Contemporary Risk Factors and Outcomes of Transfusion-Associated Circulatory Overload.

PubMed

Roubinian, Nareg H; Hendrickson, Jeanne E; Triulzi, Darrell J; Gottschall, Jerome L; Michalkiewicz, Michael; Chowdhury, Dhuly; Kor, Daryl J; Looney, Mark R; Matthay, Michael A; Kleinman, Steven H; Brambilla, Donald; Murphy, Edward L

2018-04-01

Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload. Case-control study. Four tertiary care hospitals. We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity. None. Among 20,845 transfused patients who received 128,263 blood components from May 2015 until July 2016, transfusion-associated circulatory overload incidence was one case per 100 transfused patients. In addition to cardiovascular comorbidities, multivariable analysis identified the following independent predictors of transfusion-associated circulatory overload: acute kidney injury, emergency surgery, pretransfusion diuretic use, and plasma transfusion-the latter especially in females. Compared with matched controls, transfusion-associated circulatory overload cases were more likely to require mechanical ventilation (71% vs 49%; p < 0.001), experienced longer intensive care and hospital lengths of stay following transfusion, and had higher mortality (21% vs 11%; p = 0.02) even after adjustment for other potentially confounding variables. Despite restrictive transfusion practice, transfusion-associated circulatory overload remains a frequent complication of transfusion and is an independent risk factor for in-hospital morbidity and mortality. In addition to cardiovascular and renal risk factors, plasma transfusion was associated with transfusion-associated circulatory overload after controlling for other covariates. Additional research is needed to examine the benefit of reduced erythrocyte or plasma exposure in patients at high risk for transfusion-associated circulatory overload.

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

NASA Technical Reports Server (NTRS)

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.

Steps to Take with the Board to Avoid Walking the Plank.

ERIC Educational Resources Information Center

Papallo, William R.

1990-01-01

A veteran superintendent outlines an eight-step method for achieving success, including assessing the situation, avoiding board overload, coping with stress, deemphasizing egoism, learning to live in the gray zone between policy formation and administration, ensuring effective board decisions, identifying prospective board members, and knowing…

Mindfulness, Resilience, and Burnout Subtypes in Primary Care Physicians: The Possible Mediating Role of Positive and Negative Affect.

PubMed

Montero-Marin, Jesús; Tops, Mattie; Manzanera, Rick; Piva Demarzo, Marcelo M; Álvarez de Mon, Melchor; García-Campayo, Javier

2015-01-01

Primary care health professionals suffer from high levels of burnout. The aim of the present study was to evaluate the associations of mindfulness and resilience with the features of the burnout types (overload, lack of development, neglect) in primary care physicians, taking into account the potential mediating role of negative and positive affect. A cross-sectional design was used. Six hundred and twenty-two Spanish primary care physicians were recruited from an online survey. The Mindful Attention Awareness Scale (MAAS), Connor-Davidson Resilience Scale (CD-RISC), Positive and Negative Affect Schedule (PANAS), and Burnout Clinical Subtype Questionnaire (BCSQ-12) questionnaires were administered. Polychoric correlation matrices were calculated. The unweighted least squares (ULS) method was used for developing structural equation modeling. Mindfulness and resilience presented moderately high associations (φ = 0.46). Links were found between mindfulness and overload (γ = -0.25); resilience and neglect (γ = -0.44); mindfulness and resilience, and negative affect (γ = -0.30 and γ = -0.35, respectively); resilience and positive affect (γ = 0.70); negative affect and overload (β = 0.36); positive affect and lack of development (β = -0.16). The links between the burnout types reached high and positive values between overload and lack of development (β = 0.64), and lack of development and neglect (β = 0.52). The model was a very good fit to the data (GFI = 0.96; AGFI = 0.96; RMSR = 0.06; NFI = 0.95; RFI = 0.95; PRATIO = 0.96). Interventions addressing both mindfulness and resilience can influence burnout subtypes, but their impact may occur in different ways, potentially mediated by positive and negative affect. Both sorts of trainings could constitute possible tools against burnout; however, while mindfulness seems a suitable intervention for preventing its initial stages, resilience may be more effective for treating its advanced stages.

Relationship between Hepatitis C Virus Infection and Iron Overload.

PubMed

Zou, Dong-Mei; Sun, Wan-Ling

2017-04-05

The aim of this study was to summarize the interactions between hepatitis C virus (HCV) infection and iron overload, and to understand the mechanisms of iron overload in chronic hepatitis C (CHC) and the role iron plays in HCV life cycle. This review was based on data in articles published in the PubMed databases up to January 28, 2017, with the keywords "hepatitis C virus", "iron overload", "iron metabolism", "hepcidin", "translation", and "replication". Articles related to iron metabolism, iron overload in patients with CHC, or the effects of iron on HCV life cycle were selected for the review. Iron overload is common in patients with CHC. The mechanisms involve decreased hepcidin levels caused by HCV through signal transducer and activator of transcription 3, mitogen-activated protein kinase, or bone morphogenetic protein/SMAD signaling pathways, and the altered expression of other iron-metabolism-related genes. Some studies found that iron increases HCV replication, while other studies found the opposite result. Most of the studies suggest the positive role of iron on HCV translation, the mechanisms of which involve increased expression levels of factors associated with HCV internal ribosome entry site-dependent translation, such as eukaryotic initiation factor 3 and La protein. The growing literature demonstrates that CHC leads to iron overload, and iron affects the HCV life cycle in turn. Further research should be conducted to clarify the mechanism involved in the complicated interaction between iron and HCV.

The overloaded right heart and ventricular interdependence.

PubMed

Naeije, Robert; Badagliacca, Roberto

2017-10-01

The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Choking Lake Winnipeg

NASA Astrophysics Data System (ADS)

Byrne, J. M.; Little, L. J.; Dodgson, K. A.; MacDonald, R. J.; Graham, J.

2009-12-01

The problems of waterway eutrophication and coastal zone hypoxia are reaching epidemic proportions. Fresh water and coastal marine environments around the world are suffering unprecedented pollution loadings. We are developing an education program to address the dramatic need for public, community and K-12 education about the harsh impacts of elevated nutrient loads on fresh and marine water environments. The Lake Winnipeg watershed is adopted as the poster child of fresh water eutrophication in western North America. The watershed, one of the largest on the continent, is in rapid decline due to pollution, population pressures and water diversion. A concerted education program is needed to change personal and society actions that negatively impact the Winnipeg watershed; and the confluence of the watershed - Lake Winnipeg. But the education program goes beyond Lake Winnipeg. Negative impacts of nutrient loads are adversely affecting environments right to the oceans. Major dead zones that are expanding on our continental shelves due to nutrient overloading threaten to coalesce into extensive regions of marine life die-off. This presentation outlines the documentary education production process under development. We are building a series of Public Service Announcements (PSAs) for national television networks. The PSAs will direct educators, stakeholders and citizens to an associated website with educational video clips detailing the issues of eutrophication and hypoxia. The video clips or webisodes, present interviews with leading scientists. The discussions address the causes of the problems, and presents workable solutions to nutrient overloads from a variety of sources. The webisodes are accompanied by notes and advice to teachers on ways and means to use the webisodes in classrooms. The project is fully funed by a group of Canadian Community Foundations, with the understanding the work wil be available free to educators anywhere in the world. Our education program will enhance public awareness, beg scrutiny of the issues and promote informed discussion about possible solutions. This education program will enlighten all parties and facilitate personal and societal actions to reverse and control pollution of our rivers, lakes and oceans.

Fluid overload and changes in serum creatinine after cardiac surgery: predictors of mortality and longer intensive care stay. A prospective cohort study

PubMed Central

2012-01-01

Introduction Fluid overload is a clinical problem frequently related to cardiac and renal dysfunction. The aim of this study was to evaluate fluid overload and changes in serum creatinine as predictors of cardiovascular mortality and morbidity after cardiac surgery. Methods Patients submitted to heart surgery were prospectively enrolled in this study from September 2010 through August 2011. Clinical and laboratory data were collected from each patient at preoperative and trans-operative moments and fluid overload and creatinine levels were recorded daily after cardiac surgery during their ICU stay. Fluid overload was calculated according to the following formula: (Sum of daily fluid received (L) - total amount of fluid eliminated (L)/preoperative weight (kg) × 100). Preoperative demographic and risk indicators, intra-operative parameters and postoperative information were obtained from medical records. Patients were monitored from surgery until death or discharge from the ICU. We also evaluated the survival status at discharge from the ICU and the length of ICU stay (days) of each patient. Results A total of 502 patients were enrolled in this study. Both fluid overload and changes in serum creatinine correlated with mortality (odds ratio (OR) 1.59; confidence interval (CI): 95% 1.18 to 2.14, P = 0.002 and OR 2.91; CI: 95% 1.92 to 4.40, P <0.001, respectively). Fluid overload played a more important role in the length of intensive care stay than changes in serum creatinine. Fluid overload (%): b coefficient = 0.17; beta coefficient = 0.55, P <0.001); change in creatinine (mg/dL): b coefficient = 0.01; beta coefficient = 0.11, P = 0.003). Conclusions Although both fluid overload and changes in serum creatinine are prognostic markers after cardiac surgery, it seems that progressive fluid overload may be an earlier and more sensitive marker of renal dysfunction affecting heart function and, as such, it would allow earlier intervention and more effective control in post cardiac surgery patients. PMID:22651844

Fracture and crack growth resistance studies of 304 stainless steel weldments relating to retesting of cryogenic vessels

NASA Technical Reports Server (NTRS)

Hall, L. R.; Finger, R. W.

1972-01-01

Fracture and crack growth resistance characteristics of 304 stainless steel alloy weldments as relating to retesting of cryogenic vessels were examined. Welding procedures were typical of those used in full scale vessel fabrication. Fracture resistance survey tests were conducted in room temperature air, liquid nitrogen and liquid hydrogen. In air, both surface-flawed and center-cracked panels containing cracks in weld metal, fusion line, heat-affected zone, or parent metal were tested. In liquid nitrogen and liquid hydrogen, tests were conducted using center-cracked panels containing weld centerline cracks. Load-unload, sustained load, and cyclic load tests were performed in air or hydrogen gas, liquid nitrogen, and liquid hydrogen using surface-flawed specimens containing weld centerline cracks. Results were used to evaluate the effectiveness of periodic proof overloads in assuring safe and reliable operation of over-the-road cryogenic dewars.

Effects of Outlets on Cracking Risk and Integral Stability of Super-High Arch Dams

PubMed Central

Hu, Hang

2014-01-01

In this paper, case study on outlet cracking is first conducted for the Goupitan and Xiaowan arch dams. A nonlinear FEM method is then implemented to study effects of the outlets on integral stability of the Xiluodu arch dam under two loading conditions, i.e., normal loading and overloading conditions. On the basis of the case study and the numerical modelling, the outlet cracking mechanism, risk, and corresponding reinforcement measures are discussed. Furthermore, the numerical simulation reveals that (1) under the normal loading conditions, the optimal distribution of the outlets will contribute to the tensile stress release in the local zone of the dam stream surface and decrease the outlet cracking risk during the operation period. (2) Under the overloading conditions, the cracks initiate around the outlets, then propagate along the horizontal direction, and finally coalesce with those in adjacent outlets, where the yield zone of the dam has a shape of butterfly. Throughout this study, a dam outlet cracking risk control and reinforcement principle is proposed to optimize the outlet design, select the appropriate concrete material, strengthen the temperature control during construction period, design reasonable impounding scheme, and repair the cracks according to their classification. PMID:25152907

Sex steroids do not affect muscle weight, oxidative metabolism or cytosolic androgen reception binding of functionally overloaded rat Plantaris muscles

NASA Technical Reports Server (NTRS)

Max, S. R.; Rance, N.

1983-01-01

The effects of sex steroids on muscle weight and oxidative capacity of rat planaris muscles subjected to functional overload by removal of synergistic muscles were investigated. Ten weeks after bilateral synergist removal, plantaris muscles were significantly hypertrophic compared with unoperated controls. After this period, the ability of the muscles to oxide three substrates of oxidative metabolism was assessed. Experimental procedures are discussed and results are presented herein. Results suggest a lack of beneficial effect of sex hormone status on the process of hypertrophy and on biochemical changes in overloaded muscle. Such findings are not consistent with the idea of synergistic effects of sex steroids and muscle usage.

The role of adenosine in preconditioning by brief pressure overload in rats.

PubMed

Huang, Cheng-Hsiung; Tsai, Shen-Kou; Chiang, Shu-Chiung; Lai, Chang-Chi; Weng, Zen-Chung

2015-08-01

Brief pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits has been previously reported. Its effects in other species are not known. This study investigates effects of pressure overload and the role of adenosine in rats in this study. MI was induced by 40-minute occlusion of the left anterior descending coronary artery followed by 3-hour reperfusion. MI size was determined by triphenyl tetrazolium chloride staining. Brief pressure overload was induced by two 10-minute episodes of partial snaring of the ascending aorta. Systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. The MI size (mean ± standard deviation), expressed as percentage of area at risk, was significantly reduced in the pressure overload group as well as in the ischemic preconditioning group (17.4 ± 3.0% and 18.2 ± 1.5% vs. 26.6 ± 2.4% in the control group, p < 0.001). Pretreatment with 8-(p-sulfophenyl)-theophylline (SPT), an inhibitor of adenosine receptors, did not significantly limit the protection by pressure overload and ischemic preconditioning (18.3 ± 1.5% and 18.2 ± 2.0%, respectively, p < 0.001). SPT itself did not affect the extent of infarct (25.4 ± 2.0%). The hemodynamics, area at risk and mortality were not significantly different among all groups of animals. Brief pressure overload of the left ventricle preconditioned rat myocardium against infarction. Because SPT did not significantly alter MI size reduction, our results did not support a role of adenosine in preconditioning by pressure overload in rats. Copyright © 2013. Published by Elsevier B.V.

Alleviating line overload by line switching

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, H.E.

1988-01-01

Traditionally, the method used by power system dispatchers to reduce or to eliminate line overload conditions has been to shift generation. Such shifts are generally in conflict with the carefully considered economic dispatch of generation. A proper generation schedule has taken into account many factors, such as generator limits, transmission penalties, incremental costs, var support, and system security. Any deviation from this schedule results in increased production cost. Recently, consideration has been given to alleviating line overloads by line switching. In many situations, line switching does not greatly change the transmission penalty factors and, therefore, can be undertaken without seriouslymore » affecting the economic dispatch. It would be convenient for system operators to have a fast, easy-to-operate computer and program available for the evaluation of the efficacy of a line removal (or addition) in dealing with an overload. It is imperative that the operator be properly advised, that a certain line switching reduces the overload and not aggravate the condition. After it has been determined that a line opening (or closing) produces the desired effect, the operator still must assess the consequence of such switching on system security before actually taking such action.« less

Adult daughters providing post-stroke care to a parent: a qualitative study of the impact that role overload has on lifestyle, participation and family relationships.

PubMed

Bastawrous, Marina; Gignac, Monique A; Kapral, Moira K; Cameron, Jill I

2015-06-01

To qualitatively explore daughters' experiences with and response to holding multiple roles while providing post-stroke care to a parent. Qualitative study using a descriptive approach. Semi-structured interviewing was used. Interviews were recorded, transcribed and analyzed to develop themes. General community of a metropolitan city. Twenty-three adult daughters caring for a community-dwelling parent who had suffered a stroke. Not applicable. Not applicable. Role overload is a salient issue for daughter caregivers. This overload is best captured by the analogy of "juggling" multiple role demands and responsibilities. Two key themes suggest that role overload resulting from parent care affects daughters': 1) valued relationships (e.g. challenges develop in their relationship with children and partner); and 2) ability to participate in valued activities (e.g. reduced involvement in leisure activities and restricted employment). Future support efforts should help daughters manage the caregiving role in light of other responsibilities. This can mitigate overload-related strain in valued relationships and decreased participation in valued activities, thereby contributing to better health and well-being for daughter caregivers. © The Author(s) 2014.

To Be Connected or Not To Be Connected? Mobile Messenger Overload, Fatigue, and Mobile Shunning.

PubMed

Shin, Jaewook; Shin, Mincheol

2016-10-01

With the increased adoption of mobile devices, mobile communication is all around us and we are connected anywhere, anytime. Mobile communication in general and mobile messenger service in particular make interpersonal communication in Korea so frequent and convenient. However, being connected too much anywhere and anytime via mobile messenger service appears to lead an increasing number of people to feel fatigue and to decrease mobile communication under some conditions. Based on a sample of 334 respondents, this study empirically investigated the relationships among commercial, noncommercial mobile messenger overload, mobile messenger fatigue, relational self-concept, and mobile shunning behavior. The findings show that (a) the effect of noncommercial mobile messenger overload is stronger than that of commercial mobile messenger overload in increasing mobile messenger fatigue although both positively affect mobile messenger fatigue, (b) relational self-concept has moderating effects on the relationship between mobile messenger overload and mobile messenger fatigue, and that (c) mobile messenger fatigue triggers mobile communicators' shunning behavior through which the communicators increase their intention to avoid mobile communication, to change their mobile phone numbers, and to subscribe to dual number service on one mobile device. When confronted with mobile messenger fatigue caused by mobile messenger overload, mobile messaging service users are likely to shun their mobile communication. Being constantly and conveniently connected appears to be a blessing in disguise.

A multilevel cross-cultural examination of role overload and organizational commitment: investigating the interactive effects of context.

PubMed

Fisher, David M

2014-07-01

Considering the influential nature of context, the current investigation examined whether the relationship between role overload and organizational commitment was affected by various contextual factors. Drawing on the occupational stress literature, structural empowerment and cooperative climate were examined as factors that would mitigate the negative effects of role overload on organizational commitment. In addition, national culture was examined to determine whether empowerment and cooperative climate had consistent moderating effects across cultures. The relationships among these variables were examined using hierarchical linear modeling in a sample of 6,264 employees working at a multinational organization in 337 different work locations across 18 countries. Results suggested that the negative effect of role overload on organizational commitment did not vary as a function of culture in the current sample, but empowerment and cooperative climate had a moderating influence on this relationship. Furthermore, a 3-way interaction was observed between the cultural variable of power distance, empowerment, and role overload in predicting organizational commitment, suggesting that factors that serve to mitigate the negative effects of role overload in one culture may be ineffectual in another. This 3-way interaction was observed regardless of whether Hofstede's (2001) cultural value indices were used or the cultural practice scores from the Global Leadership and Organizational Behavior Effectiveness (GLOBE) project (R. J. House, Hanges, Javidan, Dorfman, & Gupta, 2004).

Comparison of effects of overload on parameters and performance of samarium-cobalt and strontium-ferrite radially oriented permanent magnet brushless DC motors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demerdash, N.A.; Nehl, T.W.; Nyamusa, T.A.

1985-08-01

Effects of high momentary overloads on the samarium-cobalt and strontium-ferrite permanent magnets and the magnetic field in electronically commutated brushless dc machines, as well as their impact on the associated machine parameters were studied. The effect of overload on the machine parameters, and subsequently on the machine system performance was also investigated. This was accomplished through the combined use of finite element analysis of the magnetic field in such machines, perturbation of the magnetic energies to determine machine inductances, and dynamic simulation of the performance of brushless dc machines, when energized from voltage source inverters. These effects were investigated throughmore » application of the above methods to two equivalent 15 hp brushless dc motors, one of which was built with samarium-cobalt magnets, while the other was built with strontium- ferrite magnets. For momentary overloads as high as 4.5 p.u. magnet flux reductions of 29% and 42% of the no load flux were obtained in the samarium-cobalt and strontiumferrite machines, respectively. Corresponding reductions in the line to line armature inductances of 52% and 46% of the no load values were reported for the samarium-cobalt and strontium-ferrite cases, respectively. The overload affected the profiles and magnitudes of armature induced back emfs. Subsequently, the effects of overload on machine parameters were found to have significant impact on the performance of the machine systems, where findings indicate that the samarium-cobalt unit is more suited for higher overload duties than the strontium-ferrite machine.« less

Drawbacks of proactivity: Effects of daily proactivity on daily salivary cortisol and subjective well-being.

PubMed

Fay, Doris; Hüttges, Annett

2017-10-01

The benefit of proactive work behaviors for performance-related outcomes has been well established. However, this approach to studying proactivity has not yet acknowledged its potential implications for the actor's well-being. Drawing on the fact that resources at work are limited and that the workplace is a social system characterized by interdependencies, we proposed that daily proactivity could have a negative effect on daily well-being. We furthermore proposed that this effect should be mediated by work overload and negative affect. We conducted a daily diary study (N = 72) to test the potential negative effects of proactivity on daily well-being. Data was collected across 3 consecutive work days. During several daily measurement occasions, participants reported proactivity, work overload, negative affect, and fatigue. They also provided 4 saliva samples per day, from which cortisol was assayed. Based on the 4 samples, a measure of daily cortisol output was produced. Multilevel analyses showed that daily proactivity was positively associated with higher daily cortisol output. The positive association of daily proactivity with bedtime fatigue was marginally significant. There was no support for a mediating effect of work overload and negative affect. Implications for theory-building on the proactivity-well-being link are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Fetal development and renal function in adult rats prenatally subjected to sodium overload.

PubMed

Cardoso, Henriqueta D; Cabral, Edjair V; Vieira-Filho, Leucio D; Vieyra, Adalberto; Paixão, Ana D O

2009-10-01

The aims of this study were (1) to evaluate two factors that affect fetal development--placental oxidative stress (Ox) and plasma volume (PV)--in dams with sodium overload and (2) to correlate possible alterations in these factors with subsequent modifications in the renal function of adult offspring. Wistar dams were maintained on 0.17 M NaCl instead of water from 20 days before mating until either the twentieth pregnancy day/parturition or weaning. Colorimetric methods were used to measure Ox in maternal and offspring tissues, PV, 24-h urinary protein (U(Prot24 h)) and serum triacylglycerols (TG) and cholesterol (Chol). Renal hemodynamics was evaluated in the offspring at 90 days of age using a blood pressure transducer, a flow probe and inulin clearance to measure mean arterial pressure (MAP), renal blood flow and glomerular filtration rate (GFR), respectively. The number of nephrons (NN) was counted in kidney suspensions. Dams showed unchanged PV, placental Ox and fetal weight but increased U(Prot24 h) (150%, P < 0.05). Prenatally sodium-overloaded pups showed increased U(Prot24 h) (45%, P < 0.05) but unchanged MAP, renal hemodynamics, NN and kidney Ox. Prenatally and postnatally sodium-overloaded rats showed increased U(Prot24 h) (27%, P < 0.05) and kidney Ox (44%, P < 0.05), reduced GFR (12%, P < 0.05), increased PV (26%, P < 0.05) and unchanged MAP and NN. The TG increased in both groups of treated offspring (21%, P < 0.05), whereas Chol increased only in the postnatally sodium-overloaded group. We conclude that salt overload from the prenatal stage until weaning leads to alterations in lipid metabolism and in the renal function of the pups, which are additional to those alterations seen in rats only overloaded prenatally.

Brief pressure overload of the left ventricle reduces myocardial infarct size via activation of protein kinase C.

PubMed

Tang, Chia-Yu; Lai, Chang-Chi; Chiang, Shu-Chiung; Tseng, Kuo-Wei; Huang, Cheng-Hsiung

2015-09-01

We have previously reported that brief pressure overload of the left ventricle reduced myocardial infarct (MI) size. However, the role of protein kinase C (PKC) remains uncertain. In this study, we investigated whether pressure overload reduces MI size by activating PKC. MI was induced by a 40-minute occlusion of the left anterior descending coronary artery and a 3-hour reperfusion in anesthetized Sprague-Dawley rats. MI size was determined using triphenyl tetrazolium chloride staining. Brief pressure overload was achieved by two 10-minute partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and 10-minute reperfusions. Dimethyl sulfoxide (vehicle) or calphostin C (0.1 mg/kg, a specific inhibitor of PKC) was administered intravenously as pretreatment. The MI size, expressed as the percentage of the area at risk, was significantly reduced in the pressure overload group and the ischemic preconditioning group (19.0 ± 2.9% and 18.7 ± 3.0% vs. 26.1 ± 2.6% in the control group, where p < 0.001). Pretreatment with calphostin C significantly limited the protection by pressure overload and ischemic preconditioning (25.2 ± 2.4% and 25.0 ± 2.3%, where p < 0.001). Calphostin C itself did not significantly affect MI size (25.5 ± 2.4%). Additionally, the hemodynamics, area at risk, and mortality were not significantly different. Brief pressure overload of the left ventricle reduced MI size. Since calphostin C significantly limited the decrease of MI size, our results suggested that brief pressure overload reduces MI size via activation of PKC. Copyright © 2015. Published by Elsevier Taiwan.

Chronic Stress in Young German Adults: Who Is Affected? A Prospective Cohort Study.

PubMed

Herrera, Ronald; Berger, Ursula; Genuneit, Jon; Gerlich, Jessica; Nowak, Dennis; Schlotz, Wolff; Vogelberg, Christian; von Mutius, Erika; Weinmayr, Gudrun; Windstetter, Doris; Weigl, Matthias; Radon, Katja

2017-10-31

We aimed to prospectively assess changes in chronic stress among young adults transitioning from high school to university or working life. A population-based cohort in Munich and Dresden (Germany) was followed from age 16-18 (2002-2003) to age 20-23 (2007-2009) ( n = 1688). Using the Trier Inventory for the Assessment of Chronic Stress, two dimensions of stress at university or work were assessed: work overload and work discontent. In the multiple ordinal generalized estimating equations, socio-demographics, stress outside the workplace, and job history were additionally considered. At follow-up, 52% of the population were university students. Work overload increased statistically significantly from first to second follow-up, while work discontent remained constant at the population level. Students, compared to employees, reported a larger increase in work overload (adjusted odds ratio (OR): 1.33; 95% confidence interval (95% CI): 1.07, 1.67), while work discontent did not differ between the groups. In conclusion, work overload increases when young adults transition from school to university/job life, with university students experiencing the largest increase.

Chronic Stress in Young German Adults: Who Is Affected? A Prospective Cohort Study

PubMed Central

Herrera, Ronald; Berger, Ursula; Gerlich, Jessica; Nowak, Dennis; Schlotz, Wolff; Vogelberg, Christian; von Mutius, Erika; Weinmayr, Gudrun; Windstetter, Doris; Weigl, Matthias; Radon, Katja

2017-01-01

We aimed to prospectively assess changes in chronic stress among young adults transitioning from high school to university or working life. A population-based cohort in Munich and Dresden (Germany) was followed from age 16–18 (2002–2003) to age 20–23 (2007–2009) (n = 1688). Using the Trier Inventory for the Assessment of Chronic Stress, two dimensions of stress at university or work were assessed: work overload and work discontent. In the multiple ordinal generalized estimating equations, socio-demographics, stress outside the workplace, and job history were additionally considered. At follow-up, 52% of the population were university students. Work overload increased statistically significantly from first to second follow-up, while work discontent remained constant at the population level. Students, compared to employees, reported a larger increase in work overload (adjusted odds ratio (OR): 1.33; 95% confidence interval (95% CI): 1.07, 1.67), while work discontent did not differ between the groups. In conclusion, work overload increases when young adults transition from school to university/job life, with university students experiencing the largest increase. PMID:29088088

Predicting overload-affected fatigue crack growth in steels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skorupa, M.; Skorupa, A.; Ladecki, B.

1996-12-01

The ability of semi-empirical crack closure models to predict the effect of overloads on fatigue crack growth in low-alloy steels has been investigated. With this purpose, the CORPUS model developed for aircraft metals and spectra has been checked first through comparisons between the simulated and observed results for a low-alloy steel. The CORPUS predictions of crack growth under several types of simple load histories containing overloads appeared generally unconservative which prompted the authors to formulate a new model, more suitable for steels. With the latter approach, the assumed evolution of the crack opening stress during the delayed retardation stage hasmore » been based on experimental results reported for various steels. For all the load sequences considered, the predictions from the proposed model appeared to be by far more accurate than those from CORPUS. Based on the analysis results, the capability of semi-empirical prediction concepts to cover experimentally observed trends that have been reported for sequences with overloads is discussed. Finally, possibilities of improving the model performance are considered.« less

Does information overload prevent chronic patients from reading self-management educational materials?

PubMed

Liu, Chung-Feng; Kuo, Kuang-Ming

2016-05-01

Self-care management is becoming an important part of care for chronic patients. However, various kinds of self-management educational materials which government or healthcare institutions provide for patients may not achieve the expected outcome. One of the critical reasons affecting patients' use intention could be patients' perceived information overload regarding the self-management educational materials. This study proposed an extended model of the Theory of Planned Behavior (TPB), which incorporated perceived information overload, to explore if information overload will prevent chronic patients from reading educational materials for self-care management. The independent variables are attitude, subject norm, perceived behavior control and perceived information overload while the dependent variable is behavior intention to use the self-management educational materials. Perceived information overload is also referred to as an antecedent variable which may has impacts on attitude and perceived behavior control. The cross-sectional study interviewed newly diagnosed chronic patients with coronary artery disease, who are the potential users of the self-management educational materials, in a medical center in Taiwan. Data were analyzed using descriptive statistics of the basic information distribution of the respondents, and structural equation modeling to study the reliability and validity for testing hypotheses. A total of 110 respondents were enrolled in this study and successful interview data were collected from 106 respondents. The result indicates that the patients' perceived information overload of self-management educational materials was validated to have impacts on attitude and perceived behavioral control constructs of the TPB as well as contributing a direct impact on patients' intentions to use self-management educational materials. Besides, subjective norm and perceived behavioral control constructs were validated to have significant impacts on behavioral intentions, whereas the attitude construct was not. Finally, the relationships between information overload and attitude, information overload and intention, subjective norm and intention, as well as perceived behavioral control and intention varied significantly between highly- and less-educated respondents. Differing self-management educational materials for respondents of various educational levels could be formulated to substantially boost the use of self-management educational materials. This study demonstrated a comprehensive framework, which extended perceived information overload into the TPB model, to predict patients' behavioral intention of using self-management educational materials. We expect the results of this study will provide useful insights for studying self-management educational materials usage and information overload from the perspectives of academia, governments, and healthcare providers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Affective Overload: The Effect of Emotive Visual Stimuli on Target Vocabulary Retrieval

ERIC Educational Resources Information Center

Çetin, Yakup; Griffiths, Carol; Özel, Zeynep Ebrar Yetkiner; Kinay, Hüseyin

2016-01-01

There has been considerable interest in cognitive load in recent years, but the effect of affective load and its relationship to mental functioning has not received as much attention. In order to investigate the effects of affective stimuli on cognitive function as manifest in the ability to remember foreign language vocabulary, two groups of…

The relationship between low perceived numeracy and cancer knowledge, beliefs, and affect.

PubMed

Ross, Katherine; Stoler, Justin; Carcioppolo, Nick

2018-01-01

Low numeracy may skew patient perceptions of information about cancer. This paper examines the relationship between self-reported measures of perceived numeracy and cancer knowledge, beliefs, and affect, using results from 3,052 respondents to the 2007 Health Information National Trends Survey (HINTS-3). Chi-squared tests were used to identify differences in responses between high- and low-numeracy groups using three measures of perceived numeracy. Multivariable logistic regression models were used to evaluate the association between the three perceived numeracy measures and cancer information overload, cancer fatalism, cancer prevention knowledge, and cancer worry. Respondents with low perceived numeracy as expressed by discomfort with medical statistics were more likely to report information overload, to display fatalistic attitudes towards cancer, to lack knowledge about cancer prevention, and to indicate that they worried about cancer more frequently. After controlling for sociodemographic characteristics, this measure of perceived numeracy remained significantly associated with information overload, fatalism, lower prevention knowledge, and worry. The other measures of perceived numeracy, which measured understanding and use of health statistics, were not associated with cancer perceptions. Our findings suggest that individuals with low perceived numeracy broadly differ from individuals with high perceived numeracy in their perceptions of cancer and cancer prevention. By improving our understanding of how perceived numeracy affects patient perceptions of cancer, health providers can improve educational strategies and targeted health messaging.

The impact of iron overload and its treatment on quality of life: results from a literature review.

PubMed

Abetz, Linda; Baladi, Jean-Francois; Jones, Paula; Rofail, Diana

2006-09-28

To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED). Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. Few studies measuring the impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL.

Pathogenic Mechanisms Underlying Iron Deficiency and Iron Overload: New Insights for Clinical Application

PubMed Central

van Velden, DP; van Rensburg, SJ; Erasmus, R

2009-01-01

Iron uptake, utilisation, release and storage occur at the gene level. Individuals with variant forms of genes involved in iron metabolism may have different requirements for iron and are likely to respond differently to the same amount of iron in the diet, a concept termed nutrigenetics. Iron deficiency, iron overload and the anemia of inflammation are the commonest iron-related disorders. While at least four types of hereditary iron overload have been identified to date, our knowledge of the genetic basis and consequences of inherited iron deficiency remain limited. The importance of genetic risk factors in relation to iron overload was highlighted with the identification of the HFE gene in 1996. Deleterious mutations in this gene account for 80-90% of inherited iron overload and are associated with loss of iron homeostasis, alterations in inflammatory responses, oxidative stress and in its most severe form, the disorder hereditary haemochromatosis (HH). Elucidation of the genetic basis of HH has led to rapid clinical benefit through drastic reduction in liver biopsies performed as part of the diagnostic work-up of affected patients. Today, detection of a genetic predisposition in the presence of high serum ferritin and transferrin saturation levels is usually sufficient to diagnose HH, thereby addressing the potential danger of inherited iron overload which starts with the same symptoms as iron deficiency, namely chronic fatigue. This review provides the scientific back-up for application of pathology supported genetic testing, a new test concept that is well placed for optimizing clinical benefit to patients with regard to iron status. PMID:27683335

Hemochromatosis and Iron Overload Screening (HEIRS) study design for an evaluation of 100,000 primary care-based adults.

PubMed

McLaren, Christine E; Barton, James C; Adams, Paul C; Harris, Emily L; Acton, Ronald T; Press, Nancy; Reboussin, David M; McLaren, Gordon D; Sholinsky, Phyliss; Walker, Ann P; Gordeuk, Victor R; Leiendecker-Foster, Catherine; Dawkins, Fitzroy W; Eckfeldt, John H; Mellen, Beverly G; Speechley, Mark; Thomson, Elizabeth

2003-02-01

The HEIRS Study will evaluate the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of hemochromatosis and iron overload in a multiethnic, primary care-based sample of 100,000 adults over a 5-year period. Participants are recruited from 5 Field Centers. Laboratory testing and data management and analysis are performed in a Central Laboratory and Coordinating Center, respectively. Participants undergo testing for serum iron measures and common mutations of the hemochromatosis gene ( ) on chromosome 6p and answer questions on demographics, health, and genetic testing attitudes. Participants with elevated values of transferrin saturation and serum ferritin and/or C282Y homozygosity are invited to undergo a comprehensive clinical examination (CCE), as are frequency-matched control subjects. These examinations provide data on personal and family medical history, lifestyle characteristics, physical examination, genetic counseling, and assessment of ethical, legal, and social implications. Primary and secondary causes of iron overload will be distinguished by clinical criteria. Iron overload will be confirmed by quantification of iron stores. Recruiting family members of cases will permit DNA analysis for additional genetic factors that affect iron overload. Of the first 50,520 screened, 51% are white, 24% are African American, 11% are Asian, 11% are Hispanic, and 3% are of other, mixed, or unidentified race; 63% are female and 37% are male. Information from the HEIRS Study will inform policy regarding the feasibility, optimal approach, and potential individual and public health benefits and risks of primary care-based screening for iron overload and hemochromatosis.

Chronic Iron Overload Results in Impaired Bacterial Killing of THP-1 Derived Macrophage through the Inhibition of Lysosomal Acidification

PubMed Central

Kao, Jun-Kai; Wang, Shih-Chung; Ho, Li-Wei; Huang, Shi-Wei; Chang, Shu-Hao; Yang, Rei-Cheng; Ke, Yu-Yuan; Wu, Chun-Ying; Wang, Jiu-Yao; Shieh, Jeng-Jer

2016-01-01

Iron is essential for living organisms and the disturbance of iron homeostasis is associated with altered immune function. Additionally, bacterial infections can cause major complications in instances of chronic iron overload, such as patients with transfusion-dependent thalassemia. Monocytes and macrophages play important roles in maintaining systemic iron homoeostasis and in defense against invading pathogens. However, the effect of iron overload on the function of monocytes and macrophages is unclear. We elucidated the effects of chronic iron overload on human monocytic cell line (THP-1) and THP-1 derived macrophages (TDM) by continuously exposing them to high levels of iron (100 μM) to create I-THP-1 and I-TDM, respectively. Our results show that iron overload did not affect morphology or granularity of I-THP-1, but increased the granularity of I-TDM. Bactericidal assays for non-pathogenic E. coli DH5α, JM109 and pathogenic P. aeruginosa all revealed decreased efficiency with increasing iron concentration in I-TDM. The impaired P. aeruginosa killing ability of human primary monocyte derived macrophages (hMDM) was also found when cells are cultured in iron contained medium. Further studies on the bactericidal activity of I-TDM revealed lysosomal dysfunction associated with the inhibition of lysosomal acidification resulting in increasing lysosomal pH, the impairment of post-translational processing of cathepsins (especially cathepsin D), and decreased autophagic flux. These findings may explain the impaired innate immunity of thalassemic patients with chronic iron overload, suggesting the manipulation of lysosomal function as a novel therapeutic approach. PMID:27244448

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia. (b... that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron...

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia. (b... that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron...

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia. (b... that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron...

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia. (b... that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron...

Stressors of dual-qualification nursing teachers in the ChengDu-ChongQing economic zone of China--a qualitative study.

PubMed

Wu, Youfeng; Liu, Hui; He, Hongyan

2013-12-01

Nursing and teaching are considered risk professions with high levels of stress and burnout. Dual-qualification nursing teachers (DQNT) are nurses who both teach and practise. These nurses face additional stress. This study explored the stressors of DQNT in the Chengdu-Chongqing Economic Zone of China. This qualitative study used in-depth, open-ended interviews. The interview responses were analysed using a grounded theory approach. The participants in this study included 21 DQNT from 5 teaching hospitals in the Chengdu-Chongqing Economic Zone of China. The results indicated that heavy workload, personal safety, inadequate pay, role overload, and poor working environment are stressors of DQNT. Furthermore, Chinese DQNT face violence from patients and students. The study provides a theoretical basis to help DQNT to cope with stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Precision increase in electric drive speed loop of robotic complexes and process lines

NASA Astrophysics Data System (ADS)

Tulegenov, E.; Imanova, A. A.; Platonov, V. V.

2018-05-01

The article presents the principles of synthesis of control structures for highprecision electric drives of robotic complexes and manipulators. It has been theoretically shown and experimentally confirmed that improved characteristics of speed maintenance in the zone of significant overloads are achieved in systems of series excitation. They are achieved due to the redistribution of control signals both in the zone of setting the armature current and in the excitation currents. At the same time, the characteristic of the electromagnetic torque becomes linear because the demagnetizing effect of the armature response is compensated by the setting of the excitation current. It is recommended in those cases when it is necessary to extend the range of speed control with a significant reduction in load to apply structures with two-zone speed control. The regulation of the weakening of the excitation flow is more convenient as a function of the voltage in the armature windings.

Hepatic but not brain iron is rapidly chelated by deferasirox in aceruloplasminemia due to a novel gene mutation

PubMed Central

Finkenstedt, Armin; Wolf, Elisabeth; Höfner, Elmar; Gasser, Bethina Isasi; Bösch, Sylvia; Bakry, Rania; Creus, Marc; Kremser, Christian; Schocke, Michael; Theurl, Milan; Moser, Patrizia; Schranz, Melanie; Bonn, Guenther; Poewe, Werner; Vogel, Wolfgang; Janecke, Andreas R.; Zoller, Heinz

2010-01-01

Background & Aims Aceruloplasminemia is a rare autosomal recessive neurodegenerative disease associated with brain and liver iron accumulation which typically presents with movement disorders, retinal degeneration, and diabetes mellitus. Ceruloplasmin is a multi-copper ferroxidase that is secreted into plasma and facilitates cellular iron export and iron binding to transferrin. Results A novel homozygous ceruloplasmin gene mutation, c.2554+1G>T, was identified as the cause of aceruloplasminemia in three affected siblings. Two siblings presented with movement disorders and diabetes. Complementary DNA sequencing showed that this mutation causes skipping of exon 14 and deletion of amino acids 809–852 while preserving the open reading frame. Western blotting of liver extracts and sera of affected patients showed retention of the abnormal protein in the liver. Aceruloplasminemia was associated with severe brain and liver iron overload, where hepatic mRNA expression of the iron hormone hepcidin was increased, corresponding to the degree of iron overload. Hepatic iron concentration normalized after 3 and 5 months of iron chelation therapy with deferasirox, which was also associated with reduced insulin demands. During short term treatment there was no clinical or imaging evidence for significant effects on brain iron overload. Conclusions Aceruloplasminemia can show an incomplete clinical penetrance but is invariably associated with iron accumulation in the liver and in the brain. Iron accumulation in aceruloplasminemia is a result of defective cellular iron export, where hepcidin regulation is appropriate for the degree of iron overload. Iron chelation with deferasirox was effective in mobilizing hepatic iron but has no effect on brain iron. PMID:20801540

Method for Identification of Results of Dynamic Overloads in Assessment of Safety Use of the Mine Auxiliary Transportation System

NASA Astrophysics Data System (ADS)

Tokarczyk, Jarosław

2016-12-01

Method for identification the effects of dynamic overload affecting the people, which may occur in the emergency state of suspended monorail is presented in the paper. The braking curve using MBS (Multi-Body System) simulation was determined. For this purpose a computational model (MBS) of suspended monorail was developed and two different variants of numerical calculations were carried out. An algorithm of conducting numerical simulations to assess the effects of dynamic overload acting on the suspended monorails' users is also posted in the paper. An example of computational model FEM (Finite Element Method) composed of technical mean and the anthropometrical model ATB (Articulated Total Body) is shown. The simulation results are presented: graph of HIC (Head Injury Criterion) parameter and successive phases of dislocation of ATB model. Generator of computational models for safety criterion, which enables preparation of input data and remote starting the simulation, is proposed.

Sickle cell anemia: the impact of discovery, politics, and business.

PubMed

Xie, Lai-Hua; Doye, Angelia A; Conley, Eric; Gwathmey, Judith K

2013-11-01

Sickle cell anemia affects 100,000 African Americans. Frequent blood transfusions to prevent stroke lead to fatal iron-overload. Iron chelation with deferoxamine (DFO) requires expensive infusions. In the present study, we explore the feasibility of using a new delivery system for DFO, i.e., targeted liposome entrapped DFO (LDFO). Our results reveal that our novel formulation lowered the dosage requirements by 50%-75%, allowed for less frequent and shorter treatment durations, eliminating the need for a pump and the standard multi-night administration of DFO. In an iron-overloaded rat model, LDFO reduced iron in the liver, and also improved cardiac function. The lower dosage and improved safety profile makes our novel LDFO delivery system a highly desirable new therapy. Meanwhile, this system will also provide an ideal model for studying the mechanism of Fe overload-induced arrhythmias. The political and economic factors related to health care disparities are also discussed.

Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload.

PubMed

Dassanayaka, Sujith; Zheng, Yuting; Gibb, Andrew A; Cummins, Timothy D; McNally, Lindsey A; Brittian, Kenneth R; Jagatheesan, Ganapathy; Audam, Timothy N; Long, Bethany W; Brainard, Robert E; Jones, Steven P; Hill, Bradford G

2018-06-01

Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2). An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC) for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Copyright © 2018. Published by Elsevier B.V.

The impact of iron overload and its treatment on quality of life: results from a literature review

PubMed Central

Abetz, Linda; Baladi, Jean-Francois; Jones, Paula; Rofail, Diana

2006-01-01

Background To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. Methods A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED). Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. Results Few studies measuring the impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. Conclusion A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL. PMID:17007645

Pharmacologic inhibition of the enzymatic effects of tissue transglutaminase reduces cardiac fibrosis and attenuates cardiomyocyte hypertrophy following pressure overload.

PubMed

Shinde, Arti V; Su, Ya; Palanski, Brad A; Fujikura, Kana; Garcia, Mario J; Frangogiannis, Nikolaos G

2018-04-01

Tissue transglutaminase (tTG) is a multifunctional protein with a wide range of enzymatic and non-enzymatic functions. We have recently demonstrated that tTG expression is upregulated in the pressure-overloaded myocardium and exerts fibrogenic actions promoting diastolic dysfunction, while preventing chamber dilation. Our current investigation dissects the in vivo and in vitro roles of the enzymatic effects of tTG on fibrotic remodeling in pressure-overloaded myocardium. Using a mouse model of transverse aortic constriction, we demonstrated perivascular and interstitial tTG activation in the remodeling pressure-overloaded heart. tTG inhibition through administration of the selective small molecule tTG inhibitor ERW1041E attenuated left ventricular diastolic dysfunction and reduced cardiomyocyte hypertrophy and interstitial fibrosis in the pressure-overloaded heart, without affecting chamber dimensions and ejection fraction. In vivo, tTG inhibition markedly reduced myocardial collagen mRNA and protein levels and attenuated transcription of fibrosis-associated genes. In contrast, addition of exogenous recombinant tTG to fibroblast-populated collagen pads had no significant effects on collagen transcription, and instead increased synthesis of matrix metalloproteinase (MMP)3 and tissue inhibitor of metalloproteinases (TIMP)1 through transamidase-independent actions. However, enzymatic effects of matrix-bound tTG increased the thickness of pericellular collagen in fibroblast-populated pads. tTG exerts distinct enzymatic and non-enzymatic functions in the remodeling pressure-overloaded heart. The enzymatic effects of tTG are fibrogenic and promote diastolic dysfunction, but do not directly modulate the pro-fibrotic transcriptional program of fibroblasts. Targeting transamidase-dependent actions of tTG may be a promising therapeutic strategy in patients with heart failure and fibrosis-associated diastolic dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of digoxin on cardiac iron content in rat model of iron overload.

PubMed

Nasri, Hamid Reza; Shahouzehi, Beydolah; Masoumi-Ardakani, Yaser; Iranpour, Maryam

2016-07-01

Plasma iron excess can lead to iron accumulation in heart, kidney and liver. Heart failure is a clinical widespread syndrome. In thalassemia, iron overload cardiomyopathy is caused by iron accumulation in the heart that leads to cardiac damage and heart failure. Digoxin increases the intracellular sodium concentration by inhibition of Na+/K+-ATPase that affects Na+/Ca2+ exchanger (NCX), which raises intracellular calcium and thus attenuates heart failure. The mechanism of iron uptake into cardiomyocytes is not exactly understood. We assessed the effect of different concentrations of digoxin on cardiac iron content in rat model of iron overload. Digoxin had been administrated intraperitoneally (IP) for one week before main study began to assure increased digoxin levels. Group 1 received four IP injections of iron-dextran (12.5mg/100g body weight) every 5 days evenly distributed over 20 days. Groups 2-4 received 0.5, 1 and 5 mg/kg/day IP digoxin, respectively. Last three groups 5-7 received iron-dextran as group 1 and digoxin concentrations 0.5, 1 and 5 mg/kg/day, respectively. Cardiac iron contents were significantly higher in iron overload groups that received different concentrations (0.5, 1 and 5 mg/kg/day) of digoxin than their counterparts in control groups and this pattern was also observed in pathology assessment. It seems that digoxin plays an important role in iron transport into heart in iron overload state but exact mechanism of this phenomenon is not clear. L-type Ca2+ channels are good candidates that probably could be involved in iron accumulation in cardiomyocytes. Thus it would be better to reconsider digoxin administration in thalassemia and iron overload conditions.

Pathological gait in children with Legg-Calvé-Perthes disease and proposal for gait modification to decrease the hip joint loading.

PubMed

Svehlík, Martin; Kraus, Tanja; Steinwender, Gerhard; Zwick, Ernst B; Linhart, Wolfgang E

2012-06-01

Legg-Calvé-Perthes disease (LCP) severely limits the range of hip motion and hinders a normal gait. Loading of the hip joint is a major consideration in LCP treatment. The aim of this study was to evaluate gait patterns in LCP and identify gait modifications to decrease the load on the affected hip. Forty children with unilateral LCP were divided into three groups based on the time base integral of the hip abductor moments during single stance on the affected side acquired during instrumented 3D gait analysis. X-rays of the affected hip were classified according to Herring and Catterall. Children in the "unloading" group spontaneously adopted a Duchenne-like gait with pelvis elevation, hip abduction and external rotation during single support phase. The "normal-loading" group showed pelvis elevation with a neutral hip position in the frontal plane. In the "overloading" group the pelvis dropped to the swinging limb at the beginning of stance accompanied by prolonged hip adduction. The time base integral of the hip abductor moments during single stance correlated positively with the X-ray classifications of Herring and Catterall, hip abduction angle and age. Older children preferred to walk in hip adduction during single stance, had more impaired hips and tended to overload them. The hip overloading pattern should be avoided in children with LCP. Gait training to unload the hip might become an integral component of conservative treatment in children with LCP.

Strain Profiling of Fatigue Crack Overload Effects Using Energy Dispersive X-Ray Diffraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Croft,M.; Zhong, Z.; Jisrawi, N.

In this paper, an assessment of commonly used assumptions associated with {Delta}K{sub eff} and their implications on FCG predictions in light of existing experimental and numerical data is presented. In particular, the following assumptions are examined: (1). {Delta}K{sub eff} fully describes cyclic stresses and strains at the crack-tip vicinity. (2). K{sub op} can be determined experimentally or numerically with certain accuracy. (3). Overload alters K{sub op} but not K{sub max} and associated s{sub max} at the crack-tip 'process zone'. (4). Contact of crack faces curtails the crack driving force in terms of {Delta}K{sub eff}. The analysis indicates that there ismore » insufficient support to justify the above assumptions. In contrary, the analysis demonstrates that a two-parameter fatigue crack driving force in terms of {Delta}K and K{sub max}, which accounts for both applied and the internal stresses should be used in FCG analyses and predictions.« less

Managing iron overload in patients with myelodysplastic syndromes with oral deferasirox therapy.

PubMed

Jabbour, Elias; Garcia-Manero, Guillermo; Taher, Ali; Kantarjian, Hagop M

2009-05-01

Patients with myelodysplastic syndromes (MDS) often require chronic RBC transfusions, which can lead to iron overload. Without adequate management, this may cause progressive damage to hepatic, endocrine, and cardiac organs, significantly affecting overall survival. Recent retrospective analyses have suggested that iron chelation provides a survival advantage in iron-overloaded patients with MDS who are given chelation therapy compared with those who are not. Nonetheless, it is evident that iron overload in many patients with MDS is not adequately managed. Clinical evaluation of the once-daily, oral iron chelator deferasirox in MDS populations has indicated that it provides dose-dependent reductions in body iron burden and is generally well tolerated, with a manageable safety profile in adult and pediatric patients. The most common treatment-related adverse events (AEs) included transient, mild-to-moderate gastrointestinal disturbances and skin rash, which rarely required drug discontinuation and resolved spontaneously in most cases. Adequate management of AEs and practical approaches such as patient education and counseling are necessary to ensure that patients remain compliant with therapy. Regular monitoring of serum ferritin levels is key to identifying patients who require iron chelation therapy, and to ensure maintenance of iron levels below the critical level of 1,000 microg/l. The flexible dosing regimen of deferasirox allows dose adjustments to be made in response to trends in serum ferritin, to changes in a patient's transfusional iron intake, and to the objectives of treatment, allowing the full benefit of transfusion therapy without the risks associated with iron overload.

75 FR 46854 - Amendment of the Commission's Rules Regarding Amateur Radio Service Communications During...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-04

... facilities are damaged, overloaded, or destroyed. For example, during Hurricane Katrina, amateur radio... provided other technical aid to the communities affected by Hurricane Katrina. 3. Since amateur radio is...

Muscle, functional and cognitive adaptations after flywheel resistance training in stroke patients: a pilot randomized controlled trial.

PubMed

Fernandez-Gonzalo, Rodrigo; Fernandez-Gonzalo, Sol; Turon, Marc; Prieto, Cristina; Tesch, Per A; García-Carreira, Maria del Carmen

2016-04-06

Resistance exercise (RE) improves neuromuscular function and physical performance after stroke. Yet, the effects of RE emphasizing eccentric (ECC; lengthening) actions on muscle hypertrophy and cognitive function in stroke patients are currently unknown. Thus, this study explored the effects of ECC-overload RE training on skeletal muscle size and function, and cognitive performance in individuals with stroke. Thirty-two individuals with chronic stroke (≥6 months post-stroke) were randomly assigned into a training group (TG; n = 16) performing ECC-overload flywheel RE of the more-affected lower limb (12 weeks, 2 times/week; 4 sets of 7 maximal closed-chain knee extensions; <2 min of contractile activity per session) or a control group (CG; n = 16), maintaining daily routines. Before and after the intervention, quadriceps femoris volume, maximal force and power for each leg were assessed, and functional and dual task performance, and cognitive functions were measured. Quadriceps femoris volume of the more-affected leg increased by 9.4 % in TG. Muscle power of the more-affected, trained (48.2 %), and the less-affected, untrained limb (28.1 %) increased after training. TG showed enhanced balance (8.9 %), gait performance (10.6 %), dual-task performance, executive functions (working memory, verbal fluency tasks), attention, and speed of information processing. CG showed no changes. ECC-overload flywheel resistance exercise comprising 4 min of contractile activity per week offers a powerful aid to regain muscle mass and function, and functional performance in individuals with stroke. While the current intervention improved cognitive functions, the cause-effect relationship, if any, with the concomitant neuromuscular adaptations remains to be explored. Clinical Trials NCT02120846.

Regulation of DMT1 on autophagy and apoptosis in osteoblast

PubMed Central

Liu, Fei; Zhang, Wei-Lin; Meng, Hong-Zheng; Cai, Zheng-Yu; Yang, Mao-Wei

2017-01-01

Iron overload has recently been associated with the changes in the bone microstructure that occur in osteoporosis. However, the effect of iron overload on osteoblasts is unclear. The purpose of this study was to explore the function of divalent metal transporter 1 (DMT1) in the pathological processes of osteoporosis. Osteoblast hFOB1.19 cells were cultured in medium supplemented with different concentrations (0, 50, 100, 200, 300, 400, 500 μmol/L) of ferric ammonium citrate (FAC) as a donor of ferric ions. We used western blotting and immunofluorescence to determine the levels of DMT1 after treatment with FAC. Apoptosis was evaluated by detecting the levels of cleaved caspase 3, BCL2, and BAX with western blotting. Autophagy was evaluated by detecting the levels of LC3 with western blotting and immunofluorescence. Beclin-1 expression was also assessed with western blotting. The autophagy inhibitor 3-methyladenine was used to determine whether autophagy affects the apoptosis induced by FAC. Our results show that FAC increased the levels of DMT1, upregulated the expression of BCL2, and downregulated the apoptosis-related proteins cleaved caspase 3 and BAX. Both LC3I/LC3II levels and beclin-1 were also increased, indicating that FAC increases the accumulation of autophagosomes in hFOB1.19 cells. FAC-induced autophagy was increased by the apoptosis inhibitor 3-MA but was reduced in DMT1 shRNA hFOB1.19 cells. These results suggest that the increased expression of DMT1 induces iron overload and iron overload induces osteoblast autophagy and apoptosis, thus affecting the pathological processes of osteoporosis. Clarifying the mechanisms underlying the effects of DMT1 will allow the identification of novel targets for the prevention and treatment of osteoporosis. PMID:28367088

A new contribution to the classification of stressors affecting nursing professionals

PubMed Central

Puerto, Jesús Cremades; Soler, Loreto Maciá; Montesinos, Maria José López; Marcos, Azucena Pedraz; Chorda, Víctor Manuel González

2017-01-01

Objective: to identify and classify the most important occupational stressors affecting nursing professionals in the medical units within a hospital. Method: quantitative-qualitative, descriptive and prospective study performed with Delphi technique in the medical units of a general university hospital, with a sample of 30 nursing professionals. Results: the stressors were work overload, frequent interruptions in the accomplishment of their tasks, night working, simultaneity of performing different tasks, not having enough time to give emotional support to the patient or lack of time for some patients who need it, among others. Conclusion: the most consensual stressors were ranked as work overload, frequent interruptions in the accomplishment of their tasks, night working and, finally, simultaneity of performing different tasks. These results can be used as a tool in the clinical management of hospital units, aiming to improve the quality of life of nursing professionals, organizational models and, in addition, continuous improvement in clinical treatment. PMID:28562702

Immune Status 'in Children with Beta Thalassemia' in Correlation 'with Iron Overload': Single Center Egyptian Study.

PubMed

Hagag, Adel A; Elgamsy, Mohamed A; El-Asy, Hassan M; Gamal, Rasha M; Elshahaby, Walid N; Abd Elbar, Enaam S

2016-01-01

'Beta thalassemia is inherited hemoglobin disorder resulting in chronic hemolytic anemia that requires lifelong transfusion therapy'. 'Repeated blood transfusions and RBCs hemolysis are the main causes of iron overload', which in addition to immune abnormalities, are common predisposing factors to infections in patients with thalassemia. The Aim of this Work: The aim of this work was to study immune status including T lymphocyte subsets and serum immunoglobulin levels 'in children with beta- thalassemia in correlation with iron overload'. The present 'study was conducted on 40 children with beta thalassemia major under follow up at Hematology Unit, Pediatric Department, Tanta University' 'including 24 males and 16 females with mean' age value of 9. 22 ± 3.9 years and 20 'healthy children of matched age and sex as a control group'. All children included in the study were subjected to; 'complete blood count, Hb electrophoresis, serum iron status', T cell subsets including CD3, CD4 and CD8 and serum immunoglobulin levels including IgM, IgA and IgG. 'Pallor and jaundice were the most common presenting' clinical manifestations. Infective episodes 'were significantly higher in patients' compared with controls. There were significantly lower Hb, MCV and MCH levels and significantly higher WBCs and platelets counts, reticulocytes and lymphocytes percentage in patients than controls and no significant differences in MCHC between patients and controls. Serum ferritin and iron were 'significantly higher but TIBC was significantly lower in' patients than controls. CD3, CD4 and IgM were significantly lower but CD8, IgG, and IgA 'were significantly higher in patients than controls' with negative correlation between CD3, CD4, IgM and ferritin and positive correlation between CD8, IgG, IgA and ferritin. Iron overload can affect humeral and cell mediated immunity in patients with beta thalassemia with reduction of IgM, CD3 and CD4 and elevation of CD8, IgG, and IgA. Regular follow up of patients with beta thalassemia for detection of iron overload as it affects humeral and cell mediated immunity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The epidemic of distraction.

PubMed

Weksler, Marc E; Weksler, Babette B

2012-01-01

Multitasking is a rapidly growing phenomenon affecting all segments of the population but is rarely as successful as its proponents believe. The use of mobile electronic devices contributes importantly to multitasking and cognitive overload. Although personal electronic devices provide many benefits, their adverse effects are frequently overlooked. Personal observation and a review of the scientific literature supports the view that overuse or misuse of personal electronic devices promotes cognitive overload, impairs multitasking and lowers performance at all ages but particularly in the elderly. This phenomenon appears to be rapidly increasing and threatens to become a tsunami as spreading electronic waves cause an 'epidemic of distraction'. Mobile electronic devices often bring benefits to their users in terms of rapid access to information. However, there is a dark side to the increasing addiction to these devices that challenges the health and well-being of the entire population, targeting, in particular, the aged and infirm. New approaches to information gathering can foster creativity if cognitive overload is avoided. Copyright © 2012 S. Karger AG, Basel.

The impact of environmental stressors and types of work contract on occupational stress.

PubMed

Corrêa, Ana Paula; Ferreira, Maria Cristina

2011-05-01

This study aimed to investigate the impact of seven environmental stressors (role conflict, work overload, interpersonal difficulties, work-family conflict, work instability, lack of autonomy and pressure of responsibility) and the nature of the employment contract (permanent or atypical) on three psychological reactions to occupational stress (job satisfaction, positive emotions, and negative emotions at work). 305 Brazilian workers from both sexes participated in this research, distributed between permanent and atypical workers. The results showed that the role conflict and the work overload had a negative impact on job satisfaction. The role conflict had a negative impact on the positive emotions at work, while the pressure of responsibility interfered positively in it. The work overload interfered positively in the negative emotions at work, while the pressure of responsibility interfered negatively in it. The type of contract did not affect significantly any one of the dependent variables. The implications of the results for future research are discussed.

Fluid Overload and Renal Angina Index at Admission Are Associated With Worse Outcomes in Critically Ill Children.

PubMed

Sethi, Sidharth K; Raghunathan, Veena; Shah, Shilpi; Dhaliwal, Maninder; Jha, Pranaw; Kumar, Maneesh; Paluri, Sravanthi; Bansal, Shyam; Mhanna, Maroun J; Raina, Rupesh

2018-01-01

Objectives: We investigated the association of fluid overload and oxygenation in critically sick children, and their correlation with various outcomes (duration of ventilation, ICU stay, and mortality). We also assessed whether renal angina index (RAI) at admission can predict mortality or acute kidney injury (AKI) on day 3 after admission. Design and setting: Prospective study, pediatric intensive care in a tertiary hospital. Duration: June 2013-June 2014. Patients: Patients were included if they needed invasive mechanical ventilation for >24 h and had an indwelling arterial catheter. Patients with congenital heart disease or those who received renal replacement therapy (RRT) were excluded. Methods: Oxygenation index, fluid overload percent (daily, cumulative), RAI at admission and pediatric logistic organ dysfunction (PELOD) score were obtained in all critically ill children. KDIGO classification was used to define AKI, using both creatinine and urine output criteria. Admission data for determination of RAI included the use of vasopressors, invasive mechanical ventilation, percent fluid overload, and change in kidney function (estimated creatinine clearance). Univariable and multivariable approaches were used to assess the relations between fluid overload, oxygenation index and clinical outcomes. An RAI cutoff >8 was used to predict AKI on day 3 of admission and mortality. Results: One hundred and two patients were recruited. Fluid overload predicted oxygenation index in all patients, independent of age, gender and PELOD score ( p < 0.05). Fluid overload was associated with longer duration of ventilation ( p < 0.05), controlled for age, gender, and PELOD score. Day-3 AKI rates were higher in patients with a RAI of 8 or more, and higher areas under the RAI curve had better prediction rates for Day-3 AKI. An RAI <8 had high negative predictive values (80-95%) for Day-3 AKI. RAI was better than traditional markers of pediatric severity of illness (PELOD) score for prediction of AKI on day 3. Conclusions: This study emphasizes that positive fluid balance adversely affects intensive care in critically ill children. Further, the RAI prediction model may help optimize treatment and improve clinical prediction of AKI.

Fluid Overload and Renal Angina Index at Admission Are Associated With Worse Outcomes in Critically Ill Children

PubMed Central

Sethi, Sidharth K.; Raghunathan, Veena; Shah, Shilpi; Dhaliwal, Maninder; Jha, Pranaw; Kumar, Maneesh; Paluri, Sravanthi; Bansal, Shyam; Mhanna, Maroun J.; Raina, Rupesh

2018-01-01

Objectives: We investigated the association of fluid overload and oxygenation in critically sick children, and their correlation with various outcomes (duration of ventilation, ICU stay, and mortality). We also assessed whether renal angina index (RAI) at admission can predict mortality or acute kidney injury (AKI) on day 3 after admission. Design and setting: Prospective study, pediatric intensive care in a tertiary hospital. Duration: June 2013-June 2014. Patients: Patients were included if they needed invasive mechanical ventilation for >24 h and had an indwelling arterial catheter. Patients with congenital heart disease or those who received renal replacement therapy (RRT) were excluded. Methods: Oxygenation index, fluid overload percent (daily, cumulative), RAI at admission and pediatric logistic organ dysfunction (PELOD) score were obtained in all critically ill children. KDIGO classification was used to define AKI, using both creatinine and urine output criteria. Admission data for determination of RAI included the use of vasopressors, invasive mechanical ventilation, percent fluid overload, and change in kidney function (estimated creatinine clearance). Univariable and multivariable approaches were used to assess the relations between fluid overload, oxygenation index and clinical outcomes. An RAI cutoff >8 was used to predict AKI on day 3 of admission and mortality. Results: One hundred and two patients were recruited. Fluid overload predicted oxygenation index in all patients, independent of age, gender and PELOD score (p < 0.05). Fluid overload was associated with longer duration of ventilation (p < 0.05), controlled for age, gender, and PELOD score. Day-3 AKI rates were higher in patients with a RAI of 8 or more, and higher areas under the RAI curve had better prediction rates for Day-3 AKI. An RAI <8 had high negative predictive values (80–95%) for Day-3 AKI. RAI was better than traditional markers of pediatric severity of illness (PELOD) score for prediction of AKI on day 3. Conclusions: This study emphasizes that positive fluid balance adversely affects intensive care in critically ill children. Further, the RAI prediction model may help optimize treatment and improve clinical prediction of AKI. PMID:29765932

Genetic and Dietary Iron Overload Differentially Affect the Course of Salmonella Typhimurium Infection

PubMed Central

Nairz, Manfred; Schroll, Andrea; Haschka, David; Dichtl, Stefanie; Tymoszuk, Piotr; Demetz, Egon; Moser, Patrizia; Haas, Hubertus; Fang, Ferric C.; Theurl, Igor; Weiss, Günter

2017-01-01

Genetic and dietary forms of iron overload have distinctive clinical and pathophysiological features. HFE-associated hereditary hemochromatosis is characterized by overwhelming intestinal iron absorption, parenchymal iron deposition, and macrophage iron depletion. In contrast, excessive dietary iron intake results in iron deposition in macrophages. However, the functional consequences of genetic and dietary iron overload for the control of microbes are incompletely understood. Using Hfe+/+ and Hfe−/− mice in combination with oral iron overload in a model of Salmonella enterica serovar Typhimurium infection, we found animals of either genotype to induce hepcidin antimicrobial peptide expression and hypoferremia following systemic infection in an Hfe-independent manner. As predicted, Hfe−/− mice, a model of hereditary hemochromatosis, displayed reduced spleen iron content, which translated into improved control of Salmonella replication. Salmonella adapted to the iron-poor microenvironment in the spleens of Hfe−/− mice by inducing the expression of its siderophore iron-uptake machinery. Dietary iron loading resulted in higher bacterial numbers in both WT and Hfe−/− mice, although Hfe deficiency still resulted in better pathogen control and improved survival. This suggests that Hfe deficiency may exert protective effects in addition to the control of iron availability for intracellular bacteria. Our data show that a dynamic adaptation of iron metabolism in both immune cells and microbes shapes the host-pathogen interaction in the setting of systemic Salmonella infection. Moreover, Hfe-associated iron overload and dietary iron excess result in different outcomes in infection, indicating that tissue and cellular iron distribution determines the susceptibility to infection with specific pathogens. PMID:28443246

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin.

PubMed

Wagner, Mark C; Campos-Bilderback, Silvia B; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M; Wean, Sarah E; Wei, Yuan; Satlin, Lisa M; Wiggins, Roger C; Witzmann, Frank A; Molitoris, Bruce A

2016-02-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. Copyright © 2016 by the American Society of Nephrology.

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin

PubMed Central

Wagner, Mark C.; Campos-Bilderback, Silvia B.; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M.; Wean, Sarah E.; Wei, Yuan; Satlin, Lisa M.; Wiggins, Roger C.; Witzmann, Frank A.

2016-01-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. PMID:26054544

Dietary fat overload reprograms brown fat mitochondria.

PubMed

Lettieri Barbato, Daniele; Tatulli, Giuseppe; Vegliante, Rolando; Cannata, Stefano M; Bernardini, Sergio; Ciriolo, Maria R; Aquilano, Katia

2015-01-01

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 modulate health and lifespan.

USAF Damage Tolerant Design Handbook: Guidelines for the Analysis and Design of Damage Tolerant Aircraft Structures. Revision B

DTIC Science & Technology

1984-05-01

Effect of Block Programming and Block Size on Crack Growth Life (All Histories Have Same Cycle Content) Alloy : 2024 -T3 Aluminum (Reference 27...1 I 6 o T 1 >0 100 Crack Growth Life for l-in. Crack Growth 1000 Figure 5.1.10, Effect of Humidity on Fatigue Crack Propagation...Growth Life (All Histories Have Same Cycle Content) Alloy : 2024 -T3 Aluminum (Reference 27). 5.2.6 Yield Zone Due to Overload (r T), Current Crack

Overloaded and stressed: A case study of women working in the health care sector.

PubMed

Stevenson, Maggie; Duxbury, Linda

2018-04-23

Although role overload has been shown to be prevalent and consequential, there has been little attempt to develop the associated theory. The fact that the consequences of role overload can be positive or negative implies that the relationship between role overload and perceived stress depends partly on the environment within which role overload is experienced (i.e., the perceived situation) and how the situation is evaluated (i.e., appraised). Guided by cognitive appraisal theory, this study applies qualitative methodology to identify the situation properties that contribute to variable stress reactions to role overload. In this in-depth examination, overloaded female hospital workers were asked to describe what makes role overload situations potentially stressful, to gain an insight into how role overload is appraised. A taxonomy listing 12 role overload situation properties was developed from the findings, providing the first known classification of the situation properties of role overload that can create the potential for stress. The results also reveal clues as to why some people suffer more stress during role overload than others, increase our understanding of the relationship between role overload and perceived stress, and provide a useful tool for examining the environment of role overload. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Mechanical behavior and failure analysis of prosthetic retaining screws after long-term use in vivo. Part 4: Failure analysis of 10 fractured retaining screws retrieved from three patients.

PubMed

Al Jabbari, Youssef S; Fournelle, Raymond; Ziebert, Gerald; Toth, Jeffrey; Iacopino, Anthony M

2008-04-01

The aim of this study was to perform a failure analysis on fractured prosthetic retaining screws after long-term use in vivo. Additionally, the study addresses the commonly asked question regarding whether complex repeated functional occlusal forces initiate fatigue-type cracks in prosthetic retaining screws. Ten fractured prosthetic retaining screws retrieved from three patients treated with fixed detachable hybrid prostheses were subjected to a failure analysis. In patients 1 and 2, the middle three retaining screws of the prostheses were found fractured at retrieval time after they had been in service for 20 and 19 months, respectively. In patient 3, the middle three and one of the posterior retaining screws were found to be fractured at retrieval after they had been in service for 18 months. Low power stereomicroscopy and high-power scanning electron microscopy (SEM) were performed to analyze the fractured surfaces of the retaining screws examining fatigue cracks in greater detail. Typical fatigue failure characterized by ratchet mark formation was revealed by light microscopy and SEM for all examined screws. Using low magnification light microscopy, ratchet marks were visible on the fracture surfaces of only two screws. SEM examination revealed all three classical stages of fatigue failure, and it was possible to see the ratchet marks on the fracture surfaces of all specimens, indicating a fatigue zone. The final catastrophic overload fracture appeared fibrous, indicating ductile fracture. The final overload ductile fracture surfaces showed equiaxed dimples, suggesting tensile overload in all examined screws except in two specimens that showed an elongated dimple pattern indicating shear/tearing overload forces. Fracture of prosthetic retaining screws in hybrid prostheses occurs mainly through a typical fatigue mode involving mostly the middle anterior three screws. Fatigue cracks can grow in more than one prosthetic retaining screw, leading to fracture before the patient or clinician determines that any problem exists.

Co-creating healthful eating behaviors with very young children: The impact of information overload on primary caregivers.

PubMed

Norton, Julie L; Raciti, Maria M

2017-01-01

Primary caregivers of very young children are subject to excessive and often disparate information regarding the instilling of healthful eating behaviors. Our study focuses on the integration of the operant resources of primary caregivers (i.e., their knowledge and modeling skills) and that of their very young children (i.e., their self-regulation of energy intake and food preferences) to co-create healthful eating behaviors as a measure to curb overweight and obesity in adulthood. Our two-stage qualitative study makes original contributions demonstrating that primary caregivers' efforts to co-create healthful eating behaviors with their very young children are adversely affected by information overload.

Flaw Tolerance In Lap Shear Brazed Joints. Part 2

NASA Technical Reports Server (NTRS)

Wang, Len; Flom, Yury

2003-01-01

This paper presents results of the second part of an on-going effort to gain better understanding of defect tolerance in braze joints. In the first part of this three-part series, we mechanically tested and modeled the strength of the lap joints as a function of the overlap distance. A failure criterion was established based on the zone damage theory, which predicts the dependence of the lap joint shear strength on the overlap distance, based on the critical size of a finite damage zone or an overloaded region in the joint. In this second part of the study, we experimentally verified the applicability of the damage zone criterion on prediction of the shear strength of the lap joint and introduced controlled flaws into the lap joints. The purpose of the study was to evaluate the lap joint strength as a function of flaw size and its location through mechanical testing and nonlinear finite element analysis (FEA) employing damage zone criterion for definition of failure. The results obtained from the second part of the investigation confirmed that the failure of the ductile lap shear brazed joints occurs when the damage zone reaches approximately 10% of the overlap width. The same failure criterion was applicable to the lap joints containing flaws.

The role of fluid overload in the prediction of outcome in acute kidney injury.

PubMed

Selewski, David T; Goldstein, Stuart L

2018-01-01

Our understanding of the epidemiology and the impact of acute kidney injury (AKI) and fluid overload on outcomes has improved significantly over the past several decades. Fluid overload occurs commonly in critically ill children with and without associated AKI. Researchers in pediatric AKI have been at the forefront of describing the impact of fluid overload on outcomes in a variety of populations. A full understanding of this topic is important as fluid overload represents a potentially modifiable risk factor and a target for intervention. In this state-of-the-art review, we comprehensively describe the definition of fluid overload, the impact of fluid overload on kidney function, the impact of fluid overload on the diagnosis of AKI, the association of fluid overload with outcomes, the targeted therapy of fluid overload, and the impact of the timing of renal replacement therapy on outcomes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cha, Min-Ji; Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752; Jang, Jin-Kyung

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,more » 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.« less

Iron overload favors the elimination of Leishmania infantum from mouse tissues through interaction with reactive oxygen and nitrogen species.

PubMed

Vale-Costa, Sílvia; Gomes-Pereira, Sandra; Teixeira, Carlos Miguel; Rosa, Gustavo; Rodrigues, Pedro Nuno; Tomás, Ana; Appelberg, Rui; Gomes, Maria Salomé

2013-01-01

Iron plays a central role in host-parasite interactions, since both intervenients need iron for survival and growth, but are sensitive to iron-mediated toxicity. The host's iron overload is often associated with susceptibility to infection. However, it has been previously reported that iron overload prevented the growth of Leishmania major, an agent of cutaneous leishmaniasis, in BALB/c mice. In order to further clarify the impact of iron modulation on the growth of Leishmania in vivo, we studied the effects of iron supplementation or deprivation on the growth of L. infantum, the causative agent of Mediterranean visceral leishmaniasis, in the mouse model. We found that dietary iron deficiency did not affect the protozoan growth, whereas iron overload decreased its replication in the liver and spleen of a susceptible mouse strain. The fact that the iron-induced inhibitory effect could not be seen in mice deficient in NADPH dependent oxidase or nitric oxide synthase 2 suggests that iron eliminates L. infantum in vivo through the interaction with reactive oxygen and nitrogen species. Iron overload did not significantly alter the mouse adaptive immune response against L. infantum. Furthermore, the inhibitory action of iron towards L. infantum was also observed, in a dose dependent manner, in axenic cultures of promastigotes and amastigotes. Importantly, high iron concentrations were needed to achieve such effects. In conclusion, externally added iron synergizes with the host's oxidative mechanisms of defense in eliminating L. infantum from mouse tissues. Additionally, the direct toxicity of iron against Leishmania suggests a potential use of this metal as a therapeutic tool or the further exploration of iron anti-parasitic mechanisms for the design of new drugs.

Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species

PubMed Central

Vale-Costa, Sílvia; Gomes-Pereira, Sandra; Teixeira, Carlos Miguel; Rosa, Gustavo; Rodrigues, Pedro Nuno; Tomás, Ana; Appelberg, Rui; Gomes, Maria Salomé

2013-01-01

Iron plays a central role in host-parasite interactions, since both intervenients need iron for survival and growth, but are sensitive to iron-mediated toxicity. The host's iron overload is often associated with susceptibility to infection. However, it has been previously reported that iron overload prevented the growth of Leishmania major, an agent of cutaneous leishmaniasis, in BALB/c mice. In order to further clarify the impact of iron modulation on the growth of Leishmania in vivo, we studied the effects of iron supplementation or deprivation on the growth of L. infantum, the causative agent of Mediterranean visceral leishmaniasis, in the mouse model. We found that dietary iron deficiency did not affect the protozoan growth, whereas iron overload decreased its replication in the liver and spleen of a susceptible mouse strain. The fact that the iron-induced inhibitory effect could not be seen in mice deficient in NADPH dependent oxidase or nitric oxide synthase 2 suggests that iron eliminates L. infantum in vivo through the interaction with reactive oxygen and nitrogen species. Iron overload did not significantly alter the mouse adaptive immune response against L. infantum. Furthermore, the inhibitory action of iron towards L. infantum was also observed, in a dose dependent manner, in axenic cultures of promastigotes and amastigotes. Importantly, high iron concentrations were needed to achieve such effects. In conclusion, externally added iron synergizes with the host's oxidative mechanisms of defense in eliminating L. infantum from mouse tissues. Additionally, the direct toxicity of iron against Leishmania suggests a potential use of this metal as a therapeutic tool or the further exploration of iron anti-parasitic mechanisms for the design of new drugs. PMID:23459556

How Obesity Affects Tendons?

PubMed

Abate, Michele; Salini, Vincenzo; Andia, Isabel

Several epidemiological and clinical observations have definitely demonstrated that obesity has harmful effects on tendons. The pathogenesis of tendon damage is multi-factorial. In addition to overload, attributable to the increased body weight, which significantly affects load-bearing tendons, systemic factors play a relevant role. Several bioactive peptides (chemerin, leptin, adiponectin and others) are released by adipocytes, and influence tendon structure by means of negative activities on mesenchymal cells. The ensuing systemic state of chronic, sub-clinic, low-grade inflammation can damage tendon structure. Metabolic disorders (diabetes, impaired glucose tolerance, and dislipidemia), frequently associated with visceral adiposity, are concurrent pathogenetic factors. Indeed, high glucose levels increase the formation of Advanced Glycation End-products, which in turn form stable covalent cross-links within collagen fibers, modifying their structure and functionality.Sport activities, so useful for preventing important cardiovascular complications, may be detrimental for tendons if they are submitted to intense acute or chronic overload. Therefore, two caution rules are mandatory: first, to engage in personalized soft training program, and secondly to follow regular check-up for tendon pathology.

Clinical Management of Implant Prostheses in Patients with Bruxism

PubMed Central

Komiyama, Osamu; Lobbezoo, Frank; De Laat, Antoon; Iida, Takashi; Kitagawa, Tsuyoshi; Murakami, Hiroshi; Kato, Takao; Kawara, Misao

2012-01-01

There is general agreement that excessive stress to the bone-implant interface may result in implant overload and failure. Early failure of the implant due to excessive loading occurs shortly after uncovering the implant. Excess load on a final restoration after successful implant integration can result in physical failure of the implant structure. Many clinicians believe that overload of dental implants is a risk factor for vertical peri-implant bone loss and/or may be detrimental for the suprastructure in implant prostheses. It has been documented that occlusal parafunction, such as, bruxism (tooth grinding and clenching) affects the outcome of implant prostheses, but there is no evidence for a causal relation between the failures and overload of dental implants. In spite of this lack of evidence, often metal restorations are preferred instead of porcelain for patients in whom bruxism is presumed on the basis of tooth wear. The purpose of this paper is to discuss the importance of the occlusal scheme used in implant restorations for implant longevity and to suggest a clinical approach and occlusal materials for implant prostheses in order to prevent complications related to bruxism. PMID:22701484

Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy.

PubMed

Das, Subhash K; Wang, Wang; Zhabyeyev, Pavel; Basu, Ratnadeep; McLean, Brent; Fan, Dong; Parajuli, Nirmal; DesAulniers, Jessica; Patel, Vaibhav B; Hajjar, Roger J; Dyck, Jason R B; Kassiri, Zamaneh; Oudit, Gavin Y

2015-12-07

Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca(2+) homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca(2+) homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload.

Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy

PubMed Central

Das, Subhash K.; Wang, Wang; Zhabyeyev, Pavel; Basu, Ratnadeep; McLean, Brent; Fan, Dong; Parajuli, Nirmal; DesAulniers, Jessica; Patel, Vaibhav B.; Hajjar, Roger J.; Dyck, Jason R. B.; Kassiri, Zamaneh; Oudit, Gavin Y.

2015-01-01

Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca2+ homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca2+ homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload. PMID:26638758

Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

PubMed

Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

2015-04-01

Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

Applying the concept of consumer confusion to healthcare: development and validation of a patient confusion model.

PubMed

Gebele, Christoph; Tscheulin, Dieter K; Lindenmeier, Jörg; Drevs, Florian; Seemann, Ann-Kathrin

2014-01-01

As patient autonomy and consumer sovereignty increase, information provision is considered essential to decrease information asymmetries between healthcare service providers and patients. However, greater availability of third party information sources can have negative side effects. Patients can be confused by the nature, as well as the amount, of quality information when making choices among competing health care providers. Therefore, the present study explores how information may cause patient confusion and affect the behavioral intention to choose a health care provider. Based on a quota sample of German citizens (n = 198), the present study validates a model of patient confusion in the context of hospital choice. The study results reveal that perceived information overload, perceived similarity, and perceived ambiguity of health information impact the affective and cognitive components of patient confusion. Confused patients have a stronger inclination to hastily narrow down their set of possible decision alternatives. Finally, an empirical analysis reveals that the affective and cognitive components of patient confusion mediate perceived information overload, perceived similarity, and perceived ambiguity of information. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Immune cell functions in iron overload.

PubMed Central

de Sousa, M

1989-01-01

A number of studies done in the last 10 years demonstrate the importance of iron in regulating the expression of T lymphoid cell surface markers, in influencing the expansion of different T cell subsets and in affecting different immune cell functions in vitro. It has been argued that some of the results obtained could be explained by the formation of iron polymers in the experimental conditions used in vitro (Soyano Fernandez & Romano, 1985). In this review the results of studies of immunological function in clinical situations of iron overload are analysed. From this analysis, it is concluded that the majority of the observations made in vitro have a counterpart in vivo, thus providing additional compelling evidence for the importance of iron as an immunoregulator. PMID:2649280

Overloading among crash-involved vehicles in China: identification of factors associated with overloading and crash severity.

PubMed

Zhang, Guangnan; Li, Yanyan; King, Mark J; Zhong, Qiaoting

2018-03-21

Motor vehicle overloading is correlated with the possibility of road crash occurrence and severity. Although overloading of motor vehicles is pervasive in developing nations, few empirical analyses have been performed on factors that might influence the occurrence of overloading. This study aims to address this shortcoming by seeking evidence from several years of crash data from Guangdong province, China. Data on overloading and other factors are extracted for crash-involved vehicles from traffic crash records for 2006-2010 provided by the Traffic Management Bureau in Guangdong province. Logistic regression is applied to identify risk factors for overloading in crash-involved vehicles and within these crashes to identify factors contributing to greater crash severity. Driver, vehicle, road and environmental characteristics and violation types are considered in the regression models. In addition to the basic logistic models, association analysis is employed to identify the potential interactions among different risk factors during fitting the logistic models of overloading and severity. Crash-involved vehicles driven by males from rural households and in an unsafe condition are more likely to be overloaded and to be involved in higher severity overloaded vehicle crashes. If overloaded vehicles speed, the risk of severe traffic crash casualties increases. Young drivers (aged under 25 years) in mountainous areas are more likely to be involved in higher severity overloaded vehicle crashes. This study identifies several factors associated with overloading in crash-involved vehicles and with higher severity overloading crashes and provides an important reference for future research on those specific risk factors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Females Are Protected From Iron-Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress.

PubMed

Das, Subhash K; Patel, Vaibhav B; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y

2017-01-23

Sex-related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron-overload cardiomyopathy is poorly understood. Male and female wild-type and hemojuvelin-null mice were injected and fed with a high-iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron-overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron-overloaded mice based on echocardiographic and invasive pressure-volume analyses. Female mice demonstrated a marked suppression of iron-mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron-overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron-induced upregulation of ferritin, decreased myocardial SERCA2a levels, and increased NCX1 levels. 17β-Estradiol therapy rescued the iron-overload cardiomyopathy in male wild-type mice. The responses in wild-type and hemojuvelin-null female mice were remarkably similar, highlighting a conserved mechanism of sex-dependent protection from iron-overload-mediated cardiac injury. Male and female mice respond differently to iron-overload-mediated effects on heart structure and function, and females are markedly protected from iron-overload cardiomyopathy. Ovariectomy in female mice exacerbated iron-induced myocardial injury and precipitated severe cardiac dysfunction during iron-overload conditions, whereas 17β-estradiol therapy was protective in male iron-overloaded mice. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The Impact of Urban Development in the Arid Zone and its Management.

NASA Astrophysics Data System (ADS)

Gat, J. R.

2002-05-01

From the experience in humid and semi-arid settings, the immediate impact of urbanization on the hydrological system is the interference with the natural direct infiltration pathways, resulting in a decrease of groundwater recharge as well as the possibility of surface flooding. In contrast, in the arid environment the limited rain amounts and number of rain events makes the contribution of rain of marginal importance in the city's water balance. The major impact of urbanization in the arid zone is the continuous excess of discharge of treated or untreated sewage or water spills, originating from the import of water to the city's water supply. Their effect can be advantageous if properly channeled. On the other hand, the polluting potential of these water excesses as well as the possibility of mobilizing stored salinity in the downstream locations is of concern, if the natural drainage network and its remediation capacity becomes overloaded. Further, since the arid zone hydrological cycle depends naturally on a discontinuous and episodal groundwater recharge pattern, the new situation requires the re-assessment of the eco-hydrological patterns in the downstream location.

Physical activity behavior and role overload in mothers.

PubMed

Lovell, Geoff P; Butler, Frances R

2015-01-01

We examined physical activity stages of change, physical activity behavior, and role overload in different stages of motherhood in a predominantly Australian sample. Neither physical activity behavior, stages of physical activity change, nor role overload significantly differed across motherhood groups. Role overload was significantly higher for mothers in the contemplation, planning, and action stages of physical activity than in the maintenance stage of change. Role overload had a weak, although significant, negative correlation with leisure-time physical activity. We conclude that strategies focused upon reducing role overload or perceived role overload have only limited potential to meaningfully increase leisure-time physical activity in mothers.

Hypertrophic response to hemodynamic overload: role of load vs. renin-angiotensin system activation

NASA Technical Reports Server (NTRS)

Koide, M.; Carabello, B. A.; Conrad, C. C.; Buckley, J. M.; DeFreyte, G.; Barnes, M.; Tomanek, R. J.; Wei, C. C.; Dell'Italia, L. J.; Cooper, G. 4th;

Iron overload patients with unknown etiology from national survey in Japan.

PubMed

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.

Fluid imbalance

MedlinePlus

... up in the body. This is called fluid overload (volume overload). This can lead to edema (excess fluid in ... Water imbalance; Fluid imbalance - dehydration; Fluid buildup; Fluid overload; Volume overload; Loss of fluids; Edema - fluid imbalance; ...

CONIFER - Non-Interventional Study to Evaluate Therapy Monitoring During Deferasirox Treatment of Iron Toxicity in Myelodysplastic Syndrome Patients with Transfusional Iron Overload.

PubMed

Bruch, Harald-Robert; Dencausse, Yves; Heßling, Jörg; Michl, Gerlinde; Schlag, Rudolf; Skorupa, Alexandra; Schneider-Schranz, Cornelia; Wolf, Sebastian; Schulte, Clemens; Tesch, Hans

2016-01-01

The non-interventional study CONIFER was designed to assess the safety and clinical practicability of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome (MDS) patients. Patients included in the study were diagnosed with MDS and received at least 1 treatment with deferasirox. The observation period covered the time from the initial visit until the last follow-up. The data of 99 patients with MDS scored mainly as International Prognostic Scoring System (IPSS) low and intermediate 1 were evaluated. The mean age of the participants was 75 years and 58% of the patients were male. Iron overload was assessed by serum ferritin level (mean baseline serum ferritin 2,080 ± 1,244 µg/l). Patients were treated for a mean duration of 16 months (mean daily dose at baseline 11.8 ± 7.0 mg/kg). Stratification of serum ferritin levels by deferasirox dose showed a reduction at the higher but no reduction at the lower dose (< 15 mg/kg vs. ≥ 15 mg/kg and < 20 mg/kg vs. ≥ 20 mg/kg). The majority of patients (81%) were affected by at least 1 adverse event, with decreased renal creatinine clearance being the most frequent. Higher doses (≥ 15 mg/kg) of deferasirox effectively and safely reduced serum ferritin levels in MDS patients with transfusional iron overload. © 2016 S. Karger GmbH, Freiburg.

Molecular pathogenesis and clinical consequences of iron overload in liver cirrhosis.

PubMed

Sikorska, Katarzyna; Bernat, Agnieszka; Wroblewska, Anna

2016-10-01

The liver, as the main iron storage compartment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Excessive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease progression. We have also included literature on adjuvant therapeutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identification of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause significant improvement of liver functions in patients with iron overload. Phlebotomy can have beneficial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and available data suggest that it can be considered as target for adjuvant therapy in this condition.

[Evaluation of comprehensive capacity of resources and environments in Poyang Lake Eco-economic Zone].

PubMed

Song, Yan-Chun; Yu, Dan

2014-10-01

With the development of the society and economy, the contradictions among population, resources and environment are increasingly worse. As a result, the capacity of resources and environment becomes one of the focal issues for many countries and regions. Through investigating and analyzing the present situation and the existing problems of resources and environment in Poyang Lake Eco-economic Zone, seven factors were chosen as the evaluation criterion layer, namely, land resources, water resources, biological resources, mineral resources, ecological-geological environment, water environment and atmospheric environment. Based on the single factor evaluation results and with the county as the evaluation unit, the comprehensive capacity of resources and environment was evaluated by using the state space method in Poyang Lake Eco-economic Zone. The results showed that it boasted abundant biological resources, quality atmosphere and water environment, and relatively stable geological environment, while restricted by land resource, water resource and mineral resource. Currently, although the comprehensive capacity of the resources and environments in Poyang Lake Eco-economic Zone was not overloaded as a whole, it has been the case in some counties/districts. State space model, with clear indication and high accuracy, could serve as another approach to evaluating comprehensive capacity of regional resources and environment.

[The elbow joint - a diagnostic challenge : anatomy, biomechanics, and pathology].

PubMed

Schueller-Weidekamm, C; Kainberger, F

2008-12-01

The elbow is one of the most commonly injured joints in sports activities. In particular, weight lifters, golfers, tennis players, and pitchers are affected. Injuries in sports involving overhead throwing are commonly based on the pathophysiologic model of valgus extension overload syndrome. The injuries are commonly complex and demand a good knowledge of the symptoms, the exact anatomy, and the biomechanics to arrive at a precise radiologic diagnosis. The characteristic patterns of injury that occur in specific sports activities are related to a combination of increased varus or valgus and extension or flexion overload that results in tensile forces and/or compression and shear stress. Acute symptoms are frequently based on chronic degeneration of the tendons and ligamentous structures due to repetitive microtrauma from overuse syndrome.

The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis.

PubMed

Valenti, L; Conte, D; Piperno, A; Dongiovanni, P; Fracanzani, A L; Fraquelli, M; Vergani, A; Gianni, C; Carmagnola, L; Fargion, S

2004-12-01

The A16V mitochondrial targeting sequence polymorphism influences the antioxidant activity of MnSOD, an enzyme involved in neutralising iron induced oxidative stress. Patients with hereditary haemochromatosis develop parenchymal iron overload, which may lead to cirrhosis, diabetes, hypogonadism, and heart disease. The objective of this study was to determine in patients with haemochromatosis whether the presence of the Val MnSOD allele, associated with reduced enzymatic activity, affects tissue damage, and in particular heart disease, as MnSOD knockout mice develop lethal cardiomyopathy. We studied 217 consecutive unrelated probands with haemochromatosis, and 212 healthy controls. MnSOD polymorphism was evaluated by restriction analysis. The frequency distribution of the polymorphism did not differ between patients and controls. Patients carrying the Val allele had higher prevalence of cardiomyopathy (A/A 4%, A/V 11%, V/V 30%, p = 0.0006) but not of cirrhosis, diabetes, or hypogonadism, independently of age, sex, alcohol misuse, diabetes, and iron overload (odds ratio 10.1 for V/V, p = 0.006). The frequency of the Val allele was higher in patients with cardiomyopathy (0.67 v 0.45, p = 0.003). The association was significant in both C282Y+/+ (p = 0.02), and in non-C282Y+/+ patients (p = 0.003), and for both dilated (p = 0.01) and non-dilated stage (p = 0.04) cardiomyopathy, but not for ischaemic heart disease. In patients with hereditary haemochromatosis, the MnSOD genotype affects the risk of cardiomyopathy related to iron overload and possibly to other known and unknown risk factors and could represent an iron toxicity modifier gene.

An Evaluation of Overload Retardation Behavior and Overload Retardation Models of Ti-6Al-4V Sheet Titanium Alloy,

DTIC Science & Technology

1983-11-17

Oat"UaL msue.(rm ~10"ee 66147 effe% nowe. 1.12a, **04 VON"* a Poest 46"a of04 ~ ah es ie [Z-3)~ totego~is f ht * g IM M..s~U~ -• - - -- L.. s. K varying...time course.* That £ 5 , the method of combining and considering the overload retardation models on the basis of the successive accumlation method in...Hysteresis stage of overload retardation (B); 3) Maximum retardation point of overload (C); 4) weakened stage of overload retardation’CD); 5 ) Basic

Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.

PubMed

Zheng, Qing-Qing; Zhao, You-Shan; Guo, Juan; Zhao, Si-da; Song, Lu-Xi; Fei, Cheng-Ming; Zhang, Zheng; Li, Xiao; Chang, Chun-Kang

2017-07-01

Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload. Copyright © 2017 Elsevier Ltd. All rights reserved.

Guiding Exploration through Three-Dimensional Virtual Environments: A Cognitive Load Reduction Approach

ERIC Educational Resources Information Center

Chen, Chwen Jen; Fauzy Wan Ismail, Wan Mohd

2008-01-01

The real-time interactive nature of three-dimensional virtual environments (VEs) makes this technology very appropriate for exploratory learning purposes. However, many studies have shown that the exploration process may cause cognitive overload that affects the learning of domain knowledge. This article reports a quasi-experimental study that…

Rhetorical Roulette: Does Writing-Faculty Overload Disable Effective Response to Student Writing?

ERIC Educational Resources Information Center

Lee, Melanie

2009-01-01

This article describes a pilot study that suggests writing-faculty workload may affect the pedagogical focus and rhetorical effectiveness of written response to students' essays. To study the relationship between writing-faculty workload and comments that faculty write on students' essays, the author sent an eleven-question survey to 30 English…

Mechanisms of Divalent Metal Toxicity in Affective Disorders

PubMed Central

Menon, Archita Venugopal; Chang, JuOae; Kim, Jonghan

2016-01-01

Metals are required for proper brain development and play an important role in a number of neurobiological functions. The Divalent Metal Transporter 1 (DMT1) is a major metal transporter involved in the absorption and metabolism of several essential metals like iron and manganese. However, non-essential divalent metals are also transported through this transporter. Therefore, altered expression of DMT1 can modify the absorption of toxic metals and metal-induced toxicity. An accumulating body of evidence has suggested that increased metal stores in the brain are associated with elevated oxidative stress mediated by the ability of metals to catalyze redox reactions, resulting in abnormal neurobehavioral function and the progression of neurodegenerative diseases. Metal overload has also been implicated in impaired emotional behavior, although the underlying mechanisms are not well understood with limited information. The current review focuses on psychiatric dysfunction associated with imbalanced metabolism of metals that are transported by DMT1. The investigations with respect to the toxic effects of metal overload on behavior and their underlying mechanisms of toxicity could provide several new therapeutic targets to treat metal-associated affective disorders. PMID:26551072

Battling the challenges of training nurses to use information systems through theory-based training material design.

PubMed

Galani, Malatsi; Yu, Ping; Paas, Fred; Chandler, Paul

2014-01-01

The attempts to train nurses to effectively use information systems have had mixed results. One problem is that training materials are not adequately designed to guide trainees to gradually learn to use a system without experiencing a heavy cognitive load. This is because training design often does not take into consideration a learner's cognitive ability to absorb new information in a short training period. Given the high cost and difficulty of organising training in healthcare organisations, there is an urgent need for information system trainers to be aware of how cognitive overload or information overload affect a trainee's capability to acquire new knowledge and skills, and what instructional techniques can be used to facilitate effective learning. This paper introduces the concept of cognitive load and how it affects nurses when learning to use a new health information system. This is followed by the relevant strategies for instructional design, underpinned by the principles of cognitive load theory, which may be helpful for the development of effective instructional materials and activities for training nurses to use information systems.

GLUT4 Is Not Necessary for Overload-Induced Glucose Uptake or Hypertrophic Growth in Mouse Skeletal Muscle

PubMed Central

McMillin, Shawna L.; Schmidt, Denise L.; Kahn, Barbara B.

2017-01-01

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 whether 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 [3H]-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 transporters mediate overload-induced glucose uptake, chemical inhibitors were used. The facilitative GLUT inhibitor cytochalasin B, but not the sodium-dependent glucose cotransport inhibitor phloridzin, prevented overload-induced uptake demonstrating that GLUTs mediate this effect. To assess which GLUT, hexose competition experiments were performed. Overload-induced [3H]-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 twofold to fivefold. 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. PMID:28279980

GLUT4 Is Not Necessary for Overload-Induced Glucose Uptake or Hypertrophic Growth in Mouse Skeletal Muscle.

PubMed

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

2017-06-01

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 whether 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 transporters mediate overload-induced glucose uptake, chemical inhibitors were used. The facilitative GLUT inhibitor cytochalasin B, but not the sodium-dependent glucose cotransport inhibitor phloridzin, prevented overload-induced uptake demonstrating that GLUTs 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 twofold to fivefold. 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. © 2017 by the American Diabetes Association.

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

PubMed

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.

TIMP3 deficiency exacerbates iron overload-mediated cardiomyopathy and liver disease.

PubMed

Zhabyeyev, Pavel; Das, Subhash K; Basu, Ratnadeep; Shen, Mengcheng; Patel, Vaibhav B; Kassiri, Zamaneh; Oudit, Gavin Y

2018-05-01

Chronic iron overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron overload. We investigated the role of tissue inhibitor of metalloproteinase 3 (TIMP3) in iron overload-mediated tissue injury by subjecting male mice lacking Timp3 ( Timp3 -/- ) and wild-type (WT) mice to 12 wk of chronic iron overload. Whereas WT mice with iron overload developed diastolic dysfunction, iron-overloaded Timp3 -/- mice showed worsened cardiac dysfunction coupled with systolic dysfunction. In the heart, loss of Timp3 was associated with increased myocardial fibrosis, greater Timp1, matrix metalloproteinase ( Mmp) 2, and Mmp9 expression, increased active MMP-2 levels, and gelatinase activity. Iron overload in Timp3 -/- mice showed twofold higher iron accumulation in the liver compared with WT mice because of constituently lower levels of ferroportin. Loss of Timp3 enhanced the hepatic inflammatory response to iron overload, leading to greater neutrophil and macrophage infiltration and increased hepatic fibrosis. Expression of inflammation-related MMPs (MMP-12 and MMP-13) and inflammatory cytokines (IL-1β and monocyte chemoattractant protein-1) was elevated to a greater extent in iron-overloaded Timp3 -/- livers. Gelatin zymography demonstrated equivalent increases in MMP-2 and MMP-9 levels in WT and Timp3 -/- iron-overloaded livers. Loss of Timp3 enhanced the susceptibility to iron overload-mediated heart and liver injury, suggesting that Timp3 is a key protective molecule against iron-mediated pathology. NEW & NOTEWORTHY In mice, loss of tissue inhibitor of metalloproteinase 3 ( Timp3) was associated with systolic and diastolic dysfunctions, twofold higher hepatic iron accumulation (attributable to constituently lower levels of ferroportin), and increased hepatic inflammation. Loss of Timp3 enhanced the susceptibility to iron overload-mediated injury, suggesting that Timp3 plays a key protective role against iron-mediated pathology.

The initial repair response of articular cartilage after mechanically induced damage.

PubMed

van Haaften, Eline E; Ito, Keita; van Donkelaar, Corrinus C

2017-06-01

The regenerative potential of articular cartilage (AC) defects is limited and depends on defect size, biomechanical conditions, and age. Early events after overloading might be predictive for cartilage degeneration in the long term. Therefore, the present aim is to investigate the temporal response of cartilage to overloading at cell, matrix, and tissue level during the first period after mechanical overloading. In the present study, the effect of high loading (∼8 MPa) at a high rate (∼14 MPa/s) at day 0 during a 9 day period on collagen damage, gene expression, cell death, and biochemical composition in AC was investigated. A model system was developed which enabled culturing osteochondral explants after loading. Proteoglycan content was repeatedly monitored over time using μCT, whereas other evaluations required destructive measurements. Changes in matrix related gene expressions indicated a degenerative response during the first 6 h after loading. After 24 h, this was restored and data suggested an initial repair response. Cell death and microscopic damage increased after 24 h following loading. These degradative changes were not restored within the 9 day culture period, and were accompanied by a slight loss of proteoglycans at the articular surface that extended into the middle zones. The combined findings indicate that high magnitude loading of articular cartilage at a high rate induces an initial damage that later initiates a healing response that can probably not be retained due to loss of cell viability. Consequently, the matrix cannot be restored in the short term. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1265-1273, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Work Overload.

ERIC Educational Resources Information Center

Bateman, Thomas S.

1980-01-01

To investigate managerial use of work (or role) overload to increase productivity, the author studied 77 nonclerical white-collar employees and found that work overload had negative effects on productivity, supervisors' ratings, employee attitudes, job satisfaction, and health. He recommends ways for managers and employees to reduce work overload.…

30 CFR 57.12003 - Trailing cable overload protection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Trailing cable overload protection. 57.12003... Electricity Surface and Underground § 57.12003 Trailing cable overload protection. Individual overload protection or short circuit protection shall be provided for the trailing cables of mobile equipment. ...

Thermal Aging Characteristics of Insulation Paper in Mineral Oil under Overloaded Operating Transformers

NASA Astrophysics Data System (ADS)

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.

Iron overload causes osteoporosis in thalassemia major patients through interaction with transient receptor potential vanilloid type 1 (TRPV1) channels

PubMed Central

Rossi, Francesca; Perrotta, Silverio; Bellini, Giulia; Luongo, Livio; Tortora, Chiara; Siniscalco, Dario; Francese, Matteo; Torella, Marco; Nobili, Bruno; Di Marzo, Vincenzo; Maione, Sabatino

2014-01-01

The pathogenesis of bone resorption in β-thalassemia major is multifactorial and our understanding of the underlying molecular and cellular mechanisms remains incomplete. Considering the emerging importance of the endocannabinoid/endovanilloid system in bone metabolism, it may be instructive to examine a potential role for this system in the development of osteoporosis in patients with β-thalassemia major and its relationship with iron overload and iron chelation therapy. This study demonstrates that, in thalassemic-derived osteoclasts, tartrate-resistant acid phosphatase expression inversely correlates with femoral and lumbar bone mineral density, and directly correlates with ferritin levels and liver iron concentration. The vanilloid agonist resiniferatoxin dramatically reduces cathepsin K levels and osteoclast numbers in vitro, without affecting tartrate-resistant acid phosphatase expression. The iron chelators deferoxamine, deferiprone and deferasirox decrease both tartrate-resistant acid phosphatase and cathepsin K expression, as well as osteoclast activity. Taken together, these data show that transient receptor potential vanilloid type 1 activation/desensitization influences tartrate-resistant acid phosphatase expression and activity, and this effect is dependent on iron, suggesting a pivotal role for iron overload in the dysregulation of bone metabolism in patients with thalassemia major. Our applied pharmacology provides evidence for the potential of iron chelators to abrogate these effects by reducing osteoclast activity. Whether iron chelation therapy is capable of restoring bone health in humans requires further study, but the potential to provide dual benefits for patients with β-thalassemia major –preventing iron-overload and alleviating associated osteoporotic changes – is exciting. PMID:25216685

Cardiomyocyte Ogt limits ventricular dysfunction in mice following pressure overload without affecting hypertrophy.

PubMed

Dassanayaka, Sujith; Brainard, Robert E; Watson, Lewis J; Long, Bethany W; Brittian, Kenneth R; DeMartino, Angelica M; Aird, Allison L; Gumpert, Anna M; Audam, Timothy N; Kilfoil, Peter J; Muthusamy, Senthilkumar; Hamid, Tariq; Prabhu, Sumanth D; Jones, Steven P

2017-05-01

The myocardial response to pressure overload involves coordination of multiple transcriptional, posttranscriptional, and metabolic cues. The previous studies show that one such metabolic cue, O-GlcNAc, is elevated in the pressure-overloaded heart, and the increase in O-GlcNAcylation is required for cardiomyocyte hypertrophy in vitro. Yet, it is not clear whether and how O-GlcNAcylation participates in the hypertrophic response in vivo. Here, we addressed this question using patient samples and a preclinical model of heart failure. Protein O-GlcNAcylation levels were increased in myocardial tissue from heart failure patients compared with normal patients. To test the role of OGT in the heart, we subjected cardiomyocyte-specific, inducibly deficient Ogt (i-cmOgt -/- ) mice and Ogt competent littermate wild-type (WT) mice to transverse aortic constriction. Deletion of cardiomyocyte Ogt significantly decreased O-GlcNAcylation and exacerbated ventricular dysfunction, without producing widespread changes in metabolic transcripts. Although some changes in hypertrophic and fibrotic signaling were noted, there were no histological differences in hypertrophy or fibrosis. We next determined whether significant differences were present in i-cmOgt -/- cardiomyocytes from surgically naïve mice. Interestingly, markers of cardiomyocyte dedifferentiation were elevated in Ogt-deficient cardiomyocytes. Although no significant differences in cardiac dysfunction were apparent after recombination, it is possible that such changes in dedifferentiation markers could reflect a larger phenotypic shift within the Ogt-deficient cardiomyocytes. We conclude that cardiomyocyte Ogt is not required for cardiomyocyte hypertrophy in vivo; however, loss of Ogt may exert subtle phenotypic differences in cardiomyocytes that sensitize the heart to pressure overload-induced ventricular dysfunction.

The overuse of the implant motor: effect on the output torque in overloading condition.

PubMed

Lee, Du-Hyeong; Cho, Sung-Am; Lee, Cheong-Hee; Lee, Kyu-Bok

2015-06-01

The overloading of the motor affects its performance. The output torque of the implant motor under overloading condition has not been reported. The purpose of this study was to determine the reliability and the tendency of the output torque when an implant motor is consecutively used. Three implant motors were evaluated: SurgicXT/X-SG20L (NSK), INTRAsurg300/CL3-09 (KaVo), and XIP10/CRB26LX (Saeshin). The output torque was measured using an electronic torque gauge fixed with jigs. For the 40 and 50 Ncm torque settings, 300 measurements were taken at 30 rpm. Repeated measures of analysis of variance (ANOVA) and one-way ANOVA were used to compare the torque values within each group and between the groups. As repeating measures, the output torque values decreased gradually compared with the baseline. In within-group analysis, the different torque value from the first measurement appeared earliest in NSK motor, followed in order by Saeshin and KaVo motors. NSK motor showed a different torque decrease between 40 and 50 Ncm settings (p < .05). Intergroup analysis revealed Saeshin motor to have the least deviation from the baseline, followed by KaVo motor. NSK motor had the most inconsistent torque at the 6, 8, 9, and 10 repeat counts (p < .05). The actual torque decreases when the surgical motor is continuously used. The NSK motor showed more significant decreases in torque than KaVo and Saeshin motors in overloading condition. © 2014 Wiley Periodicals, Inc.

30 CFR 75.518-2 - Incandescent lamps, overload and short circuit protection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Incandescent lamps, overload and short circuit...-General § 75.518-2 Incandescent lamps, overload and short circuit protection. Incandescent lamps installed... or direct current feeder circuits, need not be provided with separate short circuit or overload...

Magnetic and quadrupolar studies of the iron storage overload in livers

NASA Astrophysics Data System (ADS)

Rimbert, J. N.; Dumas, F.; Richardot, G.; Kellershohn, C.

1986-02-01

Absorption57Fe Mössbauer spectra, performed directly on tissues of liver with iron overload due to an excessive intestinal iron absorption or induced by hypertransfusional therapeutics, have pointed out a new high spin ferric storage iron besides the ferritin and hemosiderin. Mössbauer studies, carried out on ferritin and hemosiderin fractions isolated from normal and overloaded livers, show that this compound, only present in the secondary iron overload (transfusional pathway), seems characteristic of the physiological process which induces the iron overload.

Protective effects of deferasirox and N-acetyl-L-cysteine on iron overload-injured bone marrow.

PubMed

Shen, J C; Zhang, Y C; Zhao, M F

2017-10-19

Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe) model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was then examined. Iron overload markedly decreased the number of murine HSPCs in bone marrow. Subsequent colony-forming cell assays showed that iron overload also decreased the colony forming capacity of HSPCs, the effect of which could be reversed by DFX and NAC. The bone marrow hematopoiesis damage caused by iron overload could be alleviated by DFX and NAC.

The attenuating effect of role overload on relationships linking self-efficacy and goal level to work performance.

PubMed

Brown, Steven P; Jones, Eli; Leigh, Thomas W

2005-09-01

The reported research examines the moderating effects of role overload on the antecedents and consequences of self-efficacy and personal goal level in a longitudinal study conducted in an industrial selling context. The results indicate that role overload moderates the antecedent effect of perceived organizational resources on self-efficacy beliefs. They also show that role overload moderates the direct effects of both self-efficacy and goal level on performance, such that these relationships are positive when role overload is low but not significant when role overload is high. Further, the results reveal a pattern of moderated mediation, in which goal level mediates the indirect effect of self-efficacy on performance when role overload is low but not when it is high. Implications for theory and managerial practice are discussed. Copyright 2005 APA, all rights reserved.

ROS-mediated iron overload injures the hematopoiesis of bone marrow by damaging hematopoietic stem/progenitor cells in mice

PubMed Central

Chai, Xiao; Li, Deguan; Cao, Xiaoli; Zhang, Yuchen; Mu, Juan; Lu, Wenyi; Xiao, Xia; Li, Chengcheng; Meng, Juanxia; Chen, Jie; Li, Qing; Wang, Jishi; Meng, Aimin; Zhao, Mingfeng

2015-01-01

Iron overload, caused by hereditary hemochromatosis or repeated blood transfusions in some diseases, such as beta thalassemia, bone marrow failure and myelodysplastic syndrome, can significantly induce injured bone marrow (BM) function as well as parenchyma organ dysfunctions. However, the effect of iron overload and its mechanism remain elusive. In this study, we investigated the effects of iron overload on the hematopoietic stem and progenitor cells (HSPCs) from a mouse model. Our results showed that iron overload markedly decreased the ratio and clonogenic function of murine HSPCs by the elevation of reactive oxygen species (ROS). This finding is supported by the results of NAC or DFX treatment, which reduced ROS level by inhibiting NOX4 and p38MAPK and improved the long-term and multi-lineage engrafment of iron overload HSCs after transplantation. Therefore, all of these data demonstrate that iron overload injures the hematopoiesis of BM by enhancing ROS through NOX4 and p38MAPK. This will be helpful for the treatment of iron overload in patients with hematopoietic dysfunction. PMID:25970748

Characterization of microstructure, local deformation and microchemistry in Alloy 690 heat-affected zone and stress corrosion cracking in high temperature water

NASA Astrophysics Data System (ADS)

Lu, Zhanpeng; Chen, Junjie; Shoji, Tetsuo; Takeda, Yoichi; Yamazaki, Seiya

2015-10-01

With increasing the distance from the weld fusion line in an Alloy 690 heat-affected zone, micro-hardness decreases, kernel average misorientation decreases and the fraction of Σ3 boundaries increases. Chromium depletion at grain boundaries in the Alloy 690 heat-affected zone is less significant than that in an Alloy 600 heat-affected zone. Alloy 690 heat-affected zone exhibits much higher IGSCC resistance than Alloy 600 heat-affected zone in simulated pressurized water reactor primary water. Heavily cold worked Alloy 690 exhibits localized intergranular stress corrosion cracking. The effects of metallurgical and mechanical properties on stress corrosion cracking in Alloy 690 are discussed.

Changes in rat muscle with compensatory overload occur in a sequential manner.

PubMed

Macpherson, P C; Thayer, R E; Rodgers, C; Taylor, A W; Noble, E G

1999-01-01

The present study was initiated to determine the time course of changes in the profile of selected skeletal muscle myofibril proteins during compensatory overload. Whole muscle isometric contractile properties were measured to assess the physiological consequences of the overload stimulus. Compensatory overload of plantaris muscle of rats was induced by surgical ablation of the synergistic soleus and gastrocnemius muscles. Myosin light chain (LC) and tropomyosin (TM) compositions of control (CP) and overloaded plantaris (OP) muscles were determined by electrophoresis and myofibrillar ATPase assays were performed to assess changes in contractile protein interactions. Within one week of overload decreases in the alpha:beta TM ratio and myofibrillar ATPase activity were observed. Following 30 days of overload, a transition in type II to type I fibres was associated with an increase in slow myosin LC1. Interestingly, after 77 days of overload, the TM subunit ratio returned to one resembling a fast twitch muscle. It is proposed that the early and transitory changes in the TM subunits of OP, as well as the rapid initial depression in maximum tetanic isometric force and myofibrillar ATPase activity may be explained as a result of muscle fibre degeneration-regeneration. We propose that alterations in protein expression induced by compensatory overload reflect both degenerative-regenerative change and increased neuromuscular activity.

Role overload, pain and physical dysfunction in early rheumatoid or undifferentiated inflammatory arthritis in Canada.

PubMed

Mustafa, Sally Sabry; Looper, Karl Julian; Zelkowitz, Phyllis; Purden, Margaret; Baron, Murray

2012-05-03

Inflammatory arthritis impairs participation in societal roles. Role overload arises when the demands by a given role set exceed the resources; time and energy, to carry out the required tasks. The present study examines the association between role overload and disease outcomes in early inflammatory arthritis (EIA). Patients (n = 104) of 7.61 months mean duration of inflammatory arthritis completed self-report questionnaires on sociodemographics, disease characteristics and role overload. Pain was assessed using the Short Form McGill Pain Questionnaire (MPQ) and physical functioning was measured with the Medical Outcomes Study Short Form 36 (SF-36) physical functioning score. Role overload was measured by the Role Overload Scale. Patients indicated the number of social roles they occupied from a total of the three typical roles; marital, parental and paid work. Participants' mean age was 56 years and 70.2% were female. Role overload was not correlated to the number of social roles, however, it was positively associated with pain (p = 0.004) and negatively associated with physical functioning (p = 0.001). On multivariate analysis, role overload was negatively associated with physical functioning after controlling for the relevant sociodemographic variables. This study identifies a possible reciprocal relationship between role overload and physical functioning in patients with EIA.

Clinical consequences of iron overload in patients with myelodysplastic syndromes: the case for iron chelation therapy.

PubMed

Shammo, Jamile M; Komrokji, Rami S

2018-06-14

Patients with myelodysplastic syndromes (MDS) are at increased risk of iron overload due to ineffective erythropoiesis and chronic transfusion therapy. The clinical consequences of iron overload include cardiac and/or hepatic failure, endocrinopathies, and infection risk. Areas covered: Iron chelation therapy (ICT) can help remove excess iron and ultimately reduce the clinical consequences of iron overload. The authors reviewed recent (last five years) English-language articles from PubMed on the topic of iron overload-related complications and the use of ICT (primarily deferasirox) to improve outcomes in patients with MDS. Expert Commentary: While a benefit of ICT has been more firmly established in other transfusion-dependent conditions such as thalassemia, its role in reducing iron overload in MDS remains controversial due to the lack of prospective controlled data demonstrating a survival benefit. Orally administered chelation agents (e.g., deferasirox), are now available, and observational and/or retrospective data support a survival benefit of using ICT in MDS. The placebo-controlled TELESTO trial (NCT00940602) is currently examining the use of deferasirox in MDS patients with iron overload, and is evaluating specifically whether use of ICT to alleviate iron overload can also reduce iron overload-related complications in MDS and improve survival.

Anaerobic sludge digestion in the presence of lactobacillus additive

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosh, S.; Klass, D.L.

1980-01-01

A laboratory evaluation of a lactobacillus fermentation product was performed to study its effects as an additive on the anaerobic digestion of sewage sludge under conventional and overloaded high-rate conditions. The overloaded conditions were those experienced in commercial municipal digesters. It was concluded from this work that the use of the additive at low concentrations permits digester operation at least up to double the loading of untreated digesters and at higher methane yields and volatile solids reductions without affecting effluent quality. The additive also imparts iproved digester stability and rapid response to loading rate and detention time excursions and upsets.more » The beneficial effets of the additive observed in the laboratory remain to be established with other feeds such as biomass, and in large-scale commercial digestion tests that are now in progress.« less

Coping with Work Stressors in Nursing. Effects of Adaptive versus Maladaptive Strategies.

ERIC Educational Resources Information Center

Parasuraman, Saroj; Hansen, Donna

1987-01-01

The effect of coping behaviors on nurses' affective reactions to work-generated stressors was assessed, using data gathered from 215 nurses in a medical center hospital in the Midwest. Adaptive coping, reflecting problem-solving behaviors, was found to moderate the relationships of work overload and resource inadequacy with felt stress. (Author/CH)

Decreasing Cognitive Load for Learners: Strategy of Web-Based Foreign Language Learning

ERIC Educational Resources Information Center

Zhang, Jianfeng

2013-01-01

Cognitive load is one of the important factors that influence the effectiveness and efficiency of web-based foreign language learning. Cognitive load theory assumes that human's cognitive capacity in working memory is limited and if it overloads, learning will be hampered, so that high level of cognitive load can affect the performance of learning…

Fatigue History and in-situ Loading Studies of the overload Effect Using High Resolution X-ray Strain Profiling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Croft,M.; Jisrawi, N.; Zhong, Z.

High-energy synchrotron X-ray diffraction experiments are used to perform local crack plane strain profiling of 4140 steel compact tension specimens fatigued at constant amplitude, subjected to a single overload cycle, then fatigued some more at constant amplitude. X-ray strain profiling results on a series of samples employing in-situ load cycling are correlated with the crack growth rate (da/dN) providing insight into the da/dN retardation known as the 'overload effect'. Immediately after the overload, the strain under maximum load is greatly reduced but the range of strain, between zero and maximum load, remains unchanged compared to the pre-overload values. At themore » point of maximum retardation, it is the strain range that is greatly reduced while the maximum-load strain has begun to recover to the pre-overload value. For a sample that has recovered to approximately half of the original da/dN value following the overload, the strain at maximum load is fully recovered while the strain range, though partially recovered, is still substantially reduced. The dominance of the strain range in the overload effect is clearly indicated. Subject to some assumptions, strong quantitative support for a crack growth rate driving force of the suggested form [(K{sub max}){sup -p}({Delta}K){sup p}]{sup {gamma}} is found. A dramatic nonlinear load dependence in the spatial distribution of the strain at maximum retardation is also demonstrated: at low load the response is dominantly at the overload position; whereas at high loads it is dominantly at the crack tip position. This transfer of load response away from the crack tip to the overload position appears fundamental to the overload effect for high R-ratio fatigue as studied here.« less

Enzymatically modified isoquercitrin supplementation intensifies plantaris muscle fiber hypertrophy in functionally overloaded mice.

PubMed

Kohara, Akiko; Machida, Masanao; Setoguchi, Yuko; Ito, Ryouichi; Sugitani, Masanori; Maruki-Uchida, Hiroko; Inagaki, Hiroyuki; Ito, Tatsuhiko; Omi, Naomi; Takemasa, Tohru

2017-01-01

Enzymatically modified isoquercitrin (EMIQ) is produced from rutin using enzymatic hydrolysis followed by treatment with glycosyltransferase in the presence of dextrin to add glucose residues. EMIQ is absorbed in the same way as quercetin, a powerful antioxidant reported to prevent disused muscle atrophy by targeting mitochondria and to have ergogenic effects. The present study investigated the effect of EMIQ on skeletal muscle hypertrophy induced by functional overload. In Study 1, 6-week-old ICR male mice were divided into 4 groups: sham-operated control, sham-operated EMIQ, overload-operated control, and overload-operated EMIQ groups. In Study 2, mice were divided into 3 groups: overload-operated whey control, overload-operated whey/EMIQ (low dose), and overload-operated whey/EMIQ (high dose) groups. The functional overload of the plantaris muscle was induced by ablation of the synergist (gastrocnemius and soleus) muscles. EMIQ and whey protein were administered with food. Three weeks after the operation, the cross-sectional area and minimal fiber diameter of the plantaris muscle fibers were measured. In Study 1, functional overload increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ supplementation significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle in both the sham-operated and overload-operated groups. In Study 2, EMIQ supplementation combined with whey protein administration significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ, even when administered as an addition to whey protein supplementation, significantly intensified the fiber hypertrophy of the plantaris muscle in functionally overloaded mice. EMIQ supplementation also induced fiber hypertrophy of the plantaris in sham-operated mice.

Volume Overload: Prevalence, Risk Factors, and Functional Outcome in Survivors of Septic Shock

PubMed Central

Carlbom, David; Caldwell, Ellen; Himmelfarb, Jonathan; Hough, Catherine L.

2015-01-01

Rationale: Survivors of septic shock have impaired functional status. Volume overload is associated with poor outcomes in patients with septic shock, but the impact of volume overload on functional outcome and discharge destination of survivors is unknown. Objectives: This study describes patterns of fluid management both during and after septic shock. We examined factors associated with volume overload upon intensive care unit (ICU) discharge. We then examined associations between volume overload upon ICU discharge, mobility limitation, and discharge to a healthcare facility in septic shock survivors, with the hypothesis that volume overload is associated with increased odds of these outcomes. Methods: We retrospectively reviewed the medical records of 247 patients admitted with septic shock to an academic county hospital between June 2009 and April 2012 who survived to ICU discharge. We defined volume overload as a fluid balance expected to increase the subject’s admission weight by 10%. Statistical methods included unadjusted analyses and multivariable logistic regression. Measurements and Main Results: Eighty-six percent of patients had a positive fluid balance, and 35% had volume overload upon ICU discharge. Factors associated with volume overload in unadjusted analyses included more severe illness, cirrhosis, blood transfusion during shock, and higher volumes of fluid administration both during and after shock. Blood transfusion during shock was independently associated with increased odds of volume overload (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.33–5.27; P = 0.01) after adjusting for preexisting conditions and severity of illness. Only 42% of patients received at least one dose of a diuretic during their hospitalization. Volume overload upon ICU discharge was independently associated with inability to ambulate upon hospital discharge (OR, 2.29; 95% CI, 1.24–4.25; P = 0.01) and, in patients admitted from home, upon discharge to a healthcare facility (OR, 2.34; 95% CI, 1.1–4.98; P = 0.03). Conclusions: Volume overload is independently associated with impaired mobility and discharge to a healthcare facility in survivors of septic shock. Prevention and treatment of volume overload in patients with septic shock warrants further investigation. PMID:26394090

Factory overload testing of a large power transformer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Douglas, D.H.; Lawrence, C.O.; Templeton, J.B.

1985-09-01

A factory overload test of up to 150% of the nameplate rating was run on a 224 MVA autotransformer. The results of this test were of great value and were used in identifying transformer overload limitations, in evaluating loading guide oil and winding equations, exponents and time constants, and in helping to perfect a factory overload test procedure.

c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ledee, Dolena; Smith, Lincoln; Bruce, Margaret

Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic 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 mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. 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 (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.« less

c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

DOE PAGES

Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; ...

2015-08-12

Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic 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 mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. 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 (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.« less

Tension at the borders: perceptions of role overload, conflict, strain and facilitation in work, family and health roles among employed individuals with arthritis

PubMed Central

Backman, Catherine L.; Kaptein, Simone; Lacaille, Diane; Beaton, Dorcas E.; Hofstetter, Catherine; Badley, Elizabeth M.

2012-01-01

Objective. To examine inter-relationships among arthritis (A), work (W) and personal life (P) roles and their reciprocal influences, especially experiences of role balance/imbalance among individuals with inflammatory arthritis (IA) and OA. Methods. Eight focus groups were conducted with 24 women and 16 men (aged 29–72 years). A purposive sample was recruited from community advertising. Eligibility included current employment or having been employed within the previous year. Participants were asked about ways arthritis, work and personal life roles intersected and their impact. A standardized questionnaire collected demographic, symptom and employment data for descriptive purposes. Results. Participants noted that having arthritis affected their identity and intersected with work and personal roles, creating role overload, role conflict, role strain and role facilitation. Role overload highlighted that arthritis both affected and was impacted by work and personal life (A → W; A → P; W → A; P → A). Role conflict focused on A → W and A → P difficulties, whereas role facilitation emphasized the positive impact of work and personal life roles on arthritis (W → A; P → A). Role strain was pervasive and arose from numerous sources. Personal strategies (e.g. positive framing) and contextual factors (e.g. support) were important in contributing to or ameliorating role balance/imbalance. Conclusions. By comprehensively examining multiple types of role balance/imbalance and the context within which it occurs, this study identifies gaps in patient-oriented measurement of the impact of arthritis and areas of need in the development of arthritis intervention. PMID:22039223

Tension at the borders: perceptions of role overload, conflict, strain and facilitation in work, family and health roles among employed individuals with arthritis.

PubMed

Gignac, Monique A M; Backman, Catherine L; Kaptein, Simone; Lacaille, Diane; Beaton, Dorcas E; Hofstetter, Catherine; Badley, Elizabeth M

2012-02-01

To examine inter-relationships among arthritis (A), work (W) and personal life (P) roles and their reciprocal influences, especially experiences of role balance/imbalance among individuals with inflammatory arthritis (IA) and OA. Eight focus groups were conducted with 24 women and 16 men (aged 29-72 years). A purposive sample was recruited from community advertising. Eligibility included current employment or having been employed within the previous year. Participants were asked about ways arthritis, work and personal life roles intersected and their impact. A standardized questionnaire collected demographic, symptom and employment data for descriptive purposes. Participants noted that having arthritis affected their identity and intersected with work and personal roles, creating role overload, role conflict, role strain and role facilitation. Role overload highlighted that arthritis both affected and was impacted by work and personal life (A → W; A → P; W → A; P → A). Role conflict focused on A → W and A → P difficulties, whereas role facilitation emphasized the positive impact of work and personal life roles on arthritis (W → A; P → A). Role strain was pervasive and arose from numerous sources. Personal strategies (e.g. positive framing) and contextual factors (e.g. support) were important in contributing to or ameliorating role balance/imbalance. By comprehensively examining multiple types of role balance/imbalance and the context within which it occurs, this study identifies gaps in patient-oriented measurement of the impact of arthritis and areas of need in the development of arthritis intervention.

Impact of iron overload on interleukin-10 levels, biochemical parameters and oxidative stress in patients with sickle cell anemia

PubMed Central

Barbosa, Maritza Cavalcante; dos Santos, Talyta Ellen Jesus; de Souza, Geane Félix; de Assis, Lívia Coêlho; Freitas, Max Victor Carioca; Gonçalves, Romélia Pinheiro

2013-01-01

Objective The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients. Methods A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15) and Non-iron overload (n = 15). Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0) and statistical significance was established for p-values < 0.05 in all analyses. Results Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05). The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group. Conclusion The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia. PMID:23580881

Revaluation of clinical and histological criteria for diagnosis of dysmetabolic iron overload syndrome

PubMed Central

Riva, Alessia; Trombini, Paola; Mariani, Raffaella; Salvioni, Alessandra; Coletti, Sabina; Bonfadini, Silvia; Paolini, Valentina; Pozzi, Matteo; Facchetti, Rita; Bovo, Giorgio; Piperno, Alberto

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 overload (P < 0.0001). Patients with ≥ 2 metabolic alterations and steatosis had lower amount of hepatic iron, lower transferrin saturation and higher sinusoidal iron than patients with < 2 MS components and absence of steatosis. CONCLUSION: In our patients, the presence of ≥ 2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation, suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation. These patients may have the typical dysmetabolic iron overload syndrome. By contrast, patients with transferrin saturation ≥ 60% had more severe iron overload, few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload. PMID:18720534

Fluid overload and survival in critically ill patients with acute kidney injury receiving continuous renal replacement therapy

PubMed Central

Kim, Il Young; Kim, Joo Hui; Lee, Dong Won; Lee, Soo Bong; Rhee, Harin; Seong, Eun Young; Kwak, Ihm Soo

2017-01-01

Background Fluid overload is known to be associated with increased mortality in patients with acute kidney injury (AKI) who are critically ill. In this study, we intended to uncover whether the adverse effect of fluid overload on survival could be applied to all of the patients with AKI who received continuous renal replacement therapy (CRRT). Methods We analyzed 341 patients with AKI who received CRRT in our intensive care units. The presence of fluid overload was defined as a minimum 10% increase in body weight from the baseline. Demographics, comorbid diseases, clinical data, severity of illness [the sequential organ failure assessment (SOFA) score, number of vasopressors, diagnosis of sepsis, use of ventilator] upon ICU admission, fluid overload status, and time elapsed from AKI diagnosis until CRRT initiation were reviewed from the medical charts. Results Patients with total fluid overload from 3 days before CRRT initiation to ICU discharge had a significantly lower survival rate after ICU admission, as compared to patients with no fluid overload (P < 0.001). Among patients with sepsis (P < 0.001) or with high SOFA scores (P < 0.001), there was a significant difference in survival of the patients with and without fluid overload. In patients without sepsis or with low SOFA score, there was no significant difference in survival of patients irrespective of fluid overload. Conclusion Our study demonstrates that the adverse effect of fluid overload on survival is more evident in patients with sepsis or with more severe illness, and that it might not apply to patients without sepsis or with less severe illness. PMID:28196107

Information overload in healthcare: too much of a good thing?

PubMed

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.

Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload.

PubMed

Hankins, Jane S; Smeltzer, Matthew P; McCarville, M Beth; Aygun, Banu; Hillenbrand, Claudia M; Ware, Russell E; Onciu, Mihaela

2010-07-01

The rate and pattern of iron deposition and accumulation are important determinants of liver damage in chronically transfused patients. To investigate iron distribution patterns at various tissue iron concentrations, effects of chelation on hepatic iron compartmentalization, and differences between patients with sickle cell disease (SCD) and thalassemia major (TM), we prospectively investigated hepatic histologic and biochemical findings in 44 patients with iron overload (35 SCD and 9 TM). The median hepatic iron content (HIC) in patients with TM and SCD was similar at 12.9 and 10.3 mg Fe/g dry weight, respectively (P = 0.73), but patients with SCD had significantly less hepatic fibrosis and inflammation (P < 0.05), less hepatic injury, and significantly less blood exposure. Patients with SCD had predominantly sinusoidal iron deposition, but hepatocyte iron deposition was observed even at low HIC. Chelated patients had more hepatocyte and portal tract iron than non-chelated ones, but similar sinusoidal iron deposition. These data suggest that iron deposition in patients with SCD generally follows the traditional pattern of transfusional iron overload; however, parenchymal hepatocyte deposition also occurs early and chelation removes iron preferentially from the reticuloendothelium. Pathophysiological and genetic differences affecting iron deposition and accumulation in SCD and TM warrants further investigation.

Second-trimester amniotic fluid corticotropin-releasing hormone and urocortin in relation to maternal stress and fetal growth in human pregnancy.

PubMed

La Marca-Ghaemmaghami, Pearl; Dainese, Sara M; Stalla, Günter; Haller, Marina; Zimmermann, Roland; Ehlert, Ulrike

2017-05-01

This study explored the association between the acute psychobiological stress response, chronic social overload and amniotic fluid corticotropin-releasing hormone (CRH) and urocortin (UCN) in 34 healthy, second-trimester pregnant women undergoing amniocentesis. The study further examined the predictive value of second-trimester amniotic fluid CRH and UCN for fetal growth and neonatal birth outcome. The amniocentesis served as a naturalistic stressor, during which maternal state anxiety and salivary cortisol was measured repeatedly and an aliquot of amniotic fluid was collected. The pregnant women additionally completed a questionnaire on chronic social overload. Fetal growth parameters were obtained at amniocentesis using fetal ultrasound biometry and at birth from medical records. The statistical analyzes revealed that the acute maternal psychobiological stress response was unassociated with the amniotic fluid peptides, but that maternal chronic overload and amniotic CRH were positively correlated. Moreover, amniotic CRH was negatively associated with fetal size at amniocentesis and positively with growth in size from amniocentesis to birth. Hardly any studies have previously explored whether acute maternal psychological stress influences fetoplacental CRH or UCN levels significantly. Our findings suggest that (i) chronic, but not acute maternal stress may affect fetoplacental CRH secretion and that (ii) CRH is complexly involved in fetal growth processes as previously shown in animals.

Role overload, pain and physical dysfunction in early rheumatoid or undifferentiated inflammatory arthritis in Canada

PubMed Central

2012-01-01

Background Inflammatory arthritis impairs participation in societal roles. Role overload arises when the demands by a given role set exceed the resources; time and energy, to carry out the required tasks. The present study examines the association between role overload and disease outcomes in early inflammatory arthritis (EIA). Methods Patients (n = 104) of 7.61 months mean duration of inflammatory arthritis completed self-report questionnaires on sociodemographics, disease characteristics and role overload. Pain was assessed using the Short Form McGill Pain Questionnaire (MPQ) and physical functioning was measured with the Medical Outcomes Study Short Form 36 (SF-36) physical functioning score. Role overload was measured by the Role Overload Scale. Patients indicated the number of social roles they occupied from a total of the three typical roles; marital, parental and paid work. Results Participants’ mean age was 56 years and 70.2% were female. Role overload was not correlated to the number of social roles, however, it was positively associated with pain (p = 0.004) and negatively associated with physical functioning (p = 0.001). On multivariate analysis, role overload was negatively associated with physical functioning after controlling for the relevant sociodemographic variables. Conclusion This study identifies a possible reciprocal relationship between role overload and physical functioning in patients with EIA. PMID:22554167

Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload

NASA Technical Reports Server (NTRS)

Carlson, C. J.; Fan, Z.; Gordon, S. E.; Booth, F. W.

2001-01-01

Knowledge of the molecular mechanisms by which skeletal muscle hypertrophies in response to increased mechanical loading may lead to the discovery of novel treatment strategies for muscle wasting and frailty. To gain insight into potential early signaling mechanisms associated with skeletal muscle hypertrophy, the temporal pattern of mitogen-activated protein kinase (MAPK) phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activity during the first 24 h of muscle overload was determined in the rat slow-twitch soleus and fast-twitch plantaris muscles after ablation of the gastrocnemius muscle. p38alpha MAPK phosphorylation was elevated for the entire 24-h overload period in both muscles. In contrast, Erk 2 and p54 JNK phosphorylation were transiently increased by overload, returning to the levels of sham-operated controls by 24 h. PI3-kinase activity was increased by muscle overload only at 12 h of overload and only in the plantaris muscle. In summary, sustained elevation of p38alpha MAPK phosphorylation occurred early in response to muscle overload, identifying this pathway as a potential candidate for mediating early hypertrophic signals in response to skeletal muscle overload.

Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

NASA Technical Reports Server (NTRS)

Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.

1987-01-01

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass, the subcellular protein content, and the myosin patterns of normal overloaded and suspended overloaded plantaris muscle in female rat was investigated, dividing rats into six groups: normal control (NC), overload (OV), OV steroid (OV-S), normal suspended (N-sus), OV suspended (OV-sus), and OV suspended steroid (OV-sus-S). Relative to control values, overload produced a sparing effect on the muscle weight of the OV-sus group as well as increases of muscle weight of the OV group; increased protein content; and an increased expression of slow myosin in both OV and OV-sus groups. Steroid treatment of OV animals did not after the response of any parameter analyzed for the OV group, but in the OV-sus group steroid treatment induced increases in muscle weight and in protein content of the OV-sus-S group. The treatment did not alter the pattern of isomyosin expression observed in the OV or the OV-sus groups. These result suggest that the steroid acts synergistically with functional overload only under conditions in which the effect of overload is minimized by suspension.

Impact of Volume Management on Volume Overload and Rehospitalization in CAPD Patients.

PubMed

Xu, Yi; Yang, Shen-Min; Wang, Xiao-Hua; Wang, Hai-Fang; Niu, Mei-E; Yang, Yi-Qun; Lu, Guo-Yuan; Pang, Jian-Hong; Wang, Fei; Li, Lin

2018-05-01

Heart failure due to volume overload is a major reason for rehospitalization in continuous ambulatory peritoneal dialysis patients. Strict volume control provides better cardiac functions and blood pressure in this population. Volume management, which is a volume control strategy, may decrease volume overload and related complications. Using a quasi-experimental design, 66 continuous ambulatory peritoneal dialysis patients were randomly assigned to the intervention group ( n = 34) and control group ( n = 32). The patients were followed up for 6 months with scheduled clinic and/or telephone visits; the intervention group adopted volume management strategy, while the control group adopted conventional care. Volume overload and cardiac function were compared between the two groups at the baseline and at 6 months. At Month 6, the intervention group resulted in significant improvement in volume overloaded status, cardiac function, and volume-overload-related rehospitalization. Volume management strategy allows for better control of volume overload and is associated with fewer volume-related readmissions.

Effect of proof testing on the flaw growth characteristics of 304 stainless steel. [crack propagation in welded joints

NASA Technical Reports Server (NTRS)

Finger, R. W.

1974-01-01

The effects of proof overload frequency and magnitude on the cyclic crack growth rates of 304 stainless steel weldments were investigated. The welding procedure employed was typical of those used on over-the-road cryogenic vessels. Tests were conducted at room temperature with an overload ratio of 1.50 to determine the effect of overload frequency. Effect of overload magnitude was determined from tests where a room temperature overload was applied between blocks of 1000 cycles applied at 78 K (-320 F). The cyclic stress level used in all tests was typical of the nominal membrane stress generally encountered in full scale vessels. Test results indicate that judicious selection of proof overload frequency and magnitude can reduce crack growth rates for cyclic stress levels.

Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation

PubMed Central

Atilla, Erden; Toprak, Selami K.; Demirer, Taner

2017-01-01

Iron overload is an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation (HSCT). In the HSCT setting, pretransplant and early posttransplant ferritin and transferrin saturation were found to be highly elevated due to high transfusion requirements. In addition to that, post-HSCT iron overload was shown to be related to infections, hepatic sinusoidal obstruction syndrome, mucositis, liver dysfunction, and acute graft-versus-host disease. Hyperferritinemia causes decreased survival rates in both pre- and posttransplant settings. Serum ferritin levels, magnetic resonance imaging, and liver biopsy are diagnostic tools for iron overload. Organ dysfunction due to iron overload may cause high mortality rates and therefore sufficient iron chelation therapy is recommended in this setting. In this review the management of iron overload in adult HSCT is discussed. PMID:27956374

Bone morphogenetic protein-binding endothelial regulator of liver sinusoidal endothelial cells induces iron overload in a fatty liver mouse model.

PubMed

Hasebe, Takumu; Tanaka, Hiroki; Sawada, Koji; Nakajima, Shunsuke; Ohtake, Takaaki; Fujiya, Mikihiro; Kohgo, Yutaka

2017-03-01

Non-alcoholic fatty liver disease (NAFLD) is frequently accompanied by iron overload. However, because of the complex hepcidin-regulating molecules, the molecular mechanism underlying iron overload remains unknown. To identify the key molecule involved in NAFLD-associated iron dysregulation, we performed whole-RNA sequencing on the livers of obese mice. Male C57BL/6 mice were fed a regular or high-fat diet for 16 or 48 weeks. Internal iron was evaluated by plasma iron, ferritin or hepatic iron content. Whole-RNA sequencing was performed by transcriptome analysis using semiconductor high-throughput sequencer. Mouse liver tissues or isolated hepatocytes and sinusoidal endothelial cells were used to assess the expression of iron-regulating molecules. Mice fed a high-fat diet for 16 weeks showed excess iron accumulation. Longer exposure to a high-fat diet increased hepatic fibrosis and intrahepatic iron accumulation. A pathway analysis of the sequencing data showed that several inflammatory pathways, including bone morphogenetic protein (BMP)-SMAD signaling, were significantly affected. Sequencing analysis showed 2314 altered genes, including decreased mRNA expression of the hepcidin-coding gene Hamp. Hepcidin protein expression and SMAD phosphorylation, which induces Hamp, were found to be reduced. The expression of BMP-binding endothelial regulator (BMPER), which inhibits BMP-SMAD signaling by binding BMP extracellularly, was up-regulated in fatty livers. In addition, immunohistochemical and cell isolation analyses showed that BMPER was primarily expressed in the liver sinusoidal endothelial cells (LSECs) rather than hepatocytes. BMPER secretion by LSECs inhibits BMP-SMAD signaling in hepatocytes and further reduces hepcidin protein expression. These intrahepatic molecular interactions suggest a novel molecular basis of iron overload in NAFLD.

Cardioprotection by GSK-3 inhibition: role of enhanced glycogen synthesis and attenuation of calcium overload.

PubMed

Omar, Mohamed A; Wang, Lianguo; Clanachan, Alexander S

2010-06-01

Glycogen synthase kinase-3 (GSK-3) is a multi-functional kinase that regulates signalling pathways affecting glycogen metabolism, protein synthesis, mitosis, and apoptosis. GSK-3 inhibition limits cardiac ischaemia-reperfusion (IR) injury, but mechanisms are not clearly defined. This study tested the hypothesis that acute GSK-3 inhibition stimulates glycogen synthesis, repartitions glucose away from glycolysis, reduces proton (H+) production from glucose metabolism, and attenuates intracellular Ca2+ (Ca2+(i)) overload. In isolated perfused working rat hearts subjected to global ischaemia and reperfusion, the selective GSK-3 inhibitor, SB-216763 (SB, 3 micromol/L), when added either prior to ischaemia or at the onset of reperfusion, improved recovery of left-ventricular (LV) work. SB increased glycogen synthesis during reperfusion while glycolysis and H+ production were reduced. Rates of glucose and palmitate oxidation were improved by SB. Measurement of Ca2+(i) concentration by rapid acquisition indo-1 fluorescence imaging showed that SB, when added either prior to ischaemia or at the onset of reperfusion, reduced diastolic Ca2+(i) overload during reperfusion. In aerobic hearts depleted of glycogen by substrate-free perfusion to a level similar to that measured at the onset of reperfusion, SB accelerated glycogen synthesis and reduced glycolysis and H+ production independent of changes in LV work. Our study indicates that reduction in H+ production by GSK-3 inhibition is an early and upstream event that lessens Ca2+(i) overload during ischaemia and early reperfusion independent of LV work which enhances the recovery of post-ischaemic LV function and that may ultimately contribute to previously observed reductions in cell death and infarction.

Overload and neovascularization of shoulder tendons in volleyball players

PubMed Central

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

Process Recovery after CaO Addition Due to Granule Formation in a CSTR Co-Digester—A Tool to Influence the Composition of the Microbial Community and Stabilize the Process?

PubMed Central

Liebrich, Marietta; Kleyböcker, Anne; Kasina, Monika; Miethling-Graff, Rona; Kassahun, Andrea; Würdemann, Hilke

2016-01-01

The composition, structure and function of granules formed during process recovery with calcium oxide in a laboratory-scale fermenter fed with sewage sludge and rapeseed oil were studied. In the course of over-acidification and successful process recovery, only minor changes were observed in the bacterial community of the digestate, while granules appeared during recovery. Fluorescence microscopic analysis of the granules showed a close spatial relationship between calcium and oil and/or long chain fatty acids. This finding further substantiated the hypothesis that calcium precipitated with carbon of organic origin and reduced the negative effects of overloading with oil. Furthermore, the enrichment of phosphate minerals in the granules was shown, and molecular biological analyses detected polyphosphate-accumulating organisms as well as methanogenic archaea in the core. Organisms related to Methanoculleus receptaculi were detected in the inner zones of a granule, whereas they were present in the digestate only after process recovery. This finding indicated more favorable microhabitats inside the granules that supported process recovery. Thus, the granule formation triggered by calcium oxide addition served as a tool to influence the composition of the microbial community and to stabilize the process after overloading with oil. PMID:27681911

Process Recovery after CaO Addition Due to Granule Formation in a CSTR Co-Digester-A Tool to Influence the Composition of the Microbial Community and Stabilize the Process?

PubMed

Liebrich, Marietta; Kleyböcker, Anne; Kasina, Monika; Miethling-Graff, Rona; Kassahun, Andrea; Würdemann, Hilke

2016-03-17

The composition, structure and function of granules formed during process recovery with calcium oxide in a laboratory-scale fermenter fed with sewage sludge and rapeseed oil were studied. In the course of over-acidification and successful process recovery, only minor changes were observed in the bacterial community of the digestate, while granules appeared during recovery. Fluorescence microscopic analysis of the granules showed a close spatial relationship between calcium and oil and/or long chain fatty acids. This finding further substantiated the hypothesis that calcium precipitated with carbon of organic origin and reduced the negative effects of overloading with oil. Furthermore, the enrichment of phosphate minerals in the granules was shown, and molecular biological analyses detected polyphosphate-accumulating organisms as well as methanogenic archaea in the core. Organisms related to Methanoculleus receptaculi were detected in the inner zones of a granule, whereas they were present in the digestate only after process recovery. This finding indicated more favorable microhabitats inside the granules that supported process recovery. Thus, the granule formation triggered by calcium oxide addition served as a tool to influence the composition of the microbial community and to stabilize the process after overloading with oil.

Cardiac complications in beta-thalassemia: From mice to men.

PubMed

Kumfu, Sirinart; Fucharoen, Suthat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2017-06-01

Beta-thalassemia is an inherited hemoglobin disorder caused by reduced or absent synthesis of the beta globin chains of hemoglobin. This results in variable outcomes ranging from clinically asymptomatic to severe anemia, which then typically requires regular blood transfusion. These regular blood transfusions can result in an iron overload condition. The iron overload condition can lead to iron accumulation in various organs, especially in the heart, leading to iron overload cardiomyopathy, which is the major cause of mortality in patients with thalassemia. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects that iron overload has on the hearts of β-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed. The in-depth understanding of biomolecular alterations in the heart of these iron overload thalassemic mice will help give guidance for more effective therapeutic approaches in the near future. Impact statement Iron overload cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia. Since investigation of iron overload cardiomyopathy in thalassemia patients has many limitations, a search for an animal model for this condition has been ongoing for decades. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects of iron overload on the hearts of β-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed.

Cardiac complications in beta-thalassemia: From mice to men

PubMed Central

Kumfu, Sirinart; Fucharoen, Suthat; Chattipakorn, Siriporn C.

2017-01-01

Beta-thalassemia is an inherited hemoglobin disorder caused by reduced or absent synthesis of the beta globin chains of hemoglobin. This results in variable outcomes ranging from clinically asymptomatic to severe anemia, which then typically requires regular blood transfusion. These regular blood transfusions can result in an iron overload condition. The iron overload condition can lead to iron accumulation in various organs, especially in the heart, leading to iron overload cardiomyopathy, which is the major cause of mortality in patients with thalassemia. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects that iron overload has on the hearts of β-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed. The in-depth understanding of biomolecular alterations in the heart of these iron overload thalassemic mice will help give guidance for more effective therapeutic approaches in the near future. Impact statement Iron overload cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia. Since investigation of iron overload cardiomyopathy in thalassemia patients has many limitations, a search for an animal model for this condition has been ongoing for decades. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects of iron overload on the hearts of β-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed. PMID:28485683

Curcumin Attenuates Iron Accumulation and Oxidative Stress in the Liver and Spleen of Chronic Iron-Overloaded Rats

PubMed Central

Badria, Farid A.; Ibrahim, Ahmed S.; Badria, Adel F.; Elmarakby, Ahmed A.

2015-01-01

Objectives Iron overload is now recognized as a health problem in industrialized countries, as excessive iron is highly toxic for liver and spleen. The potential use of curcumin as an iron chelator has not been clearly identified experimentally in iron overload condition. Here, we evaluate the efficacy of curcumin to alleviate iron overload-induced hepatic and splenic abnormalities and to gain insight into the underlying mechanisms. Design and Methods Three groups of male adult rats were treated as follows: control rats, rats treated with iron in a drinking water for 2 months followed by either vehicle or curcumin treatment for 2 more months. Thereafter, we studied the effects of curcumin on iron overload-induced lipid peroxidation and anti-oxidant depletion. Results Treatment of iron-overloaded rats with curcumin resulted in marked decreases in iron accumulation within liver and spleen. Iron-overloaded rats had significant increases in malonyldialdehyde (MDA), a marker of lipid peroxidation and nitric oxide (NO) in liver and spleen when compared to control group. The effects of iron overload on lipid peroxidation and NO levels were significantly reduced by the intervention treatment with curcumin (P<0.05). Furthermore, the endogenous anti-oxidant activities/levels in liver and spleen were also significantly decreased in chronic iron overload and administration of curcumin restored the decrease in the hepatic and splenic antioxidant activities/levels. Conclusion Our study suggests that curcumin may represent a new horizon in managing iron overload-induced toxicity as well as in pathological diseases characterized by hepatic iron accumulation such as thalassemia, sickle cell anemia, and myelodysplastic syndromes possibly via iron chelation, reduced oxidative stress derived lipid peroxidation and improving the body endogenous antioxidant defense mechanism. PMID:26230491

Affective science and avoidant end-of-life communication: Can the science of emotion help physicians talk with their patients about the end of life?

PubMed

Soodalter, Jesse A; Siegle, Greg J; Klein-Fedyshin, Michele; Arnold, Robert; Schenker, Yael

2018-05-01

Despite believing end-of-life (EOL) discussions with patients are important, doctors often do not have them. Multiple factors contribute to this shortfall, which interventions including reimbursement changes and communication skills training have not significantly improved to date. One commonly cited but under-researched reason for physician avoidance of EOL discussion is emotional difficulty. High occupational demand for frequent difficult discussions may overload physicians' normal emotional functioning, leading to avoidance or failure. We propose that cognitive, behavioral, and neuroscience evidence from affective science may offer helpful insights into this problem. Data from other populations show that strong emotion impairs cognitive performance and multiple demands can overload cognitive resources. We discuss several affective processes that may apply to physicians attempting EOL discussions. We then discuss selected interventions that have been shown to modify some of these processes and associated behavioral outcomes. Evidence for change in behavioral outcomes of interest includes performance and mood enhancement in healthy populations. We suggest that such mechanistically-targeted interventions may be hypothesized to help decrease physician avoidance of EOL discussion. Physicians may be motivated to adopt such interventions in order to enhance normal emotional functioning to meet supra-normal occupational demand. We propose this as a promising area of future study. Copyright © 2017 Elsevier B.V. All rights reserved.

Immunohistochemical findings in the pancreatic islets of a patient with transfusional iron overload and diabetes: case report.

PubMed

Kishimoto, Miyako; Endo, Hisako; Hagiwara, Shotaro; Miwa, Akiyoshi; Noda, Mitsuhiko

2010-08-01

Excessive iron storage sometimes causes diabetes in patients with hemochromatosis, a disease caused by iron overloading. We performed an immunohistochemical analysis to study an autopsy case of aplastic anemia and diabetic hemochromatosis caused by frequent blood transfusions, and extensive hemosiderin deposition was observed in the liver and pancreas. The pancreatic islets of the patient and a control subject were stained to detect glucagon, insulin, and proinsulin. Significantly lower levels of immunoreactivity with both insulin antibodies and proinsulin antibodies, but not with glucagon antibodies, was observed in the islet cells in the patient's tissue than in the islet cells of the control. Hemosiderin deposition in the islets is known to be exclusively distributed in the β-cells, thus, selective iron-induced damage to the β-cells may have affected insulin synthesis and secretion and led to glucose intolerance in the patient.

Antioxidants Mediate Both Iron Homeostasis and Oxidative Stress.

PubMed

Imam, Mustapha Umar; Zhang, Shenshen; Ma, Jifei; Wang, Hao; Wang, Fudi

2017-06-28

Oxidative stress is a common denominator in the pathogenesis of many chronic diseases. Therefore, antioxidants are often used to protect cells and tissues and reverse oxidative damage. It is well known that iron metabolism underlies the dynamic interplay between oxidative stress and antioxidants in many pathophysiological processes. Both iron deficiency and iron overload can affect redox state, and these conditions can be restored to physiological conditions using iron supplementation and iron chelation, respectively. Similarly, the addition of antioxidants to these treatment regimens has been suggested as a viable therapeutic approach for attenuating tissue damage induced by oxidative stress. Notably, many bioactive plant-derived compounds have been shown to regulate both iron metabolism and redox state, possibly through interactive mechanisms. This review summarizes our current understanding of these mechanisms and discusses compelling preclinical evidence that bioactive plant-derived compounds can be both safe and effective for managing both iron deficiency and iron overload conditions.

Antioxidants Mediate Both Iron Homeostasis and Oxidative Stress

PubMed Central

Zhang, Shenshen; Ma, Jifei; Wang, Hao; Wang, Fudi

2017-01-01

Oxidative stress is a common denominator in the pathogenesis of many chronic diseases. Therefore, antioxidants are often used to protect cells and tissues and reverse oxidative damage. It is well known that iron metabolism underlies the dynamic interplay between oxidative stress and antioxidants in many pathophysiological processes. Both iron deficiency and iron overload can affect redox state, and these conditions can be restored to physiological conditions using iron supplementation and iron chelation, respectively. Similarly, the addition of antioxidants to these treatment regimens has been suggested as a viable therapeutic approach for attenuating tissue damage induced by oxidative stress. Notably, many bioactive plant-derived compounds have been shown to regulate both iron metabolism and redox state, possibly through interactive mechanisms. This review summarizes our current understanding of these mechanisms and discusses compelling preclinical evidence that bioactive plant-derived compounds can be both safe and effective for managing both iron deficiency and iron overload conditions. PMID:28657578

Melatonin protects bone marrow mesenchymal stem cells against iron overload-induced aberrant differentiation and senescence.

PubMed

Yang, Fan; Yang, Lei; Li, Yuan; Yan, Gege; Feng, Chao; Liu, Tianyi; Gong, Rui; Yuan, Ye; Wang, Ning; Idiiatullina, Elina; Bikkuzin, Timur; Pavlov, Valentin; Li, Yang; Dong, Chaorun; Wang, Dawei; Cao, Yang; Han, Zhenbo; Zhang, Lai; Huang, Qi; Ding, Fengzhi; Bi, Zhengang; Cai, Benzhi

2017-10-01

Bone marrow mesenchymal stem cells (BMSCs) are an expandable population of stem cells which can differentiate into osteoblasts, chondrocytes and adipocytes. Dysfunction of BMSCs in response to pathological stimuli contributes to bone diseases. Melatonin, a hormone secreted from pineal gland, has been proved to be an important mediator in bone formation and mineralization. The aim of this study was to investigate whether melatonin protected against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Here, we found that iron overload induced by ferric ammonium citrate (FAC) caused irregularly morphological changes and markedly reduced the viability in BMSCs. Consistently, osteogenic differentiation of BMSCs was significantly inhibited by iron overload, but melatonin treatment rescued osteogenic differentiation of BMSCs. Furthermore, exposure to FAC led to the senescence in BMSCs, which was attenuated by melatonin as well. Meanwhile, melatonin was able to counter the reduction in cell proliferation by iron overload in BMSCs. In addition, protective effects of melatonin on iron overload-induced dysfunction of BMSCs were abolished by its inhibitor luzindole. Also, melatonin protected BMSCs against iron overload-induced ROS accumulation and membrane potential depolarization. Further study uncovered that melatonin inhibited the upregulation of p53, ERK and p38 protein expressions in BMSCs with iron overload. Collectively, melatonin plays a protective role in iron overload-induced osteogenic differentiation dysfunction and senescence through blocking ROS accumulation and p53/ERK/p38 activation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

NASA Technical Reports Server (NTRS)

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.

Studies on deflection area vectors of QRS and T and ventricular gradient in right ventricular hypertrophy.

PubMed

Kawaguchi, Y

1985-04-01

QRS deflection area vector (Aqrs), T deflection area vector (At) and ventricular gradient (G) in right ventricular hypertrophy were studied in 53 subjects divided on the basis of cardiac catheterization data into four subgroups; normal controls, mild MS group, right ventricular pressure overload group and right ventricular volume overload group. Aqrs, At and G of the four subgroups were calculated using a microcomputer and compared. Aqrs in right ventricular pressure overload group and volume overload group was shifted to the right and slightly anteriorly from that in normal control group. At in right ventricular pressure overload group and volume overload group was shifted slightly upwards and significantly posteriorly from that in the normal control and mild MS groups. G in right ventricular pressure overload group and volume overload group was shifted to the right and significantly posteriorly from that in normal control and mild MS groups. Using multivariative analysis, we developed criteria for diagnosing right ventricular hypertrophy with At: 0.059At(Z) - 0.0145 [At] - 0.2608 less than or equal to 0. Application of this criteria achieved 82.4% (28 of 34) sensitivity in the patients with right ventricular hypertrophy and 90.9% (10 of 11) specificity in the normal control subjects.

Non-HFE iron overload as a surrogate marker of disease severity in patients of liver cirrhosis.

PubMed

Noor, Mohd Talha; Tiwari, Manish; Kumar, Ravindra

2016-01-01

Decompensated liver cirrhosis is an important cause of mortality worldwide. Various modifiable and non-modifiable factors are involved in the pathogenesis of cirrhosis and its complications. This study was aimed to evaluate the association of iron overload and disease severity in patients of liver cirrhosis and its association with HFE gene mutation. Forty-nine patients with decompensated liver cirrhosis were recruited. Clinical and laboratory parameters were compared in patients with and without iron overload. C282Y and H63D gene mutation analysis was performed in all patients with iron overload. Iron overload was found in 20 (40.82%) patients. A significant positive correlation of transferrin saturation with Child-Turcotte-Pugh (CTP) score (r = 0.705, p < 0.001) and model for end-stage liver disease (MELD) score (r = 0.668, p < 0.001) was found. Transferrin saturation was also independently associated with high CTP and MELD score on multivariate analysis. Mortality over 3 months was significantly more common in iron-overloaded patients (p = 0.028). C282Y homozygosity or C282Y/H63D compound heterozygosity was not found in any of the patients with iron overload. Iron overload was significantly associated with disease severity and reduced survival in patients of decompensated liver cirrhosis.

[Current understanding of iron overload hazard in patients with myelodysplastic syndrome].

PubMed

Song, Lu-Xi; Su, Ji-Ying; Zhang, Zhen; Chang, Chun-Kang

2013-04-01

Patients with myelodysplastic syndromes (MDS) become dependent on blood transfusions and develop into transfusional iron overload, which is exacerbated by increased absorption of dietary iron in response to ineffective erythropoiesis. However, it is uncertain whether there is an association among iron accumulation, clinical complications, and decreased likelihood of survival in MDS patients. Thereby our current understanding of the effects of transfusion dependency and iron overload in MDS are discussed. Particular emphasis should be placed on further characterizing the role of redox-active forms of labile iron and oxidative stress in iron overload, decreased life expectancy and increased risk of leukemic transformation in MDS patients with iron overload.

Direct observation of the residual plastic deformation caused by a single tensile overload

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bichler, C.; Pippan, R.

1999-07-01

The fatigue crack growth behavior following single tensile overloads at high stress intensity ranges in a cold-rolled austenitic steel has been studied experimentally. After tensile overloads, fatigue cracks initially accelerate, followed by significant retardation, before the growth rates return to their baseline level. The initial acceleration was attributed to an immediate reduction in near-tip closure. Scanning electron micrography and stereophotogrammetric reconstruction of the fracture surface were applied to study the residual plastic deformation caused by a single tensile overload in the mid-thickness of the specimen. The measured residual opening displacement of the crack as a function of the overload ismore » presented and compared with simple estimations. Also, free specimen surface observations of the residual plastic deformation and crack growth rate were performed. In the midsection of the specimens the striation spacing-length, i.e., the microscopic growth rates, were measured before and after the applied overload. It will be shown that the measured plasticity-induced wedges from the single overload and the observed propagation behavior support the significance of the concept of crack closure.« less

Myelodysplastic syndromes and the role of iron overload.

PubMed

Harvey, R Donald

2010-04-01

The epidemiology of myelodysplastic syndromes (MDS) and iron overload, recent clinical findings that highlight the importance of actively managing iron overload, and recommendations for initiating and maintaining iron chelation therapy (ICT) are summarized. MDS are a variety of hematological disorders with differing time courses. Disease morbidities are primarily due to cytopenias and evolution to acute myeloid leukemia. Iron overload is a serious complication in patients with MDS due to the long-term use of red blood cell transfusions in patients with symptomatic anemia. Clinical consequences of iron overload include end-organ damage and dysfunction, an increased frequency of transplant-related complications, and reduced survival rates. To prevent these complications, recommendations for initiating and maintaining ICT should be followed by clinicians caring for patients with MDS and iron overload. As current therapeutic options for patients with MDS do not always reduce the transfusion burden, many patients will still need long-term transfusion therapy. Strategies for the management of iron overload in MDS should be considered early in the disease course and in appropriate patients in order to prevent negative clinical outcomes associated with excessive iron accumulation.

Spatio-temporal propagation of cascading overload failures in spatially embedded networks

NASA Astrophysics Data System (ADS)

Zhao, Jichang; Li, Daqing; Sanhedrai, Hillel; Cohen, Reuven; Havlin, Shlomo

2016-01-01

Different from the direct contact in epidemics spread, overload failures propagate through hidden functional dependencies. Many studies focused on the critical conditions and catastrophic consequences of cascading failures. However, to understand the network vulnerability and mitigate the cascading overload failures, the knowledge of how the failures propagate in time and space is essential but still missing. Here we study the spatio-temporal propagation behaviour of cascading overload failures analytically and numerically on spatially embedded networks. The cascading overload failures are found to spread radially from the centre of the initial failure with an approximately constant velocity. The propagation velocity decreases with increasing tolerance, and can be well predicted by our theoretical framework with one single correction for all the tolerance values. This propagation velocity is found similar in various model networks and real network structures. Our findings may help to predict the dynamics of cascading overload failures in realistic systems.

Spatio-temporal propagation of cascading overload failures in spatially embedded networks

PubMed Central

Zhao, Jichang; Li, Daqing; Sanhedrai, Hillel; Cohen, Reuven; Havlin, Shlomo

2016-01-01

Different from the direct contact in epidemics spread, overload failures propagate through hidden functional dependencies. Many studies focused on the critical conditions and catastrophic consequences of cascading failures. However, to understand the network vulnerability and mitigate the cascading overload failures, the knowledge of how the failures propagate in time and space is essential but still missing. Here we study the spatio-temporal propagation behaviour of cascading overload failures analytically and numerically on spatially embedded networks. The cascading overload failures are found to spread radially from the centre of the initial failure with an approximately constant velocity. The propagation velocity decreases with increasing tolerance, and can be well predicted by our theoretical framework with one single correction for all the tolerance values. This propagation velocity is found similar in various model networks and real network structures. Our findings may help to predict the dynamics of cascading overload failures in realistic systems. PMID:26754065

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

PubMed Central

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

2013-01-01

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. PMID:24282296

Bridge Analysis and Evaluation of Effects Under Overload Vehicles

DOT National Transportation Integrated Search

2009-12-01

Movement of industrial freight infrequently requires special overload vehicles weighing 5 to 6 times the normal legal truck weight to move across highway systems. The gross vehicle weight of the overload vehicles frequently exceeds 400 kips while the...

Fuse protects circuit from voltage and current overloads

NASA Technical Reports Server (NTRS)

Casey, L. O.

1969-01-01

Low-melting resistor connected in series with the load protects the circuit against current overloads. It protects test subjects and patients being monitored by electronic instrumentation from inadvertant overloads of current, and sensitive electronic equipment against high-voltage damage.

Modelling and measurement of crack closure and crack growth following overloads and underloads

NASA Technical Reports Server (NTRS)

Dexter, R. J.; Hudak, S. J.; Davidson, D. L.

1989-01-01

Ignoring crack growth retardation following overloads can result in overly conservative life predictions in structures subjected to variable amplitude fatigue loading. Crack closure is believed to contribute to the crack growth retardation, although the specific closure mechanism is dabatable. The delay period and corresponding crack growth rate transients following overload and overload/underload cycles were systematically measured as a function of load ratio and overload magnitude. These responses are correlated in terms of the local 'driving force' for crack growth, i.e. the effective stress intensity factor range. Experimental results are compared with the predictions of a Dugdale-type (1960) crack closure model, and improvements in the model are suggested.

Overload protection system for power inverter

NASA Technical Reports Server (NTRS)

Nagano, S. (Inventor)

1977-01-01

An overload protection system for a power inverter utilized a first circuit for monitoring current to the load from the power inverter to detect an overload and a control circuit to shut off the power inverter, when an overload condition was detected. At the same time, a monitoring current inverter was turned on to deliver current to the load at a very low power level. A second circuit monitored current to the load, from the monitoring current inverter, to hold the power inverter off through the control circuit, until the overload condition was cleared so that the control circuit may be deactivated in order for the power inverter to be restored after the monitoring current inverter is turned off completely.

Implementing Filters to Identify and Prioritize Industrial Base Risk: Rules of Thumb to Reduce Cognitive Overload

DTIC Science & Technology

2015-04-30

Thumb to Reduce Cognitive Overload Sally Sleeper, ODASD[M&IBP] John F. Starns, Northrop Grumman Published April 30, 2015 Disclaimer: The views...Prioritize Industrial Base Risk: Rules of Thumb to Reduce Cognitive Overload 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6... Cognitive Overload Sally Sleeper—joined the Office of the Deputy Assistant Secretary of Defense for Manufacturing and Industrial Base Policy as Senior

Association of iron overload with allogeneic hematopoietic cell transplantation outcomes: a prospective cohort study using R2-MRI–measured liver iron content

PubMed Central

Trottier, Bryan J.; Burns, Linda J.; DeFor, Todd E.; Cooley, Sarah

2013-01-01

Using liver magnetic resonance imaging (R2-MRI) to quantify liver iron content (LIC), we conducted a prospective cohort study to determine the association between iron overload and adult allogeneic hematopoietic cell transplantation (HCT) outcomes. Patients received pretransplant ferritin measurements; patients with ferritin >500 ng/mL underwent R2-MRI. Patients were defined as no iron overload (N = 28) and iron overload (LIC >1.8 mg/g; N = 60). Median LIC in the iron-overload group was 4.3 mg/g (range, 1.9-25.4). There was no difference in the 1-year probability of overall survival, nonrelapse mortality, relapse, acute or chronic graft-versus-host disease, organ failure, infections, or hepatic veno-occlusive disease between groups. We also found no difference in the cumulative incidence of a composite end point of nonrelapse mortality, any infection, organ failure, or hepatic veno-occlusive disease (1-year cumulative incidence, 71% vs 80%; P = .44). In multivariate analyses, iron-overload status did not impact risks of overall mortality (relative risk = 2.3; 95% confidence interval, 0.9-5.9; P = .08). In conclusion, we found no association between pretransplant iron overload and allogeneic HCT outcomes. Future studies in this population should use LIC to define iron overload instead of ferritin. PMID:23777771

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

PubMed

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 (p<0.05). Significant up-regulations of interleukin (IL)-1β and tumor necrosis factor mRNAs were observed in HSF1-null, but not in wild-type, mice following 2 weeks of overloading. Overloading-related increases of IL-6 and AFT3 mRNA expressions seen after 2 weeks of overloading tended to decrease after 4 weeks in both types of mice. In HSF1-null mice, however, the significant overloading-related increase in the expression of IL-6, not ATF3, mRNA was noted even at 4th week. Inhibition of muscle 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.

Heat Shock Transcription Factor 1-Deficiency Attenuates Overloading-Associated Hypertrophy of Mouse Soleus Muscle

PubMed Central

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 (p<0.05). Significant up-regulations of interleukin (IL)-1β and tumor necrosis factor mRNAs were observed in HSF1-null, but not in wild-type, mice following 2 weeks of overloading. Overloading-related increases of IL-6 and AFT3 mRNA expressions seen after 2 weeks of overloading tended to decrease after 4 weeks in both types of mice. In HSF1-null mice, however, the significant overloading-related increase in the expression of IL-6, not ATF3, mRNA was noted even at 4th week. Inhibition of muscle 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. PMID:24167582

Increased risk of volume overload with plasma compared with four‐factor prothrombin complex concentrate for urgent vitamin K antagonist reversal

PubMed Central

Refaai, Majed A.; Goldstein, Joshua N.; Lee, Martin L.; Durn, Billie L.; Milling, Truman J.; Sarode, Ravi

2015-01-01

BACKGROUND Plasma is commonly used for vitamin K antagonist (VKA) reversal, but observational studies suggest that it is associated with transfusion‐related adverse reactions (e.g., volume overload). However, this issue has not previously been addressed in a randomized controlled trial (RCT). STUDY DESIGN AND METHODS Factors associated with volume overload were examined using data from two Phase IIIb RCTs comparing plasma with four‐factor prothrombin complex concentrate (4F‐PCC, Beriplex/Kcentra, CSL Behring) for urgent VKA reversal. VKA‐treated patients with major bleeding (NCT00708435) or requiring an urgent surgical or invasive procedure (NCT00803101) were randomly assigned (1:1) to receive either plasma or 4F‐PCC, concomitant with vitamin K. Adverse events (AEs) and serious AEs were prospectively captured up to Day 10 and 45, respectively. Volume overload predictors were evaluated on a univariate and multivariate basis. RESULTS A total of 388 patients (4F‐PCC, n = 191; plasma, n = 197) were enrolled. Volume overload occurred in 34 (9%) patients (4F‐PCC, n = 9; plasma, n = 25). In univariate analyses, use of plasma (vs. 4F‐PCC), use of nonstudy plasma and/or platelets, race, history of congestive heart failure (CHF), and history of renal disease were associated with volume overload. In multivariate analyses, use of plasma (vs. 4F‐PCC), history of CHF, and history of renal disease were independent volume overload predictors. In an additional analysis restricted to volume overload events recorded up to Day 7, only use of plasma (vs. 4F‐PCC) was an independent volume overload predictor. CONCLUSIONS After adjusting for other potential risk factors, plasma use was independently associated with a greater risk of volume overload than 4F‐PCC in patients requiring urgent VKA reversal. PMID:26135740

Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload.

PubMed

Tan, Jin; Wang, Miaohong; Song, Shuling; Miao, Yuyang; Zhang, Qiang

2018-01-10

Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

Torsion bar stabilizer for a vehicle and method for mounting the stabilizer on the vehicle frame

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sauber, C.J.

This patent describes a method of mounting a stabilizing mechanism on a vehicle frame which is supported and biased on a suspension assembly at opposite sides of the frame. The frame includes overload stops riveted to opposite sides of the frame and the suspension assembly includes bracket assemblies which secure the vehicle's suspension springs to a wheel axle. The method comprises the following steps: removing an overload stop from each side of the vehicle frame; mounting a modified overload stop on each side of the frame which serves as both an overload stop and a support for the stabilizing mechanismmore » wherein the modified overload stop is mounted into the holes in the frame left from the removal of the overload stop; removing from each side of the vehicle the top bracket from the bracket assembly; inserting a modified top bracket into each bracket assembly wherein the top bracket assembly is modified to couple with the stabilizing mechanism; and mounting on the modified overload stops a torsion bar whose opposite ends are coupled to the modified top bracket by way of linkages.« less

Long-term effect of dietary overload lithium on the glucose metabolism in broiler chickens.

PubMed

Bai, Shiping; Pan, Shuqin; Zhang, Keying; Ding, Xuemei; Wang, Jianping; Zeng, Qiufeng; Xuan, Yue; Su, Zuowei

2017-09-01

Lithium, like insulin, activates glycogen synthase and stimulates glucose transport in rat adipocytes. To investigate the effect of dietary overload lithium on glucose metabolism in broiler chickens, one-day-old chicks were fed a basal diet supplemented with 0 (control) or 100mg lithium/kg (overload lithium) for 35days. Compared to controls, glucose disappearance rates were lower (p=0.035) 15-120min after glucose gavage, and blood glucose concentrations were lower (p=0.038) 30min after insulin injection in overload lithium broilers. Overload lithium decreased (p<0.05) glycogen and glucose-6-phosphate concentrations in liver, but increased (p<0.05) their concentrations in pectoralis major. Overload lithium increased (p<0.05) mRNA expression of glucose transporter (GLUT) 3 and GLUT9 in liver, and GLUT1, GLUT3, GLUT8, and GLUT9 in pectoralis major, but decreased (p<0.05) cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in liver and mitochondrial PEPCK in pectoralis major. These results suggest that dietary overload lithium decreases glucose tolerance and gluconeogenesis, but increases insulin sensitivity and glucose transport in broiler chickens. Copyright © 2017 Elsevier B.V. All rights reserved.

LTE-advanced random access mechanism for M2M communication: A review

NASA Astrophysics Data System (ADS)

Mustafa, Rashid; Sarowa, Sandeep; Jaglan, Reena Rathee; Khan, Mohammad Junaid; Agrawal, Sunil

2016-03-01

Machine Type Communications (MTC) enables one or more self-sufficient machines to communicate directly with one another without human interference. MTC applications include smart grid, security, e-Health and intelligent automation system. To support huge numbers of MTC devices, one of the challenging issues is to provide a competent way for numerous access in the network and to minimize network overload. In this article, the different control mechanisms for overload random access are reviewed to avoid congestion caused by random access channel (RACH) of MTC devices. However, past and present wireless technologies have been engineered for Human-to-Human (H2H) communications, in particular, for transmission of voice. Consequently the Long Term Evolution (LTE) -Advanced is expected to play a central role in communicating Machine to Machine (M2M) and are very optimistic about H2H communications. Distinct and unique characteristics of M2M communications create new challenges from those in H2H communications. In this article, we investigate the impact of massive M2M terminals attempting random access to LTE-Advanced all at once. We discuss and review the solutions to alleviate the overload problem by Third Generation Partnership Project (3GPP). As a result, we evaluate and compare these solutions that can effectively eliminate the congestion on the random access channel for M2M communications without affecting H2H communications.

Dietary overload lithium decreases the adipogenesis in abdominal adipose tissue of broiler chickens.

PubMed

Bai, Shiping; Pan, Shuqin; Zhang, Keying; Ding, Xuemei; Wang, Jianping; Zeng, Qiufeng; Xuan, Yue; Su, Zuowei

2017-01-01

To investigate the toxic effects of dietary overload lithium on the adipogenesis in adipose tissue of chicken and the role of hypothalamic neuropeptide Y (NPY) in this process, one-day-old male chicks were fed with the basal diet added with 0 (control) or 100mg lithium/kg diet from lithium chloride (overload lithium) for 35days. Abdominal adipose tissue and hypothalamus were collected at day 6, 14, and 35. As a percentage of body weight, abdominal fat decreased (p<0.001) at day 6, 14, and 35, and feed intake and body weight gain decreased during day 7-14, and day 15-35 in overload lithium treated broilers as compared to control. Adipocyte diameter and DNA content in abdominal adipose tissue were significantly lower in overload-lithium treatment than control at day 35, although no significant differences were observed at day 6 and 14. Dietary overload lithium decreased (p<0.01) transcriptional expression of preadipocyte proliferation makers ki-67 (KI67), microtubule-associated protein homolog (TPX2), and topoisomerase 2-alpha (TOP2A), and preadipocyte differentiation transcriptional factors peroxisome proliferator-activated receptor-γ (PPARγ), and CCAAT/enhancer binding protein (C/EBP) α mRNA abundance in abdominal adipose tissue. In hypothalamus, dietary overload lithium influenced (p<0.001) NPY, and NPY receptor (NPYR) 6 mRNA abundance at day 6 and 14, but not at day 35. In conclusion, dietary overload lithium decreased the adipogenesis in abdominal adipose tissue of chicken, which was accompanied by depressing transcriptional expression of adipogenesis-associated factors. Hypothalamic NPY had a potential role in the adipogenesis in abdominal adipose tissue of broilers with a short-term overload lithium treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

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

NASA Technical Reports Server (NTRS)

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.

Nicotinamide N‐methyltransferase expression decreases in iron overload, exacerbating toxicity in mouse hepatocytes

PubMed Central

Koppe, Tiago; Patchen, Bonnie; Cheng, Aaron; Bhasin, Manoj; Vulpe, Chris; Schwartz, Robert E.; Moreno‐Navarrete, Jose Maria; Fernandez‐Real, Jose Manuel

2017-01-01

Iron overload causes the generation of reactive oxygen species that can lead to lasting damage to the liver and other organs. The goal of this study was to identify genes that modify the toxicity of iron overload. We studied the effect of iron overload on the hepatic transcriptional and metabolomic profile in mouse models using a dietary model of iron overload and a genetic model, the hemojuvelin knockout mouse. We then evaluated the correlation of nicotinamide N‐methyltransferase (NNMT) expression with body iron stores in human patients and the effect of NNMT knockdown on gene expression and viability in primary mouse hepatocytes. We found that iron overload induced significant changes in the expression of genes and metabolites involved in glucose and nicotinamide metabolism and that NNMT, an enzyme that methylates nicotinamide and regulates hepatic glucose and cholesterol metabolism, is one of the most strongly down‐regulated genes in the liver in both genetic and dietary iron overload. We found that hepatic NNMT expression is inversely correlated with serum ferritin levels and serum transferrin saturation in patients who are obese, suggesting that body iron stores regulate human liver NNMT expression. Furthermore, we demonstrated that adenoviral knockdown of NNMT in primary mouse hepatocytes exacerbates iron‐induced hepatocyte toxicity and increases expression of transcriptional markers of oxidative and endoplasmic reticulum stress, while overexpression of NNMT partially reversed these effects. Conclusion: Iron overload alters glucose and nicotinamide transcriptional and metabolic pathways in mouse hepatocytes and decreases NNMT expression, while NNMT deficiency worsens the toxic effect of iron overload. For these reasons, NNMT may be a drug target for the prevention of iron‐induced hepatotoxicity. (Hepatology Communications 2017;1:803–815) PMID:29404495

Incidentally Detected Transfusion-associated Iron Overload in 3 Children After Cancer Chemotherapy.

PubMed

Kuo, Dennis John; Bhagia, Pooja

2018-04-01

Iron overload is a potential long-term complication among cancer survivors who received transfusions during treatment. Although there are screening guidelines for iron overload in pediatric survivors of hematopoietic stem cell transplant, these do not call for screening of other pediatric oncology patients. In our practice we incidentally discovered 3 patients in a population of 168 cancer survivors over the span of 17 years who were treated for cancer without hematopoietic stem cell transplant who had iron overload. The 3 patients had elevated liver iron on magnetic resonance imaging T2* and 2 received therapeutic phlebotomy. These cases, and others like them, suggest that collaborative groups should consider revisiting the literature to establish screening and treatment guidelines for iron overload after cancer therapy.

The interaction of fatigue cracks with a residual stress field using thermoelastic stress analysis and synchrotron X-ray diffraction experiments

PubMed Central

Amjad, Khurram; Asquith, David; Sebastian, Christopher M.; Wang, Wei-Chung

2017-01-01

This article presents an experimental study on the fatigue behaviour of cracks emanating from cold-expanded holes utilizing thermoelastic stress analysis (TSA) and synchrotron X-ray diffraction (SXRD) techniques with the aim of resolving the long-standing ambiguity in the literature regarding potential relaxation, or modification, of beneficial compressive residual stresses as a result of fatigue crack propagation. The crack growth rates are found to be substantially lower as the crack tip moved through the residual stress zone induced by cold expansion. The TSA results demonstrated that the crack tip plastic zones were reduced in size by the presence of the residual compressive stresses induced by cold expansion. The crack tip plastic zones were found to be insignificant in size in comparison to the residual stress zone resulting from cold expansion, which implied that they were unlikely to have had a notable impact on the surrounding residual stresses induced by cold expansion. The residual stress distributions measured along the direction of crack growth, using SXRD, showed no signs of any significant stress relaxation or redistribution, which validates the conclusions drawn from the TSA data. Fractographic analysis qualitatively confirmed the influence on crack initiation of the residual stresses induced by the cold expansion. It was found that the application of single compressive overload caused a relaxation, or reduction in the residual stresses, which has wider implications for improving the fatigue life. PMID:29291095

Overload protection for switching regulators

NASA Technical Reports Server (NTRS)

Lachochi, E.

1980-01-01

Circuit protects all output lines of switching regulator against overloads without requiring current sensors on every line. If overload is sensed, device short circuits bias on switching transistor so that power is rapidly cut off from loads. Circuit also includes delay network to inhibit erroneous operation during startup.

The Mythology of Information Overload.

ERIC Educational Resources Information Center

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)

Deferasirox : a review of its use in the management of transfusional chronic iron overload.

PubMed

Yang, Lily P H; Keam, Susan J; Keating, Gillian M

2007-01-01

Deferasirox (Exjade) is an oral, once-daily iron chelator widely approved for the treatment of transfusional chronic iron overload. In the EU, deferasirox is indicated in patients with beta-thalassaemia major aged > or =6 years and, in the US, in all transfusional chronic iron overload patients aged > or =2 years. Deferasirox is highly selective for iron as Fe3+. In approximately 1-year clinical trials of patients with transfusional chronic iron overload associated with beta-thalassaemia, sickle cell disease, myelodysplastic syndrome or other rare chronic anaemias, deferasirox 20 or 30 mg/kg/day had a beneficial effect on liver iron concentrations (LIC) and serum ferritin levels; tolerability issues were clinically manageable with regular patient monitoring. Although longer-term efficacy and tolerability data are required, in particular examining the prevention of iron overload-related complications and the effect of deferasirox on renal function, deferasirox is an easily administered iron chelator and is a valuable option in the management of transfusional chronic iron overload.

Diagnosis and treatment of cardiac iron overload in transfusion-dependent thalassemia patients.

PubMed

Siri-Angkul, Natthaphat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2018-05-18

Thalassemia is among the most common genetic diseases. Patients with severe forms of the disease are transfusion-dependent, leading to iron overload. A condition which can eventually develop in the iron-loaded heart is iron overload cardiomyopathy, a debilitating disease that accounts for the majority of deaths in thalassemia patients. Areas covered: This review article provides a comprehensive summary of the diagnosis and treatment of cardiac iron overload in transfusion-dependent thalassemia patients, with discussion covering current weak points and potential improvements of the relevant diagnostic and therapeutic strategies. Expert commentary: Current limitations of various diagnostic techniques for iron overload cardiomyopathy include suboptimal accuracy, untimely detection, or inadequate accessibility, and novel modalities are required to overcome these shortcomings. Treatment should address key pathophysiologic mechanisms of iron overload cardiomyopathy, which include cardiac iron mishandling and iron-induced oxidative injury. Apart from the promotion of iron removal by chelators, prevention of cardiac iron deposition and attenuation of oxidative damage should also be rigorously investigated on a cell-to-bedside basis.

Iron overload and chelation therapy in myelodysplastic syndromes.

PubMed

Temraz, Sally; Santini, Valeria; Musallam, Khaled; Taher, Ali

2014-07-01

Iron overload remains a concern in MDS patients especially those requiring recurrent blood transfusions. The consequence of iron overload may be more relevant in patients with low and intermediate-1 risk MDS who may survive long enough to experience such manifestations. It is a matter of debate whether this overload has time to yield organ damage, but it is quite evident that cellular damage and DNA genotoxic effect are induced. Iron overload may play a critical role in exacerbating pre-existing morbidity or even unmask silent ones. Under these circumstances, iron chelation therapy could play an integral role in the management of these patients. This review entails an in depth analysis of iron overload in MDS patients; its pathophysiology, effect on survival, associated risks and diagnostic options. It also discusses management options in relation to chelation therapy used in MDS patients and the impact it has on survival, hematologic response and organ function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Association Between Fluid Balance and Outcomes in Critically Ill Children: A Systematic Review and Meta-analysis.

PubMed

Alobaidi, Rashid; Morgan, Catherine; Basu, Rajit K; Stenson, Erin; Featherstone, Robin; Majumdar, Sumit R; Bagshaw, Sean M

2018-03-01

After initial resuscitation, critically ill children may accumulate fluid and develop fluid overload. Accruing evidence suggests that fluid overload contributes to greater complexity of care and worse outcomes. To describe the methods to measure fluid balance, define fluid overload, and evaluate the association between fluid balance and outcomes in critically ill children. Systematic search of MEDLINE, EMBASE, Cochrane Library, trial registries, and selected gray literature from inception to March 2017. Studies of children admitted to pediatric intensive care units that described fluid balance or fluid overload and reported outcomes of interest were included. No language restrictions were applied. All stages were conducted independently by 2 reviewers. Data extracted included study characteristics, population, fluid metrics, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale. Narrative description of fluid assessment methods and fluid overload definitions was done. When feasible, pooled analyses were performed using random-effects models. Mortality was the primary outcome. Secondary outcomes included treatment intensity, organ failure, and resource use. A total of 44 studies (7507 children) were included in this systematic review and meta-analysis. Of those, 27 (61%) were retrospective cohort studies, 13 (30%) were prospective cohort studies, 3 (7%) were case-control studies, and 1 study (2%) was a secondary analysis of a randomized trial. The proportion of children with fluid overload varied by case mix and fluid overload definition (median, 33%; range, 10%-83%). Fluid overload, however defined, was associated with increased in-hospital mortality (17 studies [n = 2853]; odds ratio [OR], 4.34 [95% CI, 3.01-6.26]; I2 = 61%). Survivors had lower percentage fluid overload than nonsurvivors (22 studies [n = 2848]; mean difference, -5.62 [95% CI, -7.28 to -3.97]; I2 = 76%). After adjustment for illness severity, there was a 6% increase in odds of mortality for every 1% increase in percentage fluid overload (11 studies [n = 3200]; adjusted OR, 1.06 [95% CI, 1.03-1.10]; I2 = 66%). Fluid overload was associated with increased risk for prolonged mechanical ventilation (>48 hours) (3 studies [n = 631]; OR, 2.14 [95% CI, 1.25-3.66]; I2 = 0%) and acute kidney injury (7 studies [n = 1833]; OR, 2.36 [95% CI, 1.27-4.38]; I2 = 78%). Fluid overload is common and is associated with substantial morbidity and mortality in critically ill children. Additional research should now ideally focus on interventions aimed to mitigate the potential for harm associated with fluid overload.

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

PubMed

Dearth, Christopher L; Goh, Qingnian; Marino, Joseph S; Cicinelli, Peter A; Torres-Palsa, Maria J; Pierre, Philippe; Worth, Randall G; Pizza, Francis X

2013-01-01

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.

Urotensin II inhibited the proliferation of cardiac side population cells in mice during pressure overload by JNK-LRP6 signalling

PubMed Central

Chen, Zhidan; Xu, Jiahong; Ye, Yong; Li, Yang; Gong, Hui; Zhang, Guoping; Wu, Jian; jia, Jianguo; Liu, Ming; Chen, Ying; Yang, Chunjie; Tang, Yu; Zhu, Yichun; Ge, Junbo; Zou, Yunzeng

2014-01-01

Cardiac side population cells (CSPs) are promising cell resource for the regeneration in diseased heart as intrinsic cardiac stem cells. However, the relative low ratio of CSPs in the heart limited the ability of CSPs to repair heart and improve cardiac function effectively under pathophysiological condition. Which factors limiting the proliferation of CSPs in diseased heart are unclear. Here, we show that urotensin II (UII) regulates the proliferation of CSPs by c-Jun N-terminal kinase (JNK) and low density lipoprotein receptor-related protein 6 (LRP6) signalling during pressure overload. Pressure overload greatly upregulated UII level in plasma, UII receptor (UT) antagonist, urantide, promoted CSPs proliferation and improved cardiac dysfunction during chronic pressure overload. In cultured CSPs subjected to mechanical stretch (MS), UII significantly inhibited the proliferation by UT. Nanofluidic proteomic immunoassay showed that it is the JNK activation, but not the extracellular signal-regulated kinase signalling, that involved in the UII-inhibited- proliferation of CSPs during pressure overload. Further analysis in vitro indicated UII-induced-phospho-JNK regulates phosphorylation of LRP6 in cultured CSPs after MS, which is important in the inhibitory effect of UII on the CSPs during pressure overload. In conclusion, UII inhibited the proliferation of CSPs by JNK/LRP6 signalling during pressure overload. Pharmacological inhibition of UII promotes CSPs proliferation in mice, offering a possible therapeutic approach for cardiac failure induced by pressure overload. PMID:24447593

Skeletal Muscle Cells Express ICAM-1 after Muscle Overload and ICAM-1 Contributes to the Ensuing Hypertrophic Response

PubMed Central

Dearth, Christopher L.; Goh, Qingnian; Marino, Joseph S.; Cicinelli, Peter A.; Torres-Palsa, Maria J.; Pierre, Philippe; Worth, Randall G.; Pizza, Francis X.

2013-01-01

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. PMID:23505517

Deferasirox for Treating Patients Who Have Undergone Allogeneic Stem Cell Transplant and Have Iron Overload

ClinicalTrials.gov

2017-11-07

Iron Overload; Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Neuroblastoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage II Ovarian Epithelial Cancer; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Malignant Testicular Germ Cell Tumor; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Ovarian Epithelial Cancer; Stage III Small Lymphocytic Lymphoma; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Breast Cancer; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Ovarian Epithelial Cancer; Stage IV Small Lymphocytic Lymphoma

Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells.

PubMed

Hu Frisk, Jun Mei; Kjellén, Lena; Kaler, Stephen G; Pejler, Gunnar; Öhrvik, Helena

2017-12-15

Copper has previously been implicated in the regulation of immune responses, but the impact of this metal on mast cells is poorly understood. In this article, we address this issue and show that copper starvation of mast cells causes increased granule maturation, as indicated by higher proteoglycan content, stronger metachromatic staining, and altered ultrastructure in comparison with nontreated cells, whereas copper overload has the opposite effects. In contrast, copper status did not impact storage of histamine in mast cells, nor did alterations in copper levels affect the ability of mast cells to degranulate in response to IgER cross-linking. A striking finding was decreased tryptase content in mast cells with copper overload, whereas copper starvation increased tryptase content. These effects were associated with corresponding shifts in tryptase mRNA levels, suggesting that copper affects tryptase gene regulation. Mechanistically, we found that alterations in copper status affected the expression of microphthalmia-associated transcription factor, a transcription factor critical for driving tryptase expression. We also found evidence supporting the concept that the effects on microphthalmia-associated transcription factor are dependent on copper-mediated modulation of MAPK signaling. Finally, we show that, in MEDNIK syndrome, a condition associated with low copper levels and a hyperallergenic skin phenotype, including pruritis and dermatitis, the number of tryptase-positive mast cells is increased. Taken together, our findings reveal a hitherto unrecognized role for copper in the regulation of mast cell gene expression and maturation. Copyright © 2017 by The American Association of Immunologists, Inc.

Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).

PubMed

Ingrassia, Rosaria; Memo, Maurizio; Garavaglia, Barbara

2017-01-01

Mutations in WDR45 gene, coding for a beta-propeller protein, have been found in patients affected by Neurodegeneration with Brain Iron Accumulation, NBIA5 (also known as BPAN). BPAN is a movement disorder with Non Transferrin Bound Iron (NTBI) accumulation in the basal ganglia as common hallmark between NBIA classes (Hayflick et al., 2013). WDR45 has been predicted to have a role in autophagy, while the impairment of iron metabolism in the different NBIA subclasses has not currently been clarified. We found the up-regulation of the ferrous iron transporter (-)IRE/Divalent Metal Transporter1 and down-regulation of Transferrin receptor in the fibroblasts of two BPAN affected patients with splicing mutations 235+1G>A (BPAN1) and 517_519ΔVal 173 (BPAN2). The BPAN patients showed a concomitant increase of intracellular ferrous iron after starvation. An altered pattern of iron transporters with iron overload is highlighted in BPAN human fibroblasts, supporting for a role of DMT1 in NBIA. We here present a novel element, about iron accumulation, to the existing knowledge in field of NBIA. Attention is focused to a starvation-dependent iron overload, possibly accounting for iron accumulation in the basal ganglia. Further investigation could clarify iron regulation in BPAN.

Learners' Perceived Information Overload in Online Learning via Computer-Mediated Communication

ERIC Educational Resources Information Center

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…

30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 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... installed so as to protect all electric equipment and circuits against short circuit and overloads. Three...

30 CFR 77.506-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... short circuit protection; minimum requirements. 77.506-1 Section 77.506-1 Mineral Resources MINE SAFETY...-1 Electric equipment and circuits; overload and short circuit protection; minimum requirements. Devices providing either short circuit protection or protection against overload shall conform to the...

Role Overload, Job Satisfaction, Leisure Satisfaction, and Psychological Health among Employed Women

ERIC Educational Resources Information Center

Pearson, Quinn M.

2008-01-01

Role overload, job satisfaction, leisure satisfaction, and psychological health were measured for 155 women who were employed full time. Role overload was negatively correlated with psychological health, job satisfaction, and leisure satisfaction. Job satisfaction and leisure satisfaction were positively correlated with psychological health.…

Testosterone and muscle hypertrophy in female rats

NASA Technical Reports Server (NTRS)

Kuhn, F. E.; Max, S. R.

1985-01-01

The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

Autoimmune Hepatitis: Diagnostic Dilemma When It Is Disguised as Iron Overload Syndrome.

PubMed

Acharya, Gyanendra K; Liao, Hung-I; Frunza-Stefan, Simona; Patel, Ronakkumar; Khaing, Moe

2017-09-01

Elevated serum ferritin level is a common finding in iron overload syndrome, autoimmune and viral hepatitis, alcoholic and nonalcoholic fatty liver diseases. High transferrin saturation is not a common finding in above diseases except for iron overload syndrome. We encountered a challenging case of 73-year-old female who presented with yellowish discoloration of skin, dark color urine and dull abdominal pain. Initial laboratory tests reported mild anemia; elevated bilirubin, liver enzymes, and transferrin saturation. We came to the final diagnosis of autoimmune hepatitis after extensive workups. Autoimmune hepatitis is a rare disease, and the diagnosis can be further complicated by a similar presentation of iron overload syndrome. Markedly elevated transferrin saturation can simulate iron overload syndrome, but a liver biopsy can guide physicians to navigate the diagnosis.

Qualitative job stress and ego aptitude in male scientific researchers.

PubMed

Sakagami, Yu

2016-11-22

Job environments have been fundamentally changed by globalization and modern technological innovation. Qualitative workload is expected to increase more than quantitative workload through this rapid technological innovation. Especially, in developed countries, qualitative workload is expected to become a primary job-related stress factor in the near future. Therefore, it is essential to clarify the characteristics of qualitative workload and to determine how to cope with it effectively. Since job stress level and ego aptitude are correlated and qualitative overload increases stress, we examined qualitative overload and ego aptitude among male Japanese cutting-edge science researchers. The Brief Job Stress Questionnaire and the Tokyo University Ego-gram New Version II were distributed to all workers at two Japanese academic institutions. Qualitative overload and adult ego aptitude, representing rationalism, were higher in male researchers than in the Japanese male general sample. In addition, adapted child aptitude, representing obedience, was lower in male researchers. Lack of supervisor support was positively associated with qualitative overload, and nurturing parent ego aptitude was negatively associated with it. Male researchers had higher levels of qualitative overload. Increasing supervisor support is essential in decreasing this qualitative overload. Furthermore, enhancement of nurturing parent ego aptitude (i.e., careful consideration for others) is also important for qualitative overload management.

Effects of intracellular iron overload on cell death and identification of potent cell death inhibitors.

PubMed

Fang, Shenglin; Yu, Xiaonan; Ding, Haoxuan; Han, Jianan; Feng, Jie

2018-06-11

Iron overload causes many diseases, while the underlying etiologies of these diseases are unclear. Cell death processes including apoptosis, necroptosis, cyclophilin D-(CypD)-dependent necrosis and a recently described additional form of regulated cell death called ferroptosis, are dependent on iron or iron-dependent reactive oxygen species (ROS). However, whether the accumulation of intracellular iron itself induces ferroptosis or other forms of cell death is largely elusive. In present study, we study the role of intracellular iron overload itself-induced cell death mechanisms by using ferric ammonium citrate (FAC) and a membrane-permeable Ferric 8-hydroxyquinoline complex (Fe-8HQ) respectively. We show that FAC-induced intracellular iron overload causes ferroptosis. We also identify 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitor GSK2334470 as a potent ferroptosis inhibitor. Whereas, Fe-8HQ-induced intracellular iron overload causes unregulated necrosis, but partially activates PARP-1 dependent parthanatos. Interestingly, we identify many phenolic compounds as potent inhibitors of Fe-8HQ-induced cell death. In conclusion, intracellular iron overload-induced cell death form might be dependent on the intracellular iron accumulation rate, newly identified cell death inhibitors in our study that target ferroptosis and unregulated oxidative cell death represent potential therapeutic strategies against iron overload related diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Lactate dehydrogenase regulation in aged skeletal muscle: Regulation by anabolic steroids and functional overload.

PubMed

Washington, Tyrone A; Healey, Julie M; Thompson, Raymond W; Lowe, Larry L; Carson, James A

2014-09-01

Aging alters the skeletal muscle response to overload-induced growth. The onset of functional overload is characterized by increased myoblast proliferation and an altered muscle metabolic profile. The onset of functional overload is associated with increased energy demands that are met through the interconversion of lactate and pyruvate via the activity of lactate dehydrogenase (LDH). Testosterone targets many of the processes activated at the onset of functional overload. However, the effect of aging on this metabolic plasticity at the onset of functional overload and how anabolic steroid administration modulates this response is not well understood. The purpose of this study was to determine if aging would alter overload-induced LDH activity and expression at the onset of functional overload and whether anabolic steroid administration would modulate this response. Five-month and 25-month male Fischer 344xF1 BRN were given nandrolone decanoate (ND) or sham injections for 14days and then the plantaris was functionally overloaded (OV) for 3days by synergist ablation. Aging reduced muscle LDH-A & LDH-B activity 70% (p<0.05). Aging also reduced LDH-A mRNA abundance, however there was no age effect on LDH-B mRNA abundance. In 5-month muscle, both ND and OV decreased LDH-A and LDH-B activity. However, there was no synergistic or additive effect. In 5-month muscle, ND and OV decreased LDH-A mRNA expression with no change in LDH-B expression. In 25-month muscle, ND and OV increased LDH-A and LDH-B activity. LDH-A mRNA expression was not altered by ND or OV in aged muscle. However, there was a main effect of OV to decrease LDH-B mRNA expression. There was also an age-induced LDH isoform shift. ND and OV treatment increased the "fast" LDH isoforms in aged muscle, whereas ND and OV increased the "slow" isoforms in young muscle. Our study provides evidence that aging alters aspects of skeletal muscle metabolic plasticity normally induced by overload and anabolic steroid administration. Copyright © 2014 Elsevier Inc. All rights reserved.

Bioaugmentation of overloaded anaerobic digesters restores function and archaeal community.

PubMed

Tale, V P; Maki, J S; Zitomer, D H

2015-03-01

Adding beneficial microorganisms to anaerobic digesters for improved performance (i.e. bioaugmentation) has been shown to decrease recovery time after organic overload or toxicity upset. Compared to strictly anaerobic cultures, adding aerotolerant methanogenic cultures may be more practical since they exhibit higher methanogenic activity and can be easily dried and stored in ambient air for future shipping and use. In this study, anaerobic digesters were bioaugmented with both anaerobic and aerated, methanogenic propionate enrichment cultures after a transient organic overload. Digesters bioaugmented with anaerobic and moderately aerated cultures recovered 25 and 100 days before non-bioaugmented digesters, respectively. Increased methane production due to bioaugmentation continued a long time, with 50-120% increases 6 to 12 SRTs (60-120 days) after overload. In contrast to the anaerobic enrichment, the aerated enrichments were more effective as bioaugmentation cultures, resulting in faster recovery of upset digester methane and COD removal rates. Sixty days after overload, the bioaugmented digester archaeal community was not shifted, but was restored to one similar to the pre-overload community. In contrast, non-bioaugmented digester archaeal communities before and after overload were significantly different. Organisms most similar to Methanospirillum hungatei had higher relative abundance in well-operating, undisturbed and bioaugmented digesters, whereas organisms similar to Methanolinea tarda were more abundant in upset, non-bioaugmented digesters. Bioaugmentation is a beneficial approach to increase digester recovery rate after transient organic overload events. Moderately aerated, methanogenic propionate enrichment cultures were more beneficial augments than a strictly anaerobic enrichment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Overload retardation due to plasticity-induced crack closure

NASA Technical Reports Server (NTRS)

Fleck, N. A.; Shercliff, H. R.

1989-01-01

Experiments are reported which show that plasticity-induced crack closure can account for crack growth retardation following an overload. The finite element method is used to provide evidence which supports the experimental observations of crack closure. Finally, a simple model is presented which predicts with limited success the retardation transient following an overload.

Managing Information Overload for Senior Leaders in the 21st Century

ERIC Educational Resources Information Center

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…

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

PubMed

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

2008-07-23

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.

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

PubMed

Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

2011-12-01

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Survivability of Autonomous Microgrid during Overload Events

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Wei; Lasseter, Robert H.; Khalsa, Amrit S.

Grid-forming sources are voltage sources that draw necessary currents to meet any load changes. A load step can cause part or all of these sources to become overloaded in a microgrid. This paper presents an overload mitigation controller that addresses the two overload issues in a microgrid by actively controlling the sources’ frequency. When part of the sources in a microgrid is overloaded, the controller autonomously transfers the extra load to other sources by rapidly reducing its frequency. The frequency difference between sources during transient results in a change of phase angle, which redistributes the power flow. When all sourcesmore » in a microgrid are overloaded, each source keeps dropping the frequency. Therefore, under frequency load shedding can be used to trip the non-critical loads resulting in the survival of microgrid. The advantages of these concepts are that communications between sources are not needed during transient, and the robust voltage control is maintained. Lastly, simulation and field tests from CERTS/AEP microgrid test site verify that the control strategy is effective in both purely inverter-based microgrids and inverter & generator mixed microgrids.« less

Thermal overload protection for electric motors on safety-related motor-operated valves: Generic Issue II. E. 6. 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothberg, O.

1988-06-01

NRC regulatory positions, as stated in Regulatory Guide 1.106, Revision 1, have been identified by the Office for Analysis and Evaluation of Operational Data (AEOD) as potential contributors to valve motor burnout. AEOD is particularly concerned about the allowed policy of bypassing thermal overload devices during normal or accident conditions. Regulatory Guide 1.106 favors compromising the function of thermal overload devices in favor of completing the safety-related action of valves. The purpose of this study was to determine if the guidance contained in Regulatory Guide 1.106 is appropriate and, if not, to recommend the necessary changes. This report describes thermalmore » overload devices commonly used to protect safety-related valve operator motors. The regulatory guidelines stated in Regulatory Guide 1.106 along with the limitations of thermal overload protection are discussed. Supplements and alternatives to thermal overload protection are also described. Findings and conclusions of several AEOD reports are discussed. Information obtained from the standard review plan, standard technical specifications, technical specifications from representative plants, and several papers are cited.« less

Survivability of Autonomous Microgrid during Overload Events

DOE PAGES

Du, Wei; Lasseter, Robert H.; Khalsa, Amrit S.

2018-04-23

Grid-forming sources are voltage sources that draw necessary currents to meet any load changes. A load step can cause part or all of these sources to become overloaded in a microgrid. This paper presents an overload mitigation controller that addresses the two overload issues in a microgrid by actively controlling the sources’ frequency. When part of the sources in a microgrid is overloaded, the controller autonomously transfers the extra load to other sources by rapidly reducing its frequency. The frequency difference between sources during transient results in a change of phase angle, which redistributes the power flow. When all sourcesmore » in a microgrid are overloaded, each source keeps dropping the frequency. Therefore, under frequency load shedding can be used to trip the non-critical loads resulting in the survival of microgrid. The advantages of these concepts are that communications between sources are not needed during transient, and the robust voltage control is maintained. Lastly, simulation and field tests from CERTS/AEP microgrid test site verify that the control strategy is effective in both purely inverter-based microgrids and inverter & generator mixed microgrids.« less

[Role of melatonin in calcium overload-induced heart injury].

PubMed

Kong, Lingheng; Wei, Ming; Sun, Na; Zhu, Juanxia; Su, Xingli

2017-06-28

To investigate the role of melatonin in calcium overload-induced heart injury.
 Methods: Thirty-two rats were divided into 4 groups: a control group (Control), a melatonin control group (Mel), a calcium overload group (CaP), and a calcium overload plus melatonin group (Mel+CaP). Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Triphenyltetrazolium chloride staining was used to measure the infarct size of myocardium. Lactate dehydrogenase (LDH) activity in the coronary flow was determined. The expressions of caspase-3 and cytochrome c were determined by Western blot. The pathological morphological changes in myocardial fiber were analyzed by HE staining.
 Results: Compared with the control group, calcium overload significantly induced an enlarged infarct size (P<0.01), accompanied by the disordered arrangement of myocardial fiber, up-regulation of cytochrome c and caspase-3 (P<0.01), and the increased activity of LDH (P<0.01). These effects were significantly attenuated by 10 μmol/L melatonin (P<0.01).
 Conclusion: Melatonin can alleviate calcium overload-induced heart injury.

Predictors of Work-Family Role Conflict and Its Impact on Professional Women in Medicine, Engineering, and Information Technology in Nigeria.

PubMed

Uzoigwe, Anthonia Ginika; Low, Wah Yun; Noor, Siti Nurani Mohd

2016-10-01

This study examines work-family role conflict and the factors predicting it, with a sample of 173 professional women in engineering and information technology (IT) firms, including 2 hospitals-1 public and 1 private. Our findings show no significant difference in the level of work-family role conflict encountered by women across medicine, engineering, and IT, whereas hours of work, family responsibilities, job demand, and work role overload were significantly correlated with work-family role conflict. Multiple linear regression analysis indicates that only work role overload, family responsibilities, and hours of work significantly predicted 45.9% of work-family role conflict. This implies that working women are burdened by work demands, which invariably affects the work-family role conflict they experience and leads to deterioration of their occupational health. It is suggested that employers should create a flexible work schedule and establish family-friendly policies in the workplace to promote a healthy work-life balance for women in science careers.

Time-controlled fasting prevents aging-like mitochondrial changes induced by persistent dietary fat overload in skeletal muscle

PubMed Central

Lettieri-Barbato, Daniele; Cannata, Stefano Maria; Casagrande, Viviana; Ciriolo, Maria Rosa

2018-01-01

A large body of evidence suggests that persistent dietary fat overload causes mitochondrial dysfunction and systemic metabolic gridlock. Mitochondrial and lipid metabolism in skeletal muscle (SkM) are severely affected upon persistent high fat diet (HFD) leading to premature tissue aging. Here, we designed weekly cycles of fasting (called as time-controlled fasting, TCF) and showed that they were effective in limiting mitochondrial damage and metabolic disturbances induced by HFD. Specifically, TCF was able to prevent the decline of adipose triglyceride lipase (Atgl), maintain efficient mitochondrial respiration in SkM as well as improve blood glucose and lipid profile. Atgl was found to be the mediator of such preventive effects as its downregulation or up-regulation in C2C12 myotubes triggers mitochondrial alteration or protects against the deleterious effects of high fat levels respectively. In conclusion, TCF could represent an effective strategy to limit mitochondrial impairment and metabolic inflexibility that are typically induced by modern western diets or during aging. PMID:29742122

Effect of olfactory manganese exposure on anxiety-related behavior in a mouse model of iron overload hemochromatosis

PubMed Central

Ye, Qi; Kim, Jonghan

2015-01-01

Manganese in excess promotes unstable emotional behavior. Our previous study showed that olfactory manganese uptake into the brain is altered in Hfe−/− mice, a model of iron overload hemochromatosis, suggesting that Hfe deficiency could modify the neurotoxicity of airborne manganese. We determined anxiety-related behavior and monoaminergic protein expression after repeated intranasal instillation of MnCl2 to Hfe−/− mice. Compared with manganese-instilled wild-type mice, Hfe−/− mice showed decreased manganese accumulation in the cerebellum. Hfe−/− mice also exhibited increased anxiety with decreased exploratory activity and elevated dopamine D1 receptor and norepinephrine transporter in the striatum. Moreover, Hfe deficiency attenuated manganese-associated impulsivity and modified the effect of manganese on the expression of tyrosine hydroxylase, vesicular monoamine transporter and serotonin transporter. Together, our data indicate that loss of HFE function alters manganese-associated emotional behavior and further suggest that HFE could be a potential molecular target to alleviate affective disorders induced by manganese inhalation. PMID:26189056

Mitochondrial function and malfunction in the pathophysiology of pancreatitis.

PubMed

Gerasimenko, Oleg V; Gerasimenko, Julia V

2012-07-01

As a primary energy producer, mitochondria play a fundamental role in pancreatic exocrine physiology and pathology. The most frequent aetiology of acute pancreatitis is either gallstones or heavy alcohol consumption. Repeated episodes of acute pancreatitis can result in the development of chronic pancreatitis and increase the lifetime risk of pancreatic cancer 100-fold. Pancreatic cancer is one of the most common causes of cancer mortality with only about 3-4 % of patients surviving beyond 5 years. It has been shown that acute pancreatitis involves Ca²⁺ overload and overproduction of reactive oxygen species in pancreatic acinar cells. Both factors significantly affect mitochondria and lead to cell death. The pathogenesis of inflammation in acute and chronic pancreatitis is tightly linked to the induction of necrosis and apoptosis. There is currently no specific therapy for pancreatitis, but recent findings of an endogenous protective mechanism against Ca²⁺ overload--and particularly the potential to boost this protection--bring hope of new therapeutic approaches.

Autism in Brazil: a systematic review of family challenges and coping strategies.

PubMed

Gomes, Paulyane T M; Lima, Leonardo H L; Bueno, Mayza K G; Araújo, Liubiana A; Souza, Nathan M

2015-01-01

To describe the challenges faced by families caring for children with autism spectrum disorder (ASD) in Brazil and the coping strategies employed. Systematic review of articles published until September of 2013, without language restrictions, using quality appraisal (AMSTAR and CASP/Oxford instruments). The literature shows parental emotional overload as one of the main challenges faced by families, especially mothers. The main stressors were diagnostic postponement, difficulty dealing with the diagnosis and associated symptoms, and poor access to health services and social support. The predominant coping strategies found included information exchange between affected families and integrated healthcare network for patient and family support. ASD exerts strong influence on family dynamics, resulting in caregiver overload, especially in mothers. The Brazilian Unified Health System needs to provide comprehensive, continuous, and coordinated care to strengthen the patient-family dyad and promote the full development and societal inclusion of children with ASD. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Time-controlled fasting prevents aging-like mitochondrial changes induced by persistent dietary fat overload in skeletal muscle.

PubMed

Lettieri-Barbato, Daniele; Cannata, Stefano Maria; Casagrande, Viviana; Ciriolo, Maria Rosa; Aquilano, Katia

2018-01-01

A large body of evidence suggests that persistent dietary fat overload causes mitochondrial dysfunction and systemic metabolic gridlock. Mitochondrial and lipid metabolism in skeletal muscle (SkM) are severely affected upon persistent high fat diet (HFD) leading to premature tissue aging. Here, we designed weekly cycles of fasting (called as time-controlled fasting, TCF) and showed that they were effective in limiting mitochondrial damage and metabolic disturbances induced by HFD. Specifically, TCF was able to prevent the decline of adipose triglyceride lipase (Atgl), maintain efficient mitochondrial respiration in SkM as well as improve blood glucose and lipid profile. Atgl was found to be the mediator of such preventive effects as its downregulation or up-regulation in C2C12 myotubes triggers mitochondrial alteration or protects against the deleterious effects of high fat levels respectively. In conclusion, TCF could represent an effective strategy to limit mitochondrial impairment and metabolic inflexibility that are typically induced by modern western diets or during aging.

Perinatal α-tocopherol overload programs alterations in kidney development and renal angiotensin II signaling pathways at birth and at juvenile age: Mechanisms underlying the development of elevated blood pressure.

PubMed

Ribeiro, Valdilene S; Cabral, Edjair V; Vieira, Leucio D; Aires, Regina S; Farias, Juliane S; Muzi-Filho, Humberto; Vieyra, Adalberto; Paixão, Ana D

2018-07-01

α-Tocopherol (α-Toc) overload increases the risk of dying in humans (E.R. Miller III et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality Ann Int Med. 142 (2005) 37-46), and overload during early development leads to elevation of blood pressure at adult life, but the mechanism(s) remains unknown. We hypothesized that α-Toc overload during organogenesis affects the renal renin angiotensin system (RAS) components and renal Na + handling, culminating with late elevated blood pressure. Pregnant Wistar rats received α-Toc or the superoxide dismutase mimetic tempol throughout pregnancy. We evaluated components of the intrarenal renin angiotensin system in neonate and juvenile offspring: Ang II-positive cells, Ang II receptors (AT 1 and AT 2 ), linked protein kinases, O 2 - production, NADPH oxidase abundance, lipid peroxidation and activity of Na + -transporting ATPases. In juvenile offspring we followed the evolution of arterial blood pressure. Neonates from α-Toc and tempol mothers presented with accentuated retardment in tubular development, pronounced decrease in glomerular Ang II-positive cells and AT 1 /AT 2 ratio, intense production of O 2 - and upregulation of the α, ε and λ PKC isoforms. α-Toc decreased or augmented the abundance of renal (Na + +K + )ATPase depending on the age and α-Toc dose. In juvenile rats the number of Ang II-positive cells returned to control values as well as PKCα, but co-existing with marked upregulation in the activity of (Na + +K + ) and Na + -ATPase and elevated arterial pressure at 30 days. We conclude that the mechanisms of these alterations rely on selective targeting of renal RAS components through genic and pro-oxidant effects of the vitamin. Copyright © 2018 Elsevier B.V. All rights reserved.

Potential nonresponse bias in a clinical examination after initial screening using iron phenotyping and HFE genotyping in the hemochromatosis and iron overload screening study.

PubMed

Speechley, Mark; Barton, James C; Passmore, Leah; Harrison, Helen; Reboussin, David M; Harris, Emily L; Rivers, Charles A; Fadojutimi-Akinsiku, Margaret; Wenzel, Lari; Diaz, Sharmin

2009-12-01

Little is known about the factors affecting participation in clinical assessments after HEmochromatosis and IRon Overload Screening. Initial screening of 101,168 primary care patients in the HEmochromatosis and IRon Overload Screening study was performed using serum iron measures and hemochromatosis gene (HFE) genotyping. Using iron phenotypes and HFE genotypes, we identified 2256 cases and 1232 controls eligible to participate in a clinical examination. To assess the potential for nonresponse bias, we compared the sociodemographic, health status, and attitudinal characteristics of participants and nonparticipants using adjusted odds ratios (ORs) and 95% confidence interval (CI). Overall participation was 74% in cases and 52% in controls; in both groups, participation was highest at a health maintenance organization and lowest among those under 45 years of age (cases: OR = 0.68; 95% CI 0.53, 0.87; controls: OR = 0.59; 95% CI 0.44, 0.78). In controls only, participation was also lower among those over 65 years of age than the reference group aged 46-64 (OR = 0.64; 95% CI 0.47, 0.88). Among cases, participation was higher in HFE C282Y homozygotes (OR = 3.98; 95% CI 2.60, 6.09), H63D homozygotes (OR = 2.79; 95% CI 1.23, 6.32), and C282Y/H63D compound heterozygotes (OR = 1.82; 95% CI 1.03, 3.22) than in other genotypes, and lower among non-Caucasians and those who preferred a non-English language than in Caucasians and those who preferred English (p < 0.0001). Subjects with greatest risk to have iron overload (C282Y homozygotes; cases > or =45 years; Caucasians) were more likely to participate in a postscreening clinical examination than other subjects. We detected no evidence of strong selection bias.

Force Limit System

NASA Technical Reports Server (NTRS)

Pawlik, Ralph; Krause, David; Bremenour, Frank

2011-01-01

The Force Limit System (FLS) was developed to protect test specimens from inadvertent overload. The load limit value is fully adjustable by the operator and works independently of the test system control as a mechanical (non-electrical) device. When a test specimen is loaded via an electromechanical or hydraulic test system, a chance of an overload condition exists. An overload applied to a specimen could result in irreparable damage to the specimen and/or fixturing. The FLS restricts the maximum load that an actuator can apply to a test specimen. When testing limited-run test articles or using very expensive fixtures, the use of such a device is highly recommended. Test setups typically use electronic peak protection, which can be the source of overload due to malfunctioning components or the inability to react quickly enough to load spikes. The FLS works independently of the electronic overload protection.

Parallel deterministic transport sweeps of structured and unstructured meshes with overloaded mesh decompositions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pautz, Shawn D.; Bailey, Teresa S.

Here, the efficiency of discrete ordinates transport sweeps depends on the scheduling algorithm, the domain decomposition, the problem to be solved, and the computational platform. Sweep scheduling algorithms may be categorized by their approach to several issues. In this paper we examine the strategy of domain overloading for mesh partitioning as one of the components of such algorithms. In particular, we extend the domain overloading strategy, previously defined and analyzed for structured meshes, to the general case of unstructured meshes. We also present computational results for both the structured and unstructured domain overloading cases. We find that an appropriate amountmore » of domain overloading can greatly improve the efficiency of parallel sweeps for both structured and unstructured partitionings of the test problems examined on up to 10 5 processor cores.« less

Parallel deterministic transport sweeps of structured and unstructured meshes with overloaded mesh decompositions

DOE PAGES

Pautz, Shawn D.; Bailey, Teresa S.

2016-11-29

Here, the efficiency of discrete ordinates transport sweeps depends on the scheduling algorithm, the domain decomposition, the problem to be solved, and the computational platform. Sweep scheduling algorithms may be categorized by their approach to several issues. In this paper we examine the strategy of domain overloading for mesh partitioning as one of the components of such algorithms. In particular, we extend the domain overloading strategy, previously defined and analyzed for structured meshes, to the general case of unstructured meshes. We also present computational results for both the structured and unstructured domain overloading cases. We find that an appropriate amountmore » of domain overloading can greatly improve the efficiency of parallel sweeps for both structured and unstructured partitionings of the test problems examined on up to 10 5 processor cores.« less

Differential Responses of Soleus and Plantaris Muscle Fibers to Overloading

NASA Astrophysics Data System (ADS)

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.

Fluid overload in the ICU: evaluation and management.

PubMed

Claure-Del Granado, Rolando; Mehta, Ravindra L

2016-08-02

Fluid overload is frequently found in acute kidney injury patients in critical care units. Recent studies have shown the relationship of fluid overload with adverse outcomes; hence, manage and optimization of fluid balance becomes a central component of the management of critically ill patients. In critically ill patients, in order to restore cardiac output, systemic blood pressure and renal perfusion an adequate fluid resuscitation is essential. Achieving an appropriate level of volume management requires knowledge of the underlying pathophysiology, evaluation of volume status, and selection of appropriate solution for volume repletion, and maintenance and modulation of the tissue perfusion. Numerous recent studies have established a correlation between fluid overload and mortality in critically ill patients. Fluid overload recognition and assessment requires an accurate documentation of intakes and outputs; yet, there is a wide difference in how it is evaluated, reviewed and utilized. Accurate volume status evaluation is essential for appropriate therapy since errors of volume evaluation can result in either in lack of essential treatment or unnecessary fluid administration, and both scenarios are associated with increased mortality. There are several methods to evaluate fluid status; however, most of the tests currently used are fairly inaccurate. Diuretics, especially loop diuretics, remain a valid therapeutic alternative. Fluid overload refractory to medical therapy requires the application of extracorporeal therapies. In critically ill patients, fluid overload is related to increased mortality and also lead to several complications like pulmonary edema, cardiac failure, delayed wound healing, tissue breakdown, and impaired bowel function. Therefore, the evaluation of volume status is crucial in the early management of critically ill patients. Diuretics are frequently used as an initial therapy; however, due to their limited effectiveness the use of continuous renal replacement techniques are often required for fluid overload treatment. Successful fluid overload treatment depends on precise assessment of individual volume status, understanding the principles of fluid management with ultrafiltration, and clear treatment goals.

Bioimpedance-Guided Fluid Management in Hemodialysis Patients

PubMed Central

Arias-Guillén, Marta; Wabel, Peter; Fontseré, Néstor; Carrera, Montserrat; Campistol, José Maria; Maduell, Francisco

2013-01-01

Summary Background and objectives Achieving and maintaining optimal fluid status remains a major challenge in hemodialysis therapy. The aim of this interventional study was to assess the feasibility and clinical consequences of active fluid management guided by bioimpedance spectroscopy in chronic hemodialysis patients. Design, setting, participants, & measurements Fluid status was optimized prospectively in 55 chronic hemodialysis patients over 3 months (November 2011 to February 2012). Predialysis fluid overload was measured weekly using the Fresenius Body Composition Monitor. Time-averaged fluid overload was calculated as the average between pre- and postdialysis fluid overload. The study aimed to bring the time-averaged fluid overload of all patients into a target range of 0.5±0.75 L within the first month and maintain optimal fluid status until study end. Postweight was adjusted weekly according to a predefined protocol. Results Time-averaged fluid overload in the complete study cohort was 0.9±1.6 L at baseline and 0.6±1.1 L at study end. Time-averaged fluid overload decreased by −1.20±1.32 L (P<0.01) in the fluid-overloaded group (n=17), remained unchanged in the normovolemic group (n=26, P=0.59), and increased by 0.59±0.76 L (P=0.02) in the dehydrated group (n=12). Every 1 L change in fluid overload was accompanied by a 9.9 mmHg/L change in predialysis systolic BP (r=0.55, P<0.001). At study end, 76% of all patients were either on time-averaged fluid overload target or at least closer to target than at study start. The number of intradialytic symptoms did not change significantly in any of the subgroups. Conclusions Active fluid management guided by bioimpedance spectroscopy was associated with an improvement in overall fluid status and BP. PMID:23949235

Differential modulation of right ventricular strain and right atrial mechanics in mild vs. severe pressure overload

PubMed Central

Voeller, Rochus K.; Aziz, Abdulhameed; Maniar, Hersh S.; Ufere, Nneka N.; Taggar, Ajay K.; Bernabe, Noel J.; Cupps, Brian P.

2011-01-01

Increased right atrial (RA) and ventricular (RV) chamber volumes are a late maladaptive response to chronic pulmonary hypertension. The purpose of the current investigation was to characterize the early compensatory changes that occur in the right heart during chronic RV pressure overload before the development of chamber dilation. Magnetic resonance imaging with radiofrequency tissue tagging was performed on dogs at baseline and after 10 wk of pulmonary artery banding to yield either mild RV pressure overload (36% rise in RV pressure; n = 5) or severe overload (250% rise in RV pressure; n = 4). The RV free wall was divided into three segments within a midventricular plane, and circumferential myocardial strain was calculated for each segment, the septum, and the left ventricle. Chamber volumes were calculated from stacked MRI images, and RA mechanics were characterized by calculating the RA reservoir, conduit, and pump contribution to RV filling. With mild RV overload, there were no changes in RV strain or RA function. With severe RV overload, RV circumferential strain diminished by 62% anterior (P = 0.04), 42% inferior (P = 0.03), and 50% in the septum (P = 0.02), with no change in the left ventricle (P = 0.12). RV filling became more dependent on RA conduit function, which increased from 30 ± 9 to 43 ± 13% (P = 0.01), than on RA reservoir function, which decreased from 47 ± 6 to 33 ± 4% (P = 0.04), with no change in RA pump function (P = 0.94). RA and RV volumes and RV ejection fraction were unchanged from baseline during either mild (P > 0.10) or severe RV pressure overload (P > 0.53). In response to severe RV pressure overload, RV myocardial strain is segmentally diminished and RV filling becomes more dependent on RA conduit rather than reservoir function. These compensatory mechanisms of the right heart occur early in chronic RV pressure overload before chamber dilation develops. PMID:21926343

Heat analysis of thermal overload relays using 3-D finite element method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawase, Yoshihiro; Ichihashi, Takayuki; Ito, Shokichi

1999-05-01

In designing a thermal overload relay, it is necessary to analyze thermal characteristics of several trial models. Up to now, this has been done by measuring the temperatures on a number of positions in the trial models. This experimental method is undoubtedly expensive. In this paper, the temperature distribution of a thermal overload relay is obtained by using 3-D finite element analysis taking into account the current distribution in current-carrying conductors. It is shown that the 3-D analysis is capable of evaluating a new design of thermal overload relays.

Deformation history and load sequence effects on cumulative fatigue damage and life predictions

NASA Astrophysics Data System (ADS)

Colin, Julie

Fatigue loading seldom involves constant amplitude loading. This is especially true in the cooling systems of nuclear power plants, typically made of stainless steel, where thermal fluctuations and water turbulent flow create variable amplitude loads, with presence of mean stresses and overloads. These complex loading sequences lead to the formation of networks of microcracks (crazing) that can propagate. As stainless steel is a material with strong deformation history effects and phase transformation resulting from plastic straining, such load sequence and variable amplitude loading effects are significant to its fatigue behavior and life predictions. The goal of this study was to investigate the effects of cyclic deformation on fatigue behavior of stainless steel 304L as a deformation history sensitive material and determine how to quantify and accumulate fatigue damage to enable life predictions under variable amplitude loading conditions for such materials. A comprehensive experimental program including testing under fully-reversed, as well as mean stress and/or mean strain conditions, with initial or periodic overloads, along with step testing and random loading histories was conducted on two grades of stainless steel 304L, under both strain-controlled and load-controlled conditions. To facilitate comparisons with a material without deformation history effects, similar tests were also carried out on aluminum 7075-T6. Experimental results are discussed, including peculiarities observed with stainless steel behavior, such as a phenomenon, referred to as secondary hardening characterized by a continuous increase in the stress response in a strain-controlled test and often leading to runout fatigue life. Possible mechanisms for secondary hardening observed in some tests are also discussed. The behavior of aluminum is shown not to be affected by preloading, whereas the behavior of stainless steel is greatly influenced by prior loading. Mean stress relaxation in strain control and ratcheting in load control and their influence on fatigue life are discussed. Some unusual mean strain test results are presented for stainless steel 304L, where in spite of mean stress relaxation fatigue lives were significantly longer than fully-reversed tests. Prestraining indicated no effect on either deformation or fatigue behavior of aluminum, while it induced considerable hardening in stainless steel 304L and led to different results on fatigue life, depending on the test control mode. In step tests for stainless steel 304L, strong hardening induced by the first step of a high-low sequence significantly affects the fatigue behavior, depending on the test control mode used. For periodic overload tests of stainless steel 340L, hardening due to the overloads was progressive throughout life and more significant than in high-low step tests. For aluminum, no effect on deformation behavior was observed due to periodic overloads. However, the direction of the overloads was found to affect fatigue life, as tensile overloads led to longer lives, while compressive overloads led to shorter lives. Deformation and fatigue behaviors under random loading conditions are also presented and discussed for the two materials. The applicability of a common cumulative damage rule, the linear damage rule, is assessed for the two types of material, and for various loading conditions. While the linear damage rule associated with a strain-life or stress-life curve is shown to be fairly accurate for life predictions for aluminum, it is shown to poorly represent the behavior of stainless steel, especially in prestrained and high-low step tests, in load control. In order to account for prior deformation effects and achieve accurate fatigue life predictions for stainless steel, parameters including both stress and strain terms are required. The Smith-Watson-Topper and Fatemi-Socie approaches, as such parameters, are shown to correlate most test data fairly accurately. For damage accumulation under variable amplitude loading, the linear damage rule associated with strain-life or stress-life curves can lead to inaccurate fatigue life predictions, especially for materials presenting strong deformation memory effect, such as stainless steel 304L. The inadequacy of this method is typically attributed to the linear damage rule itself. On the contrary, this study demonstrates that damage accumulation using the linear damage rule can be accurate, provided that the linear damage rule is used in conjunction with parameters including both stress and strain terms. By including both loading history and response of the material in damage quantification, shortcomings of the commonly used linear damage rule approach can be circumvented in an effective manner. In addition, cracking behavior was also analyzed under various loading conditions. Results on microcrack initiation and propagation are presented in relation to deformation and fatigue behaviors of the materials. Microcracks were observed to form during the first few percent of life, indicating that most of the fatigue life of smooth specimens is spent in microcrack formation and growth. Analyses of fractured specimens showed that microcrack formation and growth is dependent on the loading history, and less important in aluminum than stainless steel 304L, due to the higher toughness of this latter material.

Clinical outcomes of transfusion-associated iron overload in patients with refractory chronic anemia.

PubMed

Gao, Chong; Li, Li; Chen, Baoan; Song, Huihui; Cheng, Jian; Zhang, Xiaoping; Sun, Yunyu

2014-01-01

The purpose of this study was to evaluate the clinical outcomes of transfusion-associated iron overload in patients with chronic refractory anemia. Clinical manifestations, main organ function, results of computed tomography (CT), endocrine evaluation, and serum ferritin levels were analyzed retrospectively in 13 patients who were transfusion-dependent for more than 1 year (receiving >50 units of red blood cells) to determine the degree of iron overload and efficacy of iron-chelating therapy. Serum ferritin levels increased to 1,830-5,740 ng/mL in all patients. Ten patients had abnormal liver function. The CT Hounsfield units in the liver increased significantly in eleven patients, and were proportional to their serum ferritin levels. Skin pigmentation, liver dysfunction, and endocrine dysfunction were observed in nine patients with serum ferritin >3,500 ng/mL, eight of whom have since died. Interestingly, serum ferritin levels did not decrease significantly in nine transfusion-dependent patients who had received 15-60 days of iron-chelating therapy. Transfusion-dependent patients may progress to secondary iron overload with organ impairment, which may be fatal in those who are heavily iron-overloaded. The CT Hounsfield unit is a sensitive indicator of iron overload in the liver. Iron chelation therapy should be initiated when serum ferritin is >1,000 ng/mL and continued until it is <1,000 ng/mL in transfusional iron-overloaded patients.

Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions

PubMed Central

Chalmers, Anna W; Shammo, Jamile M

2016-01-01

Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelo-dysplastic syndromes. In the absence of a physiological mechanism to excrete excess iron, chronic transfusions ultimately cause iron overload. Without correction, iron overload can lead to end-organ damage, resulting in cardiac, hepatic, and endocrine dysfunction/failure. Iron chelating agents are utilized to reduce iron overload, as they form a complex with iron, leading to its clearance. Iron chelation has been proven to decrease organ dysfunction and improve survival in certain transfusion-dependent anemias, such as β-thalassemia. Several chelating agents have been approved by the United States Food and Drug Administration for the treatment of iron overload, including deferoxamine, deferiprone, and deferasirox. A variety of factors have to be considered when choosing an iron chelator, including dosing schedule, route of administration, tolerability, and side effect profile. Deferasirox is an orally administered iron chelator with proven efficacy and safety in multiple hematological disorders. There are two formulations of deferasirox, a tablet for suspension, and a new tablet form. This paper is intended to provide an overview of iron overload, with a focus on deferasirox, and its recently approved formulation Jadenu® for the reduction of transfusional iron overload in hematological disorders. PMID:26929633

Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions.

PubMed

Chalmers, Anna W; Shammo, Jamile M

2016-01-01

Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelo-dysplastic syndromes. In the absence of a physiological mechanism to excrete excess iron, chronic transfusions ultimately cause iron overload. Without correction, iron overload can lead to end-organ damage, resulting in cardiac, hepatic, and endocrine dysfunction/failure. Iron chelating agents are utilized to reduce iron overload, as they form a complex with iron, leading to its clearance. Iron chelation has been proven to decrease organ dysfunction and improve survival in certain transfusion-dependent anemias, such as β-thalassemia. Several chelating agents have been approved by the United States Food and Drug Administration for the treatment of iron overload, including deferoxamine, deferiprone, and deferasirox. A variety of factors have to be considered when choosing an iron chelator, including dosing schedule, route of administration, tolerability, and side effect profile. Deferasirox is an orally administered iron chelator with proven efficacy and safety in multiple hematological disorders. There are two formulations of deferasirox, a tablet for suspension, and a new tablet form. This paper is intended to provide an overview of iron overload, with a focus on deferasirox, and its recently approved formulation Jadenu(®) for the reduction of transfusional iron overload in hematological disorders.

Intracellular iron overload leading to DNA damage of lymphocytes and immune dysfunction in thalassemia major patients.

PubMed

Shaw, Jyoti; Chakraborty, Ayan; Nag, Arijit; Chattopadyay, Arnab; Dasgupta, Anjan K; Bhattacharyya, Maitreyee

2017-11-01

To investigate the cause and effects of intracellular iron overload in lymphocytes of thalassemia major patients. Sixty-six thalassemia major patients having iron overload and 10 age-matched controls were chosen for the study. Blood sample was collected, and serum ferritin, oxidative stress; lymphocyte DNA damage were examined, and infective episodes were also counted. Case-control analysis revealed significant oxidative stress, iron overload, DNA damage, and rate of infections in thalassemia cases as compared to controls. For cases, oxidative stress (ROS) and iron overload (serum ferritin) showed good correlation with R 2  = 0.934 and correlation between DNA damage and ROS gave R 2  = 0.961. We also demonstrated that intracellular iron overload in thalassemia caused oxidative damage of lymphocyte DNA as exhibited by DNA damage assay. The inference is further confirmed by partial inhibition of such damage by chelation of iron and the concurrent lowering of the ROS level in the presence of chelator deferasirox. Therefore, intracellular iron overload caused DNA fragmentation, which may ultimately hamper lymphocyte function, and this may contribute to immune dysfunction and increased susceptibility to infections in thalassemia patients as indicated by the good correlation (R 2  = 0.91) between lymphocyte DNA damage and rate of infection found in this study. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy.

PubMed

An, Shucai; Soe, Kyaw; Akamatsu, Maki; Hishikawa, Yoshitaka; Koji, Takehiko

2012-11-01

Although iron overload is implicated in hepatocarcinogenesis, the precise mechanism was not known yet. In the present study, we investigated the effect of iron overload upon the induction of hepatocyte proliferation after 70% partial hepatectomy (PH) in rats fed with rat chow with 3% carbonyl iron for 3 months. In normal-diet rats, the increase in Ki-67 labeling index (LI) commenced at 24 h post-PH and the LIs of proliferating cell nuclear antigen (PCNA) incorporated 5-bromo-2'-deoxyuridine (BrdU) and phospho-histone H3 reached maximum values at 36 and 48 h after PH, respectively. In iron-overload rats, the above parameters occurred 12 h earlier compared to that of normal-diet rats, shortening the G0-G1 transition. Interestingly, nuclear staining for metallothionein (MT), which is essential for hepatocyte proliferation, was noted even at 0 h in iron-overload rats, while MT expression occurred at 6 h in the normal rats. Moreover, nuclear factor kappa B (NF-κB) expression, which is an essential early event leading to liver regeneration, was detected in Kupffer cells at 0 h in iron-overload rats. These results may indicate that overloaded iron, maybe through the induction of MT and NF-κB, may keep liver as a state ready to regenerate in response to PH, by bypassing signal transduction cascades involved in the initiation of liver regeneration.

When more is less: An examination of the relationship between hours in telework and role overload.

PubMed

Duxbury, Linda; Halinski, Michael

2014-01-01

Proponents of telework arrangements assert that those who telework have more control over their work and family domains than their counterparts who are not permitted to work from home. Using Karasek's theory we hypothesized that the relationship between demands (hours in work per week; hours in childcare per week) and strain (work role overload; family role overload) would be moderated by the number of hours the employee spent per week teleworking (control). To determine how the number of telework hours relates to work role overload and family role overload, we follow the test for moderation and mediation using hierarchical multiple regression analysis as outlined by Frazier et al. [50] We used survey data collected from 1,806 male and female professional employees who spent at least one hour per week working from home during regular hours (i.e. teleworking). As hypothesized, the number of hours in telework per week negatively moderated the relation between work demands (total hours in paid employment per week) and work strain (work role overload). Contrary to our hypothesis, the number of hours in telework per week only partially mediated the relation between family demands (hours a week in childcare) and family role overload (strain). The findings from this study support the idea that the control offered by telework is domain specific (helps employees meet demands at work but not at home).

Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice.

PubMed

Zhang, Pengjun; Yue, Yuanyuan; Pan, Donghui; Yang, Runlin; Xu, Yuping; Wang, Lizhen; Yan, Junjie; Li, Xiaotian; Yang, Min

2016-09-01

Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin nanoparticle (MP) and firstly evaluate the pharmacokinetics of MP in iron-overload mice to provide scientific basis for treating iron-overload. To study the circulation time and biodistribution, MP was labeled with (89)Zr, a long half-life (78.4h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with (89)Zr directly at pH5, resulting in non-decay-corrected yield of 89.6% and a radiochemical purity of more than 98%. The specific activity was at least190 MBq/μmol. The (89)Zr-MP was stable in human plasma and PBS for at least 48h. The half-life of (89)Zr-MP was about 15.70±1.74h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that (89)Zr-MP mainly accumulated in liver and spleen, which are the target organ of iron-overload. The results indicate that the melanin nanoparticle is promising for further iron overload therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

“Hydraulic Cushion” Type Overload Protection Devices Usable in Mechanical Presses. A Patent Study

NASA Astrophysics Data System (ADS)

Cioară, R.

2016-11-01

The possible consequences of machine-tool overload are well-known. In order to prevent such, machine-tools are equipped with various overload protection devices. Mechanical presses, intensively strained machine-tools, are typically equipped with three protection systems: against accidental access to the working area during machine deployment, against torque overload and force overload. Force overload protection systems include either destructible parts and are used in small to medium nominal force mechanical presses, or non-destructible ones used mostly in medium to large nominal force (H-frame) presses. A particular class of force overload protection systems without destructible parts are “hydraulic cushion” type devices. While such systems do not necessarily cause the machine to stop, the slide's stroke does not reach the initial dead centre and consequently cannot exert the designed technological force on the workpiece. By a patent study referencing 19 relevant patents the paper captures both the diversity of the constrictive solutions of “hydraulic cushion” type protection devices and their positioning modalities within the structure of a mechanical press. An important aim of the study is to highlight the reserve of creativity existing in this field, at least from the viewpoint of the hydraulic cushion positioning, as well as to emphasize the essential requirement of a relative motion between the mobile and the fixed parts of the tool, a motion of opposite sense to that of the slide-crank mechanism.

Spreading the Load: Mobile Information and Communications Technologies and Their Effect on Information Overload

ERIC Educational Resources Information Center

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…

Coping with Overload and Stress: Men and Women in Dual-Earner Families

ERIC Educational Resources Information Center

Higgins, Chris A.; Duxbury, Linda E.; Lyons, Sean T.

2010-01-01

This study tested gender differences in a model positing relationships between work and family demands, overload, 4 coping mechanisms, and stress. The coping mechanisms were hypothesized to moderate the relationship between overload and stress. The sample consisted of 1,404 men and 1,623 women in dual-earner families. Respondents relied on 2…

Work Processes, Role Conflict, and Role Overload: The Case of Nurses and Engineers in the Public Sector.

ERIC Educational Resources Information Center

Bacharach, Samuel B.; And Others

1990-01-01

Study of five sets of work process variables and their relationship to role conflict and overload among public sector nurses and engineers found managerial strategies appropriate for minimizing role conflict not necessarily appropriate for minimizing role overload. Some work process predictors may be similar across professions, and managerial…

Predicting Role Conflict, Overload and Contagion in Adult Women University Students with Families and Jobs.

ERIC Educational Resources Information Center

Home, Alice M.

1998-01-01

Data from 443 women combining work, family, and schooling showed that lower income increased their vulnerability to role conflict. Perceived intensity of student demands was the strongest predictor of role conflict, overload, and contagion (preoccupation with one role while performing another). Conflict and overload were eased somewhat by distance…

Designing a Personalized Guide Recommendation System to Mitigate Information Overload in Museum Learning

ERIC Educational Resources Information Center

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…

Does oxidative stress modulate left ventricular diastolic function in asymptomatic subjects with hereditary hemochromatosis?

PubMed

Shizukuda, Yukitaka; Bolan, Charles D; Tripodi, Dorothy J; Sachdev, Vandana; Nguyen, Tammy T; Botello, Gilberto; Yau, Yu-Ying; Sidenko, Stanislav; Inez, Ernst; Ali, Mir I; Waclawiw, Myron A; Leitman, Susan F; Rosing, Douglas R

2009-11-01

Little is known about the early mechanisms mediating left ventricular (LV) diastolic dysfunction in patients with hereditary hemochromatosis (HH). However, the increased oxidative stress related to iron overload may be involved in this process, and strain rate (SR), a sensitive echocardiography-derived measure of diastolic function, may detect such changes. we evaluated the relationship between left ventricular diastolic function measured with tissue Doppler SR and oxidative stress in asymptomatic HH subjects and control normal subjects. Ninety-four consecutive visits of 43 HH subjects, age 30-74 (50 +/- 10, mean +/- SD), and 37 consecutive visits of 21 normal volunteers, age 30-63 (48 +/- 8), were evaluated over a 3-year period. SR was obtained from the basal septum in apical four-chamber views. All patients had confirmed C282Y homozygosity, a documented history of iron overload, and were New York Heart Association functional class I. Normal volunteers lacked HFE gene mutations causing HH. In the HH subjects, the SR demonstrated moderate but significant correlations with biomarkers of oxidative stress; however, no correlations were noted in normal subjects. The biomarkers of iron overload per se did not show significant correlations with the SR. Although our study was limited by the relatively small subject number, these results suggest that a possible role of oxidative stress to affect LV diastolic function in asymptomatic HH subjects and SR imaging may be a sensitive measure to detect that effect.

Inhibition of soluble epoxide hydrolase does not improve the course of congestive heart failure and the development of renal dysfunction in rats with volume overload induced by aorto-caval fistula

PubMed Central

Červenka, Luděk; Melenovský, Vojtěch; Husková, Zuzana; Sporková, Alexandra; Bürgelová, Marcela; Škaroupková, Petra; Hwang, Sung Hee; Hammock, Bruce D.; Imig, John D.; Sadowski, Janusz

2016-01-01

The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto-caval fistula (ACF) in Hannover Sprague-Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP-450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/L in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs to levels observed in sham-operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin-converting enzyme inhibition (ACEi, trandolapril, 6 mg/L in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance. Hence, renal dysfunction rather than cardiac remodeling determines long-term mortality in advanced stage of CHF due to volume overload. Strong protective actions of ACEi were associated with suppression of the vasoconstrictor/sodium retaining axis and activation of vasodilatory/natriuretic axis of the renin-angiotensin system in the circulating blood and kidney tissue. PMID:26047375

HFE gene mutation is a risk factor for tissue iron accumulation in hemodialysis patients.

PubMed

Turkmen, Ercan; Yildirim, Tolga; Yilmaz, Rahmi; Hazirolan, Tuncay; Eldem, Gonca; Yilmaz, Engin; Aybal Kutlugun, Aysun; Altindal, Mahmut; Altun, Bulent

2017-07-01

HFE gene mutations are responsible from iron overload in general population. Studies in hemodialysis patients investigated the effect of presence of HFE gene mutations on serum ferritin and transferrin saturation (TSAT) with conflicting results. However effect of HFE mutations on iron overload in hemodialysis patients was not previously extensively studied. 36 hemodialysis patients (age 51.3 ± 15.6, (18/18) male/female) and 44 healthy control subjects included in this cross sectional study. Hemoglobin, ferritin, TSAT in the preceding 2 years were recorded. Iron and erythropoietin (EPO) administered during this period were calculated. Iron accumulation in heart and liver was detected by MRI. Relationship between HFE gene mutation, hemoglobin, iron parameters and EPO doses, and tissue iron accumulation were determined. Iron overload was detected in nine (25%) patients. Hemoglobin, iron parameters, weekly EPO doses, and monthly iron doses of patients with and without iron overload were similar. There was no difference between control group and hemodialysis patients with respect to the prevalence of HFE gene mutations. Iron overload was detected in five of eight patients who had HFE gene mutations, but iron overload was present in 4 of 28 patients who had no mutations (P = 0.01). Hemoglobin, iron parameters, erythropoietin, and iron doses were similar in patients with and without gene mutations. HFE gene mutations remained the main determinant of iron overload after multivariate logistic regression analysis (P = 0.02; OR, 11.6). Serum iron parameters were not adequate to detect iron overload and HFE gene mutation was found to be an important risk factor for iron accumulation. © 2017 International Society for Hemodialysis.

Effect of inhibition of glycogen synthase kinase-3 on cardiac hypertrophy during acute pressure overload.

PubMed

Tateishi, Atsushi; Matsushita, Masayuki; Asai, Tomohiro; Masuda, Zenichi; Kuriyama, Mitsuhito; Kanki, Kazushige; Ishino, Kozo; Kawada, Masaaki; Sano, Shunji; Matsui, Hideki

2010-06-01

A large number of diverse signaling molecules in cell and animal models participate in the stimulus-response pathway through which the hypertrophic growth of the myocardium is controlled. However, the mechanisms of signaling pathway including the influence of lithium, which is known as an inhibitor of glycogen synthase kinase-3beta, in pressure overload hypertrophy remain unclear. The aim of our study was to determine whether glycogen synthase kinase-3beta inhibition by lithium has acute effects on the myocyte growth mechanism in a pressure overload rat model. First, we created a rat model of acute pressure overload cardiac hypertrophy by abdominal aortic banding. Protein expression time courses for beta-catenin, glycogen synthase kinase-3beta, and phosphoserine9-glycogen synthase kinase-3beta were then examined. The rats were divided into four groups: normal rats with or without lithium administration and pressure-overloaded rats with or without lithium administration. Two days after surgery, Western blot analysis of beta-catenin, echo-cardiographic evaluation, left ventricular (LV) weight, and LV atrial natriuretic peptide mRNA levels were evaluated. We observed an increase in the level of glycogen synthase kinase-3beta phosphorylation on Ser 9. A significant enhancement of LV heart weight (P < 0.05) and interventricular septum and posterior wall thickness (P < 0.05) with pressure-overloaded hypertrophy in animals treated with lithium were also observed. Atrial natriuretic peptide mRNA levels were significantly increased with pressure overload hypertrophy in animals treated with lithium. We have shown in an animal model that inhibition of glycogen synthase kinase-3beta by lithium has an additive effect on pressure overload cardiac hypertrophy.

Assessment of liver and cardiac iron overload using MRI in patients with chronic anemias in Latin American countries: results from ASIMILA study.

PubMed

Cancado, Rodolfo; Watman, Nora P; Lobo, Clarisse; Chona, Zulay; Manzur, Fernando; Traina, Fabiola; Park, Miriam; Drelichman, Guillermo; Zarate, Juan Pablo; Marfil, Luis

2018-04-17

A multicenter, noninterventional, observational study was conducted in the Latin American countries including Argentina, Brazil, Colombia, Mexico, and Venezuela to assess the prevalence of liver and cardiac iron overload using magnetic resonance imaging (MRI) in patients with chronic anemias except thalassemia. Patients aged >10 years with transfusion-dependent anemias, except thalassemia, either with <20 units of red blood cell (RBC) transfusions with serum ferritin (SF) levels >2000 ng/mL or with ≥20 units of RBC transfusions regardless of SF level in their lifetime, were enrolled. Iron overload was assessed using MRI. Among 175 patients included, the majority had sickle cell disease (SCD; 52%), followed by aplastic anemia (AA; 17.7%), myelodysplastic syndrome (MDS; 8.6%), Diamond-Blackfan anemia (DBA; 4%), pure red cell aplasia (1.1%), and others (16.6%). Liver iron overload was observed in 76.4% of patients, while cardiac iron overload was seen in 19.2% when assessed by MRI. The prevalence of iron overload was 80.2% in patients with SCD, 73.3% in MDS, 77.4% in AA, 100% in pure red cell aplasia, 71.4% in DBA, and 68.9% in other transfusion-related disorders. A moderate correlation between liver iron concentration (LIC) and SF was observed in patients with SCD and MDS (r = 0.47 and r = 0.61, respectively). All adverse events reported were consistent with the published data for deferasirox or underlying disease. A high prevalence of iron overload in this patient population in Latin American countries indicates that a better diagnosis and management of iron overload is required in these countries.

Crucial role of rho-kinase in pressure overload-induced right ventricular hypertrophy and dysfunction in mice.

PubMed

Ikeda, Shohei; Satoh, Kimio; Kikuchi, Nobuhiro; Miyata, Satoshi; Suzuki, Kota; Omura, Junichi; Shimizu, Toru; Kobayashi, Kenta; Kobayashi, Kazuto; Fukumoto, Yoshihiro; Sakata, Yasuhiko; Shimokawa, Hiroaki

2014-06-01

Right ventricular (RV) failure is the leading cause of death in various cardiopulmonary diseases, including pulmonary hypertension. It is generally considered that the RV is vulnerable to pressure overload as compared with the left ventricle (LV). However, as compared with LV failure, the molecular mechanisms of RV failure are poorly understood, and hence therapeutic targets of the disorder remain to be elucidated. Thus, we aimed to identify molecular therapeutic targets for RV failure in a mouse model of pressure overload. To induce pressure overload to respective ventricles, we performed pulmonary artery constriction or transverse aortic constriction in mice. We first performed microarray analysis and found that the molecules related to RhoA/Rho-kinase and integrin pathways were significantly upregulated in the RV with pulmonary artery constriction compared with the LV with transverse aortic constriction. Then, we examined the responses of both ventricles to chronic pressure overload in vivo. We demonstrated that compared with transverse aortic constriction, pulmonary artery constriction caused greater extents of mortality, Rho-kinase expression (especially ROCK2 isoform), and oxidative stress in pressure-overloaded RV, reflecting the weakness of the RV in response to pressure overload. Furthermore, mice with myocardial-specific overexpression of dominant-negative Rho-kinase showed resistance to pressure overload-induced hypertrophy and dysfunction associated with reduced oxidative stress. Finally, dominant-negative Rho-kinase mice showed a significantly improved long-term survival in both pulmonary artery constriction and transverse aortic constriction as compared with littermate controls. These results indicate that the Rho-kinase pathway plays a crucial role in RV hypertrophy and dysfunction, suggesting that the pathway is a novel therapeutic target of RV failure in humans. © 2014 American Heart Association, Inc.

Role of electrocardiographic changes in discriminating acute or chronic right ventricular pressure overload.

PubMed

Can, Mehmet Mustafa; Özveren, Olcay; Biteker, Murat; Şengül, Cihan; Uz, Ömer; Işılak, Zafer; Kırılmaz, Ata

2013-06-01

Pulmonary embolism (PE) and severe pulmonary stenosis (PS) are two distinct conditions accompanied by increased pressure load of the right ventricle (RV). Despite major advances in our understanding of the mechanisms of RV adaptation to the increased pressure, substantial gaps in our knowledge remain unsettled. One of much less known aspect of pressure overload of RV is its impact on electrocardiographic (ECG) changes. In this study, we aimed to study whether acute and chronic RV overload are accompanied by different ECG patterns. Thirty-eight patients with PE underwent ECG monitoring were compared with 20 matched patients with PS in this observational retrospective study. ECG abnormalities suggestive of RV overload were recorded and analyzed in both groups. Logistic regression analysis was used to define the predictors of chronic RV overload. Among the ECG changes studied, premature atrial contraction (OR-12.2, 95% CI, 1.3-107, p=0.008), right axis deviation (OR-20.4, 95% CI 4.2-98, p<0.001), indeterminate axis (OR-0.11, 95% CI 0.02-0.44, p=0.001 0.11), incomplete right bundle branch block (OR-4.2, 95% CI, 1.1-15.4, p=0.02), late R in aVR (OR-8.4, 95% CI 2.1-33.2, p=0.001), qR in V1 lead (OR-8.3, 95% CI 1.2-74.8, p=0.03) were found to be the independent predictors of chronic RV pressure overload. Our data indicate that the ECG changes that attributed to the acute RV pressure loading states may be more prevalent in chronic RV overload as compared with acute RV overload.

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

PubMed

Hung, Szu-Chun; Lin, Yao-Ping; Huang, Hsin-Lei; Pu, Hsiao-Fung; Tarng, Der-Cherng

2013-01-01

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. 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 (<140 pg/mL), middle (140 to 280 pg/mL) and high (>280 pg/mL). 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. 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.

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

PubMed

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. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Iron overload: what is the role of public health?

PubMed

Hulihan, Mary M; Sayers, Cindy A; Grosse, Scott D; Garrison, Cheryl; Grant, Althea M

2011-12-01

Hereditary hemochromatosis type 1, also known as hereditary hemochromatosis classical (HHC), is an iron overload disorder associated, in most cases, with mutations of the hemochromatosis (HFE) gene. Although suggested algorithms for diagnosing iron overload are available, there are still questions about options for genetic and biochemical screening for hemochromatosis and duration of treatment. This article provides a summary of an expert workgroup meeting convened on September 24-25, 2009, entitled "Iron Overload: What is the Role of Public Health?" The purpose of the meeting was to enable subject matter experts to share their most recent clinical and scientific iron overload information and to facilitate the discussion of future endeavors, with special emphasis on the role of public health in this field. The two main topics were the research priorities of the field, including clinical, genetic, and public health issues, and the concerns about the validity of current screening recommendations for the condition. Published by Elsevier Inc.

49 CFR 222.41 - How does this rule affect Pre-Rule Quiet Zones and Pre-Rule Partial Quiet Zones?

Code of Federal Regulations, 2011 CFR

2011-10-01

...-Rule Quiet Zone may be established by automatic approval and remain in effect, subject to § 222.51, if... Zone may be established by automatic approval and remain in effect, subject to § 222.51, if the Pre... 49 Transportation 4 2011-10-01 2011-10-01 false How does this rule affect Pre-Rule Quiet Zones and...

49 CFR 222.41 - How does this rule affect Pre-Rule Quiet Zones and Pre-Rule Partial Quiet Zones?

Code of Federal Regulations, 2013 CFR

2013-10-01

...-Rule Quiet Zone may be established by automatic approval and remain in effect, subject to § 222.51, if... Zone may be established by automatic approval and remain in effect, subject to § 222.51, if the Pre... 49 Transportation 4 2013-10-01 2013-10-01 false How does this rule affect Pre-Rule Quiet Zones and...

49 CFR 222.41 - How does this rule affect Pre-Rule Quiet Zones and Pre-Rule Partial Quiet Zones?

Code of Federal Regulations, 2010 CFR

2010-10-01

...-Rule Quiet Zone may be established by automatic approval and remain in effect, subject to § 222.51, if... Zone may be established by automatic approval and remain in effect, subject to § 222.51, if the Pre... 49 Transportation 4 2010-10-01 2010-10-01 false How does this rule affect Pre-Rule Quiet Zones and...

49 CFR 222.41 - How does this rule affect Pre-Rule Quiet Zones and Pre-Rule Partial Quiet Zones?

Code of Federal Regulations, 2014 CFR

2014-10-01

...-Rule Quiet Zone may be established by automatic approval and remain in effect, subject to § 222.51, if... Zone may be established by automatic approval and remain in effect, subject to § 222.51, if the Pre... 49 Transportation 4 2014-10-01 2014-10-01 false How does this rule affect Pre-Rule Quiet Zones and...

49 CFR 222.41 - How does this rule affect Pre-Rule Quiet Zones and Pre-Rule Partial Quiet Zones?

Code of Federal Regulations, 2012 CFR

2012-10-01

...-Rule Quiet Zone may be established by automatic approval and remain in effect, subject to § 222.51, if... Zone may be established by automatic approval and remain in effect, subject to § 222.51, if the Pre... 49 Transportation 4 2012-10-01 2012-10-01 false How does this rule affect Pre-Rule Quiet Zones and...

On-off nonlinear active control of floor vibrations

NASA Astrophysics Data System (ADS)

Díaz, Iván M.; Reynolds, Paul

2010-08-01

Human-induced floor vibrations can be mitigated by means of active control via an electromagnetic proof-mass actuator. Previous researchers have developed a system for floor vibration comprising linear velocity feedback control (LVFC) with a command limiter (saturation in the command signal to avoid actuator overloading). The performance of this control is highly dependent on the linear gain utilised, which has to be designed for a particular excitation and might not be optimum for other excitations. This work explores the use of on-off nonlinear velocity feedback control (NLVFC) as the natural evolution of LVFC when high gains and/or significant vibration level are present together with saturation in the control law. Firstly, the describing function tool is employed to analyse the stability properties of: (1) LVFC with saturation, (2) on-off NLVFC with a dead zone and (3) on-off NLVFC with a switching-off function. Particular emphasis is paid to the resulting limit cycle behaviour and the design of appropriate dead zone and switching-off levels to avoid it. Secondly, experimental trials using the three control laws are conducted on a laboratory test floor. The results corroborate the analytical stability predictions. The pros of on-off NLVFC are that no gain has to be chosen and maximum actuator energy is delivered to cancel the vibration. In contrast, the requirement to select a dead zone or switching-off function provides a drawback in its application.

Implications of Overwork and Overload for the Quality of Men's Family Relationships.

ERIC Educational Resources Information Center

Crouter, Ann C.; Bumpus, Matthew F.; Head, Melissa R.; McHale, Susan M.

2001-01-01

This study examined the implications of men's long work hours and role overload for the quality of relationships with wives and the firstborn (M=15 years) and secondborn adolescent offspring (M=12.3 years). Long hours were related to less time spent with wives. The combination of long hours and high overload was associated with less positive…

The Use of Graphs as Decision Aids in Relation to Information Overload and Managerial Decision Quality.

ERIC Educational Resources Information Center

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.…

Trust in management as a buffer of the relationships between overload and strain.

PubMed

Harvey, Steve; Kelloway, E Kevin; Duncan-Leiper, Leslie

2003-10-01

This study examined the role of trust in management as a moderating factor in work overload's impact on personal strain (i.e., burnout, psychological strain, and work's interference with family). Participants were 94 employees of an accounting firm responding to a survey. The results were supportive of all study propositions. Both work overload and trust in management had the expected negative and positive main effects on the outcomes variables, respectively. The impact of work overload on the outcome variables was moderated by employees' trust in management. The significance of these results and areas of future research are discussed. 2003 APA

A Cognitive Engineering Analysis of the Vertical Navigation (VNAV) Function

NASA Technical Reports Server (NTRS)

Sherry, Lance; Feary, Michael; Polson, Peter; Mumaw, Randall; Palmer, Everett

2001-01-01

A cognitive engineering analysis of the Flight Management System (FMS) Vertical Navigation (VNAV) function has identified overloading of the VNAV button and overloading of the Flight Mode Annunciator (FMA) used by the VNAV function. These two types of overloading, resulting in modal input devices and ambiguous feedback, are well known sources of operator confusion, and explain, in part, the operational issues experienced by airline pilots using VNAV in descent and approach. A proposal to modify the existing VNAV design to eliminate the overloading is discussed. The proposed design improves pilot's situational awareness of the VNAV function, and potentially reduces the cost of software development and improves safety.

Fatigue crack growth with single overload - Measurement and modeling

NASA Technical Reports Server (NTRS)

Davidson, D. L.; Hudak, S. J., Jr.; Dexter, R. J.

1987-01-01

This paper compares experiments with an analytical model of fatigue crack growth under variable amplitude. The stereoimaging technique was used to measure displacements near the tips of fatigue cracks undergoing simple variations in load amplitude-single overloads and overload/underload combinations. Measured displacements were used to compute strains, and stresses were determined from the strains. Local values of crack driving force (Delta-K effective) were determined using both locally measured opening loads and crack tip opening displacements. Experimental results were compared with simulations made for the same load variation conditions using Newman's FAST-2 model. Residual stresses caused by overloads, crack opening loads, and growth retardation periods were compared.

Sensory overload: A concept analysis.

PubMed

Scheydt, Stefan; Müller Staub, Maria; Frauenfelder, Fritz; Nielsen, Gunnar H; Behrens, Johann; Needham, Ian

2017-04-01

In the context of mental disorders sensory overload is a widely described phenomenon used in conjunction with psychiatric interventions such as removal from stimuli. However, the theoretical foundation of sensory overload as addressed in the literature can be described as insufficient and fragmentary. To date, the concept of sensory overload has not yet been sufficiently specified or analyzed. The aim of the study was to analyze the concept of sensory overload in mental health care. A literature search was undertaken using specific electronic databases, specific journals and websites, hand searches, specific library catalogues, and electronic publishing databases. Walker and Avant's method of concept analysis was used to analyze the sources included in the analysis. All aspects of the method of Walker and Avant were covered in this concept analysis. The conceptual understanding has become more focused, the defining attributes, influencing factors and consequences are described and empirical referents identified. The concept analysis is a first step in the development of a middle-range descriptive theory of sensory overload based on social scientific and stress-theoretical approaches. This specification may serve as a fundament for further research, for the development of a nursing diagnosis or for guidelines. © 2017 Australian College of Mental Health Nurses Inc.

Complementary Models of Post-traumatic Osteoarthritis Reveal Cellular Responses to Contact Stress that Damage Articular Cartilage and Present Targets for Intervention

PubMed Central

Martin, James A.; Anderson, Donald D.; Goetz, Jessica E.; Fredericks, Douglas; Pedersen, Douglas R.; Ayati, Bruce P.; Marsh, J. Lawrence; Buckwalter, Joseph A.

2016-01-01

Two categories of joint overloading cause post-traumatic osteoarthritis (PTOA): single acute traumatic loads/impactions and repetitive overloading due to incongruity/instability. We developed and refined three classes of complementary models to define relationships between joint overloading and progressive cartilage loss across the spectrum of acute injuries and chronic joint abnormalities: explant and whole joint models that allow probing of cellular responses to mechanical injury and contact stresses, animal models that enable study of PTOA pathways in living joints and pre-clinical testing of treatments, and patient-specific computational models that define the overloading that causes OA in humans. We coordinated methodologies across models so that results from each informed the others, maximizing the benefit of this complementary approach. We are incorporating results from these investigations into biomathematical models to provide predictions of PTOA risk and guide treatment. Each approach has limitations, but each provides opportunities to elucidate PTOA pathogenesis. Taken together, they help define levels of joint overloading that cause cartilage destruction, show that both forms of overloading can act through the same biologic pathways, and create a framework for initiating clinical interventions that decrease PTOA risk. PMID:27509320

Effects of Iron Overload on Cardiac Calcium Regulation: Translational Insights Into Mechanisms and Management of a Global Epidemic.

PubMed

Khamseekaew, Juthamas; Kumfu, Sirinart; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2016-08-01

Iron overload cardiomyopathy occurs in a rare primary form (ie, hemochromatosis) and a very common secondary form in a host of hemoglobinopathies (eg, thalassemia, sickle cell anemia) of substantial and growing global prevalence, which have transformed iron overload cardiomyopathy into a worldwide epidemic. Intracellular calcium ([Ca(2+)]i) is known to be a critical regulator of myocardial function, in which it plays a key role in maintaining cardiac excitation-contraction coupling. It has been proposed that a disturbance in cardiac calcium regulation is a major contributor to left ventricular dysfunction in iron overload cardiomyopathy. This review comprehensively summarizes reports concerned with the effects of iron overload on cardiac calcium regulation, including alteration in the intracellular calcium level, voltage-gated calcium channel function, and calcium cycling protein activity. Consistent reports, as well as inconsistent findings, from both in vitro and in vivo studies, are presented and discussed. The understanding of these mechanisms has provided important new pathophysiological insights and has led to the development of novel therapeutic and preventive strategies for patients with iron overload cardiomyopathy that are currently in clinical trials. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Transplantation in patients with iron overload: is there a place for magnetic resonance imaging? : Transplantation in iron overload.

PubMed

Mavrogeni, Sophie; Kolovou, Genovefa; Bigalke, Boris; Rigopoulos, Angelos; Noutsias, Michel; Adamopoulos, Stamatis

2018-03-01

In iron overload diseases (thalassemia, sickle cell, and myelodysplastic syndrome), iron is deposited in all internal organs, leading to functional abnormalities. Hematopoietic stem cell transplantation (HSCT) is the only treatment offering a potential cure in these diseases. Our aim was to describe the experience in the field and the role of magnetic resonance imaging in the evaluation of iron overload before and after HSCT. Magnetic resonance imaging (MRI), using T2*, is the most commonly used tool to diagnose myocardial-liver iron overload and guide tailored treatment. Currently, HSCT offers complete cure in thalassemia major, after overcoming the immunologic barrier, and should be considered for all patients who have a suitable donor. The overall thalassemia-free survival of low-risk, HLA-matched sibling stem cell transplantation patients is 85-90%, with a 95% overall survival. The problems of rejection and engraftment are improving with the use of adequate immunosuppression. However, a detailed iron assessment of both heart and liver is necessary for pre- and post-transplant evaluation. In iron overload diseases, heart and liver iron evaluation is indispensable not only for the patients' survival, but also for evaluation before and after HSCT.

Clonazepam increases in vivo striatal extracellular glucose in diabetic rats after glucose overload.

PubMed

Gomez, Rosane; Barros, Helena M T

2003-12-01

Hyperglycemia modulates brain function, including neuronal excitability, neurotransmitter release and behavioral changes. There may be connections between the GABAergic system, glucose sensing neurons and glucose in the neuronal environment that shed light on the mechanism by which GABA(A) agents influence depressive behavior in diabetic rats submitted to the forced swimming test. We aimed to investigate whether clonazepam (CNZ), a GABA(A) receptor positive modulator, modifies in vivo striatal extracellular glucose levels in diabetic rats under fasting condition or after oral glucose overload. Streptozotocin diabetic and nondiabetic rats were submitted to in vivo striatal microdialysis. Perfusate samples were collected at baseline, during fasting and following administration of CNZ (0.25 mg/kg) and oral glucose overload. Blood glucose and striatal extracellular glucose were measured simultaneously at several time points. Fasting striatal glucose levels were higher in diabetic than in nondiabetic rats and the differences between these animals were maintained after glucose overload. The increases in extracellular striatal glucose after glucose overload were around 40% and blood to brain transference was decreased in diabetics. CNZ treatment paradoxically increased striatal glucose after glucose overload in diabetic rats, which may mark the dysfunction in brain glucose homeostasis.

Secoisolariciresinol Diglucoside Abrogates Oxidative Stress-Induced Damage in Cardiac Iron Overload Condition

PubMed Central

Puukila, Stephanie; Bryan, Sean; Laakso, Anna; Abdel-Malak, Jessica; Gurney, Carli; Agostino, Adrian; Belló-Klein, Adriane; Prasad, Kailash; Khaper, Neelam

2015-01-01

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. PMID:25822525

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

PubMed

Puukila, Stephanie; Bryan, Sean; Laakso, Anna; Abdel-Malak, Jessica; Gurney, Carli; Agostino, Adrian; Belló-Klein, Adriane; Prasad, Kailash; Khaper, Neelam

2015-01-01

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.

Adaptations of motoneuron properties to chronic compensatory muscle overload

PubMed Central

Hałuszka, A.; Mrówczyński, W.; Gardiner, P. F.; Celichowski, J.

2015-01-01

The aim of the study was to determine whether chronic muscle overload has measurable effect on electrophysiological properties of motoneurons (MNs), and whether duration of this overload influences intensity of adaptations. The compensatory overload was induced in the rat medial gastrocnemius (MG) by bilateral tenotomy of its synergists (lateral gastrocnemius, soleus, and plantaris); as a result, only the MG was able to evoke the foot plantar flexion. To assure regular activation of the MG muscle, rats were placed in wheel-equipped cages and subjected to a low-level treadmill exercise. The intracellular recordings from MG motoneurons were made after 5 or 12 wk of the overload, and in a control group of intact rats. Some of the passive and threshold membrane properties as well as rhythmic firing properties were considerably modified in fast-type MNs, while remaining unaltered in slow-type MNs. The significant changes included a shortening of the spike duration and the spike rise time, an increase of the afterhyperpolarization amplitude, an increase of the input resistance, a decrease of the rheobase, and a decrease of the minimum current necessary to evoke steady-state firing. The data suggest higher excitability of fast-type MNs innervating the overloaded muscle, and a shift towards electrophysiological properties of slow-type MNs. All of the adaptations could be observed after 5 wk of the compensatory overload with no further changes occurring after 12 wk. This indicates that the response to an increased level of chronic activation of MNs is relatively quick and stable. PMID:25695651

Is Fluid Overload More Important than Diabetes in Renal Progression in Late Chronic Kidney Disease?

PubMed Central

Tsai, Yi-Chun; Tsai, Jer-Chia; Chiu, Yi-Wen; Kuo, Hung-Tien; Chen, Szu-Chia; Hwang, Shang-Jyh; Chen, Tzu-Hui; Kuo, Mei-Chuan; Chen, Hung-Chun

2013-01-01

Fluid overload is one of the major presentations in patients with late stage chronic kidney disease (CKD). Diabetes is the leading cause of renal failure, and progression of diabetic nephropathy has been associated with changes in extracellular fluid volume. The aim of the study was to assess the association of fluid overload and diabetes in commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate (eGFR) less than -3 ml/min per 1.73 m2/y) in 472 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. The study population was further classified into four groups according to the median of relative hydration status (△HS =fluid overload/extracellular water) and the presence or absence of diabetes. The median level of relative hydration status was 7%. Among all patients, 207(43.9 %) were diabetic. 71 (15.0%) subjects had commencing dialysis, and 187 (39.6%) subjects presented rapid renal function decline during a median 17.3-month follow-up. Patients with fluid overload had a significantly increased risk for commencing dialysis and renal function decline independent of the presence or absence of diabetes. No significantly increased risk for renal progression was found between diabetes and non-diabetes in late CKD without fluid overload. In conclusion, fluid overload has a higher predictive value of an elevated risk for renal progression than diabetes in late CKD. PMID:24349311

A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: a neurodegenerative X-linked epileptic encephalopathy with systemic iron-overload.

PubMed

Swoboda, Kathryn J; Margraf, Rebecca L; Carey, John C; Zhou, Holly; Newcomb, Tara M; Coonrod, Emily; Durtschi, Jacob; Mallempati, Kalyan; Kumanovics, Attila; Katz, Ben E; Voelkerding, Karl V; Opitz, John M

2014-01-01

Three related males presented with a newly recognized x-linked syndrome associated with neurodegeneration, cutaneous abnormalities, and systemic iron overload. Linkage studies demonstrated that they shared a haplotype on Xp21.3-Xp22.2 and exome sequencing was used to identify candidate variants. Of the segregating variants, only a PIGA mutation segregated with disease in the family. The c.328_330delCCT PIGA variant predicts, p.Leu110del (or c.1030_1032delCTT, p.Leu344del depending on the reference sequence). The unaffected great-grandfather shared his X allele with the proband but he did not have the PIGA mutation, indicating that the mutation arose de novo in his daughter. A single family with a germline PIGA mutation has been reported; affected males had a phenotype characterized by multiple congenital anomalies and severe neurologic impairment resulting in infantile lethality. In contrast, affected boys in the family described here were born without anomalies and were neurologically normal prior to onset of seizures after 6 months of age, with two surviving to the second decade. PIGA encodes an enzyme in the GPI anchor biosynthesis pathway. An affected individual in the family studied here was deficient in GPI anchor proteins on granulocytes but not erythrocytes. In conclusion, the PIGA mutation in this family likely causes a reduction in GPI anchor protein cell surface expression in various cell types, resulting in the observed pleiotropic phenotype involving central nervous system, skin, and iron metabolism. © 2013 Wiley Periodicals, Inc.

[Hygienic aspects of the production of asbestos substitutes].

PubMed

Nikitina, O V; Troitskaia, N A; Kogan, F M; Velichkovskiĭ, B T; Blokhin, V A; Kuznetsova, Z M; Vanchugova, N N

1990-01-01

Due to the high level aggressiveness of asbestos, more attempts have been made in the recent years to replace asbestos by other artificial mineral fibres. In this connection, the labour conditions were studied in the basalt and carbon fibres processing sites. The major occupational hazards of these sites included basalt and carbon fibres dusts, heating microclimate in some working zones and physical overload. An intratracheal experiment revealed a lower degree of fibrinogenicity of the basalt and carbon fibres as compared to chrysotile asbestos. The number of the induced mesothelioma in the intraperitoneal introduction of basalt and carbon fibres was markedly lower than in case with chrysotile asbestos. Hygienically, asbestos should be replaced wherever possible, and the dust control measures should by no means be inferior to those with asbestos.

"Something's Gotta Give:" Advanced-Degree Seeking Women's Experiences of Sexism, Role Overload, and Psychological Distress

ERIC Educational Resources Information Center

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)…

Early Detection of Breast Cancer via Multiplane Correlation Breast Imaging

DTIC Science & Technology

2007-04-01

thalassemia and sickle cell anemia) and Wilson’s disease (liver copper overload), are characterized by increased iron and copper concentration respectively...iron overload associated with thalassemia and sickle cell anemia) and Wilson’s disease (liver copper overload) are both characterized by increased...element concentration in the liver [4]. Patients suffering from thalassemia and sickle cell anemia often require weekly blood transfusions. With each

The Impact of Information Overload on Task Completion: A Study of Scientists and Engineers in a Typical Work Environment

ERIC Educational Resources Information Center

Salyers, Jessica L.

2013-01-01

As use of technology has increasingly infiltrated the daily lives of many Americans, information overload has become a more prevalent fixture for men and women both at home and in the workplace. While information overload has been established in the field of psychology in various forms, it lacks a universal definition within the discipline.…

The role of MR imaging in detection of hepatic iron overload in patients with cirrhosis of different origins

PubMed Central

2010-01-01

Background There are many pathological conditions with hepatic iron overload. Classical definite diagnostic methods of these disorders are invasive and based on a direct tissue biopsy material. For the last years the role of MR imaging in liver diagnostics has been increasing. MRI shows changes of liver intensity in patients with hepatic iron overload. Changes in MR signal are an indirect consequence of change of relaxation times T2 and T2*, that can be directly measured. The purpose of the study was to evaluate usefulness of MR imaging in the detection of hepatic iron overload in patients with cirrhosis of different origins. Methods MR imaging at 1.5T was prospectively performed in 44 patients with liver cirrhosis who had undergone liver biopsy with histopathological assessment of hepatic iron deposits. In all patients the following sequences were used: SE, Express, GRE in T2 and T1-weighted images. Signal intensity (SI) was measured on images obtained with each T2 weighted sequence by means of regions of interest, placed in the liver and paraspinal muscles. The correlation between iron overload, histopathological score, serum ferritin and SI ratio was analyzed. Results In 20 patients with iron overload confirmed by the biopsy, the liver parenchyma demonstrated lower signal intensity than that of paraspinal muscles. This effect was visible only in 8 patients with hepatic iron overload in Express T2-weighted images. Higher signal intensity of liver than that of skeletal muscles on GRE - T2 weighted images was noted in 24 patients with cirrhosis and without elevated hepatic iron concentration. We observed a correlation between low and high iron concentration and liver to muscle SI ratio. Conclusion MR imaging is a useful and fast noninvasive diagnostic tool for the detection of liver iron overload in patients with cirrhosis of different origins. Liver to muscle SI ratio in GRE-T2-weighted sequence facilitates to differentiate patients with low and high degree of hepatic iron overload, which correlates with the origin of liver cirrhosis. PMID:20105330

Overload training inhibits phagocytosis and ROS generation of peritoneal macrophages: role of IGF-1 and MGF.

PubMed

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

2013-01-01

We tested the hypothesis that overload training inhibits the phagocytosis and the reactive oxygen species (ROS) generation of peritoneal macrophages (Mϕs), and that insulin-like growth factor-1(IGF-1) and mechano-growth factor (MGF) produced by macrophages may contribute to this process. Rats were randomized to two groups, sedentary control group (n = 10) and overload training group (n = 10). The rats of overload training group were subjected to 11 weeks of experimental training protocol. Blood sample was used to determine the content of hemoglobin, testosterone, and corticosterone. The phagocytosis and the ROS generation of Mϕs were measured by the uptake of neutral red and the flow cytometry, respectively. IGF-1 and MGF mRNA levels in Mϕs were determined by real-time PCR. In addition, we evaluated the effects of IGF-1 and MGF peptide on phagocytosis and ROS generation of Mϕs in vitro. The data showed that overload training significantly decreased the body weight (19.3 %, P < 0.01), the hemoglobin (13.5 %, P < 0.01), the testosterone (55.3 %, P < 0.01) and the corticosterone (40.6 %, P < 0.01) in blood. Moreover, overload training significantly decreased the phagocytosis (27 %, P < 0.05) and the ROS generation (35 %, P < 0.01) of Mϕs. IGF-1 and MGF mRNA levels in Mϕs from overload training group increased significantly compared with the control group (21-fold and 92-fold, respectively; P < 0.01). In vitro experiments showed that IGF-1 had no significant effect on the phagocytosis and the ROS generation of Mϕs. Unlike IGF-1, MGF peptide impaired the phagocytosis of Mϕs in dose-independent manner. In addition, MGF peptide of some concentrations (i.e., 1, 10, 50, 100 ng/ml) significantly inhibited the ROS generation of Mϕs. These results suggest that overload training inhibits the phagocytosis and the ROS generation of peritoneal macrophages, and that MGF produced by macrophages may play a key role in this process. This may represent a novel mechanism of immune suppression induced by overload training.

Angiotensin II Evokes Angiogenic Signals within Skeletal Muscle through Co-ordinated Effects on Skeletal Myocytes and Endothelial Cells

PubMed Central

Gorman, Jennifer L.; Liu, Sammy T. K.; Slopack, Dara; Shariati, Khashayar; Hasanee, Adam; Olenich, Sara; Olfert, I. Mark; Haas, Tara L.

2014-01-01

Skeletal muscle overload induces the expression of angiogenic factors such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2, leading to new capillary growth. We found that the overload-induced increase in angiogenesis, as well as increases in VEGF, MMP-2 and MT1-MMP transcripts were abrogated in muscle VEGF KO mice, highlighting the critical role of myocyte-derived VEGF in controlling this process. The upstream mediators that contribute to overload-induced expression of VEGF have yet to be ascertained. We found that muscle overload increased angiotensinogen expression, a precursor of angiotensin (Ang) II, and that Ang II signaling played an important role in basal VEGF production in C2C12 cells. Furthermore, matrix-bound VEGF released from myoblasts induced the activation of endothelial cells, as evidenced by elevated endothelial cell phospho-p38 levels. We also found that exogenous Ang II elevates VEGF expression, as well as MMP-2 transcript levels in C2C12 myotubes. Interestingly, these responses also were observed in skeletal muscle endothelial cells in response to Ang II treatment, indicating that these cells also can respond directly to the stimulus. The involvement of Ang II in muscle overload-induced angiogenesis was assessed. We found that blockade of AT1R-dependent Ang II signaling using losartan did not attenuate capillary growth. Surprisingly, increased levels of VEGF protein were detected in overloaded muscle from losartan-treated rats. Similarly, we observed elevated VEGF production in cultured endothelial cells treated with losartan alone or in combination with Ang II. These studies conclusively establish the requirement for muscle derived VEGF in overload-induced angiogenesis and highlight a role for Ang II in basal VEGF production in skeletal muscle. However, while Ang II signaling is activated following overload and plays a role in muscle VEGF production, inhibition of this pathway is not sufficient to halt overload-induced angiogenesis, indicating that AT1-independent signals maintain VEGF production in losartan-treated muscle. PMID:24416421

The role of MR imaging in detection of hepatic iron overload in patients with cirrhosis of different origins.

PubMed

Szurowska, Edyta; Sikorska, Katarzyna; Izycka-Swieszewska, E; Nowicki, Tomasz; Romanowski, Tomasz; Bielawski, Krzysztof P; Studniarek, Michał

2010-01-27

There are many pathological conditions with hepatic iron overload. Classical definite diagnostic methods of these disorders are invasive and based on a direct tissue biopsy material. For the last years the role of MR imaging in liver diagnostics has been increasing. MRI shows changes of liver intensity in patients with hepatic iron overload. Changes in MR signal are an indirect consequence of change of relaxation times T2 and T2*, that can be directly measured. The purpose of the study was to evaluate usefulness of MR imaging in the detection of hepatic iron overload in patients with cirrhosis of different origins. MR imaging at 1.5T was prospectively performed in 44 patients with liver cirrhosis who had undergone liver biopsy with histopathological assessment of hepatic iron deposits. In all patients the following sequences were used: SE, Express, GRE in T2 and T1-weighted images. Signal intensity (SI) was measured on images obtained with each T2 weighted sequence by means of regions of interest, placed in the liver and paraspinal muscles. The correlation between iron overload, histopathological score, serum ferritin and SI ratio was analyzed. In 20 patients with iron overload confirmed by the biopsy, the liver parenchyma demonstrated lower signal intensity than that of paraspinal muscles. This effect was visible only in 8 patients with hepatic iron overload in Express T2-weighted images. Higher signal intensity of liver than that of skeletal muscles on GRE - T2 weighted images was noted in 24 patients with cirrhosis and without elevated hepatic iron concentration. We observed a correlation between low and high iron concentration and liver to muscle SI ratio. MR imaging is a useful and fast noninvasive diagnostic tool for the detection of liver iron overload in patients with cirrhosis of different origins.Liver to muscle SI ratio in GRE-T2-weighted sequence facilitates to differentiate patients with low and high degree of hepatic iron overload, which correlates with the origin of liver cirrhosis.

Iron homeostasis and its disruption in mouse lung in iron deficiency and overload.

PubMed

Giorgi, Gisela; D'Anna, María Cecilia; Roque, Marta Elena

2015-10-01

What is the central question of this study? The aim was to explore the role and hitherto unclear mechanisms of action of iron proteins in protecting the lung against the harmful effects of iron accumulation and the ability of pulmonary cells to mobilize iron in iron deficiency. What is the main finding and its importance? We show that pulmonary hepcidin appears not to modify cellular iron mobilization in the lung. We propose pathways for supplying iron to the lung in iron deficiency and for protecting the lung against iron excess in iron overload, mediated by the co-ordinated action of iron proteins, such as divalent metal transporter 1, ZRT-IRE-like-protein 14, transferrin receptor, ferritin, haemochromatosis-associated protein and ferroportin. Iron dyshomeostasis is associated with several forms of chronic lung disease, but its mechanisms of action remain to be elucidated. The aim of the present study was to determine the role of the lung in whole-animal models with iron deficiency and iron overload, studying the divalent metal transporter 1 (DMT1), ZRT-IRE-like protein 14 (ZIP14), transferrin receptor (TfR), haemochromatosis-associated protein (HFE), hepcidin, ferritin and ferroportin (FPN) expression. In each model, adult CF1 mice were divided into the following groups (six mice per group): (i) iron-overload model, iron saccharate i.p. and control group (iron adequate), 0.9% NaCl i.p.; and (ii) iron-deficiency model, induced by repeated bleeding, and control group (sham operated). Proteins were assessed by immunohistochemistry and Western blot. In control mice, DMT1 was localized in the cytoplasm of airway cells, and in iron deficiency and overload it was in the apical membrane. Divalent metal transporter 1 and TfR increased in iron deficiency, without changes in iron overload. ZRT-IRE-like protein 14 decreased in airway cells in iron deficiency and increased in iron overload. In iron deficiency, HFE and FPN were immunolocalized close to the apical membrane. Ferroportin increased in iron overload. Prohepcidin was present in control groups, with no changes in iron deficiency and iron overload. In iron overload, ferritin showed intracytoplasmic localization close to the apical membrane of airway cells and intense immunostaining in macrophage-like cells. The results show that pulmonary hepcidin does not appear to modify cellular iron mobilization in the lung. We propose the following two novel pathways in the lung: (i) for supplying iron in iron deficiency, mediated principally by DMT1 and TfR and regulated by the action of FPN and HFE; and (ii) for iron detoxification in order to protect the lung against iron overload, facilitated by the action of DMT1, ZIP14, FPN and ferritin. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Symmetrical and overloaded effect of diffusion in information filtering

NASA Astrophysics Data System (ADS)

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.

Sensory Overload and Technology in Critical Care.

PubMed

Wung, Shu-Fen; Malone, Daniel C; Szalacha, Laura

2018-06-01

In this focus group study, we identified issues associated with sensory overload from medical technology alarms/alerts for intensive care unit nurses. Participants indicated that alarms from cardiopulmonary monitors, ventilators, and intravenous pumps contributed the most to sensory overload and, yet, these alarms were also deemed the most helpful. Alerts/alarms from electronic health records and medication dispensing systems were rated low in contributing to sensory overload, as well as being the least helpful. Specific device/technology barriers, related to device alerts/alarms, are detailed. Future user-centered and integrated improvements in alarm systems associated with medical devices in the intensive care unit are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

HFE gene in primary and secondary hepatic iron overload

PubMed Central

Sebastiani, Giada; Walker, Ann P

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 non-alcoholic 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. PMID:17729389

Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging.

PubMed

Assis, Reijâne Alves de; Kassab, Carolina; Seguro, Fernanda Salles; Costa, Fernando Ferreira; Silveira, Paulo Augusto Achucarro; Wood, John; Hamerschlak, Nelson

2013-12-01

To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

Prooxidant Mechanisms in Iron Overload Cardiomyopathy

PubMed Central

Cheng, Ching-Feng; Lian, Wei-Shiung

2013-01-01

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. PMID:24350287

Unraveling the mechanisms behind iron overload and ineffective hematopoiesis in myelodysplastic syndromes.

PubMed

Angelucci, Emanuele; Cianciulli, Paolo; Finelli, Carlo; Mecucci, Cristina; Voso, Maria Teresa; Tura, Sante

2017-11-01

Myelodysplastic syndromes (MDS) are a group of clonally-acquired blood disorders characterized by ineffective hematopoiesis leading to cytopenias. Red blood cell transfusions are an important component of supportive care in patients with MDS. Prolonged exposure to transfusions can lead to iron overload, which results in iron-induced toxicity caused by the production of reactive oxygen species (ROS). ROS accumulation has detrimental effects also on hematopoietic stem cells and may contribute to MDS progression. The observation that iron chelation improves hematologic parameters and reduces transfusion dependence further indicates that iron overload impairs hematopoiesis. Over the past decade, the mechanisms regulating iron homeostasis and the complex interplay between iron overload and toxicity, ineffective hematopoiesis, and transformation to leukemia have become clearer. In this narrative review, we provide an overview of recent findings pertaining to iron overload in patients with MDS and its effects on hematopoiesis. We also briefly discuss the position of chelation therapy in the context of the new developments. Copyright © 2017. Published by Elsevier Ltd.

Information Overload and Viral Marketing: Countermeasures and Strategies

NASA Astrophysics Data System (ADS)

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.

Measurement of liver iron overload: noninvasive calibration of MRI-R2* by magnetic iron detector susceptometer.

PubMed

Gianesin, B; Zefiro, D; Musso, M; Rosa, A; Bruzzone, C; Balocco, M; Carrara, P; Bacigalupo, L; Banderali, S; Rollandi, G A; Gambaro, M; Marinelli, M; Forni, G L

2012-06-01

An accurate assessment of body iron accumulation is essential for the diagnosis and therapy of iron overload in diseases such as thalassemia or hemochromatosis. Magnetic iron detector susceptometry and MRI are noninvasive techniques capable of detecting iron overload in the liver. Although the transverse relaxation rate measured by MRI can be correlated with the presence of iron, a calibration step is needed to obtain the liver iron concentration. Magnetic iron detector provides an evaluation of the iron overload in the whole liver. In this article, we describe a retrospective observational study comparing magnetic iron detector and MRI examinations performed on the same group of 97 patients with transfusional or congenital iron overload. A biopsy-free linear calibration to convert the average transverse relaxation rate in iron overload (R(2) = 0.72), or in liver iron concentration evaluated in wet tissue (R(2) = 0.68), is presented. This article also compares liver iron concentrations calculated in dry tissue using MRI and the existing biopsy calibration with liver iron concentrations evaluated in wet tissue by magnetic iron detector to obtain an estimate of the wet-to-dry conversion factor of 6.7 ± 0.8 (95% confidence level). Copyright © 2011 Wiley-Liss, Inc.

Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome

PubMed Central

Shenoy, Niraj; Vallumsetla, Nishanth; Rachmilewitz, Eliezer; Verma, Amit

2014-01-01

Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron’s adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism–driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population. PMID:24923296

Consequences and management of iron overload in sickle cell disease.

PubMed

Porter, John; Garbowski, Maciej

2013-01-01

The aims of this review are to highlight the mechanisms and consequences of iron distribution that are most relevant to transfused sickle cell disease (SCD) patients and to address the particular challenges in the monitoring and treatment of iron overload. In contrast to many inherited anemias, in SCD, iron overload does not occur without blood transfusion. The rate of iron loading in SCD depends on the blood transfusion regime: with simple hypertransfusion regimes, rates approximate to thalassemia major, but iron loading can be minimal with automated erythrocyte apheresis. The consequences of transfusional iron overload largely reflect the distribution of storage iron. In SCD, a lower proportion of transfused iron distributes extrahepatically and occurs later than in thalassemia major, so complications of iron overload to the heart and endocrine system are less common. We discuss the mechanisms by which these differences may be mediated. Treatment with iron chelation and monitoring of transfusional iron overload in SCD aim principally at controlling liver iron, thereby reducing the risk of cirrhosis and hepatocellular carcinoma. Monitoring of liver iron concentration pretreatment and in response to chelation can be estimated using serum ferritin, but noninvasive measurement of liver iron concentration using validated and widely available MRI techniques reduces the risk of under- or overtreatment. The optimal use of chelation regimes to achieve these goals is described.

Involvement of cytosolic and mitochondrial iron in iron overload cardiomyopathy: an update.

PubMed

Gordan, Richard; Wongjaikam, Suwakon; Gwathmey, Judith K; Chattipakorn, Nipon; Chattipakorn, Siriporn C; Xie, Lai-Hua

2018-04-19

Iron overload cardiomyopathy (IOC) is a major cause of death in patients with diseases associated with chronic anemia such as thalassemia or sickle cell disease after chronic blood transfusions. Associated with iron overload conditions, there is excess free iron that enters cardiomyocytes through both L- and T-type calcium channels thereby resulting in increased reactive oxygen species being generated via Haber-Weiss and Fenton reactions. It is thought that an increase in reactive oxygen species contributes to high morbidity and mortality rates. Recent studies have, however, suggested that it is iron overload in mitochondria that contributes to cellular oxidative stress, mitochondrial damage, cardiac arrhythmias, as well as the development of cardiomyopathy. Iron chelators, antioxidants, and/or calcium channel blockers have been demonstrated to prevent and ameliorate cardiac dysfunction in animal models as well as in patients suffering from cardiac iron overload. Hence, either a mono-therapy or combination therapies with any of the aforementioned agents may serve as a novel treatment in iron-overload patients in the near future. In the present article, we review the mechanisms of cytosolic and/or mitochondrial iron load in the heart which may contribute synergistically or independently to the development of iron-associated cardiomyopathy. We also review available as well as potential future novel treatments.

Matching work capacities and demands at job placement in employees with disabilities.

PubMed

Zoer, Ilona; de Graaf, Lucinda; Kuijer, P Paul F M; Prinzie, Peter; Hoozemans, Marco J M; Frings-Dresen, Monique H W

2012-01-01

To determine whether employees with disabilities were initially assigned to jobs with work demands that matched their work capacities. Forty-six employees with various physical, mental, sensory and multiple disabilities working in a sheltered workshop. Physical and psychosocial work capacities were assessed post-offer and pre-placement using the Ergo-Kit and Melba. Work demands of the jobs were determined by workplace assessments with TRAC and Melba and were compared with the work capacities. Of the 46 employees, 25 employees were not physically overloaded. When physical overload occurred, it was most often due to regular lifting. All employees were physically underloaded on six or more work activities, most often due to finger dexterity and manipulation. Almost all employees (n=43) showed psychosocial overload or underload on one or more psychosocial characteristics. Psychosocial overload was most often due to endurance (long-term work performance), while psychosocial underload was most often due to speaking and writing. Despite the assessment of work capacities at job placement, underload and overload occurred on both physical activities and psychosocial characteristics. Assessing both work capacities and work demands before job placement is recommended. At job placement more attention should be paid to overloading due to lifting and long-term work performance.

Longitudinal trajectories of subjective care stressors: the role of personal, dyadic, and family resources.

PubMed

Bangerter, Lauren R; Liu, Yin; Zarit, Steven H

2017-11-24

Stressors are critical to the caregiver stress process, yet little work has examined resources that contribute to longitudinal changes in subjective stressors. The present study examines a variety of factors that contribute to changes in subjective stressors across time. Dementia caregivers (N = 153) completed an in-person interview and eight daily telephone interviews at baseline, and follow up interviews at 6 and 12 months. Growth curve analyses examine how care- and non-care stressors, respite, dyadic relationship quality, family support/conflict and care transitions (e.g. nursing home placement) are associated with changes in role overload and role captivity across 12 months. Caregivers who transitioned out of their role had higher overload and captivity at baseline. Among caregivers who transitioned out of caregiving, higher captivity at baseline was associated with declines in captivity and overload; more non-care stressors at baseline was linked to increased captivity and greater overload across time. Adult day service use and family support were associated with lesser captivity over time; taking more breaks from caregiving was linked to lower overload. Higher dyadic relationship quality was associated with lower captivity and overload. Findings contribute to caregiver intervention efforts by highlighting important resources associated with subjective stressors across time.

Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome.

PubMed

Shenoy, Niraj; Vallumsetla, Nishanth; Rachmilewitz, Eliezer; Verma, Amit; Ginzburg, Yelena

2014-08-07

Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron's adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism-driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population. © 2014 by The American Society of Hematology.

Nursing management of sensory overload in psychiatry – Theoretical densification and modification of the framework model

PubMed

Scheydt, Stefan; Needham, Ian; Behrens, Johann

2017-01-01

Background: Within the scope of the research project on the subjects of sensory overload and stimulus regulation, a theoretical framework model of the nursing care of patients with sensory overload in psychiatry was developed. In a second step, this theoretical model should now be theoretically compressed and, if necessary, modified. Aim: Empirical verification as well as modification, enhancement and theoretical densification of the framework model of nursing care of patients with sensory overload in psychiatry. Method: Analysis of 8 expert interviews by summarizing and structuring content analysis methods based on Meuser and Nagel (2009) as well as Mayring (2010). Results: The developed framework model (Scheydt et al., 2016b) could be empirically verified, theoretically densificated and extended by one category (perception modulation). Thus, four categories of nursing care of patients with sensory overload can be described in inpatient psychiatry: removal from stimuli, modulation of environmental factors, perceptual modulation as well as help somebody to help him- or herself / coping support. Conclusions: Based on the methodological approach, a relatively well-saturated, credible conceptualization of a theoretical model for the description of the nursing care of patients with sensory overload in stationary psychiatry could be worked out. In further steps, these measures have to be further developed, implemented and evaluated regarding to their efficacy.

Protein quality control in protection against systolic overload cardiomyopathy: the long term role of small heat shock proteins

PubMed Central

Kumarapeli, Asangi R K; Horak, Kathleen; Wang, Xuejun

2010-01-01

Molecular chaperones represent the first line of defense of intracellular protein quality control. As a major constituent of molecular chaperones, heat shock proteins (HSP) are known to confer cardiomyocyte short-term protection against various insults and injuries. Previously, we reported that the small HSP αB-crystallin (CryAB) attenuates cardiac hypertrophic response in mice subjected to 2 weeks of severe pressure overload. However, the long-term role of small HSPs in cardiac hypertrophy and failure has rarely been studied. The present study investigates the cardiac responses to chronic severe pressure overload in CryAB/HSPB2 germ line ablated (KO) and cardiac-specific CryAB overexpressingtransgenic (TG) mice. Pressure overload was induced by transverse aortic constriction in KO, TG, and non-transgenic wild type (NTG) control mice and 10 weeks later molecular, cellular, and whole organ level hypertrophic responses were analyzed. As we previously described, CryAB/HSPB2 KO mice showed abnormal baseline cardiac physiology that worsened into a restrictive cardiomyopathic phenotype with aging. Severe pressure overload in these mice led to rapid deterioration of heart function and development of congestive cardiac failure. Contrary to their short term protective phenotype, CryAB TG mice showed no significant effects on cardiac hypertrophic responses and very modest improvement of hemodynamics during chronic systolic overload. These findings indicate that small HSPs CryAB and/or HSPB2 are essential to maintain cardiac structure and function but overex-pression of CryAB is not sufficient to confer a sustained protection against chronic systolic overload. PMID:20733949

Evaluation of cardiac and hepatic iron overload in thalassemia major patients with T2* magnetic resonance imaging.

PubMed

Wahidiyat, Pustika Amalia; Liauw, Felix; Sekarsari, Damayanti; Putriasih, Siti Ayu; Berdoukas, Vasili; Pennell, Dudley J

2017-09-01

Recent advancements have promoted the use of T2* magnetic resonance imaging (MRI) in the non-invasive detection of iron overload in various organs for thalassemia major patients. This study aims to determine the iron load in the heart and liver of patients with thalassemia major using T2* MRI and to evaluate its correlation with serum ferritin level and iron chelation therapy. This cross-sectional study included 162 subjects diagnosed with thalassemia major, who were classified into acceptable, mild, moderate, or severe cardiac and hepatic iron overload following their T2* MRI results, respectively, and these were correlated to their serum ferritin levels and iron chelation therapy. The study found that 85.2% of the subjects had normal cardiac iron stores. In contrast, 70.4% of the subjects had severe liver iron overload. A significant but weak correlation (r = -0.28) was found between cardiac T2* MRI and serum ferritin, and a slightly more significant correlation (r = 0.37) was found between liver iron concentration (LIC) and serum ferritin. The findings of this study are consistent with several other studies, which show that patients generally manifest with liver iron overload prior to cardiac iron overload. Moreover, iron accumulation demonstrated by T2* MRI results also show a significant correlation to serum ferritin levels. This is the first study of its kind conducted in Indonesia, which supports the fact that T2* MRI is undoubtedly valuable in the early detection of cardiac and hepatic iron overload in thalassemia major patients.

A composite mouse model of aplastic anemia complicated with iron overload

PubMed Central

Wu, Dijiong; Wen, Xiaowen; Liu, Wenbin; Xu, Linlong; Ye, Baodong; Zhou, Yuhong

2018-01-01

Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal dosage and duration of intraperitoneal iron dextran injection for the development of an iron overload model in mice were explored. A composite model of AA was successfully established on the principle of immune-mediated bone marrow failure. Liver volume, peripheral hemogram, bone marrow pathology, serum iron, serum ferritin, pathological iron deposition in multiple organs (liver, bone marrow, spleen), liver hepcidin, and bone morphogenetic protein 6 (BMP6), SMAD family member 4 (SMAD4) and transferrin receptor 2 (TfR2) mRNA expression levels were compared among the normal control, AA, iron overload and composite model groups to validate the composite model, and explore the pathogenesis and features of iron overload in this model. The results indicated marked increases in iron deposits, with significantly increased liver/body weight ratios as well as serum iron and ferritin in the iron overload and composite model groups as compared with the normal control and AA groups (P<0.05). There were marked abnormalities in iron regulation gene expression between the AA and composite model groups, as seen by the significant decrease of hepcidin expression in the liver (P<0.01) that paralleled the changes in BMP6, SMAD4, and TfR2. In summary, a composite mouse model with iron overload and AA was successfully established, and AA was indicated to possibly have a critical role in abnormal iron metabolism, which promoted the development of iron deposits. PMID:29434729

Fluid overload and kidney failure in children with severe sepsis and septic shock: A cohort study.

PubMed

Naveda Romero, Omar E; Naveda Meléndez, Andrea F

2017-04-01

In children with sepsis, fluid overload as a result of an aggressive fluid replacement or excessive fluid administration may result in kidney impairment and increased mortality. Objective. To determine the association between fluid overload and the rate of kidney failure in a group of children with severe sepsis and septic shock. This was a prospective cohort study conducted in the intensive care unit of Hospital Universitario de Pediatría “Dr. Agustín Zubillaga” (Barquisimeto, Lara State, Venezuela), between March 2013 and May 2016, in children with severe sepsis or septic shock. One hundred and forty-nine patients were included in the analysis. Sepsis predominated in 59.7% of cases; patients' average age was 6.4 ± 3.3 years old, their average weight was 17.8 ± 3.6 kg, 30.2% had fluid overload, and overall mortality was 25.5%. Kidney failure occurred in 16.1% of cases. A binary logistic regression model was used to identify fluid overload (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.2-4.9, p = 0.028) and shock for more than 2 days (OR: 1.7; 95% CI: 1.3-6.3, p = 0.039) as independent predictors of kidney failure. In addition, a significant increase in the risk of mortality among children with kidney failure and fluid overload was observed as per the Kaplan-Meier method (p= 0.019). Fluid overload and shock for more than 2 days increase the risk for kidney failure in critically ill children with severe sepsis and septic shock.

A composite mouse model of aplastic anemia complicated with iron overload.

PubMed

Wu, Dijiong; Wen, Xiaowen; Liu, Wenbin; Xu, Linlong; Ye, Baodong; Zhou, Yuhong

2018-02-01

Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal dosage and duration of intraperitoneal iron dextran injection for the development of an iron overload model in mice were explored. A composite model of AA was successfully established on the principle of immune-mediated bone marrow failure. Liver volume, peripheral hemogram, bone marrow pathology, serum iron, serum ferritin, pathological iron deposition in multiple organs (liver, bone marrow, spleen), liver hepcidin, and bone morphogenetic protein 6 (BMP6), SMAD family member 4 (SMAD4) and transferrin receptor 2 (TfR2) mRNA expression levels were compared among the normal control, AA, iron overload and composite model groups to validate the composite model, and explore the pathogenesis and features of iron overload in this model. The results indicated marked increases in iron deposits, with significantly increased liver/body weight ratios as well as serum iron and ferritin in the iron overload and composite model groups as compared with the normal control and AA groups (P<0.05). There were marked abnormalities in iron regulation gene expression between the AA and composite model groups, as seen by the significant decrease of hepcidin expression in the liver (P<0.01) that paralleled the changes in BMP6, SMAD4, and TfR2. In summary, a composite mouse model with iron overload and AA was successfully established, and AA was indicated to possibly have a critical role in abnormal iron metabolism, which promoted the development of iron deposits.

Protein quality control in protection against systolic overload cardiomyopathy: the long term role of small heat shock proteins.

PubMed

Kumarapeli, Asangi R K; Horak, Kathleen; Wang, Xuejun

2010-07-21

Molecular chaperones represent the first line of defense of intracellular protein quality control. As a major constituent of molecular chaperones, heat shock proteins (HSP) are known to confer cardiomyocyte short-term protection against various insults and injuries. Previously, we reported that the small HSP alphaB-crystallin (CryAB) attenuates cardiac hypertrophic response in mice subjected to 2 weeks of severe pressure overload. However, the long-term role of small HSPs in cardiac hypertrophy and failure has rarely been studied. The present study investigates the cardiac responses to chronic severe pressure overload in CryAB/HSPB2 germ line ablated (KO) and cardiac-specific CryAB overexpressingtransgenic (TG) mice. Pressure overload was induced by transverse aortic constriction in KO, TG, and non-transgenic wild type (NTG) control mice and 10 weeks later molecular, cellular, and whole organ level hypertrophic responses were analyzed. As we previously described, CryAB/HSPB2 KO mice showed abnormal baseline cardiac physiology that worsened into a restrictive cardiomyopathic phenotype with aging. Severe pressure overload in these mice led to rapid deterioration of heart function and development of congestive cardiac failure. Contrary to their short term protective phenotype, CryAB TG mice showed no significant effects on cardiac hypertrophic responses and very modest improvement of hemodynamics during chronic systolic overload. These findings indicate that small HSPs CryAB and/or HSPB2 are essential to maintain cardiac structure and function but overex-pression of CryAB is not sufficient to confer a sustained protection against chronic systolic overload.

Bereavement overload and its effects on, and related coping mechanisms of health care providers and ward administrators at National District Hospital in Bloemfontein, Free State.

PubMed

Allie, Zaid; Le Roux, Edith; Mahlatsi, Khantse; Mofokeng, Boitumelo; Ramoo, Zara-Anne; Sibiya, Khanyisile; Joubert, Gina; Van Rooyen, Jan P; Brits, Hanneke

2018-06-18

Patient death is an event that all health care workers will face at some point. Beyond the family, the greatest emotional strain is on people who work directly with the patient and family. Bereavement overload occurs after multiple losses without time for normal grief in between. To investigate bereavement overload, its effects and related coping mechanisms of personnel working in adult medical wards. Four adult medical wards at National District Hospital, Bloemfontein. An analytical cross-sectional study design was performed with the aid of an intervieweradministered questionnaire. The target population included health care providers (13 doctors and 20 nurses), eight final-year medical students, and four administrative staff working in thefour adult medical wards at National District Hospital, during August to October 2016. Half (48.9%) of the 45 participants reported bereavement overload. None of the medical students reported bereavement overload compared to 60.0% of nurses, 75.0% of administrative staff and 53.9% of doctors. Nearly two-thirds (64.5%, n = 29) stated that they suffered from compassion fatigue. The majority of participants (62.2%) used only positive coping mechanisms. The use of negative coping mechanisms correlated directly with a longer duration in the medical field. With a 49% prevalence of bereavement overload, it is important that support systems are in place to prevent the effects of negative coping mechanisms. The desirable outcome is that health care providers, who suffer from bereavement overload, experience compassion satisfaction and become more dedicated to the patients' well-being without expense to themselves.

Cardiovascular responses to aerobic step dance sessions with and without appendicular overload.

PubMed

La Torre, A; Impellizzeri, F M; Rampinini, E; Casanova, F; Alberti, G; Marcora, S M

2005-09-01

Several studies showed that exercise intensity during aerobic step dance can be modified varying stepping rate, bench height and manipulating body mass using hand held or adding loads to the torso. The aim of this study was to determine the cardiovascular responses during aerobic step dance using an overload strategy not yet investigated: appendicular overload. Ten healthy and moderately trained women (mean+/-SD: age 27+/-3.4 years, height 167.8+/-4.6 cm, body mass 55.7+/-4.7 kg, body mass index 19.8+/-1.6, VO2max44.4+/-6.1 mLxkg-1xmin-1) performed an incremental treadmill test to determine VO2peak, the VO2-heart rate (HR) and rating of perceived exertion (RPE)-HR relationships. Within 1 week from the laboratory test, the subjects performed two identical aerobic step dance routines: one using a track suit with loads placed in pockets close to the legs and arms and another without overload. The appendicular overload (10% of body mass) significantly increased the exercise intensity from 84.5% to 89.8% of HRmax corresponding to 68.9% and 78.3% of VO2peak, respectively (P<0.01). Similarly, RPE increased from 12.1 to 15.7 (P<0.001). The estimated VO2 and the caloric expenditure rose from 30.3 to 34.7 mLxkg-1xmin-1 and from 251 to 288 kcal, respectively. This study shows that the use of appendicular overload significantly increases the energy cost of aerobic step session similarly to other overload strategies already reported in the literature.

Hospital treatment for fluid overload in the Medicare hemodialysis population.

PubMed

Arneson, Thomas J; Liu, Jiannong; Qiu, Yang; Gilbertson, David T; Foley, Robert N; Collins, Allan J

2010-06-01

Fluid overload in hemodialysis patients sometimes requires emergent dialysis, but the magnitude of this care has not been characterized. This study aimed to estimate the magnitude of fluid overload treatment episodes for the Medicare hemodialysis population in hospital settings, including emergency departments. Point-prevalent hemodialysis patients were identified from the Centers for Medicare and Medicaid Renal Management Information System and Standard Analytical Files. Fluid overload treatment episodes were defined by claims for care in inpatient, hospital observation, or emergency department settings with primary discharge diagnoses of fluid overload, heart failure, or pulmonary edema, and dialysis performed on the day of or after admission. Exclusion criteria included stays >5 days. Cost was defined as total Medicare allowable costs for identified episodes. Associations between patient characteristics and episode occurrence and cost were analyzed. For 25,291 patients (14.3%), 41,699 care episodes occurred over a mean follow-up time of 2 years: 86% inpatient, 9% emergency department, and 5% hospital observation. Heart failure was the primary diagnosis in 83% of episodes, fluid overload in 11%, and pulmonary edema in 6%. Characteristics associated with more frequent events included age <45 years, female sex, African-American race, causes of ESRD other than diabetes, dialysis duration of 1 to 3 years, fewer dialysis sessions per week at baseline, hospitalizations during baseline, and most comorbid conditions. Average cost was $6,372 per episode; total costs were approximately $266 million. Among U.S. hemodialysis patients, fluid overload treatment is common and expensive. Further study is necessary to identify prevention opportunities.

Unfavorable effects of history of volume overload and late referral to a nephrologist on mortality in patients initiating dialysis: a multicenter prospective cohort study in Japan.

PubMed

Okazaki, Masaki; Inaguma, Daijo; Imaizumi, Takahiro; Kada, Akiko; Yaomura, Takaaki; Tsuboi, Naotake; Maruyama, Shoichi

2018-03-14

Patients with late referral and positive history of volume overload may have a poor prognosis after initiating dialysis due to insufficient and/or inadequate management of complications of renal failure and the lack of better dialysis preparation. Little is known about the influence of the relationship between history of volume overload and late referral on prognosis. We analyzed 1475 patients who had initiated dialysis for the first time from October 2011 to September 2013. late referral was defined as referral to a nephrologist < 3 months before dialysis initiation. The major outcomes were all-cause death and deaths due to cardiovascular diseases (CVD). The impact of late referral and history of volume overload on all-cause mortality was assessed by Cox proportional hazards models. Among 1475 patients, the mean patient age was 67.5 years. During the median follow-up of 2.2 years, 260 deaths occurred; 99 were due to CVD. Cox proportional hazards models demonstrated that late referral (adjusted hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.00-1.82) and history of volume overload (adjusted HR, 1.39; 95% CI, 1.06-1.81) were risk factors for all-cause mortality. Furthermore, late referral coexisting was associated with a history of volume overload increased mortality (adjusted HR, 2.10; 95% CI, 1.39-3.16 versus absence of late referral without history of volume overload) after adjusting for age, sex, diabetes, atherosclerotic disease, and laboratory values. Both late referral and history of volume overload were associated with increased risks of all-cause mortality. University Hospital Medical Information Network (UMIN000007096). Registered 18 January 2012, retrospectively registered. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000008349 .

5-lipoxygenase activation is involved in the mechanisms of chronic hepatic injury in a rat model of chronic aluminum overload exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mai, Shaoshan

We previously confirmed that rats overloaded with aluminum exhibited hepatic function damage and increased susceptibility to hepatic inflammation. However, the mechanism of liver toxicity by chronic aluminum overload is poorly understood. In this study, we investigated changes in the 5-lipoxygenase (5-LO) signaling pathway and its effect on liver injury in aluminum-overloaded rats. A rat hepatic injury model of chronic aluminum injury was established via the intragastric administration of aluminum gluconate (Al{sup 3+} 200 mg/kg per day, 5 days a week for 20 weeks). The 5-LO inhibitor, caffeic acid (10 and 30 mg/kg), was intragastrically administered 1 h after aluminum administration.more » Hematoxylin and eosin staining was used to visualize pathological changes in rat liver tissue. A series of biochemical indicators were measured with biochemistry assay or ELISAs. Immunochemistry and RT-PCR methods were used to detect 5-LO protein and mRNA expression in the liver, respectively. Caffeic acid administration protected livers against histopathological injury, decreased plasma ALT, AST, and ALP levels, decreased TNF-α, IL-6, IL-1β and LTs levels, increased the reactive oxygen species content, and down-regulated the mRNA and protein expressions of 5-LO in aluminum overloaded rats. Our results indicate that 5-lipoxygenase activation is mechanistically involved in chronic hepatic injury in a rat model of chronic aluminum overload exposure and that the 5-LO signaling pathway, which associated with inflammation and oxidative stress, is a potential therapeutic target for chronic non-infection liver diseases. - Highlights: • 5-LO signaling contributes to mechanisms of hepatotoxicity of aluminum overload. • Oxidative and inflammatory reaction involve in chonic aluminum hepatotoxicity. • 5-LO inhibitor has a protective effect on aluminum-overload liver injury. • 5-LO signaling is a potential therapeutic target for non-infection liver diseases.« less

Both cardiomyocyte and endothelial cell Nox4 mediate protection against hemodynamic overload-induced remodelling.

PubMed

Zhang, Min; Mongue-Din, Heloise; Martin, Daniel; Catibog, Norman; Smyrnias, Ioannis; Zhang, Xiaohong; Yu, Bin; Wang, Minshu; Brandes, Ralf P; Schröder, Katrin; Shah, Ajay M

2018-03-01

NADPH oxidase-4 (Nox4) is an important reactive oxygen species (ROS) source that is upregulated in the haemodynamically overloaded heart. Our previous studies using global Nox4 knockout (Nox4KO) mice demonstrated a protective role of Nox4 during chronic abdominal aortic banding, involving a paracrine enhancement of myocardial capillary density. However, other authors who studied cardiac-specific Nox4KO mice reported detrimental effects of Nox4 in response to transverse aortic constriction (TAC). It has been speculated that these divergent results are due to cell-specific actions of Nox4 (i.e. cardiomyocyte Nox4 detrimental but endothelial Nox4 beneficial) and/or differences in the model of pressure overload (i.e. abdominal banding vs. TAC). This study aimed to (i) investigate whether the effects of Nox4 on pressure overload-induced cardiac remodelling vary according to the pressure overload model and (ii) compare the roles of cardiomyocyte vs. endothelial cell Nox4. Global Nox4KO mice subjected to TAC developed worse cardiac remodelling and contractile dysfunction than wild-type littermates, consistent with our previous results with abdominal aortic banding. Next, we generated inducible cardiomyocyte-specific Nox4 KO mice (Cardio-Nox4KO) and endothelial-specific Nox4 KO mice (Endo-Nox4KO) and studied their responses to pressure overload. Both Cardio-Nox4KO and Endo-Nox4KO developed worse pressure overload-induced cardiac remodelling and dysfunction than wild-type littermates, associated with significant decrease in protein levels of HIF1α and VEGF and impairment of myocardial capillarization. Cardiomyocyte as well as endothelial cell Nox4 contributes to protection against chronic hemodynamic overload-induced cardiac remodelling, at least in part through common effects on myocardial capillary density. © The Author 2017 Published by Oxford University Press on behalf of the European Society of Cardiology.

Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult.

PubMed

Moreira-Gonçalves, Daniel; Henriques-Coelho, Tiago; Fonseca, Hélder; Ferreira, Rita; Padrão, Ana Isabel; Santa, Cátia; Vieira, Sara; Silva, Ana Filipa; Amado, Francisco; Leite-Moreira, Adelino; Duarte, José Alberto

2015-09-01

The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. The present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg(-1) , s.c.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week(-1) for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca(2+) protein. Regarding hypertrophic pathways, ITO and Ex showed activation of the protein kinase B/mammalian target of rapamycin pathway but not calcineurin. Mitochondrial complex IV and V activities were also increased in ITO and Ex. Chronic submission to controlled intermittent cardiac overload, independently of its nature, results in an adaptive cardiac phenotype. Features of the cardiac overload, such as the duration and magnitude of the stimuli, may play a role in the development of an adaptive or maladaptive phenotype. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Fluid overload in hemodialysis patients: a cross-sectional study to determine its association with cardiac biomarkers and nutritional status

PubMed Central

2013-01-01

Background Chronic fluid overload is associated with higher mortality in dialysis patients; however, the link with cardiovascular morbidity has not formally been established and may be influenced by subclinical inflammation. We hypothesized that a relationship exists between fluid overload and [i] cardiovascular laboratory parameter as well as between fluid overload and [ii] inflammatory laboratory parameters. In addition, we aimed to confirm whether volume status correlates with nutritional status. Methods We recorded baseline characteristics of 244 hemodialysis patients at three hemodialysis facilities in Vienna (Austria) and determined associations with volume measurements using the body composition monitor (Fresenius/Germany). In one facility comprising 126 patients, we further analyzed cardiovascular, inflammatory and nutritional parameters. Results We detected predialysis fluid overload (FO) in 39% of all patients (n = 95) with FO defined as ≥15% of extracellular water (ECW). In this subgroup, the absolute FO was 4.4 +/-1.5 L or 22.9 ± 4.8% of ECW. A sub-analysis of patients from one center showed that FO was negatively associated with body mass index (r = -0.371; p = <0.001), while serum albumin was significantly lower in fluid overloaded patients (p = 0.001). FO was positively associated with D-Dimer (r = 0.316; p = 0.001), troponin T (r = 0.325; p < 0.001), and N-terminal pro-B-type natriuretic peptide (r = 0.436; p < 0.001), but not with investigated inflammatory parameters. Conclusions Fluid overload in HD patients was found to be lower in patients with high body mass index, indicating that dry weight was inadequately prescribed and/or difficult to achieve in overweight patients. The association with parameters of cardiovascular compromise and/or damage suggests that fluid overload is a biomarker for cardiovascular risk. Future studies should determine if this applies to patients prior to end-stage renal disease. PMID:24295522

Early activation of mTORC1 signalling in response to mechanical overload is independent of phosphoinositide 3-kinase/Akt signalling

PubMed Central

Miyazaki, Mitsunori; McCarthy, John J; Fedele, Mark J; Esser, Karyn A

2011-01-01

Abstract The mammalian target of rapamycin complex 1 (mTORC1) functions as a central integrator of a wide range of signals that modulate protein metabolism and cell growth. However, the contributions of individual pathways regulating mTORC1 activity in skeletal muscle are poorly defined. The purpose of this study was to determine the regulatory mechanisms that contribute to mTORC1 activation during mechanical overload-induced skeletal muscle hypertrophy. Consistent with previous studies, mechanical overload induced progressive hypertrophy of the plantaris muscle which was associated with significant increases in total RNA content and protein metabolism. mTORC1 was activated after a single day of overload as indicated by a significant increase in S6K1 phosphorylation at T389 and T421/S424. In contrast, Akt activity, as assessed by Akt phosphorylation status (T308 and S473), phosphorylation of direct downstream targets (glycogen synthase kinase 3 β, proline-rich Akt substrate 40 kDa and tuberous sclerosis 2 (TSC2)) and a kinase assay, was not significantly increased until 2–3 days of overload. Inhibition of phosphoinositide 3-kinase (PI3K) activity by wortmannin was sufficient to block insulin-dependent signalling but did not prevent the early activation of mTORC1 in response to overload. We identified that the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent pathway was activated at day 1 after overload. In addition, a target of MEK/ERK signalling, phosphorylation of TSC2 at S664, was also increased at this early time point. These observations demonstrate that in vivo, mTORC1 activation at the early phase of mechanical overload in skeletal muscle occurs independently of PI3K/Akt signalling and provide evidence that the MEK/ERK pathway may contribute to mTORC1 activation through phosphorylation of TSC2. PMID:21300751

Effect of hand paddles and parachute on backstroke coordination and stroke parameters.

PubMed

Telles, Thiago; Barroso, Renato; Figueiredo, Pedro; Salgueiro, Diego Fortes de Souza; Vilas-Boas, João Paulo; Junior, Orival Andries

2017-05-01

Hand paddles and parachutes have been used in order to overload swimmers, and consequently increase the propulsive force generation in swimming. However, their use may affect not only kinematical parameters (average speed, stroke length and stroke rate), but also time gaps between propulsive phases, assessed through the index of coordination (IdC). The objective of this study was to assess the effects of hand paddles and parachute use, isolated or combined, on kinematical parameters and coordination. Eleven swimmers (backstroke 50-m time: 29.16 ± 1.43 s) performed four 15-m trials in a randomised order at maximal intensity: (1) without implements (FREE), (2) with hand paddles (HPD), (3) with parachute (PCH) and (4) with hand paddles plus parachute (HPD+PCH). All trials were video-recorded (60 Hz) in order to assess average speed, stroke rate, stroke length, five stroke phases and index of coordination. When average swimming speed was compared to FREE, it was lower in PCH and HPD+PCH, and higher in HPD. Stroke rate decreased in all overloaded trials compared to FREE. The use of hand paddles and parachute increased and decreased stroke length, respectively. In addition, propulsive phase duration was increased when hand paddles were used, and time gaps shifted towards zero (no time gap), especially when hand paddles were combined with parachute. It is conceivable that the combined use of hand paddles and parachute, once allowing overloading both propulsive and resistive forces, provides a specific stimulus to improve muscle strength and propulsive continuity.

Transformer overload and bubble evolution: Proceedings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Addis, G.; Lindgren, S.

1988-06-01

The EPRI workshop on Transformer Overload Characteristics and Bubble Evolution was held to review the findings of investigations over the past 7-8 years to determine whether enough information is now available for utilities to establish safe loading practices. Sixteen papers were presented, including a utility review, physical and dielectric effects of gas and bubble formation from cellulose insulated transformers, transformer life characteristics, gas bubble studies and impulse test on distribution transformers, mathematical modeling of bubble evolution, transformer overload characteristics, variation of PD-strength for oil-paper insulation, survey on maximum safe operating hot spot temperature, and overload management. The meeting concluded withmore » a general discussion covering the existing state of knowledge and the need for additional research. Sixteen papers have been cataloged separately.« less

Effect of different training programs on the velocity of overarm throwing: a brief review.

PubMed

van den Tillaar, Roland

2004-05-01

Throwing velocity in overarm throwing is of major importance in sports like baseball, team handball, javelin, and water polo. The purpose of this literature review was to give an overview of the effect of different training programs on the throwing velocity in overarm throwing, provide a theoretical framework that explains findings, and give some practical applications based on these findings. The training studies were divided into 4 categories: (a) specific resistance training with an overload of velocity, (b) specific resistance training with an overload of force, (c) specific resistance training with a combination of overload of force and velocity, and (d) general resistance training according to the overload of force. Each category is presented and discussed.

The treatment of Wilson's disease, a rare genetic disorder of copper metabolism.

PubMed

Purchase, Rupert

2013-01-01

Wilson's disease is a rare autosomal recessive disease characterised by the deposition of copper in the brain, liver; cornea, and other organs. The overload of copper inevitably leads to progressive liver and neurological dysfunction. Copper overload in patients with Wilson's disease is caused by impairment to the biliary route for excretion of dietary copper A combination of neurological, psychiatric and hepatic symptoms can make the diagnosis of Wilson's disease challenging. Most symptoms appear in the second and third decades of life. The disease affects between one in 30,000 and one in 100,000 individuals, and is fatal if left untreated. Five drugs are currently available to treat Wilson's disease: British Anti-Lewisite; D-penicillamine; trientine; zinc sulfate or acetate; and ammonium tetrathiomolybdate. Each drug can reduce copper levels and/or transform copper into a metabolically inert and unavailable form in the patient. The discovery and introduction of these five drugs owes more to the inspiration of a few dedicated physicians and agricultural scientists than to the resources of the pharmaceutical industry.

Iron overload cardiomyopathy: from diagnosis to management.

PubMed

Díez-López, Carles; Comín-Colet, Josep; González-Costello, José

2018-05-01

Iron overload cardiomyopathy (IOC) is an important predictor of prognosis in a significant number of patients with hereditary hemochromatosis and hematologic diseases. Its prevalence is increasing because of improved treatment strategies, which significantly improve life expectancy. We will review diagnosis, treatment, and recent findings in the field. The development of preclinical translational disease models during the last years have helped our understanding of specific disease pathophysiological pathways that might eventually change the outcomes of these patients. IOC is an overlooked disease because of the progressive silent disease pattern and the lack of physicians' expertise. It mainly affects patients with hemochromatosis and hematologic diseases and its prevalence is expected to increase with the improvement in life expectancy of hematologic disorders. Early diagnosis of IOC in patients at risk by means of biochemical parameters and cardiac imaging can lead to early treatment and improved prognosis. The mainstay of treatment of IOC is conventional heart failure treatment, combined with phlebotomies or iron chelation in the context of anemia. The development of preclinical models has provided a comprehensive look into specific pathophysiological pathways with potential treatment strategies that must be sustained by future randomized trials.

The ANAMMOX reactor under transient-state conditions: process stability with fluctuations of the nitrogen concentration, inflow rate, pH and sodium chloride addition.

PubMed

Yu, Jin-Jin; Jin, Ren-Cun

2012-09-01

The process stability of an anaerobic ammonium oxidation (ANAMMOX) was investigated in an upflow anaerobic sludge blanket reactor subjected to overloads of 2.0- to 3.0-fold increases in substrate concentrations, inflow rates lasting 12 or 24h, extreme pH levels of 4 and 10 for 12h and a 12-h 30 g l(-1) NaCl addition. During the overloads, the nitrogen removal rate improved, and the shock period was an important factor affecting the reactor performance. In the high pH condition, the reactor performance significantly degenerated; while in the low pH condition, it did not happen. The NaCl addition caused the most serious deterioration in the reactor, which took 108 h to recover and was accompanied by a stoichiometric ratio divergence. There are well correlations between the total nitrogen and the electrical conductivity which is considered to be a convenient signal for controlling and monitoring the ANAMMOX process under transient-state conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

LATERAL EPICONDYLITIS OF THE ELBOW

PubMed Central

Cohen, Marcio; da Rocha Motta Filho, Geraldo

2015-01-01

Lateral epicondylitis, also known as tennis elbow, is a common condition that is estimated to affect 1% to 3% of the population. The word epicondylitis suggests inflammation, although histological analysis on the tissue fails to show any inflammatory process. The structure most commonly affected is the origin of the tendon of the extensor carpi radialis brevis and the mechanism of injury is associated with overloading. Nonsurgical treatment is the preferred method, and this includes rest, physiotherapy, cortisone infiltration, platelet-rich plasma injections and use of specific immobilization. Surgical treatment is recommended when functional disability and pain persist. Both the open and the arthroscopic surgical technique with resection of the degenerated tendon tissue present good results in the literature. PMID:27047843

A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloids-β accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload.

PubMed

Sripetchwandee, Jirapas; Wongjaikam, Suwakon; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2016-09-22

Iron-overload can cause cognitive impairment due to blood-brain barrier (BBB) breakdown and brain mitochondrial dysfunction. Although deferiprone (DFP) has been shown to exert neuroprotection, the head-to-head comparison among iron chelators used clinically on brain iron-overload has not been investigated. Moreover, since antioxidant has been shown to be beneficial in iron-overload condition, its combined effect with iron chelator has not been tested. Therefore, the hypothesis is that all chelators provide neuroprotection under iron-overload condition, and that a combination of an iron chelator with an antioxidant has greater efficacy than monotherapy. Male Wistar rats (n=42) were assigned to receive a normal diet (ND) or a high-iron diet (HFe) for 4months. At the 2nd month, HFe-fed rats were treated with a vehicle, deferoxamine (DFO), DFP, deferasirox (DFX), n-acetyl cysteine (NAC) or a combination of DFP with NAC, while ND-fed rats received vehicle. At the end of the experiment, rats were decapitated and brains were removed to determine brain iron level and deposition, brain mitochondrial function, BBB protein expression, brain mitochondrial dynamic, brain apoptosis, tau-hyperphosphorylation, amyloid-β (Aβ) accumulation and dendritic spine density. The results showed that iron-overload induced BBB breakdown, brain iron accumulation, brain mitochondrial dysfunction, impaired brain mitochondrial dynamics, tau-hyperphosphorylation, Aβ accumulation and dendritic spine reduction. All treatments, except DFX, attenuated these impairments. Moreover, combined therapy provided a greater efficacy than monotherapy. These findings suggested that iron-overload induced brain iron toxicity and a combination of an iron chelator with an antioxidant provided a greatest efficacy for neuroprotection than monotherapy. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Efficacy and safety of tolvaptan in heart failure patients with sustained volume overload despite the use of conventional diuretics: a phase III open-label study.

PubMed

Fukunami, Masatake; Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru

2011-12-01

Volume overload is a common complication associated with heart failure (HF) and is recommended to be treated with loop or thiazide diuretics. However, use of diuretics can cause serum electrolyte imbalances and diuretic resistance. Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients. The aim of this study was to investigate the efficacy and safety of tolvaptan in Japanese HF patients with volume overload. Fifty-one HF patients with volume overload, despite using conventional diuretics, were treated with 15 mg/day tolvaptan for 7 days. If the response was insufficient at Day 7, tolvaptan was continued for a further 7 days at either 15 mg/day or 30 mg/day. Outcomes included changes in body weight, symptoms and safety parameters. Thirty-six patients discontinued treatment within 7 days, therefore 15 patients entered the second phase of treatment. In two patients, tolvaptan was increased to 30 mg/day after 7 days. Body weight was reduced on Day 7 (-1.95 ± 1.98 kg; n = 41) and Day 14 (-2.35 ± 1.44 kg; n = 11, 15 mg/day). Symptoms of volume overload, including lower limb edema, pulmonary congestion, jugular venous distention and hepatomegaly, were improved by tolvaptan treatment for 7 or 14 days. Neither tolvaptan increased the incidence of severe or serious adverse events when administered for 7-14 days. This study confirms the efficacy and safety of 15 mg/day tolvaptan for 7-14 days in Japanese HF patients with volume overload despite conventional diuretics.

Microtubule-dependent distribution of mRNA in adult cardiocytes.

PubMed

Scholz, Dimitri; Baicu, Catalin F; Tuxworth, William J; Xu, Lin; Kasiganesan, Harinath; Menick, Donald R; Cooper, George

2008-03-01

Synthesis of myofibrillar proteins in the diffusion-restricted adult cardiocyte requires microtubule-based active transport of mRNAs as part of messenger ribonucleoprotein particles (mRNPs) to translation sites adjacent to nascent myofibrils. This is especially important for compensatory hypertrophy in response to hemodynamic overloading. The hypothesis tested here is that excessive microtubule decoration by microtubule-associated protein 4 (MAP4) after cardiac pressure overloading could disrupt mRNP transport and thus hypertrophic growth. MAP4-overexpressing and pressure-overload hypertrophied adult feline cardiocytes were infected with an adenovirus encoding zipcode-binding protein 1-enhanced yellow fluorescent protein fusion protein, which is incorporated into mRNPs, to allow imaging of these particles. Speed and distance of particle movement were measured via time-lapse microscopy. Microtubule depolymerization was used to study microtubule-based transport and distribution of mRNPs. Protein synthesis was assessed as radioautographic incorporation of [3H]phenylalanine. After microtubule depolymerization, mRNPs persist only perinuclearly and apparent mRNP production and protein synthesis decrease. Reestablishing microtubules restores mRNP production and transport as well as protein synthesis. MAP4 overdecoration of microtubules via adenovirus infection in vitro or following pressure overloading in vivo reduces the speed and average distance of mRNP movement. Thus cardiocyte microtubules are required for mRNP transport and structural protein synthesis, and MAP4 decoration of microtubules, whether directly imposed or accompanying pressure-overload hypertrophy, causes disruption of mRNP transport and protein synthesis. The dense, highly MAP4-decorated microtubule network seen in severe pressure-overload hypertrophy both may cause contractile dysfunction and, perhaps even more importantly, may prevent a fully compensatory growth response to hemodynamic overloading.

Site-specific microtubule-associated protein 4 dephosphorylation causes microtubule network densification in pressure overload cardiac hypertrophy.

PubMed

Chinnakkannu, Panneerselvam; Samanna, Venkatesababa; Cheng, Guangmao; Ablonczy, Zsolt; Baicu, Catalin F; Bethard, Jennifer R; Menick, Donald R; Kuppuswamy, Dhandapani; Cooper, George

2010-07-09

In severe pressure overload-induced cardiac hypertrophy, a dense, stabilized microtubule network forms that interferes with cardiocyte contraction and microtubule-based transport. This is associated with persistent transcriptional up-regulation of cardiac alpha- and beta-tubulin and microtubule-stabilizing microtubule-associated protein 4 (MAP4). There is also extensive microtubule decoration by MAP4, suggesting greater MAP4 affinity for microtubules. Because the major determinant of this affinity is site-specific MAP4 dephosphorylation, we characterized this in hypertrophied myocardium and then assessed the functional significance of each dephosphorylation site found by mimicking it in normal cardiocytes. We first isolated MAP4 from normal and pressure overload-hypertrophied feline myocardium; volume-overloaded myocardium, which has an equal degree and duration of hypertrophy but normal functional and cytoskeletal properties, served as a control for any nonspecific growth-related effects. After cloning cDNA-encoding feline MAP4 and obtaining its deduced amino acid sequence, we characterized by mass spectrometry any site-specific MAP4 dephosphorylation. Solely in pressure overload-hypertrophied myocardium, we identified striking MAP4 dephosphorylation at Ser-472 in the MAP4 N-terminal projection domain and at Ser-924 and Ser-1056 in the assembly-promoting region of the C-terminal microtubule-binding domain. Site-directed mutagenesis of MAP4 cDNA was then used to switch each serine to non-phosphorylatable alanine. Wild-type and mutated cDNAs were used to construct adenoviruses; microtubule network density, stability, and MAP4 decoration were assessed in normal cardiocytes following an equivalent level of MAP4 expression. The Ser-924 --> Ala MAP4 mutant produced a microtubule phenotype indistinguishable from that seen in pressure overload hypertrophy, such that Ser-924 MAP4 dephosphorylation during pressure overload hypertrophy may be central to this cytoskeletal abnormality.

Ferroportin (Q248H) mutations in African families with dietary iron overload.

PubMed

McNamara, Lynne; Gordeuk, Victor R; MacPhail, A Patrick

2005-12-01

Dietary iron overload found in sub-Saharan Africa might be caused by an interaction between dietary iron and an iron-loading gene. Caucasian people with ferroportin gene mutations have iron overload histologically similar to that found in African patients with iron overload. Ferroportin is also implicated in the hypoferremic response to inflammation. The prevalence of the ferroportin Q248H mutation, unique to African people, and its association with dietary iron overload, mean cell volume (MCV) and C-reactive protein (CRP) were examined in 19 southern African families. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the Q248H mutation. Statistical analysis was carried out to correlate the presence of the mutation with markers of iron overload and inflammation. We identified three (1.4%) Q248H homozygotes and 53 (24.1%) heterozygotes in the families examined in the present study. There was no increased prevalence of the mutation in index subjects or their families. Logistic regression showed significantly higher serum ferritin concentrations with the mutation. The mean cell volume (MCV) was significantly lower, and the serum CRP significantly higher in subjects who carried the mutation. The present study of 19 families with African iron overload failed to show evidence that the ferroportin (Q248H) mutation is responsible for the condition. Logistic regression, correcting for factors influencing iron status, did show increased ferritin levels in individuals with the mutation. The strong association with low MCV suggests the possibility that the ferroportin (Q248H) mutation might interfere with iron supply, whereas the elevated serum CRP might indicate that the ferroportin mutation influences the inflammatory response in African populations. Copyright 2005 Blackwell Publishing Asia Pty Ltd.

Hepatic iron overload is associated with hepatocyte apoptosis during Clonorchis sinensis infection.

PubMed

Han, Su; Tang, Qiaoran; Chen, Rui; Li, Yihong; Shu, Jing; Zhang, Xiaoli

2017-08-01

Hepatic iron overload has been implicated in many liver diseases; however, whether it is involved in clonorchiasis remains unknown. The purpose of this study is to investigate whether Clonorchis sinensis (C. sinensis) infection causes hepatic iron overload, analyze the relationship between the iron overload and associated cell apoptosis, so as to determine the role of excess iron plays in C. sinensis-induced liver injury. The Perls' Prussian staining and atomic absorption spectrometry methods were used to investigate the iron overload in hepatic sections of wistar rats and patients infected with C. sinensis. The hepatic apoptosis was detected by transferase uridyl nick end labeling (TUNEL) methods. Spearman analysis was used for determining the correlation of the histological hepatic iron index and the apoptotic index. Blue iron particles were deposited mainly in the hepatocytes, Kupffer cells and endothelial cells, around the liver portal and central vein area of both patients and rats. The total iron score was found to be higher in the infected groups than the respective control from 8 weeks. The hepatic iron concentration was also significantly higher in treatment groups than in control rats from 8 weeks. The hepatocyte apoptosis was found to be significantly higher in the portal area of the liver tissue and around the central vein. However, spearman's rank correlation coefficient revealed that there was a mildly negative correlation between the iron index and hepatocyte apoptosis. This present study confirmed that hepatic iron overload was found during C. sinensis infection. This suggests that iron overload may be associated with hepatocyte apoptosis and involved in liver injury during C. sinensis infection. Further studies are needed to investigate the molecular mechanism involved here.

Three Weeks of Overload Training Increases Resting Muscle Sympathetic Activity.

PubMed

Coates, Alexandra M; Incognito, Anthony V; Seed, Jeremy D; Doherty, Connor J; Millar, Philip J; Burr, Jamie F

2018-05-01

Overload training is hypothesized to alter autonomic regulation, although interpretations using indirect measures of heart rate variability are conflicting. The aim of the present study was to examine the effects of overload training on muscle sympathetic nerve activity (MSNA), a direct measure of central sympathetic outflow, in recreational endurance athletes. Measurements of heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA (microneurography), and sympathetic BRS were obtained in 17 healthy triathletes and cyclists after 1 wk of reduced training (baseline) and again after 3 wk of either regular (n = 7) or overload (n = 10) training. After training, the changes (Δ) in peak power output (10 ± 10 vs -12 ± 9 W, P < 0.001), maximal heart rate (-2 ± 4 vs -8 ± 3 bpm, P = 0.006), heart rate variability (SD of normal-to-normal intervals, 27 ± 31 vs -3 ± 25 ms; P = 0.04), and cardiac BRS (7 ± 6 vs -2 ± 8 ms·mm Hg, P = 0.02) differed between the control and overload groups. The change in MSNA burst frequency (-2 ± 2 vs 4 ± 5 bursts per minute, P = 0.02) differed between groups. Across all participants, the changes in resting MSNA and peak power output were correlated negatively (r = -0.51, P = 0.04). No between-group differences in resting heart rate or blood pressure were observed (all P > 0.05). Overload training increased MSNA and attenuated increases in cardiac BRS and heart rate variability observed with regular training. These results support neural adaptations after overload training and suggest that increased central sympathetic outflow may be linked with decreased exercise performance.

Cyclic aggradation and downcutting, fluvial response to volcanic activity, and calibration of soil-carbonate stages in the western Grand Canyon, Arizona

USGS Publications Warehouse

Lucchitta, Ivo; Curtis, Garniss H.; Davis, Marie E.; Davis, Sidney W.; Turrin, Brent

2000-01-01

In the western Grand Canyon, fluvial terraces and pediment surfaces, both associated with a Pleistocene basalt flow, document Quaternary aggradation and downcutting by the Colorado River, illuminate the river's response to overload and the end of overload, and allow calibration of soil-carbonate stages and determination of downcutting rates. Four downcutting-aggradation cycles are present. Each begins with erosion of older deposits to form a new river channel in which a characteristic suite of deposits is laid down. The current cycle (I) started ~700 yr B.P. The oldest (IV) includes the 603,000 ± 8000 to 524,000 ± 7000 yr Black Ledge basalt flow, emplaced when the river channel was ~30 m higher than it is now. The flow is overlain by basalt-cobble gravel and basalt sand. Soils reach the stage V level of carbonate development. Calibrated ages for soil stages are Stage V, ~525,000 yr; stage IV, <525,000 yr, ≥250,000 yr; stage III, <250,000 yr, ≥100,000 yr. The monolithologic basalt sand beds represent overloading by volcanic ash produced by an eruption 30-50 km upstream. The basalt-cobble beds signal breaching and rapid destruction of lava dams and erosion of flows. These deposits show that the Colorado River responds to overload by aggrading vigorously during the overload and then downcutting equally vigorously when the overload ends. The overall downcutting rate for the interval studied is 1.6 cm/1000 yr, much lower than rates upstream. The current downcutting rate, 11-14 m/1000 yr, likely is a response both to the end of late Pleistocene and early Holocene overload and to the reduction of sediment supply caused by Glen Canyon Dam.

Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus.

PubMed

Gonçalves, N; Gomes-Ferreira, C; Moura, C; Roncon-Albuquerque, R; Leite-Moreira, A F; Falcão-Pires, I

2016-08-15

Diabetic cardiomyopathy is characterized by cardiac structural and functional abnormalities. Additionally, chronic pressure overload conditions are highly prevalent amongst diabetic population and this association leads to a more severe myocardial impairment. The differences in myocardial pathophysiology between type 1 and type 2 diabetes mellitus (DM) still remain to be clarified. Thus, we aimed to investigate biventricular structural and functional changes promoted by the two types of DM and the impact of concomitant chronic pressure overload. Wistar rats were injected with streptozotocin (Type 1 DM, T1DM) or fed with a hypercaloric diet (Type 2 DM, T2DM). Pressure overload was imposed in DM animals by aortic constriction and after 5weeks of DM the cardiac function and structure were evaluated. Both types of DM promoted hypertrophy, increased fibrosis and advanced glycation end-products deposition, in the two ventricles. Interestingly, the induced myocardial alterations were distinct. While T1DM stimulated a pronounced hypertrophy and extracellular matrix remodeling, T2DM induced functional impairment. The negative impact of the association of DM with aortic constriction was more pronounced in T2DM, promoting impaired function and increased stiffness, particularly in the right ventricle. Our study demonstrated that the two types of diabetes induce distinct cardiac alterations per se or when combined with chronic pressure overload. T1DM promoted a more extensive remodeling in cardiac structure while T2DM significantly impaired ventricular function. The impact of pressure overload was more notorious in T2DM as observed by worse myocardial remodeling, suggesting a higher susceptibility to the deleterious effects of chronic pressure overload, namely hypertension, among this diabetic population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Volume overload and adverse outcomes in chronic kidney disease: clinical observational and animal studies.

PubMed

Hung, Szu-Chun; Lai, Yi-Shin; Kuo, Ko-Lin; Tarng, Der-Cherng

2015-05-05

Volume overload is frequently encountered and is associated with cardiovascular risk factors in patients with chronic kidney disease (CKD). However, the relationship between volume overload and adverse outcomes in CKD is not fully understood. A prospective cohort of 338 patients with stage 3 to 5 CKD was followed for a median of 2.1 years. The study participants were stratified by the presence or absence of volume overload, defined as an overhydration index assessed by bioimpedance spectroscopy exceeding 7%, the 90th percentile for the healthy population. The primary outcome was the composite of estimated glomerular filtration rate decline ≥50% or end-stage renal disease. The secondary outcome included a composite of morbidity and mortality from cardiovascular causes. Animal models were used to simulate fluid retention observed in human CKD. We found that patients with volume overload were at a higher risk of the primary and secondary end points in the adjusted Cox models. Furthermore, overhydration appears to be more important than hypertension in predicting an elevated risk. In rats subjected to unilateral nephrectomy and a high-salt diet, the extracellular water significantly increased. This fluid retention was associated with an increase in blood pressure, proteinuria, renal inflammation with macrophage infiltration and tumor necrosis factor-α overexpression, glomerular sclerosis, and cardiac fibrosis. Diuretic treatment with indapamide attenuated these changes, suggesting that fluid retention might play a role in the development of adverse outcomes. Volume overload contributes to CKD progression and cardiovascular diseases. Further research is warranted to clarify whether the correction of volume overload would improve outcomes for CKD patients. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

PubMed

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 reserved.

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

PubMed Central

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

Risk Factors and Outcomes in Transfusion-associated Circulatory Overload

PubMed Central

Murphy, Edward L.; Kwaan, Nicholas; Looney, Mark R.; Gajic, Ognjen; Hubmayr, Rolf D.; Gropper, Michael A.; Koenigsberg, Monique; Wilson, Greg; Matthay, Michael; Bacchetti, Peter; Toy, Pearl

2013-01-01

BACKGROUND Transfusion-associated circulatory overload is characterized by new respiratory distress and hydrostatic pulmonary edema within 6 hours after blood transfusion, but its risk factors and outcomes are poorly characterized. METHODS Using a case control design, we enrolled 83 patients with severe transfusion-associated circulatory overload identified by active surveillance for hypoxemia and 163 transfused controls at the University of California, San Francisco (UCSF) and Mayo Clinic (Rochester, Minn) hospitals. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression, and survival and length of stay were analyzed using proportional hazard models. RESULTS Transfusion-associated circulatory overload was associated with chronic renal failure (OR 27.0; 95% CI, 5.2–143), a past history of heart failure (OR 6.6; 95% CI, 2.1–21), hemorrhagic shock (OR 113; 95% CI, 14.1–903), number of blood products transfused (OR 1.11 per unit; 95% CI, 1.01–1.22), and fluid balance per hour (OR 9.4 per liter; 95% CI, 3.1–28). Patients with transfusion-associated circulatory overload had significantly increased in-hospital mortality (hazard ratio 3.20; 95% CI, 1.23–8.10) after controlling for Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score, and longer hospital and intensive care unit lengths of stay. CONCLUSIONS The risk of transfusion-associated circulatory overload increases with the number of blood products administered and a positive fluid balance, and in patients with pre-existing heart failure and chronic renal failure. These data, if replicated, could be used to construct predictive algorithms for transfusion-associated circulatory overload, and subsequent modifications of transfusion practice might prevent morbidity and mortality associated with this complication. PMID:23357450

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

PubMed Central

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

Change in job stress and job satisfaction over a two-year interval using the Brief Job Stress Questionnaire.

PubMed

Kawada, Tomoyuki; Otsuka, Toshiaki

2014-01-01

The relationship between job stress and job satisfaction by the follow-up study should be more evaluated for workers' health support. Job stress is strongly affected by the content of the job and the personality of a worker. This study was focused on determining the changes of the job stress and job satisfaction levels over a two-year interval, using the Brief Job Stress Questionnaire (BJSQ). This self-administered questionnaire was distributed to the same 310 employees of a Japanese industrial company in 2009 and 2011. Sixty-one employees were lost from 371 responders in 2009. Data of 16 items from 57 items graded on a four-point Likert-type scale to measure the job stressors, psycho-physical complaints and support for workers, job overload (six items), job control (three items), support (six items) and job satisfaction score (one item) were selected for the analysis. The age-adjusted partial correlation coefficients for job overload, job control and support were 0.684 (p< 0.001), 0.474 (p< 0.001) and 0.612 (p< 0.001), respectively. The concordance correlation coefficient (and 95% confidence interval indicated within parentheses) for job overload, job control and support were 0.681 (0.616-0.736), 0.473 (0.382-0.555), and 0.623 (0.549-0.687), respectively. There were no significant differences in the mean score for job overload, job control or support, although significant decline in the job satisfaction level was apparent at the end of the two-year period (p< 0.05). There was also a significant decline in the job satisfaction in 2009 and in 2011 for subjects with keeping low job strain. No significant changes in the scores on the three elements of job stress were observed over the two-year study period, and the job satisfaction level deteriorated significantly during this period. There was a decline in the job satisfaction in the two-year period, although subjects did not suffer from job stress at the same period.

New developments and controversies in iron metabolism and iron chelation therapy

PubMed Central

Kontoghiorghe, Christina N; Kontoghiorghes, George J

2016-01-01

Iron is essential for all organisms including microbial, cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients’ therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies. PMID:27019793

HFE gene mutations in patients with primary iron overload: is there a significant improvement in molecular diagnosis yield with HFE sequencing?

PubMed

Santos, Paulo C J L; Pereira, Alexandre C; Cançado, Rodolfo D; Schettert, Isolmar T; Sobreira, Tiago J P; Oliveira, Paulo S L; Hirata, Rosario D C; Hirata, Mario H; Figueiredo, Maria Stella; Chiattone, Carlos S; Krieger, Jose E; Guerra-Shinohara, Elvira M

2010-12-15

Rare HFE variants have been shown to be associated with hereditary hemochromatosis (HH), an iron overload disease. The low frequency of the HFE p.C282Y mutation in HH-affected Brazilian patients may suggest that other HFE-related mutations may also be implicated in the pathogenesis of HH in this population. The main aim was to screen for new HFE mutations in Brazilian individuals with primary iron overload and to investigate their relationship with HH. Fifty Brazilian patients with primary iron overload (transferrin saturation>50% in females and 60% in males) were selected. Subsequent bidirectional sequencing for each HFE exon was performed. The effect of HFE mutations on protein structure were analyzed by molecular dynamics simulation and free binding energy calculations. p.C282Y in homozygosis or in heterozygosis with p.H63D were the most frequent genotypic combinations associated with HH in our sample population (present in 17 individuals, 34%). Thirty-six (72.0%) out of the 50 individuals presented at least one HFE mutation. The most frequent genotype associated with HH was the homozygous p.C282Y mutation (n=11, 22.0%). One novel mutation (p.V256I) was indentified in heterozygosis with the p.H63D mutation. In silico modeling analysis of protein behavior indicated that the p.V256I mutation does not reduce the binding affinity between HFE and β2-microglobulin (β2M) in the same way the p.C282Y mutation does compared with the native HFE protein. In conclusion, screening of HFE through direct sequencing, as compared to p.C282Y/p.H63D genotyping, was not able to increase the molecular diagnosis yield of HH. The novel p.V256I mutation could not be implicated in the molecular basis of the HH phenotype, although its role cannot be completely excluded in HH-phenotype development. Our molecular modeling analysis can help in the analysis of novel, previously undescribed, HFE mutations. Copyright © 2010 Elsevier Inc. All rights reserved.

Hemochromatosis

MedlinePlus

... in the body. It is also called iron overload. Causes Hemochromatosis may be a genetic disorder passed ... blood transfusions over time may lead to iron overload. Long-term alcohol use and other health conditions. ...

30 CFR 250.281 - What must I do to conduct activities under the approved EP, DPP, or DOCD?

Code of Federal Regulations, 2010 CFR

2010-07-01

...: (1) All affected States with approved coastal zone management programs concur, or are conclusively presumed to concur, with the coastal zone consistency certification accompanying your EP under section 307... interest of national security; (3) If an affected State objects to the coastal zone consistency...

New targeted therapies and diagnostic methods for iron overload diseases.

PubMed

Kolnagou, Annita; Kontoghiorghe, Christina N; Kontoghiorghes, George John

2018-01-01

Millions of people worldwide suffer from iron overload toxicity diseases such as transfusional iron overload in thalassaemia and hereditary haemochromatosis. The accumulation and presence of toxic focal iron deposits causing tissue damage can also be identified in Friedreich's ataxia, Alzheimer's, Parkinson's, renal and other diseases. Different diagnostic criteria of toxicity and therapeutic interventions apply to each disease of excess or misplaced iron. Magnetic resonance imaging relaxation times T2 and T2* for monitoring iron deposits in organs and iron biomarkers such as serum ferritin and transferrin iron saturation have contributed in the elucidation of iron toxicity mechanisms and pathways, and also the evaluation of the efficacy and mode of action of chelating drugs in the treatment of diseases related to iron overload, toxicity and metabolism. Similarly, histopathological and electron microscopy diagnostic methods have revealed mechanisms of iron overload toxicity at cellular and sub-cellular levels. These new diagnostic criteria and chelator dose adjustments could apply in different or special patient categories e.g. thalassaemia patients with normal iron stores, where iron deficiency and over-chelation toxicity should be avoided.

The role of magnetic resonance imaging in the evaluation of transfusional iron overload in myelodysplastic syndromes

PubMed Central

Petrou, Emmanouil; Mavrogeni, Sophie; Karali, Vasiliki; Kolovou, Genovefa; Kyrtsonis, Marie-Christine; Sfikakis, Petros P.; Panayiotidis, Panayiotis

2015-01-01

Myelodysplastic syndromes represent a group of heterogeneous hematopoietic neoplasms derived from an abnormal multipotent progenitor cell, characterized by a hyperproliferative bone marrow, dysplasia of the cellular hemopoietic elements and ineffective erythropoiesis. Anemia is a common finding in myelodysplastic syndrome patients, and blood transfusions are the only therapeutic option in approximately 40% of cases. The most serious side effect of regular blood transfusion is iron overload. Currently, cardiovascular magnetic resonance using T2 is routinely used to identify patients with myocardial iron overload and to guide chelation therapy, tailored to prevent iron toxicity in the heart. This is a major validated non-invasive measure of myocardial iron overloading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. The indication for iron chelation therapy in myelodysplastic syndrome patients is currently controversial. However, cardiovascular magnetic resonance may offer an excellent non-invasive, diagnostic tool for iron overload assessment in myelodysplastic syndromes. Further studies are needed to establish the precise indications of chelation therapy and the clinical implications of this treatment on survival in myelodysplastic syndromes. PMID:26190429

Monocyte-derived extracellular Nampt-dependent biosynthesis of NAD+ protects the heart against pressure overload

PubMed Central

Yano, Masamichi; Akazawa, Hiroshi; Oka, Toru; Yabumoto, Chizuru; Kudo-Sakamoto, Yoko; Kamo, Takehiro; Shimizu, Yu; Yagi, Hiroki; Naito, Atsuhiko T.; Lee, Jong-Kook; Suzuki, Jun-ichi; Sakata, Yasushi; Komuro, Issei

2015-01-01

Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step in the salvage pathway for nicotinamide adenine dinucleotide (NAD+) biosynthesis, and thereby regulates the deacetylase activity of sirtuins. Here we show accommodative regulation of myocardial NAD+ by monocyte-derived extracellular Nampt (eNampt), which is essential for hemodynamic compensation to pressure overload. Although intracellular Nampt (iNampt) expression was decreased in pressure-overloaded hearts, myocardial NAD+ concentration and Sirt1 activity were preserved. In contrast, iNampt was up-regulated in spleen and monocytes, and circulating eNampt protein and nicotinamide mononucleotide (NMN), a key precursor of NAD+, were significantly increased. Pharmacological inhibition of Nampt by FK866 or depletion of monocytes/macrophages by clodronate liposomes disrupted the homeostatic mechanism of myocardial NAD+ levels and NAD+-dependent Sirt1 activity, leading to susceptibility to cardiomyocyte apoptosis and cardiac decompensation in pressure-overloaded mice. These biochemical and hemodynamic defects were prevented by systemic administration of NMN. Our studies uncover a crucial role of monocyte-derived eNampt in myocardial adaptation to pressure overload, and highlight a potential intervention controlling myocardial NAD+ against heart failure. PMID:26522369

Two novel mutations in the SLC40A1 and HFE genes implicated in iron overload in a Spanish man.

PubMed

Del-Castillo-Rueda, Alejandro; Moreno-Carralero, María-Isabel; Alvarez-Sala-Walther, Luis-Antonio; Cuadrado-Grande, Nuria; Enríquez-de-Salamanca, Rafael; Méndez, Manuel; Morán-Jiménez, María-Josefa

2011-03-01

The most common form of hemochromatosis is caused by mutations in the HFE gene. Rare forms of the disease are caused by mutations in other genes. We present a patient with hyperferritinemia and iron overload, and facial flushing. Magnetic resonance imaging was performed to measure hepatic iron overload, and a molecular study of the genes involved in iron metabolism was undertaken. The iron overload was similar to that observed in HFE hemochromatosis, and the patient was double heterozygous for two novel mutations, c.-20G>A and c.718A>G (p.K240E), in the HFE and ferroportin (FPN1 or SLC40A1) genes, respectively. Hyperferritinemia and facial flushing improved after phlebotomy. Two of the patient's children were also studied, and the daughter was heterozygous for the mutation in the SLC40A1 gene, although she did not have hyperferritinemia. The patient presented a mild iron overload phenotype probably because of the two novel mutations in the HFE and SLC40A1 genes. © 2011 John Wiley & Sons A/S.

An overload behavior detection system for engineering transport vehicles based on deep learning

NASA Astrophysics Data System (ADS)

Zhou, Libo; Wu, Gang

2018-04-01

This paper builds an overloaded truck detect system called ITMD to help traffic department automatically identify the engineering transport vehicles (commonly known as `dirt truck') in CCTV and determine whether the truck is overloaded or not. We build the ITMD system based on the Single Shot MultiBox Detector (SSD) model. By constructing the image dataset of the truck and adjusting hyper-parameters of the original SSD neural network, we successfully trained a basic network model which the ITMD system depends on. The basic ITMD system achieves 83.01% mAP on classifying overload/non-overload truck, which is a not bad result. Still, some shortcomings of basic ITMD system have been targeted to enhance: it is easy for the ITMD system to misclassify other similar vehicle as truck. In response to this problem, we optimized the basic ITMD system, which effectively reduced basic model's false recognition rate. The optimized ITMD system achieved 86.18% mAP on the test set, which is better than the 83.01% mAP of the basic ITMD system.

Myogenin, MyoD, and myosin expression after pharmacologically and surgically induced hypertrophy

NASA Technical Reports Server (NTRS)

Mozdziak, P. E.; Greaser, M. L.; Schultz, E.

1998-01-01

The relationship between myogenin or MyoD expression and hypertrophy of the rat soleus produced either by clenbuterol and 3,3', 5-triiodo-L-thyronine (CT) treatment or by surgical overload was examined. Mature female rats were subjected to surgical overload of the right soleus with the left soleus serving as a control. Another group received the same surgical treatment but were administered CT. Soleus muscles were harvested 4 wk after surgical overload and weighed. Myosin heavy chain isoforms were separated by using polyacrylamide gel electrophoresis while myogenin and MyoD expression were evaluated by Northern analysis. CT and functional overload increased soleus muscle weight. CT treatment induced the appearance of the fast type IIX myosin heavy chain isoform, depressed myogenin expression, and induced MyoD expression. However, functional overload did not alter myogenin or MyoD expression in CT-treated or non-CT-treated rats. Thus pharmacologically and surgically induced hypertrophy have differing effects on myogenin and MyoD expression, because their levels were associated with changes in myosin heavy chain composition (especially type IIX) rather than changes in muscle mass.

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

PubMed

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.

Work overload, burnout, and psychological ill-health symptoms: a three-wave mediation model of the employee health impairment process.

PubMed

de Beer, Leon T; Pienaar, Jaco; Rothmann, Sebastiaan

2016-07-01

The study reported here investigated the causal relationships in the health impairment process of employee well-being, and the mediating role of burnout in the relationship between work overload and psychological ill-health symptoms, over time. The research is deemed important due to the need for longitudinal evidence of the health impairment process of employee well-being over three waves of data. A quantitative survey design was followed. Participants constituted a longitudinal sample of 370 participants, at three time points, after attrition. Descriptive statistics and structural equation modeling methods were implemented. Work overload at time one predicted burnout at time two, and burnout at time two predicted psychological ill-health symptoms at time three. Indirect effects were found between work overload time one and psychological ill-health symptoms time three via burnout time two, and also between burnout time one and psychological ill-health symptoms time three, via burnout time two. The results provided supportive evidence for an "indirect-only" mediation effect, for burnout's causal mediation mechanism in the health impairment process between work overload and psychological ill-health symptoms.

Iron metabolism and the role of the iron-regulating hormone hepcidin in health and disease.

PubMed

Daher, Raed; Manceau, Hana; Karim, Zoubida

2017-12-01

Although iron is vital, its free form is likely to be involved in oxidation-reduction reactions, leading to the formation of free radicals and oxidative stress. Living organisms have developed protein systems to transport free iron through the cell membranes and biological fluids and store it in a non-toxic and readily mobilizable form to avoid iron toxicity. Hepcidin plays a crucial role in maintaining iron homeostasis. Hepcidin expression is directly regulated by variations in iron intake and its repression leads to an increase in bioavailable serum iron level. However, in pathological situations, prolonged repression often leads to pathological iron overload. In this review, we describe the different molecular mechanisms responsible for the maintenance of iron metabolism and the consequences of iron overload. Indeed, genetic hemochromatosis and post-transfusional siderosis are the two main conditions responsible for iron overload. Long-term iron overload is deleterious, and treatment relies on venesection therapy for genetic hemochromatosis and chelation therapy for iron overload resulting from multiple transfusions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Myocardial pressure overload induces systemic inflammation through endothelial cell IL-33

PubMed Central

Chen, Wei-Yu; Hong, Jaewoo; Gannon, Joseph; Kakkar, Rahul; Lee, Richard T.

2015-01-01

Hypertension increases the pressure load on the heart and is associated with a poorly understood chronic systemic inflammatory state. Interleukin 33 (IL-33) binds to membrane-bound ST2 (ST2L) and has antihypertrophic and antifibrotic effects in the myocardium. In contrast, soluble ST2 appears to act as a decoy receptor for IL-33, blocking myocardial and vascular benefits, and is a prognostic biomarker in patients with cardiovascular diseases. Here we report that a highly local intramyocardial IL-33/ST2 conversation regulates the heart’s response to pressure overload. Either endothelial-specific deletion of IL33 or cardiomyocyte-specific deletion of ST2 exacerbated cardiac hypertrophy with pressure overload. Furthermore, pressure overload induced systemic circulating IL-33 as well as systemic circulating IL-13 and TGF-beta1; this was abolished by endothelial-specific deletion of IL33 but not by cardiomyocyte-specific deletion of IL33. Our study reveals that endothelial cell secretion of IL-33 is crucial for translating myocardial pressure overload into a selective systemic inflammatory response. PMID:25941360

c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction

PubMed Central

Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.

2015-01-01

Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction (TAC; n = 7/group). Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group). 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, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes. PMID:26266538

Smartphone Cortex Controlled Real-Time Image Processing and Reprocessing for Concentration Independent LED Induced Fluorescence Detection in Capillary Electrophoresis.

PubMed

Szarka, Mate; Guttman, Andras

2017-10-17

We present the application of a smartphone anatomy based technology in the field of liquid phase bioseparations, particularly in capillary electrophoresis. A simple capillary electrophoresis system was built with LED induced fluorescence detection and a credit card sized minicomputer to prove the concept of real time fluorescent imaging (zone adjustable time-lapse fluorescence image processor) and separation controller. The system was evaluated by analyzing under- and overloaded aminopyrenetrisulfonate (APTS)-labeled oligosaccharide samples. The open source software based image processing tool allowed undistorted signal modulation (reprocessing) if the signal was inappropriate for the actual detection system settings (too low or too high). The novel smart detection tool for fluorescently labeled biomolecules greatly expands dynamic range and enables retrospective correction for injections with unsuitable signal levels without the necessity to repeat the analysis.

Iron metabolism and the polycystic ovary syndrome.

PubMed

Escobar-Morreale, Héctor F

2012-10-01

The polycystic ovary syndrome (PCOS) is associated with insulin resistance and abnormal glucose tolerance. Iron overload may lead also to insulin resistance and diabetes. Serum ferritin levels are increased in PCOS, especially when glucose tolerance is abnormal, suggesting mild iron overload. Factors contributing to potential iron overload in PCOS include the iron sparing effect of chronic menstrual dysfunction, insulin resistance, and a decrease in hepcidin leading to increased iron absorption. Enhancement of erythropoiesis by androgen excess is unlikely, because soluble transferrin receptor levels are not increased in PCOS. Future venues of research should address the long-term effects of PCOS treatment on iron overload and, conversely, the possible effects of iron lowering strategies on the glucose tolerance of patients with PCOS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Diagnosis and quantification of the iron overload through Magnetic resonance.

PubMed

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

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.

Hereditary Hemochromatosis (For Parents)

MedlinePlus

... buildup can be prevented. Doctors usually diagnose iron overload with these blood tests: serum ferritin : measures the ... has the disease. Treatment Doctors treat the iron overload from hereditary hemochromatosis by regularly drawing blood to ...

Mice lacking liver-specific β-catenin develop steatohepatitis and fibrosis after iron overload.

PubMed

Preziosi, Morgan E; Singh, Sucha; Valore, Erika V; Jung, Grace; Popovic, Branimir; Poddar, Minakshi; Nagarajan, Shanmugam; Ganz, Tomas; Monga, Satdarshan P

2017-08-01

Iron overload disorders such as hereditary hemochromatosis and iron loading anemias are a common cause of morbidity from liver diseases and increase risk of hepatic fibrosis and hepatocellular carcinoma (HCC). Treatment options for iron-induced damage are limited, partly because there is lack of animal models of human disease. Therefore, we investigated the effect of iron overload in liver-specific β-catenin knockout mice (KO), which are susceptible to injury, fibrosis and tumorigenesis following chemical carcinogen exposure. Iron overload diet was administered to KO and littermate control (CON) mice for various times. To ameliorate an oxidant-mediated component of tissue injury, N-Acetyl-L-(+)-cysteine (NAC) was added to drinking water of mice on iron overload diet. KO on iron diet (KO +Fe) exhibited remarkable inflammation, followed by steatosis, oxidative stress, fibrosis, regenerating nodules and occurrence of occasional HCC. Increased injury in KO +Fe was associated with activated protein kinase B (AKT), ERK, and NF-κB, along with reappearance of β-catenin and target gene Cyp2e1, which promoted lipid peroxidation and hepatic damage. Addition of NAC to drinking water protected KO +Fe from hepatic steatosis, injury and fibrosis, and prevented activation of AKT, ERK, NF-κB and reappearance of β-catenin. The absence of hepatic β-catenin predisposes mice to hepatic injury and fibrosis following iron overload, which was reminiscent of hemochromatosis and associated with enhanced steatohepatitis and fibrosis. Disease progression was notably alleviated by antioxidant therapy, which supports its chemopreventive role in the management of chronic iron overload disorders. Lack of animal models for iron overload disorders makes it hard to study the disease process for improving therapies. Feeding high iron diet to mice that lack the β-catenin gene in liver cells led to increased inflammation followed by fat accumulation, cell death and wound healing that mimicked human disease. Administration of an antioxidant prevented hepatic injury in this model. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Distinct right ventricle remodeling in response to pressure overload in the rat.

PubMed

Mendes-Ferreira, P; Santos-Ribeiro, D; Adão, R; Maia-Rocha, C; Mendes-Ferreira, M; Sousa-Mendes, C; Leite-Moreira, A F; Brás-Silva, C

2016-07-01

Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline- and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies. Copyright © 2016 the American Physiological Society.

Origins and consequences of congenital heart defects affecting the right ventricle.

PubMed

Woudstra, Odilia I; Ahuja, Suchit; Bokma, Jouke P; Bouma, Berto J; Mulder, Barbara J M; Christoffels, Vincent M

2017-10-01

Congenital heart disease is a major health issue, accounting for a third of all congenital defects. Improved early surgical management has led to a growing population of adults with congenital heart disease, including patients with defects affecting the right ventricle, which are often classified as severe. Defects affecting the right ventricle often cause right ventricular volume or pressure overload and affected patients are at high risk for complications such as heart failure and sudden death. Recent insights into the developmental mechanisms and distinct developmental origins of the left ventricle, right ventricle, and the outflow tract have shed light on the common features and distinct problems arising in specific defects. Here, we provide a comprehensive overview of the current knowledge on the development into the normal and congenitally malformed right heart and the clinical consequences of several congenital heart defects affecting the right ventricle. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Overload protection system

NASA Technical Reports Server (NTRS)

Nagano, S.

1979-01-01

Overload protection circuit utilizes one circuit for suspending inverter action when load abnormality is detected and second circuit to monitor clearance of abnormality. Device wastes no power during normal operating conditions and responds instantaneously when abnormality is cleared.

No effect of sex steroids on compensatory muscle hypertrophy

NASA Technical Reports Server (NTRS)

Max, S. R.; Rance, N. E.

1984-01-01

The effects of orchiectomy and/or subcutaneously implanted testosterone propionate (TP) on the hypertrophic response of rat plantaris muscles to functional overload (induced by bilateral removal of gastrocnemius and soleus muscles) are investigated experimentally. Muscle wet weight, metabolic substrate oxidation, and cytosolic androgen-receptor binding are measured, and the results are presented in tables. Eight weeks after surgery, the plantaris muscle weight as a percentage of body weight is found to be about twice that in rats without muscle overload, regardless of the sex-hormone status. Overloading causes decreased ability to oxidize glucose and pyruvate, decreased succinate dehydrogenase specific activity, and no change in the ability to oxidize beta-hydroxybutyrate or in androgen-receptor binding. The oxidative response is unaffected by orchiectomy or TP or both. It is argued that the actions of sex hormones and functional overload are not synergistic.

Bending and Torsion Load Alleviator With Automatic Reset

NASA Technical Reports Server (NTRS)

delaFuente, Horacio M. (Inventor); Eubanks, Michael C. (Inventor); Dao, Anthony X. (Inventor)

1996-01-01

A force transmitting load alleviator apparatus and method are provided for rotatably and pivotally driving a member to be protected against overload torsional and bending (moment) forces. The load alleviator includes at least one bias spring to resiliently bias cam followers and cam surfaces together and to maintain them in locked engagement unless a predetermined load is exceeded whereupon a center housing is pivotal or rotational with respect to a crown assembly. This pivotal and rotational movement results in frictional dissipation of the overload force by an energy dissipator. The energy dissipator can be provided to dissipate substantially more energy from the overload force than from the bias force that automatically resets the center housing and crown assembly to the normally fixed centered alignment. The torsional and bending (moment) overload levels can designed independently of each other.

Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

PubMed Central

Wang, Li-li; Miller, Dori; Wanders, Desiree; Nanayakkara, Gayani; Amin, Rajesh; Judd, Robert; Morrison, Edward E; Zhong, Ju-ming

2016-01-01

Aim: Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. Methods: Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- and 9-weeks following fistula. The protein expression of adiponectin, adiponectin receptors (AdipoR1/R2 and T-cadherin) and AMPK activity were measured using Western blot analyses. Isolated ventricular myocytes were prepared at 12 weeks post-fistula to examine the contractile performance of myocytes and intracellular Ca2+ transient. Results: A-V fistula resulted in significant reductions in serum and myocardial adiponectin levels, myocardial adiponectin receptor (AdipoR1/R2 and T-cadherin) levels, as well as myocardial AMPK activity. Consistent with these changes, the isolated myocytes exhibited significant depression in cell shortening and intracellular Ca2+ transient. Administration of adenoviral adiponectin significantly increased serum adiponectin levels and prevented myocyte contractile dysfunction in fistula rats. Furthermore, pretreatment of isolated myocytes with recombinant adiponectin (2.5 μg/mL) significantly improved their contractile performance in fistula rats, but had no effects in control or adenoviral adiponectin-administered rats. Conclusion: These results demonstrate a positive correlation between adiponectin downregulation and volume overload-induced ventricular remodeling. Adiponectin plays a protective role in volume overload-induced heart failure. PMID:26616727

Effect of hereditary haemochromatosis genotypes and iron overload on other trace elements.

PubMed

Beckett, Jeffrey M; Ball, Madeleine J

2013-02-01

Hereditary haemochromatosis is a common genetic disorder involving dysregulation of iron absorption. There is some evidence to suggest that abnormal iron absorption and metabolism may influence the status of other important trace elements. In this study, the effect of abnormal HFE genotypes and associated iron overload on the status of other trace elements was examined. Dietary data and blood samples were collected from 199 subjects (mean age = 55.4 years; range = 21-81 years). Dietary intakes, serum selenium, copper and zinc concentrations and related antioxidant enzymes (glutathione peroxidase and superoxide dismutase) in subjects with normal HFE genotype (n = 118) were compared to those with abnormal HFE genotype, with both normal iron status (n = 42) and iron overload (n = 39). For most dietary and biochemical variables measured, there were no significant differences between study groups. Red cell GPx was significantly higher in male subjects with normal genotypes and normal iron status compared to those with abnormal genotypes and normal iron status (P = 0.03) or iron overload (P = 0.001). Red cell GPx was also highest in normal women and significantly lower in the abnormal genotype and normal iron group (P = 0.016), but not in the iron overload group (P = 0.078). Although it may not be possible to exclude a small effect between the genotype groups on RBC GPx, overall, haemochromatosis genotypes or iron overload did not appear to have a significant effect on selenium, copper or zinc status.

Blunted angiogenesis and hypertrophy are associated with increased fatigue resistance and unchanged aerobic capacity in old overloaded mouse muscle.

PubMed

Ballak, Sam B; Busé-Pot, Tinelies; Harding, Peter J; Yap, Moi H; Deldicque, Louise; de Haan, Arnold; Jaspers, Richard T; Degens, Hans

2016-04-01

We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

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

PubMed

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.

Transient receptor potential vanilloid-3 (TRPV3) activation plays a central role in cardiac fibrosis induced by pressure overload in rats via TGF-β1 pathway.

PubMed

Liu, Yan; Qi, Hanping; E, Mingyao; Shi, Pilong; Zhang, Qianhui; Li, Shuzhi; Wang, Ye; Cao, Yonggang; Chen, Yunping; Ba, Lina; Gao, Jingquan; Huang, Wei; Sun, Hongli

2018-02-01

Cardiac fibrosis is a common pathologic change along with pressure overload. Recent studies indicated that transient receptor potential (TRP) channels played multiple roles in heart. However, the functional role of transient receptor potential vanilloid-3 (TRPV3) in cardiac fibrosis remained unclear. The present study was designed to investigate the relationship between TRPV3 activation and pressure overload-induced cardiac fibrosis. Pressure overload rats were successfully established by abdominal aortic constriction (AAC), and cardiac fibrosis was simulated by 100 nM angiotensin II (Ang II) in neonatal cardiac fibroblasts. Echocardiographic parameters, cardiac fibroblast proliferation, cell cycle, intracellular calcium concentration ([Ca 2+ ] i ), and the protein expressions of collagen I, collagen III, transforming growth factor beta 1 (TGF-β 1 ), cyclin E, and cyclin-dependent kinase 2 (CDK2) were measured. Echocardiographic and histological measurements suggested that the activation of TRPV3 exacerbated the cardiac dysfunction and increased interstitial fibrosis in pressure overload rats. Further results showed that TRPV3 activation upregulated the expressions of collagen I, collagen III, TGF-β 1 , cyclin E, and CDK2 in vivo and in vitro. At the same time, blocking TGF-β 1 pathway could partially reverse the effect of TRPV3 activation. These results suggested that TRPV3 activation exacerbated cardiac fibrosis by promoting cardiac fibroblast proliferation through TGF-β 1 /CDK2/cyclin E pathway in the pressure-overloaded rat hearts.

Iron overload down-regulates the expression of the HIV-1 Rev cofactor eIF5A in infected T lymphocytes.

PubMed

Mancone, Carmine; Grimaldi, Alessio; Refolo, Giulia; Abbate, Isabella; Rozera, Gabriella; Benelli, Dario; Fimia, Gian Maria; Barnaba, Vincenzo; Tripodi, Marco; Piacentini, Mauro; Ciccosanti, Fabiola

2017-01-01

Changes in iron metabolism frequently accompany HIV-1 infection. However, while many clinical and in vitro studies report iron overload exacerbates the development of infection, many others have found no correlation. Therefore, the multi-faceted role of iron in HIV-1 infection remains enigmatic. RT-qPCR targeting the LTR region, gag , Tat and Rev were performed to measure the levels of viral RNAs in response to iron overload. Spike-in SILAC proteomics comparing i) iron-treated, ii) HIV-1-infected and iii) HIV-1-infected/iron treated T lymphocytes was performed to define modifications in the host cell proteome. Data from quantitative proteomics were integrated with the HIV-1 Human Interaction Database for assessing any viral cofactors modulated by iron overload in infected T lymphocytes. Here, we demonstrate that the iron overload down-regulates HIV-1 gene expression by decreasing the levels of viral RNAs. In addition, we found that iron overload modulates the expression of many viral cofactors. Among them, the downregulation of the REV cofactor eIF5A may correlate with the iron-induced inhibition of HIV-1 gene expression. Therefore, we demonstrated that eiF5A downregulation by shRNA resulted in a significant decrease of Nef levels, thus hampering HIV-1 replication. Our study indicates that HIV-1 cofactors influenced by iron metabolism represent potential targets for antiretroviral therapy and suggests eIF5A as a selective target for drug development.

AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload

PubMed Central

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

2016-01-01

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-Prkag3225Q 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. PMID:26758685

Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis

PubMed Central

Chen, Jiao; Li, Xiaozhong; Bai, Zhenjiang; Fang, Fang; Hua, Jun; Li, Ying; Pan, Jian; Wang, Jian; Feng, Xing; Li, Yanhong

2016-01-01

Objective To evaluate whether early and acquired daily fluid overload (FO), as well as fluctuations in fluid accumulation, were associated with adverse outcomes in critically ill children with severe sepsis. Methods This study enrolled 202 children in a pediatric intensive care unit (PICU) with severe sepsis. Early fluid overload was defined as ≥5% fluid accumulation occurring in the first 24 hours of PICU admission. The maximum daily fluid accumulation ≥5% occurring during the next 6 days in patients with at least 48 hours of PICU stay was defined as PICU-acquired daily fluid overload. The fluctuation in fluid accumulation was calculated as the difference between the maximum and the minimum daily fluid accumulation obtained during the first 7 days after admission. Results Of the 202 patients, 61 (30.2%) died during PICU stay. Among all patients, 41 (20.3%) experienced early fluid overload, including 9 with a FO ≥10%. Among patients with at least 48 hours of PICU stay (n = 154), 36 (23.4%) developed PICU-acquired daily fluid overload, including 2 with a FO ≥10%. Both early fluid overload (AOR = 1.20; 95% CI 1.08–1.33; P = 0.001; n = 202) and PICU-acquired daily fluid overload (AOR = 5.47 per log increase; 95% CI 1.15–25.96; P = 0.032; n = 154) were independent risk factors associated with mortality after adjusting for age, illness severity, etc. However, fluctuations in fluid accumulation were not associated with mortality after adjustment. Length of PICU stay increased with greater fluctuations in fluid accumulation in all patients with at least 48 hours of PICU stay (FO <5%, 5%-10% vs. ≥10%: 4 [3–8], 7 [4–11] vs. 10 [6–16] days; P <0.001; n = 154) and in survivors (4 [3–8], 7 [5–11] vs. 10 [5–15] days; P <0.001; n = 121). Early fluid overload achieved an area under-the-receiver-operating-characteristic curve of 0.74 (95% CI 0.65–0.82; P <0.001; n = 202) for predicting mortality in patients with severe sepsis, with a sensitivity of 67.2% and a specificity of 80.1% at the optimal cut-off value of 2.65%. Conclusions Both early and acquired daily fluid overload were independently associated with PICU mortality in children with severe sepsis. PMID:27467522

Does Fat Suppression via Chemically Selective Saturation (CHESS) Affect R2*-MRI for Transfusional Iron Overload Assessment? A Clinical Evaluation at 1.5 and 3 Tesla

PubMed Central

Krafft, Axel J.; Loeffler, Ralf B.; Song, Ruitian; Bian, Xiao; McCarville, M. Beth; Hankins, Jane S.; Hillenbrand, Claudia M.

2015-01-01

Purpose Fat suppression (FS) via chemically selective saturation (CHESS) eliminates fat-water oscillations in multi-echo gradient echo (mGRE) R2*-MRI. However, for increasing R2* values as seen with increasing liver iron content (LIC), the water signal spectrally overlaps with the CHESS band, which may alter R2*. Here, we investigate the effect of CHESS on R2* and describe a heuristic correction for the observed CHESS-induced R2* changes. Methods Eighty patients (49/31 female/male, mean age: 18.3±11.7 years) with iron overload were scanned with a non-FS and a CHESS-FS mGRE sequence at 1.5T and 3T. Mean liver R2* values were evaluated using 3 published fitting approaches. Measured and model-corrected R2* values were compared and statistically analyzed. Results At 1.5T, CHESS led to a systematic R2* reduction (P<0.001 for all fitting algorithms) especially toward higher R2*. Our model described the observed changes well and reduced the CHESS-induced R2* bias after correction (linear regression slopes: 1.032/0.927/0.981). No CHESS-induced R2* reductions were found at 3T. Conclusion The CHESS-induced R2* bias at 1.5T needs to be considered when applying R2*-LIC biopsy calibrations for clinical LIC assessment which were established without FS at 1.5T. The proposed model corrects the R2* bias and could therefore improve clinical iron overload assessment based on linear R2*-LIC calibrations. PMID:26308155

MicroRNAs and liver cancer associated with iron overload: Therapeutic targets unravelled

PubMed Central

Greene, Catherine M; Varley, Robert B; Lawless, Matthew W

2013-01-01

Primary liver cancer is a global disease that is on the increase. Hepatocellular carcinoma (HCC) accounts for most primary liver cancers and has a notably low survival rate, largely attributable to late diagnosis, resistance to treatment, tumour recurrence and metastasis. MicroRNAs (miRNAs/miRs) are regulatory RNAs that modulate protein synthesis. miRNAs are involved in several biological and pathological processes including the development and progression of HCC. Given the poor outcomes with current HCC treatments, miRNAs represent an important new target for therapeutic intervention. Several studies have demonstrated their role in HCC development and progression. While many risk factors underlie the development of HCC, one process commonly altered is iron homeostasis. Iron overload occurs in several liver diseases associated with the development of HCC including Hepatitis C infection and the importance of miRNAs in iron homeostasis and hepatic iron overload is well characterised. Aberrant miRNA expression in hepatic fibrosis and injury response have been reported, as have dysregulated miRNA expression patterns affecting cell cycle progression, evasion of apoptosis, invasion and metastasis. In 2009, miR-26a delivery was shown to prevent HCC progression, highlighting its therapeutic potential. Several studies have since investigated the clinical potential of other miRNAs with one drug, Miravirsen, currently in phase II clinical trials. miRNAs also have potential as biomarkers for the diagnosis of HCC and to evaluate treatment efficacy. Ongoing studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have novel clinical applications for HCC in the coming years, yielding improved HCC survival rates and patient outcomes. PMID:23983424

Does fat suppression via chemically selective saturation affect R2*-MRI for transfusional iron overload assessment? A clinical evaluation at 1.5T and 3T.

PubMed

Krafft, Axel J; Loeffler, Ralf B; Song, Ruitian; Bian, Xiao; McCarville, M Beth; Hankins, Jane S; Hillenbrand, Claudia M

2016-08-01

Fat suppression (FS) via chemically selective saturation (CHESS) eliminates fat-water oscillations in multiecho gradient echo (mGRE) R2*-MRI. However, for increasing R2* values as seen with increasing liver iron content (LIC), the water signal spectrally overlaps with the CHESS band, which may alter R2*. We investigated the effect of CHESS on R2* and developed a heuristic correction for the observed CHESS-induced R2* changes. Eighty patients [female, n = 49; male, n = 31; mean age (± standard deviation), 18.3 ± 11.7 y] with iron overload were scanned with a non-FS and a CHESS-FS mGRE sequence at 1.5T and 3T. Mean liver R2* values were evaluated using three published fitting approaches. Measured and model-corrected R2* values were compared and statistically analyzed. At 1.5T, CHESS led to a systematic R2* reduction (P < 0.001 for all fitting algorithms) especially toward higher R2*. Our model described the observed changes well and reduced the CHESS-induced R2* bias after correction (linear regression slopes: 1.032/0.927/0.981). No CHESS-induced R2* reductions were found at 3T. The CHESS-induced R2* bias at 1.5T needs to be considered when applying R2*-LIC biopsy calibrations for clinical LIC assessment, which were established without FS at 1.5T. The proposed model corrects the R2* bias and could therefore improve clinical iron overload assessment based on linear R2*-LIC calibrations. Magn Reson Med 76:591-601, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Myosin light chain phosphorylation is critical for adaptation to cardiac stress.

PubMed

Warren, Sonisha A; Briggs, Laura E; Zeng, Huadong; Chuang, Joyce; Chang, Eileen I; Terada, Ryota; Li, Moyi; Swanson, Maurice S; Lecker, Stewart H; Willis, Monte S; Spinale, Francis G; Maupin-Furlowe, Julie; McMullen, Julie R; Moss, Richard L; Kasahara, Hideko

2012-11-27

Cardiac hypertrophy is a common response to circulatory or neurohumoral stressors as a mechanism to augment contractility. When the heart is under sustained stress, the hypertrophic response can evolve into decompensated heart failure, although the mechanism(s) underlying this transition remain largely unknown. Because phosphorylation of cardiac myosin light chain 2 (MLC2v), bound to myosin at the head-rod junction, facilitates actin-myosin interactions and enhances contractility, we hypothesized that phosphorylation of MLC2v plays a role in the adaptation of the heart to stress. We previously identified an enzyme that predominantly phosphorylates MLC2v in cardiomyocytes, cardiac myosin light-chain kinase (cMLCK), yet the role(s) played by cMLCK in regulating cardiac function in health and disease remain to be determined. We found that pressure overload induced by transaortic constriction in wild-type mice reduced phosphorylated MLC2v levels by ≈40% and cMLCK levels by ≈85%. To examine how a reduction in cMLCK and the corresponding reduction in phosphorylated MLC2v affect function, we generated Mylk3 gene-targeted mice and transgenic mice overexpressing cMLCK specifically in cardiomyocytes. Pressure overload led to severe heart failure in cMLCK knockout mice but not in mice with cMLCK overexpression in which cMLCK protein synthesis exceeded degradation. The reduction in cMLCK protein during pressure overload was attenuated by inhibition of ubiquitin-proteasome protein degradation systems. Our results suggest the novel idea that accelerated cMLCK protein turnover by the ubiquitin-proteasome system underlies the transition from compensated hypertrophy to decompensated heart failure as a result of reduced phosphorylation of MLC2v.

Diabetic db/db mice do not develop heart failure upon pressure overload: a longitudinal in vivo PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations.

PubMed

Abdurrachim, Desiree; Nabben, Miranda; Hoerr, Verena; Kuhlmann, Michael T; Bovenkamp, Philipp; Ciapaite, Jolita; Geraets, Ilvy M E; Coumans, Will; Luiken, Joost J F P; Glatz, Jan F C; Schäfers, Michael; Nicolay, Klaas; Faber, Cornelius; Hermann, Sven; Prompers, Jeanine J

2017-08-01

Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. Transverse aortic constriction (TAC) was performed in non-diabetic (db/+) and diabetic (db/db) mice to induce pressure overload. Magnetic resonance imaging, 31P magnetic resonance spectroscopy (MRS), 1H MRS, and 18F-fluorodeoxyglucose-positron emission tomography (PET) were applied to measure cardiac function, energy status, lipid content, and glucose uptake, respectively. In vivo measurements were complemented with ex vivo techniques of high-resolution respirometry, proteomics, and western blotting to elucidate the underlying molecular pathways. In non-diabetic mice, TAC induced progressive cardiac hypertrophy and dysfunction, which correlated with increased protein kinase D-1 (PKD1) phosphorylation and increased glucose uptake. These changes in glucose utilization preceded a reduction in cardiac energy status. At baseline, compared with non-diabetic mice, diabetic mice showed normal cardiac function, higher lipid content and mitochondrial capacity for fatty acid oxidation, and lower PKD1 phosphorylation, glucose uptake, and energetics. Interestingly, TAC affected cardiac function only mildly in diabetic mice, which was accompanied by normalization of phosphorylated PKD1, glucose uptake, and cardiac energy status. The cardiac metabolic adaptations in diabetic mice seem to prevent the heart from failing upon pressure overload, suggesting that restoring the balance between glucose and fatty acid utilization is beneficial for cardiac function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Altered expression of CD1d molecules and lipid accumulation in the human hepatoma cell line HepG2 after iron loading.

PubMed

Cabrita, Marisa; Pereira, Carlos F; Rodrigues, Pedro; Cardoso, Elsa M; Arosa, Fernando A

2005-01-01

Iron overload in the liver may occur in clinical conditions such as hemochromatosis and nonalcoholic steatohepatitis, and may lead to the deterioration of the normal liver architecture by mechanisms not well understood. Although a relationship between the expression of ICAM-1, and classical major histocompatibility complex (MHC) class I molecules, and iron overload has been reported, no relationship has been identified between iron overload and the expression of unconventional MHC class I molecules. Herein, we report that parameters of iron metabolism were regulated in a coordinated-fashion in a human hepatoma cell line (HepG2 cells) after iron loading, leading to increased cellular oxidative stress and growth retardation. Iron loading of HepG2 cells resulted in increased expression of Nor3.2-reactive CD1d molecules at the plasma membrane. Expression of classical MHC class I and II molecules, ICAM-1 and the epithelial CD8 ligand, gp180 was not significantly affected by iron. Considering that intracellular lipids regulate expression of CD1d at the cell surface, we examined parameters of lipid metabolism in iron-loaded HepG2 cells. Interestingly, increased expression of CD1d molecules by iron-loaded HepG2 cells was associated with increased phosphatidylserine expression in the outer leaflet of the plasma membrane and the presence of many intracellular lipid droplets. These data describe a new relationship between iron loading, lipid accumulation and altered expression of CD1d, an unconventional MHC class I molecule reported to monitor intracellular and plasma membrane lipid metabolism, in the human hepatoma cell line HepG2.

An Overwhelming Desire to Be Blind: Similarities and Differences between Body Integrity Identity Disorder and the Wish for Blindness.

PubMed

Gutschke, Katja; Stirn, Aglaja; Kasten, Erich

2017-01-01

The urge to be permanently blind is an extremely rare mental health disturbance. The underlying cause of this desire has not been determined yet, and it is uncertain whether the wish for blindness is a condition that can be included in the context of body integrity identity disorder, a condition where people feel an overwhelming need to be disabled, in many cases by amputation of a limb or through paralysis. The aim of this study is to test the hypothesis that people with a desire for blindness suffer from a greater degree of visual stress in daily activities than people in a healthy visual control group. We created a Likert scale questionnaire to measure visual stress, covering a wide range of everyday situations. The wish for blindness is extremely rare and worldwide only 5 people with an urge to be blind were found to participate in the study (4 female, 1 male). In addition, a control group of 35 (28 female, 7 male) visually healthy people was investigated. Questions addressing issues that may be experienced by participants with a desire to be blind were integrated into the questionnaire. The hypothesis that people with a desire for blindness suffer from a significantly higher visual overload in activities of daily living than visually healthy subjects was confirmed; the significance of visual stress between these groups was p < 0.01. In addition, an interview with the 5 affected participants supported the causal role of visual overload. The desire for blindness seems to originate from visual overload caused by either ophthalmologic or organic brain disturbances. In addition, psychological reasons such as certain personal character traits may play an active role in developing, maintaining, and reinforcing one's desire to be blind.

Albuminuria enhances NHE3 and NCC via stimulation of mitochondrial oxidative stress/angiotensin II axis.

PubMed

Jia, Zhanjun; Zhuang, Yibo; Hu, Caiyu; Zhang, Xintong; Ding, Guixia; Zhang, Yue; Rohatgi, Rajeev; Hua, Hu; Huang, Songming; He, John Ci-Jiang; Zhang, Aihua

2016-07-26

Imbalance of salt and water is a frequent and challenging complication of kidney disease, whose pathogenic mechanisms remain elusive. Employing an albumin overload mouse model, we discovered that albuminuria enhanced the expression of NHE3 and NCC but not other transporters in murine kidney in line with the stimulation of angiotensinogen (AGT)/angiotensin converting enzyme (ACE)/angiotensin (Ang) II cascade. In primary cultures of renal tubular cells, albumin directly stimulated AGT/ACE/Ang II and upregulated NHE3 and NCC expression. Blocking Ang II production with an ACE inhibitor normalized the upregulation of NHE3 and NCC in cells. Interestingly, albumin overload significantly reduced mitochondrial superoxide dismutase (SOD2), and administration of a SOD2 mimic (MnTBAP) normalized the expression of NHE3, NCC, and the components of AGT/ACE pathway affected by albuminuria, indicating a key role of mitochondria-derived oxidative stress in modulating renin-angiotensin system (RAS) and renal sodium transporters. In addition, the functional data showing the reduced urinary excretion of Na and Cl and enhanced response to specific NCC inhibitor further supported the regulatory results of sodium transporters following albumin overload. More importantly, the upregulation of NHE3 and NCC and activation of ACE/Ang II signaling pathway were also observed in albuminuric patient kidneys, suggesting that our animal model accurately replicates the human condition. Taken together, these novel findings demonstrated that albuminuria is of importance in resetting renal salt handling via mitochondrial oxidative stress-initiated stimulation of ACE/Ang II cascade. This may also offer novel, effective therapeutic targets for dealing with salt and water imbalance in proteinuric renal diseases.

Evaluation of hawthorn extract on immunomodulatory biomarkers in a pressure overload model of heart failure.

PubMed

Bleske, Barry E; Zineh, Issam; Hwang, Hyun Seok; Welder, Gregory J; Ghannam, Michael M J; Boluyt, Marvin O

2007-12-01

Hawthorn extract (Crataegeus sp.) a botanical complementary and alternative medicine is often used to treat heart failure. The mechanism(s) by which hawthorn extract may treat heart failure is unknown but may include, theoretically, immunological effects. Therefore, the purpose of this study is to determine the effect of hawthorn extract on the immunomodulatory response in a pressure overload model of heart failure. A total of 62 male Sprague-Dawley rats were randomized to either aortic constriction + vehicle (AC; n=15), aortic constriction + hawthorn 1.3 mg/kg (HL, n=17), aortic constriction + hawthorn 13 mg/kg (HM, n=15), or aortic constriction + hawthorn 130 mg/kg (HH, n=15). Six months after surgical procedure animals were sacrificed and plasma samples obtained for the measurement of the following immunomodulatory markers: interleukin (IL) IL-1ss, IL-2, IL-6, IL-10; and leptin. The mortality rate following 6 months of aortic constriction was 40% in the AC group compared to 41%, 60%, and 53% for the HL, HM, and HH groups respectively (P>0.05 compared to AC). Aortic constriction produced a similar increase in the left ventricle/body weight ratio for all groups. Hawthorn extract had no effect on the immunomodulatory markers measured in this study, although there appeared to be a trend suggesting suppression of IL-2 plasma concentrations. In this animal model of heart failure, hawthorn extract failed to significantly affect the immunomodulatory response characterized after 6 months of pressure overload at a time when approximately 50% mortality was exhibited. Mechanisms other than immunological may better define hawthorn's effect in treating heart failure.

Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload

PubMed Central

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 < 0.05) and reduced mean arterial pressure (106 ± 4 to 96 ± 4 mmHg, p < 0.05), but did not affect weight, plasma albumin concentration, haemoglobin levels or dialysate:plasma creatinine ratio. Diabetic patients (n = 12) also experienced improved glycaemic control (haemoglobin Alc decreased from 8.9 ± 0.7% to 7.9 ± 0.7%, p < 0.05). Overall PD technique survival was prolonged by a mean of 11.6 months (95% CI 6.0–17.3 months). On multivariate Cox proportional hazards analysis, extension of technique survival by icodextrin was only significantly predicted by baseline net daily peritoneal ultrafiltration (adjusted HR 2.52, 95% CI 1.13–5.62, p < 0.05). 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. PMID:11737871

Amiodarone inhibits sarcolemmal but not mitochondrial KATP channels in Guinea pig ventricular cells.

PubMed

Sato, Toshiaki; Takizawa, Taichi; Saito, Tomoaki; Kobayashi, Satoru; Hara, Yukio; Nakaya, Haruaki

2003-12-01

ATP-sensitive K(+) (KATP) channels are present on the sarcolemma (sarcKATP channels) and mitochondria (mitoKATP channels) of cardiac myocytes. Amiodarone, a class III antiarrhythmic drug, reduces sudden cardiac death in patients with organic heart disease. The objective of the present study was to investigate the effects of amiodarone on sarcKATP and mitoKATP channels. Single sarcKATP channel current and flavoprotein fluorescence were measured in guinea pig ventricular myocytes to assay sarcKATP and mitoKATP channel activity, respectively. Amiodarone inhibited the sarcKATP channel currents in a concentration-dependent manner without affecting its unitary amplitude. The IC50 values were 0.35 microM in the inside-out patch exposed to an ATP-free solution and 2.8 microM in the cell-attached patch under metabolic inhibition, respectively. Amiodarone (10 microM) alone did not oxidize the flavoprotein. In addition, the oxidative effect of the mitoKATP channel opener diazoxide (100 microM) was unaffected by amiodarone. Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca(2+) overload, and the intensity of rhod-2 fluorescence increased to 246 +/- 16% of baseline (n = 9). Amiodarone did not alter the ouabain-induced mitochondrial Ca(2+) overload (236 +/- 10% of baseline, n = 7). Treatment with diazoxide significantly reduced the ouabain-induced mitochondrial Ca(2+) overload (158 +/- 15% of baseline, n = 8, p < 0.05 versus ouabain); this effect was not abolished by amiodarone (154 +/- 10% of baseline, n = 8, p < 0.05 versus ouabain). These results suggest that amiodarone inhibits sarcKATP but not mitoKATP channels in cardiac myocytes. Such an action of amiodarone may effectively prevent ischemic arrhythmias without causing ischemic damage.

Glycolytic overload and the genesis of breast cancer.

PubMed

Robson, J R

1984-03-01

It is suggested that the development of breast cancer is due to overloading of the glycolytic pathways. An excess of substrates or an excessive delivery rate of substrates to the Krebs Cycle is believed to result in the formation of acetyl CoA. Feedback mechanisms controlling the conversion of acetyl CoA to cholesterol may be overcome; the resulting high concentration of cholesterol induces the formation of pregnenolone which may then be converted into androgens, estrogens and progesterone. These steroids are in addition to those produced by gonads and adrenal glands. Glycolytic overload is also associated with an increase in fat stores which have been shown to be the site of interconversion of sex hormones. Excess sex hormones or abnormal sex hormones are believed to be the cause of breast cancer. The hypothesis presented links glycolytic overload with clinical biochemical phenomena and explains some of the anomalies observed in breast cancer experience in different ethnic groups. Changes in dietary habits during the history of man resulting in " gorging " and the consumption of highly refined sugars are possible causes of glycolytic overload. So, also, is impaired thermogenesis due to Brown Fat deficits in certain ethnic groups.

Iron overload in myelodysplastic syndromes (MDS).

PubMed

Gattermann, Norbert

2018-01-01

Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

Hematopoietic recovery after administration of deferasirox for transfusional iron overload in a case of myelodysplastic syndrome.

PubMed

OKABE, Hiroshi; SUZUKI, Takahiro; OMORI, Tsukasa; MORI, Masaki; UEHARA, Eisuke; HATANO, Kaoru; UEDA, Masuzu; MATSUYAMA, Tomohiro; TOSHIMA, Masaki; QZAKI, Katsutoshi; NAGAI, Tadashi; MUROI, Kazuo; OZAWA, Keiya

2009-11-01

Deferasirox (DFX) is a newly developed oral iron chelator that enables effective chelation with once daily administration. We describe here a case of transfusional-iron overloaded patient who experienced hematopoietic recovery after DFX administration. A 75-year-old woman with iron overload, who had been diagnosed with MDS (RCMD) and had received a transfusion of red blood cells and platelets regularly for 3 years, enrolled in the phase I clinical trial of ICL670 (DFX) in Japan. DFX administration steadily decreased her serum ferritin levels and chelated overloaded iron effectively. Interestingly, a year after initiation of the trial, she needed fewer blood transfusions, and no more transfusions after the 17th month of the trial. Even after suspending transfusions, her hemoglobin level and platelet count increased continuously, and she now has stable disease without blood transfusions. She has not received any specific treatment for MDS during this period. Examination of the bone marrow aspirates in the 35th month revealed dysplastic cells, indicating no remarkable change in the state of MDS. This case suggests that excess iron hampers hematopoiesis and that adequate iron chelation may improve hematological data in some iron-overloaded patients.

A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload.

PubMed

Rienhoff, Hugh Young; Viprakasit, Vip; Tay, Lay; Harmatz, Paul; Vichinsky, Elliott; Chirnomas, Deborah; Kwiatkowski, Janet L; Tapper, Amy; Kramer, William; Porter, John B; Neufeld, Ellis J

2011-04-01

There is still a clinical need for a well-tolerated and safe iron chelator for the treatment of transfusional iron overload. We describe the pharmacokinetic properties and safety data after 7 days of dosing of FBS0701, a novel oral, once-daily iron chelator. This phase 1b dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload, was conducted in 16 adult patients with iron overloaded consequent to transfusions. FBS0701 was given daily for 7 days at doses up to 32 mg/kg and was well tolerated at all dose levels. Pharmacokinetics showed dose-proportionality. The maxium plasma concentration (C(max)) was reached within 60-90 minutes of dosing and the drug was rapidly distributed at the predicted therapeutic doses. The plasma elimination half-life (t(1/2)) was approximately 19 hours. There were no serious adverse events associated with the drug. Conclusions On the basis of these safety and pharmacokinetic data, FBS0701 warrants further clinical evaluation in patients with transfusional iron overload. (Clinicaltrials.gov identifier: NCT01186419).

Deferasirox: a review of its use for chronic iron overload in patients with non-transfusion-dependent thalassaemia.

PubMed

Shirley, Matt; Plosker, Greg L

2014-06-01

Deferasirox (Exjade(®)) is a once-daily orally administered iron chelator which has been approved for use in the treatment of transfusional-dependent chronic iron overload since 2005. Based primarily on the findings of the THALASSA (Assessment of Exjade(®) in Non-Transfusion-Dependent THALASSemiA) trial, the approval for deferasirox has recently been expanded to include the management of chronic iron overload in patients with non-transfusion-dependent thalassaemia (NTDT) syndromes. Despite the lack of regular blood transfusions, NTDT patients can still develop clinically relevant iron overload, primarily due to increased gastrointestinal absorption secondary to ineffective erythropoiesis, and may require chelation therapy. The THALASSA trial, the first placebo-controlled clinical trial of an iron chelator in NTDT patients, demonstrated that deferasirox was effective in reducing liver iron and serum ferritin levels in this population. Deferasirox has an acceptable tolerability profile, with the most common adverse events reported in the THALASSA trial being related to mild to moderate gastrointestinal disorders. Although further long-term studies will be required to clearly demonstrate the clinical benefit of chelation therapy in NTDT patients, deferasirox presents a useful tool in the management of iron overload in this population.

The Influence of Domestic Overload on the Association between Job Strain and Ambulatory Blood Pressure among Female Nursing Workers

PubMed Central

Portela, Luciana Fernandes; Rotenberg, Lucia; Almeida, Ana Luiza Pereira; Landsbergis, Paul; Griep, Rosane Harter

2013-01-01

Evidence suggests that the workplace plays an important etiologic role in blood pressure (BP) alterations. Associations in female samples are controversial, and the domestic environment is hypothesized to be an important factor in this relationship. This study assessed the association between job strain and BP within a sample of female nursing workers, considering the potential role of domestic overload. A cross-sectional study was conducted in a group of 175 daytime workers who wore an ambulatory BP monitor for 24 h during a working day. Mean systolic and diastolic BP were calculated. Job strain was evaluated using the Demand-Control Model. Domestic overload was based on the level of responsibility in relation to four household tasks and on the number of beneficiaries. After adjustments no significant association between high job strain and BP was detected. Stratified analyses revealed that women exposed to both domestic overload and high job strain had higher systolic BP at home. These results indicate a possible interaction between domestic overload and job strain on BP levels and revealed the importance of domestic work, which is rarely considered in studies of female workers. PMID:24287860

Stem cell therapy for the systemic right ventricle.

PubMed

Si, Ming-Sing; Ohye, Richard G

2017-11-01

In specific forms of congenital heart defects and pulmonary hypertension, the right ventricle (RV) is exposed to systemic levels of pressure overload. The RV is prone to failure in these patients because of its vulnerability to chronic pressure overload. As patients with a systemic RV reach adulthood, an emerging epidemic of RV failure has become evident. Medical therapies proven for LV failure are ineffective in treating RV failure. Areas covered: In this review, the pathophysiology of the failing RV under pressure overload is discussed, with specific emphasis on the pivotal roles of angiogenesis and oxidative stress. Studies investigating the ability of stem cell therapy to improve angiogenesis and mitigate oxidative stress in the setting of pressure overload are then reviewed. Finally, clinical trials utilizing stem cell therapy to prevent RV failure under pressure overload in congenital heart disease will be discussed. Expert commentary: Although considerable hurdles remain before their mainstream clinical implementation, stem cell therapy possesses revolutionary potential in the treatment of patients with failing systemic RVs who currently have very limited long-term treatment options. Rigorous clinical trials of stem cell therapy for RV failure that target well-defined mechanisms will ensure success adoption of this therapeutic strategy.

On the response of dynamic cracks to increasing overload

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gumbsch, P.

1996-12-01

One of the most interesting questions in the dynamics of brittle fracture is how a running brittle crack responds to an overload, i.e., to a mechanical energy release rate larger than that due to the increase in surface energy of the two cleavage surfaces. To address this question, dynamically running cracks in different crystal lattices are modelled atomistically under the condition of constant energy release rate. Stable crack propagation as well as the onset of crack tip instabilities are studied. It will be shown that small overloads lead to stable crack propagation with steady state velocities which quickly reach themore » terminal velocity of about 0.4 of the Rayleigh wave speed upon increasing the overload. Further increasing the overload does not change the steady state velocity but significantly changes the energy dissipation process towards shock wave emission at the breaking of every single atomic bond. Eventually the perfectly brittle crack becomes unstable, which then leads to dislocation generation and to the production of cleavage steps. The onset of the instability as well as the terminal velocity are related to the non-linearity of the interatomic interaction.« less

Estimation of liver T₂ in transfusion-related iron overload in patients with weighted least squares T₂ IDEAL.

PubMed

Vasanawala, Shreyas S; Yu, Huanzhou; Shimakawa, Ann; Jeng, Michael; Brittain, Jean H

2012-01-01

MRI imaging of hepatic iron overload can be achieved by estimating T(2) values using multiple-echo sequences. The purpose of this work is to develop and clinically evaluate a weighted least squares algorithm based on T(2) Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) technique for volumetric estimation of hepatic T(2) in the setting of iron overload. The weighted least squares T(2) IDEAL technique improves T(2) estimation by automatically decreasing the impact of later, noise-dominated echoes. The technique was evaluated in 37 patients with iron overload. Each patient underwent (i) a standard 2D multiple-echo gradient echo sequence for T(2) assessment with nonlinear exponential fitting, and (ii) a 3D T(2) IDEAL technique, with and without a weighted least squares fit. Regression and Bland-Altman analysis demonstrated strong correlation between conventional 2D and T(2) IDEAL estimation. In cases of severe iron overload, T(2) IDEAL without weighted least squares reconstruction resulted in a relative overestimation of T(2) compared with weighted least squares. Copyright © 2011 Wiley-Liss, Inc.

The influence of domestic overload on the association between job strain and ambulatory blood pressure among female nursing workers.

PubMed

Portela, Luciana Fernandes; Rotenberg, Lucia; Almeida, Ana Luiza Pereira; Landsbergis, Paul; Griep, Rosane Harter

2013-11-27

Evidence suggests that the workplace plays an important etiologic role in blood pressure (BP) alterations. Associations in female samples are controversial, and the domestic environment is hypothesized to be an important factor in this relationship. This study assessed the association between job strain and BP within a sample of female nursing workers, considering the potential role of domestic overload. A cross-sectional study was conducted in a group of 175 daytime workers who wore an ambulatory BP monitor for 24 h during a working day. Mean systolic and diastolic BP were calculated. Job strain was evaluated using the Demand-Control Model. Domestic overload was based on the level of responsibility in relation to four household tasks and on the number of beneficiaries. After adjustments no significant association between high job strain and BP was detected. Stratified analyses revealed that women exposed to both domestic overload and high job strain had higher systolic BP at home. These results indicate a possible interaction between domestic overload and job strain on BP levels and revealed the importance of domestic work, which is rarely considered in studies of female workers.

The occurrence of overload at work and musculoskeletal pain in young physiotherapists.

PubMed

Truszczyńska, Aleksandra; Scherer, Anna; Drzał-Grabiec, Justyna

2016-06-23

A job requiring stooping, lifting, carrying loads and multiple repetitions of the same movement patterns leads to overloading the musculoskeletal system. The aim of the study was to assess the work-related load experienced by physiotherapists and the occurrence of the musculoskeletal system overload. The study included 108 young physiotherapists, 69 women and 39 men, aged from 25 to 35 years (mean 27.12 ± 3.72 years). The study used an anonymous questionnaire and Quick Exposure Check. The most common musculoskeletal complaints were as follows: 70 physiotherapists (64.8%) reported low back pain, 60 (55.6%) cervical pain, and 34 (31.5%) pain in the wrists and fingers. Statistically significant positive correlations were revealed between the number of years worked in the profession and shoulder pain. The number of hours of work per week was positively correlated with the occurrence of pain in all analyzed body areas. Professional experience was negatively correlated with the level of stress felt. Physiotherapists dealing with manual therapy and exercise physiotherapy were particularly vulnerable to musculoskeletal overload. Popularization of knowledge regarding ergonomics among physiotherapists could reduce the occurrence of musculoskeletal overload.

Genetics Home Reference: African iron overload

MedlinePlus

... Hemochromatosis and Iron Overload Screening (HEIRS) Study. Blood Cells Mol Dis. 2007 May-Jun;38(3):247-52. Epub 2007 Feb 5. ... are genome editing and CRISPR-Cas9? What is precision medicine? What is newborn ...

Occlusal overload investigations by noninvasive technology: fluorescence microscopy and en-face optical coherence tomography

NASA Astrophysics Data System (ADS)

Marcauteanu, Corina; Negrutiu, Meda; Sinescu, Cosmin; Demjan, Enikö; Hughes, Michael; Bradu, Adrian; Dobre, George; Podoleanu, Adrian G.

2009-07-01

The aim of this study is the early detection and monitoring of occlusal overload in bruxing patients. En-Face Optical coherence tomography (eF-OCT) and fluorescence microscopy (FM) were used for the imaging of several anterior teeth extracted from patients with light active bruxism. We found a characteristic pattern of enamel cracks, that reached the tooth surface. We concluded that the combination of the en-Face OCT and FM is a promising non-invasive alternative technique for reliable monitoring of occlusal overload.

Correlation Between Intercritical Heat-Affected Zone and Type IV Creep Damage Zone in Grade 91 Steel

NASA Astrophysics Data System (ADS)

Wang, Yiyu; Kannan, Rangasayee; Li, Leijun

2018-04-01

A soft zone in Cr-Mo steel weldments has been reported to accompany the infamous Type IV cracking, the highly localized creep damage in the heat-affected zone of creep-resistant steels. However, the microstructural features and formation mechanism of this soft zone are not well understood. In this study, using microhardness profiling and microstructural verification, the initial soft zone in the as-welded condition was identified to be located in the intercritical heat-affected zone of P91 steel weldments. It has a mixed structure, consisting of Cr-rich re-austenitized prior austenite grains and fine Cr-depleted, tempered martensite grains retained from the base metal. The presence of these further-tempered retained grains, originating from the base metal, is directly responsible for the hardness reduction of the identified soft zone in the as-welded condition. The identified soft zone exhibits a high location consistency at three thermal stages. Local chemistry analysis and thermodynamic calculation show that the lower chromium concentrations inside these retained grains thermodynamically decrease their potentials for austenitic transformation during welding. Heterogeneous grain growth is observed in the soft zone during postweld heat treatment. The mismatch of strengths between the weak Cr-depleted grains and strong Cr-rich grains enhances the creep damage. Local deformation of the weaker Cr-depleted grains accelerates the formation of creep cavities.

Calcium channel blockers ameliorate iron overload-associated hepatic fibrosis by altering iron transport and stellate cell apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ying

Liver fibrosis is the principal cause of morbidity and mortality in patients with iron overload. Calcium channel blockers (CCBs) can antagonize divalent cation entry into renal and myocardial cells and inhibit fibrogenic gene expression. We investigated the potential of CCBs to resolve iron overload-associated hepatic fibrosis. Kunming mice were assigned to nine groups (n = 8 per group): control, iron overload, deferoxamine, high and low dose verapamil, high and low dose nimodipine, and high and low dose diltiazem. Iron deposition and hepatic fibrosis were measured in mouse livers. Expression levels of molecules associated with transmembrane iron transport were determined bymore » molecular biology approaches. In vitro HSC-T6 cells were randomized into nine groups (the same groups as the mice). Changes in proliferation, apoptosis, and metalloproteinase expression in cells were detected to assess the anti-fibrotic effects of CCBs during iron overload conditions. We found that CCBs reduced hepatic iron content, intracellular iron deposition, the number of hepatic fibrotic areas, collagen expression levels, and hydroxyproline content. CCBs rescued abnormal expression of α1C protein in L-type voltage-dependent calcium channel (LVDCC) and down-regulated divalent metal transporter-1 (DMT-1) expression in mouse livers. In iron-overloaded HSC-T6 cells, CCBs reduced iron deposition, inhibited proliferation, induced apoptosis, and elevated expression of matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1). CCBs are potential therapeutic agents that can be used to address hepatic fibrosis during iron overload. They resolve hepatic fibrosis probably correlated with regulating transmembrane iron transport and inhibiting HSC growth. - Highlights: • Calcium channel blockers (CCBs) reduced hepatic iron content. • CCBs decreased hepatic fibrotic areas and collagen expression levels. • CCBs resolve fibrosis by regulating iron transport and inhibiting HSC growth.« less

A single strain-based growth law predicts concentric and eccentric cardiac growth during pressure and volume overload

PubMed Central

Kerckhoffs, Roy C.P.; Omens, Jeffrey; McCulloch, Andrew D.

2011-01-01

Adult cardiac muscle adapts to mechanical changes in the environment by growth and remodeling (G&R) via a variety of mechanisms. Hypertrophy develops when the heart is subjected to chronic mechanical overload. In ventricular pressure overload (e.g. due to aortic stenosis) the heart typically reacts by concentric hypertrophic growth, characterized by wall thickening due to myocyte radial growth when sarcomeres are added in parallel. In ventricular volume overload, an increase in filling pressure (e.g. due to mitral regurgitation) leads to eccentric hypertrophy as myocytes grow axially by adding sarcomeres in series leading to ventricular cavity enlargement that is typically accompanied by some wall thickening. The specific biomechanical stimuli that stimulate different modes of ventricular hypertrophy are still poorly understood. In a recent study, based on in-vitro studies in micropatterned myocyte cell cultures subjected to stretch, we proposed that cardiac myocytes grow longer to maintain a preferred sarcomere length in response to increased fiber strain and grow thicker to maintain interfilament lattice spacing in response to increased cross-fiber strain. Here, we test whether this growth law is able to predict concentric and eccentric hypertrophy in response to aortic stenosis and mitral valve regurgitation, respectively, in a computational model of the adult canine heart coupled to a closed loop model of circulatory hemodynamics. A non-linear finite element model of the beating canine ventricles coupled to the circulation was used. After inducing valve alterations, the ventricles were allowed to adapt in shape in response to mechanical stimuli over time. The proposed growth law was able to reproduce major acute and chronic physiological responses (structural and functional) when integrated with comprehensive models of the pressure-overloaded and volume-overloaded canine heart, coupled to a closed-loop circulation. We conclude that strain-based biomechanical stimuli can drive cardiac growth, including wall thickening during pressure overload. PMID:22639476

Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle.

PubMed

Nakada, Satoshi; Ogasawara, Riki; Kawada, Shigeo; Maekawa, Takahiro; Ishii, Naokata

2016-01-01

External loads applied to skeletal muscle cause increases in the protein translation rate, which leads to muscle hypertrophy. Although some studies have demonstrated that increases in the capacity and efficiency of translation are involved in this process, it remains unclear how these two factors are related to the magnitude of muscle hypertrophy. The present study aimed to clarify the roles played by the capacity and efficiency of translation in muscle hypertrophy. We used an improved synergist ablation in which the magnitude of compensatory hypertrophy could be controlled by partial removal of synergist muscles. Male rats were assigned to four groups in which the plantaris muscle was unilaterally subjected to weak (WK), moderate (MO), middle (MI), and strong (ST) overloading by four types of synergist ablation. Fourteen days after surgery, the weight of the plantaris muscle per body weight increased by 8%, 22%, 32% and 45%, in the WK, MO, MI and ST groups, respectively. Five days after surgery, 18+28S rRNA content (an indicator of translational capacity) increased with increasing overload, with increases of 1.8-fold (MO), 2.2-fold (MI), and 2.5-fold (ST), respectively, relative to non-overloaded muscle (NL) in the WK group. rRNA content showed a strong correlation with relative muscle weight measured 14 days after surgery (r = 0.98). The phosphorylated form of p70S6K (a positive regulator of translational efficiency) showed a marked increase in the MO group, but no further increase was observed with further increase in overload (increases of 22.6-fold (MO), 17.4-fold (MI), and 18.2-fold (ST), respectively, relative to NL in the WK group). These results indicate that increases in ribosome biogenesis at the early phase of overloading are strongly dependent on the amount of overloading, and may play an important role in increasing the translational capacity for further gain of muscular size.

Site-specific Microtubule-associated Protein 4 Dephosphorylation Causes Microtubule Network Densification in Pressure Overload Cardiac Hypertrophy*

PubMed Central

Chinnakkannu, Panneerselvam; Samanna, Venkatesababa; Cheng, Guangmao; Ablonczy, Zsolt; Baicu, Catalin F.; Bethard, Jennifer R.; Menick, Donald R.; Kuppuswamy, Dhandapani; Cooper, George

2010-01-01

In severe pressure overload-induced cardiac hypertrophy, a dense, stabilized microtubule network forms that interferes with cardiocyte contraction and microtubule-based transport. This is associated with persistent transcriptional up-regulation of cardiac α- and β-tubulin and microtubule-stabilizing microtubule-associated protein 4 (MAP4). There is also extensive microtubule decoration by MAP4, suggesting greater MAP4 affinity for microtubules. Because the major determinant of this affinity is site-specific MAP4 dephosphorylation, we characterized this in hypertrophied myocardium and then assessed the functional significance of each dephosphorylation site found by mimicking it in normal cardiocytes. We first isolated MAP4 from normal and pressure overload-hypertrophied feline myocardium; volume-overloaded myocardium, which has an equal degree and duration of hypertrophy but normal functional and cytoskeletal properties, served as a control for any nonspecific growth-related effects. After cloning cDNA-encoding feline MAP4 and obtaining its deduced amino acid sequence, we characterized by mass spectrometry any site-specific MAP4 dephosphorylation. Solely in pressure overload-hypertrophied myocardium, we identified striking MAP4 dephosphorylation at Ser-472 in the MAP4 N-terminal projection domain and at Ser-924 and Ser-1056 in the assembly-promoting region of the C-terminal microtubule-binding domain. Site-directed mutagenesis of MAP4 cDNA was then used to switch each serine to non-phosphorylatable alanine. Wild-type and mutated cDNAs were used to construct adenoviruses; microtubule network density, stability, and MAP4 decoration were assessed in normal cardiocytes following an equivalent level of MAP4 expression. The Ser-924 → Ala MAP4 mutant produced a microtubule phenotype indistinguishable from that seen in pressure overload hypertrophy, such that Ser-924 MAP4 dephosphorylation during pressure overload hypertrophy may be central to this cytoskeletal abnormality. PMID:20436166

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice.

PubMed

Murach, Kevin A; White, Sarah H; Wen, Yuan; Ho, Angel; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

2017-07-10

Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. Pax7 CreER -R26R DTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6-9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers. Tamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p < 0.05). Satellite cells did not recover in SC- mice after overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p < 0.05), and mature SC- mice (p < 0.05). In contrast, muscle fiber hypertrophy was prevented in young SC- mice. Muscle fiber number increased only in mature mice after overload (p < 0.05), and eMyHC expression was variable, specifically in mature SC+ mice. Reliance on satellite cells for overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice.

Right ventricular speckle tracking assessment for differentiation of pressure- versus volume-overloaded right ventricle.

PubMed

Werther Evaldsson, Anna; Ingvarsson, Annika; Waktare, Johan; Smith, Gustav J; Thilén, Ulf; Stagmo, Martin; Roijer, Anders; Rådegran, Goran; Meurling, Carl

2017-10-26

Right ventricular (RV) dysfunction may be caused by either pressure or volume overload. RV function is conventionally assessed with echocardiography using tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), tricuspid lateral annular systolic velocity (S') and RV index of myocardial performance (RIMP). The purpose of this study was to evaluate whether RV global longitudinal strain (RVGLS) and RV-free wall strain (RV-free) could add additional information to differentiate these two causes of RV overload. The study enrolled 89 patients with an echocardiographic trans-tricuspid gradient >30 mmHg. Forty-five patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension (pressure overload) were compared with 44 patients with an atrial septum defect (volume overload). RV size was larger in the volume group (P<0·05). TAPSE and S' were lower in the pressure group (P<0·05, P<0·01). RVFAC was lower in the pressure group (P<0·001) as well as RVGLS (-12·1 ± 3·3% versus -20·2 ± 3·4%, P<0·001) and RV-free (-12·9 ± 3·3% versus -19·4 ± 3·4%, P<0·001). In this study, RVGLS and RV-free could more accurately discriminate RV pressure from volume overload than conventional measures. The reason could be that TAPSE and S' are unable to differentiate active deformation from passive entrainment caused by the left ventricle. The pressure group had evidence of marked RV hypertrophy despite standard functional parameters (TAPSE and S) within normal range. This would enhance the value of strain to more sensitively detect abnormal function. A cut-off value of below -16% for RVGLS and RV-free predicts RV pressure overload with high accuracy. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Overload-protector/fault-indicator circuit

NASA Technical Reports Server (NTRS)

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.

Analysis of permit vehicle loads in Wisconsin.

DOT National Transportation Integrated Search

2009-09-30

This study evaluated the impact of the 250-kip Wisconsin Standard Permit Vehicle against the overloaded vehicles operating on Wisconsin roads in recent years. The evaluation was conducted using three sets of data: 1) overloaded vehicle records within...

Overview of guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload.

PubMed

Gattermann, Norbert

2008-07-01

Between 2002 and 2008, a number of consensus statements and guidelines were developed by various groups around the world to educate healthcare professionals on the treatment of myelodysplastic syndromes (MDS), including the management of transfusional iron overload with iron chelation therapy. Guidelines have been developed by The Italian Society of Hematology, The UK MDS Guidelines Group, The Nagasaki Group, The National Comprehensive Cancer Network, and The MDS Foundation. These guidelines show that the approaches to managing iron overload in patients with MDS are region specific, differing in their recommendations for when iron chelation therapy should be initiated and strategies for the ongoing management of iron overload. The guidelines all agree that red blood cell transfusions are clinically beneficial to treat the symptomatic anemia in MDS, and that patients with low-risk MDS receiving transfusions are the most likely to benefit from iron chelation therapy.

Disorders associated with systemic or local iron overload: from pathophysiology to clinical practice.

PubMed

Sebastiani, Giada; Pantopoulos, Kostas

2011-10-01

In healthy subjects, the rate of dietary iron absorption, as well as the amount and distribution of body iron are tightly controlled by hepcidin, the iron regulatory hormone. Disruption of systemic iron homeostasis leads to pathological conditions, ranging from anemias caused by iron deficiency or defective iron traffic, to iron overload (hemochromatosis). Other iron-related disorders are caused by misregulation of cellular iron metabolism, which results in local accumulation of the metal in mitochondria. Brain iron overload is observed in neurodegenerative disorders. Secondary hemochromatosis develops as a complication of another disease. For example, repeated blood transfusions, a standard treatment of various anemias characterized by ineffective erythropoiesis, promote transfusional siderosis, while chronic liver diseases are often associated with mild to moderate secondary iron overload. In this critical review, we discuss pathophysiological and clinical aspects of all types of iron metabolism disorders (265 references). This journal is © The Royal Society of Chemistry 2011

Management of transfusional iron overload in Latin America: current outlook and expert panel recommendations.

PubMed

Araújo, Aderson; Drelichman, Guillermo; Cançado, Rodolfo D; Watman, Nora; Magalhães, Silvia M M; Duhalde, Mauricio; Marfil, Javier; Feliú, Aurora; Clementina, Landolfi; Linares Ballesteros, Adriana; Di Stefano, Marco

2009-02-01

The results of a meeting of physicians convening in Latin America to develop expert opinions on the diagnosis, monitoring and treatment of iron overload are as follows. An accurate diagnosis can be obtained by neonatal screening for haemoglobinopathies, especially sickle cell disease and the thalassaemias. Disease-specific registries are needed to demonstrate the extent of the problem to health authorities. Disparities in the quantity and quality of blood products must be addressed, and uniform transfusion guidelines are necessary. Serum ferritin level is a feasible marker for iron overload in the region, while magnetic resonance imaging assessment can improve the diagnosis and monitoring of cardiac and liver iron content. Medical specialists, including radiologists, pathologists and others, and health authorities, can help to implement these methods and provide adequate resources. The recently available oral deferasirox can be used to conveniently administer iron chelation to transfusional iron-overloaded patients.

HOW WE MANAGE IRON OVERLOAD IN SICKLE CELL PATIENTS

PubMed Central

Coates, Thomas D.; Wood, John C.

2017-01-01

Summary Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron-related complications that should be treated. The success of chelation therapy is dominated by patient adherence to prescribed treatment; thus, adjustment of drug regimens to increase adherence to treatment is critical. This review will discuss the current biology of iron homeostasis in patients with SCD and how this informs our clinical approach to treatment. We will present the clinical approach to treatment of iron overload at our centre using serial assessment of organ iron by magnetic resonance imaging. PMID:28295188

Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

PubMed Central

Miura, Yasuo; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Tsudo, Mitsuru

2010-01-01

Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level. PMID:20592762

The Application of Tensegrity Massage in a Professionally Active Musician - Case Report.

PubMed

Wilk, Iwona; Kurpas, Donata; Andrzejewski, Waldemar; Okręglicka-Forysiak, Ewa; Gworys, Bohdan; Kassolik, Krzysztof

2016-01-01

The purpose of our study was to present options for the application of tensegrity massage to manage pain caused by the overload of soft tissues in musicians. Tensegrity massage was applied to a 34-year-old male violinist. The methodology included a correct positioning and tensegrity massage with individually designed procedure. After therapy, the patient achieved complete pain relief, and relaxation of muscles in the shoulder girdle and free part of the upper arm. The analgesic effect lasted for 6 months after the end of therapy. Massage is an effective method in eliminating pain caused by the overload of soft tissues. If used regularly before physical effort, it can prevent muscle overload. The presented massage procedure is an effective therapy in pain caused by the overload of soft tissues in musicians and it can be one of the elements of complex physiotherapy in active musicians. © 2014 Association of Rehabilitation Nurses.

The personal costs of citizenship behavior: the relationship between individual initiative and role overload, job stress, and work-family conflict.

PubMed

Bolino, Mark C; Turnley, William H

2005-07-01

By and large, prior research has focused on the positive aspects of organizational citizenship behavior (OCB). D. W. Organ and K. Ryan (1995), though, suggest that individuals who engage in high levels of OCB may become overloaded. This research explores the relationship between a specific type of OCB--namely, individual initiative--and role overload, job stress, and work-family conflict. Results from a sample of 98 couples indicate that higher levels of individual initiative (as assessed by the spouse or significant other) are associated with higher levels of employee role overload, job stress, and work-family conflict. The findings also suggest that the relationship between individual initiative and work-family conflict is moderated by gender, such that the relationship is stronger among women than among men. Some implications of this work and directions for future research are discussed as well. Copyright 2005 APA, all rights reserved.

Information Diffusion in Facebook-Like Social Networks Under Information Overload

NASA Astrophysics Data System (ADS)

Li, Pei; Xing, Kai; Wang, Dapeng; Zhang, Xin; Wang, Hui

2013-07-01

Research on social networks has received remarkable attention, since many people use social networks to broadcast information and stay connected with their friends. However, due to the information overload in social networks, it becomes increasingly difficult for users to find useful information. This paper takes Facebook-like social networks into account, and models the process of information diffusion under information overload. The term view scope is introduced to model the user information-processing capability under information overload, and the average number of times a message appears in view scopes after it is generated is proposed to characterize the information diffusion efficiency. Through theoretical analysis, we find that factors such as network structure and view scope number have no impact on the information diffusion efficiency, which is a surprising result. To verify the results, we conduct simulations and provide the simulation results, which are consistent with the theoretical analysis results perfectly.

THE ACTION OF SOME PREPARATIONS FROM THE ARALIA FAMILY IN EXPERIMENTAL RADIATION SICKNESS (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brekhman, I.I.; Oskotskii, L.I.; Khakham, A.I.

1960-02-01

In ginseng therapy of irradiated mice (400 r), the survival was 2 1/2 times higher, and in eleutherococcus treatment the survival was almost 5 times higher as compared with the control group. In the combined action of x-ray irradiation and overloading (rotation of mice for 15 seconds in a centrifuge at 400 to 500 rounds per minute), the therapeutic effect of ginseng and eleutherococcus was more pronounced than in an isolated affection of experimental animals with x rays. (auth)

A new DOD and DOA estimation method for MIMO radar

NASA Astrophysics Data System (ADS)

Gong, Jian; Lou, Shuntian; Guo, Yiduo

2018-04-01

The battlefield electromagnetic environment is becoming more and more complex, and MIMO radar will inevitably be affected by coherent and non-stationary noise. To solve this problem, an angle estimation method based on oblique projection operator and Teoplitz matrix reconstruction is proposed. Through the reconstruction of Toeplitz, nonstationary noise is transformed into Gauss white noise, and then the oblique projection operator is used to separate independent and correlated sources. Finally, simulations are carried out to verify the performance of the proposed algorithm in terms of angle estimation performance and source overload.

Targeting focal adhesion kinase with small interfering RNA prevents and reverses load-induced cardiac hypertrophy in mice.

PubMed

Clemente, Carolina F M Z; Tornatore, Thais F; Theizen, Thais H; Deckmann, Ana C; Pereira, Tiago C; Lopes-Cendes, Iscia; Souza, José Roberto M; Franchini, Kleber G

2007-12-07

Hypertrophy is a critical event in the onset of failure in chronically overloaded hearts. Focal adhesion kinase (FAK) has attracted particular attention as a mediator of hypertrophy induced by increased load. Here, we demonstrate increased expression and phosphorylation of FAK in the hypertrophic left ventricles (LVs) of aortic-banded mice. We used an RNA interference strategy to examine whether FAK signaling plays a role in the pathophysiology of load-induced LV hypertrophy and failure. Intrajugular delivery of specific small interfering RNA induced prolonged FAK silencing ( approximately 70%) in both normal and hypertrophic LVs. Myocardial FAK silencing was accompanied by prevention, as well as reversal, of load-induced left ventricular hypertrophy. The function of LVs was preserved and the survival rate was higher in banded mice treated with small interfering RNA targeted to FAK, despite the persistent pressure overload. Studies in cardiac myocytes and fibroblasts harvested from LVs confirmed the ability of the systemically administered specific small interfering RNA to silence FAK in both cell types. Further analysis indicated attenuation of cardiac myocyte hypertrophic growth and of the rise in the expression of beta-myosin heavy chain in overloaded LVs. Moreover, FAK silencing was demonstrated to attenuate the rise in the fibrosis, collagen content, and activity of matrix metalloproteinase-2 in overloaded LVs, as well as the rise of matrix metalloproteinase-2 protein expression in fibroblasts harvested from overloaded LVs. This study provides novel evidence that FAK may be involved in multiple aspects of the pathophysiology of cardiac hypertrophy and failure induced by pressure overload.

Fluid accumulation during acute kidney injury in the intensive care unit.

PubMed

Berthelsen, R E; Perner, A; Jensen, A K; Jensen, J-U; Bestle, M H

2018-07-01

Fluid therapy is a ubiquitous intervention in patients admitted to the intensive care unit, but positive fluid balance may be associated with poor outcomes and particular in patients with acute kidney injury. Studies describing this have defined fluid overload either at specific time points or considered patients with a positive mean daily fluid balance as fluid overloaded. We wished to detail this further and performed joint model analyses of the association between daily fluid balance and outcome represented by mortality and renal recovery in patients admitted with acute kidney injury. We did a retrospective cohort study of patients admitted to the intensive care unit with acute kidney injury during a 2-year observation period. We used serum creatinine measurements to identify patients with acute kidney injury and collected sequential daily fluid balance during the first 5 days of admission to the intensive care unit. We used joint modelling techniques to correlate the development of fluid overload with survival and renal recovery adjusted for age, gender and disease severity. The cohort contained 863 patients with acute kidney injury of whom 460 (53%) and 254 (29%) developed 5% and 10% fluid overload, respectively. We found that both 5% and 10% fluid overload was correlated with reduced survival and renal recovery. Joint model analyses of fluid accumulation in patients admitted to the intensive care unit with acute kidney injury confirm that even a modest degree of fluid overload (5%) may be negatively associated with both survival and renal recovery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Pituitary iron and volume predict hypogonadism in transfusional iron overload.

PubMed

Noetzli, Leila J; Panigrahy, Ashok; Mittelman, Steven D; Hyderi, Aleya; Dongelyan, Ani; Coates, Thomas D; Wood, John C

2012-02-01

Hypogonadism is the most common morbidity in patients with transfusion-dependent anemias such as thalassemia major. We used magnetic resonance imaging (MRI) to measure pituitary R2 (iron) and volume to determine at what age these patients develop pituitary iron overload and volume loss. We recruited 56 patients (47 with thalassemia major, five with chronically transfused thalassemia intermedia and four with Blackfan-Diamond syndrome) to have pituitary MRIs to measure pituitary R2 and volume. Hypogonadism was defined clinically based on the timing of secondary sexual characteristics or the need for sex hormone replacement therapy. Patients with transfusional iron overload begin to develop pituitary iron overload in the first decade of life; however, clinically significant volume loss was not observed until the second decade of life. Severe pituitary iron deposition (Z > 5) and volume loss (Z < -2.5) were independently predictive of hypogonadism. Pituitary R2 correlated significantly with serum ferritin as well as liver, pancreatic, and cardiac iron deposition by MRI. Log pancreas R2* was the best single predictor for pituitary iron, with an area under the receiving operator characteristic curve of 0.88, but log cardiac R2* and ferritin were retained on multivariate regression with a combined r(2) of 0.71. Pituitary iron overload and volume loss were independently predictive of hypogonadism. Many patients with moderate-to-severe pituitary iron overload retained normal gland volume and function, representing a potential therapeutic window. The subset of hypogonadal patients having preserved gland volumes may also explain improvements in pituitary function observed following intensive chelation therapy. Copyright © 2011 Wiley Periodicals, Inc.

Mitochondrial division/mitophagy inhibitor (Mdivi) Ameliorates Pressure Overload Induced Heart Failure

PubMed Central

Givvimani, Srikanth; Munjal, Charu; Tyagi, Neetu; Sen, Utpal; Metreveli, Naira; Tyagi, Suresh C.

2012-01-01

Background We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during pressure overload hemodynamic stress. Several studies reported the evidence of cardiac autophagy, involving removal of cellular organelles like mitochondria (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However, little is known regarding the therapeutic role of mitochondrial division inhibitor (Mdivi) in the pressure overload induced heart failure. We hypothesize that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal mitophagy in a pressure overload heart and thus ameliorates heart failure condition. Materials and Methods To verify this, ascending aortic banding was done in wild type mice to create pressure overload induced heart failure and then treated with Mdivi and compared with vehicle treated controls. Results Expression of MMP-2, vascular endothelial growth factor, CD31, was increased, while expression of anti angiogenic factors like endostatin and angiostatin along with MMP-9, TIMP-3 was reduced in Mdivi treated AB 8 weeks mice compared to vehicle treated controls. Expression of mitophagy markers like LC3 and p62 was decreased in Mdivi treated mice compared to controls. Cardiac functional status assessed by echocardiography showed improvement and there is also a decrease in the deposition of fibrosis in Mdivi treated mice compared to controls. Conclusion Above results suggest that Mdivi inhibits the abnormal cardiac mitophagy response during sustained pressure overload stress and propose the novel therapeutic role of Mdivi in ameliorating heart failure. PMID:22479323

Iron Overload and Heart Fibrosis in Mice Deficient for Both β2-Microglobulin and Rag1

PubMed Central

Santos, Manuela M.; de Sousa, Maria; Rademakers, Luke H. P. M.; Clevers, Hans; Marx, J. J. M.; Schilham, Marco W.

2000-01-01

Genetic causes of hereditary hemochromatosis (HH) include mutations in the HFE gene, a β2-microglobulin (β2m)-associated major histocompatibility complex class I-like protein. Accordingly, mutant β2m−/− mice have increased intestinal iron absorption and develop parenchymal iron overload in the liver. In humans, other genetic and environmental factors have been suggested to influence the pathology and severity of HH. Previously, an association has been reported between low numbers of lymphocytes and the severity of clinical expression of the iron overload in HH. In the present study, the effect of a total absence of lymphocytes on iron overload was investigated by crossing β2m−/− mice (which develop iron overload resembling human disease) with mice deficient in recombinase activator gene 1 (Rag1), which is required for normal B and T lymphocyte development. Iron overload was more severe in β2mRag1 double-deficient mice than in each of the single deficient mice, with iron accumulation in parenchymal cells of the liver, in acinar cells of the pancreas, and in heart myocytes. With increasing age β2mRag1−/− mice develop extensive heart fibrosis, which could be prevented by reconstitution with normal hematopoietic cells. Thus, the development of iron-mediated cellular damage is substantially enhanced when a Rag1 mutation, which causes a lack of mature lymphocytes, is introduced into β2m−/− mice. Mice deficient in β2m and Rag1 thus offer a new experimental model of iron-related cardiomyopathy. PMID:11106561

A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity in Swiss albino mice through ROS regulation.

PubMed

Basu, Tapasree; Panja, Sourav; Shendge, Anil Khushalrao; Das, Abhishek; Mandal, Nripendranath

2018-05-01

Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron-overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron-overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron-overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl-2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron-overload induced hepatotoxicity through ROS regulation. © 2018 Wiley Periodicals, Inc.

LRRC10 is required to maintain cardiac function in response to pressure overload.

PubMed

Brody, Matthew J; Feng, Li; Grimes, Adrian C; Hacker, Timothy A; Olson, Timothy M; Kamp, Timothy J; Balijepalli, Ravi C; Lee, Youngsook

2016-01-15

We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10(-/-)) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10(-/-) mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10(-/-) mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10(-/-) cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His(150) of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis. Copyright © 2016 the American Physiological Society.

Theoretical model of impact damage in structural ceramics

NASA Technical Reports Server (NTRS)

Liaw, B. M.; Kobayashi, A. S.; Emery, A. G.

1984-01-01

This paper presents a mechanistically consistent model of impact damage based on elastic failures due to tensile and shear overloading. An elastic axisymmetric finite element model is used to determine the dynamic stresses generated by a single particle impact. Local failures in a finite element are assumed to occur when the primary/secondary principal stresses or the maximum shear stress reach critical tensile or shear stresses, respectively. The succession of failed elements thus models macrocrack growth. Sliding motions of cracks, which closed during unloading, are resisted by friction and the unrecovered deformation represents the 'plastic deformation' reported in the literature. The predicted ring cracks on the contact surface, as well as the cone cracks, median cracks, radial cracks, lateral cracks, and damage-induced porous zones in the interior of hot-pressed silicon nitride plates, matched those observed experimentally. The finite element model also predicted the uplifting of the free surface surrounding the impact site.

End Direction Overload: Foster Self-Reliant Teachers

ERIC Educational Resources Information Center

Bunting, Carolyn

2007-01-01

Teachers receive direction from national commissions, researchers, staff developers, state education personnel, superintendents, parents, private pressure groups, the courts, commercial vendors, federal regulators, and politicians. This direction overload depletes energy, blurs individuality, and erodes confidence, causing many educators to either…

Electrometer Amplifier With Overload Protection

NASA Technical Reports Server (NTRS)

Woeller, F. H.; Alexander, R.

1986-01-01

Circuit features low noise, input offset, and high linearity. Input preamplifier includes input-overload protection and nulling circuit to subtract dc offset from output. Prototype dc amplifier designed for use with ion detector has features desirable in general laboratory and field instrumentation.

Overload truck wheel load distribution on bridge decks.

DOT National Transportation Integrated Search

2009-04-01

There is a need to accurately analyze the load effects on bridge decks from permitted overload trucks on : Michigans roads. The AASHTO Standard Specifications for Highway Bridges, 17th edition, provides a : distribution width of live loads when re...

Pilot study assessing differentiation of steatosis hepatis, hepatic iron overload, and combined disease using two-point dixon MRI at 3 T: in vitro and in vivo results of a 2D decomposition technique.

PubMed

Boll, Daniel T; Marin, Daniele; Redmon, Grace M; Zink, Stephen I; Merkle, Elmar M

2010-04-01

The purpose of our study was to evaluate whether two-point Dixon MRI using a 2D decomposition technique facilitates metabolite differentiation between lipids and iron in standardized in vitro liver phantoms with in vivo patient validation and allows semiquantitative in vitro assessment of metabolites associated with steatosis, iron overload, and combined disease. The acrylamide-based phantoms were made to reproduce the T1- and T2-weighted MRI appearances of physiologic hepatic parenchyma and hepatic steatosis-iron overload by the admixture of triglycerides and ferumoxides. Combined disease was simulated using joint admixtures of triglycerides and ferumoxides at various concentrations. For phantom validation, 30 patients were included, of whom 10 had steatosis, 10 had iron overload, and 10 had no liver disease. For MRI an in-phase/opposed-phase T1-weighted sequence with TR/TE(opposed-phase)/TE(in-phase) of 4.19/1.25/2.46 was used. Fat/water series were obtained by Dixon-based algorithms. In-phase and opposed-phase and fat/water ratios were calculated. Statistical cluster analysis assessed ratio pairs of physiologic liver, steatosis, iron overload, and combined disease in 2D metabolite discrimination plots. Statistical assessment proved that metabolite decomposition in phantoms simulating steatosis (1.77|0.22; in-phase/opposed-phase|fat/water ratios), iron overload (0.75|0.21), and healthy control subjects (1.09|0.05) formed three clusters with distinct ratio pairs. Patient validation for hepatic steatosis (3.29|0.51), iron overload (0.56|0.41), and normal control subjects (0.99|0.05) confirmed this clustering (p < 0.001). One-dimensional analysis assessing in vitro combined disease only with in-phase/opposed-phase ratios would have failed to characterize metabolites. The 2D analysis plotting in-phase/opposed-phase and fat/water ratios (2.16|0.59) provided accurate semiquantitative metabolite decomposition (p < 0.001). MR Dixon imaging facilitates metabolite decomposition of intrahepatic lipids and iron using in vitro phantoms with in vivo patient validation. The proposed decomposition technique identified distinct in-phase/opposed-phase and fat/water ratios for in vitro steatosis, iron overload, and combined disease.

Future affective technology for autism and emotion communication

PubMed Central

Picard, Rosalind W.

2009-01-01

People on the autism spectrum often experience states of emotional or cognitive overload that pose challenges to their interests in learning and communicating. Measurements taken from home and school environments show that extreme overload experienced internally, measured as autonomic nervous system (ANS) activation, may not be visible externally: a person can have a resting heart rate twice the level of non-autistic peers, while outwardly appearing calm and relaxed. The chasm between what is happening on the inside and what is seen on the outside, coupled with challenges in speaking and being pushed to perform, is a recipe for a meltdown that may seem to come ‘out of the blue’, but in fact may have been steadily building. Because ANS activation both influences and is influenced by efforts to process sensory information, interact socially, initiate motor activity, produce meaningful speech and more, deciphering the dynamics of ANS states is important for understanding and helping people on the autism spectrum. This paper highlights advances in technology that can comfortably sense and communicate ANS arousal in daily life, allowing new kinds of investigations to inform the science of autism while also providing personalized feedback to help individuals who participate in the research. PMID:19884152

[Perioperative fluid therapy for surgical patients with chronic kidney disease].

PubMed

Iijima, Takehiko

2013-11-01

Chronic kidney disease (CKD) often accompanies cardiovascular complications, causing postoperative morbidity and even mortality. Since fluid and electrolyte homeostasis is deregulated in CKD patients, fluid therapy itself may cause postoperative morbidity. Recent studies have shown that forced diuresis through fluid overload offers no renoprotective effect and instead has harmful consequences. Fluid overload should be avoided, and the volume load should be used as the rationale for controlling hemodynamics. The emerging concept of a "zero-fluid balance policy" may be beneficial even for CKD patients. Hydroxyethylstarch might not be preferentially used for CKD patients. Hydroxyethylstarch is not contraindicated for CKD patients except in cases with long-term accumulation caused by increased vascular permeability, such as cases with sepsis, as long as an efficient volume expansion is beneficial to the patient. The regulation of renal function through the endocrine system (i.e., renin-angiotensin-aldosterone and vasopressin) is a key target for protecting the kidney in CKD. The recent development of a receptor blocker targeting these endocrine systems may be beneficial for correcting the fluid balance caused by excess intraoperative fluid therapy. The main issue for fluid therapy in surgical CKD patients may not be the quantity of fluid, but rational intervention affecting the endocrine system.

Influence of different propellant systems on ablation of EPDM insulators in overload state

NASA Astrophysics Data System (ADS)

Guan, Yiwen; Li, Jiang; Liu, Yang; Xu, Tuanwei

2018-04-01

This study examines the propellants used in full-scale solid rocket motors (SRM) and investigates how insulator ablation is affected by two propellant formulations (A and B) during flight overload conditions. An experimental study, theoretical analysis, and numerical simulations were performed to discover the intrinsic causes of insulator ablation rates from the perspective of lab-scaled ground-firing tests, the decoupling of thermochemical ablation, and particle erosion. In addition, the difference in propellant composition, and the insulator charring layer microstructure were analyzed. Results reveal that the degree of insulator ablation is positively correlated with the propellant burn rate, particle velocity, and aggregate concentrations during the condensed phase. A lower ratio of energetic additive material in the AP oxidizer of the propellant is promising for the reduction in particle size and increase in the burn rate and pressure index. However, the overall higher velocity of a two-phase flow causes severe erosion of the insulation material. While the higher ratio of energetic additive to the AP oxidizer imparts a smaller ablation rate to the insulator (under lab-scale test conditions), the slag deposition problem in the combustion chamber may cause catastrophic consequences for future large full-scale SRM flight experiments.

Iron Overload Is Associated With Oxidative Stress and Nutritional Immunity During Viral Infection in Fish.

PubMed

Tarifeño-Saldivia, Estefanía; Aguilar, Andrea; Contreras, David; Mercado, Luis; Morales-Lange, Byron; Márquez, Katherine; Henríquez, Adolfo; Riquelme-Vidal, Camila; Boltana, Sebastian

2018-01-01

Iron is a trace element, essential to support life due to its inherent ability to exchange electrons with a variety of molecules. The use of iron as a cofactor in basic metabolic pathways is essential to both pathogenic microorganisms and their hosts. During evolution, the shared requirement of micro- and macro-organisms for this important nutrient has shaped the pathogen-host relationship. Infectious pancreatic necrosis virus (IPNv) affects salmonids constituting a sanitary problem for this industry as it has an important impact on post-smolt survival. While immune modulation induced by IPNv infection has been widely characterized on Salmo salar , viral impact on iron host metabolism has not yet been elucidated. In the present work, we evaluate short-term effect of IPNv on several infected tissues from Salmo salar . We observed that IPNv displayed high tropism to headkidney, which directly correlates with a rise in oxidative stress and antiviral responses. Transcriptional profiling on headkidney showed a massive modulation of gene expression, from which biological pathways involved with iron metabolism were remarkable. Our findings suggest that IPNv infection increase oxidative stress on headkidney as a consequence of iron overload induced by a massive upregulation of genes involved in iron metabolism.

Monitoring of the Bonnet Carre Spillway Bridge during extreme overload.

DOT National Transportation Integrated Search

2003-10-01

This report concerns the monitoring of a portion of the Bonnet Carr Spillway Bridge during an extreme overload. On Tuesday, November 5, 2002, Tulane University was requested to monitor strain at the bottom flange of two adjacent prestressed girders...

Transitioning Patients With Iron Overload From Exjade to Jadenu.

PubMed

Tinsley, Sara M; Hoehner-Cooper, Christine M

Iron overload is a concern for patients who require chronic transfusions as a result of inherited or acquired anemias, including sickle cell disease, thalassemia, and myelodysplastic syndromes. Iron chelation therapy (ICT) is the primary treatment for iron overload in these patients. The ICT deferasirox, which has been available as an oral dispersible tablet for liquid suspension, is now also available as a once-daily, film-coated tablet (FCT). Deferasirox FCT allows greater convenience and may be associated with fewer gastrointestinal side effects versus the original formulation. Dose adjustment increments, determined by titration monitoring, are lower for the FCT because of greater bioavailability.

The associations of supervisor support and work overload with burnout and depression: a cross-sectional study in two nursing settings.

PubMed

Weigl, Matthias; Stab, Nicole; Herms, Isabel; Angerer, Peter; Hacker, Winfried; Glaser, Jürgen

2016-08-01

To investigate the moderating effects of work overload and supervisor support on the emotional exhaustion-depressive state relationship. Burnout and depression are prevalent in human service professionals and have a detrimental impact on clients. Work overload and supervisor support are two key job demands and job resources, whose role and interplay for the development and maintenance of burnout and depression are not fully understood yet. Two consecutive cross-sectional surveys: survey 1 investigated 111 hospital nursing professionals and survey 2 examined 202 day care professionals. Data collection was completed in 2010. After controlling for general well-being and sociodemographic characteristics, nurses' emotional exhaustion was associated with increased depressive state in both samples. We found a meaningful three-way interaction: our results show consistently that the relationship between emotional exhaustion and depressive state was strongest for nurses with high work overload and low supervisor support. Additionally, nurses with low work overload and low supervisor support were also found to have stronger associations between emotional exhaustion and depressive state. The findings indicate that nurses' reported supervisor support exerts its buffering effect on the burnout-depression link differentially and serves as an important resource for nurses dealing with high self-reported work stress. © 2016 John Wiley & Sons Ltd.

The role of magnetic resonance imaging in the evaluation of transfusional iron overload in myelodysplastic syndromes.

PubMed

Petrou, Emmanouil; Mavrogeni, Sophie; Karali, Vasiliki; Kolovou, Genovefa; Kyrtsonis, Marie-Christine; Sfikakis, Petros P; Panayiotidis, Panayiotis

2015-01-01

Myelodysplastic syndromes represent a group of heterogeneous hematopoietic neoplasms derived from an abnormal multipotent progenitor cell, characterized by a hyperproliferative bone marrow, dysplasia of the cellular hemopoietic elements and ineffective erythropoiesis. Anemia is a common finding in myelodysplastic syndrome patients, and blood transfusions are the only therapeutic option in approximately 40% of cases. The most serious side effect of regular blood transfusion is iron overload. Currently, cardiovascular magnetic resonance using T2 is routinely used to identify patients with myocardial iron overload and to guide chelation therapy, tailored to prevent iron toxicity in the heart. This is a major validated non-invasive measure of myocardial iron overloading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. The indication for iron chelation therapy in myelodysplastic syndrome patients is currently controversial. However, cardiovascular magnetic resonance may offer an excellent non-invasive, diagnostic tool for iron overload assessment in myelodysplastic syndromes. Further studies are needed to establish the precise indications of chelation therapy and the clinical implications of this treatment on survival in myelodysplastic syndromes. Copyright © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

Exjade® (deferasirox, ICL670) in the treatment of chronic iron overload associated with blood transfusion

PubMed Central

Cappellini, Maria Domenica

2007-01-01

Although blood transfusions are important for patients with anemia, chronic transfusions inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. Although the current reference standard iron chelator deferoxamine has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Deferasirox (Exjade®, ICL670, Novartis Pharma AG, Basel, Switzerland) is a once-daily, oral iron chelator approved for the treatment of transfusional iron overload in adult and pediatric patients. The efficacy and safety of deferasirox have been established in a comprehensive clinical development program involving patients with various transfusion-dependent anemias. Deferasirox has a dose-dependent effect on iron burden, and is as efficacious as deferoxamine at comparable therapeutic doses. Deferasirox therapy can be tailored to a patient’s needs, as response is related to both dose and iron intake. Since deferasirox has a long half-life and is present in the plasma for 24 hours with once-daily dosing, it is unique in providing constant chelation coverage with a single dose. The availability of this convenient, effective, and well tolerated therapy represents a significant advance in the management of transfusional iron overload. PMID:18360637

Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis

PubMed Central

Ramos, Emilio; Ruchala, Piotr; Goodnough, Julia B.; Kautz, Léon; Preza, Gloria C.; Nemeth, Elizabeta

2012-01-01

The deficiency of hepcidin, the hormone that controls iron absorption and its tissue distribution, is the cause of iron overload in nearly all forms of hereditary hemochromatosis and in untransfused iron-loading anemias. In a recent study, we reported the development of minihepcidins, small drug-like hepcidin agonists. Here we explore the feasibility of using minihepcidins for the prevention and treatment of iron overload in hepcidin-deficient mice. An optimized minihepcidin (PR65) was developed that had superior potency and duration of action compared with natural hepcidin or other minihepcidins, and favorable cost of synthesis. PR65 was administered by subcutaneous injection daily for 2 weeks to iron-depleted or iron-loaded hepcidin knockout mice. PR65 administration to iron-depleted mice prevented liver iron loading, decreased heart iron levels, and caused the expected iron retention in the spleen and duodenum. At high doses, PR65 treatment also caused anemia because of profound iron restriction. PR65 administration to hepcidin knockout mice with pre-existing iron overload had a more moderate effect and caused partial redistribution of iron from the liver to the spleen. Our study demonstrates that minihepcidins could be beneficial in iron overload disorders either used alone for prevention or possibly as adjunctive therapy with phlebotomy or chelation. PMID:22990014

Effects of quercetin on hemoglobin-dependent redox reactions: relationship to iron-overload rat liver injury.

PubMed

Lu, Nai-Hao; Chen, Chao; He, Ying-Jie; Tian, Rong; Xiao, Qiang; Peng, Yi-Yuan

2013-01-01

Flavonoids have been widely reported to protect liver injury in iron-overload diseases, where the mechanism of this therapeutic action is dependent on their antioxidant effects, including free radical scavenging and metal-chelating. In this study, in contrast to the significant decrease in iron content, quercetin (Qu) from lower diet (0.3%, w/w) showed pro-oxidant ability on protein carbonyl formation and exhibited unobvious effect on iron-overload rat liver injury. Furthermore, the anti- and pro-oxidant activities of Qu on hemoglobin (Hb)-dependent redox reactions (i.e. the oxidative stability of Hb and its cytotoxic ferryl intermediate, Hb-induced protein oxidation) were investigated to illustrate the elevated protein oxidation in lower Qu-treated iron-overload rat. It was found that superoxide (O₂·⁻) and hydrogen peroxide (H₂O₂) were generated during the reaction between Qu and Hb. Qu, however, effectively reduced ferryl intermediate back to ferric Hb in a biphasic kinetic reaction. Moreover, Qu could significantly aggravate Hb-H₂O₂-induced protein oxidation at low concentrations and exhibit protective effects at high concentrations. Different from the classic antioxidant mechanisms of Qu, the dual effects on Hb redox reactions in vitro, therefore, may provide new insights into the physiological and pharmacological implications of Qu with iron-overload disease.

The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy

NASA Technical Reports Server (NTRS)

Adams, G. R.; Haddad, F.

1996-01-01

Insulin-like growth factor-1 (IGF-1) is known to have anabolic effects on skeletal muscle cells. This study examined the time course of muscle hypertrophy and associated IGF-1 peptide and mRNA expression. Data were collected at 3, 7, 14, and 28 days after surgical removal of synergistic muscles of both normal and hypophysectomized (HX) animals. Overloading increased the plantaris (Plant) mass, myofiber size, and protein-to-body weight ratio in both groups (normal and HX; P < 0.05). Muscle IGF-1 peptide levels peaked at 3 (normal) and 7 (HX) days of overloading with maximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases in muscle IGF-1 preceded the hypertrophic response. Total DNA content of the overloaded Plant increased in both groups. There was a strong positive relationship between IGF-1 peptide and DNA content in the overloaded Plant from both groups. These results indicate that 1) the muscles from rats with both normal and severely depressed systemic levels of IGF-1 respond to functional overload with an increase in local IGF-1 expression and 2) this elevated IGF-1 may be contributing to the hypertrophy response, possibly via the mobilization of satellite cells to provide increases in muscle DNA.

49 CFR 1105.9 - Coastal Zone Management Act requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Coastal Zone Management Act requirements. 1105.9... ENVIRONMENTAL LAWS § 1105.9 Coastal Zone Management Act requirements. (a) If the proposed action affects land or water uses within a State coastal zone designated pursuant to the Coastal Zone Management Act (16 U.S.C...

49 CFR 1105.9 - Coastal Zone Management Act requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Coastal Zone Management Act requirements. 1105.9... ENVIRONMENTAL LAWS § 1105.9 Coastal Zone Management Act requirements. (a) If the proposed action affects land or water uses within a State coastal zone designated pursuant to the Coastal Zone Management Act (16 U.S.C...

Shock absorber protects motive components against overloads

NASA Technical Reports Server (NTRS)

1965-01-01

Shock absorber with an output shaft, hollow gear, and a pair of springs forming a resilient driving connection between shaft and gear, operates when abnormally high torques are applied. This simple durable frictional device is valuable in rotating mechanisms subject to sudden overloads.

Coping with Information Load: User Strategies and Implications for Librarians.

ERIC Educational Resources Information Center

Rudd, Joel; Rudd, Mary Jo

1986-01-01

Describes important techniques by which library users avoid information overload, clarifies the terminology in the information overload literature, and reviews the major findings of this literature in the context of library applications. Implications for users and librarians are discussed. (CDD)

INCREASED MYOCARDIAL STIFFNESS DUE TO CARDIAC TITIN ISOFORM SWITCHING IN A MOUSE MODEL OF VOLUME OVERLOAD LIMITS ECCENTRIC REMODELING

PubMed Central

Hutchinson, Kirk R; Saripalli, Chandra; Chung, Charles S.; Granzier, Henk

2014-01-01

We investigated the cellular and molecular mechanisms of diastolic dysfunction in pure volume overload induced by aortocaval fistula (ACF) surgery in the mouse. Four weeks of volume overload resulted in significant biventricular hypertrophy; protein expression analysis in left ventricular (LV) tissue showed a marked decrease in titin's N2BA/N2B ratio with no change in phosphorylation of titin's spring region. Titin-based passive tensions were significantly increased; a result of the decreased N2BA/N2B ratio. Conscious echocardiography in ACF mice revealed eccentric remodeling and pressure volume analysis revealed systolic dysfunction: reductions in ejection fraction (EF), +dP/dt, and the slope of the endsystolic pressure volume relationships (ESPVR). ACF mice also had diastolic dysfunction: increased LV end-diastolic pressure and reduced relaxation rates. Additionally, a decrease in the slope of the end diastolic pressure volume relationship (EDPVR) was found. However, correcting for altered geometry of the LV normalized the change in EDPVR and revealed, in line with our skinned muscle data, increased myocardial stiffness in vivo. ACF mice also had increased expression of the signaling proteins FHL-1, FHL-2, and CARP that bind to titin's spring region suggesting that titin stiffening is important to the volume overload phenotype. To test this we investigated the effect of volume overload in the RBM20 heterozygous (HET) mouse model, which exhibits reduced titin stiffness. It was found that LV hypertrophy was attenuated and that LV eccentricity was exacerbated. We propose that pure volume overload induces an increase in titin stiffness that is beneficial and limits eccentric remodeling. PMID:25450617

Diuretics prescribing in chronic kidney disease patients: physician assessment versus bioimpedence spectroscopy.

PubMed

Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

2017-06-01

The relationship between hypertension and fluid overload in pre-dialysis CKD patients need to be elucidated. Current study aimed to find relationship between fluid overload and hypertension along with prescribed diuretic therapy using bioimpedance spectroscopy (BIS). A prospective observational study was conducted by inviting pre-dialysis CKD patients. Fluid overload was assessed by BIS. A total of 312 CKD patients with mean eGFR 24.5 ± 11.2 ml/min/1.73 m 2 were enrolled. Based on OH value ≥7 %, 135 (43.3 %) patients were hypervolemic while euvolemia was observed in 177 (56.7 %) patients. Patients were categorized in different regions of hydration reference plot (HRP) generated by BIS i.e., 5.1 % in region-N (normal BP and fluid status), 20.5 % in region I (hypertensive with severe fluid overload), 29.5 % in region I-II (hypertensive with mild fluid overload), 22 % in region II (hypertensive with normohydration), 10.2 % in region III (underhydration with normal/low BP) and 12.5 % in region IV (normal BP with severe fluid overload). A total of 144 (46 %) patients received diuretics on basis of physician assessment of BP and edema. Maximum diuretics 100 (69.4 %) were prescribed in patients belonging to regions I and I-II of HRP. Interestingly, a similar number of diuretic prescriptions were observed in region II (13 %) and region IV (12 %). Surprisingly, 7 (4.9 %) of patients in region III who were neither hypervolemic nor hypertensive were also prescribed with diuretics. BIS can aid clinicians to categorize CKD patients on basis of their fluid status and provide individualized pharmacotherapy to manage hypertensive CKD patients.

Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.

PubMed

Lu, Yi; Zhao, Ming; Liu, Jin-Jun; He, Xi; Yu, Xiao-Jiang; Liu, Long-Zhu; Sun, Lei; Chen, Li-Na; Zang, Wei-Jin

2017-09-01

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis.

PubMed

Del-Castillo-Rueda, Alejandro; Moreno-Carralero, María-Isabel; Cuadrado-Grande, Nuria; Alvarez-Sala-Walther, Luis-Antonio; Enríquez-de-Salamanca, Rafael; Méndez, Manuel; Morán-Jiménez, María-Josefa

2012-10-15

Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutation in the HFE gene; however, rare forms of genetic iron overload must be diagnosed using a specific genetic analysis. We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis. We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene. Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype. Copyright © 2012. Published by Elsevier B.V.

Transforming growth factor-β inhibits myocardial PPARγ expression in pressure overload-induced cardiac fibrosis and remodeling in mice

PubMed Central

Gong, Kaizheng; Chen, Yiu-Fai; Li, Peng; Lucas, Jason A.; Hage, Fadi G.; Yang, Qinglin; Nozell, Susan E.; Oparil, Suzanne; Xing, Dongqi

2012-01-01

Objectives Pharmacological activation of peroxisome proliferator-activated receptor gamma (PPARγ) has been shown to attenuate pressure overload-induced cardiac fibrosis, suggesting that PPARγ has an antifibrotic effect. This study tested the hypothesis that there is a functional interaction between transforming growth factor-β (TGF-β) signaling and endogenous PPARγ expression in cardiac fibroblasts and pressure overloaded heart. Methods and results We observed that, in response to pressure overload induced by transverse aortic constriction, left-ventricular PPARγ protein levels were decreased in wild-type mice, but increased in mice with an inducible overexpression of dominant negative mutation of the human TGF-β type II receptor (DnTGFβRII), in which TGF-β signaling is blocked. In isolated mouse cardiac fibroblasts, we demonstrated that TGF-β1 treatment decreased steady state PPARγ mRNA (−34%) and protein (−52%) levels, as well as PPARγ transcriptional activity (−53%). Chromatin immunoprecipitation analysis showed that TGF-β1 treatment increased binding of Smad2/3, Smad4 and histone deacetylase 1, and decreased binding of acetylated histone 3 to the PPARγ promoter in cardiac fibroblasts. Both pharmacological activation and overexpression of PPARγ significantly inhibited TGF-β1-induced extracellular matrix molecule expression in isolated cardiac fibroblasts, whereas treatment with the PPARγ agonist rosiglitazone inhibited, and treatment with the PPARγ antagonist T0070907 exacerbated chronic pressure overload-induced cardiac fibrosis and remodeling in wild-type mice in vivo. Conclusion These data provide strong evidence that TGF-β1 directly suppresses PPARγ expression in cardiac fibroblasts via a transcriptional mechanism and suggest that the down-regulation of endogenous PPARγ expression by TGF-β may be involved in pressure overload-induced cardiac fibrosis. PMID:21836474

An Indian Desert Shrub 'Hiran Chabba', Farsetia Hamiltonii Royle, Exhibits Potent Antioxidant and Hepatoprotective Effect Against Iron-Overload Induced Liver Toxicity in Swiss Albino Mice.

PubMed

Basu, Tapasree; Kumar, Bipul; Shendge, Anil Khushalrao; Panja, Sourav; Chugh, Heerak; Gautam, Hemant K; Mandal, Nripendranath

2018-04-18

Farsetia hamiltonii Royle, also known as Hiran Chabba grows in desert regions. It is widely used as folk medicine to treat joint pains, diarrhea and diabetes. However, its antioxidant and iron chelation abilities both in vitro and in vivo have not yet been investigated. The 70% methanolic extract of F.hamiltonii (FHME) was investigated for its free radical scavenging and iron chelation potential, in vitro. An iron-overload situation was established by intraperitoneal injection of iron-dextran in Swiss albino mice, followed by oral administration of FHME. Liver damage and serum parameters due to iron-overload were measured biochemically and histopathologically to test iron-overload remediation and hepatoprotective potential of FHME. Phytochemical analyses were performed to determine its probable bioactive components. FHME showed promising antioxidant activity, scavenged various reactive oxygen and nitrogen species and chelated iron in vitro. FHME reduced liver iron, serum ferritin, normalized serum parameters, reduced oxidative stress in liver, serum and improved liver antioxidant status in iron-overloaded mice. It also alleviated liver damage and fibrosis as evident from biochemical parameters and morphological analysis of liver sections. The phytochemical analyses of FHME reflected the presence of alkaloids, phenols, flavonoids and tannins. HPLC analysis indicated presence of tannic acid, quercetin, methyl gallate, catechin, reserpine, ascorbic acid and gallic acid. Based on the experimental outcome, FHME, an ethnologically important plant can be envisaged as excellent antioxidant and iron chelator drug capable of remediating iron-overload induced hepatotoxicity and the bioactive compounds present in FHME might be responsible for its efficacy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The impact of pressure overload on coronary vascular changes following myocardial infarction in rats.

PubMed

Chen, Jiqiu; Petrov, Artiom; Yaniz-Galende, Elisa; Liang, Lifan; de Haas, Hans J; Narula, Jagat; Hajjar, Roger J

2013-03-01

This study investigates the impact of pressure overload on vascular changes after myocardial infarction (MI) in rats. To evaluate the effect of pressure overload, MI was induced in three groups: 1) left coronary artery ligation for 1 mo (MI-1m), 2) ischemia 30 min/reperfusion for 1 mo (I/R-1m), and 3) ischemia-reperfusion (I/R) was performed after pressure overload induced by aortic banding for 2 mo; 1 mo post-I/R, aortic constriction was released (Ab+I/R+DeAb). Heart function was assessed by echocardiography and in vivo hemodynamics. Resin casting and three-dimensional imaging with microcomputed tomography were used to characterize changes in coronary vasculature. TTC (triphenyltetrazohum chloride) staining and Masson's Trichrome were conducted in parallel experiments. In normal rats, MI induced by I/R and permanent occlusion was transmural or subendocardial. Occluded arterial branches vanished in MI-1m rats. A short residual tail was retained, distal to the occluded site in the ischemic area in I/R-1m hearts. Vascular pathological changes in transmural MI mostly occurred in ischemic areas and remote vasculature remained normal. In pressure overloaded rats, I/R injury induced a sub-MI in which ischemia was transmural, but myocardium in the involved area had survived. The ischemic arterial branches were preserved even though the capillaries were significantly diminished and the pathological changes were extended to remote areas, characterized by fibrosis, atrial thrombus, and pulmonary edema in the Ab+I/R+DeAb group. Pressure overload could increase vascular tolerance to I/R injury, but also trigger severe global ventricular fibrosis and results in atrial thrombus and pulmonary edema.

Albumin Overload and PINK1/Parkin Signaling-Related Mitophagy in Renal Tubular Epithelial Cells.

PubMed

Tan, Jin; Xie, Qi; Song, Shuling; Miao, Yuyang; Zhang, Qiang

2018-03-01

BACKGROUND Albumin, as a major urinary protein component, is a risk factor for chronic kidney disease progression. Mitochondrial dysfunction is one of the main causes of albumin-induced proximal tubule cells injury. Mitophagy is considered as a pivotal protective mechanism for the elimination of dysfunctional mitochondria. The objective of this research was to determine whether albumin overload-induced mitochondrial dysfunction can activate PINK1/Parkin-mediated mitophagy in renal tubular epithelial cells (TECs). MATERIAL AND METHODS Immunofluorescence assay and Western blot assay were used to detect the effects of albumin overload on autophagy marker protein LC3. Transmission electron microscopy and Western blot assay were used to investigate the role of albumin in mitochondrial injury. Western blot assay and co-localization of acidic lysosomes and mitochondria assay were employed to detect the activation of mitophagy induced by albumin. Finally, we explored the role of PINK1/Parkin signaling in albumin-induced mitophagy by inhibiting mitophagy by knockdown of PARK2 (Parkin) level. RESULTS Immunofluorescence and Western blot results showed that the expression level of LC3-II increased, and the maximum increase point was observed after 8 h of albumin treatment. Transmission electron microscopy results demonstrated that albumin overload-induced mitochondrial injury and quantity of autophagosomes increased. Additionally, expression of PINK1 and cytosolic cytochrome C increased and mitochondria cytochrome C decreased in the albumin group. The co-localization of acidic lysosomes and mitochondria demonstrated that the number of albumin overload-induced mitophagy-positive dots increased. The transient transfection of PARK2 siRNA result showed knockdown of the expression level of PARK2 can inhibit mitophagy induced by albumin. CONCLUSIONS In conclusion, our study suggests that mitochondrial dysfunction activates the PINK1/Parkin signaling and mitophagy in renal tubular epithelial cells under albumin overload condition.

LRRC10 is required to maintain cardiac function in response to pressure overload

PubMed Central

Brody, Matthew J.; Feng, Li; Grimes, Adrian C.; Hacker, Timothy A.; Olson, Timothy M.; Kamp, Timothy J.

2015-01-01

We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10−/−) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10−/− mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10−/− mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10−/− cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His150 of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis. PMID:26608339

Iatrogenic Iron Overload in Dialysis Patients at the Beginning of the 21st Century.

PubMed

Rostoker, Guy; Vaziri, Nosratola D; Fishbane, Steven

2016-05-01

Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a 'second hit' on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients.

Mitochondrial complex I and NAD(P)H oxidase are major sources of exacerbated oxidative stress in pressure-overloaded ischemic-reperfused hearts.

PubMed

Mozaffari, Mahmood S; Baban, Babak; Liu, Jun Yao; Abebe, Worku; Sullivan, Jennifer C; El-Marakby, Ahmed

2011-03-01

We tested the hypothesis that pressure overload exacerbates oxidative stress associated with augmented mitochondrial permeability transition (MPT) pore opening and cell death in ischemic-reperfused hearts. Pressure overload decreased the level of reduced glutathione but increased nitrotyrosine and 8-hydroxydeoxyguanosine levels in ischemic-reperfused hearts. The activity of catalase, but not superoxide dismutase (SOD), was lower in ischemic-reperfused hearts perfused at higher pressure. Mitochondria from ischemic-reperfused hearts subjected to higher perfusion pressure displayed significantly greater [³H]-2-deoxyglucose-6-P entrapment suggestive of greater MPT pore opening and consistent with greater necrosis and apoptosis. Tempol (SOD mimetic) reduced infarct size in both groups but it remained greater in the higher pressure group. By contrast, uric acid (peroxynitrite scavenger) markedly reduced infarct size at higher pressure, effectively eliminating the differential between the two groups. Inhibition of xanthine oxidase, with allopurinol, reduced infarct size but did not eliminate the differential between the two groups. However, amobarbital (inhibitor of mitochondrial complex I) or apocynin [inhibitor of NAD(P)H oxidase] reduced infarct size at both pressures and also abrogated the differential between the two groups. Consistent with the effect of apocynin, pressure-overloaded hearts displayed significantly higher NAD(P)H oxidase activity. Furthermore, pressure-overloaded hearts displayed increased nitric oxide synthase activity which, along with increased propensity to superoxide generation, may underlie uric acid-induced cardioprotection. In conclusion, increased oxidative and nitrosative stress, coupled with lack of augmented SOD and catalase activities, contributes importantly to the exacerbating impact of pressure overload on MPT pore opening and cell death in ischemic-reperfused hearts.

Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

NASA Technical Reports Server (NTRS)

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 the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

Factors Affecting Impact Toughness in Stabilized Intermediate Purity 21Cr Ferritic Stainless Steels and Their Simulated Heat-Affected Zones

NASA Astrophysics Data System (ADS)

Anttila, Severi; Alatarvas, Tuomas; Porter, David A.

2017-12-01

The correlation between simulated weld heat-affected zone microstructures and toughness parameters has been investigated in four intermediate purity 21Cr ferritic stainless steels stabilized with titanium and niobium either separately or in combination. Extensive Charpy V impact toughness testing was carried out followed by metallography including particle analysis using electron microscopy. The results confirmed that the grain size and the number density of particle clusters rich in titanium nitride and carbide with an equivalent circular diameter of 2 µm or more are statistically the most critical factors influencing the ductile-to-brittle transition temperature. Other inclusions and particle clusters, as well as grain boundary precipitates, are shown to be relatively harmless. Stabilization with niobium avoids large titanium-rich inclusions and also suppresses excessive grain growth in the heat-affected zone when reasonable heat inputs are used. Thus, in order to maximize the limited heat-affected zone impact toughness of 21Cr ferritic stainless steels containing 380 to 450 mass ppm of interstitials, the stabilization should be either titanium free or the levels of titanium and nitrogen should be moderated.

Study of an overload truck screening system for a sustainable highway bridge network.

DOT National Transportation Integrated Search

2009-01-01

he objective of this project was to study the use and implementation of an overload truck screening system for bridge structures. This screening system combines two advanced technologies, namely a weigh-in-motion (WIM) system and a bridge strain sens...

30 CFR 56.12001 - Circuit overload protection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity...

30 CFR 56.12001 - Circuit overload protection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity...

30 CFR 56.12001 - Circuit overload protection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity...

30 CFR 56.12001 - Circuit overload protection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity...

30 CFR 56.12001 - Circuit overload protection.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity...

Self-healing fuse

NASA Technical Reports Server (NTRS)

Jones, N. D.; Kinsinger, R. E.; Harris, L. P.

1974-01-01

Fast-acting current limiting device provides current overload protection for vulnerable circuit elements and then re-establishes conduction path within milliseconds. Fuse can also perform as fast-acting switch to clear transient circuit overloads. Fuse takes advantage of large increase in electrical resistivity that occurs when liquid metal vaporizes.

Modeling of information diffusion in Twitter-like social networks under information overload.

PubMed

Li, Pei; Li, Wei; Wang, Hui; Zhang, Xin

2014-01-01

Due to the existence of information overload in social networks, it becomes increasingly difficult for users to find useful information according to their interests. This paper takes Twitter-like social networks into account and proposes models to characterize the process of information diffusion under information overload. Users are classified into different types according to their in-degrees and out-degrees, and user behaviors are generalized into two categories: generating and forwarding. View scope is introduced to model the user information-processing capability under information overload, and the average number of times a message appears in view scopes after it is generated by a given type user is adopted to characterize the information diffusion efficiency, which is calculated theoretically. To verify the accuracy of theoretical analysis results, we conduct simulations and provide the simulation results, which are consistent with the theoretical analysis results perfectly. These results are of importance to understand the diffusion dynamics in social networks, and this analysis framework can be extended to consider more realistic situations.

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

PubMed

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.

Roles of lipocalin 2 and adiponectin in iron overload cardiomyopathy.

PubMed

Siri-Angkul, Natthaphat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2018-07-01

Thalassemia is among the most common genetic diseases worldwide. Ineffective erythropoiesis, chronic hemolysis, and regular blood transfusion in thalassemia patients lead to increased iron burden. Iron overload cardiomyopathy is the most severe co-morbidity and most common cause of mortality in thalassemia patients. Although its associated mechanisms are still not completely understood, cellular iron mishandling, chronic inflammation, and oxidative stress appear to be the key processes involved. In order to acquire a more comprehensive insight of the impact of cardiac iron overload, these alterations need to be intensively investigated. This comprehensive mini-review focuses on two emergent molecules which have been shown to potentially play significant roles in iron overload cardiomyopathy. These two molecules are an iron-transporting protein, lipocalin 2, and an anti-inflammatory adipokine, adiponectin. Reports from in vitro and in vivo studies are comprehensively summarized. Clinical studies examining the roles of these molecules in thalassemia patients are also presented and discussed. © 2017 Wiley Periodicals, Inc.

Assessment and Management of Volume Overload and Congestion in Chronic Heart Failure: Can Measuring Blood Volume Provide New Insights?

PubMed

Miller, Wayne L

2017-01-01

Volume overload and fluid congestion remain primary clinical challenges in the assessment and management of patients with chronic heart failure (HF). The pathophysiology of volume regulation is complex, and the simple concept of passive intravascular fluid accumulation is not adequate. The dynamics of interstitial and intravascular fluid compartment interactions and fluid redistribution from venous splanchnic beds to the central pulmonary circulation need to be taken into account in strategies of volume management. Clinical bedside evaluations and right heart hemodynamic assessments can alert 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 chronic HF. The quantitative assessment of intravascular volume is an effective tool to help guide individualized, appropriate therapy. Not all volume overload is the same, and the measurement of intravascular volume identifies heterogeneity to guide tailored therapy.

[Hyperhydration and dialysis in acute kidney failure].

PubMed

Saner, Fuat H; Bienholz, Anja; Tyczynski, Bartosz; Kribben, Andreas; Feldkamp, Thorsten

2015-05-01

Despite the advances in critical care medicine, the hospital mortality in patients with acute kidney injury (AKI) requiring dialysis remains high. Depending on the underlying disease the in-house mortality is reported to be up to 80%. Several observational studies demonstrated an association between mortality and fluid overload. A primary mechanism of interest is that fluid overload causes tissue edema and subsequent reduction of perfusion, oxygenation and nutrient delivery. This results in further renal damage. In addition, fluid overload-related dilution within the extracellular space causes artificially low serum creatinine, which masks AKI diagnosis. As a consequence, renal protective management strategies are deferred, which further aggravates kidney injury. This aggravation of renal damage subsequently increases the mortality. This review discusses the role of fluid overload for outcomes in critically ill patients as described in the current literature and assesses criteria for the initiation of renal replacement therapy in this critically ill population. © Georg Thieme Verlag KG Stuttgart · New York.

How we manage iron overload in sickle cell patients.

PubMed

Coates, Thomas D; Wood, John C

2017-06-01

Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron-related complications that should be treated. The success of chelation therapy is dominated by patient adherence to prescribed treatment; thus, adjustment of drug regimens to increase adherence to treatment is critical. This review will discuss the current biology of iron homeostasis in patients with SCD and how this informs our clinical approach to treatment. We will present the clinical approach to treatment of iron overload at our centre using serial assessment of organ iron by magnetic resonance imaging. © 2017 John Wiley & Sons Ltd.

Clinical Impact and Cellular Mechanisms of Iron Overload-Associated Bone Loss

PubMed Central

Jeney, Viktória

2017-01-01

Diseases/conditions with diverse etiology, such as hemoglobinopathies, hereditary hemochromatosis and menopause, could lead to chronic iron accumulation. This condition is frequently associated with a bone phenotype; characterized by low bone mass, osteoporosis/osteopenia, altered microarchitecture and biomechanics, and increased incidence of fractures. Osteoporotic bone phenotype constitutes a major complication in patients with iron overload. The purpose of this review is to summarize what we have learnt about iron overload-associated bone loss from clinical studies and animal models. Bone is a metabolically active tissue that undergoes continuous remodeling with the involvement of osteoclasts that resorb mineralized bone, and osteoblasts that form new bone. Growing evidence suggests that both increased bone resorption and decreased bone formation are involved in the pathological bone-loss in iron overload conditions. We will discuss the cellular and molecular mechanisms that are involved in this detrimental process. Fuller understanding of this complex mechanism may lead to the development of improved therapeutics meant to interrupt the pathologic effects of excess iron on bone. PMID:28270766

Overload-based cascades on multiplex networks and effects of inter-similarity

PubMed Central

Zhou, Dong

2017-01-01

Although cascading failures caused by overload on interdependent/interconnected networks have been studied in the recent years, the effect of overlapping links (inter-similarity) on robustness to such cascades in coupled networks is not well understood. This is an important issue since shared links exist in many real-world coupled networks. In this paper, we propose a new model for load-based cascading failures in multiplex networks. We leverage it to compare different network structures, coupling schemes, and overload rules. More importantly, we systematically investigate the impact of inter-similarity on the robustness of the whole system under an initial intentional attack. Surprisingly, we find that inter-similarity can have a negative impact on robustness to overload cascades. To the best of our knowledge, we are the first to report the competition between the positive and the negative impacts of overlapping links on the robustness of coupled networks. These results provide useful suggestions for designing robust coupled traffic systems. PMID:29252988

Low molecular weight fucoidan protects renal tubular cells from injury induced by albumin overload.

PubMed

Jia, Yingli; Sun, Yi; Weng, Lin; Li, Yingjie; Zhang, Quanbin; Zhou, Hong; Yang, Baoxue

2016-08-22

Albuminuria is a causative and aggravating factor for progressive renal damage in chronic kidney disease (CKD). The aim of this study was to determine if low molecular weight fucoidan (LMWF) could protect renal function and tubular cells from albumin overload caused injury. Treatment with 10 mg/g bovine serum albumin caused renal dysfunction, morphological changes, and overexpression of inflammation and fibrosis associated proteins in 129S2/Sv mice. LMWF (100 mg/kg) protected against kidney injury and renal dysfunction with decreased blood creatinine by 34% and urea nitrogen by 25%, increased creatinine clearance by 48%, and decreased significantly urinary albumin concentration. In vitro proximal tubule epithelial cell (NRK-52E) model showed that LMWF dose-dependently inhibited overexpression of proinflammatory and profibrotic factors, oxidative stress and apoptosis caused by albumin overload. These experimental results indicate that LMWF protects against albumin overload caused renal injury by inhibiting inflammation, fibrosis, oxidative stress and apoptosis, which suggests that LMWF could be a promising candidate drug for preventing CKD.

Modeling of Information Diffusion in Twitter-Like Social Networks under Information Overload

PubMed Central

Li, Wei

2014-01-01

Due to the existence of information overload in social networks, it becomes increasingly difficult for users to find useful information according to their interests. This paper takes Twitter-like social networks into account and proposes models to characterize the process of information diffusion under information overload. Users are classified into different types according to their in-degrees and out-degrees, and user behaviors are generalized into two categories: generating and forwarding. View scope is introduced to model the user information-processing capability under information overload, and the average number of times a message appears in view scopes after it is generated by a given type user is adopted to characterize the information diffusion efficiency, which is calculated theoretically. To verify the accuracy of theoretical analysis results, we conduct simulations and provide the simulation results, which are consistent with the theoretical analysis results perfectly. These results are of importance to understand the diffusion dynamics in social networks, and this analysis framework can be extended to consider more realistic situations. PMID:24795541

32 CFR 643.33 - Policy-Coastal zone management.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 4 2011-07-01 2011-07-01 false Policy-Coastal zone management. 643.33 Section... PROPERTY REAL ESTATE Policy § 643.33 Policy—Coastal zone management. (a) The Coastal Zone Management Act of... affecting the coastal zone of a state, to conduct or support those activities in a manner which is, to the...

32 CFR 643.33 - Policy-Coastal zone management.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Policy-Coastal zone management. 643.33 Section... PROPERTY REAL ESTATE Policy § 643.33 Policy—Coastal zone management. (a) The Coastal Zone Management Act of... affecting the coastal zone of a state, to conduct or support those activities in a manner which is, to the...

Free iron catalyzes oxidative damage to hematopoietic cells/mesenchymal stem cells in vitro and suppresses hematopoiesis in iron overload patients.

PubMed

Lu, Wenyi; Zhao, Mingfeng; Rajbhandary, Sajin; Xie, Fang; Chai, Xiao; Mu, Juan; Meng, Juanxia; Liu, Yongjun; Jiang, Yan; Xu, Xinnv; Meng, Aimin

2013-09-01

Transfusional iron overload is of major concern in hematological disease. Iron-overload-related dyserythropoiesis and reactive oxygen species (ROS)-related damage to hematopoietic stem cell (HSC) function are major setbacks in treatment for such disorders. We therefore aim to investigate the effect of iron overload on hematopoiesis in the patients and explore the role of ROS in iron-induced oxidative damage in hematopoietic cells and microenvironment in vitro. The hematopoietic colony-forming capacity and ROS level of bone marrow cells were tested before and after iron chelation therapy. In vitro, we first established an iron overload model of bone marrow mononuclear cells (BMMNC) and umbilical cord-derived mesenchymal stem cells (UC-MSC). ROS level, cell cycle, and apoptosis were measured by FACS. Function of cells was individually studied by Colony-forming cell (CFC) assay and co-culture system. Finally, ROS-related signaling pathway was also detected by Western blot. After administering deferoxamine (DFO), reduced blood transfusion, increased neutrophil, increased platelet, and improved pancytopenia were observed in 76.9%, 46.2%, 26.9%, and 15.4% of the patients, respectively. Furthermore, the colony-forming capacity of BMMNC from iron overload patient was deficient, and ROS level was higher, which were partially recovered following iron chelation therapy. In vitro, exposure of BMMNC to ferric ammonium citrate (FAC) for 24 h decreased the ratio of CD34(+) cell from 0.91 ± 0.12% to 0.39 ± 0.07%. Excessive iron could also induce apoptosis, arrest cell cycle, and decrease function of BMMNC and UC-MSC, which was accompanied by increased ROS level and stimulated p38MAPK, p53 signaling pathway. More importantly, N-acetyl-L-cysteine (NAC) or DFO could partially attenuate cell injury and inhibit the signaling pathway induced by excessive iron. Our study shows that iron overload injures the hematopoiesis by damaging hematopoietic cell and hematopoietic microenvironment, which is mediated by ROS-related signaling proteins. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role of liver magnetic resonance imaging in hyperferritinaemia and the diagnosis of iron overload.

PubMed

Ruefer, Axel; Bapst, Christine; Benz, Rudolf; Bremerich, Jens; Cantoni, Nathan; Infanti, Laura; Samii, Kaveh; Schmid, Mathias; Vallée, Jean-Paul

2017-11-09

Hyperferritinaemia is a frequent clinical problem. Elevated serum ferritin levels can be detected in different genetic and acquired diseases and can occur with or without anaemia. It is therefore important to determine whether hyperferritinaemia is due to iron overload or due to a secondary cause. The main causes of iron overload are intestinal iron hyperabsorption disorders and transfusion-dependent disorders. Iron homeostasis and iron overload are quantified by different diagnostic approaches. The evaluation of serum ferritin and transferrin saturation is the first diagnostic step to identify the cause of hyperferritinaemia. The assessment of liver iron concentration by liver biopsy or magnetic resonance imaging (MRI) may guide the further diagnostic and therapeutic workup. Liver biopsy is invasive and poorly accepted by patients and should only be carried out in selected patients with hereditary haemochromatosis. As a non-invasive approach, MRI is considered the standard method to diagnose and to monitor both hepatic iron overload and the effectiveness of iron chelation therapy in many clinical conditions such as thalassaemia and myelodysplastic syndromes. Accurate evaluation and monitoring of iron overload has major implications regarding adherence, quality of life and prognosis. There are different technical MRI approaches to measuring the liver iron content. Of these, T2 and T2* relaxometry are considered the standard of care. MRI with cardiac T2* mapping is also suitable for the assessment of cardiac iron. Currently there is no consensus which technique should be preferred. The choice depends on local availability and patient population. However, it is important to use the same MRI technique in subsequent visits in the same patient to get comparable results. Signal intensity ratio may be a good adjunct to R2 and R2* methods as it allows easy visual estimation of the liver iron concentration. In this review a group of Swiss haematologists and radiologists give an overview of different conditions leading to primary or secondary iron overload and on diagnostic methods to assess hyperferritinaemia with a focus on the role of liver MRI. They summarise the standard practice in Switzerland on the use of liver iron concentration MRI as well as disease-specific guideline recommendations.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao

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 cytotoxicitymore » 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{sup 2+} overload causes arrhythmia in rats. • Aconitine induces Ca{sup 2+} overload through the activation of L-type Ca{sup 2+} channels. • Aconitine-induced Ca{sup 2+} overload triggers apoptotic responses in vitro and in vivo. • Aconitine promotes apoptotic development via activation of P38 MAPK.« less

15 CFR 923.92 - Allocation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... intergovernmental cooperation in that a state, in accordance with its coastal zone management program, may allocate some of its coastal zone management responsibilities to several agencies, including local governments... could directly affect the State's coastal zone. ...

Evaluation and treatment of transfusional iron overload in children.

PubMed

Ware, Hannah M; Kwiatkowski, Janet L

2013-12-01

Red blood cell transfusions are increasingly used in the management of various anemias, including thalassemia and sickle cell disease. Because the body lacks physiologic mechanisms for removing excess iron, transfusional iron overload is a common complication in children receiving regular transfusions. Iron chelation is necessary to remove the excess iron that causes injury to the heart, liver, and endocrine organs. Three chelators, deferoxamine, deferasirox, and deferiprone, are currently available in the United States. When choosing a chelator regimen, patients, parents, and providers may consider a variety of factors, including the severity of iron overload, administration schedule, and adverse effect profile. Copyright © 2013 Elsevier Inc. All rights reserved.

Guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload.

PubMed

Gattermann, Norbert

2007-12-01

Experts believe that iron overload is an important problem which could be avoided with suitable treatment. Guidelines on treating myelodysplastic syndromes (MDS) include sections on using iron chelation therapy to prevent or ameliorate transfusional iron overload. The proportion of MDS patients who may benefit from iron chelation therapy is 35-55%, depending on the length of survival necessary for iron to accumulate to a detrimental level. Candidates for iron chelation are mainly patients with dyserythropoietic and cytopenic subtypes of disease, which fall into the International Prognostic Scoring System (IPSS) Low-risk or Intermediate-1-risk categories, with median survival of 3-6 years.

Transfusional iron overload and iron chelation therapy in thalassemia major and sickle cell disease.

PubMed

Marsella, Maria; Borgna-Pignatti, Caterina

2014-08-01

Iron overload is an inevitable consequence of blood transfusions and is often accompanied by increased iron absorption from the gut. Chelation therapy is necessary to prevent the consequences of hemosiderosis. Three chelators, deferoxamine, deferiprone, and deferasirox, are presently available and a fourth is undergoing clinical trials. The efficacy of all 3 available chelators has been demonstrated. Also, many studies have shown the efficacy of the combination of deferoxamine plus deferiprone as an intensive treatment of severe iron overload. Alternating chelators can reduce adverse effects and improve compliance. Adherence to therapy is crucial for good results. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of residual welding stresses, overload and specimen preparation on fatigue crack growth under axial compression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greasley, A.

1995-02-01

Double edge notched axial compression specimens taken from thick welded steel joints have been used to grow fatigue cracks under pulsating compressive loads at mean stresses up to 55% of that needed for general yielding. The redistribution of residual stresses during specimen preparation and during crack growth influences the nucleation, growth rate and extent of fatigue cracks. Crack growth rates which are comparable to the equivalent tensile situation have been observed in as-welded, welded plus overloaded and stress relieved plus overloaded joints. Multiple nucleation and curved crack profiles have been observed in all cases. 5 refs.

A comparison between the ANSI/IEEE and the CENELEC/IEC approach to overload protection of insulated power cables

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parise, G.; Rubino, G.

1995-12-31

The same basic principles, on which the methods of power cables protection against overloads are based, are summed up by different criteria and formulations within ANSI/IEEE and CENELEC/IEC publications. The studies carried out by the technical committees of these organizations have been examined and compared in order to point out not only their differences but also their complementary aspects. By arranging the two approaches, it has been possible to outline a third way to determine the admissible duration of overload currents and define intermediate criteria for the emergency ratings of cables and for the coordination of protective devices.

Three Dimensional Sector Design with Optimal Number of Sectors

NASA Technical Reports Server (NTRS)

Xue, Min

2010-01-01

In the national airspace system, sectors get overloaded due to high traffic demand and inefficient airspace designs. Overloads can be eliminated in some cases by redesigning sector boundaries. This paper extends the Voronoi-based sector design method by automatically selecting the number of sectors, allowing three-dimensional partitions, and enforcing traffic pattern conformance. The method was used to design sectors at Fort-Worth and Indianapolis centers for current traffic scenarios. Results show that new designs can eliminate overloaded sectors, although not in all cases, reduce the number of necessary sectors, and conform to major traffic patterns. Overall, the new methodology produces enhanced and efficient sector designs.

30 CFR 56.12003 - Trailing cable overload protection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity...

30 CFR 56.12003 - Trailing cable overload protection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity...

30 CFR 56.12003 - Trailing cable overload protection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity...

30 CFR 56.12003 - Trailing cable overload protection.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity...

30 CFR 56.12003 - Trailing cable overload protection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity...

Use of Friction Stir Processing for Improving Heat-Affected Zone Liquation Cracking Resistance of a Cast Magnesium Alloy AZ91D

NASA Astrophysics Data System (ADS)

Karthik, G. M.; Janaki Ram, G. D.; Kottada, Ravi Sankar

2017-12-01

In this work, a cast magnesium alloy AZ91D was friction stir processed. Detailed microstructural studies and Gleeble hot ductility tests were conducted on the as-cast and the FSPed samples to comparatively assess their heat-affected zone liquation cracking behavior. The results show that the use of FSP as a pretreatment to fusion welding can strikingly improve the heat-affected zone liquation cracking resistance of alloy AZ91D by reducing the amount and size of the low-melting eutectic β (Mg17Al12) as well as by refining the matrix grain size.