Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome.

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Mariane de Montalembert

Full Text Available The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS. In patients with sickle cell anemia (SCA, iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15% patients with thalassemia, none with SCA, and 4 (16% with MDS. The liver iron content (LIC ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29. Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001. Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001. Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation.

Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle.

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Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

2016-01-01

Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users. The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient.

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

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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

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

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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.

Short-Term Caloric Restriction Suppresses Cardiac Oxidative Stress and Hypertrophy Caused by Chronic Pressure Overload.

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Kobara, Miyuki; Furumori-Yukiya, Akiko; Kitamura, Miho; Matsumura, Mihoko; Ohigashi, Makoto; Toba, Hiroe; Nakata, Tetsuo

2015-08-01

Caloric restriction (CR) prevents senescent changes, in which reactive oxygen species (ROS) have a critical role. Left ventricular (LV) hypertrophy is a risk factor for cardiovascular diseases. We examined whether CR alters cardiac redox state and hypertrophy from chronic pressure overload. Male c57BL6 mice were subjected to ascending aortic constriction (AAC) with ad libitum caloric intake (AL + AAC group) or 40% restricted caloric intake (CR + AAC group). CR was initiated 2 weeks before AAC and was continued for 4 weeks. Two weeks after constriction, AAC increased LV wall thickness, impaired transmitral flow velocity, and augmented myocyte hypertrophy and fibrosis, in association with enhancement of BNP and collagen III expressions in the AL + AAC group. In the AL + AAC group, oxidative stress in cardiac tissue and mitochondria were enhanced, and NADPH oxidase activity and mitochondrial ROS production were elevated. These changes were significantly attenuated in the CR + AAC group. Additionally, in antioxidant systems, myocardial glutathione peroxidase and superoxide dismutase activities were enhanced in the CR + AAC group. Chronic pressure overload increased cardiac oxidative damage, in association with cardiac hypertrophy and fibrosis. Short-term CR suppressed oxidative stress and improved cardiac function, suggesting that short-term CR could be a useful strategy to prevent pressure overload-induced cardiac injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Niacin increases adiponectin and decreases adipose tissue inflammation in high fat diet-fed mice.

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Desiree Wanders

Full Text Available To determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity.Male C57BL/6 mice were placed on a control or high-fat diet (HFD and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2 (-/- (niacin receptor(-/- mice.Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2 (-/- mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPARγ C/EBPα or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lα, or DsbA-L (key ER chaperones involved in adiponectin production and secretion. However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1β in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice.Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expression in a niacin receptor-dependent manner.

Effects of isoniazid and niacin on experimental wound-healing

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Weinreich, Jürgen; Ågren, Sven Per Magnus; Bilali, Erol

2010-01-01

There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues.......There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues....

The Effects of Niacin on Inflammation in Patients with Non-ST Elevated Acute Coronary Syndrome

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Karacaglar, Emir; Atar, Ilyas; Altin, Cihan; Yetis, Begum; Cakmak, Abdulkadir; Bayraktar, Nilufer; Coner, Ali; Ozin, Bulent; Muderrisoglu, Haldun

2015-01-01

Background In this study, we aimed to evaluate the effects of niacin on high sensitivity C reactive protein (hs-CRP) and cholesterol levels in non-ST elevated acute coronary syndrome (NSTE-ACS) patients. Methods In this prospective, open label study, 48 NSTE-ACS were randomized to niacin or control group. Patients continued their optimal medical therapy in the control group. In the niacin group patients were assigned to receive extended-release niacin 500 mg/day. Patients were contacted 1 month later to assess compliance and side effects. Blood samples for hs-CRP were obtained upon admittance to the coronary care unit, in the third day and in the first month of the treatment. Fasting blood samples for cholesterol levels were obtained before and 30 days after the treatment. The primary end point of the study was to evaluate changes in hs-CRP, cholesterol levels, short-term cardiovascular events, and the safety of niacin in NSTE-ACS. Results Baseline demographic, clinical and laboratory characteristics were similar between the two groups. Logarithmic transformation of baseline and 3rd day hs-CRP levels were similar between the groups; but 1 month later, logarithmic transformation of hs-CRP level was significantly lower in the niacin group (0.43 ± 0.39 to 0.83 ± 0.91, p = 0.04). HDL-C level was significantly increased in the niacin group during follow-up. Drug related side effects were seen in 7 patients in the niacin group but no patients discontinued niacin. Conclusions Our findings demonstrate that lower dose extended release niacin can be used safely and decreases hs-CRP and lipid parameters successfully in NSTE-ACS patients. PMID:27122858

Pellagra-like condition is xeroderma pigmentosum/Cockayne syndrome complex and niacin confers clinical benefit.

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Hijazi, H; Salih, M A; Hamad, M H A; Hassan, H H; Salih, S B M; Mohamed, K A; Mukhtar, M M; Karrar, Z A; Ansari, S; Ibrahim, N; Alkuraya, F S

2015-01-01

An extremely rare pellagra-like condition has been described, which was partially responsive to niacin and associated with a multisystem involvement. The condition was proposed to represent a novel autosomal recessive entity but the underlying mutation remained unknown for almost three decades. The objective of this study was to identify the causal mutation in the pellagra-like condition and investigate the mechanism by which niacin confers clinical benefit. Autozygosity mapping and exome sequencing were used to identify the causal mutation, and comet assay on patient fibroblasts before and after niacin treatment to assess its effect on DNA damage. We identified a single disease locus that harbors a novel mutation in ERCC5, thus confirming that the condition is in fact xeroderma pigmentosum/Cockayne syndrome (XP/CS) complex. Importantly, we also show that the previously described dermatological response to niacin is consistent with a dramatic protective effect against ultraviolet-induced DNA damage in patient fibroblasts conferred by niacin treatment. Our findings show the power of exome sequencing in reassigning previously described novel clinical entities, and suggest a mechanism for the dermatological response to niacin in patients with XP/CS complex. This raises interesting possibilities about the potential therapeutic use of niacin in XP. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis.

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Gregor E Berger

Full Text Available Most studies provide evidence that the skin flush response to nicotinic acid (niacin stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR phase of psychotic disorders.We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55 with healthy controls (HC n = 25 and first episode schizophrenia patients (FEP n = 25 treated with atypical antipsychotics.Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA, but positively correlated with phospholipase A2 (inPLA2 activity, a marker of membrane lipid repair/remodelling.Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a "pro-inflammatory state", whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated.

Niacin and biosynthesis of PGD₂by platelet COX-1 in mice and humans.

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Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela; Alamuddin, Naji; Ibrahim, Salam; Crichton, Irene; Prempeh, Maxwell; Lawson, John A; Wilensky, Robert L; Rasmussen, Lars Melholt; Puré, Ellen; FitzGerald, Garret A

2012-04-01

The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1-dependent formation of PGD₂ and PGE₂ followed by COX-2-dependent production of PGE₂. Consistent with this, niacin-induced flushing in humans is attenuated when niacin is combined with an antagonist of the PGD₂ receptor DP1. NSAID-mediated suppression of COX-2-derived PGI₂ has negative cardiovascular consequences, yet little is known about the cardiovascular biology of PGD₂. Here, we show that PGD₂ biosynthesis is augmented during platelet activation in humans and, although vascular expression of DP1 is conserved between humans and mice, platelet DP1 is not present in mice. Despite this, DP1 deletion in mice augmented aneurysm formation and the hypertensive response to Ang II and accelerated atherogenesis and thrombogenesis. Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1-derived PGD₂ biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased thromboxane (Tx) formation. However, in platelet-rich plasma, where formation of both Tx and PGD₂ was increased, spreading was not as pronounced and was inhibited by DP1 activation. Thus, PGD₂, like PGI₂, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular relevance as a constraint on platelets during niacin therapy.

The importance of capillary density-stroke work mismatch for right ventricular adaptation to chronic pressure overload.

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Noly, Pierre-Emmanuel; Haddad, François; Arthur-Ataam, Jennifer; Langer, Nathaniel; Dorfmüller, Peter; Loisel, Fanny; Guihaire, Julien; Decante, Benoit; Lamrani, Lilia; Fadel, Elie; Mercier, Olaf

2017-12-01

Mechanisms of right ventricular (RV) adaptation to chronic pressure overload are not well understood. We hypothesized that a lower capillary density (CD) to stroke work ratio would be associated with more fibrosis and RV maladaptive remodeling. We induced RV chronic pressure overload over a 20-week period in 2 piglet models of pulmonary hypertension; that is, a shunt model (n = 5) and a chronic thromboembolic pulmonary hypertension model (n = 5). We assessed hemodynamic parameters and RV remodeling as well as RV CD, fibrosis, and angiogenic factors expression. Although RV was similarly hypertrophied in both models, maladapted RV remodeling with impaired systolic function was only seen in chronic thromboembolic pulmonary hypertension group members who had lower CD (484 ± 99 vs 1213 ± 74 cap/mm 2 ; P work ratio (0.29 ± 0.07 vs 0.82 ± 0.16; P = .02), higher myocardial fibrosis (15.4% ± 3.8% vs 8.0% ± 2.5%; P work ratio) was associated with greater degree of myocardial fibrosis and RV dysfunction and could be a promising index of RV maladaptation. Further studies are needed to understand the underlying mechanisms. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Evaluation of efficacy and safety of fixed dose lovastatin and niacinER combination in Asian Indian dyslipidemic patients: a multicentric study

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Manoj Sharma

2006-03-01

Full Text Available Manoj Sharma1, Deepika R Sharma1, Vikram Singh1, RB Panwar2, HS Hira3, Bishav Mohan4, Naveen Kumar4, SK Sharma5, Rajeev Gupta61Clinical Research Division, Panacea-Biotec Ltd, New Delhi; 2SP Medical College, Bikaner; 3Maulana Azad Medical College, New Delhi; 4Dayanand Medical College, Ludhiana; 5SMS Medical College, Jaipur; 6Monilek Hospital and Research Center, Jaipur, India.Abstract: Asian Indian dyslipidemia is characterized by: borderline high low-density lipoprotein (LDL cholesterol and apolipoprotein (apo B; high triglycerides, low high-density lipoprotein (HDL cholesterol and apoA1; and high lipoprotein(a (lp[a]. We performed a controlled multicentric trial in India to evaluate the efficacy and safety of a fixed dose combination of lovastatin and niacin extended release (niacinER formulation in patients with moderate to severe dyslipidemia. Consecutive subjects that satisfied the selection criteria, agreed to an informed consent, and with no baseline presence of liver/renal disease or heart failure were enrolled in the study. After a 4-week run-in period there were 142 patients with LDL levels ≥ 130 mg/dL. Eleven patients were excluded because of uncontrolled hyperglycemia and 131 patients were recruited. After baseline evaluation of clinical and biochemical parameters all subjects were administered lovastatin (20 mg and niacinER (500 mg combination once daily. Dose escalation was done on basis of lipid parameters at 8 weeks and in 11 patients increased to lovastatin (20 mg and niacinER (1000 mg. An intention-to-treat analysis was performed and data was analyzed using nonparametric Wilcoxon signed rank test. Thirteen patients (10% were lost to follow-up and 4 (3% withdrew because of dermatological adverse effects: flushing, pruritus, and rash. The mean values of various lipid parameters (mg/dL at baseline, and at weeks 4, 12, and 24 respectively were: total cholesterol 233.9 ± 27, 206.3 ± 27, 189.8 ± 31, and 174.9 ± 27 mg/dL; LDL

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

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Chalmers AW

2016-02-01

Full Text Available Anna W Chalmers, Jamile M Shammo Department of Internal Medicine, Division of Hematology/Oncology, Rush University Medical Center, Chicago, IL, USA Abstract: Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelodysplastic 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. Keywords: iron chelation therapy, transfusional iron overload, deferasirox

[Niacin allowance of students of a sports college].

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Borisov, I M

1977-01-01

In 227 students of the Institute for Physical Culture examined in the winter-spring and summer-fall seasons of the year, the passage of N1-methylnicotinamide (MNA) with urine per hour on an empty stomach amounted to 245 +/- 15.9 and 311 +/- 14.6 microgram/hour (the difference according to seasons in significant). These figues point to the dependence of the MNA excretion with uridine on the quantity of the niacin equivalents supplied together with the food. The content of such equivalentsin the rations of students-sprotrsmen (7-9.5 mg per 1000 calories per day) proved insufficient to maintain the MNA passage with urine at a level accepted as a standard allowance of niacin for the organism, i. e. 400-500 microgram/hour. Furthermore, the author shows changes in the niacin allowances of the student's organism, engaged in different kinds of sporting activities and also depending upon the sporting qualification of the examinees the work performed by them, the periods of training, and conditions of their every-day life.

Paraoxonase responses to exercise and niacin therapy in men with metabolic syndrome.

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Taylor, James Kyle; Plaisance, Eric P; Mahurin, A Jack; Mestek, Michael L; Moncada-Jimenez, Jose; Grandjean, Peter W

2015-01-01

Our purpose was to characterize changes in paraoxonase 1 (PON1) activity and concentration after single aerobic exercise sessions conducted before and after 6 weeks of niacin therapy in men with metabolic syndrome (MetS). Twelve men with MetS expended 500 kcal by walking at 65% of VO2max before and after a 6-week regimen of niacin. Niacin doses were titrated by 500 mg/week from 500 to 1500 mg/day and maintained at 1500 mg/day for the last 4 weeks. Fasting blood samples were collected before and 24 hours after each exercise session and analyzed for PON1 activity, PON1 concentration, myeloperoxidase (MPO), apolipoprotein A1, oxidized low-density lipoprotein (oLDL), lipoprotein particle sizes and concentrations. PON1 activity, PON1 concentration, MPO, and oLDL were unaltered following the independent effects of exercise and niacin (P > 0.05 for all). High-density lipoprotein particle size decreased by 3% (P = 0.040) and concentrations of small very low-density lipoprotein increased (P = 0.016) following exercise. PON1 activity increased 6.1% (P = 0.037) and PON1 concentrations increased 11.3% (P = 0.015) with the combination of exercise and niacin. Exercise and niacin works synergistically to increase PON1 activity and concentration with little or no changes in lipoproteins or markers of lipid oxidation.

Immediate release niacin effect at stratified lipid levels

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Elise Vo

2015-12-01

If initial LDL-C was  =130, LDL-C decreased 35% in MTG vs. 32% decrease in CTG. If initial HDL-C  150, there was a 48% decrease in MTG vs. 54% decrease in CTG. Lpa decreased 49% for all patients with initially elevated Lpa. Data except for LDL-C  130, but not significantly when LDL-C < 130. Patients in AIM-HIGH and HPS-2-THIRVE received statin therapy causing very low initial LDL-C. Our results may explain why adding niacin to statin therapy failed in AIM-HIGH and HPS-2-THRIVE since niacin did not further lower LDL-C.

Niacin results in reduced monocyte adhesion in patients with type 2 diabetes mellitus.

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Tavintharan, S; Woon, K; Pek, L T; Jauhar, N; Dong, X; Lim, S C; Sum, C F

2011-03-01

Patients with type 2 diabetes have increased expression of cell adhesion molecules (CAMs). CAMs and monocyte adhesion mediate essential processes in atherogenesis. It remains unclear if monocytes from patients on niacin have reduced adhesion function. We studied the variation of monocyte adhesion in patients with type 2 diabetes and low HDL-cholesterol, taking either extended release niacin (Niaspan®, Abbott Laboratories) or controls not on niacin. Biochemical parameters including adiponectin, CAMs and fresh monocytes from whole blood for adhesion assays, were studied at baseline and 12-weeks. Niacin 1500 mg daily raised HDL-cholesterol from 0.8 mmol/l (95% CI: 0.7-0.9) to 0.9 mmol/l (95% CI: 0.8-1.1), p=0.10, and significantly reduced PECAM-1 by 24.9% (95% CI: 10.9-39.0; p<0.05), increased adiponectin by 30.5% (95% CI: 14.1-47.0; p<0.05), with monocyte adhesion reduced by 9.2% (95%CI: 0.7-17.7; p<0.05) in endothelial cells treated in basal conditions, and 7.8% (95% CI: 3.1-12.5; p<0.05) after TNF-α stimulation. Monocytes isolated from patients on niacin had reduced adhesion to endothelial cells. Our findings suggest niacin has broad range of effects apart from lipid-modification, and these could be important in cardiovascular risk reduction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Niacin and biosynthesis of PGD2 by platelet COX-1 in mice and humans

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Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela; Alamuddin, Naji; Ibrahim, Salam; Crichton, Irene; Prempeh, Maxwell; Lawson, John A.; Wilensky, Robert L.; Rasmussen, Lars Melholt; Puré, Ellen; FitzGerald, Garret A.

2012-01-01

The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1–dependent formation of PGD2 and PGE2 followed by COX-2–dependent production of PGE2. Consistent with this, niacin-induced flushing in humans is attenuated when niacin is combined with an antagonist of the PGD2 receptor DP1. NSAID-mediated suppression of COX-2–derived PGI2 has negative cardiovascular consequences, yet little is known about the cardiovascular biology of PGD2. Here, we show that PGD2 biosynthesis is augmented during platelet activation in humans and, although vascular expression of DP1 is conserved between humans and mice, platelet DP1 is not present in mice. Despite this, DP1 deletion in mice augmented aneurysm formation and the hypertensive response to Ang II and accelerated atherogenesis and thrombogenesis. Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1–derived PGD2 biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased thromboxane (Tx) formation. However, in platelet-rich plasma, where formation of both Tx and PGD2 was increased, spreading was not as pronounced and was inhibited by DP1 activation. Thus, PGD2, like PGI2, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular relevance as a constraint on platelets during niacin therapy. PMID:22406532

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.

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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

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

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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

DIETARY AND BIOCHEMICAL PARAMETERS OF THE NIACIN DEFICIENCY IM YOUNG RATS

Directory of Open Access Journals (Sweden)

CARLOS ROBERTO VICTORIA

2009-07-01

Full Text Available

ABSTRACT: Using a defined laboratory diet composed by gelatin (6% and casein (10% as protein sources, without tryptophan and nicotinic acid supplementation, it should be possible to reproduce, in young rats, after 28 dais feeding with this deficient diet, a clinical and laboratory model of niacin deficiency. The deficient group, when compared against control, showed poor growth (63.3 g x 163.3 g; p<0.05, lower urinary excretion of N’-methylnicotinamide (0.005 mg/24 h x 0.259 mg/24 h; p<0.05, lower plasma free-tryptophan (2.1 uM/dl x 5.4 uM/dl; p<0.05, lower plasma albumin level (1.8 g/dl; p<0.05, smaller erythrocytes (48.9 u3 x 54.8 u3; p<0.05 and lower corpuscular hemoglobin (23.2 pg x 26.6 pg; p<0.05. All these changes were normalized by niacin replacement. We conclude that this dietetics model is easy and practical to be used for niacin deficiency purposes. KEYWORDS: Niacin; nicotinicacid; tryptophan; N’-methylnicotinamide; Pellagra.

Urinary Excretion of Niacin Metabolites in Humans After Coffee Consumption.

Science.gov (United States)

Kremer, Jonathan Isaak; Gömpel, Katharina; Bakuradze, Tamara; Eisenbrand, Gerhard; Richling, Elke

2018-04-01

Coffee is a major natural source of niacin in the human diet, as it is formed during coffee roasting from the alkaloid trigonelline. The intention of our study was to monitor the urinary excretion of niacin metabolites after coffee consumption under controlled diet. We performed a 4-day human intervention study on the excretion of major niacin metabolites in the urine of volunteers after ingestion of 500 mL regular coffee containing 34.8 μmol nicotinic acid (NA) and 0.58 μmol nicotinamide (NAM). In addition to NA and NAM, the metabolites N 1 -methylnicotinamide (NMNAM), N 1 -methyl-2-pyridone-5-carboxamide (2-Py), and nicotinuric acid (NUA) were identified and quantified in the collected urine samples by stable isotope dilution analysis (SIVA) using HPLC-ESI-MS/MS. Rapid urinary excretion was observed for the main metabolites (NA, NAM, NMNAM, and 2-Py), with t max values within the first hour after ingestion. NUA appeared in traces even more rapidly. In sum, 972 nmol h -1 of NA, NAM, NMNAM, and 2-Py were excreted within 12 h after coffee consumption, corresponding to 6% of the ingested NA and NAM. The results indicate regular coffee consumption to be a source of niacin in human diet. © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron overload in myelodysplastic syndromes (MDS).

Science.gov (United States)

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.

Iron overload and HFE gene mutations in Czech patients with chronic liver diseases.

Science.gov (United States)

Dostalikova-Cimburova, Marketa; Kratka, Karolina; Stransky, Jaroslav; Putova, Ivana; Cieslarova, Blanka; Horak, Jiri

2012-01-01

The aim of the study was to identify the prevalence of HFE gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of HFE gene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of HFE gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of HFE gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of HFE mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but {\\it HFE} mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.

Niacin deficiency delays DNA excision repair and increases spontaneous and nitrosourea-induced chromosomal instability in rat bone marrow.

Science.gov (United States)

Kostecki, Lisa M; Thomas, Megan; Linford, Geordie; Lizotte, Matthew; Toxopeus, Lori; Bartleman, Anne-Pascale; Kirkland, James B

2007-12-01

We have shown that niacin deficiency impairs poly(ADP-ribose) formation and enhances sister chromatid exchanges and micronuclei formation in rat bone marrow. We designed the current study to investigate the effects of niacin deficiency on the kinetics of DNA repair following ethylation, and the accumulation of double strand breaks, micronuclei (MN) and chromosomal aberrations (CA). Weanling male Long-Evans rats were fed niacin deficient (ND), or pair fed (PF) control diets for 3 weeks. We examined repair kinetics by comet assay in the 36h following a single dose of ethylnitrosourea (ENU) (30mg/kg bw). There was no effect of ND on mean tail moment (MTM) before ENU treatment, or on the development of strand breaks between 0 and 8h after ENU. Repair kinetics between 12 and 30h were significantly delayed by ND, with a doubling of area under the MTM curve during this period. O(6)-ethylation of guanine peaked by 1.5h, was largely repaired by 15h, and was also delayed in bone marrow cells from ND rats. ND significantly enhanced double strand break accumulation at 24h after ENU. ND alone increased chromosome and chromatid breaks (four- and two-fold). ND alone caused a large increase in MN, and this was amplified by ENU treatment. While repair kinetics suggest that ND may be acting by creating catalytically inactive PARP molecules with a dominant-negative effect on repair processes, the effect of ND alone on O(6)-ethylation, MN and CA, in the absence of altered comet results, suggests additional mechanisms are also leading to chromosomal instability. These data support the idea that the bone marrow cells of niacin deficient cancer patients may be more sensitive to the side effects of genotoxic chemotherapy, resulting in acute bone marrow suppression and chronic development of secondary leukemias.

The association of sleep quality and insomnia with dietary intake of tryptophan and niacin

NARCIS (Netherlands)

Verster, J.; Fernstrand, A.; Bury, D.; Roth, T.; Garssen, J.

2015-01-01

Introduction: Dietary intake of tryptophan and niacin have been related to sleep. However, the sleep-promoting effects of these nutrients are still under investigation. The aim of the current study was to examine the relationship between daily dietary intake of tryptophan and niacin and sleep.

Therapeutic role of niacin in the prevention and regression of hepatic steatosis in rat model of nonalcoholic fatty liver disease.

Science.gov (United States)

Ganji, Shobha H; Kukes, Gary D; Lambrecht, Nils; Kashyap, Moti L; Kamanna, Vaijinath S

2014-02-15

Nonalcoholic fatty liver disease (NAFLD), a leading cause of liver damage, comprises a spectrum of liver abnormalities including the early fat deposition in the liver (hepatic steatosis) and advanced nonalcoholic steatohepatitis. Niacin decreases plasma triglycerides, but its effect on hepatic steatosis is elusive. To examine the effect of niacin on steatosis, rats were fed either a rodent normal chow, chow containing high fat (HF), or HF containing 0.5% or 1.0% niacin in the diet for 4 wk. For regression studies, rats were first fed the HF diet for 6 wk to induce hepatic steatosis and were then treated with niacin (0.5% in the diet) while on the HF diet for 6 wk. The findings indicated that inclusion of niacin at 0.5% and 1.0% doses in the HF diet significantly decreased liver fat content, liver weight, hepatic oxidative products, and prevented hepatic steatosis. Niacin treatment to rats with preexisting hepatic steatosis induced by the HF diet significantly regressed steatosis. Niacin had no effect on the mRNA expression of fatty acid synthesis or oxidation genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1, fatty acid synthase, and carnitine palmitoyltransferase 1) but significantly inhibited mRNA levels, protein expression, and activity of diacylglycerol acyltrasferase 2, a key enzyme in triglyceride synthesis. These novel findings suggest that niacin effectively prevents and causes the regression of experimental hepatic steatosis. Approved niacin formulation(s) for other indications or niacin analogs may offer a very cost-effective opportunity for the clinical development of niacin for treating NAFLD and fatty liver disease.

Effects of niacin supplementation on the insulin resistance in Holstein cows during early lactation

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Talija Hristovska

2017-01-01

Full Text Available Insulin resistance in early lactation includes low glucose concentration, low insulin release and responsiveness and high lipolysis. Niacin is important antilipolytic agent and leads to increase glucose and insulin concentration. The objectives of this study were to determine the influence of niacin on the insulin resistance in cows during early lactation using the difference of value and regression analysis between blood non-esterified fatty acid (NEFA, glucose and insulin concentrations, revised quantitative insulin sensitivity check index and glucose-to-insulin ratio. Niacin supplementation led to a decrease of NEFA concentration and an increase of glucose and insulin concentrations during the first three weeks after calving. Cows in the niacin group which were more resistant to insulin showed higher concentrations of non-esterified fatty acid in comparison with more sensitive cows from the same group, but still lower than the control. The regression analyses suggest the following characteristics of cows supplemented with niacin in comparison with the control group: the insulin response to glucose was more intense; the antilipolytic effect of insulin was lower; insulin efficiency expressed as glucose-to-insulin ratio increase with a decrease in NEFA. The metabolic changes due to niacin supplementation showed a dual influence on the insulin resistance in dairy cows during early lactation: decreased NEFA concentrations led to a decrease in the insulin resistance (due to an increase in insulin efficiency and insulin sensitivity index, but increased concentrations of insulin and glucose possibly caused an increase in the insulin resistance in dairy cows (due to lower insulin sensitivity index and possibly lower antilipolytic effects of insulin.

Effects of extended-release niacin with laropiprant in high-risk patients

DEFF Research Database (Denmark)

Landray, Martin J; Haynes, Richard; Hopewell, Jemma C

2014-01-01

BACKGROUND: Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) choleste......-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.)....

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

Science.gov (United States)

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

Liver fat reduction with niacin is influenced by DGAT-2 polymorphisms in hypertriglyceridemic patients.

Science.gov (United States)

Hu, Miao; Chu, Winnie Chiu Wing; Yamashita, Shizuya; Yeung, David Ka Wai; Shi, Lin; Wang, Defeng; Masuda, Daisaku; Yang, Yaling; Tomlinson, Brian

2012-04-01

Niacin reduces plasma triglycerides, but it may increase free fatty acids and insulin resistance during long-term treatment. We examined the effect of extended-release niacin on liver fat content in Chinese patients with dyslipidemia and whether the common diacylglycerol acyltransferase-2 (DGAT2) polymorphisms influenced this effect. The 39 patients (baseline liver fat content: 12.8 ± 7.6%, triglycerides: 3.30 ± 1.67 mmol/l) were treated with niacin, gradually increasing the dose to 2 g/day for a total of 23 weeks. The liver fat content and visceral/subcutaneous fat was measured before and after treatment. Subjects were genotyped for the DGAT2 rs3060 and rs101899116 polymorphisms. There were significant (P < 0.001) reductions in plasma triglycerides (-34.9 ± 37.6%), liver fat content (-47.2 ± 32.8%), and visceral fat (-6.3 ± 15.8%, P < 0.05) after niacin treatment. Mean body weight decreased by 1.46 ± 2.7% (1.17 ± 2.44 kg, P < 0.001) during the study, but liver fat changes remained significant after adjustment for age, gender, and body weight changes [mean absolute change (95% CI): -6.1% (-8.0, -4.3), P < 0.001]. The DGAT2 variant alleles were associated with a smaller reduction in liver fat content in response to niacin after adjustment for other covariates (P < 0.01). These findings suggest that niacin treatment may reduce liver fat content in Chinese patients with dyslipidemia and that the mechanism may involve inhibition of DGAT2. However, the findings might have been confounded by the small but significant reductions in body weight during the study. Future large randomized controlled trials are needed to verify these findings.

Effects of short-term niacin treatment on plasma lipoprotein concentrations in African green monkeys (Chlorocebus aethiops)

KAUST Repository

Chauke, Chesa G.; Arieff, Zainunisha; Kaur, Mandeep; Seier, Jü rgen V.

2014-01-01

Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African

Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials.

Science.gov (United States)

Goldie, Christina; Taylor, Allen J; Nguyen, Peter; McCoy, Cody; Zhao, Xue-Qiao; Preiss, David

2016-02-01

Previous studies have suggested that niacin treatment raises glucose levels in patients with diabetes and may increase the risk of developing diabetes. We undertook a meta-analysis of published and unpublished data from randomised trials to confirm whether an association exists between niacin and new-onset diabetes. We searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials, from 1975 to 2014, for randomised controlled trials of niacin primarily designed to assess its effects on cardiovascular endpoints and cardiovascular surrogate markers. We included trials with ≥50 non-diabetic participants and average follow-up of ≥24 weeks. Published data were tabulated and unpublished data sought from investigators. We calculated risk ratios (RR) for new-onset diabetes with random-effects meta-analysis. Heterogeneity between trials was assessed using the I(2) statistic. In 11 trials with 26 340 non-diabetic participants, 1371 (725/13 121 assigned niacin; 646/13 219 assigned control) were diagnosed with diabetes during a weighted mean follow-up of 3.6 years. Niacin therapy was associated with a RR of 1.34 (95% CIs 1.21 to 1.49) for new-onset diabetes, with limited heterogeneity between trials (I(2)=0.0%, p=0.87). This equates to one additional case of diabetes per 43 (95% CI 30 to 70) initially non-diabetic individuals who are treated with niacin for 5 years. Results were consistent regardless of whether participants received background statin therapy (p for interaction=0.88) or combined therapy with laropiprant (p for interaction=0.52). Niacin therapy is associated with a moderately increased risk of developing diabetes regardless of background statin or combination laropiprant therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effects of short-term niacin treatment on plasma lipoprotein concentrations in African green monkeys (Chlorocebus aethiops).

Science.gov (United States)

Chauke, Chesa G; Arieff, Zainunisha; Kaur, Mandeep; Seier, Jurgen V

2014-02-01

Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African green monkeys for 3 months. In the treated monkeys, low-density lipoprotein cholesterol concentrations decreased by 43% from baseline, whereas concentrations of HDL cholesterol and apolipoprotein A-I increased by 49% and 34%, respectively. The results suggest that in this primate model, a low dose of niacin can effectively increase concentrations of HDL cholesterol.

Effects of short-term niacin treatment on plasma lipoprotein concentrations in African green monkeys (Chlorocebus aethiops)

KAUST Repository

Chauke, Chesa G.

2014-01-22

Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African green monkeys for 3 months. In the treated monkeys, low-density lipoprotein cholesterol concentrations decreased by 43% from baseline, whereas concentrations of HDL cholesterol and apolipoprotein A-I increased by 49% and 34%, respectively. The results suggest that in this primate model, a low dose of niacin can effectively increase concentrations of HDL cholesterol.©2014 Nature America, Inc. All rights reserved.

Effects of niacin supplementation on the insulin resistance in Holstein cows during early lactation

OpenAIRE

Talija Hristovska; Marko R. Cincović; Branislava Belić; Dragica Stojanović; Milanka Jezdimirović; Radojica Đoković; Bojan Toholj

2017-01-01

Insulin resistance in early lactation includes low glucose concentration, low insulin release and responsiveness and high lipolysis. Niacin is important antilipolytic agent and leads to increase glucose and insulin concentration. The objectives of this study were to determine the influence of niacin on the insulin resistance in cows during early lactation using the difference of value and regression analysis between blood non-esterified fatty acid (NEFA), glucose and insulin concentrations, r...

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

Science.gov (United States)

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.

Information overload and data overload in lexicography

DEFF Research Database (Denmark)

Gouws, Rufus H.; Tarp, Sven

2017-01-01

the often uncritical inclusion of too much data. This paper discusses the general term information overload and its lexicographical counterpart data overload. Different types of data overload are identified and the problems users have when retrieving the necessary information from dictionary articles...

Effects of niacin supplementation (40 weeks) and two dietary levels ...

African Journals Online (AJOL)

Meyer, Ulrich

2006-05-18

May 18, 2006 ... on performance, blood and fatty acid profiles of dairy cattle. C. Rauls1, U. ... included 40 treatment comparisons with niacin supplementation, and, in most cases, found positive ...... Effects of feeding heat-treated soybeans and.

Niacin alters the ruminal microbial composition of cattle under high-concentrate condition

Directory of Open Access Journals (Sweden)

Dan Luo

2017-06-01

Full Text Available To understand the effects of niacin on the ruminal microbial ecology of cattle under high-concentrate diet condition, Illumina MiSeq sequencing technology was used. Three cattle with rumen cannula were used in a 3 × 3 Latin-square design trial. Three diets were fed to these cattle during 3 periods for 3 days, respectively: high-forage diet (HF; forage-to-concentrate ratio = 80:20, high-concentrate diet (HC; forage-to-concentrate ratio = 20:80, and HC supplemented with 800 mg/kg niacin (HCN. Ruminal pH was measured before feeding and every 2 h after initiating feeding. Ruminal fluid was sampled at the end of each period for microbial DNA extraction. Overall, our findings revealed that subacute ruminal acidosis (SARA was induced and the α-diversity of ruminal bacterial community decreased in the cattle of HC group. Adding niacin in HC could relieve the symptoms of SARA in the cattle but the ruminal pH value and the Shannon index of ruminal bacterial community of HCN group were still lower than those of HF group. Whatever the diet was, the ruminal bacterial community of cattle was dominated by Bacteroidetes, Firmicutes and Proteobacteria. High-concentrate diet significantly increased the abundance of Prevotella, and decreased the abundance of Paraprevotella, Sporobacter, Ruminococcus and Treponema than HF. Compared with HC, HCN had a trend to decrease the percentage of Prevotella, and to increase the abundance of Succiniclasticum, Acetivibrio and Treponema. Increasing concentrate ratio could decrease ruminal pH value, and change the ruminal microbial composition. Adding niacin in HC could increase the ruminal pH value, alter the ruminal microbial composition.

Studies on the riboflavin, niacin, pantothenic acid and choline requirements of young bobwhite quail

Science.gov (United States)

Serafin, J.A.

1974-01-01

Four experiments were conducted to examine the riboflavin, niacin, pantothenic acid and choline requirements of young Bobwhite quail. Quail fed purified diets deficient in either riboflavin, niacin, pantothenic acid or choline grew poorly and high mortality occurred by 5 weeks of age. Under the conditions of these experiments, it was found that: (1) young quail require approximately 3.8 mg. riboflavin/kg. diet for satisfactory growth and survival; (2) no more than 31 mg. niacin/kg. diet are required for normal growth and survival of young quail; (3) the requirement for pantothenic acid is higher than has previously been reported, quail in these studies requiring 12.6 mg. pantothenic acid/kg. feed for growth and survival; and (4) the requirement for choline for reducing mortality is approximately 1000 mg./kg., while the amount necessary for normal growth of young quail is no greater than 1500 mg./kg. when the diet contains ample amounts of methionine. Quail fed a niacin-deficient diet developed stiff, shortened feathers and an erythema about the head; those receiving a riboflavin-deficient ration developed enlarged hocks and bowed legs, as did quail fed diets low or devoid of choline. Aside from slow growth, poor feathering was the only other indication that a deficient diet was being fed when quail were placed on a basal ration without pantothenic acid for five weeks.

Relative Bioavailability of Niacin Supplements for Dairy Cows: Effects of Rumen Protection and of Feed Processing.

Science.gov (United States)

Tienken, Reka; Kersten, Susanne; Hüther, Liane; Frahm, Jana; Meyer, Ulrich; Dänicke, Sven

2015-12-16

The present study aimed to examine the effective systemic bioavailability of niacin- with particular focus on its galenic form-and feed processing. Experiment 1 was conducted with 35 dairy cows to investigate the effects of various doses of oral supplemented nicotinic acid (NA) either in differing galenic forms (non-rumen protected (nRP) vs. rumen protected form (RP)) on serum niacin concentrations. Experiment 2 was designed as a pharmacokinetic study examining the serum niacin kinetics over 24 h after giving a single oral bolus of 24 g nRP or RP NA admixed in either pelleted or ground concentrate. In both experiments, only the niacin vitamer nicotinamide (NAM) was detected. Results of experiment 1 showed that both galenic forms at a dose of 24 g/cow daily elevated NAM concentrations at the beginning of the experiment. Despite a daily supplementation, NAM concentrations decreased continuously towards the end of the experiment which was more steeply in nRP NA ( p = 0.03). On experimental day 21, NAM concentrations were higher when feeding RP NA ( p = 0.03) and the highest dose (24 g/day and cow) ( p counterbalancing alterations. Pelleting seemed not to influence the relative bioavailability.

Niacin, poly(ADP-ribose) polymerase-1 and genomic stability

NARCIS (Netherlands)

Hageman, G.J.; Stierum, R.H.

2001-01-01

Nicotinic acid (NA) and nicotinamide (NAM), commonly called niacin, are the dietary precursors for NAD+ (nicotinamide adenine dinucleotide), which is required for DNA synthesis, as well as for the activity of the enzyme poly(ADP-ribose) polymerase-1 (PARP-1; EC 2.4.2.30) for which NAD+ is the sole

Pleiotropic effects of niacin: current possibilities for its clinical use

Czech Academy of Sciences Publication Activity Database

Zeman, M.; Vecka, M.; Perlík, F.; Staňková, B.; Hromádka, R.; Tvrzická, E.; Širc, Jakub; Hrib, Jakub; Žák, A.

2016-01-01

Roč. 66, č. 4 (2016), s. 449-469 ISSN 1330-0075 R&D Projects: GA MPO(CZ) FR-TI4/638 Institutional support: RVO:61389013 Keywords : niacin * pleiotropic effects * HCA2 receptor Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.288, year: 2016

Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

Directory of Open Access Journals (Sweden)

Sarman Singh

2015-01-01

Full Text Available BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine.

Liver steatosis correlates with iron overload but not with HFE gene mutations in chronic hepatitis C.

Science.gov (United States)

Sikorska, Katarzyna; Stalke, Piotr; Romanowski, Tomasz; Rzepko, Robert; Bielawski, Krzysztof Piotr

2013-08-01

Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non-alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serum markers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.

Work Overload.

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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.…

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

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Tsuyoshi Ogata

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

Effects of niacin supplementation and dietary concentrate proportion on body temperature, ruminal pH and milk performance of primiparous dairy cows.

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Lohölter, Malte; Meyer, Ulrich; Rauls, Caroline; Rehage, Jürgen; Dänicke, Sven

2013-06-01

The objective of this study was to investigate the effects of niacin and dietary concentrate proportion on body temperature, ruminal pH and milk production of dairy cows. In a 2 × 2 factorial design, 20 primiparous Holstein cows (179 ± 12 days in milk) were assigned to four dietary treatments aimed to receive either 0 or 24 g niacin and 30% (low) or 60% (high) concentrate with the rest being a partial mixed ration (PMR) composed of 60% corn and 40% grass silage (on dry matter basis). Ambient temperature and relative humidity were determined and combined by the calculation of temperature humidity index. Respiration rates, rectal, skin and subcutaneous temperatures were measured. Milk production and composition were determined. Ruminal pH and temperature were recorded at a frequency of 5 min using wireless devices for continuous intra-ruminal measurement (boluses). pH values were corrected for pH sensor drift. The climatic conditions varied considerably but temporarily indicated mild heat stress. Niacin did not affect skin, rectal and subcutaneous temperatures but tended to increase respiration rates. High concentrate reduced skin temperatures at rump, thigh and neck by 0.1-0.3°C. Due to the technical disturbances, not all bolus data could be subjected to statistical evaluation. However, both niacin and high concentrate influenced mean ruminal pH. High concentrate increased the time spent with a pH below 5.6 and ruminal temperatures (0.2-0.3°C). Niacin and high concentrate enhanced milk, protein and lactose yield but reduced milk fat and protein content. Milk fat yield was slightly reduced by high concentrate but increased due to niacin supplementation. In conclusion, niacin did not affect body temperature but stimulated milk performance. High concentrate partially influenced body temperatures and had beneficial effects on milk production.

Exogenous fatty acids and niacin on acute prostaglandin D2 production in human myeloid cells.

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Montserrat-de la Paz, Sergio; Bermudez, Beatriz; Lopez, Sergio; Naranjo, Maria C; Romero, Yolanda; Bando-Hidalgo, Maria J; Abia, Rocio; Muriana, Francisco J G

2017-01-01

Niacin activates HCA 2 receptor that results in the release of PGD 2 . However, little is known on PGD 2 -producing cells and the role of fatty acids. Notably M-CSF macrophages exhibited a timely dependent PGD 2 production upon niacin challenge. Short pretreatment of M-CSF macrophages with autologous postprandial TRLs induced the down-regulation of HCA 2 gene and up-regulation of genes encoding COX1 and COX2 enzymes in a fatty acid-dependent manner. These effects were paralleled by a higher PGD 2 production with postprandial TRL-SFAs. The niacin-mediated transcriptional activity of all genes involved in PGD 2 biosynthesis was desensitized in a time-dependent manner by postprandial TRLs, leading to a decreased PGD 2 release. In vivo, the net excursions of PGD 2 in plasma followed similar fatty acid-dependent patterns as those found for PGD 2 release in vitro. The predominant fatty acid class in the diet acutely modulates PGD 2 biosynthetic pathway both in vitro and in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of immediate-release niacin and dietary fatty acids on acute insulin and lipid status in individuals with metabolic syndrome.

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Montserrat-de la Paz, Sergio; Lopez, Sergio; Bermudez, Beatriz; Guerrero, Juan M; Abia, Rocio; Muriana, Francisco Jg

2018-04-01

The nature of dietary fats profoundly affects postprandial hypertriglyceridemia and glucose homeostasis. Niacin is a potent lipid-lowering agent. However, limited data exist on postprandial triglycerides and glycemic control following co-administration of high-fat meals with a single dose of niacin in subjects with metabolic syndrome (MetS). The aim of the study was to explore whether a fat challenge containing predominantly saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated (LCPUFAs) fatty acids together with a single dose of immediate-release niacin have a relevant role in postprandial insulin and lipid status in subjects with MetS. In a randomized crossover within-subject design, 16 men with MetS were given a single dose of immediate-release niacin (2 g) and ∼15 cal kg -1 body weight meals containing either SFAs, MUFAs, MUFAs plus omega-3 LCPUFAs or no fat. At baseline and hourly over 6 h, plasma glucose, insulin, C-peptide, triglycerides, free fatty acids (FFAs), total cholesterol, and both high- and low-density lipoprotein cholesterol were assessed. Co-administered with niacin, high-fat meals significantly increased the postprandial concentrations of glucose, insulin, C-peptide, triglycerides, FFAs and postprandial indices of β-cell function. However, postprandial indices of insulin sensitivity were significantly decreased. These effects were significantly attenuated with MUFAs or MUFAs plus omega-3 LCPUFAs when compared with SFAs. In the setting of niacin co-administration and compared to dietary SFAs, MUFAs limit the postprandial insulin, triglyceride and FFA excursions, and improve postprandial glucose homeostasis in MetS. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage

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Mitchell C. Coleman

2017-11-01

Full Text Available Post-traumatic osteoarthritis can develop as a result of the initial mechanical impact causing the injury and also as a result of chronic changes in mechanical loading of the joint. Aberrant mechanical loading initiates excessive production of reactive oxygen species, oxidative damage, and stress that appears to damage mitochondria in the surviving chondrocytes. To probe the benefits of increasing superoxide removal with small molecular weight superoxide dismutase mimetics under severe loads, we applied both impact and overload injury scenarios to bovine osteochondral explants using characterized mechanical platforms with and without GC4403, MnTE-2-PyP, and MnTnBuOE-2-PyP. In impact scenarios, each of these mimetics provides some dose-dependent protection from cell death and loss of mitochondrial content while in repeated overloading scenarios only MnTnBuOE-2-PyP provided a clear benefit to chondrocytes. These results support the hypothesis that superoxide is generated in excess after impact injuries and suggest that superoxide production within the lipid compartment may be a critical mediator of responses to chronic overload. This is an important nuance distinguishing roles of superoxide, and thus superoxide dismutases, in mediating damage to cellular machinery in hyper-acute impact scenarios compared to chronic scenarios.

The effects of exogenous fatty acids and niacin on human monocyte-macrophage plasticity.

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Montserrat-de la Paz, Sergio; Rodriguez, Dolores; Cardelo, Magdalena P; Naranjo, Maria C; Bermudez, Beatriz; Abia, Rocio; Muriana, Francisco J G; Lopez, Sergio

2017-08-01

Macrophage plasticity allows adapting to different environments, having a dual activity in inflammatory-related diseases. Our hypothesis is that the type of dietary fatty acids into human postprandial triglyceride-rich lipoproteins (TRLs), alone or in combination with niacin (vitamin B3), could modulate the plasticity of monocytes-macrophages. We isolated TRLs at the postprandial peak from blood samples of healthy volunteers after the ingestion of a meal rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). Autologous monocytes isolated at fasting were first induced to differentiate into naïve macrophages. We observed that postprandial TRL-MUFAs, particularly in combination with niacin, enhance competence to monocytes to differentiate and polarise into M2 macrophages. Postprandial TRL-SFAs made polarised macrophages prone to an M1 phenotype. In contrast to dietary SFAs, dietary MUFAs in the meals plus immediate-release niacin primed circulating monocytes for a reduced postprandial pro-inflammatory profile. Our study underlines a role of postprandial TRLs as a metabolic entity in regulating the plasticity of the monocyte-macrophage lineage and also brings an understanding of the mechanisms by which dietary fatty acids are environmental factors fostering the innate immune responsiveness in humans. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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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.

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

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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.

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

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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

Niacin and biosynthesis of PGD₂ by platelet COX-1 in mice and humans

DEFF Research Database (Denmark)

Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela

2012-01-01

during platelet activation in humans and, although vascular expression of DP1 is conserved between humans and mice, platelet DP1 is not present in mice. Despite this, DP1 deletion in mice augmented aneurysm formation and the hypertensive response to Ang II and accelerated atherogenesis and thrombogenesis....... Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1-derived PGD₂ biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased...... thromboxane (Tx) formation. However, in platelet-rich plasma, where formation of both Tx and PGD₂ was increased, spreading was not as pronounced and was inhibited by DP1 activation. Thus, PGD₂, like PGI₂, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular...

Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs.

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Kent, Seamus; Haynes, Richard; Hopewell, Jemma C; Parish, Sarah; Gray, Alastair; Landray, Martin J; Collins, Rory; Armitage, Jane; Mihaylova, Borislava

2016-07-01

Extended-release niacin with laropiprant did not significantly reduce the risk of major vascular events and increased the risk of serious adverse events in Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), but its net effects on health and healthcare costs are unknown. 25 673 participants aged 50 to 80 years with previous cardiovascular disease were randomized to 2 g of extended-release niacin with 40 mg of laropiprant daily versus matching placebo, in addition to effective statin-based low-density lipoprotein cholesterol-lowering treatment. The net effects of niacin-laropiprant on quality-adjusted life years and hospital care costs (2012 UK £; converted into US $ using purchasing power parity index) during 4 years in HPS2-THRIVE were evaluated using estimates of the impact of serious adverse events on health-related quality of life and hospital care costs. During the study, participants assigned niacin-laropiprant experienced marginally but not statistically significantly lower survival (0.012 fewer years [standard error (SE) 0.007]), fewer quality-adjusted life years (0.023 [SE 0.007] fewer using UK EQ-5D scores; 0.020 [SE 0.006] fewer using US EQ-5D scores) and accrued greater hospital costs (UK £101 [SE £37]; US $145 [SE $53]). Stroke, heart failure, musculoskeletal events, gastrointestinal events, and infections were associated with significant decreases in health-related quality of life in both the year of the event and in subsequent years. All serious vascular and nonvascular events were associated with substantial increases in hospital care costs. In HPS2-THRIVE, the addition of extended-release niacin-laropiprant to statin-based therapy reduced quality of life-adjusted survival and increased hospital costs. URL: http://clinicaltrials.gov. Unique identifier: NCT00461630. © 2016 American Heart Association, Inc.

Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

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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.

High dietary niacin intake is associated with decreased chromosome translocation frequency in airline pilots.

Science.gov (United States)

Yong, Lee C; Petersen, Martin R

2011-02-01

Experimental studies suggest that B vitamins such as niacin, folate, riboflavin, vitamin B6 and vitamin B12 may protect against DNA damage induced by ionising radiation (IR). However, to date, data from IR-exposed human populations are not available. We examined the intakes of these B vitamins and their food sources in relation to the frequency of chromosome translocations as a biomarker of cumulative DNA damage, in eighty-two male airline pilots. Dietary intakes were estimated by using a self-administered semi-quantitative FFQ. Translocations in peripheral blood lymphocytes were scored by using fluorescence in situ hybridisation whole-chromosome painting. Negative binomial regression was used to estimate rate ratios and 95 % CI, adjusted for age and occupational and lifestyle factors. We observed a significant inverse association between translocation frequency and dietary intake of niacin (P = 0·02): adjusted rate ratio for subjects in the highest tertile compared with the lowest tertile was 0·58 (95 % CI 0·40, 0·83). Translocation frequency was not associated with total niacin intake from food and supplements as well as dietary or total intake of folate, riboflavin or vitamin B6 or B12. However, the adjusted rate ratios were significant for subjects with ≥ median compared with food or a diet high in whole grains but low in red and processed meat may protect against cumulative DNA damage in IR-exposed persons.

[Role of hippocampal neuronal intracellular calcium overload in modulating cognitive dysfunction and the neuronprotective effect of mematine in a mouse model of chronic intermittent hypoxia].

Science.gov (United States)

Ming, Hong; Chen, Rui; Wang, Jing; Ju, Jingmei; Sun, Li; Zhang, Guoxing

2014-12-01

To investigate the role of hippocampal intracellular calcium overload in modulating cognitive dysfunction and the neuronprotective effect of mematine in a mouse model of chronic intermittent hypoxia. 45 ICR male mice were randomly divided into 3 groups: the unhandled control group (UC group, n = 15), the chronic intermittent hypoxia (CIH group, n = 15) and the pretreatment memantine group (MEM group, n = 15). CIH and MEM mice were subjected to intermittent hypoxia while UC mice to room air for 8 h per day during 4 weeks. Mice in the MEM group were pretreated with memantine (5 mg/kg) by intraperitoneal injection before the cycle started, and those in the UC group and the CIH group were treated with same volume of physiological saline. Neurobehavioral assessments were performed by Open filed and Morris water maze, [Ca²⁺]i in hippocampal neurons was evaluate by flow cytometry, and the expression of cleaved caspase-3, phospho-ERK1/2 in hippocampus were detected by Western blotting. Compared with the UC group, CIH mice displayed markedly more locomotor activity (P overload, neuron apoptosis, dephosphorylation of ERK1/2, which can be attenuated by memantine. Memantine may have a therapeutic effect in the neurocognitive impairment associated with OSAHS.

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

Science.gov (United States)

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.

Relative Bioavailability of Niacin Supplements for Dairy Cows: Effects of Rumen Protection and of Feed Processing

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Reka Tienken

2015-12-01

Full Text Available The present study aimed to examine the effective systemic bioavailability of niacin— with particular focus on its galenic form—and feed processing. Experiment 1 was conducted with 35 dairy cows to investigate the effects of various doses of oral supplemented nicotinic acid (NA either in differing galenic forms (non-rumen protected (nRP vs. rumen protected form (RP on serum niacin concentrations. Experiment 2 was designed as a pharmacokinetic study examining the serum niacin kinetics over 24 h after giving a single oral bolus of 24 g nRP or RP NA admixed in either pelleted or ground concentrate. In both experiments, only the niacin vitamer nicotinamide (NAM was detected. Results of experiment 1 showed that both galenic forms at a dose of 24 g/cow daily elevated NAM concentrations at the beginning of the experiment. Despite a daily supplementation, NAM concentrations decreased continuously towards the end of the experiment which was more steeply in nRP NA (p = 0.03. On experimental day 21, NAM concentrations were higher when feeding RP NA (p = 0.03 and the highest dose (24 g/day and cow (p < 0.01. Results of experiment 2 indicated that nRP and RP were characterized by similar pharmacokinetic profiles resulting in similar areas under the curves as a net result of the kinetic counterbalancing alterations. Pelleting seemed not to influence the relative bioavailability.

Effects of fluid overload on heart rate variability in chronic kidney disease patients on hemodialysis.

Science.gov (United States)

Ferrario, Manuela; Moissl, Ulrich; Garzotto, Francesco; Cruz, Dinna N; Clementi, Anna; Brendolan, Alessandra; Tetta, Ciro; Gatti, Emanuele; Signorini, Maria G; Cerutti, Sergio; Ronco, Claudio

2014-02-04

While fluid overload (FO) and alterations in the autonomic nervous system (ANS) such as hypersympathetic activity, are known risk factors for cardiovascular morbidity and mortality in patients on chronic hemodialysis (HD), their relationship has not been thoroughly studied. In this observational study involving 69 patients on chronic HD, FO was assessed by whole body bioimpedance measurements before the midweek HD session and ANS activity reflected by Heart Rate Variability (HRV) was measured using 24-hour Holter electrocardiogram recordings starting before the same HD treatment. In total, 13 different HRV indices were analyzed, comprising a mixture of time domain, frequency domain and complexity parameters. A correlation analysis was performed between the HRV indices and hydration status indices. Successively, patients were retrospectively assigned to a high FO (H, FO > 2.5 L) or low FO (L, FO ≤ 2.5 L) group and these were further compared also after stratification by diabetes mellitus. Finally, a small number of patients without diabetes with significant and persistent FO were followed up for 3 months post-study to investigate how normalization of fluid status affects HRV. SDANN, VLF, LZC and HF% parameters significantly correlate with FO (correlation coefficients were respectively r = -0.40, r = -0.37, r = -0.28 and r = 0.26, p-value hydration status (correlation coefficients were respectively r = -0.31 and r = -0.33, p-value hydration status is accompanied by improved HRV.

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

International Nuclear Information System (INIS)

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

2017-01-01

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

Magnetic resonance imaging of splenic iron overload

International Nuclear Information System (INIS)

Arrive, L.; Thurnher, S.; Hricak, H.; Price, D.C.

1990-01-01

The value of magnetic resonance (MR) imaging in assessing iron overload in the spleen was retrospectively investigated in 40 consecutive patients. MR appearance, mesaure of signal intensity and T1-and T2-relaxation times were correlated with the histologically determined level of iron in the spleen in each patient. Histologic examination revealed no iron overload in 19 patients, mild iron overload in seven, moderate iron overload in six, and severe iron overload in eight. All 19 patients with no splenic iron overload and 11 of the other 21 patients with splenic iron overload were correctly identified by MR imaging (sensitivity 52%, specificity 100%, accuracy 75%). Splenic iron overload was diagnosed when a decrease of signal intensity of the spleen compared with those of adipose tissue and renal cortex was demonstrated. MR images demonstrated all eight cases of severe, three of the six cases of moderate, and none of the seven cases of mild iron overload. Only spleens with severe iron overload had a significant mean decrease in signal intensity and T1- and T2-relaxation times. Although specific, MR imaging is poorly sensitive to splenic iron overload. (author). 15 refs.; 5 figs.; 3 tabs

Update on the use of deferasirox in the management of iron overload

Directory of Open Access Journals (Sweden)

Ali Taher

2009-10-01

Full Text Available Ali Taher,1 Maria Domenica Cappellini21American University of Beirut, Beirut, Lebanon; 2Universitá di Milano, Policlinico Foundation IRCCS, Milan, ItalyAbstract: Regular blood transfusions as supportive care for patients with chronic anemia inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload cause significant morbidity and mortality if not effectively treated with chelation therapy. Based on a comprehensive clinical development program, the once-daily, oral iron chelator deferasirox (Exjade® is approved for the treatment of transfusional iron overload in adult and pediatric patients with various transfusion-dependent anemias, including β-thalassemia and the myelodysplastic syndromes. Deferasirox dose should be titrated for each individual patient based on transfusional iron intake, current iron burden and whether the goal is to decrease or maintain body iron levels. Doses of >30 mg/kg/day have been shown to be effective with a safety profile consistent with that observed at doses <30 mg/kg/day. Recent data have highlighted the ability of deferasirox to decrease cardiac iron levels and to prevent the accumulation of iron in the heart. The long-term efficacy and safety of deferasirox for up to 5 years of treatment have now been established. The availability of this effective and generally well tolerated oral therapy represents a significant advance in the management of transfusional iron overload. Keywords: deferasirox, Exjade, oral, iron chelation, iron overload, cardiac iron 

Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform.

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Valent, Peter; Stauder, Reinhard; Theurl, Igor; Geissler, Klaus; Sliwa, Thamer; Sperr, Wolfgang R; Bettelheim, Peter; Sill, Heinz; Pfeilstöcker, Michael

2018-02-01

Despite the availability of effective iron chelators, transfusion-related morbidity is still a challenge in chronically transfused patients with myelodysplastic syndromes (MDS). In these patients, transfusion-induced iron overload may lead to organ dysfunction or even organ failure. In addition, iron overload is associated with reduced overall survival in MDS. Areas covered: During the past 10 years, various guidelines for the management of MDS patients with iron overload have been proposed. In the present article, we provide our updated recommendations for the diagnosis, prevention and therapy of iron overload in MDS. In addition, we propose refined treatment response criteria. As in 2006 and 2007, recommendations were discussed and formulated by participants of our Austrian MDS platform in a series of meetings in 2016 and 2017. Expert commentary: Our updated recommendations should support early recognition of iron overload, optimal patient management and the measurement of clinical responses to chelation treatment in daily practice.

Culinary plants and their potential impact on metabolic overload.

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Kim, Ji Yeon; Kwon, Oran

2011-07-01

Contemporary human behavior has led a large proportion of the population to metabolic overload and obesity. Postprandial hyperlipidemia and hyperglycemia evoke redox imbalance in the short term and lead to complex chronic disease in the long term with repeated occurrence. Complex diseases are best prevented with complex components of plants; thus, current nutrition research has begun to focus on the development of plant-based functional foods and dietary supplements for health and well-being. Furthermore, given the wide range of species, parts, and secondary metabolites, culinary plants can contribute significant variety and complexity to the human diet. Although understanding the health benefits of culinary plants has been one of the great challenges in nutritional science due to their inherent complexity, it is an advantageous pursuit. This review will address the challenges and opportunities relating to studies of the health benefits of culinary plants, with an emphasis on obesity attributed to metabolic overload. © 2011 New York Academy of Sciences.

The increase of breath ammonia induced by niacin ingestion quantified by selected ion flow tube mass spectrometry

Czech Academy of Sciences Publication Activity Database

Smith, D.; Wang, T. S.; Španěl, Patrik; Bloor, R.

2006-01-01

Roč. 27, č. 6 (2006), s. 437-444 ISSN 0967-3334 Institutional research plan: CEZ:AV0Z40400503 Keywords : SIFT-MS * ammonia * breath analysis * niacin Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.438, year: 2006

Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig

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Beaumont, Eric; Wright, Gary L.; Southerland, Elizabeth M.; Li, Ying; Chui, Ray; KenKnight, Bruce H.; Armour, J. Andrew

2016-01-01

Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15–20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID:26993230

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

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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.

Simultaneous determination of niacin and pyridoxine at trace levels by using diode array high-performance liquid chromatography and liquid chromatography with quadrupole time-of-flight tandem mass spectrometry.

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Sel, Sabriye; Öztürk Er, Elif; Bakırdere, Sezgin

2017-12-01

A highly sensitive and simple diode-array high-performance liquid chromatography and liquid chromatography with quadrupole time-of-flight tandem mass spectrometry method was developed for the simultaneous determination of niacin and pyridoxine in pharmaceutical drugs, tap water, and wastewater samples. To determine the in vivo behavior of niacin and pyridoxine, analytes were subjected to simulated gastric conditions. The calibration plots of the diode-array high-performance liquid chromatography and liquid chromatography with quadrupole time-of-flight tandem mass spectrometry method showed good linearity over a wide concentration range with close to 1.0 correlation coefficients for both analytes. The limit of detection/limit of quantitation values for liquid chromatography quadrupole time-of-flight tandem mass spectrometry analysis were 1.98/6.59 and 1.3/4.4 μg/L for niacin and pyridoxine, respectively, while limit of detection/limit of quantitation values for niacin and pyridoxine in high-performance liquid chromatography analysis were 3.7/12.3 and 5.7/18.9 μg/L, respectively. Recovery studies were also performed to show the applicability of the developed methods, and percentage recovery values were found to be 90-105% in tap water and 94-97% in wastewater for both analytes. The method was also successfully applied for the qualitative and quantitative determination of niacin and pyridoxine in drug samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aviation noise overload in the immediate proximity of the Warsaw-Okecie airport

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Koszarny, Z.; Maziarka, S.

1981-01-01

The results are presented for investigations on noise overload around the Warszawa-Okecie airport on persons inhabiting the area where it exceeds 100 dB for a single aircraft flight. Of 256 subjects, 91.1 percent complained about aircraft noise overload. In the population studied considerable differences were noted respecting the subjective sensitivity scale. Statistical analysis showed numerous correlations between the individual noise sensitivity threshold and the subject's state of health, age, sex, type of work, etc. At the same time investigations demonstrated various forms and levels of disturbance in the organism for individual subjects and groups. The most frequent complaint was chronic fatigue (68.1 percent), followed by nervousness (36.6 percent), frequent headaches (36.2 percent), hearing disturbances (30.0 percent) and sleep disorders (23.9 percent).

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

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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.

Reversed association between aldosterone and mortality in hemodialysis patients: Role of volume overload.

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Hung, Szu-Chun; Tarng, Der-Cherng

2016-07-01

The role of aldosterone has expanded from its genomic effects that involve renal sodium transport to nongenomic effects such as cardiac and renal fibrosis. Elevated aldosterone levels are associated with increased mortality in the general population. However, the association is reversed in patients with end-stage renal disease on maintenance hemodialysis. We have shown that the inverse association between aldosterone and mortality in hemodialysis patients is due to the confounding effect of volume overload. Volume overload, which is prevalent in patients with chronic kidney disease, is associated with both lower aldosterone concentrations and higher mortality. Our findings support salt and water restriction and treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control. Copyright © 2016 Elsevier Inc. All rights reserved.

Mice lacking liver-specific β-catenin develop steatohepatitis and fibrosis after iron overload.

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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

Involvement of the Niacin Receptor GPR109a in the LocalControl of Glucose Uptake in Small Intestine of Type 2Diabetic Mice

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Tung Po Wong

2015-09-01

Full Text Available Niacin is a popular nutritional supplement known to reduce the risk of cardiovascular diseases by enhancing high-density lipoprotein levels. Despite such health benefits, niacin impairs fasting blood glucose. In type 2 diabetes (T2DM, an increase in jejunal glucose transport has been well documented; however, this is intriguingly decreased during niacin deficient state. In this regard, the role of the niacin receptor GPR109a in T2DM jejunal glucose transport remains unknown. Therefore, the effects of diabetes and high-glucose conditions on GPR109a expression were studied using jejunal enterocytes of 10-week-old m+/db and db/db mice, as well as Caco-2 cells cultured in 5.6 or 25.2 mM glucose concentrations. Expression of the target genes and proteins were quantified using real-time polymerase chain reaction (RT-PCR and Western blotting. Glucose uptake in Caco-2 cells and everted mouse jejunum was measured using liquid scintillation counting. 10-week T2DM increased mRNA and protein expression levels of GPR109a in jejunum by 195.0% and 75.9%, respectively, as compared with the respective m+/db control; high-glucose concentrations increased mRNA and protein expression of GPR109a in Caco-2 cells by 130.2% and 69.0%, respectively, which was also confirmed by immunohistochemistry. In conclusion, the enhanced GPR109a expression in jejunal enterocytes of T2DM mice and high-glucose treated Caco-2 cells suggests that GPR109a is involved in elevating intestinal glucose transport observed in diabetes.

Oligofructose overload induces lameness in cattle.

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Danscher, A M; Enemark, J M D; Telezhenko, E; Capion, N; Ekstrøm, C T; Thoefner, M B

2009-02-01

The aim was to describe the clinical orthopedic implications of oligofructose overload. A group of 8 nonpregnant dairy heifers were given an oral dose of oligofructose (17 g/kg of body weight). At predefined times during a period spanning 3 d before and 9 d after oligofructose overload, the heifers underwent a clinical examination including locomotion scoring, hoof-testing, and palpation of tarso-crural joints, as well as the collection of blood and ruminal fluid samples. Locomotion sessions were videotaped; subsequently, locomotion was blind-scored. Locomotion scores increased after oligofructose overload and declined toward the end of the study period. The greatest locomotion scores were recorded on d 3 to 5 (60 to 120 h) where 12 of 42 (29%) locomotion scores were 3 and 13 of 42 (32%) were score 2. Positive reactions to hoof-testing were observed from 30 h after oligofructose overload and reached a maximum on d 7 and 9 where 12 of 28 (43%) reactions were marked positive. Distension of the tarso-crural joints was observed from 24 h after oligofructose overload, with maximum distension being observed on d 2, in which 44 of 56 (79%) of observed joints were either moderately or severely distended. The heifers developed classic signs of acute ruminal and systemic acidosis after the oligofructose overload (ruminal pH 4.3 +/- 0.07, standard base excess -10.8 +/- 2.3 at 18 h). With few exceptions, clinical and laboratory variables returned to normal within 9 d of oligofructose overload. But, good body condition and previous feeding with grass apparently predisposed the heifers to more severe systemic affection. Oligofructose overload in dairy heifers induced ruminal and systemic acidosis, diarrhea, dehydration, and, subsequently, lameness, claw pain, and joint effusion, collectively interpreted as signs of acute laminitis. Oligofructose overload at 17 g/kg of body weight represented a relatively mild laminitis model in cattle, as demonstrated by a reasonably quick

Physical activity behavior and role overload in mothers.

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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.

Polysynovitis after oligofructose overload in dairy cattle.

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Danscher, A M; Enemark, H L; Andersen, P H; Aalbaek, B; Nielsen, O L

2010-01-01

Acute bovine laminitis is a systemic disease with local manifestations primarily affecting the claws. However, distension of the tarsocrural joints has been observed after experimental oligofructose overload in dairy heifers as a part of the complex interpreted as acute, clinical laminitis. Therefore, the aim of the present study was to study bovine synovial joints and tendon sheaths after oligofructose overload. Ten dairy heifers received oral oligofructose overload (17 g/kg body weight); four were killed 24h after overload and six after 72 h. Six control heifers received tap water and were killed after 72 or 96 h. Clinical examination included locomotion scoring and palpation of the tarsocrural joints. Ruminal fluid and blood was collected for measurements of pH and hydration status. Total protein concentrations and white blood cell (WBC) counts were determined in synovial fluid collected from tarsocrural joints after death. Synovial joints and tendon sheaths were examined and synovial membranes were studied microscopically. Swabs taken from the synovial cavities were subject to bacteriological culture. Heifers with oligofructose overload developed signs of ruminal and systemic acidosis. Lameness was observed in three of ten heifers 24h after overload and in all remaining heifers after 72 h. Distension of tarsocrural joints was observed from 18 h after overload and peaked at 30 h when all examined joints were moderately or severely distended. The synovial fluid was turbid and protein content and WBC counts were increased at both 24 and 72 h compared with controls. Bacterial culture was negative. Synovial membranes 24 and 72 h after overload had a fibrinous and neutrophil inflammatory reaction that regressed in severity between 24 and 72 h after overload. Heifers subjected to oligofructose overload therefore developed generalized sterile neutrophilic polysynovitis. Focus on this aspect of bovine laminitis may shed new light on the pathogenesis of this complex

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

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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.

Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload

NARCIS (Netherlands)

Wang, Jiong-Wei; Fontes, Magda S. C.; Wang, Xiaoyuan; Chong, Suet Yen; Kessler, Elise L.; Zhang, Ya-Nan; de Haan, Judith J.; Arslan, Fatih; de Jager, Saskia C. A.; Timmers, Leo; van Veen, Toon A. B.; Lam, Carolyn S. P.; de Kleijn, Dominique P. V.

2017-01-01

An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis and dysfunction in sustained pressure

Effect of niacin supplementation on rumen fermentation characteristics and nutrient flow at the duodenum in lactating dairy cows fed a diet with a negative rumen nitrogen balance.

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Aschemann, Martina; Lebzien, Peter; Hüther, Liane; Südekum, Karl-Heinz; Dänicke, Sven

2012-08-01

The aim of the present experiment was to ascertain if a daily niacin supplementation of 6 g/cow to lactating dairy cow diets can compensate for the decrease in rumen microbial fermentation due to a negative rumen nitrogen balance (RNB). A total of nine ruminally and duodenally fistulated lactating multiparous German Holstein cows was used. The diets consisted of 10 kg dry matter (DM) maize silage and 7 kg DM concentrate and differed as follows: (i) Diet RNB- (n = 6) with energy and utilisable crude protein (CP) at the duodenum (uCP) according to the average requirement of the animals, but with a negative RNB (-0.41 g N/MJ metabolisable energy [ME]); (ii) Diet RNB0 (n = 7) with energy, uCP, and RNB (0.08 g N/MJ ME) according to the average requirement of the animals; and (iii) Diet NA (nicotinic acid; n = 5), which was the same diet as RNB-, but supplemented with 6 g niacin/d. The negative RNB affected the rumen fermentation pattern and reduced ammonia content in rumen fluid and the daily duodenal flows of microbial CP (MP) and uCP. Niacin supplementation increased the apparent ruminal digestibility of neutral detergent fibre. The efficiency of microbial protein synthesis per unit of rumen degradable CP was higher, whereby the amount of MP reaching the duodenum was unaffected by niacin supplementation. The number of protozoa in rumen fluid was higher in NA treatment. The results indicated a more efficient use of rumen degradable N due to changes in the microbial population in the rumen when niacin was supplemented to diets deficient in RNB for lactating dairy cows.

Sensory overload: A concept analysis.

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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.

LRRC10 is required to maintain cardiac function in response to pressure overload.

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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.

Overload protection system for power inverter

Science.gov (United States)

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.

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

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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

Xanthophylls, phytosterols and pre-β1-HDL are differentially affected by fenofibrate and niacin HDL-raising in a cross-over study.

Science.gov (United States)

Niesor, Eric J; Gauthamadasa, Kekulawalage; Silva, R A Gangani D; Suchankova, Gabriela; Kallend, David; Gylling, Helena; Asztalos, Bela; Damonte, Elisabetta; Rossomanno, Simona; Abt, Markus; Davidson, W Sean; Benghozi, Renee

2013-12-01

Fenofibrate and extended-release (ER) niacin similarly raise high-density lipoprotein cholesterol (HDL-C) concentration but their effects on levels of potent plasma antioxidant xanthophylls (lutein and zeaxanthin) and phytosterols obtained from dietary sources, and any relationship with plasma lipoproteins and pre-β1-HDL levels, have not been investigated. We studied these parameters in 66 dyslipidemic patients treated for 6 week with fenofibrate (160 mg/day) or ER-niacin (0.5 g/day for 3 week, then 1 g/day) in a cross-over study. Both treatments increased HDL-C (16 %) and apolipoprotein (apo) A-I (7 %) but only fenofibrate increased apoA-II (28 %). Lutein and zeaxanthin levels were unaffected by fenofibrate but inversely correlated with percentage change in apoB and low-density lipoprotein cholesterol and positively correlated with end of treatment apoA-II. ApoA-II in isolated HDL in vitro bound more lutein than apoA-I. Xanthophylls were increased by ER-niacin (each ~30 %) without any correlation to lipoprotein or apo levels. Only fenofibrate markedly decreased plasma markers of cholesterol absorption; pre-β1-HDL was significantly decreased by fenofibrate (-19 %, p xanthophylls, phytosterols and pre-β1-HDL differed markedly, suggesting differences in intestinal lipidation of HDL. In addition, the in vitro investigations suggest an important role of plasma apoA-II in xanthophyll metabolism.

The effect of single overloading on stress corrosion cracking

International Nuclear Information System (INIS)

Ito, Yuzuru; Saito, Masahiro

2008-01-01

In the normal course of nuclear power plant operation in Japan, proof testing has been performed after periodic plant inspections. In this proof test procedure, the reactor pressure vessel and pipes of the primary coolant loop are subjected to a specified overload with a slightly higher hydraulic pressure than during normal operation. This specified overload is so called a single overload' in material testing. It is well known that the fatigue crack growth rate is decreased after a single overload has been applied to the specimen. However, it is not clear whether the stress corrosion cracking rate is also decreased after a single overload. In this study, the effect of a single overload on the stress corrosion cracking rate under simulated boiling water reactor environment was evaluated by examining a singly overloaded WOL (wedge opening load) specimen. The WOL specimen for the stress corrosion cracking test was machined from sensitized 304 type austenitic stainless steel. Since the crack extension length was 3.2% longer in the case of a more severely overloaded specimen, it was observed than the stress corrosion cracking rate is also decreased after the single overload has been applied to the specimen. (author)

Dietary Fat Overload Reprograms Brown Fat Mitochondria

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DANIELE eLETTIERI BARBATO

2015-09-01

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

Effects of niacin restriction on sirtuin and PARP responses to photodamage in human skin.

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Claudia A Benavente

Full Text Available Sirtuins (SIRTs and poly(ADP-ribose polymerases (PARPs, NAD(+-dependent enzymes, link cellular energy status with responses to environmental stresses. Skin is frequently exposed to the DNA damaging effects of UV irradiation, a known etiology in skin cancer. Thus, understanding the defense mechanisms in response to UV, including the role of SIRTs and PARPs, may be important in developing skin cancer prevention strategies. Here, we report expression of the seven SIRT family members in human skin. SIRTs gene expressions are progressively upregulated in A431 epidermoid carcinoma cells (SIRTs1 and 3, actinic keratoses (SIRTs 2, 3, 5, 6, and 7 and squamous cell carcinoma (SIRTs 1-7. Photodamage induces dynamic changes in SIRT expression with upregulation of both SIRT1 and SIRT4 mRNAs. Specific losses of SIRT proteins occur early after photodamage followed by accumulation later, especially for SIRT4. Niacin restriction, which decreases NAD(+, the sirtuin substrate, results in an increase in acetylated proteins, upregulation of SIRTs 2 and 4, increased inherent DNA damage, alterations in SIRT responses to photodamage, abrogation of PARP activation following photodamage, and increased sensitivity to photodamage that is completely reversed by repleting niacin. These data support the hypothesis that SIRTs and PARPs play important roles in resistance to photodamage and identify specific SIRTs that respond to photodamage and may be targets for skin cancer prevention.

Effect of overloads on fatigue crack propagation rate

International Nuclear Information System (INIS)

Kogaev, V.P.; Bojtsov, B.V.; Petukhov, Yu.V

1986-01-01

An overload coefficient Q, the number of overload cycles Nsub(0), the value of the stress intensity coefficient swing of basic loading conditions ΔK are experimentally studied for their effect on the delay of the fatigue crack propagation Nsub(D) in 30KhGSNA steel. Results of the study are presented. It is shown that as a result of single overloads the value attains 60 - 10 thous. cycles. The delay Nsub(D) grows with the overload coefficient Q=Ksub(max)sup(0)/Ksub(max) and the number of the overload cycles Nsub(0). The regularity indicated is described by the equations valid within the limits of variation in Q and Nsub(0) values studied in the paper

Application of Chaos Theory in Trucks' Overloading Enforcement

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Abbas Mahmoudabadi

2013-01-01

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

Albumin Overload and PINK1/Parkin Signaling-Related Mitophagy in Renal Tubular Epithelial Cells.

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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

Continuous Manual Exchange Transfusion for Patients with Sickle Cell Disease: An Efficient Method to Avoid Iron Overload.

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Koehl, Bérengère; Missud, Florence; Holvoet, Laurent; Ithier, Ghislaine; Sakalian-Black, Oliver; Haouari, Zinedine; Lesprit, Emmanuelle; Baruchel, André; Benkerrou, Malika

2017-03-14

Children with sickle cell anemia (SCA) may be at risk of cerebral vasculopathy and strokes, which can be prevented by chronic transfusion programs. Repeated transfusions of packed red blood cells (PRBCs) is currently the simplest and most used technique for chronic transfusion programs. However, iron overload is one of the major side effects of this therapy. More developed methods exist, notably the apheresis of RBC (erythrapheresis), which is currently the safest and most efficient method. However, it is costly, complicated, and cannot be implemented everywhere, nor is it suitable for all patients. Manual exchange transfusions combine one or more manual phlebotomies with a PRBC transfusion. At the Reference Center of Sickle Cell Disease, we set up a continuous method of manual exchange transfusion that is feasible for all hospital settings, demands no specific equipment, and is widely applicable. In terms of HbS decrease, stroke prevention, and iron overload prevention, this method showed comparable efficiency to erythrapheresis. In cases where erythrapheresis is not available, this method can be a good alternative for patients and care centers.

Myocardial fatty acid imaging with 123I-BMIPP in patients with chronic right ventricular pressure overload. Clinical significance of reduced uptake in interventricular septum

International Nuclear Information System (INIS)

Hori, Yoshiro; Ishida, Yoshio; Fukuchi, Kazuki; Hayashida, Kouhei; Takamiya, Makoto

2002-01-01

Regionally reduced 123 I-beta-methyliodophenyl pentadecanoic acid (123I-BMIPP) uptake in the interventricular septum (SEP) is observed in some patients with chronic right ventricular (RV) pressure overload. We studied the significance of this finding by comparing it with mean pulmonary arterial pressure (mPAP). 123 I-BMIPP SPECT imaging was carried out in 21 patients with pulmonary hypertension (PH; 51+-14 years; 11 men and 10 women; 7 with primary pulmonary hypertension, 11 with pulmonary thromboembolism, and 3 with atrial septal defect). mPAP ranged from 25 to 81 mmHg (49±16 mmHg). Using a midventricular horizontal long-axis plane, regional BMIPP distributions in the RV free wall and SEP were estimated by referring to those in the LV free wall. Count ratios of the RV free wall and SEP to the LV free wall (RV/LV, SEP/LV) were determined by ROI analysis. RV/LV showed a linear correlation with mPAP (r=0.42). However, SEP/LV was inversely correlated with mPAP (r=-0.49). When SEP/RV was compared among three regions of SEP in each patient, basal SEP/RV was most sensitively decreased in response to increased mPAP (r=-0.70). These results suggest that the assessment of septal tracer uptake in 123 I-BMIPP SPECT imaging is useful for evaluating the severity of RV pressure overload in patients with PH. (author)

Myelodysplastic syndromes and the role of iron overload.

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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.

Niacin and olive oil promote skewing to the M2 phenotype in bone marrow-derived macrophages of mice with metabolic syndrome.

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Montserrat-de la Paz, Sergio; Naranjo, Maria C; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G; Bermudez, Beatriz

2016-05-18

Metabolic syndrome (MetS) is associated with obesity, dyslipemia, type 2 diabetes and chronic low-grade inflammation. The aim of this study was to determine the role of high-fat low-cholesterol diets (HFLCDs) rich in SFAs (HFLCD-SFAs), MUFAs (HFLCD-MUFAs) or MUFAs plus omega-3 long-chain PUFAs (HFLCD-PUFAs) on polarisation and inflammatory potential in bone marrow-derived macrophages (BMDMs) from niacin (NA)-treated Lep(ob/ob)LDLR(-/-) mice. Animals fed with HFLCD-SFAs had increased weight and serum triglycerides, and their BMDMs accumulated triglycerides over the animals fed with HFLCD-MUFAs or -PUFAs. Furthermore, BMDMs from animals fed with HFLCD-SFAs were polarised towards the M1 phenotype with functional competence to produce pro-inflammatory cytokines, whereas BMDMs from animals fed with HFLCD-MUFAs or -PUFAs were skewed to the anti-inflammatory M2 phenotype. These findings open opportunities for developing novel nutritional strategies with olive oil as the most important dietary source of MUFAs (notably oleic acid) to prevent development and progression of metabolic complications in the NA-treated MetS.

CCR2+ Monocyte-Derived Infiltrating Macrophages Are Required for Adverse Cardiac Remodeling During Pressure Overload

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Bindiya Patel, PhD

2018-04-01

Full Text Available Summary: Although chronic inflammation is a central feature of heart failure (HF, the immune cell profiles differ with different underlying causes. This suggests that for immunomodulatory therapy in HF to be successful, it needs to be tailored to the specific etiology. Here, the authors demonstrate that monocyte-derived C-C chemokine receptor 2 (CCR2+ macrophages infiltrate the heart early during pressure overload in mice, and that blocking this response either pharmacologically or with antibody-mediated CCR2+ monocyte depletion alleviates late pathological left ventricular remodeling and dysfunction, T-cell expansion, and cardiac fibrosis. Hence, suppression of CCR2+ monocytes/macrophages may be an important immunomodulatory therapeutic target to ameliorate pressure-overload HF. Key Words: cardiac remodeling, heart failure, inflammation, macrophages, T cells

Iron overload and chelation therapy in myelodysplastic syndromes.

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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.

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

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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.

Intelligent Overload Control for Composite Web Services

NARCIS (Netherlands)

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

2009-01-01

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

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

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

2017-10-31

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

154 Effet du chrome niacinate sur la tolérance au glucose chez le rat ...

African Journals Online (AJOL)

PR BOKO

contribution to the DEX treated groups. CrN supplementation did not correct the elevation of blood glucose ... chrome niacinate (30mg/kg/j, PO) pendant 14 jours, n=10. 2-2-2. Prélèvements. 1mL de sang a été prélevé à partir de la veine caudale sur tube hépariné à j0, j7, j14, j21 et j28. Les prélèvements ont été centrifugés ...

Lactulose efficacy in reduction of nitrogen products, blood potassium and fluid overload in patients with end-stage renal failure

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Negin Aleagha

2017-06-01

Full Text Available Introduction: Chronic kidney disease (CKD is a major public health problem that often goes unrecognized until its late-stage. Patients with chronic kidney disease face uremic toxins and hyperkalemia. Also, fluid overload in CKD patients is associated with rapid decline in kidney function. Lactulose is a hyperosmotic agent and as a prebiotic, it plays an important role in regulating serum urea and potassium levels and has some effects on fluid overload. The aim of this study was to evaluate the effect of lactulose on serum levels of biochemical products in patients with CKD. Materials and Methods: In this interventional study, 17 patients with end stage of CKD ( 76.47 % men; mean age 65.88 ± 13.4 were evaluated.All patients received lactulose, 10 ml, 3 times per day for 3 months. Blood samples from all participants were collected before and at the end of intervention to examine changes in biochemical parameters, including potassium, urea, creatinine and uric acid. Results: Lactulose significantly decreased urea levels (p=0.001, blood potassium (0.001 and fluid overload(considering the patient’s weight p=0.001 in patients with end-stage renal failure. The decrease in serum creatinine and uric acid were not significant. Conclusion: Lactulose administration in CKD patients could decrease levels of various deleterious elements, especially urea and blood potassium and its daily use can be recommended in these patients.

Fluid overload in the ICU: evaluation and management.

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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

Niacin activates the PI3K/Akt cascade via PKC- and EGFR-transactivation-dependent pathways through hydroxyl-carboxylic acid receptor 2.

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Huawang Sun

Full Text Available Niacin has been demonstrated to activate a PI3K/Akt signaling cascade to prevent brain damage after stroke and UV-induced skin damage; however, the underlying molecular mechanisms for HCA2-induced Akt activation remain to be elucidated. Using CHO-K1 cells stably expressing HCA2 and A431 cells, a human epidermoid cell line with high levels of endogenous expression of functional HCA2 receptors, we first demonstrated that niacin induced a robust Akt phosphorylation at both Thr308 and Ser473 in a time-dependent fashion, with a maximal activation at 5 min and a subsequent reduction to baseline by 30 min through HCA2, and that the activation was significantly blocked by pertussis toxin. The HCA2-mediated activation of Akt was also significantly inhibited by the PKC inhibitors GF109203x and Go6983 in both cell lines, by the PDGFR-selective inhibitor tyrphostin A9 in CHO-HCA2 cells and by the MMP inhibitor GM6001 and EGFR-specific inhibitor AG1478 in A431 cells. These results suggest that the PKC pathway and PDGFR/EGFR transactivation pathway play important roles in HCA2-mediated Akt activation. Further investigation indicated that PI3K and the Gβγ subunit were likely to play an essential role in HCA2-induced Akt activation. Moreover, Immunobloting analyses using an antibody that recognizes p70S6K1 phosphorylated at Thr389 showed that niacin evoked p70S6K1 activation via the PI3K/Akt pathway. The results of our study provide new insight into the signaling pathways involved in HCA2 activation.

Iron overload following bone marrow transplantation in children: MR findings

International Nuclear Information System (INIS)

Kornreich, L.; Horev, G.; Grunebaum, M.; Yaniv, I.; Stein, J.; Zaizov, R.

1997-01-01

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

Significance of iron reduction for the therapy of chronic hepatitis C

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Nožić Darko

2005-01-01

Full Text Available Background. It has been established that many patients with chronic hepatitis C have elevated serum iron, feritin levels and iron deposits in the liver. Therefore, the liver damage due to hepatitis C virus may be aggravated with iron overload. In many studies higher levels of iron in the blood and the liver were connected with the decreased response to interferon-alfa therapy for chronic viral hepatitis C. Recent introduction of pegylated interferons plus ribavirin has improved the therapeutic response, so it is now possible to cure more than 50% of the patients. Case report. Three patients with chronic hepatitis C and iron overload were presented. Iron reduction therapy using phlebotomy or eritrocytapheresis with plasmapheresis was done at different times in regard to specific antiviral therapy or as a sole therapy. Conclusion. It has been shown that iron reduction, sole or combined with antiviral therapy, led to the deacreased aminotransferase serum activity and might have slow down the evolution of chronic hepatitis C viral infection.

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

Science.gov (United States)

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.

Liver disease in adult transfusion-dependent beta-thalassaemic patients: investigating the role of iron overload and chronic HCV infection.

Science.gov (United States)

Kountouras, Dimitrios; Tsagarakis, Nikolaos J; Fatourou, Evangelia; Dalagiorgos, Efthimios; Chrysanthos, Nikolaos; Berdoussi, Helen; Vgontza, Niki; Karagiorga, Markissia; Lagiandreou, Athanasios; Kaligeros, Konstantinos; Voskaridou, Ersi; Roussou, Paraskevi; Diamanti-Kandarakis, Evanthia; Koskinas, John

2013-03-01

Iron overload and hepatitis-C virus (HCV) infection, have been implicated in the evolution of liver disease, in patients with transfusion-dependent beta-thalassaemia major (BTM). However, the impact of these factors in late stages of liver disease in adults with BTM, has not been extensively studied. To investigate serum indices of iron overload, HCV infection and liver disease, in a cohort of 211 adult Greek patients with BTM, in relation with the findings from liver biopsies. In this cross-sectional study, 211 patients with BTM were enrolled and studied, in relation with HCV infection, ferritin, transaminases, chelation treatment and antiviral treatment. Based on 109 patients biopsied, we correlated liver fibrosis, haemosiderosis and inflammation, with serum indices and HCV status Among all patients, 74.4% were anti-HCV positive (HCV+). Ferritin was positively correlated with transaminases and negatively correlated with age, while it was not significantly different among HCV+ and HCV- patients. Among the HCV+ patients, 55.4% reported antiviral treatment, while genotype 1 predominated. In a subfraction of 109 patients, in which liver biopsy was performed, 89% were HCV+ and 11% HCV-. Fibrosis was significantly correlated with age (P = 0.046), AST (P = 0.004), ALT (P = 0.044) and inflammation (P overload may be the critical determinant, since fibrosis is related to the minimal haemosiderosis, independently of HCV history. © 2012 John Wiley & Sons A/S.

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

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Ronald Herrera

2017-10-01

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

Reliability Analysis and Overload Capability Assessment of Oil-Immersed Power Transformers

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Chen Wang

2016-01-01

Full Text Available Smart grids have been constructed so as to guarantee the security and stability of the power grid in recent years. Power transformers are a most vital component in the complicated smart grid network. Any transformer failure can cause damage of the whole power system, within which the failures caused by overloading cannot be ignored. This research gives a new insight into overload capability assessment of transformers. The hot-spot temperature of the winding is the most critical factor in measuring the overload capacity of power transformers. Thus, the hot-spot temperature is calculated to obtain the duration running time of the power transformers under overloading conditions. Then the overloading probability is fitted with the mature and widely accepted Weibull probability density function. To guarantee the accuracy of this fitting, a new objective function is proposed to obtain the desired parameters in the Weibull distributions. In addition, ten different mutation scenarios are adopted in the differential evolutionary algorithm to optimize the parameter in the Weibull distribution. The final comprehensive overload capability of the power transformer is assessed by the duration running time as well as the overloading probability. Compared with the previous studies that take no account of the overloading probability, the assessment results obtained in this research are much more reliable.

Effects of overload on the threshold stress intensity factor for SCC

International Nuclear Information System (INIS)

Takahashi, Koji; Ando, Kotoji; Miyazaki, Yuji; Hashikura, Yasuaki

2009-01-01

The effects of overload on the threshold stress intensity factor for stress corrosion crack (K ISCC ) of stainless steel were studied. Tensile overload was applied to a wedge opening loaded (WOL) specimen of SUS316. Then, SCC tests were carried out to determine the resultant K ISCC . As a result, the apparent value of K ISCC increases as increasing a stress intensity factor by tensile overload (K OV ). The effects of tensile overload on K ISCC and the threshold stress intensity factor range for fatigue (ΔK th ) were compared. It was found that the effects of tensile overload on K ISCC were larger than that on ΔK th . (author)

Chronic activation of the low affinity site of β1-adrenoceptors stimulates haemodynamics but exacerbates pressure-overload cardiac remodelling

Science.gov (United States)

Kiriazis, Helen; Tugiono, Niquita; Xu, Qi; Gao, Xiao-Ming; Jennings, Nicole L; Ming, Ziqui; Su, Yidan; Klenowski, Paul; Summers, Roger J; Kaumann, Alberto; Molenaar, Peter; Du, Xiao-Jun

2013-01-01

BACKGROUND AND PURPOSE The β1-adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L, respectively), which mediate cardiostimulation. While β1H-adrenoceptor can be blocked by all clinically used β-blockers, β1L-adrenoceptor is relatively resistant to blockade. Thus, chronic β1L-adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of β1H-adrenoceptors. Hence, it is important to determine the potential significance of β1L-adrenoceptors in vivo, particularly in pathological situations. EXPERIMENTAL APPROACH C57Bl/6 male mice were used. Chronic (4 or 8 weeks) β1L-adrenoceptor activation was achieved by treatment, via osmotic mini pumps, with (-)-CGP12177 (10 mg·kg−1·day−1). Cardiac function was assessed by echocardiography and micromanometry. KEY RESULTS (-)-CGP12177 treatment of healthy mice increased heart rate and left ventricular (LV) contractility. (-)-CGP12177 treatment of mice subjected to transverse aorta constriction (TAC), during weeks 4–8 or 4–12 after TAC, led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (-)-CGP12177 treatment of mice with TAC also exacerbated the myocardial expression of hypertrophic, fibrogenic and inflammatory genes compared to untreated TAC mice. Washout of (-)-CGP12177 revealed a more pronounced cardiac dysfunction after 12 weeks of TAC. CONCLUSIONS AND IMPLICATIONS β1L-adrenoceptor activation provides functional support to the heart, in both normal and pathological (pressure overload) situations. Sustained β1L-adrenoceptor activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure. PMID:23750586

Low dietary intake of n-3 fatty acids, niacin, folate, and vitamin C in Korean patients with schizophrenia and the development of dietary guidelines for schizophrenia.

Science.gov (United States)

Kim, Eun Jin; Lim, So Young; Lee, Hee Jae; Lee, Ju-Yeon; Choi, Seunggi; Kim, Seon-Young; Kim, Jae-Min; Shin, Il-Seon; Yoon, Jin-Sang; Yang, Soo Jin; Kim, Sung-Wan

2017-09-01

Inappropriate dietary intake and poor nutritional status are reported to be associated with metabolic syndrome and psychopathology in patients with schizophrenia. We hypothesized that inappropriate dietary habits and insufficient dietary intake of specific nutrients are associated with schizophrenia. To test the hypothesis, we assessed the dietary habits and nutritional intake of patients with schizophrenia and then developed suitable dietary guidelines. In total, 140 subjects (73 controls and 67 patients with schizophrenia from community mental health centers) were included, and dietary intakes were analyzed using a semi-quantitative food frequency questionnaire. As a result, the proportion of overweight or obese patients was significantly higher in schizophrenia subjects (64.2%) compared with control subjects (39.7%) (P=.004). The male schizophrenia patients had significantly lower dietary intakes of protein, polyunsaturated fatty acids (PUFAs), vitamin K, niacin, folate, and vitamin C than the male control subjects. In all multiple logistic regression models, subjects with the "low" dietary intake of protein, n-3 PUFAs, niacin, folate, and vitamin C had a significantly higher odds ratios for schizophrenia compared with those with the "high" dietary intake category of each nutrient. Therefore, maintenance of a healthy body weight and sufficient dietary intake of protein, PUFAs, niacin, folate, and vitamin C are recommended for Korean patients with schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Secondary Hemochromatosis due to Chronic Oral Iron Supplementation

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Ronald Lands

2017-01-01

Full Text Available Iron may accumulate in excess due to a mutation in the HFE gene that upregulates absorption or when it is ingested or infused at levels that exceed the body’s ability to clear it. Excess iron deposition in parenchymal tissue causes injury and ultimately organ dysfunction. Diabetes mellitus and hepatic cirrhosis due to pancreas and liver damage are just two examples of diseases that result from iron overload. Despite the rapid growth of information regarding iron metabolism and iron overload states, the most effective treatment is still serial phlebotomies. We present a patient who developed iron overload due to chronic ingestion of oral ferrous sulfate. This case illustrates the importance of querying geriatric patients regarding their use of nonprescription iron products without a medical indication.

Research progress in role of iron overload in non-alcoholic fatty liver disease

Directory of Open Access Journals (Sweden)

LI Guangming

2013-12-01

Full Text Available Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD. The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iron overload and lipid metabolism, and relationship between type of iron deposition and liver damage; the significance of iron overload in the diagnosis and treatment of NAFLD is discussed from iron overload as a new marker of risk stratification and potential therapeutic target in NAFLD. It is currently considered that iron overload, whether the cause or result of NAFLD progression, will promote the progression of NAFLD once it occurs; as a new marker of risk stratification and potential therapeutic target in NAFLD, iron load is worthy of further study.

Using Pattern Recognition Techniques for Server Overload Detection

NARCIS (Netherlands)

Bezemer, C.P.; Cheplygina, V.; Zaidman, A.

2011-01-01

One of the key factors in customer satisfaction is application performance. To be able to guarantee good performance, it is necessary to take appropriate measures before a server overload occurs. While in small systems it is usually possible to predict server overload using a subjective human

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

Science.gov (United States)

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).

Thermal Characterization of the Overload Carbon Resistors

Directory of Open Access Journals (Sweden)

Ivana Kostić

2013-01-01

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

The evolution of crack-tip stresses during a fatigue overload event

International Nuclear Information System (INIS)

Steuwer, A.; Rahman, M.; Shterenlikht, A.; Fitzpatrick, M.E.; Edwards, L.; Withers, P.J.

2010-01-01

The mechanisms responsible for the transient retardation or acceleration of fatigue crack growth subsequent to overloading are a matter of intense debate. Plasticity-induced closure and residual stresses have often been invoked to explain these phenomena, but closure mechanisms are disputed, especially under conditions approximating to generalised plane strain. In this paper we exploit synchrotron radiation to report very high spatial resolution two-dimensional elastic strain and stress maps at maximum and minimum loading measured under plane strain during a normal fatigue cycle, as well as during and after a 100% overload event, in ultra-fine grained AA5091 aluminium alloy. These observations provide direct evidence of the material stress state in the vicinity of the crack-tip in thick samples. Significant compressive residual stresses were found both in front of and behind the crack-tip immediately following the overload event. The effective stress intensity at the crack-tip was determined directly from the local stress field measured deep within the bulk (plane strain) by comparison with linear elastic fracture mechanical theory. This agrees well with that nominally applied at maximum load and 100% overload. After overload, however, the stress fields were not well described by classical K fields due to closure-related residual stresses. Little evidence of overload closure was observed sometime after the overload event, in our case possibly because the overload plastic zone was very small.

Neurohumoral fluid regulation in chronic liver disease

DEFF Research Database (Denmark)

Møller, Søren; Henriksen, Jens Henrik

1998-01-01

and lungs. It is still an enigma why patients with chronic liver disease are at the same time overloaded and functional hypovolaemic with a hyperdynamic, hyporeactive circulation. Further research is needed to find the solution to this apparent haemodynamic conflict concerning the abnormal neurohumoral...

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

Science.gov (United States)

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 (Poverload-induced heart injury.

Magnetic and quadrupolar studies of the iron storage overload in livers

International Nuclear Information System (INIS)

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

1986-01-01

Absorption 57 Fe Moessbauer 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. Moessbauer 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. (Auth.)

A new approach for primary overloads allowance in ratcheting evaluation

International Nuclear Information System (INIS)

Cabrillat, M.T.; Gatt, J.M.; Lejeail, Y.

1995-01-01

Seismic loading must be taken into account in ratchetting design analysis. In LMFBR structures it mainly produces primary overloads, which are characterised by severe magnitudes but a generally low number of occurrences. Other cases of several primary overloads can also observed in pipes during emptying operations for instance. In the RCC-MR design code rule, the maximum primary stress supported by a structure is considered as permanent. No allowance is made for temporary load. Experimental ratchetting tests conducted on different structures with and without overloads clearly point out that temporary overloads lead to less ratchetting effect. A method using the RCC-MR efficiency diagram framework is proposed. A general theoretical approach allows to extend its field of application of various cases of primary loading: constant or null primary loading or overloads. Experimental results are then used to check the validity of this new approach. (author). 2 refs., 2 figs., 2 tabs

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

Directory of Open Access Journals (Sweden)

Mark D. Schuenke

2011-01-01

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

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

Science.gov (United States)

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.

Control over Permissible Short Emergency Overloads in Power Transformers

Directory of Open Access Journals (Sweden)

V. A. Anischenko

2010-01-01

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

Research progress in role of iron overload in non-alcoholic fatty liver disease

OpenAIRE

LI Guangming

2013-01-01

Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD). The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iro...

Mechanism Research of Arch Dam Abutment Forces during Overload

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Yu Xia

2015-01-01

Full Text Available This paper presents research on the abutment forces of a double-curvature arch dam during overload based on numerical calculation results obtained through finite element method by Ansys. Results show that, with an increase in elevation, the abutment forces and bending moment of the arch dam increase first and then decrease from the bottom to the top of the dam. Abutment forces and bending moment reach their maximum at the middle or middle-down portion of the dam. The distributions of abutment forces and moment do not change during overload. The magnitude of each arch layer’s forces and moment increases linearly during overload. This result indicates that each arch layer transmits bearing loads to the rocks of the left and right banks steadily. This research explains the operating mechanism of an arch dam under normal and overload conditions. It provides a simple method to calculate the distribution of forces Fx and Fy and a new method to calculate the overload factor of an arch dam through the estimation of arch layers based on the redistribution characteristic of arch abutment forces.

Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature.

Science.gov (United States)

Ito, Matthew K

2015-10-01

Hypertriglyceridemia affects approximately 33% of the US population. Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis. Guidelines for the management of severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) recommend immediate use of triglyceride-lowering agents; however, statins remain the first line of therapy for the management of mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily target elevated low-density lipoprotein cholesterol levels, but have also been shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with triglyceride levels≥3.1 mmol/L [≥273 mg/dL]). However, individuals with hypertriglyceridemia may need additional reduction in triglyceride-rich lipoproteins and remnant particles to further reduce residual CVD risk. A number of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3 fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol levels persist despite the use of high-intensity statin therapy. This review evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia. It also assesses the adverse effects and drug-drug interactions associated with these triglyceride-lowering agents, because although they have all been shown to effectively reduce triglyceride levels in patients with hypertriglyceridemia, they differ with regard to their associated benefit-risk profiles. Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin, yet further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction in patients with hypertriglyceridemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy

Directory of Open Access Journals (Sweden)

William Insull Jr

2010-11-01

Full Text Available William Insull Jr1, Peter P Toth2, H Robert Superko3, Roopal B Thakkar4, Scott Krause4, Ping Jiang4, Rhea A Parreno4, Robert J Padley41Baylor College of Medicine and Methodist Hospital, Houston, Texas; 2University of Illinois College of Medicine, Peoria, Illinois; 3Celera, Alameda, California, Mercer University, Atlanta, Georgia; 4Abbott, Abbott Park, Illinois, USAObjective: To compare the effects of combination niacin extended-release + simvastatin (NER/S versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia.Patients and methods: Patients (n = 137 with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4–5 weeks prior to the study received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher’s exact test.Results: NER/S treatment produced significantly greater percent changes in apo A-I and apo B:A-I, and, at the final visit, apo B <80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003. NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022, small LDL (55% versus 45%; P = 0.011, very low-density lipoprotein (VLDL and total chylomicrons (63% versus 39%; P < 0.001, and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007 and VLDL (9.3% versus 0.1%; P < 0.001, compared with atorvastatin.Conclusion: NER/S treatment significantly improved apo A-I levels and the apo

Information Overload and Viral Marketing: Countermeasures and Strategies

Science.gov (United States)

Cheng, Jiesi; Sun, Aaron; Zeng, Daniel

Studying information diffusion through social networks has become an active research topic with important implications in viral marketing applications. One of the fundamental algorithmic problems related to viral marketing is the Influence Maximization (IM) problem: given an social network, which set of nodes should be considered by the viral marketer as the initial targets, in order to maximize the influence of the advertising message. In this work, we study the IM problem in an information-overloaded online social network. Information overload occurs when individuals receive more information than they can process, which can cause negative impacts on the overall marketing effectiveness. Many practical countermeasures have been proposed for alleviating the load of information on recipients. However, how these approaches can benefit viral marketers is not well understood. In our work, we have adapted the classic Information Cascade Model to incorporate information overload and study its countermeasures. Our results suggest that effective control of information overload has the potential to improve marketing effectiveness, but the targeting strategy should be re-designed in response to these countermeasures.

Overload Control in a SIP Signaling Network

OpenAIRE

Masataka Ohta

2007-01-01

The Internet telephony employs a new type of Internet communication on which a mutual communication is realized by establishing sessions. Session Initiation Protocol (SIP) is used to establish sessions between end-users. For unreliable transmission (UDP), SIP message should be retransmitted when it is lost. The retransmissions increase a load of the SIP signaling network, and sometimes lead to performance degradation when a network is overloaded. The paper proposes an overload control for a S...

Thallium-201 myocardial imaging for evaluation of right-ventricular overloading

International Nuclear Information System (INIS)

Kondo, M.; Kubo, A.; Yamazaki, H.; Ohsuzu, F.; Handa, S.; Tsugu, T.; Masaki, H.; Kinoshita, F.; Hashimoto, S.

1978-01-01

This study evaluated the specificity and sensitivity of Tl-201 myocardial imaging in the detection of right-ventricular (RV) overloading. Right-ventricular visualization (RVV) after administration of Tl-201 chloride was studied on 99 patients with various heart diseases. Tracer uptake in the free wall of the RV was graded in four degrees. The degree of RVV was compared with the findings of cardiac catheterization. The comparisons indicated that the uptake increased in step with the inreases in RV systolic pressure, RV end-diastolic pressure, mean pulmonary arterial pressure, total pulmonary vascular resistance, and stroke-work index of the right ventricle (P < 0.05--P < 0.001). Of the patients with visible RV, all but three had RV overloading, and all but three of those without RVV had normal RV systolic pressure. Myocardial images also reflect the type of RV overloading. In patients with RV pressure overloading, the septum showed a tendency to appear straight. In patients with atrial septal defect leading to RV volume overloading, the RV cavity was dilated, the LV image small, and the septum convex toward the RV cavity. These results indicate that Tl-201 myocardial imaging is a sensitive and specific method for the study of RV overloading

Study of overload effects in bainitic steel by synchrotron X-ray diffraction

Directory of Open Access Journals (Sweden)

P. Lopez-Crespo

2013-07-01

Full Text Available This work presents an in-situ characterisation of crack-tip strain fields following an overload by means of synchrotron X-ray diffraction. The study is made on very fine grained bainitic steel, thus allowing a very high resolution so that small changes occurring around the crack-tip were captured along the crack plane at the mid-thickness of the specimen. We have followed the crack as it grew through the overload location. Once the crack-tip has progressed past the overload event there is strong evidence that the crack faces contact in the region of the overload event (though not in the immediate vicinity of the current locations of the crack tip at Kmin even when the crack has travelled 1mm beyond the overload location. It was also found that at Kmax the peak tensile strain ahead of the crack-tip decreases soon after the overload is applied and then gradually recovers as the crack grows past the compressive region created by the overload.

Overload road damage model

CSIR Research Space (South Africa)

Roux, MP

2005-03-01

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

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

Science.gov (United States)

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 (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.

Mitochondrial genetic background modulates bioenergetics and susceptibility to acute cardiac volume overload.

Science.gov (United States)

Fetterman, Jessica L; Zelickson, Blake R; Johnson, Larry W; Moellering, Douglas R; Westbrook, David G; Pompilius, Melissa; Sammy, Melissa J; Johnson, Michelle; Dunham-Snary, Kimberly J; Cao, Xuemei; Bradley, Wayne E; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G; Kesterson, Robert A; Dell'italia, Louis J; Darley-Usmar, Victor M; Welch, Danny R; Ballinger, Scott W

2013-10-15

Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mtDNA sequence variation contributes to disease susceptibility. In the present study we show a novel animal model of mtDNA polymorphisms, the MNX (mitochondrial-nuclear exchange) mouse, in which the mtDNA from the C3H/HeN mouse has been inserted on to the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harbouring the C57/BL6J mtDNA generate more ROS (reactive oxygen species) and have a higher mitochondrial membrane potential relative to those with C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the 'mitochondrial paradigm' for the development of disease susceptibility, and show that the mtDNA modulates cellular bioenergetics, mitochondrial ROS generation and susceptibility to cardiac stress.

The use of a hydrogel matrix for controlled delivery of niacin to the gastrointestinal tract for treatment of hyperlipidemia

Czech Academy of Sciences Publication Activity Database

Širc, Jakub; Hrib, Jakub; Vetrík, Miroslav; Hobzová, Radka; Žák, A.; Staňková, B.; Slanař, O.; Hromádka, R.; Sandrikova, V.; Michálek, Jiří

2015-01-01

Roč. 64, Suppl. 1 (2015), S51-S60 ISSN 0862-8408 R&D Projects: GA MPO(CZ) FR-TI4/638; GA MŠk(CZ) EE2.3.30.0029; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 Keywords : niacin * hyperlipidemia * hydrogel Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.643, year: 2015 http://www.biomed.cas.cz/physiolres/pdf/64%20Suppl%201/64_S51.pdf

Iron overload: what is the role of public health?

Science.gov (United States)

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.

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

Science.gov (United States)

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...

On TCP-based Session Initiation Protocol (SIP) Server Overload Control

OpenAIRE

Shen, Charles; Schulzrinne, Henning

2010-01-01

The Session Initiation Protocol (SIP) server overload management has attracted interest since SIP is being widely deployed in the Next Generation Networks (NGN) as a core signaling protocol. Yet all existing SIP overload control work is focused on SIP-over-UDP, despite the fact that TCP is increasingly seen as the more viable choice of SIP transport. This paper answers the following questions: is the existing TCP flow control capable of handling the SIP overload problem? If not, why and how c...

Glycolytic overload and the genesis of breast cancer.

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Daniela Farah

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

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

Science.gov (United States)

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

2016-01-01

The risks of chronic diseases associated with the increasing consumption of fructose-laden foods are amplified by the lack of regular physical activity and have become a serious public health issue worldwide. Moreover, childhood eating habits are strongly related to metabolic syndrome in adults. Thus, we aimed to investigate the preventive role of exercise training undertaken concurrently with a high fructose diet on cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in male rats after weaning. Male Wistar rats were divided into 4 groups (n = 8/group): Sedentary control (SC), Trained control (TC), Sedentary Fructose (SF) and Trained Fructose (TF). Training was performed on a treadmill (8 weeks, 40–60% of maximum exercise test). Evaluations of cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in plasma and in left ventricle (LV) were performed. Chronic fructose overload induced glucose intolerance and an increase in white adipose tissue (WAT) weight, in myocardial performance index (MPI) (SF:0.42±0.04 vs. SC:0.24±0.05) and in arterial pressure (SF:122±3 vs. SC:113±1 mmHg) associated with increased cardiac and vascular sympathetic modulation. Fructose also induced unfavorable changes in oxidative stress profile (plasmatic protein oxidation- SF:3.30±0.09 vs. SC:1.45±0.08 nmol/mg prot; and LV total antioxidant capacity (TRAP)- SF: 2.5±0.5 vs. SC:12.7±1.7 uM trolox). The TF group showed reduced WAT, glucose intolerance, MPI (0.35±0.04), arterial pressure (118±2mmHg), sympathetic modulation, plasmatic protein oxidation and increased TRAP when compared to SF group. Therefore, our findings indicate that cardiometabolic dysfunctions induced by fructose overload early in life may be prevented by moderate aerobic exercise training. PMID:27930685

Determination of Permissible Short-Time Emergency Overloading of Turbo-Generators and Synchronous Compensators

Directory of Open Access Journals (Sweden)

V. A. Anischenko

2011-01-01

Full Text Available The paper shows that failure to take into account variable ratio of short-time emergency overloading of turbo-generators (synchronous compensators that can lead to underestimation of overloading capacity or impermissible insulation over-heating.A method has been developed for determination of permissible duration of short-time emergency over-loading that takes into account changes of over-loading ratio in case of a failure.

Hepatic iron overload: Quantitative MR imaging

International Nuclear Information System (INIS)

Gomori, J.M.; Horev, G.; Tamary, H.; Zandback, J.; Kornreich, L.; Zaizov, R.; Freud, E.; Krief, O.; Ben-Meir, J.; Rotem, H.

1991-01-01

Iron deposits demonstrate characteristically shortened T2 relaxation times. Several previously published studies reported poor correlation between the in vivo hepatic 1/T2 measurements made by means of midfield magnetic resonance (MR) units and the hepatic iron content of iron-overloaded patients. In this study, the authors assessed the use of in vivo 1/T2 measurements obtained by means of MR imaging at 0.5 T using short echo times (13.4 and 30 msec) and single-echo-sequences as well as computed tomographic (CT) attenuation as a measure of liver iron concentration in 10 severely iron-overloaded patients with beta-thalassemia major. The iron concentrations in surgical wedge biopsy samples of the liver, which varied between 3 and 9 mg/g of wet weight (normal, less than or equal to 0.5 mg/g), correlated well (r = .93, P less than or equal to .0001) with the preoperative in vivo hepatic 1/T2 measurements. The CT attenuation did not correlate with liver iron concentration. Quantitative MR imaging is a readily available noninvasive method for the assessment of hepatic iron concentration in iron-overloaded patients, reducing the need for needle biopsies of the liver

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

Science.gov (United States)

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.

Iron overload of organism and current options of chelation treatment in onco haematology

International Nuclear Information System (INIS)

Guman, T.; Rothova, E.; Kafkova, A.; Fricova, M.; Dulova, I.; Stecova, N.; Hlebaskova, M.; Surova, M.; Takac, V.

2011-01-01

The article summarizes the biological importance of iron in the organism, primary and secondary causes of iron overload, complications in function of liver, heart and endocrine organs due to overload of iron, the pathophysiology of iron overload, transfusion risks associated with the iron overload, assessment of risk groups of patients suitable for chelation treatment fulfilling the indication criteria, treatment modalities of chelation therapy and its significance regarding the prevention and treatment effectiveness. (author)

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

Science.gov (United States)

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% (pyoung 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.

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

Science.gov (United States)

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

2016-08-01

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

Symmetrical and overloaded effect of diffusion in information filtering

Science.gov (United States)

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

2017-10-01

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

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

Science.gov (United States)

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 overload and ischemic preconditioning (18.3 ± 1.5% and 18.2 ± 2.0%, respectively, p 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.

Can We Ever Escape from Data Overload? A Cognitive Systems Diagnosis

National Research Council Canada - National Science Library

Woods, David

1998-01-01

Data overload is a generic and tremendously difficult problem. In this report, we diagnose why this is the case and how intelligence analysis presents a particularly difficult version of data overload...

Reducing unidentified MOV failures: An innovative approach to thermal overload monitoring

International Nuclear Information System (INIS)

Hill, K.; Watson, M.E.; Ali, H.S.; Schlesinger, R.

1991-01-01

Historically the failure of motor-operated valves to actuate on demand has caused plant transients, reduced safety system reliability, and lost plant availability. The typical control and indication circuit design uses thermal overload contacts in the control circuit only. This has been recognized as a significant unidentified valve failure mode that may prevent the valve from performing its safety function when required. Different approaches have been evaluated to alert operations personnel to this thermal overload condition, but no cost-effective solution has provided indication of the thermal overload while maintaining valve position indication. Iowa Electric Light and Power Company's Duane Arnold Energy Center (DAEC) is utilizing a nuclear-qualified thermal overload monitor in valve control and indication circuits. This innovative approach has proven economical as no new cabling or indicating devices are required. Indication is provided using existing valve position indicating lights. The monitor is engineered to provide indication of a thermal overload trip as well as continuous indication of valve position, consistent with Regulatory Guide 1.97 and guidance provided by Generic Letter 89-10

Learners' perceived information overload in online learning via computer-mediated communication

Directory of Open Access Journals (Sweden)

Karen L. Murphy

2011-12-01

Full Text Available 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 from two online courses in the United States. Their learning experiences in both online discussions and on the course website were explored through semi-structured interviews. They also completed a background questionnaire that assessed three constructs that limit learner readiness and are likely to lead to online students' perceived information overload: inadequate prior knowledge, inadequate English proficiency, and lack of technical skills for participating in computer-mediated communications. The findings suggest that varied learner characteristics led some students to be more susceptible than others to information overload. Emerging data-driven risk factors were: lack of efficiency in reading from computer screens, visual and auditory learning preferences, and time constraints. Difficulties associated with students' perceptions of information overload are addressed and implications for course design are offered.

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

Science.gov (United States)

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.

Role of (Pro)Renin Receptor in Albumin Overload-Induced Nephropathy in Rats.

Science.gov (United States)

Fang, Hui; Deng, Mokan; Zhang, Linlin; Lu, Aihua; Su, Jiahui; Xu, Chuanming; Zhou, Li; Wang, Lei; Ou, Jing-Song; Wang, Weidong; Yang, Tianxin

2018-05-30

Proteinuria is not only a common feature of chronic kidney diseases (CKD) but also an independent risk factor promoting CKD progression to end-stage renal failure. However, the underlying molecular mechanisms for protein overload-induced renal injury remain elusive. The present study examined the role of (pro)renin receptor (PRR) in pathogenesis of albumin overload (AO)-induced nephropathy and activation of intrarenal renin-angiotensin system (RAS) in rats. Wistar rats underwent unilateral nephrectomy and were treated for 7 weeks with vehicle, bovine serum albumin (5 g/kg/d via a single i.p. injection) alone or in conjunction with a PRR decoy inhibitor PRO20 (500 μg/kg/d via 3 s.c. injections). The AO rat model exhibited severe proteinuria, tubular necrosis, and interstitial fibrosis, oxidative stress, inflammation, accompanied by elevated urinary N-acetyl-beta-D-glucosaminidase activity and urinary β2-microglobulin secretion, all of which were significantly attenuated by PRO20. Urinary and renal levels of renin, angiotensinogen (AGT), and Ang II were elevated by AO and suppressed by PRO20, contrasting to largely unaltered plasma levels of the RAS parameters. The AO model also showed increased renal expression of full-length PRR and soluble PRR (sPRR) and urinary excretion of sPRR. Taken together, we conclude that PRR antagonism with PRO20 alleviates AO-induced nephropathy via inhibition of intrarenal RAS.

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

International Nuclear Information System (INIS)

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

1984-01-01

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

Assessment of 123I-β-methyl iodophenyl pentadecanoic acid (BMIPP) myocardial scintigraphy in patients of chronic right ventricular overload. Fatty acid metabolism in right ventricular myocardium

International Nuclear Information System (INIS)

Mutoh, Hiroshi

1997-01-01

An investigation on the right ventricular pressure level and the abnormalities in the fatty acid metabolism of myocardium was made using 123 I-βmethyl-iodophenyl pentadecanoic acid (BMIPP) myocardial SPECT in patients with chronic right ventricular overloading. Twenty patients who presented with right ventricular systolic pressure (RVSP) of 35 mmHg or more were used as the subjects. Dual myocardial SPECT with 201 TlCl (Tl) and BMIPP was carried out for the subjects and RVc/LVc, a ratio of radioactivity count incorporated in the right ventricular free wall to the left one was determined for Tl and BMIPP. And the correlations between RVc/LVc and RVSP, and RVc/LVc and RVSP/LVSP were examined. The subjects were classified into 3 groups based on the RVSP levels and the count ratio, BMIPP/Tl was compared among the three groups. With respect of Tl uptake, there were significant, positive correlations between RVc/LVc and RVSP (correlation coefficient r=0.51, p<0.05) and between RVc/LVc and RVSP/LVSP (correlation coefficient r=0.59, p<0.01). On the other hand, no significant correlation was found between them with respect of the uptake of BMIPP. The BMIPP/Tl ratio in the group with higher than 80 mmHg of RVSP was 0.82±0.06, which was significantly lower than the ratio's for two groups of less than 80 mmHg; 0.91±0.07 and 0.98±0.04 in the group with 35-49 and 50-79 mmHg of RVSP, respectively. These results show that when compared with BMIPP, Tl is superior for the estimation of right ventricular pressure. For the patients with right ventricular overloading, it was suggested that when RVSP reaches 80 mmHg or more, there appear some disorders in the fatty acid metabolism in the right ventricular myocardium. (author)

Overload Control in Smart Transformer-Fed Grid

Directory of Open Access Journals (Sweden)

Giovanni De Carne

2017-02-01

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

Fetal liver iron overload: the role of MR imaging

International Nuclear Information System (INIS)

Cassart, Marie; Avni, Freddy Efraim; Guibaud, Laurent; Molho, Marc; D'Haene, Nicky; Paupe, Alain

2011-01-01

To assess the potential role of MR imaging in the diagnosis of fetal liver iron overload. We reviewed seven cases of abnormal liver signal in fetuses referred to MR imaging in a context of suspected congenital infection (n = 2), digestive tract anomalies (n = 3) and hydrops fetalis (n = 2). The average GA of the fetuses was 31 weeks. The antenatal diagnoses were compared with histological data (n = 6) and postnatal work-up (n = 1). Magnetic resonance imaging demonstrated unexpected abnormal fetal liver signal suggestive of iron overload in all cases. The iron overload was confirmed on postnatal biopsy (n = 2) and fetopathology (n = 4). The final diagnosis was hepatic hemosiderosis (haemolytic anaemia (n = 2) and syndromal anomalies (n = 2)) and congenital haemochromatosis (n = 3). In all cases, the liver appeared normal on US. Magnetic resonance is the only imaging technique able to demonstrate liver iron overload in utero. Yet, the study outlines the fundamental role of MR imaging in cases of congenital haemochromatosis. The antenatal diagnosis of such a condition may prompt ante - (in the case of recurrence) or neonatal treatment, which might improve the prognosis. (orig.)

Fetal liver iron overload: the role of MR imaging

Energy Technology Data Exchange (ETDEWEB)

Cassart, Marie; Avni, Freddy Efraim [Erasme Hospital, Medical imaging, Brussels, Brabant (Belgium); Guibaud, Laurent [Hopital femme mere enfant, Imagerie Pediatrique et Foetale, Lyon-Bron (France); Molho, Marc [C.H.I Poissy/St Germain-en-Laye, Imagerie Medicale, Poissy (France); D' Haene, Nicky [Erasme Hospital, Anatomopathology Department, Brussels (Belgium); Paupe, Alain [C.H.I Poissy/St Germain-en-Laye, Pediatrie, Poissy (France)

2011-02-15

To assess the potential role of MR imaging in the diagnosis of fetal liver iron overload. We reviewed seven cases of abnormal liver signal in fetuses referred to MR imaging in a context of suspected congenital infection (n = 2), digestive tract anomalies (n = 3) and hydrops fetalis (n = 2). The average GA of the fetuses was 31 weeks. The antenatal diagnoses were compared with histological data (n = 6) and postnatal work-up (n = 1). Magnetic resonance imaging demonstrated unexpected abnormal fetal liver signal suggestive of iron overload in all cases. The iron overload was confirmed on postnatal biopsy (n = 2) and fetopathology (n = 4). The final diagnosis was hepatic hemosiderosis (haemolytic anaemia (n = 2) and syndromal anomalies (n = 2)) and congenital haemochromatosis (n = 3). In all cases, the liver appeared normal on US. Magnetic resonance is the only imaging technique able to demonstrate liver iron overload in utero. Yet, the study outlines the fundamental role of MR imaging in cases of congenital haemochromatosis. The antenatal diagnosis of such a condition may prompt ante - (in the case of recurrence) or neonatal treatment, which might improve the prognosis. (orig.)

Information overload an international challenge to professional engineers and technical communicators

CERN Document Server

Ulijn, J M; Fazal, Zohra

2012-01-01

"This book covers the ever-increasing problem of information overload from both the professional and academic perspectives. Focusing on the needs of practicing engineers and professional communicators, it addresses the causes and costs of information overload, along with strategies and techniques for reducing and minimizing its negative effects. The theoretical framework of information overload and ideas for future research are also presented. The book brings together an international group of authors, providing a truly global point of view on this important, rarely covered topic"--

Role of work overload toward turnover intention among newly hired public accountants

OpenAIRE

Pradana, Andika; Salehudin, Imam

2013-01-01

This paper aims to analyze how work overload influences turnover intentions of newly hired public accountants. Job satisfaction, work related stress and work life conflicts are used as mediating variable between work overload and turnover intention. This study employed 141 auditors from several accounting firms operating in the Greater Jakarta region. Six proposed hypotheses was tested using Structural Equation Modeling (SEM). Results showed that work overload has significant effect in increa...

Left ventricular remodelling in chronic primary mitral regurgitation: implications for medical therapy.

Science.gov (United States)

McCutcheon, Keir; Manga, Pravin

Surgical repair or replacement of the mitral valve is currently the only recommended therapy for severe primary mitral regurgitation. The chronic elevation of wall stress caused by the resulting volume overload leads to structural remodelling of the muscular, vascular and extracellular matrix components of the myocardium. These changes are initially compensatory but in the long term have detrimental effects, which ultimately result in heart failure. Understanding the changes that occur in the myocardium due to volume overload at the molecular and cellular level may lead to medical interventions, which potentially could delay or prevent the adverse left ventricular remodelling associated with primary mitral regurgitation. The pathophysiological changes involved in left ventricular remodelling in response to chronic primary mitral regurgitation and the evidence for potential medical therapy, in particular beta-adrenergic blockers, are the focus of this review.

Metaiodobenzylguanidine [131I] scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure

International Nuclear Information System (INIS)

Rabinovitch, M.A.; Rose, C.P.; Rouleau, J.L.

1987-01-01

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine [ 131 I] to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine [ 131 I] and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4 hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine [ 131 I] scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine [ 123 I] scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients

NAD Deficiency, Congenital Malformations, and Niacin Supplementation.

Science.gov (United States)

Shi, Hongjun; Enriquez, Annabelle; Rapadas, Melissa; Martin, Ella M M A; Wang, Roni; Moreau, Julie; Lim, Chai K; Szot, Justin O; Ip, Eddie; Hughes, James N; Sugimoto, Kotaro; Humphreys, David T; McInerney-Leo, Aideen M; Leo, Paul J; Maghzal, Ghassan J; Halliday, Jake; Smith, Janine; Colley, Alison; Mark, Paul R; Collins, Felicity; Sillence, David O; Winlaw, David S; Ho, Joshua W K; Guillemin, Gilles J; Brown, Matthew A; Kikuchi, Kazu; Thomas, Paul Q; Stocker, Roland; Giannoulatou, Eleni; Chapman, Gavin; Duncan, Emma L; Sparrow, Duncan B; Dunwoodie, Sally L

2017-08-10

Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients. We used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations. We tested the function of the variant by using assays of in vitro enzyme activity and by quantifying metabolites in patient plasma. We engineered mouse models with similar variants using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system. Variants were identified in two genes that encode enzymes of the kynurenine pathway, 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU). Three patients carried homozygous variants predicting loss-of-function changes in the HAAO or KYNU proteins (HAAO p.D162*, HAAO p.W186*, or KYNU p.V57Efs*21). Another patient carried heterozygous KYNU variants (p.Y156* and p.F349Kfs*4). The mutant enzymes had greatly reduced activity in vitro. Nicotinamide adenine dinucleotide (NAD) is synthesized de novo from tryptophan through the kynurenine pathway. The patients had reduced levels of circulating NAD. Defects similar to those in the patients developed in the embryos of Haao-null or Kynu-null mice owing to NAD deficiency. In null mice, the prevention of NAD deficiency during gestation averted defects. Disruption of NAD synthesis caused a deficiency of NAD and congenital malformations in humans and mice. Niacin supplementation during gestation prevented the malformations in mice. (Funded by the National Health and Medical Research Council of Australia and others.).

The effect of somatic awareness exercise on the chronic physical manifestations of the stress response

OpenAIRE

2013-01-01

M.Phil. (Biokinetics) Stress is an integral part of daily living and supports the ability to adapt. However, chronic activation without the ability to express the physical response results in overloading the physiological and psychological systems. Since urban South Africans are sedentary and experience high levels of stress, they are developing stress related chronic conditions and hypokinetic diseases (obesity, hypertension, depression). This study is aimed at decreasing the chronic phys...

Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage.

Science.gov (United States)

Rukavina Mikusic, Natalia L; Kouyoumdzian, Nicolás M; Del Mauro, Julieta S; Cao, Gabriel; Trida, Verónica; Gironacci, Mariela M; Puyó, Ana M; Toblli, Jorge E; Fernández, Belisario E; Choi, Marcelo R

2018-01-01

Insulin resistance induced by a high-fructose diet has been associated to hypertension and renal damage. The aim of this work was to assess alterations in the urinary L-dopa/dopamine ratio over three time periods in rats with insulin resistance induced by fructose overload and its correlation with blood pressure levels and the presence of microalbuminuria and reduced nephrin expression as markers of renal structural damage. Male Sprague-Dawley rats were randomly divided into six groups: control (C) (C4, C8 and C12) with tap water to drink and fructose-overloaded (FO) rats (FO4, FO8 and FO12) with a fructose solution (10% w/v) to drink for 4, 8 and 12 weeks. A significant increase of the urinary L-dopa/dopamine ratio was found in FO rats since week 4, which positively correlated to the development of hypertension and preceded in time the onset of microalbuminuria and reduced nephrin expression observed on week 12 of treatment. The alteration of this ratio was associated to an impairment of the renal dopaminergic system, evidenced by a reduction in renal dopamine transporters and dopamine D1 receptor expression, leading to an overexpression and overactivation of the enzyme Na + , K + -ATPase with sodium retention. In conclusion, urinary L-dopa/dopamine ratio alteration in rats with fructose overload positively correlated to the development of hypertension and preceded in time the onset of renal structural damage. This is the first study to propose the use of the urinary L-dopa/dopamine index as marker of renal dysfunction that temporarily precedes kidney structural damage induced by fructose overload. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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. �

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

Directory of Open Access Journals (Sweden)

Hecking Manfred

2012-06-01

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

Elbow arthroscopy: valgus extension overload.

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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.

Assessment of right ventricular overload using 99mTc-hexakis-methoxy-2-isobutylisonitrile (MIBI) and 123I-β-methyl iodophenyl pentadecanoic acid (BMIPP) myocardial scintigraphy

International Nuclear Information System (INIS)

Matsumoto, Katsushige

2002-01-01

Thallium-201 myocardial imaging is known to be useful for evaluating right ventricular (RV) overload. The degree of RV wall visualization has been shown to reflect RV myocardial mass and the right-to-left ventricular pressure ratio. Recently, 99m Tc-hexakis-methoxy-2-isobutylisonitrile (MIBI) and 123 I-β-methyl iodophenyl pentadecanoic acid (BMIPP) were developed and have been used to evaluate ischemic heart disease. The purpose of this study was to evaluate the RV pressure and myocardial fatty acid metabolism in the right ventricle in patients with chronic RV overloading using 99m Tc-MIBI and 123 I-BMIPP myocardial imaging. 99m Tc-MIBI myocardial scintigraphy (planar and SPECT) was performed in 76 patients with RV overloading, and 123 I-BMIPP SPECT was performed in 33 patients with RV overloading. The degree of RV wall visualization using 99m Tc-MIBI planar imaging was correlated with the elevation of RV systolic pressure. The right atrium was visualized with a high frequency in patients with RV overloading, and the degree of the right atrial wall visualization was correlated with the elevation of RV end-diastolic pressure. A count ratio of right-to-left ventricular free wall (RV/LV ratio) using 99m Tc-MIBI SPECT correlated well with a systolic pressure ratio of right-to-left ventricle (sRVp/sLVp). On the other hand, no significant correlation was found between RV/LV ratio using 123 I-BMIPP SPECT and sRVp/sLVp. For the patients with RV overloading at a RV systolic pressure of 70 mmHg or more, impaired fatty acid metabolism in the RV myocardium was noted using the quantitative analysis of 123 I-BMIPP SPECT. In conclusion, RV pressure can be evaluated by quantitative analysis using 99m Tc-MIBI myocardial scintigraphy. Myocardial metabolism in the RV wall may be impaired in patients with severe RV overloading. (author)

Development of an overload control strategy for the Republic of Senegal

CSIR Research Space (South Africa)

Nordengen, Paul A

2006-09-01

Full Text Available , particularly because there are currently no weighbridges in the country being used for overload control law enforcement. Recognising the need for an effective overload strategy for Senegal, the Ministry of Public Works and Transport decided to initiate a study...

Mitochondrial Genetic Background Modulates Bioenergetics and Susceptibility to Acute Cardiac Volume – Overload

Science.gov (United States)

Fetterman, Jessica L.; Zelickson, Blake R.; Johnson, Larry W.; Moellering, Douglas R.; Westbrook, David G.; Pompilius, Melissa; Sammy, Melissa J.; Johnson, Michelle; Dunham-Snary, Kimberly J.; Cao, Xuemei; Bradley, Wayne E.; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G.; Kesterson, Robert A.; Dell’Italia, Louis J.; Darley-Usmar, Victor M.; Welch, Danny R.; Ballinger, Scott W.

2013-01-01

Synopsis Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mitochondrial DNA (mtDNA) sequence variation contributes to disease susceptibility. In this study we present a novel animal model of mtDNA polymorphisms, the mitochondrial nuclear exchange mouse (MNX), in which the mtDNA from C3H/HeN mouse has been inserted onto the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harboring the C57/BL6J mtDNA generate more reactive oxygen species (ROS) and have a higher mitochondrial membrane potential relative to those having the C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the “mitochondrial paradigm” for the development of disease susceptibility, and show that the mtDNA modulates, cellular bioenergetics, mitochondrial reactive oxygen species generation and susceptibility to cardiac stress. PMID:23924350

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

International Nuclear Information System (INIS)

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

2016-01-01

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 (78.4 h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with 89 Zr directly at pH 5, 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 48 h. The half-life of 89 Zr-MP was about 15.70 ± 1.74 h 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.

Acute iron overload and oxidative stress in brain

International Nuclear Information System (INIS)

Piloni, Natacha E.; Fermandez, Virginia; Videla, Luis A.; Puntarulo, Susana

2013-01-01

An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6 h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A·)/ascorbate (AH − ) ratio, taken as oxidative stress index, was assessed. The A·/AH − ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR·) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8 h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21 h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6 h after Fe administration. CAT activity was significantly increased after 8 h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR· generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR· generation rate after 6

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

Science.gov (United States)

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 (Poverload 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.

Changes in bacteria composition and efficiency of constructed wetlands under sustained overloads: A modeling experiment.

Science.gov (United States)

Boano, F; Rizzo, A; Samsó, R; García, J; Revelli, R; Ridolfi, L

2018-01-15

The average organic and hydraulic loads that Constructed Wetlands (CWs) receive are key parameters for their adequate long-term functioning. However, over their lifespan they will inevitably be subject to either episodic or sustained overloadings. Despite that the consequences of sustained overloading are well known (e.g., clogging), the threshold of overloads that these systems can tolerate is difficult to determine. Moreover, the mechanisms that might sustain the buffering capacity (i.e., the reduction of peaks in nutrient load) during overloads are not well understood. The aim of this work is to evaluate the effect of sudden but sustained organic and hydraulic overloads on the general functioning of CWs. To that end, the mathematical model BIO_PORE was used to simulate five different scenarios, based on the features and operation conditions of a pilot CW system: a control simulation representing the average loads; 2 simulations representing +10% and +30% sustained organic overloads; one simulation representing a sustained +30% hydraulic overload; and one simulation with sustained organic and hydraulic overloads of +15% each. Different model outputs (e.g., total bacterial biomass and its spatial distribution, effluent concentrations) were compared among different simulations to evaluate the effects of such operation changes. Results reveal that overloads determine a temporary decrease in removal efficiency before microbial biomass adapts to the new conditions and COD removal efficiency is recovered. Increasing organic overloads cause stronger temporary decreases in COD removal efficiency compared to increasing hydraulic loads. The pace at which clogging develops increases by 10% for each 10% increase on the organic load. Copyright © 2017 Elsevier B.V. All rights reserved.

Work Overload and Turnover Intention of Junior Auditors in Greater Jakarta, Indonesia

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Andika Pradana

2015-11-01

Full Text Available This paper aims to analyze how work overload influences turnover intentions of newly hired junior auditors in public accounting offices. Job satisfaction, work related stress and work life conflicts are used as mediating variables between work overload and turnover intention. This study employed 141 auditors from several accounting firms operating in the Greater Jakarta region. The sample was selected using purposive sampling. Three mediation hypotheses were tested using Structural Equation Modeling (SEM. The results show that work overload has a significant effect on increasing turnover intention through both job satisfaction and work related stress. In comparison, work overload does not influence turnover intention through work life balance. This may be due to the nature of the respondents, in which a majority of the newly hired accountants employed in this study are unmarried.

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

Science.gov (United States)

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.

Effect of short-term overloads on crack propagation under creep

International Nuclear Information System (INIS)

Sushok, V.V.; Sobolev, N.D.; Zolotukhin, S.Yu.

1986-01-01

Kinetics of crack propagation after overload has been studied using plane samples of Kh18N10T steel. Tests of samples with a notch have been carried out in the air at 293 K. Observation of the crack growth has been carried out by the microscope and the method of electric potential difference. It is established that during overload besides crack tip blunting, decrease of creep rate of the material stregthened near it, that leads to crack retardation, decrease of plasticity and formation of microcracks in front of the tip of the main-line crack occurs. It is marked that, estimating serviceability of a member, it is necessary to take into account the decrease of crack propagation rate after short term overloads

Iron overload impact on P-ATPases.

Science.gov (United States)

Sousa, Leilismara; Pessoa, Marco Tulio C; Costa, Tamara G F; Cortes, Vanessa F; Santos, Herica L; Barbosa, Leandro Augusto

2018-03-01

Iron is a chemical element that is active in the fundamental physiological processes for human life, but its burden can be toxic to the body, mainly because of the stimulation of membrane lipid peroxidation. For this reason, the action of iron on many ATPases has been studied, especially on P-ATPases, such as the Na + ,K + -ATPase and the Ca 2+ -ATPase. On the Fe 2+ -ATPase activity, the free iron acts as an activator, decreasing the intracellular Fe 2+ and playing a protection role for the cell. On the Ca 2+ -ATPase activity, the iron overload decreases the enzyme activity, raising the cytoplasmic Ca 2+ and decreasing the sarco/endoplasmic reticulum and the Golgi apparatus Ca 2+ concentrations, which could promote an enzyme oxidation, nitration, and fragmentation. However, the iron overload effect on the Na + ,K + -ATPase may change according to the tissue expressions. On the renal cells, as well as on the brain and the heart, iron promotes an enzyme inactivation, whereas its effect on the erythrocytes seems to be the opposite, directly stimulating the ATPase activity, or stimulating it by signaling pathways involving ROS and PKC. Modulations in the ATPase activity may impair the ionic transportation, which is essential for cell viability maintenance, inducing irreversible damage to the cell homeostasis. Here, we will discuss about the iron overload effect on the P-ATPases, such as the Na + ,K + -ATPase, the Ca 2+ -ATPase, and the Fe 2+ -ATPase.

A study on fatigue crack growth behavior subjected to a single tensile overload

International Nuclear Information System (INIS)

Lee, S.Y.; Liaw, P.K.; Choo, H.; Rogge, R.B.

2011-01-01

Neutron diffraction and electric potential experiments were carried out to investigate the growth behavior of a fatigue crack subjected to a single tensile overload. The specific objectives were to (i) probe the crack tip deformation and fracture behaviors under applied loads; (ii) examine the overload-induced transient crack growth micromechanism; (iii) validate the effective stress intensity factor range based on the crack closure approach as the fatigue crack tip driving force; and (iv) establish a quantitative relationship between the crack tip driving force and crack growth behavior. Immediately after a single tensile overload was introduced and then unloaded, the crack tip became blunt and enlarged compressive residual stresses in both magnitude and zone size were observed around the crack tip. The results show that the combined contributions of the overload-induced enlarged compressive residual stresses and crack tip blunting with secondary cracks are responsible for the observed changes in the crack opening load and the resultant post-overload transient crack growth behavior.

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

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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…

Expression of Hepcidin and Growth Differentiation Factor 15 (GDF-15 Levels in Thalassemia Patients with Iron Overload and Positive Anti Hepatitis C Virus

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Nuri Dyah Indrasari

2016-09-01

Full Text Available Background: Thalassemia patients who undergo life-long recurrent blood transfusion will experience iron overload in various organs including the liver and possibly suffer from chronic hepatitis C infection which may lead to liver impairment. The liver produces hepcidin, a hormone which plays role in the regulation of iron level in the blood. Various factors may influence hepcidin level in the blood. Chronic hepatitis C causes iron overload and liver impairment. Liver impairment and haemolytic anaemia due to haemoglobinopathy will suppress hepcidin production. Anaemia stimulates growth differentiation factor 15 (GDF-15 to increase erythropoiesis and suppress hepcidin production. Iron overload causes increase in hepcidin level. Presence of factors which decrease or increase hepcidin production will express various levels of hepcidin. This study aimed to identify the expression of hepcidin and GDF-15 levels in thalassemia patients with iron overload and positive anti-HCV. Information on hepcidin and GDF-15 levels are beneficial in the management of iron overload in thalassemia with positive anti-HCV. Method: This study was a descriptive analytic study in thalassemia patients who had received recurrent blood transfusion ≥ 12 times, suffered from iron overload (transferrin saturation > 55% and ferritin > 1,000 ng/mL, which consisted of 31 individuals with positive anti-HCV and 27 individuals with negative anti-HCV. This study was performed in Thalassemia Centre Department of Child Health and Department of Clinical Pathology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, in October 2011–January 2012. Serum hepcidin and GDF-15 examinations were performed using enzyme-linked immunosorbent assay (ELISA method. Aspartate aminotransferase (AST and alanine aminotransferase (ALT examinations were performed using colorimetry method. Data on ferritin and transferrin saturation were obtained from medical records in the last 3

Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

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Wen Liang

Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

Overload prevention in model supports for wind tunnel model testing

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Anton IVANOVICI

2015-09-01

Full Text Available Preventing overloads in wind tunnel model supports is crucial to the integrity of the tested system. Results can only be interpreted as valid if the model support, conventionally called a sting remains sufficiently rigid during testing. Modeling and preliminary calculation can only give an estimate of the sting’s behavior under known forces and moments but sometimes unpredictable, aerodynamically caused model behavior can cause large transient overloads that cannot be taken into account at the sting design phase. To ensure model integrity and data validity an analog fast protection circuit was designed and tested. A post-factum analysis was carried out to optimize the overload detection and a short discussion on aeroelastic phenomena is included to show why such a detector has to be very fast. The last refinement of the concept consists in a fast detector coupled with a slightly slower one to differentiate between transient overloads that decay in time and those that are the result of aeroelastic unwanted phenomena. The decision to stop or continue the test is therefore conservatively taken preserving data and model integrity while allowing normal startup loads and transients to manifest.

Influence of overloads on dwell time fatigue crack growth in Inconel 718

Energy Technology Data Exchange (ETDEWEB)

Saarimäki, Jonas, E-mail: jonas.saarimaki@liu.se [Division of Engineering Materials, Department of Management and Engineering, Linköping University, SE-58183 Linköping (Sweden); Moverare, Johan [Division of Engineering Materials, Department of Management and Engineering, Linköping University, SE-58183 Linköping (Sweden); Siemens Industrial Turbomachinery AB, Materials Technology, SE-61283 Finspång (Sweden); Eriksson, Robert; Johansson, Sten [Division of Engineering Materials, Department of Management and Engineering, Linköping University, SE-58183 Linköping (Sweden)

2014-08-26

Inconel 718 is one of the most commonly used superalloys for high temperature applications in gasturbines and aeroengines and is for example used for components such as turbine discs. Turbine discs can be subjected to temperatures up to ∼700 °C towards the outer radius of the disc. During service, the discs might start to develop cracks due to fatigue and long dwell times. Additionally, temperature variations during use can lead to large thermal transients during start-up and shutdown which can lead to overload peaks in the normal dwell time cycle. In this study, tests at 550 °C with an overload prior to the start of each dwell time, have been performed. The aim of the investigation was to get a better understanding of the effects of overloads on the microstructure and crack mechanisms. The microstructure was studied using electron channelling contrast imaging (ECCI). The image analysis toolbox in Matlab was used on cross sections of the cracks to quantify: crack length, branch length, and the number of branches in each crack. It was found that the amount of crack branching increases with an increasing overload and that the branch length decreases with an increasing overload. When the higher overloads were applied, the dwell time effect was almost cancelled out. There is a strong tendency for an increased roughness of the crack path with an increasing crack growth rate.

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

Directory of Open Access Journals (Sweden)

Stephanie Puukila

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

Influence of overloads on dwell time fatigue crack growth in Inconel 718

International Nuclear Information System (INIS)

Saarimäki, Jonas; Moverare, Johan; Eriksson, Robert; Johansson, Sten

2014-01-01

Inconel 718 is one of the most commonly used superalloys for high temperature applications in gasturbines and aeroengines and is for example used for components such as turbine discs. Turbine discs can be subjected to temperatures up to ∼700 °C towards the outer radius of the disc. During service, the discs might start to develop cracks due to fatigue and long dwell times. Additionally, temperature variations during use can lead to large thermal transients during start-up and shutdown which can lead to overload peaks in the normal dwell time cycle. In this study, tests at 550 °C with an overload prior to the start of each dwell time, have been performed. The aim of the investigation was to get a better understanding of the effects of overloads on the microstructure and crack mechanisms. The microstructure was studied using electron channelling contrast imaging (ECCI). The image analysis toolbox in Matlab was used on cross sections of the cracks to quantify: crack length, branch length, and the number of branches in each crack. It was found that the amount of crack branching increases with an increasing overload and that the branch length decreases with an increasing overload. When the higher overloads were applied, the dwell time effect was almost cancelled out. There is a strong tendency for an increased roughness of the crack path with an increasing crack growth rate

Managing Information Overload for Senior Leaders in the 21st Century

Science.gov (United States)

Jackson, Jason M.

2013-01-01

Information overload is a state where information input exceeds processing capability by an individual, and adverse effects of information overload, such as becoming less productive, making bad decisions, and becoming highly selective, are growing. Guided by Glaser and Strauss' work on grounded theory, this study examined adverse impact of…

WORK OVERLOAD AND TURNOVER INTENTION OF JUNIOR AUDITORS IN GREATER JAKARTA, INDONESIA

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Andika Pradana

2015-11-01

Full Text Available This paper aims to analyze how work overload influences turnover intentions of newly hired junior auditors in public accounting offices. Job satisfaction, work related stress and work life conflicts are used as mediating variables between work overload and turnover intention. This study employed 141 auditors from several accounting firms operating in the Greater Jakarta region. The sample was selected using purposive sampling. Three mediation hypotheses were tested using Structural Equation Modeling (SEM. The results show that work overload has a significant effect on increas- ing turnover intention through both job satisfaction and work related stress. In comparison, work overload does not influence turnover intention through work life balance. This may be due to the nature of the respondents, in which a majority of the newly hired accountants employed in this study are unmarried.

Mild iron overload in patients carrying the HFE S65C gene mutation: a retrospective study in patients with suspected iron overload and healthy controls

OpenAIRE

Holmström, P; Marmur, J; Eggertsen, G; Gåfvels, M; Stål, P

2002-01-01

Background and aims: The role of the HFE S65C mutation in the development of hepatic iron overload is unknown. The aim of the present study was: (A) to determine the HFE S65C frequency in a Northern European population; and (B) to evaluate whether the presence of the HFE S65C mutation would result in a significant hepatic iron overload.

An Improved Overloading Scheme for Downlink CDMA

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Marc Moeneclaey

2005-04-01

Full Text Available An improved overloading scheme is presented for single-user detection in the downlink of multiple-access systems based on OCDMA/OCDMA (O/O. By displacing in time the orthogonal signatures of the two user sets that make up the overloaded system, the cross-correlation between the users of the two sets is reduced. For random O/O with square-root cosine rolloff chip pulses, the multiuser interference can be decreased by up to 50% (depending on the chip pulse bandwidth as compared to quasiorthogonal sequences (QOS that are presently part of the downlink standard of Cdma2000. This reduction of the multiuser interference gives rise to an increase of the achievable signal-to-interference-plus-noise ratio for a particular channel load.

A low noise preamplifier with optoelectronic overload protection for radioactivity measurement

International Nuclear Information System (INIS)

Sephton, J.P.; Williams, J.M.; Johansson, L.C.; Philips, H.C.

2012-01-01

Pulses from detectors used for radioactivity measurement can vary in size by several orders of magnitude. Large pulses will lead to saturation at the preamplifier output and extension of the pulse length. As a consequence, the dead time of the system increases and pulses may be lost. Electronic design techniques employed to protect against overloading tend to increase the amplifier noise level. However, an optoelectronic method of overload protection has been devised which has only a negligible effect on noise. An infrared light emitting diode interfaced to the output of the preamplifier is linked by fibre optic cable to an ultra-low leakage photodiode at the input. The conduction of the photodiode increases with the amplitude of the preamplifier output signal. Excess current is thereby prevented from entering the preamplifier and causing saturation. The preamplifier has been tested on 4π beta–gamma and gas counting systems and found to give good protection against overloading. - Highlights: ► A preamplifier for radioactivity measurements has been developed. ► Low noise. ► Current sensitive. ► Optoelectronic overload protection.

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

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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 sodium-overloaded pups showed increased U(Prot24 h) (45%, P sodium-overloaded rats showed increased U(Prot24 h) (27%, P 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.

Plasma insulin levels are increased by sertraline in rats under oral glucose overload

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Gomez R.

2001-01-01

Full Text Available Recognition and control of depression symptoms are important to increase patient compliance with treatment and to improve the quality of life of diabetic patients. Clinical studies indicate that selective serotonin reuptake inhibitors (SSRI are better antidepressants for diabetic patients than other drugs. However, preclinical trials have demonstrated that not all SSRI reduce plasma glucose levels. In fact, fluoxetine increases and sertraline decreases glycemia in diabetic and non-diabetic rats. In the present study we evaluated plasma insulin levels during fasting and after glucose overload after treatment with sertraline. Adult male Wistar rats were fasted and treated with saline or 30 mg/kg sertraline and submitted or not to glucose overload (N = 10. Blood was collected and plasma insulin was measured. The mean insulin levels were: fasting group: 25.9 ± 3.86, sertraline + fasting group: 31.10 ± 2.48, overload group: 34.1 ± 3.40, and overload + sertraline group: 43.73 ± 5.14 µU/ml. Insulinemia was significantly increased in the overload + sertraline group. There were no differences between the other groups. No difference in glucose/insulin ratios could be detected between groups. The overload + sertraline group was the only one in which a significant number of individuals exceeded the upper confidence limit of insulin levels. This study demonstrates that sertraline increases glucose-stimulated insulin secretion without any change in peripheral insulin sensitivity.

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

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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.

Why cross-national differences in role overload? Don't overlook ambient temperature!

NARCIS (Netherlands)

Van de Vliert, E.; Van Yperen, N.W.

The finding that, across nations, power distance (expected and accepted unequal interpersonal influence) Is positively related to role overload (Peterson et al., 1995) might he an artifact of the relation between role overload and ambient temperature or other third factors. We related data on power

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

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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.…

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

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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.

Changes in cardiac output and incidence of volume overload in cirrhotics receiving 20% albumin infusion.

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Shasthry, Saggere M; Kumar, Manoj; Khumuckham, Jelen S; Sarin, Shiv Kumar

2017-08-01

Patients with cirrhosis are prone to develop volume over load, have increased capillary permeability and latent or overt cardiomyopathy. Whether albumin infusion causes volume overload in cirrhotics has not been adequately studied. Ninety nine consecutive cirrhotic patients receiving 1gm per kg albumin infusion were evaluated for development of volume overload. Clinical, echocardiographic and haemodynamic changes were closely monitored during and after albumin infusion. Thirty (30.30%) patients developed volume overload. Patients with higher BMI (P=.003), lower CTP (P=.01) and MELD (P=.034) were more often associated with the development of volume overload. Though baseline diastolic dysfunction was present in 82.8% of the patients, it did not influence the development of volume overload or changes in the cardiac output. The cardiac output increased significantly after albumin infusion (4.9±1.554 L/min to 5.86±1.85 L/min, Palbumin infusion develop volume overload, specially, those with higher BMI and lower severity of liver disease. Cardiac output increases after albumin infusion, and, baseline diastolic dysfunction has little effect on the development of volume overload or changes in cardiac output. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Science.gov (United States)

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.

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

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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 overload training significantly decreased the phagocytosis (27 %, P overload training group increased significantly compared with the control group (21-fold and 92-fold, respectively; P 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.

Information Diffusion in Facebook-Like Social Networks Under Information Overload

Science.gov (United States)

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.

Fatigue crack growth behaviour of carbon steel piping material subjected to single overload/under-load

International Nuclear Information System (INIS)

Arora, Punit; Tripathi, R.; Singh, P.K.; Bhasin, V.; Vijayan, P.K.

2016-01-01

The objective of the present study is to understand the Fatigue Crack Growth Rate (FCGR) behaviour after single over-load/ under-load event on carbon steel piping material. The tests have been carried out on standard Compact Tension (CT) specimens. The effect of different crack length to width ratio (a/W) of specimen and overload/under-load ratios on FCGR have been studied. The studies have shown significant reduction in FCG rate after overload event. The strain field has been measured using Digital Image Correlation (DIC) technique ahead of the crack tip to quantify the plastic zone size due to overload and constant amplitude load. In addition, plastic zone calculations have also been carried out using 3D finite element analyses for the prediction of post overload FCGR/ life. The predicted FCGR are in agreement with experimentally determined FCGR. (author)

Formal Constraints on Memory Management for Composite Overloaded Operations

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Damian W.I. Rouson

2006-01-01

Full Text Available The memory management rules for abstract data type calculus presented by Rouson, Morris & Xu [15] are recast as formal statements in the Object Constraint Language (OCL and applied to the design of a thermal energy equation solver. One set of constraints eliminates memory leaks observed in composite overloaded expressions with three current Fortran 95/2003 compilers. A second set of constraints ensures economical memory recycling. The constraints are preconditions, postconditions and invariants on overloaded operators and the objects they receive and return. It is demonstrated that systematic run-time assertion checking inspired by the formal constraints facilitated the pinpointing of an exceptionally hard-to-reproduce compiler bug. It is further demonstrated that the interplay between OCL's modeling capabilities and Fortran's programming capabilities led to a conceptual breakthrough that greatly improved the readability of our code by facilitating operator overloading. The advantages and disadvantages of our memory management rules are discussed in light of other published solutions [11,19]. Finally, it is demonstrated that the run-time assertion checking has a negligible impact on performance.

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

Science.gov (United States)

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.

Effect of overload on SCC growth in stainless steels in high temperature water

International Nuclear Information System (INIS)

Xue, He; Peng, Qunjia; Shoji, Tetsuo

2009-01-01

By incorporating the film slip-dissolution/oxidation model and the elastic-plastic finite element method (EPFEM), the effect of the overload on stress corrosion cracking (SCC) growth rate of stainless steel in high temperature water is discussed in this paper. Results show that SCC growth rate of a 20% cold worked 316L stainless steel in high temperature water decrease in the overload affected zone ahead of the growing crack tip. Therefore, a reasonable overload could availably reduce the SCC growth rate during a certain in-service period. (author)

A study on fatigue crack growth behavior subjected to a single tensile overload: Part II. Transfer of stress concentration and its role in overload-induced transient crack growth

International Nuclear Information System (INIS)

Lee, S.Y.; Choo, H.; Liaw, P.K.; An, K.; Hubbard, C.R.

2011-01-01

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 load 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 Δε eff and ΔK eff provides experimental support for the hypothesis that ΔK eff can be considered as the fatigue crack tip driving force.

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

Science.gov (United States)

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.

Miso (Japanese soybean paste) soup attenuates salt-induced sympathoexcitation and left ventricular dysfunction in mice with chronic pressure overload.

Science.gov (United States)

Ito, Koji; Hirooka, Yoshitaka; Sunagawa, Kenji

2014-02-01

The hypothalamic mineralocorticoid receptor (MR)-angiotensin II type 1 receptor (AT1R) pathway is activated in mice with chronic pressure overload (CPO). When this activation is combined with high salt intake, it leads to sympathoexcitation, hypertension, and left ventricular (LV) dysfunction. Salt intake is thus an important factor that contributes to heart failure. Miso, a traditional Japanese food made from fermented soybeans, rice, wheat, or oats, can attenuate salt-induced hypertension in rats. However, its effects on CPO mice with salt-induced sympathoexcitation and LV dysfunction are unclear. Here, we investigated whether miso has protective effects in these mice. We also evaluated mechanisms associated with the hypothalamic MR-AT1R pathway. Aortic banding was used to produce CPO, and a sham operation was performed for controls. At 2 weeks after surgery, the mice were given water containing high NaCl levels (0.5%, 1.0%, and 1.5%) for 4 weeks. The high salt loading in CPO mice increased excretion of urinary norepinephrine (uNE), a marker of sympathetic activity, in an NaCl concentration-dependent manner; however, this was not observed in Sham mice. Subsequently, CPO mice were administered 1.0% NaCl water (CPO-H) or miso soup (1.0% NaCl equivalent, CPO-miso). The expression of hypothalamic MR, serum glucocorticoid-induced kinase-1 (SGK-1), and AT1R was higher in the CPO-H mice than in the Sham mice; however, the expression of these proteins was attenuated in the CPO-miso group. Although the CPO-miso mice had higher sodium intake, salt-induced sympathoexcitation was lower in these mice than in the CPO-H group. Our findings indicate that regular intake of miso soup attenuates salt-induced sympathoexcitation in CPO mice via inhibition of the hypothalamic MR-AT1R pathway.

Designing immersive surgical training against information technology-related overload in the operating room

NARCIS (Netherlands)

Pluyter, J.R.

2012-01-01

On a theoretical level, this dissertation demonstrates that the “classical” conceptualization of overload in the field of Information Systems being an excessive amount of information is too simplistic. Based on the Emotional-Cognitive Overload Model by Rutkowski and Saunders (2011) this dissertation

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

Science.gov (United States)

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

2015-01-01

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

Information Overload in Multi-Stage Selection Procedures

NARCIS (Netherlands)

S.S. Ficco (Stefano); V.A. Karamychev (Vladimir)

2004-01-01

textabstractThe paper studies information processing imperfections in a fully rational decision-making network. It is shown that imperfect information transmission and imperfect information acquisition in a multi-stage selection game yield information overload. The paper analyses the mechanisms

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

Science.gov (United States)

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…

Testing of camera performance standards at steady and local overloading

International Nuclear Information System (INIS)

Keszthelyine Landori, S.; Adorjanne Farkas, M.; Csirik, J.

1983-01-01

Camera performance standards are usually given for low count rates and uniform irradiation. A conventional analog gamma camera system (Gamma MB 9100 manufactured under the know-how of Picker DC 4/12 in Hungary) was studied on the basis of the Picker test procedure and the NEMA standard system. Uniformity, linearity, spatial and energy resolution were measured at high count rates and uniform irradiation (steady overloading). Linearity was studied at local overloading. Linearity, spatial and energy resolution were measured by a 1024-channel analyzer-computer system of KFKI, Hungary. The data were evaluated on the basis of NEMA standards, while uniformity was measured by the Gamma data processing system and evaluated by special SEGAMS programs. Performance variations were studied between 7500 cps and 75.000 cps pulse rates. Spatial and energy resolution were influenced strongly, uniformity slightly by pulse rates, while linearity did not change at all. Linearity was not influenced even by local overloading. (author)

Association between filial responsibility when caring for parents and the caregivers overload

Directory of Open Access Journals (Sweden)

Marinês Aires

Full Text Available ABSTRACT Objective: To analyze the association between filial responsibility and the overload of the children when caring for their older parents. Method: Cross-sectional study with 100 caregiver children of older adults. Filial liability was assessed by the attitudes of the responsible child (scale of expectation and filial duty and by care behaviors (assistance in activities of daily living, emotional and financial support, and keeping company. The overload was assessed by the Caregiver Burden Inventory. To assess the associations, the correlation coefficients of Pearson and Spearman, Kruskal-Wallis Test, and Mann-Whitney were employed. Variables that presented p-value<0.20 in the bivariate analysis were inserted in a multivariate linear regression model. Results: The factors associated with overload were: formal employment (p=0.002, feelings regarding family life (p<0.001, financial support (p=0.027, and assistance with Activities of Daily Living (ADLs (p<0.001. Conclusion: Children who were more involved with the ADLs and provided financial support showed higher levels of overload.

Effect of overloading types on fatigue crack growth threshold for stainless steel SUS316

International Nuclear Information System (INIS)

Osada, Toshio; Sano, Hayato; Takahashi, Koji

2013-01-01

Effect of overloading types on the fatigue crack growth threshold of SUS316 was studied. Three types of overloading: tensile (type I), tensile+compression (type II), and tensile+compression+tensile (type III) were applied to compact tension specimens, then the fatigue tests were carried out to determine the apparent threshold stress intensity factor range Δ N K th . The results showed that the Δ N K th values increased with increasing the single tensile overload stress intensity factor K ov above the K ov > ΔK th . Additional compressive loading (type II) led to decrease in Δ N K th to the ΔK th =6MPa×m 1/2 within the all tested K ov values ranging from -45MPa×m 1/2 ≤K ov 1/2 . This is due to the fact that the compressive residual stress field at crack tip changed to the tensile stress field by the compressive loading. Furthermore, the Δ N K th values increased again by additional tensile overloading (type III) from ΔK th to the almost same Δ N K th values as that by Type I loading. This means that the almost same compressive residual stress field formed by type III overloading as the type I overloading. The experimental Δ N K th increasing behaviors were discussed by Finite Element Method (FEM). (author)

Over-exposed portraits : Technology overload and the identities of the young

OpenAIRE

Lutz, Christoph; Ranzini, Giulia; Meckel, Miriam

2013-01-01

Technostress and information overload represent serious challenges of the Information Age. An alarming number of people exhibit dangerously intensive media consumption, while Internet and mobile phone addictions are a widespread phenomenon, especially among teens. Despite increasing evidence for technostress and information overload within the literature, the consequences of new media overexposure on young individuals are so far understudied. When it comes to Social Network Sites (SNS), in pa...

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

Science.gov (United States)

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...

Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials.

Science.gov (United States)

McKenney, James; Bays, Harold; Gleim, Gilbert; Mitchel, Yale; Kuznetsova, Olga; Sapre, Aditi; Sirah, Waheeda; Maccubbin, Darbie

2015-01-01

The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) showed that adding extended-release niacin-laropiprant (ERN-LRPT) to statin provided no incremental cardiovascular benefit vs placebo (PBO). ERN-LRPT was also associated with an excess of serious adverse experiences (AEs), some of which were unexpected (infections and bleeding). These findings led to the withdrawal of ERN-LRPT from all markets. We examined the safety profile of ERN-LRPT vs the comparators ERN alone and statins in the ERN-LRPT development program to assess whether similar safety signals were observed to those seen in HPS-THRIVE and whether these might be attributed to ERN or LRPT. Postrandomization safety data from 12 clinical studies, 12 to 52 weeks in duration and involving 11,310 patients, were analyzed across 3 treatments: (1) ERN-LRPT; (2) ERN-NSP (ERN, Merck & Co, Inc or Niaspan [NSP], Abbott Laboratories); and (3) statin-PBO (statin or PBO). The safety profiles of ERN-LRPT and ERN-NSP were similar, except for less flushing with ERN-LRPT. Nonflushing AEs reported more frequently with ERN-LRPT or ERN-NSP than with statin-PBO were mostly nonserious and typical of niacin (nausea, diarrhea, and increased blood glucose). There was no evidence for an increased risk of serious AEs related to diabetes, muscle, infection, or bleeding. Pooled data from 11,310 patients revealed that, except for reduced flushing, the safety profile of ERN-LRPT was similar to that of ERN-NSP; LRPT did not appear to adversely affect the side-effect profile of ERN. The inability to replicate the unexpected AE findings in HPS2-THRIVE could be because of the smaller sample size and substantially shorter duration of these studies. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Yeast culture increased plasma niacin concentration, evaporative heat loss, and feed efficiency of dairy cows in a hot environment.

Science.gov (United States)

Dias, Julia D L; Silva, Rayana B; Fernandes, Tatiane; Barbosa, Eugenio F; Graças, Larissa E C; Araujo, Rafael C; Pereira, Renata A N; Pereira, Marcos N

2018-04-04

The supplementation of dairy cows with yeast culture may increase diet digestibility, plasma niacin concentration, heat dissipation, and lactation performance. Our objective was to evaluate the response of Holstein cows in late lactation (234 ± 131 d in milk) to dead yeast culture (YC, 15 g/d, Factor SC, GRASP, Saccharomyces cerevisiae) during Brazilian summer (temperature-humidity index >68 for 92.2% of the time). Thirty-two cows were individually fed a standard total mixed ration for 14 d and control (CTL) or YC treatments for 35 d, in a covariate adjusted complete randomized block design. Response was evaluated in wk 5 or as repeated measures over time. Cows were milked 3 times per day and treatments (YC or placebo) were orally dosed to each cow before each milking. Plasma niacin was 1.50 for CTL and 1.66 µg/mL for YC. The YC reduced rectal temperature, respiration rate, and skin temperature, whereas it tended to increase sweating rate. The proportion of cows with rectal temperature ≥39.2°C on CTL and YC was, respectively, 8 and 0% at 0730 h, 52 and 25% at 1500 h, and 35 and 26% at 2200 h. Plasma glucose was increased by YC. The total-tract apparent digestibility of nutrients, plasma urea N concentration, molar proportion of ruminal VFA, and urinary allantoin excretion were not affected by YC. Cows fed YC were less selective against feed particles >19 mm in the morning, in the afternoon were more selective against long feed particles and in favor of particles loss, and feed efficiency of late lactation dairy cows by reducing intake at similar milk yield. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

Quantitative estimation of the right ventricular overloading by thallium-201 myocardial scintigraphy

International Nuclear Information System (INIS)

Owada, Kenji; Machii, Kazuo; Tsukahara, Yasunori

1982-01-01

Thallium-201 myocardial scintigraphy was performed on 55 patients with various types of right ventricular overloading. The right ventricular (RV) free wall was visualized in 39 out of the 55 patients (71%). The mean values of right ventricular systolic pressure (RVSP) and pulmonary artery mean pressure (PAMP) in the visualized cases (uptakers) were 54.6 +- 24.1 and 30.5 +- 15.3 mmHg, respectively. These values were significantly higher than those of the non-visualized cases (non-uptakers). There were 12 RVSP-''normotensive'' uptakers and 15 PAMP-''normotensive'' uptakers. The RV free wall images were classified into three types according to their morphological features. Type I was predominantly seen in cases of RV pressure overloading, type II in RV volume overloading and type III in combined ventricular overloading. RVSP in the type III group was significantly higher than that in other two groups. The radioactivity ratio in RV free wall and interventricular septum (IVS), the RV/IVS uptake ratio was calculated using left anterior oblique (LAO) view images. The RV/IVS uptake ratio closely correlated with RVSP and PAMP (r = 0.88 and 0.82, respectively). In each group of RV free wall image, there were also close correlations between the RV/IVS uptake ratio and both RVSP and PAMP. Our results indicate that the RV/IVS uptake ratio can be used as a parameter for the semi-quantitative estimation of right ventricular overloading. (author)

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

Science.gov (United States)

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

2016-03-15

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

Ischemic preconditioning improves mitochondrial tolerance to experimental calcium overload.

Science.gov (United States)

Crestanello, Juan A; Doliba, Nicolai M; Babsky, Andriy M; Doliba, Natalia M; Niibori, Koki; Whitman, Glenn J R; Osbakken, Mary D

2002-04-01

Ca(2+) overload leads to mitochondrial uncoupling, decreased ATP synthesis, and myocardial dysfunction. Pharmacologically opening of mitochondrial K(ATP) channels decreases mitochondrial Ca(2+) uptake, improving mitochondrial function during Ca(2+) overload. Ischemic preconditioning (IPC), by activating mitochondrial K(ATP) channels, may attenuate mitochondrial Ca(2+) overload and improve mitochondrial function during reperfusion. The purpose of these experiments was to study the effect of IPC (1) on mitochondrial function and (2) on mitochondrial tolerance to experimental Ca(2+) overload. Rat hearts (n = 6/group) were subjected to (a) 30 min of equilibration, 25 min of ischemia, and 30 min of reperfusion (Control) or (b) two 5-min episodes of ischemic preconditioning, 25 min of ischemia, and 30 min of reperfusion (IPC). Developed pressure (DP) was measured. Heart mitochondria were isolated at end-Equilibration (end-EQ) and at end-Reperfusion (end-RP). Mitochondrial respiratory function (state 2, oxygen consumption with substrate only; state 3, oxygen consumption stimulated by ADP; state 4, oxygen consumption after cessation of ADP phosphorylation; respiratory control index (RCI, state 3/state 4); rate of oxidative phosphorylation (ADP/Deltat), and ADP:O ratio) was measured with polarography using alpha-ketoglutarate as a substrate in the presence of different Ca(2+) concentrations (0 to 5 x 10(-7) M) to simulate Ca(2+) overload. IPC improved DP at end-RP. IPC did not improve preischemic mitochondrial respiratory function or preischemic mitochondrial response to Ca(2+) loading. IPC improved state 3, ADP/Deltat, and RCI during RP. Low Ca(2+) levels (0.5 and 1 x 10(-7) M) stimulated mitochondrial function in both groups predominantly in IPC. The Control group showed evidence of mitochondrial uncoupling at lower Ca(2+) concentrations (1 x 10(-7) M). IPC preserved state 3 at high Ca(2+) concentrations. The cardioprotective effect of IPC results, in part, from

Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

OpenAIRE

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

2017-01-01

We aimed to prospectively assess changes in chronic stress among young adults transitioning from high school to university or working life. A population-based cohort in Munich and Dresden (Germany) was followed from age 16–18 (2002–2003) to age 20–23 (2007–2009) (n = 1688). Using the Trier Inventory for the Assessment of Chronic Stress, two dimensions of stress at university or work were assessed: work overload and work discontent. In the multiple ordinal generalized estimating equations, soc...

The Family in Care for the Elderly: Managing the Overload and Coping with Difficulties

Directory of Open Access Journals (Sweden)

Lisete dos Santos Mendes Mónico

2017-08-01

Full Text Available Introduction: Family is considered the main support of the elderly in a situation of dependency. Caregiving often results in overloading, leading to diverse problems. Aim: To evaluate the self-perception of the family caregiver’s overload and the strategies used to provide informal care to the dependent elderly considering their level of dependence. Method: The sample consisted of 21 children, 16 spouses, and nine other relatives of elderly dependents who responded to the Caregiver’s Overload Scale (Sequeira, 2007, the Portuguese version of Caregivers’ Assessment Management Index (CAMI, Nolan, Keady, & Grant, 1995 and the Barthel Index (Mahoney & Barthel, 1965. Results: The Barthel Index showed 34.8% of the elderly as severely dependent and 37.0% as totally dependent. The care most provided respected to medication, hygiene, food, and monitoring. Above 56.5% of the caregivers had an intense overload, both at the objective (impact of care and interpersonal relationship and subjective (F3-Expectations regarding care and F4-Perceived self-efficacy levels. The main reason for maintaining caregivers was family/personal obligation (95.7%. Caregivers reasonably assessed the effectiveness of their strategies in dealing with their dependent elderly (CAMI; M = 101.0, SD = 15.0. There was a negative relationship between the perception of the caregiver’s overload and the age and health status of the elderly, as well as between the number of strategies used by the caregiver to overcome difficulties and the self-perception of the overload. Conclusion: The multiplicity of daily tasks performed in support of a family member in a situation of severe dependence translates into situations of intense overload, negatively impacting on care, interpersonal relationship, expectations regarding caring, and perception of self-efficacy of care.

Iron overload detection in rats by means of a susceptometer operating at room temperature

International Nuclear Information System (INIS)

Marinelli, M; Gianesin, B; Avignolo, C; Parodi, S; Minganti, V

2008-01-01

Biosusceptometry is a non-invasive procedure for determination of iron overload in a human body; it is essentially an assessment of the diamagnetic (water) and paramagnetic (iron) properties of tissues. We measured in vivo iron overload in the liver region of 12 rats by a room temperature susceptometer. The rats had been injected with sub-toxic doses of iron dextran. A quantitative relationship has been observed between the measurements and the number of treatments. The assessment of iron overload requires evaluating the magnetic signal corresponding to the same rat ideally without the overload. This background value was extrapolated on the basis of the signal measured in control rats versus body weight (R 2 = 0.73). The mean iron overload values for the treated rats, obtained after each iron injection, were significantly different from the means of the corresponding control rats (p 2 = 0.89). The magnetic moment of iron atoms in liver tissues was measured to be 3.6 Bohr magneton. Evaluation of the background signal is the limit to the measure; the error corresponds to about 30 mg (1 SD) of iron while the instrument sensitivity is more than a factor of 10 better.

A new approach to quantify the additional effect of primary overloads on ratcheting

International Nuclear Information System (INIS)

Waeckel, N.; Faure, O.; Sperandio, M.; Cousin, M.; Taleb, L.

1991-01-01

Taking into account the temporary nature of overloads reduces the conservatism of the current RCC-MR rules for prevention of ratcheting. An empirical K factor determined by the BITUBE tests carried out at INSA LYON, permits to quantify the influence of short-term mechanical overloads by comparison with the case without overload. The prediction of ratcheting risks by the RCC-MR efficiency diagram using a fictitious increased primary load by a K-factor is more fitted to the design of structures submitted to seisms. From then on, taking advantage of the workability of the experimental device BITUBE a new tests program has begun to confirm the results expressed above. (author)

2D mapping of plane stress crack-tip fields following an overload

Directory of Open Access Journals (Sweden)

P. J. Withers

2015-07-01

Full Text Available The evolution of crack-tip strain fields in a thin (plane stress compact tension sample following an overload (OL event has been studied using two different experimental techniques. Surface behaviour has been characterised by Digital Image Correlation (DIC, while the bulk behaviour has been characterised by means of synchrotron X-ray diffraction (XRD. The combination of both surface and bulk information allowed us to visualise the through-thickness evolution of the strain fields before the OL event, during the overload event, just after OL and at various stages after it. Unlike previous work, complete 2D maps of strains around the crack-tip were acquired at 60m spatial resolution by XRD. The DIC shows less crack opening after overload and the XRD a lower crack-tip peak stress after OL until the crack has grown past the compressive crack-tip residual stress introduced by the overload after which the behaviour returned to that for the baseline fatigue response. While the peak crack-tip stress is supressed by the compressive residual stress, the crack-tip stress field changes over each cycle are nevertheless the same for all Kmax cycles except at OL.

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

Science.gov (United States)

Huang, Yong-Ming; Liu, Chien-Hung; Lee, Chun-Yi; Huang, Yueh-Min

2012-01-01

Museum learning has received a lot of attention in recent years. Museum learning refers to people's use of museums to acquire knowledge. However, a problem with information overload has caused in engaging in such learning. Information overload signifies that users encounter a mass of information and need to determine whether certain information…

Resilience of electricity grids against transmission line overloads under wind power injection at different nodes.

Science.gov (United States)

Schiel, Christoph; Lind, Pedro G; Maass, Philipp

2017-09-14

A steadily increasing fraction of renewable energy sources for electricity production requires a better understanding of how stochastic power generation affects the stability of electricity grids. Here, we assess the resilience of an IEEE test grid against single transmission line overloads under wind power injection based on the dc power flow equations and a quasi-static grid response to wind fluctuations. Thereby we focus on the mutual influence of wind power generation at different nodes. We find that overload probabilities vary strongly between different pairs of nodes and become highly affected by spatial correlations of wind fluctuations. An unexpected behaviour is uncovered: for a large number of node pairs, increasing wind power injection at one node can increase the power threshold at the other node with respect to line overloads in the grid. We find that this seemingly paradoxical behaviour is related to the topological distance of the overloaded line from the shortest path connecting the wind nodes. In the considered test grid, it occurs for all node pairs, where the overloaded line belongs to the shortest path.

Effects of acute and chronic stress on telencephalic neurochemistry and gene expression in rainbow trout (Oncorhynchus mykiss)

DEFF Research Database (Denmark)

Moltesen, Maria; Laursen, Danielle Caroline; Thörnqvist, Per Ove

2016-01-01

By filtering relevant sensory inputs and initiating stress responses, the brain is an essential organ in stress coping and adaptation. However, exposure to chronic or repeated stress can lead to allostatic overload, where neuroendocrinal and behavioral reactions to stress become maladaptive. This...

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

International Nuclear Information System (INIS)

Croft, M.; Jisrawi, N.; Zhong, Z.; Holtz, R.; Sadananda, K.; Skaritka, J.; Tsakalakos, T.

2007-01-01

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 the 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 max ) -p (ΔK) p ] γ 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

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

Science.gov (United States)

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.

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to a combination of thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, D-biotin and pumpkin seed oil and maintenance of normal hair pursuant to Article 13

DEFF Research Database (Denmark)

Tetens, Inge

Following two applications from Nutrilinks Sarl, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health...... claim related to a combination of thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, D-biotin and pumpkin seed oil (Cucurbita pepo L.) and maintenance of normal hair. The Panel considers that the specified combination is sufficiently characterised. The claimed effects are “contributes to reduce......, riboflavin, niacin, pantothenic acid, pyridoxine, D-biotin and pumpkin seed oil (Cucurbita pepo L.) and maintenance of normal hair....

Overload effects on a ferritic-baintic steel and a cast aluminium alloy: two very different behaviours

Energy Technology Data Exchange (ETDEWEB)

Saintier, N. [Arts et Metiers Paris Tech, I2M, UMR CNRS, Universite Bordeaux 1, Talene Cedex (France); El Dsoki, C.; Kaufmann, H.; Sonsino, C.M. [Fraunhofer-Institute for Structural Durability and System Reliability LBF, Darmstadt (Germany); Dumas, C. [RENAULT, Technocentre, Guyancourt Cedex (France); Voellmecke, F.J. [BORBET GmbH, Hallenberg-Hesborn (Germany); Palin-Luc, T.; Bidonard, H.

2011-10-15

Load controlled fatigue tests were performed up to 10{sup 7} cycles on flat notched specimens (K{sub t} = 2.5) under constant amplitude and variable amplitude loadings with and without periodical overloads. Two materials are studied: a ferritic-bainitic steel (HE400M steel) and a cast aluminium alloy (AlSi7Mg0.3). These materials have a very different cyclic behaviour: the steel exhibits cyclic strain softening whereas the Al alloy shows cyclic strain hardening. The fatigue tests show that, for the steel, periodical overload applications reduce significantly the fatigue life for fully reversed load ratio (R{sub {sigma}} = -1), while they have no influence under pulsating loading (R{sub {sigma}} = 0). For the Al alloy overloads have an effect (fatigue life decreasing) only for variable amplitude loadings. The detrimental effect of overloads on the steel is due to ratcheting at the notch root which evolution is overload's dependent. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Influences of overload on low cycle fatigue behaviors of elbow pipe with local wall thinning

International Nuclear Information System (INIS)

Sato, Kyohei; Ogino, Kanako; Takahashi, Koji; Ando, Kotoji; Urabe, Yoshio

2011-01-01

Low cycle fatigue tests were conducted using 100A elbow pipe specimens with or without local wall thinning. Local wall thinning was machined on the inside of the extrados of test elbows to simulate metal loss due to flow-accelerated corrosion or liquid droplet impingement erosion. Low cycle fatigue tests were carried out under displacement control with an inner pressure of 9 MPa. To simulate seismic events, low cycle fatigue tests were carried out on elbow pipe subjected to cyclic overloads. Regardless of local wall thinning, fatigue life of overload pipe was not so different from that of the non-overload pipe in appearance. Miner's rule can be applied to evaluate fatigue life of the elbow pipes with and without wall thinning, even if overload is applied. (author)

Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model.

Science.gov (United States)

Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

2017-02-01

Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. Copyright© Ferrata Storti Foundation.

β-Thalassemia and Polycythemia vera: targeting chronic stress erythropoiesis.

Science.gov (United States)

Crielaard, Bart J; Rivella, Stefano

2014-06-01

β-Thalassemia and Polycythemia vera are genetic disorders which affect the synthesis of red blood cells, also referred to as erythropoiesis. Although essentially different in clinical presentation - patients with β-thalassemia have an impairment in β-globin synthesis leading to defective erythrocytes and anemia, while patients with Polycythemia vera present with high hemoglobin levels because of excessive red blood cell synthesis - both pathologies may characterized by lasting high erythropoietic activity, i.e. chronic stress erythropoiesis. In both diseases, therapeutic strategies targeting chronic stress erythropoiesis may improve the address phenotype and prevent secondary pathology, such as iron overload. The current review will address the basic concepts of these strategies to reduce chronic stress erythropoiesis, which may have significant clinical implications in the near future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dietary iron rural blacks overload In southern African

African Journals Online (AJOL)

1990-09-15

Sep 15, 1990 ... suggest that iron overload from any cause may predispose to infection7 and there are .... consumption and acute inflammatory diseases. However, it ..... Addison GM, Beamish MR, Hales C ',Hodgkins M, Jacobs A, Llewellin P.

The overloaded right heart and ventricular interdependence.

Science.gov (United States)

Naeije, Robert; Badagliacca, Roberto

2017-10-01

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

Work Overload and Turnover Intention of Junior Auditors in Greater Jakarta, Indonesia

OpenAIRE

Andika Pradana; Imam Salehudin

2015-01-01

This paper aims to analyze how work overload influences turnover intentions of newly hired junior auditors in public accounting offices. Job satisfaction, work related stress and work life conflicts are used as mediating variables between work overload and turnover intention. This study employed 141 auditors from several accounting firms operating in the Greater Jakarta region. The sample was selected using purposive sampling. Three mediation hypotheses were tested using Structural Equation M...

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Crack growth retardation due to micro-roughness: a mechanism for overload effects in fatigue

International Nuclear Information System (INIS)

Suresh, S.

1982-01-01

A new mechanism for fatigue crack growth retardation following an overload is presented in this paper, based on a micro-roughness model. It is reasoned, with the aid of extensive experimental evidence available in the literature, that retardation following an overload is governed by the micromechanisms of near-threshold crack growth. This model is found to rationalize a number of hitherto unexplained experimental observations. Moreover, the present arguments, which suggest that plasticity-induced crack closure is not likely to be the primary mechanism for retardation following single overloads, do not exclude the role of residual stresses or blunting, but provide further mechanistic basis to account for the inconsistencies in the previous models. Additional sources of prolonged retardation, in terms of crack closure due to corrosion debris formed in moist environments, are suggested. It is pointed out that such environmental effects could play an important role in post-overload crack growth in certain alloy systems

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

Energy Technology Data Exchange (ETDEWEB)

Assis, Reijâne Alves de; Kassab, Carolina; Seguro, Fernanda Salles [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Costa, Fernando Ferreira [Universidade Estadual de Campinas, Campinas, SP (Brazil); Silveira, Paulo Augusto Achucarro [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Wood, John [University of Southern California, California (United States); Hamerschlak, Nelson [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)

2013-07-01

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

2016-03-01

Inflammation plays a key role in pressure overload-induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High-mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload-induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild-type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin-embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up-regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload-induced cardiac hypertrophy and cardiac dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice.

Science.gov (United States)

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 overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p overload (p overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice.

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

Science.gov (United States)

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.

Neurohumoral fluid regulation in chronic liver disease

DEFF Research Database (Denmark)

Møller, Søren; Henriksen, Jens Henrik Sahl

1998-01-01

oxide and vasodilating peptides seem to play an important role. The development of central hypovolaemia and activation of potent vasoconstricting systems such as the renin-angiotensin-aldosterone system and the sympathetic nervous system lead to a hyperdynamic circulation with increased heart rate...... and lungs. It is still an enigma why patients with chronic liver disease are at the same time overloaded and functional hypovolaemic with a hyperdynamic, hyporeactive circulation. Further research is needed to find the solution to this apparent haemodynamic conflict concerning the abnormal neurohumoral...

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

Science.gov (United States)

Miller, Wayne L; Mullan, Brian P

2014-06-01

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

Controlling Price-Responsive Heat Pumps for Overload Elimination in Distribution Systems

DEFF Research Database (Denmark)

Csetvei, Zsuzsa; Østergaard, Jacob; Nyeng, Preben

2011-01-01

This paper investigates the possibility of applying electric heat pumps with the control-by-price-concept in order to avoid overload in a local distribution system. The proposed control algorithm is based upon a centrally dispatched real-time market price, reflecting the state of a larger power...... system, and is extended with a local price control for overload elimination on the corresponding feeder. The paper presents the mathematical models of a two-node system with price-responsive heat pumps, the chosen methodology of the central price calculation, and the proposed local feedback control...

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

Science.gov (United States)

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

2013-01-01

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

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

Directory of Open Access Journals (Sweden)

Sara Sanz-Blasco

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

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

Science.gov (United States)

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

2008-07-23

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.

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

Science.gov (United States)

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).

VOLUME OVERLOAD IS ASSOCIATED WITH MALNUTRITION IN PERITONEAL DIALYSIS

Directory of Open Access Journals (Sweden)

Jin Joo Cha

2012-06-01

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

Information Overload in the New World of Work: Qualitative Study into the Reasons and Countermeasures

NARCIS (Netherlands)

ter Heerdt, Jeroen; Bondarouk, Tatiana; Ruel, Hubertus Johannes Maria; Guiderdoni-Jourdain, Karine; Oiry, Ewan

2009-01-01

In this chapter the authors present a revision of the information overload concept elaborated by Eppler and Mengis (2004). The main elements of our approach are literature synopsis and analysis, qualitative semi-structured interviews, and discussion. Their review of the information overload concept

Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle.

Directory of Open Access Journals (Sweden)

Satoshi Nakada

Full Text Available 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.

Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle.

Science.gov (United States)

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.

Information overload, choice deferral, and moderating role of need for cognition: Empirical evidence

Directory of Open Access Journals (Sweden)

Luis Eduardo Pilli

2016-03-01

Full Text Available ABSTRACT Choice deferral due to information overload is an undesirable result of competitive environments. The neoclassical maximization models predict that choice avoidance will not increase as more information is offered to consumers. The theories developed in the consumer behavior field predict that some properties of the environment may lead to behavioral effects and an increase in choice avoidance due to information overload. Based on stimuli generated experimentally and tested among 1,000 consumers, this empirical research provides evidence for the presence of behavioral effects due to information overload and reveals the different effects of increasing the number of options or the number of attributes. This study also finds that the need for cognition moderates these behavioral effects, and it proposes psychological processes that may trigger the effects observed.

Vitamin D attenuates pressure overload-induced cardiac remodeling and dysfunction in mice.

Science.gov (United States)

Zhang, Liang; Yan, Xiao; Zhang, Yun-Long; Bai, Jie; Hidru, Tesfaldet Habtemariam; Wang, Qing-Shan; Li, Hui-Hua

2018-04-01

Vitamin D (VD) and its analogues play critical roles in metabolic and cardiovascular diseases. Recent studies have demonstrated that VD exerts a protective role in cardiovascular diseases. However, the beneficial effect of VD on pressure overload-induced cardiac remodeling and dysfunction and its underlying mechanisms are not fully elucidated. In this study, cardiac dysfunction and hypertrophic remodeling in mice were induced by pressure overload. Cardiac function was evaluated by echocardiography, and myocardial histology was detected by H&E and Masson's trichrome staining. Cardiomyocyte size was detected by wheat germ agglutinin staining. The protein levels of signaling mediators were examined by western blotting while mRNA expression of hypertrophic and fibrotic markers was examined by qPCR analysis. Oxidative stress was detected by dihydroethidine staining. Our results showed that administration of VD3 significantly ameliorates pressure overload-induced contractile dysfunction, cardiac hypertrophy, fibrosis and inflammation in mice. In addition, VD3 treatment also markedly inhibited cardiac oxidative stress and apoptosis. Moreover, protein levels of calcineurin A, ERK1/2, AKT, TGF-β, GRP78, cATF6, and CHOP were significantly reduced whereas SERCA2 level was upregulated in the VD3-treated hearts compared with control. These results suggest that VD3 attenuates cardiac remodeling and dysfunction induced by pressure overload, and this protective effect is associated with inhibition of multiple signaling pathways. Copyright © 2018 Elsevier Ltd. All rights reserved.

PENGARUH WORK OVERLOAD DAN WORK FAMILY CONFLICT TERHADAP TURNOVER INTENTION YANG DIMEDIASI OLEH WORK EXHAUSTION

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Nurul Hidayatin Nisa

2016-01-01

Full Text Available The purpose of this research was to examine factors that determine turnover intention in medical representative at PT. APL. To be known before that medical representatives have high percentage in turnover. The research using work exhaustion as mediation to determine the relationship between works overload and work family conflict of turnover intention. Research method is quantitative approach in causal research. The analysis tools are AMOS and T-Sobel. Findings of this research are both work overload and work family conflict berpengaruh with work exhaustion and turnover intention, work exhaustion mediated work overload and work family conflict over turnover intention.

Random fluid limit of an overloaded polling model

NARCIS (Netherlands)

M. Frolkova (Masha); S.G. Foss (Sergey); A.P. Zwart (Bert)

2014-01-01

htmlabstractIn the present paper, we study the evolution of an overloaded cyclic polling model that starts empty. Exploiting a connection with multitype branching processes, we derive fluid asymptotics for the joint queue length process. Under passage to the fluid dynamics, the server switches

Random fluid limit of an overloaded polling model

NARCIS (Netherlands)

M. Frolkova (Masha); S.G. Foss (Sergey); A.P. Zwart (Bert)

2013-01-01

htmlabstractIn the present paper, we study the evolution of an~overloaded cyclic polling model that starts empty. Exploiting a~connection with multitype branching processes, we derive fluid asymptotics for the joint queue length process. Under passage to the fluid dynamics, the server switches

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

Science.gov (United States)

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.

Peculiarities on voltage - current characteristics of HTS tapes at overloading conditions cooled by liquid nitrogen

International Nuclear Information System (INIS)

Vysotsky, V S; Fetisov, S S; Sytnikov, V E

2008-01-01

Electro - technical devices are considered as the most prospective use for high temperature superconductors. For such devices the overload currents due to faults in grids are the operational reality. In these cases the fault currents may forcibly go to superconductors being sometimes dozens times more than the critical currents of HTS. Overloads are the working modes for fault current limiters also. To understand the behavior of HTS devices at overloads it is important to study voltage-current characteristics (VCC) of basic HTS tapes in real cooling conditions. The knowledge of VCC permits to model and to simulate properly HTS devices behavior at overloads. We performed the study of VCC of several HTS tapes at currents several times more than their critical ones. Both, 1-G and 2-G tapes were tested. There were found peculiarities or 'spikes' on VCC at rising currents that vanished at decaying currents. It was shown that such peculiarities are determined by the change of cooling conditions from the convective heat exchange to the nucleate boiling. Nucleate boiling activation and development times were determined. Their dependencies on heat release were measured. The data obtained can be used in simulation of heating of real superconducting devices at overload conditions

Designing immersive surgical training against information technology-related overload in the operating room

OpenAIRE

Pluyter, J.R.

2012-01-01

On a theoretical level, this dissertation demonstrates that the “classical” conceptualization of overload in the field of Information Systems being an excessive amount of information is too simplistic. Based on the Emotional-Cognitive Overload Model by Rutkowski and Saunders (2011) this dissertation outlines the importance of the personal mental organization of Long-Term Memory (LTM) and the congruence of the information stimulus with cognitive schemata encoded in LTM.

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

Science.gov (United States)

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 overload and ischemic preconditioning (25.2 ± 2.4% and 25.0 ± 2.3%, where p 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.

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

Science.gov (United States)

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

2017-06-01

Silent mating type information regulation 2 homologue 1 (SIRT1) activity and content increased significantly in overload-induced hypertrophy. SIRT1-mediated signalling through Akt, the endothelial nitric oxide synthase mediated pathway, regulates anabolic process in the hypertrophy of skeletal muscle. The regulation of catabolic signalling via forkhead box O 1 and protein ubiquitination is SIRT1 dependent. Overload-induced changes in microRNA levels regulate SIRT1 and insulin-like growth factor 1 signalling. Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in silent mating type information regulation 2 homologue 1 (SIRT1) content and activity (P overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload-induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Performance analysis of SS7 congestion controls under sustained overload

Science.gov (United States)

Manfield, David R.; Millsteed, Gregory K.; Zukerman, Moshe

1994-04-01

Congestion controls are a key factor in achieving the robust performance required of common channel signaling (CCS) networks in the face of partial network failures and extreme traffic loads, especially as networks become large and carry high traffic volume. The CCITT recommendations define a number of types of congestion control, and the parameters of the controls must be well set in order to ensure their efficacy under transient and sustained signalling network overload. The objective of this paper is to present a modeling approach to the determination of the network parameters that govern the performance of the SS7 congestion controls under sustained overload. Results of the investigation by simulation are presented and discussed.

Iron deficiency and overload in relation to nutrition

NARCIS (Netherlands)

Spanjersberg MQI; Jansen EHJM; LEO

2000-01-01

Nutritional iron intake in the Netherlands has been reviewed with respect to both iron deficiency and iron overload. In general, iron intake and iron status in the Netherlands are adequate and therefore no change in nutrition policy is required. The following aspects and developments, however, need

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

Science.gov (United States)

Rodriguez, Jacinto

2013-01-01

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

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

Science.gov (United States)

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…

Effect of tensile overloads on fatigue crack growth of high strength steel wires

International Nuclear Information System (INIS)

Haag, J.; Reguly, A.; Strohaecker, T.R.

2013-01-01

Highlights: • A proof load process may be an option to increase the fatigue life of flexible pipelines. • There is possibility to produce plastic deformation at crack tip of tensile armor wires. • Controlled overloads provide effective crack growth retardation. • Crack growth retardation is also evident at higher stress ratios. - Abstract: Fatigue of the tensile armor wires is the main failure mode of flexible risers. Techniques to increase the life of these components are required to improve the processes safety on oil exploration. This work evaluates the crack growth retardation of high strength steel wires used in flexible pipelines. Fracture toughness tests were performed to establish the level of stress intensity factor wherein the wires present significant plastic deformation at the crack tip. The effect of tensile overload on fatigue behavior was assessed by fatigue crack growth testing under constant ΔK control and different overload ratios with two different load ratios. The outcomes show that the application of controlled overloads provides crack retardation and increases the fatigue life of the wires more than 31%. This behavior is also evident at stress ratio of 0.5, in spite of the crack closure effect being minimized by increasing the applied mean stress

Evaluation Of The Overload Of Care In Families Of Psychiatric Patients In Psychosocial Care Center

Directory of Open Access Journals (Sweden)

Mayron Morais Almeida

2017-07-01

Full Text Available Introduction: The burden of care in family refers to the weight caused by the primary caregiver role to psychiatric patients and the difficulties encountered in performing this function in daily life. Objectives: Assessing the objective and subjective overload of family members who live with the reality of psychiatric disorder in a child day-care psychosocial care center. Methods: Cross-sectional study, descriptive-exploratory, of quantitative approach, with non-probabilistic samples of accidental type with 80 families of psychiatric patients held in a Psychosocial Care Center. For overload evaluation, the subscales "B" and "D" of the Family Overload Rating Scale (FBIS-BR were used. Results: The study was conducted with 80 families of psychiatric patients. The average age of female caregivers was 39,6 years old, and 40,7 years old for male caregivers, with female predominance (87,5% compared to men (12,5%, with low education for both genres. Family caregivers presented high objective burden due to excessive demand attention (p<0,001, heteroaggressiveness (p<0,001 and perplexing behavior of psychiatric patients regarding the supervision of problematic behaviors (p<0,001. The items on the impact on the family's daily routine have not helped to generate objective overload for the family members. On subjective overload, it was clear to observe familiar members with high degree of disturbance in all the dimensions assessed (p < 0,001. Conclusion: The high degree of care overload observed in family members indicates the need to develop contacts with the family of the psychiatric patient to answer questions, offer support and assistance to the family caregiver. Keywords: Caregivers. Patients. Mental Health Services.

Retarding effect of prior-overloading on stress corrosion cracking of cold rolled 316L SS in simulated PWR water environment

Science.gov (United States)

Chen, Junjie; Lu, Zhanpeng; Xiao, Qian; Ru, Xiangkun; Ma, Jiarong; Shoji, Tetsuo

2017-12-01

The effect of prior single tensile overloading on the stress corrosion cracking behavior of cold rolled 316L in a simulated PWR water environment at 310 °C was investigated. SCC growth retardation by overloading was observed in cold rolled 316L specimens in both the T-L and L-T orientations. The stretch zone observed on the fracture surfaces of the overloaded specimens affected SCC propagation. The compressive residual stress induced by overloading process reduced the effective driving force of SCC propagation. The negative dK/da effect ahead of the crack tip likely contributes to the retardation of SCC growth. The duration of overloading is dependent on water chemistry and the local stress conditions.

Increase in Vascular Injury of Sodium Overloaded Mice May be Related to Vascular Angiotensin Modulation.

Directory of Open Access Journals (Sweden)

Cintia Taniguti Lima

Full Text Available This study aimed to analyzing the effect of chronic sodium overload upon carotid and femoral injury, and its relation to vascular angiotensin modulation. Male C57Bl6 mice were divided in: control (cont, receiving 1% NaCl solution for 2 weeks (salt-2 or 12 weeks (salt-12. Two-weeks before the end of the study, a 2mm catheter was implanted around the left femoral and carotid arteries to induce injury. Blood pressure (BP and heart rate (HR were measured at the end of the study by tail plethysmography. Arteries were collected and prepared for histological analysis to determine arterial thickening and perivascular collagen deposition. Angiotensin II and Ang(1-7 were quantified in fresh arteries using the HPLC method. There were no differences in body weight, BP and HR. Intima/media ratio had a similar increase in both injured arteries of cont and salt-2 mice, but a more pronounced increase was observed in salt-12 mice (31.1±6%. On the other hand, sodium overload modified perivascular collagen deposition, increasing thick fibers (cont: 0.5%; salt-2: 3.4%; salt-12: 0.6% and decreasing thin fibers (cont: 7.4%; salt-2: 0.5%; salt-12: 6.8% in non-injured arteries. Injured arteries presented similar collagen fiber distribution. Angiotensin quantification showed increased Ang(1-7 in salt treated mice (salt-2: +72%; salt-12: +45% with a concomitant decrease in Ang II (salt-2: -54%; salt-12: -60%. Vascular injury increased significantly Ang(1-7 in salt-12 mice (+80%, maintaining Ang II reduction similar to that of a non-injured artery. The lack of changes in BP and HR suggests that the structural changes observed may be due to non-hemodynamic mechanisms such as local renin-angiotensin system. Collagen evaluation suggests that sodium overload induces time-related changes in vascular remodeling. The increase of artery injury with concomitant increase in Ang(1-7 in 12-week treated mice shows a direct association between the duration of salt treatment and the

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

Science.gov (United States)

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

2013-01-01

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

Thermal and electrodynamical formation mechanisms of overloaded AC states and charging rate influence on their stable dynamics

International Nuclear Information System (INIS)

Romanovskii, V.; Watanabe, K.; Awaji, S.

2013-01-01

Highlights: •Overloaded AC states are investigated to understand the mechanisms of there formation. •There exist characteristic time windows defining the existence of stable overloaded AC states. •Limiting values of the electric field, current and temperature are higher than the quench ones. -- Abstract: The macroscopic thermal and electrodynamical phenomena occurring in high-T c superconductors during overloaded AC states are theoretically investigated to understand the basic physical mechanisms, which are characteristic for the stable formation of the operating modes when the peak current exceeds the critical current of a superconductor during AC modes. It is shown that there exist characteristic time windows defining the existence of stable overloaded AC states. They identify the stability boundary of the overloaded AC states. Therefore, there is the maximum allowable value of a peak current of stable overloaded AC regimes at the given charging rate, cooling conditions and properties of a superconductor and a matrix. The results obtained prove that the limiting peak current is higher than the corresponding quench current defining the stability margin of DC states. It monotonically increases with the charging rate. Besides, in the stable overloaded AC states, the peak values of the electric field and temperature may be also noticeably higher than the corresponding quench values. They depend on the peak current and charging rate at the given cooling conditions. As a result, high-T c superconducting tapes can stably work under intensive AC modes without instability onset when the peak of applied currents may significantly exceed not only the critical current but also the corresponding values of DC-quench currents

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

Science.gov (United States)

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...

Lung congestion in chronic heart failure: haemodynamic, clinical, and prognostic implications

DEFF Research Database (Denmark)

Melenovsky, Vojtech; Andersen, Mads Jønsson; Andress, Krystof

2015-01-01

AIMS:The goal of the study was to examine the prognostic impact, haemodynamic and clinical features associated with lung congestion in patients with chronic heart failure (HF). METHODS AND RESULTS:HF patients (n = 186) and HF-free controls (n = 21) underwent right heart catheterization...... days (interquartile range 80-875), 59 patients (32%) died. Lung congestion was associated with reduced survival (P renal dysfunction. CONCLUSION:Interstitial lung oedema is associated with pulmonary vascular disease, RV overload...

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

Science.gov (United States)

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.

Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease

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Joana Neves

2017-06-01

Full Text Available Emerging evidence suggests that pulmonary iron accumulation is implicated in a spectrum of chronic lung diseases. However, the mechanism(s involved in pulmonary iron deposition and its role in the in vivo pathogenesis of lung diseases remains unknown. Here we show that a point mutation in the murine ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1C326S, increases iron levels in alveolar macrophages, epithelial cells lining the conducting airways and lung parenchyma, and in vascular smooth muscle cells. Pulmonary iron overload is associated with oxidative stress, restrictive lung disease with decreased total lung capacity and reduced blood oxygen saturation in homozygous Slc40a1C326S/C326S mice compared to wild-type controls. These findings implicate iron in lung pathology, which is so far not considered a classical iron-related disorder.

Niacin metabolism and indoleamine 2,3-dioxygenase activation in malnourished patients with flaky paint dermatosis.

Science.gov (United States)

Maltos, André Luiz; Portari, Guilherme Vannucchi; Moraes, Giselle Vanessa; Monteiro, Marina Casteli Rodrigues; Vannucchi, Helio; da Cunha, Daniel Ferreira

2015-06-01

Flaky paint dermatosis, characterized by extensive, often bilateral areas of flaking and pigmentation, mostly in sun unexposed areas is considered a feature of kwashiorkor in both children and adults, and must be differentiated from other dermatosis, including chapped and xerotica skin, and pellagra. In this case series we provide evidence that malnourished patients with flaky paint dermatosis and infection/inflammation shown laboratory data suggestive of indoleamine 2,3-dioxygenase (IDO) activation, besides decreased urinary excretion of N1-methylnicotinamide (N1 MN), a marker of pellagra. We study nine adult patients showing flaky paint dermatosis and clinical features of infection or inflammation, and increased serum C-reactive protein, characteristic of the presence of acute phase response syndrome. As a group, they had low or deficient urinary N1 MN excretion (0.52 ± 0.39 mg/g creatinine) compatible with pellagra. They also showed low serum tryptophan levels (dermatosis showed laboratory data suggestive of IDO activation, besides decreased N1 MN urinary excretion. Taken together, the data support the idea that flaky paint dermatosis could be a skin manifestation of niacin deficiency. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

West, Lindsey M.

2014-01-01

With the rise in advanced-degree seeking women and the minimal research on the dual impact of sexism and role overload, the current study aims to better understand the impact of sexism and role overload on psychological distress in a particular sample of advanced-degree seeking women. Seventy-six female medical student participants (mean age 24.7)…

Chronic high-fat diet-induced obesity decreased survival and increased hypertrophy of rats with experimental eccentric hypertrophy from chronic aortic regurgitation.

Science.gov (United States)

Dhahri, Wahiba; Drolet, Marie-Claude; Roussel, Elise; Couet, Jacques; Arsenault, Marie

2014-09-24

The composition of a diet can influence myocardial metabolism and development of left ventricular hypertrophy (LVH). The impact of a high-fat diet in chronic left ventricular volume overload (VO) causing eccentric LVH is unknown. This study examined the effects of chronic ingestion of a high-fat diet in rats with chronic VO caused by severe aortic valve regurgitation (AR) on LVH, function and on myocardial energetics and survival. Male Wistar rats were divided in four groups: Shams on control or high-fat (HF) diet (15 rats/group) and AR rats fed with the same diets (ARC (n = 56) and ARHF (n = 32)). HF diet was started one week before AR induction and the protocol was stopped 30 weeks later. As expected, AR caused significant LV dilation and hypertrophy and this was exacerbated in the ARHF group. Moreover, survival in the ARHF group was significantly decreased compared the ARC group. Although the sham animals on HF also developed significant obesity compared to those on control diet, this was not associated with heart hypertrophy. The HF diet in AR rats partially countered the expected shift in myocardial energy substrate preference usually observed in heart hypertrophy (from fatty acids towards glucose). Systolic function was decreased in AR rats but HF diet had no impact on this parameter. The response to HF diet of different fatty acid oxidation markers as well as the increase in glucose transporter-4 translocation to the plasma membrane compared to ARC was blunted in AR animals compared to those on control diet. HF diet for 30 weeks decreased survival of AR rats and worsened eccentric hypertrophy without affecting systolic function. The expected adaptation of myocardial energetics to volume-overload left ventricle hypertrophy in AR animals seemed to be impaired by the high-fat diet suggesting less metabolic flexibility.

Modeling of Unidirectional-Overloaded Transition in Catalytic Tubular Microjets

NARCIS (Netherlands)

Klingner, Anke; Khalil, Islam S. M.; Magdanz, Veronika; Fomin, Vladimir M.; Schmidt, Oliver G.; Misra, Sarthak

2017-01-01

A numerical time-resolved model is presented for predicting the transition between unidirectional and overloaded motion of catalytic tubular microjets (Ti/Fe/Pt rolled-up microtubes) in an aqueous solution of hydrogen peroxide. Unidirectional movement is achieved by periodic ejection of gas bubbles

Stress 2.0: Social Media Overload among Swiss Teenagers

NARCIS (Netherlands)

Lutz, Christoph; Ranzini, Giulia; Meckel, Miriam

2014-01-01

Technostress and information overload are serious challenges of the information age. An alarming number of people exhibit dangerously intensive media consumption, while Internet and mobile phone addictions are a widespread phenomenon. At the same time, new media overexposure among young people is

Radionuclide stroke count ratios for assessment of right and left ventricular volume overload in children

International Nuclear Information System (INIS)

Parrish, M.D.; Graham, T.P. Jr.; Born, M.L.; Jones, J.P.; Boucek, R.J. Jr.; Artman, M.; Partain, C.L.

1983-01-01

The ratio of left ventricular to right ventricular stroke counts measured by radionuclide angiography has been used in adults to estimate the severity of left-sided valvular regurgitation. The validation of this technique in children for assessment of right and left ventricular volume overload is reported herein. Radionuclide stroke count ratios in 60 children aged 0.5 to 19 years (mean 11) were determined. Based on their diagnoses, the patients were divided into 3 groups: (1) normal--40 patients with no shunts or valvular regurgitation, (2) left ventricular volume overload--13 patients with mitral or aortic regurgitation, or both, and (3) right ventricular volume overload--7 patients, 2 with severe tricuspid regurgitation, 3 with atrial septal defects, and 2 with total anomalous pulmonary venous drainage. The radionuclide stroke count ratio clearly differentiated these groups (p less than 0.05): normal patients had a stroke count ratio of 1.04 +/- 0.17 (mean +/- 1 standard deviation), the left ventricular volume overload group had a stroke count ratio of 2.43 +/- 0.86, and the right ventricular volume overload group had a stroke count ratio of 0.44 +/- 0.17. In 22 of our 60 patients, radionuclide stroke count ratios were compared with cineangiographic stroke volume ratios, resulting in a correlation coefficient of 0.88. It is concluded that radionuclide ventriculography is an excellent tool for qualitative and quantitative assessment of valvular regurgitation in children

Fatigue crack growth due to overloads in plain concrete using ...

Indian Academy of Sciences (India)

cation of overload on concrete structures, acceleration in the crack growth process .... study by the same authors, Ray & Chandra Kishen (2010), they have employed the population growth ...... Institute of Technology, University of Trondheim.

THE EFFECT OF HAEMOCHROMATOSIS MUTATION ON IRON OVERLOAD IN THALASSAEMIA MAJOR PATIENTS

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Tapas Ranjan Behera

2016-11-01

Full Text Available BACKGROUND Haemochromatosis is a genetic form of iron overload due to a defective HFE gene. Secondary iron overload is the main complication in transfusion-dependent thalassaemia major patients. This study aims at evaluating the degree of iron overload in β-thalassaemia major patients with and without HFE mutations (C282Y, H63D and S65C. MATERIALS AND METHODS A descriptive observational study was conducted including fifty diagnosed -thalassaemia major cases. Detailed clinical history and iron profile was estimated. DNA analysis by PCR-RFLP method for HFE gene mutations was performed. RESULTS After DNA analysis of all the thalassaemia major cases, two groups were identified, one with HFE gene mutation and other without HFE gene mutation. Iron profile of both the groups (with and without HFE gene mutation was estimated and compared. Only H63D mutation (out of three HFE gene mutations was detected in 16% cases (8 out of 50 cases, which comprised the group with mutation. Comparison of iron parameters between two groups (with and without HFE gene mutation showed significant difference in percent transferrin saturation (p=0.02, while other iron parameters (serum iron and serum ferritin did not show significant difference. CONCLUSION No significant difference between serum ferritin values (a marker of iron overload of groups with and without mutation (mean ferritin level 4641±2166 ng/mL and 4170±2461 ng/mL, respectively was found (p=0.61, in a patient population in whom transfusion protocol and proper chelation regimen was followed.

Experimental detection of iron overload in liver through neutron stimulated emission spectroscopy

International Nuclear Information System (INIS)

Kapadia, A J; Tourassi, G D; Sharma, A C; Crowell, A S; Kiser, M R; Howell, C R

2008-01-01

Iron overload disorders have been the focus of several quantification studies involving non-invasive imaging modalities. Neutron spectroscopic techniques have demonstrated great potential in detecting iron concentrations within biological tissue. We are developing a neutron spectroscopic technique called neutron stimulated emission computed tomography (NSECT), which has the potential to diagnose iron overload in the liver at clinically acceptable patient dose levels through a non-invasive scan. The technique uses inelastic scatter interactions between atomic nuclei in the sample and incoming fast neutrons to non-invasively determine the concentration of elements in the sample. This paper discusses a non-tomographic application of NSECT investigating the feasibility of detecting elevated iron concentrations in the liver. A model of iron overload in the human body was created using bovine liver tissue housed inside a human torso phantom and was scanned with a 5 MeV pulsed beam using single-position spectroscopy. Spectra were reconstructed and analyzed with algorithms designed specifically for NSECT. Results from spectroscopic quantification indicate that NSECT can currently detect liver iron concentrations of 6 mg g -1 or higher and has the potential to detect lower concentrations by optimizing the acquisition geometry to scan a larger volume of tissue. The experiment described in this paper has two important outcomes: (i) it demonstrates that NSECT has the potential to detect clinically relevant concentrations of iron in the human body through a non-invasive scan and (ii) it provides a comparative standard to guide the design of iron overload phantoms for future NSECT liver iron quantification studies

Quantification of liver fat in the presence of iron overload.

Science.gov (United States)

Horng, Debra E; Hernando, Diego; Reeder, Scott B

2017-02-01

To evaluate the accuracy of R2* models (1/T 2 * = R2*) for chemical shift-encoded magnetic resonance imaging (CSE-MRI)-based proton density fat-fraction (PDFF) quantification in patients with fatty liver and iron overload, using MR spectroscopy (MRS) as the reference standard. Two Monte Carlo simulations were implemented to compare the root-mean-squared-error (RMSE) performance of single-R2* and dual-R2* correction in a theoretical liver environment with high iron. Fatty liver was defined as hepatic PDFF >5.6% based on MRS; only subjects with fatty liver were considered for analyses involving fat. From a group of 40 patients with known/suspected iron overload, nine patients were identified at 1.5T, and 13 at 3.0T with fatty liver. MRS linewidth measurements were used to estimate R2* values for water and fat peaks. PDFF was measured from CSE-MRI data using single-R2* and dual-R2* correction with magnitude and complex fitting. Spectroscopy-based R2* analysis demonstrated that the R2* of water and fat remain close in value, both increasing as iron overload increases: linear regression between R2* W and R2* F resulted in slope = 0.95 [0.79-1.12] (95% limits of agreement) at 1.5T and slope = 0.76 [0.49-1.03] at 3.0T. MRI-PDFF using dual-R2* correction had severe artifacts. MRI-PDFF using single-R2* correction had good agreement with MRS-PDFF: Bland-Altman analysis resulted in -0.7% (bias) ± 2.9% (95% limits of agreement) for magnitude-fit and -1.3% ± 4.3% for complex-fit at 1.5T, and -1.5% ± 8.4% for magnitude-fit and -2.2% ± 9.6% for complex-fit at 3.0T. Single-R2* modeling enables accurate PDFF quantification, even in patients with iron overload. 1 J. Magn. Reson. Imaging 2017;45:428-439. © 2016 International Society for Magnetic Resonance in Medicine.

Thermal overload protection for electric motors on safety-related motor-operated valves: Generic Issue II.E.6.1

International Nuclear Information System (INIS)

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 thermal 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

Analysis of overload conditions in distance relay under severe system contingencies

Energy Technology Data Exchange (ETDEWEB)

Halim Abu Bakar, Ab. [Department of Electrical Engineering, Universiti Malaya (Malaysia); Yatim, Fazilah Mat; Othman, Mohd Ridzal [Transmission Division, Tenaga Nasional Berhad (Malaysia); Yusof, Sallehuddin [Advanced Powor Solutions (Malaysia)

2010-06-15

Distance relay protection is widely used worldwide for protection scheme on high voltage transmission lines. This protection tends to be prone to load encroachment condition causing possible undesired tripping condition. Investigations of two system disturbances that occurred in TNB's (Tenaga Nasional Berhad) Grid in the year 2003 and 2005 have clearly revealed the occurrence of load encroachment condition following line overloads after large number of line tripping. Examination of the impedance locus trajectory during the overload events have enabled a distinction be made between power swing and load encroachment phenomena. This paper presents the analysis and findings of the investigation of the load encroachment phenomena of the two events, including other related transmission line contingencies. (author)

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

Science.gov (United States)

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

Dangers of bypassing thermal overload relays in nuclear power plant motor operated valve circuits

International Nuclear Information System (INIS)

Baxter, F.D.

1980-01-01

Operation of motor operated valves is analyzed under various abnormal conditions such as frozen bearing, tight packing, mid-travel obstruction, torque switch failure, limit switch failure, and post-accident operation. Each condition has been reviewed to show that an adverse situation results if the thermal overload relays in the circuit are bypassed. In conclusion, there appears to be no technical basis for bypassing or oversizing the thermal overload relay provided it is selected correctly

Influence of subject choice, work overload and work stress on expatriate higher education teachers.

OpenAIRE

Naithani, Pranav

2013-01-01

Subject choice, work overload and work stress influence personal and professional lives of higher education teachers. Though the majority of higher education teachers in the Gulf Cooperation Council (GCC) countries are expatriates, yet research on expatriate higher education teachers working in the GCC countries is limited. This paper presents one part of the work life balance survey and focuses on the influence of subject choice, work overload and work stress on higher education teachers in ...

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

Directory of Open Access Journals (Sweden)

Karen van Eunen

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

Renal perfusion in chronic liver diseases: Evaluation by radiotechnetium renography

International Nuclear Information System (INIS)

Fanfani, G.; Fratello, A.; Mele, M.; Conte, E.; D'Addabbo, A.; Greco, L.

1985-01-01

Twenty-four patients with chronic liver diseases and seven normal controls were studied using renal and hepatic radiotechnetium angiography. The time-activity histograms generated were employed to calculate both the renal perfusion index (RPI) and the hepatic perfusion index (HPI). Renal perfusion proved to be reduced not only in cirrhotic patients but also in patients with aggressive chronic hepatitis, as well as in those with persistent chronic hepatitis. The HPI, which is to be considered as being strictly dependent on portal flow, only fell significantly in the group of cirrhotic patients. In all patient groups, the correlation coefficient between the HPI and RPI (mean of the two kidneys) was low (r=0.275) and not significant (P>0.05). After Warren's splenorenal derivation, renal perfusion did not improve but worsened, particularly in the left kidney where derivation anastomosis probably caused a venous overload. (orig.)

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

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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.

Diagnosis of hepatic iron overload: a family study illustrating pitfalls in diagnosing hemochromatosis.

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Schranz, Melanie; Talasz, Heribert; Graziadei, Ivo; Winder, Thomas; Sergi, Consolato; Bogner, Klaus; Vogel, Wolfgang; Zoller, Heinz

2009-03-01

Recent identification of genetic variants in iron storage disease has changed the classification system and diagnostic algorithms for hemochromatosis. Clinical diagnosis of the disease requires phenotypic evidence of iron overload because the commonly disease-associated HFE genotypes have an incomplete penetrance. Furthermore, approximately 20% of patients with a clinical diagnosis of hemochromatosis have no disease-associated genotype, which underlines the importance of clear phenotypic criteria of hemochromatosis. A diagnosis of hemochromatosis cannot be made even in patients with liver cirrhosis simply on the basis of genetic testing that indicates that iron overload is the cause of the disease and not its consequence. Proper diagnosis requires integration of clinical presentation, family history, and the results of biochemical and histopathologic tests. Here we propose a rational diagnostic algorithm for hepatic iron overload syndromes and illustrate potential pitfalls by presenting a family study in a pedigree with rare HFE variants (H63D and E168Q), in cis on the same chromosome. Although the clinical suspicion of hemochromatosis was confirmed by histology, chemical analysis of liver tissue revealed a normal hepatic iron concentration, which is compatible with the genetic finding of 1 normal and 1 doubly mutated allele. In conclusion, clinical suspicion of hemochromatosis and elevated serum iron parameters should prompt HFE genotyping for C282Y and H63D. Should they be uninformative, further genetic tests should be recommended only if iron overload in liver tissue has been confirmed chemically.

MicroRNA-145 suppresses ROS-induced Ca2+ overload of cardiomyocytes by targeting CaMKIIδ

International Nuclear Information System (INIS)

Cha, Min-Ji; Jang, Jin-Kyung; Ham, Onju; Song, Byeong-Wook; Lee, Se-Yeon; Lee, Chang Yeon; Park, Jun-Hee; Lee, Jiyun; Seo, Hyang-Hee; Choi, Eunhyun; Jeon, Woo-min; Hwang, Hye Jin; Shin, Hyun-Taek

2013-01-01

Highlights: •CaMKIIδ mediates H 2 O 2 -induced Ca 2+ overload in cardiomyocytes. •miR-145 can inhibit Ca 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 2+ ) is a common signaling mechanism of reperfusion-induced cardiomyocyte death. Calcium/calmodulin dependent protein kinase II (CaMKII) is a critical regulator of Ca 2+ signaling and mediates signaling pathways responsible for functions in the heart including hypertrophy, apoptosis, arrhythmia, and heart disease. MicroRNAs (miRNA) are involved in the regulation of cell response, including survival, proliferation, apoptosis, and development. However, the roles of miRNAs in Ca 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 2 O 2 -mediated Ca 2+ overload, we selected and tested 6 putative miRNAs that targeted CaMKIIδ, and showed that miR-145 represses CaMKIIδ protein expression and Ca 2+ overload. We confirmed CaMKIIδ as a direct downstream target of miR-145. Furthermore, miR-145 regulates Ca 2+ -related signals and ameliorates apoptosis. This study demonstrates that miR-145 regulates reactive oxygen species (ROS)-induced Ca 2+ overload in cardiomyocytes. Thus, miR-145 affects ROS-mediated gene regulation and cellular injury responses

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

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Dhiraj J. Trivedi

2014-07-01

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

Role of liver magnetic resonance imaging in hyperferritinaemia and the diagnosis of iron overload.

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Ruefer, Axel; Bapst, Christine; Benz, Rudolf; Bremerich, Jens; Cantoni, Nathan; Infanti, Laura; Samii, Kaveh; Schmid, Mathias; Vallée, Jean-Paul

2017-11-09

Hyperferritinaemia is a frequent clinical problem. Elevated serum ferritin levels can be detected in different genetic and acquired diseases and can occur with or without anaemia. It is therefore important to determine whether hyperferritinaemia is due to iron overload or due to a secondary cause. The main causes of iron overload are intestinal iron hyperabsorption disorders and transfusion-dependent disorders. Iron homeostasis and iron overload are quantified by different diagnostic approaches. The evaluation of serum ferritin and transferrin saturation is the first diagnostic step to identify the cause of hyperferritinaemia. The assessment of liver iron concentration by liver biopsy or magnetic resonance imaging (MRI) may guide the further diagnostic and therapeutic workup. Liver biopsy is invasive and poorly accepted by patients and should only be carried out in selected patients with hereditary haemochromatosis. As a non-invasive approach, MRI is considered the standard method to diagnose and to monitor both hepatic iron overload and the effectiveness of iron chelation therapy in many clinical conditions such as thalassaemia and myelodysplastic syndromes. Accurate evaluation and monitoring of iron overload has major implications regarding adherence, quality of life and prognosis. There are different technical MRI approaches to measuring the liver iron content. Of these, T2 and T2* relaxometry are considered the standard of care. MRI with cardiac T2* mapping is also suitable for the assessment of cardiac iron. Currently there is no consensus which technique should be preferred. The choice depends on local availability and patient population. However, it is important to use the same MRI technique in subsequent visits in the same patient to get comparable results. Signal intensity ratio may be a good adjunct to R2 and R2* methods as it allows easy visual estimation of the liver iron concentration. In this review a group of Swiss haematologists and radiologists

Signaling pathway-focused gene expression profiling in pressure overloaded hearts

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Marco Musumeci

2011-01-01

Full Text Available The β-blocker propranolol displays antihypertrophic and antifibrotic properties in the heart subjected to pressure overload. Yet the underlying mechanisms responsible for these important effects remain to be completely understood. The purpose of this study was to determine signaling pathway-focused gene expression profile associated with the antihypertrophic action of propranolol in pressure overloaded hearts. To address this question, a focused real-time PCR array was used to screen left ventricular RNA expression of 84 gene transcripts representative of 18 different signaling pathways in C57BL/6 mice subjected to transverse aortic constriction (TAC or sham surgery. On the surgery day, mice received either propranolol (80 mg/kg/day or vehicle for 14 days. TAC caused a 49% increase in the left ventricular weight-to-body weight (LVW/BW ratio without changing gene expression. Propranolol blunted LVW/BW ratio increase by approximately 50% while causing about a 3-fold increase in the expression of two genes, namely Brca1 and Cdkn2a, belonging to the TGF-beta and estrogen pathways, respectively. In conclusion, after 2 weeks of pressure overload, TAC hearts show a gene expression profile superimposable to that of sham hearts. Conversely, propranolol treatment is associated with an increased expression of genes which negatively regulate cell cycle progression. It remains to be established whether a mechanistic link between gene expression changes and the antihypertrophic action of propranolol occurs.

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

Energy Technology Data Exchange (ETDEWEB)

Pardo Andreu, G.L. [Centro de Quimica Farmaceutica, Departamento de Investigaciones Biomedicas, Ciudad de La Habana (Cuba); Inada, N.M.; Vercesi, A.E. [Universidade Estadual de Campinas, Departamento de Patologia Clinica, Faculdade de Ciencias Medicas, Campinas, SP (Brazil); Curti, C. [Universidade de Sao Paulo, Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, SP (Brazil)

2009-01-15

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{sup +} leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria. (orig.)

Iatrogenic Iron Overload in Dialysis Patients at the Beginning of the 21st Century.

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Rostoker, Guy; Vaziri, Nosratola D; Fishbane, Steven

2016-05-01

Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a 'second hit' on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients.

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

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

2017-08-01

To determine the impact of cumulative, postoperative thoracostomy output, amount of bolus IV fluids and peak fluid overload on the incidence and odds of developing a deep surgical site infection following pediatric cardiothoracic surgery. A single-center, nested, retrospective, matched case-control study. A 26-bed cardiac ICU in a 303-bed tertiary care pediatric hospital. Cases with deep surgical site infection following cardiothoracic surgery were identified retrospectively from January 2010 through December 2013 and individually matched to controls at a ratio of 1:2 by age, gender, Risk Adjustment for Congenital Heart Surgery score, Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery category, primary cardiac diagnosis, and procedure. None. Twelve cases with deep surgical site infection were identified and matched to 24 controls without detectable differences in perioperative clinical characteristics. Deep surgical site infection cases had larger thoracostomy output and bolus IV fluid volumes at 6, 24, and 48 hours postoperatively compared with controls. For every 1 mL/kg of thoracostomy output, the odds of developing a deep surgical site infection increase by 13%. By receiver operative characteristic curve analysis, a cutoff of 49 mL/kg of thoracostomy output at 48 hours best discriminates the development of deep surgical site infection (sensitivity 83%, specificity 83%). Peak fluid overload was greater in cases than matched controls (12.5% vs 6%; p operative characteristic curve analysis, a threshold value of 10% peak fluid overload was observed to identify deep surgical site infection (sensitivity 67%, specificity 79%). Conditional logistic regression of peak fluid overload greater than 10% on the development of deep surgical site infection yielded an odds ratio of 9.4 (95% CI, 2-46.2). Increased postoperative peak fluid overload and cumulative thoracostomy output were associated with deep surgical site infection after pediatric

Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy

Directory of Open Access Journals (Sweden)

Toth PP

2012-01-01

Full Text Available Peter P Toth1, Kamlesh M Thakker2, Ping Jiang2, Robert J Padley21University of Illinois College of Medicine, Peoria, and CGH Medical Center, Sterling, 2Abbott, Abbott Park, IL, USABackground: The purpose of this research was to compare the effects of niacin extended-release in combination with simvastatin (NER/S versus atorvastatin monotherapy on high-density lipoprotein (HDL particle number and size in patients with hyperlipidemia or dyslipidemia from the SUPREME study.Methods: This was a post hoc analysis of patients (n = 137 who completed the SUPREME study and who had lipid particle number and size measurements at both baseline and at week 12 by nuclear magnetic resonance spectroscopy. Following ≥4 weeks without lipid-modifying therapy (washout period, the patients received NER/S 1000/40 mg/day for 4 weeks followed by NER/S 2000/40 mg/day for 8 weeks, or atorvastatin 40 mg/day for 12 weeks. Median percent changes in HDL particle number and size from baseline to week 12 were compared between the NER/S and atorvastatin treatment groups using the Wilcoxon rank-sum test. Distribution of HDL particle subclasses at week 12 was compared between the treatment groups using the Cochran–Mantel–Haenszel test.Results: Treatment with NER/S resulted in a significantly greater percent reduction in small HDL particle number at week 12 compared with atorvastatin monotherapy (-1.8% versus 4.2%, P = 0.014, and a numerically greater percent increase in large HDL particle number (102.4% versus 39.2%, P = 0.078 compared with atorvastatin monotherapy. A significantly greater percent increase in HDL particle size from baseline at week 12 was observed with NER/S compared with atorvastatin (6.0% versus 1.3%, P < 0.001. NER/S treatment also resulted in a significant shift in HDL particle size from small and medium at baseline to large at week 12 (P < 0.0001.Conclusion: Treatment with NER/S resulted in larger favorable changes in number and size of HDL particle

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

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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…

Shift Work, Role Overload, and the Transition to Parenthood

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Perry-Jenkins, Maureen; Goldberg, Abbie E.; Pierce, Courtney P.; Sayer, Aline G.

2007-01-01

This article examines how the work hours, work schedules, and role overload of working-class couples are related to depressive symptoms and relationship conflict across the transition to parenthood. Data are from 132 dual-earner couples interviewed 5 times across the transition. Multilevel modeling analyses revealed that working evening or night…

On the formation of niacin (vitamin B3) and pyridine carboxylic acids in interstellar model ices

Energy Technology Data Exchange (ETDEWEB)

McMurtry, Brandon M.; Turner, Andrew M.; Saito, Sean E.J.; Kaiser, Ralf I. [W. M. Keck Research Laboratory in Astrochemistry, University of Hawaii at Manoa, Honolulu, Hawaii, HI 96822 (United States); Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii, HI 96822 (United States)

2016-06-15

The formation of pyridine carboxylic acids in interstellar ice grains was simulated by electron exposures of binary pyridine (C{sub 5}H{sub 5}N)-carbon dioxide (CO{sub 2}) ice mixtures at 10 K under contamination-free ultrahigh vacuum conditions. Chemical processing of the pristine ice and subsequent warm-up phase was monitored on line and in situ via Fourier transform infrared spectroscopy to probe for the formation of new radiation induced species. In the infrared spectra of the irradiated ice, bands assigned to nicotinic acid (niacin; vitamin B3; m-C{sub 5}H{sub 4}NCOOH) along with 2,3-, 2,5-, 3,4-, and 3,5-pyridine dicarboxylic acid (C{sub 5}H{sub 3}N(COOH){sub 2}) were unambiguously identified along with the hydroxycarbonyl (HOCO) radical. Our study suggests that the reactive pathway responsible for pyridine carboxylic acids formation involves a HOCO intermediate, which forms through the reaction of suprathermal hydrogen ejected from pyridine with carbon dioxide. The newly formed pyridinyl radical may then undergo radical–radical recombination with a hydroxycarbonyl radical to form a pyridine carboxylic acid.

Occlusal overload investigations by noninvasive technology: fluorescence microscopy and en-face optical coherence tomography

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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.

Effects of quercetin on hemoglobin-dependent redox reactions: relationship to iron-overload rat liver injury.

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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.

Attenuated hypertrophic response to pressure overload in a lamin A/C haploinsufficiency mouse.

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Cupesi, Mihaela; Yoshioka, Jun; Gannon, Joseph; Kudinova, Anastacia; Stewart, Colin L; Lammerding, Jan

2010-06-01

Inherited mutations cause approximately 30% of all dilated cardiomyopathy cases, with autosomal dominant mutations in the LMNA gene accounting for more than one third of these. The LMNA gene encodes the nuclear envelope proteins lamins A and C, which provide structural support to the nucleus and also play critical roles in transcriptional regulation. Functional deletion of a single allele is sufficient to trigger dilated cardiomyopathy in humans and mice. However, whereas Lmna(-/-) mice develop severe muscular dystrophy and dilated cardiomyopathy and die by 8 weeks of age, heterozygous Lmna(+/-) mice have a much milder phenotype, with changes in ventricular function and morphology only becoming apparent at 1 year of age. Here, we studied 8- to 20-week-old Lmna(+/-) mice and wild-type littermates in a pressure overload model to examine whether increased mechanical load can accelerate or exacerbate myocardial dysfunction in the heterozygotes. While overall survival was similar between genotypes, Lmna(+/-) animals had a significantly attenuated hypertrophic response to pressure overload as evidenced by reduced ventricular mass and myocyte size. Analysis of pressure overload-induced transcriptional changes suggested that the reduced hypertrophy in the Lmna(+/-) mice was accompanied by impaired activation of the mechanosensitive gene Egr-1. In conclusion, our findings provide further support for a critical role of lamins A and C in regulating the cellular response to mechanical stress in cardiomyocytes and demonstrate that haploinsufficiency of lamins A and C alone is sufficient to alter hypertrophic responses and cardiac function in the face of pressure overload in the heart. (c) 2009 Elsevier Ltd. All rights reserved.

Design of overload vehicle monitoring and response system based on DSP

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Yu, Yan; Liu, Yiheng; Zhao, Xuefeng

2014-03-01

The overload vehicles are making much more damage to the road surface than the regular ones. Many roads and bridges are equipped with structural health monitoring system (SHM) to provide early-warning to these damage and evaluate the safety of road and bridge. However, because of the complex nature of SHM system, it's expensive to manufacture, difficult to install and not well-suited for the regular bridges and roads. Based on this application background, this paper designs a compact structural health monitoring system based on DSP, which is highly integrated, low-power, easy to install and inexpensive to manufacture. The designed system is made up of sensor arrays, the charge amplifier module, the DSP processing unit, the alarm system for overload, and the estimate for damage of the road and bridge structure. The signals coming from sensor arrays go through the charge amplifier. DSP processing unit will receive the amplified signals, estimate whether it is an overload signal or not, and convert analog variables into digital ones so that they are compatible with the back-end digital circuit for further processing. The system will also restrict certain vehicles that are overweight, by taking image of the car brand, sending the alarm, and transferring the collected pressure data to remote data center for further monitoring analysis by rain-flow counting method.

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

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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).

Sport coaching officials and their stressors: Work overload, role ...

African Journals Online (AJOL)

Sport officials' concerns over job stressors have become common due to the adverse effect on health. The study sought to examine the associations of work overload, role ambiguity and role conflict, as well as their predictive influence on job satisfaction of sport coaches in Gauteng, South Africa. Data were collected from a ...

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

OpenAIRE

Mustafa Sally; Looper Karl; Zelkowitz Phyllis; Purden Margaret; Baron Murray

2012-01-01

Abstract 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 character...

Quantitative evaluation of right ventricular overload with thallium-201 myocardial perfusion scintigraphy

International Nuclear Information System (INIS)

Watanabe, Toshiya; Miyakoda, Hiroyuki; Koike, Yoshihiro; Itatsu, Hidetaka; Kawai, Naoki; Sotobata, Iwao.

1983-01-01

Thallium-201 myocardial perfusion scintigraphy and right-heart catheterization were performed on patients with right ventricular pressure overload (RVPO) or right ventricular volume overload (RVVO). In 18 patients with RVPO, right ventricular systolic pressure correlated significantly both with the RV/LV wall thallium-201 uptake ratios (r=0.54, p<0.02) and the RV wall/background thallium-201 uptake ratios (r=0.70, p<0.01). RV/LV work ratios also significantly correlated with RV/LV wall thallium-201 uptake ratios (r=0.57, p<0.02). In 19 patients with RVVO, Qp/Qs and RV/LV work ratios both significantly correlated with RV/LV wall thallium-201 uptake ratios (r=0.78 and 0.87, respectively; p<0.001 for both) and RV wall/background thallium-201 uptake ratios (r=0.69, p<0.01 for both parameters). Right ventricular systolic pressure also correlated with RV/LV wall thallium-201 uptake ratios (r=0.57, p<0.02). Feasibility of the differentiation between RVPO and RVVO was suggested with use of ''transitional view angle'' and RV/LV diameter ratios obtained from the scintigram. In patients who underwent cardiac surgery, post-operative alleviations of the right ventricular overload were evaluated. There was a significant decrease in RV/LV wall thallium-201 uptake ratios, but no significant decrease in RV wall/background thallium-201 uptake ratios in patients with RVPO. On the other hand, there was a significant decrease both in RV/LV wall thallium-201 uptake ratios and RV wall/background thallium-201 uptake ratios in patients with RVVO. No significant changes were observed between the scintigraphic measurements obtained 1 month and 1 year after the surgery, irrespective of the type of right ventricular overloading. (J.P.N.)

Probabilistic modeling of material resistance to crack initiation due to hydrided region overloads in CANDU Zr-2.5%Nb pressure tubes

International Nuclear Information System (INIS)

Gutkin, L.; Scarth, D.A.

2014-01-01

Zr-2.5%Nb pressure tubes in CANDU nuclear reactors are susceptible to hydride-assisted cracking at the locations of stress concentration, such as in-service flaws. Probabilistic methodology is being developed to evaluate such flaws for crack initiation due to hydrided region overloads, which occur when the applied stress acting on a flaw with an existing hydrided region at its tip exceeds the stress at which the hydrided region is formed. As part of this development, probabilistic modeling of pressure tube material resistance to overload crack initiation has been performed on the basis of a set of test data specifically designed to study the effects of non-ratcheting hydride formation conditions and load reduction prior to hydride formation. In the modeling framework, the overload resistance is represented as a power-law function of the material resistance to initiation of delayed hydride cracking under constant loading, where both the overload crack initiation coefficient and the overload crack initiation exponent vary with the flaw geometry. In addition, the overload crack initiation coefficient varies with the extent of load reduction prior to hydride formation as well as the number of non-ratcheting hydride formation thermal cycles. (author)

Probabilistic modeling of material resistance to crack initiation due to hydrided region overloads in CANDU Zr-2.5%Nb pressure tubes

Energy Technology Data Exchange (ETDEWEB)

Gutkin, L.; Scarth, D.A. [Kinectrics Inc., Toronto, ON (Canada)

2014-07-01

Zr-2.5%Nb pressure tubes in CANDU nuclear reactors are susceptible to hydride-assisted cracking at the locations of stress concentration, such as in-service flaws. Probabilistic methodology is being developed to evaluate such flaws for crack initiation due to hydrided region overloads, which occur when the applied stress acting on a flaw with an existing hydrided region at its tip exceeds the stress at which the hydrided region is formed. As part of this development, probabilistic modeling of pressure tube material resistance to overload crack initiation has been performed on the basis of a set of test data specifically designed to study the effects of non-ratcheting hydride formation conditions and load reduction prior to hydride formation. In the modeling framework, the overload resistance is represented as a power-law function of the material resistance to initiation of delayed hydride cracking under constant loading, where both the overload crack initiation coefficient and the overload crack initiation exponent vary with the flaw geometry. In addition, the overload crack initiation coefficient varies with the extent of load reduction prior to hydride formation as well as the number of non-ratcheting hydride formation thermal cycles. (author)

Investigating turnover intentions by role overload, job satisfaction and social support moderation

Directory of Open Access Journals (Sweden)

J Pienaar

2007-01-01

Full Text Available Gold mining in South Africa has played a significant role in the economic development of the country. However, the current economic, personnel and rationalisation pressures could imply a loss of production in this industry. The focus of this research fell on investigating the role that social support may play in the translation of employees’ role overload and job satisfaction on their intentions to leave the organisation. A cross-sectional survey design with a random sample was used (n = 206. Results indicate that job satisfaction is the most significant predictor of turnover intention, but that collegial support plays an important role in moderating the effects of role overload on turnover intention.

In vivo cardiac role of migfilin during experimental pressure overload.

Science.gov (United States)

Haubner, Bernhard Johannes; Moik, Daniel; Schuetz, Thomas; Reiner, Martin F; Voelkl, Jakob G; Streil, Katrin; Bader, Kerstin; Zhao, Lei; Scheu, Claudia; Mair, Johannes; Pachinger, Otmar; Metzler, Bernhard

2015-06-01

Increased myocardial wall strain triggers the cardiac hypertrophic response by increasing cardiomyocyte size, reprogramming gene expression, and enhancing contractile protein synthesis. The LIM protein, migfilin, is a cytoskeleton-associated protein that was found to translocate in vitro into the nucleus in a Ca(2+)-dependent manner, where it co-activates the pivotal cardiac transcription factor Csx/Nkx2.5. However, the in vivo role of migfilin in cardiac function and stress response is unclear. To define the role of migfilin in cardiac hypertrophy, we induced hypertension by transverse aortic constriction (TAC) and compared cardiac morphology and function of migfilin knockout (KO) with wild-type (WT) hearts. Heart size and myocardial contractility were comparable in untreated migfilin KO and WT hearts, but migfilin-null hearts presented a reduced extent of hypertrophic remodelling in response to chronic hypertensile stress. Migfilin KO mice maintained their cardiac function for a longer time period compared with WT mice, which presented extensive fibrosis and death due to heart failure. Migfilin translocated into the nucleus of TAC-treated cardiomyocytes, and migfilin KO hearts showed reduced Akt activation during the early response to pressure overload. Our findings indicate an important role of migfilin in the regulation of cardiac hypertrophy upon experimental TAC. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Calcium channel blockers ameliorate iron overload-associated hepatic fibrosis by altering iron transport and stellate cell apoptosis

Energy Technology Data Exchange (ETDEWEB)

Zhang, Ying [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Department of Pathology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang 050200, Hebei (China); Zhao, Xin [Department of Hepatobiliary Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei (China); Chang, Yanzhong [Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei (China); Zhang, Yuanyuan [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Chu, Xi [Department of Pharmacy, The Forth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei (China); Zhang, Xuan [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Liu, Zhenyi; Guo, Hui [Department of Medicinal Chemistry, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Wang, Na [Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Gao, Yonggang [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Zhang, Jianping, E-mail: zhangjianping14@126.com [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Chu, Li, E-mail: chuli0614@126.com [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei (China)

2016-06-15

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 by 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

Decreased erythrocyte CCS content is a biomarker of copper overload in rats.

Science.gov (United States)

Bertinato, Jesse; Sherrard, Lindsey; Plouffe, Louise J

2010-07-02

Copper (Cu) is an essential trace metal that is toxic in excess. It is therefore important to be able to accurately assess Cu deficiency or overload. Cu chaperone for Cu/Zn superoxide dismutase (CCS) protein expression is elevated in tissues of Cu-deficient animals. Increased CCS content in erythrocytes is particularly sensitive to decreased Cu status. Given the lack of a non-invasive, sensitive and specific biomarker for the assessment of Cu excess, we investigated whether CCS expression in erythrocytes reflects Cu overload. Rats were fed diets containing normal or high levels of Cu for 13 weeks. Diets contained 6.3 +/- 0.6 (Cu-N), 985 +/- 14 (Cu-1000) or 1944 +/- 19 (Cu-2000) mg Cu/kg diet. Rats showed a variable response to the high Cu diets. Some rats showed severe Cu toxicity, while other rats showed no visible signs of toxicity and grew normally. Also, some rats had high levels of Cu in liver, whereas others had liver Cu concentrations within the normal range. Erythrocyte CCS protein expression was 30% lower in Cu-2000 rats compared to Cu-N rats (P CCS (47% reduction, P CCS content is associated with Cu overload in rats and should be evaluated further as a potential biomarker for assessing Cu excess in humans.

Provider role attitudes, marital satisfaction, role overload, and housework: a dyadic approach.

Science.gov (United States)

Helms, Heather M; Walls, Jill K; Crouter, Ann C; McHale, Susan M

2010-10-01

Treating the marital dyad as the unit of analysis, this study examined the within-couple patterning of 272 dual-earner spouses' provider role attitudes and their longitudinal associations with marital satisfaction, role overload, and the division of housework. Based on the congruence of husbands' and wives' provider role attitudes, couples were classified into one of four types: (a) main-secondary, (b) coprovider, (c) ambivalent coprovider, and (d) mismatched couples. Nearly half of all spouses differed in their attitudes about breadwinning. A series of mixed model ANCOVAs revealed significant between- and within-couple differences in human capital characteristics, spouses' perceptions of marital satisfaction and role overload, and the division of housework across 3 years of measurement. Coprovider couples reported higher levels of marital satisfaction and a more equitable division of housework than the other couple groups. Wives in the ambivalent coprovider couples' group reported higher levels of role overload than their husbands to a greater extent than was found in the other couple groups. As the first study to adopt a dyadic approach that considers the meanings that both spouses in dual-earner couples ascribe to paid employment, these findings advance understanding of how dual-earner spouses' provider role attitudes serve as contexts for marital quality, behavior, and role-related stress.

Hepatic iron overload following liver transplantation of a C282y homozygous allograft: a case report and literature review.

LENUS (Irish Health Repository)

Dwyer, Jeremy P

2011-11-01

Hereditary haemochromatosis is a common genetic disease associated with progressive iron overload and parenchymal organ damage including liver, pancreas and heart. We report a case of inadvertent transplantation of a liver from a haemochromatosis donor to a 56-year-old Asian female. Progressive iron overload occurred over a 2 year follow up as assessed by liver biopsy and iron studies in the absence of a secondary cause of iron overload, supporting a primary role of liver rather than small intestine in the regulation of iron homeostasis in hereditary haemochromatosis.

The impact of faulty response of overload protection systems on the reliability of electricity supply

International Nuclear Information System (INIS)

Schweigert, J.; Schnuerer, G.

1988-01-01

Protection equipment of the engineered safety system which is to prevent the triggering of actions via signals from the reactor protection system is to be made so reliable that it has no impact on the non-availability of the supplied systems. Design and functional mode of the various overload protection equipment and the relevant switching device and combinations are explained together with the requirements such as choice, design, and adjustment of the protection equipment, followed by a survey of possible causes of faulty response of overload protection device and of the means and measures available for improvement. The now presented version of September 1987 of the 'overload protection report deals basically with all main topics of the Juli 1985 version, but has been updated and extended by material taking into account practice-oriented data on the new developments in convoy power plant design. (orig./HP) [de

Incidental splenic nodules found on MR imaging done for assessment of iron overload in children

International Nuclear Information System (INIS)

Ahyad, Rayan A.; Lam, Christopher Z.; Navarro, Oscar M.; Shearkhani, Omid

2017-01-01

MR imaging is used to assess iron overload in patients with hemoglobinopathies and in those who have undergone multiple blood transfusions. Sometimes splenic nodules are found incidentally on these examinations and this may cause diagnostic uncertainty. To determine the prevalence, imaging characteristics and evolution of splenic nodules found on MR imaging for iron overload evaluation. Retrospective review of all MR imaging examinations performed for iron overload assessment from 2005 to 2015 in a tertiary pediatric hospital. The presence of focal splenic nodules including number, size, signal characteristics and changes on follow-up MR imaging were recorded. Relevant patient clinical information including underlying hematological disease was also documented. A total of 318 patients had MR imaging for iron overload assessment. Of these, 25 (8%) had at least one incidental splenic nodule. Sickle cell disease was present in 22 patients (88%) and thalassemia in 3 (12%). On intermediate-weighted spin-echo images, the nodules had high signal intensity compared to the remainder of the spleen in 23 patients (92%) and low signal intensity in the remaining 2 (8%). In all patients (100%) the nodules showed progressive loss of signal intensity with increasing echo time values. Follow-up MR imaging was performed in 20 (80%) patients, which showed an increase in the size of the splenic nodules in 7 patients (35%) stability in 11 (55%) and a decrease in size in 2 (10%). It is not uncommon to find splenic nodules during MR evaluation of iron overload. In patients with sickle cell disease, most of these nodules are thought to represent preserved splenic tissue and appear hyperintense compared to the remainder of the spleen. They frequently remain stable on follow-up imaging, although about a third of them may show growth. Awareness of these nodules is important to avoid concern for potential malignancy and unnecessary investigations. (orig.)

Incidental splenic nodules found on MR imaging done for assessment of iron overload in children

Energy Technology Data Exchange (ETDEWEB)

Ahyad, Rayan A.; Lam, Christopher Z.; Navarro, Oscar M. [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); Shearkhani, Omid [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada)

2017-06-15

MR imaging is used to assess iron overload in patients with hemoglobinopathies and in those who have undergone multiple blood transfusions. Sometimes splenic nodules are found incidentally on these examinations and this may cause diagnostic uncertainty. To determine the prevalence, imaging characteristics and evolution of splenic nodules found on MR imaging for iron overload evaluation. Retrospective review of all MR imaging examinations performed for iron overload assessment from 2005 to 2015 in a tertiary pediatric hospital. The presence of focal splenic nodules including number, size, signal characteristics and changes on follow-up MR imaging were recorded. Relevant patient clinical information including underlying hematological disease was also documented. A total of 318 patients had MR imaging for iron overload assessment. Of these, 25 (8%) had at least one incidental splenic nodule. Sickle cell disease was present in 22 patients (88%) and thalassemia in 3 (12%). On intermediate-weighted spin-echo images, the nodules had high signal intensity compared to the remainder of the spleen in 23 patients (92%) and low signal intensity in the remaining 2 (8%). In all patients (100%) the nodules showed progressive loss of signal intensity with increasing echo time values. Follow-up MR imaging was performed in 20 (80%) patients, which showed an increase in the size of the splenic nodules in 7 patients (35%) stability in 11 (55%) and a decrease in size in 2 (10%). It is not uncommon to find splenic nodules during MR evaluation of iron overload. In patients with sickle cell disease, most of these nodules are thought to represent preserved splenic tissue and appear hyperintense compared to the remainder of the spleen. They frequently remain stable on follow-up imaging, although about a third of them may show growth. Awareness of these nodules is important to avoid concern for potential malignancy and unnecessary investigations. (orig.)

Competitive On-Line Scheduling for Overloaded Real-Time Systems

Science.gov (United States)

1993-09-01

Real - Time Systems by Gilad Koren a dissertation submitted in partial fulfillment of the requirements...Overloaded Real - Time Systems 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK...1.1 Introduction : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 2 1.1.1 Real - Time Systems : : : : : : : : : : : : : : : : : : : : : : : : : : : :

A Confirmatory Factor Analysis of Reilly's Role Overload Scale

Science.gov (United States)

Thiagarajan, Palaniappan; Chakrabarty, Subhra; Taylor, Ronald D.

2006-01-01

In 1982, Reilly developed a 13-item scale to measure role overload. This scale has been widely used, but most studies did not assess the unidimensionality of the scale. Given the significance of unidimensionality in scale development, the current study reports a confirmatory factor analysis of the 13-item scale in two samples. Based on the…

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

Science.gov (United States)

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;

Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.

Science.gov (United States)

Zhang, Qia; Joshi, Sunil K; Lovett, David H; Zhang, Bryon; Bodine, Sue; Kim, Hubert T; Liu, Xuhui

2014-01-01

extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

Decision processes in choice overload: a product of delay and probability discounting?

Science.gov (United States)

Kaplan, Brent A; Reed, Derek D

2013-07-01

Recent research in the behavioral decision making literature has demonstrated that humans hyperbolically discount the subjective value of options as the number of options increases (Reed et al., 2012). These findings provide a cognitive-behavioral synthesis of the "choice overload" phenomenon, also known as the "paradox of choice." Specifically, these findings suggest that temporal discounting may serve as the underlying process contributing to this effect. As an extension, this study examined the effects of reward magnitude sizes had on rates temporal and options discounting. This manipulation was conducted to determine what role temporal discounting plays in discounting of options. The present results suggest that temporal discounting may not be the only process contributing to the choice overload effect. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-06-14

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

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

Science.gov (United States)

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.

Analysis of short and long crack behavior and single overload effect by crack opening stress

International Nuclear Information System (INIS)

Song, Sam Hong; Lee, Kyeong Ro

1999-01-01

The study analyzed the behaviors of short and long crack as well as the effect of single tensile overload on the crack behaviors by using fatigue crack opening behavior. Crack opening stress is measured by an elastic compliance method which may precisely and continuously provide many data using strain gages during experiment. The unusual growth behaviors of short crack and crack after the single tensile overload applied, was explained by the variations of crack opening stress. In addition, fatigue crack growth rate was expressed as a linear form for short crack as for long crack by using effective stress intensity factor range as fracture mechanical parameter, which is based on crack closure concept. And investigation is performed with respect to the relation between plastic zone size formed at the crack tip and crack retardation, crack length and the number of cycles promoted or retarded, and the overload effect on the fatigue life

Left ventricular function in right ventricular overload

International Nuclear Information System (INIS)

Iwanaga, Shiro; Handa, Shunnosuke; Abe, Sumihisa; Onishi, Shohei; Nakamura, Yoshiro; Kunieda, Etsuo; Ogawa, Koichi; Kubo, Atsushi

1989-01-01

This study clarified regional and global functions of the distorted left ventricle due to right ventricular overload by gated radionuclide ventriculography (RNV). Cardiac catheterization and RNV were performed in 13 cases of atrial septal defect (ASD), 13 of pure mitral stenosis (MS), 10 of primary pulmonary hypertension (PPH), and 10 of normal subjects (NL). Right ventricular systolic pressure (RVSP) was 32.9±13.9, 45.0±12.2, 88.3±17.1, and 21.2±4.5 mmHg, respectively. The end-systolic LAO view of the left ventricle was halved into septal and free-wall sides. The end-diastolic halves were determined in the same plane. Ejection fractions of the global left ventricle (LVEF), global right ventricle (RVEF), the septal half of the left ventricle (SEPEF), and the free-wall half of the left ventricle (FWEF) were obtained. LVEF was 56.8±9.8% in NL, 52.8±10.5% in ASD, and 49.5±12.9% in PPH. In MS, LVEF (47.0±13.0%) was smaller than those in the other groups. RVEF was 37.0±5.2% in NL, 43.7±15.5% in ASD, and 32.8±11.5% in MS. In PPH, RVEF (25.0±10.6%) was smaller than those in the other groups. SEPEF was smaller in ASD (42.5±13.2%), MS (40.4±13.1%), PPH (40.5±12.5%) than in NL (53.5±8.5%). Systolic function of the septal half of the left ventricle was disturbed by right ventricular overload. RVEF (r=-0.35, p<0.05) and SEPEF (r=-0.51, p<0.01) had negative correlations with RVSP. As RVSP rose, systolic function of the septal half of the left ventricle was more severely disturbed. FWEF was the same among the four groups; NL (57.0±12.6%), ASD (48.6±15.2%), MS (50.5±12.0%), and PPH (51.1±12.3%). There was a good correlation between SEPEF and LVEF in NL (r=0.81), although in PPH this correlation was poor (r=0.64). These data showed that the distorted left ventricular due to right ventricular overload maintains its global function with preserved function of the free-wall side. (J.P.N.)

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

OpenAIRE

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

2017-01-01

Background 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. Methods and Results 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 geneti...

Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload.

Science.gov (United States)

Payne, Krista A; Rofail, Diana; Baladi, Jean-François; Viala, Muriel; Abetz, Linda; Desrosiers, Marie-Pierre; Lordan, Noreen; Ishak, Khajak; Proskorovsky, Irina

2008-08-01

This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.

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

Science.gov (United States)

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.

A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity in Swiss albino mice through ROS regulation.

Science.gov (United States)

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.

Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

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Gabriele G. Schiattarella

2018-05-01

Full Text Available Left ventricular hypertrophy (LVH is a major contributor to the development of heart failure (HF. Alterations in cyclic adenosine monophosphate (cAMP-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA anchor proteins (AKAPs, tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 (Akap1-/-, Akap1 heterozygous (Akap1+/-, and their wild-type (wt littermates underwent transverse aortic constriction (TAC or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1-/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 (Siah2 knockout mice (Siah2-/-. Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure.

Science.gov (United States)

Schiattarella, Gabriele G; Boccella, Nicola; Paolillo, Roberta; Cattaneo, Fabio; Trimarco, Valentina; Franzone, Anna; D'Apice, Stefania; Giugliano, Giuseppe; Rinaldi, Laura; Borzacchiello, Domenica; Gentile, Alessandra; Lombardi, Assunta; Feliciello, Antonio; Esposito, Giovanni; Perrino, Cinzia

2018-01-01

Left ventricular hypertrophy (LVH) is a major contributor to the development of heart failure (HF). Alterations in cyclic adenosine monophosphate (cAMP)-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA) anchor proteins (AKAPs), tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs) promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 ( Akap1 -/- ), Akap1 heterozygous ( Akap1 +/- ), and their wild-type ( wt ) littermates underwent transverse aortic constriction (TAC) or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1 -/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 ( Siah2 ) knockout mice ( Siah2 -/- ). Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

The effect of a single tensile overload on stress corrosion cracking growth of stainless steel in a light water reactor environment

International Nuclear Information System (INIS)

Xue He; Li Zhijun; Lu Zhanpeng; Shoji, Tetsuo

2011-01-01

Research highlights: → The affect of a single tensile overload on SCC growth rate is investigated. → A single tensile overload would produce a residual plastic strain in the SCC tip. → The residual plastic strain would decrease the plastic strain rate in the SCC tip. → A single tensile overload would cause crack growth rate retardation in the SCC tip. → SCC growth rate in the quasi-stationary crack tip is relatively lower. - Abstract: It has been found that a single tensile overload applied during constant load amplitude might cause crack growth rate retardation in various crack propagating experiments which include fatigue test and stress corrosion cracking (SCC) test. To understand the affecting mechanism of a single tensile overload on SCC growth rate of stainless steel or nickel base alloy in light water reactor environment, based on elastic-plastic finite element method (EPFEM), the residual plastic strain in both tips of stationary and growing crack of contoured double cantilever beam (CDCB) specimen was simulated and analyzed in this study. The results of this investigation demonstrate that a residual plastic strain in the region immediately ahead of the crack tips will be produced when a single tensile overload is applied, and the residual plastic strain will decrease the plastic strain rate level in the growing crack tip, which will causes crack growth rate retardation in the tip of SCC.

Global transcriptional response to Hfe deficiency and dietary iron overload in mouse liver and duodenum.

Directory of Open Access Journals (Sweden)

Alejandra Rodriguez

2009-09-01

Full Text Available Iron is an essential trace element whose absorption is usually tightly regulated in the duodenum. HFE-related hereditary hemochromatosis (HH is characterized by abnormally low expression of the iron-regulatory hormone, hepcidin, which results in increased iron absorption. The liver is crucial for iron homeostasis as it is the main production site of hepcidin. The aim of this study was to explore and compare the genome-wide transcriptome response to Hfe deficiency and dietary iron overload in murine liver and duodenum. Illumina arrays containing over 47,000 probes were used to study global transcriptional changes. Quantitative RT-PCR (Q-RT-PCR was used to validate the microarray results. In the liver, the expression of 151 genes was altered in Hfe(-/- mice while dietary iron overload changed the expression of 218 genes. There were 173 and 108 differentially expressed genes in the duodenum of Hfe(-/- mice and mice with dietary iron overload, respectively. There was 93.5% concordance between the results obtained by microarray analysis and Q-RT-PCR. Overexpression of genes for acute phase reactants in the liver and a strong induction of digestive enzyme genes in the duodenum were characteristic of the Hfe-deficient genotype. In contrast, dietary iron overload caused a more pronounced change of gene expression responsive to oxidative stress. In conclusion, Hfe deficiency caused a previously unrecognized increase in gene expression of hepatic acute phase proteins and duodenal digestive enzymes.

Effect of Andrographolide‭ Extract on Blood Glucose and Lipid Profile in Rats with Secondary Iron Overload

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َArash Mehri Pirayvatlo

2017-01-01

Full Text Available Background & objectives: Iron overload is involved in the pathophysiology of many diseases including diabetes. In fact, the excess iron by creating free radicals makes damage to pancreas and leads to insulin resistance and diabetes. Andrographolide extract has hypoglycemic and antioxidant properties. This study has surveyed the effects of andrographolide on blood glucose and lipid profile in rats with secondary iron overload. Methods: In this experimental study, 36 male Wistar rats were randomly divided into 6 groups: the healthy control group, secondary iron overload group, secondary iron overload groups treated with a dose of 3.5 and 7 mg/kg of andrographolide extract, and andrographolide groups treated with a dose of 3.5 and 7 mg/kg of extract. Iron and extract were injected for 6 and 12 days, respectively. Blood samples were taken for measurement of blood glucose and lipid profiles. Data were analyzed using ANOVA test. Results: The pathological results of samples from liver of animals receiving iron showed that the iron was deposited in the liver tissues. Iron injection significantly increased blood glucose levels compared to healthy control group (p<0.05. In the iron overload group, andrographolide extract with a dose of 3.5 mg/kg or 7 mg/kg significantly decreased blood glucose levels (p<0.05. Iron injections did not increase the serum triglyceride and cholesterollevels. Injections of andrographolide extract with a dose of 3.5 mg/kg and 7 mg/kg, significantly decreased the cholesterol levels compared to iron receiving group (p<0.05. Conclusion: Results of this study showed that the andrographolide with different doses may be effective in the treatment of diabetes by reducing serum glucose and cholesterol levels.

A quantitative approach to modeling the information processing of NPP operators under input information overload

International Nuclear Information System (INIS)

Kim, Jong Hyun; Seong, Poong Hyun

2002-01-01

This paper proposes a quantitative approach to modeling the information processing of NPP operators. The aim of this work is to derive the amount of the information processed during a certain control task under input information overload. We primarily develop the information processing model having multiple stages, which contains information flow. Then the uncertainty of the information is quantified using the Conant's model, a kind of information theory. We also investigate the applicability of this approach to quantifying the information reduction of operators under the input information overload

Technologies for dealing with information overload : an engineers' point of view

NARCIS (Netherlands)

Calders, T.G.K.; Fletcher, G.H.L.; Kamiran, F.; Pechenizkiy, M.; Strother, J.B.; Ulijn, J.M.; Fazal, Z.

2012-01-01

In this chapter, we provide an overview of the technological side of the information overload problem. We discuss the challenges and opportunities offered by the ever-growing and emerging stream of information from an engineering point of view. More concretely, we survey storage and querying

Blunted angiogenesis and hypertrophy are associated with increased fatigue resistance and unchanged aerobic capacity in old overloaded mouse muscle.

Science.gov (United States)

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 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.

Tools to Reduce Overload in the School Social Worker Role

Science.gov (United States)

Leyba, Erin Gleason

2009-01-01

This article addresses how school social workers can decrease overload in their roles. A two-step process of envisioning an ideal role is outlined: (1) indentifying priorities and activities that are effective or in need of expansion and (2) weeding out activities that could be done differently or no longer serve their purpose. The author…

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

Science.gov (United States)

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

1992-01-01

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

The ''red'' decline of Norway spruce or ''røde rødgraner'' - is it ammonium overload or top-dying?

DEFF Research Database (Denmark)

Engvild, K.C.

2005-01-01

by nitrogen overload was investigated. A sensitive biochemical indicator of nitrogen status of conifer trees is the content of free amino acids of the urea cycle,arginine and ornithine. In pot experiments with four times overload of N as ammonium nitrate the free arginine content increased more than 100 times....... There was no indication of nitrogen overload. The “red” Norway spruce maysuffer from “top-dying” a common disorder of Norway spruce in Great Britain, believed to be caused by several mild winters in a row. In that case the symptoms should diminish after the very cold winter 1995-96....

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

Directory of Open Access Journals (Sweden)

Jones Paula

2006-09-01

Full Text Available Abstract 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.

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

International Nuclear Information System (INIS)

Cui, J.; Shek, G.K.; Wang, Z.R.

2007-01-01

Service-induced flaws in Zr-2.5Nb alloy pressure tubes in Candu (Canada Deuterium Uranium Reactors) nuclear reactors are susceptible to a crack initiation and growth mechanism known as Delayed Hydride Cracking (DHC), which is a repetitive process that involves hydrogen diffusion, hydride precipitation, growth and fracture of a hydride region at the flaw-tip under a constant load. Crack initiation may also occur under another loading condition when the hydride region is subjected to an overload. An overload occurs when the hydride region at the flaw tip is loaded to a stress higher than that at which this region is formed such as when the reactor experiences a transient pressure higher than the normal operating pressure where the hydride region is formed. Flaw disposition requires justification that the hydride region overload will not fracture the hydride region, and initiate DHC. In this work, monotonically increasing load experiments were performed on unirradiated Zr-2.5Nb pressure tube specimens containing simulated debris frets (V-notch) and bearing pad frets (BPF, U-shape notch) to examine overload fracture behavior of flaw-tip hydrides formed under hydride ratcheting conditions. Hydride cracking in the overload tests was detected by the acoustic emission technique and confirmed by post-test metallurgical examination. Test results indicate that the resistance to overload fracture is affected by a number of parameters including hydride formation stress, flaw shape (V-notch vs. BPF) and flaw radius (0.015 mm vs. 0.1 mm). The notch-tip hydride morphologies were examined by optical microscopy and scanning electron microscopy (SEM) which show that they are affected by the hydride formation conditions, resulting in different overload fracture resistance. Finite element stress analyses were also performed to obtain flaw-tip stress distributions for interpretation of the test results. (authors)

TNF-α as a potential mediator of cardiac dysfunction due to intracellular Ca2+-overload

International Nuclear Information System (INIS)

Zhang Ming; Xu Yanjun; Saini, Harjot K.; Turan, Belma; Liu, Peter P.; Dhalla, Naranjan S.

2005-01-01

TNF-α has been shown to be involved in cardiac dysfunction during ischemia/reperfusion injury; however, no information regarding the status of TNF-α production in myocardial injury due to intracellular Ca 2+ -overload is available in the literature. The intracellular Ca 2+ -overload was induced in the isolated rat hearts subjected to 5 min Ca 2+ -depletion and 30 min Ca 2+ -repletion (Ca 2+ -paradox). The Ca 2+ -paradox hearts exhibited a dramatic depression in left ventricular developed pressure, a marked elevation in left ventricular end diastolic pressure, and more than a 4-fold increase in TNF-α content. The ratio of cytosolic to homogenate nuclear factor-κB (NFκB) was decreased whereas the ratio of phospho-NFκB to total NFκB was increased in the Ca 2+ -paradox hearts. All these changes due to Ca 2+ -paradox were significantly attenuated upon treating the hearts with 100 μM pentoxifylline. These results suggest that activation of NFκB and increased production of TNF-α may play an important role in cardiac injury due to intracellular Ca 2+ -overload

Analysis of occupational stress in a high fashion clothing factory with upper limb biomechanical overload.

Science.gov (United States)

Forcella, Laura; Bonfiglioli, Roberta; Cutilli, Piero; Siciliano, Eugenio; Di Donato, Angela; Di Nicola, Marta; Antonucci, Andrea; Di Giampaolo, Luca; Boscolo, Paolo; Violante, Francesco Saverio

2012-07-01

To study job stress and upper limb biomechanical overload due to repetitive and forceful manual activities in a factory producing high fashion clothing. A total of 518 workers (433 women and 85 men) were investigated to determine anxiety, occupational stress (using the Italian version of the Karasek Job Content Questionnaire) and perception of symptoms (using the Italian version of the Somatization scale of Symptom Checklist SCL-90). Biomechanical overload was analyzed using the OCRA Check list. Biomechanical assessment did not reveal high-risk jobs, except for cutting. Although the perception of anxiety and job insecurity was within the normal range, all the workers showed a high level of job strain (correlated with the perception of symptoms) due to very low decision latitude. Occupational stress resulted partially in line with biomechanical risk factors; however, the perception of low decision latitude seems to play a major role in determining job strain. Interactions between physical and psychological factors cannot be demonstrated. Anyway, simultaneous long-term monitoring of occupational stress features and biomechanical overload could guide workplace interventions aimed at reducing the risk of adverse health effects.

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

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Yuki Aoki

2017-03-01

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

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

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Leilismara Sousa

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

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

Science.gov (United States)

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.

CT findings of transfusional hemosiderosis in patients with chronic renal failure : clinical correlation

International Nuclear Information System (INIS)

Park, Tae Joon; Lee, Hae Kyung; Hong, Hyun Sook; Kim, Gun Woo; Kim, Hyung Hwan; Choi, Gyo Chang; Kwon, Kui Hyang; Choi, Deuk Lin

1997-01-01

The purpose of this study is to evaluate whether there is any correlation between the CT features of hemosiderosis and clinical findings in patients with chronic renal failure who have received multiple blood transfusion. Among chronic renal failure patients who had undergone long-tern dialysis and received multiple blood transfusions, CT findings in 16 cases in which increased liver attenuation was seen on images obtained for other purpose, were analyzed by three radiologic specialists. The attenuation values of liver, spleen and pancreas compared with that of back muscle were correlated with the amount and duration of transfusion, and blood ferritin level. There is no correlation between the CT features of hemosiderosis and clinical findings. In patients with chronic renal failure and no clinical symptoms, the status of iron overload was relatively easily detected on CT. Close observation of CT findings is thus thought to prevent significant permanent functional deformity of organs in patients with chronic renal failure who have received multiple blood transfusions. (author). 14 refs., 1 tab., 1 fig

Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

International Nuclear Information System (INIS)

Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao; Hu, Jin; Zhang, Qiang; Liu, Bo; Wang, Min; Xu, Hui-bo; Sun, Xiao-bo

2014-01-01

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

Geiger-mueller radiation detector with means for detecting and indicating the existence of radiation overload

International Nuclear Information System (INIS)

Kovacs, T.; Mills, A.P.; Pfeiffer, L.N.

1981-01-01

When subjected to radiation overload existing geiger-mueller counters may give an erroneously low reading, resulting in possible hazard to personnel. The instant invention discloses simple and inexpensive apparatus to remedy this dangerous shortcoming. Depending on the geometry of the detector tube, two possible failure modes have been identified, and circuitry is disclosed to detect the existence of these respective failure modes. The disclosed apparatus indicates the absence of an overload condition, in addition to signaling, by both visible and audible means, the existence of excessive radiation that might result in erroneously low reading of the geiger-mueller counter

Sobrecarga e quelação de ferro na anemia falciforme Iron overload and iron chelation in sickle cell disease

Directory of Open Access Journals (Sweden)

Rodolfo D. Cançado

2007-09-01

Full Text Available Pacientes cronicamente transfundidos desenvolvem sobrecarga de ferro que ocasiona lesão orgânica e morte. Nos últimos trinta anos, pacientes com sobrecarga de ferro transfusional dependem de infusões noturnas de desferroxamina para quelação de ferro. Apesar da dramática melhora da expectativa de vida na era da desferroxamina para pacientes com anemias dependentes de transfusão, 50% dos pacientes com talassemia maior morrem antes dos 30 anos de idade, predominantemente devido à insuficiência cardíaca induzida pelo ferro. A difícil natureza desse tratamento com infusão subcutânea prolongada por meio de aparelho infusor portátil motivou o desenvolvimento de formas alternativas de tratamento que facilitasse a aderência do paciente. Estratégias para reduzir a sobrecarga de ferro e suas conseqüências, através da melhora dos regimes de quelação, foram as prioridades mais importantes nos últimos anos. Nesta revisão, descrevemos os avanços mais importantes da terapia quelante de ferro. Em particular, analisamos os dois quelantes de ferro ativos por via oral: deferiprona e o novo quelante de ferro oral deferasirox.Patients who are chronically dependent on transfusions will develop iron overload that leads to organ damage and eventually to death. For nearly 30 years, patients with transfusional iron overload have been subject to overnight deferoxamine infusions for iron chelation. Despite dramatic gains in terms of life expectancy in the deferoxamine era for patients with transfusion-dependent anemias, 50% of patients with thalassemia major die before the age of 35 years, predominantly due to iron-induced heart failure. The very demanding nature of this treatment with prolonged subcutaneous infusion via portable pump infusions has been the motivation for attempts to develop alternative forms of treatment that would facilitate the patients' compliance. Strategies to reduce iron overload and its consequences by improving chelation

Iron overload across the spectrum of non-transfusion-dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions.

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Porter, John B; Cappellini, Maria Domenica; Kattamis, Antonis; Viprakasit, Vip; Musallam, Khaled M; Zhu, Zewen; Taher, Ali T

2017-01-01

Non-transfusion-dependent thalassaemias (NTDT) encompass a spectrum of anaemias rarely requiring blood transfusions. Increased iron absorption, driven by hepcidin suppression secondary to erythron expansion, initially causes intrahepatic iron overload. We examined iron metabolism biomarkers in 166 NTDT patients with β thalassaemia intermedia (n = 95), haemoglobin (Hb) E/β thalassaemia (n = 49) and Hb H syndromes (n = 22). Liver iron concentration (LIC), serum ferritin (SF), transferrin saturation (TfSat) and non-transferrin-bound iron (NTBI) were elevated and correlated across diagnostic subgroups. NTBI correlated with soluble transferrin receptor (sTfR), labile plasma iron (LPI) and nucleated red blood cells (NRBCs), with elevations generally confined to previously transfused patients. Splenectomised patients had higher NTBI, TfSat, NRBCs and SF relative to LIC, than non-splenectomised patients. LPI elevations were confined to patients with saturated transferrin. Erythron expansion biomarkers (sTfR, growth differentiation factor-15, NRBCs) correlated with each other and with iron overload biomarkers, particularly in Hb H patients. Plasma hepcidin was similar across subgroups, increased with >20 prior transfusions, and correlated inversely with TfSat, NTBI, LPI and NRBCs. Hepcidin/SF ratios were low, consistent with hepcidin suppression relative to iron overload. Increased NTBI and, by implication, risk of extra-hepatic iron distribution are more likely in previously transfused, splenectomised and iron-overloaded NTDT patients with TfSat >70%. © 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Desmin loss and mitochondrial damage precede left ventricular systolic failure in volume overload heart failure.

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Guichard, Jason L; Rogowski, Michael; Agnetti, Giulio; Fu, Lianwu; Powell, Pamela; Wei, Chih-Chang; Collawn, James; Dell'Italia, Louis J

2017-07-01

Heart failure due to chronic volume overload (VO) in rats and humans is characterized by disorganization of the cardiomyocyte desmin/mitochondrial network. Here, we tested the hypothesis that desmin breakdown is an early and continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later. Desmin/mitochondrial ultrastructure was examined by transmission electron microscopy (TEM) and immunohistochemistry (IHC). Protein and kinome analysis were performed in isolated cardiomyocytes, and desmin cleavage was assessed by mass spectrometry in left ventricular (LV) tissue. Echocardiography demonstrated a 40% decrease in the LV mass-to-volume ratio with spherical remodeling at 4 wk with ACF and LV systolic dysfunction at 12 wk. Starting at 24 h and continuing to 4 and 12 wk, with ACF there is TEM evidence of extensive mitochondrial clustering, IHC evidence of disorganization associated with desmin breakdown, and desmin protein cleavage verified by Western blot analysis and mass spectrometry. IHC results revealed that ACF cardiomyocytes at 4 and 12 wk had perinuclear translocation of αB-crystallin from the Z disk with increased α, β-unsaturated aldehyde 4-hydroxynonelal. Use of protein markers with verification by TUNEL staining and kinome analysis revealed an absence of cardiomyocyte apoptosis at 4 and 12 wk of ACF. Significant increases in protein indicators of mitophagy were countered by a sixfold increase in p62/sequestosome-1, which is indicative of an inability to complete autophagy. An early and continuous disruption of the desmin/mitochondrial architecture, accompanied by oxidative stress and inhibition of apoptosis and mitophagy, suggests its causal role in LV dilatation and systolic dysfunction in VO. NEW & NOTEWORTHY This study provides new evidence of early onset (24 h) and continuous (4-12 wk) desmin misarrangement and disruption of the normal sarcomeric and mitochondrial

An Investigation of Data Overload in Team-Based Distributed Cognition Systems

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Hellar, David Benjamin

2009-01-01

The modern military command center is a hybrid system of computer automated surveillance and human oriented decision making. In these distributed cognition systems, data overload refers simultaneously to the glut of raw data processed by information technology systems and the dearth of actionable knowledge useful to human decision makers.…

Current concepts on ventricular fibrillation: A Vicious Circle of Cardiomyocyte Calcium Overload in the Initiation, Maintenance, and Termination of Ventricular Fibrillation

Directory of Open Access Journals (Sweden)

Christian E. Zaugg

2004-04-01

Full Text Available Based on recent experimental studies, this review article introduces the novel concept that cardiomyocyte Ca2+ and ventricular fibrillation (VF are mutually related, forming a self-maintaining vicious circle in the initiation, maintenance, and termination of VF. On the one hand, elevated myocyte Ca2+ can cause delayed afterdepolarizations, triggered activity, and consequently life-threatening ventricular tachyarrhythmias in various pathological conditions such as digitalis toxicity, myocardial ischemia, or heart failure. On the other hand, VF itself directly and rapidly causes progressive myocyte Ca2+ overload that maintains VF and renders termination of VF increasingly difficult. Accordingly, energy levels for successful electrical defibrillation (defibrillation thresholds increase as both VF and Ca2+ overload progress. Furthermore, VF-induced myocyte Ca2+ overload can promote re-induction of VF after defibrillation and/or postfibrillatory myocardial dysfunction (postresuscitation stunning due to reduced myofilament Ca2+ responsiveness. The probability of these adverse events is best reduced by early detection and rapid termination of VF to prevent or limit Ca2+ overload. Early additional therapy targeting transsarcolemmal Ca2+ entry, particularly during the first 2 min of VF, may partially prevent myocyte Ca2+ overload and thus, increase the likelihood of successful defibrillation as well as prevent postfibrillatory myocardial dysfunction.

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

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Sujith Dassanayaka

2018-07-01

Full Text Available 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. Keywords: Heart failure, Hypertrophy, Oxidative stress, Aldehydes, Cardiac remodeling, Hormesis

The Influence of Domestic Overload on the Association between Job Strain and Ambulatory Blood Pressure among Female Nursing Workers

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Luciana Fernandes Portela

2013-11-01

Full Text Available 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.

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

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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.

Effects of Exogenous Antioxidants on Dietary Iron Overload

OpenAIRE

Asare, George A.; Kew, Michael C.; Mossanda, Kensese S.; Paterson, Alan C.; Siziba, Kwanele; Kahler-Venter, Christiana P.

2008-01-01

In dietary iron overload, excess hepatic iron promotes liver damage. The aim was to attenuate free radical-induced liver damage using vitamins. Four groups of 60 Wistar rats were studied: group 1 (control) was fed normal diet, group 2 (Fe) 2.5% pentacarbonyl iron (CI) followed by 0.5% Ferrocene, group 3 (Fe + V gp) CI, Ferrocene, plus vitamins A and E (42× and 10× RDA, respectively), group 4 (Fe – V gp) CI, Ferrocene diet, minus vitamins A and E. At 20 months, glutathione peroxidase (GPx), su...

Functional overload attenuates plantaris atrophy in tumor-bearing rats

International Nuclear Information System (INIS)

Otis, Jeffrey S; Lees, Simon J; Williams, Jay H

2007-01-01

Late stage cancer malignancies may result in severe skeletal muscle wasting, fatigue and reduced quality of life. Resistance training may attenuate these derangements in cancer patients, but how this hypertrophic response relates to normal muscle adaptations in healthy subjects is unknown. Here, we determined the effect of resistance training on muscle mass and myosin heavy chain (MHC) isoform composition in plantaris muscles from tumor-bearing (TB) rats. Age- and gender-matched Buffalo rats were used for all studies (n = 6/group). Suspensions of Morris Hepatoma MH7777 cells or normal saline were injected subcutaneously into the dorsum. Six weeks after cell implantation, muscles from TB rats were harvested, weighed and processed for ATP-independent proteasome activity assays. Once tumor-induced atrophy had been established, subgroups of TB rats underwent unilateral, functional overload (FO). Healthy, sham-operated rats served as controls. After six weeks, the extent of plantaris hypertrophy was calculated and MHC isoform compositions were determined by gel electrophoresis. Six weeks of tumor growth reduced body mass and the relative masses of gastrocnemius, plantaris, tibialis anterior, extensor digitorum longus, and diaphragm muscles (p ≤ 0.05). Percent reductions in body mass had a strong, negative correlation to final tumor size (r = -0.78). ATP-independent proteasome activity was increased in plantaris muscles from TB rats (p ≤ 0.05). In healthy rats, functional overload (FO) increased plantaris mass ~44% compared to the contralateral control muscle, and increased the relative percentage of MHC type I and decreased the relative percentage of MHC type IIb compared to the sham-operated controls (p ≤ 0.05). Importantly, plantaris mass was increased ~24% in TB-FO rats and adaptations to MHC isoform composition were consistent with normal, resistance-trained muscles. Despite significant skeletal muscle derangements due to cancer, muscle retains the capacity to

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-08-15

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

Changes in right ventricular function assessed by echocardiography in dog models of mild RV pressure overload.

Science.gov (United States)

Morita, Tomoya; Nakamura, Kensuke; Osuga, Tatsuyuki; Yokoyama, Nozomu; Morishita, Keitaro; Sasaki, Noboru; Ohta, Hiroshi; Takiguchi, Mitsuyoshi

2017-07-01

The assessment of hemodynamic change by echocardiography is clinically useful in patients with pulmonary hypertension. Recently, mild elevation of the mean pulmonary arterial pressure (PAP) has been shown to be associated with increased mortality. However, changes in the echocardiographic indices of right ventricular (RV) function are still unknown. The objective of this study was to validate the relationship between echocardiographic indices of RV function and right heart catheterization variables under a mild RV pressure overload condition. Echocardiography and right heart catheterization were performed in dog models of mild RV pressure overload induced by thromboxane A 2 analog (U46619) (n=7). The mean PAP was mildly increased (19.3±1.1 mm Hg), and the cardiac index was decreased. Most echocardiographic indices of RV function were significantly impaired even under a mild RV pressure overload condition. Multivariate analysis revealed that the RV free wall longitudinal strain (RVLS), standard deviation of the time-to-peak longitudinal strain of RV six segments (RV-SD) by speckle-tracking echocardiography, and Tei index were independent echocardiographic predictors of the mean PAP (free wall RVLS, β=-0.60, P<.001; RV-SD, β=0.40, P=.011), pulmonary vascular resistance (free wall RVLS, β=-0.39, P=.020; RV-SD, β=0.47, P=.0086; Tei index, β=0.34, P=.047), and cardiac index (Tei index, β=-0.65, P<.001). Free wall RVLS, RV-SD, and Tei index are useful for assessing the hemodynamic change under a mild RV pressure overload condition. © 2017, Wiley Periodicals, Inc.

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

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

2014-11-04

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

Study on the distribution of radioactive trace elements in vitamin D-overloaded rats using the multitracer technique

International Nuclear Information System (INIS)

Hirunuma, Rieko; Enomoto, Shuichi; Ambe, Fumitoshi; Endo, Kazutoyo; Ambe, Shizuko

1999-01-01

The uptake and distribution of radioisotopes of beryllium, calcium, scandium, vanadium, chromium, manganese, iron, cobalt, nickel, zinc, gallium, arsenic, strontium and barium in vitamin D (VD)-overloaded rats were investigated and compared with those in control rats, using the multitracer technique. Each element revealed its characteristic distribution among various organs in control and VD-overloaded rats. For some elements, such as cobalt and chromium, the distribution patterns in them were significantly different. These results are discussed in terms of the metabolism of the elements in rats

Reduced firing rates of high threshold motor units in response to eccentric overload.

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Balshaw, Tom G; Pahar, Madhu; Chesham, Ross; Macgregor, Lewis J; Hunter, Angus M

2017-01-01

Acute responses of motor units were investigated during submaximal voluntary isometric tasks following eccentric overload (EO) and constant load (CL) knee extension resistance exercise. Ten healthy resistance-trained participants performed four experimental test sessions separated by 5 days over a 20 day period. Two sessions involved constant load and the other two used eccentric overload. EO and CL used both sessions for different target knee eccentric extension phases; one at 2 sec and the other at 4 sec. Maximal voluntary contractions (MVC) and isometric trapezoid efforts for 10 sec at 70% MVC were completed before and after each intervention and decomposed electromyography was used to measure motor unit firing rate. The firing rate of later recruited, high-threshold motor units declined following the 2-sec EO but was maintained following 2sec CL (P motor units were maintained for both loading types following 4-sec extension phases. MVC and rate of force development where maintained following both EO and CL and 2 and 4 sec phases. This study demonstrates a slower firing rate of high-threshold motor units following fast eccentric overload while MVC was maintained. This suggests that there was a neuromuscular stimulus without cost to the force-generating capacity of the knee extensors. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy

DEFF Research Database (Denmark)

Christoffersen, Tue E.H.; Aplin, Mark; Strom, Claes C.

2006-01-01

also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg.kg(-1).day(-1)) to investigate a possible role of the renin-angiotensin system......RNAs for the natriuretic peptides or their receptors. Although increased gene expression does not necessarily convey a higher concentration of the protein, the data suggest that pressure overload is accompanied by upregulation of not only ANP and BNP but also their receptors NPR-A and NPR-C in the left ventricle....

Electrochemical sensor for predicting transformer overload by phenol measurement

Energy Technology Data Exchange (ETDEWEB)

Bosworth, Timothy; Setford, Steven; Saini, Selwayan [Cranfield Centre for Analytical Science, Cranfield University, Silsoe, Beds MK45 4DT (United Kingdom); Heywood, Richard [National Grid Company Plc, Kelvin Avenue, Leatherhead, Surrey KT22 7ST (United Kingdom)

2003-03-10

Transformer overload is a significant problem to the power transmission industry, with severe safety and cost implications. Overload may be predicted by measuring phenol levels in the transformer-insulating oil, arising from the thermolytic degradation of phenol-formaldehyde resins. The development of two polyphenol oxidase (PPO) sensors, based on monitoring the enzymatic consumption of oxygen using an oxygen electrode, or reduction of enzymatically generated o-quinone at a screen-printed electrode (SPE), for the measurement of phenol in transformer oil is reported. Ex-service oils were prepared either by extraction into aqueous electrolyte-buffer, or by direct dilution in propan-2-ol, the latter method being more amenable to simple at-line operation. The oxygen electrode, with a sensitivity of 2.87 nA {mu}g{sup -1} ml{sup -1}, RSD of 7.0-19.9% and accuracy of {+-}8.3% versus the industry standard International Electrotechnical Commission (IEC) method, proved superior to the SPE (sensitivity: 3.02 nA {mu}g{sup -1} ml{sup -1}; RSD: 8.9-18.3%; accuracy: {+-}7.9%) and was considerably more accurate at low phenol concentrations. However, the SPE approach is more amenable to field-based usage for reasons of device simplicity. The method has potential as a rapid and simple screening tool for the at-site monitoring of phenol in transformer oils, thereby reducing incidences of transformer failure.

Analysis of HFE gene mutations and HLA-A alleles in Brazilian patients with iron overload

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Rodolfo Delfini Cançado

Full Text Available CONTEXT AND OBJECTIVE: Hemochromatosis is a common inherited disorder of iron metabolism and one of the most important causes of iron overload. The objective was to analyze the presence of C282Y, H63D and S65C mutations in the HFE gene and HLA-A alleles for a group of Brazilian patients with iron overload, and to correlate genotype with clinical and laboratory variables. DESIGN AND SETTING: Prospective study, in Discipline of Hematology and Oncology, Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo. METHODS: We studied 35 patients with iron overload seen at our outpatient unit between January 2001 and December 2003. Fasting levels of serum iron and ferritin, and total iron-binding capacity, were assayed using standard techniques. Determinations of C282Y, H63D and S65C mutations in the HFE gene and of HLA-A alleles were performed by polymerase chain reaction (PCR. RESULTS: Twenty-six out of 35 patients (74% presented at least one of the HFE gene mutations analyzed. Among these, five (14% were C282Y/C282Y, four (11% C282Y/H63D, one (3% H63D/H63D, six (17% C282Y/WT and ten (29% H63D/WT. No patients had the S65C mutation and nine (25% did not present any of the three HFE mutations. Four out of five patients with C282Y/C282Y genotype (80% and three out of four patients with C282Y/H63D genotype (75% were HLA A*03. CONCLUSION: Analysis of HFE gene mutations constitutes an important procedure in identifying patients with hereditary hemochromatosis, particularly for patients with iron overload.

Iron overload triggers mitochondrial fragmentation via calcineurin-sensitive signals in HT-22 hippocampal neuron cells

International Nuclear Information System (INIS)

Park, Junghyung; Lee, Dong Gil; Kim, Bokyung; Park, Sun-Ji; Kim, Jung-Hak; Lee, Sang-Rae; Chang, Kyu-Tae; Lee, Hyun-Shik; Lee, Dong-Seok

2015-01-01

Highlights: • FAC-induced iron overload promotes neuronal apoptosis. • Iron overload causes mitochondrial fragmentation in a Drp1-dependent manner. • Iron-induced Drp1 activation depends on dephosphorylation of Drp1(Ser637). • Calcineurin is a key regulator of Drp1-dependent mitochondrial fission by iron. - Abstract: The accumulation of iron in neurons has been proposed to contribute to the pathology of numerous neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. However, insufficient research has been conducted on the precise mechanism underlying iron toxicity in neurons. In this study, we investigated mitochondrial dynamics in hippocampal HT-22 neurons exposed to ferric ammonium citrate (FAC) as a model of iron overload and neurodegeneration. Incubation with 150 μM FAC for 48 h resulted in decreased cell viability and apoptotic death in HT-22 cells. The FAC-induced iron overload triggered mitochondrial fragmentation, which was accompanied by Drp1(Ser637) dephosphorylation. Iron chelation with deferoxamine prevented the FAC-induced mitochondrial fragmentation and apoptotic cell death by inhibiting Drp1(Ser637) dephosphorylation. In addition, a S637D mutation of Drp1, which resulted in a phosphorylation-mimetic form of Drp1 at Ser637, protected against the FAC-induced mitochondrial fragmentation and neuronal apoptosis. FK506 and cyclosporine A, inhibitors of calcineurin activation, determined that calcineurin was associated with the iron-induced changes in mitochondrial morphology and the phosphorylation levels of Drp1. These results indicate that the FAC-induced dephosphorylation of Drp1-dependent mitochondrial fragmentation was rescued by the inhibition of calcineurin activation. Therefore, these findings suggest that calcineurin-mediated phosphorylation of Drp1(Ser637) acts as a key regulator of neuronal cell loss by modulating mitochondrial dynamics in iron-induced toxicity. These results may contribute to the

Transient upregulation of protein kinase C in pressure-overloaded neonatal rat myocardium

Czech Academy of Sciences Publication Activity Database

Hamplová, B.; Novák, F.; Kolář, František; Nováková, O.

2010-01-01

Roč. 59, č. 1 (2010), s. 25-33 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : protein kinase C * cardiac development * pressure overload Subject RIV: ED - Physiology Impact factor: 1.646, year: 2010

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

Science.gov (United States)

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

2015-06-01

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

Chelation Therapy with Oral Solution of Deferiprone in Transfusional Iron-Overloaded Children with Hemoglobinopathies

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Alexandros Makis

2013-01-01

Full Text Available Iron overload in hemoglobinopathies is secondary to blood transfusions, chronic hemolysis, and increased iron absorption and leads to tissue injury requiring the early use of chelating agents. The available agents are parenteral deferoxamine and oral deferiprone and deferasirox. There are limited data on the safety and efficacy of deferiprone at a very young age. The aim of our study was the presentation of data regarding the use of oral solution of deferiprone in 9 children (mean age 6.5, range 2–10 with transfusion dependent hemoglobinopathies (6 beta thalassemia major, 1 thalassemia intermedia, and 2 sickle cell beta thalassemia. The mean duration of treatment was 21.5 months (range 15–31. All children received the oral solution without any problems of compliance. Adverse reactions were temporary abdominal discomfort and diarrhea (1 child, mild neutropenia (1 child that resolved with no need of discontinuation of treatment, and transient arthralgia (1 child that resolved spontaneously. The mean ferritin levels were significantly reduced at the end of 12 months (initial 2440 versus final 1420 μg/L, . This small study shows that oral solution of deferiprone was well tolerated by young children and its use was not associated with major safety concerns. Furthermore, it was effective in decreasing serum ferritin.

Intake of niacin, folate, vitamin B-6, and vitamin B-12 through young adulthood and cognitive function in midlife: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Science.gov (United States)

Qin, Bo; Xun, Pengcheng; Jacobs, David R; Zhu, Na; Daviglus, Martha L; Reis, Jared P; Steffen, Lyn M; Van Horn, Linda; Sidney, Stephen; He, Ka

2017-10-01

Background: Epidemiologic evidence regarding niacin, folate, vitamin B-6, and vitamin B-12 intake in relation to cognitive function is limited, especially in midlife. Objective: We hypothesize that higher intake of these B vitamins in young adulthood is associated with better cognition later in life. Design: This study comprised a community-based multicenter cohort of black and white men and women aged 18-30 y in 1985-1986 (year 0, i.e., baseline) from the Coronary Artery Risk Development in Young Adults (CARDIA) study ( n = 3136). We examined participants' CARDIA diet history at years 0, 7, and 20 to assess nutrient intake, including dietary and supplemental B vitamins. We measured cognitive function at year 25 (mean ± SD age: 50 ± 4 y) through the use of the Rey Auditory Verbal Learning Test (RAVLT) for verbal memory, the Digit Symbol Substitution Test (DSST) for psychomotor speed, and a modified Stroop interference test for executive function. Higher RAVLT and DSST scores and a lower Stroop score indicated better cognitive function. We used multivariable-adjusted linear regressions to estimate mean differences in cognitive scores and 95% CIs. Results: Comparing the highest quintile with the lowest (quintile 5 compared with quintile 1), cumulative total intake of niacin was significantly associated with 3.92 more digits on the DSST (95% CI: 2.28, 5.55; P -trend vitamin B-6 (quartile 5 compared with quartile 1: 2.62; 95% CI: 0.97, 4.28; P -trend = 0.02) and vitamin B-12 (quartile 5 compared with quartile 1: 2.08; 95% CI: 0.52, 3.65; P -trend = 0.02) resulted in better psychomotor speed measured by DSST scores. Conclusion: Higher intake of B vitamins throughout young adulthood was associated with better cognitive function in midlife. © 2017 American Society for Nutrition.

Functional Role of HSP47 in the Periodontal Ligament Subjected to Occlusal Overload in Mice.

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Mimura, Hiroaki; Takaya, Tatsuo; Matsuda, Saeka; Nakano, Keisuke; Muraoka, Rina; Tomida, Mihoko; Okafuji, Norimasa; Fujii, Takeo; Kawakami, Toshiyuki

2016-01-01

We carried out an experiment to induce traumatic occlusion in mice periodontal tissue and analyzed the expression of HSP47. Continuous traumatic occlusion resulted to damage and remodeling of periodontal ligament as well as increase in osteoclasts and bone resorption. Four days after traumatic occlusion, osteoclasts did not increase but Howship's lacunae became enlarged. That is, the persistent occlusal overload can destroy collagen fibers in the periodontal ligament. This was evident by the increased in HSP47 expression with the occlusal overload. HSP47 is maintained in fibroblasts for repair of damaged collagen fibers. On the other hand, osteoclasts continue to increase although the load was released. The osteoclasts that appeared on the alveolar bone surface were likely due to sustained activity. The increase in osteoclasts was estimated to occur after load application at day 4. HSP47 continued to increase until day 6 in experiment 2 but then reduced at day 10. Therefore, HSP47 appears after a period of certain activities to repair damaged collagen fibers, and the activity was returned to a state of equilibrium at day 30 with significantly diminished expression. Thus, the results suggest that HSP47 is actively involved in homeostasis of periodontal tissue subjected to occlusal overload.

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

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Marko Kostic

2015-10-01

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

Competing for Attention in Social Media under Information Overload Conditions.

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Feng, Ling; Hu, Yanqing; Li, Baowen; Stanley, H Eugene; Havlin, Shlomo; Braunstein, Lidia A

2015-01-01

Modern social media are becoming overloaded with information because of the rapidly-expanding number of information feeds. We analyze the user-generated content in Sina Weibo, and find evidence that the spread of popular messages often follow a mechanism that differs from the spread of disease, in contrast to common belief. In this mechanism, an individual with more friends needs more repeated exposures to spread further the information. Moreover, our data suggest that for certain messages the chance of an individual to share the message is proportional to the fraction of its neighbours who shared it with him/her, which is a result of competition for attention. We model this process using a fractional susceptible infected recovered (FSIR) model, where the infection probability of a node is proportional to its fraction of infected neighbors. Our findings have dramatic implications for information contagion. For example, using the FSIR model we find that real-world social networks have a finite epidemic threshold in contrast to the zero threshold in disease epidemic models. This means that when individuals are overloaded with excess information feeds, the information either reaches out the population if it is above the critical epidemic threshold, or it would never be well received.

Competing for Attention in Social Media under Information Overload Conditions.

Directory of Open Access Journals (Sweden)

Ling Feng

Full Text Available Modern social media are becoming overloaded with information because of the rapidly-expanding number of information feeds. We analyze the user-generated content in Sina Weibo, and find evidence that the spread of popular messages often follow a mechanism that differs from the spread of disease, in contrast to common belief. In this mechanism, an individual with more friends needs more repeated exposures to spread further the information. Moreover, our data suggest that for certain messages the chance of an individual to share the message is proportional to the fraction of its neighbours who shared it with him/her, which is a result of competition for attention. We model this process using a fractional susceptible infected recovered (FSIR model, where the infection probability of a node is proportional to its fraction of infected neighbors. Our findings have dramatic implications for information contagion. For example, using the FSIR model we find that real-world social networks have a finite epidemic threshold in contrast to the zero threshold in disease epidemic models. This means that when individuals are overloaded with excess information feeds, the information either reaches out the population if it is above the critical epidemic threshold, or it would never be well received.

Iron overload in very low birth weight infants: Serum Ferritin and adverse outcomes

LENUS (Irish Health Repository)

Barrett, M

2011-11-01

Adequate iron isessential for growth and haematpoiesis. Oral iron supplementation is the standard of care in VLBW infants. Post mortem evidence has confirmed significant iron overload. Excessive free iron has been associated with free radical formation and brain injury in term infants.

Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

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Koide, M.; Hamawaki, M.; Narishige, T.; Sato, H.; Nemoto, S.; DeFreyte, G.; Zile, M. R.; Cooper G, I. V.; Carabello, B. A.

2000-01-01

BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

Risk of iron overload is decreased in beating heart coronary artery surgery compared to conventional bypass.

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Mumby, S; Koh, T W; Pepper, J R; Gutteridge, J M

2001-11-29

Conventional cardiopulmonary bypass surgery (CCPB) increases the iron loading of plasma transferrin often to a state of plasma iron overload, with the presence of low molecular mass iron. Such iron is a potential risk factor for oxidative stress and microbial virulence. Here we assess 'off-pump' coronary artery surgery on the beating heart for changes in plasma iron chemistry. Seventeen patients undergoing cardiac surgery using the 'Octopus' myocardial wall stabilisation device were monitored at five time points for changes in plasma iron chemistry. This group was further divided into those (n=9) who had one- or two- (n=8) vessel grafts, and compared with eight patients undergoing conventional coronary artery surgery. Patients undergoing beating heart surgery had significantly lower levels of total plasma non-haem iron, and a decreased percentage saturation of their transferrin at all time points compared to conventional bypass patients. Plasma iron overload occurred in only one patient undergoing CCPB. Beating heart surgery appears to decrease red blood cell haemolysis, and tissue damage during the operative procedures and thereby significantly decreases the risk of plasma iron overload associated with conventional bypass.

Evaluation of bone loss due to primary occlusal trauma in two experimental models of occlusal overload

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Ana Cristina Távora de Albuquerque LOPES

Full Text Available Abstract Introduction Primary occlusal trauma (OT is an injury of the periodontium with normal height as a result of occlusal forces which exceed their adaptive capacity. Objective To evaluate, histometrically, the alveolar bone loss in the furcation region of rats experimentally submitted to 2 models of occlusal overload. Material and method 45 animals randomly divided into 3 groups: Occlusal Interference (OI, n = 15 - fixing an orthodontic wire segment on the occlusal surface of the first lower molar; Occlusal Overload (OO, n = 15 - wearing of the cusps of the lower contralateral molars, the second and third molars next to the first molar that had its dimensions maintained; Negative Control (NC, n = 15 - evaluation of the initial dimensions of the periodontal ligament (PL. Five animals / group were sacrificed after 14, 21 and 28 days. Result Intergroup evaluation showed significant bone loss in OI (p0.05. The thickness of the PL remained stable in NC (p>0.05. Conclusion OI and OO were effective in the experimental reproduction of OT, and OI promoted greater alveolar bone loss compared to OO, showing that the impact of occlusal overload in OI increased the extent of the OT injury.

Assessment of β-methyl iodophenyl pentadecanoic acid myocardial scintigraphy in patients with chronic pulmonary diseases

International Nuclear Information System (INIS)

Matsumoto, Hiroyuki; Takeuchi, Katsuro; Ogasa, Tomoyuki

1999-01-01

The purpose of this study was to determine whether impaired fatty acid metabolism occurs in the right ventricle of patients with chronic pulmonary diseases (TB sequelae, TB seq.: 8, and chronic pulmonary emphysema, CPE: 14). 123 I-BMIPP myocardial scintigraphy was performed on 22 subjects. The RV-BMIPP index (ratio of radioactivity in the right ventricle to that in the upper mediastinum), LV-BMIPP index (ratio of radioactivity in the left ventricle to that in the upper mediastinum), and RVc/LVc (ratio of radioactivity in the right ventricle to that in the left ventricle) were calculated to compare the distribution of radioactivity in the right and left ventricles. We also examined the correlations between these parameters and parameters of blood gas analysis and pulmonary hemodynamics. The RV-BMIPP index, LV-BMIPP index, and RVc/LVc were elevated in the TB seq. and CPE patient groups compared to the control group. The RV-BMIPP and LV-BMIPP indices demonstrated significant, negative correlations with PaO 2 ; also a significant positive correlation was observed between the RV-BMIPP index and mean pulmonary arterial pressure. On the other hand, no significant correlation was found between the LV-BMIPP index and mean pulmonary arterial pressure. In the arm-stretching test under right heart catheterization, the RV-BMIPP and LV-BMIPP indices demonstrated significant, positive correlations with the cardiac index during exercise. These results suggest that hypoxemia accelerates fatty acid metabolism in the myocardium, and that local pressure overloading accelerates fatty acid metabolism in the right ventricle. Anomalies of fatty acid metabolism in the right ventricle may appear in patients with chronic pulmonary disease, and could be an adaptation to hypoxemia and overload, not an impairment. (author)

The spring balance: a simple monitoring system for fluid overload during hysteroscopic surgery

NARCIS (Netherlands)

Ankum, W. M.; Vonk, J.

1994-01-01

Fluid overload may arise during hysteroscopic surgery, caused by absorption of fluid used to distend the uterus. Continuous monitoring of the fluid balance is required to prevent this serious complication. Commercial equipment does not serve this purpose adequately. We describe a simple solution. We

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

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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, 30ms, weak relationship. All subjects 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.

77 FR 11598 - Thermal Overload Protection for Electric Motors on Motor-Operated Valves

Science.gov (United States)

2012-02-27

... application of thermal overload protection devices that are integral with the motor starter for electric... Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone: 301-251-7455; email... Development Branch, Division of Engineering, Office of Nuclear Regulatory Research. [FR Doc. 2012-4552 Filed 2...

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

Science.gov (United States)

2010-07-01

... short-circuit protection. 77.506 Section 77.506 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... circuits; overload and short-circuit protection. Automatic circuit-breaking devices or fuses of the correct type and capacity shall be installed so as to protect all electric equipment and circuits against short...

The associations of supervisor support and work overload with burnout and depression: a cross-sectional study in two nursing settings.

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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.

Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of Grape seed proanthocyanidin extract.

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Niu, Qiang; He, Ping; Xu, Shangzhi; Ma, Ruling; Ding, Yusong; Mu, Lati; Li, Shugang

2018-01-01

Emerging evidence has demonstrated that iron overload plays an important role in oxidative stress in the liver. This study aimed to explore whether fluoride-induced hepatic oxidative stress is associated with iron overload and whether grape seed proanthocyanidin extract (GSPE) alleviates oxidative stress by reducing iron overload. Forty Kunming male mice were randomly divided into 4 groups and treated for 5 weeks with distilled water (control), sodium fluoride (NaF) (100 mg/L), GSPE (400 mg/kg bw), or NaF (100 mg/L) + GSPE (400 mg/kg bw). Mice exposed to NaF showed typical poisoning changes of morphology, increased aspartate aminotransferase and alanine aminotransferase activities in the liver. NaF treatment also increased MDA accumulation, decreased GSH-Px, SOD and T-AOC levels in liver, indicative of oxidative stress. Intriguingly, all these detrimental effects were alleviated by GSPE. Further study revealed that NaF induced disorders of iron metabolism, as manifested by elevated iron level with increased hepcidin but decreased ferroportin expression, which contributed to hepatic oxidative stress. Importantly, the iron dysregulation induced by NaF could be normalized by GSPE. Collectively, these data provide a novel insight into mechanisms underlying fluorosis and highlight the potential of GSPE as a naturally occurring prophylactic treatment for fluoride-induced hepatotoxicity associated with iron overload.

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

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Porter John B

2010-04-01

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

Inherent overload protection for the series resonant converter

Science.gov (United States)

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).

Mental Strain and Chronic Stress among University Students with Symptoms of Irritable Bowel Syndrome

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Marco D. Gulewitsch

2013-01-01

Full Text Available Aim. To investigate the degree of mental strain and chronic stress in a German community sample of students with IBS-like symptoms. Methods and Materials. Following an internet-based survey about stress, this study recruited 176 German university students (23.45±2.48 years; 48.3% males with IBS-like symptoms according to Rome III and 181 students without IBS (23.55±2.82 years; 50.3% males and compared them regarding current mental strain (SCL-90-R and the extend of chronic stress. Beyond this, IBS subtypes, IBS severity, and health care utilization were assessed. Results. Students fulfilling IBS criteria showed significantly elevated values of mental strain and chronic stress. Nearly 40% of the IBS group (versus 20% of the controls reached a clinically relevant value on the SCL-90-R global severity scale. IBS subtypes did not differ in terms of mental distress or chronic stress. Somatization, anxiety, and the chronic stressors “work overload,” “social tension,” and “dissatisfaction with job” were most closely connected to IBS symptom severity. Regarding health care utilization, our results show that consulting a physician frequently was not associated significantly with elevated mental strain or chronic stress but with IBS symptom severity. Conclusion. Our data contribute additional evidence to the distinct association between psychological stress and IBS in community samples.

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

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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.

Extremely low-frequency magnetic exposure appears to have no effect on pathogenesis of Alzheimer's disease in aluminum-overloaded rat.

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Cheng Zhang

Full Text Available OBJECTIVE: Extremely low-frequency magnetic field (ELF-MF has been reported to be of potential pathogenetic relevance to Alzheimer's disease (AD for years. However, evidence confirming this function remains inconclusive. Chronic Al treatment has been identified as a contributing factor to cognitive function impairment in AD. This study aims to examine whether or not ELF-MF and Al have synergistic effects toward AD pathogenesis by investigating the effects of ELF-MF with or without chronic Al treatment on SD rats. METHODS: Sprague-Dawley (SD rats were subjected one of the following treatments: sham (control group, oral Al (Al group, ELF-MF (100 µT at 50 Hz with oral Al (MF+Al group, or ELF-MF (100 µT at 50 Hz without oral Al (MF group. RESULTS: After 12 wk of treatment, oral Al treatment groups (Al and MF+Al groups showed learning and memory impairment as well as morphological hallmarks, including neuronal cell loss and high density of amyloid-β (Aβ in the hippocampus and cerebral cortex. ELF-MF without Al treatment showed no significant effect on AD pathogenesis. ELF-MF+Al treatment induced no more damage than Al treatment did. CONCLUSIONS: Our results showed no evidence of any association between ELF-MF exposure (100 µT at 50 Hz and AD, and ELF-MF exposure does not influence the pathogenesis of AD induced by Al overload.

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

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Audrius Kilikevicius

2016-11-01

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

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

NARCIS (Netherlands)

Liang, W.

2015-01-01

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

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

Science.gov (United States)

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…

Comparison of FDG-PET/CT images between chronic renal failure patients on hemodialysis and controls.

Science.gov (United States)

Toriihara, Akira; Kitazume, Yoshio; Nishida, Hidenori; Kubota, Kazunori; Nakadate, Masashi; Tateishi, Ukihide

2015-01-01

The whole-body 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) distribution in chronic renal failure (CRF) patients on hemodialysis would be different from that in subjects with normal renal function, because they lack urinary FDG excretion and remain in a constant volume overload. We evaluated the difference in the physiological uptake pattern of FDG between chronic renal failure patients on hemodialysis and control subjects. The subjects for this retrospective study consisted of 24 chronic renal failure patients on hemodialysis (HD group) and 24 age- and sex-matched control subjects (NC group). Standardized uptake values normalized by the body weight (SUVbw), ideal body weight (SUVibw), lean body mass (SUVlbm), and body surface area (SUVbsa) in the cerebellum, lungs, liver, gluteal muscles and subcutaneous fat, spleen, thoracolumbar spine, thoracic and abdominal aorta, and right atrium were calculated in positron emission tomography/computed tomography (PET/CT) images. SUVbw in the gluteal muscles, subcutaneous fat, spleen and right atrium was significantly higher in the HD group as compared to that in the NC group (p chronic renal failure patients on hemodialysis show significantly higher physiological FDG uptake in the soft tissues, spleen and blood pool.

Comparison of FDG-PET/CT images between chronic renal failure patients on hemodialysis and controls

Science.gov (United States)

Toriihara, Akira; Kitazume, Yoshio; Nishida, Hidenori; Kubota, Kazunori; Nakadate, Masashi; Tateishi, Ukihide

2015-01-01

The whole-body 2-deoxy-2-[18F]fluoro-D-glucose (FDG) distribution in chronic renal failure (CRF) patients on hemodialysis would be different from that in subjects with normal renal function, because they lack urinary FDG excretion and remain in a constant volume overload. We evaluated the difference in the physiological uptake pattern of FDG between chronic renal failure patients on hemodialysis and control subjects. The subjects for this retrospective study consisted of 24 chronic renal failure patients on hemodialysis (HD group) and 24 age- and sex-matched control subjects (NC group). Standardized uptake values normalized by the body weight (SUVbw), ideal body weight (SUVibw), lean body mass (SUVlbm), and body surface area (SUVbsa) in the cerebellum, lungs, liver, gluteal muscles and subcutaneous fat, spleen, thoracolumbar spine, thoracic and abdominal aorta, and right atrium were calculated in positron emission tomography/computed tomography (PET/CT) images. SUVbw in the gluteal muscles, subcutaneous fat, spleen and right atrium was significantly higher in the HD group as compared to that in the NC group (p chronic renal failure patients on hemodialysis show significantly higher physiological FDG uptake in the soft tissues, spleen and blood pool. PMID:25973341

Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress.

Science.gov (United States)

Camacho, A; Simão, M; Ea, H-K; Cohen-Solal, M; Richette, P; Branco, J; Cancela, M L

2016-03-01

Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

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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.

Iron overload of human colon adenocarcinoma cells studied by synchrotron-based X-ray techniques

NARCIS (Netherlands)

Mihucz, Victor G.; Meirer, Florian; Polgári, Zsófia; Réti, Andrea; Pepponi, Giancarlo; Ingerle, Dieter; Szoboszlai, Norbert; Streli, Christina

2016-01-01

Fast- and slow-proliferating human adenocarcinoma colorectal cells, HT-29 and HCA-7, respectively, overloaded with transferrin (Tf), Fe(III) citrate, Fe(III) chloride and Fe(II) sulfate were studied by synchrotron radiation total-reflection X-ray spectrometry (TXRF), TXRF-X-ray absorption near edge

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-04-15

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

Vitamin paradox in obesity: Deficiency or excess?

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Zhou, Shi-Sheng; Li, Da; Chen, Na-Na; Zhou, Yiming

2015-08-25

Since synthetic vitamins were used to fortify food and as supplements in the late 1930s, vitamin intake has significantly increased. This has been accompanied by an increased prevalence of obesity, a condition associated with diabetes, hypertension, cardiovascular disease, asthma and cancer. Paradoxically, obesity is often associated with low levels of fasting serum vitamins, such as folate and vitamin D. Recent studies on folic acid fortification have revealed another paradoxical phenomenon: obesity exhibits low fasting serum but high erythrocyte folate concentrations, with high levels of serum folate oxidation products. High erythrocyte folate status is known to reflect long-term excess folic acid intake, while increased folate oxidation products suggest an increased folate degradation because obesity shows an increased activity of cytochrome P450 2E1, a monooxygenase enzyme that can use folic acid as a substrate. There is also evidence that obesity increases niacin degradation, manifested by increased activity/expression of niacin-degrading enzymes and high levels of niacin metabolites. Moreover, obesity most commonly occurs in those with a low excretory reserve capacity (e.g., due to low birth weight/preterm birth) and/or a low sweat gland activity (black race and physical inactivity). These lines of evidence raise the possibility that low fasting serum vitamin status in obesity may be a compensatory response to chronic excess vitamin intake, rather than vitamin deficiency, and that obesity could be one of the manifestations of chronic vitamin poisoning. In this article, we discuss vitamin paradox in obesity from the perspective of vitamin homeostasis.

Iron overload in the liver diagnostic and quantification

Energy Technology Data Exchange (ETDEWEB)

Alustiza, Jose M. [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain)]. E-mail: jmalustiza@osatek.es; Castiella, Agustin [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Juan, Maria D. de [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Emparanza, Jose I. [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Artetxe, Jose [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Uranga, Maite [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain)

2007-03-15

Hereditary Hemochromatosis is the most frequent modality of iron overload. Since 1996 genetic tests have facilitated significantly the non-invasive diagnosis of the disease. There are however many cases of negative genetic tests that require confirmation by hepatic iron quantification which is traditionally performed by hepatic biopsy. There are many studies that have demonstrated the possibility of performing hepatic iron quantification with Magnetic Resonance. However, a consensus has not been reached yet regarding the technique or the possibility to reproduce the same method of calculus in different machines. This article reviews the state of the art of the question and delineates possible future lines to standardise this non-invasive method of hepatic iron quantification.

Iron overload in the liver diagnostic and quantification

International Nuclear Information System (INIS)

Alustiza, Jose M.; Castiella, Agustin; Juan, Maria D. de; Emparanza, Jose I.; Artetxe, Jose; Uranga, Maite

2007-01-01

Hereditary Hemochromatosis is the most frequent modality of iron overload. Since 1996 genetic tests have facilitated significantly the non-invasive diagnosis of the disease. There are however many cases of negative genetic tests that require confirmation by hepatic iron quantification which is traditionally performed by hepatic biopsy. There are many studies that have demonstrated the possibility of performing hepatic iron quantification with Magnetic Resonance. However, a consensus has not been reached yet regarding the technique or the possibility to reproduce the same method of calculus in different machines. This article reviews the state of the art of the question and delineates possible future lines to standardise this non-invasive method of hepatic iron quantification

Hemochromatosis C282Y gene mutation as a potential susceptibility factor for iron-overload in Egyptian beta-thalassemia patients

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G.M. Mokhtar

2018-04-01

Full Text Available Background: Hereditary hemochromatosis is the most frequent cause of primary iron overload that is associated with HFE gene’s mutation especially the C282Y mutation. The interaction between hemoglobin chain synthesis’ disorders and the C282Y mutation may worsen the clinical picture of beta-thalassemia major (β-TM. Aim: To establish the prevalence of the C282Y mutations in Egyptian β-TM patients and to address its adverse effects. Methods: Two-hundred and five β-TM patients were recruited and divided into two groups based on their serum ferritin (SF; group I (N = 125 (SF ≤ 2500 ng/dl and group II (N = 80 (SF > 2500 ng/dl. All patients were subjected to clinical and laboratory assessment with special emphasis on iron overload complications. Genotyping was assessed by polymerase chain reaction for detection of C282Y mutation in HFE gene. Results: The C282Y mutation was not detected in the studied β-TM neither in homozygous nor heterozygous state. There were several iron overload complications including cardiac complication (9.1%, liver disease (36.6%, delayed puberty (56.6%, primary (35.71% and secondary amenorrhea (21.42%, short stature (27.3%, diabetes (3.4%, neutropenia (9.7%, arthralgia (10.2%, gastrointestinal (21.1%, depression (2.9% and others (12.05%. Group I showed a statistically significant lower rate of taking iron-rich diet when compared to group II. Group II showed significant longer mean duration of disease, higher total transfusion rate per life, lower mean HbF% level, higher mean HbA% level, and higher rate of elevated liver enzymes than patients with SF ≤ 2500 ng/dl. Conclusion: The C282Y mutation was not detected in the studied cohort of Egyptian β-TM patients neither in homozygous nor heterozygous state in spite of manifestations of iron overload complications. Keywords: Beta-thalassemia major, Hereditary hemochromatosis, The C282Y mutation, Iron overload complications, Egyptian

Information overload or search-amplified risk? Set size and order effects on decisions from experience.

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Hills, Thomas T; Noguchi, Takao; Gibbert, Michael

2013-10-01

How do changes in choice-set size influence information search and subsequent decisions? Moreover, does information overload influence information processing with larger choice sets? We investigated these questions by letting people freely explore sets of gambles before choosing one of them, with the choice sets either increasing or decreasing in number for each participant (from two to 32 gambles). Set size influenced information search, with participants taking more samples overall, but sampling a smaller proportion of gambles and taking fewer samples per gamble, when set sizes were larger. The order of choice sets also influenced search, with participants sampling from more gambles and taking more samples overall if they started with smaller as opposed to larger choice sets. Inconsistent with information overload, information processing appeared consistent across set sizes and choice order conditions, reliably favoring gambles with higher sample means. Despite the lack of evidence for information overload, changes in information search did lead to systematic changes in choice: People who started with smaller choice sets were more likely to choose gambles with the highest expected values, but only for small set sizes. For large set sizes, the increase in total samples increased the likelihood of encountering rare events at the same time that the reduction in samples per gamble amplified the effect of these rare events when they occurred-what we call search-amplified risk. This led to riskier choices for individuals whose choices most closely followed the sample mean.

Severe pulmonary hypertension in a young patient with end-stage renal disease on chronic hemodialysis

International Nuclear Information System (INIS)

Sharma, Satyavan; Kirpalani, Ashok L; Kulkarni, Amit

2010-01-01

Severe pulmonary hypertension in a teenager with end-stage renal disease on chronic hemodialysis via arteriovenous access is reported. Clinical presentation included persistent volume overload and pericardial effusion. Serial hemodynamic data obtained at cardiac catheterization confirmed the diagnosis. In addition, detailed biochemical and imaging data (echo- Doppler, computed tomography of chest, computed tomographic pulmonary angiography, VQ lung scan, etc.) were obtained to find out the mechanism. The exact cause of pulmonary hypertension remains unclear, and a multi- factorial mechanism is postulated. This rare case is presented to highlight the role of aggressive dialysis, pericardiocentesis, and use of sildenafil and bosentan in the management

Role of Three-Dimensional Speckle Tracking Echocardiography in the Quantification of Myocardial Iron Overload in Patients with Beta-Thalassemia Major.

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Li, Shu-Juan; Hwang, Yu-Yan; Ha, Shau-Yin; Chan, Godfrey C F; Mok, Amanda S P; Wong, Sophia J; Cheung, Yiu-Fai

2016-09-01

The new three-dimensional speckle tracking echocardiography (3DSTE) may enable comprehensive quantification of global left ventricular (LV) myocardial mechanics. Twenty-four patients aged 29.3 ± 5.2 years and 22 controls were studied. 3DSTE was performed to assess LV 3D global strain, twist and torsion, ejection fraction, and systolic dyssynchrony index (SDI). The LV SDI was calculated as % of SD of times-to-peak strain of 16 segments/RR interval. The global performance index (GPI) was calculated as (global 3D strain·torsion)/SDI. Area under the receiver operating characteristic curve (AUC) was calculated to determine the capability of 3DSTE parameters to discriminate between patients with (cardiac magnetic resonance T2* overload. Compared with controls, patients had significantly lower LV global 3D strain (P overload. The LV composite index of strain, torsion, and dyssynchrony derived from 3DSTE enables sensitive detection of myocardial iron overload in patients with thalassemia. © 2016, Wiley Periodicals, Inc.

Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction

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Afzal, Muhammad R.; Samanta, Anweshan; Xuan, Yu-Ting; Girgis, Magdy; Elias, Harold K; Zhu, Yanqing; Davani, Arash; Yang, Yanjuan; Chen, Xing; Ye, Sheng; Wang, Ou-Li; Chen, Lei; Hauptman, Jeryl; Vincent, Robert J.; Dawn, Buddhadeb

2016-01-01

Rationale The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial. Objective To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Methods and Results Wild-type (WT) and IL-6 knockout (IL-6−/−) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6−/− mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6−/− hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from WT and IL-6−/− mice exposed to pro-hypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling. Conclusions Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension. PMID:27126808

Fuzzy ranking based non-dominated sorting genetic algorithm-II for network overload alleviation

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Pandiarajan K.

2014-09-01

Full Text Available This paper presents an effective method of network overload management in power systems. The three competing objectives 1 generation cost 2 transmission line overload and 3 real power loss are optimized to provide pareto-optimal solutions. A fuzzy ranking based non-dominated sorting genetic algorithm-II (NSGA-II is used to solve this complex nonlinear optimization problem. The minimization of competing objectives is done by generation rescheduling. Fuzzy ranking method is employed to extract the best compromise solution out of the available non-dominated solutions depending upon its highest rank. N-1 contingency analysis is carried out to identify the most severe lines and those lines are selected for outage. The effectiveness of the proposed approach is demonstrated for different contingency cases in IEEE 30 and IEEE 118 bus systems with smooth cost functions and their results are compared with other single objective evolutionary algorithms like Particle swarm optimization (PSO and Differential evolution (DE. Simulation results show the effectiveness of the proposed approach to generate well distributed pareto-optimal non-dominated solutions of multi-objective problem

Exploration of overloaded cation exchange chromatography for monoclonal antibody purification.

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Liu, Hui F; McCooey, Beth; Duarte, Tiago; Myers, Deanna E; Hudson, Terry; Amanullah, Ashraf; van Reis, Robert; Kelley, Brian D

2011-09-28

Cation exchange chromatography using conventional resins, having either diffusive or perfusive flow paths, operated in bind-elute mode has been commonly employed in monoclonal antibody (MAb) purification processes. In this study, the performance of diffusive and perfusive cation exchange resins (SP-Sepharose FF (SPSFF) and Poros 50HS) and a convective cation exchange membrane (Mustang S) and monolith (SO(3) Monolith) were compared. All matrices were utilized in an isocratic state under typical binding conditions with an antibody load of up to 1000 g/L of chromatographic matrix. The dynamic binding capacity of the cation exchange resins is typically below 100 g/L resin, so they were loaded beyond the point of anticipated MAb break through. All of the matrices performed similarly in that they effectively retained host cell protein and DNA during the loading and wash steps, while antibody flowed through each matrix after its dynamic binding capacity was reached. The matrices differed, though, in that conventional diffusive and perfusive chromatographic resins (SPSFF and Poros 50HS) demonstrated a higher binding capacity for high molecular weight species (HMW) than convective flow matrices (membrane and monolith); Poros 50HS displayed the highest HMW binding capacity. Further exploration of the conventional chromatographic resins in an isocratic overloaded mode demonstrated that the impurity binding capacity was well maintained on Poros 50HS, but not on SPSFF, when the operating flow rate was as high as 36 column volumes per hour. Host cell protein and HMW removal by Poros 50HS was affected by altering the loading conductivity. A higher percentage of host cell protein removal was achieved at a low conductivity of 3 mS/cm. HMW binding capacity was optimized at 5 mS/cm. Our data from runs on Poros 50HS resin also showed that leached protein A and cell culture additive such as gentamicin were able to be removed under the isocratic overloaded condition. Lastly, a MAb

A new technique for the use of microspheres for the study of intra-cortical distribution of renal blood flow. Results for a normal and sodium overloaded rat. Report of internship performed in the Laboratoire de Physiologie Physico-Chimique (C.E.N. Saclay)

International Nuclear Information System (INIS)

Poujeol, P.

1972-06-01

This academic work reports the simultaneous study on the same kidney of the distribution of glomerular filtrations and the distribution of blood flow rate in the renal cortex. Th author combined the technique of perfusion of sodium "1"4C ferro-cyanide which allows the measurement of individual glomerular filtrations, and a technique based on the use of microspheres which allows the assessment of blood flow distribution in the glomeruli of different nephron classes. Experiments have been performed on a normal rat, and on a rat submitted to a chronic NaCl overload [fr

When Enough Is Not Enough: Information Overload and Metacognitive Decisions to Stop Studying Information

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Murayama, Kou; Blake, Adam B.; Kerr, Tyson; Castel, Alan D.

2016-01-01

People are often exposed to more information than they can actually remember. Despite this frequent form of information overload, little is known about how much information people choose to remember. Using a novel "stop" paradigm, the current research examined whether and how people choose to stop receiving new--possibly…

Glutathione S transferase polymorphisms influence on iron overload in β-thalassemia patients

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Serena Sclafani

2013-11-01

Full Text Available In patients with β-thalassemia iron overload that leads to damage to vital organs is observed. Glutathione S transferase (GST enzymes have an antioxidant role in detoxification processes of toxic substances. This role is determined genetically. In this study, we correlated GSTT1 and GSTM1 genotypes with iron overload measured with direct and indirect non-invasive methods; in particular, we used serum ferritin and signal intensity of the magnetic resonance image (MRI in 42 patients with β-thalassemia, which were regularly subjected to chelation and transfusion therapy. Multiplex polymerase chain reaction was used to determine the genotype. The loss of both alleles leads to a decreased value of liver and heart MRI-signal intensity with a consequent iron accumulation in these organs; the loss of only one allele doesn’t lead to relevant overload. Serum ferritin doesn’t appear to be correlated to iron overload instead. 对于β-地中海贫血患者，由于铁过量而造成重要器官受损的情况也在观察之中。谷胱甘肽S转移酶(GST 酶类在对有毒物质进行解毒的过程中有着抗氧化剂的作用。该作用是由基因决定的。 在这份研究中，我们运用了直接和间接非侵入性的方法对基因型铁过量GSTT1 和GSTM1进行了相关性测量；特别地，我们对４２位定期接受螯合和输血治疗的β-地中海贫血患者进行了血清铁蛋白和磁共振强度图像(MRI 的测试。 多重聚合酶链反应的测试也被运用来确定该基因型。 该两种等位基因的缺失，导致了肝功能减损及心脏磁共振强度的下降，并造成了在这些器官中铁含量的积累；其中一种等位基因的缺失并不会导致过度的铁含量。血清蛋白和铁过量之间，看起来并不存在相关性。

Protection of insulated cables and lines in case of overload

Energy Technology Data Exchange (ETDEWEB)

Goltz, M

1983-01-01

After DIN 57100 Part 430/VDE 0100 part 430 for the protection of lines and cables was published in June 1981, the discussion flared up again whether this DIN/VDE-regulation is sufficient. Some papers have already been published on the right selection and arrangement of overload protection under normal operational conditions. The aim of this contribution is to explain abnormal operational conditions which are dealt with in DIN 57100 part 430/VDE 0100 part 430 in comments and the annex, and to supply some help for planning and projecting.

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

Science.gov (United States)

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 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.

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

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Supranee Upanan

2015-12-01

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

The body of women and the overload of sexuality

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Rosa Cobo Bedia

2015-12-01

Full Text Available This work is approaching to a historically recent social phenomenon: the hipersexualization of women. It looks into its origins and finds that the idea of the sexual freedom that is developed in the 60s, on one side, and the exaltation of the free market, which was developed from the 80s, on the other, come together in the goal of overloading women sexuality. The context in which this process takes place is a free and unlimited market which has understood that women`s bodies are a commodity from which are extracted necessaries appreciations for the social reproduction of contemporary patriarchy and neoliberal capitalism.

Correlates of Cancer Information Overload: Focusing on Individual Ability and Motivation.

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Chae, Jiyoung; Lee, Chul-joo; Jensen, Jakob D

2016-01-01

The present study defined cancer information overload (CIO) as an aversive disposition wherein a person is confused and overwhelmed by cancer information, which occurs when he or she fails to effectively categorize new information due to a lack of resources for effective learning. Based on the definition and informed by previous studies on information overload and the cognitive mediation model, we hypothesized that low ability and motivation to process cancer information would lead to CIO. We used education level and trait anxiety as factors related to ability. Cancer history and the use of active media channels (such as the Internet and print media) were adopted as motivational factors. Four samples (three from the United States and one from South Korea) were used to explore the relationship between ability/motivation and CIO. Among them, only Sample 4 participants answered questions about stomach cancer, and other participants were asked about cancer in general. In all four samples, trait anxiety was positively associated with CIO. Health information use from active media channels (print or the Internet) was negatively associated with CIO in three samples. The associations between family history and CIO, and between education and CIO, were found in two samples. In short, the present study demonstrated that CIO partly depends on individual ability and motivation, thereby showing that CIO is influenced by personal characteristics as well as environmental factors.

The influence of overload on the orientation of hydraulic fractures in Fazenda Alvorada - state of Bahia - Brazil

International Nuclear Information System (INIS)

Araujo, Paulo Fernando de

2000-01-01

Based on density logs, the overload of Fazenda Alvorada field located in the state of Bahia (Brazil) presents an anomalous behavior in relation to the same sedimentary package of the Reconcavo Basin. This anomaly is in function of a relative uplift accompanied of a concomitant bearing or not, with the uplift doing with that the gradients of fracture propagation usually present high values. Comparisons among the gradients of fracture propagation, obtained step-rate-tests accomplished in reservoirs different from 7-FAV-83-BA well, and the overload of this field allowed to identify occurrences of vertical and horizontal fractures. The objective of this work is to present as these results were obtained, as well as its importance in the stimulation projects and of secondary recovery. (author)

Greenness and job-related chronic stress in young adults: a prospective cohort study in Germany.

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

2018-06-04

We aimed to prospectively study the association between normalised difference vegetation index (NDVI) as a measure of greenness around homes and occupational stress. A population-based cohort in Munich and Dresden cities was followed from age 16-18 years to age 20-23 years (n=1632). At baseline, all participants attended high-school while at follow-up some had started working and others studying at university. At baseline and in each follow-up, we assigned NDVI based on participants' residential geocoded addresses and categorised it by quartiles. School-related, university-related or job-related self-reported chronic stress was assessed at the two follow-ups by the Trier Scale for Assessment of Chronic Stress using work discontent and work overload as outcomes. We modelled the association employing ordinal generalised estimating equations model accounting for changes in sociodemographics, non-job-related stress, job history and environmental covariates. Stratified analysis by each city was performed. NVDI at baseline was higher for participants from Dresden (median=0.36; IQR 0.31-0.41) than Munich (0.31; 0.26-0.34). At follow-up, it decreased only for participants in Dresden (0.34; 0.30-0.40). Higher greenness (quartile 4 vs quartile 1) was associated with less work discontent (OR 0.89; 95% CI 0.80 to 0.99) and less work overload (OR 0.87; 95% CI 0.78 to 0.96). In stratified analyses, results were more consistent for Munich than for Dresden. Our results suggest that residential green spaces, using the vegetation index as a proxy for exposure, are inversely associated with two types of job-related chronic stress in German young adults transitioning from school to university or working life. © 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.

Fatty emaciation: a case report of suspected fat overload syndrome in oral refeeding.

Science.gov (United States)

Macher, Arielle D; Palazuelos, Daniel; Maviglia, Saverio M

2012-07-01

Refeeding syndrome has been observed in patients receiving nutrition after a prolonged period of malnourishment and is characterized by multiple metabolic derangements. Besides hypophosphatemia and hypoglycemia, lipemia has been described in association with parenteral nutrition administration to the malnourished. The authors describe one anorexic patient who developed lipemia during oral refeeding, followed by a precipitous drop in hematocrit suggestive of fat overload syndrome.

Iron Overload Leading to Torsades de Pointes in β-Thalassemia and Long QT Syndrome

DEFF Research Database (Denmark)

Refaat, Marwan M; El Hage, Lea; Steffensen, Annette Buur

2016-01-01

The authors present a unique case of torsades de pointes in a β-thalassemia patient with early iron overload in the absence of any structural abnormalities as seen in hemochromatosis. Genetic testing showed a novel KCNQ1 gene mutation 1591C>T [Gln531Ter(X)]. Testing of the gene mutation in Xenopus...

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.

Science.gov (United States)

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.

Attitudes of Doctors and Nurses toward the Chronic Care Model

Directory of Open Access Journals (Sweden)

Rolando Bonal Ruiz

2015-06-01

Full Text Available Background: the fact that chronic diseases replace traditional causes of morbidity and mortality in a country, or are on a par with major common health problems, demands the development of new strategies to address them. Objective: to explore attitudes of doctors and nurses from the Rolando López Peña Polyclinic toward the Chronic Care Model. Methods: a quantitative and qualitative cross-sectional study was conducted including the 22 family physicians and 26 nurses who provide care to patients with chronic diseases and were at the polyclinic at the time of the study. All were administered a 5 point Likert scale and a focus group interview, which was taped, transcribed and analyzed. Results: the attitudinal results correspond with the actions assessed in each component of the model, being the most common barriers: the lack of awareness and training on the new approaches to care of these patients, work overload created by other programs such as the maternal-child and vector control programs, uncertainties on the effectiveness of patient education and ignorance of the practice guidelines. Conclusions: favorable attitudes toward the introduction of the model to the practice of the family physician and nurse predominated as long as organizational changes are made and the suggestions of these service providers are put into practice with the support of the decision makers of the health sector.

Pivotal role of cardiomyocyte TGF-β signaling in the murine pathological response to sustained pressure overload

NARCIS (Netherlands)

Koitabashi, Norimichi; Danner, Thomas; Zaiman, Ari L.; Pinto, Yigal M.; Rowell, Janelle; Mankowski, Joseph; Zhang, Dou; Nakamura, Taishi; Takimoto, Eiki; Kass, David A.

2011-01-01

The cardiac pathological response to sustained pressure overload involves myocyte hypertrophy and dysfunction along with interstitial changes such as fibrosis and reduced capillary density. These changes are orchestrated by mechanical forces and factors secreted between cells. One such secreted

Role Overload, Role Self Distance, Role Stagnation as Determinants of Job Satisfaction and Turnover Intention in Banking Sector

Science.gov (United States)

Kunte, Monica; Gupta, Priya; Bhattacharya, Sonali; Neelam, Netra

2017-01-01

Purpose: This study examined the relationship of the organizational role stress: Role overload, role self-distance, and role stagnation with job satisfaction and turnover intention with a sample of banking employees in India. Methodology: In this research, we used the RODS scale developed by Prohit and Pareek (2010) for measuring occupational role scale. The reliability of the scale came out to be 0.71. Findings: The majority of employees of all ranks, in both private and public sector banks, suffer from high role stress of all types. It was found that role overload and role stagnation are inversely associated with banking employees' job satisfaction. Private sector bank employees have more role stress and more unsatisfied than employees of public sector banks. Employees Turnover intention was found to be positively impacted by job satisfaction, contrary to many other studies. Possible reasons have been suggested. Job satisfaction was found to play a partial mediating role in the relationship between role overload and turnover intention with 40% mediation. Further, employees with longer tenure (work experience) have less role stress and are more satisfied. Originality: This study is unique in the sense there is hardly any study linking role stress to job satisfaction and turnover intention, specially in Indian context. PMID:29200554

Role Overload, Role Self Distance, Role Stagnation as Determinants of Job Satisfaction and Turnover Intention in Banking Sector.

Science.gov (United States)

Kunte, Monica; Gupta, Priya; Bhattacharya, Sonali; Neelam, Netra

2017-01-01

This study examined the relationship of the organizational role stress: Role overload, role self-distance, and role stagnation with job satisfaction and turnover intention with a sample of banking employees in India. In this research, we used the RODS scale developed by Prohit and Pareek (2010) for measuring occupational role scale. The reliability of the scale came out to be 0.71. The majority of employees of all ranks, in both private and public sector banks, suffer from high role stress of all types. It was found that role overload and role stagnation are inversely associated with banking employees' job satisfaction. Private sector bank employees have more role stress and more unsatisfied than employees of public sector banks. Employees Turnover intention was found to be positively impacted by job satisfaction, contrary to many other studies. Possible reasons have been suggested. Job satisfaction was found to play a partial mediating role in the relationship between role overload and turnover intention with 40% mediation. Further, employees with longer tenure (work experience) have less role stress and are more satisfied. This study is unique in the sense there is hardly any study linking role stress to job satisfaction and turnover intention, specially in Indian context.

Spreading the load: mobile information and communications technologies and their effect on information overload

Directory of Open Access Journals (Sweden)

D.K. Allan

2005-01-01

Full Text Available 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 approach was adopted, as complementary to an incremental approach to theory building. An inductive approach is adopted, in which data are collected and the findings are interpreted in the light of previous work. The case site was West Yorkshire Police Force in the UK where BlackBerry handhelds were being used by senior officers. Analysis. A semi-structured interview schedule was developed and applied in face-to-face interviews with the Senior Management Team and their secretaries. All interviews were recorded and the transcripts of the interviews analysed, using qualitative coding. Results. A conceptual model of the interactions and relationships among the key elements that drive and mediate the information flows and information behaviour within a complex organizational environment was developed. Managers' information behaviour and coping strategies were found to have changed since the introduction of mobile devices. Officers are more likely to deal with information received sooner, thereby resulting in less queuing of messages (although filtering strategies still prevail. Approximation (responding in a non-precise way was also found to have increased. In this particular implementation, the mobile technology has not altered the information-pull behaviour of managers. Conclusion. The main finding is that personal information management is now distributed more evenly throughout the day. Thus, the technology has enabled officers to 'spread the load' and, in doing so, has helped to ease some of the pressures created by information overload.

Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats.

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Dai, Shuhui; Hua, Ya; Keep, Richard F; Novakovic, Nemanja; Fei, Zhou; Xi, Guohua

2018-06-05

Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocycline reduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2 ⁎ -weighted and T2 ⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain iron content, ventricle volume, lesion volume and brain swelling. Immunohistochemistry was used to examine changes in iron handling proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal iron overload with upregulated iron handling proteins, neuroinflammation, brain atrophy, neuronal loss and neurological deficits. Minocycline significantly reduced ICH-induced perihematomal iron overload and iron handling proteins. It further reduced brain swelling, neuroinflammation, neuronal loss, delayed brain atrophy and neurological deficits. These effects may be linked to the role of minocycline as an iron chelator as well as an inhibitor of neuroinflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

Transient receptor potential vanilloid-3 (TRPV3) activation plays a central role in cardiac fibrosis induced by pressure overload in rats via TGF-β1 pathway.

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Liu, Yan; Qi, Hanping; E, Mingyao; Shi, Pilong; Zhang, Qianhui; Li, Shuzhi; Wang, Ye; Cao, Yonggang; Chen, Yunping; Ba, Lina; Gao, Jingquan; Huang, Wei; Sun, Hongli

2018-02-01

Cardiac fibrosis is a common pathologic change along with pressure overload. Recent studies indicated that transient receptor potential (TRP) channels played multiple roles in heart. However, the functional role of transient receptor potential vanilloid-3 (TRPV3) in cardiac fibrosis remained unclear. The present study was designed to investigate the relationship between TRPV3 activation and pressure overload-induced cardiac fibrosis. Pressure overload rats were successfully established by abdominal aortic constriction (AAC), and cardiac fibrosis was simulated by 100 nM angiotensin II (Ang II) in neonatal cardiac fibroblasts. Echocardiographic parameters, cardiac fibroblast proliferation, cell cycle, intracellular calcium concentration ([Ca 2+ ] i ), and the protein expressions of collagen I, collagen III, transforming growth factor beta 1 (TGF-β 1 ), cyclin E, and cyclin-dependent kinase 2 (CDK2) were measured. Echocardiographic and histological measurements suggested that the activation of TRPV3 exacerbated the cardiac dysfunction and increased interstitial fibrosis in pressure overload rats. Further results showed that TRPV3 activation upregulated the expressions of collagen I, collagen III, TGF-β 1 , cyclin E, and CDK2 in vivo and in vitro. At the same time, blocking TGF-β 1 pathway could partially reverse the effect of TRPV3 activation. These results suggested that TRPV3 activation exacerbated cardiac fibrosis by promoting cardiac fibroblast proliferation through TGF-β 1 /CDK2/cyclin E pathway in the pressure-overloaded rat hearts.

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).

Science.gov (United States)

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).

Estudo das mutações C282Y, H63D e S65C do gene HFE em doentes brasileiros com sobrecarga de ferro Study of C282Y, H63D and S65C mutations in the HFE gene in Brazilian patients with iron overload

Directory of Open Access Journals (Sweden)

Rodolfo D. Cançado

2007-12-01

Full Text Available Hemocromatose é uma das doenças genéticas mais freqüentes no ser humano e uma das causas mais importantes de sobrecarga de ferro. Os objetivos deste estudo foram determinar a freqüência das mutações C282Y, H63D e S65C do gene HFE em doentes brasileiros com sobrecarga de ferro, verificar a coexistência de anemia hemolítica hereditária, hepatite C e consumo excessivo de bebida alcoólica nestes doentes e avaliar a influência destas variáveis sobre os depósitos de ferro do organismo. Saturação da transferrina, ferritina sérica e análise das mutações C282Y, H63D e S65C do gene HFE, pelo método da PCR, foram determinadas em cinqüenta doentes com sobrecarga de ferro atendidos no Hemocentro da Santa Casa de São Paulo entre janeiro de 2000 e maio de 2004. A freqüência de mutação do gene HFE nos doentes com sobrecarga de ferro foi de 76,0% (38/50. Saturação da transferrina e ferritina foram significativamente maiores nos doentes homozigotos para a mutação C282Y confirmando a correlação entre genótipo C282Y/C282Y e maior risco de sobrecarga de ferro. A coexistência de hepatite C, consumo excessivo de bebida alcoólica ou anemia hemolítica hereditária estão implicados em aumento dos estoques de ferro e constituem fator de risco adicional em pacientes com mutação do gene HFE para a condição de sobrecarga de ferro.Hemochromatosis is one of the most frequent genetic diseases in humans and one of the most important causes of iron overload. The aims of this study were to determine the frequency of C282Y, H63D and S65C mutations of the HFE gene in Brazilian patients with iron overload, to verify the coexistence of chronic hemolytic anemia, hepatitis C and excessive alcohol consumption and to evaluate the influence of these variables on body iron deposits. Transferrin saturation, serum ferritin and C282Y, H63D and S65C HFE gene mutations (by PCR method were determined in 50 patients with iron overload in the Hemocentro da

Self-Control, Self-Efficacy, Role Overload, and Stress Responses among Siblings of Children with Cancer

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Hamama, Liat; Ronen, Tammie; Rahav, Giora

2008-01-01

The study focuses on healthy children's responses to a sibling's cancer and its aftermath, with particular scrutiny directed toward these healthy siblings' stress factors, duress responses, and coping resources. The authors investigated role overload as these siblings' stress factor, anxiety and psychosomatic symptoms as their duress responses,…

Operator overloading as an enabling technology for automatic differentiation

International Nuclear Information System (INIS)

Corliss, G.F.; Griewank, A.

1993-01-01

We present an example of the science that is enabled by object-oriented programming techniques. Scientific computation often needs derivatives for solving nonlinear systems such as those arising in many PDE algorithms, optimization, parameter identification, stiff ordinary differential equations, or sensitivity analysis. Automatic differentiation computes derivatives accurately and efficiently by applying the chain rule to each arithmetic operation or elementary function. Operator overloading enables the techniques of either the forward or the reverse mode of automatic differentiation to be applied to real-world scientific problems. We illustrate automatic differentiation with an example drawn from a model of unsaturated flow in a porous medium. The problem arises from planning for the long-term storage of radioactive waste

Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

International Nuclear Information System (INIS)

Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Zhou, Heng; Xu, Dachun; Shan, Tichao; Zhang, Fan; Guo, Yuan; Chen, Yuguo; Wu, Dawei

2015-01-01

Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

Energy Technology Data Exchange (ETDEWEB)

Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: chen919085@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)

2015-09-01

Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

Peripheral Venous Waveform Analysis for Detecting Hemorrhage and Iatrogenic Volume Overload in a Porcine Model.

Science.gov (United States)

Hocking, Kyle M; Sileshi, Ban; Baudenbacher, Franz J; Boyer, Richard B; Kohorst, Kelly L; Brophy, Colleen M; Eagle, Susan S

2016-10-01

Unrecognized hemorrhage and unguided resuscitation is associated with increased perioperative morbidity and mortality. The authors investigated peripheral venous waveform analysis (PIVA) as a method for quantitating hemorrhage as well as iatrogenic fluid overload during resuscitation. The authors conducted a prospective study on Yorkshire Pigs (n = 8) undergoing hemorrhage, autologous blood return, and administration of balanced crystalloid solution beyond euvolemia. Intra-arterial blood pressure, electrocardiogram, and pulse oximetry were applied to each subject. Peripheral venous pressure was measured continuously through an upper extremity standard peripheral IV catheter and analyzed with LabChart. The primary outcome was comparison of change in the first fundamental frequency (f1) of PIVA with standard and invasive monitoring and shock index (SI). Hemorrhage, return to euvolemia, and iatrogenic fluid overload resulted in significantly non-zero slopes of f1 amplitude. There were no significant differences in heart rate or mean arterial pressure, and a late change in SI. For the detection of hypovolemia the PIVA f1 amplitude change generated an receiver operator curves (ROC) curve with an area under the curve (AUC) of 0.93; heart rate AUC = 0.61; mean arterial pressure AUC = 0.48, and SI AUC = 0.72. For hypervolemia the f1 amplitude generated an ROC curve with an AUC of 0.85, heart rate AUC = 0.62, mean arterial pressure AUC = 0.63, and SI AUC = 0.65. In this study, PIVA demonstrated a greater sensitivity for detecting acute hemorrhage, return to euvolemia, and iatrogenic fluid overload compared with standard monitoring and SI. PIVA may provide a low-cost, minimally invasive monitoring solution for monitoring and resuscitating patients with perioperative hemorrhage.

Acute bovine laminitis: a new induction model using alimentary oligofructose overload.

Science.gov (United States)

Thoefner, M B; Pollitt, C C; Van Eps, A W; Milinovich, G J; Trott, D J; Wattle, O; Andersen, P H

2004-09-01

Twelve dairy heifers were used to examine the clinical response of an alimentary oligofructose overload. Six animals were divided into 3 subgroups, and each was given a bolus dose of 13, 17, or 21 g/kg of oligofructose orally. The control group (n = 6) was sham-treated with tap water. Signs of lameness, cardiovascular function, and gastrointestinal function were monitored every 6 h during development of rumen acidosis. The heifers were euthanized 48 and 72 h after administration of oligofructose. All animals given oligofructose developed depression, anorexia, and diarrhea 9 to 39 h after receiving oligofructose. By 33 to 45 h after treatment, the feces returned to normal consistency and the heifers began eating again. Animals given oligofructose developed transient fever, severe metabolic acidosis, and moderate dehydration, which were alleviated by supportive therapy. Four of 6 animals given oligofructose displayed clinical signs of laminitis starting 39 to 45 h after receiving oligofructose and lasting until euthanasia. The lameness was obvious, but could easily be overlooked by the untrained eye, because the heifers continued to stand and walk, and did not interrupt their eating behavior. No positive pain reactions or lameness were seen in control animals. Based on these results, we conclude that an alimentary oligofructose overload is able to induce signs of acute laminitis in cattle. This model offers a new method, which can be used in further investigation of the pathogenesis and pathophysiology of bovine laminitis.

Desferrioxamine treatment of iron overload secondary to RH isoimmunization and intrauterine transfusion in a newborn infant.

Science.gov (United States)

Yalaz, Mehmet; Bilgin, Betül Siyah; Köroğlu, Ozge Altun; Ay, Yılmaz; Arıkan, Ciğdem; Sagol, Sermet; Akısü, Mete; Kültürsay, Nilgün

2011-11-01

Intrauterine transfusion is the standard of care in the management of severe Rh isoimmunization. Desferrioxamine has been used for the treatment of iron overload secondary to hemolysis and intrauterine transfusions in Rh isoimmunization cases. Here, we report a preterm infant born at 34 weeks of gestational age who had formerly received intrauterine transfusions for Rhesus hemolytic disease and presented with severe hyperferritinemia and elevated liver enzymes in the first week of life. Desferrioxamine treatment was started due to a ferritin level of 28,800 ng/ml and continued for 13 weeks. Although the treatment was successful, we observed resistant leukopenia which resolved after the cessation of treatment. In conclusion, iron overload secondary to intrauterine transfusions can be treated successfully with desferrioxamine; however, neonatologists must be aware of the possible side effects of this drug which has been used in only a limited number of newborns.

Fear of Success: A Personality Trait or a Response to Occupational Deviance and Role Overload?

Science.gov (United States)

Bremer, Teresa Hargrave; Wittig, Michele Andrisin

1980-01-01

Clarifies the extent to which an individual's fear of success scores may vary with the presence or absence of occupational deviance and/or role overload in stimulus materials describing situations of female competitive success. Results suggest that fear of success is a misnomer for responses to women's role descriptions. (Author/JLF)

Evaluation of thermal overload in boiler operators.

Science.gov (United States)

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

2012-01-01

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

Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.

Science.gov (United States)

Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza

2017-02-05

The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca 2+ ) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca 2+ and cause an increase in activity of calcium pumps, including Ca 2+ -ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

On the efficacy of using the transfer-controlled procedure during periods of STP processor overloads in SS7 networks

Science.gov (United States)

Rumsewicz, Michael

1994-04-01

In this paper, we examine call completion performance, rather than message throughput, in a Common Channel Signaling network in which the processing resources, and not transmission resources, of a Signaling Transfer Point (STP) are overloaded. Specifically, we perform a transient analysis, via simulation, of a network consisting of a single Central Processor-based STP connecting many local exchanges. We consider the efficacy of using the Transfer Controlled (TFC) procedure when the network call attempt rate exceeds the processing capability of the STP. We find the following: (1) the success of the control depends critically on the rate at which TFC's are sent; (2) use of the TFC procedure in theevent of processor overload can provide reasonable call completion rates.

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

NARCIS (Netherlands)

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

2007-01-01

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

The analysis of overloaded trucks in indonesia based on weigh in motion data (east of sumatera national road case study

Directory of Open Access Journals (Sweden)

Jihanny Jongga

2018-01-01

Full Text Available Overloaded trucks phenomena generally common in developing countries where the traffic control is poor. In Indonesia, the percentage of overloaded trucks can reach more than 60% in the total number of trucks and may be one of the substantial factors that reduce the service life of the road pavements. This paper presents the analysis results of the weigh in motion survey data at East of Sumatera National Road (Jalintim in Indonesia and the impact of overloaded trucks on the pavement. For the analysis the simplified approach was used, the axle loads were converted into representative single-axle loads based on 4th power formula by AASHTO 1993 equation. The vehicle damage factor of vehicles is presented and will be compared with the Highways National Standard to estimate the remaining service life of pavement and IRI value prediction. The analysis showed that the vehicle damage factor that determined from weigh in motion data is extremely greater than vehicle damage factor of the national standard in Indonesia which may lead to accelerated deterioration, reducing the service life of the pavement structures and significantly influence the IRI value.

Hepcidin is directly regulated by insulin and plays an important role in iron overload in streptozotocin-induced diabetic rats.

Science.gov (United States)

Wang, Heyang; Li, Hongxia; Jiang, Xin; Shi, Wencai; Shen, Zhilei; Li, Min

2014-05-01

Iron overload is frequently observed in type 2 diabetes mellitus (DM2), but the underlying mechanisms remain unclear. We hypothesize that hepcidin may be directly regulated by insulin and play an important role in iron overload in DM2. We therefore examined the hepatic iron content, serum iron parameters, intestinal iron absorption, and liver hepcidin expression in rats treated with streptozotocin (STZ), which was given alone or after insulin resistance induced by a high-fat diet. The direct effect of insulin on hepcidin and its molecular mechanisms were furthermore determined in vitro in HepG2 cells. STZ administration caused a significant reduction in liver hepcidin level and a marked increase in intestinal iron absorption and serum and hepatic iron content. Insulin obviously upregulated hepcidin expression in HepG2 cells and enhanced signal transducer and activator of transcription 3 protein synthesis and DNA binding activity. The effect of insulin on hepcidin disappeared when the signal transducer and activator of transcription 3 pathway was blocked and could be partially inhibited by U0126. In conclusion, the current study suggests that hepcidin can be directly regulated by insulin, and the suppressed liver hepcidin synthesis may be an important reason for the iron overload in DM2.

Role of phenolics from Spondias pinnata bark in amelioration of iron overload induced hepatic damage in Swiss albino mice.

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