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

Amphiphile-induced heart muscle-cell (myocyte) injury: effects of intracellular fatty acid overload.

PubMed

Janero, D R; Burghardt, C; Feldman, D

1988-10-01

Lipid amphiphile toxicity may be an important contributor to myocardial injury, especially during ischemia/reperfusion. In order to investigate directly the potential biochemical and metabolic effects of amphiphile overload on the functioning heart muscle cell (myocyte), a novel model of nonesterified fatty acid (NEFA)-induced myocyte damage has been defined. The model uses intact, beating neonatal rat myocytes in primary monolayer culture as a study object and 5-(tetradecyloxy)-2-furoic acid (TOFA) as a nonmetabolizable fatty acid. Myocytes incubated with TOFA accumulated it as NEFA, and the consequent NEFA amphiphile overload elicited a variety of cellular defects (including decreased beating rate, depletion of high-energy stores and glycogen pools, and breakdown of myocyte membrane phospholipid) and culminated in cell death. The amphiphile-induced cellular pathology could be reversed by removing TOFA from the culture medium, which resulted in intracellular TOFA "wash-out." Although the development and severity of amphiphile-induced myocyte injury could be correlated with both the intracellular TOFA/NEFA content (i.e., the level of TOFA to which the cells were exposed) and the duration of this exposure, removal of amphiphile overload did not inevitably lead to myocyte recovery. TOFA had adverse effects on myocyte mitochondrial function in situ (decoupling of oxidative phosphorylation, impairing respiratory control) and on myocyte oxidative catabolism (transiently increasing fatty acid beta oxidation, citric acid cycle flux, and glucose oxidation). The amphiphile-induced bioenergetic abnormalities appeared to constitute a state of "metabolic anoxia" underlying the progression of myocyte injury to cell death. This anoxic state could be ameliorated to some extent, but not prevented, by carbohydrate catabolism.

Control and protection system for paralleled modular static inverter-converter systems

NASA Technical Reports Server (NTRS)

Birchenough, A. G.; Gourash, F.

1973-01-01

A control and protection system was developed for use with a paralleled 2.5-kWe-per-module static inverter-converter system. The control and protection system senses internal and external fault parameters such as voltage, frequency, current, and paralleling current unbalance. A logic system controls contactors to isolate defective power conditioners or loads. The system sequences contactor operation to automatically control parallel operation, startup, and fault isolation. Transient overload protection and fault checking sequences are included. The operation and performance of a control and protection system, with detailed circuit descriptions, are presented.

Dynamic characteristics of a 20 kHz resonant power system - Fault identification and fault recovery

NASA Technical Reports Server (NTRS)

Wasynczuk, O.

1988-01-01

A detailed simulation of a dc inductor resonant driver and receiver is used to demonstrate the transient characteristics of a 20 kHz resonant power system during fault and overload conditions. The simulated system consists of a dc inductor resonant inverter (driver), a 50-meter transmission cable, and a dc inductor resonant receiver load. Of particular interest are the driver and receiver performance during fault and overload conditions and on the recovery characteristics following removal of the fault. The information gained from these studies sets the stage for further work in fault identification and autonomous power system control.

Interdisciplinary Research and Information Overload.

ERIC Educational Resources Information Center

Wilson, Patrick

1996-01-01

Discusses information overload and examines several ways in which actual and potential overload affects research choices for the solo researcher in interdisciplinary areas. Topics include information overload and teamwork; entry barriers to certain specialties, including necessary background knowledge; and information utilization and knowledge…

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

Lee, S. Y.; Choo, Hahn; Liaw, Peter K

The combined effects of overload-induced enlarged compressive residual stresses and crack tip blunting with secondary cracks are suggested to be responsible for the observed changes in the crack opening load and resultant post-overload transient crack growth behavior [Lee SY, Liaw PK, Choo H, Rogge RB, Acta Mater 2010;59:485-94]. In this article, in situ neutron diffraction experiments were performed to quantify the influence of the combined effects by investigating the internal-stress evolution at various locations away from the crack tip. In the overload-retardation period, stress concentration occurs in the crack blunting region (an overload point) until a maximum crack arrest loadmore » is reached. The stress concentration is then transferred from the blunting region to the propagating crack tip (following the overload), requiring a higher applied load, as the closed crack is gradually opened. The transfer phenomena of the stress concentration associated with a crack opening process account for the nonlinearity of strain response in the vicinity of the crack tip. The delaying action of stress concentration at the crack tip is understood in conjunction with the concept of a critical stress (i.e. the stress required to open the closed crack behind the crack tip). A linear relationship between {Delta}{var_epsilon}{sub eff} and {Delta}K{sub eff} provides experimental support for the hypothesis that {Delta}K{sub eff} can be considered as the fatigue crack tip driving force.« less

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.

Deferoxamine synergistically enhances iron-mediated AP-1 activation: a showcase of the interplay between extracellular-signal-regulated kinase and tyrosine phosphatase.

PubMed

Huang, Xi; Dai, Jisen; Huang, Chuanshu; Zhang, Qi; Bhanot, Opinder; Pelle, Edward

2007-10-01

Deferoxamine (DFO) is a drug widely used for iron overload treatment to reduce body iron burden. In the present study, it was shown in mouse epidermal JB6 cells that all iron compounds transiently induced extracellular signal-regulated kinases (ERK) phosphorylation, whereas DFO further enhanced ERK phosphorylation over long periods. The ERK phosphorylation by DFO treatment appears to be due to the inhibition of MAPK phosphatases (MKP) by DFO. The combined effects of iron-initiated MAPK activation and DFO-mediated MKP inhibition resulted in a synergistic enhancement on AP-1 activities. The results indicate that the interplay between MAPK and MKP is important in regulating the extent of AP-1 activation. It is known that administration of DFO in iron overload patients often results in allergic responses at the injection sites. The results suggest that this synergistic AP-1 activation might play a role in DFO-induced skin immune responses of iron overload patients.

Beneficial effects of leptin treatment in a setting of cardiac dysfunction induced by transverse aortic constriction in mouse.

PubMed

Gómez-Hurtado, Nieves; Domínguez-Rodríguez, Alejandro; Mateo, Philippe; Fernández-Velasco, María; Val-Blasco, Almudena; Aizpún, Rafael; Sabourin, Jessica; Gómez, Ana María; Benitah, Jean-Pierre; Delgado, Carmen

2017-07-01

Leptin, is a 16 kDa pleiotropic peptide not only primarily secreted by adipocytes, but also produced by other tissues, including the heart. Controversy exists regarding the adverse and beneficial effects of leptin on the heart We analysed the effect of a non-hypertensive dose of leptin on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction. We find that leptin activates mechanisms that contribute to cardiac dysfunction under physiological conditions. However, after the establishment of pressure overload, an increase in leptin levels has protective cardiac effects with respect to rescuing the cellular heart failure phenotype. These beneficial effects of leptin involve restoration of action potential duration via normalization of transient outward potassium current and sarcoplasmic reticulum Ca 2+ content via rescue of control sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase levels and ryanodine receptor function modulation, leading to normalization of Ca 2+ handling parameters. Leptin, is a 16 kDa pleiotropic peptide not only primary secreted by adipocytes, but also produced by other tissues, including the heart. Evidence indicates that leptin may have either adverse or beneficial effects on the heart. To obtain further insights, in the present study, we analysed the effect of leptin treatment on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction (TAC). Three weeks after surgery, animals received either leptin (0.36 mg kg -1  day -1 ) or vehicle via osmotic minipumps for 3 weeks. Echocardiographic measurements showed that, although leptin treatment was deleterious on cardiac function in sham, leptin had a cardioprotective effect following TAC. [Ca 2+ ] i transient in cardiomyocytes followed similar pattern. Patch clamp experiments showed prolongation of action potential duration (APD) in TAC and leptin-treated sham animals, whereas, following TAC, leptin reduced the APD towards control values. APD variations were associated with decreased transient outward potassium current and Kv4.2 and KChIP2 protein expression. TAC myocytes showed a higher incidence of triggered activities and spontaneous Ca 2+ waves. These proarrhythmic manifestations, related to Ca 2+ /calmodulin-dependent protein kinase II and ryanodine receptor phosphorylation, were reduced by leptin. The results of the present study demonstrate that, although leptin treatment was deleterious on cardiac function in control animals, leptin had a cardioprotective effect following TAC, normalizing cardiac function and reducing arrhythmogeneity at the cellular level. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

An Investigation of the Effects of Different Types of Activities during Pauses in a Segmented Instructional Animation

ERIC Educational Resources Information Center

Cheon, Jongpil; Chung, Sungwon; Crooks, Steven M.; Song, Jaeki; Kim, Jeakyeong

2014-01-01

Since the complex and transient information in instructional animations requires more cognitive resources, the segmenting principle has been proposed to reduce cognitive overload by providing smaller chunks with pauses between segments. This study examined the effects of different types of activities during pauses in a segmented animation. Four…

The serine/threonine-protein kinase/endoribonuclease IRE1α protects the heart against pressure overload-induced heart failure.

PubMed

Steiger, DeAnna; Yokota, Tomohiro; Li, Jin; Ren, Shuxun; Minamisawa, Susumu; Wang, Yibin

2018-05-16

Heart failure is associated with induction of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). The serine/threonine protein kinase/endoribonuclease IRE1α is a key protein in ER stress signal transduction. IRE1α activity can induce both protective UPR and apoptotic downstream signaling events, but the specific role for IRE1α activity in the heart is unknown. A major aim of this study was to characterize the specific contribution of IRE1α in cardiac physiology and pathogenesis. We used both cultured myocytes and a transgenic mouse line with inducible and cardiomyocyte-specific IRE1α overexpression as experimental models to achieve targeted IRE1α activation. IRE1α expression induced a potent but transient ER stress response in cardiomyocytes and did not cause significant effects in the intact heart under normal physiological condition. Furthermore, the IRE1α-activated transgenic heart responding to pressure overload exhibited preserved function and reduced fibrotic area, associated with increased adaptive UPR signaling and with blunted inflammatory and pathological gene expression. Therefore, we conclude that IRE1α induces transient ER stress signaling and confers a protective effect against pressure overload-induced pathological remodeling in the heart. To our knowledge, this report provides first direct evidence of a specific and protective role for IRE1α in the heart and reveals an interaction between ER stress signaling and inflammatory regulation in the pathologically stressed heart. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Development and evaluation of a Fault-Tolerant Multiprocessor (FTMP) computer. Volume 2: FTMP software

NASA Technical Reports Server (NTRS)

Lala, J. H.; Smith, T. B., III

1983-01-01

The software developed for the Fault-Tolerant Multiprocessor (FTMP) is described. The FTMP executive is a timer-interrupt driven dispatcher that schedules iterative tasks which run at 3.125, 12.5, and 25 Hz. Major tasks which run under the executive include system configuration control, flight control, and display. The flight control task includes autopilot and autoland functions for a jet transport aircraft. System Displays include status displays of all hardware elements (processors, memories, I/O ports, buses), failure log displays showing transient and hard faults, and an autopilot display. All software is in a higher order language (AED, an ALGOL derivative). The executive is a fully distributed general purpose executive which automatically balances the load among available processor triads. Provisions for graceful performance degradation under processing overload are an integral part of the scheduling algorithms.

Inhibition of Transient Receptor Potential Channel Mucolipin-1 (TRPML1) by Lysosomal Adenosine Involved in Severe Combined Immunodeficiency Diseases*

PubMed Central

Zhong, Xi Zoë; Zou, Yuanjie; Sun, Xue; Dong, Gaofeng; Cao, Qi; Pandey, Aditya; Rainey, Jan K.; Zhu, Xiaojuan; Dong, Xian-Ping

2017-01-01

Impaired adenosine homeostasis has been associated with numerous human diseases. Lysosomes are referred to as the cellular recycling centers that generate adenosine by breaking down nucleic acids or ATP. Recent studies have suggested that lysosomal adenosine overload causes lysosome defects that phenocopy patients with mutations in transient receptor potential channel mucolipin-1 (TRPML1), a lysosomal Ca2+ channel, suggesting that lysosomal adenosine overload may impair TRPML1 and then lead to subsequent lysosomal dysfunction. In this study, we demonstrate that lysosomal adenosine is elevated by deleting adenosine deaminase (ADA), an enzyme responsible for adenosine degradation. We also show that lysosomal adenosine accumulation inhibits TRPML1, which is rescued by overexpressing ENT3, the adenosine transporter situated in the lysosome membrane. Moreover, ADA deficiency results in lysosome enlargement, alkalinization, and dysfunction. These are rescued by activating TRPML1. Importantly, ADA-deficient B-lymphocytes are more vulnerable to oxidative stress, and this was rescued by TRPML1 activation. Our data suggest that lysosomal adenosine accumulation impairs lysosome function by inhibiting TRPML1 and subsequently leads to cell death in B-lymphocytes. Activating TRPML1 could be a new therapeutic strategy for those diseases. PMID:28087698

A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease.

PubMed

Vichinsky, Elliott; Onyekwere, Onyinye; Porter, John; Swerdlow, Paul; Eckman, James; Lane, Peter; Files, Beatrice; Hassell, Kathryn; Kelly, Patrick; Wilson, Felicia; Bernaudin, Françoise; Forni, Gian Luca; Okpala, Iheanyi; Ressayre-Djaffer, Catherine; Alberti, Daniele; Holland, Jaymes; Marks, Peter; Fung, Ellen; Fischer, Roland; Mueller, Brigitta U; Coates, Thomas

2007-02-01

Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11.4%) and deferoxamine (11.1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.

Rotating electric machine with fluid supported parts

DOEpatents

Smith, Jr., Joseph L.; Kirtley, Jr., James L.

1981-01-01

A rotating electric machine in which the armature winding thereof and other parts are supported by a liquid to withstand the mechanical stresses applied during transient overloads and the like. In particular, a narrow gap is provided between the armature winding and the stator which supports it and this gap is filled with an externally pressurized viscous liquid. The liquid is externally pressurized sufficiently to balance the static loads on the armature winding. Transient mechanical loads which deform the armature winding alter the gap dimensions and thereby additionally pressurize the viscous liquid to oppose the armature winding deformation and more nearly uniformly to distribute the resulting mechanical stresses.

The interaction of transient receptor potential melastatin 7 with macrophages promotes vascular adventitial remodeling in transverse aortic constriction rats.

PubMed

Li, Yan; Jiang, Hui; Ruan, Chengchao; Zhong, Jiuchang; Gao, Pingjin; Zhu, Dingliang; Niu, Wenquan; Guo, Shujie

2014-01-01

Transient receptor potential melastatin 7 (TRPM7), a novel channel kinase, has been recently identified in the vasculature. However, its regulation and function in vascular diseases remain poorly understood. To address this lack of knowledge, we sought to examine whether TRPM7 can mediate the vascular remodeling process induced by pressure overload in the right common carotid artery proximal to the band (RCCA-B) in male Sprague-Dawley rats with transverse aortic constriction (TAC). The contribution of TRPM7 to amplified vascular remodeling after TAC was tested using morphometric and western blot analyses. Pressure overload-induced vascular wall thickening, especially in the adventitia, was readily detected in RCCA-B. The TRPM7 level was increased with a simultaneous accumulation of macrophages in the adventitia of RCCA-B, whereas the anti-inflammatory molecule annexin-1, a TRPM7 downstream target, was decreased. After the addition of the TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB), significant reductions in macrophage accumulation as well as the expression of monocyte chemotactic protein-1, SM-22-α and collagen I were observed, whereas annexin-1 was rescued. Finally, in cultured vascular adventitial fibroblasts treated with macrophage-conditioned medium, there were marked increases in the expression of TRPM7 and SM-22-α with a concurrent reduction in annexin-1 expression; these effects were largely prevented by treatment with 2-APB and specific anti-TRPM7 small interfering RNA. Our findings provide the first demonstration of the potential regulatory roles of TRPM7 in the vascular inflammation, pressure overload-mediated vascular adventitial collagen accumulation and cell phenotypic transformation in TAC rats. The targeting of TRPM7 has potential therapeutic importance for vascular diseases.

The paradox of transient worsening renal function in patients with acute heart failure: the role of B-type natriuretic peptide and diuretic response.

PubMed

Ruocco, Gaetano; Nuti, Ranuccio; Giambelluca, Amalia; Evangelista, Isabella; De Vivo, Oreste; Daniello, Cosimo; Palazzuoli, Alberto

2017-11-01

Worsening renal function (WRF) occurs in one-third of patients hospitalized for acute decompensated heart failure. Recently, WRF was categorized in two subtypes: persistent and transient WRF. Thus, we sought to investigate the different prognostic impact of persistent vs. transient WRF; we also evaluate the relation of two WRF phenotypes with congestion, B-type natriuretic peptide (BNP) changes, and diuretic response at discharge. The prospective was a single centre study including patients screened for interventional Diur-heart failure Trial (NCT01441245). Patients were eligible if they were admitted with a primary diagnosis of acute heart failure with evidence of volume overload. Persistent WRF was defined as a sustained creatinine increase by at least 0.3 mg/dl throughout the hospitalisation; transient WRF was defined as creatinine increase by at least 0.3 mg/dl within 72 h and a return to baseline levels at discharge. Patients were followed for 6 months after discharge. Our population included 192 acute decompensated heart failure patients. In total, 61 patients developed persistent WRF and 29 developed transient WRF. Patients with persistent WRF showed a lower mean urine output with respect to the transient WRF group and patients with preserved renal function (1618 ± 374 vs. 2132 ± 392 vs. 2075 ± 442 ml; P < 0.001). Similarly, patients with transient WRF demonstrated a higher rate of BNP decrease more than 30% than seen in patients with stable creatinine levels and in the persistent WRF group (95 vs. 76 vs. 54%; P = 0.001). Univariate Cox regression analysis demonstrated that BNP decrease less than 30% [HR 2.15 (1.40-3.40); P < 0.001] and persistent WRF [HR 1.70 (1.11-2.61); P = 0.01] were related to poor outcome; conversely, transient WRF should be considered as a protective factor [HR 0.42 (0.19-0.93); P = 0.03]. In the multivariable model, only persistent WRF appeared to be related to poor prognosis [HR 1.61 (1.02-2.57); P = 0.04]. WRF occurring during hospitalization has a different significance: transient deterioration appears to be associated with a favourable clinical course; conversely, persistent WRF is related to poor outcome.

A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease

PubMed Central

Vichinsky, Elliott; Onyekwere, Onyinye; Porter, John; Swerdlow, Paul; Eckman, James; Lane, Peter; Files, Beatrice; Hassell, Kathryn; Kelly, Patrick; Wilson, Felicia; Bernaudin, Françoise; Forni, Gian Luca; Okpala, Iheanyi; Ressayre-Djaffer, Catherine; Alberti, Daniele; Holland, Jaymes; Marks, Peter; Fung, Ellen; Fischer, Roland; Mueller, Brigitta U; Coates, Thomas

2007-01-01

Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11·4%) and deferoxamine (11·1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease. PMID:17233848

Enhanced ubiquitination of cytoskeletal proteins in pressure overloaded myocardium is accompanied by changes in specific E3 ligases.

PubMed

Balasubramanian, Sundaravadivel; Mani, Santhoshkumar; Shiraishi, Hirokazu; Johnston, Rebecca K; Yamane, Kentaro; Willey, Christopher D; Cooper, George; Tuxworth, William J; Kuppuswamy, Dhandapani

2006-10-01

Ubiquitin conjugation of proteins is critical for cell homeostasis and contributes to both cell survival and death. Here we studied ubiquitination of proteins in pressure overloaded (PO) myocardium in the context of cardiomyocyte survival. Analysis using a feline right ventricular pressure overload (RVPO) model revealed a robust and transient increase in ubiquitination of proteins present in the Triton X-100-insoluble fraction in 24 to 48 h PO myocardium, and confocal micrographs indicate this increase in ubiquitination occurs subsarcolemmaly near the intercalated disc area of cardiomyocytes. The ubiquitination was accompanied by changes in E3 ligases including Cbl, E6AP, Mdm2 and cIAP in the same period of PO, although atrophy-related E3 ligases, MuRF1 and MuRF3 were unaltered. Furthermore, Cbl displayed a substantial increase in both levels of expression and tyrosine phosphorylation in 48 h PO myocardium. Confocal studies revealed enrichment of Cbl at the intercalated discs of 48 h PO cardiomyocytes, as evidenced by its colocalization with N-cadherin. Although apoptosis was observed in 48 h PO myocardium by TUNEL staining, cardiomyocytes showing ubiquitin staining were not positive for TUNEL staining. Furthermore, 48 h PO resulted in the phosphorylation of inhibitor of nuclear factor kappa B (IkappaB), suggesting its ubiquitin-mediated degradation and the nuclear localization of NFkappaB for the expression of specific cell survival factors such as cIAPs. Together these data indicate that increased levels of E3 ligases that regulate cell homeostasis and promote cell survival could ubiquitinate multiple cytoskeletal protein targets and that these events that occur during the early phase of PO may contribute to both cardiomyocyte survival and hypertrophy.

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.

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.

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.

Echocardiographic evaluation of myocardial changes observed after closure of patent ductus arteriosus in dogs.

PubMed

Hamabe, L; Kim, S; Yoshiyuki, R; Fukayama, T; Nakata, T M; Fukushima, R; Tanaka, R

2015-01-01

Closure of PDA can be associated with echocardiographic changes including deterioration of LV systolic function. Although PDA is commonly encountered in dogs, few comprehensive reports of echocardiographic changes in dogs with PDA closure are available. To evaluate the short-term echocardiographic changes observed after PDA closure in dogs using strain analysis. Seventeen client-owned dogs with left-to-right PDA. Echocardiographic evaluations, including standard echocardiography and two-dimensional tissue tracking (2DTT), were performed before and within 3 days of PDA closure. Preclosure examination showed LV and left atrial dilatation indicating volume overload as a result of PDA. Closure of PDA resulted in significant reduction of LVIDd (<.0001) and LA/Ao (0.01) without change in LVIDs, suggestive of decreased preload. Postclosure LV systolic dysfunction was observed with significant decreased in FS (<.0001) and strain values (P = .0039 for radial strains, P = .0005 for circumferential strains). Additionally, significant LV dyssynchrony (P = .0162) was observed after closure of PDA. Closure of PDA resulted in decreased preload as a result of alleviation of LV volume overload, which in turn caused transient deterioration of LV systolic function. Additionally, this study demonstrated that strain analysis is load dependent. Therefore, care should be taken when interpreting strain measurements as an indicator of LV systolic function. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

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

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.

Foreign Object Impact Design Criteria. Volume 3

DTIC Science & Technology

1982-02-01

of turbine engine fan and compressor blading . The program will aid in the design of more efficient, damage-tolerant Iblading by replacing trial-and...sign criteria that account for the transient overloads produced by bird and ice impacts on turbine engine first-stage fan/compressor blades . This pro...3.81 cm (0.15 in.) thick was chosen as repre- sentative of medium-sized jet engine fan blades . The geometry is sh’wn ill Figure 19. The material

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

Deferiprone therapy for transfusional iron overload.

PubMed

Victor Hoffbrand, A

2005-06-01

Iron chelation is needed to prevent damage to the heart, liver and endocrine glands from iron overload in patients with refractory anaemias who receive regular blood transfusions. Desferrioxamine is still the first-line drug, but because of its expense in many countries, and lack of compliance because of difficulty with administration, there is a major need for an orally active (and cheaper) chelating drug. Seventeen years after the first clinical trials deferiprone, which is orally active, has emerged as suitable for patients for whom desferrioxamine is, for one reason or another, inadequate. Many patients are successfully chelated at a dose of deferiprone 75 mg/kg/day. Some patients may need higher doses (up to 100 mg/kg), or combination therapy of deferiprone every day and desferrioxamine on several days each week. Recent data suggest that deferiprone may be superior to desferrioxamine at protecting the heart from iron overload. The side-effects of deferiprone--agranulocytosis, neutropenia, gastrointestinal symptoms, arthropathy, transient changes in liver enzymes, and zinc deficiency--are now well recognized; they result in discontinuation of the drug in only 5-10% of patients. Deferiprone is now licensed in 43 countries for thalassaemia major patients for whom desferrioxamine is inadequate. If results of current trials confirm its superiority at reducing cardiac damage, it may well become the first-line drug for many patients.

The safety, tolerability, and efficacy of a liquid formulation of deferiprone in young children with transfusional iron overload.

PubMed

ElAlfy, Moshen S; El Alfy, Moshen; Sari, Teny Tjitra; Lee, Chan Lee; Tricta, Fernando; El-Beshlawy, Amal

2010-11-01

Limited data are available on the use of deferiprone in children younger than 10 years of age. This study evaluated the safety and efficacy of a new liquid formulation of deferiprone for the treatment of transfusional iron overload in children 1-10 years old. One hundred children (91 thalassemia major, 8 Hb E-β thalassemia, and 1 sickle cell disease) were enrolled for a 6-month treatment with deferiprone (50 to 100 mg/kg/d). The safety profile was similar to or better than that reported in earlier studies with deferiprone tablets in older children and adults. No unexpected adverse reactions were observed. Gastrointestinal intolerance (GI) was observed in 11% and an increased serum ALT in 12% of the children. Both events were transient. Mild neutropenia, observed in 6% of patients, did not progress to agranulocytosis and resolved despite continuous deferiprone treatment. Two patients experienced agranulocytosis that resolved without complications upon discontinuation of therapy. Deferiprone use was associated with a significant decline in mean serum ferritin level from 2532±1463 μg/L at baseline to 2176±1144 μg/L (P<0.0005). The results of this study show a favorable benefit/risk ratio of deferiprone oral solution for the treatment of young children with transfusional iron overload.

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.

The alkaloid matrine of the root of Sophora flavescens prevents arrhythmogenic effect of ouabain.

PubMed

Zhou, Yuhong; Wu, Yun; Deng, Lin; Chen, Lanlan; Zhao, Dandan; Lv, Lifang; Chen, Xu; Man, Jinyu; Wang, Yansong; Shan, Hongli; Lu, Yanjie

2014-06-15

Matrine, a alkaloid of the root of Sophora flavescens, has multiple protective effects on the cardiovascular system including cardiac arrhythmias. However, the molecular and ionic mechanisms of matrine have not been well investigated. Our study aimed at to shed a light on the issue to investigate the antiarrhythmic effects of matrine by using ouabain to construct an arrhythmic model of cardiomyocytes. In this experiment, matrine significantly and dose-dependently increased the doses of ouabain required to induce cardiac arrhythmias and decreased the duration of arrhythmias in guinea pigs. In cardiomyocytes of guinea pigs, ouabain 10 μM prolonged action potential duration by 80% (p<0.05) and increased L-type Ca(2+) currents and Ca(2+) transients induced by KCl (p<0.05). Matrine 100 μM shortened the prolongation of APD and prevented the increase of L-type Ca(2+) currents and Ca(2+) transients induced by ouabain. Taken together, these findings provide the first evidence that matrine possessed arrhythmogenic effect of ouabain by inhibiting of L-type Ca(2+) currents and Ca(2+) overload in guinea pigs. Copyright © 2014 Elsevier GmbH. All rights reserved.

Neck pain brought into focus.

PubMed

Richter, Hans O

2014-01-01

A time honored dictum states that the eyes "lead the body", i.e., that the body typically adjusts its position to compensate for an impoverished retinal image (e.g., as due to optical blur, and/or inappropriately sized visual target). But only moderate or low level of evidence exists in support of this view. Inconclusive evidence does not, however, equal negative evidence. The accommodation/vergence system does exhibit signs of overload in contemporary working life, including eye discomfort, transient myopia, altered pattern of eye-lens oscillations, and associated phoria. Accommodation/vergence overload, caused by non-ergonomic near work, may also emerge as quickly as within one regular workday. Long-term musculoskeletal consequences of high accommodation/vergence demands have nevertheless not yet been studied in any detail. A research agenda which aims to provide multi-scientific evidence for eye-neck/shoulder interactions with public health implications and which also, in addition, study the eye-neck/shoulder mechanisms and elucidates the operating characteristics, should consequently be highly warranted. This new knowledge would be useful for physiotherapists, ergonomists and opticians, who in their profession treat patients experiencing vision- and musculoskeletal disorders. If both visual and the musculoskeletal aspects are given full and equal weight in the design and evaluation of work places, it is predicted to lead to an improved quality of life for the individual worker, and an enhanced productivity for the employer.

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.

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.

Functional and geometrical interference and interdependency between the right and left ventricle in cor pulmonale: an experimental study on simultaneous measurement of biventricular geometry of acute right ventricular pressure overload.

PubMed

Yamashita, H; Onodera, S; Imamoto, T; Obara, A; Tanazawa, S; Takashio, T; Morimoto, H; Inoue, H

1989-10-01

To clarify the effects of right ventricular (RV) pressure overload on functional and geometrical interference and interdependency between the right and left ventricle, both ventricular internal diameters were measured by the microcrystal technique during lycopodium induced pulmonary embolization in the dog. By repeated embolization, RV systolic pressure was increased progressively until it reached a peak value of about 60-70 mmHg, then it began to fall. At the same time, the hemodynamics deteriorated progressively resulting in death. During the experiment, gradual leftward displacement of the interventricular septum (IVS) without any change in left ventricular (LV) free wall geometry was observed. In pulmonary embolic shock, which showed a fall in LV pressure to about 60 mmHg and cardiac output to about 40% of control, the leftward displacement of IVS became marked, and the cooperative movement of IVS to LV contraction disappeared. The IVS position during acute RV pressure overload was able to account for the transseptal pressure gradient. The importance of IVS position and motion in cardiac function during acute RV pressure overload was stressed. Furthermore, to establish the theoretical treatment in acute cardiopulmonary resuscitation, ligation of the descending aorta (AoL) or norepinephrine ("N") or isoproterenol ("I") administration were examined in a canine pulmonary embolic shock model. AoL or "N" improved the deteriorated hemodynamics with restoration of biventricular geometry. However, "I" did not restore the biventricular geometry despite the transiently improved hemodynamics, and the experimental animals were unable to survive. These results suggest the importance of the maintainance of systemic pressure for the restoration of failed RV function. Further integrated studies are required to understand biventricular interference and interdependency.

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.

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.

Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart.

PubMed

Abdul-Ghani, Mohammad; Suen, Colin; Jiang, Baohua; Deng, Yupu; Weldrick, Jonathan J; Putinski, Charis; Brunette, Steve; Fernando, Pasan; Lee, Tom T; Flynn, Peter; Leenen, Frans H H; Burgon, Patrick G; Stewart, Duncan J; Megeney, Lynn A

2017-10-01

The post-natal heart adapts to stress and overload through hypertrophic growth, a process that may be pathologic or beneficial (physiologic hypertrophy). Physiologic hypertrophy improves cardiac performance in both healthy and diseased individuals, yet the mechanisms that propagate this favorable adaptation remain poorly defined. We identify the cytokine cardiotrophin 1 (CT1) as a factor capable of recapitulating the key features of physiologic growth of the heart including transient and reversible hypertrophy of the myocardium, and stimulation of cardiomyocyte-derived angiogenic signals leading to increased vascularity. The capacity of CT1 to induce physiologic hypertrophy originates from a CK2-mediated restraining of caspase activation, preventing the transition to unrestrained pathologic growth. Exogenous CT1 protein delivery attenuated pathology and restored contractile function in a severe model of right heart failure, suggesting a novel treatment option for this intractable cardiac disease.

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.

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.

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.

Self organized spatio-temporal structure within the fractured Vadose Zone: The influence of dynamic overloading at fracture intersections

NASA Astrophysics Data System (ADS)

LaViolette, Randall A.; Glass, Robert J.

2004-09-01

Under low flow conditions (where gravity and capillary forces dominate) within an unsaturated fracture network, fracture intersections act as capillary barriers to integrate flow from above and then release it as a pulse below. Water exiting a fracture intersection is often thought to enter the single connected fracture with the lowest invasion pressure. When the accumulated volume varies between intersections, the smaller volume intersections can be overloaded to cause all of the available fractures exiting an intersection to flow. We included the dynamic overloading process at fracture intersections within our previously discussed model where intersections were modeled as tipping buckets connected within a two-dimensional diamond lattice. With dynamic overloading, the flow behavior transitioned smoothly from diverging to converging flow with increasing overload parameter, as a consequence of a heterogeneous field, and they impose a dynamic structure where additional pathways activate or deactivate in time.

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.

Prevention of ventricular arrhythmia and calcium dysregulation in a catecholaminergic polymorphic ventricular tachycardia mouse model carrying calsequestrin-2 mutation.

PubMed

Alcalai, Ronny; Wakimoto, Hiroko; Arad, Michael; Planer, David; Konno, Tetsuo; Wang, Libin; Seidman, Jon G; Seidman, Christine E; Berul, Charles I

2011-03-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca(2+) overload and increased Ca(2+) leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. CPVT mouse models that lack CASQ2 were treated with Ca(2+) -channel inhibitors, β-adrenergic inhibitors, or Mg(2+) . Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca(2+) transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca(2+) channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca(2+) content in mutant myocytes, diminished diastolic Ca(2+) overload, increased systolic Ca(2+) amplitude, and prevented Ca(2+) oscillations in stressed mutant myocytes. Ca(2+) channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca(2+) content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca(2+) buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT. © 2010 Wiley Periodicals, Inc.

Prevention of Ventricular Arrhythmia and Calcium Dysregulation in a Catecholaminergic Polymorphic Ventricular Tachycardia Mouse Model Carrying Calsequestrin-2 Mutation

PubMed Central

Alcalai, Ronny; Wakimoto, Hiroko; Arad, Michael; Planer, David; Konno, Tetsuo; Wang, Libin; Seidman, Jon G.; Seidman, Christine E.; Berul, Charles I

2010-01-01

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca2+ overload and increased Ca2+ leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. Method and results CPVT mouse models that lack CASQ2 were treated with Ca2+-channel inhibitors, β-adrenergic inhibitors, or Mg2+. Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca2+ transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca2+ channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca2+ content in mutant myocytes, diminished diastolic Ca2+ overload, increased systolic Ca2+ amplitude, and prevented Ca2+ oscillations in stressed mutant myocytes. Conclusions Ca2+ channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca2+ content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca2+ buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT. PMID:20807279

Control Design Strategies to Enhance Long-Term Aircraft Structural Integrity

NASA Technical Reports Server (NTRS)

Newman, Brett A.

1999-01-01

Over the operational lifetime of both military and civil aircraft, structural components are exposed to hundreds of thousands of low-stress repetitive load cycles and less frequent but higher-stress transient loads originating from maneuvering flight and atmospheric gusts. Micro-material imperfections in the structure, such as cracks and debonded laminates, expand and grow in this environment, reducing the structural integrity and shortening the life of the airframe. Extreme costs associated with refurbishment of critical load-bearing structural components in a large fleet, or altogether reinventoring the fleet with newer models, indicate alternative solutions for life extension of the airframe structure are highly desirable. Increased levels of operational safety and reliability are also important factors influencing the desirability of such solutions. One area having significant potential for impacting crack growth/fatigue damage reduction and structural life extension is flight control. To modify the airframe response dynamics arising from command inputs and gust disturbances, feedback loops are routinely applied to vehicles. A dexterous flight control system architecture senses key vehicle motions and generates critical forces/moments at multiple points distributed throughout the airframe to elicit the desired motion characteristics. In principle, these same control loops can be utilized to influence the level of exposure to harmful loads during flight on structural components. Project objectives are to investigate and/or assess the leverage control has on reducing fatigue damage and enhancing long-term structural integrity, without degrading attitude control and trajectory guidance performance levels. In particular, efforts have focused on the effects inner loop control parameters and architectures have on fatigue damage rate. To complete this research, an actively controlled flexible aircraft model and a new state space modeling procedure for crack growth have been utilized. Analysis of the analytical state space model for crack growth revealed the critical mathematical factors, and hence the physical mechanism they represent, that influenced high rates of airframe crack growth. The crack model was then exercised with simple load inputs to uncover and expose key crack growth behavior. To characterize crack growth behavior, both "short-term" laboratory specimen test type inputs and "long-term" operational flight type inputs were considered. Harmonic loading with a single overload revealed typical exponential crack growth behavior until the overload application, after which time the crack growth was retarded for a period of time depending on the overload strength. An optimum overload strength was identified which leads to maximum retardation of crack growth. Harmonic loading with a repeated overload of varying strength and frequency again revealed an optimum overload trait for maximizing growth retardation. The optimum overload strength ratio lies near the range of 2 to 3 with dependency on frequency. Experimental data was found to correlate well with the analytical predictions.

Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

PubMed

Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

2015-03-01

A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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

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.

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.

Estimation of metallic structure durability for a known law of stress variation

NASA Astrophysics Data System (ADS)

Mironov, V. I.; Lukashuk, O. A.; Ogorelkov, D. A.

2017-12-01

Overload of machines working in transient operational modes leads to such stresses in their bearing metallic structures that considerably exceed the endurance limit. The estimation of fatigue damages based on linear summation offers a more accurate prediction in terms of machine durability. The paper presents an alternative approach to the estimation of the factors of the cyclic degradation of a material. Free damped vibrations of the bridge girder of an overhead crane, which follow a known logarithmical decrement, are studied. It is shown that taking into account cyclic degradation substantially decreases the durability estimated for a product.

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

Ca2+ Overload and Sarcoplasmic Reticulum Instability in tric-a Null Skeletal Muscle*

PubMed Central

Zhao, Xiaoli; Yamazaki, Daiju; Park, Ki Ho; Komazaki, Shinji; Tjondrokoesoemo, Andoria; Nishi, Miyuki; Lin, Peihui; Hirata, Yutaka; Brotto, Marco; Takeshima, Hiroshi; Ma, Jianjie

2010-01-01

The sarcoplasmic reticulum (SR) of skeletal muscle contains K+, Cl−, and H+ channels may facilitate charge neutralization during Ca2+ release. Our recent studies have identified trimeric intracellular cation (TRIC) channels on SR as an essential counter-ion permeability pathway associated with rapid Ca2+ release from intracellular stores. Skeletal muscle contains TRIC-A and TRIC-B isoforms as predominant and minor components, respectively. Here we test the physiological function of TRIC-A in skeletal muscle. Biochemical assay revealed abundant expression of TRIC-A relative to the skeletal muscle ryanodine receptor with a molar ratio of TRIC-A/ryanodine receptor ∼5:1. Electron microscopy with the tric-a−/− skeletal muscle showed Ca2+ overload inside the SR with frequent formation of Ca2+ deposits compared with the wild type muscle. This elevated SR Ca2+ pool in the tric-a−/− muscle could be released by caffeine, whereas the elemental Ca2+ release events, e.g. osmotic stress-induced Ca2+ spark activities, were significantly reduced likely reflecting compromised counter-ion movement across the SR. Ex vivo physiological test identified the appearance of “alternan” behavior with isolated tric-a−/− skeletal muscle, i.e. transient and drastic increase in contractile force appeared within the decreasing force profile during repetitive fatigue stimulation. Inhibition of SR/endoplasmic reticulum Ca2+ ATPase function could lead to aggravation of the stress-induced alternans in the tric-a−/− muscle. Our data suggests that absence of TRIC-A may lead to Ca2+ overload in SR, which in combination with the reduced counter-ion movement may lead to instability of Ca2+ movement across the SR membrane. The observed alternan behavior with the tric-a−/− muscle may reflect a skeletal muscle version of store overload-induced Ca2+ release that has been reported in the cardiac muscle under stress conditions. PMID:20858894

Optimizing therapy for iron overload in the myelodysplastic syndromes: recent developments.

PubMed

Leitch, Heather A

2011-01-22

The myelodysplastic syndromes (MDS) are characterized by cytopenias and risk of progression to acute myeloid leukaemia (AML). Most MDS patients eventually require transfusion of red blood cells for anaemia, placing them at risk of transfusional iron overload. In β-thalassaemia major, transfusional iron overload leads to organ dysfunction and death; however, with iron chelation therapy, organ function is improved, and survival improved to near normal and correlated with the degree of compliance with chelation. In lower-risk MDS, several nonrandomized studies suggest an adverse effect of iron overload on survival and that lowering iron with chelation may minimize this impact. Emerging data indicate that chelation may improve organ function, particularly hepatic function, and a minority of patients may have improvement in cell counts and decreased transfusion requirements. While guidelines for MDS generally recommend chelation in selected lower-risk patients, data from nonrandomized trials suggest iron overload may impact adversely on the outcome of higher-risk MDS and stem cell transplantation (SCT). This effect may be due to increased transplant-related mortality, infection and AML progression, and preliminary data suggest that lowering iron may be beneficial in this patient group. Other areas of active and future investigation include optimizing the monitoring of iron overload using imaging such as T2* MRI and measures of labile iron and oxidative stress; correlating new methods of measuring iron to clinical outcomes; clarifying the contribution of different cellular and extracellular iron pools to iron toxicity; optimizing chelation by using agents that access the appropriate iron pools to minimize the relevant clinical consequences in individual patients; and incorporating measures of quality of life and co-morbidities into clinical trials of chelation in MDS. It should be noted that chelation is costly and potentially toxic, and in MDS should be initiated after weighing potential risks and benefits for each patient until more definitive data are available. In this review, data on the impact of iron overload in MDS and SCT are discussed; for example, several noncontrolled studies show inferior survival in patients with iron overload in these clinical settings, including an increase in transplant-related mortality and infection risk. Possible mechanisms of iron toxicity include oxidative stress, which can damage cellular components, and the documented impact of lowering iron on organ function with measures such as iron chelation therapy includes an improvement in elevated liver transaminases. Lowering iron also appears to improve survival in both lower-risk MDS and SCT in nonrandomized studies. Selected aspects of iron metabolism, transport, storage and distribution that may be amenable to future intervention and improved removal of iron from important cellular sites are discussed, as are attempts to quantify quality of life and the importance of co-morbidities in measures to treat MDS, including chelation therapy.

Overload, autonomy, and burnout as predictors of physicians' quality of care.

PubMed

Shirom, Arie; Nirel, Nurit; Vinokur, Amiram D

2006-10-01

A model in which perceived overload and burnout mediated the relations of workload and autonomy with physicians' quality of care to their patients was examined. The study was based on data from 890 specialists representing six medical specialties. Including global burnout as well as its three first-order facets of physical fatigue, cognitive weariness, and emotional exhaustion improved the fit between the structural model and the data relative to an alternative model that included only global burnout. Workload (number of work hours) indirectly predicted quality of care through perceived overload. Additionally, the authors found that the paths from the first order factors of emotional exhaustion, physical fatigue, and cognitive weariness predicted quality of care negatively, positively, and nonsignificantly, respectively.

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

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.

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.

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.

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.

“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.

Acetylcholine Attenuates Hydrogen Peroxide-Induced Intracellular Calcium Dyshomeostasis Through Both Muscarinic and Nicotinic Receptors in Cardiomyocytes.

PubMed

Palee, Siripong; Apaijai, Nattayaporn; Shinlapawittayatorn, Krekwit; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2016-01-01

Oxidative stress induced intracellular Ca2+ overload plays an important role in the pathophysiology of several heart diseases. Acetylcholine (ACh) has been shown to suppress reactive oxygen species generation during oxidative stress. However, there is little information regarding the effects of ACh on the intracellular Ca2+ regulation in the presence of oxidative stress. Therefore, we investigated the effects of ACh applied before or after hydrogen peroxide (H2O2) treatment on the intracellular Ca2+ regulation in isolated cardiomyocytes. Single ventricular myocytes were isolated from the male Wistar rats for the intracellular Ca2+ transient study by a fluorimetric ratio technique. H2O2 significantly decreased both of intracellular Ca2+ transient amplitude and decay rate. ACh applied before, but not after, H2O2 treatment attenuated the reduction of intracellular Ca2+ transient amplitude and decay rate. Both atropine (a muscarinic acetylcholine receptor blocker) and mecamylamine (a nicotinic acetylcholine receptor blocker) significantly decreased the protective effects of acetylcholine on the intracellular Ca2+ regulation. Moreover, the combination of atropine and mecamylamine completely abolished the protective effects of acetylcholine on intracellular Ca2+ transient amplitude and decay rate. ACh pretreatment attenuates H2O2-induced intracellular Ca2+ dyshomeostasis through both muscarinic and nicotinic receptors. © 2016 The Author(s) Published by S. Karger AG, Basel.

The "Tyranny of Choice": Choice Overload as a Possible Instance of Effort Discounting

ERIC Educational Resources Information Center

Reed, Derek D.; Reed, Florence D. DiGennaro; Chok, James; Brozyna, Gary A.

2011-01-01

When making a choice, people like to have options, but an emerging literature on "choice overload" suggests that the provision of too many options results in adverse experiences, including a depletion of cognitive resources and postdecision feelings of regret. A strong implication is that individuals should shy away from situations…

Rapid ionic modifications during the aequorin-detected calcium transient in a skinned canine cardiac Purkinje cell

PubMed Central

1985-01-01

A microprocessor-controlled system of microinjections and microaspirations has been developed to change, within approximately 1 ms, the [free Ca2+] at the outer surface of the sarcoplasmic reticulum (SR) wrapped around individual myofibrils (0.3-0.4 micron radius) of a skinned canine cardiac Purkinje cell (2.5-4.5 micron overall radius) at different phases of a Ca2+ transient. Simultaneously monitoring tension and aequorin bioluminescence provided two methods for estimating the peak myoplasmic [free Ca2+] reached during the spontaneous cyclic Ca2+ release from the SR obtained in the continuous presence of a bulk solution [free Ca2+] sufficiently high to overload the SR. These methods gave results in excellent agreement for the spontaneous Ca2+ release under a variety of conditions of pH and [free Mg2+], and of enhancement of Ca2+ release by calmodulin. Disagreement was observed, however, when the Ca2+ transient was modified during its ascending phase. The experiments also permitted quantification of the aequorin binding within the myofibrils and determination of its operational apparent affinity constant for Ca2+ at various [free Mg2+] levels. An increase of [free Ca2+] at the outer surface of the SR during the ascending phase of the Ca2+ transient induced further release of Ca2+. In contrast, an increase of [free Ca2+] during the descending phase of the Ca2+ transient did not cause further Ca2+ release. Varying [free H+], [free Mg2+], or the [Na+]/[K+] ratio had no significant effect on the Ca2+ transient during which the modification was applied, but it altered the subsequent Ca2+ transient. Therefore, Ca2+ appears to be the major, if not the only, ion controlling Ca2+ release from the SR rapidly enough to alter a Ca2+ transient during its course. PMID:3981128

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.

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.

Coinheritance of hereditary spherocytosis and reversibility of cirrhosis in a young female patient with hereditary hemochromatosis.

PubMed

Höblinger, A; Erdmann, C; Strassburg, C P; Sauerbruch, T; Lammert, F

2009-04-16

Here we report a 33-years-old woman with hereditary spherocytosis and hemochromatosis due to homozygosity for the C282Y mutation of the HFE gene. The coinheritance of both conditions led to severe iron overload and liver cirrhosis at young age. The patient was treated by repeated phlebotomy, and reversibility of cirrhosis was documented by transient elastography. This report discusses the pathophysiology of iron accumulation in patients with hemolytic anemia combined with HFE C282Y homozygosity. The case indicates that patients with hematological disorders characterized by increased erythropoetic activity should be screened for HFE mutations.

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

Deferasirox in patients with iron overload secondary to hereditary hemochromatosis: results of a 1-yr Phase 2 study.

PubMed

Cançado, Rodolfo; Melo, Murilo R; de Moraes Bastos, Roberto; Santos, Paulo C J L; Guerra-Shinohara, Elivira M; Chiattone, Carlos; Ballas, Samir K

2015-12-01

This open-label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12-month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P < 0.001), mean transferrin saturation (P < 0.05), median liver iron concentration (P < 0.001), and mean alanine aminotransferase (P < 0.05). The median time to achieve serum ferritin reduction ≥50% compared to baseline was 7.53 months. The most common adverse events were mild, transient diarrhea (n = 5) and nausea (n = 2). No patient experienced an increase in serum creatinine that exceeded the upper limit of normal. These data confirm that deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

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.

Thrombogenic potential of transcatheter aortic valve implantation with trivial paravalvular leakage

PubMed Central

Siegel, Rolland

2014-01-01

Background Significant paravalvular leakage after transcatheter aortic valve implantation (TAVI) correlates with increased morbidity and mortality, but adverse consequences of trivial paravalvular leakage have stimulated few investigations. Using a unique method distinctly different from other diagnostic approaches, we previously reported elevated backflow velocities of short duration (transients) in mechanical valve closure. In this study, similar transients were found in a transcatheter valve paravalvular leakage avatar. Methods Paravalvular leakage rate (zero to 58 mL/second) and aortic valve incompetence (volumetric back flow/forward flow; zero to 32%) were made adjustable using a mock transcatheter aortic valve device and tested in quasi-steady and pulsatile flow test systems. Projected dynamic valve area (PDVA) from the back illuminated mock transcatheter aortic valve device was measured and regional backflow velocities were derived by dividing volumetric flow rate by the PDVA over the open and closing valve phase and the total closed valve area derived from backflow leakage. Results Aortic incompetence from 1-32% generated negative backflow transients from 8 to 267 meters/second, a range not dissimilar to that measured in mechanical valves with zero paravalvular leakage. Optimal paravalvular leakage was identified; not too small generating high backflow transients, not too large considering volume overload and cardiac energy loss caused by defective valve behavior and fluid motion. Conclusions Thrombogenic potential of transcatheter aortic valves with trivial aortic incompetence and high magnitude regional backflow velocity transients was comparable to mechanical valves. This may have relevance to stroke rate, asymptomatic microembolic episodes and indications for anticoagulation therapy after transcatheter valve insertion. PMID:25333018

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.

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.

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.

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.

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

PubMed

Salerno, Silvana

2018-02-01

In Italy and in Europe occupational diseases (OD) claims are growing among women, and international studies show women's lower compensation rate. Analysis of occupational diseases compensation rate among "Italian" women (country of birth: Italy) and "immigrant" women (country of birth: not Italy) focusing on biomechanical overload of the upper limb, the most common OD in Italy. INAIL (Italian National Institute for Insurance against Accidents at Work) statistical data (2010-2013) on ascertained OD in Industry-Services (I-S) were analyzed by gender and country of birth with particular attention to biomechanical overload of the upper limb and to occupational diseases not included in the official OD list. A significantly lower compensation rate was found among women (Italy: 39% females vs 43% males; not Italy: 32.5% females vs 36% males). Women's lower success rate was also found for biomechanical overload of the upper limb (Italy: 73% females vs 76% males; not Italy: 64% females vs 70% males), including carpal tunnel syndrome (Italy: 72% females vs 74% males; not Italy: 62% females vs 64% males) and supraspinatus muscle tendinitis (Italy: 71% females vs 79% males; not Italy: 62.5% females vs 72.5% males). Women's claims were more frequent for OD not in the official list (Italy: 53% females vs 51% males; not Italy: 54% females vs 53% males) and had a lower rate of recognition and compensation (Italy: 13% females vs 19% males; not Italy 10% females vs 14% males). Since 2010 women compensation rate has shown a reduction after the initial amelioration in 2008 when biomechanical overload of the upper limb was included in the official list of OD. An overall lower compensation rate among "Italian" and "immigrant" women was found for biomechanical overload disorders of the upper limb and for not officially recognized occupational diseases. Good gender-oriented preventive practices should be promoted.

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.

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.

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.

The association between role overload and women's mental health.

PubMed

Glynn, Keva; Maclean, Heather; Forte, Tonia; Cohen, Marsha

2009-02-01

To determine the importance of role overload (the extent to which a person feels overwhelmed by her total responsibilities) relative to other known social determinants of women's mental health. A Canadian national, random sample, cross-sectional telephone survey in 2003 assessed the association among role overload, types and quality of roles (parent, employee, spouse), sociodemographics, and mental health (using the SF-12) using linear regression. Analysis included 716 women aged 25-54 who indicated that their youngest child living in the household was aged < or =17 years. Perceptions of greater role overload were associated with poorer mental health (p < 0.0001). Women working <35 hours per week (p = 0.04) or 35-40 hours per week (p 5 0.002) reported better mental health than nonemployed women, as did women with the highest annual household income ($70,000+)(p = 0.001). Also associated with better mental health were higher marital status quality scores for both married and single women (p < 0.001), higher job quality scores among employed women (p = 0.02), greater homemaking quality scores among unemployed women (p = 0.03), and women reporting high parental quality (p = 0.04) Role overload showed a stronger relationship to mental health than other sociodemographic variables, including income. Our findings indicate the importance of measuring women's experience of their multiple roles rather than focusing on single roles. More research is warranted on the totality of women's experiences of their many social role obligations.

Mechanisms of pro-arrhythmic abnormalities in ventricular repolarisation and anti-arrhythmic therapies in human hypertrophic cardiomyopathy.

PubMed

Passini, Elisa; Mincholé, Ana; Coppini, Raffaele; Cerbai, Elisabetta; Rodriguez, Blanca; Severi, Stefano; Bueno-Orovio, Alfonso

2016-07-01

Hypertrophic cardiomyopathy (HCM) is a cause of sudden arrhythmic death, but the understanding of its pro-arrhythmic mechanisms and an effective pharmacological treatment are lacking. HCM electrophysiological remodelling includes both increased inward and reduced outward currents, but their role in promoting repolarisation abnormalities remains unknown. The goal of this study is to identify key ionic mechanisms driving repolarisation abnormalities in human HCM, and to evaluate anti-arrhythmic effects of single and multichannel inward current blocks. Experimental ionic current, action potential (AP) and Ca(2+)-transient (CaT) recordings were used to construct populations of human non-diseased and HCM AP models (n=9118), accounting for inter-subject variability. Simulations were conducted for several degrees of selective and combined inward current block. Simulated HCM cardiomyocytes exhibited prolonged AP and CaT, diastolic Ca(2+) overload and decreased CaT amplitude, in agreement with experiments. Repolarisation abnormalities in HCM models were consistently driven by L-type Ca(2+) current (ICaL) re-activation, and ICaL block was the most effective intervention to normalise repolarisation and diastolic Ca(2+), but compromised CaT amplitude. Late Na(+) current (INaL) block partially abolished repolarisation abnormalities, with small impact on CaT. Na(+)/Ca(2+) exchanger (INCX) block effectively restored repolarisation and CaT amplitude, but increased Ca(2+) overload. Multichannel block increased efficacy in normalising repolarisation, AP biomarkers and CaT amplitude compared to selective block. Experimentally-calibrated populations of human AP models identify ICaL re-activation as the key mechanism for repolarisation abnormalities in HCM, and combined INCX, INaL and ICaL block as effective anti-arrhythmic therapies also able to partially reverse the HCM electrophysiological phenotype. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Elbow arthroscopy: valgus extension overload.

PubMed

Ahmad, Christopher S; Conway, John E

2011-01-01

Valgus torque combined with deceleration produces high compression and shear forces acting on the posteromedial olecranon and the posteromedial trochlea. This valgus extension overload process may cause posteromedial trochlea chondromalacia, chondral flap formation, osteochondrosis, subchondral erosion, a subchondral insufficiency fracture, and marginal exostosis formation. Olecranon pathologies include proximal stress reaction, a posteromedial tip stress fracture, a transverse proximal process stress fracture, exostosis formation, exostosis fragmentation, and intra-articular loose bodies. Symptoms include posteromedial elbow pain during the deceleration phase of the throwing motion. The extension impingement test reproduces posterior or posteromedial pain similar to that experienced while throwing. Special radiographic techniques and CT scans can show loose bodies and osteophyte fragmentation. Surgical treatment is indicated when symptoms persist despite nonsurgical management. Based on clinical and basic science research, all patients with valgus extension overload should be comprehensively evaluated for medial ulnar collateral ligament insufficiency. Surgical treatment is limited to the resection of osteophytes only; normal olecranon should not be resected.

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).

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 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.

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

Valgus extension overload syndrome and stress injury of the olecranon.

PubMed

Ahmad, Christopher S; ElAttrache, Neal S

2004-10-01

Basic science studies have improved our understanding of the pathomechanics for valgus extension overload and olecranon stress fractures. These disorders result from repetitive abutment of the olecranon into the olecranon fossa combined with valgus torques, resulting in impaction and shear along the posteromedial olecranon. The patient history and physical examination are similar for each disorder. Imaging studies including plain radiographs, computed tomography, MRI or bone scan may be necessary for accurate diagnosis. Clinical and basic science support mandatory and careful assessment of the medial collateral ligament when valgus extension overload is identified and limited debridement of the olecranon when surgery is indicated. For stress fractures that fail nonoperative management, treatment with internal fixation provides good results.

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.

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.

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.

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.

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.

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

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.

Data assimilation of surface altimetry on the North-Easter Ice Stream using the Ice Sheet System Model (ISSM)

NASA Astrophysics Data System (ADS)

Larour, Eric; Utke, Jean; Morlighem, Mathieu; Seroussi, Helene; Csatho, Beata; Schenk, Anton; Rignot, Eric; Khazendar, Ala

2014-05-01

Extensive surface altimetry data has been collected on polar ice sheets over the past decades, following missions such as Envisat and IceSat. This data record will further increase in size with the new CryoSat mission, the ongoing Operation IceBridge Mission and the soon to launch IceSat-2 mission. In order to make the best use of these dataset, ice flow models need to improve on the way they ingest surface altimetry to infer: 1) parameterizations of poorly known physical processes such as basal friction; 2) boundary conditions such as Surface Mass Balance (SMB). Ad-hoc sensitivity studies and adjoint-based inversions have so far been the way ice sheet models have attempted to resolve the impact of 1) on their results. As for boundary conditions or the lack thereof, most studies assume that they are a fixed quantity, which, though prone to large errors from the measurement itself, is not varied according to the simulated results. Here, we propose a method based on automatic differentiation to improve boundary conditions at the base and surface of the ice sheet during a short-term transient run for which surface altimetry observations are available. The method relies on minimizing a cost-function, the best fit between modeled surface evolution and surface altimetry observations, using gradients that are computed for each time step from automatic differentiation of the ISSM (Ice Sheet System Model) code. The approach relies on overloaded operators using the ADOLC (Automatic Differentiation by OverLoading in C++) package. It is applied to the 79 North Glacier, Greenland, for a short term transient spanning a couple of decades before the start of the retreat of the Zachariae Isstrom outlet glacier. Our results show adjustments required on the basal friction and the SMB of the whole basin to best fit surface altimetry observations, along with sensitivities each one of these parameters has on the overall cost function. Our approach presents a pathway towards assimilating multiple datasets in transient ice flow models of Greenland and Antarctica, which will become increasingly important as the amount of available observations becomes too large to assess on a case by case basis. This work was performed at the California Institute of Technology's Jet Propulsion Laboratory under a contract with the National Aeronautics and Space Administration's Cryosphere Science Program.

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

Maternity leave, women's employment, and marital incompatibility.

PubMed

Hyde, J S; Essex, M J; Clark, R; Klein, M H

2001-09-01

This research investigated the relationship between the length of women's maternity leave and marital incompatibility, in the context of other variables including the woman's employment, her dissatisfaction with the division of household labor, and her sense of role overload. Length of leave, work hours, and family salience were associated with several forms of dissatisfaction, which in turn predicted role overload. Role overload predicted increased marital incompatibility for experienced mothers but did not for first-time mothers, for whom discrepancies between preferred and actual child care were more important. Length of maternity leave showed significant interactions with other variables, supporting the hypothesis that a short leave is a risk factor that, when combined with another risk factor, contributes to personal and marital distress.

Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis.

PubMed

Pirdel, Leila; Pirdel, Manijeh

2014-06-01

This article presents an overview of the involvement of iron overload-induced nitric oxide (NO) overproduction in apoptosis of peritoneal macrophages of women with endometriosis. We have postulated that the peritoneal iron overload originated from retrograde menstruation or bleeding lesions in the ectopic endometrium, which may contribute to the development of endometriosis by a wide range of mechanisms, including oxidative damage and chronic inflammation. Excessive NO production may also be associated with impaired clearance of endometrial cells by macrophages, which promotes cell growth in the peritoneal cavity. Therefore, further research of the mechanisms and consequences of macrophage apoptosis in endometriosis helps discover novel therapeutic strategies that are designed to prevent progression of endometriosis. © 2014 Society for Reproduction and Fertility.

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.

Infections in myelodysplastic syndromes

PubMed Central

Toma, Andréa; Fenaux, Pierre; Dreyfus, François; Cordonnier, Catherine

2012-01-01

Myelodysplastic syndromes are associated with a risk of severe infections. While neutropenia is likely to be the main predisposing factor, several other immune defects have been reported, including impaired neutrophil function, B-, T- and NK-cell defects and the possible consequences of iron overload due to red blood cell transfusions. The advanced age of most patients, their frequent comorbidities, and the fact that drugs such as hypomethylating agents and lenalidomide, which are effective in myelodysplastic syndromes but can transiently worsen neutropenia, may increase the risk of infection and their severity in this context. The majority of infections in myelodysplastic syndromes are bacterial, while the incidence of fungal infections is not well known and viral infections seem to be rare. No prophylactic measures against infections have demonstrated efficacy in myelodysplastic syndromes. However, pending more data, we propose here some recommendations for the management of patients with myelodysplastic syndromes. In the future, an important contribution can be made by prospective trials testing the efficacy of prophylactic and therapeutic approaches to infection in these patients, especially in the context of the new drugs available for myelodysplastic syndromes. PMID:22733024

Effects of load and thermal histories on mechanical behavior of materials; Proceedings of the Symposium, Denver, CO, Feb. 25, 26, 1987

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

Liaw, P.K.; Nicholas, T.

This volume includes topics on fatigue crack propagation; isothermal and thermal-mechanical fatigue; and microstructure, fracture, and damage. Papers are presented on transients in fatigue crack growth, elevated-temperature fatigue crack propagation, the role of crack closure in crack retardation in P/M and I/M aluminum alloys, the acoustic interrogation of fatigue overload effects, and the effects of frequency and environment on crack growth in Inconel 718. Special attention is given to isothermal fatigue failure mechanisms in low-tin lead-based solder, the stress and strain controlled low-cycle fatigue of Pb-Sn solder for electronic packaging applications, load sequence effects on the deformation of isolated microplasticmore » grains, and thermal fatigue of stainless steel. Other papers are on the influence of thermal aging on the creep crack growth behavior of a Cr-Mo steel, the effect of cyclic loading on the fracture toughness of a modified 4340 steel, and the effects of hot rolling condition and boron microalloying on phase transformation and microstructure in niobium-bearing interstitial free steel.« less

Overload effect and fatigue crack propagation in amorphous metallic alloys

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

Chaki, T.K.; Li, J.C.M.

1984-07-01

Fatigue crack propagation in amorphous metals has an overload effect which usually increases with the number of overload cycles. The variation of overload effect with delta K is explained by the size of the plastic zone which depends on delta K. A comparison of the spacing between striations and da/dN shows that the crack jumps a step about every hundred cycles. The featureless region is probably due to shear fracture along a shear band during overload. Both crack tip blunting and branching occur during the application of overload. Work hardening is not a necessary factor for the overloading effect.

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.

Toxicity of iron overload and iron overload reduction in the setting of hematopoietic stem cell transplantation for hematologic malignancies.

PubMed

Leitch, Heather A; Fibach, Eitan; Rachmilewitz, Eliezer

2017-05-01

Iron is an essential element for key cellular metabolic processes. However, transfusional iron overload (IOL) may result in significant cellular toxicity. IOL occurs in transfusion dependent hematologic malignancies (HM), may lead to pathological clinical outcomes, and IOL reduction may improve outcomes. In hematopoietic stem cell transplantation (SCT) for HM, IOL may have clinical importance; endpoints examined regarding an impact of IOL and IOL reduction include transplant-related mortality, organ function, infection, relapse risk, and survival. Here we review the clinical consequences of IOL and effects of IOL reduction before, during and following SCT for HM. IOL pathophysiology is discussed as well as available tests for IOL quantification including transfusion history, serum ferritin level, transferrin saturation, hepcidin, labile plasma iron and other parameters of iron-catalyzed oxygen free radicals, and organ IOL by imaging. Data-based recommendations for IOL measurement, monitoring and reduction before, during and following SCT for HM are made. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

Hecking, Manfred; Antlanger, Marlies; Winnicki, Wolfgang; Reiter, Thomas; Werzowa, Johannes; Haidinger, Michael; Weichhart, Thomas; Polaschegg, Hans-Dietrich; Josten, Peter; Exner, Isabella; Lorenz-Turnheim, Katharina; Eigner, Manfred; Paul, Gernot; Klauser-Braun, Renate; Hörl, Walter H; Sunder-Plassmann, Gere; Säemann, Marcus D

2012-06-08

Data generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients. BCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, 'final' dry weight is set to normohydration weight -7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters). Patients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients. ClinicalTrials.gov, NCT01416753.

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

PubMed Central

2012-01-01

Background Data generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients. Methods/design BCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, ‘final’ dry weight is set to normohydration weight −7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters). Discussion Patients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients. Trial registration ClinicalTrials.gov, NCT01416753 PMID:22682149

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

Monitoring training load, recovery-stress state, immune-endocrine responses, and physical performance in elite female basketball players during a periodized training program.

PubMed

Nunes, João A; Moreira, Alexandre; Crewther, Blair T; Nosaka, Ken; Viveiros, Luis; Aoki, Marcelo S

2014-10-01

This study investigated the effect of a periodized training program on internal training load (ITL), recovery-stress state, immune-endocrine responses, and physical performance in 19 elite female basketball players. The participants were monitored across a 12-week period before an international championship, which included 2 overloading and tapering phases. The first overloading phase (fourth to sixth week) was followed by a 1-week tapering, and the second overloading phase (eighth to 10th week) was followed by a 2-week tapering. ITL (session rating of perceived exertion method) and recovery-stress state (RESTQ-76 Sport questionnaire) were assessed weekly and bi-weekly, respectively. Pretraining and posttraining assessments included measures of salivary IgA, testosterone and cortisol concentrations, strength, jumping power, running endurance, and agility. Internal training load increased across all weeks from 2 to 11 (p ≤ 0.05). After the first tapering period (week 7), a further increase in ITL was observed during the second overloading phase (p ≤ 0.05). After the second tapering period, a decrease in ITL was detected (p ≤ 0.05). A disturbance in athlete stress-recovery state was noted during the second overloading period (p ≤ 0.05), before returning to baseline level in end of the second tapering period. The training program led to significant improvements in the physical performance parameters evaluated. The salivary measures did not change despite the fluctuations in ITL. In conclusion, a periodized training program evoked changes in ITL in elite female basketball players, which appeared to influence their recovery-stress state. The training plan was effective in preparing participants for competition, as indicated by improvements in recovery-stress state and physical performance after tapering.

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.

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

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.

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; ...

Physiology and Pathophysiology of Iron in Hemoglobin-Associated Diseases

PubMed Central

Coates, Thomas D

2016-01-01

Iron overload and iron toxicity, whether because of increased absorption or iron loading from repeated transfusions, can be major causes of morbidity and mortality in a number of chronic anemias. Significant advances have been made in our understanding of iron homeostasis over the past decade. At the same time, advances in magnetic resonance imaging have allowed clinicians to monitor and quantify iron concentrations non-invasively in specific organs. Furthermore, effective iron chelators are now available, including preparations that can be taken orally. This has resulted in substantial improvement in mortality and morbidity for patients with severe chronic iron overload. This paper reviews the key points of iron homeostasis and attempts to place clinical observations in patients with transfusional iron overload in context with the current understanding of iron homeostasis in humans. PMID:24726864

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

Deep brain stimulation for patients with Parkinson's disease: Effect on caregiver burden.

PubMed

Crespo-Burillo, J A; Rivero-Celada, D; Saenz-de Cabezón, A; Casado-Pellejero, J; Alberdi-Viñas, J; Alarcia-Alejos, R

2018-04-01

Our aim is to assess the burden on caregivers of patients with Parkinson's disease treated with deep brain stimulation (DBS) compared to those caring for patients at advanced stages and undergoing other treatments. We have also assessed the variables associated with presence of caregiver overload. We included consecutive patients with Parkinson's disease treated with DBS. Our control group included patients in advanced stages of Parkinson's disease undergoing other treatments. Patients were assessed with the following scales: UPDRS-II, UPDRS-III, UPDRS-IV, Hoehn and Yahr, Schwab & England, Barthel, PDQ-39, MoCA, Apathy Evaluation Scale, HADS, and the abbreviated QUIP. Caregiver burden was evaluated with the Zarit caregiver burden interview and their moods were assessed with the HADS scale. We included 11 patients treated with DBS and 11 with other treatments. For patients treated with DBS, we observed a better quality of life according to the PDQ-39 questionnaire (P=.028), and a lower score on the HADS anxiety subscale (P=.010). Caregiver overload was observed in 54.5% of the caregivers of patients in both groups (P=1.000); Zarit scores were similar (P=.835). Caregiver overload was associated with higher scores on the caregiver's Apathy Evaluation Scale (P=.048) and on the HADS anxiety subscale (P=.006). According to our results, treatment with DBS is not associated with lower caregiver burden. Apathy in patients and anxiety in caregivers are factors associated with the appearance of overload. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Population pharmacokinetic modeling of furosemide in patients with hypertension and fluid overload conditions.

PubMed

Kodati, Devender; Yellu, Narsimhareddy

2017-06-01

Furosemide is a loop diuretic drug frequently indicated in hypertension and fluid overload conditions such as congestive heart failure and hepatic cirrhosis. The purpose of the study was to establish a population pharmacokinetic model for furosemide in Indian hypertensive and fluid overload patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of furosemide. A total of 188 furosemide plasma sample concentrations from 63 patients with hypertension or fluid overload conditions were collected in this study. The population pharmacokinetic model for furosemide was built using Phoenix NLME 1.3 software. The covariates included age, sex, body surface area, bodyweight, height and creatinine clearance (CRCL). The pharmacokinetic data of furosemide was adequately explained by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and Vd/F of furosemide in the patients were 15.054Lh -1 and 4.419L, respectively. Analysis of covariates showed that CRCL was significantly influencing the clearance of furosemide. The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of furosemide in Indian patients with hypertension and fluid overload conditions. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

Iron overload may promote alteration of NK cells and hematopoietic stem/progenitor cells by JNK and P38 pathway in myelodysplastic syndromes.

PubMed

Hua, Yanni; Wang, Chaomeng; Jiang, Huijuan; Wang, Yihao; Liu, Chunyan; Li, Lijuan; Liu, Hui; Shao, Zonghong; Fu, Rong

2017-08-01

The objective of the study was to examine levels of intracellular iron, reactive oxygen species (ROS) and the expression of JNK and p38MAPK in NK cells and hematopoietic stem/progenitor cells (HSPCs) in MDS patients, and explore potential mechanisms by which iron overload (IOL) promotes MDS progression. Thirty-four cases of MDS and six cases of AML transformed from MDS (MDS/AML) were included. HSPCs and NK cells were isolated by magnetic absorption cell sorting. We used flow cytometry to detect the levels of ROS and intracellular JNK and P38 in NK cells and HSPCs. Total RNA and protein were extracted from NK cells and CD34 + cells to examine the expression of JNK and p38MAPK using RT-PCR and Western blotting. Intracellular iron concentration was detected. Data were analyzed by SPSS 21 statistical software. Intracellular iron concentration and ROS were increased in both NK cells and HSPCs in MDS patients with iron overload (P < 0.05). MDS patients with iron overload had higher JNK expression and lower p38 expression in NK cells, and higher p38 expression in HSPCs compared with non-iron overload group. IOL may cause alterations in NK cells and HSPCs through the JNK and p38 pathways, and play a role in the transformation to AML from MDS.

Inherent overload protection for the series resonant converter

NASA Technical Reports Server (NTRS)

King, R. J.; Stuart, T. A.

1983-01-01

The overload characteristics of the full bridge series resonant power converter are considered. This includes analyses of the two most common control methods presently in use. The first of these uses a current zero crossing detector to synchronize the control signals and is referred to as the alpha controller. The second is driven by a voltage controlled oscillator and is referred to as the gamma controller. It is shown that the gamma controller has certain reliability advantages in that it can be designed with inherent short circuit protection. Experimental results are included for an 86 kHz converter using power metal-oxide-semiconductor field-effect transistors (MOSFETs).

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

Multi-stage rescheduling of generation, load shedding and short-term transmission capacity for emergency state control

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

Krogh, B.; Chow, J.H.; Javid, H.S.

1983-05-01

A multi-stage formulation of the problem of scheduling generation, load shedding and short term transmission capacity for the alleviation of a viability emergency is presented. The formulation includes generation rate of change constraints, a linear network solution, and a model of the short term thermal overload capacity of transmission lines. The concept of rotating transmission line overloads for emergency state control is developed. The ideas are illustrated by a numerical example.

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

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.

TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling

PubMed Central

Kuwahara, Koichiro; Wang, Yanggan; McAnally, John; Richardson, James A.; Bassel-Duby, Rhonda; Hill, Joseph A.; Olson, Eric N.

2006-01-01

The heart responds to injury and chronic pressure overload by pathologic growth and remodeling, which frequently result in heart failure and sudden death. Calcium-dependent signaling pathways promote cardiac growth and associated changes in gene expression in response to stress. The calcium/calmodulin-dependent phosphatase calcineurin, which signals to nuclear factor of activated T cells (NFAT) transcription factors, serves as a transducer of calcium signals and is sufficient and necessary for pathologic cardiac hypertrophy and remodeling. Transient receptor potential (TRP) proteins regulate cation entry into cells in response to a variety of signals, and in skeletal muscle, expression of TRP cation channel, subfamily C, member 3 (TRPC3) is increased in response to neurostimulation and calcineurin signaling. Here we show that TRPC6 was upregulated in mouse hearts in response to activated calcineurin and pressure overload, as well as in failing human hearts. Two conserved NFAT consensus sites in the promoter of the TRPC6 gene conferred responsiveness to cardiac stress. Cardiac-specific overexpression of TRPC6 in transgenic mice resulted in heightened sensitivity to stress, a propensity for lethal cardiac growth and heart failure, and an increase in NFAT-dependent expression of β–myosin heavy chain, a sensitive marker for pathologic hypertrophy. These findings implicate TRPC6 as a positive regulator of calcineurin-NFAT signaling and a key component of a calcium-dependent regulatory loop that drives pathologic cardiac remodeling. PMID:17099778

A Novel Interaction Between Aging and ER Overload in a Protein Conformational Dementia

PubMed Central

Schipanski, Angela; Lange, Sascha; Segref, Alexandra; Gutschmidt, Aljona; Lomas, David A.; Miranda, Elena; Schweizer, Michaela; Hoppe, Thorsten; Glatzel, Markus

2013-01-01

Intraneuronal deposition of aggregated proteins in tauopathies, Parkinson disease, or familial encephalopathy with neuroserpin inclusion bodies (FENIB) leads to impaired protein homeostasis (proteostasis). FENIB represents a conformational dementia, caused by intraneuronal polymerization of mutant variants of the serine protease inhibitor neuroserpin. In contrast to the aggregation process, the kinetic relationship between neuronal proteostasis and aggregation are poorly understood. To address aggregate formation dynamics, we studied FENIB in Caenorhabditis elegans and mice. Point mutations causing FENIB also result in aggregation of the neuroserpin homolog SRP-2 most likely within the ER lumen in worms, recapitulating morphological and biochemical features of the human disease. Intriguingly, we identified conserved protein quality control pathways to modulate protein aggregation both in worms and mice. Specifically, downregulation of the unfolded protein response (UPR) pathways in the worm favors mutant SRP-2 accumulation, while mice overexpressing a polymerizing mutant of neuroserpin undergo transient induction of the UPR in young but not in aged mice. Thus, we find that perturbations of proteostasis through impairment of the heat shock response or altered UPR signaling enhance neuroserpin accumulation in vivo. Moreover, accumulation of neuroserpin polymers in mice is associated with an age-related induction of the UPR suggesting a novel interaction between aging and ER overload. These data suggest that targets aimed at increasing UPR capacity in neurons are valuable tools for therapeutic intervention. PMID:23335331

Quantification of Liver Iron with MRI: State of the Art and Remaining Challenges

PubMed Central

Hernando, Diego; Levin, Yakir S; Sirlin, Claude B; Reeder, Scott B

2015-01-01

Liver iron overload is the histological hallmark of hereditary hemochromatosis and transfusional hemosiderosis, and can also occur in chronic hepatopathies. Iron overload can result in liver damage, with the eventual development of cirrhosis, liver failure and hepatocellular carcinoma. Assessment of liver iron levels is necessary for detection and quantitative staging of iron overload, and monitoring of iron-reducing treatments. This article discusses the need for non-invasive assessment of liver iron, and reviews qualitative and quantitative methods with a particular emphasis on MRI. Specific MRI methods for liver iron quantification include signal intensity ratio as well as R2 and R2* relaxometry techniques. Methods that are in clinical use, as well as their limitations, are described. Remaining challenges, unsolved problems, and emerging techniques to provide improved characterization of liver iron deposition are discussed. PMID:24585403

Quality Submissions and Editorial Commentaries Require Heavy Lifting: Journal Growth Risks Information Overload.

PubMed

Lubowitz, James H; Brand, Jefferson C; Rossi, Michael J

2018-05-01

Our journal has grown in pages including more articles plus commentary. On the one hand, we see this as a subscriber benefit, but we also recognize that more is not always better. We risk information overload resulting in fatigue and the inability to read every word of every article. The challenge of information overload has expanded since the explosion of the internet and electronic communications. We could increase our already high rejection rates, but at the risk of rejecting high-quality research, which we do not prefer. In the end, guided by our Journal Board of Trustees and the Arthroscopy Association of North America Board of Directors, our Editors and Associate Editors will continue to grapple with the positive challenge of robust growth. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

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.

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. ...

Pathophysiology of transfusional iron overload: contrasting patterns in thalassemia major and sickle cell disease.

PubMed

Porter, John B

2009-01-01

The pathophysiological consequences of transfusional iron overload largely reflect the pattern of excess iron distribution and include cardiomyopathy, endocrinopathy, cirrhosis, and hepatocellular carcinoma. Since the introduction of desferrioxamine (DFO) in the late 1970s, these complications have fallen substantially but approximately half of the chelated adult patients with thalassemia major (TM) still show evidence of increased myocardial iron loading by MRI. An understanding of the factors that determine the propensity to extrahepatic iron distribution may be a key to minimizing the pathophysiological consequences of transfusional iron overload. Transfused patients with sickle cell disease (SCD) appear less likely to develop these extrahepatic complications, possibly because plasma nontransferrin-bound iron (NTBI) levels are typically lower than in TM patients at matched levels of iron loading. Other mechanisms that may reduce the extrahepatic iron distribution in SCD include raised plasma hepcidin due to chronic inflammation, lower growth differentiation factor 15 (GDF15) levels because of less ineffective erythropoiesis (IE), and induction of heme oxygenase (HO1) by intravascular hemolysis. Further understanding of these mechanisms may help in designing strategies to decrease extrahepatic iron distribution in TM.

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.

Effect of overload on the fatigue crack propagation in metastable beta Ti-V alloys

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

Chakrabortty, S.B.; Starke, E.A. Jr.; Lee, E.W.

1984-03-01

The effects of overload on the fatigue crack propagation behavior of two Ti-V alloys having different deformation mechanisms were studied. The results are explained in terms of residual stress effects associated with the overload and the removal of these stresses during post-overload cycling. An additional effect occurs during multiple cycle overload when the deformation structure representative of the strain amplitude is believed to form in the overload reverse plastic zone. This structure must be rearranged during cycling at Delta Kb before the baseline FCGR is reached and the process is responsible for part of the delay period. 46 references.

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.

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.

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...

Iron does not cause arrhythmias in the guinea pig model of transfusional iron overload.

PubMed

Kaiser, Lana; Davis, John; Patterson, Jon; Boyd, Ryan F; Olivier, N Bari; Bohart, George; Schwartz, Kenneth A

2007-08-01

Cardiac events, including heart failure and arrhythmias, are the leading cause of death in patients with beta thalassemia. Although cardiac arrhythmias in humans are believed to result from iron overload, excluding confounding factors in the human population is difficult. The goal of the current study was to determine whether cardiac arrhythmias occurred in the guinea pig model of secondary iron overload. Electrocardiograms were recorded by using surgically implanted telemetry devices in guinea pigs loaded intraperitoneally with iron dextran (test animals) or dextran alone (controls). Loading occurred over approximately 6 wk. Electrocardiograms were recorded for 1 wk prior to loading, throughout loading, and for approximately 4 wk after loading was complete. Cardiac and liver iron concentrations were significantly increased in the iron-loaded animals compared with controls and were in the range of those reported for humans with thalassemia. Arrhythmias were rare in both iron-loaded and control guinea pigs. No life-threatening arrhythmias were detected in either group. These data suggest that iron alone may be insufficient to cause cardiac arrhythmias in the iron-loaded guinea pig model and that arrhythmias detected in human patients with iron overload may be the result of a complex interplay of factors.

Bubble generation during transformer overload

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

Oommen, T.V.

1990-03-01

Bubble generation in transformers has been demonstrated under certain overload conditions. The release of large quantities of bubbles would pose a dielectric breakdown hazard. A bubble prediction model developed under EPRI Project 1289-4 attempts to predict the bubble evolution temperature under different overload conditions. This report details a verification study undertaken to confirm the validity of the above model using coil structures subjected to overload conditions. The test variables included moisture in paper insulation, gas content in oil, and the type of oil preservation system. Two aged coils were also tested. The results indicated that the observed bubble temperatures weremore » close to the predicted temperatures for models with low initial gas content in the oil. The predicted temperatures were significantly lower than the observed temperatures for models with high gas content. Some explanations are provided for the anomalous behavior at high gas levels in oil. It is suggested that the dissolved gas content is not a significant factor in bubble evolution. The dominant factor in bubble evolution appears to be the water vapor pressure which must reach critical levels before bubbles can be released. Further study is needed to make a meaningful revision of the bubble prediction model. 8 refs., 13 figs., 11 tabs.« less

Inclusion bodies of aggregated hemosiderins in liver macrophages.

PubMed

Hayashi, Hisao; Tatsumi, Yasuaki; Wakusawa, Shinya; Shigemasa, Ryota; Koide, Ryoji; Tsuchida, Ken-Ichi; Morotomi, Natsuko; Yamashita, Tetsuji; Kumagai, Kotaro; Ono, Yukiya; Hayashi, Kazuhiko; Ishigami, Masatoshi; Goto, Hidemi; Kato, Ayako; Kato, Koichi

2017-12-01

Hemosiderin formation is a structural indication of iron overload. We investigated further adaptations of the liver to excess iron. Five patients with livers showing iron-rich inclusions larger than 2 µm were selected from our database. The clinical features of patients and structures of the inclusions were compared with those of 2 controls with mild iron overload. All patients had severe iron overload with more than 5000 ng/mL of serum ferritin. Etiologies were variable, from hemochromatosis to iatrogenic iron overload. Their histological stages were either portal fibrosis or cirrhosis. Inclusion bodies were ultra-structurally visualized as aggregated hemosiderins in the periportal macrophages. X-ray analysis always identified, in addition to a large amount of iron complexes including oxygen and phosphorus, a small amount of copper and sulfur in the mosaic matrixes of inclusions. There were no inclusions in the control livers. Inclusion bodies, when the liver is loaded with excess iron, may appear in the macrophages as isolated organella of aggregated hemosiderins. Trace amounts of copper-sulfur complexes were always identified in the mosaic matrices of the inclusions, suggesting cuproprotein induction against excess iron. In conclusion, inclusion formation in macrophages may be an adaptation of the liver loaded with excess iron.

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.

Iron overload in patients with myelodysplastic syndromes: An updated overview.

PubMed

Moukalled, Nour M; El Rassi, Fuad A; Temraz, Sally N; Taher, Ali T

2018-06-15

Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by a broad clinical spectrum related to ineffective hematopoiesis leading to unilineage or multilineage cytopenias, with a high propensity for transformation to acute myeloid leukemia. Iron overload has been recently identified as one of the important conditions complicating the management of these diverse disorders. The accumulation of iron is mainly related to chronic transfusions; however, evidence suggests a possible role for ineffective erythropoiesis and increased intestinal absorption of iron, related to altered hepcidin and growth differentiation factor-15 levels in the development of hemosiderosis in patients with MDS. In addition to its suggested role in the exacerbation of ineffective erythropoiesis, multiple reports have identified a prognostic implication for the development of iron overload in patients with MDS, with an improvement in overall survival after the initiation of iron chelation therapy. This review includes a detailed discussion of iron overload in patients with MDS whether they are undergoing supportive therapy or curative hematopoietic stem cell transplantation, with a focus on the mechanism, diagnosis, and effect on survival as well as the optimal management of this highly variable complication. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms.

PubMed

Macchi, Chiara; Steffani, Liliana; Oleari, Roberto; Lettieri, Antonella; Valenti, Luca; Dongiovanni, Paola; Romero-Ruiz, Antonio; Tena-Sempere, Manuel; Cariboni, Anna; Magni, Paolo; Ruscica, Massimiliano

2017-10-15

Iron overload leads to multiple organ damage including endocrine organ dysfunctions. Hypogonadism is the most common non-diabetic endocrinopathy in primary and secondary iron overload syndromes. To explore the molecular determinants of iron overload-induced hypogonadism with specific focus on hypothalamic derangements. A dysmetabolic male murine model fed iron-enriched diet (IED) and cell-based models of gonadotropin-releasing hormone (GnRH) neurons were used. Mice fed IED showed severe hypogonadism with a significant reduction of serum levels of testosterone (-83%) and of luteinizing hormone (-86%), as well as reduced body weight gain, body fat and plasma leptin. IED mice had a significant increment in iron concentration in testes and in the pituitary. Even if iron challenge of in vitro neuronal models (GN-11 and GT1-7 GnRH cells) resulted in 10- and 5-fold iron content increments, respectively, no iron content changes were found in vivo in hypothalamus of IED mice. Conversely, mice placed on IED showed a significant increment in hypothalamic GnRH gene expression (+34%) and in the intensity of GnRH-neuron innervation of the median eminence (+1.5-fold); similar changes were found in the murine model HFE -/- , resembling human hemochromatosis. IED-fed adult male mice show severe impairment of hypothalamus-pituitary-gonadal axis without a relevant contribution of the hypothalamic compartment, which thus appears sufficiently protected from systemic iron overload. Copyright © 2017 Elsevier B.V. All rights reserved.

Resilient and Corrosion-Proof Rolling Element Bearings Made from Superelastic Ni-Ti Alloys for Aerospace

NASA Technical Reports Server (NTRS)

Dellacorte, Christopher

2014-01-01

Mechanical components (bearings, gears, mechanisms) typically utilize hardened construction materials to minimize wear and attain long life. In such components, loaded contact points (e.g., meshing gear teeth, bearing balls-raceway contacts) experience high contact stresses. The combination of high hardness and high elastic modulus often leads to damaging contact stress and denting, particularly during transient overload events such as shock impacts that occur during the launching of space vehicles or the landing of aircraft. In this webinar, Dr. DellaCorte will introduce the results of a research project that employs a superelastic alloy, Ni-Ti for rolling element bearing applications. Bearings and components made from such alloys can alleviate many problems encountered in advanced aerospace applications and may solve many terrestrial applications as well

Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes

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

Feng, Shan-Li; Sun, Ming-Rui; Li, Ting-Ting

Research highlights: {yields} Calcium-sensing receptor (CaR) activation stimulates TRP channels. {yields} CaR promoted transient receptor potential C3 (TRPC3) expression. {yields} Adult rat ventricular myocytes display capacitative calcium entry (CCE), which was operated by TRPCs. {yields} TRPC channels activation induced by CaR activator sustained the increased [Ca{sup 2+}]{sub i} to evoke cardiomyocytes apoptosis. -- Abstract: Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca{sup 2+} overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue andmore » promote the apoptosis of cardiomyocytes by Ca{sup 2+} overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca{sup 2+}]{sub i} levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca{sup 2+} stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca{sup 2+}]{sub i} in the absence of [Ca{sup 2+}]{sub o} and the subsequent restoration of [Ca{sup 2+}]{sub o} sustained the increased [Ca{sup 2+}]{sub i} for a few minutes, whereas, the persisting elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl{sub 3}) or spermine also resulted in the same effect and the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of [Ca{sup 2+}]{sub o}. In adult and neonatal rat cardiomyocytes, GdCl{sub 3} increased the expression of TRPC3 mRNA and protein, which were reversed by SKF96365 but not by inhibitors of the L-type channels and the Na{sup +}/Ca{sup 2+} exchangers. However, GdCl{sub 3} had no obvious effect on the expression of TRPC1 protein. These results suggested that CaR stimulation induced activation of TRP channels and promoted the expression of TRPC3, but not TRPC1, that sustained the increased [Ca{sup 2+}]{sub i}.« less

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.

Working memory overload: fronto-limbic interactions and effects on subsequent working memory function.

PubMed

Yun, Richard J; Krystal, John H; Mathalon, Daniel H

2010-03-01

The human working memory system provides an experimentally useful model for examination of neural overload effects on subsequent functioning of the overloaded system. This study employed functional magnetic resonance imaging in conjunction with a parametric working memory task to characterize the behavioral and neural effects of cognitive overload on subsequent cognitive performance, with particular attention to cognitive-limbic interactions. Overloading the working memory system was associated with varying degrees of subsequent decline in performance accuracy and reduced activation of brain regions central to both task performance and suppression of negative affect. The degree of performance decline was independently predicted by three separate factors operating during the overload condition: the degree of task failure, the degree of amygdala activation, and the degree of inverse coupling between the amygdala and dorsolateral prefrontal cortex. These findings suggest that vulnerability to overload effects in cognitive functioning may be mediated by reduced amygdala suppression and subsequent amygdala-prefrontal interaction.

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.

Evolution of Residual-Strain Distribution through an Overload-Induced Retardation Period during Fatigue Crack Growth

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

Lee, S. Y.; Sun, Yinan; An, Ke

2010-01-01

Neutron diffraction was employed to investigate the crack-growth retardation phenomenon after a single tensile overload by mapping both one-dimensional and two-dimensional residual-strain distributions around the crack tip in a series of compact-tension specimens representing various crack-growth stages through an overload-induced retardation period. The results clearly show a large compressive residual-strain field near the crack tip immediately after the overload. As the fatigue crack propagates through the overload-induced plastic zone, the compressive residual strains are gradually relaxed, and a new compressive residual-strain field is developed around the propagating crack tip, illustrating that the subsequent fatigue-induced plastic zone grows out of themore » large plastic zone caused by the overloading. The relationship between the overload-induced plastic zone and subsequent fatigue-induced plastic zone, and its influence on the residual-strain distributions in the perturbed plastic zone are discussed.« less

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

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.

Measurement and analysis of critical crack tip processes during fatigue crack growth

NASA Technical Reports Server (NTRS)

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

1985-01-01

The mechanics of fatigue crack growth under constant-amplitudes and variable-amplitude loading were examined. Critical loading histories involving relatively simple overload and overload/underload cycles were studied to provide a basic understanding of the underlying physical processes controlling crack growth. The material used for this study was 7091-T7E69, a powder metallurgy aluminum alloy. Local crack-tip parameters were measured at various times before, during, and after the overloads, these include crack-tip opening loads and displacements, and crack-tip strain fields. The latter were useed, in combination with the materials cyclic and monotonic stress-strain properties, to compute crack-tip residual stresses. The experimental results are also compared with analytical predictions obtained using the FAST-2 computer code. The sensitivity of the analytical model to constant-amplitude fatigue crack growth rate properties and to through-thickness constrain are studied.

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.

Acute Respiratory Distress Syndrome after Onyx Embolization of Arteriovenous Malformation

PubMed Central

Tawil, Isaac; Carlson, Andrew P.; Taylor, Christopher L.

2011-01-01

Purpose. We report a case of a 60-year-old male who underwent sequential Onyx embolizations of a cerebral arteriovenous malformation (AVM) which we implicate as the most likely etiology of subsequent acute respiratory distress syndrome (ARDS). Methods. Case report and literature review. Results. Shortly after the second Onyx embolization procedure, the patient declined from respiratory failure secondary to pulmonary edema. Clinical entities typically responsible for pulmonary edema including cardiac failure, renal failure, iatrogenic volume overload, negative-pressure pulmonary edema, and infectious etiologies were evaluated and excluded. The patient required mechanical ventilatory support for several days, delaying operative resection. The patient met clinical and radiographic criteria for ARDS. After excluding other etiologies of ARDS, we postulate that ARDS developed as a result of Onyx administration. The Onyx copolymer is dissolved in dimethyl sulfoxide (DMSO), a solvent excreted through the lungs and has been implicated in transient pulmonary side effects. Additionally, a direct toxic effect of the Onyx copolymer is postulated. Conclusion. Onyx embolization and DMSO toxicity are implicated as the etiology of ARDS given the lack of other inciting factors and the close temporal relationship. A strong physiologic rationale provides further support. Clinicians should consider this uncommon but important complication. PMID:21687580

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.

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

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

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

Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

PubMed

Torlasco, Camilla; Cassinerio, Elena; Roghi, Alberto; Faini, Andrea; Capecchi, Marco; Abdel-Gadir, Amna; Giannattasio, Cristina; Parati, Gianfranco; Moon, James C; Cappellini, Maria D; Pedrotti, Patrizia

2018-01-01

Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload

PubMed Central

Preza, Gloria C.; Ruchala, Piotr; Pinon, Rogelio; Ramos, Emilio; Qiao, Bo; Peralta, Michael A.; Sharma, Shantanu; Waring, Alan; Ganz, Tomas; Nemeth, Elizabeta

2011-01-01

Iron overload is the hallmark of hereditary hemochromatosis and a complication of iron-loading anemias such as β-thalassemia. Treatment can be burdensome and have significant side effects, and new therapeutic options are needed. Iron overload in hereditary hemochromatosis and β-thalassemia intermedia is caused by hepcidin deficiency. Although transgenic hepcidin replacement in mouse models of these diseases prevents iron overload or decreases its potential toxicity, natural hepcidin is prohibitively expensive for human application and has unfavorable pharmacologic properties. Here, we report the rational design of hepcidin agonists based on the mutagenesis of hepcidin and the hepcidin-binding region of ferroportin and computer modeling of their docking. We identified specific hydrophobic/aromatic residues required for hepcidin-ferroportin binding and obtained evidence in vitro that a thiol-disulfide interaction between ferroportin C326 and the hepcidin disulfide cage may stabilize binding. Guided by this model, we showed that 7–9 N-terminal amino acids of hepcidin, including a single thiol cysteine, comprised the minimal structure that retained hepcidin activity, as shown by the induction of ferroportin degradation in reporter cells. Further modifications to increase resistance to proteolysis and oral bioavailability yielded minihepcidins that, after parenteral or oral administration to mice, lowered serum iron levels comparably to those after parenteral native hepcidin. Moreover, liver iron concentrations were lower in mice chronically treated with minihepcidins than those in mice treated with solvent alone. Minihepcidins may be useful for the treatment of iron overload disorders. PMID:22045566

Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload.

PubMed

Preza, Gloria C; Ruchala, Piotr; Pinon, Rogelio; Ramos, Emilio; Qiao, Bo; Peralta, Michael A; Sharma, Shantanu; Waring, Alan; Ganz, Tomas; Nemeth, Elizabeta

2011-12-01

Iron overload is the hallmark of hereditary hemochromatosis and a complication of iron-loading anemias such as β-thalassemia. Treatment can be burdensome and have significant side effects, and new therapeutic options are needed. Iron overload in hereditary hemochromatosis and β-thalassemia intermedia is caused by hepcidin deficiency. Although transgenic hepcidin replacement in mouse models of these diseases prevents iron overload or decreases its potential toxicity, natural hepcidin is prohibitively expensive for human application and has unfavorable pharmacologic properties. Here, we report the rational design of hepcidin agonists based on the mutagenesis of hepcidin and the hepcidin-binding region of ferroportin and computer modeling of their docking. We identified specific hydrophobic/aromatic residues required for hepcidin-ferroportin binding and obtained evidence in vitro that a thiol-disulfide interaction between ferroportin C326 and the hepcidin disulfide cage may stabilize binding. Guided by this model, we showed that 7–9 N-terminal amino acids of hepcidin, including a single thiol cysteine, comprised the minimal structure that retained hepcidin activity, as shown by the induction of ferroportin degradation in reporter cells. Further modifications to increase resistance to proteolysis and oral bioavailability yielded minihepcidins that, after parenteral or oral administration to mice, lowered serum iron levels comparably to those after parenteral native hepcidin. Moreover, liver iron concentrations were lower in mice chronically treated with minihepcidins than those in mice treated with solvent alone. Minihepcidins may be useful for the treatment of iron overload disorders.

Protecting Mitochondrial Bioenergetic Function during Resuscitation from Cardiac Arrest

PubMed Central

Gazmuri, Raúl J.; Radhakrishnan, Jeejabai

2012-01-01

Synopsis Successful resuscitation from cardiac arrest requires reestablishment of aerobic metabolism by reperfusion with oxygenated blood of tissues that have been deprived of oxygen for variables periods of time. However, reperfusion concomitantly activates pathogenic mechanisms known as “reperfusion injury.” At the core of reperfusion injury are mitochondria, playing a critical role as effectors and targets of such injury. Mitochondrial injury compromises oxidative phosphorylation and also prompts release of cytochrome c to the cytosol and bloodstream where it correlates with severity of injury. Main drivers of such injury include Ca2+ overload and oxidative stress. Preclinical work shows that limiting myocardial cytosolic Na+ overload at the time of reperfusion attenuates mitochondrial Ca2+ overload and maintains oxidative phosphorylation yielding functional myocardial benefits that include preservation of left ventricular distensibility. Preservation of left ventricular distensibility enables hemodynamically more effective chest compression. Similar myocardial effect have been reported using erythropoietin hypothesized to protect mitochondrial bioenergetic function presumably through activation of pathways similar to those activated during preconditioning. Incorporation of novel and clinical relevant strategies to protect mitochondrial bioenergetic function are expected to attenuate injury at the time of reperfusion and enhance organ viability ultimately improving resuscitation and survival from cardiac arrest. PMID:22433486

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

Clinical penetrance in hereditary hemochromatosis: estimates of the cumulative incidence of severe liver disease among HFE C282Y homozygotes.

PubMed

Grosse, Scott D; Gurrin, Lyle C; Bertalli, Nadine A; Allen, Katrina J

2018-04-01

Iron overload (hemochromatosis) can cause serious, symptomatic disease that is preventable if detected early and managed appropriately. The leading cause of hemochromatosis in populations of predominantly European ancestry is homozygosity of the C282Y variant in the HFE gene. Screening of adults for iron overload or associated genotypes is controversial, largely because of a belief that severe phenotypes are uncommon, although cascade testing of first-degree relatives of patients is widely endorsed. We contend that severe liver disease (cirrhosis or hepatocellular cancer) is not at all uncommon among older males with hereditary hemochromatosis. Our review of the published data from a variety of empirical sources indicates that roughly 1 in 10 male HFE C282Y homozygotes is likely to develop severe liver disease during his lifetime unless iron overload is detected early and treated. New evidence from a randomized controlled trial of treatment allows for evidence-based management of presymptomatic patients. Although population screening for HFE C282Y homozygosity faces multiple barriers, a potentially effective strategy for increasing the early detection and prevention of clinical iron overload and severe disease is to include HFE C282Y homozygosity in lists of medically actionable gene variants when reporting the results of genome or exome sequencing.

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

TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice.

PubMed

Oda, Sayaka; Numaga-Tomita, Takuro; Kitajima, Naoyuki; Toyama, Takashi; Harada, Eri; Shimauchi, Tsukasa; Nishimura, Akiyuki; Ishikawa, Tatsuya; Kumagai, Yoshito; Birnbaumer, Lutz; Nishida, Motohiro

2017-08-08

Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.

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.

Dynamic remedial action scheme using online transient stability analysis

NASA Astrophysics Data System (ADS)

Shrestha, Arun

Economic pressure and environmental factors have forced the modern power systems to operate closer to their stability limits. However, maintaining transient stability is a fundamental requirement for the operation of interconnected power systems. In North America, power systems are planned and operated to withstand the loss of any single or multiple elements without violating North American Electric Reliability Corporation (NERC) system performance criteria. For a contingency resulting in the loss of multiple elements (Category C), emergency transient stability controls may be necessary to stabilize the power system. Emergency control is designed to sense abnormal conditions and subsequently take pre-determined remedial actions to prevent instability. Commonly known as either Remedial Action Schemes (RAS) or as Special/System Protection Schemes (SPS), these emergency control approaches have been extensively adopted by utilities. RAS are designed to address specific problems, e.g. to increase power transfer, to provide reactive support, to address generator instability, to limit thermal overloads, etc. Possible remedial actions include generator tripping, load shedding, capacitor and reactor switching, static VAR control, etc. Among various RAS types, generation shedding is the most effective and widely used emergency control means for maintaining system stability. In this dissertation, an optimal power flow (OPF)-based generation-shedding RAS is proposed. This scheme uses online transient stability calculation and generator cost function to determine appropriate remedial actions. For transient stability calculation, SIngle Machine Equivalent (SIME) technique is used, which reduces the multimachine power system model to a One-Machine Infinite Bus (OMIB) equivalent and identifies critical machines. Unlike conventional RAS, which are designed using offline simulations, online stability calculations make the proposed RAS dynamic and adapting to any power system configuration and operating state. The generation-shedding cost is calculated using pre-RAS and post-RAS OPF costs. The criteria for selecting generators to trip is based on the minimum cost rather than minimum amount of generation to shed. For an unstable Category C contingency, the RAS control action that results in stable system with minimum generation shedding cost is selected among possible candidate solutions. The RAS control actions update whenever there is a change in operating condition, system configuration, or cost functions. The effectiveness of the proposed technique is demonstrated by simulations on the IEEE 9-bus system, the IEEE 39-bus system, and IEEE 145-bus system. This dissertation also proposes an improved, yet relatively simple, technique for solving Transient Stability-Constrained Optimal Power Flow (TSC-OPF) problem. Using the SIME method, the sets of dynamic and transient stability constraints are reduced to a single stability constraint, decreasing the overall size of the optimization problem. The transient stability constraint is formulated using the critical machines' power at the initial time step, rather than using the machine rotor angles. This avoids the addition of machine steady state stator algebraic equations in the conventional OPF algorithm. A systematic approach to reach an optimal solution is developed by exploring the quasi-linear behavior of critical machine power and stability margin. The proposed method shifts critical machines active power based on generator costs using an OPF algorithm. Moreover, the transient stability limit is based on stability margin, and not on a heuristically set limit on OMIB rotor angle. As a result, the proposed TSC-OPF solution is more economical and transparent. The proposed technique enables the use of fast and robust commercial OPF tool and time-domain simulation software for solving large scale TSC-OPF problem, which makes the proposed method also suitable for real-time application.

Giant Pulse Phenomena in a High Gain Erbium Doped Fiber Amplifier

NASA Technical Reports Server (NTRS)

Li, Stephen X.; Merritt, Scott; Krainak, Michael A.; Yu, Anthony

2018-01-01

High gain Erbium Doped Fiber Amplifiers (EDFAs), while revolutionizing optical communications, remain vulnerable to optical damage when unseeded, e.g. due to nonlinear effects that produce random pulses with high peak power, i.e. giant pulses. Giant pulses can damage the components in a high gain EDFA or external components and systems coupled to the EDFA. We explore the conditions under which a reflective, polarization-maintaining (PM), core-pumped high gain EDFA generates giant pulses, provide details on conditions under which normal pulses evolve into giant pulses, and provide results on the transient effects of giant pulses on amplifier's fused-fiber couplers, an effect which we call Fiber Overload Induced Leakage (FOIL). While FOIL's effect on fused-fiber couplers is temporary, its damage to forward pump lasers in a high gain EDFA can be permanent.

Giant Pulse Phenomena in a High Gain Erbium Doped Fiber Amplifier

NASA Technical Reports Server (NTRS)

Li, Stephen X.; Merritt, Scott; Krainak, Michael A.; Yu, Anthony

2018-01-01

High gain Erbium Doped Fiber Amplifiers (EDFAs) are vulnerable to optical damage when unseeded, e.g. due to nonlinear effects that produce random, spontaneous Q-switched (SQS) pulses with high peak power, i.e. giant pulses. Giant pulses can damage either the components within a high gain EDFA or external components and systems coupled to the EDFA. We explore the conditions under which a reflective, polarization-maintaining (PM), core-pumped high gain EDFA generates giant pulses, provide details on the evolution of normal pulses into giant pulses, and provide results on the transient effects of giant pulses on an amplifier's fused-fiber couplers, an effect which we call Fiber Overload Induced Leakage (FOIL). While FOIL's effect on fused-fiber couplers is temporary, its damage to forward pump lasers in a high gain EDFA can be permanent.

[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

Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology.

PubMed

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

2015-11-23

Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)-plant, chele (χηλή)-claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries.

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

Increased risk of death from iron overload among 422 treated probands with HFE hemochromatosis and serum levels of ferritin greater than 1000 μg/L at diagnosis.

PubMed

Barton, James C; Barton, J Clayborn; Acton, Ronald T; So, Jeffrey; Chan, Susanne; Adams, Paul C

2012-04-01

We investigated the risk of death from iron overload among treated hemochromatosis probands who were homozygous for HFE C282Y and had serum levels of ferritin greater than 1000 μg/L at diagnosis. We compared serum levels of ferritin at diagnosis and other conditions with the rate of iron overload-associated death using data from 2 cohorts of probands with hemochromatosis who were homozygous for HFE C282Y (an Alabama cohort, n = 294, 63.9% men and an Ontario cohort, n = 128, 68.8% men). We defined iron overload-associated causes of death as cirrhosis (including hepatic failure and primary liver cancer) caused by iron deposition and cardiomyopathy caused by myocardial siderosis. All probands received phlebotomy and other appropriate therapy. The mean survival times after diagnosis were 13.2 ± 7.3 y and 12.5 ± 8.3 y in Alabama and Ontario probands, respectively. Serum levels of ferritin greater than 1000 μg/L at diagnosis were observed in 30.1% and 47.7% of Alabama and Ontario probands, respectively. In logistic regressions of serum ferritin greater than 1000 μg/L, there were significant positive associations with male sex and cirrhosis in Alabama probands and with age, male sex, increased levels of alanine and aspartate aminotransferases, and cirrhosis in Ontario probands. Of probands with serum levels of ferritin greater than 1000 μg/L at diagnosis, 17.9% of those from Alabama and 14.8% of those from Ontario died of iron overload. Among probands with serum levels of ferritin greater than 1000 μg/L, the relative risk of iron overload-associated death was 5.4 for the Alabama group (95% confidence interval [CI], 2.2-13.1; P = .0002) and 4.9 for the Ontario group (95% CI, 1.1-22.0; P = .0359). In hemochromatosis probands homozygous for HFE C282Y, serum levels of ferritin greater than 1000 μg/L at diagnosis were positively associated with male sex and cirrhosis. Even with treatment, the relative risk of death from iron overload was 5-fold greater in probands with serum levels of ferritin greater than 1000 μg/L. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

A computer program to perform dynamic thermal analysis for bare overhead conductors during short-time overload conditions

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

Shrestha, P.; Pham, K.

1995-12-31

Under emergency conditions, a bare overhead conductor can carry an increased amount of current that is well in excess of its normal rating. When there is this increase in current flow on a bare overhead conductor, the temperature does not rise instantaneously. but increases along a curve determined by the current, the conductor properties and the ambient conditions. The conductor temperature at the end of a short-time overload period must be restricted to its maximum design value. This paper presents a simplified approach in analyzing the dynamic performance for bare overhead conductors during short-time overload condition. A computer program wasmore » developed to calculate the short-time ratings for bare overhead conductors. The following parameters: current induced heating. solar load, convective/conductive cooling, radiative cooling, altitude, wind velocity and ampacity of the bare conductor were considered. Several sample graphical output lots are included with the paper.« less

Aerospace technology development of three types of solid state remote power controllers for 120VDC with current ratings of five, and thirty amperes, one type having current limiting

NASA Technical Reports Server (NTRS)

Baker, D. E.

1975-01-01

The first generation of remote power controllers (RPC) developed included: a 5-ampere design (Type 1), capable of limiting maximum overload current to 15 amperes for .1 sec; and 5-ampere noncurrent (Type 2) and 30-ampere noncurrent (Type 3) limiting designs, both with selectable instant trip levels for high-current overload. Each design provides overcurrent protection through an inverse I squared T trip-out function with an automatic reset option and demonstrates step-applied fault capability with a 4000-ampere surge, fast-risetime (low-inductance) power source. They also meet MIL - STD - 461A specification for electromagnetic interference. The second generation RPCs traded off specification compliance for reduction in cost and complexity for the Type 1 and 2 designs and give comparable or improved performance in most areas. The noncurrent limiting RPC proved to be a more economical and feasible method of overload protection for certain load types.

Ferritin iron minerals are chelator targets, antioxidants, and coated, dietary iron.

PubMed

Theil, Elizabeth C

2010-08-01

Cellular ferritin is central for iron balance during transfusions therapies; serum ferritin is a small fraction of body ferritin, albeit a convenient reporter. Iron overload induces extra ferritin protein synthesis but the protein is overfilled with the extra iron that damages ferritin, with conversion to toxic hemosiderin. Three new approaches that manipulate ferritin to address excess iron, hemosiderin, and associated oxidative damage in Cooley's Anemia and other iron overload conditions are faster removal of ferritin iron with chelators guided to ferritin gated pores by peptides; more ferritin protein synthesis using ferritin mRNA activators, by metal complexes that target mRNA 3D structures; and determining if endocytotic absorption of iron from legumes, which is mostly ferritin, is regulated during iron overload to prevent excess iron entry while providing protein. More of a focus on ferritin features, including protein cage structure, iron mineral, regulatable mRNA, and specific gut absorption properties, will achieve the three novel experimental goals for managing iron homeostasis with transfusion therapies.

I just want to be left alone: Daily overload and marital behavior.

PubMed

Sears, Meredith S; Repetti, Rena L; Robles, Theodore F; Reynolds, Bridget M

2016-08-01

Stressful, busy days have been linked with increases in angry and withdrawn marital behavior. The process by which stressors in 1 domain, such as work, affect an individual’s behavior in another domain, such as the marital relationship, is known as spillover . Using 56 days of daily diary reports in a diverse sample of 47 wives and 39 husbands, this study examined associations between daily experiences of overload and 3 marital behaviors: overt expressions of anger, disregard of the spouse’s needs (“disregard”), and reductions in affection and disclosure (“distancing”). Two potential mechanisms by which daily overload spills over into marital behavior were examined: negative mood and the desire to avoid social interaction. Among husbands, negative mood mediated the association between overload and angry behavior. Associations between overload and wives’ angry behavior, as well as overload and husbands’ and wives’ disregard of their partners’ needs, were mediated by both negative mood and the desire to withdraw socially. Desire to withdraw, but not negative mood, mediated the association between overload and distancing behavior among husbands and wives. In addition, associations between marital satisfaction and spouses’ typical marital behavior, as well as behavioral responses to overload, were examined. Husbands’ and wives’ average levels of expressed anger and disregard, and husbands’ distancing, were associated with lower marital satisfaction in 1 or both partners. Both spouses reported lower marital satisfaction if husbands tended to express marital anger, disregard, or distancing on busy, overloaded days. PsycINFO Database Record (c) 2016 APA, all rights reserved

Iron overload prevents oxidative damage to rat brain after chlorpromazine administration.

PubMed

Piloni, Natacha E; Caro, Andres A; Puntarulo, Susana

2018-05-15

The hypothesis tested is that Fe administration leads to a response in rat brain modulating the effects of later oxidative challenges such as chlorpromazine (CPZ) administration. Either a single dose (acute Fe overload) or 6 doses every second day (sub-chronic Fe overload) of 500 or 50 mg Fe-dextran/kg, respectively, were injected intraperitoneally (ip) to rats. A single dose of 10 mg CPZ/kg was injected ip 8 h after Fe treatment. DNA integrity was evaluated by quantitative PCR, lipid radical (LR · ) generation rate by electron paramagnetic resonance (EPR), and catalase (CAT) activity by UV spectrophotometry in isolated brains. The maximum increase in total Fe brain was detected after 6 or 2 h in the acute and sub-chronic Fe overload model, respectively. Mitochondrial and nuclear DNA integrity decreased after acute Fe overload at the time of maximal Fe content; the decrease in DNA integrity was lower after sub-chronic than after acute Fe overload. CPZ administration increased LR · generation rate in control rat brain after 1 and 2 h; however, CPZ administration after acute or sub-chronic Fe overload did not affect LR · generation rate. CPZ treatment did not affect CAT activity after 1-4 h neither in control rats nor in acute Fe-overloaded rats. However, CPZ administration to rats treated sub-chronically with Fe showed increased brain CAT activity after 2 or 4 h, as compared to control values. Fe supplementation prevented brain damage in both acute and sub-chronic models of Fe overload by selectively activating antioxidant pathways.

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.

Potential Adverse Cardiovascular Effects From Excessive Endurance Exercise

PubMed Central

O'Keefe, James H.; Patil, Harshal R.; Lavie, Carl J.; Magalski, Anthony; Vogel, Robert A.; McCullough, Peter A.

2012-01-01

A routine of regular exercise is highly effective for prevention and treatment of many common chronic diseases and improves cardiovascular (CV) health and longevity. However, long-term excessive endurance exercise may induce pathologic structural remodeling of the heart and large arteries. Emerging data suggest that chronic training for and competing in extreme endurance events such as marathons, ultramarathons, ironman distance triathlons, and very long distance bicycle races, can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which return to normal within 1 week. Over months to years of repetitive injury, this process, in some individuals, may lead to patchy myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, creating a substrate for atrial and ventricular arrhythmias. Additionally, long-term excessive sustained exercise may be associated with coronary artery calcification, diastolic dysfunction, and large-artery wall stiffening. However, this concept is still hypothetical and there is some inconsistency in the reported findings. Furthermore, lifelong vigorous exercisers generally have low mortality rates and excellent functional capacity. Notwithstanding, the hypothesis that long-term excessive endurance exercise may induce adverse CV remodeling warrants further investigation to identify at-risk individuals and formulate physical fitness regimens for conferring optimal CV health and longevity. PMID:22677079

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

HDAC1 Governs Iron Homeostasis Independent of Histone Deacetylation in Iron-Overload Murine Models.

PubMed

Yin, Xiangju; Wu, Qian; Monga, Jitender; Xie, Enjun; Wang, Hao; Wang, Shufen; Zhang, Huizhen; Wang, Zhan-You; Zhou, Tianhua; Shi, Yujun; Rogers, Jack; Lin, Hening; Min, Junxia; Wang, Fudi

2018-05-01

Iron-overload disorders are common and could lead to significant morbidity and mortality worldwide. Due to limited treatment options, there is a great need to develop novel strategies to remove the excess body iron. To discover potential epigenetic modulator in hepcidin upregulation and subsequently decreasing iron burden, we performed an epigenetic screen. The in vivo effects of the identified compounds were further tested in iron-overload mouse models, including Hfe -/- , Hjv -/- , and hepatocyte-specific Smad4 knockout (Smad4 fl/fl ;Alb-Cre + ) mice. Entinostat (MS-275), the clinical used histone deacetylase 1 (HDAC1) inhibitor, was identified the most potent hepcidin agonist. Consistently, Hdac1-deficient mice also presented higher hepcidin levels than wild-type controls. Notably, the long-term treatment with entinostat in Hfe -/- mice significantly alleviated iron overload through upregulating hepcidin transcription. In contrast, entinostat showed no effect on hepcidin expression and iron levels in Smad4 fl/fl ;Alb-Cre + mice. Further mechanistic studies revealed that HDAC1 suppressed expression of hepcidin through interacting with SMAD4 rather than deacetylation of SMAD4 or histone-H3 on the hepcidin promoter. The findings uncovered HDAC1 as a novel hepcidin suppressor through complexing with SMAD4 but not deacetylation of either histone 3 or SMAD4. In addition, our study suggested a novel implication of entinostat in treating iron-overload disorders. Based on our results, we conclude that entinostat strongly activated hepcidin in vivo and in vitro. HDAC1 could serve as a novel hepcidin suppressor by binding to SMAD4, effect of which is independent of BMP/SMAD1/5/8 signaling. Antioxid. Redox Signal. 28, 1224-1237.

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

Management Strategies for Dual-Career Couples.

ERIC Educational Resources Information Center

Kater, Donna

1985-01-01

Suggestions are presented that focus on strategies to alleviate those stresses arising from internal sources. These strategies include enhancing communication skills, relieving role overload, and minimizing multiple role-cycling. (CT)

Nephrotic syndrome

MedlinePlus

... and related heart diseases Chronic kidney disease Fluid overload, heart failure , fluid buildup in lungs Infections, including ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

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.

[Effects of Losartan on expression of heme oxygenases in volume-overloaded rats with left-to-right shunt].

PubMed

Yuan, Li-Xing; Liu, Han-Min; Li, Mi; Gao, Ju; Zhou, Tong-Fu

2005-09-01

To study the expression of heme oxygenase-1 mRNA and pulmonary remodeling before and after surgical establishment of left-to-right shunt in volume-overloaded SD rats and rats with Losartan intervention. Left-to-right shunt volume-overloaded SD rat models were established by aortocaval shunt operation. Seven rats with shunt were placed on Losartan (Losartan group), 7 rats with but not given Losartan were included in the operation group, and 4 rats after sham operation served as controls. Pulmonary pressure and right ventricular pressure were measured during catheterization. The relative weights ventricles were determined after execution of the rats. Pulmonary vascular remodeling parameters, including percentage arterial wall thickness and percentage muscularized small arteries, were assessed by morphometry. Heme oxygenase-1 (HO-1) mRNA expression and heme oxygenase-2 (HO-2) mRNA expression were detected RT-PCR method. Pulmonary artery pressure and right ventricular relative weight decreased significantly in the rats of Losartan group; in addition, the percentage arterial wall thickness and percentage of muscularized small arteries in the Losartan group were reduced as compared with those in the operation group. The level 1 mRAN expression in rats with shunt was significantly higher than that in rats without shunt. The level mRNA expression in the Losartan group decreased remarkably as compared against that in the operation The level of HO-1 mRNA expression in lungs was significantly higher than that in ventricles. There statistically significant differences in HO-2 mRNA expression levels between the three rat groups. Losartan intervention can markedly reduce pulmonary pressure, inhibit vascular remodeling in volume-overloaded left-to-right shunt rats, and result in down-regulation of HO-1 mRNA expression.

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

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.

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.

Acetylcholine attenuated TNF-α-induced intracellular Ca2+ overload by inhibiting the formation of the NCX1-TRPC3-IP3R1 complex in human umbilical vein endothelial cells.

PubMed

Zhao, Ming; Jia, Hang-Huan; Liu, Long-Zhu; Bi, Xue-Yuan; Xu, Man; Yu, Xiao-Jiang; He, Xi; Zang, Wei-Jin

2017-06-01

The endoplasmic reticulum (ER) forms discrete junctions with the plasma membrane (PM) that play a critical role in the regulation of Ca 2+ signaling during cellular bioenergetics, apoptosis and autophagy. We have previously confirmed that acetylcholine can inhibit ER stress and apoptosis after inflammatory injury. However, limited research has focused on the effects of acetylcholine on ER-PM junctions. In this work, we evaluated the structure and function of the supramolecular sodium-calcium exchanger 1 (NCX1)-transient receptor potential canonical 3 (TRPC3)-inositol 1,4,5-trisphosphate receptor 1 (IP3R1) complex, which is involved in regulating Ca 2+ homeostasis during inflammatory injury. The width of the ER-PM junctions of human umbilical vein endothelial cells (HUVECs) was measured in nanometres using transmission electron microscopy and a fluorescent probe for Ca 2+ . Protein-protein interactions were assessed by immunoprecipitation. Ca 2+ concentration was measured using a confocal microscope. An siRNA assay was employed to silence specific proteins. Our results demonstrated that the peripheral ER was translocated to PM junction sites when induced by tumour necrosis factor-alpha (TNF-α) and that NCX1-TRPC3-IP3R1 complexes formed at these sites. After down-regulating the protein expression of NCX1 or IP3R1, we found that the NCX1-mediated inflow of Ca 2+ and the release of intracellular Ca 2+ stores were reduced in TNF-α-treated cells. We also observed that acetylcholine attenuated the formation of NCX1-TRPC3-IP3R1 complexes and maintained calcium homeostasis in cells treated with TNF-α. Interestingly, the positive effects of acetylcholine were abolished by the selective M3AChR antagonist darifenacin and by AMPK siRNAs. These results indicate that acetylcholine protects endothelial cells from TNF-alpha-induced injury, [Ca 2+ ] cyt overload and ER-PM interactions, which depend on the muscarinic 3 receptor/AMPK pathway, and that acetylcholine may be a new inhibitor for suppressing [Ca 2+ ] cyt overload. Copyright © 2017 Elsevier Ltd. All rights reserved.

How to Express C++ Concepts in Fortran90

NASA Technical Reports Server (NTRS)

Decyk, V.; Norton, C.; Szymanski, B.

1997-01-01

r summarizes techniques for emulating in Fortran90 the most important object-oriented concepts of C++ classes (including abstract data types, encapsulation and function overloading), inheritance and dynamic dispatching.

How to Express C++ Concepts in Fortran90

DOE PAGES

Decyk, Viktor K.; Norton, Charles D.; Szymanski, Boleslaw K.

1997-01-01

This paper summarizes techniques for emulating in Fortran90 the most important objectoriented concepts of C++: classes (including abstract data types, encapsulation and function overloading), inheritance and dynamic dispatching.

Pressure overload differentially affects respiratory capacity in interfibrillar and subsarcolemmal mitochondria.

PubMed

Schwarzer, Michael; Schrepper, Andrea; Amorim, Paulo A; Osterholt, Moritz; Doenst, Torsten

2013-02-15

Years ago a debate arose as to whether two functionally different mitochondrial subpopulations, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), exist in heart muscle. Nowadays potential differences are often ignored. Presumably, SSM are providing ATP for basic cell function, whereas IFM provide energy for the contractile apparatus. We speculated that two distinguishable subpopulations exist that are differentially affected by pressure overload. Male Sprague-Dawley rats were subjected to transverse aortic constriction for 20 wk or sham operation. Contractile function was assessed by echocardiography. Heart tissue was analyzed by electron microscopy. Mitochondria were isolated by differential centrifugation, and respiratory capacity was analyzed using a Clark electrode. Pressure overload induced left ventricular hypertrophy with increased posterior wall diameter and impaired contractile function. Mitochondrial state 3 respiration in control was 50% higher in IFM than in SSM. Pressure overload significantly impaired respiratory rates in both IFM and SSM, but in SSM to a lower extent. As a result, there were no differences between SSM and IFM after 20 wk of pressure overload. Pressure overload reduced total citrate synthase activity, suggesting reduced total mitochondrial content. Electron microscopy revealed normal morphology of mitochondria but reduced total mitochondrial volume density. In conclusion, IFM show greater respiratory capacity in the healthy rat heart and a greater depression of respiratory capacity by pressure overload than SSM. The differences in respiratory capacity of cardiac IFM and SSM in healthy hearts are eliminated with pressure overload-induced heart failure. The strong effect of pressure overload on IFM together with the simultaneous appearance of mitochondrial and contractile dysfunction may support the notion of IFM primarily producing ATP for contractile function.

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

Non-transferrin bound iron: a key role in iron overload and iron toxicity.

PubMed

Brissot, Pierre; Ropert, Martine; Le Lan, Caroline; Loréal, Olivier

2012-03-01

Besides transferrin iron, which represents the normal form of circulating iron, non-transferrin bound iron (NTBI) has been identified in the plasma of patients with various pathological conditions in which transferrin saturation is significantly elevated. To show that: i) NTBI is present not only during chronic iron overload disorders (hemochromatosis, transfusional iron overload) but also in miscellaneous diseases which are not primarily iron overloaded conditions; ii) this iron species represents a potentially toxic iron form due to its high propensity to induce reactive oxygen species and is responsible for cellular damage not only at the plasma membrane level but also towards different intracellular organelles; iii) the NTBI concept may be expanded to include intracytosolic iron forms which are not linked to ferritin, the major storage protein which exerts, at the cellular level, the same type of protective effect towards the intracellular environment as transferrin in the plasma. Plasma NTBI and especially labile plasma iron determinations represent a new important biological tool since elimination of this toxic iron species is a major therapeutic goal. The NTBI approach represents an important mechanistic concept for explaining cellular iron excess and toxicity and provides new important biochemical diagnostic tools. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

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 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.

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.

Novel treatment options for transfusional iron overload in patients with myelodysplastic syndromes.

PubMed

Goldberg, Stuart L

2007-12-01

Red blood cell transfusion dependency is common in myelodysplastic syndromes and is associated with inferior survival. The use of parenteral deferoxamine therapy for transfusional iron overload has been sparse, in part due to cumbersome administration schedules. Deferasirox is an oral iron-chelating agent with favorable pharmacokinetics, including a long half-life allowing continuous 24-hour chelation with once-daily dosing. Deferasirox produces dose-dependent reductions in liver iron content and reduces cardiac iron levels. In-vitro studies with deferasirox suggest improved cardiomyocyte contractility potentially important in reducing excess cardiac mortality noted in transfusion-dependent MDS. Deferasirox has a manageable safety profile with favorable patient satisfaction reports.

MRI for Iron Overload in Thalassemia.

PubMed

Fernandes, Juliano Lara

2018-04-01

MRI is a key tool in the current management of patients with thalassemia. Given its capability of assessing iron overload in different organs noninvasively and without contrast, it has significant advantages over other metrics, including serum ferritin. Liver iron concentration can be measured either with relaxometry methods T2*/T2 or signal intensity ratio techniques. Myocardial iron can be assessed in the same examination through T2* imaging. In this review, we focus on showing how MRI evaluates iron in both organs and the clinical applications as well as practical approaches to using this tool by clinicians taking care of patients with thalassemia. Copyright © 2017 Elsevier Inc. All rights reserved.

Fractography of induction-hardened steel fractured in fatigue and overload

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

Santos, C.G.; Laird, C.

1997-07-01

The fracture surfaces of induction-hardened steel specimens obtained from an auto axle were characterized, macroscopically and microscopically, after being fractured in fatigue and monotonic overload. Specimens were tested in cyclic three-point bending under load control, and the S-N curve was established for specimens that had been notched by spark machining to facilitate fractography. Scanning electron microscopy of the fractured surfaces obtained for lives spanning the range 17,000 to 418,000 cycles revealed diverse fracture morphologies, including intergranular fracture and transgranular fatigue fracture. The results are being offered to assist in the analysis of complex field failures in strongly hardened steel.

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

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;

High voltage space plasma interactions. [charging the solar power satellites

NASA Technical Reports Server (NTRS)

Mccoy, J. E.

1980-01-01

Two primary problems resulted from plasma interactions; one of concern to operations in geosynchronous orbit (GEO), the other in low orbits (LEO). The two problems are not the same. Spacecraft charging has become widely recognized as a problem, particularly for communications satellites operating in GEO. The very thin thermal plasmas at GEO are insufficient to bleed off voltage buildups due to higher energy charged particle radiation collected on outer surfaces. Resulting differential charging/discharging causes electrical transients, spurious command signals and possible direct overload damage. An extensive NASA/Air Force program has been underway for several years to address this problem. At lower altitudes, the denser plasmas of the plasmasphere/ionosphere provide sufficient thermal current to limit such charging to a few volts or less. Unfortunately, these thermal plasma currents which solve the GEO spacecraft charging problem can become large enough to cause just the opposite problem in LEO.

The research on the temperature measurement technology of aluminum atomic emission spectroscopy

NASA Astrophysics Data System (ADS)

Hu, Xiaotao; Hao, Xiaojian; Tang, Huijuan; Sun, Yongkai

2018-02-01

Aimed to the testing requirement of the transient high temperature in the bore of barrel weapon, which has the problems of high temperature, high pressure, high overload and narrow adverse environment, the photoelectric pyrometer was researched based on the temperature measurement technology of double line of atomic emission spectrum and storage measurement technology, which used silicon photomultiplier. Al I 690.6nm and 708.5nm were selected as the temperature measurement element spectral lines, spectral line intensity was converted into a voltage value by silicon photomultiplier, the temperature was obtained through the ratio of two spectrum lines. The temperature is measured by the photoelectric thermometer and the infrared thermometer when heating aluminum by oxyhydrogen flame, and the relative error was 1.75%. Results show the temperature dependence of the two methods is better, and prove the feasibility of the method.

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.

Diagnosis and management of transfusion iron overload: The role of imaging

PubMed Central

Wood, John C.

2010-01-01

The characterization of iron stores is important to prevent and treat iron overload. Serum markers such as ferritin, serum iron, iron binding capacity, transferrin saturation, and nontransferrin-bound iron can be used to follow trends in iron status; however, variability in these markers limits predictive power for any given individual. Liver iron represents the best single marker of total iron balance. Measures of liver iron include biopsy, superconducting quantum interference device, computer tomography, and magnetic resonance imaging (MRI). MRI is the most accurate and widely available noninvasive tool to assess liver iron. The main advantages of MRI include a low-rate of variability between measurements and the ability to assess iron loading in endocrine tissues, the heart and the liver. This manuscript describes the principles, validation, and clinical utility of MRI for tissue iron estimation. PMID:17963249

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.

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…

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).

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

[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.

Upgrading of a small overloaded activated sludge plant using a MBBR system.

PubMed

Andreottola, G; Foladori, P; Gatti, G; Nardelli, P; Pettena, M; Ragazzi, M

2003-01-01

The aim of this research was the application of a biofilm system for the upgrading of a full-scale overloaded activated sludge MWWTP using the MBBR (Moving Bed Biofilm Reactor) technology. The choice of this fixed biomass system appeared appropriate because it offers several advantages including good potential in nitrification process, easiness of management and above all, the possibility to use the existing tank with very few modifications. MBBR system counts only few full-scale plants in Italy at the moment, thus a pilot-scale experimentation was preliminarily carried out. The acquired parameters were used for the fullscale MWWTP upgrading. The upgrading of the activated sludge reactor in the MBBR system has given (1) a relevant increase in the flowrate treated up to 60%; (2) a good efficiency in organic carbon removal and nitrification, equal to 88% and 90% respectively, with HRTs of 5.5-7 h; (3) the overcoming of the hydraulic overload of the secondary settler, applying a lamellar settler. It was observed a good correlation between the results obtained at pilot-scale and those observed in the full-scale plant.

Stress and counterproductive work behavior: multiple relationships between demands, control, and soldier indiscipline over time.

PubMed

Tucker, Jennifer S; Sinclair, Robert R; Mohr, Cynthia D; Thomas, Jeffrey L; Salvi, Angela D; Adler, Amy B

2009-07-01

Cognitive Resource Theory (CRT) suggests that under high levels of stress, employees are more prone to committing indiscipline. As few studies have examined this relationship over time, the authors conducted a six-wave longitudinal study examining the relationship of soldiers' indiscipline with work demands and control. The study included archival data collected quarterly over 2 years from 1,701 soldiers representing 10 units in garrison (Germany and Italy), in training rotations (Grafenwoehr, Germany), and on peacekeeping deployments (Kosovo, Kuwait). No main effects were found for work overload, and the findings for the moderating effects of control were contradictory. Within each time point, as work overload increased, soldiers who felt less control committed more indiscipline, supporting CRT. Over time, however, as work overload increased, soldiers who perceived less control 6 months earlier committed less indiscipline. Additionally, the authors found reverse causal effects for control such that prior perceptions of a lack of control were associated with indiscipline and prior incidents of indiscipline with less control. (c) 2009 APA, all rights reserved.

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

76 FR 23812 - Reliability and Continuity of Communications Networks, Including Broadband Technologies; Effects...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-28

... FEDERAL COMMUNICATIONS COMMISSION [PS Docket Nos. 11-60 and 10-92; ET Docket No. 06-119] Reliability and Continuity of Communications Networks, Including Broadband Technologies; Effects on Broadband Communications Networks of Damage or Failure of Network Equipment or Severe Overload; Independent Panel Reviewing...

An Analysis of the Status of Curriculum Reform and Textbook Production in Indonesia.

ERIC Educational Resources Information Center

Theisen, Gary; And Others

Curriculum reform in Indonesia during the past 2 decades has been marked by several themes. These themes include an increased emphasis on educational outcomes, greater standardization in instructional practices, improved teacher quality, and increased locally relevant curricula. Some problems recognized include an overloading of instructional time…

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

Vestibulo-oculomotor behaviour in rats following a transient unilateral vestibular loss induced by lidocaine.

PubMed

Magnusson, A K; Tham, R

2003-01-01

The effects of a transient vestibular nerve blockade, achieved by intra-tympanic instillation of lidocaine, were studied in rats by recording horizontal eye movements in darkness. Evaluation of the dose-response relationship showed that a maximal effect was attained with a concentration of 4% lidocaine. Within 15 min of lidocaine instillation, a vigorous spontaneous nystagmus was observed which reached maximal frequency and velocity of the slow phase after about 20 min. Subsequently, the nystagmus failed for approximately half an hour before it reappeared. This could be avoided by providing visual feedback in between the recordings in darkness or by a contralateral instillation of 2.5% lidocaine. It is suggested that the failure reflects an overload of the vestibulo-oculomotor circuits. After recovery from the nerve blockade, when the gaze was stable, dynamic vestibular tests were performed. They revealed that a decrease of the slow phase velocity gain and the dominant time constant during, respectively, sinusoidal- and step stimulation toward the unanaesthetised side, had developed with the nerve blockade. These modulations were impaired by a nodulo-uvulectomy but not by bilateral flocculectomy, which is consistent with the concept of vestibular habituation. A GABA(B) receptor antagonist, CGP 56433A, given systemically during the nerve blockade, aggravated the vestibular asymmetry. The same effect has previously been demonstrated in both short- (days) and long-term (months) compensated rats, by antagonising the GABA(B) receptor. In summary, this study provides the first observations of vestibulo-oculomotor disturbances during the first hour after a rapid and transient unilateral vestibular loss in the rat. By using this method, it is possible to study immediate behavioural consequences and possible neural changes that might outlast the nerve blockade.

TRPC3 contributes to regulation of cardiac contractility and arrhythmogenesis by dynamic interaction with NCX1

PubMed Central

Doleschal, Bernhard; Primessnig, Uwe; Wölkart, Gerald; Wolf, Stefan; Schernthaner, Michaela; Lichtenegger, Michaela; Glasnov, Toma N.; Kappe, C. Oliver; Mayer, Bernd; Antoons, Gudrun; Heinzel, Frank; Poteser, Michael; Groschner, Klaus

2015-01-01

Aim TRPC3 is a non-selective cation channel, which forms a Ca2+ entry pathway involved in cardiac remodelling. Our aim was to analyse acute electrophysiological and contractile consequences of TRPC3 activation in the heart. Methods and results We used a murine model of cardiac TRPC3 overexpression and a novel TRPC3 agonist, GSK1702934A, to uncover (patho)physiological functions of TRPC3. GSK1702934A induced a transient, non-selective conductance and prolonged action potentials in TRPC3-overexpressing myocytes but lacked significant electrophysiological effects in wild-type myocytes. GSK1702934A transiently enhanced contractility and evoked arrhythmias in isolated Langendorff hearts from TRPC3-overexpressing but not wild-type mice. Interestingly, pro-arrhythmic effects outlasted TRPC3 current activation, were prevented by enhanced intracellular Ca2+ buffering, and suppressed by the NCX inhibitor 3′,4′-dichlorobenzamil hydrochloride. GSK1702934A substantially promoted NCX currents in TRPC3-overexpressing myocytes. The TRPC3-dependent electrophysiologic, pro-arrhythmic, and inotropic actions of GSK1702934A were mimicked by angiotensin II (AngII). Immunocytochemistry demonstrated colocalization of TRPC3 with NCX1 and disruption of local interaction upon channel activation by either GSK1702934A or AngII. Conclusion Cardiac TRPC3 mediates Ca2+ and Na+ entry in proximity of NCX1, thereby elevating cellular Ca2+ levels and contractility. Excessive activation of TRPC3 is associated with transient cellular Ca2+ overload, spatial uncoupling between TRPC3 and NCX1, and arrhythmogenesis. We propose TRPC3-NCX micro/nanodomain communication as determinant of cardiac contractility and susceptibility to arrhythmogenic stimuli. PMID:25631581

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.

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.

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.

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.

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.

Reverse remodeling is associated with changes in extracellular matrix proteases and tissue inhibitors after mesenchymal stem cell (MSC) treatment of pressure overload hypertrophy.

PubMed

Molina, Ezequiel J; Palma, Jon; Gupta, Dipin; Torres, Denise; Gaughan, John P; Houser, Steven; Macha, Mahender

2009-02-01

Changes in ventricular extracellular matrix (ECM) composition of pressure overload hypertrophy determine clinical outcomes. The effects of mesenchymal stem cell (MSC) transplantation upon determinants of ECM composition in pressure overload hypertrophy have not been studied. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After an absolute decrease in fractional shortening of 25% from baseline, 1 x 10(6) MSC (n = 28) or PBS (n = 20) was randomly injected intracoronarily. LV protein analysis, including matrix metalloproteinases (MMP-2, MMP-3, MMP-6, MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3), was performed after sacrifice on postoperative day 7, 14, 21 or 28. Left ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3 were demonstrated to be decreased in the MSC group compared with controls after 28 days. Expression of MMP-2 and TIMP-2 remained relatively stable in both groups. Successful MSCs delivery was confirmed by histological analysis and visualization of labelled MSCs. In this model of pressure overload hypertrophy, intracoronary delivery of MSCs during heart failure was associated with specific changes in determinants of ECM composition. LV reverse remodeling was associated with decreased ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3, which were upregulated in the control group as heart failure progressed. These effects were most significant at 28 days following injection. (c) 2008 John Wiley & Sons, Ltd.

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.

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…

Data Overload Impact on Project Management: How Knowledge Management Systems Can Improve Federal Agencies Effectiveness

ERIC Educational Resources Information Center

Rodriguez, Jacinto

2013-01-01

This mixed method exploratory case study was used to explore the effect data overload has on project management, how data overload affects project management effectiveness, how prepared program office staff is to manage multiple projects effectively, and how the program office's organizational structure and data management systems affect project…

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 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.

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.

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.

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.

Stress and coping in Australian nurses: a systematic review.

PubMed

Lim, J; Bogossian, F; Ahern, K

2010-03-01

To identify factors that contribute to stress in Australian nurses, consider the coping strategies they use and examine the effects of stressors on nurses' health and well-being. Stress is a major concern in the nursing profession with work overload, nurse shortages and high turnover rates as the common stressors. Although nursing stress has been studied extensively, there is a lack of clarity on the nursing situation in Australia. A systematic review of the current literature was conducted on stress and coping strategies within the Australian nursing population. Stressors included work overload, role conflicts and experiences of aggression. Coping strategies included seeking support, problem solving and self-control. The majority of the studies reported detrimental effects on nurses' physical and mental well-being with little consideration given to the spillover effects of nursing work stress to their family and social relationships. Recommendations included factoring in personal and work stresses, promoting the use of effective coping strategies and maintaining supportive social relationships.

Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States.

PubMed

Delea, Thomas E; Hagiwara, May; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

2008-04-01

Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97-12/04 and representing 40 million members in >70 health plans. Study subjects (n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs. (c) 2007 Wiley-Liss, Inc.

Pre-diabetes Modifiable Risk Factors

MedlinePlus

... for example, if you are a highly trained athlete or if you are underweight.) Eating healthy foods in the right amounts Diets that include high levels of sugar, starches and fats often overload the body with more glucose than ...

Iron overload and HFE gene mutations in Polish patients with liver cirrhosis.

PubMed

Sikorska, Katarzyna; Romanowski, Tomasz; Stalke, Piotr; Iżycka-Świeszewska, Ewa; Bielawski, Krzysztof Piotr

2011-06-01

Increased liver iron stores may contribute to the progression of liver injury and fibrosis, and are associated with a higher risk of hepatocellular carcinoma development. Pre-transplant symptoms of iron overload in patients with liver cirrhosis are associated with higher risk of infectious and malignant complications in liver transplant recipients. HFE gene mutations may be involved in the pathogenesis of liver iron overload and influence the progression of chronic liver diseases of different origins. This study was designed to determine the prevalence of iron overload in relation to HFE gene mutations among Polish patients with liver cirrhosis. Sixty-one patients with liver cirrhosis included in the study were compared with a control group of 42 consecutive patients subjected to liver biopsy because of chronic liver diseases. Liver function tests and serum iron markers were assessed in both groups. All patients were screened for HFE mutations (C282Y, H63D, S65C). Thirty-six of 61 patients from the study group and all controls had liver biopsy performed with semiquantitative assessment of iron deposits in hepatocytes. The biochemical markers of iron overload and iron deposits in the liver were detected with a higher frequency (70% and 47% respectively) in patients with liver cirrhosis. There were no differences in the prevalence of all HFE mutations in both groups. In patients with a diagnosis of hepatocellular carcinoma, no significant associations with iron disorders and HFE gene mutations were found. Iron disorders were detected in patients with liver cirrhosis frequently but without significant association with HFE gene mutations. Only the homozygous C282Y mutation seems to occur more frequently in the selected population of patients with liver cirrhosis. As elevated biochemical iron indices accompanied liver iron deposits more frequently in liver cirrhosis compared to controls with chronic liver disease, there is a need for more extensive studies searching for the possible influence of non-HFE iron homeostasis regulators and their modulation on the course of chronic liver disease and liver cirrhosis.

Continuing Treatment with Salvia miltiorrhiza Injection Attenuates Myocardial Fibrosis in Chronic Iron-Overloaded Mice

PubMed Central

Zhang, Ying; Wang, Hao; Cui, Lijing; Zhang, Yuanyuan; Liu, Yang; Chu, Xi; Liu, Zhenyi; Zhang, Jianping; Chu, Li

2015-01-01

Iron overload cardiomyopathy results from iron accumulation in the myocardium that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza (SM, also known as Danshen), a traditional Chinese medicinal herb, has been widely used for hundreds of years to treat cardiovascular diseases. Here, we investigated the effect and potential mechanism of SM on myocardial fibrosis induced by chronic iron overload (CIO) in mice. Kunming male mice (8 weeks old) were randomized to six groups of 10 animals each: control (CONT), CIO, low-dose SM (L-SM), high-dose SM (H-SM), verapamil (VRP) and deferoxamine (DFO) groups. Normal saline was injected in the CONT group. Mice in the other five groups were treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and those in the latter four groups also received corresponding daily treatments, including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron deposition was estimated histologically using Prussian blue staining. Myocardial fibrosis was determined by Masson’s trichrome staining and hydroxyproline (Hyp) quantitative assay. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and protein expression levels of type I collagen (COL I), type I collagen (COL III), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) were analyzed to investigate the mechanisms underlying the effects of SM against iron-overloaded fibrosis. Treatment of chronic iron-overloaded mice with SM dose-dependently reduced iron deposition levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL III, as well as upregulated the expression of TGF- β1 and MMP-9 proteins in the heart. Moreover, SM treatment decreased MDA content and increased SOD activity. In conclusion, SM exerted activities against cardiac fibrosis induced by CIO, which may be attributed to its inhibition of iron deposition, as well as collagen metabolism and oxidative stress. PMID:25850001

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

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.

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

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.

Predictive abilities of baseline measurements of fluid overload, assessed by bioimpedance spectroscopy and serum N-terminal pro-B-type natriuretic peptide, for mortality in hemodialysis patients

PubMed Central

Siriopol, Ianis; Voroneanu, Luminita; Covic, Adrian

2017-01-01

Introduction Fluid overload is one of the most important, yet modifiable, risk factors associated with worse outcomes in hemodialysis (HD) patients. However, its precise assessment in clinical practice is still under investigation. Material and methods This is an observational prospective study which included 285 stable patients with end-stage renal disease on standard thrice-weekly HD therapy. Overhydration was assessed by the combination of relative fluid overload (RFO), using bioimpedance spectroscopy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The outcome of interest was all-cause mortality. Results The median values for NT-proBNP and RFO were 4595 pg/ml and 6.9%, respectively. We divided the study population into four groups according to these median levels: group 1 – low NT-proBNP and low RFO; group 2 – high NT-proBNP and low RFO; group 3 – low NT-proBNP and high RFO; group 4 – high NT-proBNP and high RFO. During the follow-up (mean: 41.1, median: 48.7 months), 89 (31.2%) patients died. In the univariable Cox survival analysis only patients in group 4, and not those from group 2 or 3, had significantly higher HRs as compared to those in group 1 (HR = 1.5, 95% CI: 0.8–2.8, HR = 1.6, 95% CI: 0.8–2.9 and HR = 2.4, 95% CI: 1.3–4.2, for group 2, 3 and 4, respectively). Furthermore, these results were maintained in the multivariable Cox analysis. Conclusions Including both bioimpedance and NT-proBNP monitoring in a more comprehensive fluid status assessment could improve the diagnosis of fluid overload with a final improvement in patients’ outcome. PMID:28883854

Cognitive Load Theory and the Acquisition of Complex Cognitive Skills in the Elderly: Towards an Integrative Framework.

ERIC Educational Resources Information Center

Van Gerven, Pascal W. M.; Paas, Fred G. W. C.; Van Merrienboer, Jeroen J. G.; Schmidt, Henk G.

2000-01-01

Cognitive load (CL) theory suggests minimizing extraneous CL and maximizing germane CL in order not to overload working memory. Instructional design for older adults should therefore include goal-free problems, worked examples, and different modalities and avoid splitting attention and including redundant information. (SK)

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.

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

"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.

Non preemptive soft real time scheduler: High deadline meeting rate on overload

NASA Astrophysics Data System (ADS)

Khalib, Zahereel Ishwar Abdul; Ahmad, R. Badlishah; El-Shaikh, Mohamed

2015-05-01

While preemptive scheduling has gain more attention among researchers, current work in non preemptive scheduling had shown promising result in soft real time jobs scheduling. In this paper we present a non preemptive scheduling algorithm meant for soft real time applications, which is capable of producing better performance during overload while maintaining excellent performance during normal load. The approach taken by this algorithm has shown more promising results compared to other algorithms including its immediate predecessor. We will present the analysis made prior to inception of the algorithm as well as simulation results comparing our algorithm named gutEDF with EDF and gEDF. We are convinced that grouping jobs utilizing pure dynamic parameters would produce better performance.

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.

New insights into transfusion-related iron toxicity: Implications for the oncologist.

PubMed

Porter, John B; de Witte, Theo; Cappellini, M Domenica; Gattermann, Norbert

2016-03-01

Iron overload is a potentially life-threatening consequence of multiple red-blood-cell transfusions. Here, we review factors affecting excess iron distribution and its damage to specific tissues, as well as mechanisms of oncogenesis by iron. Although consequences of transfusional iron overload are best described in thalassemia major and related inherited anemias, they are increasingly recognized in acquired conditions, such as myelodysplastic syndromes (MDS). Iron overload in MDS not only impacts on certain tissues, but may affect the clonal evolution of MDS through generation of reactive oxygen species. Iron overload may also influence hematopoietic-stem-cell-transplantation outcomes. Novel MRI methods for assessing body iron have impacted significantly on outcome in inherited anemias by allowing monitoring of iron burden and iron chelation therapy. This approach is increasingly being used in MDS and stem-cell-transplant procedures. Knowledge gained from managing transfusional iron overload in inherited anemias may be translated to general oncology, with potential for improved patient outcomes. Copyright © 2016. Published by Elsevier Ireland Ltd.

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.

Spatial learning, monoamines and oxidative stress in rats exposed to 900 MHz electromagnetic field in combination with iron overload.

PubMed

Maaroufi, Karima; Had-Aissouni, Laurence; Melon, Christophe; Sakly, Mohsen; Abdelmelek, Hafedh; Poucet, Bruno; Save, Etienne

2014-01-01

The increasing use of mobile phone technology over the last decade raises concerns about the impact of high frequency electromagnetic fields (EMF) on health. More recently, a link between EMF, iron overload in the brain and neurodegenerative disorders including Parkinson's and Alzheimer's diseases has been suggested. Co-exposure to EMF and brain iron overload may have a greater impact on brain tissues and cognitive processes than each treatment by itself. To examine this hypothesis, Long-Evans rats submitted to 900 MHz exposure or combined 900 MHz EMF and iron overload treatments were tested in various spatial learning tasks (navigation task in the Morris water maze, working memory task in the radial-arm maze, and object exploration task involving spatial and non spatial processing). Biogenic monoamines and metabolites (dopamine, serotonin) and oxidative stress were measured. Rats exposed to EMF were impaired in the object exploration task but not in the navigation and working memory tasks. They also showed alterations of monoamine content in several brain areas but mainly in the hippocampus. Rats that received combined treatment did not show greater behavioral and neurochemical deficits than EMF-exposed rats. None of the two treatments produced global oxidative stress. These results show that there is an impact of EMF on the brain and cognitive processes but this impact is revealed only in a task exploiting spontaneous exploratory activity. In contrast, there are no synergistic effects between EMF and a high content of iron in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Presence of hemochromatosis-associated mutations in Hispanic patients with iron overload.

PubMed

Nieves-Santiago, Paul; Cancel, Dilany; Canales, Dialma; Toro, Doris H

2011-09-01

To determine the characteristics of the Puerto Rico Veteran population with iron overload in terms of demographic features, clinical manifestations, and the presence of hereditary hemochromatosis (HH) mutations, and to compare such characteristics in patients with and without HH mutations. A retrospective study was conducted in patients with iron overload (transferrin saturation > or = 45%) who were tested for HH mutations from January 2003 to June 2007. Data collected included age, gender, body mass index, hemoglobin level, platelet count, ferritin level, transferrin saturation, ceruloplasmin, alfa-1 antitrypsin, anti-nuclear antibodies, aspartate aminotransferase, alanine aminotransferase, alfa-fetoprotein, viral hepatitis profile, imaging studies, and comorbid conditions. Patients were grouped according to the results of the commercially available HH DNA mutation analysis as homozygote, heterozygote, compound heterozygote, or negative. 94 patients were studied. Most patients were male (90/94); the mean age was 60 years. Of the study group, 36% (34/94) was found positive for HH mutations. The most common mutation was H63D, which was found in 85% (29/34) of patients; 4 homozygotes and 25 heterozygotes. C282Y mutation was identified in only 12% (4/34) of patients, of which one was homozygote. A compound heterozygote (C282Y/ H63D) was also identified. After analyzing the data for confounding factors, 6 of 29 heterozygotes had no other risk factors for liver disease other than the H63D mutation. The predominance of H63D mutations in our population deserves further investigation since it considerably differs from other studied populations with iron overload in which C282Y is the most common mutation.

Mitochondrial proteome remodelling in pressure overload-induced heart failure: the role of mitochondrial oxidative stress

PubMed Central

Dai, Dao-Fu; Hsieh, Edward J.; Liu, Yonggang; Chen, Tony; Beyer, Richard P.; Chin, Michael T.; MacCoss, Michael J.; Rabinovitch, Peter S.

2012-01-01

Aims We investigate the role of mitochondrial oxidative stress in mitochondrial proteome remodelling using mouse models of heart failure induced by pressure overload. Methods and results We demonstrate that mice overexpressing catalase targeted to mitochondria (mCAT) attenuate pressure overload-induced heart failure. An improved method of label-free unbiased analysis of the mitochondrial proteome was applied to the mouse model of heart failure induced by transverse aortic constriction (TAC). A total of 425 mitochondrial proteins were compared between wild-type and mCAT mice receiving TAC or sham surgery. The changes in the mitochondrial proteome in heart failure included decreased abundance of proteins involved in fatty acid metabolism, an increased abundance of proteins in glycolysis, apoptosis, mitochondrial unfolded protein response and proteolysis, transcription and translational control, and developmental processes as well as responses to stimuli. Overexpression of mCAT better preserved proteins involved in fatty acid metabolism and attenuated the increases in apoptotic and proteolytic enzymes. Interestingly, gene ontology analysis also showed that monosaccharide metabolic processes and protein folding/proteolysis were only overrepresented in mCAT but not in wild-type mice in response to TAC. Conclusion This is the first study to demonstrate that scavenging mitochondrial reactive oxygen species (ROS) by mCAT not only attenuates most of the mitochondrial proteome changes in heart failure, but also induces a subset of unique alterations. These changes represent processes that are adaptive to the increased work and metabolic requirements of pressure overload, but which are normally inhibited by overproduction of mitochondrial ROS. PMID:22012956

Virtual Libraries: Meeting the Corporate Challenge.

ERIC Educational Resources Information Center

DiMattia, Susan S.; Blumenstein, Lynn C.

1999-01-01

Discusses virtual libraries in corporate settings from the viewpoint of five special librarians. Highlights include competitive advantage, space and related collection issues, the use of technology, corporate culture, information overload, library vulnerability and downsizing, and the importance of service over format. (LRW)

Summer Doldrums.

ERIC Educational Resources Information Center

Muchnick, Bruce

2002-01-01

For camp staff, factors that contribute to the summer doldrums are weather, level of general fatigue, unsatisfied expectations, sensory overload, accumulation of negative "self-talk," and an underlying sense of hurry. Strategies for overcoming summer doldrums involve novelty and stress management, and include promoting health, challenging…

Is More Always Better?

ERIC Educational Resources Information Center

Bell, Steven J.

2003-01-01

Discusses full-text databases and whether existing aggregator databases are meeting user needs. Topics include the need for better search interfaces; concepts of quality research and information retrieval; information overload; full text in electronic journal collections versus aggregator databases; underrepresentation of certain disciplines; and…

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.

Adapting Semantic Natural Language Processing Technology to Address Information Overload in Influenza Epidemic Management

PubMed Central

Keselman, Alla; Rosemblat, Graciela; Kilicoglu, Halil; Fiszman, Marcelo; Jin, Honglan; Shin, Dongwook; Rindflesch, Thomas C.

2013-01-01

Explosion of disaster health information results in information overload among response professionals. The objective of this project was to determine the feasibility of applying semantic natural language processing (NLP) technology to addressing this overload. The project characterizes concepts and relationships commonly used in disaster health-related documents on influenza pandemics, as the basis for adapting an existing semantic summarizer to the domain. Methods include human review and semantic NLP analysis of a set of relevant documents. This is followed by a pilot-test in which two information specialists use the adapted application for a realistic information seeking task. According to the results, the ontology of influenza epidemics management can be described via a manageable number of semantic relationships that involve concepts from a limited number of semantic types. Test users demonstrate several ways to engage with the application to obtain useful information. This suggests that existing semantic NLP algorithms can be adapted to support information summarization and visualization in influenza epidemics and other disaster health areas. However, additional research is needed in the areas of terminology development (as many relevant relationships and terms are not part of existing standardized vocabularies), NLP, and user interface design. PMID:24311971

Overexpression of SerpinE2/protease nexin-1 Contribute to Pathological Cardiac Fibrosis via increasing Collagen Deposition

PubMed Central

Li, Xuelian; Zhao, Dandan; Guo, Zhenfeng; Li, Tianshi; Qili, Muge; Xu, Bozhi; Qian, Ming; Liang, Haihai; E, Xiaoqiang; Chege Gitau, Samuel; Wang, Lu; Huangfu, Longtao; Wu, Qiuxia; Xu, Chaoqian; Shan, Hongli

2016-01-01

Although increases in cardiovascular load (pressure overload) are known to elicit ventricular remodeling including cardiomyocyte hypertrophy and interstitial fibrosis, the molecular mechanisms of pressure overload or AngII -induced cardiac interstitial fibrosis remain elusive. In this study, serpinE2/protease nexin-1 was over-expressed in a cardiac fibrosis model induced by pressure-overloaded via transverse aortic constriction (TAC) in mouse. Knockdown of serpinE2 attenuates cardiac fibrosis in a mouse model of TAC. At meantime, the results showed that serpinE2 significantly were increased with collagen accumulations induced by AngII or TGF-β stimulation in vitro. Intriguingly, extracellular collagen in myocardial fibroblast was reduced by knockdown of serpinE2 compared with the control in vitro. In stark contrast, the addition of exogenous PN-1 up-regulated the content of collagen in myocardial fibroblast. The MEK1/2- ERK1/2 signaling probably promoted the expression of serpinE2 via transcription factors Elk1 in myocardial fibroblast. In conclusion, stress-induced the ERK1/2 signaling pathway activation up-regulated serpinE2 expression, consequently led accumulation of collagen protein, and contributed to cardiac fibrosis. PMID:27876880

Minerals in thalassaemia major patients: An overview.

PubMed

Ozturk, Zeynep; Genc, Gizem Esra; Gumuslu, Saadet

2017-05-01

Thalassaemia major (TM) is a hereditary blood disease characterised by reduced or absent production of beta globin chains. Erythrocyte transfusions are given to raise the haemoglobin level in patients with thalassaemia major. However, transfusions have been related to increased risk of iron overload and tissue damage related to excess iron. Both elevated oxidative stress due to iron overload and increased hemolysis lead to over utilisation of minerals required for antioxidant enzymes activities. Iron chelators have been used to prevent iron overload in thalassaemia major patients, but these chelators have the possibility of removing minerals from the body. Thalassaemia patients are more at risk for mineral deficiency because of increased oxidative stress and iron chelation therapies. Growth and maturational delay, cardiomyopathy, endocrinopathies and osteoporosis are the complications of thalassaemia. Minerals may play a particular role to prevent these complications. In the current review, we provide an overview of minerals including zinc (Zn), copper (Cu), selenium (Se), magnesium (Mg) and calcium (Ca) in thalassaemia major patients. We, also, underline that some complications of thalassaemia can be caused by an increased need for minerals or lack of the minerals. Copyright © 2017 Elsevier GmbH. All rights reserved.

Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of mechanical load variation.

PubMed

Ibrahim, Michael; Kukadia, Punam; Siedlecka, Urszula; Cartledge, James E; Navaratnarajah, Manoraj; Tokar, Sergiy; Van Doorn, Carin; Tsang, Victor T; Gorelik, Julia; Yacoub, Magdi H; Terracciano, Cesare M

2012-12-01

Cardiac transverse (t)-tubules are altered during disease and may be regulated by stretch-sensitive molecules. The relationship between variations in the degree and duration of load and t-tubule structure remains unknown, as well as its implications for local Ca(2+)-induced Ca(2+) release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart-lung transplantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t-tubule structure were assessed using confocal-microscopy, patch-clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart-only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time-dependent manner. Ca(2+) release synchronicity was reduced at 8 weeks moderate unloading only. Ca(2+) sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t-tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t-tubule morphology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37% reduction in cell volume at 4 weeks compared to 56% reduction after severe mechanical unloading) and did not cause depression and delay of the Ca(2+) transient, increased Ca(2+) spark frequency or impaired t-tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t-tubule structure in a time- and degree-dependent manner, and that physiological states of increased and reduced cell size, without pathological changes are possible. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Comparison of deferiprone and deferrioxamine for the treatment of transfusional iron overload in children with beta thalassemia major.

PubMed

Waheed, Nadia; Ali, Shafqut; Butt, Muhammad Asghar

2014-01-01

Thalassemia major is the most common genetic disorder in Pakistan. The study was done to compare the efficacy and safety of the deferiprone with deferrioxamine for the treatment of iron overload in children with thalassemia major. This randomized controlled trail was conducted at thalassemia blood transfusion unit of Allied Hospital, Faisalabad (AHF)/District Headquarter Hospital (DHQ), Faisalabad. Thalassemia-Unit Hilal-e-Ahmar, Alizeb Foundation and Blood Bank Services Faisalabad from November 2010 to December 2011.Children with beta thalassemia major of age more than 2 years and less than 16 years with transfusion iron over load were randomly allocated to one of the two groups each comprising of 67 patients. One group received deferiprone given at a daily dose of 75mg/kg in three divided doses orally while the other group received deferrioxamine at dose 50 mg/kg/24hrs for 5 days/week as parental infusion. Changes in the serum ferritin level were assessed. Cardiac function and toxicity were also examined. Serum ferritin was significantly reduced after 1 year in both treatment arms (p=0.01). Neutropenia observed in 13 (19.40%) non-splenectomized patients taking deferiprone. Transient elevations in ALT were observed in 3 (4.47%) children taking deferiprone. Left ventricular ejection fraction (LVEF) remained in normal range in both treatment arm but has decreased significantly in Deferrioxamine group compliance. Compliance was better in deferiprone as compared to deferrioxamine. Discontinuing percentage 2 (3%) vs 9 (13.43%). Deferiprone is a highly efficacious and safe chelation therapy for patients with thalassemia major who are non-compliant to Deferrioxamine. Deferiprone have an efficacy profile comparable to standard Deferrioxamine.

Temporal and Molecular Analyses of Cardiac Extracellular Matrix Remodeling following Pressure Overload in Adiponectin Deficient Mice

PubMed Central

Dadson, Keith; Turdi, Subat; Boo, Stellar; Hinz, Boris; Sweeney, Gary

2015-01-01

Adiponectin, circulating levels of which are reduced in obesity and diabetes, mediates cardiac extracellular matrix (ECM) remodeling in response to pressure overload (PO). Here, we performed a detailed temporal analysis of progressive cardiac ECM remodelling in adiponectin knockout (AdKO) and wild-type (WT) mice at 3 days and 1, 2, 3 and 4 weeks following the induction of mild PO via minimally invasive transverse aortic banding. We first observed that myocardial adiponectin gene expression was reduced after 4 weeks of PO, whereas increased adiponectin levels were detected in cardiac homogenates at this time despite decreased circulating levels of adiponectin. Scanning electron microscopy and Masson’s trichrome staining showed collagen accumulation increased in response to 2 and 4 weeks of PO in WT mice, while fibrosis in AdKO mice was notably absent after 2 weeks but highly apparent after 4 weeks of PO. Time and intensity of fibroblast appearance after PO was not significantly different between AdKO and WT animals. Gene array analysis indicated that MMP2, TIMP2, collagen 1α1 and collagen 1α3 were induced after 2 weeks of PO in WT but not AdKO mice. After 4 weeks MMP8 was induced in both genotypes, MMP9 only in WT mice and MMP1α only in AdKO mice. Direct stimulation of primary cardiac fibroblasts with adiponectin induced a transient increase in total collagen detected by picrosirius red staining and collagen III levels synthesis, as well as enhanced MMP2 activity detected via gelatin zymography. Adiponectin also enhanced fibroblast migration and attenuated angiotensin-II induced differentiation to a myofibroblast phenotype. In conclusion, these data indicate that increased myocardial bioavailability of adiponectin mediates ECM remodeling following PO and that adiponectin deficiency delays these effects. PMID:25910275

Peroxisome proliferator-activated receptor-α expression induces alterations in cardiac myofilaments in a pressure-overload model of hypertrophy

PubMed Central

Karam, Chehade N.; Warren, Chad M.; Henze, Marcus; Banke, Natasha H.; Lewandowski, E. Douglas

2017-01-01

Although alterations in fatty acid (FA) metabolism have been shown to have a negative impact on contractility of the hypertrophied heart, the targets of action remain elusive. In this study we compared the function of skinned fiber bundles from transgenic (Tg) mice that overexpress a relatively low level of the peroxisome proliferator-activated receptor α (PPARα), and nontransgenic (NTg) littermates. The mice (NTg-T and Tg-T) were stressed by transverse aortic constriction (TAC) and compared with shams (NTg-S and Tg-S). There was an approximate 4-fold increase in PPARα expression in Tg-S compared with NTg-S, but Tg-T hearts showed the same PPARα expression as NTg-T. Expression of PPARα did not alter the hypertrophic response to TAC but did reduce ejection fraction (EF) in Tg-T hearts compared with other groups. The rate of actomyosin ATP hydrolysis was significantly higher in Tg-S skinned fiber bundles compared with all other groups. Tg-T hearts showed an increase in phosphorylation of specific sites on cardiac myosin binding protein-C (cMyBP-C) and β-myosin heavy chain isoform. These results advance our understanding of potential signaling to the myofilaments induced by altered FA metabolism under normal and pathological states. We demonstrate that chronic and transient PPARα activation during pathological stress alters myofilament response to Ca2+ through a mechanism that is possibly mediated by MyBP-C phosphorylation and myosin heavy chain isoforms. NEW & NOTEWORTHY Data presented here demonstrate novel signaling to sarcomeric proteins by chronic alterations in fatty acid metabolism induced by PPARα. The mechanism involves modifications of key myofilament regulatory proteins modifying cross-bridge dynamics with differential effects in controls and hearts stressed by pressure overload. PMID:28130336

Brain and retinal ferroportin 1 dysregulation in polycythaemia mice.

PubMed

Iacovelli, Jared; Mlodnicka, Agnieska E; Veldman, Peter; Ying, Gui-Shuang; Dunaief, Joshua L; Schumacher, Armin

2009-09-15

Disruption of iron homeostasis within the central nervous system (CNS) can lead to profound abnormalities during both development and aging in mammals. The radiation-induced polycythaemia (Pcm) mutation, a 58-bp microdeletion in the promoter region of ferroportin 1 (Fpn1), disrupts transcriptional and post-transcriptional regulation of this pivotal iron transporter. This regulatory mutation induces dynamic alterations in peripheral iron homeostasis such that newborn homozygous Pcm mice exhibit iron deficiency anemia with increased duodenal Fpn1 expression while adult homozygotes display decreased Fpn1 expression and anemia despite organismal iron overload. Herein we report the impact of the Pcm microdeletion on iron homeostasis in two compartments of the central nervous system: brain and retina. At birth, Pcm homozygotes show a marked decrease in brain iron content and reduced levels of Fpn1 expression. Upregulation of transferrin receptor 1 (TfR1) in brain microvasculature appears to mediate the compensatory iron uptake during postnatal development and iron content in Pcm brain is restored to wild-type levels by 7 weeks of age. Similarly, changes in expression are transient and expression of Fpn1 and TfR1 is indistinguishable between Pcm homozygotes and wild-type by 12 weeks of age. Strikingly, the adult Pcm brain is effectively protected from the peripheral iron overload and maintains normal iron content. In contrast to Fpn1 downregulation in perinatal brain, the retina of Pcm homozygotes reveals increased levels of Fpn1 expression. While retinal morphology appears normal at birth and during early postnatal development, adult Pcm mice demonstrate a marked, age-dependent loss of photoreceptors. This phenotype demonstrates the importance of iron homeostasis in retinal health.

Brain and retinal ferroportin 1 dysregulation in polycythaemia mice

PubMed Central

Iacovelli, Jared; Mlodnicka, Agnieska E.; Veldman, Peter; Ying, Gui-Shuang; Dunaief, Joshua L.; Schumacher, Armin

2009-01-01

Disruption of iron homeostatsis within the central nervous system (CNS) can lead to profound abnormalities during both development and aging in mammals. The radiation-induced polycythaemia (Pcm) mutation, a 58-bp microdeletion in the promoter region of ferroportin 1 (Fpn1), disrupts transcriptional and post-transcriptional regulation of this pivotal iron transporter. This regulatory mutation induces dynamic alterations in peripheral iron homeostatis such that newborn homozygous Pcm mice exhibit iron deficiency anemia with increased duodenal Fpn1 expression while adult homozygotes display decreased Fpn1 expression and anemia despite organismal iron overload. Herein we report the impact of the Pcm microdeletion on iron homeostasis in two compartments of the the central nervous system: brain and retina. At birth, Pcm homozygotes show a marked decrease in brain iron content and reduced levels of Fpn1 expression. Upregulation of transferrin receptor 1 (TfR1) in brain microvasculature appears to mediate the compensatory iron uptake during postnatal development and iron content in Pcm brain is restored to wildtype levels by 7 weeks of age. Similarly, changes in expression are transient and expression of Fpn1 and TfR1 is indistinguishable between Pcm homozygotes and wildtype by 12 weeks of age. Strikingly, the adult Pcm brain is effectively protected from the peripheral iron overload and maintains normal iron content. In contrast to Fpn1 downregulation in perinatal brain, the retina of Pcm homozygotes reveals increased levels of Fpn1 expression. While retinal morphology appears normal at birth and during early postnatal development, adult Pcm mice demonstrate a marked, age-dependent loss of photoreceptors. This phenotype demonstrates the importance of iron homeostasis in retinal health. PMID:19596281

An approach to computing discrete adjoints for MPI-parallelized models applied to Ice Sheet System Model 4.11

NASA Astrophysics Data System (ADS)

Larour, Eric; Utke, Jean; Bovin, Anton; Morlighem, Mathieu; Perez, Gilberto

2016-11-01

Within the framework of sea-level rise projections, there is a strong need for hindcast validation of the evolution of polar ice sheets in a way that tightly matches observational records (from radar, gravity, and altimetry observations mainly). However, the computational requirements for making hindcast reconstructions possible are severe and rely mainly on the evaluation of the adjoint state of transient ice-flow models. Here, we look at the computation of adjoints in the context of the NASA/JPL/UCI Ice Sheet System Model (ISSM), written in C++ and designed for parallel execution with MPI. We present the adaptations required in the way the software is designed and written, but also generic adaptations in the tools facilitating the adjoint computations. We concentrate on the use of operator overloading coupled with the AdjoinableMPI library to achieve the adjoint computation of the ISSM. We present a comprehensive approach to (1) carry out type changing through the ISSM, hence facilitating operator overloading, (2) bind to external solvers such as MUMPS and GSL-LU, and (3) handle MPI-based parallelism to scale the capability. We demonstrate the success of the approach by computing sensitivities of hindcast metrics such as the misfit to observed records of surface altimetry on the northeastern Greenland Ice Stream, or the misfit to observed records of surface velocities on Upernavik Glacier, central West Greenland. We also provide metrics for the scalability of the approach, and the expected performance. This approach has the potential to enable a new generation of hindcast-validated projections that make full use of the wealth of datasets currently being collected, or already collected, in Greenland and Antarctica.

An Approach to Computing Discrete Adjoints for MPI-Parallelized Models Applied to the Ice Sheet System Model}

NASA Astrophysics Data System (ADS)

Perez, G. L.; Larour, E. Y.; Morlighem, M.

2016-12-01

Within the framework of sea-level rise projections, there is a strong need for hindcast validation of the evolution of polar ice sheets in a way that tightly matches observational records (from radar and altimetry observations mainly). However, the computational requirements for making hindcast reconstructions possible are severe and rely mainly on the evaluation of the adjoint state of transient ice-flow models. Here, we look at the computation of adjoints in the context of the NASA/JPL/UCI Ice Sheet System Model, written in C++ and designed for parallel execution with MPI. We present the adaptations required in the way the software is designed and written but also generic adaptations in the tools facilitating the adjoint computations. We concentrate on the use of operator overloading coupled with the AdjoinableMPI library to achieve the adjoint computation of ISSM. We present a comprehensive approach to 1) carry out type changing through ISSM, hence facilitating operator overloading, 2) bind to external solvers such as MUMPS and GSL-LU and 3) handle MPI-based parallelism to scale the capability. We demonstrate the success of the approach by computing sensitivities of hindcast metrics such as the misfit to observed records of surface altimetry on the North-East Greenland Ice Stream, or the misfit to observed records of surface velocities on Upernavik Glacier, Central West Greenland. We also provide metrics for the scalability of the approach, and the expected performance. This approach has the potential of enabling a new generation of hindcast-validated projections that make full use of the wealth of datasets currently being collected, or alreay collected in Greenland and Antarctica, such as surface altimetry, surface velocities, and/or gravity measurements.

Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy

PubMed Central

Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.

2015-01-01

The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

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

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

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

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.

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.

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.

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.

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

Plant phenolics and their potential role in mitigating iron overload disorder in wild animals.

PubMed

Lavin, Shana R

2012-09-01

Phenolic compounds are bioactive chemicals found in all vascular plants but are difficult to characterize and quantify, and comparative analyses on these compounds are challenging due to chemical structure complexity and inconsistent laboratory methodologies employed historically. These chemicals can elicit beneficial or toxic effects in consumers, depending on the compound, dose and the species of the consumer. In particular, plant phenolic compounds such as tannins can reduce the utilization of iron in mammalian and avian consumers. Multiple zoo-managed wild animal species are sensitive to iron overload, and these species tend to be offered diets higher in iron than most of the plant browse consumed by these animals in the wild and in captivity. Furthermore, these animals likely consume diets higher in polyphenols in the wild as compared with in managed settings. Thus, in addition to reducing dietary iron concentrations in captivity, supplementing diets with phenolic compounds capable of safely chelating iron in the intestinal lumen may reduce the incidence of iron overload in these animal species. It is recommended to investigate various sources and types of phenolic compounds for use in diets intended for iron-sensitive species. Candidate compounds should be screened both in vitro and in vivo using model species to reduce the risk of toxicity in target species. In particular, it would be important to assess potential compounds in terms of 1) biological activity including iron-binding capacity, 2) accessibility, 3) palatability, and 4) physiological effects on the consumer, including changes in nutritional and antioxidant statuses.

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.

Good Principals, Good Schools.

ERIC Educational Resources Information Center

Adams, Jeanne P.

1999-01-01

A three-county survey of administrative credential students in California found that 26% of respondents serving in administrative positions are considering leaving their jobs; 62% of qualified candidates are staying in the classroom. Solutions to principal overload include hiring more assistant principals and grooming inhouse talent. (MLH)

The Whys and Wherefores of Information Literacy.

ERIC Educational Resources Information Center

Winkler, Stanley

2001-01-01

Discusses information literacy and its importance for the workplace. Topics include literacy for economic and social upward mobility; the use of computers to help achieve information literacy; adult information literacy; the roles of professional associations, government agencies, teachers, and print media; information overload; information…

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.

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.

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.

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.

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

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).

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. ...

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.

The effect of an overload on the rate of fatigue crack propagation under plane stress conditions

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

Bao, H.; McEvily, A.J.

1995-07-01

It has been shown that the retardation in the rate of fatigue crack growth following an overload is largely the result of surface-related, plane-stress deformation. In the present article, in order to isolate the plane-stress behavior, the effect of an overload on the subsequent rate of fatigue crack growth of 0.3-mm-thick specimens of 9Cr-1Mo steel has been investigated and compared to results obtained using 6.35-mm-thick specimens. It was found that for the 0.3-mm thickness, as with thicker specimens, two opening load levels were associated with the overload process. The upper opening load is associated with plane-stress deformation in the overloadmore » plastic zone, and this opening process is more clearly observed with thin as compared to thicker specimens. Based upon the determined level of the upper opening load, a semiempirical analysis is developed for calculating the number of delay cycles due to an overload as a function of thickness.« less

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

Work-Role Stress and Attitudes toward Co-Workers.

ERIC Educational Resources Information Center

Beehr, Terry A.

1981-01-01

Research in interviews with 651 employees of five work organizations indicated that role stresses (role ambiguity, role overload and skill underutilization) were related to employee outcomes including: overall job dissatisfaction, life dissatisfaction, low self-esteem, depressed mood, and fatigue. Concluded that people experiencing job stress…

CD-ROM Stress.

ERIC Educational Resources Information Center

Bunge, Charles A.

1991-01-01

Discussion of stress in library reference departments focuses on stress caused by CD-ROM reference tools. Topics discussed include work overload; nonreference duties; patron attitudes and behavior; staff attitudes; the need for proper staff training; and the need for library administrators to be sensitive to reference staff needs. (LRW)

The Identity Crisis in Early Childhood Special Education: A Call for Professional Role Clarification.

ERIC Educational Resources Information Center

Buysse, Virginia; Wesley, Patricia W.

1993-01-01

Professional roles in early childhood special education (ECSE) are expanding beyond traditional frameworks of direct service, to include consultation services, program planning and evaluating, and marketing. Potential dangers of role conflict and role overload are noted. (Author/DB)

Coping with Stress in the Special Education Classroom.

ERIC Educational Resources Information Center

Brownell, Mary

1997-01-01

Discusses the stress that special education teachers may feel by role overload and lack of autonomy. Stress relieving strategies are described, including setting realistic expectations, making distinctions between the job and personal life, increasing autonomy, looking for alternative sources of reinforcement, increasing efficacy, and developing…

The Perceived Stress Levels of Primary and Secondary Principals.

ERIC Educational Resources Information Center

Savery, Lawson K.; Detiuk, Michael

1986-01-01

Research conducted in Western Australian government schools indicates perceived stress among principals, particularly role overload and role conflict. Primary principals experienced greater stress than secondary principals. Suggestions on how the education department can reduce employee stress include altering leadership styles and offering stress…

Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

PubMed Central

Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

2011-01-01

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. PMID:21592110

Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

PubMed

Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

2011-08-01

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. © 2011 Blackwell Publishing Ltd.

A tissue adaptation model based on strain-dependent collagen degradation and contact-guided cell traction.

PubMed

Heck, T A M; Wilson, W; Foolen, J; Cilingir, A C; Ito, K; van Donkelaar, C C

2015-03-18

Soft biological tissues adapt their collagen network to the mechanical environment. Collagen remodeling and cell traction are both involved in this process. The present study presents a collagen adaptation model which includes strain-dependent collagen degradation and contact-guided cell traction. Cell traction is determined by the prevailing collagen structure and is assumed to strive for tensional homeostasis. In addition, collagen is assumed to mechanically fail if it is over-strained. Care is taken to use principally measurable and physiologically meaningful relationships. This model is implemented in a fibril-reinforced biphasic finite element model for soft hydrated tissues. The versatility and limitations of the model are demonstrated by corroborating the predicted transient and equilibrium collagen adaptation under distinct mechanical constraints against experimental observations from the literature. These experiments include overloading of pericardium explants until failure, static uniaxial and biaxial loading of cell-seeded gels in vitro and shortening of periosteum explants. In addition, remodeling under hypothetical conditions is explored to demonstrate how collagen might adapt to small differences in constraints. Typical aspects of all essentially different experimental conditions are captured quantitatively or qualitatively. Differences between predictions and experiments as well as new insights that emerge from the present simulations are discussed. This model is anticipated to evolve into a mechanistic description of collagen adaptation, which may assist in developing load-regimes for functional tissue engineered constructs, or may be employed to improve our understanding of the mechanisms behind physiological and pathological collagen remodeling. Copyright © 2014 Elsevier Ltd. All rights reserved.

The MR appearance of volume overload in the lower extremities

NASA Technical Reports Server (NTRS)

Meler, J. D.; Solomon, M. A.; Steele, J. R.; Yancy, C. W. Jr; Parkey, R. W.; Fleckenstein, J. L.; Blomqvist, C. G. (Principal Investigator)

1997-01-01

PURPOSE: Our goal was to describe the MR findings of volume overload (VO) in the lower extremities. METHOD: Fifteen individuals were studied, including eight healthy controls and seven patients with VO (four cardiac, three renal). MR evaluation included various SE techniques. Edema detection, localization, and symmetry were assessed subjectively. Relaxation time estimates were also made of the subcutaneous tissue, marrow, and three muscles. RESULTS: Subcutaneous tissue was markedly edematous in seven of seven patients and asymmetric in four of seven, whereas marrow was normal in all patients. Muscle edema was mild and asymmetric in six and two of seven patients, respectively. Perifascial fluid collections were identified in six of seven patients. CONCLUSION: Subcutaneous tissue edema is the dominant feature of VO in the lower extremities. Perifascial fluid is common but does not necessarily distribute symmetrically. Muscle edema is relatively mild. These findings should aid in identifying VO as the potential cause of swelling in patients with swollen legs.

Model-specific selection of molecular targets for heart failure gene therapy

PubMed Central

Katz, Michael G.; Fargnoli, Anthony S.; Tomasulo, Catherine E.; Pritchette, Louella A.; Bridges, Charles R.

2013-01-01

Heart failure (HF) is a complex multifaceted problem of abnormal ventricular function and structure. In recent years, new information has been accumulated allowing for a more detailed understanding of the cellular and molecular alterations that are the underpinnings of diverse causes of HF, including myocardial ischemia, pressure-overload, volume-overload or intrinsic cardiomyopathy. Modern pharmacological approaches to treat HF have had a significant impact on the course of the disease, although they do not reverse the underlying pathological state of the heart. Therefore gene-based therapy holds a great potential as a targeted treatment for cardiovascular diseases. Here, we survey the relative therapeutic efficacy of genetic modulation of β-adrenergic receptor signaling, Ca2+ handling proteins and angiogenesis in the most common extrinsic models of HF. PMID:21954055

Proportion of various types of thyroid disorders among newborns with congenital hypothyroidism and normally located gland: a regional cohort study.

PubMed

Gaudino, Rossella; Garel, Catherine; Czernichow, Paul; Léger, Juliane

2005-04-01

To determine the proportion of the various types of thyroid disorders among newborns detected by the neonatal TSH screening programme, with a normally located thyroid gland. Patients and methods Of the 882 575 infants screened in our centre between 1981 and 2002, 85 infants with a normally located gland had persistent elevation of serum TSH values (an incidence of 1/10 383). Six of these 85 patients were lost to follow-up and were therefore excluded from the study. During follow-up, patients were classified as having permanent or transient hypothyroidism. Among the 79 patients included in the study, transient (n = 30, 38% of cases) and permanent (n = 49, 62% of cases) congenital hypothyroidism (CH) was demonstrated during the follow-up at the age of 0.7 +/- 0.6 years and 2.6 +/- 1.8 years (P < 0.0001), respectively. The proportion of premature births was significantly higher in the group with transient CH (57%) than in the group with permanent CH (2%) (P < 0.0001). A history of iatrogenic iodine overload was identified during the neonatal period in 69% of transient cases. Among permanent CH cases (n = 49), patients were classified as having a goitre (n = 27, 55% of cases), a normal sized and shaped thyroid gland (n = 14, 29% of cases) or a hypoplastic gland (n = 8, 16% of cases). The latter patients demonstrated global thyroid hypoplasia (n = 3), a right hemithyroid (n = 2), hypoplasia of the left lobe (n = 2), or asymmetry in the location of the two lobes (n = 1). Patients with a normal sized and shaped thyroid gland showed a significantly less severe form of hypothyroidism than those with a goitre or a hypoplastic thyroid gland (P < 0.0002). Among permanent CH cases, those with a goitre (n = 27) had an iodine organification defect (n = 10), Pendred syndrome (n = 1), a defect of thyroglobulin synthesis (n = 8), or a defect of sodium iodine symporter (n = 1), and in seven patients no aetiology could be determined. Among permanent cases with a normal sized and shaped thyroid gland (n = 14), a specific aetiology was found in only one patient (pseudohypoparathyroidism) and two patients had Down's syndrome. Among those with a globally hypoplastic gland, a TSH receptor gene mutation was found in two patients. A precise description of the phenotype can enhance our understanding of various forms of neonatal hypothyroidism as well as their prevalence and management. It also helps to identify cases of congenital hypothyroidism of unknown aetiology, which will need to be investigated in collaboration with molecular biologists.

Role of myocardial hypertrophy on acute and chronic right ventricular performance in relation to chronic volume overload in a porcine model: relevance for the surgical management of tetralogy of Fallot.

PubMed

Bove, Thierry; Vandekerckhove, Kristof; Bouchez, Stefaan; Wouters, Patrick; Somers, Pamela; Van Nooten, Guido

2014-06-01

The age for correction of tetralogy of Fallot has progressively declined to the postnatal period, often despite an increased rate of transannular patch repair. However, the long-term effect of premature exposure to chronic pulmonary insufficiency on the right ventricle remains unknown. On the basis of the relationship between the duration of pressure overload and age, the role of previous pressure load-related hypertrophy on right ventricular (RV) performance after chronic volume overload was investigated in a porcine model. RV hypertrophy (RVH), induced by pulmonary artery banding, was studied in pigs with (RVH plus pulmonary insufficiency [PI]) and without (RVH) subsequent PI. The effect of volume overload was compared between these 2 groups and pigs without RVH but with PI and controls (sham). Both acute and chronic effects on RV function were studied using conductance technology and validated using echocardiography. After chronic volume overload, the end-systolic and end-diastolic volumes were smaller in the RVH+PI group than in the PI group, including a lower pulmonary regurgitation fraction (25% ± 5% vs 35% ± 5%; P = .002). RVH resulted in better preserved systolic function, confirmed by an increased preload recruitable stroke work slope (14.7 ± 1.8 vs 9.3 ± 1.3 Mw.s/mL; P = .025) and higher RV ejection fraction (51% ± 3% vs 45% ± 4%; P = .05). Myocardial stiffness was impaired in the RVH+PI group versus the PI group (β, 0.19 ± 0.03 vs 0.12 ± 0.02 mL(-1); P = .001), presenting restrictive physiology only in the condition associating RVH and PI. The results of the present study have demonstrated that RVH attenuates the RV remodeling process related to chronic PI. It enables better preservation of contractility but at the cost of sustained diastolic impairment. These findings might help to determine the timing and strategy for repair of tetralogy of Fallot when RV outflow tract morphology indicates a definite need for transannular reconstruction. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Fructose increases corticosterone production in association with NADPH metabolism alterations in rat epididymal white adipose tissue.

PubMed

Prince, Paula D; Santander, Yanina A; Gerez, Estefania M; Höcht, Christian; Polizio, Ariel H; Mayer, Marcos A; Taira, Carlos A; Fraga, Cesar G; Galleano, Monica; Carranza, Andrea

2017-08-01

Metabolic syndrome is an array of closely metabolic disorders that includes glucose intolerance/insulin resistance, central obesity, dyslipidemia, and hypertension. Fructose, a highly lipogenic sugar, has profound metabolic effects in adipose tissue, and has been associated with the etiopathology of many components of the metabolic syndrome. In adipocytes, the enzyme 11 β-HSD1 amplifies local glucocorticoid production, being a key player in the pathogenesis of central obesity and metabolic syndrome. 11 β-HSD1 reductase activity is dependent on NADPH, a cofactor generated by H6PD inside the endoplasmic reticulum. Our focus was to explore the effect of fructose overload on epididymal white adipose tissue (EWAT) machinery involved in glucocorticoid production and NADPH and oxidants metabolism. Male Sprague-Dawley rats fed with a fructose solution (10% (w/v) in tap water) during 9 weeks developed some characteristic features of metabolic syndrome, such as hypertriglyceridemia, and hypertension. In addition, high levels of plasma and EWAT corticosterone were detected. Activities and expressions of H6PD and 11 β-HSD1, NAPDH content, superoxide anion production, expression of NADPH oxidase 2 subunits, and indicators of oxidative metabolism were measured. Fructose overloaded rats showed an increased potential in oxidant production respect to control rats. In parallel, in EWAT from fructose overloaded rats we found higher expression/activity of H6PD and 11 β-HSD1, and NADPH/NADP + ratio. Our in vivo results support that fructose overload installs in EWAT conditions favoring glucocorticoid production through higher H6PD expression/activity supplying NADPH for enhanced 11 β-HSD1 expression/activity, becoming this tissue a potential extra-adrenal source of corticosterone under these experimental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome.

PubMed

Escudero-Vilaplana, V; Garcia-Gonzalez, X; Osorio-Prendes, S; Romero-Jimenez, R M; Sanjurjo-Saez, M

2016-02-01

Regular blood transfusions in the management of myelodysplastic syndrome (MDS) often lead to iron overload. The main objective of this study was to evaluate the impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in patients with MDS. Secondary objectives were to describe treatment effectiveness and safety in daily clinical practice. A longitudinal, retrospective, observational study was carried out in a university hospital. The inclusion criteria were age over 18 years, MDS diagnosis and treatment with deferasirox for transfusion-dependent iron overload during the period of study (from January 2011 to April 2015). Treatment effectiveness was estimated by serum ferritin (SF), and adherence was measured by medication possession ratio (MPR). Clinically relevant analytical alterations during the treatment and reasons for treatment discontinuation were also assessed. Thirty-five patients were included in the study. Median SF at baseline was 1636 μg/L, and it decreased to 1399 μg/L during follow-up. The median adherence rate was 92%, although only 54·8% of the patients maintained deferasirox adherence ≥90% during the whole duration of treatment. Adherence rate was inversely correlated to SF (r = -0·288, P = 0·004). The median (p25, p75) duration of treatment was 11 (3·0, 37·8) months. The most common reasons for treatment discontinuation were renal toxicity (35%) and patient's death (25%). Deferasirox's effectiveness, measured by the decrease in SF, was significantly better in adherent patients. The most frequent reason for treatment discontinuation was renal toxicity. Developing strategies to improve deferasirox treatment adherence and monitoring renal function in those patients should be key points in pharmaceutical care. © 2016 John Wiley & Sons Ltd.

Sizing community energy storage systems to reduce transformer overloading with emphasis on plug-in electric vehicle loads

NASA Astrophysics Data System (ADS)

Trowler, Derik Wesley

The research objective of this study was to develop a sizing method for community energy storage systems with emphasis on preventing distribution transformer overloading due to plug-in electric vehicle charging. The method as developed showed the formulation of a diversified load profile based upon residential load data for several customers on the American Electric Power system. Once a load profile was obtained, plug-in electric vehicle charging scenarios which were based upon expected adoption and charging trends were superimposed on the load profile to show situations where transformers (in particular 25 kVA, 50 kVA, and 100 kVA) would be overloaded during peak hours. Once the total load profiles were derived, the energy and power requirements of community energy storage systems were calculated for a number of scenarios with different combinations of numbers of homes and plug-in electric vehicles. The results were recorded and illustrated into charts so that one could determine the minimum size per application. Other topics that were covered in this thesis were the state of the art and future trends in plug-in electric vehicle and battery chemistry adoption and development. The goal of the literature review was to confirm the already suspected notion that Li-ion batteries are best suited and soon to be most cost-effective solution for applications requiring small, efficient, reliable, and light-weight battery systems such as plug-in electric vehicles and community energy storage systems. This thesis also includes a chapter showing system modeling in MATLAB/SimulinkRTM. All in all, this thesis covers a wide variety of considerations involved in the designing and deploying of community energy storage systems intended to mitigate the effects of distribution transformer overloading.

Pulmonary macrophages: Phenomena associated with the particle ``overload`` condition

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

Lehnert, B.E.; Sebring, R.J.; Oberdoerster, G.

1993-05-01

Numerous lines of evidence support the generalization that alveolar macrophage (AM)-mediated particle clearance, or the transport of particle-containing AM from the alveoli out of the lung via the mucociliary apparatus, is a prominent mechanism that determines the pulmonary retention characteristics of relatively insoluble particles. Studies have also shown that the alveolar deposition of excessive burdens of particles with even low intrinsic cytotoxicity can result in impairments of the AM-mediated panicle clearance mechanism and the development of pathologic disorders including pulmonary fibrosis and lung cancer, at least in the lungs of rats. We briefly review evidence consistent with the idea thatmore » the high volumetric loads of particles contained in AM during particle overload conditions underlies their inabilities to translocate from the lung. Using a condition of particle overload brought about by subchronic exposure of rats to ultra-fine titanium dioxide as an experimental model, we have obtained ultrastructural and other evidence that indicates an association between particle overload and: The occurrence of aggregates of particle-containing AM in alveoli, Type II cell hyperplasia in alveoli that contain the AM aggregates, a loss in patent pores of Kohn in alveoli that contain the AM aggregates and show Type II cell hyperplasia, the interstitialization of particles at the sites where these phenomena collectively occur, and the development of fibrosis in alveolar regions where particle interstitialization occurs. The loss of pores of Kohn in the alveoli that contain aggregates of particle-laden AM suggests that these interalveolar pores normally serve as passageways through which AM may migrate to neighboring alveoli as they perform their function of phagocytizing particles that have deposited on the alveolar surface. The pores of Kohn also serve as short-cut pathways for AM to reach the mucociliary apparatus from more distal alveoli.« less

Pulmonary macrophages: Phenomena associated with the particle overload'' condition

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

Lehnert, B.E.; Sebring, R.J.; Oberdoerster, G.

1993-01-01

Numerous lines of evidence support the generalization that alveolar macrophage (AM)-mediated particle clearance, or the transport of particle-containing AM from the alveoli out of the lung via the mucociliary apparatus, is a prominent mechanism that determines the pulmonary retention characteristics of relatively insoluble particles. Studies have also shown that the alveolar deposition of excessive burdens of particles with even low intrinsic cytotoxicity can result in impairments of the AM-mediated panicle clearance mechanism and the development of pathologic disorders including pulmonary fibrosis and lung cancer, at least in the lungs of rats. We briefly review evidence consistent with the idea thatmore » the high volumetric loads of particles contained in AM during particle overload conditions underlies their inabilities to translocate from the lung. Using a condition of particle overload brought about by subchronic exposure of rats to ultra-fine titanium dioxide as an experimental model, we have obtained ultrastructural and other evidence that indicates an association between particle overload and: The occurrence of aggregates of particle-containing AM in alveoli, Type II cell hyperplasia in alveoli that contain the AM aggregates, a loss in patent pores of Kohn in alveoli that contain the AM aggregates and show Type II cell hyperplasia, the interstitialization of particles at the sites where these phenomena collectively occur, and the development of fibrosis in alveolar regions where particle interstitialization occurs. The loss of pores of Kohn in the alveoli that contain aggregates of particle-laden AM suggests that these interalveolar pores normally serve as passageways through which AM may migrate to neighboring alveoli as they perform their function of phagocytizing particles that have deposited on the alveolar surface. The pores of Kohn also serve as short-cut pathways for AM to reach the mucociliary apparatus from more distal alveoli.« less

Role of vitamin C as an adjuvant therapy to different iron chelators in young β-thalassemia major patients: efficacy and safety in relation to tissue iron overload.

PubMed

Elalfy, Mohsen S; Saber, Maha M; Adly, Amira Abdel Moneam; Ismail, Eman A; Tarif, Mohamed; Ibrahim, Fatma; Elalfy, Omar M

2016-03-01

Vitamin C, as antioxidant, increases the efficacy of deferoxamine (DFO). To investigate the effects of vitamin C as an adjuvant therapy to the three used iron chelators in moderately iron-overloaded young vitamin C-deficient patients with β-thalassemia major (β-TM) in relation to tissue iron overload. This randomized prospective trial that included 180 β-TM vitamin C-deficient patients were equally divided into three groups (n = 60) and received DFO, deferiprone (DFP), and deferasirox (DFX). Patients in each group were further randomized either to receive vitamin C supplementation (100 mg daily) or not (n = 30). All patients received vitamin C (group A) or no vitamin C (group B) were followed up for 1 yr with assessment of transfusion index, hemoglobin, iron profile, liver iron concentration (LIC) and cardiac magnetic resonance imaging (MRI) T2*. Baseline vitamin C was negatively correlated with transfusion index, serum ferritin (SF), and LIC. After vitamin C therapy, transfusion index, serum iron, SF, transferrin saturation (Tsat), and LIC were significantly decreased in group A patients, while hemoglobin and cardiac MRI T2* were elevated compared with baseline levels or those in group B without vitamin C. The same improvement was found among DFO-treated patients post-vitamin C compared with baseline data. DFO-treated patients had the highest hemoglobin with the lowest iron, SF, and Tsat compared with DFP or DFX subgroups. Vitamin C as an adjuvant therapy possibly potentiates the efficacy of DFO more than DFP and DFX in reducing iron burden in the moderately iron-overloaded vitamin C-deficient patients with β-TM, with no adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Changes in functioning of rat submandibular salivary gland under streptozotocin-induced diabetes are associated with alterations of Ca2+ signaling and Ca2+ transporting pumps.

PubMed

Fedirko, N V; Kruglikov, I A; Kopach, O V; Vats, J A; Kostyuk, P G; Voitenko, N V

2006-03-01

Xerostomia and pathological thirst are troublesome complications of diabetes mellitus associated with impaired functioning of salivary glands; however, their cellular mechanisms are not yet determined. Isolated acinar cells were loaded with Ca2+ indicators fura-2/AM for measuring cytosolic Ca2+ concentration ([Ca2+]i) or mag-fura-2/AM-inside the endoplasmic reticulum (ER). We found a dramatic decrease in pilocarpine-stimulated saliva flow, protein content and amylase activity in rats after 6 weeks of diabetes vs. healthy animals. This was accompanied with rise in resting [Ca2+]i and increased potency of acetylcholine (ACh) and carbachol (CCh) but not norepinephrine (NE) to induce [Ca2+]i transients in acinar cells from diabetic animals. However, [Ca2+]i transients mediated by Ca2+ release from ER stores (induced by application of either ACh, CCh, NE, or ionomycin in Ca2+-free extracellular medium) were decreased under diabetes. Application of inositol-1,4,5-trisphosphate led to smaller Ca2+ release from ER under the diabetes. Both plasmalemma and ER Ca2+-ATPases activity was reduced and the latter showed the increased affinity to ATP under the diabetes. We conclude that the diabetes caused impairment of salivary cells functions that, on the cellular level, associates with Ca2+ overload, increased Ca2+-mobilizing ability of muscarinic but not adrenergic receptors, decreased Ca2+-ATPases activity and ER Ca2+ content.

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.

Helping Self-Harming Students

ERIC Educational Resources Information Center

Selekman, Matthew D.

2009-01-01

Approximately 14 to 17 percent of adolescents today self-harm, deliberately cutting, burning, or bruising themselves. Most self-harming adolescents use the behavior as a coping strategy to get immediate relief from emotional distress or other stressors in their lives. Stressors include fitting in with peers, activity and homework overload, fears…

How to Survive the First Year of Teaching.

ERIC Educational Resources Information Center

Harris, Judy J.

2003-01-01

Discusses the unique challenges of the first year of teaching. Challenges include over enrollment, long hours, and overload of paperwork. Gives advice on how new teachers can overcome problems by creating alliances within the spiritual community, working with administrators, and taking care of their health. (MZ)

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.

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.

Transfusional iron overload in children with sickle cell anemia on chronic transfusion therapy for secondary stroke prevention.

PubMed

Kwiatkowski, Janet L; Cohen, Alan R; Garro, Julian; Alvarez, Ofelia; Nagasubramanian, Ramamorrthy; Sarnaik, Sharada; Thompson, Alexis; Woods, Gerald M; Schultz, William; Mortier, Nicole; Lane, Peter; Mueller, Brigitta; Yovetich, Nancy; Ware, Russell E

2012-02-01

Chronic transfusion reduces the risk of recurrent stroke in children with sickle cell anemia (SCA) but leads to iron loading. Management of transfusional iron overload in SCA has been reported as suboptimal [1], but studies characterizing monitoring and treatment practices for iron overload in children with SCA, particularly in recent years with the expansion of chelator options, are lacking. We investigated the degree of iron loading and treatment practices of 161 children with SCA receiving transfusions for a history of stroke who participated in the Stroke with Transfusions Changing to Hydroxyurea (SWiTCH) trial. Data obtained during screening, including past and entry liver iron concentration (LIC) measurements, ferritin values, and chelation were analyzed. The mean age at enrollment was 12.9 ± 4 years and the mean duration of transfusion was 7 ± 3.8 years. Baseline LIC (median 12.94 mg/g dw) and serum ferritin (median 3,164 ng/mL) were elevated. Chelation therapy was initiated after a mean of 2.6 years of transfusions. At study entry, 137 were receiving chelation, most of whom (90%) were receiving deferasirox. This study underscores the need for better monitoring of iron burden with timely treatment adjustments in chronically transfused children with SCA.

Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis.

PubMed

Shashaty, George; Frankewich, Raymond; Chakraborti, Tamal; Choudary, Jasti; Al-Fayoumi, Suliman; Kacuba, Alice; Castillo, Sonia; Robie-Suh, Kathy; Rieves, Dwaine; Weiss, Karen; Pazdur, Richard

2006-12-01

This report describes the Food and Drug Administration's review of data and analyses leading to the approval of the oral iron chelator, deferasirox for the treatment of chronic iron overload due to transfusional hemosiderosis. The FDA reviewed findings of a controlled, open-label, randomized multicenter phase III study of deferasirox vs. deferoxamine in 586 patients with beta-thalessemia and transfusional hemosiderosis. The study results as well as the results of the FDA review of chemistry, preclinical pharmacology, and supportive studies are described. Following 48 weeks of treatment in the phase III study, patients' liver iron concentrations (a key endpoint variable) had decreased an average of 2.4 mg of iron (Fe)/g dry weight (dw) and 2.9 mg Fe/g dw in the deferasirox and deferoxamine groups, respectively, despite continued blood transfusions in both cohorts. Deferasirox was associated with serum creatinine increases in approximately a third of patients. Common adverse events included gastrointestinal symptoms and skin rash. Other data provided supportive evidence of deferasirox safety and efficacy. The FDA granted deferasirox accelerated approval on November 2, 2005, for use in treating chronic iron overload due to transfusional hemosiderosis in patients > or =2 years of age. The sponsor must obtain clinical data demonstrating the drug's long-term safety and effectiveness.

Synthetic and natural iron chelators: therapeutic potential and clinical use

PubMed Central

Hatcher, Heather C; Singh, Ravi N; Torti, Frank M; Torti, Suzy V

2013-01-01

Iron-chelation therapy has its origins in the treatment of iron-overload syndromes. For many years, the standard for this purpose has been deferoxamine. Recently, considerable progress has been made in identifying synthetic chelators with improved pharmacologic properties relative to deferoxamine. Most notable are deferasirox (Exjade®) and deferiprone (Ferriprox®), which are now available clinically. In addition to treatment of iron overload, there is an emerging role for iron chelators in the treatment of diseases characterized by oxidative stress, including cardiovascular disease, atherosclerosis, neurodegenerative diseases and cancer. While iron is not regarded as the underlying cause of these diseases, it does play an important role in disease progression, either through promotion of cellular growth and proliferation or through participation in redox reactions that catalyze the formation of reactive oxygen species and increase oxidative stress. Thus, iron chelators may be of therapeutic benefit in many of these conditions. Phytochemicals, many of which bind iron, may also owe some of their beneficial properties to iron chelation. This review will focus on the advances in iron-chelation therapy for the treatment of iron-overload disease and cancer, as well as neurodegenerative and chronic inflammatory diseases. Established and novel iron chelators will be discussed, as well as the emerging role of dietary plant polyphenols that effectively modulate iron biochemistry. PMID:21425984

Protective effects of intercalated disk protein afadin on chronic pressure overload-induced myocardial damage

PubMed Central

Zankov, Dimitar P.; Shimizu, Akio; Tanaka-Okamoto, Miki; Miyoshi, Jun; Ogita, Hisakazu

2017-01-01

Adhesive intercellular connections at cardiomyocyte intercalated disks (IDs) support contractile force and maintain structural integrity of the heart muscle. Disturbances of the proteins at IDs deteriorate cardiac function and morphology. An adaptor protein afadin, one of the components of adherens junctions, is expressed ubiquitously including IDs. At present, the precise role of afadin in cardiac physiology or disease is unknown. To explore this, we generated conditional knockout (cKO) mice with cardiomyocyte-targeted deletion of afadin. Afadin cKO mice were born according to the expected Mendelian ratio and have no detectable changes in cardiac phenotype. On the other hand, chronic pressure overload induced by transverse aortic constriction (TAC) caused systolic dysfunction, enhanced fibrogenesis and apoptosis in afadin cKO mice. Afadin deletion increased macrophage infiltration and monocyte chemoattractant protein-1 expression, and suppressed transforming growth factor (TGF) β receptor signaling early after TAC procedure. Afadin also associated with TGFβ receptor I at IDs. Pharmacological antagonist of TGFβ receptor I (SB431542) augmented mononuclear infiltration and fibrosis in the hearts of TAC-operated control mice. In conclusion, afadin is a critical molecule for cardiac protection against chronic pressure overload. The beneficial effects are likely to be a result from modulation of TGFβ receptor signaling pathways by afadin. PMID:28045017

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.

Fatigue crack closure behavior at high stress ratios

NASA Technical Reports Server (NTRS)

Turner, C. Christopher; Carman, C. Davis; Hillberry, Ben M.

1988-01-01

Fatigue crack delay behavior at high stress ratio caused by single peak overloads was investigated in two thicknesses of 7475-T731 aluminum alloy. Closure measurements indicated no closure occurred before or throughout the overload plastic zones following the overload. This was further substantiated by comparing the specimen compliance following the overload with the compliance of a low R ratio test when the crack was fully open. Scanning electron microscope studies revealed that crack tunneling and possibly reinitiation of the crack occurred, most likely a result of crack-tip blunting. The number of delay cycles was greater for the thinner mixed mode stress state specimen than for the thicker plane strain stress state specimen, which is similar to low R ratio test results and may be due to a larger plastic zone for the mixed mode cased.

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.

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.

Employed Mexican women as mothers and partners: valued, empowered and overloaded.

PubMed

Meleis, A I; Douglas, M K; Eribes, C; Shih, F; Messias, D K

1996-01-01

This study was designed to explore the daily lived experiences of a group of employed, low-income Mexican women in their maternal and spousal roles. The participants were 41 auxiliary nurses recruited from two large urban hospitals in Mexico. Data were collected through the Women's Roles Interview Protocol (WRIP), which solicited the participants' perceptions of the satisfaction and stresses they experienced in their roles as mothers and spouses, and their descriptions of the coping strategies and the resources they used to deal with stressful life experiences related to these roles. Data analysis consisted of a qualitative thematic analysis of the narrative responses to open-ended questions in the WRIP. Satisfying aspects of the maternal and spousal roles, as identified by the participants, included giving to and receiving from their children and being valued and supported by their partners. Spousal approval of their work was also satisfying. These employed mothers, however, experienced many stressful aspects of functioning in multiple roles, including lack of resources, being absent from their children, self-doubt about their maternal role functioning, role overload and spousal absences. The women coped by juggling priorities and utilizing family resources. From the data analysis, the investigators developed a conceptual framework for understanding these women's experiences with parenting and marriage. The centrality of the family, a sense of value and empowerment as women in maternal and spousal roles, and the reality of role overload are discussed within the Mexican culture context of machismo, its female counterpart hembrismo, and family life. Implications for women's health are framed within a context of family and work.

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).

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

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

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.

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.

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.

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 ...

Teacher Stress: Perceived and Objective Sources, and Quality of Life.

ERIC Educational Resources Information Center

Mykletun, Reidar J.

1984-01-01

A study of 912 Norwegian comprehensive school teachers, using a 74-item job stress rating scale to identify stressors in teachers' work and the General Health Questionnaire as an index of quality of life, identified nine stress factors, including work overload, pupils' misbehavior, change, organizational climate/staff relations. (MH)

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…

Living by Learning, Learning by Living: The Quest for Meaning

ERIC Educational Resources Information Center

Carneiro, Roberto

2013-01-01

In our current age of rapid social, economic and technological change, including urbanisation, globalisation and information overload, human beings are more than ever seeking orientation and meaning. In this situation, education is the potential key to individual empowerment, cultural prosperity, social cohesion and economic development. Arguing…

Does Anthropogenic Noise in National Parks Impair Memory?

ERIC Educational Resources Information Center

Benfield, Jacob A.; Bell, Paul A.; Troup, Lucy J.; Soderstrom, Nick

2010-01-01

Research on noise shows that a variety of effects including stress, annoyance, and performance decrements exist for certain types of sounds. Noise interferes with cognitive ability by overloading the attentional system or simply distracting from efficient encoding or rehearsal, but very little research has extended those findings to recreation or…

Physician Internet Medical Information Seeking and On-line Continuing Education Use Patterns.

ERIC Educational Resources Information Center

Casebeer, Linda; Bennett, Nancy; Kristofco, Robert; Carillo, Anna; Centor, Robert

2002-01-01

Responses from 2,200 physicians indicated that nearly all have Internet access and use it primarily for medical information and professional development, not for communicating with patients. Credibility of source, speed, accessibility, and searching ease were most important. Barriers included information overload and too little information…

Testing of Two-Speed Transmission Configurations for Use in Rotorcraft

NASA Technical Reports Server (NTRS)

Lewicki, David G.; Stevens, Mark A.

2015-01-01

Large civil tiltrotors have been identified to replace regional airliners over medium ranges to alleviate next-generation air traffic. Variable rotor speed for these vehicles is required for efficient high-speed operation. Two-speed drive system research has been performed to support these advanced rotorcraft applications. Experimental tests were performed on two promising two-speed transmission configurations. The offset compound gear (OCG) transmission and the dual star/idler (DSI) planetary transmission were tested in the NASA Glenn Research Center variable-speed transmission test facility. Both configurations were inline devices with concentric input and output shafts and designed to provide 1:1 and 2:1 output speed reduction ratios. Both were designed for 200 hp and 15,000 rpm input speed and had a dry shift clutch configuration. Shift tests were performed on the transmissions at input speeds of 5,000, 8,000, 10,000, 12,500, and 15,000 rpm. Both the OCG and DSI configurations successfully perform speed shifts at full rated 15,000 rpm input speed. The transient shifting behavior of the OCG and DSI configurations were very similar. The shift clutch had more of an effect on shifting dynamics than the reduction gearing configuration itself since the same shift clutch was used in both configurations. For both OCG and DSI configurations, low-to-high speed shifts were limited in applied torque levels in order to prevent overloads on the transmission due to transient torque spikes. It is believed that the relative lack of appreciable slippage of the dry shifting clutch at operating conditions and pressure profiles tested was a major cause of the transient torque spikes. For the low-to-high speed shifts, the output speed ramp-up time slightly decreased and the peak out torque slightly increased as the clutch pressure ramp-down rate increased. This was caused by slightly less clutch slippage as the clutch pressure ramp-down rate increased.

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.

Nursing management of sensory overload in psychiatry – development of a theoretical framework model

PubMed

Scheydt, Stefan; Needham, Ian; Nielsen, Gunnar H; Behrens, Johann

2016-09-01

Background: The concept of “removal from stimuli” has already been examined by a Delphi-Study. However, some knowledge gaps remained open, which have now been further investigated. Aim: Examination of the concept “management of sensory overload in inpatient psychiatry” including its sub-concepts and specific measures. Method: Analysis of qualitative data about “removal from stimuli” by content analysis according to Mayring. Results: A theoretical description and definition of the concept could be achieved. In addition, sub-concepts (removal from stimuli, modulation of environmental factors, help somebody to help him-/herself) could be identified, theoretical defined and complemented by possible specific measures. Conclusions: The conceptual descriptions provide a further step to raise awareness of professionals in the subject area. Furthermore, we created a theoretical basis for further empirical studies.

[Current management of thalassemia intermedia].

PubMed

Thuret, I

2014-11-01

Thalassemia intermedia is a clinical entity where anemia is mild or moderate, requiring no or occasional transfusion. Non-transfusion-dependent thalassemia encompasses 3 main clinical forms: beta-thalassemia intermedia, hemoglobin E/beta-thalassemia and alpha-thalassemia intermedia (HbH disease). Clinical severity of thalassemia intermedia increases with age, with more severe anemia and more frequent complications such as extramedullary hematopoiesis and iron overload mainly related to increased intestinal absorption. Numerous adverse events including pulmonary hypertension and hypercoagulability have been associated with splenectomy, often performed in thalassemia intermedia patients. The potential preventive benefit of transfusion and chelation therapies on the occurrence of numerous complications supports the strategy of an earlier therapeutic intervention. Increasing knowledge about pathophysiological mechanisms involved in thalassemia erythropoiesis and related iron overload is currently translating in novel therapeutic approaches. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

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...

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

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

Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload.

PubMed

Pardo Andreu, G L; Inada, N M; Vercesi, A E; Curti, C

2009-01-01

One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21 +/- 4 to 130 +/- 7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H+ leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria.

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 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.

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

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.

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.

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

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…

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...

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...

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

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.

An Empirical Comparison of Visualization Tools To Assist Information Retrieval on the Web.

ERIC Educational Resources Information Center

Heo, Misook; Hirtle, Stephen C.

2001-01-01

Discusses problems with navigation in hypertext systems, including cognitive overload, and describes a study that tested information visualization techniques to see which best represented the underlying structure of Web space. Considers the effects of visualization techniques on user performance on information searching tasks and the effects of…

Language Learning on the World Wide Web: An Investigation of EFL Learners' Attitudes and Perceptions.

ERIC Educational Resources Information Center

Yang, Shu Ching

2001-01-01

Describes the integration of Web resources as instructional and learning tools in an EFL (English as a Foreign Language) class in Taiwan. Highlights include challenges and advantages of using the Web; learners' perceptions; intentional and incidental learning; disorientation and cognitive overload; and information seeking as problem-solving. A…