activation of PKB. This inhibition could not be attributed to enhanced mitochondrial fatty acid uptake/oxidation or ceramide synthesis, which were unaffected by palmitate. In contrast, diacylglycerol synthesis was elevated suggesting increased palmitate esterification rather than oxidation may contribute to impaired stimulus-secretion coupling. Consistent with this, 2-bromopalmitate, a non-oxidisable palmitate analogue, inhibited GSIS as effectively as palmitate. Our results exclude changes in ceramide content or mitochondrial fatty acid handling as factors initiating palmitate-induced defects in insulin release from MIN6 β cells, but suggest that reduced CaMKII and ERK activation associated with palmitate overload may contribute to impaired stimulus-induced insulin secretion.

  14. Chronic effects of palmitate overload on nutrient-induced insulin secretion and autocrine signalling in pancreatic MIN6 beta cells.

    Directory of Open Access Journals (Sweden)

    Maria L Watson

    Full Text Available BACKGROUND: Sustained exposure of pancreatic β cells to an increase in saturated fatty acids induces pleiotropic effects on β-cell function, including a reduction in stimulus-induced insulin secretion. The objective of this study was to investigate the effects of chronic over supply of palmitate upon glucose- and amino acid-stimulated insulin secretion (GSIS and AASIS, respectively and autocrine-dependent insulin signalling with particular focus on the importance of ceramide, ERK and CaMKII signalling. PRINCIPAL FINDINGS: GSIS and AASIS were both stimulated by >7-fold resulting in autocrine-dependent activation of protein kinase B (PKB, also known as Akt. Insulin release was dependent upon nutrient-induced activation of calcium/calmodulin-dependent protein kinase II (CaMKII and extracellular signal-regulated kinase (ERK as their pharmacological inhibition suppressed GSIS/AASIS significantly. Chronic (48 h, 0.4 mM palmitate treatment blunted glucose/AA-induced activation of CaMKII and ERK and caused a concomitant reduction (~75% in GSIS/AASIS and autocrine-dependent activation of PKB. This inhibition could not be attributed to enhanced mitochondrial fatty acid uptake/oxidation or ceramide synthesis, which were unaffected by palmitate. In contrast, diacylglycerol synthesis was elevated suggesting increased palmitate esterification rather than oxidation may contribute to impaired stimulus-secretion coupling. Consistent with this, 2-bromopalmitate, a non-oxidisable palmitate analogue, inhibited GSIS as effectively as palmitate. CONCLUSIONS: Our results exclude changes in ceramide content or mitochondrial fatty acid handling as factors initiating palmitate-induced defects in insulin release from MIN6 β cells, but suggest that reduced CaMKII and ERK activation associated with palmitate overload may contribute to impaired stimulus-induced insulin secretion.

  15. Inositol hexa phosphoric acid (phytic acid), a nutraceuticals, attenuates iron-induced oxidative stress and alleviates liver injury in iron overloaded mice.

    Science.gov (United States)

    Bhowmik, Anwesha; Ojha, Durbadal; Goswami, Debayan; Das, Rashmi; Chandra, Nidhi S; Chatterjee, Tapan K; Chakravarty, Amit; Chakravarty, Sudipa; Chattopadhyay, Debprasad

    2017-03-01

    Inositol hexa phosphoric acid (IP6) or Phytic acid, a natural antioxidant of some leguminous plants, known to act as a protective agent for seed storage in plants by suppressing iron catalyzed oxidative process. Following the same mechanism, we have tested the effect of IP6 on iron overloaded in vitro oxidative stress, and studied it's in vivo hepatoprotective ability in iron-dextran (injection)-induced iron overloaded liver injury in mice (intraperitoneal). Our results showed that IP6 had in vitro iron chelation (IC50 38.4μg/ml) activity, with the inhibition of iron-induced lipid peroxidation (IC50 552μg/ml), and deoxyribose sugar degrading hydroxyl radicals (IC50 448.6μg/ml). Oral administration of IP6 (0-200mg/kg) revealed significant decrease in biochemical markers such as serum iron, total iron binding, serum ferritin and serum enzymes. Histopathology of liver stained with hematoxylin-eosin and Prussian blue showed reduced hepatocellular necrosis, ballooning and inflammation, indicating the restoration of normal cellular integrity. Interestingly, the IP6 was found to down-regulate the mRNA expression of tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, and IL-6 in iron overloaded liver tissues. Thus, we provide an insight that IP6, a natural food component, can serve as an iron chelator against iron overload diseases like Thalassemia, and also as a dietary hepatoprotective supplement.

  16. Targeting at SUR2B/Kir6.1 subtype of ATP-sensitive potassium channel opener natakalim improves pressure overload-induced heart failure

    Institute of Scientific and Technical Information of China (English)

    TANG Yuan; LONG Chao-liang; WANG Hai

    2008-01-01

    Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure. Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic banding (AAB) .The effects of natakalim (1,3, 9 mg·kg-1·d-1, 10 weeks) were assessed on myocardial hypertrophy and heart failure, cardiac histology, vasoactive compounds, and gene expression. Isolated working heart and isolated tail artery helical strips were used to examine the influence of natakalim on heart and resistant vessels. Results Ten weeks after the onset of pressure overload, natakalim therapy potently inhibited cardiac hypertrophy and prevented heart failure. Natakalim inhibited the changes of left ventricular haemodynamic parameters, reversed the increase of heart mass index, left ventricular weight index and lung weight index remarkably. Histological examination demonstrated that there were no significant hypertrophy and fibrosis in hearts of pressure overload rat treated with natakalim. Ultrastructural examination of heart revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in natakalim group rats. The content of serum NO and plasma PGI2 was increased, while that of plasma ET-1 and cardiac tissue hydroxyproline, ANP and BNP mRNA was down-regulated in natakalim-treated rats. Natakalim at concentrations ranging from 0.01-100 μM had no effects on isolated working heart derived from Wistar rats; however, natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE. Conclusions These results indicate that natakalim improves heart failure due to pressure overload by activating KATP channel SUR2B/Kir6.1 subtype and reversing endothelial dysfunction.

  17. Non-invasive diagnosis and follow-up of right ventricular overload

    NARCIS (Netherlands)

    Henkens, Ivo Reinier

    2008-01-01

    Right ventricular overload covers a spectrum ranging from volume overload to pressure overload, and often is a combination of these, compromising cardiac function. Part I focuses on right ventricular volume overload in adults with Fallot’s tetralogy corrected in early childhood. We determined whic

  18. The ATP-binding cassette transporter ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response.

    Science.gov (United States)

    Higashikuni, Yasutomi; Sainz, Julie; Nakamura, Kazuto; Takaoka, Minoru; Enomoto, Soichiro; Iwata, Hiroshi; Tanaka, Kimie; Sahara, Makoto; Hirata, Yasunobu; Nagai, Ryozo; Sata, Masataka

    2012-03-01

    ATP-binding cassette transporter subfamily G member 2 (ABCG2), expressed in microvascular endothelial cells in the heart, has been suggested to regulate several tissue defense mechanisms. This study was performed to elucidate its role in pressure overload-induced cardiac hypertrophy. Pressure overload was induced in 8- to 12-week-old wild-type and Abcg2-/- mice by transverse aortic constriction (TAC). Abcg2-/- mice showed exaggerated cardiac hypertrophy and ventricular remodeling after TAC compared with wild-type mice. In the early phase after TAC, functional impairment in angiogenesis and antioxidant response in myocardium was found in Abcg2-/- mice. In vitro experiments demonstrated that ABCG2 regulates transport of glutathione, an important endogenous antioxidant, from microvascular endothelial cells. Besides, glutathione transported from microvascular endothelial cells in ABCG2-dependent manner ameliorated oxidative stress-induced cardiomyocyte hypertrophy. In vivo, glutathione levels in plasma and the heart were increased in wild-type mice but not in Abcg2-/- mice after TAC. Treatment with the superoxide dismutase mimetic ameliorated cardiac hypertrophy in Abcg2-/- mice after TAC to the same extent as that in wild-type mice, although cardiac dysfunction with impaired angiogenesis was observed in Abcg2-/- mice. ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response.

  19. Olmesartan ameliorates pressure overload-induced cardiac remodeling through inhibition of TAK1/p38 signaling in mice.

    Science.gov (United States)

    Wu, Lianpin; Mei, Liqin; Chong, Lin; Huang, Yinqing; Li, Yuechun; Chu, Maoping; Yang, Xiangjun

    2016-01-15

    Many studies have demonstrated the potent effects of ARB administration on heart failure. However, the mechanism of the potent effects of ARB on cardiac remodeling is less well understood. We investigated the role of Olmesartan on the fibrosis and hypertrophy in mouse heart. We employed TAC surgery, a mouse model of chronic cardiac failure. All the mice were separated into three groups: the sham group, TAC group and TAC plus Olmesartan group (given Olmesartan treatment after TAC). We analyzed left ventricle remodeling, and function by echocardiography or pathology. We further detected the level of marker genes involved in fibrosis and hypertrophy and in cultured neonatal rat cardiac fibroblasts and myocytes infected by constitutively active TAK1 and p38MAPK. After TAC, all the mice developed hypertrophy, worse cardiac function and malignant remodeling in left ventricle. Olmesartan improved heart remodeling and function without changing pressure of blood. Moreover, Olmesartan reduced the level of transforming growth factor β activated kinase-1 (TAK1) and phospho-p38MAPK. In neonatal rat cardiac fibroblast cells and cardiomyocytes, Olmesartan also decreased TAK1 and p38MAPK activation triggered by TGFβ1 or AngII. The inhibitory effect of Olmesartan was abrogated by overexpression of constitutively active TAK1 and p38MAPK by adenovirus system. Our results suggest Olmesartan improves heart remodeling and function induced by pressure overload. P38MAPK inactivation attenuated by olmesartan via inhibition of TAK1 pathway plays an important role in the process. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Connective tissue growth factor inhibition attenuates left ventricular remodeling and dysfunction in pressure overload-induced heart failure.

    Science.gov (United States)

    Szabó, Zoltán; Magga, Johanna; Alakoski, Tarja; Ulvila, Johanna; Piuhola, Jarkko; Vainio, Laura; Kivirikko, Kari I; Vuolteenaho, Olli; Ruskoaho, Heikki; Lipson, Kenneth E; Signore, Pierre; Kerkelä, Risto

    2014-06-01

    Connective tissue growth factor (CTGF) is involved in the pathogenesis of various fibrotic disorders. However, its role in the heart is not clear. To investigate the role of CTGF in regulating the development of cardiac fibrosis and heart failure, we subjected mice to thoracic aortic constriction (TAC) or angiotensin II infusion, and antagonized the function of CTGF with CTGF monoclonal antibody (mAb). After 8 weeks of TAC, mice treated with CTGF mAb had significantly better preserved left ventricular (LV) systolic function and reduced LV dilatation compared with mice treated with control immunoglobulin G. CTGF mAb-treated mice exhibited significantly smaller cardiomyocyte cross-sectional area and reduced expression of hypertrophic marker genes. CTGF mAb treatment reduced the TAC-induced production of collagen 1 but did not significantly attenuate TAC-induced accumulation of interstitial fibrosis. Analysis of genes regulating extracellular matrix proteolysis showed decreased expression of plasminogen activator inhibitor-1 and matrix metalloproteinase-2 in mice treated with CTGF mAb. In contrast to TAC, antagonizing the function of CTGF had no effect on LV dysfunction or LV hypertrophy in mice subjected to 4-week angiotensin II infusion. Further analysis showed that angiotensin II-induced expression of hypertrophic marker genes or collagens was not affected by treatment with CTGF mAb. In conclusion, CTGF mAb protects from adverse LV remodeling and LV dysfunction in hearts subjected to pressure overload by TAC. Antagonizing the function of CTGF may offer protection from cardiac end-organ damage in patients with hypertension.

  1. Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress

    Directory of Open Access Journals (Sweden)

    Michel eKINDO

    2012-08-01

    Full Text Available Objective: Increased mechanical stress and contractility characterizes normal left ventricular subendocardium (Endo but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi and whether pressure overload-induced left ventricular hypertrophy (LVH might modulate transmural gradients through increased reactive oxygen species (ROS production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function were determined with echocardiography and catheterization in sham-operated and LVH rats (n=10 for each group. Mitochondrial respiration rates, coupling, content and ROS production were measured in LV Endo and Epi, using saponin-permeabilised fibres, Amplex Red fluorescence and citrate synthase activity.Results: In sham, a transmural respiratory gradient was observed with decreases in endo maximal oxidative capacity (-36.7%, P<0.01 and complex IV activity (-57.4%, P<0.05. Mitochondrial hydrogen peroxide (H2O2 production was similar in both LV layers.Aortic banding induced mild LVH (+31.7% LV mass, associated with normal LV fractional shortening and end diastolic pressure. LVH reduced maximal oxidative capacity (-23.6 and -33.3%, increased mitochondrial H2O2 production (+86.9 and +73.1%, free radical leak (+27.2% and +36.3% and citrate synthase activity (+27.2% and +36.3% in Endo and Epi, respectively.Transmural mitochondrial respiratory chain complex IV activity was reduced in LVH (-57.4 vs –12.2%; P=0.02. Conclusions: Endo mitochondrial respiratory chain complexes activities are reduced compared to LV Epi. Mild LVH impairs mitochondrial oxidative capacity, increases oxidative stress and reduces transmural complex IV activity. Further studies will be helpful to determine whether reduced LV transmural gradient in mitochondrial respiration might be a new marker of a transition from uncomplicated toward complicated LVH.

  2. Hypoglycemic of Cajanus scarabaeoides in glucose overloaded and streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Suman Pattanayak

    2009-06-01

    Full Text Available In light of traditional claim of Cajanus scarabaeoides (L in the treatment of diabetes, we studied the effects of different solvent extracts in normal, glucose over loaded normal and streptozotocin-induced diabetic rats. The methanolic extract (500 mg/kg orally was produce significantly reduce blood glucose level at normal, glucose over loaded normal rats, and streptozotocin-induced diabetic rats 15 days treatment whereas petroleum ether and chloroform extract (500 mg/kg orally did not exhibit any significant effect on three groups of rats. Histopathology studies on pancreas streptozotocin-induced diabetic rats inflammatory changes were detected in pancreatic islets results from selectively destroy of insulin producing β-cells. These changes are inhibited by C. scarabaeoides methanolic extract and gliclazide. The antidiabetic activity of methanolic extract may be due to the presence of flavonoids.

  3. Sophocarpine attenuates the Na(+)-dependent Ca2(+) overload induced by Anemonia sulcata toxin-increased late sodium current in rabbit ventricular myocytes.

    Science.gov (United States)

    Zhang, Shuo; Ma, Ji-Hua; Zhang, Pei-Hua; Luo, An-Tao; Ren, Zhi-Qiang; Kong, Ling-Hao

    2012-10-01

    Many studies indicate that an increase in late sodium current (I(Na.L)) of cardiomyocytes causes intracellular Na overload and subsequently raises the reverse Na/Ca exchanger current (INCX), ultimately resulting in intracellular Ca overload. Therefore, using drugs to inhibit the increased INa.L under various pathological conditions can lower intracellular Ca overload. This study was intended to explore the effect of sophocarpine (SOP) on the increase in INa.L, INCX, calcium transient and contraction in rabbit ventricular myocytes induced by Anemonia sulcata toxin II (ATX II), an opener of sodium channel, with the application of whole-cell patch-clamp techniques, the video-based motion edge detection system, and the intracellular calcium concentration determination system. The results indicate that tetrodotoxin (TTX, 4 μM ) obviously decreased INa.L and INCX enlarged by ATX II (30 nM), and SOP (20, 40, and 80 μM) also inhibited both the parameters concentration dependently in rabbit ventricular myocytes. However, transient sodium current remained unaffected by the above-mentioned concentrations of ATX II, TTX, and SOP. In addition, SOP also reversed diastolic calcium concentration, calcium transient amplitude, and ventricular muscle contractility augmented by ATX II. Its effects were similar to those of TTX, a specific inhibitor of the sodium channel. In conclusion, SOP inhibits INa.L, INCX, diastolic Ca concentration, and contractility in rabbit ventricular myocytes, which suggests that relief of intracellular Ca overload through inhibiting INa.L is likely to become a new therapeutic mechanism of SOP against arrhythmia and myocyte damage associated with intracellular Ca overload.

  4. Aconitine-induced Ca{sup 2+} overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Hu, Jin; Zhang, Qiang; Liu, Bo [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Xu, Hui-bo, E-mail: xhb_6505@163.com [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Sun, Xiao-bo, E-mail: sun_xiaobo163@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China)

    2014-08-15

    Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na{sup +} channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca{sup 2+} in aconitine poisoning. In this study, we explored the importance of pathological Ca{sup 2+} signaling in aconitine poisoning in vitro and in vivo. We found that Ca{sup 2+} overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca{sup 2+} handling proteins demonstrated that aconitine promoted Ca{sup 2+} overload through the expression regulation of Ca{sup 2+} handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca{sup 2+} overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca

  5. Loss of Bmx Non-Receptor Tyrosine Kinase Prevents Pressure Overload-Induced Cardiac Hypertrophy

    OpenAIRE

    2008-01-01

    Bmx non-receptor tyrosine kinase has an established role in endothelial and lymphocyte signaling, however its role in the heart is unknown. To determine whether Bmx participates in cardiac growth, we subjected mice deficient in the molecule (Bmx KO mice) to transverse aortic constriction (TAC). In comparison to WT mice, which progressively developed massive hypertrophy following TAC, Bmx KO mice were resistant to TAC-induced cardiac growth at the organ and cell level. Loss of Bmx preserved ca...

  6. Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance

    OpenAIRE

    Jiwon Kim; Medicherla, Chaitanya B.; Ma, Claudia L.; Attila Feher; Nina Kukar; Alexi Geevarghese; Parag Goyal; Evelyn Horn; Devereux, Richard B; Weinsaft, Jonathan W.

    2016-01-01

    Background Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress. Methods and Results The population comprised patients with RV dysfunction (EF

  7. Combination Treatment With Antihypertensive Agents Enhances the Effect of Qiliqiangxin on Chronic Pressure Overload-induced Cardiac Hypertrophy and Remodeling in Male Mice.

    Science.gov (United States)

    Ye, Yong; Gong, Hui; Wang, Xingxu; Wu, Jian; Wang, Shijun; Yuan, Jie; Yin, Peipei; Jiang, Guoliang; Li, Yang; Ding, Zhiwen; Zhang, Weijing; Zhou, Jingmin; Ge, Junbo; Zou, Yunzeng

    2015-06-01

    We previously showed that Qiliqiangxin (QL) capsules could ameliorate cardiac hypertrophy and remodeling in a mouse model of pressure overload. Here, we compared the effects of QL alone with those of QL combined with the following 3 types of antihypertensive drugs on cardiac remodeling and dysfunction induced by pressure overload for 4 weeks in mice: an angiotensin II type 1 receptor (AT1-R) blocker (ARB), an angiotensin-converting enzyme inhibitor (ACEI), and a β-adrenergic receptor (β-AR) blocker (BB). Adult male mice (C57B/L6) were subjected to either transverse aortic constriction or sham operation for 4 weeks, and the drugs (or saline) were orally administered through gastric tubes. Cardiac function and remodeling were evaluated through echocardiography, catheterization, histology, and analysis of hypertrophic gene expression. Cardiomyocyte apoptosis and autophagy, AT1-R and β1-AR expression, and cell proliferation-related molecules were also examined. Although pressure overload-induced cardiac remodeling and dysfunction, hypertrophic gene reprogramming, AT1-R and β1-AR expression, and ERK phosphorylation were significantly attenuated by QL alone, QL + ARB, QL + ACEI, and QL + BB, the attenuation was stronger in the combination treatment groups. Moreover, apoptosis was reduced to a larger extent by each combination treatment than by QL alone, whereas autophagy was more strongly attenuated by either QL + ARB or QL + ACEI. None of the treatments significantly upregulated ErbB2 or ErbB4 phosphorylation, and none significantly downregulated C/EBPβ expression. Therefore, the effects of QL on chronic pressure overload-induced cardiac remodeling may be significantly increased when QL is combined with an ARB, an ACEI, or a BB.

  8. Salubrinal Alleviates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Endoplasmic Reticulum Stress Pathway

    Science.gov (United States)

    Rani, Shilpa; Sreenivasaiah, Pradeep Kumar; Cho, Chunghee; Kim, Do Han

    2017-01-01

    Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit (p-eIF2)-α, the key signaling process in the ERS pathway. In this study, the effects of salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs). Treatment of TAC-induced mice with salubrinal (0.5 mg·kg−1·day−1) alleviated cardiac hypertrophy and tissue fibrosis. Salubrinal also alleviated hypertrophic growth in endothelin 1 (ET1)-treated NRVMs. Therefore, the present results suggest that salubrinal may be a potentially efficacious drug for treating pathological cardiac remodeling. PMID:28152298

  9. Information overload and data overload in lexicography

    DEFF Research Database (Denmark)

    Tarp, Sven; Gouws, Rufus H.

    2018-01-01

    the often uncritical inclusion of too much data. This paper discusses the general term information overload and its lexicographical counterpart data overload. Different types of data overload are identified and the problems users have when retrieving the necessary information from dictionary articles......Too often online dictionaries still display too many features determined by the restrictions that applied to printed dictionaries. Data overload in dictionary articles can be regarded as one such relic from the past. However, the idea that online dictionaries have unlimited space has furthered...

  10. Velvet antler peptide prevents pressure overload-induced cardiac fibrosis via transforming growth factor (TGF)-β1 pathway inhibition.

    Science.gov (United States)

    Zhao, Lihong; Mi, Yang; Guan, Hongya; Xu, Yan; Mei, Yingwu

    2016-07-15

    Velvet antlers (VAs) are commonly used in traditional Chinese medicine and invigorant and contain many functional components for health promotion. The velvet antler peptide sVAP32 is one of active components in VAs; based on structural study, the sVAP32 interacts with TGF-β1 receptors and disrupts the TGF-β1 pathway. We hypothesized that sVAP32 prevents cardiac fibrosis from pressure overload by blocking TGF-β1 signaling. Sprague-Dawley rats underwent transverse aortic constriction (TAC) or a sham operation. After one month, rats received either sVAP32 (15mg/kg/day) or vehicle for an additional one month. TAC surgery induced significant cardiac dysfunction, fibroblast activation and fibrosis; these effects were improved by treatment with sVAP32. In the heart tissue, TAC remarkably increased the expression of TGF-β1 and connective tissue growth factor (CTGF), reactive oxygen species levels, and the phosphorylation levels of Smad2/3 and extracellular signal-regulated kinases 1/2 (ERK1/2). SVAP32 inhibited the increases in reactive oxygen species levels, CTGF expression and the phosphorylation of Smad2/3 and ERK1/2, but not TGF-β1 expression. In cultured cardiac fibroblasts, angiotensin II (Ang II) had similar effects compared to TAC surgery, such as increases in α-SMA-positive cardiac fibroblasts and collagen synthesis. SVAP32 eliminated these effects by disrupting TGF-β1 binding to its receptors and blocking Ang II/TGF-β1 downstream signaling. These results demonstrated that sVAP32 has anti-fibrotic effects by blocking the TGF-β1 pathway in cardiac fibroblasts.

  11. Cardiac-Specific PID1 Overexpression Enhances Pressure Overload-Induced Cardiac Hypertrophy in Mice

    Directory of Open Access Journals (Sweden)

    Yaoqiu Liu

    2015-03-01

    Full Text Available Background/Aims: PID1 was originally described as an insulin sensitivity relevance protein, which is also highly expressed in heart tissue. However, its function in the heart is still to be elucidated. Thus this study aimed to investigate the role of PID1 in the heart in response to hypertrophic stimuli. Methods: Samples of human failing hearts from the left ventricles of dilated cardiomyopathy (DCM patients undergoing heart transplants were collected. Transgenic mice with cardiomyocyte-specific overexpression of PID1 were generated, and cardiac hypertrophy was induced by transverse aortic constriction (TAC. The extent of cardiac hypertrophy was evaluated by echocardiography as well as pathological and molecular analyses of heart samples. Results: A significant increase in PID1 expression was observed in failing human hearts and TAC-treated wild-type mouse hearts. When compared with TAC-treated wild-type mouse hearts, PID1-TG mouse showed a significant exacerbation of cardiac hypertrophy, fibrosis, and dysfunction. Further analysis of the signaling pathway in vivo suggested that these adverse effects of PID1 were associated with the inhibition of AKT, and activation of MAPK pathway. Conclusion: Under pathological conditions, over-expression of PID1 promotes cardiac hypertrophy by regulating the Akt and MAPK pathway.

  12. Cardiac-specific PID1 overexpression enhances pressure overload-induced cardiac hypertrophy in mice.

    Science.gov (United States)

    Liu, Yaoqiu; Shen, Yahui; Zhu, Jingai; Liu, Ming; Li, Xing; Chen, Yumei; Kong, Xiangqing; Song, Guixian; Qian, Lingmei

    2015-01-01

    PID1 was originally described as an insulin sensitivity relevance protein, which is also highly expressed in heart tissue. However, its function in the heart is still to be elucidated. Thus this study aimed to investigate the role of PID1 in the heart in response to hypertrophic stimuli. Samples of human failing hearts from the left ventricles of dilated cardiomyopathy (DCM) patients undergoing heart transplants were collected. Transgenic mice with cardiomyocyte-specific overexpression of PID1 were generated, and cardiac hypertrophy was induced by transverse aortic constriction (TAC). The extent of cardiac hypertrophy was evaluated by echocardiography as well as pathological and molecular analyses of heart samples. A significant increase in PID1 expression was observed in failing human hearts and TAC-treated wild-type mouse hearts. When compared with TAC-treated wild-type mouse hearts, PID1-TG mouse showed a significant exacerbation of cardiac hypertrophy, fibrosis, and dysfunction. Further analysis of the signaling pathway in vivo suggested that these adverse effects of PID1 were associated with the inhibition of AKT, and activation of MAPK pathway. Under pathological conditions, over-expression of PID1 promotes cardiac hypertrophy by regulating the Akt and MAPK pathway. © 2015 S. Karger AG, Basel.

  13. Role of Excessive Autophagy Induced by Mechanical Overload in Vein Graft Neointima Formation: Prediction and Prevention

    Science.gov (United States)

    Chang, Ya-Ju; Huang, Hui-Chun; Hsueh, Yuan-Yu; Wang, Shao-Wei; Su, Fong-Chin; Chang, Chih-Han; Tang, Ming-Jer; Li, Yi-Shuan; Wang, Shyh-Hau; Shung, Kirk K.; Chien, Shu; Wu, Chia-Ching

    2016-02-01

    Little is known regarding the interplays between the mechanical and molecular bases for vein graft restenosis. We elucidated the stenosis initiation using a high-frequency ultrasonic (HFU) echogenicity platform and estimated the endothelium yield stress from von-Mises stress computation to predict the damage locations in living rats over time. The venous-arterial transition induced the molecular cascades for autophagy and apoptosis in venous endothelial cells (ECs) to cause neointimal hyperplasia, which correlated with the high echogenicity in HFU images and the large mechanical stress that exceeded the yield strength. The ex vivo perfusion of arterial laminar shear stress to isolated veins further confirmed the correlation. EC damage can be rescued by inhibiting autophagy formation using 3-methyladenine (3-MA). Pretreatment of veins with 3-MA prior to grafting reduced the pathological increases of echogenicity and neointima formation in rats. Therefore, this platform provides non-invasive temporal spatial measurement and prediction of restenosis after venous-arterial transition as well as monitoring the progression of the treatments.

  14. Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance.

    Directory of Open Access Journals (Sweden)

    Jiwon Kim

    Full Text Available Non-ischemic fibrosis (NIF on cardiac magnetic resonance (CMR has been linked to poor prognosis, but its association with adverse right ventricular (RV remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress.The population comprised patients with RV dysfunction (EF 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001.Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling.

  15. Effects of acute dietary iron overload in pigs (Sus scrofa) with induced type 2 diabetes mellitus.

    Science.gov (United States)

    Espinoza, A; Morales, S; Arredondo, M

    2014-06-01

    Epidemiological studies have reported an association between high iron (Fe) levels and elevated risk of developing type 2 diabetes mellitus (T2D). It is believed that the formation of Fe-catalyzed hydroxyl radicals may contribute to the development of diabetes. Our goal was to determine the effect of a diet with a high Fe content on type 2 diabetic pigs. Four groups of piglets were studied: (1) control group, basal diet; (2) Fe group, basal diet with 3,000 ppm ferrous sulfate; (3) diabetic group (streptozotocin-induced type 2 diabetes) with basal diet; (4) diabetic/Fe group, diabetic animals/3,000 ppm ferrous sulfate. For 2 months, biochemical and hematological parameters were evaluated. Tissue samples of liver and duodenum were obtained to determine mRNA relative abundance of DMT1, ferroportin (Fpn), ferritin (Fn), hepcidin (Hpc), and transferrin receptor by qRT-PCR. Fe group presented increased levels of hematological (erythrocytes, hematocrit, and hemoglobin) and iron parameters. Diabetic/Fe group showed similar behavior as Fe group but in lesser extent. The relative abundance of different genes in the four study groups yielded a different expression pattern. DMT1 showed a lower expression in the two iron groups compared with control and diabetic animals, and Hpc showed an increased on its expression in Fe and diabetic/Fe groups. Diabetic/Fe group presents greater expression of Fn and Fpn. These results suggest that there is an interaction between Fe nutrition, inflammation, and oxidative stress in the diabetes development.

  16. Intense exercise can cause excessive apoptosis and synapse plasticity damage in rat hippocampus through Ca2+ overload and endoplasmic reticulum stress-induced apoptosis pathway

    Institute of Scientific and Technical Information of China (English)

    Ding Yi; Chang Cunqing; Xie Lan; Chen Zhimin; Ai Hua

    2014-01-01

    Background Intense exercise can cause injury and apoptosis,but few studies have reported its effect on the central nervous system (CNS).The initial reason for hippocampus injury is the excitotoxicity of glutamate and calcium overload.Intracellular free Ca2+ ([Ca2+]i) overload may trigger the apoptosis pathway and neuron damage.The aim of this study was to investigate whether intense exercise could cause hippocampus apoptosis and neuron damage and then to determine which pathway was activated by this apoptosis.Methods We used one bout of swimming exhaustion rats as models.Intracellular [Ca2+]i was measured to estimate the calcium overload by Fura-2/AM immediately after exhaustion; glial fibrillary acidic protein (GFAP) and synaptophysin (SYP)immunofluorescence were performed for estimating astrocyte activation and synapse plasticity 24 hours after exhaustion.Apoptosis cells were displayed using dUTP nick end labelling (TUNEL) stain; endoplasmic reticulum (ER) stress-induced apoptosis pathway and mitochondrial apoptosis pathway were synchronously detected by Western blotting.Results An increasing level of intracellular [Ca2+]i (P <0.01) was found in the hippocampus immediately after exhaustion.GFAP and SYP immunofluorescence showed that the astrocytes are activated,and the synapse plasticity collapsed significantly 24 hours after exhaustion.TUNEL stain showed that the number of apoptosis cells were notably raised (P <0.01); Western blotting of the apoptosis pathway showed increasing levels of caspase-3 cleavage (P <0.01),Bax (P <0.01),caspase-12 cleavage (P <0.01),C/EBP-homologous protein (CHOP) (P <0.01),and phospho-Junaminoterminal kinases (p-JNK; P <0.01) and decreasing level of Bcl-2 (P <0.01).Our results proved that exhaustion can induce hippocampus injury and apoptosis by [Ca2+]i overload,with collapsed synaptic plasticity as the injury pattern and ER stress-induced apoptosis as the activated pathway.Conclusion Intense exercise can cause

  17. Chronic overload induced hypertrophy is associated with age-related muscle mass loss and diminished mTOR signaling

    Science.gov (United States)

    The purpose of this study was to assess activation of the mTOR signaling pathway in young and aging rats in response to chronic muscle overload. Young (6 mo; n = 16) and older (30 mo; n = 23) male rats (F344xBN) were subjected to 4 weeks of bilateral surgical ablation (SA) of two-thirds of the gastr...

  18. The\tRelationship\tBetween\tNt-ProBNP\tand\tVolume\tOverload\tin\tDiabetic Nephropathy\tProgression

    Directory of Open Access Journals (Sweden)

    Yaşar Yıldırım

    2016-12-01

    Full Text Available Objectives: The\tearly\tdiagnosis of volume overload\tin\tchronic kidney\tdisease (CKD\tis very\timportant.\tN-terminal\tprobrain natriuretic\tpeptide\t(NT-proBNP\tis\ta\tvaluable\tbiomarker\tfor\tthis\tpurpose.\tOur\tstudy\taimed\tto\tdetect\tthe\trelationship between NT-proBNP and left ventricular hypertrophy (LVH, hypertension (HT, GFR, and proteinuria among diabetic patients\twith\tstage\t3-4\tCKD. Methods: 160\tdiabetic\tpatients\twith\tstage\t3-4\tCKD\t[80\tpatients\tin\tstage\t3\tCKD\t(group\t1\tand\t80\tpatients\tin\tstage\t4\tCKD (group 2] were enrolled. NT-proBNP levels were evaluated in serum, and proteinuria was determined from 24-hour collected urine. Left ventricular hypertrophy was evaluated by M-mode echocardiography. NT-proBNP levels were compared\taccording\tto\ttheir\tleft\tventricular\thypertrophy,\thypertension,\tand\tproteinuria\tlevels. Results: NT-proBNP\tlevels\twas\tsignificantly\thigher,\tand\tGFR\twas\tlower\tin\tgroup\t2\tcompared to\tgroup1 (p\t<\t0.05.\tNTproBNP was higher in patients with LVH (+ HT (+ and proteinuria ≥ 1gr/d than patients with LVH (-, HT (-, and proteinuria\t<\t1g/d\t(p\t<\t0.05.\tWe\tfound\ta\tsignificant\tcorrelation\tbetween\tNT-proBNP\tlevels\tand\tleft\tventricular\tposterior wall thickness, diastole (LVPWTd, proteinuria, SBP, and DBP. Proteinuria was the major contributor to increased NTproBNP levels\tamong\tthe\tindependent\tvariables. Conclusion: We\tdetected\tthat\tNT-proBNP\tlevels\tare\tincreased\tduring\tthe\tprogression\tof\tCKD,\tand\tproteinuria\tis\tthe\tmajor cause\tof\tincreased\tNT-proBNP\tlevels\tamong\tthe\tindependent\tvariables.

  19. Splenectomy exacerbates atrial inflammatory fibrosis and vulnerability to atrial fibrillation induced by pressure overload in rats: Possible role of spleen-derived interleukin-10.

    Science.gov (United States)

    Kondo, Hidekazu; Takahashi, Naohiko; Gotoh, Koro; Fukui, Akira; Saito, Shotaro; Aoki, Kohei; Kume, Osamu; Shinohara, Tetsuji; Teshima, Yasushi; Saikawa, Tetsunori

    2016-01-01

    The spleen is important for cardiac remodeling induced by myocardial infarction. However, the role of the spleen in inflammatory atrial fibrosis induced by pressure overload is unknown. The purpose of this study was to investigate whether splenectomy (SPX) attenuates or exacerbates pressure overload-induced atrial inflammatory fibrosis and vulnerability to atrial fibrillation (AF) in rats. Male Sprague-Dawley rats (6 weeks old) were divided into Sham+Sham, Sham+SPX, abdominal aortic constriction (AAC)+Sham, and AAC+SPX groups, and were evaluated for inflammation, fibrosis, and AF on days 2, 4, 14, and 28. On day 4, an AAC-induced rise in interleukin-10 (IL-10) level was observed in the spleen, serum, and left atrium (LA), with SPX showing inhibitory effects in the latter 2 instances. In addition, AAC-induced M2 macrophage recruitment into the LA was decreased by SPX, as determined by immunofluorescence labeling (P <.05). On day 28, AAC-induced heterogeneous interstitial fibrosis of the LA was enhanced by SPX (P <.05). Electrophysiologic recordings revealed that the duration of AF and prolongation of interatrial conduction time induced by AAC were increased by SPX (P < .01 and P <.05, respectively). Furthermore, in the AAC+SPX group, the number of macrophages infiltrating into the LA on day 2 was marginal, but increased on day 28 relative to the AAC+Sham group. IL-10 administration attenuated the AAC-induced atrial remodeling that was aggravated by SPX. The study results suggest that SPX exacerbates AAC-induced inflammatory atrial fibrosis and increases vulnerability to AF after 4 weeks, likely because of depletion of spleen-derived IL-10. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  20. Long-Term Sodium Ferulate Supplementation Scavenges Oxygen Radicals and Reverses Liver Damage Induced by Iron Overloading

    Directory of Open Access Journals (Sweden)

    Yang Qiao

    2016-09-01

    Full Text Available Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect of SF on iron-overloaded mice in comparison to a standard antioxidant, taurine (TAU. We determined the protective role of SF against liver injury by examining liver-to-body ratio (%, transaminase and hepatocyte apoptosis in rats supplied with 10% dextrose intraperitoneal injection. In addition, antioxidative enzymes activities, ROS formation, mitochondrial swelling, and mitochondrial membrane potential (MMP were all evaluated to clarify the mechanism of protective effect of SF associated with oxidative stress. After 15 weeks of SF treatment, we found a significant reduction in liver-to-body weight radio and elevation in both transaminase and hepatocyte apoptosis associated with iron-injected to levels comparable to those achieved with TAU. Both SF and TAU significantly attenuated the impaired liver function associated with iron-overloaded in mice, whereas neither showed any significant effect on the iron uptake. Furthermore, treatment with either SF or TAU in iron-overloaded mice attenuated oxidative stress, associated with elevated oxidant enzymes activities, decreased ROS production, prevented mitochondrial swelling and dissipation of MMP and then inhibited hepatic apoptosis. Taken together, the current study shows that, SF alleviated oxidative stress and liver damage associated with iron-overload conditions compared to the standard ROS scavenger (TAU, and potentially could encourage higher consumption and utilization as healthy and sustainable ingredients by the food and drink.

  1. Alteration of Mevalonate Pathway Related Enzyme Expressions in Pressure Overload-Induced Cardiac Hypertrophy and Associated Heart Failure with Preserved Ejection Fraction

    Directory of Open Access Journals (Sweden)

    Bin Chen

    2013-12-01

    Full Text Available Background: Abnormalities of the mevalonate pathway, an important cellular metabolic pathway, are common in many diseases including cardiovascular disease. The mevalonate pathway related enzyme expressions in pressure overload-induced cardiac hypertrophy and associated diastolic dysfunction remains largely unknown. This study aims to investigate whether the expression of mevalonate pathway related enzyme is altered during the progression of cardiac hypertrophy and associated diastolic dysfunction induced by pressure overload. Methods: Male Sprague-Dawley (SD rats were randomly divided into two groups: the suprarenal abdominal aortic coarctation (AAC group and the sham group. Results: Histological and echocardiographic assessments showed that there was a significant cardiovascular remodeling in the AAC group compared with the sham group after 3 weeks post-operatively, and the left ventricular (LV diastolic function was reduced at 8 and 14 weeks post-operatively in the AAC group, without any change in systolic function during the study. The tissue of the heart and the abdominal aorta proximal to the coarctation showed over-expression of several enzymes, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR, farnesyl diphosphate synthase (FDPS, farnesyltransferase-α (FNTA, farnesyltransferase-β (FNTB, geranylgeranyltransferase type I (GGTase-I and the activation of their downstream proteins was enhanced. Conclusions: AAC induced compensatory LV hypertrophy to decompensatory diastolic dysfunction, accompanied by altered expression of several key enzymes in the mevalonate pathway.

  2. Quantitative overload: a source of stress in data-entry VDT work induced by time pressure and work difficulty.

    Science.gov (United States)

    Mazloum, Adel; Kumashiro, Masaharu; Izumi, Hiroyuki; Higuchi, Yoshiyuki

    2008-07-01

    It is hypothesized that quantitative overload impacts psycho-physiological attributes of data-entry operators, although previous research has focused primarily on different aspects of VDT work, such as working time and environment, work station, keyboards and so forth. The objective of this study was to examine the influence on psycho-physiological responses of time pressure, task demand and their combined effect as underlying causes of quantitative overload while typing. A total of 12 subjects completed four 1-h typing tasks representing two levels of time pressure and task demand. Levels were manipulated by requiring participants to achieve a least number of character strings during each block, and by changing the number of letters in the character strings. Outcomes were measured in subjective assessment of workload, performance-related and physiological measures. Overall, increased time pressure increased perceived workload, productivity rate and heart rate, and decreased initial response time and typing duration. However, increased task demand increased error rate and initial response time with no change in heart rate. Heart rate variability did not indicate increased levels of time pressure or task demand. Quantitative overload as a consequence of time pressure and task demand influenced the subjective and psycho-physiological measures of data-entry operators to some extent.

  3. Celecoxib aggravates cardiac apoptosis in L-NAME-induced pressure overload model in rats: Immunohistochemical determination of cardiac caspase-3, Mcl-1, Bax and Bcl-2.

    Science.gov (United States)

    Mosaad, Sarah M; Zaitone, Sawsan A; Ibrahim, Abdelazim; El-Baz, Amani A; Abo-Elmatty, Dina M; Moustafa, Yasser M

    2017-06-25

    The mechanism of celecoxib cardiovascular adverse events was earlier investigated; yet in-depth investigations are needed to assess the involvement of its pro-apoptotic effect throughout this process. An in-vivo chronic rat model of pressure overload employing Nʷ-nitro-l-arginine methyl ester (L-NAME) was tested at different time intervals to ensure the occurrence of persistent myocardial apoptosis along with pressure overload. Seven groups of male Wistar rats were assigned as (i) distilled water; (ii-iv) L-NAME (60 mg/kg) for 6, 12 or 16 weeks; (v-vii) L-NAME [16 weeks] + celecoxib (25, 50 or 100 mg/kg), from week 13 to week 16. Treatment with L-NAME for 6, 12 or 16 weeks increased systolic blood pressure, serum level of creatine kinase-MB and lactate dehydrogenase. Further, it induced cardiac hypertrophy, detected in terms of greater heart weight index and cardiomyocyte cross-sectional area and produced interstitial and perivascular fibrosis. Moreover, administration of L-NAME increased cardiac immunostaining for activated caspase-3 and Bax/Bcl-2 ratio whereas; immunostaining for Mcl-1 was decreased. Administration of celecoxib (25, 50 or 100 mg/kg) aggravated the L-NAME-induced toxicity. The work results shed the light on the putative pro-apoptotic effect of celecoxib at a risk state of pressure overload comparable to the clinical condition of essential hypertension. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Fatigue Crack Growth and Retardation Due to Overloads in Metal-matrix Composites Volume I. Fatigue Crack Growth In Boron-Aluminum Metal-Matrix Composites

    Science.gov (United States)

    1986-08-01

    a - 9313 psi, R a 0.01. (c) Specimen A13 - a - 9313 psi, R - 0.01. (d) Specimen C1 - a= 5780 psi, R = 0.04. (e) Specimen C4 - ao = 5780 psi, R...psi, R - 0.01, 1.5x overload (b) Specimen A12 - Ao = 9313 psi, R - 0.01, 1.5x overload (c) Specimen A13 - ac - 9313 psi, R a 0.01, 2.Ox overload (d...and R2 , R3 , and R fixed reduces (2.7) to: &E a 1(2.8) The strain is computed from: ea - j 1=4 g (2.9) where Sg a gage factor A series of loadings were

  5. Wild Edible Fruit of Prunus nepalensis Ser. (Steud), a Potential Source of Antioxidants, Ameliorates Iron Overload-Induced Hepatotoxicity and Liver Fibrosis in Mice.

    Science.gov (United States)

    Chaudhuri, Dipankar; Ghate, Nikhil Baban; Panja, Sourav; Das, Abhishek; Mandal, Nripendranath

    2015-01-01

    The antioxidant and restoration potentials of hepatic injury by Prunus nepalensis Ser. (Steud), a wild fruit plant from the Northeastern region of India, were investigated. The fruit extract (PNME) exhibited excellent antioxidant and reducing properties and also scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (IC50 = 30.92 ± 0.40 μg/ml). PNME demonstrated promising scavenging potency, as assessed by the scavenging of different reactive oxygen and nitrogen species. Moreover, the extract revealed an exceptional iron chelation capacity with an IC50 of 25.64 ± 0.60 μg/ml. The extract induced significant improvement of hepatic injury and liver fibrosis against iron overload induced hepatotoxicity in mice in a dose-dependent manner, and this effect was supported by different histopathological studies. The phytochemical constitutions and their identification by HPLC confirmed the presence of purpurin, tannic acid, methyl gallate, reserpine, gallic acid, ascorbic acid, catechin and rutin. The identified compounds were investigated for their individual radical scavenging and iron chelation activity; some compounds exhibited excellent radical scavenging and iron chelation properties, but most were toxic towards normal cells (WI-38). On the other hand, crude PNME was found to be completely nontoxic to normal cells, suggesting its feasibility as a safe oral drug. The above study suggests that different phytochemicals in PNME contributed to its free radical scavenging and iron chelation activity; however, further studies are required to determine the pathway in which PNME acts to treat iron-overload diseases.

  6. Death by information overload.

    Science.gov (United States)

    Hemp, Paul

    2009-09-01

    The value of information in the knowledge economy is indisputable, but so is its capacity to overwhelm consumers of it. HBR contributing editor Hemp reports on practical ways for individuals and organizations to avoid getting too much of a good thing. Ready access to useful information comes at a cost: As the volume increases, the line between the worthwhile and the distracting starts to blur. And ready access to you--via e-mail, social networking, and so on--exacerbates the situation: On average, Intel executives get 300 e-mails a day, and Microsoft workers need 24 minutes to return to work after each e-mail interruption. Clearly, productivity is taking a hit. Technological aids can help, such as e-mail management software for you, a message-volume regulation system for your organization, or even more-sophisticated solutions being developed by Microsoft, IBM, and others. Yet, battling technological interruptions on their own turf only goes so far. You also need to change your mind-set, perhaps by seeking help from personal-productivity experts or by simply accepting that you can't respond to every distraction that flits across your screen. Similarly, organizations must change their cultures, for instance by establishing clear e-communication protocols. In the end, only a multipronged approach will help you and your organization subdue the multiheaded monster of information overload. The secret is to manage the beast while still respecting it for the beautiful creature it is.

  7. Hepatic reduction of carbamoyl-PROXYL in ferric nitrilotriacetate induced iron overloaded mice: an in vivo ESR study.

    Science.gov (United States)

    Morales, Noppawan Phumala; Yamaguchi, Yumiko; Murakami, Kimiyo; Kosem, Nuttavut; Utsumi, Hideo

    2012-01-01

    Reduction of a nitroxyl radical, carbamoyl-PROXYL in association of free radical production and hepatic glutathione (GSH) was investigated in iron overloaded mice using an in vivo L-band electron spin resonance (ESR) spectrometer. Significant increases in hepatic iron, lipid peroxidation and decrease in hepatic GSH were observed in mice intraperitoneally (i.p.) administrated with ferric nitrilotriacetate (Fe(III)-NTA, a total 45 µmol/mouse over a period of 3 weeks). Free radical production in iron overloaded mice was evidenced by significantly enhanced rate constant of ESR signal decay of carbamoyl-PROXYL, which was slightly reduced by treatment with iron chelator, deferoxamine. Moreover, the rate constant of ESR signal decay was negatively correlated with hepatic GSH level (r=-0.586, p80%) in mice through daily i.p. injection and drinking water supplementation of L-buthionine-[S,R]-sulfoximine (BSO) significantly retarded ESR signal decay, while there were no changes in serum aspartate aminotransferase and liver thiobarbituric acid-reactive substances levels. In conclusion, GSH plays two distinguish roles on ESR signal decay of carbamoyl-PROXYL, as an antioxidant and as a reducing agent, dependently on its concentration. Therefore, it should be taken into account in the interpretation of free radical production in each specific experimental setting.

  8. EGFR trans-activation by urotensin II receptor is mediated by β-arrestin recruitment and confers cardioprotection in pressure overload-induced cardiac hypertrophy.

    Science.gov (United States)

    Esposito, Giovanni; Perrino, Cinzia; Cannavo, Alessandro; Schiattarella, Gabriele G; Borgia, Francesco; Sannino, Anna; Pironti, Gianluigi; Gargiulo, Giuseppe; Di Serafino, Luigi; Franzone, Anna; Scudiero, Laura; Grieco, Paolo; Indolfi, Ciro; Chiariello, Massimo

    2011-06-01

    Urotensin II (UTII) and its seven trans-membrane receptor (UTR) are up-regulated in the heart under pathological conditions. Previous in vitro studies have shown that UTII trans-activates the epidermal growth factor receptor (EGFR), however, the role of such novel signalling pathway stimulated by UTII is currently unknown. In this study, we hypothesized that EGFR trans-activation by UTII might exert a protective effect in the overloaded heart. To test this hypothesis, we induced cardiac hypertrophy by transverse aortic constriction (TAC) in wild-type mice, and tested the effects of the UTII antagonist Urantide (UR) on cardiac function, structure, and EGFR trans-activation. After 7 days of pressure overload, UR treatment induced a rapid and significant impairment of cardiac function compared to vehicle. In UR-treated TAC mice, cardiac dysfunction was associated with reduced phosphorylation levels of the EGFR and extracellular-regulated kinase (ERK), increased apoptotic cell death and fibrosis. In vitro UTR stimulation induced membrane translocation of β-arrestin 1/2, EGFR phosphorylation/internalization, and ERK activation in HEK293 cells. Furthermore, UTII administration lowered apoptotic cell death induced by serum deprivation, as shown by reduced TUNEL/Annexin V staining and caspase 3 activation. Interestingly, UTII-mediated EGFR trans-activation could be prevented by UR treatment or knockdown of β-arrestin 1/2. Our data show, for the first time in vivo, a new UTR signalling pathway which is mediated by EGFR trans-activation, dependent by β-arrestin 1/2, promoting cell survival and cardioprotection.

  9. Transfusion-associated circulatory overload (TACO): prevention, management, and patient outcomes

    National Research Council Canada - National Science Library

    Murphy, Edward; Roubinian, Nareg

    2015-01-01

    ..., San Francisco, CA, USA Abstract: Transfusion-associated circulatory overload (TACO) is acute pulmonary edema associated with left atrial hypertension or volume overload occurring within 6 hours following a blood transfusion...

  10. Endogenous muscle atrophy F-box mediates pressure overload-induced cardiac hypertrophy through regulation of nuclear factor-kappaB.

    Science.gov (United States)

    Usui, Soichiro; Maejima, Yasuhiro; Pain, Jayashree; Hong, Chull; Cho, Jaeyeaon; Park, Ji Yeon; Zablocki, Daniela; Tian, Bin; Glass, David J; Sadoshima, Junichi

    2011-07-08

    Overexpression of muscle atrophy F-box (MAFbx/atrogin-1), an E3 ubiquitin ligase, induces proteasomal degradation in cardiomyocytes. The role of endogenous MAFbx in regulating cardiac hypertrophy and failure remains unclear. We investigated the role of MAFbx in regulating cardiac hypertrophy and function in response to pressure overload. Transverse aortic constriction (TAC) was applied to MAFbx knockout (KO) and wild-type (WT) mice. Expression of MAFbx in WT mice was significantly increased by TAC. TAC-induced increases in cardiac hypertrophy were significantly smaller in MAFbx KO than in WT mice. There was significantly less lung congestion and interstitial fibrosis in MAFbx KO than in WT mice. MAFbx KO also inhibited β-adrenergic cardiac hypertrophy. DNA microarray analysis revealed that activation of genes associated with the transcription factor binding site for the nuclear factor-κB family were inhibited in MAFbx KO mice compared with WT mice after TAC. Although the levels of IκB-α were significantly decreased after TAC in WT mice, they were increased in MAFbx KO mice. MAFbx regulates ubiquitination and proteasomal degradation of IκB-α in cardiomyocytes. In primary cultured rat cardiomyocytes, phenylephrine-induced activation of nuclear factor-κB and hypertrophy were significantly suppressed by MAFbx knockdown but were partially rescued by overexpression of nuclear factor-κB p65. MAFbx plays an essential role in mediating cardiac hypertrophy in response to pressure overload. Downregulation of MAFbx inhibits cardiac hypertrophy in part through stabilization of IκB-α and inactivation of nuclear factor-κB. Taken together, inhibition of MAFbx attenuates pathological hypertrophy, thereby protecting the heart from progression into heart failure.

  11. Information overload and data overload in lexicography

    DEFF Research Database (Denmark)

    Tarp, Sven; Gouws, Rufus H.

    2016-01-01

    Too often online dictionaries still display too many features determined by the restrictions that applied to printed dictionaries. Data overload in dictionary articles can be regarded as one such relic from the past. However, the idea that online dictionaries have unlimited space has furthered th...

  12. Loss of the eIF2α kinase GCN2 protects mice from pressure overload induced congestive heart failure without affecting ventricular hypertrophy

    Science.gov (United States)

    Lu, Zhongbing; Xu, Xin; Fassett, John; Kwak, Dongmin; Liu, Xiaoyu; Hu, Xinli; Wang, Huan; Guo, Haipeng; Xu, Dachun; Yan, Shuo; McFalls, Edward O.; Lu, Fei; Bache, Robert J.; Chen, Yingjie

    2016-01-01

    In response to a number of stresses, including nutrient deprivation, General Control Nonderepressible 2 kinase (GCN2) attenuates mRNA translation by phosphorylating eukaryotic initiation factor 2 alpha (eIF2αSer51). Energy starvation is known to exacerbate congestive heart failure (CHF) and eIF2αSer51 phosphorylation is increased in the failing heart. However, the impact of GCN2 during the evolution of CHF has not been tested. In this study we examined the influence of GCN2 expression in response to a cardiac stress by inducing chronic pressure overload with Transverse Aortic Constriction (TAC) in Wild Type (WT) and GCN2 knockout (GCN2−/−) mice. Under basal conditions, GCN2−/− had normal LV structure or function but following TAC, demonstrated less contractile dysfunction, less increase of lung weight, less increase of lung inflammation and vascular remodeling, and less myocardial apoptosis and fibrosis compared with WT mice, despite an equivalent degree of LV hypertrophy. As expected, GCN2−/− attenuated TAC induced cardiac eif2αSer51 phosphorylation and preserved Sarcoplasmic reticulum Ca2+ ATPase (Serca2a) expression compared with WT mice. Interestingly, expression of the anti-apoptotic protein Bcl-2 was significantly elevated in GCN2−/− hearts, while in isolated neonatal cardiomyocytes, selective knockdown of GCN2 increased Bcl-2 protein expression and enhanced myocyte resistance to an apoptotic stress. Collectively, our data support the notion that GCN2 impairs the ventricular adaptation to chronic pressure overload by reducing Bcl-2 expression and increasing cardiomyocyte susceptibility to apoptotic stimuli. Our findings suggest that strategies to reduce GCN2 activity in cardiac tissue may be a novel approach to attenuate congestive heart failure development. PMID:24166753

  13. Wild Edible Fruit of Prunus nepalensis Ser. (Steud, a Potential Source of Antioxidants, Ameliorates Iron Overload-Induced Hepatotoxicity and Liver Fibrosis in Mice.

    Directory of Open Access Journals (Sweden)

    Dipankar Chaudhuri

    Full Text Available The antioxidant and restoration potentials of hepatic injury by Prunus nepalensis Ser. (Steud, a wild fruit plant from the Northeastern region of India, were investigated. The fruit extract (PNME exhibited excellent antioxidant and reducing properties and also scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH radical (IC50 = 30.92 ± 0.40 μg/ml. PNME demonstrated promising scavenging potency, as assessed by the scavenging of different reactive oxygen and nitrogen species. Moreover, the extract revealed an exceptional iron chelation capacity with an IC50 of 25.64 ± 0.60 μg/ml. The extract induced significant improvement of hepatic injury and liver fibrosis against iron overload induced hepatotoxicity in mice in a dose-dependent manner, and this effect was supported by different histopathological studies. The phytochemical constitutions and their identification by HPLC confirmed the presence of purpurin, tannic acid, methyl gallate, reserpine, gallic acid, ascorbic acid, catechin and rutin. The identified compounds were investigated for their individual radical scavenging and iron chelation activity; some compounds exhibited excellent radical scavenging and iron chelation properties, but most were toxic towards normal cells (WI-38. On the other hand, crude PNME was found to be completely nontoxic to normal cells, suggesting its feasibility as a safe oral drug. The above study suggests that different phytochemicals in PNME contributed to its free radical scavenging and iron chelation activity; however, further studies are required to determine the pathway in which PNME acts to treat iron-overload diseases.

  14. Signs of Overload

    Science.gov (United States)

    ... Listen Text Size Email Print Share Signs of Overload Page Content Article Body Although stress is a ... 12 (Copyright © 2004 American Academy of Pediatrics) The information contained on this Web site should not be ...

  15. Shear-induced Volume Decrease in MDCK Cells

    Science.gov (United States)

    Heo, Jinseok; Sachs, Frederick; Wang, Jianbin; Hua, Susan Z.

    2013-01-01

    Using a microfluidic cell volume sensor we measured the change in the cell volume of Madin-Darby Canine Kidney (MDCK) cells induced by shear stress. An increase in shear stress from 0.2 to 2.0 dyn/cm2 resulted in a volume decrease to a steady state volume ~ 20 – 30 % smaller than the initial resting cell volume. Independent experiments based on fluorescence quenching confirmed the volume reduction. This shear-induced cell shrinkage was irreversible on the time scale of the experiment (~ 30 min). Treatment of 0.1 μM Hg2+ significantly inhibited the volume decrease, suggesting that the shear-induced cell shrinkage is associated with water efflux through aquaporins. The volume decrease cannot be inhibited by 75 mM TEA, 100 μM DIDS, or 100 μM Gd3+ suggesting that volume reduction is not directly mediated by K+ and Cl− channels that typically function during regulatory volume decrease (RVD), nor is it through cationic stretch-activated ion channels (SACs). The process also appears to be Ca2+ independent because it was insensitive to intracellular Ca2+ level. Since cell volume is determined by the intracellular water content, we postulate that the shear induced reductions in cell volume may arise from increased intracellular hydrostatic pressure as the cell is deformed under flow, which promotes the efflux of water. The increase in internal pressure in a deformable object under the flow is supported by the finite element mechanical model. PMID:22759987

  16. Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation

    Science.gov (United States)

    Rivero-Segura, Nadia A.; Flores-Soto, Edgar; García de la Cadena, Selene; Coronado-Mares, Isabel; Gomez-Verjan, Juan C.; Ferreira, Diana G.; Cabrera-Reyes, Erika Alejandra; Lopes, Luísa V.; Massieu, Lourdes

    2017-01-01

    Prolactin (PRL) is a peptidic hormone that displays pleiotropic functions in the organism including different actions in the brain. PRL exerts a neuroprotective effect against excitotoxicity produced by glutamate (Glu) or kainic acid in both in vitro and in vivo models. It is well known that Glu excitotoxicity causes cell death through apoptotic or necrotic pathways due to intracellular calcium ([Ca2+] i) overload. Therefore, the aim of the present study was to assess the molecular mechanisms by which PRL maintains cellular viability of primary cultures of rat hippocampal neurons exposed to Glu excitotoxicity. We determined cell viability by monitoring mitochondrial activity and using fluorescent markers for viable and dead cells. The intracellular calcium level was determined by a fluorometric assay and proteins involved in the apoptotic pathway were determined by immunoblot. Our results demonstrated that PRL afforded neuroprotection against Glu excitotoxicity, as evidenced by a decrease in propidium iodide staining and by the decrease of the LDH activity. In addition, the MTT assay shows that PRL maintains normal mitochondrial activity even in neurons exposed to Glu. Furthermore, the Glu-induced intracellular [Ca2+]i overload was attenuated by PRL. These data correlate with the reduction found in the level of active caspase-3 and the pro-apoptotic ratio (Bax/Bcl-2). Concomitantly, PRL elicited the nuclear translocation of the transcriptional factor NF-κB, which was detected by immunofluorescence and confocal microscopy. To our knowledge, this is the first report demonstrating that PRL prevents Glu excitotoxicity by a mechanism involving the restoration of the intracellular calcium homeostasis and mitochondrial activity, as well as an anti-apoptotic action possibly mediated by the activity of NF-κB. Overall, the current results suggest that PRL could be of potential therapeutic advantage in the treatment of neurodegenerative diseases. PMID:28475602

  17. Iron overload and immunity

    Institute of Scientific and Technical Information of China (English)

    Gra(c)a Porto; Maria De Sousa

    2007-01-01

    Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage.Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes,will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating how the disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.

  18. Suppression of hepcidin expression and iron overload mediate Salmonella susceptibility in ankyrin 1 ENU-induced mutant.

    Science.gov (United States)

    Yuki, Kyoko E; Eva, Megan M; Richer, Etienne; Chung, Dudley; Paquet, Marilène; Cellier, Mathieu; Canonne-Hergaux, François; Vaulont, Sophie; Vidal, Silvia M; Malo, Danielle

    2013-01-01

    Salmonella, a ubiquitous Gram-negative intracellular bacterium, is a food borne pathogen that infects a broad range of hosts. Infection with Salmonella Typhimurium in mice is a broadly recognized experimental model resembling typhoid fever in humans. Using a N-ethyl-N-nitrosurea (ENU) mutagenesis recessive screen, we report the identification of Ity16 (Immunity to Typhimurium locus 16), a locus responsible for increased susceptibility to infection. The position of Ity16 was refined on chromosome 8 and a nonsense mutation was identified in the ankyrin 1 (Ank1) gene. ANK1 plays an important role in the formation and stabilization of the red cell cytoskeleton. The Ank1(Ity16/Ity16) mutation causes severe hemolytic anemia in uninfected mice resulting in splenomegaly, hyperbilirubinemia, jaundice, extramedullary erythropoiesis and iron overload in liver and kidneys. Ank1(Ity16/Ity16) mutant mice demonstrated low levels of hepcidin (Hamp) expression and significant increases in the expression of the growth differentiation factor 15 (Gdf15), erythropoietin (Epo) and heme oxygenase 1 (Hmox1) exacerbating extramedullary erythropoiesis, tissue iron deposition and splenomegaly. As the infection progresses in Ank1(Ity16/Ity16), the anemia worsens and bacterial load were high in liver and kidneys compared to wild type mice. Heterozygous Ank1(+/Ity16) mice were also more susceptible to Salmonella infection although to a lesser extent than Ank1(Ity16/Ity16) and they did not inherently present anemia and splenomegaly. During infection, iron accumulated in the kidneys of Ank1(+/Ity16) mice where bacterial loads were high compared to littermate controls. The critical role of HAMP in the host response to Salmonella infection was validated by showing increased susceptibility to infection in Hamp-deficient mice and significant survival benefits in Ank1(+/Ity16) heterozygous mice treated with HAMP peptide. This study illustrates that the regulation of Hamp and iron balance are crucial

  19. Suppression of hepcidin expression and iron overload mediate Salmonella susceptibility in ankyrin 1 ENU-induced mutant.

    Directory of Open Access Journals (Sweden)

    Kyoko E Yuki

    Full Text Available Salmonella, a ubiquitous Gram-negative intracellular bacterium, is a food borne pathogen that infects a broad range of hosts. Infection with Salmonella Typhimurium in mice is a broadly recognized experimental model resembling typhoid fever in humans. Using a N-ethyl-N-nitrosurea (ENU mutagenesis recessive screen, we report the identification of Ity16 (Immunity to Typhimurium locus 16, a locus responsible for increased susceptibility to infection. The position of Ity16 was refined on chromosome 8 and a nonsense mutation was identified in the ankyrin 1 (Ank1 gene. ANK1 plays an important role in the formation and stabilization of the red cell cytoskeleton. The Ank1(Ity16/Ity16 mutation causes severe hemolytic anemia in uninfected mice resulting in splenomegaly, hyperbilirubinemia, jaundice, extramedullary erythropoiesis and iron overload in liver and kidneys. Ank1(Ity16/Ity16 mutant mice demonstrated low levels of hepcidin (Hamp expression and significant increases in the expression of the growth differentiation factor 15 (Gdf15, erythropoietin (Epo and heme oxygenase 1 (Hmox1 exacerbating extramedullary erythropoiesis, tissue iron deposition and splenomegaly. As the infection progresses in Ank1(Ity16/Ity16, the anemia worsens and bacterial load were high in liver and kidneys compared to wild type mice. Heterozygous Ank1(+/Ity16 mice were also more susceptible to Salmonella infection although to a lesser extent than Ank1(Ity16/Ity16 and they did not inherently present anemia and splenomegaly. During infection, iron accumulated in the kidneys of Ank1(+/Ity16 mice where bacterial loads were high compared to littermate controls. The critical role of HAMP in the host response to Salmonella infection was validated by showing increased susceptibility to infection in Hamp-deficient mice and significant survival benefits in Ank1(+/Ity16 heterozygous mice treated with HAMP peptide. This study illustrates that the regulation of Hamp and iron balance are

  20. Tanshinone IIA inhibits myocardial remodeling induced by pressure overload via suppressing oxidative stress and inflammation: Possible role of silent information regulator 1.

    Science.gov (United States)

    Feng, Jun; Li, Shusheng; Chen, Huawen

    2016-11-15

    Tanshinone IIA (Tan) exerts potential protective effects against cardiovascular diseases. Oxidative stress and inflammation are involved in cardiac hypertrophy. Activation of silent information regulator 1 (SIRT1) signaling has been suggested to attenuate cardiac hypertrophy. This study aims to evaluate the antioxidative and anti-inflammatory effects of Tan treatment in pressure overload-induced myocardial remodeling and elucidated its potential mechanisms. Sprague-Dawley rats were treated with Tan in the absence or presence of the SIRT1 inhibitor sirtinol (Snl) and then subjected to transverse aortic constriction (TAC). Tan conferred cardioprotective effects by improving cardiac function, reducing apoptosis and myocardial remodeling, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Snl attenuated these effects by inhibiting SIRT1 signaling. Tan treatment also reduced myocardium malondialdehyde (MDA) content, and cardiac inflammatory cytokines (TNF-α and IL-6) and increased myocardium superoxide dismutase (SOD) level. However, these effects were also abolished by Snl. In conclusion, these results indicate that Tan significantly attenuates TAC-induced myocardial remodeling possibly due to its strong anti-oxidative and anti-inflammatory activity. Importantly, SIRT1 signaling activation is involved in this process. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. CD28/B7 Deficiency Attenuates Systolic Overload-Induced Congestive Heart Failure, Myocardial and Pulmonary Inflammation, and Activated T Cell Accumulation in the Heart and Lungs.

    Science.gov (United States)

    Wang, Huan; Kwak, Dongmin; Fassett, John; Hou, Lei; Xu, Xin; Burbach, Brandon J; Thenappan, Thenappan; Xu, Yawei; Ge, Jun-Bo; Shimizu, Yoji; Bache, Robert J; Chen, Yingjie

    2016-09-01

    The inflammatory response regulates congestive heart failure (CHF) development. T cell activation plays an important role in tissue inflammation. We postulate that CD28 or B7 deficiency inhibits T cell activation and attenuates CHF development by reducing systemic, cardiac, and pulmonary inflammation. We demonstrated that chronic pressure overload-induced end-stage CHF in mice is characterized by profound accumulation of activated effector T cells (CD3(+)CD44(high) cells) in the lungs and a mild but significant increase of these cells in the heart. In knockout mice lacking either CD28 or B7, there was a dramatic reduction in the accumulation of activated effector T cells in both hearts and lungs of mice under control conditions and after transverse aortic constriction. CD28 or B7 knockout significantly attenuated transverse aortic constriction-induced CHF development, as indicated by less increase of heart and lung weight and less reduction of left ventricle contractility. CD28 or B7 knockout also significantly reduced transverse aortic constriction-induced CD45(+) leukocyte, T cell, and macrophage infiltration in hearts and lungs, lowered proinflammatory cytokine expression (such as tumor necrosis factor-α and interleukin-1β) in lungs. Furthermore, CD28/B7 blockade by CTLA4-Ig treatment (250 μg/mouse every 3 days) attenuated transverse aortic constriction-induced T cell activation, left ventricle hypertrophy, and left ventricle dysfunction. Our data indicate that CD28/B7 deficiency inhibits activated effector T cell accumulation, reduces myocardial and pulmonary inflammation, and attenuates the development of CHF. Our findings suggest that strategies targeting T cell activation may be useful in treating CHF.

  2. News and the overloaded consumer: factors influencing information overload among news consumers.

    Science.gov (United States)

    Holton, Avery E; Chyi, Hsiang Iris

    2012-11-01

    News producers continue to increase their volume of production and delivery platforms in an effort to reach and maintain news consumers. However, consumers may not necessarily find more news desirable. Previous studies have suggested that information surplus can lead to negative outcomes for consumers, but research of outcomes related to news production and consumption has been scant. This study explores novel areas of news surplus and overload, empirically examining factors associated with the degree of perceived overload across a broad spectrum of news delivery platforms. The findings reveal that the majority of today's news consumers feel overloaded with the amount of news they are confronted with. Gender, news interest, and the use of specific news platforms and outlets predict the degree of that overload. News access through platforms and outlets such as computers, e-readers, and Facebook is positively associated with overload, whereas other platforms such as television and the iPhone are negatively associated with overload. Implications for media psychology and news consumption are discussed.

  3. Combined treatment of 3-hydroxypyridine-4-one derivatives and green tea extract to induce hepcidin expression in iron-overloaded β-thalassemic mice

    Directory of Open Access Journals (Sweden)

    Supranee Upanan

    2015-12-01

    Conclusions: The GTE + DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent β-thalassemic mice, by chelating toxic iron in plasma and tissues, and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen. There is probably an advantage in giving GTE with DFP when treating patients with iron overload.

  4. The autocrine role of tryptase in pressure overload-induced mast cell activation, chymase release and cardiac fibrosis

    Directory of Open Access Journals (Sweden)

    Jianping Li

    2016-03-01

    Results and conclusion: The results indicate the presence of PAR-2 on MCs and that tryptase inhibition and nedocromil prevented TAC-induced fibrosis and increases in MC density, activation, and chymase release. Tryptase also significantly increased chymase concentration in ventricular slice culture media, which was prevented by the tryptase inhibitor. Hydroxyproline concentration in culture media was significantly increased with tryptase incubation as compared to the control group and the tryptase group incubated with nafamostat mesilate or chymostatin. We conclude that tryptase contributes to TAC-induced cardiac fibrosis primarily via activation of MCs and the amplified release of chymase.

  5. Overload road damage model

    CSIR Research Space (South Africa)

    Roux, MP

    2005-03-01

    Full Text Available Not only do overloaded vehicles pose an increased safety risk on the road (reduced stability and braking efficiency etc.), but they also accelerate the rate of deterioration of the road network and increase road maintenance costs, which in turn...

  6. Are the different patterns of stress-induced (Takotsubo) cardiomyopathy explained by regional mechanical overload and demand: supply mismatch in selected ventricular regions?

    Science.gov (United States)

    Redfors, Bjorn; Shao, Yangzhen; Ali, Anwar; Omerovic, Elmir

    2013-11-01

    Takotsubo cardiomyopathy (TCM) or stress-induced cardiomyopathy is an increasingly recognized syndrome characterized by severe regional left ventricular dysfunction in the absence of an explanatory coronary lesion. TCM may lead to lethal complications but is completely reversible if the patient survives the acute phase. The pathogenesis of TCM and the mechanism behind this remarkable recovery are unknown. Plasma levels of catecholamine are elevated in many TCM patients and exogenously administered catecholamine induces TCM-like cardiac dysfunction in both humans and rats. A catecholamine excess increases myocardial metabolic demand by increasing the force of contraction as well as the heart rate, and also alters cardiac depolarization patterns. We propose that an altered spatiotemporal pattern of cardiac contraction and excessive force of contraction may lead to a redistribution of wall stresses in the left ventricle. This redistribution of wall stress causes regional mechanical overload of regions where wall tension becomes disproportionately great and renders these cardiomyocytes "metabolically insufficient". In other words, these cardiomyocytes experience a demand: supply mismatch on the basis of excessive metabolic demand. In order to prevent the death of these cardiomyocytes and to prevent excessive wall tension from developing in neighboring regions, a protective metabolic shutdown occurs in the affected cardiomyocytes. This metabolic shutdown, i.e., acute down regulation of non-vital cellular functions, serves to protect the affected regions from necrosis and explains the apparently complete recovery observed in TCM. We propose that this phenomenon may share important characteristics with phenomena such as ischemic conditioning, stunning and hibernation. In this manuscript, we discuss our hypothesis in the context of available knowledge and discuss important experiments that would help to corroborate or refute the hypothesis. Copyright © 2013 Elsevier Ltd

  7. Postnatal ablation of Foxm1 from cardiomyocytes causes late onset cardiac hypertrophy and fibrosis without exacerbating pressure overload-induced cardiac remodeling.

    Science.gov (United States)

    Bolte, Craig; Zhang, Yufang; York, Allen; Kalin, Tanya V; Schultz, Jo El J; Molkentin, Jeffery D; Kalinichenko, Vladimir V

    2012-01-01

    Heart disease remains a leading cause of morbidity and mortality in the industrialized world. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1 transcription factor (also known as HFH-11B, Trident, Win or MPP2) plays an important role in the pathogenesis of various cancers and is a critical mediator of post-injury repair in multiple organs. Foxm1 has been previously shown to be essential for heart development and proliferation of embryonic cardiomyocytes. However, the role of Foxm1 in postnatal heart development and in cardiac injury has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, αMHC-Cre/Foxm1(fl/fl) mice were generated. Surprisingly, αMHC-Cre/Foxm1(fl/fl) mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had no defects in cardiac structure or function but developed cardiac hypertrophy and fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac fibrosis in aged Foxm1-deficient mice was associated with reduced expression of Hey2, an important regulator of cardiac homeostasis, and increased expression of genes critical for cardiac remodeling, including MMP9, αSMA, fibronectin and vimentin. We also found that following aortic constriction Foxm1 mRNA and protein were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate cardiac hypertrophy or fibrosis following chronic pressure overload. Our results demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte hypertrophy and cardiac fibrosis.

  8. Temperature-based on-column solute focusing in capillary liquid chromatography reduces peak broadening from pre-column dispersion and volume overload when used alone or with solvent-based focusing.

    Science.gov (United States)

    Groskreutz, Stephen R; Horner, Anthony R; Weber, Stephen G

    2015-07-31

    On-column focusing is essential for satisfactory performance using capillary scale columns. On-column focusing results from generating transient conditions at the head of the column that lead to high solute retention. Solvent-based on-column focusing is a well-known approach to achieve this. Temperature-assisted on-column focusing (TASF) can also be effective. TASF improves focusing by cooling a short segment of the column inlet to a temperature that is lower than the column temperature during the injection and then rapidly heating the focusing segment to the match the column temperature. A troublesome feature of an earlier implementation of TASF was the need to leave the capillary column unpacked in that portion of the column inside the fitting connecting it to the injection valve. We have overcome that problem in this work by packing the head of the column with solid silica spheres. In addition, technical improvements to the TASF instrumentation include: selection of a more powerful thermo-electric cooler to create faster temperature changes and electronic control for easy incorporation into conventional capillary instruments. Used in conjunction with solvent-based focusing and with isocratic elution, volumes of paraben samples (esters of p-hydroxybenzoic acid) up to 4.5-times the column liquid volume can be injected without significant bandspreading due to volume overload. Interestingly, the shapes of the peaks from the lowest volume injections that we can make, 30nL, are improved when using TASF. TASF is very effective at reducing the detrimental effects of pre-column dispersion using isocratic elution. Finally, we show that TASF can be used to focus the neuropeptide galanin in a sample solvent with elution strength stronger than the mobile phase. Here, the stronger solvent is necessitated by the need to prevent peptide adsorption prior to and during analysis.

  9. [The fructose induced "glycogenosis". I. Ultrastructural and morphometric analysis of rat hepatocytes 7 days after fructose overload (author's transl)].

    Science.gov (United States)

    Riede, U N; Uhl, H; Seufer, G; Robausch, T; Böhm, N; Sasse, D

    1975-01-01

    Infusion of fructose has been shown to stimulate the SER and to reduce the RER in rat liver cells. After feeding fructose of 7 days a glycogenosis of unknown pathogenesis occurs, which was analysed morphometrically. 60% fructose in water, was given as drinking water to animals deprived of other food. Controls had free access to Altromin-R-standard diet and drinking water. Liver tissue was analysed morphometrically according to the methods described by Weibel. Rat hepatocytes accumulate a material with histochemical properties of glycogen. The enlargement of hepatic nuclei is probably due to a pathological edema. The SER is decreased suggesting a drop of glycogen catabolizing enzymes. The drastic reduction of the RER and the non-membrane bound ribosomes are signs of inpeeded protein synthesis. According to this, the peroxisomes, which arise from the RER, are decreased in volume and number. The hepatocellular chondrioma is transformed morphometrically in a smaller number of larger, pleomorphic and cup-shaped mitochondria. The ATP level drops while, on the other hand, the cristeal membranes increase. This might be caused by a negative feed back mechanism. The hepatocellular cytoarchitecture described is similar to the one found in glycogenosis type I and in the cerebrohepato-renal syndrom.

  10. Prevention of contrast-induced nephropathy with volume expansion.

    Science.gov (United States)

    Weisbord, Steven D; Palevsky, Paul M

    2008-01-01

    Contrast-induced nephropathy is one of the few preventable forms of acute kidney injury. Several pharmacologic agents have been evaluated for the prevention of contrast-induced nephropathy, yet disappointingly, few have been shown conclusively to reduce the risk for this condition. A series of studies have demonstrated that volume expansion, particularly with intravenous fluids, is an effective intervention to reduce the risk for contrast-induced nephropathy. This article reviews the clinical trials that have assessed the role of volume expansion for the prevention of contrast-induced nephropathy. The administration of isotonic sodium chloride before and after radiocontrast injection seems to be more protective than equivalent volumes of hypotonic saline and, when feasible, should be administered over a sustained period of time. Recent clinical trials suggested that an abbreviated regimen of intravenous sodium bicarbonate may be superior to a comparable protocol of sodium chloride. Although a small number of studies have found that volume supplementation by mouth may be effective in preventing contrast-induced nephropathy, the routine use of enteral fluids or solute in lieu of intravenous fluids in high-risk patients cannot be recommended at this time. Rather, liberal oral fluid and solute intake should complement intravenous fluid administration to minimize risk. Future studies will be required to define clearly the optimal prophylactic intravenous fluid regimen for contrast-induced nephropathy and further delineate the independent role of oral volume expansion for the prevention of this condition.

  11. Transfusion associated circulatory overload

    Directory of Open Access Journals (Sweden)

    Naveen Agnihotri

    2014-01-01

    Full Text Available Transfusion associated circulatory overload (TACO is an established, but grossly under diagnosed and underreported complication of blood transfusion. We present the case of a 46-year-old diabetic and hypertensive patient admitted to our hospital for recurrent episodes of urinary retention. Over initial 3 days of the admission, the patient received multiple units of packed red blood cells (RBC and fresh frozen plasma, uneventfully. However, the patient developed signs and symptoms suggestive of TACO with only small amount of the 4 th unit of RBC. The patient had to be shifted to the Intensive Care Unit for further management of this complication. Etiology of TACO is more complex than a mere circulatory overload and is still not completely understood. TACO leads to a prolonged hospital stay and morbidity in the patients developing this complication. TACO thus needs to be suspected in patients at risk for this complication.

  12. Pretreatment of Mouse Neural Stem Cells with Carbon Monoxide-Releasing Molecule-2 Interferes with NF-κB p65 Signaling and Suppresses Iron Overload-Induced Apoptosis.

    Science.gov (United States)

    Xie, Zhengxing; Han, Ping; Cui, Zhenwen; Wang, Baofeng; Zhong, Zhihong; Sun, Yuhao; Yang, Guoyuan; Sun, Qingfang; Bian, Liuguan

    2016-11-01

    Neural stem cell (NSC) transplantation is a promising approach to repair the damaged brain after hemorrhagic stroke; however, it is largely limited by the poor survival of donor cells. Breakdown products of the hematoma and subsequent iron overload contribute to the impairment of survival of neural cells. There is little information regarding the mechanism involved in the death of grafted cells. Furthermore, therapeutic research targeted to improving the survival of grafted neural stem cells (NSCs) is strikingly lacking. Here, we showed that iron overload induced apoptosis of C17.2 cells, a cell line originally cloned from mouse NSCs and immortalized by v-myc. Pretreatment with carbon monoxide-releasing molecule-2 (CORM-2) markedly protected C17.2 cells against iron overload in a dose-dependent manner. Moreover, CORM-2 interfered with NF-κB signaling, including inhibition of nuclear translocation and down-regulation of NF-κB p65. TUNEL staining showed that preconditioning C17.2 cells with CORM-2 enhanced their resistance to apoptosis induced by iron overload, which was concomitant with down-regulation of the pro-apoptotic proteins (Bax and cleaved caspase-3) and up-regulation of the anti-apoptotic protein Bcl2. The protective effect of CORM-2 could be simulated by BAY11-7082, a special inhibitor of NF-κB p65. These results provide a novel and effective strategy to enhance the survival of NSCs after transplantation and, therefore, their efficacy in repairing brain injury due to hemorrhagic stroke.

  13. Remodelação miocárdica na sobrecarga crônica de pressão ou de volume no coração de ratos Myocardial remodeling in chronic pressure or volume overload in the rat heart

    Directory of Open Access Journals (Sweden)

    Luiz Shiguero Matsubara

    2006-02-01

    Full Text Available OBJETIVO: Comparar as alterações estruturais cardíacas em modelos experimentais de sobrecarga de pressão e de volume. MÉTODOS: Foram analisados ratos com hipertensão renovascular (HRV, n = 8, normotensos com sobrecarga de volume por fístula aortocava (FAV, n = 10 e animais controles (CONT, n = 8. Após quatro semanas, registrou-se a pressão arterial caudal (PAS e obtiveram-se os pesos dos ventrículos direito (PVD e esquerdo (PVE. Em cortes histológicos, foram medidas as áreas seccionais dos miócitos (AM, a espessura da parede do VE (E, o diâmetro da cavidade (DVE, a relação E/DVE, e a fração de colágeno (CVF. As comparações foram feitas pela ANOVA e teste de Tukey para nível de significância de 5%. RESULTADOS: A PAS (mmHg foi maior no grupo HRV (HRV = 187 ± 22; CONT = 125 ± 10; FAV = 122 ± 6, p OBJECTIVE: To compare cardiac structural changes in experimental pressure and volume overload models. METHODS: The study analysis included renovascular hypertensive rats (RVH, n=8, normotensive rats with volume overload caused by an aortocaval fistula (ACF, n=10 and control rats (CONT, n=8. After four weeks, tail cuff blood pressure (SBP was recorded. Rats were killed, the hearts were excised and the right and left ventricles (RV&LV were weighed (RVW&LVW. Using histological sections, myocyte cross sectional areas (MA. LV wall thickness (LVWT LV cavity diameter (LVD, normalized LVWT (LVWT/LVD and collagen volume fraction (CVF were measured. The comparisons were made using the ANOVA and Tukey test for a significance level of 5%. RESULTS: Tail cuff blood pressure (mmHg was higher in the RVH group (RVH = 187 ± 22; CONT = 125 ± 10; ACF = 122 ± 6, p<0.05. LV hypertrophy was observed in the RVH and ACF groups. The ACF group presented a significant increase in size of LVD, compared to CONT and RVH. The absolute and normalized ventricular wall thickness were similar among the groups. The RVH group presented a significant increase in CVF

  14. Prooxidant Mechanisms in Iron Overload Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ching-Feng Cheng

    2013-01-01

    Full Text Available Iron overload cardiomyopathy (IOC, defined as the presence of systolic or diastolic cardiac dysfunction secondary to increased deposition of iron, is emerging as an important cause of heart failure due to the increased incidence of this disorder seen in thalassemic patients and in patients of primary hemochromatosis. At present, although palliative treatment by regular iron chelation was recommended; whereas IOC is still the major cause for mortality in patient with chronic heart failure induced by iron-overloading. Because iron is a prooxidant and the associated mechanism seen in iron-overload heart is still unclear; therefore, we intend to delineate the multiple signaling pathways involved in IOC. These pathways may include organelles such as calcium channels, mitochondria; paracrine effects from both macrophages and fibroblast, and novel mediators such as thromboxane A2 and adiponectin; with increased oxidative stress and inflammation found commonly in these signaling pathways. With further understanding on these complex and inter-related molecular mechanisms, we can propose potential therapeutic strategies to ameliorate the cardiac toxicity induced by iron-overloading.

  15. Correlation between left ventricular diastolic function before and after valve replacement surgery and myocardial ultrastructural changes in patients with left ventricular volume-overloaded valvular heart diseases; Evaluation with gated blood pool scintigraphy using [sup 99m]Tc

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Tomiro (Okayama Univ. (Japan). School of Medicine)

    1993-06-01

    Left ventricular (LV) diastolic functions in 23 patients with aortic regurgitation (AR) and 22 patients with mitral regurgitation (MR) were evaluated by gated blood pool scintigraphy. LV myocardial biopsy was performed during open heart surgery, and LV myocardial ultrastructural changes were evaluated by electron microscope. Correlation between LV diastolic function and myocardial ultrastructural changes was examined. It was suggested that preoperative LV diastolic dysfunction occurred earlier than LV systolic dysfunction in patients with AR and MR. LV early diastolic dysfunction was especially significant in patients with AR. LV systolic function was significantly improved postoperatively compared with LV diastolic function in patients with AR and MR. It was suggested that LV interstitial fibrosis caused LV diastolic dysfunction in patients with AR and MR, and insufficiency of myocardial thickening as compensation in patients with MR. It was presumed that LV diastolic dysfunction was irreversible in patients with AR and MR in the distant postoperative period due to persistence of the preoperative myocardial ultrastructural change, e.g., interstitial fibrosis. These LV diastolic indices measured by gated pool scintigraphy were useful in predicting LV ultrastructural changes and postoperative LV dysfunction in patients with LV volume-overloaded valvular heart disease. (author).

  16. 黄芪多糖对压力超负荷诱导的大鼠心肌肥大的影响%Effect of Astragalus polysaccharides on cardiac hypertrophy induced by pressure overload in rat

    Institute of Scientific and Technical Information of China (English)

    李素娟; 吴伟平; 李杰锋; 张贵平; 魏毅; 宜全; 罗健东; 刘英华

    2012-01-01

    目的:探讨黄芪多糖(astragalus polysaccharides,APS)对压力超负荷所致大鼠心肌肥大的抑制作用.方法:SD大鼠随机分为5组:假手术手组、模型组、APS低剂量组(AP1)、APS高剂量组(AP2)和卡托普利组.给药8周后,分别进行心脏超声和HE染色检测心脏肥大指数及形态学改变.结果:超声检测发现,与假手术组相比,模型组左右心室质量比明显增加,舒张期左心室容量、左心室射血分数和左心室短轴缩短速率均明显降低;AP2组与模型组相比,以上指标均有显著性改善,而AP1组和模型组比较无明显差异.HE染色显示,模型组肌细胞排列疏松、肥大,AP1组和AP2组细胞排列整齐,有少量肥大细胞夹杂.结论:高剂量APS对压力超负荷大鼠的心肌肥大有明显保护作用.%Objective To investigate the inhibition of the astragalus polysaccharides (APS) on cardiac hypertrophy induced by pressure overload in rat. Methods 60 SD rats were randomly divided into 5 groups:Sham, Model, Captopril, low-dose APS and high-dose APS group. All these drugs were administrated for 8 weeks respectively. Echocardiography and cardiac hypertrophy index were detected respectively for the heart function, HE staining was detected to observe the cardiac morphology. Results Echocardiography showed that compared with the sham group, left and right ventricular mass ratio (LVM/RVM) of the model group significantly increased, diastolic left ventricular volume (LV Vol, d), left ventricular ejection fraction (EF) and left ventricular fractional shortening rate (FS) of the model group decreased significantly. While comparing with the model group, the indexes of the above in APS group significantly improved. HE staining showed that myocardial cells became hypertrophic and arranged loosely in model group, while the myocardial cells in AP2 group arranged in order, and the hypertrophy cells obviously decreased. But there was no significant difference between the API and

  17. How will you need me, how will you read me, when I'm 64 (or more!)?: volume computed tomographic scanning and information overload in the emergency department.

    Science.gov (United States)

    Chason, David P; Anderson, Jon A; Stephens, Jason S; Suss, Richard A; Guild, Jeffrey B; Blackburn, Timothy J; Champine, Julie G; Lane, Thomas J

    2010-01-01

    Computed tomographic (CT) scanning technology now employs up to 320 detector rows of 0.5-mm width and allows rapid acquisition of isotropic volume datasets over the entire body. Data from a single CT acquisition can be reconstructed into image series that would formerly have required multiple acquisitions. Small isotropic voxels permit scan parameters to be general while reconstruction algorithms remain specific to anatomy. While this results in more efficient operation in the Emergency Department, it necessitates new ways of displaying, interpreting, and archiving the information. Critical decisions include how much of the patient to scan and how to time contrast injections when imaging multiple organs. These choices must be made in light of dose considerations to the patient and the general population of patients. The technical basis of high-density CT scanning is discussed, including detector configurations and reconstruction techniques. Volumetric scanning in the Emergency Department can improve patient care but requires a change of technical habits. 2010 Mosby, Inc. All rights reserved.

  18. The Mythology of Information Overload.

    Science.gov (United States)

    Tidline, Tonyia J.

    1999-01-01

    Combines ideas from mythology, folklore, and library and information science to conclude that information overload is a myth of modern culture. Reports results of a pilot project intended to describe information overload experienced by a particular folk group composed of future library and information professionals. (Author/LRW)

  19. Volume changes in glass induced by an electron beam

    Energy Technology Data Exchange (ETDEWEB)

    Gavenda, Tadeáš, E-mail: gavendat@vscht.cz [Department of Glass and Ceramics, Institute of Chemical Technology, Technická 5, CZ-166 28 Prague (Czech Republic); Gedeon, Ondrej [Department of Glass and Ceramics, Institute of Chemical Technology, Technická 5, CZ-166 28 Prague (Czech Republic); Jurek, Karel [Institute of Physics, Academy of the Czech Republic, Na Slovance 2, CZ-182 21 Prague (Czech Republic)

    2014-03-01

    Three glasses (float, borosilicate float and Schott D263 glasses) were irradiated by 50 keV electron beams with doses within the range of 0.21–318.5 kC/m{sup 2}. Volume changes induced by electron bombarding were monitored by means of Atomic Force Microscopy. Incubation doses, related to mobility of alkali ions, were measured. Low doses showed compaction of all glasses while higher doses revealed volume inflation, except for borosilicate float glass. Both surfaces of float glass were irradiated and significant differences between them were found.

  20. Volume changes in glass induced by an electron beam

    Science.gov (United States)

    Gavenda, Tadeáš; Gedeon, Ondrej; Jurek, Karel

    2014-03-01

    Three glasses (float, borosilicate float and Schott D263 glasses) were irradiated by 50 keV electron beams with doses within the range of 0.21-318.5 kC/m2. Volume changes induced by electron bombarding were monitored by means of Atomic Force Microscopy. Incubation doses, related to mobility of alkali ions, were measured. Low doses showed compaction of all glasses while higher doses revealed volume inflation, except for borosilicate float glass. Both surfaces of float glass were irradiated and significant differences between them were found.

  1. Upregulation of the kappa opioidergic system in left ventricular rat myocardium in response to volume overload: Adaptive changes of the cardiac kappa opioid system in heart failure.

    Science.gov (United States)

    Treskatsch, Sascha; Shaqura, Mohammed; Dehe, Lukas; Feldheiser, Aarne; Roepke, Torsten K; Shakibaei, Mehdi; Spies, Claudia D; Schäfer, Michael; Mousa, Shaaban A

    2015-12-01

    Opioids have long been known for their analgesic effects and are therefore widely used in anesthesia and intensive care medicine. However, in the last decade research has focused on the opioidergic influence on cardiovascular function. This project thus aimed to detect the precise cellular localization of kappa opioid receptors (KOR) in left ventricular cardiomyocytes and to investigate putative changes in KOR and its endogenous ligand precursor peptide prodynorphin (PDYN) in response to heart failure. After IRB approval, heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. All rats of the control and ACF group were characterized by their morphometrics and hemodynamics. In addition, the existence and localization as well as adaptive changes of KOR and PDYN were investigated using radioligand binding, double immunofluorescence confocal analysis, RT-PCR and Western blot. Similar to the brain and spinal cord, [(3)H]U-69593 KOR selective binding sites were detected the left ventricle (LV). KOR colocalized with Cav1.2 of the outer plasma membrane and invaginated T-tubules and intracellular with the ryanodine receptor of the sarcoplasmatic reticulum. Interestingly, KOR could also be detected in mitochondria of rat LV cardiomyocytes. As a consequence of heart failure, KOR and PDYN were up-regulated on the mRNA and protein level in the LV. These findings suggest that the cardiac kappa opioidergic system might modulate rat cardiomyocyte function during heart failure.

  2. Effect of Yiqi Huoxue Recipe(益气活血方)on Cardiac Function and Ultrastructure in Regression of Pressure Overload-induced Myocardial Hypertrophy in Rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To investigate the effect of Yiqi Huoxue Recipe(YHR,益气活血方)on the cardiac function and ultrastructure during the regression of myocardial hypertrophy induced by pressure overload in rats.Methods:The model of myocardial hypertrophy was established by abdominal aortic banding.Eighty male Wistar rats were divided into six groups,the normal control group Ⅰ(n=20),the normal control group Ⅱ(n=12),the hypertension model group [(n=12),the hypertension model group Ⅱ(n=12),the YHR group(n=12)and the Captopril group(n=12).The observation was carried out in the normal control group Ⅰ and the hypertension model group Ⅰ after 4weeks of modeling,and the other four groups were observed after 16 weeks of modeling(12 weeks of administration).The cardiac function was measured with a multichannel biological signal analysis system,and the myocardium ultrastructure was observed by a transmission electron microscope.Results:(1)Compared with the normal control group Ⅰ,the systolic blood pressure and cardiac coefficient(left ventricular weight/body weight)in the model Ⅰ group was higher(P<0.05,P<0.01).(2)In the YHR group,cardiac coefficient and -dp/dtmax were lower,left ventricular systolic pressure and +dp/dtmin were higher when compared with the model group Ⅱ and the Captopril group(P<0.05or P<0.01).In the Captopril group,only cardiac coefficient was lower when compared with the mode group Ⅱ(P<0.05).(3)Compared with the normal control group Ⅱ,+dp/dtrmax was higher(P<0.01),-dp/dtnmax and isovolumetric contraction time(ICT)was lower(P<0.05,P<0.01)in both the YHR group and the Captopril group.(4)Results of the myocardium ultrastructure showed edema under myocardium plasmalemma,enlarged sarcoplasmic reticulum and T tube,and significantly enlarged intercalated disc of the cardiac muscle in the model groups.In the Captopril group,the extension of sarcoplasmic reticulum and T tube as well as the pathological changes of intercalated disc

  3. Combined treatment of 3-hydroxypyridine-4-one derivatives and green tea extract to induce hepcidin expression in iron-overloaded b-thalassemic mice

    Institute of Scientific and Technical Information of China (English)

    Supranee; Upanan; Kanjana; Pangjit; Chairat; Uthaipibull; Suthat; Fucharoen; Andrew; T.Mc; Kie; Somdet; Srichairatanakool

    2015-01-01

    Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron overload in b-globin knockout thalassemic mice.Methods:The b-globin knockout thalassemic mice were fed with a ferrocenesupplemented diet for 2 months and oral administration of deionized water,DFP(50 mg/kg),CM1(50 mg/kg),GTE(50 mg epigallocatechin 3-gallate equivalent/kg),GTE along with DFP(50 mg/kg),and GTE along with CM1(50 mg/kg)every day for 3months.Levels of hepatic Hamp1 m RNA,plasma non-transferrin bound iron,plasma alanine aminotransferase activity and tissue iron content were determined.Results:All chelation treatments could reduce plasma non-transferrin bound iron concentrations.Additionally,hepatic Hamp1 m RNA expression was significantly upregulated in the mice in a GTE+DFP combined treatment,correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron deposition.Conclusions:The GTE+DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent b-thalassemic mice,by chelating toxic iron in plasma and tissues,and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen.There is probably an advantage in giving GTE with DFP when treating patients with iron overload.

  4. Combined treatment of 3-hydroxypyridine-4-one derivatives and green tea extract to induce hepcidin expression in iron-overloaded b-thalassemic mice

    Institute of Scientific and Technical Information of China (English)

    Supranee Upanan; Kanjana Pangjit; Chairat Uthaipibull; Suthat Fucharoen; Andrew T McKie; Somdet Srichairatanakool

    2015-01-01

    Objective: To evaluate the efficacy of deferiprone (DFP), 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) or green tea extract (GTE) in enhancing expres-sion of hepatic hepcidin1 (Hamp1) mRNA and relieving iron overload in b-globin knockout thalassemic mice. Methods: The b-globin knockout thalassemic mice were fed with a ferrocene-supplemented diet for 2 months and oral administration of deionized water, DFP (50 mg/kg), CM1 (50 mg/kg), GTE (50 mg epigallocatechin 3-gallate equivalent/kg), GTE along with DFP (50 mg/kg), and GTE along with CM1 (50 mg/kg) every day for 3 months. Levels of hepatic Hamp1 mRNA, plasma non-transferrin bound iron, plasma alanine aminotransferase activity and tissue iron content were determined. Results: All chelation treatments could reduce plasma non-transferrin bound iron con-centrations. Additionally, hepatic Hamp1 mRNA expression was significantly up-regulated in the mice in a GTE+DFP combined treatment, correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron deposition. Conclusions: The GTE + DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent b-thalassemic mice, by chelating toxic iron in plasma and tissues, and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen. There is probably an advantage in giving GTE with DFP when treating patients with iron overload.

  5. 铁过载巨噬细胞体外模型的建立及氧化应激对铁过载巨噬细胞的损伤作用%Establishment of macrophage model of iron overload in vitro and the injury induced by oxidative stress on macrophage with iron overload

    Institute of Scientific and Technical Information of China (English)

    曹小立; 赵明峰; 李德冠; 邢艺; 张宇辰; 陈洁; 贺小圆; 崔蕊; 孟娟霞

    2016-01-01

    ,i.e.nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX 4) gene related with ROS production and inducible nitric oxide synthase (iNOS) gene related with reactive nitrogen production,down-regulated mRNA expression of glutathione peroxidase 1 (GPX1) gene which participated in ROS clearance.Moreover,mRNA expression of phosphatidylinositol-3-kinase (PI3K) gene involved in oxidative stress signaling pathway in the iron overload group was up-regulated,while fork head protein O3 (FOXO3) which regulated oxidative stress through negative feedback showed a down-regulation level of mRNA expression compared with the control group.(5) After iron chelation and antioxidant treatment,the above-mentioned damage in the iron overload group were partially reversed.Conclusions The damages of iron overload on macrophages may be mediated by inducing oxidative stress and activating oxidative stress signaling pathways.Our established model provides a method to explore the mechanism of iron overload on macrophage,and may shed some new light on possible therapeutic target in treating iron overload patients.%目的 通过铁与巨噬细胞共培养,建立体外铁过载巨噬细胞模型,检验铁过载对细胞氧化应激水平的影响以及氧化应激升高对巨噬细胞的影响.方法 在巨噬细胞培养的过程中分别添加不同浓度(5、10、20、40、80 μmol/L)枸橼酸铁铵(FAC)建立铁过载巨噬细胞模型(铁过载组),以不添加FAC作为对照组,检验这一过程中细胞数量及状态、细胞活性、细胞吞噬功能的变化,细胞生成活性氧、活性氮水平以及与之相关的氧化应激信号通路的变化.再用地拉罗司(DFX)去铁及抗氧化剂N-乙酰半胱氨酸(NAC)清除过多的氧化应激后,检测上述指标的变化.结果 (1)在培养液中加入不同浓度FAC培养,发现巨噬细胞内可变铁池(LIP)水平升高,且具有浓度依赖性,在含80 μmol/LFAC的培养液中LIP水平达到最高.(2)随着FAC浓度的提高,巨噬细胞的活

  6. Pathology of hepatic iron overload

    Institute of Scientific and Technical Information of China (English)

    Yves Deugnier; Bruno Turlin

    2007-01-01

    Although progress in imaging and genetics allow for a noninvasive diagnosis of most cases of genetic iron overload, liver pathology remains often useful (1) to assess prognosis by grading fibrosis and seeking for associated lesions and (2) to guide the etiological diagnosis, especially when no molecular marker is available.Then, the type of liver siderosis (parenchymal, mesenchymal or mixed) and its distribution throughout the lobule and the liver are useful means for suggesting its etiology: HLA-linked hemochromatosis gene (HFE) hemochromatosis or other rare genetic hemochromatosis,nonhemochromatotic genetic iron overload (ferroportin disease, aceruloplasminemia), or iron overload secondary to excessive iron supply, inflammatory syndrome,noncirrhotic chronic liver diseases including dysmetabolic iron overload syndrome, cirrhosis, and blood disorders.

  7. Effects of chronic Akt/mTOR inhibition by rapamycin on mechanical overload-induced hypertrophy and myosin heavy chain transition in masseter muscle.

    Science.gov (United States)

    Umeki, Daisuke; Ohnuki, Yoshiki; Mototani, Yasumasa; Shiozawa, Kouichi; Fujita, Takayuki; Nakamura, Yoshiki; Saeki, Yasutake; Okumura, Satoshi

    2013-01-01

    To examine the effects of the Akt/mammalian target of rapamycin (mTOR) pathway on masseter muscle hypertrophy and myosin heavy chain (MHC) transition in response to mechanical overload, we analyzed the effects of bite-opening (BO) on the hypertrophy and MHC composition of masseter muscle of BO-rats treated or not treated with rapamycin (RAPA), a selective mTOR inhibitor. The masseter muscle weight in BO-rats was significantly greater than that in controls, and this increase was attenuated by RAPA treatment. Expression of slow-twitch MHC isoforms was significantly increased in BO-rats with/without RAPA treatment, compared with controls, but the magnitude of the increase was much smaller in RAPA-treated BO-rats. Phosphorylation of p44/42 MAPK (ERK1/2), which preserves fast-twitch MHC isoforms in skeletal muscle, was significantly decreased in BO-rats, but the decrease was abrogated by RAPA treatment. Calcineurin signaling is known to be important for masseter muscle hypertrophy and fast-to-slow MHC isoform transition, but expression of known calcineurin activity modulators was unaffected by RAPA treatment. Taken together, these results indicate that the Akt/mTOR pathway is involved in both development of masseter muscle hypertrophy and fast-to-slow MHC isoform transition in response to mechanical overload with inhibition of the ERK1/2 pathway and operates independently of the calcineurin pathway.

  8. Early changes in left atrial volume after acute myocardial infarction. Relation to invasive hemodynamics at rest and during exercise

    DEFF Research Database (Denmark)

    Bakkestrøm, Rine; Andersen, Mads J; Ersbøll, Mads

    2016-01-01

    BACKGROUND: Dilatation of left atrium (LA) reflects chronic LA pressure or volume overload that possesses considerable prognostic information. Little is known regarding the interaction between LA remodeling after acute myocardial infarction (MI) and left atrial pressure at rest and during exercise...... associated with resting and exercise induced changes in LA pressure overload. The dilatation was however associated with lower e' and higher MR-proANP....

  9. Laser-induced incandescence: Towards quantitative soot volume fraction measurements

    Energy Technology Data Exchange (ETDEWEB)

    Tzannis, A.P.; Wienbeucker, F.; Beaud, P.; Frey, H.-M.; Gerber, T.; Mischler, B.; Radi, P.P. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    Laser-Induced Incandescence has recently emerged as a versatile tool for measuring soot volume fraction in a wide range of combustion systems. In this work we investigate the essential features of the method. LII is based on the acquisition of the incandescence of soot when heated through a high power laser pulse. Initial experiments have been performed on a model laboratory flame. The behaviour of the LII signal is studied experimentally. By applying numerical calculations we investigate the possibility to obtain two-dimensional soot volume fraction distributions. For this purpose a combination of LII with other techniques is required. This part is discussed in some extent and the future work is outlined. (author) 4 figs., 3 refs.

  10. Inducible Knock-Down of the Mineralocorticoid Receptor in Mice Disturbs Regulation of the Renin-Angiotensin-Aldosterone System and Attenuates Heart Failure Induced by Pressure Overload.

    Directory of Open Access Journals (Sweden)

    Elena Montes-Cobos

    Full Text Available Mineralocorticoid receptor (MR inactivation in mice results in early postnatal lethality. Therefore we generated mice in which MR expression can be silenced during adulthood by administration of doxycycline (Dox. Using a lentiviral approach, we obtained two lines of transgenic mice harboring a construct that allows for regulatable MR inactivation by RNAi and concomitant expression of eGFP. MR mRNA levels in heart and kidney of inducible MR knock-down mice were unaltered in the absence of Dox, confirming the tightness of the system. In contrast, two weeks after Dox administration MR expression was significantly diminished in a variety of tissues. In the kidney, this resulted in lower mRNA levels of selected target genes, which was accompanied by strongly increased serum aldosterone and plasma renin levels as well as by elevated sodium excretion. In the healthy heart, gene expression and the amount of collagen were unchanged despite MR levels being significantly reduced. After transverse aortic constriction, however, cardiac hypertrophy and progressive heart failure were attenuated by MR silencing, fibrosis was unaffected and mRNA levels of a subset of genes reduced. Taken together, we believe that this mouse model is a useful tool to investigate the role of the MR in pathophysiological processes.

  11. [Chronic nicotinamide overload and type 2 diabetes].

    Science.gov (United States)

    Zhou, Shi-Sheng; Li, Da; Zhou, Yi-Ming; Sun, Wu-Ping; Liu, Xing-Xing; Lun, Yong-Zhi

    2010-02-25

    Type 2 diabetes is a major global health problem. It is generally accepted that type 2 diabetes is the result of gene-environmental interaction. However, the mechanism underlying the interaction is unclear. Diet change is known to play an important role in type 2 diabetes. The fact that the global high prevalence of type 2 diabetes has occurred following the spread of food fortification worldwide suggests a possible involvement of excess niacin intake. Our recent study found that nicotinamide overload and low nicotinamide detoxification may induce oxidative stress associated with insulin resistance. Based on the relevant facts, this review briefly summarized the relationship between the prevalence of type 2 diabetes and the nicotinamide metabolism changes induced by excess niacin intake, aldehyde oxidase inhibitors, liver diseases and functional defects of skin. We speculate that the gene-environmental interaction in type 2 diabetes may be a reflection of the outcome of the association of chronic nicotinamide overload-induced toxicity and the relatively low detoxification/excretion capacity of the body. Reducing the content of niacin in foods may be a promising strategy for the control of type 2 diabetes.

  12. OVERLOAD ANALYSIS OF MARKOVIAN MODELS

    Institute of Scientific and Technical Information of China (English)

    Yiqiang Q. ZHAO

    1999-01-01

    A new procedure for computing stationary probabilities for an overloaded Markovian model is proposed interms of the rotated Markov chain.There are two advantages to use this procedure:i) This procedure allows us to approximate an overloaded finite model by using a stable infinite Markov chain. This will makethe study easier when the infinite model has a simpler solution.ii) Numerically, this procedure often significantly reduces the number of computations and the requirement of computer memory. By using different examples,we specifically demonstratethe process of implementing this rotating procedure.

  13. Bioimpedance can solve problems of fluid overload.

    Science.gov (United States)

    Abbas, Samer R; Zhu, Fansan; Levin, Nathan W

    2015-03-01

    Bioimpedance (BI) techniques for measuring normal hydration status (NHS) can be generally classified as (1) by frequency as single frequency at 50 kHz, BI analysis, and multifrequency BI spectroscopy and (2) by method as whole body (wrist to ankle) measurement and calf BI spectroscopy. The aim of this article was to review current BI methods for clinical practice in patients with end-stage of kidney disease. BI vector analysis using whole-body single-frequency BI at 50 kHz may be useful for population studies to indicate a range of degree of fluid loading and of nutritional status. Whole body multifrequency BI spectroscopy is used to estimate extracellular (ECV), intracellular fluid volume, and total body water in dialysis patients. The whole-body BI model is used in the body composition monitor (BCM). The whole-body BI model is established with ECV, intracellular fluid volume, and body weight based on parameters from regression analysis in healthy subjects to calculate fluid overload in dialysis patients. Calf BI methods have been developed to measure NHS by 2 ways: (1) continuous measurement of the intradialytic resistance curve until flattening occurs; (2) calf normalized resistivity in the range of healthy subjects (18.5 × 10(-2) Ω m(3)/kg in male and 19.1 × 10(-2) Ω m(3)/kg in female). In general, for population studies, BI vector analysis or ECV/total body water may be useful; BCM is a commercially available device that can certainly guide volume reduction safely over time. For more exact measure of fluid overload, calf BI methods appear to be most accurate, but these are at present research tools. BI techniques are not only useful in assessing NHS but also in the study of nutrition and body composition.

  14. Dietary glutamine supplementation partly reverses impaired macrophage function resulting from overload training in rats.

    Science.gov (United States)

    Xiao, Weihua; Chen, Peijie; Dong, Jingmei; Wang, Ru; Luo, Beibei

    2015-04-01

    The aim of this study was to evaluate the effect of overload training on the function of peritoneal macrophages in rats, and to test the hypothesis that glutamine in vivo supplementation would partly reverse the eventual functional alterations induced by overload training in these cells. Forty male Wistar rats were randomly divided into 5 groups: control group (C), overload training group (E1), overload training and restore one week group (E2), glutamine-supplementation group (EG1), and glutamine-supplementation and restore 1-week group (EG2). All rats, except those placed on sedentary control were subjected to 11 weeks of overload training protocol. Blood hemoglobin, serum testosterone, and corticosterone of rats were measured. Moreover, the functions (chemotaxis, phagocytosis, cytokines synthesis, reactive oxygen species generation) of peritoneal macrophages were determined. Data showed that blood hemoglobin, serum testosterone, corticosterone and body weight in the overload training group decreased significantly as compared with the control group. Meanwhile, the chemotaxis capacity (decreased by 31%, p = .003), the phagocytosis capacity (decreased by 27%, p = .005), the reactive oxygen species (ROS) generation (decreased by 35%, p = .003) and the cytokines response capability of macrophages were inhibited by overload training. However, the hindering of phagocytosis and the cytokines response capability of macrophages induced by overload training could be ameliorated and reversed respectively, by dietary glutamine supplementation. These results suggest that overload training impairs the function of peritoneal macrophages, which is essential for the microbicidal actions of macrophages. This may represent a novel mechanism of immunodepression induced by overload training. Nonetheless, dietary glutamine supplementation could partly reverse the impaired macrophage function resulting from overload training.

  15. Information overload in medical practice.

    Science.gov (United States)

    Zeldes, Nathan; Baum, Neil

    2011-01-01

    Most practices are inundated with an excess of information. This information overload, or "infoglut," results in distractions and a loss of productivity. This article will discuss the concept of infoglut and what every practice can do to manage the tsunami of information that threatens to consume our practices.

  16. Brief left ventricular pressure overload reduces myocardial apoptosis.

    Science.gov (United States)

    Huang, Hsien-Hao; Lai, Chang-Chi; Chiang, Shu-Chiung; Chang, Shi-Chuan; Chang, Chung-Ho; Lin, Jin-Ching; Huang, Cheng-Hsiung

    2015-03-01

    Both apoptosis and necrosis contribute to cell death after myocardial ischemia and reperfusion. We previously reported that brief left ventricular pressure overload (LVPO) decreased myocardial infarct (MI) size. In this study, we investigated whether brief pressure overload reduces apoptosis and the mechanisms involved. MI was induced by a 40-min occlusion of the left anterior descending coronary artery and 3-h reperfusion in male anesthetized Sprague-Dawley rats. Brief LVPO was achieved by two 10-min partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-min coronary artery occlusions and 10-min reperfusions. Brief LVPO and ischemic preconditioning significantly decreased MI size (P Brief pressure overload significantly reduced myocardial apoptosis, as evidenced by the decrease in the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei (P brief pressure overload significantly increased Bcl-2 (P brief pressure overload (P Brief left LVPO significantly reduces myocardial apoptosis. The underlying mechanisms might be related to modulation of Bcl-2 and Bax, inhibition of p53, increased Akt phosphorylation, and suppressed c-Jun N-terminal kinase phosphorylation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Dietary Fat Overload Reprograms Brown Fat Mitochondria

    Directory of Open Access Journals (Sweden)

    DANIELE eLETTIERI BARBATO

    2015-09-01

    Full Text Available Chronic nutrient overload accelerates the onset of several aging-related diseases reducing life expectancy. Although the mechanisms by which overnutrition affects metabolic processes in many tissues are known, its role on BAT physiology is still unclear. Herein, we investigated the mitochondrial responses in BAT of female mice exposed to high fat diet (HFD at different steps of life. Although adult mice showed an unchanged mitochondrial amount, both respiration and OxPHOS subunits were strongly affected. Differently, offspring pups exposed to HFD during pregnancy and lactation displayed reduced mitochondrial mass but high oxidative efficiency that, however, resulted in increased bioenergetics state of BAT rather than augmented uncoupling respiration. Interestingly, the metabolic responses triggered by HFD were accompanied by changes in mitochondrial dynamics characterized by decreased content of the fragmentation marker Drp1 both in mothers and offspring pups. HFD-induced inactivation of the FoxO1 transcription factor seemed to be the up-stream modulator of Drp1 levels in brown fat cells. Furthermore, HFD offspring pups weaned with normal diet only partially reverted the mitochondrial dysfunctions caused by HFD. Finally these mice failed in activating the thermogenic program upon cold exposure. Collectively our findings suggest that maternal dietary fat overload irreversibly commits BAT unresponsiveness to physiological stimuli such as cool temperature and this dysfunction in the early stage of life might negatively modulates health and lifespan.

  18. [Genetics of hereditary iron overload].

    Science.gov (United States)

    Le Gall, Jean-Yves; Jouanolle, Anne-Marie; Fergelot, Patricia; Mosser, Jean; David, Véronique

    2004-01-01

    The classification of hereditary abnormalities of iron metabolism was recently expanded and diversified. Genetic hemochromatosis now corresponds to six diseases, namely classical hemochromatosis HFE 1; juvenile hemochromatosis HFE 2 due to mutations in an unidentified gene on chromosome 1; hemochromatosis HFE 3 due to mutations in the transferrin receptor 2 (TfR2); hemochromatosis HFE 4 caused by a mutation in the H subunit of ferritin; and hemochromatosis HFE 6 whose gene is hepcidine (HAMP). Systemic iron overload is also associated with aceruloplasminemia, atransferrinemia and the "Gracile" syndrome caused by mutations in BCS1L. The genes responsible for neonatal and African forms of iron overload are unknown. Other genetic diseases are due to localized iron overload: Friedreich's ataxia results from the expansion of triple nucleotide repeats within the frataxin (FRDA) gene; two forms of X-linked sideroblastic anemia are due to mutations within the delta aminolevulinate synthetase (ALAS 2) or ABC-7 genes; Hallervorden-Spatz syndrome is caused by a pantothenate kinase 2 gene (PANK-2) defect; neuroferritinopathies; and hyperferritinemia--cataract syndrome due to a mutation within the L-ferritin gene. In addition to this wide range of genetic abnormalities, two other features characterize these iron disorders: 1) most are transmitted by an autosomal recessive mechanism, but some, including hemochromatosis type 4, have dominant transmission; and 2) most correspond to cytosolic iron accumulation while some, like Friedreich's ataxia, are disorders of mitochondrial metabolism.

  19. Peritoneal residual volume induces variability of ultrafiltration with icodextrin.

    Science.gov (United States)

    Akonur, Alp; Holmes, Clifford J; Leypoldt, John K

    2014-01-01

    Icodextrin induces ultrafiltration (UF) during long-dwell exchanges by creating a difference in oncotic pressure between the peritoneal cavity and plasma; however, the mechanisms governing intra-patient and inter-patient variability in UF when icodextrin is used remain largely unexplained. In the present study, we show theoretically that differences in peritoneal residual volume (VR) have a more profound effect on UF with icodextrin use than with glucose use. This phenomenon is attributed to a differential effect of VR on oncotic, rather than osmotic, pressure between the peritoneal cavity and plasma. ♢ The three-pore model was used to calculate the effect on UF of VR between 150 mL and 1200 mL when 7.5% icodextrin (ICO) or 3.86% glucose solution is used at the end of a 12-hour dwell in the four patient transport groups (that is, fast to slow). Oncotic (with ICO) and osmotic (with glucose) pressure differences averaged over the entire dwell were also calculated. ♢ As expected, at a nominal VR of 300 mL, UF with glucose differed substantially between the four patient transport groups (2 - 804 mL), whereas UF with ICO did not (556 - 573 mL). When VR was increased to 1200 mL from 150 mL, the concentrations of the oncotic and osmotic agents at the start of the dwell with an infusion volume of 2 L decreased to 4.9% from 7.0% with ICO and to 2.5% from 3.6% with glucose. The decrease in UF on average was greater with ICO [to 252 mL from 624 mL: that is, a reduction of 372 mL (60%)] than with glucose [to 292 mL from 398 mL: that is, a reduction of 106 mL (27%)]. Those trends agreed with the calculated reductions in the oncotic pressure difference with ICO [reduction of 12 mmHg (49%)] and the osmotic pressure difference with glucose [reduction of 19 mmHg (33%)]. ♢ When ICO is used, VR modifies the oncotic pressure difference between the peritoneal cavity and plasma to substantially alter UF. This modification suggests that potential causes of increased VR should be

  20. Gypenosides Induce Apoptosis by Ca2+ Overload Mediated by Endoplasmic-Reticulum and Store-Operated Ca2+ Channels in Human Hepatoma Cells

    Science.gov (United States)

    Sun, Da-Peng; Li, Xiao-Xi; Liu, Xin-Li; Zhao, Dan; Qiu, Feng-Qi; Li, Yan

    2013-01-01

    Abstract Gypenosides (Gyps) are triterpenoid saponins contained in an extract from Gynostemma pentaphyllum Makino and reported to induce apoptosis in human hepatoma cells through Ca2+-implicated endoplasmic reticulum (ER) stress and mitochondria-dependent pathways. The mechanism underlying the Gyp-increased intracellular Ca2+ concentration ([Ca2+]i) is unclear. Here, we examined Gyp-induced necrosis and apoptosis in human hepatoma HepG2 cells. Gyp-induced apoptotic cell death was accompanied by a sustained increase in [Ca2+]i level. Gyp-increased [Ca2+]i level was partly inhibited by removal of extracellular Ca2+ by Ca2+ chelator EGTA, store-operated Ca2+ channel (SOC) inhibitor 2- aminoethoxydiphenyl borate (2-APB), and ER Ca2+-release-antagonist 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8). The strongest inhibitory effect was observed with TMB-8. EGTA, 2-APB, and TMB-8 also protected against Gyp-induced apoptosis in HepG2 cells. The combination of 2-APB and TMB-8 almost completely abolished the Gyp-induced Ca2+ response and apoptosis. In contrast, the sarco/endoplasmic-reticulum-Ca2+-ATPase (SERCA) inhibitor thapsigargin slightly elevated Gyp-induced [Ca2+]i increase and apoptosis in HepG2 cells. Exposure to 300 μg/mL Gyp for 24 hours upregulated protein levels of inositol 1,4,5-trisphosphate receptor and SOC and downregulated that of SERCA for at least 72 hours. Thus, Gyp-induced increase in [Ca2+]i level and consequent apoptosis in HepG2 cells may be mainly due to enhanced Ca2+ release from ER stores and increased store-operated Ca2+ entry. PMID:25310348

  1. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Qi Xu

    2016-01-01

    Full Text Available Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD. However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P<0.0001 upregulated ferroportin 1 expression and significantly (P<0.05 decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05 and DNA fragmentation by 29% (P=0.086 and increased cell viability by 22% (P<0.05. In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05 and intracellular iron by 28% (P<0.01, indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.

  2. Planetary Overload, Limits to Growth and Health.

    Science.gov (United States)

    Butler, Colin D

    2016-12-01

    Since the use of atomic weapons in 1945 visionaries have warned that without major changes the survival of global civilization is in question. These concerns deepened in following decades, during the Cold War, with The Limits to Growth, the best-selling environmental book of the 1970s. Yet, since then, most concern has faded, fuelled by technological developments and a shift in dominant global ideology. Public health, with a few exceptions (one of which is the book Planetary Overload), has been slow to recognize this debate, even as evidence emerges that civilization may indeed be at risk, driven by an increasingly ominous complex of events. This article outlines the key relevant literature and concepts, attempting to bring emerging and future health consequences to the attention of health workers, including the idea of a "social vaccine," conveying sufficient anxiety to provoke action for environmental protection, but insufficient to induce paralysis.

  3. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    Science.gov (United States)

    Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th

    1997-01-01

    We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on

  4. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    Science.gov (United States)

    Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th

    1997-01-01

    We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on

  5. Use of nucleotides in weanling rats with diarrhea induced by a lactose overload: effect on the evolution of diarrhea and weight and on the histopathology of intestine, liver and spleen

    Directory of Open Access Journals (Sweden)

    Norton R.

    2001-01-01

    Full Text Available Until recently, dietary sources of nucleotides were thought not to be essential for good nutrition. Certain states with higher metabolic demands may require larger amounts that cannot be provided by endogenous production. The objective of the present study was to determine the action of nucleotides on the recovery from lactose-induced diarrhea in weaned rats. Thirty-six weanling Fisher rats were divided into two groups. Group 1 received a standard diet and group 2 received a diet containing lactose in place of starch. On the 10th day, six animals per group were sacrificed for histopathological evaluation. The remaining animals were divided into two other subgroups, each with 6 animals, receiving a control diet, a control diet with nucleotides (0.05% adenosine monophosphate, 0.05% guanosine monophosphate, 0.05% cytidine monophosphate, 0.05% uridine monophosphate and 0.05% inosine monophosphate, a diet with lactose, and a diet with lactose and nucleotides. On the 32nd day of the experiment all animals were sacrificed. Animals with diarrhea weighed less than animals without diarrhea. The introduction of nucleotides did not lead to weight gain. Mean diet consumption was lower in the group that continued to ingest lactose, with the group receiving lactose plus nucleotides showing a lower mean consumption. Animals receiving lactose had inflammatory reaction and deposits of periodic acid-Schiff-positive material in intestinal, hepatic and splenic tissues. The introduction of nucleotides led to an improvement of the intestinal inflammatory reaction. In lactose-induced diarrhea, when the stimulus is maintained - lactose overload - the nucleotides have a limited action on the weight gain and on recovery of intestinal morphology, although they have a protective effect on hepatic injury and improve the inflammatory response.

  6. Resveratrol attenuates the Na(+-dependent intracellular Ca(2+ overload by inhibiting H(2O(2-induced increase in late sodium current in ventricular myocytes.

    Directory of Open Access Journals (Sweden)

    Chunping Qian

    Full Text Available BACKGROUND/AIMS: Resveratrol has been demonstrated to be protective in the cardiovascular system. The aim of this study was to assess the effects of resveratrol on hydrogen peroxide (H(2O(2-induced increase in late sodium current (I(Na.L which augmented the reverse Na(+-Ca(2+ exchanger current (I(NCX, and the diastolic intracellular Ca(2+ concentration in ventricular myocytes. METHODS: I(Na.L, I(NCX, L-type Ca(2+ current (I(Ca.L and intracellular Ca(2+ properties were determined using whole-cell patch-clamp techniques and dual-excitation fluorescence photomultiplier system (IonOptix, respectively, in rabbit ventricular myocytes. RESULTS: Resveratrol (10, 20, 40 and 80 µM decreased I(Na.L in myocytes both in the absence and presence of H(2O(2 (300 µM in a concentration dependent manner. Ranolazine (3-9 µM and tetrodotoxin (TTX, 4 µM, I(Na.L inhibitors, decreased I(Na.L in cardiomyocytes in the presence of 300 µM H(2O(2. H(2O(2 (300 µM increased the reverse I(NCX and this increase was significantly attenuated by either 20 µM resveratrol or 4 µM ranolazine or 4 µM TTX. In addition, 10 µM resveratrol and 2 µM TTX significantly depressed the increase by 150 µM H(2O(2 of the diastolic intracellular Ca(2+ fura-2 fluorescence intensity (FFI, fura-fluorescence intensity change (△FFI, maximal velocity of intracellular Ca(2+ transient rise and decay. As expected, 2 µM TTX had no effect on I(Ca.L. CONCLUSION: Resveratrol protects the cardiomyocytes by inhibiting the H(2O(2-induced augmentation of I(Na.L.and may contribute to the reduction of ischemia-induced lethal arrhythmias.

  7. Mineralocorticoid Receptor Deficiency in T Cells Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction Through Modulating T-Cell Activation.

    Science.gov (United States)

    Li, Chao; Sun, Xue-Nan; Zeng, Meng-Ru; Zheng, Xiao-Jun; Zhang, Yu-Yao; Wan, Qiangyou; Zhang, Wu-Chang; Shi, Chaoji; Du, Lin-Juan; Ai, Tang-Jun; Liu, Yuan; Liu, Yan; Du, Li-Li; Yi, Yi; Yu, Ying; Duan, Sheng-Zhong

    2017-07-01

    Although antagonists of mineralocorticoid receptor (MR) have been widely used to treat heart failure, the underlying mechanisms are incompletely understood. Recent reports show that T cells play important roles in pathologic cardiac hypertrophy and heart failure. However, it is unclear whether and how MR functions in T cells under these pathologic conditions. We found that MR antagonist suppressed abdominal aortic constriction-induced cardiac hypertrophy and decreased the accumulation and activation of CD4(+) and CD8(+) T cells in mouse heart. T-cell MR knockout mice manifested suppressed cardiac hypertrophy, fibrosis, and dysfunction compared with littermate control mice after abdominal aortic constriction. T-cell MR knockout mice had less cardiac inflammatory response, which was illustrated by decreased accumulation of myeloid cells and reduced expression of inflammatory cytokines. Less amounts and activation of T cells were observed in the heart of T-cell MR knockout mice after abdominal aortic constriction. In vitro studies showed that both MR antagonism and deficiency repressed activation of T cells, whereas MR overexpression elevated activation of T cells. These results demonstrated that MR blockade in T cells protected against abdominal aortic constriction-induced cardiac hypertrophy and dysfunction. Mechanistically, MR directly regulated T-cell activation and modulated cardiac inflammation. Targeting MR in T cells specifically may be a feasible strategy for more effective treatment of pathologic cardiac hypertrophy and heart failure. © 2017 American Heart Association, Inc.

  8. Intelligent Overload Control for Composite Web Services

    NARCIS (Netherlands)

    Meulenhoff, P.J.; Ostendorf, D.R.; Zivkovic, M.; Meeuwissen, H.B.; Gijsen, B.M.M.

    2009-01-01

    In this paper, we analyze overload control for composite web services in service oriented architectures by an orchestrating broker, and propose two practical access control rules which effectively mitigate the effects of severe overloads at some web services in the composite service. These two rules

  9. Intelligent overload control for composite web services

    NARCIS (Netherlands)

    Meulenhoff, P.J.; Ostendorf, D.R.; Živković, M.; Meeuwissen, H.B.; Gijsen, B.M.M.

    2009-01-01

    In this paper, we analyze overload control for composite web services in service oriented architectures by an orchestrating broker, and propose two practical access control rules which effectively mitigate the effects of severe overloads at some web services in the composite service. These two rules

  10. Genetics Home Reference: African iron overload

    Science.gov (United States)

    ... more about the gene associated with African iron overload SLC40A1 Related Information What is a gene? What is a gene mutation and how do mutations occur? How can gene mutations affect health and development? More about ... Pattern African iron overload seems to run in families, and high iron ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-08

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

  12. [Genetic iron overloads and hepatic insulin-resistance iron overload syndrome: an update].

    Science.gov (United States)

    Ruivard, M

    2009-01-01

    Hepcidin inhibits intestinal absorption of iron through internalisation of ferroportin. Its discovery helps to better understand the genetic iron overloads. The insulin resistance-hepatic iron overload (IR-HIO)--also coined as the dysmetabolic iron overload syndrome--is a common cause or iron overload. This article is a review about genetic iron overloads and IR-HIO. Type 1 haemochromatosis C282Y +/+ accounts for 95% of the haemochromatosis. Hepatic fibrosis may develop if serum ferritin is higher than 1000 microg/l but can be partially reversible with phlebotomies. Juvenile haemochromatosis (type 2) and type 3 haemochromatosis (mutation of the transferrin receptor 2) are very uncommon. Several mutations of the ferroportin gene can cause usually mild iron overload of autosomal dominant inheritance. Aceruleoplasminemia is an uncommon disorder involving cerebral iron overload. The causes and consequences of the IR-HIO are unknown. Treatment of IR-HIO is focused on metabolic syndrome and phlebotomies are questionable because the overload is moderate and intestinal absorption of iron seems to be low. MRI (or other non invasive methods) is needed to truly assess iron overload because serum ferritin overestimates it in metabolic syndrome. Several points have to be elucidated: how HFE interferes with hepcidin in type 1 haemochromatosis; the causes of variability of iron overload; the benefits of populations screening; the advantage of phlebotomies in IR-HIO; the use of new oral iron chelators.

  13. 铁过载引发人肝细胞HH4 N-糖链表达差异研究%Study on differential expression of N-linked glycans in iron overload-induced human hepatocytes HH4

    Institute of Scientific and Technical Information of China (English)

    李士伟; 关锋; 李想

    2015-01-01

    Hepatic iron overload is common in patients undergoing hematopoietic cell transplantation and may be associated with hepatic injury. Here iron overload model of HH4 cells induced by FAC (ferric ammonium citrate) was established. The total proteins of HH4 cells treated with or without FAC were extracted, and total glycopeptides were isolated by an ultrafiltration unit. The glycopeptides were enzymatically hydrolyzed by Peptide-N-glycosidase F (PNGase F) and the released N-linked glycans were desalinated using Sepharose 4B. The structures of the purified N-glycans were identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS). Furthermore, the comparative expression of N-glycans was analyzed by lectin immunohistochemistry. The result indicated that 16 N-glycans were differentially expressed in HH4 cells treated with or without FAC. The levels of high-mannose-type N-glycans were decreased significantly, while the expression of hybrid type, complex type, bisecting type, fucosylation and sialylation of glycans were enhanced markedly in FAC-treated HH4 cells. Consistent with MS analysis, lectin immunohistochemistry study showed that the binding affinity to lectin ConA was reduced in FAC-treated HH4 cells, but the binding affinities to 4 lectins PHA-E, AAL, LCA and MAL-II were significantly increased. The present research provides the fundamental observations for further understanding functional roles of differential expression of N-linked glycans in iron-overload HH4 cells.%肝脏铁过载是血液系统疾病患者进行骨髓移植后的典型并发症之一,长期铁过载可引发肝脏细胞凋亡和器官损坏,然而铁过载的分子调控机理迄今仍不清楚。以培养的枸橼酸铁铵过载人肝细胞HH4和正常人肝细胞HH4为研究对象,细胞裂解提取总蛋白,分子筛超滤管分离获得总糖肽,PNGase F酶解释放出N-糖链,Sepharose 4B除盐纯化N-糖链,再利用基质

  14. Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy A redução da pressão de perfusão coronariana está associada com a fibrose endocárdica no modelo de hipertrofia por sobrecarga de volume em ratos

    Directory of Open Access Journals (Sweden)

    Maria Carolina Guido

    2004-01-01

    Full Text Available Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula. PURPOSE: To investigate the role of acute hemodynamic changes in subsequent deposition of cardiac fibrosis in response to aortocaval fistula. METHOD: Aortocaval fistula were created in 4 groups of Wistar rats that were followed over 4 and 8 weeks: aortocaval fistula 4 and aortocaval fistula 8 (10 rats each and their respective controls (sham-operated controls - Sh, Sh4 and Sh8 (8 rats each. Hemodynamic measurements were performed 1 week after surgery. Hypertrophy and fibrosis were quantified by myocyte diameter and collagen volume fraction at the end of follow up. RESULT: Compared with Sh4 and Sh8, pulse pressure, left ventricular end-diastolic pressure, and +dP/dt were higher in aortocaval fistula 4 and aortocaval fistula 8, but -dP/dt was similar. Coronary driving pressure (mm Hg, used as an estimate of perfusion pressure, was lower in aortocaval fistula 8 (52.6 ± 4.1 than in Sh8 (100.8 ± 1.3, but comparable between aortocaval fistula 4 (50.0 ± 8.9 and Sh4 (84.8 ± 2.3. Myocyte diameter was greater in aortocaval fistula 8, whereas interstitial and subendocardial fibrosis were greater in aortocaval fistula 4 and aortocaval fistula 8. Coronary driving pressure correlated inversely and independently with subendocardial fibrosis (r² = .86, P No remodelamento que se segue às sobrecargas de volume não é descrito o aumento de fibrose miocárdica. Após o infarto, entretanto, há hipertrofia do miocárdio remoto com acúmulo de fibrose, particularmente no subendoc

  15. Hyperferritinaemia in the absence of iron overload

    OpenAIRE

    Arnold, J.; Mumford, A.; Lindsay, J; Hegde, U; Hagan, M; Hawkins, J.

    1997-01-01

    Background—Serum ferritin is normally a marker of iron overload. Ferritin genes are sited at chromosomes 19 and 11. Regulation of ferritin synthesis involves an interaction between an iron regulatory protein (IRP) and part of the ferritin mRNA designated the iron regulatory element (IRE). A disorder of ferritin synthesis resulting in hyperferritinaemia in the absence of iron overload has been described recently. 
Patients and methods—Hyperferriti- naemia in the absence of iron ove...

  16. Thermal Characterization of the Overload Carbon Resistors

    Directory of Open Access Journals (Sweden)

    Ivana Kostić

    2013-01-01

    Full Text Available In many applications, the electronic component is not continuously but only intermittently overloaded (e.g., inrush current, short circuit, or discharging interference. With this paper, we provide insight into carbon resistors that have to hold out a rarely occurring transient overload. Using simple electrical circuit, the resistor is overheating with higher current than declared, and dissipation is observed by a thermal camera.

  17. Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.

    Directory of Open Access Journals (Sweden)

    Sara Sanz-Blasco

    Full Text Available Dysregulation of intracellular Ca(2+ homeostasis may underlie amyloid beta peptide (Abeta toxicity in Alzheimer's Disease (AD but the mechanism is unknown. In search for this mechanism we found that Abeta(1-42 oligomers, the assembly state correlating best with cognitive decline in AD, but not Abeta fibrils, induce a massive entry of Ca(2+ in neurons and promote mitochondrial Ca(2+ overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Abeta oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca(2+ overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca(2+ overload, cytochrome c release and cell death induced by Abeta oligomers. Our results indicate that i mitochondrial Ca(2+ overload underlies the neurotoxicity induced by Abeta oligomers and ii inhibition of mitochondrial Ca(2+ overload provides a novel mechanism of neuroprotection by NSAIDs against Abeta oligomers and AD.

  18. Mitochondrial Ca2+ Overload Underlies Aβ Oligomers Neurotoxicity Providing an Unexpected Mechanism of Neuroprotection by NSAIDs

    Science.gov (United States)

    Sanz-Blasco, Sara; Valero, Ruth A.; Rodríguez-Crespo, Ignacio; Villalobos, Carlos; Núñez, Lucía

    2008-01-01

    Dysregulation of intracellular Ca2+ homeostasis may underlie amyloid β peptide (Aβ) toxicity in Alzheimer's Disease (AD) but the mechanism is unknown. In search for this mechanism we found that Aβ1–42 oligomers, the assembly state correlating best with cognitive decline in AD, but not Aβ fibrils, induce a massive entry of Ca2+ in neurons and promote mitochondrial Ca2+ overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Aβ oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca2+ overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs) including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca2+ overload, cytochrome c release and cell death induced by Aβ oligomers. Our results indicate that i) mitochondrial Ca2+ overload underlies the neurotoxicity induced by Aβ oligomers and ii) inhibition of mitochondrial Ca2+ overload provides a novel mechanism of neuroprotection by NSAIDs against Aβ oligomers and AD. PMID:18648507

  19. 容量超负荷心力衰竭大鼠模型的制备及心脏功能的超声评价%Establishment of rat model of volume-overloaded heart failure and reviewing on heart function by echocardiography

    Institute of Scientific and Technical Information of China (English)

    韩克; 吴格如; 席雨涛; 杜媛; 卢群; 马爱群

    2013-01-01

    Objective To improve the method of establishing the rat model of volume-overloaded heart failure, and discuss the accuracy and reliability of echocardiography in observing heart function in rats with volume-overloaded heart failure. Methods The rat model of volume-overloaded heart failure was established by using abdominal aortocaval shunts (model group, n=40), and a sham-operation group was set (n=20). The changes of LVEDD, LVESD, LAD and LVEF were detected by using color echocardiography. The changes of CABP, LVSP, LVDP and ±dp/dtmax were detected by using carotid artery intubation for reviewing hemodynamic changes in two groups. The heart mass indexes and ratio of heart weight to body weight were compared between two groups after the operation for 12 weeks. Results After modeling for 8 weeks, the outcomes of echocardiography showed left ventricular globular dilation in model group. Compared with sham-operation group, LVEF and LVFS decreased significantly [LVEF: (61.31±3.07)% vs. (77.20±2.41)%;LVFS: (30.37±2.39)% vs. (41.08±2.13)%], LVMI increased [(2.85±0.41) vs. (1.59±0.15)],ratio of heart weight to body weight increased [(5.89±0.56) vs. (2.99± 0.21)] in model group (all P<0.01). After modeling for 12 weeks, LVDP [(12.53±22.63) mmHg vs. (2.27±1.77) mmHg] and-dp/dtmax [(-3.78±2.14) vs. (-5.80±2.26)] increased, and LVSP [(108.88±34.39) mmHg vs. (126.48 ±19.44) mmHg] and+dp/dtmax [(4.89±2.93) vs. (6.92±1.65)] decreased in model group compared with sham-operation group (P<0.05). Conclusion Echocardiography can review dynamically the cardiac morphology and heart function of rat model of volume-overloading heart failure established by using abdominal aortocaval shunts.%目的:改进容量超负荷大鼠模型制备的方法并探讨超声心动图观察大鼠容量超负荷心力衰竭模型心功能状况的准确性与可靠性。方法采用大鼠腹主动脉下腔静脉造瘘方法建立容量超负荷心力衰竭模型,同

  20. Interactions of Aging, Overload, and Creatine Supplementation in Rat Plantaris Muscle

    Directory of Open Access Journals (Sweden)

    Mark D. Schuenke

    2011-01-01

    Full Text Available Attenuation of age-related sarcopenia by creatine supplementation has been equivocal. In this study, plantaris muscles of young (Y; 5m and aging (A; 24m Fisher 344 rats underwent four weeks of either control (C, creatine supplementation (Cr, surgical overload (O, or overload plus creatine (OCr. Creatine alone had no effect on muscle fiber cross-sectional area (CSA or heat shock protein (HSP70 and increased myonuclear domain (MND only in young rats. Overload increased CSA and HSP70 content in I and IIA fibers, regardless of age, and MND in IIA fibers of YO rats. CSA and MND increased in all fast fibers of YOCr, and CSA increased in I and IIA fibers of AOCr. OCR did not alter HSP70, regardless of age. MND did not change in aging rats, regardless of treatment. These data indicate creatine alone had no significant effect. Creatine with overload produced no additional hypertrophy relative to overload alone and attenuated overload-induced HSP70 expression.

  1. Liver cirrhosis as a consequence of iron overload caused by hereditary nonspherocytic hemolytic anemia

    Institute of Scientific and Technical Information of China (English)

    Philip Hilgard; Guido Gerken

    2005-01-01

    Nonspherocytic hereditary anemias are occasionally accompanied by significant iron overload but the significance for the development of chronic liver disease is not clear. We described two cases of patients with chronic liver d isease and severeiron overload due to chronic hereditary hemolysis. Both patients have had signs of liver cirrhosis and severe hemolysis since childhood. A hereditary pyruvate kinase deficiency (PKD) was discovered as the underlying reason for the hemolysis.Sequencing of the pyruvate kinase gene showed a mutation within exon 11. Liver histology in both patients revealed cirrhosis and a severe iron overload but primary hemochromatosis was excluded by HFE-gene analysis.An iron reduction therapy with desferrioxamine led to significant decrease of serum ferritin and sustained clinical improvement. PKD-induced hemolysis may cause severe iron overload even in the absence of HFE-genotype abnormalities. This secondary iron overload can lead to chronic liver disease and cirrhosis. Therefore, the iron metabolism of PKD patients has to be closely monitored and iron overload should be consequently treated.

  2. Intestinal HIF2α promotes tissue-iron accumulation in disorders of iron overload with anemia.

    Science.gov (United States)

    Anderson, Erik R; Taylor, Matthew; Xue, Xiang; Ramakrishnan, Sadeesh K; Martin, Angelical; Xie, Liwei; Bredell, Bryce X; Gardenghi, Sara; Rivella, Stefano; Shah, Yatrik M

    2013-12-10

    Several distinct congenital disorders can lead to tissue-iron overload with anemia. Repeated blood transfusions are one of the major causes of iron overload in several of these disorders, including β-thalassemia major, which is characterized by a defective β-globin gene. In this state, hyperabsorption of iron is also observed and can significantly contribute to iron overload. In β-thalassemia intermedia, which does not require blood transfusion for survival, hyperabsorption of iron is the leading cause of iron overload. The mechanism of increased iron absorption in β-thalassemia is unclear. We definitively demonstrate, using genetic mouse models, that intestinal hypoxia-inducible factor-2α (HIF2α) and divalent metal transporter-1 (DMT1) are activated early in the pathogenesis of β-thalassemia and are essential for excess iron accumulation in mouse models of β-thalassemia. Moreover, thalassemic mice with established iron overload had significant improvement in tissue-iron levels and anemia following disruption of intestinal HIF2α. In addition to repeated blood transfusions and increased iron absorption, chronic hemolysis is the major cause of tissue-iron accumulation in anemic iron-overload disorders caused by hemolytic anemia. Mechanistic studies in a hemolytic anemia mouse model demonstrated that loss of intestinal HIF2α/DMT1 signaling led to decreased tissue-iron accumulation in the liver without worsening the anemia. These data demonstrate that dysregulation of intestinal hypoxia and HIF2α signaling is critical for progressive iron overload in β-thalassemia and may be a novel therapeutic target in several anemic iron-overload disorders.

  3. Effects of a seven day overload-period of high-intensity training on performance and physiology of competitive cyclists.

    Directory of Open Access Journals (Sweden)

    Bradley Clark

    Full Text Available Competitive endurance athletes commonly undertake periods of overload training in the weeks prior to major competitions. This investigation examined the effects of two seven-day high-intensity overload training regimes (HIT on performance and physiological characteristics of competitive cyclists.The study was a matched groups, controlled trial.Twenty-eight male cyclists (mean ± SD, Age: 33±10 years, Mass 74±7 kg, VO2 peak 4.7±0.5 L·min-1 were assigned to a control group or one of two training groups for seven consecutive days of HIT. Before and after training cyclists completed an ergometer based incremental exercise test and a 20-km time-trial. The HIT sessions were ∼120 minutes in duration and consisted of matched volumes of 5, 10 and 20 second (short or 15, 30 and 45 second (long maximal intensity efforts.Both the short and long HIT regimes led to significant (p0.05 increases (mean ± SD in VO2 peak (2.3%±4.7% vs 3.5%±6.2%, lactate threshold power (3.6%±3.5% vs 2.9%±5.3% and gross efficiency (3.2%±2.4% vs 5.1%±3.9% with only small differences between HIT regimes.Seven days of overload HIT induces substantial enhancements in time-trial performance despite non-significant increases in physiological measures with competitive cyclists.

  4. [Role of paraventricular nucleus in natriuresis and diuresis induced by volume expansion in rabbits].

    Science.gov (United States)

    Zhang, B; Lin, M Z; Han, G C

    2000-02-01

    In sham-lesioned and paraventricular nucleus (PVN) lesioned rabbits, the peak increases of urine volume (UV) induced by volume expansion (VE) were 0.59+/-0.09 and 0.31+/-0.03 ml/min (P0.05). In rabbits with renal denervation there was no significant change in natriuretic response after PVN lesion (P>0.05), but lesion of PVN significantly attenuated diuretic response (P0.05). These results suggest that PVN is involved in the regulation of natriuresis and diuresis induced by VE, which are mediated by vagal afferent nerve, whereas the renal sympathetic efferent nerve may be involved in natriuretic response.

  5. Basic research of the relationship between irradiation dose and volume in radiation-induced pulmonary injury

    Institute of Scientific and Technical Information of China (English)

    PANG Qing-song; WANG Ping; WANG Jing; WANG Wei; WANG Jun; YUAN Zhi-yong

    2009-01-01

    Background Irradiation dose and volume are the major physical factors of radiation-induced lung injury.The study investigated the relationships between the irradiation dose and volume in radiation-induced lung injury by setting up a model of graded volume irradiation of the rat lung.Methods Animals were randomly assigned to three groups.The ELEKTA precise 2.03 treatment plan system was applied to calculate the irradiation dose and volume.The treatment plan for the three groups was:group 1 received a "high dose to a small volume" (25% volume group) with the mean irradiation volume being 1.748 cm3 (25% lung volume);the total dose and mean lung dose (MLD) were 4610 cGy and 2006 cGy,respectively (bilateral AP-PA fields,source to axis distance (SAD)=100 cm,6MVX,single irradiation);Group 2 received a "low dose to a large volume" (100% volume group) with the mean irradiation volume being 6.99 cm3 (100% lung volume);the total dose was 1153 cGy.MLD was 2006 cGy,which was the same as that of group 1 (bilateral AP-PA fields,SAD = 100 cm,6MVX,single irradiation);Group 3 was a control group.With the exception of receiving no irradiation,group 3 had rest steps that were the same as those of the experimental groups.After irradiation,functional,histopathological,and CT changes were compared every two weeks till the 16th week.Results Functionally,after irradiation breath rate (BR) increases were observed in both group 1 and group 2,especially during the period of 6th-8th weeks.The changes of BR in the 100% volume group were earlier and faster.For the 25% volume group,although pathology was more severe,hardly any obvious increase in BR was observed.Radiographic changes were observed during the early period (the 4th week) and the most obvious changes manifested during the mediated period (the 8th week).The extensiveness of high density and the decreased lung permeability were presented in the 100% volume group,and ground glass opacity and patchy consolidation were presented in the 25

  6. Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload.

    Science.gov (United States)

    Beetz, Nadine; Rommel, Carolin; Schnick, Tilman; Neumann, Elena; Lother, Achim; Monroy-Ordonez, Elsa Beatriz; Zeeb, Martin; Preissl, Sebastian; Gilsbach, Ralf; Melchior-Becker, Ariane; Rylski, Bartosz; Stoll, Monika; Schaefer, Liliana; Beyersdorf, Friedhelm; Stiller, Brigitte; Hein, Lutz

    2016-12-01

    Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading remains elusive. Thus, the aim of the present study was to assess the effect of biglycan on cardiac remodeling in a mouse model of left ventricular pressure overload and unloading. Left ventricular pressure overload induced by transverse aortic constriction (TAC) in mice resulted in left ventricular dysfunction, fibrosis and increased biglycan expression. Fluorescence- and magnetic-assisted sorting of cardiac cell types revealed upregulation of biglycan in the fibroblast population, but not in cardiomyocytes, endothelial cells or leukocytes after TAC. Removal of the aortic constriction (rTAC) after short-term pressure overload (3weeks) improved cardiac contractility and reversed ventricular hypertrophy but not fibrosis in wild-type (WT) mice. Biglycan ablation (KO) enhanced functional recovery but did not resolve cardiac fibrosis. After long-term TAC for 9weeks, ablation of biglycan attenuated the development of cardiac hypertrophy and fibrosis. In vitro, biglycan induced hypertrophy of neonatal rat cardiomyocytes and led to activation of a hypertrophic gene program. Putative downstream mediators of biglycan signaling include Rcan1, Abra and Tnfrsf12a. These genes were concordantly induced by TAC in WT but not in biglycan KO mice. Left ventricular pressure overload induces biglycan expression in cardiac fibroblasts. Ablation of biglycan improves cardiac function and attenuates left ventricular hypertrophy and fibrosis after long-term pressure overload. In vitro biglycan induces hypertrophy of cardiomyocytes, suggesting that biglycan may act as a signaling molecule between cell types to modulate cardiac remodeling. Copyright © 2016 Elsevier Ltd. All rights

  7. [The use of gravitation overloading in the treatment of obliterative atherosclerosis of lower extremity arteries].

    Science.gov (United States)

    Galkin, R A; Kotel'nikov, G P; Makarov, I V; Oparin, A N

    2003-01-01

    The article sums up results of treatment of 152 patients with obliterating atherosclerosis of the lower extremity arteries which were exposed to 2-3 G gravitation overloading made in a centrifuge of a short radius in direction head--pelvis. The gravitation overloading in the regimen followed were not found to have negative effects of central hemodynamics. Peripheral circulation was noted to considerably improve which is confirmed: 1) by clinical data showing 2-5 times longer distance of painless walking; 2) by the data of ultrasound dopplerography manifested as larger volume rate of blood flow and regional perfusion index; 3) by thermographic explorations evidencing the recovery of the thermoprophile of the legs and feet. Thus, the application of gravitation overloading is a new effective method of conservative treatment of patients with the pathology in question.

  8. Advancing knowledge of right ventricular pathophysiology in chronic pressure overload: Insights from experimental studies.

    Science.gov (United States)

    Guihaire, Julien; Noly, Pierre Emmanuel; Schrepfer, Sonja; Mercier, Olaf

    2015-10-01

    The right ventricle (RV) has to face major changes in loading conditions due to cardiovascular diseases and pulmonary vascular disorders. Clinical experience supports evidence that the RV better compensates for volume than for pressure overload, and for chronic than for acute changes. For a long time, right ventricular (RV) pathophysiology has been restricted to patterns extrapolated from left heart studies. However, the two ventricles are anatomically, haemodynamically and functionally distinct. RV metabolic properties may also result in a different behaviour in response to pathological conditions compared with the left ventricle. In this review, current knowledge of RV pathophysiology is reported in the setting of chronic pressure overload, including recent experimental findings and emerging concepts. After a time-varying compensated period with preserved cardiac output despite overload conditions, RV failure finally occurs, leading to death. The underlying mechanisms involved in the transition from compensatory hypertrophy to maladaptive remodelling are not completely understood. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Global end-diastolic volume increases to maintain fluid responsiveness in sepsis-induced systolic dysfunction

    NARCIS (Netherlands)

    R.J. Trof (R.); I. Danad (Ibrahim); A.B.J. Groeneveld (Johan)

    2013-01-01

    textabstractBackground: Sepsis-induced cardiac dysfunction may limit fluid responsiveness and the mechanism thereof remains unclear. Since cardiac function may affect the relative value of cardiac filling pressures, such as the recommended central venous pressure (CVP), versus filling volumes in gui

  10. Can flow-volume loops be used to diagnose exercise induced laryngeal obstructions?

    DEFF Research Database (Denmark)

    Christensen, Pernille M; Maltbæk, Niels; Jørgensen, Inger M

    2013-01-01

    BACKGROUND: Pre- and post-exercise flow-volume loops are often recommended as an easy non-invasive method for diagnosing or excluding exercise-induced laryngeal obstructions in patients with exercise-related respiratory symptoms. However, at present there is no evidence for this recommendation....... AIMS: To compare physician evaluated pre- and post-exercise flow-volume loops and flow data with laryngoscopic findings during exercise. METHODS: Data from 100 consecutive exercise tests with continuous laryngoscopy during the test were analysed. Laryngoscopic images were compared...... with the corresponding pre- and post-exercise flow-volume loops assessed by four separate physicians and with data from the loops (forced inspiratory flow (FIF) at 25% vs. FIF at 75% of forced inspiratory vital capacity (FIVC), forced expiratory flow at 50% of forced expiratory volume vs. FIF at 50% of FIVC, and FIVC vs...

  11. Influência da heparina sódica na ocorrência de laminite eqüina induzida por sobrecarga de carboidratos Influence of heparin in occurrence of carbohydrate overload-induced equine laminitis

    Directory of Open Access Journals (Sweden)

    L.P. Martins Filho

    2008-12-01

    Full Text Available Avaliou-se a eficiência da infusão intravenosa de heparina sódica (100UI/kg/8h, a partir de 24h após o fornecimento de carboidrato, até completar 48h no controle da laminite eqüina experimentalmente induzida por sobrecarga de carboidrato (17,6g de amido de milho/kg de peso corpóreo. Foram utilizados 15 eqüinos adultos, distribuídos em três grupos experimentais: GI (grupo-controle; GII (grupo laminite e GIII (grupo laminite+heparina. Posteriormente ao fornecimento de carboidrato, os animais foram submetidos a exames físicos e laboratoriais durante um período de 48 horas. Ao final do experimento, os animais foram submetidos à eutanásia pela aplicação intravenosa de 5ml de maleato de acepromazina seguida de 1g de tiopental sódico e 1 litro de solução saturada de KCl para a obtenção de amostras de tecidos dos cascos, necessárias ao exame histológico. Os animais de GII e GIII, submetidos à sobrecarga de carboidratos, desenvolveram laminite, exibindo claudicação 12 e 24h após o fornecimento de carboidrato, respectivamente, bem como aumentos da freqüência cardíaca e do tempo de preenchimento capilar. As alterações histológicas, semelhantes em GII e GIII, eram do tipo degenerativo, como adelgaçamento de lâminas epidérmicas, retração, achatamento e deslocamento de lâminas dérmicas, vacuolização epidérmica e desorganização do tecido epidérmico. A infusão da heparina sódica não preveniu ou atenuou a degeneração laminar.The efficacy of intravenous heparin administration (100UI/kg/8h, from 24 to 48h after carbohydrate administration in the control of carbohydrate overload-induced equine laminitis (17.6g of corn starch/kg live weight was evaluated. Fifteen horses were allocated into three experimental groups: GI (control group, GII (laminitis group, and GIII (laminitis+heparin group. These animals were submitted to physical and laboratorial examination during 48h. After that time, they were euthanized with

  12. Meloxicam protects aluminum overload-induced chronic reproductive deterioration in rats%美洛昔康对铝过负荷致雄鼠生殖损害的保护作用

    Institute of Scientific and Technical Information of China (English)

    汤召兵; 苟欣; 王明; 何卫阳; 刘朝东; 邓远忠

    2011-01-01

    目的 探讨COX-2抑制剂美洛昔康对慢性铝过负荷所致雄性大鼠生殖损害的保护作用.方法 雄性大鼠分为5组,每组6只,即正常对照组、铝负荷组[葡萄糖酸铝Al3+ 200 mg/(kg·d)灌胃]、美洛昔康组[美洛昔康3 mg/(kg·d)灌胃]、铝负荷+小剂量美洛昔康组[葡萄糖酸铝Al3+ 200 mg/(kg·d) +美洛昔康1 mg/(kg·d)灌胃]及铝负荷+大剂量美洛昔康组[葡萄糖酸铝Al3+ 200 mg/(kg·d)+美洛昔康3 mg/(kg·d)灌胃].每周给药5 d,连续20周后处死大鼠取出睾丸附睾称质量,分别计算每只大鼠睾丸、附睾系数(脏器质量/体质量);HE染色观察睾丸附睾的形态学变化.结果 正常对照组、美洛昔康组、铝负荷组、铝负荷+小剂量美洛昔康组、铝负荷+大剂量美洛昔康组大鼠体质量均值分别是572.2、568.8、451.8、552.3、565.7 g,睾丸质量均值分别是4.92、4.91、4.07、4.65、4.86 g,附睾质量均值分别是1.36、1.33、1.12、1.25、1.32 g,铝负荷组大鼠的体质量、睾丸及附睾质量明显降低(P0.05),铝负荷+小剂量美洛昔康组大鼠体质量降低无显著意义(P>0.05),但睾丸附睾质量降低具有显著差异(P0.05).HE染色见铝负荷组曲细精管的生精上皮明显变薄且几乎看不到精细胞、在曲细精管腔内精子数量很少或没有;铝负荷+大剂量美洛昔康组在曲细精管内见大量的各级精细胞及精子;美洛昔康组见睾丸的组织学形态完全正常.铝负荷组大鼠睾丸组织COX-2蛋白表达明显增加(P<0.05);美洛昔康可明显抑制COX-2蛋白表达,大剂量美洛昔康(3 mg/kg)组抑制效应更明显(P<0.05).结论 美洛昔康具有改善铝所致的生殖损害的潜能;其机制可能与抑制COX-2活性,减轻炎症反应和氧化应激损伤有关.%Objective To determine the protective effects of meloxicam on deterioration in reproductive performance induced by chronic aluminum overload in rats. Methods A total of 30 Wistar male rats were

  13. Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.

    Science.gov (United States)

    Koya, Tomoyuki; Nishizawa, Sono; Ohno, Yoshitaka; Goto, Ayumi; Ikuta, Akihiro; Suzuki, Miho; Ohira, Tomotaka; Egawa, Tatsuro; Nakai, Akira; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Beppu, Moroe; Goto, Katsumasa

    2013-01-01

    Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J) mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (pmuscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy.

  14. Skeletal muscle cells express ICAM-1 after muscle overload and ICAM-1 contributes to the ensuing hypertrophic response.

    Directory of Open Access Journals (Sweden)

    Christopher L Dearth

    Full Text Available We previously reported that leukocyte specific β2 integrins contribute to hypertrophy after muscle overload in mice. Because intercellular adhesion molecule-1 (ICAM-1 is an important ligand for β2 integrins, we examined ICAM-1 expression by murine skeletal muscle cells after muscle overload and its contribution to the ensuing hypertrophic response. Myofibers in control muscles of wild type mice and cultures of skeletal muscle cells (primary and C2C12 did not express ICAM-1. Overload of wild type plantaris muscles caused myofibers and satellite cells/myoblasts to express ICAM-1. Increased expression of ICAM-1 after muscle overload occurred via a β2 integrin independent mechanism as indicated by similar gene and protein expression of ICAM-1 between wild type and β2 integrin deficient (CD18-/- mice. ICAM-1 contributed to muscle hypertrophy as demonstrated by greater (p<0.05 overload-induced elevations in muscle protein synthesis, mass, total protein, and myofiber size in wild type compared to ICAM-1-/- mice. Furthermore, expression of ICAM-1 altered (p<0.05 the temporal pattern of Pax7 expression, a marker of satellite cells/myoblasts, and regenerating myofiber formation in overloaded muscles. In conclusion, ICAM-1 expression by myofibers and satellite cells/myoblasts after muscle overload could serve as a mechanism by which ICAM-1 promotes hypertrophy by providing a means for cell-to-cell communication with β2 integrin expressing myeloid cells.

  15. Control over Permissible Short Emergency Overloads in Power Transformers

    Directory of Open Access Journals (Sweden)

    V. A. Anischenko

    2010-01-01

    Full Text Available The paper proposes a method for determination a permissible duration of short intermittent overloads of power transformers that permits to avoid non-permissible over-heating of winding insulation and fully utilize overloading transformer ability.

  16. Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Tanaka, Hiroyuki; Takano, Kazuhiko; Iijima, Hiroaki; Kubo, Hajime; Maruyama, Nobuko; Hashimoto, Toshio; Arakawa, Kenji; Togo, Masanori; Inagaki, Nobuya; Kaku, Kohei

    2017-02-01

    Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients. Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days. Blood and urine samples were collected at predetermined time points. The primary endpoint was evaluation of correlations between changes from baseline in urine volume and factors that are known to affect urine volume and between actual urine volume and these factors. Canagliflozin transiently increased urine volume and urinary sodium excretion on Day 1 with a return to baseline levels thereafter. Canagliflozin administration increased urinary glucose excretion, which was sustained during repeated-dose administration. Plasma atrial natriuretic peptide (ANP) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels decreased, while plasma renin activity increased. On Day 1 of treatment, changes in sodium and potassium excretion were closely correlated with changes in urine output. A post hoc multiple regression analysis showed changes in sodium excretion and water intake as factors that affected urine volume change at Day 1. Furthermore, relative to that at baseline, canagliflozin decreased blood glucose throughout the day and increased plasma total GLP-1 after breakfast. Canagliflozin induced transient sodium excretion and did not induce water intake at Day 1; hence, natriuresis rather than glucose-induced osmotic diuresis may be a major factor involved in the canagliflozin-induced transient increase in urine output. In addition, canagliflozin decreased plasma ANP and NT-proBNP levels and

  17. Overload-protector/fault-indicator circuit

    Science.gov (United States)

    Paluka, J. R.; Moore, S. F.

    1977-01-01

    Circuit incorporates three-terminal current limiter (78M24) to increase overall reliability and to eliminate transistor burnouts resulting from shorted interconnection lines and other overloads. Fact-acting light emitting diodes across the limiters show status of transistor output circuits.

  18. Aggradation in rivers due to overloading

    NARCIS (Netherlands)

    Ribberink, J.S.; Van der Sande, J.T.M.

    1984-01-01

    The problem of aggradation in a river due to overloading is tackled with a mathematical model consisting of a set of one-dimensional (in space) basic equations in which the water motion is assumed to be quasi-steady and the sediment transport is determined by local conditions. Analytical solutions a

  19. Salt wastage, plasma volume contraction and hypokalemic paralysis in self-induced water intoxication.

    Science.gov (United States)

    Tanneau, R S; Pennec, Y L; Morin, J F; Codet, J P; Bourbigot, B; Garre, M; Le Menn, G

    1993-01-01

    Eleven episodes of severe hyponatremia secondary to hiccup-induced potomania were recorded in 3 years in a man who had essential hypertension, a low protein intake and a normal diluting ability. Paradoxical increase in hematocrit and plasma protein with acute extensive natriuresis was associated as well as urine potassium loss and hypokalemia producing paralysis in 1 episode. During a chronic water loading test, the defect in water excretion was related to a low urine solute delivery which was partially reverted by the natriuretic response to plasma volume expansion, promoting water diuresis. In acute water intoxication, this natriuretic response was exaggerated, producing a brisk water diuresis. Plasma volume was rapidly normalized but without any improvement in plasma sodium due to the concomitant negative sodium balance. Thus, water diuresis persisted until plasma volume was significantly contracted. Potassium loss appeared to be related to sodium excretion. Metabolic disturbances have not reoccurred despite persistent hiccup and potomania during 2 years of urea therapy.

  20. Screening for Iron Overload: Lessons from the HEmochromatosis and IRon Overload Screening (HEIRS Study

    Directory of Open Access Journals (Sweden)

    Paul C Adams

    2009-01-01

    Full Text Available BACKGROUND: The HEmochromatosis and IRon Overload Screening (HEIRS Study provided data on a racially, ethnically and geographically diverse cohort of participants in North America screened from primary care populations.

  1. Role of metabolic overload and metabolic inflammation in the development of Nonalcoholic Steatohepatitis (NASH)

    NARCIS (Netherlands)

    Liang, Wen

    2015-01-01

    Overload of nutrients can lead to diet-induced inflammation, also called metabolic inflammation, which is thought to play an important role in many metabolic diseases, including the development of nonalcoholic fatty liver disease (NAFLD). NAFLD encompasses a spectrum of pathologies that range from s

  2. 30 CFR 56.12001 - Circuit overload protection.

    Science.gov (United States)

    2010-07-01

    ... § 56.12001 Circuit overload protection. Circuits shall be protected against excessive overload by fuses or circuit breakers of the correct type and capacity. ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Circuit overload protection. 56.12001...

  3. 30 CFR 57.12001 - Circuit overload protection.

    Science.gov (United States)

    2010-07-01

    ... Electricity Surface and Underground § 57.12001 Circuit overload protection. Circuits shall be protected against excessive overloads by fuses or circuit breakers of the correct type and capacity. ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Circuit overload protection. 57.12001...

  4. Effect of COX-2 inhibitor on 5-LO expression of hippocampus in chronic aluminum overload-induced neurodegenerative rats%COX-2抑制剂对慢性铝过负荷大鼠海马5-脂氧酶表达的影响

    Institute of Scientific and Technical Information of China (English)

    苏强; 杨俊卿; 唐捷

    2012-01-01

    目的 探讨COX-2抑制剂美洛昔康对慢性铝过负荷大鼠海马5-LO表达的影响.方法 葡萄糖酸铝灌胃给予Wistar大鼠,1次/d,每周5d,连续20 w,建立慢性铝过负荷致神经元退变大鼠模型.美洛昔康(1和3 mg/kg),在每次给予铝盐后30 min灌胃给予.RT-PCR检测大鼠海马5-LO mRNA的表达变化,Western印迹方法检测5-LO蛋白表达情况.结果 慢性铝过负荷致大鼠海马5-LO mRNA和蛋白表达明显增加.美洛昔康能明显阻遏慢性铝过负荷诱导的大鼠海马5-LO mRNA和蛋白表达的增加.结论 COX-2抑制剂明显下调慢性铝过负荷大鼠海马5-LO表达.%Objective To investigate the effect of meloxicam on 5-LO expression of hippocampus in chronic aluminum overload induced neurodegeneration rats. Methods Neurodegeneration model of Wistar rats were established by intragastric administration of aluminum gluconate ( Al3 + 200 mg/kg) , once a day, 5 d/week, for 20 weeks. Meloxicam (1 and 3 mg/kg) was intragastrically administered 30 min after each aluminum administration. The expression of 5-LO mRNA and protein in hippocampus were detected by RT-PCR and Western blot respectively. Results Expression of 5-LO mRNA and protein in hippocampus obviously were increased. Meloxicam obviously protected rats from learning and memory function impairment and neuron death, significantly inhibited increase of the expression of 5-LO mRNA and protein induced by chronic aluminum overload. Conclusions Meloxicam can downregulate the 5-LO expression of hippocampus in chronic aluminum overload induced neurodegenerative rats.

  5. Assessment of Iron Overload in Homozygous and Heterozygous Beta Thalassemic Children below 5 Years of Age

    Directory of Open Access Journals (Sweden)

    Dhiraj J. Trivedi

    2014-07-01

    Full Text Available Background: Thalassemia is a genetic disease having 3-7% carrier rate in Indians. It is transfusion dependent anemia having high risk of iron overloading. A clinical symptom of iron overload becomes detectable in second decade causing progressive liver, heart and endocrine glands damage. There is a need to assess iron overload in thalassemics below 5 years of age to protect them from complications at later age of life. Aims and objectives: Present study was undertaken to estimate serum iron status and evaluate serum transferrin saturation in both homozygous & heterozygous form of thalassemia as an index of iron overload among children of one to five years of age. Materials and Methods: Clinically diagnosed thirty cases of β thalassemia major & thirty cases of β thalassemia minor having severe anemia, hepatospleenomegaly and between 1 year to 5 years of age were included in study group and same age matched healthy controls were included in the study. RBC indices and HbA, HbA2 and HbF were estimated along with serum iron & serum Total Iron Binding Capacity (TIBC and serum transferrin levels. Results: Significant difference was observed in hemoglobin levels between control and both beta thalassemia groups. Mean Corpuscular Volume (MCV and Mean Corpuscular Hemoglobin (MCH values were reduced. Hemoglobin electrophoresis showed the elevated levels of HbF and HbA2 in both beta thalassemia groups. Among serum iron parameters, serum iron, TIBC and transferrin saturation were elevated whereas serum transferrin levels were low in thalassemia major in children below 5 years of age. Conclusion: Although clinical symptoms of iron overload have been absent in thalassemic children below five years of age, biochemical iron overloading has started at much lower age which is of great concern.

  6. VARIATION AND SIGNIFICANCE OF C-MYC PROTEIN IN RAT CARDIAC VOLUME-OVERLOAD HYPERTROPHY

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:To investigate the change of c-myc protein,which was chosen as the response indicator to volume-overloab.Methods:The time and spatial course of c-myc protein expression on the model of rat cardiac volume-overload hypertrophy was examined by immunohistochemical study.Results:The immunohistochemical study indicated the expression of c-myc protein was increased obviously at 4-6 hours(62.73%)than that of control(45.41%,P<0.01) after the volume-overload,then decreased gradually along with development of volume-overload hypertrophy and was decreased extremely at 5 months(r=-0.514,p<0.01),Conclusion:There are disorders in the signal transduction pathways governing the hypertrophic response of cardiomyocytes in hypertrophic myocardium.C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy.Once switching on,c-myc gene and the product of it do not act anymore;While it may be that c-myc gene and the product of it increased following with myocardial hypertrophy,and have not direct relation to the occurrence and development of myocardial hypertrophy.

  7. A prediction model of radiation-induced necrosis for intracranial radiosurgery based on target volume.

    Science.gov (United States)

    Zhao, Bo; Wen, Ning; Chetty, Indrin J; Huang, Yimei; Brown, Stephen L; Snyder, Karen C; Siddiqui, Farzan; Movsas, Benjamin; Siddiqui, M Salim

    2017-08-01

    This study aims to extend the observation that the 12 Gy-radiosurgical-volume (V12Gy) correlates with the incidence of radiation necrosis in patients with intracranial tumors treated with radiosurgery by using target volume to predict V12Gy. V12Gy based on the target volume was used to predict the radiation necrosis probability (P) directly. Also investigated was the reduction in radiation necrosis rates (ΔP) as a result of optimizing the prescription isodose lines for linac-based SRS. Twenty concentric spherical targets and 22 patients with brain tumors were retrospectively studied. For each case, a standard clinical plan and an optimized plan with prescription isodose lines based on gradient index were created. V12Gy were extracted from both plans to analyze the correlation between V12Gy and target volume. The necrosis probability P as a function of V12Gy was evaluated. To account for variation in prescription, the relation between V12Gy and prescription was also investigated. A prediction model for radiation-induced necrosis was presented based on the retrospective study. The model directly relates the typical prescribed dose and the target volume to the radionecrosis probability; V12Gy increased linearly with the target volume (R(2)  > 0.99). The linear correlation was then integrated into a logistic model to predict P directly from the target volume. The change in V12Gy as a function of prescription was modeled using a single parameter, s (=-1.15). Relatively large ΔP was observed for target volumes between 7 and 28 cm(3) with the maximum reduction (8-9%) occurring at approximately 18 cm(3) . Based on the model results, optimizing the prescription isodose line for target volumes between 7 and 28 cm(3) results in a significant reduction in necrosis probability. V12Gy based on the target volume could provide clinicians a predictor of radiation necrosis at the contouring stage thus facilitating treatment decisions. © 2017 American Association of

  8. 2,3-Dihydroxybenzoic acid attenuates kanamycin-induced volume reduction in mouse utricular type I hair cells

    DEFF Research Database (Denmark)

    Severinsen, Stig Åvall; Kirkegaard, Mette; Nyengaard, Jens Randel

    2006-01-01

    injection. Total volume of the utricle, as well as total number of hair and supporting cells, were estimated on light microscopic sections. Total volume and mean volume of hair cell types I and II and supporting cells were estimated on digital transmission electron micrographs. Total volume of the utricular...... macula, hair cell type I and supporting cells decreased significantly in animals injected with kanamycin but not in animals co-treated with DHB. Hair and supporting cell numbers remained unchanged in all three groups. In conclusion, the kanamycin-induced volume reduction of type I hair cells...

  9. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Shin Fujimaki

    2016-01-01

    Full Text Available Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

  10. Interleukin-1 inhibits osmotically-induced calcium signaling and volume regulation in articular chondrocytes

    Science.gov (United States)

    Pritchard, Scott; Votta, Bartholomew J.; Kumar, Sanjay; Guilak, Farshid

    2011-01-01

    OBJECTIVE Articular chondrocytes respond to osmotic stress with transient changes in cell volume and the intracellular concentration of calcium ion ([Ca2+]i). The goal of this study was to examine the hypothesis that interleukin-1 (IL-1), a pro-inflammatory cytokine associated with osteoarthritis, influences osmotically-induced Ca2+ signaling. METHODS Fluorescence ratio imaging was used to measure [Ca2+]i and cell volume in response to hypo- or hyper-osmotic stress in isolated porcine chondrocytes, with or without pre-exposure to 10 ng/ml IL-1α. Inhibitors of IL-1 (IL-1 receptor antagonist, IL-Ra), Ca2+ mobilization (thapsigargin, an inhibitor of Ca-ATPases), and cytoskeletal remodeling (Toxin B, an inhibitor of the Rho family of small GTPases) were used to determine the mechanisms involved in increased [Ca2+]i, F-actin remodeling, volume adaptation and active volume recovery. RESULTS In response to osmotic stress, chondrocytes exhibited transient increases in [Ca2+]i, generally followed by decaying oscillations. Pre-exposure to IL-1 significantly inhibited regulatory volume decrease following hypo-osmotic swelling and reduced the change in cell volume and the time to peak [Ca2+]i in response to hyper-osmotic stress, but did not affect the peak magnitudes of [Ca2+]i in those cells that did response. Co-treatment with IL-1Ra, thapsigargin, or Toxin B restored these responses to control levels. The effects were associated with alterations in F-actin organization. CONCLUSIONS IL-1 alters the normal volumetric and Ca2+ signaling response of chondrocytes to osmotic stress through mechanisms involving F-actin remodeling via small Rho GTPases. These findings provide further insights into the mechanisms by which IL-1 may interfere with normal physiologic processes in the chondrocyte, such as the adaptation or regulatory responses to mechanical and osmotic loading. PMID:18495501

  11. CQ Switch Analysis under Traffic Overload

    Directory of Open Access Journals (Sweden)

    I. Maljević

    2011-06-01

    Full Text Available An analysis of 2x2 crossbar packet switch with buffers at crosspoints and round robin scheduling algorithm is presented in this paper. The analysis is performed for a non-admissible traffic pattern, where output ports are overloaded. The case of full offered load is observed and output ports are loaded with packets that have different arrival probabilities. In addition to the parameters that are commonly observed in such an analysis (throughput and average packet delay, memory requirements for the implementation of the buffer, as well as fair representation when servicing the buffer - the so-called fairness are also analyzed. The results show that even for a switch with a small number of ports very large buffers should be implemented, if we want to achieve satisfactory performance under traffic overload.

  12. Changes in Stroke Volume Induced by Lung Recruitment Maneuver Predict Fluid Responsiveness in Mechanically Ventilated Patients in the Operating Room.

    Science.gov (United States)

    Biais, Matthieu; Lanchon, Romain; Sesay, Musa; Le Gall, Lisa; Pereira, Bruno; Futier, Emmanuel; Nouette-Gaulain, Karine

    2017-02-01

    Lung recruitment maneuver induces a decrease in stroke volume, which is more pronounced in hypovolemic patients. The authors hypothesized that the magnitude of stroke volume reduction through lung recruitment maneuver could predict preload responsiveness. Twenty-eight mechanically ventilated patients with low tidal volume during general anesthesia were included. Heart rate, mean arterial pressure, stroke volume, and pulse pressure variations were recorded before lung recruitment maneuver (application of continuous positive airway pressure of 30 cm H2O for 30 s), during lung recruitment maneuver when stroke volume reached its minimal value, and before and after volume expansion (250 ml saline, 0.9%, infused during 10 min). Patients were considered as responders to fluid administration if stroke volume increased greater than or equal to 10%. Sixteen patients were responders. Lung recruitment maneuver induced a significant decrease in mean arterial pressure and stroke volume in both responders and nonresponders. Changes in stroke volume induced by lung recruitment maneuver were correlated with those induced by volume expansion (r = 0.56; P recruitment maneuver predicted fluid responsiveness with a sensitivity of 88% (95% CI, 62 to 98) and a specificity of 92% (95% CI, 62 to 99). Pulse pressure variations more than 6% before lung recruitment maneuver discriminated responders with a sensitivity of 69% (95% CI, 41 to 89) and a specificity of 75% (95% CI, 42 to 95). The area under receiver operating curves generated for changes in stroke volume induced by lung recruitment maneuver (0.96; 95% CI, 0.81 to 0.99) was significantly higher than that for pulse pressure variations (0.72; 95% CI, 0.52 to 0.88; P recruitment maneuver could predict preload responsiveness in mechanically ventilated patients in the operating room.

  13. Valgus Extension Overload in Baseball Players.

    Science.gov (United States)

    Paulino, Franklin E; Villacis, Diego C; Ahmad, Christopher S

    2016-01-01

    Repetitive throwing, such as in baseball pitching, applies massive stress on the elbow. This can often lead to a predictable constellation of elbow injuries, such as valgus extension overload syndrome (VEO). The following review of VEO provides an understanding of relevant anatomy, explanation of pathomechanics, key aspects to clinical evaluation, effective treatment options, and indications for surgery. In addition, we provide the senior author's (CSA) preferred arthroscopic technique for cases of VEO refractory to conservative management.

  14. Function of cGMP-dependent protein kinase II in volume load-induced diuresis.

    Science.gov (United States)

    Schramm, Andrea; Schinner, Elisabeth; Huettner, Johannes P; Kees, Frieder; Tauber, Philipp; Hofmann, Franz; Schlossmann, Jens

    2014-10-01

    Atrial natriuretic peptide (ANP)/cGMPs cause diuresis and natriuresis. Their downstream effectors beyond cGMP remain unclear. To elucidate a probable function of cGMP-dependent protein kinase II (cGKII), we investigated renal parameters in different conditions (basal, salt diets, starving, water load) using a genetically modified mouse model (cGKII-KO), but did not detect any striking differences between WT and cGKII-KO. Thus, cGKII is proposed to play only a marginal role in the adjustment of renal concentration ability to varying salt loads without water restriction or starving conditions. When WT mice were subjected to a volume load (performed by application of a 10-mM glucose solution (3% of BW) via feeding needle), they exhibited a potent diuresis. In contrast, urine volume was decreased significantly in cGKII-KO. We showed that AQP2 plasma membrane (PM) abundance was reduced for about 50% in WT upon volume load, therefore, this might be a main cause for the enhanced diuresis. In contrast, cGKII-KO mice almost completely failed to decrease AQP2-PM distribution. This significant difference between both genotypes is not induced by an altered p-Ser256-AQP2 phosphorylation, as phosphorylation at this site decreases similarly in WT and KO. Furthermore, sodium excretion was lowered in cGKII-KO mice during volume load. In summary, cGKII is only involved to a minor extent in the regulation of basal renal concentration ability. By contrast, cGKII-KO mice are not able to handle an acute volume load. Our results suggest that membrane insertion of AQP2 is inhibited by cGMP/cGKII.

  15. Cholesterol overload induces apoptosis in SH-SY5Y human neuroblastoma cells through the up regulation of flotillin-2 in the lipid raft and the activation of BDNF/Trkb signaling.

    Science.gov (United States)

    Huang, Yen-Ning; Lin, Ching-I; Liao, Hsiang; Liu, Chin-Yu; Chen, Yue-Hua; Chiu, Wan-Chun; Lin, Shyh-Hsiang

    2016-07-22

    Epidemiological investigations have shown that Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. It has been indicated that the cholesterol concentration in the brain of AD patients is higher than that in normal people. In this study, we investigated the effects of cholesterol concentrations, 0, as the control, 3.125, 12.5, and 25μM, on cholesterol metabolism, neuron survival, AD-related protein expressions, and cell morphology and apoptosis using SH-SY5Y human neuroblastoma cells. We observed that expressions of cholesterol hydroxylase (Cyp46), flotillin-2 (a marker of lipid raft content), and truncated tyrosine kinase B (TrkBtc) increased, while expressions of brain-derived neurotrophic factor (BDNF) and full-length TrkB (TrkBfl) decreased as the concentration of cholesterol loading increased. Down-regulation of the PI3K-Akt-glycogen synthase kinase (GSK)-3β cascade and cell apoptosis were also observed at higher concentrations of cholesterol, along with elevated levels of β-amyloid (Aβ), β-secretase (BACE), and reactive oxygen species (ROS). In conclusion, we found that cholesterol overload in neuronal cells imbalanced the cholesterol homeostasis and increased the protein expressions causing cell apoptosis, which illustrates the neurodegenerative pathology of abnormally elevated cholesterol concentrations found in AD patients.

  16. Experimental study of acute lung injury induced by different tidal volume ventilation in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin-ri; DU Yong-cheng; JIANG Hong-ying; XU Jian-ying; XU Yong-jian

    2005-01-01

    @@ Mechanical ventilation (MV) is a dual blade sward which if misused could lead to lung injury, called ventilator induced lung injury (VILI). Pathogenesis of VILI is very complex with various manifestations, which is the focus in MV field in recent years.1 In our research, the rats were ventilated with different tidal volume, then the pathological changes of the lungs were observed under macroscopy, light and electronic microscope, and various laboratory tests in blood and bronchoalveolar lavage fluid (BALF) were also carried out in order to probe further the pathologic characteristics and the pathogenesis of VILI.

  17. Iron Overload in Patients Undergoing Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Vinod Pullarkat

    2010-01-01

    Full Text Available Recipients of hematopoietic stem cell transplantation (HSCT frequently have iron overload resulting from chronic transfusion therapy for anemia. In some cases, for example, in patients with myelodysplastic syndromes and thalassemia, this can be further exacerbated by increased absorption of iron from the gut as a result of ineffective erythropoiesis. Accumulating evidence has established the negative impact of elevated pretransplantation serum ferritin, a surrogate marker of iron overload, on overall survival and nonrelapse mortality after HSCT. Complications of HSCT associated with iron overload include increased bacterial and fungal infections as well as sinusoidal obstruction syndrome and possibly other regimen-related toxicities. Based on current evidence, particular attention should be paid to prevention and management of iron overload in allogeneic HSCT candidates, especially in patients with thalassemia and myelodysplastic syndromes. The pathophysiology of iron overload in the HSCT patient and optimum strategies to deal with iron overload during and after HSCT require further study.

  18. Coupled wave analysis of holographically induced transparency (HIT) generated by two multiplexed volume gratings.

    Science.gov (United States)

    Carretero, Luis; Blaya, Salvador; Acebal, Pablo; Fimia, Antonio; Madrigal, Roque; Murciano, Angel

    2011-04-11

    We present a holographic system that can be used to manipulate the group velocity of light pulses. The proposed structure is based on the multiplexing of two sequential holographic volume gratings, one in transmission and the other in reflection geometry, where one of the recording beams must be the same for both structures. As in other systems such as grating induced transparency (GIT) or coupled-resonator-induced transparency (CRIT), by using the coupled wave theory it is shown that this holographic structure represents a classical analogue of the electromagnetically induced transparency (EIT). Analytical expressions were obtained for the transmittance induced at the forbidden band (spectral hole) and conditions where the group velocity was slowed down were analyzed. Moreover, the propagation of Gaussian pulses is analyzed for this system by obtaining, after further approximations, analytical expressions for the distortion of the transmitted field. As a result, we demonstrate the conditions where the transmitted pulse is slowed down and its shape is only slightly distorted. Finally, by comparing with the exact solutions obtained, the range of validity of all the analytical formulae was verified, demonstrating that the error is very low.

  19. Design of vehicle overload detection system based on geophone

    Science.gov (United States)

    Hu, Siquan; Kong, Min; She, Chundong

    2017-08-01

    A vehicle overload detection system is proposed based on geophone. Under normal circumstances, when overloaded vehicles and ordinary vehicles pass through the road, the amplitude of the ground vibration will be different, and the geophone sensor can detect tiny vibrations of the ground. The system includes information acquisition module, signal conditioning module and wireless transmission module. The collected vibration data is transmitted through the wireless transmission module to the background, and the SVM algorithm is used to classify the information and determine whether the vehicle is overloaded. Experiments show that the system can detect overload accurately.

  20. Volume analysis of heat-induced cracks in human molars: A preliminary study

    Directory of Open Access Journals (Sweden)

    Michael A. Sandholzer

    2014-01-01

    Full Text Available Context: Only a few methods have been published dealing with the visualization of heat-induced cracks inside bones and teeth. Aims : As a novel approach this study used nondestructive X-ray microtomography (micro-CT for volume analysis of heat-induced cracks to observe the reaction of human molars to various levels of thermal stress. Materials and Methods: Eighteen clinically extracted third molars were rehydrated and burned under controlled temperatures (400, 650, and 800°C using an electric furnace adjusted with a 25°C increase/min. The subsequent high-resolution scans (voxel-size 17.7 μm were made with a compact micro-CT scanner (SkyScan 1174. In total, 14 scans were automatically segmented with Definiens XD Developer 1.2 and three-dimensional (3D models were computed with Visage Imaging Amira 5.2.2. The results of the automated segmentation were analyzed with an analysis of variance (ANOVA and uncorrected post hoc least significant difference (LSD tests using Statistical Package for Social Sciences (SPSS 17. A probability level of P < 0.05 was used as an index of statistical significance. Results: A temperature-dependent increase of heat-induced cracks was observed between the three temperature groups (P < 0.05, ANOVA post hoc LSD. In addition, the distributions and shape of the heat-induced changes could be classified using the computed 3D models. Conclusion: The macroscopic heat-induced changes observed in this preliminary study correspond with previous observations of unrestored human teeth, yet the current observations also take into account the entire microscopic 3D expansions of heat-induced cracks within the dental hard tissues. Using the same experimental conditions proposed in the literature, this study confirms previous results, adds new observations, and offers new perspectives in the investigation of forensic evidence.

  1. Insulin Protects Pancreatic Acinar Cells from Cytosolic Calcium Overload and Inhibition of Plasma Membrane Calcium Pump*

    Science.gov (United States)

    Mankad, Parini; James, Andrew; Siriwardena, Ajith K.; Elliott, Austin C.; Bruce, Jason I. E.

    2012-01-01

    Acute pancreatitis is a serious and sometimes fatal inflammatory disease of the pancreas without any reliable treatment or imminent cure. In recent years, impaired metabolism and cytosolic Ca2+ ([Ca2+]i) overload in pancreatic acinar cells have been implicated as the cardinal pathological events common to most forms of pancreatitis, regardless of the precise causative factor. Therefore, restoration of metabolism and protection against cytosolic Ca2+ overload likely represent key therapeutic untapped strategies for the treatment of this disease. The plasma membrane Ca2+-ATPase (PMCA) provides a final common path for cells to “defend” [Ca2+]i during cellular injury. In this paper, we use fluorescence imaging to show for the first time that insulin treatment, which is protective in animal models and clinical studies of human pancreatitis, directly protects pancreatic acinar cells from oxidant-induced cytosolic Ca2+ overload and inhibition of the PMCA. This protection was independent of oxidative stress or mitochondrial membrane potential but appeared to involve the activation of Akt and an acute metabolic switch from mitochondrial to predominantly glycolytic metabolism. This switch to glycolysis appeared to be sufficient to maintain cellular ATP and thus PMCA activity, thereby preventing Ca2+ overload, even in the face of impaired mitochondrial function. PMID:22128146

  2. Mechanisms of fatigue crack retardation following single tensile overloads in powder metallurgy aluminum alloys

    Science.gov (United States)

    Bray, G. H.; Reynolds, A. P.; Starke, E. A., Jr.

    1992-01-01

    In ingot metallurgy (IM) alloys, the number of delay cycles following a single tensile overload typically increases from a minimum at an intermediate baseline stress intensity range, Delta-K(B), with decreasing Delta-K(B) approaching threshold and increasing Delta-K(B) approaching unstable fracture to produce a characteristic 'U' shaped curve. Two models have been proposed to explain this behavior. One model is based on the interaction between roughness and plasticity-induced closure, while the other model only utilizes plasticity-induced closure. This article examines these models, using experimental results from constant amplitude and single overload fatigue tests performed on two powder metallurgy (PM) aluminum alloys, AL-905XL and AA 8009. The results indicate that the 'U'-shaped curve is primarily due to plasticity-induced closure, and that the plasticity-induced retardation effect is through-thickness in nature, occurring in both the surface and interior regions. However, the retardation effect is greater at the surface, because the increase in plastic strain at the crack tip and overload plastic zone size are larger in the plane-stress surface regions than in the plane-strain interior regions. These results are not entirely consistent with either of the proposed models.

  3. Iron age: novel targets for iron overload.

    Science.gov (United States)

    Casu, Carla; Rivella, Stefano

    2014-12-05

    Excess iron deposition in vital organs is the main cause of morbidity and mortality in patients affected by β-thalassemia and hereditary hemochromatosis. In both disorders, inappropriately low levels of the liver hormone hepcidin are responsible for the increased iron absorption, leading to toxic iron accumulation in many organs. Several studies have shown that targeting iron absorption could be beneficial in reducing or preventing iron overload in these 2 disorders, with promising preclinical data. New approaches target Tmprss6, the main suppressor of hepcidin expression, or use minihepcidins, small peptide hepcidin agonists. Additional strategies in β-thalassemia are showing beneficial effects in ameliorating ineffective erythropoiesis and anemia. Due to the suppressive nature of the erythropoiesis on hepcidin expression, these approaches are also showing beneficial effects on iron metabolism. The goal of this review is to discuss the major factors controlling iron metabolism and erythropoiesis and to discuss potential novel therapeutic approaches to reduce or prevent iron overload in these 2 disorders and ameliorate anemia in β-thalassemia.

  4. Fluid Overload and Cumulative Thoracostomy Output Are Associated With Surgical Site Infection After Pediatric Cardiothoracic Surgery.

    Science.gov (United States)

    Sochet, Anthony A; Nyhan, Aoibhinn; Spaeder, Michael C; Cartron, Alexander M; Song, Xiaoyan; Klugman, Darren; Brown, Anna T

    2017-08-01

    To determine the impact of cumulative, postoperative thoracostomy output, amount of bolus IV fluids and peak fluid overload on the incidence and odds of developing a deep surgical site infection following pediatric cardiothoracic surgery. A single-center, nested, retrospective, matched case-control study. A 26-bed cardiac ICU in a 303-bed tertiary care pediatric hospital. Cases with deep surgical site infection following cardiothoracic surgery were identified retrospectively from January 2010 through December 2013 and individually matched to controls at a ratio of 1:2 by age, gender, Risk Adjustment for Congenital Heart Surgery score, Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery category, primary cardiac diagnosis, and procedure. None. Twelve cases with deep surgical site infection were identified and matched to 24 controls without detectable differences in perioperative clinical characteristics. Deep surgical site infection cases had larger thoracostomy output and bolus IV fluid volumes at 6, 24, and 48 hours postoperatively compared with controls. For every 1 mL/kg of thoracostomy output, the odds of developing a deep surgical site infection increase by 13%. By receiver operative characteristic curve analysis, a cutoff of 49 mL/kg of thoracostomy output at 48 hours best discriminates the development of deep surgical site infection (sensitivity 83%, specificity 83%). Peak fluid overload was greater in cases than matched controls (12.5% vs 6%; p thoracostomy output were associated with deep surgical site infection after pediatric cardiothoracic surgery. We suspect the observed increased thoracostomy output, fluid overload, and IV fluid boluses may have altered antimicrobial prophylaxis. Although analysis of additional pharmacokinetic data is warranted, providers may consider modification of antimicrobial prophylaxis dosing or alterations in fluid management and diuresis in response to assessment of peak fluid overload and fluid

  5. Body sodium overload modulates the firing rate and fos immunoreactivity of serotonergic cells of dorsal raphe nucleus.

    Directory of Open Access Journals (Sweden)

    Andrea Godino

    Full Text Available In order to determine whether serotonergic (5HT dorsal raphe nucleus (DRN cells are involved in body sodium status regulation, the effect of a s.c. infusion of either 2 M or 0.15 M NaCl on 5HT DRN neuron firing was studied using single unit extracellular recordings. In separate groups of 2 M and 0.15 M NaCl-infused rats, water intake, oxytocin (OT plasma concentration, urine and plasma sodium and protein concentrations were also measured. Also, to determine the involvement of particular brain nuclei and neurochemical systems in body sodium overload (SO, animals from both groups were perfused for brain immunohistochemical detection of Fos, Fos-OT and Fos-5HT expression. SO produced a significant increase in serotonergic DRN neuron firing rate compared to baseline and 0.15 M NaCl-infused rats. As expected, 2 M NaCl s.c. infusion also induced a significant increase of water intake, diuresis and natriuresis, plasma sodium concentration and osmolality, even though plasma volume did not increase as indicated by changes in plasma protein concentration. The distribution of neurons along the forebrain and brainstem expressing Fos after SO showed the participation of the lamina terminalis, extended amygdala, supraoptic and paraventricular hypothalamic nuclei in the neural network that controls osmoregulatory responses. Both Fos-OT immunoreactive and plasma OT concentration increased after s.c. hypertonic sodium infusion. Finally, matching the "in vivo" electrophysiological study, SO doubled the number of Fos-5HT immunolabeled cells within the DRN. In summary, the results characterize the behavioral, renal and endocrine responses after body sodium overload without volume expansion and specify the cerebral nuclei that participate at different CNS levels in the control of these responses. The electrophysiological approach also allows us to determine in an "in vivo" model that DRN 5HT neurons increase their firing frequency during an increase in systemic

  6. Can serpentinization induce fracturing? Fluid pathway development and the volume increase enigma

    Science.gov (United States)

    Plümper, Oliver; Jamtveit, Bjørn; Røyne, Anja

    2013-04-01

    focused on this topic so far. Here, we investigate the feasibility of reaction-induced fracturing and pore space evolution during serpentinization by combining microstructural investigations using scanning/transmission electron microscopy and synchrotron micro-tomography of natural samples with theoretical considerations on the forces exerted during solid volume increasing reactions. We particularly focus on the interface-scale mechanism of reaction-induced fracturing (Plümper et al. 2012) and the establishment of microstructural markers (e.g., inert exsolutions in olivine) to identify volume changes and estimate crystallization pressures (Kelemen and Hirth 2012). Our investigations suggest that reaction-induced fracturing during serpentinization is possible and during certain physico-chemical circumstances a positive feedback to alter vast amounts of originally impermeable rock is established. Plümper O., Røyne A., Magraso A., Jamtveit B. (2012) The interface-scale mechanism of reaction-induced fracturing during serpentinization. Geology. 40, 1103-1106. Kelemen, P. B. & Hirth, G. (2012) Reaction-driven cracking during retrograde metamorphism: Olivine hydration and carbonation. Earth and Planetary Science Letters 345, 81-89.

  7. Study of laser induced thermo-acoustic signals in a large ice volume

    Energy Technology Data Exchange (ETDEWEB)

    Bissok, Martin; Laihem, Karim; Meures, Thomas; Paul, Larissa; Wiebusch, Christopher; Zierke, Simon [III. Physikalisches Institut, RWTH Aachen (Germany)

    2010-07-01

    A goal for next generation neutrino-telescopes is the exploration of the extremely high energy region (>EeV). Expected neutrino event rates in this energy range are low (<1 event/km{sup 3}/year) and therefore a detector volume which is increased by more than one order of magnitude compared to IceCube is desireable. A possible approach to achieve such an increase in a cost-effective way is the acoustic detection of neutrinos, based on the principle of thermoacoustic signal generation in neutrino-induced hadronic cascades. The Aachen Acoustic Laboratory (AAL) provides the means to study the thermoacoustic effect in a controlled environment. It consists of a large water-filled tank inside a cooling container. The freezing process is controlled and a large volume of bubble-free clear ice({proportional_to}3m{sup 3}) is produced. Thermoacoustic signals are generated by a pulsed Nd:YAG laser with an energy of up to 55 mJ/pulse. The acoustic signals are recorded by an array of 19 piezo-based sensors embedded in the ice. In this talk we give a description of this test experiment and present results from an initial freezing period.

  8. Iron overload following bone marrow transplantation in children: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Kornreich, L.; Horev, G.; Grunebaum, M. [Department of Imaging, Schneider Children`s Medical Center of Israel, Beilinson Medical Campus, 49202 Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University (Israel); Yaniv, I.; Stein, J.; Zaizov, R. [Department of Pediatric Hematology-Oncology, Schneider Children`s Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University (Israel)

    1997-11-01

    Objective. The purpose of this study was to determine the incidence of post-transfusional iron overload in children after bone marrow transplantation by reviewing their magnetic resonance imaging (MR) findings. Materials and methods. We reviewed the abdominal MR studies of 13 children after autologous bone marrow transplantation. Nine of the children had also undergone MR prior to transplantation. Iron deposition in the liver, spleen and bone marrow was graded semi-quantitatively on both T1- and T2-weighted images. Serum ferritin levels and number of blood units given after bone marrow transplantation were recorded. Results. None of the pre-transplantation MR studies revealed iron overload. After bone marrow transplantation, three children showed normal liver and spleen. Iron overload in the liver was noted in ten patients (77 %), six of whom also showed iron overload in the spleen (46 %) and five in the bone marrow (38.5 %). The degree of hepatic iron overload was correlated significantly and splenic iron overload was correlated weakly with the number of blood transfusions (P = 0.01 and P > 0.01, respectively), but neither was correlated with the serum ferritin level. Conclusion. Iron overload commonly accompanies bone marrow transplantation. The observed pattern of iron deposition, in which the spleen was uninvolved in 40 % of patients demonstrating iron overload, is not typical of post-transfusional hemochromatosis. (orig.) With 1 fig., 2 tabs., 15 refs.

  9. Dysmetabolic Hyperferritinemia: All Iron Overload Is Not Hemochromatosis

    Directory of Open Access Journals (Sweden)

    Jasbir Makker

    2015-01-01

    Full Text Available Disturbances in iron metabolism can be genetic or acquired and accordingly manifest as primary or secondary iron overload state. Organ damage may result from iron overload and manifest clinically as cirrhosis, diabetes mellitus, arthritis, endocrine abnormalities and cardiomyopathy. Hemochromatosis inherited as an autosomal recessive disorder is the most common genetic iron overload disorder. Expert societies recommend screening of asymptomatic and symptomatic individuals with hemochromatosis by obtaining transferrin saturation (calculated as serum iron/total iron binding capacity × 100. Further testing for the hemochromatosis gene is recommended if transferrin saturation is >45% with or without hyperferritinemia. However, management of individuals with low or normal transferrin saturation is not clear. In patients with features of iron overload and high serum ferritin levels, low or normal transferrin saturation should alert the physician to other - primary as well as secondary - causes of iron overload besides hemochromatosis. We present here a possible approach to patients with hyperferritinemia but normal transferrin saturation.

  10. Dysmetabolic hyperferritinemia: all iron overload is not hemochromatosis.

    Science.gov (United States)

    Makker, Jasbir; Hanif, Ahmad; Bajantri, Bharat; Chilimuri, Sridhar

    2015-01-01

    Disturbances in iron metabolism can be genetic or acquired and accordingly manifest as primary or secondary iron overload state. Organ damage may result from iron overload and manifest clinically as cirrhosis, diabetes mellitus, arthritis, endocrine abnormalities and cardiomyopathy. Hemochromatosis inherited as an autosomal recessive disorder is the most common genetic iron overload disorder. Expert societies recommend screening of asymptomatic and symptomatic individuals with hemochromatosis by obtaining transferrin saturation (calculated as serum iron/total iron binding capacity × 100). Further testing for the hemochromatosis gene is recommended if transferrin saturation is >45% with or without hyperferritinemia. However, management of individuals with low or normal transferrin saturation is not clear. In patients with features of iron overload and high serum ferritin levels, low or normal transferrin saturation should alert the physician to other - primary as well as secondary - causes of iron overload besides hemochromatosis. We present here a possible approach to patients with hyperferritinemia but normal transferrin saturation.

  11. Iron overload in Brazilian thalassemic patients

    Directory of Open Access Journals (Sweden)

    Reijane Alves de Assis

    2011-06-01

    Full Text Available Objectives: To evaluate the use of magnetic resonance imaging inpatients with β-thalassemia and to compare T2* magnetic resonanceimaging results with serum ferritin levels and the redox active fraction of labile plasma iron. Methods: We have retrospectively evaluated 115 chronically transfused patients (65 women. We tested serum ferritin with chemiluminescence, fraction of labile plasma iron by cellular fluorescence and used T2* MRI to assess iron content in the heart, liver, and pancreas. Hepatic iron concentration was determined in liver biopsies of 11 patients and the results were compared with liver T2* magnetic resonance imaging. Results: The mean serum ferritin was 2,676.5 +/- 2,051.7 ng/mL. A fraction of labile plasma iron was abnormal (> 0,6 Units/mL in 48/83 patients (57%. The mean liver T2* value was 3.91 ± 3.95 ms, suggesting liver siderosis in most patients (92.1%. The mean myocardial T2* value was 24.96 ± 14.17 ms and the incidence of cardiac siderosis (T2* < 20 ms was 36%, of which 19% (22/115 were severe cases (T2* < 10 ms. The mean pancreas T2* value was 11.12 ± 11.20 ms, and 83.5% of patients had pancreatic iron deposition (T2* < 21 ms. There was significant curvilinear and inverse correlation between liver T2* magnetic resonance imaging and hepatic iron concentration (r= -0.878; p < 0.001 and moderate correlation between pancreas and myocardial T2* MRI (r = 0.546; p < 0.0001. Conclusion: A high rate of hepatic, pancreatic and cardiac impairment by iron overload was demonstrated. Ferritin levels could not predict liver, heart or pancreas iron overload as measured by T2* magnetic resonance imaging. There was no correlation between liver, pancreas, liver and myocardial iron overload, neither between ferritin and fraction of labile plasma iron with liver, heart and pancreas T2* values.

  12. Pressure-induced volume expansion of zeolites in the natrolite family.

    Science.gov (United States)

    Lee, Yongjae; Vogt, Thomas; Hriljac, Joseph A; Parise, John B; Artioli, Gilberto

    2002-05-15

    Powder diffraction patterns of the zeolites natrolite (Na(16)Al(16)Si(24)O(80).16H(2)O), mesolite (Na(5.33)Ca(5.33)Al(16)Si(24)O(80).21.33H(2)O), scolecite (Ca(8)Al(16)Si(24)O(80).24H(2)O), and a gallosilicate analogue of natrolite (K(16)Ga(16)Si(24)O(80).12H(2)O), all crystallizing with a natrolite framework topology, were measured as a function of pressure up to 5.0 GPa with use of a diamond-anvil cell and a 200 microm focused monochromatic synchrotron X-ray beam. Under the hydrostatic conditions mediated by an alcohol and water mixture, all these materials showed an abrupt volume expansion (ca. 2.5% in natrolite) between 0.8 and 1.5 GPa without altering the framework topology. Rietveld refinements using the data collected on natrolite show that the anomalous swelling is due to the selective sorption of water from the pressure-transmission fluid expanding the channels along the a- and b-unit cell axes. This gives rise to a "superhydrated" phase of natrolite with an approximate formula of Na(16)Al(16)Si(24)O(80).32H(2)O, which contains hydrogen-bonded helical water nanotubes along the channels. In mesolite, which at ambient pressure is composed of ordered layers of sodium- and calcium-containing channels in a 1:2 ratio along the b-axis, this anomalous swelling is accompanied by a loss of the superlattice reflections (b(mesolite) = 3b(natrolite)). This suggests a pressure-induced order-disorder transition involving the motions of sodium and calcium cations either through cross-channel diffusion or within the respective channels. The powder diffraction data of scolecite, a monoclinic analogue of natrolite where all sodium cations are substituted by calcium and water molecules, reveal a reversible pressure-induced partial amorphization under hydrostatic conditions. Unlike the 2-dimensional swelling observed in natrolite and mesolite, the volume expansion of the potassium gallosilicate natrolite is 3-dimensional and includes the lengthening of the channel axis. In

  13. Evaluation of thermal overload in boiler operators.

    Science.gov (United States)

    Braga, Camila Soares; Rodrigues, Valéria Antônia Justino; Campos, Julio César Costa; de Souza, Amaury Paulo; Minette, Luciano José; de Moraes, Angêlo Casali; Sensato, Guilherme Luciano

    2012-01-01

    The Brazilians educational institutions need a large energy demand for the operation of laundries, restaurants and accommodation of students. Much of that energy comes from steam generated in boilers with wood fuel. The laboral activity in boiler may present problems for the operator's health due to exposure to excessive heat, and its operation has a high degree of risk. This paper describes an analysis made the conditions of thermal environment in the operation of a B category boiler, located at a Higher Education Institution, located in the Zona da Mata Mineira The equipments used to collect data were Meter WBGT of the Heat Index; Meter of Wet Bulb Index and Globe Thermometer (WBGT); Politeste Instruments, an anemometer and an Infrared Thermometer. By the application of questionnaires, the second phase consisted of collecting data on environmental factors (temperature natural environment, globe temperature, relative humidity and air velocity). The study concluded that during the period evaluated, the activity had thermal overload.

  14. Self-* overload control for distributed web systems

    CERN Document Server

    Bartolini, Novella; Silvestri, Simone

    2008-01-01

    Unexpected increases in demand and most of all flash crowds are considered the bane of every web application as they may cause intolerable delays or even service unavailability. Proper quality of service policies must guarantee rapid reactivity and responsiveness even in such critical situations. Previous solutions fail to meet common performance requirements when the system has to face sudden and unpredictable surges of traffic. Indeed they often rely on a proper setting of key parameters which requires laborious manual tuning, preventing a fast adaptation of the control policies. We contribute an original Self-* Overload Control (SOC) policy. This allows the system to self-configure a dynamic constraint on the rate of admitted sessions in order to respect service level agreements and maximize the resource utilization at the same time. Our policy does not require any prior information on the incoming traffic or manual configuration of key parameters. We ran extensive simulations under a wide range of operati...

  15. Iron chelating agents for iron overload diseases

    Directory of Open Access Journals (Sweden)

    Guido Crisponi

    2014-09-01

    Full Text Available Although iron is an essential element for life, an excessive amount may become extremely toxic both for its ability to generate reactive oxygen species, and for the lack in humans of regulatory mechanisms for iron excretion. Chelation therapy has been introduced in clinical practice in the seventies of last century to defend thalassemic patients from the effects of iron overload and, in spite of all its limitations, it has dramatically changed both life expectancy and quality of life of patients. It has to be considered that the drugs in clinical use present some disadvantages too, this makes urgent new more suitable chelating agents. The requirements of an iron chelator have been better and better defined over the years and in this paper they will be discussed in detail. As a final point the most interesting ligands studied in the last years will be presented.

  16. Disodium cromoglycate attenuates hypoxia induced enlargement of end-expiratory lung volume in rats.

    Science.gov (United States)

    Maxová, H; Hezinová, A; Vízek, M

    2011-01-01

    Mechanism responsible for the enlargement of end-expiratory lung volume (EELV) induced by chronic hypoxia remains unclear. The fact that the increase in EELV persists after return to normoxia suggests involvement of morphological changes. Because hypoxia has been also shown to activate lung mast cells, we speculated that they could play in the mechanism increasing EELV similar role as in vessel remodeling in hypoxic pulmonary hypertension (HPH). We, therefore, tested an effect of mast cells degranulation blocker disodium cromoglycate (DSCG) on hypoxia induced EELV enlargement. Ventilatory parameters, EELV and right to left heart weight ratio (RV/LV+S) were measured in male Wistar rats. The experimental group (H+DSCG) was exposed to 3 weeks of normobaric hypoxia and treated with DSCG during the first four days of hypoxia, control group was exposed to hypoxia only (H), two others were kept in normoxia as non-treated (N) and treated (N+DSCG) groups. DSCG treatment significantly attenuated the EELV enlargement (H+DSCG = 6.1+/-0.8; H = 9.2+/-0.9; ml +/-SE) together with the increase in minute ventilation (H + DSCG = 190+/-8; H = 273 +/- 10; ml/min +/- SE) and RV/LV + S (H + DSCG = 0.39 +/- 0.03; H = 0.50 +/- 0.06).

  17. SUBCHRONIC PULMONARY PATHOLOGY, IRON-OVERLOAD AND TRANSCRIPTIONAL ACTIVITY AFTER LIBBY AMPHIBOLE EXPOSURE IN RAT MODELS OF CARDIOVASCULAR DISEASE

    Science.gov (United States)

    Background: Surface-available iron (Fe) is proposed to contribute to asbestos-induced toxicity through the production of reactive oxygen species.Objective: Our goal was to evaluate the hypothesis that rat models of cardiovascular disease with coexistent Fe overload would be incre...

  18. In vitro effect of iron overload on bone marrow cell function by inducing the reactive oxygen species%铁过载诱导活性氧物质生成对骨髓造血功能影响的体外实验研究

    Institute of Scientific and Technical Information of China (English)

    谢芳; 吕海蓉; 赵明峰; 李玉明; 朱海波; 江燕; 徐新女; 肖霞; 穆娟; 刘鹏江

    2011-01-01

    Objective To investigate the in vitro effect of iron overload on the generation of reactive oxygen species (ROS) and of bone marrow (BM) cell function. Methods BM mononuclear cells (BMMNCs) were cultured with ferric citrate(FAC) at different concentrations and for different time to create iron overload and confirmed by the detection of cellular labile iron pool (LIP). The changes of ROS, apoptosis, hematopoietic colony formation ( CFU-E, BFU-E, CFU-GM and CFU-mix) and the percentage of the CD34 + cells percentage were analyzed. The differences of these index were tested after the iron overload treated with deferasirox (DFO) or antioxidants ( N-acetyl-L-cysteine, NAC). Results ①When BMMNCs were cultured with FAC, the LIP was found to increase in a time and concentration dependent manner. The intra cellular LIP reached maximum at 400 μmol/L of FAC for 24 hours. ② The ROS of total cells, leukocytes and erythrocytes increased to 1.77, 1.75 and 2.12 fold respectively compared with that of normal control when cells were cultured at 400 μmol/L of FAC for 24 hours . DFO and NAC could reduce the ROS efficiently (P < 0.05 ). ③ The apoptotic rates of the FAC treated cells[( 24.80 ± 2.99 ) %]increased significantly compared with that of normal control[(8.90 ± 0. 96) %]. The capacity of hematopoietic colony formation in FAC treated cells decreased markedly compared with that of normal control ( P < 0.05 ). The percentage of CD34 + cells of FAC treated cells[(0.39 ± 0.07 )%]also decreased significantly compared with that of nor mal control[(0.91 ±0. 12)%]. And these changes could be recovered by addition of NAC or DFO. Condusion Iron overload can affect the hematopoiesis by inducing the generation of ROS and this damage could be corrected by removing the excess iron and ROS of the BM cells. These findings might improve the treatment of dyshematopoiesis in patients with iron overload.%目的 建立体外铁过载骨髓造血细胞模型,检验铁过载

  19. PKA Phosphorylation of NCLX Reverses Mitochondrial Calcium Overload and Depolarization, Promoting Survival of PINK1-Deficient Dopaminergic Neurons

    Directory of Open Access Journals (Sweden)

    Marko Kostic

    2015-10-01

    Full Text Available Mitochondrial Ca2+ overload is a critical, preceding event in neuronal damage encountered during neurodegenerative and ischemic insults. We found that loss of PTEN-induced putative kinase 1 (PINK1 function, implicated in Parkinson disease, inhibits the mitochondrial Na+/Ca2+ exchanger (NCLX, leading to impaired mitochondrial Ca2+ extrusion. NCLX activity was, however, fully rescued by activation of the protein kinase A (PKA pathway. We further show that PKA rescues NCLX activity by phosphorylating serine 258, a putative regulatory NCLX site. Remarkably, a constitutively active phosphomimetic mutant of NCLX (NCLXS258D prevents mitochondrial Ca2+ overload and mitochondrial depolarization in PINK1 knockout neurons, thereby enhancing neuronal survival. Our results identify an mitochondrial Ca2+ transport regulatory pathway that protects against mitochondrial Ca2+ overload. Because mitochondrial Ca2+ dyshomeostasis is a prominent feature of multiple disorders, the link between NCLX and PKA may offer a therapeutic target.

  20. Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans.

    Science.gov (United States)

    Wang, Haizhen; Jiang, Xue; Wu, Jieyu; Zhang, Linqiang; Huang, Jingfei; Zhang, Yuru; Zou, Xiaoju; Liang, Bin

    2016-05-01

    The trace element iron is crucial for living organisms, since it plays essential roles in numerous cellular functions. Systemic iron overload and the elevated level of ferritin, a ubiquitous intracellular protein that stores and releases iron to maintain the iron homeostasis in cells, has long been epidemiologically associated with obesity and obesity-related diseases. However, the underlying mechanisms of this association remain unclear. Here, using Caenorhabditis elegans, we show that iron overload induces the expression of sgk-1, encoding the serum and glucocorticoid-inducible kinase, to promote the level of ferritin and fat accumulation. Mutation of cyp-23A1, encoding a homolog of human cytochrome P450 CYP7B1 that is related to neonatal hemochromatosis, further enhances the elevated expression of ftn-1, sgk-1, and fat accumulation. sgk-1 positively regulates the expression of acs-20 and vit-2, genes encoding homologs of the mammalian FATP1/4 fatty acid transport proteins and yolk lipoproteins, respectively, to facilitate lipid uptake and translocation for storage under iron overload. This study reveals a completely novel pathway in which sgk-1 plays a central role to synergistically regulate iron and lipid homeostasis, offering not only experimental evidence supporting a previously unverified link between iron and obesity, but also novel insights into the pathogenesis of iron and obesity-related human metabolic diseases.

  1. Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: dose/volume-response relations

    Energy Technology Data Exchange (ETDEWEB)

    Levegruen, S.; Schlegel, W. [Dept. of Medical Physics, German Cancer Research Center (DKFZ), Heidelberg (Germany); Hof, H.; Debus, J. [Dept. of Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Essig, M. [Dept. of Radiology, German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2004-12-01

    Purpose: to evaluate late radiation effects in the brain after radiosurgery of patients with cerebral arteriovenous malformations (AVMs) and to quantify dose/volume-response relations for radiation-induced changes of brain tissue identified on follow-up neuroimaging. Patients and methods: data from 73 AVM patients who had stereotactic linac radiosurgery at DKFZ (German Cancer Research Center), Heidelberg, Germany, were retrospectively analyzed. The endpoint of radiation-induced changes of brain tissue on follow-up magnetic resonance (MR) neuroimaging (i.e., edema and blood-brain-barrier breakdown [BBBB]) was evaluated. Each endpoint was further differentiated into three levels with respect to the extent of the image change (small, intermediate, and large). A previous analysis of the data found correlation of the endpoints with several dose/volume variables (DV) derived from each patient's dose distribution in the brain, including the mean dose in a volume of 20 cm{sup 3} (Dmean20) and the absolute brain volume (including the AVM target) receiving a dose of at least 12 Gy (V12). To quantify dose/volume-response relations, patients were ranked according to DV (i.e., Dmean20 and V12) and classified into four groups of equal size. For each group, the actuarial rates of developing the considered endpoints within 2.5 years after radiosurgery were determined from Kaplan-Meier estimates. The dose/volume-response curves were fitted with a sigmoid-shape logistic function and characterized by DV{sub 50}, the dose for a 50% incidence, and the slope parameter k. Results: dose/volume-response relations, based on two alternative, but correlated, dose distribution variables that are a function of both dose and volume, were observed for radiation-induced changes of brain tissue. DV{sub 50} values of fitted dose/volume-response curves for tissue changes of large extent (e.g., V12{sub 50} = 22.0 {+-} 2.6 cm{sup 3} and Dmean20{sub 50} = 17.8 {+-} 2.0 Gy for the combined endpoint

  2. Islands of surviving cells within necrotic volume at liver induced by PDT

    Science.gov (United States)

    Ferreira, J.; Kurachi, C.; Zucoloto, S.; Castro e Silva, O., Jr.; Bagnato, V. S.

    2009-06-01

    Tissue heterogeneities as well as distinct metabolic status and cellular types within a tumor may results in a nonhomogenous necrosis. The possibility of PDT surviving cells within a treated volume has relevant clinical significance. The major aim of this study was to analyze, on normal rat liver, the cell viability and surviving after PDT. The porphyrin was injected through the cava vein at concentration of 1.5 mg/Kg. The induced necrosis was qualitatively investigated varying the used drug light interval (30 min, 1, 3, 6, 24 and 36 h) and total delivered dose (20, 50, 100, 150 and 200 J/cm2). A diode laser at 630 nm and irradiance of 150 mW/cm2 was employed. The exposed livers were removed after the animals were killed by anesthesia overdose, 30 h after illumination. Slides were processed by HE analysis for the determination of the overall aspects of the necrotic and non-treated liver. We observed necrosis of central vein and presence of surviving cell around the portal triad within the necrotic volume, suggesting PDT-resistant regions of the tissue. Possible hypothesis for the observation may be: the absence of photosensitizer; insufficient light dose (below threshold); and distinct metabolic status in the portal triad microregions decreases oxygen availability to photodynamic reaction. The cells surrounding portal triad presented a higher resistance even when 200 J/cm2 was applied. In contrast, the cells closer to the central vein after 20 J/cm2 were already susceptible to the action of PDT. Different aspects of the problem are presented.

  3. Acute volume expansion attenuates hyperthermia-induced reductions in cerebral perfusion during simulated hemorrhage

    DEFF Research Database (Denmark)

    Schlader, Zachary J; Seifert, Thomas; Wilson, Thad E

    2013-01-01

    Hyperthermia reduces the capacity to withstand a simulated hemorrhagic challenge, but volume loading preserves this capacity. This study tested the hypotheses that acute volume expansion during hyperthermia increases cerebral perfusion and attenuates reductions in cerebral perfusion during a simu...

  4. Tetrahydrocurcumin in combination with deferiprone attenuates hypertension, vascular dysfunction, baroreflex dysfunction, and oxidative stress in iron-overloaded mice.

    Science.gov (United States)

    Sangartit, Weerapon; Pakdeechote, Poungrat; Kukongviriyapan, Veerapol; Donpunha, Wanida; Shibahara, Shigeki; Kukongviriyapan, Upa

    2016-12-01

    Excessive iron can generate reactive oxygen species (ROS), leading to oxidative stress that is closely associated with cardiovascular dysfunction. Iron overload was induced in male ICR mice by injection of iron sucrose (10mg/kg/day) for eight weeks. Iron overload was evidenced by increased serum iron indices. The mice developed increased blood pressure, impaired vascular function and blunted response of the autonomic nervous system. These effects were accompanied by increased malondialdehyde levels in various tissues, increased nitric oxide metabolites in plasma and urine, and decreased blood glutathione. Tetrahydrocurcumin (THU, 50mg/kg/day), deferiprone (or L1, 50mg/kg/day) or both was orally administered throughout the period of iron sucrose injection. The treatments significantly alleviated the deleterious cardiovascular effects of iron overload, and were associated with modulation of nitric oxide levels. An imbalance between endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) expression in response to iron overload was normalized by THU, L1 or the combination treatment. Moreover, the treatment decreased the upregulated expression levels of gp91(phox), p47(phox) and HO-1. The combination of THU and L1 exerted a greater effect than THU or L1 monotherapy. These results suggest beneficial effects of THU and L1 on iron-induced oxidative stress, hypertension, and vascular dysfunction.

  5. 芪苈强心胶囊通过抑制血管紧张素Ⅱ改善压力超负荷致小鼠心肌肥厚%Qiliqiangxin Capsules Ameliorate Pressure Overload-Induced Cardiac Hypertrophy in Mice Via Reducing the Expression of Angiotensin Ⅱ

    Institute of Scientific and Technical Information of China (English)

    叶勇; 邹云增; 李磊; 蒋国良; 吴剑; 周宁; 马宏; 关爱丽; 龚惠; 葛均波

    2011-01-01

    目的 探讨探讨芪苈强心胶囊是否通过抑制血管紧张素Ⅱ(AngⅡ)表达改善压力超负荷下小鼠心肌肥厚.方法 小鼠行升主动脉缩窄手术(TAC)建立心肌肥厚模型,8-10周龄野生型雄性小鼠(WT)和雄性血管紧张素原基因敲除小鼠(ATG-)随机分为假手术组,生理盐水组、芪苈强心胶囊三组,TAC组小鼠给予生理盐水或1.0mg/(kg.d)药物灌胃处理,术后2周行心超及血流动力学检查,同时分析心肌组织学指标以及肥厚相关基因表达,酶联免疫吸附法(ELISA)检测血浆和心肌组织AngⅡ浓度,蛋白印迹法检测磷酸化细胞外信号调节激酶(p-ERK)及血管紧张素Ⅱ-Ⅰ型(AT1)受体表达.结果 WT和ATG-小鼠TAC后2周,主动脉血压及左室收缩末期压显著升高,芪苈强心胶囊对其均正影响.WT小鼠中,此药显著抑制TAC介导AngⅡ的升高(P<0.05),抑制TAC介导的左室前壁,左室后壁增厚以及心肌细胞横截面积 (CSA)和纤维化面积增大,同时抑制肥厚相关基因,AT1受体和p-ERK表达上调(P<0.05),ATG-小鼠中,在AngⅡ缺失的情况下,TAC两组间左室前后壁、CSA、纤维化面积以及肥厚相关基因、AT1、受体和p-ERK表达无明显差异(P>0.05).结论 芪苈强心胶囊改善压力超负荷致小鼠心肌肥厚是通过抑制AngⅡ表达来减弱AT1受体激活,非直接抑制压力超负荷机械刺激引起AT1,受体的激活.%Objective To investigate whether downregulation of Angiotensin U was involved in ihe mechanism by which Qiliqianipan Capsules inhibits (he pressure overload-induced cardiac hypertrophy in mice. Methods Pressure-overload model was eslablished in (I-10 weeks old wild lype (WT) und angiotensmogen-deficifnl {AT(? ) (lacking endogenous Ang 11) male mice performed with Transverse Anna Constricting (TAC) surgery for 2 weeks. All the miee were treated with Sham or TAC operation, and all TAC mice was administered with salme or Qiliqiang*inCapsuks(l.l)mg*g.d) through

  6. Resistance exercise-induced fluid shifts: change in active muscle size and plasma volume

    Science.gov (United States)

    Ploutz-Snyder, L. L.; Convertino, V. A.; Dudley, G. A.

    1995-01-01

    The purpose of this study was to test the hypothesis that the reduction in plasma volume (PV) induced by resistance exercise reflects fluid loss to the extravascular space and subsequently selective increase in cross-sectional area (CSA) of active but not inactive skeletal muscle. We compared changes in active and inactive muscle CSA and PV after barbell squat exercise. Magnetic resonance imaging (MRI) was used to quantify muscle involvement in exercise and to determine CSA of muscle groups or individual muscles [vasti (VS), adductor (Add), hamstring (Ham), and rectus femoris (RF)]. Muscle involvement in exercise was determined using exercise-induced contrast shift in spin-spin relaxation time (T2)-weighted MR images immediately postexercise. Alterations in muscle size were based on the mean CSA of individual slices. Hematocrit, hemoglobin, and Evans blue dye were used to estimate changes in PV. Muscle CSA and PV data were obtained preexercise and immediately postexercise and 15 and 45 min thereafter. A hierarchy of muscle involvement in exercise was found such that VS > Add > Ham > RF, with the Ham and RF showing essentially no involvement. CSA of the VS and Add muscle groups were increased 10 and 5%, respectively, immediately after exercise in each thigh with no changes in Ham and RF CSA. PV was decreased 22% immediately following exercise. The absolute loss of PV was correlated (r2 = 0.75) with absolute increase in muscle CSA immediately postexercise, supporting the notion that increased muscle size after resistance exercise reflects primarily fluid movement from the vascular space into active but not inactive muscle.

  7. Serotoninergic Modulation of Basal Cardiovascular Responses and Responses Induced by Isotonic Extracellular Volume Expansion in Rats

    Science.gov (United States)

    Semionatto, Isadora Ferraz; Raminelli, Adrieli Oliveira; Alves, Angelica Cristina; Capitelli, Caroline Santos; Chriguer, Rosangela Soares

    2017-01-01

    Background Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. Objective To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. Methods We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. Results No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). Discussion The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. Conclusion These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats. PMID:28099586

  8. The involvement of PI3K-mediated and L-VGCC-gated transient Ca2+ influx in 17β-estradiol-mediated protection of retinal cells from H2O2-induced apoptosis with Ca2+ overload.

    Directory of Open Access Journals (Sweden)

    Yan Feng

    Full Text Available Intracellular calcium concentration ([Ca(2+]i plays an important role in regulating most cellular processes, including apoptosis and survival, but its alterations are different and complicated under diverse conditions. In this study, we focused on the [Ca(2+]i and its control mechanisms in process of hydrogen peroxide (H2O2-induced apoptosis of primary cultured Sprague-Dawley (SD rat retinal cells and 17β-estradiol (βE2 anti-apoptosis. Fluo-3AM was used as a Ca(2+ indicator to detect [Ca(2+]i through fluorescence-activated cell sorting (FACS, cell viability was assayed using MTT assay, and apoptosis was marked by Hoechst 33342 and annexin V/Propidium Iodide staining. Besides, PI3K activity was detected by Western blotting. Results showed: a 100 μM H2O2-induced retinal cell apoptosis occurred at 4 h after H2O2 stress and increased in a time-dependent manner, but [Ca(2+]i increased earlier at 2 h, sustained to 12 h, and then recovered at 24 h after H2O2 stress; b 10 μM βE2 treatment for 0.5-24 hrs increased cell viability by transiently increasing [Ca(2+]i, which appeared only at 0.5 h after βE2 application; c increased [Ca(2+]i under 100 µM H2O2 treatment for 2 hrs or 10 µM βE2 treatment for 0.5 hrs was, at least partly, due to extracellular Ca(2+ stores; d importantly, the transiently increased [Ca(2+]i induced by 10 µM βE2 treatment for 0.5 hrs was mediated by the phosphatidylinositol-3-kinase (PI3K and gated by the L-type voltage-gated Ca(2+ channels (L-VGCC, but the increased [Ca(2+]i induced by 100 µM H2O2 treatment for 2 hrs was not affected; and e pretreatment with 10 µM βE2 for 0.5 hrs effectively protected retinal cells from apoptosis induced by 100 µM H2O2, which was also associated with its transient [Ca(2+]i increase through L-VGCC and PI3K pathway. These findings will lead to better understanding of the mechanisms of βE2-mediated retinal protection and to exploration of the novel therapeutic strategies for retina

  9. HFE gene in primary and secondary hepatic iron overload

    Institute of Scientific and Technical Information of China (English)

    Giada Sebastiani; Ann P Walker

    2007-01-01

    Distinct from hereditary haemochromatosis, hepatic iron overload is a common finding in several chronic liver diseases. Many studies have investigated the prevalence, distribution and possible contributory role of excess hepatic iron in non-haemochromatotic chronic liver diseases. Indeed, some authors have proposed iron removal in liver diseases other than hereditary haemochromatosis. However, the pathogenesis of secondary iron overload remains unclear. The High Fe (HFE) gene has been implicated, but the reported data are controversial. In this article, we summarise current concepts regarding the cellular role of the HFE protein in iron homeostasis. We review the current status of the literature regarding the prevalence, hepatic distribution and possible therapeutic implications of iron overload in chronic hepatitis C, hepatitis B, alcoholic and nonalcoholic fatty liver diseases and porphyria cutanea tarda.We discuss the evidence regarding the role of HFE gene mutations in these liver diseases. Finally, we summarize the common and specific features of iron overload in liver diseases other than haemochromatosis.

  10. Differential Responses of Soleus and Plantaris Muscle Fibers to Overloading

    Science.gov (United States)

    Kawano, Fuminori; Shibaguchi, Tsubasa; Ohira, Takashi; Nakai, Naoya; Ohira, Yoshinobu

    2013-02-01

    Responses of slow and fast fibers in soleus and plantaris muscles of adult rats to overloading by the tendon transection of synergists were studied. Overloading-related hypertrophy was noted in the slow fibers of plantaris and soleus, although the magnitude was greater in plantaris. Five genes with minor expression in slow soleus muscle were identified by microarray analysis. Base-line expressions of these genes in slow fibers of plantaris were also low. Further, repressive effects of overloading on these genes were seen in some fast fibers of plantaris, not in whole plantaris and soleus. The data suggested that the repression of particular genes might be related to the pronounced morphological response of fibers expressing type II, including I+II, myosin heavy chain (MyHC), although these genes with lower base-line expression in slow fibers did not respond to overloading.

  11. OVERLOAD CAPABILITY OF POWER CABLES IN ACTUAL POWER CONSUMPTION SYSTEMS

    Directory of Open Access Journals (Sweden)

    L.A. Szhebenyuk

    2013-09-01

    Full Text Available Results of overload capability calculations for 6-kV power cables are analyzed. The work is aimed at creating a computation system for the current rating of high-voltage cross-linked polyethylene power cables.

  12. [Navigation aid through the information overload].

    Science.gov (United States)

    Günther, Judith; Schindler, Birgit; Suter, Katja

    2014-10-01

    We live in the modern information society. "To be informed" has a crucial impact on the personal, professional, economic and social development. The knowledge of things and their relationships is essential for acute decisions as well as for long-term planning. And at no time it was easier to get the information required within shorter time periods--no matter to whatsoever. The offer of information of the World Wide Web is inexhaustible. This also applies to information about all possible therapeutic and pharmaceutical issues. But is the information found reliable, too? And are easily accessible sources credible? Can we deal with the information overload at these days or do we actually risk paddling only on the surface of the "information-sea", without ever perceiving the actual information depth and width, less to use it? How can we protect being taken in by marketing strategies? The present article describes a structured proceed when seeking literature to find useful medical and pharmaceutical information in a time saving manner.

  13. Ciprofloxacin: a novel therapeutic agent for iron overload?

    Directory of Open Access Journals (Sweden)

    Mitra Elmi

    2009-09-01

    Full Text Available Objective: Major thalassemia is one of the hematological diseases requiring multiple blood transfusions, which results in iron overload in the liver, heart and other organs. Current iron chelation therapy consists of intravenous (IV deferoxamine and oral deferasirox and deferiprone. Although these chelators are effective, many side effects are reported. In the present study, the iron-chelating effect of ciprofloxacin with good oral absorption was investigated. Material and Methods: Thirty male albino Wistar rats were used for the study. Ciprofloxacin (7 or 14 mg/kg per day was administered simultaneously with iron (0.03 g/kg per day or after one-month administration of iron. Ciprofloxacin effect on iron absorption in the liver and heart was studied carefully using atomic absorption. Results: A significant decrease in the liver and heart iron following the ciprofloxacin (14 mg/kg per day administration was observed, when compared with the control group. This ciprofloxacin-induced tissue iron depletion was more pronounced when it was administered simultaneously with iron, when it was administered for a longer duration (2 months rather than 1 month and when it was given in higher doses (14 mg/kg per day. Conclusion: Administration of ciprofloxacin may help to decrease the burden of parenteral administration, thereby improving compliance and also the life expectancy of thalassemic patients.

  14. Overload and neovascularization of shoulder tendons in volleyball players

    Directory of Open Access Journals (Sweden)

    Notarnicola Angela

    2012-08-01

    Full Text Available Abstract Background In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the supraspinatus tendons by oximetry. Results No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7% than middle hitters (53.7% (p = 0.01, opposite hitters (55.5% (p = 0.02 and libero players (54.4% (p = 0.008, whereas there were no differences in setters (56.2% (p > 0.05. Conclusions The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles.

  15. Overload and neovascularization of shoulder tendons in volleyball players

    Science.gov (United States)

    2012-01-01

    Background In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the supraspinatus tendons by oximetry. Results No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7%) than middle hitters (53.7%) (p = 0.01), opposite hitters (55.5%) (p = 0.02) and libero players (54.4%) (p = 0.008), whereas there were no differences in setters (56.2%) (p > 0.05). Conclusions The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles. PMID:22853746

  16. Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model.

    Science.gov (United States)

    Chaillou, Thomas; Koulmann, Nathalie; Simler, Nadine; Meunier, Adélie; Serrurier, Bernard; Chapot, Rachel; Peinnequin, Andre; Beaudry, Michèle; Bigard, Xavier

    2012-03-01

    Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70(S6K) and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70(S6K) pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

  17. Deferasirox, an oral chelator in the treatment of iron overload

    OpenAIRE

    I. Portioli

    2013-01-01

    BACKGROUND Deferasirox is a once-daily oral iron chelator developed for treating iron overload complicating long-term transfusion therapy in patients with diseases such as beta-thalassemia and myelodysplastic syndromes. Iron overload can damage the liver, pancreas and the heart. Deferoxamine, the only other drug approved for iron chelation, can prevent these effects but requires parenteral administration. Deferasirox has been approved after a one-year, open-label trial in patients ≥ 2 years o...

  18. Effects of Iron Overload on the Activity of Na,K-ATPase and Lipid Profile of the Human Erythrocyte Membrane

    Science.gov (United States)

    Sousa, Leilismara; Garcia, Israel J. P.; Costa, Tamara G. F.; Silva, Lilian N. D.; Renó, Cristiane O.; Oliveira, Eneida S.; Tilelli, Cristiane Q.; Santos, Luciana L.; Cortes, Vanessa F.; Santos, Herica L.; Barbosa, Leandro A.

    2015-01-01

    Iron is an essential chemical element for human life. However, in some pathological conditions, such as hereditary hemochromatosis type 1 (HH1), iron overload induces the production of reactive oxygen species that may lead to lipid peroxidation and a change in the plasma-membrane lipid profile. In this study, we investigated whether iron overload interferes with the Na,K-ATPase activity of the plasma membrane by studying erythrocytes that were obtained from the whole blood of patients suffering from iron overload. Additionally, we treated erythrocytes of normal subjects with 0.8 mM H2O2 and 1 μM FeCl3 for 24 h. We then analyzed the lipid profile, lipid peroxidation and Na,K-ATPase activity of plasma membranes derived from these cells. Iron overload was more frequent in men (87.5%) than in women and was associated with an increase (446%) in lipid peroxidation, as indicated by the amount of the thiobarbituric acid reactive substances (TBARS) and an increase (327%) in the Na,K-ATPase activity in the plasma membrane of erythrocytes. Erythrocytes treated with 1 μM FeCl3 for 24 h showed an increase (132%) in the Na,K-ATPase activity but no change in the TBARS levels. Iron treatment also decreased the cholesterol and phospholipid content of the erythrocyte membranes and similar decreases were observed in iron overload patients. In contrast, erythrocytes treated with 0.8 mM H2O2 for 24 h showed no change in the measured parameters. These results indicate that erythrocytes from patients with iron overload exhibit higher Na,K-ATPase activity compared with normal subjects and that this effect is specifically associated with altered iron levels. PMID:26197432

  19. Effects of Iron Overload on the Activity of Na,K-ATPase and Lipid Profile of the Human Erythrocyte Membrane.

    Directory of Open Access Journals (Sweden)

    Leilismara Sousa

    Full Text Available Iron is an essential chemical element for human life. However, in some pathological conditions, such as hereditary hemochromatosis type 1 (HH1, iron overload induces the production of reactive oxygen species that may lead to lipid peroxidation and a change in the plasma-membrane lipid profile. In this study, we investigated whether iron overload interferes with the Na,K-ATPase activity of the plasma membrane by studying erythrocytes that were obtained from the whole blood of patients suffering from iron overload. Additionally, we treated erythrocytes of normal subjects with 0.8 mM H2O2 and 1 μM FeCl3 for 24 h. We then analyzed the lipid profile, lipid peroxidation and Na,K-ATPase activity of plasma membranes derived from these cells. Iron overload was more frequent in men (87.5% than in women and was associated with an increase (446% in lipid peroxidation, as indicated by the amount of the thiobarbituric acid reactive substances (TBARS and an increase (327% in the Na,K-ATPase activity in the plasma membrane of erythrocytes. Erythrocytes treated with 1 μM FeCl3 for 24 h showed an increase (132% in the Na,K-ATPase activity but no change in the TBARS levels. Iron treatment also decreased the cholesterol and phospholipid content of the erythrocyte membranes and similar decreases were observed in iron overload patients. In contrast, erythrocytes treated with 0.8 mM H2O2 for 24 h showed no change in the measured parameters. These results indicate that erythrocytes from patients with iron overload exhibit higher Na,K-ATPase activity compared with normal subjects and that this effect is specifically associated with altered iron levels.

  20. Ascending aortic constriction in rats for creation of pressure overload cardiac hypertrophy model.

    Science.gov (United States)

    Gs, Ajith Kumar; Raj, Binil; Santhosh, Kumar S; Sanjay, G; Kartha, Chandrasekharan Cheranellore

    2014-06-29

    Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart failure. Here, we describe a detailed surgical procedure for creating pressure overload and cardiac hypertrophy in rats by constriction of the ascending aorta using a small metallic clip. After anesthesia, the trachea is intubated by inserting a cannula through a half way incision made between two cartilage rings of trachea. Then a skin incision is made at the level of the second intercostal space on the left chest wall and muscle layers are cleared to locate the ascending portion of aorta. The ascending aorta is constricted to 50-60% of its original diameter by application of a small sized titanium clip. Following aortic constriction, the second and third ribs are approximated with prolene sutures. The tracheal cannula is removed once spontaneous breathing was re-established. The animal is allowed to recover on the heating pad by gradually lowering anesthesia. The intensity of pressure overload created by constriction of the ascending aorta is determined by recording the pressure gradient using trans-thoracic two dimensional Doppler-echocardiography. Overall this protocol is useful to study the remodeling events and contractile properties of the heart during the gradual onset and progression from compensated cardiac hypertrophy to heart failure stage.

  1. Stable overload conditions of high-temperature superconductors at alternating current injection

    Science.gov (United States)

    Romanovskii, V. R.

    2015-01-01

    The stability of alternating current injected into a high-temperature superconductor or into a current-carrying element on its basis is studied under weak cooling. The stability conditions of the current varying with time by a sinusoidal law are studied versus its frequency. It is shown that before unstable states set in, the peak values of the electric field intensity, current, and temperature in the superconductor are higher than the values determining a thermal electrodynamic stability boundary of the current permanently flowing through the superconductor—the so-called thermal quench current. It is found that ultimate stable alternating currents cause high stable thermal losses in superconductors; these losses being not considered in the modern theory of losses. Such stable conditions can be referred to as overload conditions. Analysis shows that there are characteristic times determining the time intervals within which alternating current is stable under overload conditions. Main thermoelectrodynamic mechanisms behind the existence of these intervals are formulated. They explain why the superconductor stable overheating and induced electric field reach high values before the injected alternating current becomes unstable. The existence of overload conditions considerably extends the application area of high-temperature superconductors.

  2. Biochemical competition makes fatty-acid β-oxidation vulnerable to substrate overload.

    Directory of Open Access Journals (Sweden)

    Karen van Eunen

    Full Text Available Fatty-acid metabolism plays a key role in acquired and inborn metabolic diseases. To obtain insight into the network dynamics of fatty-acid β-oxidation, we constructed a detailed computational model of the pathway and subjected it to a fat overload condition. The model contains reversible and saturable enzyme-kinetic equations and experimentally determined parameters for rat-liver enzymes. It was validated by adding palmitoyl CoA or palmitoyl carnitine to isolated rat-liver mitochondria: without refitting of measured parameters, the model correctly predicted the β-oxidation flux as well as the time profiles of most acyl-carnitine concentrations. Subsequently, we simulated the condition of obesity by increasing the palmitoyl-CoA concentration. At a high concentration of palmitoyl CoA the β-oxidation became overloaded: the flux dropped and metabolites accumulated. This behavior originated from the competition between acyl CoAs of different chain lengths for a set of acyl-CoA dehydrogenases with overlapping substrate specificity. This effectively induced competitive feedforward inhibition and thereby led to accumulation of CoA-ester intermediates and depletion of free CoA (CoASH. The mitochondrial [NAD⁺]/[NADH] ratio modulated the sensitivity to substrate overload, revealing a tight interplay between regulation of β-oxidation and mitochondrial respiration.

  3. Application of Chaos Theory in Trucks' Overloading Enforcement

    Directory of Open Access Journals (Sweden)

    Abbas Mahmoudabadi

    2013-01-01

    Full Text Available Trucks' overloading is considered as one of the most substantial concerns in road transport due to a possible road surface damage, as well as, are less reliable performance of trucks' braking system. Sufficient human resource and adequate time scheduling are to be planned for surveying trucks' overloading; hence, it seems required to prepare an all-around model to be able to predict the number of overloaded vehicles. In the present research work, the concept of chaos theory has been utilized to predict the ratio of trucks which might be guessed overloaded. The largest Lyapunov exponent is utilized to determine the presence of chaos using experimental data and concluded that the ratio of overloaded trucks reflects chaotic behavior. The prediction based on chaos theory is compared with the results of simple smoothing and moving average methods according to the well-known criterion of mean square errors. The results have also revealed that the chaotic prediction model would act more capably comparing the analogous methods including simple smoothing and moving average to predict the ratio of passing trucks to be possibly overloaded.

  4. Echocardiographic evaluation of pressure overload-induced cardiac remodeling in mice using different ultrasound machines%小动物超声仪与临床用超声仪评价小鼠心脏重构的对比分析

    Institute of Scientific and Technical Information of China (English)

    赵静; 曾智; 颜亮; 纪丽景; 罗滔; 宾建平; 廖禹林

    2011-01-01

    目的 比较不同类型超声仪对小鼠压力负荷下心脏重构的评价结果.方法 C57 BL/6小鼠18只,随机分为假手术(sham)组和主动脉弓缩窄(TAC)组,每组9只.手术8周后,首先应用连接15L8高频探头的临床用西门子超声仪测定TAC组小鼠心功能,并比较清醒和麻醉状态下的差异.然后比较西门子超声仪和小动物用高分辨超声仪(Vevo770)对心功能评价的影响.结果 与清醒状态相比,异氟烷吸入麻醉小鼠的心率和左室短轴缩短率显著降低(P<0.001),而左室内径显著增加(P<0.05).但与相应的sham组比较,两种仪器都可以较敏感地反映TAC组的心脏重构.与西门子超声仪相比,小动物超声仪的分辨率明显增高,并可通过二尖瓣血流频谱图评价左室舒张功能,但暂不能在小鼠清醒状态下评价心功能.结论 麻醉本身会降低心功能,但在反映干预手段对心脏重构的影响程度上与清醒状态下有可比性.高分辨小动物超声仪在评价左室舒张功能方面优于西门子超声仪.%To compare the results of echocardiographic evaluation of pressure overload-induced cardiac remodeling in mice using different ultrasound machines. Methods Eighteen C57 BL/6 mice were randomly divided into the sham-operated and the transverse aortic constriction (TAC) groups (n=9). Eight weeks after the operation, the cardiac function of TAC group was evaluated using Siemens ultrasonic instrument with 15L8 probe and the differences between the awake and anesthetized states were compared. The heart rate, left ventricular (LV) dimensions, systolic and diastolic functions were measured in both sham-operated and TAC groups using the Siemens ultrasonic instrument and a high-resolution ultrasonic imaging system for small animals (Vevo 770). Results Compared with the mice in wakefulness, the anesthetized mice showed significantly decreased heart rate and LV fractional shortening (P<0.001) and markedly increased LV end

  5. Effects of Mechanical Overloading on the Properties of Soleus Muscle Fibers, with or without Damage in MDX and Wild Type Mice

    Science.gov (United States)

    Terada, Masahiro; Kawano, Fuminori; Ohira, Takashi; Oke, Yoshihiko; Nakai, Naoya; Ohira, Yoshinobu

    2008-06-01

    Effects of mechanical overloading on the characteristics of regenerating or not-regenerating soleus muscle fibers were studied. The muscle fibers of mdx mice were characterized by the localization of myonuclei. Muscle damage was also induced in wild type (WT) mice by injection of cardiotoxin (CTX) into soleus muscle. Overloading was applied for 14 days to the left soleus muscle in mdx and intact and CTX-injected WT mice by removing the distal tendons of plantaris and gastrocnemius muscles. The contralateral muscle served as the normal control. These animals were then allowed ambulation recovery in the cage. Central myonuclei were noted in many fibers of mdx and CTX-injected mice with or without overloading. In general, the fibers with central nuclei were considered as regenerating fibers. The fibers with more central nuclei were increased in mdx mice, but the fibers with more peripheral nuclei were increased in CTX-injected WT mice by overloading. The muscle satellite cells, neuromuscular junctions (NMJ), and myonuclei were stained. Most of the properties, such as number of myonuclei and satellite cells, size of NMJ, and fiber length, were not influenced by mechanical overloading in all mice. Approximately 0.6% branched fibers were seen in the intact soleus of mdx mice, although these fibers were not detected in WT mice. However, the percentage of these fibers was increased by overloading especially in mdx mice (~50% vs. ~2.5% in WT). In CTX-injected WT mice, these fibers were ~15% with or without overloading. The fiber cross sectional area in normal WT, but not in mdx and CTX-injected WT mice, was increased by overloading (pmuscle damage in mdx mice, but promoted the regeneration in CTX-injected WT mice.

  6. Serotoninergic Modulation of Basal Cardiovascular Responses and Responses Induced by Isotonic Extracellular Volume Expansion in Rats

    Directory of Open Access Journals (Sweden)

    Isadora Ferraz Semionatto

    Full Text Available Abstract Background: Isotonic blood volume expansion (BVE induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. Objective: To evaluate the effect of saline or serotonergic agonist (DOI administration in the hypothalamic paraventricular nucleus (PVN on cardiovascular responses after BVE. Methods: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP, systolic (SBP and diastolic blood pressure (DBP, heart rate (HR and the sympathetic-vagal ratio (LF/HF of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. Results: No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17; SBP (147.23±14.31 vs 129.39±10.70; DBP (98.01 ±4.91 vs 87.31±8.61; HR (421.02±43.32 vs 356.35±41.99; and LF/HF ratio (2.32±0.80 vs 0.27±0.32. Discussion: The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. Conclusion: These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats.

  7. Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance

    Science.gov (United States)

    Kurtz, Baptiste; Thibault, Helene B.; Raher, Michael J.; Popovich, John R.; Cawley, Sharon; Atochin, Dmitriy N.; Hayton, Sarah; Shakartzi, Hannah R.; Huang, Paul L.; Bloch, Kenneth D.; Buys, Emmanuel

    2011-01-01

    Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3−/−) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2′,7′-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3−/− mice than in SD-fed WT mice. In contrast, HFD-fed NOS3−/− developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3−/− than in those from HFD-fed WT. Nω-nitro-l-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltrifluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3−/− mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts. PMID:21856905

  8. Modulation of cadmium-induced mitochondrial dysfunction and volume changes by temperature in rainbow trout (Oncorhynchus mykiss)

    Energy Technology Data Exchange (ETDEWEB)

    Onukwufor, John O. [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Kibenge, Fred [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Stevens, Don [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Kamunde, Collins, E-mail: ckamunde@upei.ca [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada)

    2015-01-15

    Highlights: • Interactions of Cd and temperature exacerbate mitochondrial dysfunction and enhance Cd accumulation. • Cd uptake by mitochondria occurs through the Ca uniporter. • Temperature exacerbates Cd-induced mitochondrial volume changes. • Low concentrations of Cd inhibit mitochondrial swelling. - Abstract: We investigated how temperature modulates cadmium (Cd)-induced mitochondrial bioenergetic disturbances, metal accumulation and volume changes in rainbow trout (Oncorhynchus mykiss). In the first set of experiments, rainbow trout liver mitochondrial function and Cd content were measured in the presence of complex I substrates, malate and glutamate, following exposure to Cd (0–100 μM) at three (5, 13 and 25 °C) temperatures. The second set of experiments assessed the effect of temperature on Cd-induced mitochondrial volume changes, including the underlying mechanisms, at 15 and 25 °C. Although temperature stimulated both state 3 and 4 rates of respiration, the coupling efficiency was reduced at temperature extremes due to greater inhibition of state 3 at low temperature and greater stimulation of state 4 at the high temperature. Cadmium exposure reduced the stimulatory effect of temperature on state 3 respiration but increased that on state 4, consequently exacerbating mitochondrial uncoupling. The interaction of Cd and temperature yielded different responses on thermal sensitivity of state 3 and 4 respiration; the Q{sub 10} values for state 3 respiration increased at low temperature (5–13 °C) while those for state 4 increased at high temperature (13–25 °C). Importantly, the mitochondria accumulated more Cd at high temperature suggesting that the observed greater impairment of oxidative phosphorylation with temperature was due, at least in part, to a higher metal burden. Cadmium-induced mitochondrial volume changes were characterized by an early phase of contraction followed by swelling, with temperature changing the kinetics and

  9. Extended free-volume defects in chalcogenide glassy semiconductors induced by high-energy {gamma}-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Balitska, Valentina [Lviv Institute of Materials of SRC (Ukraine); State University of Vital Activity Safety, Lviv 79007 (Ukraine); Filipecki, Jacek; Shpotyuk, Oleh [Institute of Physics, Jan Dlugosz University, Czestochowa (Poland)

    2009-08-15

    It was shown that under-coordinated topological defects induced by high-energy {gamma}-irradiation can be a reason for significant changes in positron annihilation lifetime spectra of multicomponent chalcogenide glassy semiconductors within ternary Ge-As(Sb)-S systems. In the case of negatively-charged sulphur and arsenic atoms, the excess of free volume is quite enough to produce additional input in the second defect-related channel of positron trapping, while under-coordinated germanium atoms are practically non-detectable with this technique because of low associated free volume. Despite radiation-induced densification, the average positron lifetime demonstrate both growing and decaying tendencies after {gamma}-irradiation depending on glass composition. (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  10. Central administration of kisspeptin-10 inhibits natriuresis and diuresis induced by blood volume expansion in anesthetized male rats

    OpenAIRE

    Han, Xu; Yan, Ming; An, Xiao-fei; HE Ming; Yu, Jiang-Yi

    2009-01-01

    Aim: To investigate the possible role of hypothalamic kisspeptin in the regulation of body fluid metabolism and maintenance of internal homeostasis. Methods: Natriuresis and diuresis were induced by blood volume expansion (VE) in anesthetized male rats and kisspeptin-10 was intracerebroventricularly (icv) administered. Radioimmunoassay (RIA) was used to measure the plasma arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) concentrations during the VE. The mediation of the renal s...

  11. Extent, risk factors, and outcome of fluid overload after pediatric heart surgery*.

    Science.gov (United States)

    Seguin, Jade; Albright, Benjamin; Vertullo, Laura; Lai, Pamela; Dancea, Adrian; Bernier, Pierre-Luc; Tchervenkov, Christo I; Calaritis, Christos; Drullinsky, David; Gottesman, Ronald; Zappitelli, Michael

    2014-12-01

    Fluid overload is associated with poor PICU outcomes in different populations. Little is known about fluid overload in children undergoing cardiac surgery. We described fluid overload after cardiac surgery, identified risk factors of worse fluid overload and also determined if fluid overload predicts longer length of PICU stay, prolonged mechanical ventilation (length of ventilation) and worse lung function as estimated by the oxygenation index. Retrospective cohort study. Montreal Children's Hospital PICU, Montreal, Canada. Patients 18 years or younger undergoing cardiac surgery (2005-2007). None. Cumulative fluid overload % was calculated as [(total fluid in - out in L)/admission weight (kg) × 100] and expressed as PICU peak cumulative fluid overload % throughout admission and PICU day 2 cumulative fluid overload %. Primary outcomes were length of stay and length of ventilation. The secondary outcome was oxygenation index. Fluid overload risk factors were evaluated using stepwise linear regression. Fluid overload-outcome relations were evaluated using stepwise Cox regression (length of stay, length of ventilation) and generalized estimating equations (daily PICU cumulative fluid overload % and oxygenation index repeated measures). There were 193 eligible surgeries. Peak cumulative fluid overload % was 7.4% ± 11.2%. Fluid overload peaked on PICU day 2. Lack of past cardiac surgery (p = 0.04), cyanotic heart disease (p = 0.03), and early postoperative fluids (p = 0.0001) was independently associated with higher day 2 fluid overload %. Day 2 fluid overload % predicted longer length of stay (adjusted hazard ratio, 0.95; 95% CI, 0.92-0.99; p = 0.009) and length of ventilation (adjusted hazard ratio, 0.97; 95% CI, 0.94-0.99; p = 0.03). In patients without cyanotic heart disease, worse daily fluid overload % predicted worse daily oxygenation index. Fluid overload occurs early after cardiac surgery and is associated with prolonged PICU length of stay and ventilation

  12. Quantitative phosphoproteomic study of pressure-overloaded mouse heart reveals dynamin-related protein 1 as a modulator of cardiac hypertrophy.

    Science.gov (United States)

    Chang, Yu-Wang; Chang, Ya-Ting; Wang, Qinchuan; Lin, Jim Jung-Ching; Chen, Yu-Ju; Chen, Chien-Chang

    2013-11-01

    Pressure-overload stress to the heart causes pathological cardiac hypertrophy, which increases the risk of cardiac morbidity and mortality. However, the detailed signaling pathways induced by pressure overload remain unclear. Here we used phosphoproteomics to delineate signaling pathways in the myocardium responding to acute pressure overload and chronic hypertrophy in mice. Myocardial samples at 4 time points (10, 30, 60 min and 2 weeks) after transverse aortic banding (TAB) in mice underwent quantitative phosphoproteomics assay. Temporal phosphoproteomics profiles showed 360 phosphorylation sites with significant regulation after TAB. Multiple mechanical stress sensors were activated after acute pressure overload. Gene ontology analysis revealed differential phosphorylation between hearts with acute pressure overload and chronic hypertrophy. Most interestingly, analysis of the cardiac hypertrophy pathway revealed phosphorylation of the mitochondrial fission protein dynamin-related protein 1 (DRP1) by prohypertrophic kinases. Phosphorylation of DRP1 S622 was confirmed in TAB-treated mouse hearts and phenylephrine (PE)-treated rat neonatal cardiomyocytes. TAB-treated mouse hearts showed phosphorylation-mediated mitochondrial translocation of DRP1. Inhibition of DRP1 with the small-molecule inhibitor mdivi-1 reduced the TAB-induced hypertrophic responses. Mdivi-1 also prevented PE-induced hypertrophic growth and oxygen consumption in rat neonatal cardiomyocytes. We reveal the signaling responses of the heart to pressure stress in vivo and in vitro. DRP1 may be important in the development of cardiac hypertrophy.

  13. Volume reductions in frontopolar and left perisylvian cortices in methamphetamine induced psychosis.

    Science.gov (United States)

    Aoki, Yuta; Orikabe, Lina; Takayanagi, Yoichiro; Yahata, Noriaki; Mozue, Yuriko; Sudo, Yasuhiko; Ishii, Tatsuji; Itokawa, Masanari; Suzuki, Michio; Kurachi, Masayoshi; Okazaki, Yuji; Kasai, Kiyoto; Yamasue, Hidenori

    2013-07-01

    Consumption of methamphetamine disturbs dopaminergic transmission and sometimes provokes schizophrenia-like-psychosis, named methamphetamine-associated psychosis (MAP). While previous studies have repeatedly reported regional volume reductions in the frontal and temporal areas as neuroanatomical substrates for psychotic symptoms, no study has examined whether such neuroanatomical substrates exist or not in patients with MAP. Magnetic resonance images obtained from twenty patients with MAP and 20 demographically-matched healthy controls (HC) were processed for voxel-based morphometry (VBM) using Diffeomorphic Anatomical Registration using Exponentiated Lie Algebra. An analysis of covariance model was adopted to identify volume differences between subjects with MAP and HC, treating intracranial volume as a confounding covariate. The VBM analyses showed significant gray matter volume reductions in the left perisylvian structures, such as the posterior inferior frontal gyrus and the anterior superior temporal gyrus, and the frontopolar cortices, including its dorsomedial, ventromedial, dorsolateral, and ventrolateral portions, and white matter volume reduction in the orbitofrontal area in the patients with MAP compared with the HC subjects. The smaller regional gray matter volume in the medial portion of the frontopolar cortex was significantly correlated with the severe positive symptoms in the individuals with MAP. The volume reductions in the left perisylvian structure suggest that patients with MAP have a similar pathophysiology to schizophrenia, whereas those in the frontopolar cortices and orbitofrontal area suggest an association with antisocial traits or vulnerability to substance dependence. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Large Eddy Simulations of Volume Restriction Effects on Canopy-Induced Increased-Uplift Regions

    Science.gov (United States)

    Chatziefstratiou, E.; Bohrer, G.; Velissariou, V.

    2012-12-01

    ABSTRACT Previous modeling and empirical work have shown the development of important areas of increased uplift past forward-facing steps, and recirculation zones past backward-facing steps. Forests edges represent a special kind of step - a semi-porous one. Current models of the effects of forest edges on the flow represent the forest with a prescribed drag term and does not account for the effects of the solid volume in the forest that restrict the airflow. The RAMS-based Forest Large Eddy Simulation (RAFLES) resolves flows inside and above forested canopies. RAFLES is spatially explicit, and uses the finite volume method to solve a descretized set of Navier-Stokes equations. It accounts for vegetation drag effects on the flow and on the flux exchange between the canopy and the canopy air, proportional to the local leaf density. For a better representation of the vegetation structure in the numerical grid within the canopy sub-domain, the model uses a modified version of the cut cell coordinate system. The hard volume of vegetation elements, in forests, or buildings, in urban environments, within each numerical grid cell is represented via a sub-grid-scale process that shrinks the open apertures between grid cells and reduces the open cell volume. We used RAFLES to simulate the effects of a canopy of varying foliage and stem densities on flow over virtual qube-shaped barriers under neutrally buoyant conditions. We explicitly tested the effects of the numerical representation of volume restriction, independent of the effects of the leaf drag by comparing drag-only simulations, where we prescribed no volume or aperture restriction to the flow, restriction-only simulations, where we prescribed no drag, and control simulations, where both drag and volume plus aperture restriction were included. Our simulations show that representation of the effects of the volume and aperture restriction due to obstacles to flow is important (figure 1) and leads to differences in the

  15. Iron overload and apoptosis of HL-1 cardiomyocytes: effects of calcium channel blockade.

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    Mei-pian Chen

    Full Text Available Iron overload cardiomyopathy that prevails in some forms of hemosiderosis is caused by excessive deposition of iron into the heart tissue and ensuing damage caused by a raise in labile cell iron. The underlying mechanisms of iron uptake into cardiomyocytes in iron overload condition are still under investigation. Both L-type calcium channels (LTCC and T-type calcium channels (TTCC have been proposed to be the main portals of non-transferrinic iron into heart cells, but controversies remain. Here, we investigated the roles of LTCC and TTCC as mediators of cardiac iron overload and cellular damage by using specific Calcium channel blockers as potential suppressors of labile Fe(II and Fe(III ingress in cultured cardiomyocytes and ensuing apoptosis.Fe(II and Fe(III uptake was assessed by exposing HL-1 cardiomyocytes to iron sources and quantitative real-time fluorescence imaging of cytosolic labile iron with the fluorescent iron sensor calcein while iron-induced apoptosis was quantitatively measured by flow cytometry analysis with Annexin V. The role of calcium channels as routes of iron uptake was assessed by cell pretreatment with specific blockers of LTCC and TTCC.Iron entered HL-1 cardiomyocytes in a time- and dose-dependent manner and induced cardiac apoptosis via mitochondria-mediated caspase-3 dependent pathways. Blockade of LTCC but not of TTCC demonstrably inhibited the uptake of ferric but not of ferrous iron. However, neither channel blocker conferred cardiomyocytes with protection from iron-induced apoptosis.Our study implicates LTCC as major mediators of Fe(III uptake into cardiomyocytes exposed to ferric salts but not necessarily as contributors to ensuing apoptosis. Thus, to the extent that apoptosis can be considered a biological indicator of damage, the etiopathology of cardiosiderotic damage that accompanies some forms of hemosiderosis would seem to be unrelated to LTCC or TTCC, but rather to other routes of iron ingress present in

  16. Paradoxical relationship between atriopeptin plasma levels and diuresis-natriuresis induced by acute volume expansion.

    OpenAIRE

    Sakata, M.; Greenwald, J E; Needleman, P

    1988-01-01

    Surgical removal of one or both atrial appendages was employed in rats to reduce the intrinsic stores of atriopeptin (AP). In conscious rats (with intact baroreceptor reflexes), bilateral or unilateral atrial appendectomy suppressed the diuresis and natriuresis produced by acute volume expansion. Surprisingly, volume expansion (with 4% bovine serum albumin in saline at 1.5 ml/kg per min for 15 min) did not result in an increase in plasma AP immunoreactivity (APir) in control or atrial-appende...

  17. Antioxidants and NOS inhibitors selectively targets manganese-induced cell volume via Na-K-Cl cotransporter-1 in astrocytes.

    Science.gov (United States)

    Alahmari, Khalid A; Prabhakaran, Harini; Prabhakaran, Krishnan; Chandramoorthy, Harish C; Ramugounder, Ramakrishnan

    2015-06-12

    Manganese has shown to be involved in astrocyte swelling. Several factors such as transporters, exchangers and ion channels are attributed to astrocyte swelling as a result in the deregulation of cell volume. Products of oxidation and nitration have been implied to be involved in the pathophysiology of swelling; however, the direct link and mechanism of manganese induced astrocyte swelling has not been fully elucidated. In the current study, we used rat primary astrocyte cultures to investigate the activation of Na-K-Cl cotransporter-1 (NKCC1) a downstream mechanism for free radical induced astrocyte swelling as a result of manganese toxicity. Our results showed manganese, oxidants and NO donors as potent inducer of oxidation and nitration of NKCC1. Our results further confirmed that manganese (50 μM) increased the total protein, phosphorylation and activity of NKCC1 as well as cell volume (p manganese or oxidants and NO induced activation, oxidation/nitration of NKCC1 play an important role in the astrocyte swelling. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Acute Experimental Hyperthyroidism Does Not Affect Basal and Volume-Induced Atrial Natriuretic Peptide Secretion in Healthy Subjects

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    Gregory Giamouzis

    2011-01-01

    Full Text Available Background. Excess circulating thyroid hormones are associated with increased cardiac atrial natriuretic peptide (ANP secretion but the exact mechanisms involved have not been fully elucidated in vivo. Methods. To examine whether thyroid hormone regulation of ANP secretion is the result of a direct action on the myocardium and/or of an indirect action through alterations in the peripheral circulation, plasma ANP levels (baseline and volume expansion-induced were evaluated in 14 healthy men, before and after triiodothyronine (T3 administration. Results. T3 administration was followed by a significant increase in serum T3 levels and a significant decrease in serum TSH levels, without significantly affecting ANP levels. Systemic vascular resistance, plasma rennin activity (PRA, and aldosterone (ALDO levels, as well as indices of left atrial function, were not significantly altered, despite a significant increase in cardiac output. Plasma volume expansion, induced by a 1500 ml normal saline (NSal infusion, both before and after T3 administration, was followed by a significant decrease in PRA and ALDO and a significant increase in plasma ANP levels, without significantly affecting the mean blood pressure (BP and heart rate (HR in each study period. The NSal-induced response, measured as the integrated area under the curve corrected for baseline values (-AUC, was not different after T3 administration for ANP, ALDO, PRA, HR, and mean BP. Conclusion. In vivo thyroid hormone-induced myocardial ANP secretion is the result of an indirect action mainly through hemodynamic changes that increase atrial stretch.

  19. Black Tea High-Molecular-Weight Polyphenol-Rich Fraction Promotes Hypertrophy during Functional Overload in Mice.

    Science.gov (United States)

    Aoki, Yuki; Ozawa, Tetsuo; Takemasa, Tohru; Numata, Osamu

    2017-03-29

    Mitochondria activation factor (MAF) is a high-molecular-weight polyphenol extracted from black tea that stimulates training-induced 5' adenosine monophosphate-activated protein kinase (AMPK) activation and improves endurance capacity. Originally, MAF was purified from black tea using butanol and acetone, making it unsuitable for food preparation. Hence, we extracted a MAF-rich sample "E80" from black tea, using ethanol and water only. Here, we examined the effects of E80 on resistance training. Eight-week old C57BL/6 mice were fed with a normal diet or a diet containing 0.5% E80 for 4, 7 and 14 days under conditions of functional overload. It was found that E80 administration promoted overload-induced hypertrophy and induced phosphorylation of the Akt/mammalian target of rapamycin (mTOR) pathway proteins, such as Akt, P70 ribosomal protein S6 kinase (p70S6K), and S6 in the plantaris muscle. Therefore, functional overload and E80 administration accelerated mTOR signaling and increased protein synthesis in the muscle, thereby inducing hypertrophy.

  20. Black Tea High-Molecular-Weight Polyphenol-Rich Fraction Promotes Hypertrophy during Functional Overload in Mice

    Directory of Open Access Journals (Sweden)

    Yuki Aoki

    2017-03-01

    Full Text Available Mitochondria activation factor (MAF is a high-molecular-weight polyphenol extracted from black tea that stimulates training-induced 5′ adenosine monophosphate-activated protein kinase (AMPK activation and improves endurance capacity. Originally, MAF was purified from black tea using butanol and acetone, making it unsuitable for food preparation. Hence, we extracted a MAF-rich sample “E80” from black tea, using ethanol and water only. Here, we examined the effects of E80 on resistance training. Eight-week old C57BL/6 mice were fed with a normal diet or a diet containing 0.5% E80 for 4, 7 and 14 days under conditions of functional overload. It was found that E80 administration promoted overload-induced hypertrophy and induced phosphorylation of the Akt/mammalian target of rapamycin (mTOR pathway proteins, such as Akt, P70 ribosomal protein S6 kinase (p70S6K, and S6 in the plantaris muscle. Therefore, functional overload and E80 administration accelerated mTOR signaling and increased protein synthesis in the muscle, thereby inducing hypertrophy.

  1. Serotoninergic Modulation of Basal Cardiovascular Responses and Responses Induced by Isotonic Extracellular Volume Expansion in Rats.

    Science.gov (United States)

    Semionatto, Isadora Ferraz; Raminelli, Adrieli Oliveira; Alves, Angelica Cristina; Capitelli, Caroline Santos; Chriguer, Rosangela Soares

    2017-02-01

    Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats. Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas. Avaliar o efeito da administração de salina ou agonista serotonin

  2. Induction of ROS Overload by Alantolactone Prompts Oxidative DNA Damage and Apoptosis in Colorectal Cancer Cells

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    Yushuang Ding

    2016-04-01

    Full Text Available Cancer cells typically display higher than normal levels of reactive oxygen species (ROS, which may promote cancer development and progression but may also render the cancer cells more vulnerable to further ROS insult. Indeed, many of the current anticancer therapeutics kill cancer cells via induction of oxidative stress, though they target both cancer and normal cells. Recently, alantolactone (ATL, a natural sesquiterpene lactone, has been shown to induce apoptosis by increasing ROS levels specifically in cancer cells; however, the molecular mechanisms linking ROS overproduction to apoptosis remain unclear. Here we show that the ATL-induced ROS overload in human SW480 and SW1116 colorectal cancer cells was followed by a prominent accumulation of cellular oxidized guanine (8-oxoG and immediate increase in the number of DNA strand breaks, indicating that increased ROS resulted in extensive oxidative DNA damage. Consequently, the G1/S-CDK suppresser CDKN1B (p21 and pro-apoptotic proteins Bax and activated caspase-3 were upregulated, while anti-apoptotic Bcl-2 was downregulated, which were followed by cell cycle arrest at G1 and marked apoptosis in ATL-treated cancer but not non-cancer cells. These results suggest that the ATL-induced ROS overload triggers cell death through induction of massive oxidative DNA damage and subsequent activation of the intrinsic apoptosis pathway.

  3. Induction of ROS Overload by Alantolactone Prompts Oxidative DNA Damage and Apoptosis in Colorectal Cancer Cells.

    Science.gov (United States)

    Ding, Yushuang; Wang, Hongge; Niu, Jiajing; Luo, Manyu; Gou, Yangmei; Miao, Lining; Zou, Zhihua; Cheng, Ying

    2016-04-14

    Cancer cells typically display higher than normal levels of reactive oxygen species (ROS), which may promote cancer development and progression but may also render the cancer cells more vulnerable to further ROS insult. Indeed, many of the current anticancer therapeutics kill cancer cells via induction of oxidative stress, though they target both cancer and normal cells. Recently, alantolactone (ATL), a natural sesquiterpene lactone, has been shown to induce apoptosis by increasing ROS levels specifically in cancer cells; however, the molecular mechanisms linking ROS overproduction to apoptosis remain unclear. Here we show that the ATL-induced ROS overload in human SW480 and SW1116 colorectal cancer cells was followed by a prominent accumulation of cellular oxidized guanine (8-oxoG) and immediate increase in the number of DNA strand breaks, indicating that increased ROS resulted in extensive oxidative DNA damage. Consequently, the G₁/S-CDK suppresser CDKN1B (p21) and pro-apoptotic proteins Bax and activated caspase-3 were upregulated, while anti-apoptotic Bcl-2 was downregulated, which were followed by cell cycle arrest at G₁ and marked apoptosis in ATL-treated cancer but not non-cancer cells. These results suggest that the ATL-induced ROS overload triggers cell death through induction of massive oxidative DNA damage and subsequent activation of the intrinsic apoptosis pathway.

  4. Symmetrical and overloaded effect of diffusion in information filtering

    Science.gov (United States)

    Zhu, Xuzhen; Tian, Hui; Chen, Guilin; Cai, Shimin

    2017-10-01

    In physical dynamics, mass diffusion theory has been applied to design effective information filtering models on bipartite network. In previous works, researchers unilaterally believe objects' similarities are determined by single directional mass diffusion from the collected object to the uncollected, meanwhile, inadvertently ignore adverse influence of diffusion overload. It in some extent veils the essence of diffusion in physical dynamics and hurts the recommendation accuracy and diversity. After delicate investigation, we argue that symmetrical diffusion effectively discloses essence of mass diffusion, and high diffusion overload should be published. Accordingly, in this paper, we propose an symmetrical and overload penalized diffusion based model (SOPD), which shows excellent performances in extensive experiments on benchmark datasets Movielens and Netflix.

  5. Diagnosis and quantification of the iron overload through Magnetic resonance.

    Science.gov (United States)

    Alústiza Echeverría, J M; Portillo, M C Barrera; Iñiguiz, A Guisasola; Muño, A Ugarte

    2017-09-15

    There are different magnetic resonance techniques and models to quantify liver iron concentration. T2 relaxometry methods evaluate the iron concentration in the myocardium, and they are able to discriminate all the levels of iron overload in the liver. Signal intensity ratio methods saturate with high levels of liver overload and can not assess iron concentration in the myocardium but they are more accessible and are very standardized. This article reviews, in different clinical scenarios, when Magnetic Resonance must be used to assess iron overload in the liver and myocardium and analyzes the current challenges to optimize the aplication of the technique and to be it included in the clinical guidelines. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. PPAR-γ is involved in the protective effect of 2,3,4',5-tetrahydroxystilbene-2-O-beta-D-glucoside against cardiac fibrosis in pressure-overloaded rats.

    Science.gov (United States)

    Peng, Yi; Zeng, Yi; Xu, Jin; Huang, Xing Lan; Zhang, Wei; Xu, Xiao Le

    2016-11-15

    2, 3, 4', 5-tetrahydroxystilbene-2-0-β-D glucoside (TSG) could inhibit cardiac remodeling in response to pressure overload. Peroxisome proliferator-activated receptor gamma (PPAR-γ) has been recognized as a potent, endogenous antifibrotic factor and maintaining a proper expression level in myocardium is necessary for assuring that structure and function of heart adapt to pressure overload stress. The aim of the present study was to investigate whether PPAR-γ is involved in the beneficial effect of TSG on pressure overload-induced cardiac fibrosis. TSG (120mg/kg/day) or TSG (120mg/kg/day) plus the PPAR-γ antagonist GW9662 (1mg/kg/day) was administered to rats with pressure overload induced by abdominal aortic banding. 30 days later, pressure overload-induced hypertension, cardiac dysfunction and fibrosis were significantly inhibited by TSG. TSG also significantly reduced collagen I, collagen III, fibronectin and plasminogen activator inhibitor (PAI)-1 expression, as makers of myocardial fibrosis. Theses anti-fibrotic effects of TSG in pressure overloaded hearts could be abrogated by co-treatment with GW9662. Accordingly, upregulated PPAR-γ protein expression by TSG in pressure overloaded hearts was also reversed by co-treatment with GW9662. Additionally, the inhibitory effects of TSG on angiotensin II induced cardiac fibroblasts proliferation, differentiation and expression of collagen I and III, fibronectin and PAI-1 were abrogated by PPAR-γ antagonist GW9662 and PPAR-γ silencing. Furthermore, TSG directly increased PPAR-γ gene expression at gene promoter, mRNA and protein level in angiotensin II-treated cardiac fibroblats in vitro. Our results suggested that upregualtion of endogenous PPAR-γ expression by TSG may be involved in its beneficial effect on pressure overload-induced cardiac fibrosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Penicillin-induced epilepsy model in rats: dose-dependant effect on hippocampal volume and neuron number.

    Science.gov (United States)

    Akdogan, Ilgaz; Adiguzel, Esat; Yilmaz, Ismail; Ozdemir, M Bulent; Sahiner, Melike; Tufan, A Cevik

    2008-10-22

    This study was designed to evaluate the penicillin-induced epilepsy model in terms of dose-response relationship of penicillin used to induce epilepsy seizure on hippocampal neuron number and hippocampal volume in Sprague-Dawley rats. Seizures were induced with 300, 500, 1500 and 2000IU of penicillin-G injected intracortically in rats divided in four experimental groups, respectively. Control group was injected intracortically with saline. Animals were decapitated on day 7 of treatment and brains were removed. The total neuron number of pyramidal cell layer from rat hippocampus was estimated using the optical fractionator method. The volume of same hippocampal areas was estimated using the Cavalieri method. Dose-dependent decrease in hippocampal neuron number was observed in three experimental groups (300, 500 and 1500IU of penicillin-G), and the effects were statistically significant when compared to the control group (P<0.009). Dose-dependent decrease in hippocampal volume, on the other hand, was observed in all three of these groups; however, the difference compared to the control group was only statistically significant in 1500IU of penicillin-G injected group (P<0.009). At the dose of 2000IU penicillin-G, all animals died due to status seizures. These results suggest that the appropriate dose of penicillin has to be selected for a given experimental epilepsy study in order to demonstrate the relevant epileptic seizure and its effects. Intracortical 1500IU penicillin-induced epilepsy model may be a good choice to practice studies that investigate neuroprotective mechanisms of the anti-epileptic drugs.

  8. Postnatal iron overload destroys NA-DA functional interactions.

    Science.gov (United States)

    Fredriksson, A; Archer, T

    2007-02-01

    C57/BL6 mice were administered either postnatal iron (Fe(2+) 7.5 mg/kg, on postnatal days 10-12) or vehicle, followed by administration of either DSP4 (50 mg/kg, s.c., 30 min after injection of zimeldine, 20 mg/kg, s.c.) or vehicle (saline) at 63 days of age. Three weeks later, iron/vehicle treated, DSP4/vehicle treated mice were injected with either a low dose of MPTP (2 x 20 mg/kg, with a 24-hr interval between injections) or vehicle. Behaviour testing took place a further three weeks (spontaneous behaviour and L-Dopa induced) and two weeks (clonidine-L-Dopa induced) later. Postnatal iron administration exacerbated the bradykinesia induced by MPTP and virtually abolished all spontaneous motor activity in NA-denervated mice that were MPTP-treated. Postnatal iron administration reduced markedly the restoration of motor activity by suprathreshold L-Dopa (20 mg/kg) following a 60-min habituation to the test chambers. Pretreatment with DSP4 effectively eliminated the restorative effect of L-Dopa in the MPTP mice. The synergistic effects of co-administration of clinidine (1 mg/kg) with a subthreshold dose of L-Dopa (5 mg/kg) in elevating the motor activity of MPTP mice were reduced markedly by postnatal iron administration, as well as by pretreatment with DSP4. NA-denervation by DSP4, after postnatal iron treatment, totally abolished the activity-elevating effects of the alpha-adrenoceptor agonist + DA-precursor combination in MPTP mice, and virtually eliminated these effects in saline (non-MPTP) mice. Postnatal iron administration caused enduring higher levels of total iron content in all the groups with an increased level in mice treated with DSP4 followed by MPTP. These divergent findings confirm the direct influence of NA innervation upon dopaminergic functional expression and indicate a permanent vulnerability both in the noradrenergic and dopaminergic pathways following the postnatal infliction of an iron overload.

  9. Overload Control in Smart Transformer-Fed Grid

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    Giovanni De Carne

    2017-02-01

    Full Text Available Renewable energy resources and new loads—such as electric vehicles—challenge grid management. Among several scenarios, the smart transformer represents a solution for simultaneously managing low- and medium-voltage grids, providing ancillary services to the distribution grid. However, unlike conventional transformers, the smart transformer has a very limited overload capability, because the junction temperature—which must always be below its maximum limit—is characterized by a short time constant. In this work, an overload control for smart transformer by means of voltage and frequency variations has been proposed and verified by means of simulations and experiments.

  10. Low-intensity pulsed ultrasound enhances angiogenesis and ameliorates contractile dysfunction of pressure-overloaded heart in mice.

    Science.gov (United States)

    Ogata, Tsuyoshi; Ito, Kenta; Shindo, Tomohiko; Hatanaka, Kazuaki; Eguchi, Kumiko; Kurosawa, Ryo; Kagaya, Yuta; Monma, Yuto; Ichijo, Sadamitsu; Taki, Hirofumi; Kanai, Hiroshi; Shimokawa, Hiroaki

    2017-01-01

    Chronic left ventricular (LV) pressure overload causes relative ischemia with resultant LV dysfunction. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS) improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we thus examined whether LIPUS also ameliorates contractile dysfunction in LV pressure-overloaded hearts. Chronic LV pressure overload was induced with transverse aortic constriction (TAC) in mice. LIPUS was applied to the whole heart three times in the first week after TAC and was repeated once a week for 7 weeks thereafter (n = 22). Animals in the control groups received the sham treatment without LIPUS (n = 23). At 8 weeks after TAC, LV fractional shortening was depressed in the TAC-Control group, which was significantly ameliorated in the TAC-LIPUS group (30.4±0.5 vs. 36.2±3.8%, P<0.05). Capillary density was higher and perivascular fibrosis was less in the LV in the TAC-LIPUS group than in the TAC-Control group. Myocardial relative ischemia evaluated with hypoxyprobe was noted in the TAC-Control group, which was significantly attenuated in the TAC-LIPUS group. In the TAC-LIPUS group, as compared with the control group, mRNA expressions of BNP and collagen III were significantly lower (both P<0.05) and protein expressions of VEGF and eNOS were significantly up-regulated associated with Akt activation (all P<0.05). No adverse effect related to the LIPUS therapy was noted. These results indicate that the LIPUS therapy ameliorates contractile dysfunction in chronically pressure-overloaded hearts through enhanced myocardial angiogenesis and attenuated perivascular fibrosis. Thus, the LIPUS therapy may be a promising, non-invasive treatment for cardiac dysfunction due to chronic pressure overload.

  11. Reduced defense of central blood volume during acute lower body negative pressure-induced hypovolemic circulatory stress in aging women.

    Science.gov (United States)

    Lindenberger, Marcus; Länne, Toste

    2012-06-01

    Elderly humans are more vulnerable to trauma and hemorrhage than young and elderly men and respond with decreased defense of central blood volume during acute experimental hypovolemia induced by lower body negative pressure (LBNP). However, these defense mechanisms have not been evaluated in elderly women. The aim of this study was to determine the effectiveness of compensatory responses to defend central blood volume during experimental hypovolemia in elderly and young women. Cardiovascular responses in 34 women, 12 elderly (66 ± 1 years) and 22 young women (23 ± 0.4 years), were studied during experimental hypovolemia induced by LBNP of 11 to 44 mmHg. Air plethysmography was used to assess the capacitance response (redistribution of peripheral venous blood to the central circulation) as well as net capillary fluid transfer from tissue to blood in the arm. Lower body negative pressure seemed to create comparable hypovolemia measured as total calf volume increase in elderly and young women. Heart rate increased less in elderly women (LBNP of 44 mmHg: 20 ± 2 vs. 37 ± 4%; P < 0.01) but with similar (%) increase in forearm vascular resistance. Mobilization of capacitance blood from the peripheral circulation was both slower and decreased by ∼60% in elderly women (P < 0.001), and net capillary fluid absorption from surrounding tissues was reduced by ∼40% (P < 0.01, LBNP of 44 mmHg). Elderly women responded with less increase in heart rate but with equal forearm vascular resistance (%) response during LBNP. Furthermore, the compensatory capacitance response was both slower and substantially decreased, and net capillary fluid absorption considerably reduced, collectively indicating less efficiency to defend central blood volume in elderly than in young women.

  12. Examination of parameters affecting overload fracture behavior of flaw-tip hydrides in Zr-2.5Nb pressure tubes in Candu reactors

    Energy Technology Data Exchange (ETDEWEB)

    Cui, J.; Shek, G.K. [Kinectrics Inc., Toronto, Ontario (Canada); Wang, Z.R. [Toronto Univ., Dept. of Materials Science and Engineering, Toronto, Ontario (Canada)

    2007-07-01

    Service-induced flaws in Zr-2.5Nb alloy pressure tubes in Candu (Canada Deuterium Uranium Reactors) nuclear reactors are susceptible to a crack initiation and growth mechanism known as Delayed Hydride Cracking (DHC), which is a repetitive process that involves hydrogen diffusion, hydride precipitation, growth and fracture of a hydride region at the flaw-tip under a constant load. Crack initiation may also occur under another loading condition when the hydride region is subjected to an overload. An overload occurs when the hydride region at the flaw tip is loaded to a stress higher than that at which this region is formed such as when the reactor experiences a transient pressure higher than the normal operating pressure where the hydride region is formed. Flaw disposition requires justification that the hydride region overload will not fracture the hydride region, and initiate DHC. In this work, monotonically increasing load experiments were performed on unirradiated Zr-2.5Nb pressure tube specimens containing simulated debris frets (V-notch) and bearing pad frets (BPF, U-shape notch) to examine overload fracture behavior of flaw-tip hydrides formed under hydride ratcheting conditions. Hydride cracking in the overload tests was detected by the acoustic emission technique and confirmed by post-test metallurgical examination. Test results indicate that the resistance to overload fracture is affected by a number of parameters including hydride formation stress, flaw shape (V-notch vs. BPF) and flaw radius (0.015 mm vs. 0.1 mm). The notch-tip hydride morphologies were examined by optical microscopy and scanning electron microscopy (SEM) which show that they are affected by the hydride formation conditions, resulting in different overload fracture resistance. Finite element stress analyses were also performed to obtain flaw-tip stress distributions for interpretation of the test results. (authors)

  13. Variations in gastric compliance induced by acute blood volume changes in anesthetized rats

    Directory of Open Access Journals (Sweden)

    Graça J.R.V.

    2002-01-01

    Full Text Available The impact of acute volume imbalances on gastric volume (GV was studied in anesthetized rats (250-300 g. After cervical and femoral vessel cannulation, a balloon catheter was positioned in the proximal stomach. The opposite end of the catheter was connected to a barostat with an electronic sensor coupled to a plethysmometer. A standard ionic solution was used to fill the balloon (about 3.0 ml and the communicating vessel system, and to raise the reservoir liquid level 4 cm above the animals' xiphoid appendix. Due to constant barostat pressure, GV values were considered to represent the gastric compliance index. All animals were monitored for 90 min. After a basal interval, they were randomly assigned to normovolemic, hypervolemic, hypovolemic or restored protocols. Data were compared by ANOVA followed by Bonferroni's test. Mean arterial pressure (MAP, central venous pressure (CVP and GV values did not change in normovolemic animals (N = 5. Hypervolemic animals (N = 12 were transfused at 0.5 ml/min with a suspension of red blood cells in Ringer-lactate solution with albumin (12.5 ml/kg, which reduced GV values by 11.3% (P0.05. MAP and CVP values increased (P<0.05 after hypervolemia but decreased (P<0.05 with hypovolemia. In conclusion, blood volume level modulates gastric compliance, turning the stomach into an adjustable reservoir, which could be part of the homeostatic process to balance blood volume.

  14. Continuing treatment with Salvia miltiorrhiza injection attenuates myocardial fibrosis in chronic iron-overloaded mice.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available Iron overload cardiomyopathy results from iron accumulation in the myocardium that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza (SM, also known as Danshen, a traditional Chinese medicinal herb, has been widely used for hundreds of years to treat cardiovascular diseases. Here, we investigated the effect and potential mechanism of SM on myocardial fibrosis induced by chronic iron overload (CIO in mice. Kunming male mice (8 weeks old were randomized to six groups of 10 animals each: control (CONT, CIO, low-dose SM (L-SM, high-dose SM (H-SM, verapamil (VRP and deferoxamine (DFO groups. Normal saline was injected in the CONT group. Mice in the other five groups were treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and those in the latter four groups also received corresponding daily treatments, including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron deposition was estimated histologically using Prussian blue staining. Myocardial fibrosis was determined by Masson's trichrome staining and hydroxyproline (Hyp quantitative assay. Superoxide dismutase (SOD activity, malondialdehyde (MDA content and protein expression levels of type I collagen (COL I, type I collagen (COL III, transforming growth factor-β1 (TGF-β1 and matrix metalloproteinase-9 (MMP-9 were analyzed to investigate the mechanisms underlying the effects of SM against iron-overloaded fibrosis. Treatment of chronic iron-overloaded mice with SM dose-dependently reduced iron deposition levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL III, as well as upregulated the expression of TGF- β1 and MMP-9 proteins in the heart. Moreover, SM treatment decreased MDA content and increased SOD activity. In conclusion, SM exerted activities against cardiac fibrosis induced by CIO, which may be attributed to its inhibition of iron deposition, as well as collagen metabolism and oxidative

  15. Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model

    Science.gov (United States)

    Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

    2017-01-01

    Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. PMID:28143953

  16. Determination of Permissible Short-Time Emergency Overloading of Turbo-Generators and Synchronous Compensators

    Directory of Open Access Journals (Sweden)

    V. A. Anischenko

    2011-01-01

    Full Text Available The paper shows that failure to take into account variable ratio of short-time emergency overloading of turbo-generators (synchronous compensators that can lead to underestimation of overloading capacity or impermissible insulation over-heating.A method has been developed for determination of permissible duration of short-time emergency over-loading that takes into account changes of over-loading ratio in case of a failure.

  17. Information Overload in Multi-Stage Selection Procedures

    NARCIS (Netherlands)

    S.S. Ficco (Stefano); V.A. Karamychev (Vladimir)

    2004-01-01

    textabstractThe paper studies information processing imperfections in a fully rational decision-making network. It is shown that imperfect information transmission and imperfect information acquisition in a multi-stage selection game yield information overload. The paper analyses the mechanisms resp

  18. Overload prevention in model supports for wind tunnel model testing

    Directory of Open Access Journals (Sweden)

    Anton IVANOVICI

    2015-09-01

    Full Text Available Preventing overloads in wind tunnel model supports is crucial to the integrity of the tested system. Results can only be interpreted as valid if the model support, conventionally called a sting remains sufficiently rigid during testing. Modeling and preliminary calculation can only give an estimate of the sting’s behavior under known forces and moments but sometimes unpredictable, aerodynamically caused model behavior can cause large transient overloads that cannot be taken into account at the sting design phase. To ensure model integrity and data validity an analog fast protection circuit was designed and tested. A post-factum analysis was carried out to optimize the overload detection and a short discussion on aeroelastic phenomena is included to show why such a detector has to be very fast. The last refinement of the concept consists in a fast detector coupled with a slightly slower one to differentiate between transient overloads that decay in time and those that are the result of aeroelastic unwanted phenomena. The decision to stop or continue the test is therefore conservatively taken preserving data and model integrity while allowing normal startup loads and transients to manifest.

  19. Iron deficiency and overload in relation to nutrition

    NARCIS (Netherlands)

    Spanjersberg MQI; Jansen EHJM; LEO

    2000-01-01

    Nutritional iron intake in the Netherlands has been reviewed with respect to both iron deficiency and iron overload. In general, iron intake and iron status in the Netherlands are adequate and therefore no change in nutrition policy is required. The following aspects and developments, however, need

  20. New Power Estimation Methods for Highly Overloaded Synchronous CDMA Systems

    CERN Document Server

    Nashtaali, Damoun; Pad, Pedram; Moghadasi, Seyed Reza; Marvasti, Farokh

    2011-01-01

    In CDMA systems, the received user powers vary due to moving distance of users. Thus, the CDMA receivers consist of two stages. The first stage is the power estimator and the second one is a Multi-User Detector (MUD). Conventional methods for estimating the user powers are suitable for underor fully-loaded cases (when the number of users is less than or equal to the spreading gain). These methods fail to work for overloaded CDMA systems because of high interference among the users. Since the bandwidth is becoming more and more valuable, it is worth considering overloaded CDMA systems. In this paper, an optimum user power estimation for over-loaded CDMA systems with Gaussian inputs is proposed. We also introduce a suboptimum method with lower complexity whose performance is very close to the optimum one. We shall show that the proposed methods work for highly over-loaded systems (up to m(m + 1) =2 users for a system with only m chips). The performance of the proposed methods is demonstrated by simulations. In ...

  1. Information Overload in Multi-Stage Selection Procedures

    NARCIS (Netherlands)

    S.S. Ficco (Stefano); V.A. Karamychev (Vladimir)

    2004-01-01

    textabstractThe paper studies information processing imperfections in a fully rational decision-making network. It is shown that imperfect information transmission and imperfect information acquisition in a multi-stage selection game yield information overload. The paper analyses the mechanisms

  2. Effects of Information Overload on Brazilian E-Consumers

    Directory of Open Access Journals (Sweden)

    Rafael Lucian

    2009-01-01

    Full Text Available Problem statement: E-commerce is a reality; Companies must consider this media as an important trade channel without distances between products and consumers. A key issue of e-commerce is how companies are disclosing information to its customers. This study aims to measure if there is relationship between the information overload in the virtual environment and the response of satisfaction and confusion of consumers. Approach: Research had exploratory-experimental character and it was used a quasi-experiment. Due to the methodology adopted, two samples were obtained, the first of control with 114 respondents and the second of experiment with 178 cases reported. Data analysis was made though descriptive statistics (central tendency and dispersion, multivariate (factor analysis and non-parametric (Mann-Whitney U test. Results: A factorial matrix was built and it was found that information overload relates to the responses of satisfaction and confusion in the environment of e-commerce. There was a statistical significance level supporting these relationships. Conclusion/Recommendation: The main implication of information load was the feeling of not having done the best buy, generating a possible repentance. Related to the feeling of confusion generated by the large amount of information, the physical and virtual environment has the same properties. The performed analyses in this study indicated that there is a relationship between the e-commerce consumer satisfaction and the experience of information overload. Future studies might investigate the relationship between information overload and other responses.

  3. Fetal liver iron overload: the role of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Cassart, Marie; Avni, Freddy Efraim [Erasme Hospital, Medical imaging, Brussels, Brabant (Belgium); Guibaud, Laurent [Hopital femme mere enfant, Imagerie Pediatrique et Foetale, Lyon-Bron (France); Molho, Marc [C.H.I Poissy/St Germain-en-Laye, Imagerie Medicale, Poissy (France); D' Haene, Nicky [Erasme Hospital, Anatomopathology Department, Brussels (Belgium); Paupe, Alain [C.H.I Poissy/St Germain-en-Laye, Pediatrie, Poissy (France)

    2011-02-15

    To assess the potential role of MR imaging in the diagnosis of fetal liver iron overload. We reviewed seven cases of abnormal liver signal in fetuses referred to MR imaging in a context of suspected congenital infection (n = 2), digestive tract anomalies (n = 3) and hydrops fetalis (n = 2). The average GA of the fetuses was 31 weeks. The antenatal diagnoses were compared with histological data (n = 6) and postnatal work-up (n = 1). Magnetic resonance imaging demonstrated unexpected abnormal fetal liver signal suggestive of iron overload in all cases. The iron overload was confirmed on postnatal biopsy (n = 2) and fetopathology (n = 4). The final diagnosis was hepatic hemosiderosis (haemolytic anaemia (n = 2) and syndromal anomalies (n = 2)) and congenital haemochromatosis (n = 3). In all cases, the liver appeared normal on US. Magnetic resonance is the only imaging technique able to demonstrate liver iron overload in utero. Yet, the study outlines the fundamental role of MR imaging in cases of congenital haemochromatosis. The antenatal diagnosis of such a condition may prompt ante - (in the case of recurrence) or neonatal treatment, which might improve the prognosis. (orig.)

  4. Information Overload and Viral Marketing: Countermeasures and Strategies

    Science.gov (United States)

    Cheng, Jiesi; Sun, Aaron; Zeng, Daniel

    Studying information diffusion through social networks has become an active research topic with important implications in viral marketing applications. One of the fundamental algorithmic problems related to viral marketing is the Influence Maximization (IM) problem: given an social network, which set of nodes should be considered by the viral marketer as the initial targets, in order to maximize the influence of the advertising message. In this work, we study the IM problem in an information-overloaded online social network. Information overload occurs when individuals receive more information than they can process, which can cause negative impacts on the overall marketing effectiveness. Many practical countermeasures have been proposed for alleviating the load of information on recipients. However, how these approaches can benefit viral marketers is not well understood. In our work, we have adapted the classic Information Cascade Model to incorporate information overload and study its countermeasures. Our results suggest that effective control of information overload has the potential to improve marketing effectiveness, but the targeting strategy should be re-designed in response to these countermeasures.

  5. measurements of iron status and survival in african iron overload

    African Journals Online (AJOL)

    iron status to diagnose this form of iron overload has not been clarified. Methods. ..... U-test and categorical variables were compared with the Fisher exact or the Pearson ..... 5eftel He, Keeley Iq, lsaacson C, BothweU TH. Siderosis in the ...

  6. Finite volume analysis of temperature effects induced by active MRI implants: 2. Defects on active MRI implants causing hot spots

    Directory of Open Access Journals (Sweden)

    Grönemeyer Dietrich HW

    2006-05-01

    Full Text Available Abstract Background Active magnetic resonance imaging implants, for example stents, stent grafts or vena cava filters, are constructed as wireless inductively coupled transmit and receive coils. They are built as a resonator tuned to the Larmor frequency of a magnetic resonance system. The resonator can be added to or incorporated within the implant. This technology can counteract the shielding caused by eddy currents inside the metallic implant structure. This may allow getting diagnostic information of the implant lumen (in stent stenosis or thrombosis for example. The electro magnetic rf-pulses during magnetic resonance imaging induce a current in the circuit path of the resonator. A by material fatigue provoked partial rupture of the circuit path or a broken wire with touching surfaces can set up a relatively high resistance on a very short distance, which may behave as a point-like power source, a hot spot, inside the body part the resonator is implanted to. This local power loss inside a small volume can reach ¼ of the total power loss of the intact resonating circuit, which itself is proportional to the product of the resonator volume and the quality factor and depends as well from the orientation of the resonator with respect to the main magnetic field and the imaging sequence the resonator is exposed to. Methods First an analytical solution of a hot spot for thermal equilibrium is described. This analytical solution with a definite hot spot power loss represents the worst case scenario for thermal equilibrium inside a homogeneous medium without cooling effects. Starting with this worst case assumptions additional conditions are considered in a numerical simulation, which are more realistic and may make the results less critical. The analytical solution as well as the numerical simulations use the experimental experience of the maximum hot spot power loss of implanted resonators with a definite volume during magnetic resonance imaging

  7. Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

    Directory of Open Access Journals (Sweden)

    Wen Liang

    Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

  8. Glue embolization of the giant aneurysm by reducing thrombosis-induced volume expansion effect

    Energy Technology Data Exchange (ETDEWEB)

    Yeom, Yoo Kyung; Suh, Dae Chul [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2015-04-15

    A giant aneurysm due to a large intra-aneurysmal volume can be complicated by a delayed massive volume expansion caused by thrombus formation. To prevent such a severe mass effect, we obliterated the aneurysmal lumen by gluing and prevented further development of thrombosis. A 52-year-old female with a giant aneurysm at the cavernous segment of the internal carotid artery presented with tinnitus and intermittent diplopia. After confirming with a negative occlusion test, the right internal carotid artery was trapped by coiling and with further obliteration of the aneurysmal lumen by gluing. She developed a mild diplopia after the procedure and recovered without any deficit. The magnetic resonance angiography showed a stable occlusion of the aneurysm and good collateral filling of the cerebral vessel 15 months later.

  9. Daily Suction Provided by External Volume Expansion Inducing Regeneration of Grafted Fat in a Murine Model.

    Science.gov (United States)

    Ye, Yuan; Liao, Yunjun; Lu, Feng; Gao, Jianhua

    2017-02-01

    Fat grafting has variable and sometimes poor outcomes, and therefore new methods are needed. Multiple studies have demonstrated the excellent performance of external volume expansion and focused only on preexpansion with emphasis on the recipient. Two mouse models (a suction model and a fat-exchange transplantation model) were established to investigate changes in the origins and biological behaviors of regeneration-related cells in grafted fat under daily suction provided by external volume expansion. Blood supply increased from new host-derived capillaries or macrophage infiltration under suction. CD34-positive cells showed increased migration from the host into the grafts under suction. At week 12, nearly half of the mature adipocytes regenerated in the grafts in the suction group were derived from the host. Peroxisome proliferator-activated receptor γ expression of the suction group was significantly higher than that of controls at weeks 2 and 4 during adipogenesis. The normalized sample weight of the grafted fat was significantly greater than that of controls at 1 (0.081 ± 0.001 versus 0.072 ± 0.005; p suction provided by external volume expansion favors the regeneration of grafted fat and improves retention by promoting the migration of regeneration-related cells and the differentiation of adipocytes. Thus, more mature fat tissue with a well-organized structure was formed under suction.

  10. A new microscopic method to analyse desiccation-induced volume changes in aeroterrestrial green algae.

    Science.gov (United States)

    Lajos, K; Mayr, S; Buchner, O; Blaas, K; Holzinger, A

    2016-08-01

    Aeroterrestrial green algae are exposed to desiccation in their natural habitat, but their actual volume changes have not been investigated. Here, we measure the relative volume reduction (RVRED ) in Klebsormidium crenulatum and Zygnema sp. under different preset relative air humidities (RH). A new chamber allows monitoring RH during light microscopic observation of the desiccation process. The RHs were set in the range of ∼4 % to ∼95% in 10 steps. RVRED caused by the desiccation process was determined after full acclimation to the respective RHs. In K. crenulatum, RVRED (mean ± SE) was 46.4 ± 1.9%, in Zygnema sp. RVRED was only 34.3 ± 2.4% at the highest RH (∼95%) tested. This indicates a more pronounced water loss at higher RHs in K. crenulatum versus Zygnema sp. By contrast, at the lowest RH (∼4%) tested, RVRED ranged from 75.9 ± 2.7% in K. crenulatum to 83.9 ± 2.2% in Zygnema sp. The final volume reduction is therefore more drastic in Zygnema sp. These data contribute to our understanding of the desiccation process in streptophytic green algae, which are considered the closest ancestors of land plants.

  11. C-Myc regulates substrate oxidation patterns during early pressure-overload hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena R. [Seattle Children' s Research Inst., Seattle, WA (United States); Smith, Lincoln [Seattle Children' s Hospital, Seattle, WA (United States); Kajimoto, Masaki [Seattle Children' s Research Inst., Seattle, WA (United States); Bruce, Margaret [Seattle Children' s Research Inst., Seattle, WA (United States); Isern, Nancy G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL); Xu, Chun [Seattle Children' s Research Inst., Seattle, WA (United States); Portman, Michael A. [Seattle Children' s Research Inst., Seattle, WA (United States); Olson, Aaron [Seattle Children' s Research Inst., Seattle, WA (United States)

    2013-11-26

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of glycolytic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected FVB mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketones and unlabeled glucose and insulin. Western blots were used to evaluate metabolic enzymes. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (presumably glucose) contribution. Myc inactivation (MycKO-TAC) inhibited these metabolic changes. Hypertrophy in general increased protein levels of PKM2; however this change was not linked to Myc status. Protein post-translation modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. In conclusion, Myc regulates substrate utilization during early pressure overload hypertrophy. Our results show that the metabolic switch during hypertrophy is not necessary to maintain cardiac function, but it may be important mechanism to promote cardiomyocyte growth. Myc also regulates protein O-GlcNAcylation during hypertrophy.

  12. Rat liver antioxidant response to iron and copper overloads.

    Science.gov (United States)

    Musacco-Sebio, Rosario; Saporito-Magriñá, Christian; Semprine, Jimena; Torti, Horacio; Ferrarotti, Nidia; Castro-Parodi, Mauricio; Damiano, Alicia; Boveris, Alberto; Repetto, Marisa G

    2014-08-01

    The rat liver antioxidant response to Fe and Cu overloads (0-60mg/kg) was studied. Dose- and time-responses were determined and summarized by t1/2 and C50, the time and the liver metal content for half maximal oxidative responses. Liver GSH (reduced glutathione) and GSSG (glutathione disulfide) were determined. The GSH content and the GSH/GSSG ratio markedly decreased after Fe (58-66%) and Cu (79-81%) loads, with t1/2 of 4.0 and 2.0h. The C50 were in a similar range for all the indicators (110-124μgFe/g and 40-50μgCu/g) and suggest a unique free-radical mediated process. Hydrophilic antioxidants markedly decreased after Fe and Cu (60-75%; t1/2: 4.5 and 4.0h). Lipophilic antioxidants were also decreased (30-92%; t1/2: 7.0 and 5.5h) after Fe and Cu. Superoxide dismutase (SOD) activities (Cu,Zn-SOD and Mn-SOD) and protein expression were adaptively increased after metal overloads (Cu,Zn-SOD: t1/2: 8-8.5h and Mn-SOD: t1/2: 8.5-8.0h). Catalase activity was increased after Fe (65%; t1/2: 8.5h) and decreased after Cu (26%; t1/2: 8.0h), whereas catalase expression was increased after Fe and decreased after Cu overloads. Glutathione peroxidase activity decreased after metal loads by 22-39% with a t1/2 of 4.5h and with unchanged protein expression. GSH is the main and fastest responder antioxidant in Fe and Cu overloads. The results indicate that thiol (SH) content and antioxidant enzyme activities are central to the antioxidant defense in the oxidative stress and damage after Fe and Cu overloads.

  13. The importance of trabecular hypertrophy in right ventricular adaptation to chronic pressure overload.

    Science.gov (United States)

    van de Veerdonk, Mariëlle C; Dusoswa, Sophie A; Marcus, J Tim; Bogaard, Harm-Jan; Spruijt, Onno; Kind, Taco; Westerhof, Nico; Vonk-Noordegraaf, Anton

    2014-02-01

    To assess the contribution of right ventricular (RV) trabeculae and papillary muscles (TPM) to RV mass and volumes in controls and patients with pulmonary arterial hypertension (PAH). Furthermore, to evaluate whether TPM shows a similar response as the RV free wall (RVFW) to changes in pulmonary artery pressure (PAP) during follow-up. 50 patients underwent cardiac magnetic resonance (CMR) and right heart catheterization at baseline and after one-year follow-up. Furthermore 20 controls underwent CMR. RV masses were assessed with and without TPM. TPM constituted a larger proportion of total RV mass and RV end-diastolic volume (RVEDV) in PAH than in controls (Mass: 35 ± 7 vs. 25 ± 5 %; p TPM mass was related to the RVFW mass in patients (baseline: R = 0.65; p TPM from the assessment resulted in altered RV mass, volumes and function than when included (all p TPM mass (β = 0.44; p = 0.004) but not the changes in RVFW mass (p = 0.095) were independently related to changes in PAP during follow-up. RV TPM showed a larger contribution to total RV mass in PAH (~35 %) compared to controls (~25 %). Inclusion of TPM in the analyses significantly influenced the magnitude of the RV volumes and mass. Furthermore, TPM mass was stronger related to changes in PAP than RVFW mass. Our results implicate that TPM are important contributors to RV adaptation during pressure overload and cannot be neglected from the RV assessment.

  14. Application of Nuclear Volume Measurements to Comprehend the Cell Cycle in Root-Knot Nematode-Induced Giant Cells

    Directory of Open Access Journals (Sweden)

    José Dijair Antonino de Souza Junior

    2017-06-01

    Full Text Available Root-knot nematodes induce galls that contain giant-feeding cells harboring multiple enlarged nuclei within the roots of host plants. It is recognized that the cell cycle plays an essential role in the set-up of a peculiar nuclear organization that seemingly steers nematode feeding site induction and development. Functional studies of a large set of cell cycle genes in transgenic lines of the model host Arabidopsis thaliana have contributed to better understand the role of the cell cycle components and their implication in the establishment of functional galls. Mitotic activity mainly occurs during the initial stages of gall development and is followed by an intense endoreduplication phase imperative to produce giant-feeding cells, essential to form vigorous galls. Transgenic lines overexpressing particular cell cycle genes can provoke severe nuclei phenotype changes mainly at later stages of feeding site development. This can result in chaotic nuclear phenotypes affecting their volume. These aberrant nuclear organizations are hampering gall development and nematode maturation. Herein we report on two nuclear volume assessment methods which provide information on the complex changes occurring in nuclei during giant cell development. Although we observed that the data obtained with AMIRA tend to be more detailed than Volumest (Image J, both approaches proved to be highly versatile, allowing to access 3D morphological changes in nuclei of complex tissues and organs. The protocol presented here is based on standard confocal optical sectioning and 3-D image analysis and can be applied to study any volume and shape of cellular organelles in various complex biological specimens. Our results suggest that an increase in giant cell nuclear volume is not solely linked to increasing ploidy levels, but might result from the accumulation of mitotic defects.

  15. 钙通道阻滞剂改善内质网应激抑制压力过负荷高血压大鼠的心肌重构%Protective effect of calcium channel blocker on hypertensive rat myocardial remodeling of pressure overload induced by endoplasmic reticulum stress

    Institute of Scientific and Technical Information of China (English)

    槐勇; 赵连友; 李炜; 郑强荪; 刘静; 郭丽; 丁璐

    2012-01-01

    . Expressions of CRT and caspase-12 in rat cardiac myocytes were examined by immunohistochemistry, and cardiac myocyte apoptosis was detected by TUNEL fluorescent staining. RESULTS: Compared with those in control group, MAP (mean arterial pressure) , IVST (interventricular septal thickness) , LVPWT (left ventricular posterior wall thickness) , LVWI (left ventricular weight index) , expressions of CRT and caspase-12 in cardiac myocytes, and incidence of cardiac myocyte apoptosis remarkably increased in TAC group ( P < 0. 01 ). Compared with those in TAC group, MAP, IVST, LVPWT, LVW1 and incidence of cardiac myocyte apoptosis in TAC + lacidipine group decreased significantly, whereas expressions of CRT and caspase-12 in cardiac myocytes were significantly downregulated ( P < 0. 05 ). CONCLUSION; The endoplasmic reticulum stress may be involved in the process of myocardium remodeling caused by pressure overload induced-hypertension. Lacidipine may exert a protective effect on the heart by ameliorating the endoplasmic reticulum stress via downregulating the expression of CRT and caspase-12 and decreasing the incidence of cardiac myocyte apoptosis.

  16. Thermal Aging Characteristics of Insulation Paper in Mineral Oil under Overloaded Operating Transformers

    Science.gov (United States)

    Miyagi, Katsunori; Oe, Etsuo; Yamagata, Naoki; Miyahara, Hideyuki

    A sudden capacity increase in demand during the summer peak, or in contingencies such as malfunctioning transformers, may cause overload for normal transformers. In this paper, on the basis of examples of overloaded transformer operation in distributing substations, thermal aging testing in oil was carried out under various overload patterns, such as short time overload and long time overload, but with the winding insulation paper's life loss kept constant. From the results, various characteristics such as mean degree of polymerization and productions of furfural and (CO2+CO), and their effects on the life loss of the insulation paper were obtained.

  17. Osmosis-induced water uptake by Eurobitum bituminized radioactive waste and pressure development in constant volume conditions

    Science.gov (United States)

    Mariën, A.; Mokni, N.; Valcke, E.; Olivella, S.; Smets, S.; Li, X.

    2013-01-01

    The chemo-hydro-mechanical (CHM) interaction between swelling Eurobitum radioactive bituminized waste (BW) and Boom Clay is investigated to assess the feasibility of geological disposal for the long-term management of this waste. These so-called compatibility studies include laboratory water uptake tests at the Belgian Nuclear Research Center SCK•CEN, and the development of a coupled CHM formulation for Eurobitum by the International Center for Numerical Methods and Engineering (CIMNE, Polytechnical University of Cataluña, Spain). In the water uptake tests, the osmosis-induced swelling, pressure increase and NaNO3 leaching of small cylindrical BW samples (diameter 38 mm, height 10 mm) is studied under constant total stress conditions and nearly constant volume conditions; the actual geological disposal conditions should be intermediate between these extremes. Two nearly constant volume tests were stopped after 1036 and 1555 days to characterize the morphology of the hydrated BW samples and to visualize the hydrated part with microfocus X-ray Computer Tomography (μCT) and Environmental Scanning Electron Microscopy (ESEM). In parallel, a coupled CHM formulation is developed that describes chemically and hydraulically coupled flow processes in porous materials with salt crystals, and that incorporates a porosity dependent membrane efficiency, permeability and diffusivity. When Eurobitum BW is hydrated in (nearly) constant volume conditions, the osmosis-induced water uptake results in an increasing pressure to values that can be (in theory) as high as 42.8 MPa, being the osmotic pressure of a saturated NaNO3 solution. After about four years of hydration in nearly constant volume water uptake tests, pressures up to 20 MPa are measured. During this hydration period only the outer layers with a thickness of 1-2 mm were hydrated (as derived from μCT and ESEM analyses), and only about 10-20% of the initial NaNO3 content was released by the samples. In the studied test

  18. RADIATION DOSE–VOLUME EFFECTS IN RADIATION-INDUCED RECTAL INJURY

    Science.gov (United States)

    Michalski, Jeff M.; Gay, Hiram; Jackson, Andrew; Tucker, Susan L.; Deasy, Joseph O.

    2010-01-01

    The available dose/volume/outcome data for rectal injury were reviewed. The volume of rectum receiving ≥60Gy is consistently associated with the risk of Grade ≥2 rectal toxicity or rectal bleeding. Parameters for the Lyman-Kutcher-Burman normal tissue complication probability model from four clinical series are remarkably consistent, suggesting that high doses are predominant in determining the risk of toxicity. The best overall estimates (95% confidence interval) of the Lyman-Kutcher-Burman model parameters are n = 0.09 (0.04–0.14); m = 0.13 (0.10–0.17); and TD50 = 76.9 (73.7–80.1) Gy. Most of the models of late radiation toxicity come from three-dimensional conformal radiotherapy dose-escalation studies of early-stage prostate cancer. It is possible that intensity-modulated radiotherapy or proton beam dose distributions require modification of these models because of the inherent differences in low and intermediate dose distributions. PMID:20171506

  19. Fluid overload in infants following congenital heart surgery.

    Science.gov (United States)

    Hazle, Matthew A; Gajarski, Robert J; Yu, Sunkyung; Donohue, Janet; Blatt, Neal B

    2013-01-01

    To describe postoperative fluid overload patterns and correlate degree of fluid overload with intensive care morbidity and mortality in infants undergoing congenital heart surgery. Prospective, observational study. Fluid overload (%) was calculated by two methods: 1) (Total fluid in - Total fluid out)/(Preoperative weight) × 100; and 2) (Current weight - Preoperative weight)/(Preoperative weight) × 100. Composite poor outcome included: need for renal replacement therapy, upper quartile time to extubation or intensive care length of stay (> 6.5 and 9.9 days, respectively), or death ≤ 30 days after surgery. University hospital pediatric cardiac ICU. Forty-nine infants heart surgery with cardiopulmonary bypass during the period of July 2009 to July 2010. None. Patients had a median age of 53 days (21 neonates) and mean weight of 4.5 ± 1.3 kg. Forty-two patients (86%) developed acute kidney injury by meeting at least Acute Kidney Injury Network and Kidney Disease Improving Global Outcomes stage 1 criteria (serum creatinine rise of 50% or ≥ 0.3mg/dL). The patients with adverse outcomes (n = 17, 35%) were younger (7 [5 - 10] vs. 98 [33 - 150] days, p = 0.001), had lower preoperative weight (3.7 ± 0.7 vs. 4.9 ± 1.4 kg, p = 0.0002), higher postoperative mean peak serum creatinine (SCr) (0.9 ± 0.3 vs. 0.6 ± 0.3mg/dL, p = 0.005), and higher mean maximum fluid overload by both method 1 (12% ± 10% vs. 6% ± 4%, p = 0.03) and method 2 (24% ± 15% vs. 14% ± 8%, p = 0.02). Predictors of a poor outcome from multivariate analyses were cardiopulmonary bypass time, use of circulatory arrest, and increased vasoactive medication requirements postoperatively. Early postoperative fluid overload is associated with suboptimal outcomes in infants following cardiac surgery. Because the majority of patients developed kidney injury without needing renal replacement therapy, fluid overload may be an important risk factor for adverse outcomes with all degrees of acute kidney injury.

  20. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: chen919085@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)

    2015-09-01

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  1. Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways

    Directory of Open Access Journals (Sweden)

    Dan Bao

    2015-08-01

    Full Text Available Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnTR92Q transgenic mice and thoracic aorta constriction (TAC-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy.

  2. Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways.

    Science.gov (United States)

    Bao, Dan; Lu, Dan; Liu, Ning; Dong, Wei; Lu, Ying-Dong; Qin, Chuan; Zhang, Lian-Feng

    2015-08-01

    Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS) function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnT(R92Q) transgenic mice and thoracic aorta constriction (TAC)-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK) pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy. © 2015. Published by The Company of Biologists Ltd.

  3. Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia.

    Science.gov (United States)

    Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita

    2017-01-01

    Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison

  4. Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload

    Science.gov (United States)

    Johnson, David Wayne; Arndt, Mary; O'Shea, Amanda; Watt, Rhonda; Hamilton, Jan; Vincent, Kaia

    2001-01-01

    Background Icodextrin is a high molecular weight, starch-derived glucose polymer, which is capable of inducing sustained ultrafiltration over prolonged (12–16 hour) peritoneal dialysis (PD) dwells. The aim of this study was to evaluate the ability of icodextrin to alleviate refractory, symptomatic fluid overload and prolong technique survival in PD patients. Methods A prospective, open-label, pre-test/post-test study was conducted in 17 PD patients (8 females/9 males, mean age 56.8 ± 2.9 years) who were on the verge of being transferred to haemodialysis because of symptomatic fluid retention that was refractory to fluid restriction, loop diuretic therapy, hypertonic glucose exchanges and dwell time optimisation. One icodextrin exchange (2.5 L 7.5%, 12-hour dwell) was substituted for a long-dwell glucose exchange each day. Results Icodextrin significantly increased peritoneal ultrafiltration (885 ± 210 ml to 1454 ± 215 ml, p icodextrin was only significantly predicted by baseline net daily peritoneal ultrafiltration (adjusted HR 2.52, 95% CI 1.13–5.62, p Icodextrin significantly improved peritoneal ultrafiltration and extended technique survival in PD patients with symptomatic fluid overload, especially those who had substantially impaired peritoneal ultrafiltration. PMID:11737871

  5. Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload

    Directory of Open Access Journals (Sweden)

    Watt Rhonda

    2001-12-01

    Full Text Available Abstract Background Icodextrin is a high molecular weight, starch-derived glucose polymer, which is capable of inducing sustained ultrafiltration over prolonged (12–16 hour peritoneal dialysis (PD dwells. The aim of this study was to evaluate the ability of icodextrin to alleviate refractory, symptomatic fluid overload and prolong technique survival in PD patients. Methods A prospective, open-label, pre-test/post-test study was conducted in 17 PD patients (8 females/9 males, mean age 56.8 ± 2.9 years who were on the verge of being transferred to haemodialysis because of symptomatic fluid retention that was refractory to fluid restriction, loop diuretic therapy, hypertonic glucose exchanges and dwell time optimisation. One icodextrin exchange (2.5 L 7.5%, 12-hour dwell was substituted for a long-dwell glucose exchange each day. Results Icodextrin significantly increased peritoneal ultrafiltration (885 ± 210 ml to 1454 ± 215 ml, p Conclusions Icodextrin significantly improved peritoneal ultrafiltration and extended technique survival in PD patients with symptomatic fluid overload, especially those who had substantially impaired peritoneal ultrafiltration.

  6. Overloading ion-exchange membranes as a purification step for monoclonal antibodies.

    Science.gov (United States)

    Brown, Arick; Bill, Jerome; Tully, Timothy; Radhamohan, Asha; Dowd, Chris

    2010-06-11

    The present study examined the overloading of ion-exchange membrane adsorbers, a form of frontal chromatography, as the final purification step in the production of mAbs (monoclonal antibodies) produced from CHO (Chinese-hamster ovary) cells. Preferential binding of impurities over antibody product was exploited using commercially available cation- and anion-exchange membranes. Three different antibody feedstreams previously purified over Protein A and ion-exchange column chromatography were tested. Feedstream conductivity and pH were adjusted to induce product and impurity adsorption. Membranes were then overloaded in a normal flow mode, resulting in retention of impurities and breakthrough of purified antibody. Although some amount of the product also binds to the membranes (usually or =99% were achieved by marginalizing the losses, typically by loading more than 3 kg mAb/l membrane. Analyses of the purified pools show consistent removal of impurities despite strong mAb-ligand interactions and high membrane loadings. The clearance of host cell proteins was affected by pH and conductivity, but was unaffected by flow rate, membrane properties or scale. The importance of the present study lies in our demonstration of an alternative use of ion-exchange membranes for fast, effective and high yielding purification of mAbs.

  7. Finite volume analysis of temperature effects induced by active MRI implants with cylindrical symmetry: 1. Properly working devices

    Directory of Open Access Journals (Sweden)

    Schnorr Jörg

    2005-04-01

    Full Text Available Abstract Background Active Magnetic Resonance Imaging implants are constructed as resonators tuned to the Larmor frequency of a magnetic resonance system with a specific field strength. The resonating circuit may be embedded into or added to the normal metallic implant structure. The resonators build inductively coupled wireless transmit and receive coils and can amplify the signal, normally decreased by eddy currents, inside metallic structures without affecting the rest of the spin ensemble. During magnetic resonance imaging the resonators generate heat, which is additional to the usual one described by the specific absorption rate. This induces temperature increases of the tissue around the circuit paths and inside the lumen of an active implant and may negatively influence patient safety. Methods This investigation provides an overview of the supplementary power absorbed by active implants with a cylindrical geometry, corresponding to vessel implants such as stents, stent grafts or vena cava filters. The knowledge of the overall absorbed power is used in a finite volume analysis to estimate temperature maps around different implant structures inside homogeneous tissue under worst-case assumptions. The "worst-case scenario" assumes thermal heat conduction without blood perfusion inside the tissue around the implant and mostly without any cooling due to blood flow inside vessels. Results The additional power loss of a resonator is proportional to the volume and the quality factor, as well as the field strength of the MRI system and the specific absorption rate of the applied sequence. For properly working devices the finite volume analysis showed only tolerable heating during MRI investigations in most cases. Only resonators transforming a few hundred mW into heat may reach temperature increases over 5 K. This requires resonators with volumes of several ten cubic centimeters, short inductor circuit paths with only a few 10 cm and a quality

  8. Mechanical overload protection of cutting unit in roadheader

    Energy Technology Data Exchange (ETDEWEB)

    Liu, G.; Huang, S. [Central Coal Mining Research Institute (China). Tangshau Branch

    1995-11-01

    When a roadheader is in operation, especially in semi-coal or rock cutting, the gearbox of the cutting unit is often subjected to the effect of sudden load and the peak load may be up to 4 times of the rated load. A mechanical overload protection device installed in the cutting unit is an effective way to protect the gear tooth. This paper evaluates the structural features and performances of the mechanical protection device of the gearbox system of the cutting unit of various roadheaders and presents a new safety pin flexible coupling for mechanical overload protection. This coupling has been successfully applied in a newly designed EBZ-90 roadheader. The safety pin flexible coupling combines both the functions of the elastic pillar pin coupling and safety pin protection. The safety parameter of the safety pin should be 10 to 12 times higher than the rated load. 2 refs., 3 figs.

  9. Hepcidin and Hfe in iron overload in beta-thalassemia.

    Science.gov (United States)

    Gardenghi, Sara; Ramos, Pedro; Follenzi, Antonia; Rao, Niva; Rachmilewitz, Eliezer A; Giardina, Patricia J; Grady, Robert W; Rivella, Stefano

    2010-08-01

    Hepcidin (HAMP) negatively regulates iron absorption, degrading the iron exporter ferroportin at the level of enterocytes and macrophages. We showed that mice with beta-thalassemia intermedia (th3/+) have increased anemia and iron overload. However, their hepcidin expression is relatively low compared to their iron burden. We also showed that the iron metabolism gene Hfe is down-regulated in concert with hepcidin in th3/+ mice. These observations suggest that low hepcidin levels are responsible for abnormal iron absorption in thalassemic mice and that down-regulation of Hfe might be involved in the pathway that controls hepcidin synthesis in beta-thalassemia. Therefore, these studies suggest that increasing hepcidin and/or Hfe expression could be a strategy to reduces iron overload in these animals. The goal of this paper is to review recent findings that correlate hepcidin, Hfe, and iron metabolism in beta-thalassemia and to discuss potential novel therapeutic approaches based on these recent discoveries.

  10. Hepcidin and Hfe in iron overload in β-thalassemia

    Science.gov (United States)

    Gardenghi, Sara; Ramos, Pedro; Follenzi, Antonia; Rao, Niva; Rachmilewitz, Eliezer A.; Giardina, Patricia J.; Grady, Robert W.; Rivella, Stefano

    2013-01-01

    Hepcidin (HAMP) negatively regulates iron absorption, degrading the iron exporter ferroportin at the level of enterocytes and macrophages. We showed that mice with β-thalassemia intermedia (th3/+) have increased anemia and iron overload. However, their hepcidin expression is relatively low compared to their iron burden. We also showed that the iron metabolism gene Hfe is down-regulated in concert with hepcidin in th3/+ mice. These observations suggest that low hepcidin levels are responsible for abnormal iron absorption in thalassemic mice and that down-regulation of Hfe might be involved in the pathway that controls hepcidin synthesis in β-thalassemia. Therefore, these studies suggest that increasing hepcidin and/or Hfe expression could be a strategy to reduces iron overload in these animals. The goal of this paper is to review recent findings that correlate hepcidin, Hfe, and iron metabolism in β-thalassemia and to discuss potential novel therapeutic approaches based on these recent discoveries. PMID:20712796

  11. Deferiprone for the treatment of transfusional iron overload in thalassemia.

    Science.gov (United States)

    Belmont, Ami; Kwiatkowski, Janet L

    2017-06-01

    Transfusional iron overload can lead to hepatic fibrosis, arrhythmias and congestive heart failure and a number of endocrinopathies. Deferiprone is an oral iron chelator approved for use in the United States as a second line agent for the treatment of transfusional iron overload in patients with thalassemia. Areas covered: This article will review the data regarding the efficacy of deferiprone for iron chelation and prevention and reversal of iron related complications, the drug's adverse effect profile, and the use of this drug in combination regimens. Expert commentary: Extensive data support that deferiprone is particularly efficacious at cardiac iron removal and therefore, a chelator regimen that contains deferiprone is generally recommended when there is significant cardiac iron loading and/or in the setting of iron-related cardiac disease. The most concerning side effects of deferiprone are agranulocytosis and milder forms of neutropenia, which require appropriate monitoring and patient/provider education.

  12. Epidemiology and diagnostic testing for hemochromatosis and iron overload.

    Science.gov (United States)

    Adams, P C

    2015-05-01

    Hemochromatosis is the most common genetic disease in northern European populations. Body iron stores progressively increase in most patients, which can lead to cirrhosis of the liver, hepatocellular carcinoma, heart failure, arthritis, and pigmentation. Simple blood tests such as the serum ferritin and transferrin saturation are useful to suggest the diagnosis which can be confirmed in most cases with a simple genetic test for the C282Y mutation of the HFE gene. However, these blood tests are often misinterpreted and there are rare patients with iron overload without HFE mutations. A diagnostic approach is presented based on a large referral practice and a population-based study (HEIRS) which screened for iron overload in 101,168 participants.

  13. Culinary plants and their potential impact on metabolic overload.

    Science.gov (United States)

    Kim, Ji Yeon; Kwon, Oran

    2011-07-01

    Contemporary human behavior has led a large proportion of the population to metabolic overload and obesity. Postprandial hyperlipidemia and hyperglycemia evoke redox imbalance in the short term and lead to complex chronic disease in the long term with repeated occurrence. Complex diseases are best prevented with complex components of plants; thus, current nutrition research has begun to focus on the development of plant-based functional foods and dietary supplements for health and well-being. Furthermore, given the wide range of species, parts, and secondary metabolites, culinary plants can contribute significant variety and complexity to the human diet. Although understanding the health benefits of culinary plants has been one of the great challenges in nutritional science due to their inherent complexity, it is an advantageous pursuit. This review will address the challenges and opportunities relating to studies of the health benefits of culinary plants, with an emphasis on obesity attributed to metabolic overload. © 2011 New York Academy of Sciences.

  14. Information overload, retrieval strategies and Internet user empowerment

    OpenAIRE

    Carlson, Christopher N.

    2003-01-01

    Initial user benefits from search engine technology have been critically degraded over time by the rapid increase of Internet pages. Traditional retrieval strategies therefore yield increasingly poor results due to a dramatic increase in ballast in the results. Search engine users thus increasingly experience information overload. Technical approaches to dealing with this problem have caused an initial euphoria, yet have proven ineffective in solving the problem. Enhancement of user empow...

  15. Indecisiveness, Undesirability and Overload Revealed Through Rational Choice Deferral

    OpenAIRE

    Gerasimou, Georgios

    2015-01-01

    Three reasons why decision makers may defer choice are *indecisiveness* between various feasible options, *unattractiveness* of these options, and *choice overload*. This paper provides a choice-theoretic explanation for each of these phenomena by means of three deferral-permitting models of decision making that are driven by preference incompleteness, undesirability and complexity constraints, respectively. These models feature *rational* choice deferral in the sense that whenever the indivi...

  16. Intermittent hypoxia protects cerebral mitochondrial function from calcium overload.

    Science.gov (United States)

    Chen, Jian; Liao, Weigong; Gao, Wenxiang; Huang, Jian; Gao, Yuqi

    2013-12-01

    Hypoxia leads to Ca(2+) overload and results in mitochondrial uncoupling, decreased ATP synthesis, and neuronal death. Inhibition of mitochondrial Ca(2+) overload protects mitochondrial function after hypoxia. The present study was aimed to investigate the effect of intermittent hypoxia on mitochondrial function and mitochondrial tolerance to Ca(2+) overload. Wistar rats were divided into control and intermittent hypoxia (IH) groups. The IH group was subject to hypoxia for 4 h daily in a hypobaric cabin (5,000 m) for 7 days. Brain mitochondria were isolated on day 7 following hypoxia. The baseline mitochondrial functions, such as ST3, ST4, and respiratory control ratio (RCR = ST3/ST4), were measured using a Clark-type oxygen electrode. Mitochondrial adenine nucleotide concentrations were measured by HPLC. Mitochondrial membrane potential was determined by measuring rhodamine 123 (Rh-123) fluorescence in the absence and presence of high Ca(2+) concentration (0.1 M), which simulates Ca(2+) overload. Our results revealed that IH did not affect mitochondrial respiratory functions, but led to a reduction in AMP and an increase in ADP concentrations in mitochondria. Both control and IH groups demonstrated decreased mitochondrial membrane potential in the presence of high Ca(2+) (0.1 M), while the IH group showed a relative higher mitochondrial membrane potential. These results indicated that the neuroprotective effect of intermittent hypoxia was resulted partly from preserving mitochondrial membrane potential, and increasing mitochondrial tolerance to high calcium levels. The increased ADP and decreased AMP in mitochondria following intermittent hypoxia may be a mechanism underlying this protection.

  17. 2,3-Dihydroxybenzoic acid attenuates kanamycin-induced volume reduction in mouse utricular type I hair cells

    DEFF Research Database (Denmark)

    Severinsen, Stig Åvall; Kirkegaard, Mette; Nyengaard, Jens Randel

    2006-01-01

    The aminoglycoside kanamycin is a commonly used antibiotic, but unfortunately it is oto- and nephrotoxic in large doses. The negative effects are thought to be due to the formation of free radicals which is why strong antioxidants and iron chelators like 2,3-dihydroxybenzoic acid (DHB) are of great...... interest. This study estimates cellular quantitative changes in the utricular macula of mice following systemic treatment with kanamycin alone or in combination with DHB. The animals were injected with either saline, kanamycin or kanamycin+DHB for 15 days and perfusion fixed three weeks after last...... macula, hair cell type I and supporting cells decreased significantly in animals injected with kanamycin but not in animals co-treated with DHB. Hair and supporting cell numbers remained unchanged in all three groups. In conclusion, the kanamycin-induced volume reduction of type I hair cells...

  18. Formal Constraints on Memory Management for Composite Overloaded Operations

    Directory of Open Access Journals (Sweden)

    Damian W.I. Rouson

    2006-01-01

    Full Text Available The memory management rules for abstract data type calculus presented by Rouson, Morris & Xu [15] are recast as formal statements in the Object Constraint Language (OCL and applied to the design of a thermal energy equation solver. One set of constraints eliminates memory leaks observed in composite overloaded expressions with three current Fortran 95/2003 compilers. A second set of constraints ensures economical memory recycling. The constraints are preconditions, postconditions and invariants on overloaded operators and the objects they receive and return. It is demonstrated that systematic run-time assertion checking inspired by the formal constraints facilitated the pinpointing of an exceptionally hard-to-reproduce compiler bug. It is further demonstrated that the interplay between OCL's modeling capabilities and Fortran's programming capabilities led to a conceptual breakthrough that greatly improved the readability of our code by facilitating operator overloading. The advantages and disadvantages of our memory management rules are discussed in light of other published solutions [11,19]. Finally, it is demonstrated that the run-time assertion checking has a negligible impact on performance.

  19. Influence, information overload, and information technology in health care.

    Science.gov (United States)

    Rebitzer, James B; Rege, Mari; Shepard, Christopher

    2008-01-01

    We investigate whether information technology (IT) can help physicians more efficiently acquire new knowledge in a clinical environment characterized by information overload. We combine analysis of data from a randomized trial with a theoretical model of the influence that IT has on the acquisition of new medical knowledge. Although the theoretical framework we develop is conventionally microeconomic, the model highlights the non-market and non-pecuniary influence activities that have been emphasized in the sociological literature on technology diffusion. We report three findings. First, empirical evidence and theoretical reasoning suggests that computer-based decision support will speed the diffusion of new medical knowledge when physicians are coping with information overload. Second, spillover effects will likely lead to "underinvestment" in this decision support technology. Third, alternative financing strategies common to new IT, such as the use of marketing dollars to pay for the decision support systems, may lead to undesirable outcomes if physician information overload is sufficiently severe and if there is significant ambiguity in how best to respond to the clinical issues identified by the computer. This is the first paper to analyze empirically and theoretically how computer-based decision support influences the acquisition of new knowledge by physicians.

  20. Natural history and information overload: The case of Linnaeus.

    Science.gov (United States)

    Müller-Wille, Staffan; Charmantier, Isabelle

    2012-03-01

    Natural History can be seen as a discipline paradigmatically engaged in 'data-driven research.' Historians of early modern science have begun to emphasize its crucial role in the Scientific Revolution, and some observers of present day genomics see it as engaged in a return to natural history practices. A key concept that was developed to understand the dynamics of early modern natural history is that of 'information overload.' Taxonomic systems, rules of nomenclature, and technical terminologies were developed in botany and zoology to catch up with the ever increasing amount of information on hitherto unknown plant and animal species. In our contribution, we want to expand on this concept. After all, the same people who complain about information overload are usually the ones who contribute to it most significantly. In order to understand this complex relationship, we will turn to the annotation practices of the Swedish naturalist Carl Linnaeus (1707-1778). The very tools that Linnaeus developed to contain and reduce information overload, as we aim to demonstrate, facilitated a veritable information explosion that led to the emergence of a new research object in botany: the so-called 'natural' system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Deferasirox, an oral chelator in the treatment of iron overload

    Directory of Open Access Journals (Sweden)

    I. Portioli

    2013-05-01

    Full Text Available BACKGROUND Deferasirox is a once-daily oral iron chelator developed for treating iron overload complicating long-term transfusion therapy in patients with diseases such as beta-thalassemia and myelodysplastic syndromes. Iron overload can damage the liver, pancreas and the heart. Deferoxamine, the only other drug approved for iron chelation, can prevent these effects but requires parenteral administration. Deferasirox has been approved after a one-year, open-label trial in patients ≥ 2 years old with beta-thalassemia and transfusional emosiderosis randomized to once-daily oral 5, 10, 20, 30 mg/kg/day in comparison of subcutaneous deferoxamine 20-60 mg/mg/kg/day x 5/week. CONCLUSIONS Deferasirox 20-30 mg/kg/day produced reductions in liver iron concentration (LIC similar to those with deferoxamine. Adverse effect of deferasirox (increases of serum creatinine and aminotransferases, including the gastrointestinal ones, are similar but more frequent than those occurring with deferoxamine. Information is lacking on the effects of deferasirox on cardiac iron and cardiac dysfunction which is the most serious complication of transfusional iron overload.

  2. Arterial pressure allows monitoring the changes in cardiac output induced by volume expansion but not by norepinephrine.

    Science.gov (United States)

    Monnet, Xavier; Letierce, Alexia; Hamzaoui, Olfa; Chemla, Denis; Anguel, Nadia; Osman, David; Richard, Christian; Teboul, Jean-Louis

    2011-06-01

    To evaluate to which extent the systemic arterial pulse pressure could be used as a surrogate of cardiac output for assessing the effects of a fluid challenge and of norepinephrine. Observational study. Medical intensive care unit. Patients with an acute circulatory failure who received a fluid challenge (228 patients, group 1) or in whom norepinephrine was introduced or increased (145 patients, group 2). We measured the systolic, diastolic, and mean arterial pressure, pulse pressure, and the transpulmonary thermodilution cardiac output before and after the therapeutic interventions. In group 1, the fluid challenge significantly increased cardiac output by 24% ± 25%. It significantly increased cardiac output by ≥15% (+35% ± 27%) in 142 patients ("responders"). The fluid-induced changes in cardiac output were correlated with the changes in pulse pressure (r = .56, p arterial pressure (r = .55, p arterial pressure (r = .37, p arterial pressure (r = .52, p pressure were significantly related to changes in stroke volume (multiple r = .52) and to age (r = .12). A fluid-induced increase in pulse pressure of ≥17% allowed detecting a fluid-induced increase in cardiac output of ≥15% with a sensitivity of 65[56-72]% and a specificity of 85[76-92]%. The area under the receiver operating characteristic curves for the fluid-induced changes in mean arterial pressure and in diastolic arterial pressure was significantly lower than for pulse pressure. In group 2, the introduction/increase of norepinephrine significantly increased cardiac output by 14% ± 18%. The changes in cardiac output induced by the introduction/increase in the dose of norepinephrine were correlated with the changes in pulse pressure and systolic arterial pressure (r = .21 and .29, respectively, p = .001) but to a significantly lesser extent than in group 1. Pulse pressure and systolic arterial pressure could be used for detecting the fluid-induced changes in cardiac output, in spite of a significant

  3. Plasma volume substitution does not inhibit plasma noradrenaline and muscle nerve sympathetic responses to insulin-induced hypoglycaemia in healthy humans

    DEFF Research Database (Denmark)

    Frandsen, Henrik Lund; Berne, C; Fagius, J;

    1989-01-01

    underly the sympathetic activation. To study the effect of prevention of plasma volume reduction during hypoglycaemia, saline containing albumin was infused intravenously in healthy adult volunteers during hypoglycaemia. Hypoglycaemia was induced by an intravenous injection of soluble insulin in a dose...... of 0.15 IU/kg body weight. Peripheral venous plasma noradrenaline concentrations were identical in experiments without and with plasma volume substitution. Muscle nerve sympathetic activity increased to the same extent during hypoglycaemia with and without plasma volume substitution. It is concluded...

  4. Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

    Science.gov (United States)

    Koide, M.; Hamawaki, M.; Narishige, T.; Sato, H.; Nemoto, S.; DeFreyte, G.; Zile, M. R.; Cooper G, I. V.; Carabello, B. A.

    2000-01-01

    BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

  5. Iron overload patients with unknown etiology from national survey in Japan.

    Science.gov (United States)

    Ikuta, Katsuya; Hatayama, Mayumi; Addo, Lynda; Toki, Yasumichi; Sasaki, Katsunori; Tatsumi, Yasuaki; Hattori, Ai; Kato, Ayako; Kato, Koichi; Hayashi, Hisao; Suzuki, Takahiro; Kobune, Masayoshi; Tsutsui, Miyuki; Gotoh, Akihiko; Aota, Yasuo; Matsuura, Motoo; Hamada, Yuzuru; Tokuda, Takahiro; Komatsu, Norio; Kohgo, Yutaka

    2017-03-01

    Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.

  6. A longitudinal study of stress-induced hippocampal volume changes in mice that are susceptible or resilient to chronic social defeat.

    Science.gov (United States)

    Tse, Yiu Chung; Montoya, Ixchel; Wong, Alice S; Mathieu, Axel; Lissemore, Jennifer; Lagace, Diane C; Wong, Tak Pan

    2014-09-01

    Hippocampal shrinkage is a commonly found neuroanatomical change in stress-related mood disorders such as depression and post-traumatic stress disorders (PTSD). Since the onset and severity of these disorders have been found to be closely related to stressful life events, and as stress alone has been shown to reduce hippocampal volume in animal studies, vulnerability to mood disorders may be related to a susceptibility to stress-induced hippocampal shrinkage. However, a smaller hippocampal volume before stress exposure has also been suggested to confer vulnerability of stressed individuals to PTSD or depression. In this study, we examined the contribution of either innate hippocampal volume differences or hippocampal susceptibility to stress-induced shrinkage to the formation of stress-related psychopathology using longitudinal MRI measurements of hippocampal volume in inbred C57 mice before and after chronic social defeat stress. We found that only half of the stressed C57 mice were susceptible to stress and developed psychopathological behaviors such as social avoidance. The other half was resilient to stress and exhibited no social avoidance. Before exposure to stress, we observed a positive correlation between hippocampal volume and social avoidance. After chronic social defeat stress, we found significant increases in left hippocampal volume in resilient and nonstressed control mice. Intriguingly, this increase in hippocampal volume was not found in susceptible mice, suggesting an arrestment of hippocampal growth in these mice. Our findings suggest that both a susceptibility to stress-induced hippocampal volume changes and a larger hippocampus before stress exposure confer vulnerability to psychopathology after chronic stress. © 2014 Wiley Periodicals, Inc.

  7. Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.

    LENUS (Irish Health Repository)

    Frodl, T

    2012-01-01

    Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and\\/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.

  8. Wind induces variations in spider web geometry and sticky spiral droplet volume.

    Science.gov (United States)

    Wu, Chao-Chia; Blamires, Sean J; Wu, Chung-Lin; Tso, I-Min

    2013-09-01

    Trap building by animals is rare because it comes at a substantial cost. Using materials with properties that vary across environments maintains trap functionality. The sticky spiral silks of spider orb webs are used to catch flying prey. Web geometry, accompanied by compensatory changes in silk properties, may change across environments to sustain web functionality. We exposed the spider Cyclosa mulmeinensis to wind to test whether wind-induced changes in web geometry are accompanied by changes in aggregate silk droplet morphology, axial thread width or spiral stickiness. We compared: (i) web catching area, (ii) length of total silks, (iii) mesh height, (iv) number of radii, (v) aggregate droplet morphology and (vi) spiral thread stickiness, between webs made by spiders exposed to wind and those made by spiders not exposed to wind. We interpreted co-variation in droplet morphology or spiral stickiness with web capture area, mesh height or spiral length as the silk properties functionally compensating for changes in web geometry to reduce wind drag. Wind-exposed C. mulmeinensis built webs with smaller capture areas, shorter capture spiral lengths and more widely spaced capture spirals, resulting in the expenditure of less silk. Individuals that were exposed to wind also deposited larger droplets of sticky silk but the stickiness of the spiral threads remained unchanged. The larger droplets may be a product of a greater investment in water, or low molecular weight compounds facilitating atmospheric water uptake. Either way, droplet dehydration in wind is likely to be minimized.

  9. Effect of band-overload on fatigue crack growth rate of HSLA steel

    Science.gov (United States)

    Abhinay, S. V.; Tenduwe, Om Prakash; Kumar, Ajit; Dutta, K.; Verma, B. B.; Ray, P. K.

    2015-02-01

    Fatigue crack growth behavior is important parameter of structural materials. This parameters can be used to predict their life, service reliability and operational safety in different conditions. The material used in this investigation is an HSLA steel. In this investigation effect of single overload and band-overload on fatigue crack growth of same steel are studied using compact tension (CT) specimens under mode-I condition and R=0.3. It is observed that overload and band-overload applications resulted retardation on the fatigue crack growth rate in most of the cases. It is also noticed that maximum retardation took place on application of seven successive overload cycles. Application of ten and more overload cycles caused no crack growth retardation.

  10. EFFECT OF OVERLOAD ON CRACK GROWTH IN FIBER REINFORCED METAL LAMINATES

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    This paper is concerned with fatigue behavior of glass fiber reinforced aluminium laminates (GLARE) under overload fatigue loading. The effect of single overload on the crack growth rates in GLARE was investigated, and the mechanism of the retardation of crack growth determined. Crack growth retardation by overload was observed in GLARE, but much smaller than monolithic metals. The retardation of crack growth in GLARE is only controlled by the effective stress intensity factor experienced by the constituent metals at crack tips.

  11. Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains

    Directory of Open Access Journals (Sweden)

    Agarwal Anupam

    2005-12-01

    Full Text Available Abstract Background Despite multiple causes, Chronic Kidney Disease is commonly associated with proteinuria. A previous study on Non Obese Diabetic mice (NOD, which spontaneously develop type 1 diabetes, described histological and gene expression changes incurred by diabetes in the kidney. Because proteinuria is coincident to diabetes, the effects of proteinuria are difficult to distinguish from those of other factors such as hyperglycemia. Proteinuria can nevertheless be induced in mice by peritoneal injection of Bovine Serum Albumin (BSA. To gain more information on the specific effects of proteinuria, this study addresses renal changes in diabetes resistant NOD-related mouse strains (NON and NOD.B10 that were made to develop proteinuria by BSA overload. Methods Proteinuria was induced by protein overload on NON and NOD.B10 mouse strains and histology and microarray technology were used to follow the kidney response. The effects of proteinuria were assessed and subsequently compared to changes that were observed in a prior study on NOD diabetic nephropathy. Results Overload treatment significantly modified the renal phenotype and out of 5760 clones screened, 21 and 7 kidney transcripts were respectively altered in the NON and NOD.B10. Upregulated transcripts encoded signal transduction genes, as well as markers for inflammation (Calmodulin kinase beta. Down-regulated transcripts included FKBP52 which was also down-regulated in diabetic NOD kidney. Comparison of transcripts altered by proteinuria to those altered by diabetes identified mannosidase 2 alpha 1 as being more specifically induced by proteinuria. Conclusion By simulating a component of diabetes, and looking at the global response on mice resistant to the disease, by virtue of a small genetic difference, we were able to identify key factors in disease progression. This suggests the power of this approach in unraveling multifactorial disease processes.

  12. Mitochondrial calcium overload is a key determinant in heart failure.

    Science.gov (United States)

    Santulli, Gaetano; Xie, Wenjun; Reiken, Steven R; Marks, Andrew R

    2015-09-08

    Calcium (Ca2+) released from the sarcoplasmic reticulum (SR) is crucial for excitation-contraction (E-C) coupling. Mitochondria, the major source of energy, in the form of ATP, required for cardiac contractility, are closely interconnected with the SR, and Ca2+ is essential for optimal function of these organelles. However, Ca2+ accumulation can impair mitochondrial function, leading to reduced ATP production and increased release of reactive oxygen species (ROS). Oxidative stress contributes to heart failure (HF), but whether mitochondrial Ca2+ plays a mechanistic role in HF remains unresolved. Here, we show for the first time, to our knowledge, that diastolic SR Ca2+ leak causes mitochondrial Ca2+ overload and dysfunction in a murine model of postmyocardial infarction HF. There are two forms of Ca2+ release channels on cardiac SR: type 2 ryanodine receptors (RyR2s) and type 2 inositol 1,4,5-trisphosphate receptors (IP3R2s). Using murine models harboring RyR2 mutations that either cause or inhibit SR Ca2+ leak, we found that leaky RyR2 channels result in mitochondrial Ca2+ overload, dysmorphology, and malfunction. In contrast, cardiac-specific deletion of IP3R2 had no major effect on mitochondrial fitness in HF. Moreover, genetic enhancement of mitochondrial antioxidant activity improved mitochondrial function and reduced posttranslational modifications of RyR2 macromolecular complex. Our data demonstrate that leaky RyR2, but not IP3R2, channels cause mitochondrial Ca2+ overload and dysfunction in HF.

  13. Acetaminophen protects against iron-induced cardiac damage in gerbils.

    Science.gov (United States)

    Walker, Ernest M; Epling, Christopher P; Parris, Cordel; Cansino, Silvestre; Ghosh, Protip; Desai, Devashish H; Morrison, Ryan G; Wright, Gary L; Wehner, Paulette; Mangiarua, Elsa I; Walker, Sandra M; Blough, Eric R

    2007-01-01

    There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and drug treatments. Liver and cardiac iron contents were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Iron-overloaded controls had 232-fold and 16-fold increases in liver and cardiac iron content, respectively, compared to saline controls. In iron-overloaded controls, echocardiography showed cardiac hypertrophy, right and left ventricular distension, significant reduction in left ventricular ejection fraction (-22%), and fractional shortening (-31%) during systole. Treatments with acetaminophen (ip or oral) or deferoxamine (ip) were equally effective in reducing cardiac iron content and in preventing cardiac structural and functional changes. Both agents also significantly reduced excess hepatic iron content, although acetaminophen was less effective than deferoxamine. The results suggest that acetaminophen may be useful for treatment of iron-induced pathology.

  14. Aeronautical Magnetic Torque Limiter for Passive Protection against Overloads

    Directory of Open Access Journals (Sweden)

    Cristian Cristache

    2016-09-01

    Full Text Available Actual aerospace and defense technologies present multiple limitations that need to be overcome in order to evolve to less contaminating and more efficient aircraft solutions. Contactless technologies come with essential advantages such as the absence of wear and friction. This work describes the design, prototype, and performance test according to RTCA-DO-160 of an aeronautical magnetic torque limiter. The results show correct continuous transmission operation (2250 rpm and 24 Nm from −50 °C to +90 °C. Moreover, overload protection has been demonstrated for more than 200 jamming events without damage or required maintenance to the device.

  15. Quantum Overloading Cryptography Using Single-Photon Nonlocality

    Institute of Scientific and Technical Information of China (English)

    TAN Yong-Gang; CAI Qing-Yu; SHI Ting-Yun

    2007-01-01

    @@ Using the single-photon nonlocality, we propose a quantum novel overloading cryptography scheme, in which a single photon carries two bits information in one-way quantum channel. Two commutative modes of the single photon, the polarization mode and the spatial mode, are used to encode secret information. Strict time windows are set to detect the impersonation attack. The spatial mode which denotes the existence of photons is noncommutative with the phase of the photon, so that our scheme is secure against photon-number-splitting attack. Our protocol may be secure against individual attack.

  16. Cell-permeable gomesin peptide promotes cell death by intracellular Ca(2+) overload.

    Science.gov (United States)

    Paredes-Gamero, Edgar J; Casaes-Rodrigues, Rafael L; Moura, Gioconda E D D; Domingues, Tatiana M; Buri, Marcus V; Ferreira, Victor H C; Trindade, Edvaldo S; Moreno-Ortega, Ana J; Cano-Abad, María F; Nader, Helena B; Ferreira, Alice T; Miranda, Antonio; Justo, Giselle Z; Tersariol, Ivarne L S

    2012-09-04

    In recent years, the antitumoral activity of antimicrobial peptides (AMPs) has been the goal of many research studies. Among AMPs, gomesin (Gm) displays antitumor activity by unknown mechanisms. Herein, we studied the cytotoxicity of Gm in the Chinese hamster ovary (CHO) cell line. Furthermore, we investigated the temporal ordering of organelle changes and the dynamics of Ca(2+) signaling during Gm-induced cell death. The results indicated that Gm binds to the plasma membrane and rapidly translocates into the cytoplasm. Moreover, 20 μM Gm increases the cytosolic Ca(2+) and induces membrane permeabilization after 30 min of treatment. Direct Ca(2+) measurements in CHO cells transfected with the genetically encoded D1-cameleon to the endoplasmic reticulum (ER) revealed that Gm induces ER Ca(2+) depletion, which in turn resulted in oscillatory mitochondrial Ca(2+) signal, as measured in cells expressing the genetically encoded probe to the mitochondrial matrix (mit)Pericam. This leads to mitochondria disruption, loss of mitochondrial membrane potential and increased reactive oxygen species prior to membrane permeabilization. Gm-induced membrane permeabilization by a Ca(2+)-dependent pathway involving Gm translocation into the cell, ER Ca(2+) depletion and disruption, mitochondrial Ca(2+) overload and oxidative stress.

  17. Adipocyte ALK7 links nutrient overload to catecholamine resistance in obesity.

    Science.gov (United States)

    Guo, Tingqing; Marmol, Patricia; Moliner, Annalena; Björnholm, Marie; Zhang, Chao; Shokat, Kevan M; Ibanez, Carlos F

    2014-08-25

    Obesity is associated with blunted β-adrenoreceptor (β-AR)-mediated lipolysis and lipid oxidation in adipose tissue, but the mechanisms linking nutrient overload to catecholamine resistance are poorly understood. We report that targeted disruption of TGF-β superfamily receptor ALK7 alleviates diet-induced catecholamine resistance in adipose tissue, thereby reducing obesity in mice. Global and fat-specific Alk7 knock-out enhanced adipose β-AR expression, β-adrenergic signaling, mitochondrial biogenesis, lipid oxidation, and lipolysis under a high fat diet, leading to elevated energy expenditure, decreased fat mass, and resistance to diet-induced obesity. Conversely, activation of ALK7 reduced β-AR-mediated signaling and lipolysis cell-autonomously in both mouse and human adipocytes. Acute inhibition of ALK7 in adult mice by a chemical-genetic approach reduced diet-induced weight gain, fat accumulation, and adipocyte size, and enhanced adipocyte lipolysis and β-adrenergic signaling. We propose that ALK7 signaling contributes to diet-induced catecholamine resistance in adipose tissue, and suggest that ALK7 inhibitors may have therapeutic value in human obesity. Copyright © 2014, Guo et al.

  18. Increasing inspiratory time exacerbates ventilator-induced lung injury during high-pressure/high-volume mechanical ventilation.

    Science.gov (United States)

    Casetti, Alfredo V; Bartlett, Robert H; Hirschl, Ronald B

    2002-10-01

    Ventilator-induced lung injury may be caused by overdistension of alveoli during high-pressure ventilation. In this study, we examined the effects of increasing inspiratory time on ventilator-induced lung injury. Sprague-Dawley rats were divided into four different groups with ten animals per group. Each group was then ventilated for 30 mins with one of four ventilator strategies. All groups were ventilated with an Fio2 of 1.0 and a positive end-expiratory pressure of 0 cm H2O. Group LoP was the negative control group and was ventilated with low pressures (peak inspiratory pressure = 12 cm H2O, rate = 30, and inspiratory time = 0.5 secs). Groups iT = 0.5, iT = 1.0, and iT = 1.5 were the experimental groups and were ventilated with high pressures (peak inspiratory pressure = 45 cm H2O, rate = 10, and inspiratory times = 0.5 secs, iT = 1.0 sec, and iT = 1.5 secs, respectively). Outcome measures included lung compliance, Pao /Fio ratio, wet/dry lung weight, and dry lung/body weight. Final static lung compliance (p =.0002) and Pao2/Fio2 (p =.001) decreased as inspiratory time increased. Wet/dry lung weights (p <.0001) and dry lung/body weights (p <.0001) increased as inspiratory time increased. Light microscopy revealed evidence of intra-alveolar edema and hemorrhage in the iT = 1.0 and iT = 1.5 animals but not the LoP and iT = 0.5 animals. Increasing inspiratory time during high-pressure/high-volume mechanical ventilation is associated with an increase in variables of lung injury.

  19. Pyridoxine responsive hereditary sideroblastic erythropoiesis and iron overload: two microcytic subpopulations in the affected male, one normocytic and one microcytic subpopulation in the obligate female carrier.

    Science.gov (United States)

    Harris, J W; Danish, E H; Brittenham, G M; McLaren, C E

    1993-04-01

    Mild hepatic iron overload has been demonstrated by magnetic susceptibility measurements in a 22-year-old man with hereditary sideroblastic erythropoiesis despite hemoglobin levels in the normal range and a normal erythropoietin level. His grandfather's sideroblastic anemia has been found to be responsive to pyridoxine; his mother's hemoglobin has persisted in the normal range but red cell volume distribution analysis demonstrated two subpopulations; 30% with estimated geometric mean of 68 fl and 70% an estimated mean of 93 fl. Red cell distribution analysis of the grandson demonstrated two microcytic subpopulations; 46% with an estimated geometric mean of 45 fl and 54% an estimated mean of 70 fl. A therapeutic regimen is outlined to reduce to normal his iron stores and to prevent the future development of excessive iron overload.

  20. Right and left ventricular function and myocardial scarring in adult patients with sickle cell disease: a comprehensive magnetic resonance assessment of hepatic and myocardial iron overload.

    Science.gov (United States)

    Junqueira, Flávia P; Fernandes, Juliano L; Cunha, Guilherme M; T A Kubo, Tadeu; M A O Lima, Claudio; B P Lima, Daniel; Uellendhal, Marly; Sales, Sidney R; A S Cunha, Carolina; L R de Pessoa, Viviani; L C Lobo, Clarisse; Marchiori, Edson

    2013-09-19

    Patients with Sickle cell disease (SCD) who receive regular transfusions are at risk for developing cardiac toxicity from iron overload. The aim of this study was to assess right and left cardiac volumes and function, late gadolinium enhancement (LGE) and iron deposits in patients with SCD using CMR, correlating these values with transfusion burden, ferritin and hemoglobin levels. Thirty patients with SCD older than 20 years of age were studied in a 1.5 T scanner and compared to age- and sex-matched normal controls. Patients underwent analysis of biventricular volumes and function, LGE and T2* assessment of the liver and heart. When compared to controls, patients with SCD presented higher left ventricular (LV) volumes with decreased ejection fraction (EF) with an increase in stroke volume (SV) and LV hypertrophy. The right ventricle (RV) also presented with a decreased EF and hypertrophy, with an increased end-systolic volume. Although twenty-six patients had increased liver iron concentrations (median liver iron concentration value was 11.83 ± 9.66 mg/g), only one patient demonstrated an abnormal heart T2* < 20 msec. Only four patients (13%) LGE, with only one patient with an ischemic pattern. Abnormal heart iron levels and myocardial scars are not a common finding in SCD despite increased liver iron overload. The significantly different ventricular function seen in SCD compared to normal suggests the changes in RV and LV function may not be due to the anemia alone. Future studies are necessary to confirm this association.

  1. Lithium prevents early cytosolic calcium increase and secondary injurious calcium overload in glycolytically inhibited endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Bosche, Bert, E-mail: bert.bosche@uk-essen.de [Department of Neurology, University of Duisburg-Essen (Germany); Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne (Germany); Schäfer, Matthias, E-mail: matthias.schaefer@sanofi.com [Institute of Physiology, Justus-Liebig-University Giessen (Germany); Graf, Rudolf, E-mail: rudolf.graf@nf.mpg.de [Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne (Germany); Härtel, Frauke V., E-mail: frauke.haertel@tu-dresden.de [Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden (Germany); Schäfer, Ute, E-mail: ute.schaefer@medunigraz.at [Research Unit for Experimental Neurotraumatology, Medical University of Graz (Austria); Noll, Thomas, E-mail: thomas.noll@tu-dresden.de [Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden (Germany)

    2013-05-03

    Highlights: •We investigate free calcium as a central signalling element in endothelial cells. •Inhibition of glycolysis with 2-deoxy-D-glucose reduces cellular ATP. •This manoeuvre leads to a biphasic increase and overload of free calcium. •Pre-treatment with lithium for 24 h abolishes both phases of the calcium increase. •This provides a new strategy to protect endothelial calcium homeostasis and barrier function. -- Abstract: Cytosolic free calcium concentration ([Ca{sup 2+}]{sub i}) is a central signalling element for the maintenance of endothelial barrier function. Under physiological conditions, it is controlled within narrow limits. Metabolic inhibition during ischemia/reperfusion, however, induces [Ca{sup 2+}]{sub i} overload, which results in barrier failure. In a model of cultured porcine aortic endothelial monolayers (EC), we addressed the question of whether [Ca{sup 2+}]{sub i} overload can be prevented by lithium treatment. [Ca{sup 2+}]{sub i} and ATP were analysed using Fura-2 and HPLC, respectively. The combined inhibition of glycolytic and mitochondrial ATP synthesis by 2-desoxy-D-glucose (5 mM; 2-DG) plus sodium cyanide (5 mM; NaCN) caused a significant decrease in cellular ATP content (14 ± 1 nmol/mg protein vs. 18 ± 1 nmol/mg protein in the control, n = 6 culture dishes, P < 0.05), an increase in [Ca{sup 2+}]{sub i} (278 ± 24 nM vs. 71 ± 2 nM in the control, n = 60 cells, P < 0.05), and the formation of gaps between adjacent EC. These observations indicate that there is impaired barrier function at an early state of metabolic inhibition. Glycolytic inhibition alone by 10 mM 2-DG led to a similar decrease in ATP content (14 ± 2 nmol/mg vs. 18 ± 1 nmol/mg in the control, P < 0.05) with a delay of 5 min. The [Ca{sup 2+}]{sub i} response of EC was biphasic with a peak after 1 min (183 ± 6 nM vs. 71 ± 1 nM, n = 60 cells, P < 0.05) followed by a sustained increase in [Ca{sup 2+}]{sub i}. A 24-h pre-treatment with 10 mM of lithium

  2. [Predictive factors of response to erytrhocytapheresis in patients with biochemical iron overload with or without hereditary hemochromatosis type 1].

    Science.gov (United States)

    Parra Salinas, Ingrid; Montes Limon, Anel; Recasens Flores, Valle; Fernandez-Mosteirin, Nuria; Garcia-Erce, Jose Antonio

    2014-03-04

    Progressive increase of iron stores leads to the development of varied diseases, some of them irreversible. Until now, phlebotomy has been the cornerstone in the treatment of iron overload. Nevertheless, each erytrhocytapheresis procedure removes more than twice the volume of red cells and iron than phlebotomy, allowing to achieve iron depletion in shorter time. Our aim was to describe clinical features and analytical tests parameters of patients with iron overload, to analyze global and subsets results, to suggest predictive factors of response and to evaluate security of the procedure. Descriptive, longitudinal and prospective study of 663 procedures corresponding to 35 patients (December 2002 to October 2011). Response was defined as a serum ferritine value lower than 50 ng/mL during two months. Statistical analysis was done with SPSS(®) v 17.0 and the minimum level of statistical significance was defined as p-value < 0,05. Seventy-seven percent of patients reached response with 11 (interquartile range 1-42) erytrhocytapheresis procedures and at 11 (1-108) months. Eighty-seven point five percent of patients who did not achieve response had their ferritine values reduced in more than 50%. The decrease of all iron metabolism parameters was statistically significant. Statistically significant predictive factors of response to erytrhocytapheresis were: patients younger than 60 years-old, hereditary hemochromatosis cases, and patients who had received treatment with phlebotomies prior to erytrhocytapheresis. Erytrhocytapheresis is a secure and effective procedure for iron depletion in patients with iron overload, especially in high risk hereditary hemochromatosis cases that do not respond to phlebotomies. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  3. Myocardial iron overload in thalassaemia major. How early to check?

    Science.gov (United States)

    Borgna-Pignatti, Caterina; Meloni, Antonella; Guerrini, Giulia; Gulino, Letizia; Filosa, Aldo; Ruffo, Giovan B; Casini, Tommaso; Chiodi, Elisabetta; Lombardi, Massimo; Pepe, Alessia

    2014-02-01

    The age at which it is necessary to start Cardiovascular Magnetic Resonance (CMR) T2* screening in thalassaemia major (TM) is still uncertain. To clarify this point, we evaluated the prevalence of myocardial iron overload (MIO), function and fibrosis by CMR in TM patients younger than 10 years. We retrospectively selected 35 TM patients enrolled in the Myocardial Iron Overload in Thalassaemia network. MIO was measured by T2* multislice multiecho technique. Biventricular function parameters were evaluated by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Patients' age ranged from 4·2 to 9·7 years. All scans were performed without sedation. Nine patients showed no MIO, 22 patients had heterogeneous MIO with a T2* global value ≥20 ms; two patients had heterogeneous MIO with a T2* global value <20 ms and two patients showed homogeneous MIO. No patient showed myocardial fibrosis. Among the patients with heart T2*<20 ms, the youngest was 6 years old, none showed heart dysfunction and the iron transfused was <35 g in all cases. Cardiac iron loading can occur much earlier than previously described. The first cardiac T2* assessment should be performed as early as feasible without sedation, especially if chelation is started late or if poor compliance is suspected.

  4. Information overload within the health care system: a literature review.

    Science.gov (United States)

    Hall, Amanda; Walton, Graham

    2004-06-01

    There is a widespread view held by health clinicians that their work effectiveness is impaired by 'information overload.' Building upon a previous work by Wilson, a review of the literature was undertaken to look for the evidence of this. It was found that the literature, particularly in the context of the clinical environment, was limited. This review explores the diverse overarching theories of information overload, effects of the phenomenon that are perceived to occur and proposed solutions to this problem. Many of the papers noted an information explosion but only three authors explicitly attempted to measure both the quantity and the complexity of this information. It was also found that the typology of the information studied was severely limited with most studies exploring information such as guidelines, access to journals, research findings and other knowledge intensive areas. Solutions proposed seem to concentrate on technological means rather than exploring the use of humans either in management of information or as a step in the filtering process.

  5. Information overload in healthcare: too much of a good thing?

    Science.gov (United States)

    Klerings, Irma; Weinhandl, Alexandra S; Thaler, Kylie J

    2015-01-01

    The rapidly growing production of healthcare information - both scientific and popular - increasingly leads to a situation of information overload affecting all actors of the healthcare system and threatening to impede the adoption of evidence-based practice. In preparation for the 2015 Cochrane Colloquium in Vienna, we discuss the issues faced by three major actors of this system: patients, healthcare practitioners, and systematic reviewers. We analyze their situation through the concept of "filter failure", positing that the main problem is not that there is "too much information", but that the traditional means of managing and evaluating information are ill-suited to the realities of the digital age. Some of the major instances of filter failure are inadequate information retrieval systems for point-of-care settings, the problem of identifying all relevant evidence in an exceedingly diverse landscape of information resources, and the very basic lack of health information literacy, concerning not only the general public. Finally, we give an overview of proposed solutions to the problem of information overload. These new or adapted filtering systems include adapting review literature to the specific needs of practitioners or patients, technological improvements to information systems, strengthening the roles of intermediaries, as well as improving health literacy. Copyright © 2015. Published by Elsevier GmbH.

  6. Competing for Attention in Social Media under Information Overload Conditions.

    Science.gov (United States)

    Feng, Ling; Hu, Yanqing; Li, Baowen; Stanley, H Eugene; Havlin, Shlomo; Braunstein, Lidia A

    2015-01-01

    Modern social media are becoming overloaded with information because of the rapidly-expanding number of information feeds. We analyze the user-generated content in Sina Weibo, and find evidence that the spread of popular messages often follow a mechanism that differs from the spread of disease, in contrast to common belief. In this mechanism, an individual with more friends needs more repeated exposures to spread further the information. Moreover, our data suggest that for certain messages the chance of an individual to share the message is proportional to the fraction of its neighbours who shared it with him/her, which is a result of competition for attention. We model this process using a fractional susceptible infected recovered (FSIR) model, where the infection probability of a node is proportional to its fraction of infected neighbors. Our findings have dramatic implications for information contagion. For example, using the FSIR model we find that real-world social networks have a finite epidemic threshold in contrast to the zero threshold in disease epidemic models. This means that when individuals are overloaded with excess information feeds, the information either reaches out the population if it is above the critical epidemic threshold, or it would never be well received.

  7. Iron Loading and Overloading due to Ineffective Erythropoiesis

    Directory of Open Access Journals (Sweden)

    Toshihiko Tanno

    2010-01-01

    Full Text Available Erythropoiesis describes the hematopoietic process of cell proliferation and differentiation that results in the production of mature circulating erythrocytes. Adult humans produce 200 billion erythrocytes daily, and approximately 1 billion iron molecules are incorporated into the hemoglobin contained within each erythrocyte. Thus, iron usage for the hemoglobin production is a primary regulator of plasma iron supply and demand. In many anemias, additional sources of iron from diet and tissue stores are needed to meet the erythroid demand. Among a subset of anemias that arise from ineffective erythropoiesis, iron absorption and accumulation in the tissues increases to levels that are in excess of erythropoiesis demand even in the absence of transfusion. The mechanisms responsible for iron overloading due to ineffective erythropoiesis are not fully understood. Based upon data that is currently available, it is proposed in this review that loading and overloading of iron can be regulated by distinct or combined mechanisms associated with erythropoiesis. The concept of erythroid regulation of iron is broadened to include both physiological and pathological hepcidin suppression in cases of ineffective erythropoiesis.

  8. Nicotinamide overload may play a role in the development of type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Shi-Sheng Zhou; Li-Bin Zhang; Ning Luo; Fu-Ning Bian; Wei Zou; Lai-Bin Dong; Zhi-Gang Zhao; Sheng-Fan Li; Xiao-Jie Gong; Zeng-Guo Yu; Chang-Bin Sun; Da Li; Cong-Long Zheng; Dong-Ju Jiang; Zheng-Ning Li; Wu-Ping Sun; Ming Guo; Yong-Zhi Lun; Yi-Ming Zhou; Fu-Cheng Xiao; Li-Xin Jing; Shen-Xia Sun

    2009-01-01

    AIM: To investigate whether nicotinamide overload plays a role in type 2 diabetes.METHODS: Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N~1-methylnicotinamide on glucose metabolism, plasma H_2O_2 levels and tissue nicotinamide adenine dinucleotide (NAD) contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively.RESULTS: Diabetic subjects had significantly higher plasma N~1-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P< 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N~1-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N~1-methylnicotinamide. Moreover, cumulative exposure to N~1-methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio, and increased plasma H_2O_2 levels. Decrease in NAD/NADH ratio and increase in H_2O_2 generation were also observed in human erythrocytes after exposure to N~1-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide (5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load). Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N~1-methylnicotinamide clearance.CONCLUSION: These findings suggest that nicotinamide overload, which induced an increase in plasma N~1-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.

  9. Muscle damage responses and adaptations to eccentric-overload resistance exercise in men and women.

    Science.gov (United States)

    Fernandez-Gonzalo, Rodrigo; Lundberg, Tommy R; Alvarez-Alvarez, Lucia; de Paz, José A

    2014-05-01

    This study assessed markers of muscle damage and training adaptations to eccentric-overload flywheel resistance exercise (RE) in men and women. Dynamic strength (1 RM), jump performance, maximal power at different percentages of 1 RM, and muscle mass in three different portions of the thigh were assessed in 16 men and 16 women before and after 6 weeks (15 sessions) of flywheel supine squat RE training. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations were measured before, 24, 48 and 72 h after the first and the last training session. After training, increases in 1 RM were somewhat greater (interaction P < 0.001) in men (25 %) than in women (20 %). Squat and drop jump height and power performance at 50, 60, 70 and 80 % of 1 RM increased after training in both sexes (P < 0.05). Power improvement at 80 % of 1 RM was greater (interaction P < 0.02) in men than women. Muscle mass increased ~5 % in both groups (P < 0.05). CK increased in men after the first training session (P < 0.001), whereas the response in women was unaltered. In both sexes, LDH concentration was greater after the first training session compared with basal values (P < 0.05). After the last session, CK and LDH remained at baseline in both groups. These results suggest that although improvements in maximal strength and power at high loads may be slightly greater for men, eccentric-overload RE training induces comparable and favorable gains in strength, power, and muscle mass in both men and women. Equally important, it appears muscle damage does not interfere with the adaptations triggered by this training paradigm.

  10. Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats

    Science.gov (United States)

    Guo, Yuanxin; Lei, Wenjuan; Wang, Jianfeng; Hu, Xinyue; Wei, Yuling; Ji, Chaonan; Yang, Junqing

    2016-01-01

    Although COX-2 inhibition in animal models of neurodegenerative diseases has shown neuroprotection, recent studies have revealed some serious side effects (ulcers, bleeding, fatal cerebrovascular diseases etc.) and the limited benefits of COX-2 inhibitors. A more focused approach is necessary to explore the therapeutic effect of the COX downstream signaling pathway in neurological research. The aim of this study was to explore the alterations of the PGES-PGE2-EP signal pathway and the effect of misoprostol on neurodegeneration by chronic aluminum-overload in rats. Adult rats were treated by intragastric administration of aluminum gluconate. The PGE2 content and expression of PGES and EPs in the hippocampi of rats were detected using ELISA, q-PCR and Western blot analysis, respectively. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the rat hippocampi were also detected. The misoprostol treatment dose-dependently improved spatial learning and memory function as well as healing after hippocampal neuron damage induced by chronic aluminum-overload in rats. Meanwhile, the administration of misoprostol resulted in a decrease in the PGE2 level and down-regulation of the mPGES-1, EP2 and EP4 expression levels, while there was a dose-dependent up-regulation of EP3 expression. These results suggest that misoprostol possesses a neuroprotective property, and the mechanism involves affecting the EP3 level and reducing the endogenous production of PGE2 through a negative feedback mechanism, increasing the EP3 expression level, decreasing the EP2 and EP4 expression levels, and rebuilding the mPGES-1-PGE2-EP1-4 signal pathway balance. In this way, misoprostol has a counteractive effect on oxidant stress and inflammation in the central nervous system. The PGES-PGE2-EPs signaling pathway is a potential therapeutic strategy for treating neurodegeneration in patients. PMID:27033056

  11. Nicotinamide overload may play a role in the development of type 2 diabetes.

    Science.gov (United States)

    Zhou, Shi-Sheng; Li, Da; Sun, Wu-Ping; Guo, Ming; Lun, Yong-Zhi; Zhou, Yi-Ming; Xiao, Fu-Cheng; Jing, Li-Xin; Sun, Shen-Xia; Zhang, Li-Bin; Luo, Ning; Bian, Fu-Ning; Zou, Wei; Dong, Lai-Bin; Zhao, Zhi-Gang; Li, Sheng-Fan; Gong, Xiao-Jie; Yu, Zeng-Guo; Sun, Chang-Bin; Zheng, Cong-Long; Jiang, Dong-Ju; Li, Zheng-Ning

    2009-12-07

    To investigate whether nicotinamide overload plays a role in type 2 diabetes. Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N(1)-methylnicotinamide on glucose metabolism, plasma H(2)O(2) levels and tissue nicotinamide adenine dinucleotide (NAD) contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. Diabetic subjects had significantly higher plasma N(1)-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 +/- 0.13 micromol/L vs 0.6 +/- 0.13 micromol/L, P nicotinamide (2 g/kg) significantly increased rat plasma N(1)-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N(1)-methylnicotinamide. Moreover, cumulative exposure to N(1)-methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/NADH ratio, and increased plasma H(2)O(2) levels. Decrease in NAD/NADH ratio and increase in H(2)O(2) generation were also observed in human erythrocytes after exposure to N(1)-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide (5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load). Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N(1)-methylnicotinamide clearance. These findings suggest that nicotinamide overload, which induced an increase in plasma N(1)-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.

  12. Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport Proteins in Iron-Overloaded Rats.

    Science.gov (United States)

    Du, Fang; Qian, Zhong-Ming; Luo, Qianqian; Yung, Wing-Ho; Ke, Ya

    2015-08-01

    Iron accumulates progressively in the brain with age, and iron-induced oxidative stress has been considered as one of the initial causes for Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the role of hepcidin in peripheral organs and its expression in the brain, we hypothesized that this peptide has a role to reduce iron in the brain and hence has the potential to prevent or delay brain iron accumulation in iron-associated neurodegenerative disorders. Here, we investigated the effects of hepcidin expression adenovirus (ad-hepcidin) and hepcidin peptide on brain iron contents, iron transport across the brain-blood barrier, iron uptake and release, and also the expression of transferrin receptor-1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin 1 (Fpn1) in cultured microvascular endothelial cells and neurons. We demonstrated that hepcidin significantly reduced brain iron in iron-overloaded rats and suppressed transport of transferrin-bound iron (Tf-Fe) from the periphery into the brain. Also, the peptide significantly inhibited expression of TfR1, DMT1, and Fpn1 as well as reduced Tf-Fe and non-transferrin-bound iron uptake and iron release in cultured microvascular endothelial cells and neurons, while downregulation of hepcidin with hepcidin siRNA retrovirus generated opposite results. We concluded that, under iron-overload, hepcidin functions to reduce iron in the brain by downregulating iron transport proteins. Upregulation of brain hepcidin by ad-hepcidin emerges as a new pharmacological treatment and prevention for iron-associated neurodegenerative disorders.

  13. Lack of association between overload and peri-implant tissue loss in healthy conditions.

    Science.gov (United States)

    Afrashtehfar, Kelvin I; Afrashtehfar, Cyrus Dm

    2016-09-01

    Data sourcesPubMed, Ovid, EMBASE and LILACS were searched up to December 2011. In addition, the reference lists of the selected review papers were further hand searched. Language was limited to studies published only in English.Study selectionHuman and animal randomised clinical trials (RCT), systematic reviews of RCTs, non-randomised trials, case series that reported on the clinical, radiographic, and/or histological outcomes of dental/oral implants exposed to excessive load were considered eligible for inclusion.Data extraction and synthesisIdentified studies were evaluated by one non-blinded reviewer according to the selection criteria. When doubt arose co-authors assisted until consensus was reached. The data extracted from the clinical studies included study design, patients/implants/prostheses/loading time/follow-up time, type of intervention/methods, outcome, and, specific to animal studies, the animal model, intention to overload (ie yes or no), load mode, type of loading (ie dynamic or static), and microbial control if any. The heterogeneity among studies did not allow data to be combined.ResultsThe search strategy in addition to hand searching retrieved 726 potentially eligible studies after de-duplication. After screening the 41 full-text relevant studies and applying the selection criteria assessment, only three non-randomised split-mouth animal studies and one systematic review of animal experimental data were considered for inclusion. The non-randomised studies could not reveal any relationship between increased leverage on dental implants and marginal loss. The systematic review suggested that supra-occlusal contacts on uninflamed peri-implant bone tissue did not cause catabolism, whereas supra-occlusal contacts combined with inflammation significantly increased the plaque-induced catabolism.ConclusionsThe effect of implant overload on bone/implant loss in clinically well-integrated implants is poorly reported and provides little unbiased evidence to

  14. Data Overload Impact on Project Management: How Knowledge Management Systems Can Improve Federal Agencies Effectiveness

    Science.gov (United States)

    Rodriguez, Jacinto

    2013-01-01

    This mixed method exploratory case study was used to explore the effect data overload has on project management, how data overload affects project management effectiveness, how prepared program office staff is to manage multiple projects effectively, and how the program office's organizational structure and data management systems affect project…

  15. Eccentric overload training in patients with a chronic Achilles tendinopathy: a systematic review.

    NARCIS (Netherlands)

    R. de Knikker; T. Takken; J.J. Kingma; Dr. H.M. Wittink

    2007-01-01

    Background: Eccentric overload training seems to be a promising conservative intervention in patients with chronic Achilles tendinopathy. The efficacy of eccentric overload training on the outcome measures of pain and physical functioning are not exactly clear. Study design: Systematic review of the

  16. "Something's Gotta Give:" Advanced-Degree Seeking Women's Experiences of Sexism, Role Overload, and Psychological Distress

    Science.gov (United States)

    West, Lindsey M.

    2014-01-01

    With the rise in advanced-degree seeking women and the minimal research on the dual impact of sexism and role overload, the current study aims to better understand the impact of sexism and role overload on psychological distress in a particular sample of advanced-degree seeking women. Seventy-six female medical student participants (mean age 24.7)…

  17. Designing a Personalized Guide Recommendation System to Mitigate Information Overload in Museum Learning

    Science.gov (United States)

    Huang, Yong-Ming; Liu, Chien-Hung; Lee, Chun-Yi; Huang, Yueh-Min

    2012-01-01

    Museum learning has received a lot of attention in recent years. Museum learning refers to people's use of museums to acquire knowledge. However, a problem with information overload has caused in engaging in such learning. Information overload signifies that users encounter a mass of information and need to determine whether certain information…

  18. Eccentric overload training in patients with a chronic Achilles tendinopathy: a systematic review.

    NARCIS (Netherlands)

    Kingma, J.J.; Knikker, R. de; Wittink, H.M.; Takken, T.

    2007-01-01

    Background: Eccentric overload training seems to be a promising conservative intervention in patients with chronic Achilles tendinopathy. The efficacy of eccentric overload training on the outcome measures of pain and physical functioning are not exactly clear. Study design: Systematic review of the

  19. Designing immersive surgical training against information technology-related overload in the operating room

    NARCIS (Netherlands)

    Pluyter, J.R.

    2012-01-01

    On a theoretical level, this dissertation demonstrates that the “classical” conceptualization of overload in the field of Information Systems being an excessive amount of information is too simplistic. Based on the Emotional-Cognitive Overload Model by Rutkowski and Saunders (2011) this dissertation

  20. Information Overload in the New World of Work: Qualitative Study into the Reasons and Countermeasures

    NARCIS (Netherlands)

    ter Heerdt, Jeroen; Bondarouk, Tatiana; Ruel, Hubertus Johannes Maria; Guiderdoni-Jourdain, Karine; Oiry, Ewan

    2009-01-01

    In this chapter the authors present a revision of the information overload concept elaborated by Eppler and Mengis (2004). The main elements of our approach are literature synopsis and analysis, qualitative semi-structured interviews, and discussion. Their review of the information overload concept

  1. Designing a Personalized Guide Recommendation System to Mitigate Information Overload in Museum Learning

    Science.gov (United States)

    Huang, Yong-Ming; Liu, Chien-Hung; Lee, Chun-Yi; Huang, Yueh-Min

    2012-01-01

    Museum learning has received a lot of attention in recent years. Museum learning refers to people's use of museums to acquire knowledge. However, a problem with information overload has caused in engaging in such learning. Information overload signifies that users encounter a mass of information and need to determine whether certain information…

  2. The Use of Graphs as Decision Aids in Relation to Information Overload and Managerial Decision Quality.

    Science.gov (United States)

    Chan, Siu Y.

    2001-01-01

    Discussion of information overload focuses on a study of masters degree students at a Hong Kong university that investigated the effectiveness of graphs as decision aids to reduce adverse effects of information overload on decision quality. Results of a simulation of a business prediction task with a sample of business managers are presented.…

  3. Managing Information Overload for Senior Leaders in the 21st Century

    Science.gov (United States)

    Jackson, Jason M.

    2013-01-01

    Information overload is a state where information input exceeds processing capability by an individual, and adverse effects of information overload, such as becoming less productive, making bad decisions, and becoming highly selective, are growing. Guided by Glaser and Strauss' work on grounded theory, this study examined adverse impact of…

  4. Spreading the Load: Mobile Information and Communications Technologies and Their Effect on Information Overload

    Science.gov (United States)

    Allen, David K.; Shoard, M.

    2005-01-01

    Introduction: We report on a small-scale research project which examined the impact of mobile technologies on the users' experience of information overload. The project focused on a group of worker who have had relatively little attention in both the mobile technology and information overload literatures: senior managers. Method: The case study…

  5. Managing Information Overload for Senior Leaders in the 21st Century

    Science.gov (United States)

    Jackson, Jason M.

    2013-01-01

    Information overload is a state where information input exceeds processing capability by an individual, and adverse effects of information overload, such as becoming less productive, making bad decisions, and becoming highly selective, are growing. Guided by Glaser and Strauss' work on grounded theory, this study examined adverse impact of…

  6. I just want to be left alone: Daily overload and marital behavior.

    Science.gov (United States)

    Sears, Meredith S; Repetti, Rena L; Robles, Theodore F; Reynolds, Bridget M

    2016-08-01

    Stressful, busy days have been linked with increases in angry and withdrawn marital behavior. The process by which stressors in 1 domain, such as work, affect an individual’s behavior in another domain, such as the marital relationship, is known as spillover. Using 56 days of daily diary reports in a diverse sample of 47 wives and 39 husbands, this study examined associations between daily experiences of overload and 3 marital behaviors: overt expressions of anger, disregard of the spouse’s needs (“disregard”), and reductions in affection and disclosure (“distancing”). Two potential mechanisms by which daily overload spills over into marital behavior were examined: negative mood and the desire to avoid social interaction. Among husbands, negative mood mediated the association between overload and angry behavior. Associations between overload and wives’ angry behavior, as well as overload and husbands’ and wives’ disregard of their partners’ needs, were mediated by both negative mood and the desire to withdraw socially. Desire to withdraw, but not negative mood, mediated the association between overload and distancing behavior among husbands and wives. In addition, associations between marital satisfaction and spouses’ typical marital behavior, as well as behavioral responses to overload, were examined. Husbands’ and wives’ average levels of expressed anger and disregard, and husbands’ distancing, were associated with lower marital satisfaction in 1 or both partners. Both spouses reported lower marital satisfaction if husbands tended to express marital anger, disregard, or distancing on busy, overloaded days.

  7. Why cross-national differences in role overload? Don't overlook ambient temperature!

    NARCIS (Netherlands)

    Van de Vliert, E.; Van Yperen, N.W.

    1996-01-01

    The finding that, across nations, power distance (expected and accepted unequal interpersonal influence) Is positively related to role overload (Peterson et al., 1995) might he an artifact of the relation between role overload and ambient temperature or other third factors. We related data on power

  8. 30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and short circuit protection. 75.518 Section 75.518 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Equipment-General § 75.518 Electric equipment and circuits; overload and short circuit protection....

  9. 30 CFR 77.506 - Electric equipment and circuits; overload and short-circuit protection.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and short-circuit protection. 77.506 Section 77.506 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... circuits; overload and short-circuit protection. Automatic circuit-breaking devices or fuses of the...

  10. Reliability Analysis and Overload Capability Assessment of Oil-Immersed Power Transformers

    Directory of Open Access Journals (Sweden)

    Chen Wang

    2016-01-01

    Full Text Available Smart grids have been constructed so as to guarantee the security and stability of the power grid in recent years. Power transformers are a most vital component in the complicated smart grid network. Any transformer failure can cause damage of the whole power system, within which the failures caused by overloading cannot be ignored. This research gives a new insight into overload capability assessment of transformers. The hot-spot temperature of the winding is the most critical factor in measuring the overload capacity of power transformers. Thus, the hot-spot temperature is calculated to obtain the duration running time of the power transformers under overloading conditions. Then the overloading probability is fitted with the mature and widely accepted Weibull probability density function. To guarantee the accuracy of this fitting, a new objective function is proposed to obtain the desired parameters in the Weibull distributions. In addition, ten different mutation scenarios are adopted in the differential evolutionary algorithm to optimize the parameter in the Weibull distribution. The final comprehensive overload capability of the power transformer is assessed by the duration running time as well as the overloading probability. Compared with the previous studies that take no account of the overloading probability, the assessment results obtained in this research are much more reliable.

  11. Learners' Perceived Information Overload in Online Learning via Computer-Mediated Communication

    Science.gov (United States)

    Chen, Chun-Ying; Pedersen, Susan; Murphy, Karen L.

    2011-01-01

    Many studies report information overload as one of the main problems that students encounter in online learning via computer-mediated communication. This study aimed to explore the sources of online students' information overload and offer suggestions for increasing students' cognitive resources for learning. Participants were 12 graduate students…

  12. Data Overload Impact on Project Management: How Knowledge Management Systems Can Improve Federal Agencies Effectiveness

    Science.gov (United States)

    Rodriguez, Jacinto

    2013-01-01

    This mixed method exploratory case study was used to explore the effect data overload has on project management, how data overload affects project management effectiveness, how prepared program office staff is to manage multiple projects effectively, and how the program office's organizational structure and data management systems affect project…

  13. Involvement of veratridine-induced increase of reverse Na+/Ca2+ exchange current in intracellular Ca2+ overload and extension of action potential duration in rabbit ventricular myocytes%藜芦定增强反向Na+/Ca2+交换电流诱导家兔心室肌细胞内Ca2+超载和动作电位异常延长

    Institute of Scientific and Technical Information of China (English)

    孔令浩; 马季骅; 张培华; 罗岸涛; 张硕; 任志强; 冯娟; 陈玖玲

    2012-01-01

    ventricular myocytes from (123.18 ±23.70) to (271.90 ±32.81) and from (146.94 ± 24.15) to (429.79 ± 32.04) ms (P < 0.01, n = 6) respectively. Early afterdepolarizations (EADs) appeared in 3 out of the 6 cases. After adding 4 umol/L TTX, APD50 and APD90 were reduced to (99.07 ± 22.81) and (163.84 ± 26.06) ms (P < 0.01, n = 6) respectively, and EADs disappeared accordingly in 3 cases. It could be suggested that: (1) As a specific agonist of the INas.p VER could result in INas.p increase and intracellular Na overload, and subsequently intracellular Ca2 overload with the increase of reverse ⅠNCX. (2) The VER-increased ⅠNa.p could further extend the action potential duration (APD) and induce EADs. (3) TTX could restrain the abnormal VER-induced changes of the above-mentioned indexes, indicating that these abnormal changes were caused by the increase of ⅠNa.p. Based on this study, it is concluded that as the ⅠNa.p agonist, VER can enhance reverse ⅠNCX by increasing ⅠNa.p leading to intracellular Ca2+ overload and APD abnormal extension.%本文应用全细胞膜片钳记录技术、可视化动缘探测系统及细胞内钙测定系统和多道生理信号采集处理系统,研究藜芦定(veratridine,VER)对家兔心室肌细胞持续钠电流(persistent sodium current,INa.P)、Na/Ca2+交换电流(Na+/Ca2+ exchange current,InNCX)、钙瞬变及动作电位(action potential,AP)的影响,并探讨其引起细胞内Ca2+超载和增强心肌收缩的发生机制.结果显示,给予心室肌细胞10、20 μmol/L VER后,INa.P和反向INCX电流密度均增大,再加入4μmol/L河脉毒素(tetrodotoxin,TTX)后,INa.P和反向IMCX电流密度均又明显减小.在另一组实验中,特异性INa.P阻断剂雷喏嗪(ranolazine,RAN)也明显抑制由VER诱导增大的INa.P和反向INCX.加入2.5 μmol/L VER后,心室肌细胞最大收缩速率、收缩幅度和钙瞬变基线(舒张期Ca2+浓度)均增大,加入2 μmol/L TTX后上述三项指标均明显减小.VER (20 μmol/L

  14. Research on the overload protection reliability of moulded case circuit-breakers and its test device

    Institute of Scientific and Technical Information of China (English)

    LI Kui; LU Jian-guo; WU Yi; QIN Zhi-jun; YAO Dong-mei

    2007-01-01

    This paper analyzed the reliability and put forward the reliability index of overload protection for moulded case circuit breaker. The success rate was adopted as its reliability index of overload protection. Based on the reliability index and the reliability level, the reliability examination plan was analyzed and a test device for the overload protection of moulded case circuit-breaker was developed. In the reliability test of overload protection, two power sources were used, which reduced the time of conversion and regulation between two different test currents in the overload protection test, which made the characteristic test more accurate. The test device was designed on the base of a Windows system, which made its operation simple and friendly.

  15. Deferasirox for managing iron overload in people with myelodysplastic syndrome.

    Science.gov (United States)

    Meerpohl, Joerg J; Schell, Lisa K; Rücker, Gerta; Fleeman, Nigel; Motschall, Edith; Niemeyer, Charlotte M; Bassler, Dirk

    2014-10-28

    The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia, most people with MDS require supportive therapy including repeated red blood cell (RBC) transfusions. In combination with increased iron absorption, this contributes to the accumulation of iron resulting in secondary iron overload and the risk of organ dysfunction and reduced life expectancy. Since the human body has no natural means of removing excess iron, iron chelation therapy, i.e. the pharmacological treatment of iron overload, is usually recommended. However, it is unclear whether or not the newer oral chelator deferasirox leads to relevant benefit. To evaluate the effectiveness and safety of oral deferasirox for managing iron overload in people with myelodysplastic syndrome (MDS). We searched the following databases up to 03 April 2014: MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web of Science, Derwent Drug File and four trial registries: Current Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), ICTRP (www.who.int./ictrp/en/), and German Clinical Trial Register (www.drks.de). Randomised controlled trials (RCTs) comparing deferasirox with no therapy, placebo or with another iron-chelating treatment schedule. We did not identify any trials eligible for inclusion in this review. No trials met our inclusion criteria. However, we identified three ongoing and one completed trial (published as an abstract only and in insufficient detail to permit us to decide on inclusion) comparing deferasirox with deferoxamine, placebo or no treatment. We planned to report evidence from RCTs that evaluated the effectiveness of deferasirox compared to either placebo, no treatment or other chelating regimens, such as deferoxamine, in people with MDS. However, we did not identify any completed RCTs addressing this question.We found three ongoing and one completed RCT (published as an abstract only and

  16. Effect of activation volume on the pressure-induced anomalous resistances in EuFe{sub 2}As{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Kwang-Hua, Chu W., E-mail: xajialj@gmail.com [School of Mechanical Engineering, Qinghai University, Xining 810016 (China); Transfer Centre, 3/F, No. 24, Lane 260, Section 1, Mucha Road, Taipei 116, Taiwan, ROC (China)

    2013-03-29

    Highlights: ► Use quantum chemistry to capture the anomalous transition of EuFe{sub 2}As{sub 2}. ► Activation energy and volume are crucial to the critical temperature. ► Pressure effect of EuFe{sub 2}As{sub 2}-resistances can be captured via our approach. - Abstract: We illustrate the effect of activation volume on the pressure-induced anomalous transitional resistances in EuFe{sub 2}As{sub 2} as well as the frictionless transport of many condensed electrons in FeAs based materials by using the verified transition-state approach which is borrowed from the quantum chemistry. Our results suggest that tuning of activation volume could enhance the onset temperature of critical transitional states.

  17. Parathyroid hormone-related protein (PTHrP) signal cascade modulates myocardial dysfunction in the pressure overloaded heart.

    Science.gov (United States)

    Meyer, Rainer; Schreckenberg, Rolf; Kretschmer, Frank; Bittig, Anne; Conzelmann, Charlotte; Grohé, Christian; Schlüter, Klaus-Dieter

    2007-12-01

    Pressure overload induces the cardiac expression of parathyroid hormone-related protein (PTHrP). Plasma levels are elevated in patients with heart disease. It is unknown whether this represents an epiphenomenon or suggests involvement in hypertrophy. To identify a potential role of PTHrP in pressure induced hypertrophy and heart failure. Pressure load was produced via thoracic aortic constriction (TAC) and application of a PTHrP antagonist (PTHrP(7-34)) via osmotic minipumps in mice. Main findings were confirmed in vitro by exposing isolated adult ventricular mice cardiomyocytes to PTHrP(1-34) (100 nmol/l). TAC treated animals developed myocardial hypertrophy within 2 weeks. The heart weight to body weight ratio increased from 5.02+/-0.14 mg/g (sham/vehicle) and 5.16+/-0.19 mg/g (sham/antagonist) to 6.59+/-0.85 mg/g (TAC/vehicle) and 7.07+/-0.80 mg/g (TAC/antagonist) (each n=6-8; pPTHrP(1-34) developed reduced cell shortening. This reduction in cell function was abolished in the co-presence of the antagonist. PTHrP contributes to the progression of cardiac dysfunction in the pressure overloaded heart.

  18. Iron overload in the liver diagnostic and quantification

    Energy Technology Data Exchange (ETDEWEB)

    Alustiza, Jose M. [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain)]. E-mail: jmalustiza@osatek.es; Castiella, Agustin [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Juan, Maria D. de [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Emparanza, Jose I. [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Artetxe, Jose [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Uranga, Maite [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain)

    2007-03-15

    Hereditary Hemochromatosis is the most frequent modality of iron overload. Since 1996 genetic tests have facilitated significantly the non-invasive diagnosis of the disease. There are however many cases of negative genetic tests that require confirmation by hepatic iron quantification which is traditionally performed by hepatic biopsy. There are many studies that have demonstrated the possibility of performing hepatic iron quantification with Magnetic Resonance. However, a consensus has not been reached yet regarding the technique or the possibility to reproduce the same method of calculus in different machines. This article reviews the state of the art of the question and delineates possible future lines to standardise this non-invasive method of hepatic iron quantification.

  19. Biological tissue magnetism in the frame of iron overload diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lazaro, Francisco J. [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, Zaragoza 50018 (Spain) and Instituto de Nanociencia de Aragon, Universidad de Zaragoza, Zaragoza 50009 (Spain)]. E-mail: osoro@unizar.es; Gutierrez, Lucia [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, Zaragoza 50018 (Spain); Abadia, Ana R. [Departamento de Farmacologia y Fisiologia, Universidad de Zaragoza, Zaragoza 50013 (Spain); Romero, Maria S. [Departamento de Medicina y Psiquiatria, Universidad de Zaragoza, Zaragoza 50009 (Spain); Lopez, A. [CNAM-Salesianos Zaragoza, Zaragoza 50009 (Spain)

    2007-09-15

    The conspicuous magnetic properties of iron, paradoxically, rarely participate in the methods routinely employed in the clinical environment to detect iron containing species in tissues. In the organism iron is just a trace metal and it mostly occurs as part of haemoproteins or ferritin, which show paramagnetic, diamagnetic or antiferromagnetic behaviour, hence resulting in a very low contribution to the tissue susceptibility. Detailed magnetic measurements make it nowadays possible to identify such species in tissues that correspond to individuals with iron overload pathologies. Since, as alternatives to the conventional biopsy, magnetism-based noninvasive techniques to diagnose and manage such diseases are recently under development, the deep knowledge of the magnetic properties of the different forms of iron in tissues is of high applied interest.

  20. Deferasirox for managing iron overload in people with thalassaemia.

    Science.gov (United States)

    Bollig, Claudia; Schell, Lisa K; Rücker, Gerta; Allert, Roman; Motschall, Edith; Niemeyer, Charlotte M; Bassler, Dirk; Meerpohl, Joerg J

    2017-08-15

    Thalassaemia is a hereditary anaemia due to ineffective erythropoiesis. In particular, people with thalassaemia major develop secondary iron overload resulting from regular red blood cell transfusions. Iron chelation therapy is needed to prevent long-term complications.Both deferoxamine and deferiprone are effective; however, a review of the effectiveness and safety of the newer oral chelator deferasirox in people with thalassaemia is needed. To assess the effectiveness and safety of oral deferasirox in people with thalassaemia and iron overload. We searched the Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 12 August 2016.We also searched MEDLINE, Embase, the Cochrane Library, Biosis Previews, Web of Science Core Collection and three trial registries: ClinicalTrials.gov; the WHO International Clinical Trials Registry Platform; and the Internet Portal of the German Clinical Trials Register: 06 and 07 August 2015. Randomised controlled studies comparing deferasirox with no therapy or placebo or with another iron-chelating treatment. Two authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. Sixteen studies involving 1807 randomised participants (range 23 to 586 participants) were included. Twelve two-arm studies compared deferasirox to placebo (two studies) or deferoxamine (seven studies) or deferiprone (one study) or the combination of deferasirox and deferoxamine to deferoxamine alone (one study). One study compared the combination of deferasirox and deferiprone to deferiprone in combination with deferoxamine. Three three-arm studies compared deferasirox to deferoxamine and deferiprone (two studies) or the combination of deferasirox and deferiprone to deferiprone and deferasirox monotherapy respectively (one study). One four-arm study compared two different doses of deferasirox to matching placebo groups.The two studies (a pharmacokinetic and a dose-escalation study

  1. Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle

    Science.gov (United States)

    Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

    2016-01-01

    Background Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. Methods A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Results Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users. Conclusions The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient. PMID:27442587

  2. Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle.

    Directory of Open Access Journals (Sweden)

    Yusra Habib Khan

    Full Text Available Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy.A total 312 non-dialysis dependent CKD (NDD-CKD patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI equation.Out of 312 patients, 64 (20.5% were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1% and 135 (43.4% patients. Overall 144 patients were using diuretics among which 98 (72.6% were hypervolemic, 35 (30.9% euvolemic and 11 (17.2% were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5% patients initiated renal replacement therapy (RRT and need of RRT was more profound among diuretic users.The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient.

  3. Oxidative damage to rat brain in iron and copper overloads.

    Science.gov (United States)

    Musacco-Sebio, Rosario; Ferrarotti, Nidia; Saporito-Magriñá, Christian; Semprine, Jimena; Fuda, Julián; Torti, Horacio; Boveris, Alberto; Repetto, Marisa G

    2014-08-01

    This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 μg of Fe per g and from 3.6 to 34 μg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 μg of Fe per g of brain and 15 μg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 μg of Fe per g and 20 μg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 μg of Fe per g and 18% for Cu with a C50 of 10 μg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.

  4. β3 integrin in cardiac fibroblast is critical for extracellular matrix accumulation during pressure overload hypertrophy in mouse.

    Directory of Open Access Journals (Sweden)

    Sundaravadivel Balasubramanian

    Full Text Available The adhesion receptor β3 integrin regulates diverse cellular functions in various tissues. As β3 integrin has been implicated in extracellular matrix (ECM remodeling, we sought to explore the role of β3 integrin in cardiac fibrosis by using wild type (WT and β3 integrin null (β3-/- mice for in vivo pressure overload (PO and in vitro primary cardiac fibroblast phenotypic studies. Compared to WT mice, β3-/- mice upon pressure overload hypertrophy for 4 wk by transverse aortic constriction (TAC showed a substantially reduced accumulation of interstitial fibronectin and collagen. Moreover, pressure overloaded LV from β3-/- mice exhibited reduced levels of both fibroblast proliferation and fibroblast-specific protein-1 (FSP1 expression in early time points of PO. To test if the observed impairment of ECM accumulation in β3-/- mice was due to compromised cardiac fibroblast function, we analyzed primary cardiac fibroblasts from WT and β3-/- mice for adhesion to ECM proteins, cell spreading, proliferation, and migration in response to platelet derived growth factor-BB (PDGF, a growth factor known to promote fibrosis stimulation. Our results showed that β3-/- cardiac fibroblasts exhibited a significant reduction in cell-matrix adhesion, cell spreading, proliferation and migration. In addition, the activation of PDGF receptor associated tyrosine kinase and non-receptor tyrosine kinase Pyk2, upon PDGF stimulation were impaired in β3-/- cells. Adenoviral expression of a dominant negative form of Pyk2 (Y402F resulted in reduced accumulation of fibronectin. These results indicate that β3 integrin-mediated Pyk2 signaling in cardiac fibroblasts plays a critical role in PO-induced cardiac fibrosis.

  5. The relevance of the rat lung response to particle overload for human risk assessment: a workshop consensus report.

    Science.gov (United States)

    2000-01-01

    On 23-24 March 1998, the International Life Sciences Institute (ILSI) Risk Science Institute convened a workshop entitled "Relevance of the Rat Lung Response to Particle Overload for Human Risk Assessment." The workshop addressed the numerous study reports of lung tumors in rats resulting from chronic inhalation exposures to poorly soluble, nonfibrous particles of low acute toxicity and not directly genotoxic. These poorly soluble particles, indicated by the acronym PSPs (e.g., carbon black, coal dust, diesel soot, nonasbestiform talc, and titanium dioxide), elicit tumors in rats when deposition overwhelms the clearance mechanisms of the lung resulting in a condition referred to as "overload." These PSPs have been shown not to induce tumors in mice and hamsters, and the available data in humans are consistently negative. The objectives were twofold: (1) to provide guidance for risk assessment on the interpretation of neoplastic and nonneoplastic responses of the rat lung to PSPs; and (2) to identify important data gaps in our understanding of the lung responses of rats and other species to PSPs. Utilizing the five critical reviews of relevant literature that follow herein and the combined expertise and experience of the 30 workshop participants, a number of questions were addressed. The consensus views of the workshop participants are presented in this report. Because it is still not known with certainty whether high lung burdens of PSPs can lead to lung cancer in humans via mechanisms similar to those of the rat, in the absence of mechanistic data to the contrary it must be assumed that the rat model can identify potential carcinogenic hazards to humans. Since the apparent responsiveness of the rat model at overload is dependent on coexistent chronic active inflammation and cell proliferation, at lower lung doses where chronic active inflammation and cell proliferation are not present, no lung cancer hazard is anticipated.

  6. Post bubble-closeoff fractionation of gases in polar firn and ice cores: effects of accumulation rate on permeation through overloading pressure

    Science.gov (United States)

    Kobashi, T.; Ikeda-Fukazawa, T.; Suwa, M.; Schwander, J.; Kameda, T.; Lundin, J.; Hori, A.; Döring, M.; Leuenberger, M.

    2015-06-01

    Gases in ice cores are invaluable archives of past environmental changes (e.g., the past atmosphere). However, gas fractionation processes after bubble closure in the firn are poorly understood, although increasing evidence indicates preferential leakages of smaller molecules (e.g., neon, oxygen, and argon) from the closed bubbles through ice crystals. These fractionation processes are believed to be responsible for the observed millennial δO2/N2 variations in ice cores, linking ice core chronologies with orbital parameters. Herein, we found that δAr/N2 at decadal resolution on the gas age scale in the GISP2 ice core has a significant negative correlation with accumulation rate over the past 6000 years. Furthermore, the precise temperature and accumulation rate records over the past 4000 years are found to have nearly equal effects on δAr/N2 with sensitivities of 0.72 ± 0.1 ‰ °C-1 and -0.58 ± 0.09 ‰ (0.01 m ice yr-1)-1, respectively. To understand the fractionation processes, we applied a permeation model to "microbubbles (firn. The model indicates that δAr/N2 in the microbubbles is negatively correlated with the accumulation rate as found in the observation, due to changes in overloading pressure. Colder (warmer) temperatures in the firn induce more (less) depletions in δAr/N2. The microbubbles are so depleted in δAr/N2 at the bubble closeoff depth that they dominate the total δAr/N2 changes in spite of their smaller volumes. The model also indicates that δAr/N2 of GISP2 and NGRIP should have experienced several permil of depletion during the storage 14 years after coring. Further understanding of the δAr/N2 and δO2/N2 fractionation processes in the firn may lead to a new proxy for the past temperature and accumulation rate.

  7. Post bubble-closeoff fractionation of gases in polar firn and ice cores: effects of accumulation rate on permeation through overloading pressure

    Directory of Open Access Journals (Sweden)

    T. Kobashi

    2015-06-01

    Full Text Available Gases in ice cores are invaluable archives of past environmental changes (e.g., the past atmosphere. However, gas fractionation processes after bubble closure in the firn are poorly understood, although increasing evidence indicates preferential leakages of smaller molecules (e.g., neon, oxygen, and argon from the closed bubbles through ice crystals. These fractionation processes are believed to be responsible for the observed millennial δO2/N2 variations in ice cores, linking ice core chronologies with orbital parameters. Herein, we found that δAr/N2 at decadal resolution on the gas age scale in the GISP2 ice core has a significant negative correlation with accumulation rate over the past 6000 years. Furthermore, the precise temperature and accumulation rate records over the past 4000 years are found to have nearly equal effects on δAr/N2 with sensitivities of 0.72 ± 0.1 ‰ °C−1 and −0.58 ± 0.09 ‰ (0.01 m ice yr−1−1, respectively. To understand the fractionation processes, we applied a permeation model to "microbubbles (2 in the microbubbles is negatively correlated with the accumulation rate as found in the observation, due to changes in overloading pressure. Colder (warmer temperatures in the firn induce more (less depletions in δAr/N2. The microbubbles are so depleted in δAr/N2 at the bubble closeoff depth that they dominate the total δAr/N2 changes in spite of their smaller volumes. The model also indicates that δAr/N2 of GISP2 and NGRIP should have experienced several permil of depletion during the storage 14 years after coring. Further understanding of the δAr/N2 and δO2/N2 fractionation processes in the firn may lead to a new proxy for the past temperature and accumulation rate.

  8. Relationship between lipidslevelsand right ventricular volume overload in congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    Ying CHEN; Yu TIAN; Gang LIU; Zhen-Guo JI; Kun-Shen LIU; Chao LIU; Xiao-Mei HE; Hong MENG; Qing-Zhen ZHAO; Yu-Zhi ZHEN; Li TIAN; Le WANG; Li-Shuang JI; Guo-Ping MA

    2014-01-01

    BackgroundThe relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechan-isms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels.MethodsWe collected data of clinical characteristics, echocardio-graph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels[including total cho-lesterol(TCL), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), and triglycerides(TG)]and right ventricle end diastolic diameter (RVEDD), left ventricle end diastolic diameter (LVEDD), right atrium diameter (RA), left atrium diameter (LA), or left ventricle ejection fraction (LVEF) were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area.ResultsThere was a significantly inverse correlation between TCL le-vels and RVEDD (r=-0.34,P<0.001) and RA (r=-0.36,P<0.001). Other lipids such as LDL-C, HDL-C, and TG had asimilar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use.ConclusionsLipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as wellas identify a causal relationship, if any.

  9. Sulfite triggers sustained calcium overload in cultured cortical neurons via a redox-dependent mechanism.

    Science.gov (United States)

    Wang, Xiao; Cao, Hui; Guan, Xin-Lei; Long, Li-Hong; Hu, Zhuang-Li; Ni, Lan; Wang, Fang; Chen, Jian-Guo; Wu, Peng-Fei

    2016-09-06

    Sulfite is a compound commonly used as preservative in foods and pharmaceuticals. Many studies have examined the neurotoxicity of sulfite, but its effect on neuronal calcium homeostasis has not yet been reported. Here, we observed the effect of sulfite on the cytosolic free calcium concentration ([Ca(2+)]i) in cultured cortical neurons using Fura-2/AM based calcium imaging technique. Sulfite (250-1000μM) caused a sustained increase in [Ca(2+)]i in the neurons via a dose-dependent manner. In Ca(2+)-free solution, sulfite failed to increase [Ca(2+)]i. After the depletion of the intracellular calcium store, the effect of sulfite on the [Ca(2+)]i was largely abolished. Pharmacological inhibition of phospholipase C (PLC)-inositol 1,4,5-triphosphate (IP3) signaling pathway blocked sulfite-induced increase of [Ca(2+)]i. Interestingly, antioxidants such as trolox and dithiothreitol, abolished the increase of [Ca(2+)]i induced by sulfite. Exposure to sulfite triggered generation of sulfur- and oxygen-centered free radicals in neurons and increased oxidative stress both in the cultured cortical neurons and the prefrontal cortex of rats. Furthemore, sulfite decreased cell viability in cultured cortical neurons via a calcium-dependent manner. Thus, our current study suggests that the redox-dependent calcium overload triggered by sulfite in cortical neuronsmay be involved in its neurotoxicity. Copyright © 2016. Published by Elsevier Ireland Ltd.

  10. Aged Muscle Demonstrates Fiber-Type Adaptations in Response to Mechanical Overload, in the Absence of Myofiber Hypertrophy, Independent of Satellite Cell Abundance.

    Science.gov (United States)

    Lee, Jonah D; Fry, Christopher S; Mula, Jyothi; Kirby, Tyler J; Jackson, Janna R; Liu, Fujun; Yang, Lin; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

    2016-04-01

    Although sarcopenia, age-associated loss of muscle mass and strength, is neither accelerated nor exacerbated by depletion of muscle stem cells, satellite cells, we hypothesized that adaptation in sarcopenic muscle would be compromised. To test this hypothesis, we depleted satellite cells with tamoxifen treatment of Pax7(CreER)-DTA mice at 4 months of age, and 20 months later subjected the plantaris muscle to 2 weeks of mechanical overload. We found myofiber hypertrophy was impaired in aged mice regardless of satellite cell content. Even in the absence of growth, vehicle-treated mice mounted a regenerative response, not apparent in tamoxifen-treated mice. Further, myonuclear accretion occurred in the absence of growth, which was prevented by satellite cell depletion, demonstrating that myonuclear addition is insufficient to drive myofiber hypertrophy. Satellite cell depletion increased extracellular matrix content of aged muscle that was exacerbated by overload, potentially limiting myofiber growth. These results support the idea that satellite cells regulate the muscle environment, and that their loss during aging may contribute to fibrosis, particularly during periods of remodeling. Overload induced a fiber-type composition improvement, independent of satellite cells, suggesting that aged muscle is very responsive to exercise-induced enhancement in oxidative capacity, even with an impaired hypertrophic response. © The Author 2015. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Mycobacterium avium Complex Infection in a Patient with Sickle Cell Disease and Severe Iron Overload

    Directory of Open Access Journals (Sweden)

    Kamal Shemisa

    2014-01-01

    Full Text Available A 34-year-old female with sickle cell anemia (hemoglobin SS disease and severe iron overload presented to our institution with the subacute presentation of recurrent pain crisis, fever of unknown origin, pancytopenia, and weight loss. A CT scan demonstrated both lung and liver nodules concerning for granulomatous disease. Subsequent biopsies of the liver and bone marrow confirmed the presence of noncaseating granulomas and blood cultures isolated Mycobacterium avium complex MAC. Disseminated MAC is considered an opportunistic infection typically diagnosed in the immunocompromised and rarely in immunocompetent patients. An appreciable number of mycobacterial infection cases have been reported in sickle cell disease patients without immune dysfunction. It has been reported that iron overload is known to increase the risk for mycobacterial infection in vitro and in vivo studies. While iron overload is primarily known to cause end organ dysfunction, the clinical relationship with sickle cell disease and disseminated MAC infection has not been reported. Clinical iron overload is a common condition diagnosed in the sub-Saharan African population. High dietary iron, genetic defects in iron trafficking, as well as hemoglobinopathy are believed to be the etiologies for iron overload in this region. Patients with iron overload in this region were 17-fold more likely to die from Mycobacterium tuberculosis. Both experimental and clinical evidence suggest a possible link to iron overload and mycobacterial infections; however larger observational studies are necessary to determine true causality.

  12. Overload of families taking care of elderly people with Alzheimer's Disease: a comparative study

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    Ana Carla Borghi

    2013-07-01

    Full Text Available OBJECTIVE: to compare the overload of the main and secondary family carers of patients with Alzheimer's Disease, and identify which dimension generates most impact. METHOD: a comparative study conducted in the city of Maringá, State of Paraná, with 20 primary carers of elderly patients with Alzheimer's Disease and 20 secondary caregivers. The data was collected in May and June 2012, using the Scale for Assessment of Overload of Members of Psychiatric Patients' Families (FBIS-BR, and the results were analysed using the Mann-Whitney test and analysis of variance. RESULTS: the global objective overload, and also in each subscale, was significantly greater in the group of main caregivers; the subjective overload showed no difference between the groups. Comparing the subscales, the routine assistance provided to the patient had greater influence on objective overload in both groups, and the concern with the elderly patient was the dimension that had most influence on the subjective overload of main caregivers and also of secondary caregivers. CONCLUSION: the differences in overload between the different groups reinforces the need for planning of health care actions for each type of caregiver, seeking to reduce these differences.

  13. Mutation analysis of the transferrin receptor-2 gene in patients with iron overload.

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    Lee, P L; Halloran, C; West, C; Beutler, E

    2001-01-01

    Three mutations in the transferrin receptor-2 gene have recently been identified in four Sicilian families with iron overload who had a normal hemochromatosis gene, HFE (C. Camaschella, personal communication). To determine the extent to which mutations in the transferrin receptor-2 gene occur in other populations with iron overload, we have completely sequenced this gene in 17 whites, 10 Asians, and 8 African Americans with iron overload and a C282C/C282C HFE genotype, as well as 4 subjects without iron overload and homozygous for the mutant HFE C282Y genotype, 5 patients with iron overload and homozygous for the mutant HFE C282Y genotype, and 5 normal individuals. None of the individuals exhibited the Sicilian mutations, Y250X in exon 6, M172K in exon 4, and E60X in exon 2. One iron-overloaded individual of Asian descent exhibited a I238M mutation which was subsequently found to be a polymorphism present in the Asian population at a frequency of 0.0192. The presence of the I238M mutation was not associated with an increase in ferritin or transferrin saturation levels. Three silent polymorphisms were also identified, nt 1770 (D590D) and nt 1851 (A617A) and a polymorphism at nt 2255 in the 3' UTR. Thus, mutations in the transferrin receptor-2 gene were not responsible for the iron overload seen in our subjects.

  14. [Association between fluid overload and acute renal injury after congenital heart disease surgery in infants].

    Science.gov (United States)

    Luo, De-Qiang; Chen, Zi-Li; Dai, Wei; Chen, Feng

    2017-04-01

    To study the association between fluid overload and acute kidney injury (AKI) after congenital heart disease surgery in infants. A retrospective analysis was performed on 88 infants aged less than 6 months who underwent a radical surgery for congenital heart disease. The treatment outcomes were compared between the infants with AKI after surgery and those without. The effect of cumulative fluid overload on treatment outcomes 2 days after surgery was analyzed. The risk factors for the development of AKI after surgery were assessed by logistic regression analysis. Compared with those without AKI after surgery, the patients with AKI had younger age, lower body weights, higher serum creatinine levels and higher vasoactive-inotropic score, as well as longer durations of intraoperative extracorporeal circulation and aortic occlusion (Pfluid overload 2 and 3 days after surgery (Pfluid overload and low cardiac output syndrome were major risk factors for the development of AKI after surgery. The children with cumulative fluid overload >5% at 2 days after surgery had a higher incidence rate of low cardiac output syndrome, a longer duration of mechanical ventilation, a longer length of stay in the ICU, a longer length of hospital stay, and a higher mortality rate (Pfluid overload after surgery for congenital heart disease tend to develop AKI, and fluid overload may be associated with poor outcomes after surgery.

  15. Revaluation of clinical and histological criteria for diagnosis of dysrnetabolic iron overload syndrome

    Institute of Scientific and Technical Information of China (English)

    Alessia Riva; Giorgio Bovo; Alberto Piperno; Paola Trombini; Raffaella Mariani; Alessandra Salvioni; Sabina Coletti; Silvia Bonfadini; Valentina Paolini; Matteo Pozzi; Rita Facchetti

    2008-01-01

    AIM: To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical,biochemical and histopathological findings.METHODS: We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes.The metabolic syndrome (MS) was defined according to ATPⅢ criteria.Iron overload was assessed by liver biopsy.Liver histology was evaluated by Ishak's score and iron accumulation by Deugnier's score; steatosis was diagnosed when present in ≥ 5% of hepatocytes.RESULTS: According to transferrin saturation levels,we observed significant differences in the amount of hepatic iron overload and iron distribution,as well as the number of metabolic abnormalities.Using Receiving Operating Curve analysis,we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overlo